Predonation Volume of Future Remnant Cortical Kidney Helps Predict Postdonation Renal Function in Live Kidney Donors.

PubMed

Fananapazir, Ghaneh; Benzl, Robert; Corwin, Michael T; Chen, Ling-Xin; Sageshima, Junichiro; Stewart, Susan L; Troppmann, Christoph

2018-07-01

Purpose To determine whether the predonation computed tomography (CT)-based volume of the future remnant kidney is predictive of postdonation renal function in living kidney donors. Materials and Methods This institutional review board-approved, retrospective, HIPAA-compliant study included 126 live kidney donors who had undergone predonation renal CT between January 2007 and December 2014 as well as 2-year postdonation measurement of estimated glomerular filtration rate (eGFR). The whole kidney volume and cortical volume of the future remnant kidney were measured and standardized for body surface area (BSA). Bivariate linear associations between the ratios of whole kidney volume to BSA and cortical volume to BSA were obtained. A linear regression model for 2-year postdonation eGFR that incorporated donor age, sex, and either whole kidney volume-to-BSA ratio or cortical volume-to-BSA ratio was created, and the coefficient of determination (R 2 ) for the model was calculated. Factors not statistically additive in assessing 2-year eGFR were removed by using backward elimination, and the coefficient of determination for this parsimonious model was calculated. Results Correlation was slightly better for cortical volume-to-BSA ratio than for whole kidney volume-to-BSA ratio (r = 0.48 vs r = 0.44, respectively). The linear regression model incorporating all donor factors had an R 2 of 0.66. The only factors that were significantly additive to the equation were cortical volume-to-BSA ratio and predonation eGFR (P = .01 and P < .01, respectively), and the final parsimonious linear regression model incorporating these two variables explained almost the same amount of variance (R 2 = 0.65) as did the full model. Conclusion The cortical volume of the future remnant kidney helped predict postdonation eGFR at 2 years. The cortical volume-to-BSA ratio should thus be considered for addition as an important variable to living kidney donor evaluation and selection guidelines. �

A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers.

PubMed

Chowdhury, Abeed H; Cox, Eleanor F; Francis, Susan T; Lobo, Dileep N

2012-07-01

We compared the effects of intravenous infusions of 0.9% saline ([Cl] 154 mmol/L) and Plasma-Lyte 148 ([Cl] 98 mmol/L, Baxter Healthcare) on renal blood flow velocity and perfusion in humans using magnetic resonance imaging (MRI). Animal experiments suggest that hyperchloremia resulting from 0.9% saline infusion may affect renal hemodynamics adversely, a phenomenon not studied in humans. Twelve healthy adult male subjects received 2-L intravenous infusions over 1 hour of 0.9% saline or Plasma-Lyte 148 in a randomized, double-blind manner. Crossover studies were performed 7 to 10 days apart. MRI scanning proceeded for 90 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled and weight recorded hourly for 4 hours. Sustained hyperchloremia was seen with saline but not with Plasma-Lyte 148 (P < 0.0001), and fall in strong ion difference was greater with the former (P = 0.025). Blood volume changes were identical (P = 0.867), but there was greater expansion of the extravascular fluid volume after saline (P = 0.029). There was a significant reduction in mean renal artery flow velocity (P = 0.045) and renal cortical tissue perfusion (P = 0.008) from baseline after saline, but not after Plasma-Lyte 148. There was no difference in concentrations of urinary neutrophil gelatinase-associated lipocalin after the 2 infusions (P = 0.917). This is the first human study to demonstrate that intravenous infusion of 0.9% saline results in reductions in renal blood flow velocity and renal cortical tissue perfusion. This has implications for intravenous fluid therapy in perioperative and critically ill patients. NCT01087853.

Proton-coupled oligopeptide transport by rat renal cortical brush border membrane vesicles: a functional analysis using ACE inhibitors to determine the isoform of the transporter.

PubMed

Temple, C S; Boyd, C A

1998-08-14

We demonstrate that the angiotensin-converting enzyme inhibitors enalapril and captopril inhibit the transport of D-Phe-L-Gln into PepT1-expressing Xenopus oocytes and into rat renal cortical brush border membrane vesicles (BBMV). The kinetics of inhibition are competitive. Enalapril and captopril are not substrates for PepT2 (Boll et al., Proc. Natl. Acad. Sci. 93 (1996) 284-289). Therefore we conclude that in rat renal cortical BBMV this neutral dipeptide is transported via PepT1.

Validity of /sup 99m/Tc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function

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

Kawamura, J.; Hosakawa, S.; Yoshida, O.

/sup 99m/Tc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a /sup 131/I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. /sup 99m/Tc dimercaptosuccinic acidmore » scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.« less

Quantitative architectural analysis: a new approach to cortical mapping.

PubMed

Schleicher, A; Palomero-Gallagher, N; Morosan, P; Eickhoff, S B; Kowalski, T; de Vos, K; Amunts, K; Zilles, K

2005-12-01

Recent progress in anatomical and functional MRI has revived the demand for a reliable, topographic map of the human cerebral cortex. Till date, interpretations of specific activations found in functional imaging studies and their topographical analysis in a spatial reference system are, often, still based on classical architectonic maps. The most commonly used reference atlas is that of Brodmann and his successors, despite its severe inherent drawbacks. One obvious weakness in traditional, architectural mapping is the subjective nature of localising borders between cortical areas, by means of a purely visual, microscopical examination of histological specimens. To overcome this limitation, more objective, quantitative mapping procedures have been established in the past years. The quantification of the neocortical, laminar pattern by defining intensity line profiles across the cortical layers, has a long tradition. During the last years, this method has been extended to enable a reliable, reproducible mapping of the cortex based on image analysis and multivariate statistics. Methodological approaches to such algorithm-based, cortical mapping were published for various architectural modalities. In our contribution, principles of algorithm-based mapping are described for cyto- and receptorarchitecture. In a cytoarchitectural parcellation of the human auditory cortex, using a sliding window procedure, the classical areal pattern of the human superior temporal gyrus was modified by a replacing of Brodmann's areas 41, 42, 22 and parts of area 21, with a novel, more detailed map. An extension and optimisation of the sliding window procedure to the specific requirements of receptorarchitectonic mapping, is also described using the macaque central sulcus and adjacent superior parietal lobule as a second, biologically independent example. Algorithm-based mapping procedures, however, are not limited to these two architectural modalities, but can be applied to all images in

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A randomized, controlled, double-blind crossover study on the effects of 1-L infusions of 6% hydroxyethyl starch suspended in 0.9% saline (voluven) and a balanced solution (Plasma Volume Redibag) on blood volume, renal blood flow velocity, and renal cortical tissue perfusion in healthy volunteers.

PubMed

Chowdhury, Abeed H; Cox, Eleanor F; Francis, Susan T; Lobo, Dileep N

2014-05-01

We compared the effects of intravenous administration of 6% hydroxyethyl starch (maize-derived) in 0.9% saline (Voluven; Fresenius Kabi, Runcorn, United Kingdom) and a "balanced" preparation of 6% hydroxyethyl starch (potato-derived) [Plasma Volume Redibag (PVR); Baxter Healthcare, Thetford, United Kingdom] on renal blood flow velocity and renal cortical tissue perfusion in humans using magnetic resonance imaging. Hyperchloremia resulting from 0.9% saline infusion may adversely affect renal hemodynamics when compared with balanced crystalloids. This phenomenon has not been studied with colloids. Twelve healthy adult male subjects received 1-L intravenous infusions of Voluven or PVR over 30 minutes in a randomized, double-blind manner, with crossover studies 7 to 10 days later. Magnetic resonance imaging proceeded for 60 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled, and weight was recorded at 0, 30, 60, 120, 180, and 240 minutes. Mean peak serum chloride concentrations were 108 and 106 mmol/L, respectively, after Voluven and PVR infusion (P = 0.032). Changes in blood volume (P = 0.867), strong ion difference (P = 0.219), and mean renal artery flow velocity (P = 0.319) were similar. However, there was a significant increase in mean renal cortical tissue perfusion after PVR when compared with Voluven (P = 0.033). There was no difference in urinary neutrophil gelatinase-associated liopcalin to creatinine ratios after the infusion (P = 0.164). There was no difference in the blood volume-expanding properties of the 2 preparations of 6% hydroxyethyl starch. The balanced starch produced an increase in renal cortical tissue perfusion, a phenomenon not seen with starch in 0.9% saline.

Femoral Neck X-Ray Absorptiometry Parameters and Peripheral Quantitative Computer Tomography Tibial Cortical Density Predict Survival in Dialysis Patients.

PubMed

Yap, Natalie; Wong, Phillip; McGinn, Stella; Nery, Maria-Liza; Doyle, Jean; Wells, Lynda; Clifton-Bligh, Phillip; Clifton-Bligh, Roderick J

2017-01-01

Low bone mineral density (BMD) is a known independent predictor of mortality in the general elderly population. However, studies in patients with end-stage renal disease (ESRD) are limited. The present study evaluated mortality during long-term follow-up in a population of patients having dialysis for ESRD, in whom BMD was also measured. Fifty-eight patients with ESRD were recruited consecutively from a dialysis clinic and followed prospectively for 6 years. Baseline BMD of the lumbar spine and femoral neck (FN) were measured by X-ray absorptiometry and by peripheral quantitative CT at the radius and tibia. Serum calcium, phosphate, parathyroid hormone (PTH), and albumin were measured at baseline. During follow-up, 25 patients died. Univariate analysis showed that mortality was significantly associated with FN-BMD: hazards ratio (HR) per 0.1 g/cm2 decrease 1.50 (95% CI 1.07-2.10), p = 0.019; FN-T score: HR per 1-SD decrease 1.84 (95% CI 1.16-2.92), p = 0.009; and tibial cortical density: HR per 10 mg/cm3 decrease 1.08 (95% CI 1.02-1.14), p = 0.010. In multivariate analysis with stepwise adjustment for age, sex, transplant status, albumin, PTH, phosphate, dialysis duration, diabetes, and smoking, FN-T score remained significantly associated with mortality: HR per 1-SD decrease 1.82 (95% CI 1.02-3.24), p = 0.044, whereas the HR for FN-BMD and tibial cortical density were no longer significant. When 4 patients who had peritoneal dialysis were excluded, the HR relating FN-BMD, FN-T score, and tibial cortical density to mortality remained significant but became insignificant when albumin was included in the multivariate analysis. Reduced FN-BMD, FN-T score, and tibial cortical density were significantly associated with an increased risk of death in patients with ESRD. © 2017 S. Karger AG, Basel.

Mechanism of grape seeds extract protection against paracetamol renal cortical damage in male Albino rats.

PubMed

Abdel-Hafez, S M N; Rifaai, R A; Abd Elzaher, W Y

2017-01-01

The aim of the study was to assess the possible protective role of grape seeds extract (GSE) in ameliorating the toxic effects of paracetamol overdose on the rat renal cortical tissue. Paracetamol is one of the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Unfortunately, it was reported as the most common cause of toxic ingestion in the world. Grape seeds extract (GSE) is known to have a strong antioxidant and anti-inflammatory properties. The rats were divided into 4 groups; control group, GSE group, paracetamol group and GSE with paracetamol group. Kidney specimens were processed for biochemical, histological and immunohisto-chemical studies. The study showed marked biological changes in the form of significant increase in serum urea and creatinine levels with significant decrease in renal superoxide dismutase with paracetamol group. Furthermore, Proximal (PCT) and distal convoluted tubules showed marked degeneration, dense nuclear staining, cytoplasmic vacuolization, and partial loss of the brush borders. Most tubules were dilated, irregular and were filled with hyaline casts. PCT and DCT showed less PAS reaction and more COX-2 and caspase expression if compared with the control and the GSE groups. Concomitant administration of grape seeds extract with paracetamol revealed a noticeable amelioration of these biochemical and histological changes. Proximal and distal convoluted tubules showed less PAS reaction and more COX2 and caspase expression if compared with the control and the GSE. Concomitant administration of GSE with paracetamol revealed a noticeable amelioration of these biochemical and histological changes. Grape seeds extract provided biochemical and histo-pathological improvement in paracetamol induced renal cortical toxicity. These findings revealed that this improvement was associated with a decrease in oxidative damage and apoptosis (Tab. 1, Fig. 7, Ref. 55).

Quantitative two-dimensional ultrashort echo time magnetization transfer (2D UTE-MT) imaging of cortical bone.

PubMed

Ma, Ya-Jun; Tadros, Anthony; Du, Jiang; Chang, Eric Y

2018-04-01

To investigate quantitative 2D ultrashort echo time magnetization transfer (UTE-MT) imaging in ex vivo bovine cortical bone and in vivo human tibial cortical bone. Data were acquired from five fresh bovine cortical bone samples and five healthy volunteer tibial cortical bones using a 2D UTE-MT sequence on a clinical 3T scanner. The 2D UTE-MT sequence used four or five MT powers with five frequency offsets. Results were analyzed with a two-pool quantitative MT model, providing measurements of macromolecular fraction (f), macromolecular proton transverse relaxation times (T 2m ), proton exchange rates from water/macromolecular to the macromolecular/water pool (RM 0m /RM 0w ), and spin-lattice relaxation rate of water pool (R 1w ). A sequential air-drying study for a small bovine cortical bone chip was used to investigate whether above MT modeling parameters were sensitive to the water loss. Mean fresh bovine cortical bone values for f, T 2m , R 1w , RM 0m , and RM 0w were 59.9 ± 7.3%, 14.6 ± 0.3 μs, 9.9 ± 2.4 s -1 , 17.9 ± 3.6 s -1 , and 11.8 ± 2.0 s -1 , respectively. Mean in vivo human cortical bone values for f, T 2m , R 1w , RM 0m and RM 0w were 54.5 ± 4.9%, 15.4 ± 0.6 μs, 8.9 ± 1.1 s -1 , 11.5 ± 3.5 s -1 , and 9.5 ± 1.9 s -1 , respectively. The sequential air-drying study shows that f, RM 0m , and R 1w were increased with longer drying time. UTE-MT two-pool modeling provides novel and useful quantitative information for cortical bone. Magn Reson Med 79:1941-1949, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

PubMed

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all

Renal artery anatomy assessed by quantitative analysis of selective renal angiography in 1,000 patients with hypertension.

PubMed

Lauder, Lucas; Ewen, Sebastian; Tzafriri, Abraham Rami; Edelman, Elazer Reuven; Lüscher, Thomas Felix; Blankenstijn, Peter J; Dörr, Oliver; Schlaich, Markus; Sharif, Faisal; Voskuil, Michiel; Zeller, Thomas; Ukena, Christian; Scheller, Bruno; Böhm, Michael; Mahfoud, Felix

2018-05-20

With increasing attention to renovascular causes and targets for hypertension there arises a critical need for more detailed knowledge of renal arterial anatomy. However, a standardised nomenclature is lacking. The present study sought to develop a standardised nomenclature for renal anatomy considering the complexity and variation of the renal arterial tree and to assess the applicability of the nomenclature. One thousand hypertensive patients underwent invasive selective renal artery angiography in nine centres. Further, renovasography was performed in 249 healthy swine as a surrogate for normotensive anatomy. Anatomical parameters were assessed by quantitative vascular analysis. Patients' mean blood pressure was 168/90±26/17 mmHg. The right main renal artery was longer than the left (41±15 mm vs. 35±13 mm, p<0.001), but the left had a greater diameter (5.4±1.2 vs. 5.2±1.2 mm, p<0.001). Accessory renal arteries and renal artery disease were documented in 22% and 9% of the patients, respectively. Other than exhibiting a longer left main renal artery in uncontrolled hypertensives (+2.7 mm, p=0.034) there was no anatomical difference between patients with controlled and uncontrolled hypertension. Main renal artery mean diameter was smaller in patients with impaired kidney function (GFR <90 ml/min, left -0.5 mm, right -0.4 mm, both p<0.001). Renal arterial anatomy differs between sides but shows no difference between patients with and without blood pressure control. Impaired GFR was associated with small main renal artery diameter.

Stent revascularization restores cortical blood flow and reverses tissue hypoxia in atherosclerotic renal artery stenosis but fails to reverse inflammatory pathways or glomerular filtration rate.

PubMed

Saad, Ahmed; Herrmann, Sandra M S; Crane, John; Glockner, James F; McKusick, Michael A; Misra, Sanjay; Eirin, Alfonso; Ebrahimi, Behzad; Lerman, Lilach O; Textor, Stephen C

2013-08-01

Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow, glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulointerstitial injury in the poststenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury. Inpatient studies were performed in patients with ARAS (n=17; >60% occlusion) before and 3 months after stent revascularization, or in patients with essential hypertension (n=32), during fixed Na(+) intake and angiotensin converting enzyme/angiotensin receptors blockers Rx. Single kidney cortical, medullary perfusion, and renal blood flow were measured using multidetector computed tomography, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels (R(2)*) were measured by blood oxygen level-dependent MRI at 3T, as was fractional kidney hypoxia (percentage of axial area with R(2)*>30/s). In addition, we measured renal vein levels of neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Pre-stent single kidney renal blood flow, perfusion, and GFR were reduced in the poststenotic kidney. Renal vein neutrophil gelatinase-associated lipocalin, tumor necrosis factor-α, monocyte chemoattractant protein-1, and fractional hypoxia were higher in untreated ARAS than in essential hypertension. After stent revascularization, fractional hypoxia fell (P<0.002) with increased cortical perfusion and blood flow, whereas GFR and neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α remained unchanged. These data demonstrate that despite reversal of renal hypoxia and partial restoration of renal blood flow after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to

Clinical application of calculated split renal volume using computed tomography-based renal volumetry after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic acid renal scan data.

PubMed

Lee, Chan Ho; Park, Young Joo; Ku, Ja Yoon; Ha, Hong Koo

2017-06-01

To evaluate the clinical application of computed tomography-based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium-99m dimercaptosuccinic acid renal scan. The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The renal cortical volume of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate and split renal volume calculated using this renal cortical volume were compared with the split renal function measured with technetium-99m dimercaptosuccinic acid renal scan. A strong correlation between split renal function and split renal volume of the tumor-bearing kidney was observed before and after surgery (r = 0.89, P < 0.001 and r = 0.94, P < 0.001). The preoperative and postoperative split estimated glomerular filtration rate of the operated kidney showed a moderate correlation with split renal function (r = 0.39, P = 0.004 and r = 0.49, P < 0.001). The correlation between reductions in split renal function and split renal volume of the operated kidney (r = 0.87, P < 0.001) was stronger than that between split renal function and percent reduction in split estimated glomerular filtration rate (r = 0.64, P < 0.001). The split renal volume calculated using computed tomography-based renal volumetry had a strong correlation with the split renal function measured using technetium-99m dimercaptosuccinic acid renal scan. Computed tomography-based split renal volume measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney. © 2017 The Japanese Urological Association.

Use of quantitative SPECT/CT reconstruction in 99mTc-sestamibi imaging of patients with renal masses.

PubMed

Jones, Krystyna M; Solnes, Lilja B; Rowe, Steven P; Gorin, Michael A; Sheikhbahaei, Sara; Fung, George; Frey, Eric C; Allaf, Mohamad E; Du, Yong; Javadi, Mehrbod S

2018-02-01

Technetium-99m ( 99m Tc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has previously been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma (RCC) showing low uptake based on uptake ratios from non-quantitative single-photon emission computed tomography (SPECT) reconstructions. However, in this study, several tumors fell close to the uptake ratio cutoff, likely due to limitations in conventional SPECT/CT reconstruction methods. We hypothesized that application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by our group would provide more robust separation of hot and cold lesions, serving as an imaging framework on which quantitative biomarkers can be validated for evaluation of renal masses with 99m Tc-sestamibi. Single-photon emission computed tomography data were reconstructed using the clinical Flash 3D reconstruction and QSPECT methods. Two blinded readers then characterized each tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing lesion activity by background renal activity for both Flash 3D and QSPECT reconstructions. The difference between median (mean) hot and cold tumor uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with the conventional method, resulting in increased separation between hot and cold tumors. Sub-analysis of 7 lesions near the separation point showed a higher absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios compared to the remaining lesions. Our finding of improved separation between uptake ratios of hot and cold lesions using QSPECT reconstruction lays the foundation for additional quantitative SPECT techniques such as SPECT-UV in the setting of renal 99m Tc-sestamibi and other SPECT/CT exams. With robust

Longitudinal assessment of mouse renal injury using high-resolution anatomic and magnetization transfer MR imaging.

PubMed

Wang, Feng; Jiang, Rosie; Takahashi, Keiko; Gore, John; Harris, Raymond C; Takahashi, Takamune; Quarles, C Chad

2014-11-01

The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T1-weighted, T2-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T1 and T2 weighted images were collected in UUO mice on day 0 (~3h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (p<0.05) changes in thickness of cortex and outer medulla, and regional changes in T2 signal intensity and MTR values. Histological changes included tubular cell death, tubular dilation, urine retention, and interstitial fibrosis, assessed by histology. The MRI measures of renal cortical and medullary atrophy, cortical-medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Pyrogenic renal hyperemia: the role of prostaglandins.

PubMed

Gagnon, J A; Ramwell, P W; Flamenbaum, W

1978-01-01

The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a significant increase in renal blood flow accompanied by a modest decline in systemic blood pressure. This renal hyperemia was associated with elevated renal secretory rates of renin and prostaglandin E and F. Measurements of the intracortical distribution of radiolabeled microspheres revealed a progressive decrease in outer cortical blood flow rates and a progressive increase in inner cortical flow rates. When meclofenamate, an inhibitor of prostaglandin synthetase, was administered concomitantly with triple typhoid vaccine renal hyperemia did not develop. The renal renin secretory rate increased modestly and intracortical renal blood flow was not redistributed. The increased renal blood flow after triple typhoid vaccine administration to unanesthetized dogs was also reversed by meclofenamate. The marked increase in prostaglandin secretion by the kidney during renal hyperemia following triple typhoid vaccine administration (pyrogen), and the effect of meclofenamate, is consonant with a role for increased renal synthesis and release of prostaglandins.

Renal cortical and medullary blood flow responses to altered NO availability in humans.

PubMed

Damkjær, Mads; Vafaee, Manoucher; Møller, Michael L; Braad, Poul Erik; Petersen, Henrik; Høilund-Carlsen, Poul Flemming; Bie, Peter

2010-12-01

The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed at baseline, during constant intravenous infusion of nitric oxide (NO) donor glyceryl nitrate and after intravenous injection of NO synthase inhibitor N(ω)-monomethyl-L-arginine (L-NMMA). Using the CT image, the kidney pole areas were delineated as volumes of interest (VOI). In the data analysis, tissue layers with a thickness of one voxel were eliminated stepwise from the external surface of the VOI (voxel peeling), and the blood flow subsequently was determined in each new, reduced VOI. Blood flow in the shrinking VOIs decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ± 0.17 ml·g tissue(-1)·min(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ± 0.18 ml·g tissue(-1)·min(-1) (P < 0.05) and decreased after L-NMMA injection to 1.57 ± 0.17 ml·g tissue(-1)·min(-1) (P < 0.05). Cortical blood flow was 4.67 ± 0.31 ml·g tissue(-1)·min(-1) during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 ± 0.23 ml·(g·min)(-1), P < 0.05]. PET/CT scanning allows identification of a renal medullary region in which the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans.

Assessment of Renal Hemodynamics and Oxygenation by Simultaneous Magnetic Resonance Imaging (MRI) and Quantitative Invasive Physiological Measurements.

PubMed

Cantow, Kathleen; Arakelyan, Karen; Seeliger, Erdmann; Niendorf, Thoralf; Pohlmann, Andreas

2016-01-01

In vivo assessment of renal perfusion and oxygenation under (patho)physiological conditions by means of noninvasive diagnostic imaging is conceptually appealing. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and quantitative parametric mapping of the magnetic resonance (MR) relaxation times T 2* and T 2 are thought to provide surrogates of renal tissue oxygenation. The validity and efficacy of this technique for quantitative characterization of local tissue oxygenation and its changes under different functional conditions have not been systematically examined yet and remain to be established. For this purpose, the development of an integrative multimodality approaches is essential. Here we describe an integrated hybrid approach (MR-PHYSIOL) that combines established quantitative physiological measurements with T 2* (T 2) mapping and MR-based kidney size measurements. Standardized reversible (patho)physiologically relevant interventions, such as brief periods of aortic occlusion, hypoxia, and hyperoxia, are used for detailing the relation between the MR-PHYSIOL parameters, in particular between renal T 2* and tissue oxygenation.

[Investigation of renal corticomedullary differentiation with age-related change on non-contrast-enhanced MRI].

PubMed

Shang, J N; Ren, K; Wu, W S; Lu, T; Sun, W G; Zhang, H G; Li, X D; Liu, Y

2016-05-24

To evaluate the relationship between renal corticomedullary differentiation, renal cortical thickness and age-related changes with non-contrast-enhanced steady-state free precession(SSFP) magnetic resonance imaging (MRI) and spatially selective inversion recovery(IR) pulse technology as well as its applied value . A total of 76 healthy volunteers had been recruited from August 2014 to June 2015 in First Hospital of China Medical University.All volunteers were divided into three groups: 2-40 years old, 41-60 years old, 61-80 years old. All 76 volunteers underwent non-contrast-enhanced steady-state free precession(SSFP) 3.0 T MRI scan using variable inversion times (TIs)(TI=1 000, 1 100, 1 200, 1 300, 1 400, 1 500, 1 600, 1 700 ms). The renal corticomedullary differentiation was observed and the signal intensity of renal cortex and medulla were measured respectively as well in order to calculate renal corticomedullary contrast ratio. Besides, renal cortical thickness and renal size were measured. All 76 volunteers were successfully performed all the sequences of MRI scan, including 152 useful imaging of kidney in total. The renal corticomedullary differentiation was clearly shown in all subjects. There was negative correlation between the optimal inversion time(TI) and age(r=-0.65, P<0.01). Similarly, negative correlation was observed between renal corticomedullary contrast ratio and age(r=-0.35, P<0.01). The mean renal cortical thickness of all subjects was (5.33±0.71)mm and there were statistically significant difference among those different groups, which was negative-related with age(r=-0.79, P<0.01). There was no statistically significant difference between sexuality and renal cortical thickness.Additionally, renal cortical thickness had no statistically significant difference in both sides of kidneys. The renal corticomedullary differentiation is depicted clearly by means of non-contrast-enhanced steady-state free precession MRI with spatially selective

Diagnostic value of quantitative contrast-enhanced ultrasound (CEUS) for early detection of renal hyperperfusion in diabetic kidney disease.

PubMed

Wang, Ling; Wu, Jian; Cheng, Jia-Fen; Liu, Xin-Ying; Ma, Fang; Guo, Le-Hang; Xu, Jun-Mei; Wu, Tianfu; Mohan, Chandra; Peng, Ai; Xu, Hui-Xiong; Song, Ya-Xiang

2015-12-01

To investigate the diagnostic value of quantitative contrast-enhanced ultrasound (CEUS) for early detection of renal hyperperfusion in diabetic kidney disease (DKD). 55 DKD patients with estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m(2) and 26 normal controls (NCs) were enrolled. Clinical data was well documented. Blood samples were drawn for evaluation of renal function including blood urea nitrogen (BUN), serum creatinine (SCr) and serum uric acid (SUA), and urine samples were assayed for total protein quantification, and various microprotein markers. According to eGFR level, DKD patients were divided into early-stage DKD (eGFR ≥90 ml/min/1.73 m(2), n = 18) and middle-stage DKD (eGFR 30-90 ml/min/1.73 m(2), n = 37). Based on urinary microalbumin/creatinine ratio (MALB/UCR), early-stage DKD patients were further classified into two groups: MALB/UCR <10 g/mol (n = 11) and MALB/UCR ≥10 g/mol (n = 7). Then, CEUS was performed to observe the real-time renal perfusion, and low acoustic power contrast-specific imaging was used for quantitative analysis. The renal perfusion images of CEUS were well developed successively. The corresponding perfusion curves based on echo-power signals in time series were constructed. Quantitative analysis showed that area under the descending curve (AUC2) was significantly increased in early-stage DKD compared to middle-stage DKD (p < 0.05), but AUC showed no significant difference. Further comparison between different MALB/UCR levels of early-stage DKD showed that patients with MALB/UCR ≥10 g/mol had significantly increased levels of AUC, AUC2 and proteinuria than patients with low MALB/UCR (p < 0.05). Also, high MALB/UCR DKD patients had increased proteinuria but similar eGFR compared to low MALB/UCR patients. Renal microvascular hyperperfusion may be responsible for overt proteinuria until decline of renal filtration in DKD. AUC2 could be an early and sensitive marker for early renal injury and renal microvascular

Reproducibility of Direct Quantitative Measures of Cortical Bone Micro-architecture of the Distal Radius and Tibia by HR-pQCT

PubMed Central

Burghardt, Andrew J.; Buie, Helen R.; Laib, Andres; Majumdar, Sharmila; Boyd, Steven K.

2010-01-01

Quantitative cortical micro-architectural endpoints are important for understanding structure-function relations in the context of fracture risk and therapeutic efficacy. This technique study details new image-processing methods to automatically segment and directly quantify cortical density, geometry, and micro-architecture from HR-pQCT images of the distal radius and tibia. An automated segmentation technique was developed to identify the periosteal and endosteal margins of the distal radius and tibia, and detect intra-cortical pore space morphologically consistent with Haversian canals. The reproducibility of direct quantitative cortical bone indices based on this method was assessed in a pooled dataset of 56 subjects with two repeat acquisitions for each site. The in vivo precision error was characterized using root mean square coefficient of variation (RMSCV%) from which, the least significant change (LSC) was calculated. Bland-Altman plots were used to characterize bias in the precision estimates. The reproducibility of cortical density and cross-sectional area measures was high (RMSCV <1% and <1.5%, respectively) with good agreement between young and elder medians. The LSC for cortical porosity (Ct.Po) was somewhat smaller in the radius (0.58%) compared with the distal tibia (0.84%) and significantly different between young and elder medians in the distal tibia (LSC: 0.75% vs. 0.92%; p<0.001). The LSC for pore diameter and distribution (Po.Dm and Po.Dm.SD) ranged between 15 and 23μm. Bland-Altman analysis revealed moderate bias for integral measures of area and volume, but not density nor microarchitecture. This study indicates HR-pQCT measures of cortical bone density and architecture can be measured in vivo with high reproducibility and limited bias across a biologically relevant range of values. The results of this study provide informative data for the design of future clinical studies of bone quality. PMID:20561906

Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.

PubMed

Jiang, Xiaoliang; Zhang, Yanrong; Yang, Yu; Yang, Jian; Asico, Laureano D; Chen, Wei; Felder, Robin A; Armando, Ines; Jose, Pedro A; Yang, Zhiwei

2017-01-01

Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. Copyright © 2017 the American Physiological Society.

Towards assessing cortical bone porosity using low-frequency quantitative acoustics: A phantom-based study.

PubMed

Vogl, Florian; Bernet, Benjamin; Bolognesi, Daniele; Taylor, William R

2017-01-01

Cortical porosity is a key characteristic governing the structural properties and mechanical behaviour of bone, and its quantification is therefore critical for understanding and monitoring the development of various bone pathologies such as osteoporosis. Axial transmission quantitative acoustics has shown to be a promising technique for assessing bone health in a fast, non-invasive, and radiation-free manner. One major hurdle in bringing this approach to clinical application is the entanglement of the effects of individual characteristics (e.g. geometry, porosity, anisotropy etc.) on the measured wave propagation. In order to address this entanglement problem, we therefore propose a systematic bottom-up approach, in which only one bone property is varied, before addressing interaction effects. This work therefore investigated the sensitivity of low-frequency quantitative acoustics to changes in porosity as well as individual pore characteristics using specifically designed cortical bone phantoms. 14 bone phantoms were designed with varying pore size, axial-, and radial pore number, resulting in porosities (bone volume fraction) between 0% and 15%, similar to porosity values found in human cortical bone. All phantoms were manufactured using laser sintering, measured using axial-transmission acoustics and analysed using a full-wave approach. Experimental results were compared to theoretical predictions based on a modified Timoshenko theory. A clear dependence of phase velocity on frequency and porosity produced by increasing pore size or radial pore number was demonstrated, with the velocity decreasing by between 2-5 m/s per percent of additional porosity, which corresponds to -0.5% to -1.0% of wave speed. While the change in phase velocity due to axial pore number was consistent with the results due to pore size and radial pore number, the relative uncertainties for the estimates were too high to draw any conclusions for this parameter. This work has shown the

Towards assessing cortical bone porosity using low-frequency quantitative acoustics: A phantom-based study

PubMed Central

Vogl, Florian; Bernet, Benjamin; Bolognesi, Daniele; Taylor, William R.

2017-01-01

Purpose Cortical porosity is a key characteristic governing the structural properties and mechanical behaviour of bone, and its quantification is therefore critical for understanding and monitoring the development of various bone pathologies such as osteoporosis. Axial transmission quantitative acoustics has shown to be a promising technique for assessing bone health in a fast, non-invasive, and radiation-free manner. One major hurdle in bringing this approach to clinical application is the entanglement of the effects of individual characteristics (e.g. geometry, porosity, anisotropy etc.) on the measured wave propagation. In order to address this entanglement problem, we therefore propose a systematic bottom-up approach, in which only one bone property is varied, before addressing interaction effects. This work therefore investigated the sensitivity of low-frequency quantitative acoustics to changes in porosity as well as individual pore characteristics using specifically designed cortical bone phantoms. Materials and methods 14 bone phantoms were designed with varying pore size, axial-, and radial pore number, resulting in porosities (bone volume fraction) between 0% and 15%, similar to porosity values found in human cortical bone. All phantoms were manufactured using laser sintering, measured using axial-transmission acoustics and analysed using a full-wave approach. Experimental results were compared to theoretical predictions based on a modified Timoshenko theory. Results A clear dependence of phase velocity on frequency and porosity produced by increasing pore size or radial pore number was demonstrated, with the velocity decreasing by between 2–5 m/s per percent of additional porosity, which corresponds to -0.5% to -1.0% of wave speed. While the change in phase velocity due to axial pore number was consistent with the results due to pore size and radial pore number, the relative uncertainties for the estimates were too high to draw any conclusions for this

Detailing the relation between renal T2* and renal tissue pO2 using an integrated approach of parametric magnetic resonance imaging and invasive physiological measurements.

PubMed

Pohlmann, Andreas; Arakelyan, Karen; Hentschel, Jan; Cantow, Kathleen; Flemming, Bert; Ladwig, Mechthild; Waiczies, Sonia; Seeliger, Erdmann; Niendorf, Thoralf

2014-08-01

This study was designed to detail the relation between renal T2* and renal tissue pO2 using an integrated approach that combines parametric magnetic resonance imaging (MRI) and quantitative physiological measurements (MR-PHYSIOL). Experiments were performed in 21 male Wistar rats. In vivo modulation of renal hemodynamics and oxygenation was achieved by brief periods of aortic occlusion, hypoxia, and hyperoxia. Renal perfusion pressure (RPP), renal blood flow (RBF), local cortical and medullary tissue pO2, and blood flux were simultaneously recorded together with T2*, T2 mapping, and magnetic resonance-based kidney size measurements (MR-PHYSIOL). Magnetic resonance imaging was carried out on a 9.4-T small-animal magnetic resonance system. Relative changes in the invasive quantitative parameters were correlated with relative changes in the parameters derived from MRI using Spearman analysis and Pearson analysis. Changes in T2* qualitatively reflected tissue pO2 changes induced by the interventions. T2* versus pO2 Spearman rank correlations were significant for all interventions, yet quantitative translation of T2*/pO2 correlations obtained for one intervention to another intervention proved not appropriate. The closest T2*/pO2 correlation was found for hypoxia and recovery. The interlayer comparison revealed closest T2*/pO2 correlations for the outer medulla and showed that extrapolation of results obtained for one renal layer to other renal layers must be made with due caution. For T2* to RBF relation, significant Spearman correlations were deduced for all renal layers and for all interventions. T2*/RBF correlations for the cortex and outer medulla were even superior to those between T2* and tissue pO2. The closest T2*/RBF correlation occurred during hypoxia and recovery. Close correlations were observed between T2* and kidney size during hypoxia and recovery and for occlusion and recovery. In both cases, kidney size correlated well with renal vascular conductance

Assessment of quantitative cortical biomarkers in the developing brain of preterm infants

NASA Astrophysics Data System (ADS)

Moeskops, Pim; Benders, Manon J. N. L.; Pearlman, Paul C.; Kersbergen, Karina J.; Leemans, Alexander; Viergever, Max A.; Išgum, Ivana

2013-02-01

The cerebral cortex rapidly develops its folding during the second and third trimester of pregnancy. In preterm birth, this growth might be disrupted and influence neurodevelopment. The aim of this work is to extract quantitative biomarkers describing the cortex and evaluate them on a set of preterm infants without brain pathology. For this study, a set of 19 preterm - but otherwise healthy - infants scanned coronally with 3T MRI at the postmenstrual age of 30 weeks were selected. In ten patients (test set), the gray and white matter were manually annotated by an expert on the T2-weighted scans. Manual segmentations were used to extract cortical volume, surface area, thickness, and curvature using voxel-based methods. To compute these biomarkers per region in every patient, a template brain image has been generated by iterative registration and averaging of the scans of the remaining nine patients. This template has been manually divided in eight regions, and is transformed to every test image using elastic registration. In the results, gray and white matter volumes and cortical surface area appear symmetric between hemispheres, but small regional differences are visible. Cortical thickness seems slightly higher in the right parietal lobe than in other regions. The parietal lobes exhibit a higher global curvature, indicating more complex folding compared to other regions. The proposed approach can potentially - together with an automatic segmentation algorithm - be applied as a tool to assist in early diagnosis of abnormalities and prediction of the development of the cognitive abilities of these children.

Combining Ultrasound Pulse-Echo and Transmission Computed Tomography for Quantitative Imaging the Cortical Shell of Long Bone Replicas

NASA Astrophysics Data System (ADS)

Shortell, Matthew P.; Althomali, Marwan A. M.; Wille, Marie-Luise; Langton, Christian M.

2017-11-01

We demonstrate a simple technique for quantitative ultrasound imaging of the cortical shell of long bone replicas. Traditional ultrasound computed tomography instruments use the transmitted or reflected waves for separate reconstructions but suffer from strong refraction artefacts in highly heterogenous samples such as bones in soft tissue. The technique described here simplifies the long bone to a two-component composite and uses both the transmitted and reflected waves for reconstructions, allowing the speed of sound and thickness of the cortical shell to be calculated accurately. The technique is simple to implement, computationally inexpensive and sample positioning errors are minimal.

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

Comparison of four decontamination treatments on porcine renal decellularized extracellular matrix structure, composition, and support of human renal cortical tubular epithelium cells.

PubMed

Poornejad, Nafiseh; Nielsen, Jeffery J; Morris, Ryan J; Gassman, Jason R; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D

2016-03-01

Engineering whole organs from porcine decellularized extracellular matrix and human cells may lead to a plentiful source of implantable organs. Decontaminating the porcine decellularized extracellular matrix scaffolds is an essential step prior to introducing human cells. However, decontamination of whole porcine kidneys is a major challenge because the decontamination agent or irradiation needs to diffuse deep into the structure to eliminate all microbial contamination while minimizing damage to the structure and composition of the decellularized extracellular matrix. In this study, we compared four decontamination treatments that could be applicable to whole porcine kidneys: 70% ethanol, 0.2% peracetic acid in 1 M NaCl, 0.2% peracetic acid in 4% ethanol, and gamma (γ)-irradiation. Porcine kidneys were decellularized by perfusion of 0.5% (w/v) aqueous solution of sodium dodecyl sulfate and the four decontamination treatments were optimized using segments (n = 60) of renal tissue to ensure a consistent comparison. Although all four methods were successful in decontamination, γ-irradiation was very damaging to collagen fibers and glycosaminoglycans, leading to less proliferation of human renal cortical tubular epithelium cells within the porcine decellularized extracellular matrix. The effectiveness of the other three optimized solution treatments were then all confirmed using whole decellularized porcine kidneys (n = 3). An aqueous solution of 0.2% peracetic acid in 1 M NaCl was determined to be the best method for decontamination of porcine decellularized extracellular matrix. © The Author(s) 2015.

Anatomic and Quantitative Temporal Bone CT for Preoperative Assessment of Branchio-Oto-Renal Syndrome.

PubMed

Ginat, D T; Ferro, L; Gluth, M B

2016-12-01

We describe the temporal bone computed tomography (CT) findings of an unusual case of branchio-oto-renal syndrome with ectopic ossicles that are partially located in the middle cranial fossa. We also describe quantitative temporal bone CT assessment pertaining to cochlear implantation in the setting of anomalous cochlear anatomy associated with this syndrome.

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

Influence of the renal endothelin system on the autoregulation of renal blood flow in spontaneously hypertensive rats.

PubMed

Braun, C; Lang, C; Hocher, B; Gretz, N; van der Woude, F J; Rohmeiss, P

1997-01-01

The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.

Atherosclerotic renal artery stenosis in the post-CORAL era part 1: the renal penumbra concept and next-generation functional diagnostic imaging.

PubMed

Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet

2016-04-01

After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria.

PubMed

Wong, Dickson W L; Yiu, Wai Han; Chan, Kam Wa; Li, Ye; Li, Bin; Lok, Sarah W Y; Taketo, Makoto M; Igarashi, Peter; Chan, Loretta Y Y; Leung, Joseph C K; Lai, Kar Neng; Tang, Sydney C W

2018-06-01

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration. Four weeks after tamoxifen injection, uninephrectomized Tubcat mice displayed proteinuria and elevated blood urea nitrogen levels compared to non-transgenic mice, implying a detrimental effect of the activated signaling. This was associated with infiltration of the tubulointerstitium predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by intraperitoneal injection of low-endotoxin bovine serum albumin following uninephrectomy for four weeks aggravated proteinuria and increased blood urea nitrogen levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1, and ICAM-1. There was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, independent of bovine serum albumin injection. Finally, there was no fibrosis, activation of epithelial-mesenchymal transition or non-canonical Wnt pathways observed in the kidneys of Tubcat mice. Thus, conditional activation of renal tubular Wnt/β-catenin signaling in a novel transgenic mouse model demonstrates that this pathway enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated haemorrhage.

PubMed

Jönsson, Sofia; Melville, Jacqueline M; Becirovic-Agic, Mediha; Hultström, Michael

2018-04-18

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and haemorrhage. We found that Losartan does not cause renal cortical hypoxia after haemorrhage in rats because of decreased renal vascular resistance, but did not evaluate resuscitation. Study Losartan´s effect on renal cortical and medullary oxygenation, and norepinephrine´s vasopressor effect in a model of resuscitated haemorrhage. After seven days Losartan (60 mg/kg/day) or control treatment, male Wistar rats were haemorrhaged 20 % of the blood volume and resuscitated with Ringer's Acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation was measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, Losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated haemorrhage. Smaller increase of renal vascular resistance in Losartan group translated to smaller decrease in cortical oxygen tension, but no significant difference seen in medullary oxygen tension either between groups or after haemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in controls and Losartan treated rats. Losartan does not decrease renal oxygenation after resuscitated haemorrhage because of a smaller increase in renal vascular resistance. Further, Losartan does not decrease the efficiency of norepinephrine as a vasopressor indicating that blood pressure may be managed effectively during Losartan treatment.

Renal involvement in leprosy: evaluation of patients in Turkey.

PubMed

Ozturk, Savas; Ozturk, Tulin; Can, Ilkay

2017-06-01

Renal involvement in leprosy has previously been described in the literature and can include amyloidosis, glomerulonephritis, nephrosclerosis, tubulointerstitial nephritis, and granulomas. To evaluate renal involvement in Turkish patients with leprosy. In total, 32 patients with lepromatous leprosy but without any co-morbidities and 35 healthy control subjects were evaluated for renal involvement at the Elazig Training and Research Hospital in Turkey. The laboratory tests and radiological results concerning renal function were taken from both the patients' medical records and from current examinations. The levels of creatinine, urea, and leukocyturia in the lepromatous leprosy patients were significantly higher than in the controls ( p < 0.001, p < 0.001; p = 0.001, p < 0.01; p = 0.036, p < 0.05, respectively). No significant differences in the proteinuria, hematuria, sodium, or potassium levels were found between the leprosy and control groups ( p > 0.05). On ultrasonographic examination, the prevalence of renal cortical cysts and renal cortical echogenicity in the leprosy patients was significantly higher than in the controls ( p = 0.020, p < 0.05, respectively). There were no significant differences in terms of nephrolithiasis, parapelvic cysts, or hydronephrosis between the leprosy and control groups ( p > 0.05). Evaluating the renal function in all leprosy patients is important to detect abnormalities and to prevent renal failure, which remains a potential cause of death in this disease.

Evaluation of anabolic steroid induced renal damage with sonography in bodybuilders.

PubMed

Kantarci, Umut H; Punduk, Zekine; Senarslan, Omer; Dirik, Alper

2017-11-17

The aim of this study was to investigate the effect of anabolic steroids on kidneys in bodybuilders. Twenty two bodybuilders were included in the study. Participants were divided into three groups according to the scheme of steroid usage: Group 1 (n=8, intramuscular 500 mg testosterone enanthate, intramuscular 400 mg nandrolone decanoate and oral 40 mg methandrostenolone for 12 weeks), Group 2 (n=7, intramuscular 500 mg testosterone enanthate, intramuscular 300 mg nandrolone decanoate and intramuscular 300 mg boldenone undecylenate for 16 weeks) and Group 3 (n=7, no steroid intake). Blood urea nitrogen (BUN), creatinine (Cr), urine microalbumin and electrolyte levels were measured. Renal volume, cortical thickness and echogenicity were obtained in ultrasonographic scans. Renal volume, cortical thickness, echogenicity and protein intake value were significantly higher in group 2 than group 1 and 3. Plasma levels of BUN and Cr in group 2 were significantly higher than other groups (p ˂ 0.001). Urine microalbumin and electrolyte levels were normal in all groups. The results of this study indicate that high protein intake, steroid usage, particularly the schemes, including boldenone undecylenate increases cortical echogenicity, thickness of renal parenchyma and renal volume in bodybuilders.

High temporal resolution dynamic contrast-enhanced MRI using compressed sensing-combined sequence in quantitative renal perfusion measurement.

PubMed

Chen, Bin; Zhao, Kai; Li, Bo; Cai, Wenchao; Wang, Xiaoying; Zhang, Jue; Fang, Jing

2015-10-01

To demonstrate the feasibility of the improved temporal resolution by using compressed sensing (CS) combined imaging sequence in dynamic contrast-enhanced MRI (DCE-MRI) of kidney, and investigate its quantitative effects on renal perfusion measurements. Ten rabbits were included in the accelerated scans with a CS-combined 3D pulse sequence. To evaluate the image quality, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the proposed CS strategy and the conventional full sampling method. Moreover, renal perfusion was estimated by using the separable compartmental model in both CS simulation and realistic CS acquisitions. The CS method showed DCE-MRI images with improved temporal resolution and acceptable image contrast, while presenting significantly higher SNR than the fully sampled images (p<.01) at 2-, 3- and 4-X acceleration. In quantitative measurements, renal perfusion results were in good agreement with the fully sampled one (concordance correlation coefficient=0.95, 0.91, 0.88) at 2-, 3- and 4-X acceleration in CS simulation. Moreover, in realistic acquisitions, the estimated perfusion by the separable compartmental model exhibited no significant differences (p>.05) between each CS-accelerated acquisition and the full sampling method. The CS-combined 3D sequence could improve the temporal resolution for DCE-MRI in kidney while yielding diagnostically acceptable image quality, and it could provide effective measurements of renal perfusion. Copyright © 2015 Elsevier Inc. All rights reserved.

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

Development of CD3 cell quantitation algorithms for renal allograft biopsy rejection assessment utilizing open source image analysis software.

PubMed

Moon, Andres; Smith, Geoffrey H; Kong, Jun; Rogers, Thomas E; Ellis, Carla L; Farris, Alton B Brad

2018-02-01

Renal allograft rejection diagnosis depends on assessment of parameters such as interstitial inflammation; however, studies have shown interobserver variability regarding interstitial inflammation assessment. Since automated image analysis quantitation can be reproducible, we devised customized analysis methods for CD3+ T-cell staining density as a measure of rejection severity and compared them with established commercial methods along with visual assessment. Renal biopsy CD3 immunohistochemistry slides (n = 45), including renal allografts with various degrees of acute cellular rejection (ACR) were scanned for whole slide images (WSIs). Inflammation was quantitated in the WSIs using pathologist visual assessment, commercial algorithms (Aperio nuclear algorithm for CD3+ cells/mm 2 and Aperio positive pixel count algorithm), and customized open source algorithms developed in ImageJ with thresholding/positive pixel counting (custom CD3+%) and identification of pixels fulfilling "maxima" criteria for CD3 expression (custom CD3+ cells/mm 2 ). Based on visual inspections of "markup" images, CD3 quantitation algorithms produced adequate accuracy. Additionally, CD3 quantitation algorithms correlated between each other and also with visual assessment in a statistically significant manner (r = 0.44 to 0.94, p = 0.003 to < 0.0001). Methods for assessing inflammation suggested a progression through the tubulointerstitial ACR grades, with statistically different results in borderline versus other ACR types, in all but the custom methods. Assessment of CD3-stained slides using various open source image analysis algorithms presents salient correlations with established methods of CD3 quantitation. These analysis techniques are promising and highly customizable, providing a form of on-slide "flow cytometry" that can facilitate additional diagnostic accuracy in tissue-based assessments.

Alterations of bone microstructure and strength in end-stage renal failure.

PubMed

Trombetti, A; Stoermann, C; Chevalley, T; Van Rietbergen, B; Herrmann, F R; Martin, P-Y; Rizzoli, R

2013-05-01

End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular bone microstructure and of bone strength and stiffness in ESRD patients. Fragility fractures are common in ESRD patients on dialysis. Alterations of bone microstructure contribute to skeletal fragility, independently of areal bone mineral density. We compared microstructure and finite-element analysis estimates of strength and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 33 ESRD patients on dialysis (17 females and 16 males; mean age, 47.0 ± 12.6 years) and 33 age-matched healthy controls. Dialyzed women had lower radius and tibia cortical density with higher radius cortical porosity and lower tibia cortical thickness, compared to controls. Radius trabecular number was lower with higher heterogeneity of the trabecular network. Male patients displayed only a lower radius cortical density. Radius and tibia cortical thickness correlated negatively with bone-specific alkaline phosphatase (BALP). Microstructure did not correlate with parathyroid hormone (PTH) levels. Cortical porosity correlated positively with "Kidney Disease: Improving Global Outcomes" working group PTH level categories (r = 0.36, p < 0.04). BMI correlated positively with trabecular number (r = 0.4, p < 0.02) and negatively with trabecular spacing (r = -0.37, p < 0.03) and trabecular network heterogeneity (r = -0.4, p < 0.02). Biomechanics positively correlated with BMI and negatively with BALP. Cortical and trabecular bone microstructure and calculated bone strength are altered in ESRD patients, predominantly in women. Bone microstructure and biomechanical assessment by HR-pQCT may be of major clinical relevance in the evaluation of bone

Age-related change in renal corticomedullary differentiation: evaluation with noncontrast-enhanced steady-state free precession (SSFP) MRI with spatially selective inversion pulse using variable inversion time.

PubMed

Noda, Yasufumi; Kanki, Akihiko; Yamamoto, Akira; Higashi, Hiroki; Tanimoto, Daigo; Sato, Tomohiro; Higaki, Atsushi; Tamada, Tsutomu; Ito, Katsuyoshi

2014-07-01

To evaluate age-related change in renal corticomedullary differentiation and renal cortical thickness by means of noncontrast-enhanced steady-state free precession (SSFP) magnetic resonance imaging (MRI) with spatially selective inversion recovery (IR) pulse. The Institutional Review Board of our hospital approved this retrospective study and patient informed consent was waived. This study included 48 patients without renal diseases who underwent noncontrast-enhanced SSFP MRI with spatially selective IR pulse using variable inversion times (TIs) (700-1500 msec). The signal intensity of renal cortex and medulla were measured to calculate renal corticomedullary contrast ratio. Additionally, renal cortical thickness was measured. The renal corticomedullary junction was clearly depicted in all patients. The mean cortical thickness was 3.9 ± 0.83 mm. The mean corticomedullary contrast ratio was 4.7 ± 1.4. There was a negative correlation between optimal TI for the best visualization of renal corticomedullary differentiation and age (r = -0.378; P = 0.001). However, there was no significant correlation between renal corticomedullary contrast ratio and age (r = 0.187; P = 0.20). Similarly, no significant correlation was observed between renal cortical thickness and age (r = 0.054; P = 0.712). In the normal kidney, noncontrast-enhanced SSFP MRI with spatially selective IR pulse can be used to assess renal corticomedullary differentiation and cortical thickness without the influence of aging, although optimal TI values for the best visualization of renal corticomedullary junction were shortened with aging. © 2013 Wiley Periodicals, Inc.

Generation of induced pluripotent stem cells with high efficiency from human embryonic renal cortical cells.

PubMed

Yao, Ling; Chen, Ruifang; Wang, Pu; Zhang, Qi; Tang, Hailiang; Sun, Huaping

2016-01-01

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts. These iPSCs show pluripotency in vitro and in vivo, as evidenced by expression of pluripotency associated genes, differentiation into three embryonic germ layers by teratoma tests, as well as neuronal fate specification by embryoid body formation. Moreover, the four exogenous genes are effectively silenced in these iPSCs. This study highlights the use of hERCCs to generate highly functional human iPSCs which may aid the study of genetic kidney diseases and accelerate the development of cell-based regenerative therapy.

Renal involvement in leprosy: evaluation of patients in Turkey

PubMed Central

Ozturk, Tulin; Can, Ilkay

2017-01-01

Introduction Renal involvement in leprosy has previously been described in the literature and can include amyloidosis, glomerulonephritis, nephrosclerosis, tubulointerstitial nephritis, and granulomas. Aim To evaluate renal involvement in Turkish patients with leprosy. Material and methods In total, 32 patients with lepromatous leprosy but without any co-morbidities and 35 healthy control subjects were evaluated for renal involvement at the Elazig Training and Research Hospital in Turkey. The laboratory tests and radiological results concerning renal function were taken from both the patients’ medical records and from current examinations. Results The levels of creatinine, urea, and leukocyturia in the lepromatous leprosy patients were significantly higher than in the controls (p < 0.001, p < 0.001; p = 0.001, p < 0.01; p = 0.036, p < 0.05, respectively). No significant differences in the proteinuria, hematuria, sodium, or potassium levels were found between the leprosy and control groups (p > 0.05). On ultrasonographic examination, the prevalence of renal cortical cysts and renal cortical echogenicity in the leprosy patients was significantly higher than in the controls (p = 0.020, p < 0.05, respectively). There were no significant differences in terms of nephrolithiasis, parapelvic cysts, or hydronephrosis between the leprosy and control groups (p > 0.05). Conclusions Evaluating the renal function in all leprosy patients is important to detect abnormalities and to prevent renal failure, which remains a potential cause of death in this disease. PMID:28670253

Normal distribution and medullary-to-cortical shift of Nestin-expressing cells in acute renal ischemia.

PubMed

Patschan, D; Michurina, T; Shi, H K; Dolff, S; Brodsky, S V; Vasilieva, T; Cohen-Gould, L; Winaver, J; Chander, P N; Enikolopov, G; Goligorsky, M S

2007-04-01

Nestin, a marker of multi-lineage stem and progenitor cells, is a member of intermediate filament family, which is expressed in neuroepithelial stem cells, several embryonic cell types, including mesonephric mesenchyme, endothelial cells of developing blood vessels, and in the adult kidney. We used Nestin-green fluorescent protein (GFP) transgenic mice to characterize its expression in normal and post-ischemic kidneys. Nestin-GFP-expressing cells were detected in large clusters within the papilla, along the vasa rectae, and, less prominently, in the glomeruli and juxta-glomerular arterioles. In mice subjected to 30 min bilateral renal ischemia, glomerular, endothelial, and perivascular cells showed increased Nestin expression. In the post-ischemic period, there was an increase in fluorescence intensity with no significant changes in the total number of Nestin-GFP-expressing cells. Time-lapse fluorescence microscopy performed before and after ischemia ruled out the possibility of engraftment by the circulating Nestin-expressing cells, at least within the first 3 h post-ischemia. Incubation of non-perfused kidney sections resulted in a medullary-to-cortical migration of Nestin-GFP-positive cells with the rate of expansion of their front averaging 40 microm/30 min during the first 3 h and was detectable already after 30 min of incubation. Explant matrigel cultures of the kidney and aorta exhibited sprouting angiogenesis with cells co-expressing Nestin and endothelial marker, Tie-2. In conclusion, several lines of circumstantial evidence identify a sub-population of Nestin-expressing cells with the mural cells, which are recruited in the post-ischemic period to migrate from the medulla toward the renal cortex. These migrating Nestin-positive cells may be involved in the process of post-ischemic tissue regeneration.

Quantitative analysis of the renal aging in rats. Stereological study.

PubMed

Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins, Eduardo Lopes; Fraga, Rogério de

2016-05-01

To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glom]) of the renal glomeruli and average glomerular volume (Vol[glom])) and also it was evaluated the renal function for the dosage of serum creatinine and urea. There was significant decrease of the renal function in the oldest rats. The renal volume presented gradual increase during the development of the rats with the biggest values registered in the group of animals at 12 months of age and significant progressive decrease in older animals. Vv[glom] presented statistically significant gradual reduction between the groups and the Nv[glom] also decreased significantly. The renal function proved to be inferior in senile rats when compared to the young rats. The morphometric and stereological analysis evidenced renal atrophy, gradual reduction of the volume density and numerical density of the renal glomeruli associated to the aging process.

Neurofilament protein defines regional patterns of cortical organization in the macaque monkey visual system: a quantitative immunohistochemical analysis

NASA Technical Reports Server (NTRS)

Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1995-01-01

Visual function in monkeys is subserved at the cortical level by a large number of areas defined by their specific physiological properties and connectivity patterns. For most of these cortical fields, a precise index of their degree of anatomical specialization has not yet been defined, although many regional patterns have been described using Nissl or myelin stains. In the present study, an attempt has been made to elucidate the regional characteristics, and to varying degrees boundaries, of several visual cortical areas in the macaque monkey using an antibody to neurofilament protein (SMI32). This antibody labels a subset of pyramidal neurons with highly specific regional and laminar distribution patterns in the cerebral cortex. Based on the staining patterns and regional quantitative analysis, as many as 28 cortical fields were reliably identified. Each field had a homogeneous distribution of labeled neurons, except area V1, where increases in layer IVB cell and in Meynert cell counts paralleled the increase in the degree of eccentricity in the visual field representation. Within the occipitotemporal pathway, areas V3 and V4 and fields in the inferior temporal cortex were characterized by a distinct population of neurofilament-rich neurons in layers II-IIIa, whereas areas located in the parietal cortex and part of the occipitoparietal pathway had a consistent population of large labeled neurons in layer Va. The mediotemporal areas MT and MST displayed a distinct population of densely labeled neurons in layer VI. Quantitative analysis of the laminar distribution of the labeled neurons demonstrated that the visual cortical areas could be grouped in four hierarchical levels based on the ratio of neuron counts between infragranular and supragranular layers, with the first (areas V1, V2, V3, and V3A) and third (temporal and parietal regions) levels characterized by low ratios and the second (areas MT, MST, and V4) and fourth (frontal regions) levels characterized by

Renal potassium physiology: integration of the renal response to dietary potassium depletion.

PubMed

Kamel, Kamel S; Schreiber, Martin; Halperin, Mitchell L

2018-01-01

We summarize the current understanding of the physiology of the renal handling of potassium (K + ), and present an integrative view of the renal response to K + depletion caused by dietary K + restriction. This renal response involves contributions from different nephron segments, and aims to diminish the rate of excretion of K + as a result of: decreasing the rate of electrogenic (and increasing the rate of electroneutral) reabsorption of sodium in the aldosterone-sensitive distal nephron (ASDN), decreasing the abundance of renal outer medullary K + channels in the luminal membrane of principal cells in the ASDN, decreasing the flow rate in the ASDN, and increasing the reabsorption of K + in the cortical and medullary collecting ducts. The implications of this physiology for the association between K + depletion and hypertension, and K + depletion and formation of calcium kidney stones are discussed. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy.

PubMed

Goel, Utsav O; Maddox, Michael M; Elfer, Katherine N; Dorsey, Philip J; Wang, Mei; McCaslin, Ian Ross; Brown, J Quincy; Lee, Benjamin R

2014-01-01

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals ). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy

NASA Astrophysics Data System (ADS)

Goel, Utsav O.; Maddox, Michael M.; Elfer, Katherine N.; Dorsey, Philip J.; Wang, Mei; McCaslin, Ian Ross; Brown, J. Quincy; Lee, Benjamin R.

2014-10-01

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Anthropometric Renal Anatomic Alterations Between Supine and Prone Positions in Percutaneous Renal Ablation for Renal Cortical Neoplasms.

PubMed

Lusch, Achim; Fujimoto, Scott; Findeiss, Laura K; Okhunov, Zhamshid; McDougall, Elspeth M; Landman, Jaime

2016-02-01

To establish patterns of anatomic changes relevant to the kidney and colon during positional change between the supine and prone positions as noted on CT scans performed during percutaneous cryoablation for renal cortical neoplasms (RCN). Nineteen patients undergoing percutaneous cryoablation for RCN with abdominal CT scan in both the supine and prone positions were included in the study. We documented the anterior/posterior, medial/lateral, and cranial/caudal anatomic changes of the kidney, kidney rotation, and the proportion of the kidney whose access was limited by the liver, spleen, and lung. We also calculated the length of the percutaneous access tract and the distance between the colon and kidney in hilar position as well as the anterior/posterior location of the colon relative to the kidney. In the prone position, the kidney lies significantly more anteriorly on both sides: 4.7 cm vs 4.3 cm (L) and 4.4 cm vs 4.1 cm (R) (p = 0.02 and p = 0.03, respectively). On prone CT images, both kidneys are more cranial when compared with the supine position: 80.4 mm vs 60.8 mm (L) and 87.2 mm vs 57.4 mm (R) (p = 0.002 and p < 0.001, respectively). The skin to tumor distance is significantly shorter in the prone position (p < 0.0001 [L], p = 0.005 [R]). The colon lies closer to the hilum of the kidney and is more posteriorly located in the prone position: 1.21 cm vs 1.04 cm (L) and 0.80 cm vs 0.70 cm (R) (p = 0.005 and p = 0.005, respectively). In the prone position, the lung covers a significantly larger proportion of the right kidney (27.3 mm vs 6.05 mm, p = 0.0001). We documented clinically significant anatomic alterations between supine and prone CT imaging. The changes associated with the prone position modify percutaneous access, particularly for right upper pole tumors. Prone imaging before surgery may be helpful in selected cases.

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.

Renal MR angiography and perfusion in the pig using hyperpolarized water.

PubMed

Wigh Lipsø, Kasper; Hansen, Esben Søvsø Szocska; Tougaard, Rasmus Stilling; Laustsen, Christoffer; Ardenkjaer-Larsen, Jan Henrik

2017-09-01

To study hyperpolarized water as an angiography and perfusion tracer in a large animal model. Protons dissolved in deuterium oxide (D 2 O) were hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP) polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T). Approximately 15 mL of hyperpolarized water was injected in the renal artery by hand over 4-5 s. A liquid state polarization of 5.3 ± 0.9% of 3.8 M protons in 15 mL of deuterium oxide was achieved with a T 1 of 24 ± 1 s. This allowed injection through an arterial catheter into the renal artery and subsequently high-contrast imaging of the entire kidney parenchyma over several seconds. The dynamic images allow quantification of tissue perfusion, with a mean cortical perfusion of 504 ± 123 mL/100 mL/min. Hyperpolarized water MR imaging was successfully demonstrated as a renal angiography and perfusion method. Quantitative perfusion maps of the kidney were obtained in agreement with literature and control experiments with gadolinium contrast. Magn Reson Med 78:1131-1135, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

PREVENTING AUTOIMMUNITY PROTECTS AGAINST THE DEVELOPMENT OF HYPERTENSION AND RENAL INJURY

PubMed Central

Mathis, Keisa W.; Wallace, Kedra; Flynn, Elizabeth R.; Maric-Bilkan, Christine; LaMarca, Babbette; Ryan, Michael J.

2015-01-01

Several studies suggest a link between autoimmunity and essential hypertension in humans. However, whether autoimmunity can drive the development of hypertension remains unclear. The autoimmune disease systemic lupus erythematosus is characterized by autoantibody production and the prevalence of hypertension is markedly increased in this patient population compared to normal healthy women. We hypothesized that preventing the development of autoimmunity would prevent the development of hypertension in a mouse model of lupus. Female lupus (NZBWF1) and control mice (NZW) were treated weekly with anti-CD20 or IgG antibodies (both 10 mg/kg, IV) starting at 20 weeks of age for 14 weeks. Anti-CD20 therapy markedly attenuated lupus disease progression as evidenced by reduced CD45R+ B cells and lower double-stranded DNA autoantibody activity. In addition, renal injury in the form of urinary albumin, glomerulosclerosis, and tubulointerstitial fibrosis, as well as tubular injury (indicated by renal cortical expression of neutrophil gelatinase-associated lipocalin) was prevented by anti-CD20 therapy in lupus mice. Finally, lupus mice treated with anti-CD20 antibody did not develop hypertension. The protection against the development of hypertension was associated with lower renal cortical tumor necrosis factor-α expression, a cytokine that has been previously reported by us to contribute to the hypertension in this model, as well as renal cortical monocyte chemoattractant protein -1 expression and circulating T cells. These data suggest that the development of autoimmunity and the resultant increase in renal inflammation is an important underlying factor in the prevalent hypertension that occurs during systemic lupus erythematosus. PMID:25024282

Direct Inhibitory Effect of Hypercalcemia on Renal Actions of Parathyroid Hormone

PubMed Central

Beck, Nama; Singh, Harbans; Reed, Sarah W.; Davis, Bernard B.

1974-01-01

The effects of calcium on the renal actions of parathyroid hormone (PTH) were studied in vivo and in vitro. In parathyroidectomized rats, variable levels of blood calcium concentration were induced by intravenous infusion of calcium. The renal responses to the injected PTH, i.e. phosphate and cyclic AMP excretion, were compared in these animals. After PTH injection, the increases of both phosphate and cyclic AMP excretion were less in the calcium-infused animals than in the control group without calcium infusion. There was an inverse correlation between the renal responses to PTH and plasma calcium concentration of 4.2-13.5 mg/100 ml. But calcium had no effect on phosphate excretion induced by infusion of dibutyryl cyclic AMP. In the in vitro experiments, the increase of cyclic AMP concentration in response to PTH was less in renal cortical slices taken from the calcium-infused animals than in ones from the control group without calcium infusion. Calcium also inhibited the activation of renal cortical adenylate cyclase in response to PTH, but calcium had no effect on phosphodiesterase. The data indicate that calcium directly inhibits renal actions of PTH both in vivo and in vitro. Such inhibitory mechanism is probably at or before the step of PTH-dependent cyclic AMP generation in the kidney. PMID:4359938

Magnetization Transfer Magnetic Resonance Imaging Noninvasively Detects Renal Fibrosis in Swine Atherosclerotic Renal Artery Stenosis at 3.0 T.

PubMed

Jiang, Kai; Ferguson, Christopher M; Woollard, John R; Zhu, Xiangyang; Lerman, Lilach O

2017-11-01

Renal fibrosis is a useful biomarker for diagnosis and evaluation of therapeutic interventions of renal diseases but often requires invasive testing. Magnetization transfer magnetic resonance imaging (MT-MRI), which evaluates the presence of macromolecules, offers a noninvasive tool to probe renal fibrosis in murine renal artery stenosis (RAS) at 16.4 T. In this study, we aimed to identify appropriate imaging parameters for collagen detection at 3.0 T MRI and to test the utility of MT-MRI in measuring renal fibrosis in a swine model of atherosclerotic RAS (ARAS). To select the appropriate offset frequency, an MT-MRI study was performed on a phantom containing 0% to 40% collagen I and III with offset frequencies from -1600 to +1600 Hz and other MT parameters empirically set as pulse width at 16 milliseconds and flip angle at 800 degrees. Then selected MT parameters were used in vivo on pigs 12 weeks after sham (n = 8) or RAS (n = 10) surgeries. The ARAS pigs were fed with high-cholesterol diet to induce atherosclerosis. The MT ratio (MTR) was compared with ex vivo renal fibrosis measured using Sirius-red staining. Offset frequencies at 600 and 1000 Hz were selected for collagen detection without direct saturation of free water signal, and subsequently applied in vivo. The ARAS kidneys showed mild cortical and medullary fibrosis by Sirius-red staining. The cortical and medullary MTRs at 600 and 1000 Hz were both increased. Renal fibrosis measured ex vivo showed good linear correlations with MTR at 600 (cortex: Pearson correlation coefficient r = 0.87, P < 0.001; medulla: r = 0.70, P = 0.001) and 1000 Hz (cortex: r = 0.75, P < 0.001; medulla: r = 0.83, P < 0.001). Magnetization transfer magnetic resonance imaging can noninvasively detect renal fibrosis in the stenotic swine kidney at 3.0 T. Therefore, MT-MRI may potentially be clinically applicable and useful for detection and monitoring of renal pathology in subjects with RAS.

Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI

PubMed Central

Zhang, Yue; Udayakumar, Durga; Cai, Ling; Hu, Zeping; Kapur, Payal; Kho, Eun-Young; Pavía-Jiménez, Andrea; Fulkerson, Michael; de Leon, Alberto Diaz; Yuan, Qing; Dimitrov, Ivan E.; Ye, Jin; Mitsche, Matthew A.; Kim, Hyeonwoo; McDonald, Jeffrey G.; Madhuranthakam, Ananth J.; Dwivedi, Durgesh K.; Lenkinski, Robert E.; Cadeddu, Jeffrey A.; Margulis, Vitaly; Brugarolas, James; DeBerardinis, Ralph J.

2017-01-01

BACKGROUND. Dysregulated lipid and glucose metabolism in clear cell renal cell carcinoma (ccRCC) has been implicated in disease progression, and whole tumor tissue–based assessment of these changes is challenged by the tumor heterogeneity. We studied a noninvasive quantitative MRI method that predicts metabolic alterations in the whole tumor. METHODS. We applied Dixon-based MRI for in vivo quantification of lipid accumulation (fat fraction [FF]) in targeted regions of interest of 45 primary ccRCCs and correlated these MRI measures to mass spectrometry–based lipidomics and metabolomics of anatomically colocalized tissue samples isolated from the same tumor after surgery. RESULTS. In vivo tumor FF showed statistically significant (P < 0.0001) positive correlation with histologic fat content (Spearman correlation coefficient, ρ = 0.79), spectrometric triglycerides (ρ = 0.56) and cholesterol (ρ = 0.47); it showed negative correlation with free fatty acids (ρ = –0.44) and phospholipids (ρ = –0.65). We observed both inter- and intratumoral heterogeneity in lipid accumulation within the same tumor grade, whereas most aggressive tumors (International Society of Urological Pathology [ISUP] grade 4) exhibited reduced lipid accumulation. Cellular metabolites in tumors were altered compared with adjacent renal parenchyma. CONCLUSION. Our results support the use of noninvasive quantitative Dixon-based MRI as a biomarker of reprogrammed lipid metabolism in ccRCC, which may serve as a predictor of tumor aggressiveness before surgical intervention. FUNDING. NIH R01CA154475 (YZ, MF, PK, IP), NIH P50CA196516 (IP, JB, RJD, JAC, PK), Welch Foundation I-1832 (JY), and NIH P01HL020948 (JGM). PMID:28768909

Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

PubMed

Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

2017-02-01

Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N ω -nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes. Copyright © 2017 the American Physiological Society.

Real-time quantitative reverse transcription-PCR assay for renal cell carcinoma-associated antigen G250.

PubMed

Chuanzhong, Ye; Ming, Guan; Fanglin, Zhang; Haijiao, Chen; Zhen, Lin; Shiping, Chen; YongKang, Zhang

2002-04-01

Gene amplification/expression of G250 is a major event in human renal tumorigenesis. G250-based therapeutic agents and G250-specific gene therapy are under development. These new perspectives call for a sensitive and accurate method to screen G250 alterations in renal cell cancer (RCC) patients and investigate the relationship between G250 mRNA expression and RCC. We developed a quantitative RT-PCR assay for the measurement of G250 mRNA expression using a real-time procedure based on the use of fluorogenic probes and the ABI PRISM 7700 Sequence Detector System. The method has been applied to the measurement of quantitative mRNA level of G250 in 31 cases RCC and 6 normal renal tissues. The dynamic range was 10(3)-10(8). The relationship between Ct and log starting concentration was linear (r=0.99). G250 expression was present in all RCCs with G250 amplification but was absent in normal ones. G250 mRNA expression ranged from 2.9 x 10(3) to 6.5 x 10(7) copy/microg RNA, with a mean value of 3.5 x 10(6) copy/microg RNA. The expression of G250 revealed an inverse correlation to tumor grade. G250 mRNA level did not correlate with the cell types and clinical stages (P>0.05). G250 has the potential to be used as a marker of diagnosis and increasing proliferation in RCC. This new simple, rapid, semi-automated assay was a major alternative to competitive PCR and Northern blot analysis for gene alteration analysis in human tumors and might be a powerful tool for large randomized, prospective cooperative group trials and supporting future G250-based biological and gene therapy approaches.

Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.

PubMed

Ohm, D T; Kim, G; Gefen, T; Rademaker, A; Weintraub, S; Bigio, E H; Mesulam, M-M; Rogalski, E; Geula, C

2018-04-21

Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy. © 2018 British Neuropathological Society.

Differential patterns of injury to the proximal tubule of renal cortical slices following in vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions.

PubMed

Ruegg, C E; Gandolfi, A J; Nagle, R B; Brendel, K

1987-09-15

The innate susceptibility of renal cell types to these agents was investigated using precision-cut rabbit renal cortical slices made perpendicular to the cortical-papillary axis. Slices were incubated in DME/F12 medium containing 10 microM, 100 microM, or 1 mM concentrations of either metal for 12 hr or in Krebs-Hepes buffer gassed with nitrogen (100%) for 0.75 to 5 hr of hypoxic exposure. To simulate postischemic reperfusion, some slices were transferred to vessels gassed with oxygen after an initial hypoxic period. Mercuric chloride (100 microM) exposure resulted in damage to the straight regions of proximal tubules by 12 hr leaving convoluted regions unaffected. Hypoxia (2.25 hr) and potassium dichromate (100 microM for 12 hr) both caused injury to the convoluted proximal tubules without affecting straight proximal tubular regions. Mercury concentrations of 10 microM and 1 mM had no effect or injured all cell types within the slice, respectively. Similar results were observed for hypoxic periods less than 1.5 hr or greater than 3 hr of exposure. Potassium dichromate had no measurable affect at 10 microM, but at 1 mM focal lesions were observed after 4 hr of exposure, and by 12 hr all cell types within the slice were affected. Intracellular potassium content normalized to DNA correlated well, but always preceded the pathological lesions observed. These results demonstrate that injury to specific regions of the proximal tubule by these agents relates to an innate susceptibility of the intoxicated cell type independent of physiologic feedback or blood delivery patterns proposed as mechanisms of selective injury from in vivo studies.

Use of MRI in Differentiation of Papillary Renal Cell Carcinoma Subtypes: Qualitative and Quantitative Analysis.

PubMed

Doshi, Ankur M; Ream, Justin M; Kierans, Andrea S; Bilbily, Matthew; Rusinek, Henry; Huang, William C; Chandarana, Hersh

2016-03-01

The purpose of this study was to determine whether qualitative and quantitative MRI feature analysis is useful for differentiating type 1 from type 2 papillary renal cell carcinoma (PRCC). This retrospective study included 21 type 1 and 17 type 2 PRCCs evaluated with preoperative MRI. Two radiologists independently evaluated various qualitative features, including signal intensity, heterogeneity, and margin. For the quantitative analysis, a radiology fellow and a medical student independently drew 3D volumes of interest over the entire tumor on T2-weighted HASTE images, apparent diffusion coefficient parametric maps, and nephrographic phase contrast-enhanced MR images to derive first-order texture metrics. Qualitative and quantitative features were compared between the groups. For both readers, qualitative features with greater frequency in type 2 PRCC included heterogeneous enhancement, indistinct margin, and T2 heterogeneity (all, p < 0.035). Indistinct margins and heterogeneous enhancement were independent predictors (AUC, 0.822). Quantitative analysis revealed that apparent diffusion coefficient, HASTE, and contrast-enhanced entropy were greater in type 2 PRCC (p < 0.05; AUC, 0.682-0.716). A combined quantitative and qualitative model had an AUC of 0.859. Qualitative features within the model had interreader concordance of 84-95%, and the quantitative data had intraclass coefficients of 0.873-0.961. Qualitative and quantitative features can help discriminate between type 1 and type 2 PRCC. Quantitative analysis may capture useful information that complements the qualitative appearance while benefiting from high interobserver agreement.

Hippocampal neurogenesis and cortical cellular plasticity in Wahlberg's epauletted fruit bat: a qualitative and quantitative study.

PubMed

Gatome, Catherine W; Mwangi, Deter K; Lipp, Hans-Peter; Amrein, Irmgard

2010-01-01

Species-specific characteristics of neuronal plasticity emerging from comparative studies can address the functional relevance of hippocampal or cortical plasticity in the light of ecological adaptation and evolutionary history of a given species. Here, we present a quantitative and qualitative analysis of neurogenesis in young and adult free-living Wahlberg's epauletted fruit bats. Using the markers for proliferating cell nuclear antigen (PCNA), bromodeoxyuridine (BrdU), doublecortin (DCX) and polysialic acid neural cell adhesion molecule (PSA-NCAM), our findings in the hippocampus, olfactory bulb and cortical regions are described and compared to reports in other mammals. Expressed as a percentage of the total number of granule cells, PCNA- and BrdU-positive cells accounted for 0.04 in young to 0.01% in adult animals; DCX-positive cells for 0.05 (young) to 0.01% (adult); PSA-NCAM-positive cells for 0.1 (young) to 0.02% (adult), and pyknotic cells for 0.007 (young) to 0.005% (adult). The numbers were comparable to other long-lived, late-maturing mammals such as primates. A significant increase in the total granule cell number from young to adult animals demonstrated the successful formation and integration of new cells. In adulthood, granule cell number appeared stable and was surprisingly low in comparison to other species. Observations in the olfactory bulb and rostral migratory stream were qualitatively similar to descriptions in other species. In the ventral horn of the lateral ventricle, we noted prominent expression of DCX and PSA-NCAM forming a temporal migratory stream targeting the piriform cortex, possibly reflecting the importance of olfaction to these species. Low, but persistent hippocampal neurogenesis in non-echolocating fruit bats contrasted the findings in echolocating microbats, in which hippocampal neurogenesis was largely absent. Together with the observed intense cortical plasticity in the olfactory system of fruit bats we suggest a

Quantitative validation of a nonlinear histology-MRI coregistration method using Generalized Q-sampling Imaging in complex human cortical white matter

PubMed Central

Gangolli, Mihika; Holleran, Laurena; Kim, Joong Hee; Stein, Thor D.; Alvarez, Victor; McKee, Ann C.; Brody, David L.

2017-01-01

Advanced diffusion MRI methods have recently been proposed for detection of pathologies such as traumatic axonal injury and chronic traumatic encephalopathy which commonly affect complex cortical brain regions. However, radiological-pathological correlations in human brain tissue that detail the relationship between the multi-component diffusion signal and underlying pathology are lacking. We present a nonlinear voxel based two dimensional coregistration method that is useful for matching diffusion signals to quantitative metrics of high resolution histological images. When validated in ex vivo human cortical tissue at a 250 × 250 × 500 micron spatial resolution, the method proved robust in correlations between generalized q-sampling imaging and histologically based white matter fiber orientations, with r = 0.94 for the primary fiber direction and r = 0.88 for secondary fiber direction in each voxel. Importantly, however, the correlation was substantially worse with reduced spatial resolution or with fiber orientations derived using a diffusion tensor model. Furthermore, we have detailed a quantitative histological metric of white matter fiber integrity termed power coherence capable of distinguishing between architecturally complex but intact white matter from disrupted white matter regions. These methods may allow for more sensitive and specific radiological-pathological correlations of neurodegenerative diseases affecting complex gray and white matter. PMID:28365421

Fructokinase activity mediates dehydration-induced renal injury.

PubMed

Roncal Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Rivard, Christopher J; Nakagawa, Takahiko; Ejaz, A Ahsan; Cicerchi, Christina; Inaba, Shinichiro; Le, MyPhuong; Miyazaki, Makoto; Glaser, Jason; Correa-Rotter, Ricardo; González, Marvin A; Aragón, Aurora; Wesseling, Catharina; Sánchez-Lozada, Laura G; Johnson, Richard J

2014-08-01

The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

Effect of a stable prostacyclin analogue on canine renal allograft rejection.

PubMed Central

Tobimatsu, M; Ueda, Y; Toyoda, K; Saito, S; Konomi, K

1987-01-01

The effect of OP-41483 (Ono Pharmaceutical Co., Osaka, Japan), a stable prostacyclin analogue, on canine renal allograft rejection was investigated. Administration for 4 days after transplantation significantly increased renal cortical blood flow and urine output when compared with untreated dogs with renal allografts. Serum creatinine levels remained relatively low during postoperative days 1-4. Mean animal survival time was prolonged. Vascular lesions and mononuclear cell infiltration were greatly diminished in biopsy specimens removed on day 4. This stable prostacyclin analogue provided a degree of protection against canine renal allograft rejection. Images Figs. 1A and B. PMID:3545109

Reduced Cortical Thickness in Mental Retardation

PubMed Central

Wang, Chao; Wang, Jiaojian; Zhang, Yun; Yu, Chunshui; Jiang, Tianzi

2011-01-01

Mental retardation is a developmental disorder associated with impaired cognitive functioning and deficits in adaptive behaviors. Many studies have addressed white matter abnormalities in patients with mental retardation, while the changes of the cerebral cortex have been studied to a lesser extent. Quantitative analysis of cortical integrity using cortical thickness measurement may provide new insights into the gray matter pathology. In this study, cortical thickness was compared between 13 patients with mental retardation and 26 demographically matched healthy controls. We found that patients with mental retardation had significantly reduced cortical thickness in multiple brain regions compared with healthy controls. These regions include the bilateral lingual gyrus, the bilateral fusiform gyrus, the bilateral parahippocampal gyrus, the bilateral temporal pole, the left inferior temporal gyrus, the right lateral orbitofrontal cortex and the right precentral gyrus. The observed cortical thickness reductions might be the anatomical substrates for the impaired cognitive functioning and deficits in adaptive behaviors in patients with mental retardation. Cortical thickness measurement might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications. PMID:22216343

Effects of a stable prostacyclin analog on experimental ischemic acute renal failure.

PubMed Central

Tobimatsu, M; Ueda, Y; Saito, S; Tsumagari, T; Konomi, K

1988-01-01

The effect of OP-41483, a stable prostacyclin (PGI2) analog, on ischemic acute renal failure (ARF) was investigated in dogs. Administration of OP-41483 for three days after ischemia significantly increased renal cortical blood flow (RCBF) when compared with dogs treated with the saline vehicle. In the OP-41483-treated group, serum creatinine levels remained relatively low during postoperative days 1-3 and mean survival time was prolonged. Injection of a silicone rubber vascular casting compound (Microfil) revealed increased numbers of visible renal cortical glomeruli and microvessels compared to the saline vehicle group. Histologic sections showed only very limited tubular necrosis, whereas sections of kidneys treated with saline showed extensive tubular necrosis. In conclusion, this stable prostacyclin analog provided a significant degree of protection for the kidneys from ischemic injury and may be useful in a clinical setting. Images Figs. 3A-D. Figs. 4A-D. PMID:3291800

Cortical maturation and myelination in healthy toddlers and young children.

PubMed

Deoni, Sean C L; Dean, Douglas C; Remer, Justin; Dirks, Holly; O'Muircheartaigh, Jonathan

2015-07-15

The maturation of cortical structures, and the establishment of their connectivity, are critical neurodevelopmental processes that support and enable cognitive and behavioral functioning. Measures of cortical development, including thickness, curvature, and gyrification have been extensively studied in older children, adolescents, and adults, revealing regional associations with cognitive performance, and alterations with disease or pathology. In addition to these gross morphometric measures, increased attention has recently focused on quantifying more specific indices of cortical structure, in particular intracortical myelination, and their relationship to cognitive skills, including IQ, executive functioning, and language performance. Here we analyze the progression of cortical myelination across early childhood, from 1 to 6 years of age, in vivo for the first time. Using two quantitative imaging techniques, namely T1 relaxation time and myelin water fraction (MWF) imaging, we characterize myelination throughout the cortex, examine developmental trends, and investigate hemispheric and gender-based differences. We present a pattern of cortical myelination that broadly mirrors established histological timelines, with somatosensory, motor and visual cortices myelinating by 1 year of age; and frontal and temporal cortices exhibiting more protracted myelination. Developmental trajectories, defined by logarithmic functions (increasing for MWF, decreasing for T1), were characterized for each of 68 cortical regions. Comparisons of trajectories between hemispheres and gender revealed no significant differences. Results illustrate the ability to quantitatively map cortical myelination throughout early neurodevelopment, and may provide an important new tool for investigating typical and atypical development. Copyright © 2015. Published by Elsevier Inc.

Ipsilateral corticotectal projections from the primary, premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study

PubMed Central

Fregosi, Michela; Rouiller, Eric M.

2018-01-01

The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non-human primates, previous studies reported that cortical projections to the superior colliculus originated from the premotor cortex and the primary motor cortex, whereas no projection originated from the supplementary motor area. The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n=9). The anterograde tracer BDA was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral superior colliculus. The data confirmed the presence of strong corticotectal projections from the premotor cortex. A new observation was that strong corticotectal projections were also found to originate from the supplementary motor area (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or supplementary motor areas. The corticotectal projection from each motor area was directed mainly to the deep layer of the superior colliculus, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non-primary motor areas are in position to influence the preparation and planning of voluntary movements. PMID:28921678

A quantitative comparison of the hemispheric, areal, and laminar origins of sensory and motor cortical projections to the superior colliculus of the cat.

PubMed

Butler, Blake E; Chabot, Nicole; Lomber, Stephen G

2016-09-01

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a substantial projection. Conversely, only one area of the auditory orienting system, the auditory field of the anterior ectosylvian sulcus (fAES), and no area involved in somatosensory orienting, shows significant corticotectal inputs. Although small relative to visual inputs, the projection from the fAES is of particular interest, as it represents the only bilateral cortical input to the SC. This detailed, quantitative study allows for comparison across modalities in an animal that serves as a useful model for both auditory and visual perception. Moreover, the differences in patterns of corticotectal projections between modalities inform the ways in which orienting systems are modulated by cortical feedback. J. Comp. Neurol. 524:2623-2642, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Three new renal simulators for use in nuclear medicine

NASA Astrophysics Data System (ADS)

Dullius, Marcos; Fonseca, Mateus; Botelho, Marcelo; Cunha, Clêdison; Souza, Divanízia

2014-03-01

Renal scintigraphy is useful to provide both functional and anatomic information of renal flow of cortical functions and evaluation of pathological collecting system. The objective of this study was develop and evaluate the performance of three renal phantoms: Two anthropomorphic static and another dynamic. The static images of the anthropomorphic phantoms were used for comparison with static renal scintigraphy with 99mTc-DMSA in different concentrations. These static phantoms were manufactured in two ways: one was made of acrylic using as mold a human kidney preserved in formaldehyde and the second was built with ABS (acrylonitrile butadiene styrene) in a 3D printer. The dynamic renal phantom was constructed of acrylic to simulate renal dynamics in scintigraphy with 99mTc-DTPA. These phantoms were scanned with static and dynamic protocols and compared with clinical data. Using these phantoms it is possible to acquire similar renal images as in the clinical scintigraphy. Therefore, these new renal phantoms can be very effective for use in the quality control of renal scintigraphy, and image processing systems.

Sickle cell disease: renal manifestations and mechanisms

PubMed Central

Nath, Karl A.; Hebbel, Robert P.

2015-01-01

Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

Sorting the Alphabet Soup of Renal Pathology: A Review.

PubMed

Curran-Melendez, Sheilah M; Hartman, Matthew S; Heller, Matthew T; Okechukwu, Nancy

2016-01-28

Diseases of the kidney often have their names shortened, creating an arcane set of acronyms which can be confusing to both radiologists and clinicians. This review of renal pathology aims to explain some of the most commonly used acronyms within the field. For each entity, a summary of the clinical features, pathophysiology, and radiological findings is included to aid in the understanding and differentiation of these entities. Discussed topics include acute cortical necrosis, autosomal dominant polycystic kidney disease, angiomyolipoma, autosomal recessive polycystic kidney disease, acute tubular necrosis, localized cystic renal disease, multicystic dysplastic kidney, multilocular cystic nephroma, multilocular cystic renal cell carcinoma, medullary sponge kidney, paroxysmal nocturnal hemoglobinuria, renal papillary necrosis, transitional cell carcinoma, and xanthogranulomatous pyelonephritis. Copyright © 2016 Mosby, Inc. All rights reserved.

Quantitative Architectural Analysis: A New Approach to Cortical Mapping

ERIC Educational Resources Information Center

Schleicher, Axel; Morosan, Patricia; Amunts, Katrin; Zilles, Karl

2009-01-01

Results from functional imaging studies are often still interpreted using the classical architectonic brain maps of Brodmann and his successors. One obvious weakness in traditional, architectural mapping is the subjective nature of localizing borders between cortical areas by means of a purely visual, microscopical examination of histological…

Development and prospective evaluation of an automated software system for quality control of quantitative 99mTc-MAG3 renal studies.

PubMed

Folks, Russell D; Garcia, Ernest V; Taylor, Andrew T

2007-03-01

Quantitative nuclear renography has numerous potential sources of error. We previously reported the initial development of a computer software module for comprehensively addressing the issue of quality control (QC) in the analysis of radionuclide renal images. The objective of this study was to prospectively test the QC software. The QC software works in conjunction with standard quantitative renal image analysis using a renal quantification program. The software saves a text file that summarizes QC findings as possible errors in user-entered values, calculated values that may be unreliable because of the patient's clinical condition, and problems relating to acquisition or processing. To test the QC software, a technologist not involved in software development processed 83 consecutive nontransplant clinical studies. The QC findings of the software were then tabulated. QC events were defined as technical (study descriptors that were out of range or were entered and then changed, unusually sized or positioned regions of interest, or missing frames in the dynamic image set) or clinical (calculated functional values judged to be erroneous or unreliable). Technical QC events were identified in 36 (43%) of 83 studies. Clinical QC events were identified in 37 (45%) of 83 studies. Specific QC events included starting the camera after the bolus had reached the kidney, dose infiltration, oversubtraction of background activity, and missing frames in the dynamic image set. QC software has been developed to automatically verify user input, monitor calculation of renal functional parameters, summarize QC findings, and flag potentially unreliable values for the nuclear medicine physician. Incorporation of automated QC features into commercial or local renal software can reduce errors and improve technologist performance and should improve the efficiency and accuracy of image interpretation.

Toxicity of cephaloridine to carnitine transport and fatty acid metabolism in rabbit renal cortical mitochondria: structure-activity relationships.

PubMed

Tune, B M; Hsu, C Y

1994-09-01

Cephaloridine (Cld), the most widely studied nephrotoxic cephalosporin, has significant structural homology with carnitine, which facilitates the transport of long-chain fatty acids into the mitochondrial inner matrix. Because of this homology, and evidence of a role of lipids in cephaloglycin (Cgl) nephrotoxicity, protocols were designed to compare the effects of Cld and Cgl on renal cortical mitochondrial carnitine transport, on long-chain fatty acylcarnitine-mediated respiration and on the in situ mitochondrial pools and urinary excretion of carnitine and acylcarnitines. The following was found: 1) both cephalosporins reduced carnitine-facilitated pyruvate oxidation (CFPO) and palmitoylcarnitine-mediated respiration (PCMR) by 40 to 50% in mitochondria exposed in vivo (300 mg/kg b.wt., 1 hr). CFPO could be decreased by reduction of carnitine uptake, pyruvate oxidation or carnitine acetyltransferase activity; 2) neither cephalosporin reduced mitochondrial carnitine acetyltransferase or carnitine palmitoyltransferase; 3) with in vitro exposure (2000 micrograms/ml, immediate effect) Cgl had no significant toxicity to mitochondrial CFPO. Cld inhibited CFPO in a dose-dependent manner, up to 100% at 2000 micrograms/ml; this effect was reduced by increasing carnitine concentrations; 4) in vitro Cld prevented the potentiation of PCMR by preloading with carnitine, reduced mitochondrial acetylcarnitine/carnitine exchange by 70% and reduced PCMR by 30%; 5) in vivo Cld increased mitochondrial-free carnitine in the in situ kidney by 100%; and 6) in vivo Cld increased the fractional renal excretion of carnitine from 0 +/- 0 to 0.29 +/- 0.03 and the fractional excretion of long-chain acylcarnitines from 0.06 +/- 0.01 to 0.79 +/- 0.17.(ABSTRACT TRUNCATED AT 250 WORDS)

The kidney in the pathogenesis of hypertension: the role of renal nerves.

PubMed

DiBona, G F

1985-04-01

The intrinsic efferent innervation of the kidney consists of exclusively noradrenergic fibers that innervate the preglomerular and postgomerular vasculature, all elements of the juxtagomerular apparatus and virtually all segments of the nephron in both cortical and medullo-papillary regions. Increases in efferent renal sympathetic nerve activity produce renal vasoconstriction, release of renin, catecholamines, prostaglandins and other vasoactive substances, and increases in renal tubular sodium reabsorption; these responses are graded and differentiated. The intrinsic afferent innervation of the kidney consists of mechanoreceptors and chemoreceptors which participate in reno-renal and reno-systemic reflexes that modulate sympathetic neural outflow in an organ-specific differentiated pattern. Therefore, alterations in efferent and afferent renal nerve activity produce changes in several important renal functions known to contribute to the development and maintenance of hypertension.

Segmentation of cortical bone using fast level sets

NASA Astrophysics Data System (ADS)

Chowdhury, Manish; Jörgens, Daniel; Wang, Chunliang; Smedby, Årjan; Moreno, Rodrigo

2017-02-01

Cortical bone plays a big role in the mechanical competence of bone. The analysis of cortical bone requires accurate segmentation methods. Level set methods are usually in the state-of-the-art for segmenting medical images. However, traditional implementations of this method are computationally expensive. This drawback was recently tackled through the so-called coherent propagation extension of the classical algorithm which has decreased computation times dramatically. In this study, we assess the potential of this technique for segmenting cortical bone in interactive time in 3D images acquired through High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The obtained segmentations are used to estimate cortical thickness and cortical porosity of the investigated images. Cortical thickness and Cortical porosity is computed using sphere fitting and mathematical morphological operations respectively. Qualitative comparison between the segmentations of our proposed algorithm and a previously published approach on six images volumes reveals superior smoothness properties of the level set approach. While the proposed method yields similar results to previous approaches in regions where the boundary between trabecular and cortical bone is well defined, it yields more stable segmentations in challenging regions. This results in more stable estimation of parameters of cortical bone. The proposed technique takes few seconds to compute, which makes it suitable for clinical settings.

Renal damage detected by DMSA, despite normal renal ultrasound, in children with febrile UTI.

PubMed

Bush, N C; Keays, M; Adams, C; Mizener, K; Pritzker, K; Smith, W; Traylor, J; Villanueva, C; Snodgrass, W T

2015-06-01

2011 American Academy of Pediatrics guidelines recommended renal-bladder ultrasound (RBUS) as the only evaluation after febrile urinary tract infection (FUTI) in infants aged 2-24 months. We determined the sensitivity, specificity, and false negative rate of RBUS to identify DMSA-detected renal damage in this age group as well as in older children. Consecutive patients referred to pediatric urology with a history of FUTI underwent DMSA ≥ 3 months after FUTI. Abnormal RBUS was defined as: Society of Fetal Urology hydronephrosis grades I-IV; hydroureter ≥ 7 mm; renal scar defined as focal parenchymal thinning; and/or size discrepancy ≥ 1 cm between kidneys. Abnormal DMSA was presence of any focal uptake defects and/or split renal function < 44%. We calculated sensitivity, specificity, positive and negative predictive values, and false negative rates of RBUS compared to DMSA. 618 patients (79% female), median age 3.4 years, were referred for FUTIs. Of the 512 (83%) with normal RBUS, 99 (19%) had abnormal DMSA. Children with normal RBUS after their first FUTI had abnormal DMSA in 15/151 (10%) aged ≤ 24 months and 23/119 (19%) aged > 24 months. RBUS had poor sensitivity (34%) and low positive predictive value (47%) to identify patients with renal damage. 99/149 (66%) children with renal damage on DMSA had normal RBUS. After FUTI, 66% of children with reduced renal function and/or renal cortical defects found by DMSA scintigraphy had a normal RBUS. Since abnormal DMSA may correlate with increased risk for VUR, recurrent FUTI and renal damage, our data suggest RBUS alone will fail to detect a significant proportion of patients at risk. The data suggest that imaging after FUTI should include acute RBUS and delayed DMSA, reserving VCUG for patients with abnormal DMSA and/or recurrent FUTI. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Quantitative Features of Liver Lesions, Lung Nodules, and Renal Stones at Multi-Detector Row CT Examinations: Dependency on Radiation Dose and Reconstruction Algorithm.

PubMed

Solomon, Justin; Mileto, Achille; Nelson, Rendon C; Roy Choudhury, Kingshuk; Samei, Ehsan

2016-04-01

To determine if radiation dose and reconstruction algorithm affect the computer-based extraction and analysis of quantitative imaging features in lung nodules, liver lesions, and renal stones at multi-detector row computed tomography (CT). Retrospective analysis of data from a prospective, multicenter, HIPAA-compliant, institutional review board-approved clinical trial was performed by extracting 23 quantitative imaging features (size, shape, attenuation, edge sharpness, pixel value distribution, and texture) of lesions on multi-detector row CT images of 20 adult patients (14 men, six women; mean age, 63 years; range, 38-72 years) referred for known or suspected focal liver lesions, lung nodules, or kidney stones. Data were acquired between September 2011 and April 2012. All multi-detector row CT scans were performed at two different radiation dose levels; images were reconstructed with filtered back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction (MBIR) algorithms. A linear mixed-effects model was used to assess the effect of radiation dose and reconstruction algorithm on extracted features. Among the 23 imaging features assessed, radiation dose had a significant effect on five, three, and four of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). Adaptive statistical iterative reconstruction had a significant effect on three, one, and one of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). MBIR reconstruction had a significant effect on nine, 11, and 15 of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). Of note, the measured size of lung nodules and renal stones with MBIR was significantly different than those for the other two algorithms (P < .002 for all comparisons). Although lesion texture was significantly affected by the

A Pilot Study of Quantitative MRI Measurements of Ventricular Volume and Cortical Atrophy for the Differential Diagnosis of Normal Pressure Hydrocephalus

PubMed Central

Moore, Dana W.; Kovanlikaya, Ilhami; Heier, Linda A.; Raj, Ashish; Huang, Chaorui; Chu, King-Wai; Relkin, Norman R.

2012-01-01

Current radiologic diagnosis of normal pressure hydrocephalus (NPH) requires a subjective judgment of whether lateral ventricular enlargement is disproportionate to cerebral atrophy based on visual inspection of brain images. We investigated whether quantitative measurements of lateral ventricular volume and total cortical thickness (a correlate of cerebral atrophy) could be used to more objectively distinguish NPH from normal controls (NC), Alzheimer's (AD), and Parkinson's disease (PD). Volumetric MRIs were obtained prospectively from patients with NPH (n = 5), PD (n = 5), and NC (5). Additional NC (n = 5) and AD patients (n = 10) from the ADNI cohort were examined. Although mean ventricular volume was significantly greater in the NPH group than all others, the range of values overlapped those of the AD group. Individuals with NPH could be better distinguished when ventricular volume and total cortical thickness were considered in combination. This pilot study suggests that volumetric MRI measurements hold promise for improving NPH differential diagnosis. PMID:21860791

MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis

PubMed Central

Mehdi, Muhammad Zain; Nagi, Abdul Hanan; Naseem, Nadia

2016-01-01

ABSTRACT Introduction/Background: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. Material and Methods: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. Results: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. Conclusion: Both Ki-67 and MCM-2 are

MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis.

PubMed

Mehdi, Muhammad Zain; Nagi, Abdul Hanan; Naseem, Nadia

2016-01-01

Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they

Changes in jawbones of male patients with chronic renal failure on digital panoramic radiographs.

PubMed

Dagistan, Saadettin; Miloglu, Ozkan; Caglayan, Fatma

2016-01-01

To compare the existence of gonial cortical bone thickness, antegonial index, mandibular canal bone resorption and gonial angle values and pathologies like ground-glass appearance in jawbones and brown tumor in male patients undergoing dialysis due to chronic renal failure and men from the healthy control group on panoramic radiographs. Panoramic radiographs were taken from 80 male individuals in total (40 normal and 40 dialysis patients). Values obtained from the right and left sides of the mandible were summed and their means were calculated. Gonial cortical thickness, antegonial index and gonial angle values were assessed with the Student's t-test, mandibular canal wall resorption with the Chi-square test, and pathologies such as ground-glass appearance and Brown tumor as "available" or "not available." Statistically significant differences were observed among the antegonial index (P < 0.001), gonial cortical bone thickness (P < 0.001), and gonial angle (P < 0.001) values of study and control groups. Besides, mandibular canal wall resorption (P < 0.001) was also statistically significant. In the study group, pathologies with ground-glass appearance were encountered in mandible, but no radiographic findings were observed similar to brown tumor. Compared to the control group, decreases were found in gonial cortical bone thicknesses, antegonial index values, mandibular canal wall resorption, and gonial angle values of the patients receiving dialysis treatment due to chronic renal failure. Although it is not statistically significant, pathology with ground-glass appearance was detected in a patient, but no pathologies like brown tumor were observed. These findings from patients with chronic renal failure must be evaluated in panoramic radiography.

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia.

PubMed

Saad, Ahmed; Wang, Wei; Herrmann, Sandra M S; Glockner, James F; Mckusick, Michael A; Misra, Sanjay; Bjarnason, Haraldur; Lerman, Lilach O; Textor, Stephen C

2016-11-01

Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging. Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia. Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; P< 0.0001); baseline IGFBP-7 correlated inversely with hypoxia developing 24 h after contrast injection (r = -0.73, P< 0.0001) and with prestent cortical blood flow (r = -0.59, P= 0.004). These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with 'ischemic preconditioning'. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A comparative kinetic RT/-PCR strategy for the quantitation of mRNAs in microdissected human renal biopsy specimens.

PubMed

Del Prete, D; Forino, M; Gambaro, G; D'Angelo, A; Baggio, B; Anglani, F

1998-01-01

Molecular biology techniques, to be applicable to a diagnostic renal biopsy specimen, should (1) be highly sensitive to be performed on a very small quantity of tissue; (2) be quantitative because they have to analyze genes normally expressed in the tissue and (3) allow the analysis of as large a number of genes as possible. Among different methods, only the reverse-transcriptase polymerase chain reaction (RT/-PCR) might comply with previous requisites, but the few RT/-PCR examples on renal biopsies in the literature do not allow starting RNA quantification and quality control; furthermore they have the drawback of analyzing only few genes. In an ongoing study to assess the expression of a number of genes in glomeruli and in tubulointerstitium of patients with different nephropathies, we developed a comparative RT/-PCR kinetic strategy based on the purification and quantification of total glomerular and tubulointerstitial RNA and on the use of an internal standard, the housekeeping gene G3PDH. We demonstrate that in microdissected diagnostic renal biopsies (1) glomerular and interstitial starting RNA can be quantified; (2) the G3PDH gene may be used both as an internal standard and as an indirect marker of RNA integrity; (3) as low as 28 ng of total RNA is sufficient to obtain PCR products of eight genes, and (4) it is worth to operate on microdissected biopsy specimens because of the different expression of genes in the two renal compartments.

Dietary zinc modifies diabetic-induced renal pathology in rats

PubMed Central

Elsaed, Wael M.; Mohamed, Hazem Abdelhamid

2017-01-01

Abstract This study was conducted to investigate how far dietary zinc (Zn) modifies the histomorphological alterations induced by diabetes in rat kidneys. The animals were divided into negative control group (10 rats). Diabetes was induced in thirty animals by streptozotocin. After confirming diabetes, the animals were divided into three groups (n = 10). Group II served as the positive control group (fed on standard diet), group III was fed on Zn deficient diet, and group IV was fed on Zn supplemented diet. Caspase-3 immune staining was used to estimate the caspase activity. Stereological procedures were used to measure the quantity of the immune stain and the surface area of the Bowman’s space. The renal cortices of group II rats revealed apparent widening of Bowman’s spaces with few apoptotic figures. The filtration barrier showed thickening of the basement membrane. The proximal convoluted tubules showed patchy loss of the apical microvilli with swollen mitochondria. The distal convoluted tubules revealed area of irregular basal enfolding. The picture was aggravated by Zn deficiency in group III besides areas of cortical interstitial fibrosis. The histopathological alterations were minimal in the cortices of group IV. A significant increase of the Bowman’s space surface area in group II and IV while decrease in group III compared with group I. The expression of Caspase-3 density was significantly increased in group II and III compared with group I while in group IV was non significant. In conclusion, dietary Zn modulated renal cortical changes caused by diabetes in rats. PMID:27882813

The Role of Biotransformation and Oxidative Stress in 3,5-Dichloroaniline (3,5-DCA) Induced Nephrotoxicity in Isolated Renal Cortical Cells from Male Fischer 344 Rats

PubMed Central

Racine, Christopher R.; Ferguson, Travis; Preston, Debbie; Ward, Dakota; Ball, John; Anestis, Dianne; Valentovic, Monica; Rankin, Gary O.

2016-01-01

Among the mono- and dichloroanilines, 3,5-Dichloroaniline (3,5-DCA) is the most potent nephrotoxicant in vivo and in vitro. However, the role of renal biotransformation in 3,5-DCA induced nephrotoxicity is unknown. The current study was designed to determine the in vitro nephrotoxic potential of 3,5-DCA in isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats, and the role of renal bioactivation and oxidative stress in 3,5-DCA nephrotoxicity. IRCC (~4 million cells/ml) from male rats were exposed to 3,5-DCA (0-1.0 mM) for up to 120 min. In IRCC, 3,5-DCA was cytotoxic at 1.0 mM by 60 min as evidenced by the increased release of lactate dehydrogenase (LDH), but 120 min was required for 3,5-DCA 0.5 mM to increase LDH release. In subsequent studies, IRCC were exposed to a pretreatment (antioxidant or enzyme inhibitor) prior to exposure to 3,5-DCA (1.0 mM) for 90 min. Cytotoxicity induced by 3,5-DCA was attenuated by pretreatment with inhibitors of flavin-containing monooxygenase (FMO; methimazole, N-octylamine), cytochrome P450 (CYP; piperonyl butoxide, metyrapone), or peroxidase (indomethacin, mercaptosuccinate) enzymes. Use of more selective CYP inhibitors suggested that the CYP 2C family contributed to 3,5-DCA bioactivation. Antioxidants (glutathione, N-acetyl-L-cysteine, α-tocopherol, ascorbate, pyruvate) also attenuated 3,5-DCA nephrotoxicity, but oxidized glutathione levels and the oxidized/reduced glutathione ratios were not increased. These results indicate that 3,5-DCA may be activated via several renal enzyme systems to toxic metabolites, and that free radicals, but not oxidative stress, contribute to 3,5-DCA induced nephrotoxicity in vitro. PMID:26808022

Obstetric acute renal failure 1956-1987.

PubMed

Turney, J H; Ellis, C M; Parsons, F M

1989-06-01

A total of 142 women with severe acute renal failure (ARF) resulting from obstetric causes was treated by dialysis at a single centre from 1956 to 1987. One-year survival was 78.6%, which compares favourably with other causes of ARF. Abortion, haemorrhage and preclampsia comprised 95% of cases, with survival being best (82.9%) with abortion. Survival was adversely affected by increasing age. Acute cortical necrosis (12.7% of patients) carried 100% mortality after 6 years. Follow-up of survivors showed normal renal function up to 31 years following ARF; 25-year patient survival was 71.6%. Improvements in obstetric care and the disappearance of illegal abortions have resulted in a dramatic decline in the incidence of obstetric ARF.

[Renal elastography].

PubMed

Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

2016-04-01

Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

[Asymptomatic Renal Stones: Do they really Exist?].

PubMed

Seseke, S; Rudolph, R; Rebmann, U

2011-11-01

Asymptomatic renal calculi without any history of colic, hematuria or infection can be found as an incidental finding during preven-tive check-ups. The aim of our study was to eval-uate whether these stones provoke symptoms with the need for further treatment during the follow-up and whether they cause cortical defects which may consecutively affect the renal func-tion. In a prospective study we evaluated 104  patients with renal calculi. The -medical history, radiological findings and functional imaging as well as urine and blood analyses were recorded and evaluated. The influence of stone size and localisation on the development of acute stone-related symptoms, renal function and renal scarring were evaluated. Furthermore, we analysed whether localised pathological findings in radiographic or functional imaging may influence the creatinine level. The follow-up was be-tween 12 and 48  months (median: 25  months). During the study period 27 / 104 of our patients (26 %) developed symptomatic events (renal colic, hematuria, infection) in which patients with middle pole calculi with a mean -cumulative stone diameter of 9.8  mm had the -highest risk. A localised renal scarring could be found in 36.6 %. These patients had a significantly higher risk in presenting an increased creatinine level. Increasing stone size was diagnosed in 39  cases (37.5 %). Asymptomatic renal stones have to be controlled regularly in order to prevent the -patient from loss of renal function and hypertension caused by increasing stones or urinary tract infection. © Georg Thieme Verlag KG Stuttgart ˙ New York.

Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons

PubMed Central

Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew CN; Swindale, Nicholas V; Murphy, Timothy H

2017-01-01

Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps. DOI: http://dx.doi.org/10.7554/eLife.19976.001 PMID:28160463

Metabolic bone disease in chronic renal failure. II. Renal transplant patients.

PubMed Central

Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.; Starzl, T. E.

1975-01-01

Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy. Images Fig 1 PMID:1091152

Comparison of ASL and DCE MRI for the non-invasive measurement of renal blood flow: quantification and reproducibility.

PubMed

Cutajar, Marica; Thomas, David L; Hales, Patrick W; Banks, T; Clark, Christopher A; Gordon, Isky

2014-06-01

To investigate the reproducibility of arterial spin labelling (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and quantitatively compare these techniques for the measurement of renal blood flow (RBF). Sixteen healthy volunteers were examined on two different occasions. ASL was performed using a multi-TI FAIR labelling scheme with a segmented 3D-GRASE imaging module. DCE MRI was performed using a 3D-FLASH pulse sequence. A Bland-Altman analysis was used to assess repeatability of each technique, and determine the degree of correspondence between the two methods. The overall mean cortical renal blood flow (RBF) of the ASL group was 263 ± 41 ml min(-1) [100 ml tissue](-1), and using DCE MRI was 287 ± 70 ml min(-1) [100 ml tissue](-1). The group coefficient of variation (CVg) was 18 % for ASL and 28 % for DCE-MRI. Repeatability studies showed that ASL was more reproducible than DCE with CVgs of 16 % and 25 % for ASL and DCE respectively. Bland-Altman analysis comparing the two techniques showed a good agreement. The repeated measures analysis shows that the ASL technique has better reproducibility than DCE-MRI. Difference analysis shows no significant difference between the RBF values of the two techniques. Reliable non-invasive monitoring of renal blood flow is currently clinically unavailable. Renal arterial spin labelling MRI is robust and repeatable. Renal dynamic contrast-enhanced MRI is robust and repeatable. ASL blood flow values are similar to those obtained using DCE-MRI.

Vasopressin Receptor Signaling and Cycling of Water Channels in Renal Epithelia.

DTIC Science & Technology

1994-08-31

functional similarities to the renal cortical collecting tubule (Bentley, 1958; DiBona , 1981 and others). Recently, we demonstrated that the apical...changes in the toad urinary bladder epithelial surface. J. Cell Biol., 61, 544-547. 27 DiBona , D. R. 1981. Vasopressin action of the conformational state

A biphasic parameter estimation method for quantitative analysis of dynamic renal scintigraphic data

NASA Astrophysics Data System (ADS)

Koh, T. S.; Zhang, Jeff L.; Ong, C. K.; Shuter, B.

2006-06-01

Dynamic renal scintigraphy is an established method in nuclear medicine, commonly used for the assessment of renal function. In this paper, a biphasic model fitting method is proposed for simultaneous estimation of both vascular and parenchymal parameters from renal scintigraphic data. These parameters include the renal plasma flow, vascular and parenchymal mean transit times, and the glomerular extraction rate. Monte Carlo simulation was used to evaluate the stability and confidence of the parameter estimates obtained by the proposed biphasic method, before applying the method on actual patient study cases to compare with the conventional fitting approach and other established renal indices. The various parameter estimates obtained using the proposed method were found to be consistent with the respective pathologies of the study cases. The renal plasma flow and extraction rate estimated by the proposed method were in good agreement with those previously obtained using dynamic computed tomography and magnetic resonance imaging.

Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study

PubMed Central

Doltra, Adelina; Hartmann, Arthur; Stawowy, Philipp; Goubergrits, Leonid; Kuehne, Titus; Wellnhofer, Ernst; Gebker, Rolf; Schneeweis, Christopher; Schnackenburg, Bernhard; Esler, Murray; Fleck, Eckart; Kelle, Sebastian

2016-01-01

Aim To study the effects of RD on renal artery wall function non-invasively using magnetic resonance. Methods and Results 32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders. Conclusions RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress. PMID:27003912

Thrombotic microangiopathy: An unusual cause of renal failure in rheumatoid arthritis.

PubMed

Sakthirajan, R; Dhanapriya, J; Dineshkumar, T; Gopalakrishnan, N; Murugan, S; Balasubramaniyan, T

2017-01-01

Rheumatoid arthritis (RA) is one of the commonest rheumatological diseases. Renal involvement is not common but can occur as a result of chronic inflammation as part of disease process or drug toxicity. Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. Only a few cases of TMA in patients with RA were reported to date. We describe a 45-year-old female patient with RA who presented with oliguria and edema. Renal biopsy showed TMA with patchy cortical necrosis. She improved with hemodialysis and plasmapheresis.

Measurement of arterial transit time and renal blood flow using pseudocontinuous ASL MRI with multiple post-labeling delays: Feasibility, reproducibility, and variation.

PubMed

Kim, Dong Won; Shim, Woo Hyun; Yoon, Seong Kuk; Oh, Jong Yeong; Kim, Jeong Kon; Jung, Hoesu; Matsuda, Tsuyoshi; Kim, Dongeun

2017-09-01

To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers. PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland-Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined. Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m 2 . Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland-Altman plot for cortical RBF showed good agreement between the two measurements. PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813-819. © 2017 International Society for Magnetic Resonance in Medicine.

Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics

PubMed Central

Handel, Adam E.; Chintawar, Satyan; Lalic, Tatjana; Whiteley, Emma; Vowles, Jane; Giustacchini, Alice; Argoud, Karene; Sopp, Paul; Nakanishi, Mahito; Bowden, Rory; Cowley, Sally; Newey, Sarah; Akerman, Colin; Ponting, Chris P.; Cader, M. Zameel

2016-01-01

Induced pluripotent stem cell (iPSC)-derived cortical neurons potentially present a powerful new model to understand corticogenesis and neurological disease. Previous work has established that differentiation protocols can produce cortical neurons, but little has been done to characterize these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single-cell multiplex reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Totally, 93.6% of single cells derived from iPSCs expressed genes indicative of neuronal identity. High proportions of single neurons derived from iPSCs expressed glutamatergic receptors and synaptic genes. And, 68.4% of iPSC-derived neurons expressing at least one layer marker could be assigned to a laminar identity using canonical cortical layer marker genes. We compared single-cell RNA-seq of our iPSC-derived neurons to available single-cell RNA-seq data from human fetal and adult brain and found that iPSC-derived cortical neurons closely resembled primary fetal brain cells. Unexpectedly, a subpopulation of iPSC-derived neurons co-expressed canonical fetal deep and upper cortical layer markers. However, this appeared to be concordant with data from primary cells. Our results therefore provide reassurance that iPSC-derived cortical neurons are highly similar to primary cortical neurons at the level of single cells but suggest that current layer markers, although effective, may not be able to disambiguate cortical layer identity in all cells. PMID:26740550

DICCCOL: Dense Individualized and Common Connectivity-Based Cortical Landmarks

PubMed Central

Zhu, Dajiang; Guo, Lei; Jiang, Xi; Zhang, Tuo; Zhang, Degang; Chen, Hanbo; Deng, Fan; Faraco, Carlos; Jin, Changfeng; Wee, Chong-Yaw; Yuan, Yixuan; Lv, Peili; Yin, Yan; Hu, Xiaolei; Duan, Lian; Hu, Xintao; Han, Junwei; Wang, Lihong; Shen, Dinggang; Miller, L Stephen

2013-01-01

Is there a common structural and functional cortical architecture that can be quantitatively encoded and precisely reproduced across individuals and populations? This question is still largely unanswered due to the vast complexity, variability, and nonlinearity of the cerebral cortex. Here, we hypothesize that the common cortical architecture can be effectively represented by group-wise consistent structural fiber connections and take a novel data-driven approach to explore the cortical architecture. We report a dense and consistent map of 358 cortical landmarks, named Dense Individualized and Common Connectivity–based Cortical Landmarks (DICCCOLs). Each DICCCOL is defined by group-wise consistent white-matter fiber connection patterns derived from diffusion tensor imaging (DTI) data. Our results have shown that these 358 landmarks are remarkably reproducible over more than one hundred human brains and possess accurate intrinsically established structural and functional cross-subject correspondences validated by large-scale functional magnetic resonance imaging data. In particular, these 358 cortical landmarks can be accurately and efficiently predicted in a new single brain with DTI data. Thus, this set of 358 DICCCOL landmarks comprehensively encodes the common structural and functional cortical architectures, providing opportunities for many applications in brain science including mapping human brain connectomes, as demonstrated in this work. PMID:22490548

Renal nerve stimulation leads to the activation of the Na+/H+ exchanger isoform 3 via angiotensin II type I receptor.

PubMed

Pontes, Roberto B; Crajoinas, Renato O; Nishi, Erika E; Oliveira-Sales, Elizabeth B; Girardi, Adriana C; Campos, Ruy R; Bergamaschi, Cássia T

2015-04-15

Renal nerve stimulation at a low frequency (below 2 Hz) causes water and sodium reabsorption via α1-adrenoreceptor tubular activation, a process independent of changes in systemic blood pressure, renal blood flow, or glomerular filtration rate. However, the underlying mechanism of the reabsorption of sodium is not fully understood. Since the sympathetic nervous system and intrarenal ANG II appear to act synergistically to mediate the process of sodium reabsorption, we hypothesized that low-frequency acute electrical stimulation of the renal nerve (ESRN) activates NHE3-mediated sodium reabsorption via ANG II AT1 receptor activation in Wistar rats. We found that ESRN significantly increased urinary angiotensinogen excretion and renal cortical ANG II content, but not the circulating angiotensinogen levels, and also decreased urinary flow and pH and sodium excretion via mechanisms independent of alterations in creatinine clearance. Urinary cAMP excretion was reduced, as was renal cortical PKA activity. ESRN significantly increased NHE3 activity and abundance in the apical microvillar domain of the proximal tubule, decreased the ratio of phosphorylated NHE3 at serine 552/total NHE3, but did not alter total cortical NHE3 abundance. All responses mediated by ESRN were completely abolished by a losartan-mediated AT1 receptor blockade. Taken together, our results demonstrate that higher NHE3-mediated proximal tubular sodium reabsorption induced by ESRN occurs via intrarenal renin angiotensin system activation and triggering of the AT1 receptor/inhibitory G-protein signaling pathway, which leads to inhibition of cAMP formation and reduction of PKA activity. Copyright © 2015 the American Physiological Society.

Febuxostat ameliorates diabetic renal injury in a streptozotocin-induced diabetic rat model.

PubMed

Lee, Hong-Joo; Jeong, Kyung Hwan; Kim, Yang Gyun; Moon, Joo Young; Lee, Sang Ho; Ihm, Chun Gyoo; Sung, Ji Youn; Lee, Tae Won

2014-01-01

Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions. Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group. Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat. Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the

Biomechanics of Single Cortical Neurons

PubMed Central

Bernick, Kristin B.; Prevost, Thibault P.; Suresh, Subra; Socrate, Simona

2011-01-01

This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude – 10, 1, and 0.1 μm/s. Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper-) elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented into a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements. PMID:20971217

Linking contemporary high resolution magnetic resonance imaging to the von Economo legacy: A study on the comparison of MRI cortical thickness and histological measurements of cortical structure.

PubMed

Scholtens, Lianne H; de Reus, Marcel A; van den Heuvel, Martijn P

2015-08-01

The cerebral cortex is a distinctive part of the mammalian nervous system, displaying a spatial variety in cyto-, chemico-, and myelinoarchitecture. As part of a rich history of histological findings, pioneering anatomists von Economo and Koskinas provided detailed mappings on the cellular structure of the human cortex, reporting on quantitative aspects of cytoarchitecture of cortical areas. Current day investigations into the structure of human cortex have embraced technological advances in Magnetic Resonance Imaging (MRI) to assess macroscale thickness and organization of the cortical mantle in vivo. However, direct comparisons between current day MRI estimates and the quantitative measurements of early anatomists have been limited. Here, we report on a simple, but nevertheless important cross-analysis between the histological reports of von Economo and Koskinas on variation in thickness of the cortical mantle and MRI derived measurements of cortical thickness. We translated the von Economo cortical atlas to a subdivision of the commonly used Desikan-Killiany atlas (as part of the FreeSurfer Software package and a commonly used parcellation atlas in studies examining MRI cortical thickness). Next, values of "width of the cortical mantle" as provided by the measurements of von Economo and Koskinas were correlated to cortical thickness measurements derived from high-resolution anatomical MRI T1 data of 200+ subjects of the Human Connectome Project (HCP). Cross-correlation revealed a significant association between group-averaged MRI measurements of cortical thickness and histological recordings (r = 0.54, P < 0.001). Further validating such a correlation, we manually segmented the von Economo parcellation atlas on the standardized Colin27 brain dataset and applied the obtained three-dimensional von Economo segmentation atlas to the T1 data of each of the HCP subjects. Highly consistent with our findings for the mapping to the Desikan-Killiany regions, cross

Quantitative 3D analysis of bone in hip osteoarthritis using clinical computed tomography.

PubMed

Turmezei, Tom D; Treece, Graham M; Gee, Andrew H; Fotiadou, Anastasia F; Poole, Kenneth E S

2016-07-01

To assess the relationship between proximal femoral cortical bone thickness and radiological hip osteoarthritis using quantitative 3D analysis of clinical computed tomography (CT) data. Image analysis was performed on clinical CT imaging data from 203 female volunteers with a technique called cortical bone mapping (CBM). Colour thickness maps were created for each proximal femur. Statistical parametric mapping was performed to identify statistically significant differences in cortical bone thickness that corresponded with the severity of radiological hip osteoarthritis. Kellgren and Lawrence (K&L) grade, minimum joint space width (JSW) and a novel CT-based osteophyte score were also blindly assessed from the CT data. For each increase in K&L grade, cortical thickness increased by up to 25 % in distinct areas of the superolateral femoral head-neck junction and superior subchondral bone plate. For increasing severity of CT osteophytes, the increase in cortical thickness was more circumferential, involving a wider portion of the head-neck junction, with up to a 7 % increase in cortical thickness per increment in score. Results were not significant for minimum JSW. These findings indicate that quantitative 3D analysis of the proximal femur can identify changes in cortical bone thickness relevant to structural hip osteoarthritis. • CT is being increasingly used to assess bony involvement in osteoarthritis • CBM provides accurate and reliable quantitative analysis of cortical bone thickness • Cortical bone is thicker at the superior femoral head-neck with worse osteoarthritis • Regions of increased thickness co-locate with impingement and osteophyte formation • Quantitative 3D bone analysis could enable clinical disease prediction and therapy development.

A local renal renin-angiotensin system activation via renal uptake of prorenin and angiotensinogen in diabetic rats.

PubMed

Tojo, Akihiro; Kinugasa, Satoshi; Fujita, Toshiro; Wilcox, Christopher S

2016-01-01

The mechanism of activation of local renal renin-angiotensin system (RAS) has not been clarified in diabetes mellitus (DM). We hypothesized that the local renal RAS will be activated via increased glomerular filtration and tubular uptake of prorenin and angiotensinogen in diabetic kidney with microalbuminuria. Streptozotocin (STZ)-induced DM and control rats were injected with human prorenin and subsequently with human angiotensinogen. Human prorenin uptake was increased in podocytes, proximal tubules, macula densa, and cortical collecting ducts of DM rats where prorenin receptor (PRR) was expressed. Co-immunoprecipitation of kidney homogenates in DM rats revealed binding of human prorenin to the PRR and to megalin. The renal uptake of human angiotensinogen was increased in DM rats at the same nephron sites as prorenin. Angiotensin-converting enzyme was increased in podocytes, but decreased in the proximal tubules in DM rats, which may have contributed to unchanged renal levels of angiotensin despite increased angiotensinogen. The systolic blood pressure increased more after the injection of 20 μg of angiotensinogen in DM rats than in controls, accompanied by an increased uptake of human angiotensinogen in the vascular endothelium. In conclusion, endocytic uptake of prorenin and angiotensinogen in the kidney and vasculature in DM rats was contributed to increased tissue RAS and their pressor response to angiotensinogen.

The effects of furosemide on remal blood flow and cortical perfusion during methoxyflurane and halothane anaesthesia.

PubMed

Leighton, K M; Bruce, C; Machin, R

1976-01-01

Nephrotoxicity due to methoxyflurane may be due in part to alterations in intra-renal perfusion. Furosemide is believed to alter the intra-renal distribution of blood flow. Studies have been carried out to observe the effects of systemic furosemide administration during methoxyflurane and halothane anaesthesia in normotensive animals and in animals made hypotensive by increasing inspired concentrations of the anaesthetics. During halothane anaesthesia normotensive dogs showed a rise in total renal blood flow during the infusion of furosemide. Hypotensive dogs showed no increase in flow. During methoxyflurane anaesthesia no change in total renal blood flow followed furosemide administration to normotensive animals. Some diminution in total blood flow followed the administration of furosemide in hypotensive dogs during methoxyflurane anaesthesia. In normotensive dogs during halothane anaesthesia there was a significant increase in deep cortical perfusion after furosemide. Furosemide, therefore, is unlikely to mitigate the potential for nephrotoxicity which methoxyflurane possesses. Furthermore, this diuretic may adversely influence renal function when administered during halothane anaesthesia.

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.

A pseudo-three-dimensional model for quantification of oxygen diffusion from preglomerular arteries to renal tissue and renal venous blood.

PubMed

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

2017-08-01

To assess the physiological significance of arterial-to-venous (AV) oxygen shunting, we generated a new pseudo-three-dimensional computational model of oxygen diffusion from intrarenal arteries to cortical tissue and veins. The model combines the 11 branching levels (known as "Strahler" orders) of the preglomerular renal vasculature in the rat, with an analysis of an extensive data set obtained using light microscopy to estimate oxygen mass transfer coefficients for each Strahler order. Furthermore, the AV shunting model is now set within a global oxygen transport model that includes transport from arteries, glomeruli, peritubular capillaries, and veins to tissue. While a number of lines of evidence suggest AV shunting is significant, most importantly, our AV oxygen shunting model predicts AV shunting is small under normal physiological conditions (~0.9% of total renal oxygen delivery; range 0.4-1.4%), but increases during renal ischemia, glomerular hyperfiltration (~2.1% of total renal oxygen delivery; range 0.84-3.36%), and some cardiovascular disease states (~3.0% of total renal oxygen delivery; range 1.2-4.8%). Under normal physiological conditions, blood Po 2 is predicted to fall by ~16 mmHg from the root of the renal artery to glomerular entry, with AV oxygen shunting contributing ~40% and oxygen diffusion from arteries to tissue contributing ~60% of this decline. Arterial Po 2 is predicted to fall most rapidly from Strahler order 4 , under normal physiological conditions. We conclude that AV oxygen shunting normally has only a small impact on renal oxygenation, but may exacerbate renal hypoxia during renal ischemia, hyperfiltration, and some cardiovascular disease states. Copyright © 2017 the American Physiological Society.

Magnetic Resonance Imaging-Derived Renal Oxygenation and Perfusion During Continuous, Steady-State Angiotensin-II Infusion in Healthy Humans.

PubMed

van der Bel, René; Coolen, Bram F; Nederveen, Aart J; Potters, Wouter V; Verberne, Hein J; Vogt, Liffert; Stroes, Erik S G; Krediet, C T Paul

2016-03-28

The role of kidney hypoxia is considered pivotal in the progression of chronic kidney disease. A widely used method to assess kidney oxygenation is blood oxygen level dependent (BOLD)-magnetic resonance imaging (MRI), but its interpretation remains problematic. The BOLD-MRI signal is the result of kidney oxygen consumption (a proxy of glomerular filtration) and supply (ie, glomerular perfusion). Therefore, we hypothesized that with pharmacological modulation of kidney blood flow, renal oxygenation, as assessed by BOLD-MRI, correlates to filtration fraction (ie, glomerular filtration rate/effective renal plasma flow) in healthy humans. Eight healthy volunteers were subjected to continuous angiotensin-II infusion at 0.3, 0.9, and 3.0 ng/kg per minute. At each dose, renal oxygenation and blood flow were assessed using BOLD and phase-contrast MRI. Subsequently, "gold standard" glomerular filtration rate/effective renal plasma flow measurements were performed under the same conditions. Renal plasma flow decreased dose dependently from 660±146 to 467±103 mL/min per 1.73 m(2) (F[3, 21]=33.3, P<0.001). Glomerular filtration rate decreased from 121±23 to 110±18 mL/min per 1.73 m(2) (F[1.8, 2.4]=6.4, P=0.013). Cortical transverse relaxation rate (R2*; increases in R2* represent decreases in oxygenation) increased by 7.2±3.8% (F[3, 21]=7.37, P=0.001); medullar R2* did not change. Cortical R2* related to filtration fraction (R(2) 0.46, P<0.001). By direct comparison between "gold standard" kidney function measurements and BOLD MRI, we showed that cortical oxygenation measured by BOLD MRI relates poorly to glomerular filtration rate but is associated with filtration fraction. For future studies, there may be a need to include renal plasma flow measurements when employing renal BOLD-MRI. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Histomorphometry and cortical robusticity of the adult human femur.

PubMed

Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

2018-01-13

Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

A forskolin derivative, colforsin daropate hydrochloride, inhibits the decrease in cortical renal blood flow induced by noradrenaline or angiotensin II in anesthetized rats.

PubMed

Ogata, Junichi; Minami, Kouichiro; Segawa, Kayoko; Uezono, Yasuhito; Shiraishi, Munehiro; Yamamoto, Chikako; Sata, Takeyoshi; Sung-Teh, Kim; Shigematsu, Akio

2004-01-01

A forskolin derivative, colforsin daropate hydrochloride (CDH), acts directly on adenylate cyclase to increase the intracellular cyclic adenosine monophosphate levels which produce a positive inotropic effect and a lower blood pressure. However, little is known about the effects of CDH on the renal function. We used laser Doppler flowmetry to measure the cortical renal blood flow (RBF) in male Wistar rats given a continuous intravenous infusion of CDH and evaluated the effects of CDH on the noradrenaline (NA) and angiotensin II (AngII) induced increases in blood pressure and reductions in RBF. Continuous intravenous administration of CDH at 0.25 microg/kg/min did not affect the mean arterial pressure (MAP), but increased heart rate and RBF. Continuous intravenous administration of CDH at high doses (0.5-0.75 microg/kg/min) decreased the MAP, with little effect on the RBF. The administration of exogenous NA (1.7 microg/kg) increased the MAP and decreased the RBF. However, a bolus injection of NA did not decrease the RBF during continuous intravenous administration of CDH, and CDH did not affect the NA-induced increase in MAP. The administration of exogenous AngII (100 ng/kg) increased MAP and decreased RBF and heart rate, but a bolus injection of AngII did not decrease RBF during continuous intravenous administration of CDH. These results suggest that CDH plays a protective role against the pressor effects and the decrease in RBF induced by NA or AngII. Copyright 2004 S. Karger AG, Basel

Ultrashort echo time magnetization transfer (UTE-MT) imaging of cortical bone.

PubMed

Chang, Eric Y; Bae, Won C; Shao, Hongda; Biswas, Reni; Li, Shihong; Chen, Jun; Patil, Shantanu; Healey, Robert; D'Lima, Darryl D; Chung, Christine B; Du, Jiang

2015-07-01

Magnetization transfer (MT) imaging is one way to indirectly assess pools of protons with fast transverse relaxation. However, conventional MT imaging sequences are not applicable to short T2 tissues such as cortical bone. Ultrashort echo time (UTE) sequences with TE values as low as 8 µs can detect signals from different water components in cortical bone. In this study we aim to evaluate two-dimensional UTE-MT imaging of cortical bone and its application in assessing cortical bone porosity as measured by micro-computed tomography (μCT) and biomechanical properties. In total, 38 human cadaveric distal femur and proximal tibia bones were sectioned to produce 122 rectangular pieces of cortical bone for quantitative UTE-MT MR imaging, μCT, and biomechanical testing. Off-resonance saturation ratios (OSRs) with a series of MT pulse frequency offsets (Δf) were calculated and compared with porosity assessed with μCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation and linear regression. A moderately strong negative correlation was observed between OSR and μCT porosity (R(2)  = 0.46-0.51), while a moderate positive correlation was observed between OSR and yield stress (R(2)  = 0.25-0.30) and failure stress (R(2)  = 0.31-0.35), and a weak positive correlation (R(2)  = 0.09-0.12) between OSR and Young's modulus at all off-resonance saturation frequencies. OSR determined with the UTE-MT sequence provides quantitative information on cortical bone and is sensitive to μCT porosity and biomechanical function. Copyright © 2015 John Wiley & Sons, Ltd.

Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

PubMed Central

2010-01-01

Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist) and parecoxib (a selective cyclooxygenase-2 inhibitor) on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals) were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG) desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity), while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect. PMID:20089200

Intracellular angiotensin II directly induces in vitro transcription of TGF-β1, MCP-1 and NHE-3 mRNAs in isolated rat renal cortical nuclei via activation of nuclear AT1 receptors

PubMed Central

Li, Xiao C.; Zhuo, Jia L.

2008-01-01

The present study tested the hypothesis that intracellular angiotensin II (Ang II) directly induces transcriptional effects by stimulating AT1 receptors in the nucleus of rat renal cortical cells. Intact nuclei were freshly isolated from the rat renal cortex and transcriptional responses to Ang II were studied using in vitro RNA transcription assays and semi-quantitative RT-PCR. High power phase contrast micrographs showed that isolated nuclei were encircled by an intact nuclear envelop, stained strongly by the DNA marker DAPI, but not by the membrane or endosomal markers. FITC-labeled Ang II and [125I]-Val5-Ang II binding confirmed the presence of Ang II receptors in the nuclei with a predominance of AT1 receptors. RT-PCR showed that AT1a mRNA expression was 3-fold greater than AT1b receptor mRNAs in these nuclei. In freshly isolated nuclei, Ang II increased in vitro [α-32P]CTP incorporation in a concentration manner, and the effect was confirmed by autoradiography and RNA electrophoresis. Ang II markedly increased in vitro transcription of mRNAs for transforming growth factor-β1 by 143% (p < 0.01), macrophage chemoattractant protein-1 by 89% (p < 0.01), and the sodium and hydrogen exchanger-3 by 110% (p < 0.01). These transcriptional effects of Ang II on the nuclei were completely blocked by the AT1 receptor antagonist losartan (p < 0.01). By contrast, Ang II had no effects on transcription of angiotensinogne and GAPDH mRNAs. Since these transcriptional effects of Ang II in isolated nuclei were induced by Ang II in the absence of cell surface receptor-mediated signaling and completely blocked by losartan, we concluded that Ang II may directly stimulate nuclear AT1a receptors to induce transcriptional responses that are associated with tubular epithelial sodium transport, cellular growth and hypertrophy, and proinflammatory cytokines. PMID:18256274

Antagonistic actions of renal dopamine and 5-hydroxytryptamine: increase in Na+, K(+)-ATPase activity in renal proximal tubules via activation of 5-HT1A receptors.

PubMed Central

Soares-da-Silva, P.; Pinto-do-O, P. C.; Bertorello, A. M.

1996-01-01

1. 5-Hydroxytryptamine (5-HT) is antinatriuretic. Since this effect of 5-HT is not accomplished by changes in glomerular haemodynamics, we have examined in this study whether 5-HT may influence sodium excretion by affecting the Na+, K(+)-ATPase activity in renal cortical tubules. 2. Na+, K(+)-ATPase activity was determined as the rate of [32P]-ATP hydrolysis in renal cortical tubules in suspension. Basal Na+, K(+)-ATPase activity in renal tubules was 4.8 +/- 0.4 mumol Pi mg-1 protein h-1 (n = 8). The 5-HT1A receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) (10 to 3000 nM) induced a concentration-dependent increase (P < 0.05) in Na+, K(+)-ATPase activity with an EC50 value of 355 nM (95% confidence limits: 178, 708). Maximal stimulation elicited by 3000 nM of 8-OH-DPAT was antagonized by the selective 5-HT1A receptor antagonist, (+)-WAY 100135 10 to 1000 nM) with an IC50 value of 20 nM (14, 29); 0.3 microM (+)-WAY 100135 completely abolished (P < 0.01) the stimulatory effect of 8-OH-DPAT. The stimulatory effect of 8-OH-DPAT was found to be time-dependent (15 +/- 2% and 66 +/- 7% increase at 2.5 and 5.0 min, respectively). The 5-HT2 receptor agonist alpha-methyl-5-HT (100 to 3000 nM) did not induce any significant changes in Na+, K(+)-ATPase activity (5.0 +/- 1.5 mumol Pi mg-1 protein h-1; n = 4). 3. The stimulatory effect 8-OH-DPAT was absent when homogenates were used. Stimulation occurred at a Vmax concentration (70 mM) of sodium supporting the notion that stimulation occurs independently of increasing sodium permeability. 4. The inhibitory effect of dopamine (P < 0.05) on Na+, K(+)-ATPase activity was blunted by co-incubation with 8-OH-DPAT (0.5 microM). 5. It is concluded that activation of 5-HT1A receptors increases Na+, K(+)-ATPase activity in renal cortical tubules; this effect may represent an important cellular mechanism, at the tubule level, responsible for the antinatriuretic effect of 5-HT. Images Figure 4 PMID:8882616

In situ assessment of the renal microcirculation in mechanically ventilated rats using sidestream dark-field imaging.

PubMed

Astapenko, D; Jor, O; Lehmann, C; Cerny, V

2015-02-01

For microcirculation research there is a need for baseline data and feasibility protocols describing microcirculation of various organs. The aim of our study was to examine the reliability and reproducibility of sidestream dark-field (SDF) imaging within the renal cortical microcirculation in rats. Renal microcirculation was observed using SDF probe placed on the exposed renal surface via the upper midline laparotomy. Video sequences recorded intermittently in short apneic pauses were analyzed off-line by using AVA 3.0 software (MicroVision Medical, Amsterdam, the Netherlands). Results are expressed as mean (SD) or median (25-75% percentiles). We obtained 60 clear sequences from all recorded analyzable videos from all the animals. The total small vessel and all vessel density (in mm.mm(-2) ) were (28.79 ± 0.40) and (28.95 ± 0.40), respectively. The perfused small and all vessel density were (28.79 ± 0.40) and (28.95 ± 0.40), respectively. The DeBacker Score was (19.14 ± 0.43), the proportion of perfused vessels was 100% (100-100%) and the microvascular flow index was 3.49 (3-3.75). We conclude SDF imaging provides a reliable method to examine the renal microvascular bed in vivo and thus can be used for the study of the renal cortical vascular network in various experimental diseases models and clinical settings. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

Age-related pathophysiological changes in rats with unilateral renal agenesis.

PubMed

Amakasu, Kohei; Suzuki, Katsushi; Katayama, Kentaro; Suzuki, Hiroetsu

2011-06-01

Affected rats of the unilateral urogenital anomalies (UUA) strain show renal agenesis restricted to the left side. To determine whether unilateral renal agenesis is a risk factor for the progression of renal insufficiency, we studied age-related pathophysiological alterations in affected rats. Although body growth and food intake were normal, polydipsia and polyuria with low specific gravity were present at 10 weeks and deteriorated further with age. Blood hemoglobin concentrations were normal, though there was slight erythropenia with increased MCV and MCH. Although hypoalbuminemia, hypercholesterolemia, azotemia, and hypermagnesemia were manifested after age 20 weeks, neither hyperphosphatemia nor hypocalcemia was observed. Plasma Cre and UN concentrations gradually increased with age. Cre clearance was almost normal, whereas fractional UN excretion was consistently lower than normal. Proteinuria increased with age, and albumin was the major leakage protein. In addition to cortical lesions, dilated tubules, cast formation, and interstitial fibrosis were observed in the renal medulla of 50 week-old affected rats. Renal weight was increased 1.7-fold and glomerular number 1.2-fold compared with normal rats. These findings show that the remaining kidney in UUA rats is involved not only in compensatory reactions but experiences pathophysiological alterations associated with progressive renal insufficiency.

Quantitative 3D analysis of the canal network in cortical bone by micro-computed tomography.

PubMed

Cooper, D M L; Turinsky, A L; Sensen, C W; Hallgrímsson, B

2003-09-01

Cortical bone is perforated by an interconnected network of porous canals that facilitate the distribution of neurovascular structures throughout the cortex. This network is an integral component of cortical microstructure and, therefore, undergoes continual change throughout life as the cortex is remodeled. To date, the investigation of cortical microstructure, including the canal network, has largely been limited to the two-dimensional (2D) realm due to methodological hurdles. Thanks to continuing improvements in scan resolution, micro-computed tomography (muCT) is the first nondestructive imaging technology capable of resolving cortical canals. Like its application to trabecular bone, muCT provides an efficient means of quantifying aspects of 3D architecture of the canal network. Our aim here is to introduce the use of muCT for this application by providing examples, discussing some of the parameters that can be acquired, and relating these to research applications. Although several parameters developed for the analysis of trabecular microstructure are suitable for the analysis of cortical porosity, the algorithm used to estimate connectivity is not. We adapt existing algorithms based on skeletonization for this task. We believe that 3D analysis of the dimensions and architecture of the canal network will provide novel information relevant to many aspects of bone biology. For example, parameters related to the size, spacing, and volume of the canals may be particularly useful for investigation of the mechanical properties of bone. Alternatively, parameters describing the 3D architecture of the canal network, such as connectivity between the canals, may provide a means of evaluating cumulative remodeling related change. Copyright 2003 Wiley-Liss, Inc.

The effect of renal denervation on kidney oxygenation as determined by BOLD MRI in patients with hypertension.

PubMed

Vink, E E; Boer, A; Verloop, W L; Spiering, W; Voskuil, M; Vonken, E; Hoogduin, J M; Leiner, T; Bots, M L; Blankestijn, P J

2015-07-01

Renal denervation (RDN) is a promising therapy for resistant hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN can potentially increase renal oxygenation. Blood oxygen level-dependent MRI (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the effect of RDN on renal oxygenation as determined by BOLD-MRI. Patients with resistant hypertension or the inability to follow a stable drug regimen due to unacceptable side effects were included. BOLD-MRI was performed before and 12 months after RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI systems. Fifty-four patients were included, 46 patients (23 men, mean age 57 years) completed the study. Mean 24-h BP changed from 163(±20)/98(±14) mmHg to 154(±22)/92(±13) mmHg (p = 0.001 and p < 0.001). eGFR did not change after RDN [77(±18) vs. 79(±20) mL/min/1.73 m(2); p = 0.13]. RDN did not affect renal oxygenation [1.5 T: cortical R2*: 12.5(±0.9) vs. 12.5(±0.9), p = 0.94; medullary R2*: 19.6(±1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*: 18.1(±0.8) vs. 17.8(±1.2), p = 0.47; medullary R2*: 27.4(±1.9) vs. 26.7(±1.8), p = 0.19]. The current study shows that RDN does not lead to changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. • Renal denervation significantly decreased ambulatory blood pressure. • Renal denervation did not change renal oxygenation as determined by BOLD-MRI. • Absence of a change in renal oxygenation might be explained by autoregulation.

Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

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

Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi

Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessmentmore » by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be

Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats.

PubMed

Rodríguez-Gómez, Isabel; Banegas, Inmaculada; Wangensteen, Rosemary; Quesada, Andrés; Jiménez, Rosario; Gómez-Morales, Mercedes; O'Valle, Francisco; Duarte, Juan; Vargas, Félix

2013-01-01

The purpose was to analyse the cardiac and renal capillary density and glomerular morphology resulting from a chronic excess or deficiency of thyroid hormones (THs) in rats. We performed histopathological, morphometrical and immunohistochemical analyses in hypothyroid and hyperthyroid rats to evaluate the density of mesenteric, renal and cardiac vessels at 4 weeks after induction of thyroid disorders. The main angiogenic factors in plasma, heart and kidney were measured as possible mediators of vascular changes. Mesenteric vessel branching was augmented and decreased in hyper- and hypothyroid rats respectively. The numerical density of CD31-positive capillaries was higher in left and right ventricles and in cortical and medullary kidney from both hyper- and hypothyroid rats vs controls. Numbers of podocytes and glomeruli per square millimetre were similar among groups. Glomerular area and percentage mesangium were greater in the hyperthyroid vs control or hypothyroid groups. No morphological renal lesions were observed in any group. Vascularisation of the mesenteric bed is related to TH levels, but an increased capillarity was observed in heart and kidney in both thyroid disorders. This increase may be produced by higher tissue levels of angiogenic factors in hypothyroid rats, whereas haemodynamic factors would predominate in hyperthyroid rats. Our results also indicate that the renal dysfunctions of thyroid disorders are not related to cortical or medullary microvascular rarefaction and that the proteinuria of hyperthyroidism is not secondary to a podocyte deficit. Finally, TH or its analogues may be useful to increase capillarity in renal diseases associated with microvascular rarefaction.

Inhibiting glycogen synthase kinase-3 reduces endotoxaemic acute renal failure by down-regulating inflammation and renal cell apoptosis

PubMed Central

Wang, Y; Huang, WC; Wang, CY; Tsai, CC; Chen, CL; Chang, YT; Kai, JI; Lin, CF

2009-01-01

Background and purpose: Excessive inflammation and apoptosis are pathological features of endotoxaemic acute renal failure. Activation of glycogen synthase kinase-3 (GSK-3) is involved in inflammation and apoptosis. We investigated the effects of inhibiting GSK-3 on lipopolysaccharide (LPS)-induced acute renal failure, nuclear factor-κB (NF-κB), inflammation and apoptosis. Experimental approach: The effects of inhibiting GSK-3 with inhibitors, including lithium chloride (LiCl) and 6-bromo-indirubin-3′-oxime (BIO), on LPS-treated (15 mg·kg−1) C3H/HeN mice (LiCl, 40 mg·kg−1 and BIO, 2 mg·kg−1) and LPS-treated (1 µg·mL−1) renal epithelial cells (LiCl, 20 mM and BIO, 5 µM) were studied. Mouse survival was monitored and renal function was analysed by histological and serological examination. Cytokine and chemokine production, and cell apoptosis were measured by enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP–biotin nick-end labelling staining, respectively. Activation of NF-κB and GSK-3 was determined by immunostaining and Western blotting, respectively. Key results: Mice treated with GSK-3 inhibitors showed decreased mortality, renal tubular dilatation, vacuolization and sloughing, blood urea nitrogen, creatinine and renal cell apoptosis in response to endotoxaemia. Inhibiting GSK-3 reduced LPS-induced tumour necrosis factor-α (TNF-α) and CCL5/RANTES (released upon activation of normal T-cells) in vivo in mice and in vitro in murine kidney cortical collecting duct epithelial M1 cells. Inhibiting GSK-3 did not block TNF-α-induced cytotoxicity in rat kidney proximal tubular epithelial NRK52E or in M1 cells. Conclusions and implications: These results suggest that GSK-3 inhibition protects against endotoxaemic acute renal failure mainly by down-regulating pro-inflammatory TNF-α and RANTES. PMID:19508392

Characteristics of renal papillae in kidney stone formers.

PubMed

Marien, Tracy P; Miller, Nicole L

2016-12-01

The mechanism of kidney stone formation is not well understood. In order to better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones. A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini's duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed. The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini's duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini's duct plugging and pathology is theorized to occur via free

Renal arterial resistive index is associated with severe histological changes and poor renal outcome during chronic kidney disease

PubMed Central

2012-01-01

Background Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome. Methods RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson’s correlation, Mann–Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis. Results Most patients had glomerulonephritis (82%). Median age was 46 years [21–87], eGFR 59 mL/min/ 1.73m2 [5–130], percentage of interstitial fibrosis 10% [0–90], glomerulosclerosis 13% [0–96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = −0.275, p = 0.038) and renal dysfunction (r = −0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic

The Efficacy of Low-intensity Vibration to Improve Bone Health in Patients with End-stage Renal Disease Is Highly Dependent on Compliance and Muscle Response.

PubMed

Rajapakse, Chamith S; Leonard, Mary B; Kobe, Elizabeth A; Slinger, Michelle A; Borges, Kelly A; Billig, Erica; Rubin, Clinton T; Wehrli, Felix W

2017-11-01

Low intensity vibration (LIV) may represent a nondrug strategy to mitigate bone deficits in patients with end-stage renal disease. Thirty end-stage renal patients on maintenance hemodialysis were randomized to stand for 20 minutes each day on either an active or placebo LIV device. Analysis at baseline and completion of 6-month intervention included magnetic resonance imaging (tibia and fibula stiffness; trabecular thickness, number, separation, bone volume fraction, plate-to-rod ratio; and cortical bone porosity), dual-energy X-ray absorptiometry (hip and spine bone mineral density [BMD]), and peripheral quantitative computed tomography (tibia trabecular and cortical BMD; calf muscle cross-sectional area). Intention-to-treat analysis did not show any significant changes in outcomes associated with LIV. Subjects using the active device and with greater than the median adherence (70%) demonstrated an increase in distal tibia stiffness (5.3%), trabecular number (1.7%), BMD (2.3%), and plate-to-rod ratio (6.5%), and a decrease in trabecular separation (-1.8%). Changes in calf muscle cross-sectional area were associated with changes in distal tibia stiffness (R = 0.85), trabecular bone volume/total volume (R = 0.91), number (R = 0.92), and separation (R = -0.94) in the active group but not in the placebo group. Baseline parathyroid hormone levels were positively associated with increased cortical bone porosity over the 6-month study period in the placebo group (R = 0.55) but not in the active group (R = 0.01). No changes were observed in the nondistal tibia locations for either group except a decrease in hip BMD in the placebo group (-1.7%). Outcomes and adherence thresholds identified from this pilot study could guide future longitudinal studies involving vibration therapy. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Asymmetry of cortical decline in subtypes of primary progressive aphasia.

PubMed

Rogalski, Emily; Cobia, Derin; Martersteck, Adam; Rademaker, Alfred; Wieneke, Christina; Weintraub, Sandra; Mesulam, M-Marsel

2014-09-23

The aim of this study was to provide quantitative measures of changes in cortical atrophy over a 2-year period associated with 3 subtypes of primary progressive aphasia (PPA) using whole-brain vertex-wise and region-of-interest (ROI) neuroimaging methods. The purpose was to quantitate disease progression, establish an empirical basis for clinical expectations, and provide outcome measures for therapeutic trials. Changes in cortical thickness and volume loss as well as neuropsychological performance were assessed at baseline and 2-year follow-up in 26 patients who fulfilled criteria for logopenic (8 patients), agrammatic (10 patients), and semantic (8 patients) PPA subtypes. Whole-brain vertex-wise and ROI imaging analysis were conducted using the FreeSurfer longitudinal pipeline. Clinical deficits and cortical atrophy patterns showed distinct patterns of change among the subtypes over 2 years. Results confirmed that progression for each of the 3 subtypes showed left greater than right hemisphere asymmetry. An ROI analysis also revealed that progression was greater within, rather than outside, the language network. Preferential neurodegeneration of the left hemisphere language network is a common denominator for all 3 PPA subtypes, even as the disease progresses. Using a focal cortical language network ROI as an outcome measure of disease progression appears to be more sensitive than whole-brain or ventricular volume measures of change and may be helpful for designing future clinical trials in PPA. © 2014 American Academy of Neurology.

Asymmetry of cortical decline in subtypes of primary progressive aphasia

PubMed Central

Cobia, Derin; Martersteck, Adam; Rademaker, Alfred; Wieneke, Christina; Weintraub, Sandra; Mesulam, M.-Marsel

2014-01-01

Objective: The aim of this study was to provide quantitative measures of changes in cortical atrophy over a 2-year period associated with 3 subtypes of primary progressive aphasia (PPA) using whole-brain vertex-wise and region-of-interest (ROI) neuroimaging methods. The purpose was to quantitate disease progression, establish an empirical basis for clinical expectations, and provide outcome measures for therapeutic trials. Methods: Changes in cortical thickness and volume loss as well as neuropsychological performance were assessed at baseline and 2-year follow-up in 26 patients who fulfilled criteria for logopenic (8 patients), agrammatic (10 patients), and semantic (8 patients) PPA subtypes. Whole-brain vertex-wise and ROI imaging analysis were conducted using the FreeSurfer longitudinal pipeline. Results: Clinical deficits and cortical atrophy patterns showed distinct patterns of change among the subtypes over 2 years. Results confirmed that progression for each of the 3 subtypes showed left greater than right hemisphere asymmetry. An ROI analysis also revealed that progression was greater within, rather than outside, the language network. Conclusions: Preferential neurodegeneration of the left hemisphere language network is a common denominator for all 3 PPA subtypes, even as the disease progresses. Using a focal cortical language network ROI as an outcome measure of disease progression appears to be more sensitive than whole-brain or ventricular volume measures of change and may be helpful for designing future clinical trials in PPA. PMID:25165386

Renal embolic protection devices improve blood flow after stenting for atherosclerotic renal artery stenosis.

PubMed

Paul, Timir K; Lee, John H; White, Christopher J

2012-11-15

We sought to measure angiographic renal frame counts (RFC), as a quantitative angiographic assessment of renal blood flow, to evaluate microvascular compromise due to atheroembolism associated with RAS. Atheroembolism associated with renal artery stenting (RAS) has been implicated as a cause for worsening renal function following successful intervention. Use of a distal embolic protection device (EPD) during RAS has been shown to be safe with debris capture in a high percentage of cases. However, objective benefit for renal function with EPD has been difficult to demonstrate. A control group of 30 consecutive patients (33 kidneys) who underwent RAS without EPD were compared with 33 consecutive patients (33 kidneys) who underwent RAS with EPD using RFC measurement. The prestent and poststent mean RFC for the control group was 30.4 ± 12.1 vs. 23.7 ± 9.9 (P = 0.002) and for the EPD group it was 42.6 ± 12.6 vs. 28.3 ± 9.2 (P < 0.0001). The EPD group had a greater improvement in renal blood flow, manifested by a greater reduction of the RFC (Δ RFC) 14.2 ± 15.2 vs. 6.7 ± 11.7 (P = 0.03) compared with the control group. The use of an EPD was associated with a much larger improvement in renal blood flow (lower RFC) following RAS. This suggests that EPD's may be effective in preventing renal atheroembolic injury and that a controlled trial measuring the impact of EPD's on renal blood flow following RAS should be performed. Copyright © 2012 Wiley Periodicals, Inc.

Neural regulation of the kidney function in rats with cisplatin induced renal failure

PubMed Central

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

Correction of Gradient Nonlinearity Bias in Quantitative Diffusion Parameters of Renal Tissue with Intra Voxel Incoherent Motion.

PubMed

Malyarenko, Dariya I; Pang, Yuxi; Senegas, Julien; Ivancevic, Marko K; Ross, Brian D; Chenevert, Thomas L

2015-12-01

Spatially non-uniform diffusion weighting bias due to gradient nonlinearity (GNL) causes substantial errors in apparent diffusion coefficient (ADC) maps for anatomical regions imaged distant from magnet isocenter. Our previously-described approach allowed effective removal of spatial ADC bias from three orthogonal DWI measurements for mono-exponential media of arbitrary anisotropy. The present work evaluates correction feasibility and performance for quantitative diffusion parameters of the two-component IVIM model for well-perfused and nearly isotropic renal tissue. Sagittal kidney DWI scans of a volunteer were performed on a clinical 3T MRI scanner near isocenter and offset superiorly. Spatially non-uniform diffusion weighting due to GNL resulted both in shift and broadening of perfusion-suppressed ADC histograms for off-center DWI relative to unbiased measurements close to isocenter. Direction-average DW-bias correctors were computed based on the known gradient design provided by vendor. The computed bias maps were empirically confirmed by coronal DWI measurements for an isotropic gel-flood phantom. Both phantom and renal tissue ADC bias for off-center measurements was effectively removed by applying pre-computed 3D correction maps. Comparable ADC accuracy was achieved for corrections of both b -maps and DWI intensities in presence of IVIM perfusion. No significant bias impact was observed for IVIM perfusion fraction.

Correction of Gradient Nonlinearity Bias in Quantitative Diffusion Parameters of Renal Tissue with Intra Voxel Incoherent Motion

PubMed Central

Malyarenko, Dariya I.; Pang, Yuxi; Senegas, Julien; Ivancevic, Marko K.; Ross, Brian D.; Chenevert, Thomas L.

2015-01-01

Spatially non-uniform diffusion weighting bias due to gradient nonlinearity (GNL) causes substantial errors in apparent diffusion coefficient (ADC) maps for anatomical regions imaged distant from magnet isocenter. Our previously-described approach allowed effective removal of spatial ADC bias from three orthogonal DWI measurements for mono-exponential media of arbitrary anisotropy. The present work evaluates correction feasibility and performance for quantitative diffusion parameters of the two-component IVIM model for well-perfused and nearly isotropic renal tissue. Sagittal kidney DWI scans of a volunteer were performed on a clinical 3T MRI scanner near isocenter and offset superiorly. Spatially non-uniform diffusion weighting due to GNL resulted both in shift and broadening of perfusion-suppressed ADC histograms for off-center DWI relative to unbiased measurements close to isocenter. Direction-average DW-bias correctors were computed based on the known gradient design provided by vendor. The computed bias maps were empirically confirmed by coronal DWI measurements for an isotropic gel-flood phantom. Both phantom and renal tissue ADC bias for off-center measurements was effectively removed by applying pre-computed 3D correction maps. Comparable ADC accuracy was achieved for corrections of both b-maps and DWI intensities in presence of IVIM perfusion. No significant bias impact was observed for IVIM perfusion fraction. PMID:26811845

Machine learning-based quantitative texture analysis of CT images of small renal masses: Differentiation of angiomyolipoma without visible fat from renal cell carcinoma.

PubMed

Feng, Zhichao; Rong, Pengfei; Cao, Peng; Zhou, Qingyu; Zhu, Wenwei; Yan, Zhimin; Liu, Qianyun; Wang, Wei

2018-04-01

To evaluate the diagnostic performance of machine-learning based quantitative texture analysis of CT images to differentiate small (≤ 4 cm) angiomyolipoma without visible fat (AMLwvf) from renal cell carcinoma (RCC). This single-institutional retrospective study included 58 patients with pathologically proven small renal mass (17 in AMLwvf and 41 in RCC groups). Texture features were extracted from the largest possible tumorous regions of interest (ROIs) by manual segmentation in preoperative three-phase CT images. Interobserver reliability and the Mann-Whitney U test were applied to select features preliminarily. Then support vector machine with recursive feature elimination (SVM-RFE) and synthetic minority oversampling technique (SMOTE) were adopted to establish discriminative classifiers, and the performance of classifiers was assessed. Of the 42 extracted features, 16 candidate features showed significant intergroup differences (P < 0.05) and had good interobserver agreement. An optimal feature subset including 11 features was further selected by the SVM-RFE method. The SVM-RFE+SMOTE classifier achieved the best performance in discriminating between small AMLwvf and RCC, with the highest accuracy, sensitivity, specificity and AUC of 93.9 %, 87.8 %, 100 % and 0.955, respectively. Machine learning analysis of CT texture features can facilitate the accurate differentiation of small AMLwvf from RCC. • Although conventional CT is useful for diagnosis of SRMs, it has limitations. • Machine-learning based CT texture analysis facilitate differentiation of small AMLwvf from RCC. • The highest accuracy of SVM-RFE+SMOTE classifier reached 93.9 %. • Texture analysis combined with machine-learning methods might spare unnecessary surgery for AMLwvf.

Severe renal hemorrhage caused by pyelonephritis in 7 horses: clinical and ultrasonographic evaluation.

PubMed Central

Kisthardt, K K; Schumacher, J; Finn-Bodner, S T; Carson-Dunkerley, S; Williams, M A

1999-01-01

Case records of 7 horses diagnosed with pyelonephritis were reviewed to determine common features that might aid in diagnosis, treatment, and prognosis of this disease. All 7 horses had been admitted for evaluation of hematuria. During cystoscopy of 5 horses, hemorrhage was observed from one or both ureters. Renal biopsy of 1 horse, laboratory analysis of ureteral discharge of 2 horses, and renal ultrasonography of all horses indicated that pyelonephritis was the cause of hemorrhage. Sonographic renal changes included decreased length, increased echogenicity, abnormal outline, loss of corticomedullary distinction, pyelectasia, and focal hypoechoic or hyperechoic cortical defects. Renal hemorrhage in all horses eventually resolved but recurred in 4 of 5 horses that were followed long-term. Images Figure 1. Figure 2. Figure 3. Figure 4A. Figure 4B. Figure 4C. Figure 5A. Figure 5B. Figure 5C. Figure 6A. Figure 6B. Figure 7. PMID:12001337

Ultrasound hepatic/renal ratio and hepatic attenuation rate for quantifying liver fat content.

PubMed

Zhang, Bo; Ding, Fang; Chen, Tian; Xia, Liang-Hua; Qian, Juan; Lv, Guo-Yi

2014-12-21

To establish and validate a simple quantitative assessment method for nonalcoholic fatty liver disease (NAFLD) based on a combination of the ultrasound hepatic/renal ratio and hepatic attenuation rate. A total of 170 subjects were enrolled in this study. All subjects were examined by ultrasound and (1)H-magnetic resonance spectroscopy ((1)H-MRS) on the same day. The ultrasound hepatic/renal echo-intensity ratio and ultrasound hepatic echo-intensity attenuation rate were obtained from ordinary ultrasound images using the MATLAB program. Correlation analysis revealed that the ultrasound hepatic/renal ratio and hepatic echo-intensity attenuation rate were significantly correlated with (1)H-MRS liver fat content (ultrasound hepatic/renal ratio: r = 0.952, P = 0.000; hepatic echo-intensity attenuation r = 0.850, P = 0.000). The equation for predicting liver fat content by ultrasound (quantitative ultrasound model) is: liver fat content (%) = 61.519 × ultrasound hepatic/renal ratio + 167.701 × hepatic echo-intensity attenuation rate -26.736. Spearman correlation analysis revealed that the liver fat content ratio of the quantitative ultrasound model was positively correlated with serum alanine aminotransferase, aspartate aminotransferase, and triglyceride, but negatively correlated with high density lipoprotein cholesterol. Receiver operating characteristic curve analysis revealed that the optimal point for diagnosing fatty liver was 9.15% in the quantitative ultrasound model. Furthermore, in the quantitative ultrasound model, fatty liver diagnostic sensitivity and specificity were 94.7% and 100.0%, respectively, showing that the quantitative ultrasound model was better than conventional ultrasound methods or the combined ultrasound hepatic/renal ratio and hepatic echo-intensity attenuation rate. If the (1)H-MRS liver fat content had a value < 15%, the sensitivity and specificity of the ultrasound quantitative model would be 81.4% and 100%, which still shows that using

Real-time measurement of renal blood flow in healthy subjects using contrast-enhanced ultrasound.

PubMed

Kalantarinia, Kambiz; Belcik, J Todd; Patrie, James T; Wei, Kevin

2009-10-01

Current methods for measuring renal blood flow (RBF) are time consuming and not widely available. Contrast-enhanced ultrasound (CEU) is a safe and noninvasive imaging technique suitable for assessment of tissue blood flow, which has been used clinically to assess myocardial blood flow. We tested the utility of CEU in monitoring changes in RBF in healthy volunteers. We utilized CEU to monitor the expected increase in RBF following a high protein meal in healthy adults. Renal cortical perfusion was assessed by CEU using low mechanical index (MI) power modulation Angio during continuous infusions of Definity. Following destruction of tissue microbubbles using ultrasound at a MI of 1.0, the rate of tissue replenishment with microbubbles and the plateau acoustic intensity (AI) were used to estimate the RBF velocity and cortical blood volume, respectively. Healthy adults (n = 19, mean age 26.6 yr) were enrolled. The A.beta parameter of CEU, representing mean RBF increased by 42.8%from a baseline of 17.05 +/- 6.23 to 23.60 +/- 6.76 dB/s 2 h after the ingestion of the high-protein meal (P = 0.002). Similarly, there was a 37.3%increase in the beta parameter, representing the geometric mean of blood velocity after the high protein meal (P < 0.001). The change in cortical blood volume was not significant (P = 0.89). Infusion time of Definity was 6.3 +/- 2.0 min. The ultrasound contrast agent was tolerated well with no serious adverse events. CEU is a fast, noninvasive, and practical imaging technique that may be useful for monitoring renal blood velocity, volume, and flow.

Renal Type A Intercalated Cells Contain Albumin in Organelles with Aldosterone-Regulated Abundance

PubMed Central

Jensen, Thomas Buus; Cheema, Muhammad Umar; Szymiczek, Agata; Damkier, Helle Hasager; Praetorius, Jeppe

2015-01-01

Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1), late endosomes/lysosomes (cathepsin D) or recycling endosomes (Rab11). Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells. PMID:25874770

Arterial spin labelling MRI for detecting pseudocapsule defects and predicting renal capsule invasion in renal cell carcinoma.

PubMed

Zhang, H; Wu, Y; Xue, W; Zuo, P; Oesingmann, N; Gan, Q; Huang, Z; Wu, M; Hu, F; Kuang, M; Song, B

2017-11-01

To evaluate prospectively the performance of combining morphological and arterial spin labelling (ASL) magnetic resonance imaging (MRI) for detecting pseudocapsule defects in renal cell carcinoma (RCC), and to predict renal capsule invasion confirmed histopathologically. Twenty consecutive patients with suspicious renal tumours underwent MRI. Renal ASL imaging was performed and renal blood flow was measured quantitatively. The diagnostic performance of T2-weighted images alone, and a combination of T2-weighted and ASL images for predicting renal capsule invasion were assessed. Twenty renal lesions were evaluated in 20 patients. All lesions were clear cell RCCs (ccRCCs) confirmed at post-surgical histopathology. Fifteen ccRCCs showed pseudocapsule defects on T2-weighted images, of which 12 cases showed existing blood flow in defect areas on perfusion images. To predict renal capsule invasion, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71.4%, 86.7%, 100%, respectively, for T2-weighted images alone, and 92.3%, 100%, 100%, 87.5%, respectively, for the combination of T2-weighted and ASL images. ASL images can reflect the perfusion of pseudocapsule defects and as such, the combination of T2-weighted and ASL images produces promising diagnostic accuracy for predicting renal capsule invasion. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Concerted regulation of renal plasma flow and glomerular filtration rate by renal dopamine and NOS I in rats on high salt intake.

PubMed

Ibarra, Mariano E; Albertoni Borghese, Maria F; Majowicz, Mónica P; Ortiz, María C; Loidl, Fabián; Rey-Funes, Manuel; Di Ciano, Luis A; Ibarra, Fernando R

2017-03-01

Under high sodium intake renal dopamine (DA) increases while NOS I expression in macula densa cells (MD) decreases. To explore whether renal DA and NOS I, linked to natriuresis and to the stability of the tubuloglomerular feedback, respectively, act in concert to regulate renal plasma flow (RPF) and glomerular filtration rate (GFR). Male Wistar rats were studied under a normal sodium intake (NS, NaCl 0.24%) or a high sodium intake (HS, NaCl 1% in drinking water) during the 5 days of the study. For the last two days, the specific D 1 -like receptor antagonist SCH 23390 (1 mg kg bwt -1  day -1 , sc) or a vehicle was administered. HS intake increased natriuresis, diuresis, and urinary DA while it decreased cortical NOS I expression ( P  < 0.05 vs. NS), Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in MD ( P  < 0.001 vs. NS) and cortical nitrates+nitrites (NOx) production (NS 2.04 ± 0.22 vs. HS 1.28 ± 0.10 nmol mg protein -1 , P  < 0.01). Treatment with SCH 23390 to rats on HS sharply decreased hydroelectrolyte excretion ( P  < 0.001 vs. HS) while NOS I expression, NADPH-d activity and NOx production increased ( P  < 0.05 vs. HS for NOS I and P  < 0.001 vs. HS for NADPH-d and NOx). SCH 23390 increased RPF and GFR in HS rats ( P  < 0.01 HS+SCH vs. HS). It did not cause variations in NS rats. Results indicate that when NS intake is shifted to a prolonged high sodium intake, renal DA through the D 1 R, and NOS I in MD cells act in concert to regulate RPF and GFR to stabilize the delivery of NaCl to the distal nephron. © 2017 Universidad De Buenos Aires. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Large Renal Corpuscle: Clinical Significance of Evaluation of the Largest Renal Corpuscle in Kidney Biopsy Specimens.

PubMed

Kataoka, Hiroshi; Mochizuki, Toshio; Nitta, Kosaku

2018-01-01

Renal prognostic factors of chronic kidney disease are important concerns for patients. Kidney biopsy can be used to evaluate not only the activity of the original disease but also various risk factors related to the lifestyle of patients. Considering that lifestyle-related factors, including obesity and metabolic syndrome, are crucial prognostic risk factors of kidney disease progression and all-cause mortality, evaluation of lifestyle-related prognostic factors in kidney biopsy of all kidney diseases is important. Renal corpuscle size (glomerular size) is an easily measured parameter and potentially acts as a predictor of long-term renal function. Large renal corpuscle found on kidney biopsy is a classic and simple indicator, and has merit owing to its quantitative nature, but it has yet to be used to its full potential in clinical settings. Large renal corpuscle is an index that includes not only the activity of the original disease but also the damage of various metabolic risk states as represented by obesity, diabetes, and metabolic syndrome. Large renal corpuscles could be used to guide therapy. In this review, after identifying the pitfalls regarding the assessment of mean values in medical research, we propose that measurement of the maximum renal corpuscle profile (glomerular profile) in renal biopsies would provide valuable insights into the diagnosis, prognosis, and management of kidney diseases. © 2018 S. Karger AG, Basel.

Impaired renal function is associated with brain atrophy and poststroke cognitive decline.

PubMed

Auriel, Eitan; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Molad, Jeremy; Berliner, Shlomo; Shapira, Itzhak; Ben-Bashat, Dafna; Shopin, Ludmila; Tene, Oren; Rosenberg, Gary A; Bornstein, Natan M; Ben Assayag, Einor

2016-05-24

To evaluate the interrelationship among impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The Tel Aviv Brain Acute Stroke Cohort study is a prospective cohort of mild-moderate ischemic stroke/TIA survivors without dementia who underwent a 3T MRI and were cognitively assessed at admission and for 24 months following stroke. Renal function was evaluated at admission by creatinine clearance (CCl) estimation. The volumes of ischemic lesions and preexisting white matter hyperintensities (WMH), brain atrophy, and microstructural changes of the normal-appearing white matter tissue were measured using previously validated methods. Baseline data were available for 431 participants. Participants with a CCl <60 mL/min at baseline performed significantly worse in all cognitive tests over time (p = 0.001) than those with a CCl ≥60 mL/min and had larger WMH volume and cortical atrophy and smaller hippocampal volume (all p < 0.001). After 2 years, 15.5% of the participants were diagnosed with cognitive impairment. Multiple logistic regression analysis, controlling for traditional risk factors, suggested CCl <60 mL/min at baseline as a significant predictor for the development of cognitive impairment 2 years after the index stroke (odds ratio 2.01 [95% confidence interval 1.03-3.92], p = 0.041). Impaired renal function is associated with increased WMH volume and cortical atrophy, known biomarkers of the aging brain, and is a predictor for cognitive decline 2 years after stroke/TIA. Decreased renal function may be associated with cerebral small vessel disease underlying poststroke cognitive decline, suggesting a new target for early intervention. © 2016 American Academy of Neurology.

Quantified acoustic-optical speech signal incongruity identifies cortical sites of audiovisual speech processing

PubMed Central

Bernstein, Lynne E.; Lu, Zhong-Lin; Jiang, Jintao

2008-01-01

A fundamental question about human perception is how the speech perceiving brain combines auditory and visual phonetic stimulus information. We assumed that perceivers learn the normal relationship between acoustic and optical signals. We hypothesized that when the normal relationship is perturbed by mismatching the acoustic and optical signals, cortical areas responsible for audiovisual stimulus integration respond as a function of the magnitude of the mismatch. To test this hypothesis, in a previous study, we developed quantitative measures of acoustic-optical speech stimulus incongruity that correlate with perceptual measures. In the current study, we presented low incongruity (LI, matched), medium incongruity (MI, moderately mismatched), and high incongruity (HI, highly mismatched) audiovisual nonsense syllable stimuli during fMRI scanning. Perceptual responses differed as a function of the incongruity level, and BOLD measures were found to vary regionally and quantitatively with perceptual and quantitative incongruity levels. Each increase in level of incongruity resulted in an increase in overall levels of cortical activity and in additional activations. However, the only cortical region that demonstrated differential sensitivity to the three stimulus incongruity levels (HI > MI > LI) was a subarea of the left supramarginal gyrus (SMG). The left SMG might support a fine-grained analysis of the relationship between audiovisual phonetic input in comparison with stored knowledge, as hypothesized here. The methods here show that quantitative manipulation of stimulus incongruity is a new and powerful tool for disclosing the system that processes audiovisual speech stimuli. PMID:18495091

Quantitative analysis of elevation of serum creatinine via renal transporter inhibition by trimethoprim in healthy subjects using physiologically-based pharmacokinetic model.

PubMed

Nakada, Tomohisa; Kudo, Toshiyuki; Kume, Toshiyuki; Kusuhara, Hiroyuki; Ito, Kiyomi

2018-02-01

Serum creatinine (SCr) levels rise during trimethoprim therapy for infectious diseases. This study aimed to investigate whether the elevation of SCr can be quantitatively explained using a physiologically-based pharmacokinetic (PBPK) model incorporating inhibition by trimethoprim on tubular secretion of creatinine via renal transporters such as organic cation transporter 2 (OCT2), OCT3, multidrug and toxin extrusion protein 1 (MATE1), and MATE2-K. Firstly, pharmacokinetic parameters in the PBPK model of trimethoprim were determined to reproduce the blood concentration profile after a single intravenous and oral administration of trimethoprim in healthy subjects. The model was verified with datasets of both cumulative urinary excretions after a single administration and the blood concentration profile after repeated oral administration. The pharmacokinetic model of creatinine consisted of the creatinine synthesis rate, distribution volume, and creatinine clearance (CL cre ), including tubular secretion via each transporter. When combining the models for trimethoprim and creatinine, the predicted increments in SCr from baseline were 29.0%, 39.5%, and 25.8% at trimethoprim dosages of 5 mg/kg (b.i.d.), 5 mg/kg (q.i.d.), and 200 mg (b.i.d.), respectively, which were comparable with the observed values. The present model analysis enabled us to quantitatively explain increments in SCr during trimethoprim treatment by its inhibition of renal transporters. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex.

PubMed

Quiñones, Henry; Collazo, Roberto; Moe, Orson W

2004-07-01

The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na(+) homeostasis. l-Dihydroxyphenylalanine (l-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule l-DOPA uptake has not been characterized. Renal cortical poly-A(+) RNA injected into Xenopus laevis oocytes induced l-DOPA uptake in a time- and dose-dependent fashion with biphasic K(m)s in the millimolar and micromolar range and independent of inward Na(+), K(+), or H(+) gradients, suggesting the presence of low- and high-affinity l-DOPA carriers. Complementary RNA from two amino acid transporters yielded l-DOPA uptake significantly above water-injected controls the rBAT/b(0,+)AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A(+), l-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with K(m)s in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced l-DOPA transport and cortical poly-A(+)-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A(+)-induced l-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited l-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral l-DOPA uptake into the proximal tubule, respectively. Additional l-DOPA transport mechanisms exist in the renal cortex that remain to be identified.

[Quality assurance of the renal applications software].

PubMed

del Real Núñez, R; Contreras Puertas, P I; Moreno Ortega, E; Mena Bares, L M; Maza Muret, F R; Latre Romero, J M

2007-01-01

The need for quality assurance of all technical aspects of nuclear medicine studies is widely recognised. However, little attention has been paid to the quality assurance of the applications software. Our work reported here aims at verifying the analysis software for processing of renal nuclear medicine studies (renograms). The software tools were used to build a synthetic dynamic model of renal system. The model consists of two phases: perfusion and function. The organs of interest (kidneys, bladder and aortic artery) were simple geometric forms. The uptake of the renal structures was described by mathematic functions. Curves corresponding to normal or pathological conditions were simulated for kidneys, bladder and aortic artery by appropriate selection of parameters. There was no difference between the parameters of the mathematic curves and the quantitative data produced by the renal analysis program. Our test procedure is simple to apply, reliable, reproducible and rapid to verify the renal applications software.

Antithrombin III/SerpinC1 insufficiency exacerbates renal ischemia/reperfusion injury

PubMed Central

Wang, Feng; Zhang, Guangyuan; Lu, Zeyuan; Geurts, Aron M; Usa, Kristie; Jacob, Howard J; Cowley, Allen W; Wang, Niansong; Liang, Mingyu

2015-01-01

Antithrombin III, encoded by SerpinC1, is a major anti-coagulation molecule in vivo and has anti-inflammatory effects. We found that patients with low antithrombin III activities presented a higher risk of developing acute kidney injury after cardiac surgery. To study this further, we generated SerpinC1 heterozygous knockout rats and followed the development of acute kidney injury in a model of modest renal ischemia/reperfusion injury. Renal injury, assessed by serum creatinine and renal tubular injury scores after 24 h of reperfusion, was significantly exacerbated in SerpinC1+/− rats compared to wild-type littermates. Concomitantly, renal oxidative stress, tubular apoptosis, and macrophage infiltration following this injury were significantly aggravated in SerpinC1+/− rats. However, significant thrombosis was not found in the kidneys of any group of rats. Antithrombin III is reported to stimulate the production of prostaglandin I2, a known regulator of renal cortical blood flow, in addition to having anti-inflammatory effects and to protect against renal failure. Prostaglandin F1α, an assayable metabolite of prostaglandin I2, was increased in the kidneys of the wild-type rats at 3 h after reperfusion. The increase of prostaglandin F1α was significantly blunted in SerpinC1+/− rats, which preceded increased tubular injury and oxidative stress. Thus, our study found a novel role of SerpinC1 insufficiency in increasing the severity of renal ischemia/reperfusion injury. PMID:26108065

Many Specialists for Suppressing Cortical Excitation

PubMed Central

Burkhalter, Andreas

2008-01-01

Cortical computations are critically dependent on GABA-releasing neurons for dynamically balancing excitation with inhibition that is proportional to the overall level of activity. Although it is widely accepted that there are multiple types of interneurons, defining their identities based on qualitative descriptions of morphological, molecular and physiological features has failed to produce a universally accepted ‘parts list’, which is needed to understand the roles that interneurons play in cortical processing. A list of features has been published by the Petilla Interneurons Nomenclature Group, which represents an important step toward an unbiased classification of interneurons. To this end some essential features have recently been studied quantitatively and their association was examined using multidimensional cluster analyses. These studies revealed at least 3 distinct electrophysiological, 6 morphological and 15 molecular phenotypes. This is a conservative estimate of the number of interneuron types, which almost certainly will be revised as more quantitative studies will be performed and similarities will be defined objectively. It is clear that interneurons are organized with physiological attributes representing the most general, molecular characteristics the most detailed and morphological features occupying the middle ground. By themselves, none of these features are sufficient to define classes of interneurons. The challenge will be to determine which features belong together and how cell type-specific feature combinations are genetically specified. PMID:19225588

[Acute renal failure in the transretinoic syndrome].

PubMed

Sastre, A; Gago, E; Baños, M; Gómez, E

2007-01-01

The all-trans retinoic acid (ATRA) is the treatment of first line of acute promyelocytic leukemia (APL). ATRA is usually well tolerated, but a few major side effects can be observed, ATRA syndrome (RAS) being the most important of them, potentially fatal. The manifestations of this Syndrome are fever, weight gain, pulmonary infiltrates, pleural or pericardial effusions, hypotension, liver dysfunction and renal failure. We studied to the 29 patients diagnosed in (January of 2002 - December of 2004) of acute promyelocytic leukemia (APL), which were treated with ATRA, all received the 45 dose of mg/m(2)/d . The diagnosis of the leukemia was made by citomorphologist analysis. The criterion of renal insufficiency, it was an increase of the creatinina superior to 20% of the basal level. The definition of the transretinoico acid Syndrome was based on the clinical criteria of Frankel. Fourteen patients presented the Transretinoico Syndrome (48.3%), 11 of which (37.9%) died. The fundamental differences between the patients with or without ATRA were: fever (14 vs. 9, p=0,017), gain of weight (14 vs 0, p=0,000), pleural effusion (14 vs 2, p=0.000), pulmonary infiltrates (13 vs 1, p=0,000), cardiac failure (12 versus 2, p=0,000), respiratory distress (12 versus 4, p=0,003), presence of renal failure (10 vs 4, p=0,02), necessity of substitute renal treatment (6 vs 0, p=0,006) and arterial hypotension (12 vs. 3, p=0,001). The acute renal failure appeared in 10 of the 14 patients with SAR (71.4%), to 12+/-5 (1-25) days of the beginning of the treatment and their duration it was of 14+/-5 (1-46) days. Six (60%) needed substitute renal treatment and 5 (50%) died. Of the patients who survived, only a patient continues in dialysis. In both patient in that renal biopsy was made, the study showed signs of cortical necrosis. The appearance of acute renal failure in the course of the SAR is frequent, being observed deterioration of the renal function that needs substitute renal treatment

Analysis of Altered Micro RNA Expression Profiles in Focal Cortical Dysplasia IIB.

PubMed

Li, Lin; Liu, Chang-Qing; Li, Tian-Fu; Guan, Yu-Guang; Zhou, Jian; Qi, Xue-Ling; Yang, Yu-Tao; Deng, Jia-Hui; Xu, Zhi-Qing David; Luan, Guo-Ming

2016-04-01

Focal cortical dysplasia type IIB is a commonly encountered subtype of developmental malformation of the cerebral cortex and is often associated with pharmacoresistant epilepsy. In this study, to investigate the molecular etiology of focal cortical dysplasia type IIB, the authors performed micro ribonucleic acid (RNA) microarray on surgical specimens from 5 children (2 female and 3 male, mean age was 73.4 months, range 50-112 months) diagnosed of focal cortical dysplasia type IIB and matched normal tissue adjacent to the lesion. In all, 24 micro RNAs were differentially expressed in focal cortical dysplasia type IIB, and the microarray results were validated using quantitative real-time polymerase chain reaction (PCR). Then the putative target genes of the differentially expressed micro RNAs were identified by bioinformatics analysis. Moreover, biological significance of the target genes was evaluated by investigating the pathways in which the genes were enriched, and the Hippo signaling pathway was proposed to be highly related with the pathogenesis of focal cortical dysplasia type IIB. © The Author(s) 2015.

Preparation of positional renal slices for study of cell-specific toxicity.

PubMed

Ruegg, C E; Gandolfi, A J; Nagle, R B; Krumdieck, C L; Brendel, K

1987-04-01

To reduce structural complexity, rabbit kidneys were sliced perpendicular to their cortical-papillary axis to isolate four distinct cell groupings. This positional orientation allows identification of each renal cell type based on its location within the slice. A mechanical slicer was used to make several precision-cut slices rapidly from an oriented cylindrical core of renal tissue, with minimal tissue trauma. Slices were then submerged under a gently circulating oxygenated media in a fritted glass support system that maintains viability (intracellular K+/DNA ratio) and structural integrity (histology) for at least 30 h. A high dose of mercuric chloride (10(-3) M) was used to demonstrate the structural and biochemical changes of intoxicated slices. This method provides a controlled subchronic in vitro system for the study of the individual cell types involved in cell-specific renal toxicities and may also be a useful tool for addressing other pharmacological and physiological research questions.

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

PubMed

Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

2018-05-01

Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

WWSSF - a worldwide study on radioisotopic renal split function: reproducibility of renal split function assessment in children.

PubMed

Geist, Barbara Katharina; Dobrozemsky, Georg; Samal, Martin; Schaffarich, Michael P; Sinzinger, Helmut; Staudenherz, Anton

2015-12-01

The split or differential renal function is the most widely accepted quantitative parameter derived from radionuclide renography. To examine the intercenter variance of this parameter, we designed a worldwide round robin test. Five selected dynamic renal studies have been distributed all over the world by e-mail. Three of these studies are anonymized patient data acquired using the EANM standardized protocol and two studies are phantom studies. In a simple form, individual participants were asked to measure renal split function as well as to provide additional information such as data analysis software, positioning of background region of interest, or the method of calculation. We received the evaluation forms from 34 centers located in 21 countries. The analysis of the round robin test yielded an overall z-score of 0.3 (a z-score below 1 reflecting a good result). However, the z-scores from several centers were unacceptably high, with values greater than 3. In particular, the studies with impaired renal function showed a wide variance. A wide variance in the split renal function was found in patients with impaired kidney function. This study indicates the ultimate importance of quality control and standardization of the measurement of the split renal function. It is especially important with respect to the commonly accepted threshold for significant change in split renal function by 10%.

Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: A cross-sectional observational study of 565 consecutive patients

PubMed Central

Snodgrass, Warren T.; Shah, Anjana; Yang, Mary; Kwon, Jeannie; Villanueva, Carlos; Traylor, Janelle; Pritzker, Karen; Nakonezny, Paul A.; Haley, Robert W.; Bush, Nicol Corbin

2013-01-01

Purpose To determine prevalence and risk factors for renal scar in children referred for urologic assessment of febrile UTI and/or VUR. Methods Pre-determined risk factors for renal scar were prospectively recorded in consecutive patients referred for UTI/VUR. Age, gender, VUR grade, and reported number of febrile and non-febrile UTIs were analyzed with logistic regression to determine risk for focal cortical defects on non-acute DMSA. Results Of 565 consecutive children, 24 (4%) had congenital renal dysplasia and 84 (15.5%) had focal defect(s). VUR, especially grades IV–V, recurrent febrile UTI, and older age increased risk. For any age child with the same number of UTIs, VUR increased odds of renal defect 5.4-fold (OR = 5.4, 95% CI = 2.7–10.6, AUC = 0.759). Conclusions Focal DMSA defects were present in 15.5% of 565 consecutive children referred for febrile UTI and/or VUR; 4% had presumed congenital reflux nephropathy without cortical defect. All VUR grades increased risk for these defects, as did recurrent febrile UTIs and older age. However, 43% with grades IV–V VUR and 76% with recurrent UTI had normal DMSA. PMID:23465483

Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: a cross-sectional observational study of 565 consecutive patients.

PubMed

Snodgrass, Warren T; Shah, Anjana; Yang, Mary; Kwon, Jeannie; Villanueva, Carlos; Traylor, Janelle; Pritzker, Karen; Nakonezny, Paul A; Haley, Robert W; Bush, Nicol Corbin

2013-12-01

To determine prevalence and risk factors for renal scar in children referred for urologic assessment of febrile UTI and/or VUR. Pre-determined risk factors for renal scar were prospectively recorded in consecutive patients referred for UTI/VUR. Age, gender, VUR grade, and reported number of febrile and non-febrile UTIs were analyzed with logistic regression to determine risk for focal cortical defects on non-acute DMSA. Of 565 consecutive children, 24 (4%) had congenital renal dysplasia and 84 (15.5%) had focal defect(s). VUR, especially grades IV-V, recurrent febrile UTI, and older age increased risk. For any age child with the same number of UTIs, VUR increased odds of renal defect 5.4-fold (OR = 5.4, 95% CI = 2.7-10.6, AUC = 0.759). Focal DMSA defects were present in 15.5% of 565 consecutive children referred for febrile UTI and/or VUR; 4% had presumed congenital reflux nephropathy without cortical defect. All VUR grades increased risk for these defects, as did recurrent febrile UTIs and older age. However, 43% with grades IV-V VUR and 76% with recurrent UTI had normal DMSA. Published by Elsevier Ltd.

[Current role of color Doppler ultrasound in acute renal failure].

PubMed

Bertolotto, M; Quaia, E; Rimondini, A; Lubin, E; Pozzi Mucelli, R

2001-01-01

another useful diagnostic tool in patients with ARF which has been recently introduced in clinical practice. Microbubble administration may reduce technical failure in the evaluation of the renal artery. Moreover, perfusion defects due to stenosis or thrombosis of the renal segmentary vessels are better recognized. New diagnostic possibilities of enhanced US include evaluation of both cortical and medullar vessels, and functional evaluation of renal perfusion. Measuring the transit time of the microbubbles is useful for the diagnosis of renal artery stenosis and, in transplanted kidneys, for differential diagnosis between ATN and acute rejection.

Comparison of two models for evaluation histopathology of experimental renal ischemia.

PubMed

Tirapelli, L F; Barione, D F; Trazzi, B F M; Tirapelli, D P C; Novas, P C; Silva, C S; Martinez, M; Costa, R S; Tucci, S; Suaid, H J; Cologna, A J; Martins, A C P

2009-12-01

Renal ischemia/reperfusion (I/R) injury is one of the frequent causes of acute renal failure (ARF) due to the complex, interrelated sequence of events, that result in damage to and death of kidney cells. Cells of the proximal tubular epithelium are especially susceptible to I/R injury, leading to acute tubular necrosis, which plays a pivotal role in the pathogenesis of ARF. Several models have been explicated to assess morphological changes, including those of Jabonski et al. and Goujon et al. We compared the 2 models for histopathological evaluation of 30- or 120-minute periods of renal ischemia followed by 24-hour reperfusion in rats. Several changes were observed after application of the 2 models: proximal tubular cell necrosis, loss of brush border, vacuolization, denudation of tubular basement membrane as a consequence of flattening of basal cells, and presence of intratubular exfoliated cells in the lumen of proximal convoluted tubules at various stages of degeneration (karyorexis, kariopyknosis and karyolysis). Evaluating tubular lesions after 2 periods of experimental ischemia with light microscopy allowed us to conclude that the Goujon classification better characterized the main changes in cortical renal tubules after ischemia.

[Differential diagnosis between renal cell carcinoma associated with XP11.2 translocation/TFE gene fusion and papillary renal cell carcinoma based on CT and MRI findings].

PubMed

Zhu, Qingqiang; Zhu, Wenrong; Wu, Jingtao; Fu, Jianxiong; Chen, Wenxin; Wang, Zhongqiu

2014-05-20

To comparative study of CT and MRI appearances in renal cell carcinoma associated with XP11.2 translocation/TFE gene fusion (XP11.2 RCC) and papillary renal cell carcinoma (PRCC). 12 patients with XP11.2 RCC and 18 patients with PRCC were retrospectively studied, and the data was analyzed by AVONA and chi-square text. 12 patients with XP11.2 RCC and 18 patients with PRCC, cystic components (2 vs 11, P < 0.05), calcification (0 vs 6, P < 0.05), hemorrhage (9 vs 5, P < 0.05), homogeneous enhancement (10 vs 7, P < 0.05) and had lymph node (3 vs 0) or hepatic metastasis (1vs 0) (P < 0.05). On unenhanced CT, the density of XP11.2 RCC was greater than PRCC, normal renal cortex or medulla (P < 0.05). Their degree of enhancement were less than normal renal cortex on all enhanced phases (P < 0.05). The enhancement degree of XP11.2 RCC was higher than PRCC (on all phases) and renal medulla (on cortical and medullary phase) (P < 0.05), but less than normal renal medulla on the delayed phase (P < 0.05). The enhancement degree of PRCC was lower than renal medulla on all phases (P < 0.05). The XP11.2 RCC was isointense on T1-weighted imaging, hypointense on T2-weighted imaging. The PRCC was isointense or hypointense on T1-weighted imaging, isointense on T2-weighted imaging. The CT and MRI could show imagings features of XP11.2 RCC and PRCC, and these features were helpful in predicting a specific subtype of renal cell carcinoma.

Evaluation of renal allografts function early after transplantation using intravoxel incoherent motion and arterial spin labeling MRI.

PubMed

Ren, Tao; Wen, Cheng-Long; Chen, Li-Hua; Xie, Shuang-Shuang; Cheng, Yue; Fu, Ying-Xin; Oesingmann, Niels; de Oliveira, Andre; Zuo, Pan-Li; Yin, Jian-Zhong; Xia, Shuang; Shen, Wen

2016-09-01

To evaluate renal allografts function early after transplantation using intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) MRI. This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. A total of 82 participants with 62 renal allograft recipients (2-4weeks after kidney transplantation) and 20 volunteers were enrolled to be scanned using IVIM and ASL MRI on a 3.0T MR scanner. Recipients were divided into two groups with either normal or impaired function according to the estimated glomerular filtration rate (eGFR) with a threshold of 60ml/min/1.73m(2). The apparent diffusion coefficient (ADC) of pure diffusion (ADCslow), the ADC of pseudodiffusion (ADCfast), perfusion fraction (PF), and renal blood flow (RBF) of cortex were compared among three groups. The correlation of ADCslow, ADCfast, PF and RBF with eGFR was evaluated. The receiver operating characteristic (ROC) curve and binary logistic regression analyses were performed to assess the diagnostic efficiency of using IVIM and ASL parameters to discriminate allografts with impaired function from normal function. P<0.05 was considered statistically significant. In allografts with normal function, no significant difference of mean cortical ADCslow, ADCfast, and PF was found compared with healthy controls (P>0.05). Cortical RBF in allografts with normal function was statistically lower than that of healthy controls (P<0.001). Mean cortical ADCslow, ADCfast, PF and RBF were lower for allografts with impaired function than that with normal function (P<0.05). Mean cortical ADCslow, ADCfast, PF and RBF showed a positive correlation with eGFR (all P<0.01) for recipients. The combination of IVIM and ASL MRI showed a higher area under the ROC curve (AUC) (0.865) than that of ASL MRI alone (P=0.02). Combined IVIM and ASL MRI can better evaluate the diffusion and perfusion properties for allografts early after kidney transplantation

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model.

PubMed

Damasceno-Ferreira, José Aurelino; Bechara, Gustavo Ruschi; Costa, Waldemar Silva; Pereira-Sampaio, Marco Aurélio; Sampaio, Francisco José Barcellos; Souza, Diogo Benchimol De

2017-05-01

To investigate the glomerular number after different warm ischemia times. Thirty two pigs were assigned into four groups. Three groups (G10, G20, and G30) were treated with 10, 20, and 30 minutes of left renal warm ischemia. The sham group underwent the same surgery without renal ischemia. The animals were euthanized after 3 weeks, and the kidneys were collected. Right kidneys were used as controls. The kidney weight, volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted mean glomerular volume, and the total number of glomeruli per kidney were obtained. Serum creatinine levels were assessed pre and postoperatively. Serum creatinine levels did not differ among the groups. All parameters were similar for the sham, G10, and G20 groups upon comparison of the right and left organs. The G30 group pigs' left kidneys had lower weight, volume, and cortical-medullar ratio and 24.6% less glomeruli compared to the right kidney. A negative correlation was found between warm ischemia time and glomerular number. About one quarter of glomeruli was lost after 30 minutes of renal warm ischemia. No glomeruli loss was detected before 20 minutes of warm ischemia. However, progressive glomerular loss was associated with increasing warm ischemia time.

Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.

PubMed

Homma-Takeda, Shino; Kitahara, Keisuke; Suzuki, Kyoko; Blyth, Benjamin J; Suya, Noriyoshi; Konishi, Teruaki; Terada, Yasuko; Shimada, Yoshiya

2015-12-01

Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney. Copyright © 2015 John Wiley & Sons, Ltd.

Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

PubMed Central

Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

2013-01-01

How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later

Short-term menhaden oil rich diet changes renal lipid profile in acute kidney injury.

PubMed

Ossani, Georgina P; Denninghoff, Valeria C; Uceda, Ana M; Díaz, Maria L; Uicich, Raúl; Monserrat, Alberto J

2015-01-01

Weanling male Wistar rats fed a choline-deficient diet develop acute kidney injury. Menhaden oil, which is a very important source of omega-3 fatty acids, has a notorious protective effect. The mechanism of this protection is unknown; one possibility could be that menhaden oil changes renal lipid profile, with an impact on the functions of biological membranes. The aim of this work was to study the renal lipid profile in rats fed a choline-deficient diet with menhaden oil or vegetable oil as lipids. Rats were divided into 4 groups and fed four different diets for 7 days: choline-deficient or choline-supplemented diets with corn and hydrogenated oils or menhaden oil. Serum homocysteine, vitamin B12, and folic acid were analyzed. Renal lipid profile, as well as the fatty acid composition of the three oils, was measured. Choline-deficient rats fed vegetable oils showed renal cortical necrosis. Renal omega-6 fatty acids were higher in rats fed a cholinedeficient diet and a choline-supplemented diet with vegetable oils, while renal omega-3 fatty acids were higher in rats fed a choline-deficient diet and a choline-supplemented diet with menhaden oil. Rats fed menhaden oil diets had higher levels of renal eicosapentaenoic and docosahexaenoic acids. Renal myristic acid was increased in rats fed menhaden oil. The lipid renal profile varied quickly according to the type of oil present in the diet.

A novel approach for monitoring writing interferences during navigated transcranial magnetic stimulation mappings of writing related cortical areas.

PubMed

Rogić Vidaković, Maja; Gabelica, Dragan; Vujović, Igor; Šoda, Joško; Batarelo, Nikolina; Džimbeg, Andrija; Zmajević Schönwald, Marina; Rotim, Krešimir; Đogaš, Zoran

2015-11-30

It has recently been shown that navigated repetitive transcranial magnetic stimulation (nTMS) is useful in preoperative neurosurgical mapping of motor and language brain areas. In TMS mapping of motor cortices the evoked responses can be quantitatively monitored by electromyographic (EMG) recordings. No such setup exists for monitoring of writing during nTMS mappings of writing related cortical areas. We present a novel approach for monitoring writing during nTMS mappings of motor writing related cortical areas. To our best knowledge, this is the first demonstration of quantitative monitoring of motor evoked responses from hand by EMG, and of pen related activity during writing with our custom made pen, together with the application of chronometric TMS design and patterned protocol of rTMS. The method was applied in four healthy subjects participating in writing during nTMS mapping of the premotor cortical area corresponding to BA 6 and close to the superior frontal sulcus. The results showed that stimulation impaired writing in all subjects. The corresponding spectra of measured signal related to writing movements was observed in the frequency band 0-20 Hz. Magnetic stimulation affected writing by suppressing normal writing frequency band. The proposed setup for monitoring of writing provides additional quantitative data for monitoring and the analysis of rTMS induced writing response modifications. The setup can be useful for investigation of neurophysiologic mechanisms of writing, for therapeutic effects of nTMS, and in preoperative mapping of language cortical areas in patients undergoing brain surgery. Copyright © 2015 Elsevier B.V. All rights reserved.

Hippocampal coupling with cortical and subcortical structures in the context of memory consolidation.

PubMed

Skelin, Ivan; Kilianski, Scott; McNaughton, Bruce L

2018-04-13

Memory consolidation is a gradual process through which episodic memories become incorporated into long-term 'semantic' representations. It likely involves reactivation of neural activity encoding the recent experience during non-REM sleep. A critical prerequisite for memory consolidation is precise coordination of reactivation events between the hippocampus and cortical/subcortical structures, facilitated by the coupling of local field potential (LFP) oscillations (slow oscillations, sleep spindles and sharp wave/ripples) between these structures. We review the rapidly expanding literature on the qualitative and quantitative aspects of hippocampal oscillatory and neuronal coupling with cortical/subcortical structures in the context of memory reactivation. Reactivation in the hippocampus and cortical/subcortical structures is tightly coupled with sharp wave/ripples. Hippocampal-cortical/subcortical coupling is rich in dimensionality and this dimensionality is likely underestimated due to the limitations of the current methodology. Copyright © 2018 Elsevier Inc. All rights reserved.

Renal Clearance: Using an Interactive Activity to Visualize a Tricky Concept

ERIC Educational Resources Information Center

Hull, Kerry

2016-01-01

Renal clearance, the volume of blood cleared of a substance in a particular time period, is commonly recognized as one of the most difficult concepts in physiology. This difficulty may in part reflect the quantitative nature of renal clearance since many life sciences majors perceive that mathematics is irrelevant to their discipline. Students may…

Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy

PubMed Central

Singh, Reetu R.; Lankadeva, Yugeesh R.

2013-01-01

Renin-angiotensin system (RAS) is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x) female sheep have low renin hypertension and reduced renal function. By 5 years of age, these uni-x sheep had augmented decrease in renal blood flow (RBF) compared to sham. We hypothesised that this decrease in RBF in 5 year old uni-x sheep was due to an up-regulation in components of the intra-renal RAS. In this study, renal responses to angiotensin II (AngII) infusion and AngII type 1 receptor (AT1R) blockade were examined in the same 5 year old sheep. We also administered AngII in the presence of losartan to increase AngII bioavailability to the AT2R in order to understand AT2R contribution to renal function in this model. Uni-x animals had significantly lower renal cortical content of renin, AngII (∼40%) and Ang 1–7 (∼60%) and reduced cortical expression of AT1R gene than sham animals. In response to both AngII infusion and AT1R blockade via losartan, renal hemodynamic responses and tubular sodium excretion were significantly attenuated in uni-x animals compared to sham. However, AngII infusion in the presence of losartan caused ∼33% increase in RBF in uni-x sheep compared to ∼14% in sham (P<0.05). This was associated with a significant decrease in renal vascular resistance in the uni-x animals (22% vs 15%, P<0.05) without any changes in systemic blood pressure. The present study shows that majority of the intra-renal RAS components are suppressed in this model of low renin hypertension. However, increasing the availability of AngII to AT2R by AT1R blockade improved renal blood flow in uni-x sheep. This suggests that manipulation of the AT2R maybe a potential therapeutic target for treatment of renal dysfunction associated with a congenital nephron deficit. PMID:23840884

Assessment of myocardial mechanics in patients with end-stage renal disease and renal transplant recipients using speckle tracking echocardiography.

PubMed

Pirat, Bahar; Bozbas, Huseyin; Simsek, Vahide; Sade, L Elif; Sayin, Burak; Muderrisoglu, Haldun; Haberal, Mehmet

2015-04-01

Velocity vector imaging allows quantitation of myocardial strain and strain rate from 2-dimensional images based on speckle tracking echocardiography. The aim of this study was to analyze the changes in myocardial strain and strain rate patterns in patients with end-stage renal disease and renal transplant recipients. We studied 33 patients with end-stage renal disease on hemodialysis (19 men; mean age, 36 ± 8 y), 24 renal transplant recipients with functional grafts (21 men; mean age, 36 ± 7 y) and 26 age- and sex-matched control subjects. Longitudinal peak systolic strain and strain rate for basal, mid, and apical segments of the left ventricular wall were determined by velocity vector imaging from apical 4- and 2-chamber views. The average longitudinal strain and strain rate for the left ventricle were noted. From short-axis views at the level of papillary muscles, average circumferential, and radial strain, and strain rate were assessed. Mean heart rate and systolic and diastolic blood pressure during imaging were similar between the groups. Longitudinal peak systolic strain and strain rate at basal and mid-segments of the lateral wall were significantly higher in renal transplant recipients and control groups than endstage renal disease patients. Average longitudinal systolic strain from the 4-chamber view was highest in control subjects (-14.5% ± 2.9%) and was higher in renal transplant recipients (-12.5% ± 3.0%) than end-stage renal disease patients (-10.2% ± 1.6%; P ≤ .001). Radial and circumferential strain and strain rate at the level of the papillary muscle were lower in patients with end-stage renal disease than other groups. Differences in myocardial function in patients with end-stage renal disease, renal transplant recipients, and normal controls can be quantified by strain imaging. Myocardial function is improved in renal transplant recipients compared with end-stage renal disease patients.

Pueraria mirifica alleviates cortical bone loss in naturally menopausal monkeys.

PubMed

Kittivanichkul, Donlaporn; Charoenphandhu, Narattaphol; Khemawoot, Phisit; Malaivijitnond, Suchinda

2016-11-01

Since the in vitro and in vivo anti-osteoporotic effects of Pueraria mirifica (PM) in rodents have been verified, its activity in menopausal monkeys was evaluated as required before it can be applicable for human use. In this study, postmenopausal osteoporotic monkeys were divided into two groups (five per group), and fed daily with standard diet alone (PMP0 group) or diet mixed with 1000 mg/kg body weight (BW) of PM powder (PMP1000 group) for 16 months. Every 2 months, the bone mineral density (BMD), bone mineral content (BMC) and bone geometry parameters (cortical area and thickness and periosteal and endosteal circumference) at the distal radius and proximal tibia were determined using peripheral quantitative computed tomography together with plasma and urinary bone markers. Compared with the baseline (month 0) values, the cortical, but not trabecular, BMDs and BMCs and the cortical area and thickness at the metaphysis and diaphysis of the radius and tibia of the PMP0 group continuously decreased during the 16-month study period. In contrast, PMP1000 treatment ameliorated the bone loss mainly at the cortical diaphysis by decreasing bone turnover, as indicated by the lowered plasma bone-specific alkaline phosphatase and osteocalcin levels. Generally, changes in the cortical bone geometry were in the opposite direction to the cortical bone mass after PMP1000 treatment. This study indicated that postmenopausal monkeys continuously lose their cortical bone compartment, and they have a higher possibility for long bone fractures. Oral PMP treatment could improve both the bone quantity (BMC and BMD) and quality (bone geometry). © 2016 Society for Endocrinology.

Acoustic radiation force impulse (ARFI) elastography for detection of renal damage in children.

PubMed

Göya, Cemil; Hamidi, Cihad; Ece, Aydın; Okur, Mehmet Hanifi; Taşdemir, Bekir; Çetinçakmak, Mehmet Güli; Hattapoğlu, Salih; Teke, Memik; Şahin, Cahit

2015-01-01

Acoustic radiation force impulse (ARFI) imaging is a promising method for noninvasive evaluation of the renal parenchyma. To investigate the contribution of ARFI quantitative US elastography for the detection of renal damage in kidneys with and without vesicoureteral reflux (VUR). One hundred seventy-six kidneys of 88 children (46 male, 42 female) who had been referred for voiding cystourethrography and 20 healthy controls were prospectively investigated. Patients were assessed according to severity of renal damage on dimercaptosuccinic acid (DMSA) scintigraphy. Ninety-eight age- and gender-matched healthy children constituted the control group. Quantitative shear wave velocity (SWV) measurements were performed in the upper and lower poles and in the interpolar region of each kidney. DMSA scintigraphy was performed in 62 children (124 kidneys). Comparisons of SWV values of kidneys with and without renal damage and/or VUR were done. Significantly higher SWV values were found in non-damaged kidneys. Severely damaged kidneys had the lowest SWV values (P < 0.001). High-grade (grade V-IV) refluxing kidneys had the lowest SWV values, while non-refluxing kidneys had the highest values (P < 0.05). Significant negative correlations were found between the mean quantitative US elastography values and DMSA scarring score (r = -0.788, P < 0.001) and VUR grade (r = -0.634, P < 0.001). SWV values of the control kidneys were significantly higher than those of damaged kidneys (P < 0.05). Our findings suggest decreasing SWV of renal units with increasing grades of vesicoureteric reflux, increasing DMSA-assessed renal damage and decreasing DMSA-assessed differential function.

Live Donor Renal Anatomic Asymmetry and Post-Transplant Renal Function

PubMed Central

Tanriover, Bekir; Fernandez, Sonalis; Campenot, Eric S.; Newhouse, Jeffrey H.; Oyfe, Irina; Mohan, Prince; Sandikci, Burhaneddin; Radhakrishnan, Jai; Wexler, Jennifer J.; Carroll, Maureen A.; Sharif, Sairah; Cohen, David J.; Ratner, Lloyd E.; Hardy, Mark A.

2014-01-01

Background Relationship between live donor renal anatomic asymmetry and post-transplant recipient function has not been studied extensively. Methods We analyzed 96 live-kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from CT angiograms) and their matching recipients. Split function differences (SFD) were quantified with 99mTc-DMSA renography. Implantation biopsies at time-zero were semi-quantitatively scored. A comprehensive model utilizing donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at one-year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60ml/min/1.73 m2 at one-year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the CKD-EPI formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). Results In the study cohort, the mean Vol/Wgt and eGFR at one-year were 2.04 ml/kg and 60.4 ml/min/1.73m2, respectively. Volume and split ratios between two donor kidneys were strongly correlated (r=0.79, p-value<0.001). The biopsy scores among SFD categories (<5%, 5–10%, >10%) were not different (p=0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR>60ml/min/1.73 m2 (OR=8.94, 95% CI 2.47–32.25, p=0.001) and had a strong discriminatory power in predicting the risk of eGFR<60ml/min/1.73m2 at one-year (ROC curve=0.78, 95% CI 0.68–0.89). Conclusion In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at one-year post-transplantation. Renography can be replaced with CT volume calculation in estimating split renal function. PMID:25719258

Coordinated Optimization of Visual Cortical Maps (I) Symmetry-based Analysis

PubMed Central

Reichl, Lars; Heide, Dominik; Löwel, Siegrid; Crowley, Justin C.; Kaschube, Matthias; Wolf, Fred

2012-01-01

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of orientation columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about a hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference. From basic symmetry assumptions we obtain a comprehensive phenomenological classification of possible inter-map coupling energies and examine representative examples. We show that each individual coupling energy leads to a different class of OP solutions with different correlations among the maps such that inferences about the optimization principle from map layout appear viable. We systematically assess whether quantitative laws resembling

Renal cytochrome P450 omega-hydroxylase and epoxygenase activity are differentially modified by nitric oxide and sodium chloride.

PubMed

Oyekan, A O; Youseff, T; Fulton, D; Quilley, J; McGiff, J C

1999-10-01

Renal function is perturbed by inhibition of nitric oxide synthase (NOS). To probe the basis of this effect, we characterized the effects of nitric oxide (NO), a known suppressor of cytochrome P450 (CYP) enzymes, on metabolism of arachidonic acid (AA), the expression of omega-hydroxylase, and the efflux of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated kidney. The capacity to convert [(14)C]AA to HETEs and epoxides (EETs) was greater in cortical microsomes than in medullary microsomes. Sodium nitroprusside (10-100 microM), an NO donor, inhibited renal microsomal conversion of [(14)C]AA to HETEs and EETs in a dose-dependent manner. 8-bromo cGMP (100 microM), the cell-permeable analogue of cGMP, did not affect conversion of [(14)C]AA. Inhibition of NOS with N(omega)-nitro-L-arginine-methyl ester (L-NAME) significantly increased conversion of [(14)C]AA to HETE and greatly increased the expression of omega-hydroxylase protein, but this treatment had only a modest effect on epoxygenase activity. L-NAME induced a 4-fold increase in renal efflux of 20-HETE, as did L-nitroarginine. Oral treatment with 2% sodium chloride (NaCl) for 7 days increased renal epoxygenase activity, both in the cortex and the medulla. In contrast, cortical omega-hydroxylase activity was reduced by treatment with 2% NaCl. Coadministration of L-NAME and 2% NaCl decreased conversion of [(14)C]AA to HETEs without affecting epoxygenase activity. Thus, inhibition of NOS increased omega-hydroxylase activity, CYP4A expression, and renal efflux of 20-HETE, whereas 2% NaCl stimulated epoxygenase activity.

A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus)

PubMed Central

Prozesky, Leon; Lawrence, John

2018-01-01

The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the

A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus).

PubMed

Mitchell, Emily P; Prozesky, Leon; Lawrence, John

2018-01-01

The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the

Contributions of nuclear magnetic resonance to renal biochemistry

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

Ross, B.; Freeman, D.; Chan, L.

/sup 31/P NMR as a descriptive technique is of interest to nephrologists. Particular contributions of /sup 31/P NMR to our understanding of renal function may be enumerated.: Free metabolite levels are different from those classically accepted; in particular, ADP and Pi are low with implications for the control of renal metabolism and Pi transport, and, via the phosphorylation potential, for Na+ transport. Renal pH is heterogeneous; between cortex, outer medulla, and papilla, and between cell and lumen, a large pH gradient exists. Also, quantitation between cytosol and mitochondrion of the pH gradient is now feasible. In acute renal failure ofmore » either ischemic or nonischemic origin, both ATP depletion and acidification of the renal cell result in damage, with increasing evidence for the importance of the latter. Measurements of renal metabolic rate in vivo suggest the existence of a prodromal phase of acute renal failure, which could lead to its detection at an earlier and possibly reversible stage. Human renal cancers show a unique /sup 31/P NMR spectrum and a very acidic environment. Cancer chemotherapy may alter this and detection of such changes with NMR offers a method of therapeutic monitoring with significance beyond nephrology. Renal cortex and medulla have a different T1 relaxation time, possibly due to differences in lipid composition. It seems that NMR spectroscopy has much to offer to the future understanding of the relationship between renal biochemistry and function. 56 references.« less

Renal geology (quantitative renal stone analysis) by 'Fourier transform infrared spectroscopy'.

PubMed

Singh, Iqbal

2008-01-01

To prospectively determine the precise stone composition (quantitative analysis) by using infrared spectroscopy in patients with urinary stone disease presenting to our clinic. To determine an ideal method for stone analysis suitable for use in a clinical setting. After routine and a detailed metabolic workup of all patients of urolithiasis, stone samples of 50 patients of urolithiasis satisfying the entry criteria were subjected to the Fourier transform infrared spectroscopic analysis after adequate sample homogenization at a single testing center. Calcium oxalate monohydrate and dihydrate stone mixture was most commonly encountered in 35 (71%) followed by calcium phosphate, carbonate apatite, magnesium ammonium hexahydrate and xanthine stones. Fourier transform infrared spectroscopy allows an accurate, reliable quantitative method of stone analysis. It also helps in maintaining a computerized large reference library. Knowledge of precise stone composition may allow the institution of appropriate prophylactic therapy despite the absence of any detectable metabolic abnormalities. This may prevent and or delay stone recurrence.

Increased cortical curvature reflects white matter atrophy in individual patients with early multiple sclerosis

PubMed Central

Deppe, Michael; Marinell, Jasmin; Krämer, Julia; Duning, Thomas; Ruck, Tobias; Simon, Ole J.; Zipp, Frauke; Wiendl, Heinz; Meuth, Sven G.

2014-01-01

Objective White matter atrophy occurs independently of lesions in multiple sclerosis. In contrast to lesion detection, the quantitative assessment of white matter atrophy in individual patients has been regarded as a major challenge. We therefore tested the hypothesis that white matter atrophy (WMA) is present at the very beginning of multiple sclerosis (MS) and in virtually each individual patient. To find a new sensitive and robust marker for WMA we investigated the relationship between cortical surface area, white matter volume (WMV), and whole-brain-surface-averaged rectified cortical extrinsic curvature. Based on geometrical considerations we hypothesized that cortical curvature increases if WMV decreases and the cortical surface area remains constant. Methods In total, 95 participants were enrolled: 30 patients with early and advanced relapsing–remitting MS; 30 age-matched control subjects; 30 patients with Alzheimer's disease (AD) and 5 patients with clinically isolated syndrome (CIS). Results 29/30 MS and 5/5 CIS patients showed lower WMV than expected from their intracranial volume (average reduction 13.0%, P < 10− 10), while the cortical surface area showed no significant differences compared with controls. The estimated WMV reductions were correlated with an increase in cortical curvature (R = 0.62, P = 0.000001). Discriminant analysis revealed that the curvature increase was highly specific for the MS and CIS groups (96.7% correct assignments between MS and control groups) and was significantly correlated with reduction of white matter fractional anisotropy, as determined by diffusion tensor imaging and the Expanded Disability Status Scale. As expected by the predominant gray and WM degeneration in AD, no systematic curvature increase was observed in AD. Conclusion Whole-brain-averaged cortical extrinsic curvature appears to be a specific and quantitative marker for a WMV–cortex disproportionality and allows us to assess “pure” WMA

Protective effect of Urtica dioica L. on renal ischemia/reperfusion injury in rat.

PubMed

Sayhan, Mustafa Burak; Kanter, Mehmet; Oguz, Serhat; Erboga, Mustafa

2012-12-01

Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. This study was designed to investigate the effect of Urtica dioica L. (UD), in I/R induced renal injury. A total of 32 male Sprague-Dawley rats were divided into four groups: control, UD alone, I/R and I/R + UD; each group contain 8 animals. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. In the UD group, 3 days before I/R, UD (2 ml/kg/day intraperitoneal) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and kidney tissues samples were obtained for histopathological investigation in all groups. To date, no more histopathological changes on intestinal I/R injury in rats by UD treatment have been reported. Renal I/R caused severe histopathological injury including tubular damage, atrophy dilatation, loss of brush border and hydropic epithelial cell degenerations, renal corpuscle atrophy, glomerular shrinkage, markedly focal mononuclear cell infiltrations in the kidney. UD treatment significantly attenuated the severity of intestinal I/R injury and significantly lowered tubulointerstitial damage score than the I/R group. The number of PCNA and TUNEL positive cells in the control and UD alone groups was negligible. When kidney sections were PCNA and TUNEL stained, there was a clear increase in the number of positive cells in the I/R group rats in the renal cortical tissues. However, there is a significant reduction in the activity of PCNA and TUNEL in kidney tissue of renal injury induced by renal I/R with UD therapy. Our results suggest that administration of UD attenuates renal I/R injury. These results suggest that UD treatment has a protective effect against renal damage induced by renal I/R. This protective effect is possibly due to its ability to inhibit I/R induced renal damage, apoptosis and cell proliferation.

Cortical fibers orientation mapping using in-vivo whole brain 7 T diffusion MRI.

PubMed

Gulban, Omer F; De Martino, Federico; Vu, An T; Yacoub, Essa; Uğurbil, Kamil; Lenglet, Christophe

2018-05-10

Diffusion MRI of the cortical gray matter is challenging because the micro-environment probed by water molecules is much more complex than within the white matter. High spatial and angular resolutions are therefore necessary to uncover anisotropic diffusion patterns and laminar structures, which provide complementary (e.g. to anatomical and functional MRI) microstructural information about the cortex architectonic. Several ex-vivo and in-vivo MRI studies have recently addressed this question, however predominantly with an emphasis on specific cortical areas. There is currently no whole brain in-vivo data leveraging multi-shell diffusion MRI acquisition at high spatial resolution, and depth dependent analysis, to characterize the complex organization of cortical fibers. Here, we present unique in-vivo human 7T diffusion MRI data, and a dedicated cortical depth dependent analysis pipeline. We leverage the high spatial (1.05 mm isotropic) and angular (198 diffusion gradient directions) resolution of this whole brain dataset to improve cortical fiber orientations mapping, and study neurites (axons and/or dendrites) trajectories across cortical depths. Tangential fibers in superficial cortical depths and crossing fiber configurations in deep cortical depths are identified. Fibers gradually inserting into the gyral walls are visualized, which contributes to mitigating the gyral bias effect. Quantitative radiality maps and histograms in individual subjects and cortex-based aligned datasets further support our results. Copyright © 2018 Elsevier Inc. All rights reserved.

Low cortical bone density measured by computed tomography in children and adolescents with untreated hyperthyroidism.

PubMed

Numbenjapon, Nawaporn; Costin, Gertrude; Gilsanz, Vicente; Pitukcheewanont, Pisit

2007-05-01

To determine whether increased thyroid hormones levels have an effect on various bone components (cortical vs cancellous bone). The anthropometric and 3-dimensional quantitative computed tomography (CT) bone measurements, including bone density (BD), cross-sectional area (CSA) of the lumbar spine and femur, and cortical bone area (CBA) of the femur, of 18 children and adolescents with untreated hyperthyroidism were reviewed and compared with those of age-, sex-, and ethnicity-matched historical controls. No significant differences in height, weight, body mass index (BMI), or pubertal staging between patients and controls were found. Cortical BD was significantly lower (P < .001) in children and adolescents with hyperthyroidism compared with historical controls. After adjusting for weight and height, no difference in femur CSA between hyperthyroid children and historical controls was evident. No significant correlations among thyroid hormone levels, antithyroid antibody levels, and cortical BD values were found. As determined by CT, cortical bone is the preferential site of bone loss in children and adolescents with untreated hyperthyroidism.

Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score.

PubMed

Kutikov, Alexander; Smaldone, Marc C; Egleston, Brian L; Manley, Brandon J; Canter, Daniel J; Simhan, Jay; Boorjian, Stephen A; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2011-08-01

Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available. All patients in the cohort underwent either partial or radical nephrectomy. The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Assessment of MRI-Based Automated Fetal Cerebral Cortical Folding Measures in Prediction of Gestational Age in the Third Trimester.

PubMed

Wu, J; Awate, S P; Licht, D J; Clouchoux, C; du Plessis, A J; Avants, B B; Vossough, A; Gee, J C; Limperopoulos, C

2015-07-01

Traditional methods of dating a pregnancy based on history or sonographic assessment have a large variation in the third trimester. We aimed to assess the ability of various quantitative measures of brain cortical folding on MR imaging in determining fetal gestational age in the third trimester. We evaluated 8 different quantitative cortical folding measures to predict gestational age in 33 healthy fetuses by using T2-weighted fetal MR imaging. We compared the accuracy of the prediction of gestational age by these cortical folding measures with the accuracy of prediction by brain volume measurement and by a previously reported semiquantitative visual scale of brain maturity. Regression models were constructed, and measurement biases and variances were determined via a cross-validation procedure. The cortical folding measures are accurate in the estimation and prediction of gestational age (mean of the absolute error, 0.43 ± 0.45 weeks) and perform better than (P = .024) brain volume (mean of the absolute error, 0.72 ± 0.61 weeks) or sonography measures (SDs approximately 1.5 weeks, as reported in literature). Prediction accuracy is comparable with that of the semiquantitative visual assessment score (mean, 0.57 ± 0.41 weeks). Quantitative cortical folding measures such as global average curvedness can be an accurate and reliable estimator of gestational age and brain maturity for healthy fetuses in the third trimester and have the potential to be an indicator of brain-growth delays for at-risk fetuses and preterm neonates. © 2015 by American Journal of Neuroradiology.

Infra-renal angles, entry into inferior vena cava and vertebral levels of renal veins.

PubMed

Satyapal, K S

1999-10-01

Current norms for renal vasculature hold true in only half the population. Standard textbooks perpetuate old misconceptions regarding renal venous anatomy. This study is aimed to determine left and right infra-renal angles (L-IRA, R-IRA); entry level of renal veins into the inferior vena cava (IVC), and height of IVC under renal vein influence; and their vertebral level. One hundred morphologically normal en-bloc renal specimens randomly selected from post-mortem examinations were dissected and resin casted. IRA were also measured from venograms of 32 adult and 11 foetal cadavers, as were vertebral entry levels. IRA measurements (degrees) were as follows: left, 55 degrees +/- 16 degrees (20 degrees -102 degrees ); right, 60 degrees +/- 17 degrees (10 degrees -93 degrees ). Left vein entered IVC higher than right 54%, lower 36%, and opposite each other 10%. Vertical distance between lower borders of veins was 1.0 +/- 0.9 cm. Vertical distance of IVC under renal vein influence was 2.3 +/- 1.0 cm. Vertebral level of veins in adults lies between TI2-L2. In foetuses, IRA was as follows: left, 65 degrees +/- 12 degrees (45 degrees -90 degrees ); right, 58 degrees +/- 7 degrees (40 degrees -70 degrees ); vertebral level between T12 and L3. Similar IRA values from literature noted on right, 51 degrees (26 degrees -100 degrees ); differences on left, 77 degrees (43 degrees -94 degrees ), clearly differing from Williams et al. (Gray's Anatomy, 37(th) ed, 1989) statement that renal veins "open into the inferior vena cava almost at right angles." Large variations of IRA are not surprising since kidneys are considered normally "floating viscera," varying position with posture and respiratory movement as well as in live vs. cadaveric subjects. The entry level into the IVC also differs from Williams et al. This study uniquely quantitated actual height difference between lower borders of left and right veins. The data presented appears to be the first documentation of vertebral

Unilateral renal ischaemia in rats induces a rapid secretion of inflammatory markers to renal lymph and increased capillary permeability

PubMed Central

Bivol, Liliana Monica; Iversen, Bjarne Magnus; Hultström, Michael; Wallace, Paal William; Reed, Rolf Kåre

2015-01-01

Key points Transient reduction in renal blood flow results in inflammation and is a primary cause of acute kidney injury, thereby representing a major clinical problem.It is not known whether the inflammatory reaction is local only or part of a systemic response.We accessed the renal microenvironment through isolation of lymph and were in this way able to investigate whether the inflammatory reaction is local or systemic.Transient ischaemia followed by reperfusion resulted in a rapid production of inflammatory mediators locally in the renal interstitium.We moreover showed that the injury response affected the glomerular as well as the non‐glomerular barrier and resulted in a reduced size and charge selectivity of the glomerular capillaries. Abstract A better understanding of the inflammatory process associated with renal ischaemia–reperfusion (IR) injury may be clinically important. In this study we examined the role of the kidney in production of inflammatory mediators by analysing renal lymph after 30 min unilateral occlusion of renal artery followed by 120 min reperfusion, as well as the effect of IR on size selectivity for proteins in both glomerular and peritubular capillaries. All measured mediators increased dramatically in renal hilar lymph, plasma and renal cortical tissue samples and returned to control levels after 120 min reperfusion. The responses were differentiated; interleukin‐1β, monocyte chemoattractant protein‐1 and leptin were markedly increased in plasma before reperfusion, reflecting an extrarenal response possibly induced by afferent renal nerve activity from the ischaemic kidney. Tumour necrosis factor‐α  was the only mediator showing elevated lymph‐to‐plasma ratio following 30 min reperfusion, indicating that most cytokines were released directly into the bloodstream. The IR‐induced rise in cytokine levels was paralleled by a significant increase in high molecular weight plasma proteins in both lymph and urine. The

Longitudinal development of cortical thickness, folding, and fiber density networks in the first 2 years of life.

PubMed

Nie, Jingxin; Li, Gang; Wang, Li; Shi, Feng; Lin, Weili; Gilmore, John H; Shen, Dinggang

2014-08-01

Quantitatively characterizing the development of cortical anatomical networks during the early stage of life plays an important role in revealing the relationship between cortical structural connection and high-level functional development. The development of correlation networks of cortical-thickness, cortical folding, and fiber-density is systematically analyzed in this article to study the relationship between different anatomical properties during the first 2 years of life. Specifically, longitudinal MR images of 73 healthy subjects from birth to 2 year old are used. For each subject at each time point, its measures of cortical thickness, cortical folding, and fiber density are projected to its cortical surface that has been partitioned into 78 cortical regions. Then, the correlation matrices for cortical thickness, cortical folding, and fiber density at each time point can be constructed, respectively, by computing the inter-regional Pearson correlation coefficient (of any pair of ROIs) across all 73 subjects. Finally, the presence/absence pattern (i.e., binary pattern) of the connection network is constructed from each inter-regional correlation matrix, and its statistical and anatomical properties are adopted to analyze the longitudinal development of anatomical networks. The results show that the development of anatomical network could be characterized differently by using different anatomical properties (i.e., using cortical thickness, cortical folding, or fiber density). Copyright © 2013 Wiley Periodicals, Inc.

Production and actions of the anandamide metabolite prostamide E2 in the renal medulla.

PubMed

Ritter, Joseph K; Li, Cao; Xia, Min; Poklis, Justin L; Lichtman, Aron H; Abdullah, Rehab A; Dewey, William L; Li, Pin-Lan

2012-09-01

Medullipin has been proposed to be an antihypertensive lipid hormone released from the renal medulla in response to increased arterial pressure and renal medullary blood flow. Because anandamide (AEA) possesses characteristics of this purported hormone, the present study tested the hypothesis that AEA or one of its metabolites represents medullipin. AEA was demonstrated to be enriched in the kidney medulla compared with cortex. Western blotting and enzymatic analyses of renal cortical and medullary microsomes revealed opposite patterns of enrichment of two AEA-metabolizing enzymes, with fatty acid amide hydrolase higher in the renal cortex and cyclooxygenase-2 (COX-2) higher in the renal medulla. In COX-2 reactions with renal medullary microsomes, prostamide E2, the ethanolamide of prostaglandin E₂, was the major product detected. Intramedullarily infused AEA dose-dependently increased urine volume and sodium and potassium excretion (15-60 nmol/kg/min) but had little effect on mean arterial pressure (MAP). The renal excretory effects of AEA were blocked by intravenous infusion of celecoxib (0.1 μg/kg/min), a selective COX-2 inhibitor, suggesting the involvement of a prostamide intermediate. Plasma kinetic analysis revealed longer elimination half-lives for AEA and prostamide E2 compared with prostaglandin E₂. Intravenous prostamide E2 reduced MAP and increased renal blood flow (RBF), actions opposite to those of angiotensin II. Coinfusion of prostamide E2 inhibited angiotensin II effects on MAP and RBF. These results suggest that AEA and/or its prostamide metabolites in the renal medulla may represent medullipin and function as a regulator of body fluid and MAP.

Quantitative analysis of neuronal response properties in primary and higher-order auditory cortical fields of awake house mice (Mus musculus)

PubMed Central

Joachimsthaler, Bettina; Uhlmann, Michaela; Miller, Frank; Ehret, Günter; Kurt, Simone

2014-01-01

Because of its great genetic potential, the mouse (Mus musculus) has become a popular model species for studies on hearing and sound processing along the auditory pathways. Here, we present the first comparative study on the representation of neuronal response parameters to tones in primary and higher-order auditory cortical fields of awake mice. We quantified 12 neuronal properties of tone processing in order to estimate similarities and differences of function between the fields, and to discuss how far auditory cortex (AC) function in the mouse is comparable to that in awake monkeys and cats. Extracellular recordings were made from 1400 small clusters of neurons from cortical layers III/IV in the primary fields AI (primary auditory field) and AAF (anterior auditory field), and the higher-order fields AII (second auditory field) and DP (dorsoposterior field). Field specificity was shown with regard to spontaneous activity, correlation between spontaneous and evoked activity, tone response latency, sharpness of frequency tuning, temporal response patterns (occurrence of phasic responses, phasic-tonic responses, tonic responses, and off-responses), and degree of variation between the characteristic frequency (CF) and the best frequency (BF) (CF–BF relationship). Field similarities were noted as significant correlations between CFs and BFs, V-shaped frequency tuning curves, similar minimum response thresholds and non-monotonic rate-level functions in approximately two-thirds of the neurons. Comparative and quantitative analyses showed that the measured response characteristics were, to various degrees, susceptible to influences of anesthetics. Therefore, studies of neuronal responses in the awake AC are important in order to establish adequate relationships between neuronal data and auditory perception and acoustic response behavior. PMID:24506843

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.

Quantitative Contour Analysis as an Image-based Discriminator Between Benign and Malignant Renal Tumors.

PubMed

Yap, Felix Y; Hwang, Darryl H; Cen, Steven Y; Varghese, Bino A; Desai, Bhushan; Quinn, Brian D; Gupta, Megha Nayyar; Rajarubendra, Nieroshan; Desai, Mihir M; Aron, Manju; Liang, Gangning; Aron, Monish; Gill, Inderbir S; Duddalwar, Vinay A

2018-04-01

To investigate whether morphologic analysis can differentiate between benign and malignant renal tumors on clinically acquired imaging. Between 2009 and 2014, 3-dimensional tumor volumes were manually segmented from contrast-enhanced computerized tomography (CT) images from 150 patients with predominantly solid, nonmacroscopic fat-containing renal tumors: 100 renal cell carcinomas and 50 benign lesions (eg, oncocytoma and lipid-poor angiomyolipoma). Tessellated 3-dimensional tumor models were created from segmented voxels using MATLAB code. Eleven shape descriptors were calculated: sphericity, compactness, mean radial distance, standard deviation of the radial distance, radial distance area ratio, zero crossing, entropy, Feret ratio, convex hull area and convex hull perimeter ratios, and elliptic compactness. Morphometric parameters were compared using the Wilcoxon rank-sum test to investigate whether malignant renal masses demonstrate more morphologic irregularity than benign ones. Only CHP in sagittal orientation (median 0.96 vs 0.97) and EC in coronal orientation (median 0.92 vs 0.93) differed significantly between malignant and benign masses (P = .04). When comparing these 2 metrics between coronal and sagittal orientations, similar but nonsignificant trends emerged (P = .07). Other metrics tested were not significantly different in any imaging plane. Computerized image analysis is feasible using shape descriptors that otherwise cannot be visually assessed and used without quantification. Shape analysis via the transverse orientation may be reasonable, but encompassing all 3 planar dimensions to characterize tumor contour can achieve a more comprehensive evaluation. Two shape metrics (CHP and EC) may help distinguish benign from malignant renal tumors, an often challenging goal to achieve on imaging and biopsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Kv channel subunits that contribute to voltage-gated K+ current in renal vascular smooth muscle.

PubMed

Fergus, Daniel J; Martens, Jeffrey R; England, Sarah K

2003-03-01

The rat renal arterial vasculature displays differences in K(+) channel current phenotypes along its length. Small arcuate to cortical radial arteries express a delayed rectifier phenotype, while the predominant Kv current in larger arcuate and interlobar arteries is composed of both transient and sustained components. We sought to determine whether Kvalpha subunits in the rat renal interlobar and arcuate arteries form heterotetramers, which may account for the unique currents, and whether modulatory Kvbeta subunits are present in renal vascular smooth muscle cells. RT-PCR indicated the presence of several different Kvalpha subunit isoform transcripts. Co-immunoprecipitation with immunoblotting and immunohistochemical evidence suggests that a portion of the K(+) current phenotype is a heteromultimer containing delayed-rectifier Kv1.2 and A-type Kv1.4 channel subunits. RT-PCR and immunoblot analyses also demonstrated the presence of both Kvbeta1.2 and Kvbeta1.3 in renal arteries. These results suggest that heteromultimeric formation of Kvalpha subunits and the presence of modulatory Kvbeta subunits are important factors in mediating Kv currents in the renal microvasculature and suggest a potentially critical role for these channel subunits in blood pressure regulation.

Renal mechanoreceptor dysfunction: an intermediate phenotype in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Kopp, U C

1999-01-01

This study tested the hypothesis that decreased responsiveness of renal mechanosensitive neurons constitutes an intermediate phenotype in spontaneously hypertensive rats (SHR). Decreased responsiveness of these sensory neurons would contribute to increased renal sympathetic nerve activity and sodium retention, characteristic findings in hypertension. A backcross population, developed by mating borderline hypertensive rats with Wistar-Kyoto rats (WKY) (the F1 of a cross between an SHR and a normotensive WKY), was fed 8% NaCl food for 12 weeks from age 4 to 16 weeks. Responses to increases in ureteral pressure to 20 and 40 mm Hg in 80 backcross rats instrumented for measurement of mean arterial pressure and afferent renal nerve activity were determined. Mean arterial pressure ranged from 110 to 212 mm Hg and was inversely correlated with the magnitude of the increase in afferent renal nerve activity during increased ureteral pressure. Thus, decreased responsiveness of renal mechanosensitive neurons cosegregated with hypertension in this backcross population. This aspect of the complex quantitative trait of altered renal sympathetic neural control of renal function, ie, decreased renal mechanoreceptor responsiveness, is part of an intermediate phenotype in SHR.

Application of an in vitro OAT assay in drug design and optimization of renal clearance.

PubMed

Soars, Matthew G; Barton, Patrick; Elkin, Lisa L; Mosure, Kathleen W; Sproston, Joanne L; Riley, Robert J

2014-07-01

1. Optimization of renal clearance is a complex balance between passive and active processes mediated by renal transporters. This work aimed to characterize the interaction of a series of compounds with rat and human organic anion transporters (OATs) and develop quantitative structure-activity relationships (QSARs) to optimize renal clearance. 2. In vitro inhibition assays were established for human OAT1 and rat Oat3 and rat in vivo renal clearance was obtained. Statistically significant quantitative relationships were explored between the compounds' physical properties, their affinity for OAT1 and oat3 and the inter-relationship with unbound renal clearance (URC) in rat. 3. Many of the compounds were actively secreted and in vitro analysis demonstrated that these were ligands for rat and human OAT transporters (IC50 values ranging from <1 to >100 µM). Application of resultant QSAR models reduced renal clearance in the rat from 24 to <0.1 ml/min/kg. Data analysis indicated that the properties associated with increasing affinity at OATs are the same as those associated with reducing URC but orthogonal in nature. 4. This study has demonstrated that OAT inhibition data and QSAR models can be successfully used to optimize rat renal clearance in vivo and provide confidence of translation to humans.

Modulation of renal CNG-A3 sodium channel in rats subjected to low- and high-sodium diets.

PubMed

Novaira, Horacio J; Botelho, Bruno F; Goldenberg, Regina C; Guggino, Sandra E; Morales, Marcelo M

2004-10-11

In this work, we studied the mRNA distribution of CNG-A3, an amiloride-sensitive sodium channel that belongs to the cyclic nucleotide-gated (CNG) family of channels, along the rat nephron. The possible involvement of aldosterone in this process was also studied. We also evaluated its expression in rats subjected to diets with different concentrations of sodium or to alterations in aldosterone plasma levels. Total RNA isolated from whole kidney and/or dissected nephron segments of Wistar rats subjected to low- and high-sodium diets, furosemide treatment, adrenalectomy, and adrenalectomy with replacement by aldosterone were analyzed by the use of Western blot, ribonuclease protection assay (RPA) and/or reverse transcription followed by semi-quantitative polymerase chain reaction (RT-PCR). CNG-A3 sodium channel mRNA and protein expression, in whole kidneys of rats subjected to high-Na+ diet, were lower than those in animals given a low-salt diet. Renal CNG-A3 mRNA expression was also decreased in adrenalectomized rats, and was normalized by aldosterone replacement. Moreover, a CNG-A3 mRNA expression study in different nephron segments revealed that aldosterone modulation is present in the cortical thick ascending loop (cTAL) and cortical collecting duct (CCD). This result suggests that CNG-A3 is responsive to the same hormone signaling as the amiloride sensitive sodium channel ENaC and suggests the CNG-A3 may have a physiological role in sodium reabsorption.

Ultrasonic Wave Properties in Bone Axis Direction of Bovine Cortical Bone

NASA Astrophysics Data System (ADS)

Yamamoto, Kazufumi; Yaoi, Yuichiro; Yamato, Yu; Yanagitan, Takahiko; Matsukawa, Mami; Yamazaki, Kaoru

2008-05-01

Quantitative ultrasonography (QUS) is a good method for measuring elastic properties of bone in vivo. Bovine cortical bone has two typical microstructures, plexiform and Haversian. In this study, the relationship between the speed of sound (SOS) and the hydroxyapatite (HAp) crystallite orientation in the axial direction was investigated in two different aged bovine cortical bones. The dependence of attenuation on anatomical position was also investigated. Two ring-permanent hyphen shaped cortical bone samples were obtained from 36- and 24-month-old bovine femurs. SOS was measured with a conventional ultrasonic pulse system. The integrated intensity of the (0002) peak obtained by X-ray diffraction was determine to evaluate the amount of preferred orientation. Regardless of the age of the bovine femurs, a significant correlation between SOS and the preferred orientation of HAp crystallites was observed in parts of the plexiform structure, and the gradient of the relationship showed a similar tendency. Attenuation seemed to depend on bone microstructure.

Effects of Alprazolam on Cortical Activity and Tremors in Patients with Essential Tremor

PubMed Central

Ibáñez, Jaime; González de la Aleja, Jesús; Gallego, Juan A.; Romero, Juan P.; Saíz-Díaz, Rosana A.; Benito-León, Julián; Rocon, Eduardo

2014-01-01

Background Essential tremor (ET) is characterised by postural and action tremors with a frequency of 4–12 Hz. Previous studies suggest that the tremor activity originates in the cerebello-thalamocortical pathways. Alprazolam is a short-acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate the therapeutic action of alprazolam are unknown; however, in healthy subjects, benzodiazepines increase cortical beta activity. In this study, we investigated the effect of alprazolam both on beta and tremor-related cortical activity and on alterations in tremor presentation in ET patients. Therefore, we characterised the dynamics of tremor and cortical activity in ET patients after alprazolam intake. Methods We recorded hand tremors and contralateral cortical activity in four recordings before and after a single dose of alprazolam. We then computed the changes in tremors, cortico-muscular coherence, and cortical activity at the tremor frequency and in the beta band. Results Alprazolam significantly attenuated tremors (EMG: 76.2±22.68%), decreased cortical activity in the tremor frequency range and increased cortical beta activity in all patients (P<0.05). At the same time, the cortico-muscular coherence at the tremor frequency became non-significant (P<0.05). We also found a significant correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the increased ratio of cortical activity in the beta band to the activity observed in the tremor frequency range. Conclusions This study provides the first quantitative analysis of tremor reduction following alprazolam intake. We observed that the tremor severity decreased in association with an increased ratio of beta to tremor-related cortical activity. We hypothesise that the increase in cortical beta activity may act as a blocking mechanism and may dampen the pathological oscillatory activity, which in turn attenuates the observed tremor. PMID:24667763

Effects of alprazolam on cortical activity and tremors in patients with essential tremor.

PubMed

Ibáñez, Jaime; González de la Aleja, Jesús; Gallego, Juan A; Romero, Juan P; Saíz-Díaz, Rosana A; Benito-León, Julián; Rocon, Eduardo

2014-01-01

Essential tremor (ET) is characterised by postural and action tremors with a frequency of 4-12 Hz. Previous studies suggest that the tremor activity originates in the cerebello-thalamocortical pathways. Alprazolam is a short-acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate the therapeutic action of alprazolam are unknown; however, in healthy subjects, benzodiazepines increase cortical beta activity. In this study, we investigated the effect of alprazolam both on beta and tremor-related cortical activity and on alterations in tremor presentation in ET patients. Therefore, we characterised the dynamics of tremor and cortical activity in ET patients after alprazolam intake. We recorded hand tremors and contralateral cortical activity in four recordings before and after a single dose of alprazolam. We then computed the changes in tremors, cortico-muscular coherence, and cortical activity at the tremor frequency and in the beta band. Alprazolam significantly attenuated tremors (EMG: 76.2 ± 22.68%), decreased cortical activity in the tremor frequency range and increased cortical beta activity in all patients (P<0.05). At the same time, the cortico-muscular coherence at the tremor frequency became non-significant (P<0.05). We also found a significant correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the increased ratio of cortical activity in the beta band to the activity observed in the tremor frequency range. This study provides the first quantitative analysis of tremor reduction following alprazolam intake. We observed that the tremor severity decreased in association with an increased ratio of beta to tremor-related cortical activity. We hypothesise that the increase in cortical beta activity may act as a blocking mechanism and may dampen the pathological oscillatory activity, which in turn attenuates the observed tremor.

Properties permitting the renal cortex to be the oxygen sensor for the release of erythropoietin: clinical implications.

PubMed

Halperin, Mitchell L; Cheema-Dhadli, Surinder; Lin, Shih-Hua; Kamel, Kamel S

2006-09-01

The PO2 at this site where erythropoietin release is regulated should vary only when the hemoglobin concentration changes in capillary blood. The kidney cortex is an ideal location for this O2 sensor for four reasons. First, it extracts a small proportion of the oxygen that is delivered in each liter of blood; this makes the PO2 signal easier to recognize. Second, there is a constant ratio of the work performed (consumption of O2) to the renal blood flow rate (delivery of O2). Third, the high renal blood flow rate improves diffusion of O2 from capillaries to this O2 receptor. Fourth, a high renal cortical PCO2 prevents an additional shift of the O2:hemoglobin dissociation curve by other factors from being a confounding variable. This suggests that the GFR and the renal blood flow rate should be examined in patients with unexplained anemia or erythrocytosis.

Regulation of transport in the connecting tubule and cortical collecting duct.

PubMed

Staruschenko, Alexander

2012-04-01

The central goal of this overview article is to summarize recent findings in renal epithelial transport,focusing chiefly on the connecting tubule (CNT) and the cortical collecting duct (CCD).Mammalian CCD and CNT are involved in fine-tuning of electrolyte and fluid balance through reabsorption and secretion. Specific transporters and channels mediate vectorial movements of water and solutes in these segments. Although only a small percent of the glomerular filtrate reaches the CNT and CCD, these segments are critical for water and electrolyte homeostasis since several hormones, for example, aldosterone and arginine vasopressin, exert their main effects in these nephron sites. Importantly, hormones regulate the function of the entire nephron and kidney by affecting channels and transporters in the CNT and CCD. Knowledge about the physiological and pathophysiological regulation of transport in the CNT and CCD and particular roles of specific channels/transporters has increased tremendously over the last two decades.Recent studies shed new light on several key questions concerning the regulation of renal transport.Precise distribution patterns of transport proteins in the CCD and CNT will be reviewed, and their physiological roles and mechanisms mediating ion transport in these segments will also be covered. Special emphasis will be given to pathophysiological conditions appearing as a result of abnormalities in renal transport in the CNT and CCD. © 2012 American Physiological Society. Compr Physiol 2:1491-1539, 2012.

Regulation of transport in the connecting tubule and cortical collecting duct

PubMed Central

Staruschenko, Alexander

2012-01-01

The central goal of this overview article is to summarize recent findings in renal epithelial transport, focusing chiefly on the connecting tubule (CNT) and the cortical collecting duct (CCD). Mammalian CCD and CNT are involved in fine tuning of electrolyte and fluid balance through reabsorption and secretion. Specific transporters and channels mediate vectorial movements of water and solutes in these segments. Although only a small percent of the glomerular filtrate reaches the CNT and CCD, these segments are critical for water and electrolyte homeostasis since several hormones, e.g. aldosterone and arginine vasopressin, exert their main effects in these nephron sites. Importantly, hormones regulate the function of the entire nephron and kidney by affecting channels and transporters in the CNT and CCD. Knowledge about the physiological and pathophysiological regulation of transport in the CNT and CCD and particular roles of specific channels/transporters has increased tremendously over the last two decades. Recent studies shed new light on several key questions concerning the regulation of renal transport. Precise distribution patterns of transport proteins in the CCD and CNT will be reviewed, and their physiological roles and mechanisms mediating ion transport in these segments will be also covered. Special emphasis will be given to pathophysiological conditions appearing as a result of abnormalities in renal transport in the CNT and CCD. PMID:23227301

A Task-Optimized Neural Network Replicates Human Auditory Behavior, Predicts Brain Responses, and Reveals a Cortical Processing Hierarchy.

PubMed

Kell, Alexander J E; Yamins, Daniel L K; Shook, Erica N; Norman-Haignere, Sam V; McDermott, Josh H

2018-05-02

A core goal of auditory neuroscience is to build quantitative models that predict cortical responses to natural sounds. Reasoning that a complete model of auditory cortex must solve ecologically relevant tasks, we optimized hierarchical neural networks for speech and music recognition. The best-performing network contained separate music and speech pathways following early shared processing, potentially replicating human cortical organization. The network performed both tasks as well as humans and exhibited human-like errors despite not being optimized to do so, suggesting common constraints on network and human performance. The network predicted fMRI voxel responses substantially better than traditional spectrotemporal filter models throughout auditory cortex. It also provided a quantitative signature of cortical representational hierarchy-primary and non-primary responses were best predicted by intermediate and late network layers, respectively. The results suggest that task optimization provides a powerful set of tools for modeling sensory systems. Copyright © 2018 Elsevier Inc. All rights reserved.

Intelligence and cortical thickness in children with complex partial seizures.

PubMed

Tosun, Duygu; Caplan, Rochelle; Siddarth, Prabha; Seidenberg, Michael; Gurbani, Suresh; Toga, Arthur W; Hermann, Bruce

2011-07-15

Prior studies on healthy children have demonstrated regional variations and a complex and dynamic relationship between intelligence and cerebral tissue. Yet, there is little information regarding the neuroanatomical correlates of general intelligence in children with epilepsy compared to healthy controls. In vivo imaging techniques, combined with methods for advanced image processing and analysis, offer the potential to examine quantitative mapping of brain development and its abnormalities in childhood epilepsy. A surface-based, computational high resolution 3-D magnetic resonance image analytic technique was used to compare the relationship of cortical thickness with age and intelligence quotient (IQ) in 65 children and adolescents with complex partial seizures (CPS) and 58 healthy controls, aged 6-18 years. Children were grouped according to health status (epilepsy; controls) and IQ level (average and above; below average) and compared on age-related patterns of cortical thickness. Our cross-sectional findings suggest that disruption in normal age-related cortical thickness expression is associated with intelligence in pediatric CPS patients both with average and below average IQ scores. Copyright © 2011 Elsevier Inc. All rights reserved.

Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

PubMed

Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

2011-07-01

Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss. Copyright © 2011 Elsevier Inc. All rights reserved.

Dependence of renal (Na+ + k+)-adenosine triphosphatase activity on thyroid status.

PubMed

Lo, S C; August, T R; Liberman, U A; Edelman, I S

1976-12-25

In thyroidectomized rats, a single injection of L-2,,5,2'-triiodothyronine (T3) (50mug/100 g body weight) elicited at 45% increase in (Na+ + k+)-dependent adenosine triphosphatase (NaK-ATPase) activity of the membrane-rich fraction of renal cortex at the optimal time of response, 48 h after injection. Three successive doses of T3 (50 mug/100 g body weight), given on alternate days, increased NaK-ATPase by 67% in the renal cortex but had no significant effect on the outer medulla or the papilla. Moreover, T3 had no effect on Mg2+-dependent adenosine trisphatase (MgATPase) in cortex, cedulla, or papilla. Three doses of T3 (50 mug/100 g body weight) given on alternate days to thyroidectomized rats elecited a 134, 79, and 46% increase in Vmax for ATP, Na4, and K+, respectively. There were no changes in the Km for ATP or the K1/2 values for Na+ and K+. Two methods were used to estimate the effect of T3 on the number of NaK-ATPase units (assumed to represent the number of Na+ pump sites); rat renal plasma membrane fractions were incubated with [gamma-32P]ATP, Mg2+, and Na+; the 32P-labeled membrane protein yeild was quantitatively dependent on Na+ and was hydrolyzed on addition of K+. There was a linear correlation between the specific activity of NaK-ATPase (Vmax) and the amount of phosphorylated intermediate formed, in renal cortical membrane fractions from thyroidectomized rats given T3 or the diluent. There was also a linear correlation between the specific activity of NaK-ATPase (Vmax) and the amount of [3H]ouabain specifically bound (Na+-, Mg2+-, APT-dependent) to the NaK-ATPase preparation. Injection of T3 resulted in a 70% increase in NaK-ATPase activity, a 79% increase in formation of the phosphorylated intermediate, and a 65% increase in the [H]ouabain specifically bound to the NaK-ATPase system. The T3-dependent increases in Vmax for ATP, Na+, and K+ and the proportionate increases in the phosphorylated intermediate and in the amount of [3H]ouabain bound

Cortical tremor: a variant of cortical reflex myoclonus.

PubMed

Ikeda, A; Kakigi, R; Funai, N; Neshige, R; Kuroda, Y; Shibasaki, H

1990-10-01

Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus.

Cortical Porosity Identifies Women with Osteopenia at Increased Risk for Forearm Fractures

PubMed Central

Bala, Yohann; Zebaze, Roger; Ghasem-Zadeh, Ali; Atkinson, Elizabeth J.; Iuliano, Sandra; Peterson, James M.; Amin, Shreyasee; Bjørnerem, Åshild; Melton, L. Joseph; Johansson, Helena; Kanis, John A.; Khosla, Sundeep; Seeman, Ego

2014-01-01

Background Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. Methods We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high-resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10-year fracture probability using the country-specific FRAX tool in 68 postmenopausal women with forearm fractures and 70 age-matched community controls in Olmsted County, Minnesota. Results Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact-appearing cortical porosity predicted fracture independent of aBMD; odds ratio [OR] 1.92 (95%CI, 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with, from those without, fractures because high porosity was present in 92% and 86% of each group respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact-appearing cortex conferred an OR for fracture of 4.00 (95%CI, 1.15–13.90). Conclusion In women with osteoporosis, porosity is captured by aBMD and so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. PMID:24519558

Development of Cortical Morphology Evaluated with Longitudinal MR Brain Images of Preterm Infants

PubMed Central

Moeskops, Pim; Benders, Manon J. N. L.; Kersbergen, Karina J.; Groenendaal, Floris; de Vries, Linda S.; Viergever, Max A.; Išgum, Ivana

2015-01-01

Introduction The cerebral cortex develops rapidly in the last trimester of pregnancy. In preterm infants, brain development is very vulnerable because of their often complicated extra-uterine conditions. The aim of this study was to quantitatively describe cortical development in a cohort of 85 preterm infants with and without brain injury imaged at 30 and 40 weeks postmenstrual age (PMA). Methods In the acquired T2-weighted MR images, unmyelinated white matter (UWM), cortical grey matter (CoGM), and cerebrospinal fluid in the extracerebral space (CSF) were automatically segmented. Based on these segmentations, cortical descriptors evaluating volume, surface area, thickness, gyrification index, and global mean curvature were computed at both time points, for the whole brain, as well as for the frontal, temporal, parietal, and occipital lobes separately. Additionally, visual scoring of brain abnormality was performed using a conventional scoring system at 40 weeks PMA. Results The evaluated descriptors showed larger change in the occipital lobes than in the other lobes. Moreover, the cortical descriptors showed an association with the abnormality scores: gyrification index and global mean curvature decreased, whereas, interestingly, median cortical thickness increased with increasing abnormality score. This was more pronounced at 40 weeks PMA than at 30 weeks PMA, suggesting that the period between 30 and 40 weeks PMA might provide a window of opportunity for intervention to prevent delay in cortical development. PMID:26161536

Role of TGF-β in a Mouse Model of High Turnover Renal Osteodystrophy†

PubMed Central

Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

2014-01-01

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystropy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-βs role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. μCT confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum PTH levels indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore

Cortical network models of impulse firing in the resting and active states predict cortical energetics

PubMed Central

Bennett, Maxwell R.; Farnell, Les; Gibson, William G.; Lagopoulos, Jim

2015-01-01

Measurements of the cortical metabolic rate of glucose oxidation [CMRglc(ox)] have provided a number of interesting and, in some cases, surprising observations. One is the decline in CMRglc(ox) during anesthesia and non-rapid eye movement (NREM) sleep, and another, the inverse relationship between the resting-state CMRglc(ox) and the transient following input from the thalamus. The recent establishment of a quantitative relationship between synaptic and action potential activity on the one hand and CMRglc(ox) on the other allows neural network models of such activity to probe for possible mechanistic explanations of these phenomena. We have carried out such investigations using cortical models consisting of networks of modules with excitatory and inhibitory neurons, each receiving excitatory inputs from outside the network in addition to intermodular connections. Modules may be taken as regions of cortical interest, the inputs from outside the network as arising from the thalamus, and the intermodular connections as long associational fibers. The model shows that the impulse frequency of different modules can differ from each other by less than 10%, consistent with the relatively uniform CMRglc(ox) observed across different regions of cortex. The model also shows that, if correlations of the average impulse rate between different modules decreases, there is a concomitant decrease in the average impulse rate in the modules, consistent with the observed drop in CMRglc(ox) in NREM sleep and under anesthesia. The model also explains why a transient thalamic input to sensory cortex gives rise to responses with amplitudes inversely dependent on the resting-state frequency, and therefore resting-state CMRglc(ox). PMID:25775588

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.

High maternal sodium intake alters sex-specific renal renin-angiotensin system components in newborn Wistar offspring.

PubMed

Maia, D R R; Lopes, K L; Heimann, J C; Furukawa, L N S

2016-01-28

This study aimed to evaluate the systemic and renal renin-angiotensin-aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin-converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring.

Mapping longitudinal development of local cortical gyrification in infants from birth to 2 years of age.

PubMed

Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Lin, Weili; Gilmore, John H; Shen, Dinggang

2014-03-19

Human cortical folding is believed to correlate with cognitive functions. This likely correlation may have something to do with why abnormalities of cortical folding have been found in many neurodevelopmental disorders. However, little is known about how cortical gyrification, the cortical folding process, develops in the first 2 years of life, a period of dynamic and regionally heterogeneous cortex growth. In this article, we show how we developed a novel infant-specific method for mapping longitudinal development of local cortical gyrification in infants. By using this method, via 219 longitudinal 3T magnetic resonance imaging scans from 73 healthy infants, we systemically and quantitatively characterized for the first time the longitudinal cortical global gyrification index (GI) and local GI (LGI) development in the first 2 years of life. We found that the cortical GI had age-related and marked development, with 16.1% increase in the first year and 6.6% increase in the second year. We also found marked and regionally heterogeneous cortical LGI development in the first 2 years of life, with the high-growth regions located in the association cortex, whereas the low-growth regions located in sensorimotor, auditory, and visual cortices. Meanwhile, we also showed that LGI growth in most cortical regions was positively correlated with the brain volume growth, which is particularly significant in the prefrontal cortex in the first year. In addition, we observed gender differences in both cortical GIs and LGIs in the first 2 years, with the males having larger GIs than females at 2 years of age. This study provides valuable information on normal cortical folding development in infancy and early childhood.

Estimation of total glomerular number in stable renal transplants.

PubMed

Fulladosa, Xavier; Moreso, Francesc; Narváez, Jose A; Grinyó, Josep M; Serón, Daniel

2003-10-01

Glomerular number (N(g)) is considered a major determinant of renal function and outcome. In the dog, it has been shown that Ng can be estimated with reasonable precision in vivo by means of a renal biopsy and magnetic resonance imaging (MRI). Thus, this method was applied to study anatomoclinical correlations in stable human renal transplants. Thirty-nine stable renal transplants were included. A protocol renal allograft biopsy was done at 4 mo. Biopsies were evaluated according to Banff criteria. Glomerular volume fraction (Vv(glom/cortex)) was measured by means of a point-counting method, and mean glomerular volume (V(g)) was estimated by means of Weibel and Gomez (V(g)-W&G) and maximal profile area (V(g)-MPA) methods. MRI was used to estimate renal cortical volume (V(cortex)). N(g) was calculated as (Vv(glom/cortex) x V(cortex))/V(g). GFR was estimated by the inulin clearance. Ten age-matched donor biopsies served as controls for V(g). Histologic diagnosis was as follows: normal (n = 20), borderline (n = 7), acute rejection (n = 1), and chronic allograft nephropathy (n = 11). Vv(glom/cortex) was 3.4 +/- 1.1%, V(cortex) was 167 +/- 46 cm(3), V(g)-W&G was 3.2 +/- 1.2 x 10(6) micro m(3), and V(g)-MPA was 3.3 +/- 1.0 x 10(6) micro m(3). V(g)-W&G in donor and recipient biopsies was not different (3.6 +/- 1.1 versus 3.2 +/- 1.2 x 10(6) micro m(3)). Total glomerular number estimated by means of V(g)-W&G (N(g)-W&G) was 0.73 +/- 0.33 x 10(6) and by V(g)-MPA (N(g)-MPA) was 0.74 +/- 0.31 x 10(6). A positive correlation between GFR and N(g)-W&G (r = 0.47, P = 0.002) was observed. Furthermore, the older the donor, the higher V(g)-W&G (r = 0.37, P = 0.01) and the lower N(g)-W&G (r = -0.40, P = 0.01). Total glomerular number can be estimated in stable renal allografts by means of a renal biopsy and MRI. Our data show that N(g) depends on donor age and positively correlates with GFR.

Evaluation of Renal Oxygenation Level Changes after Water Loading Using Susceptibility-Weighted Imaging and T2* Mapping.

PubMed

Ding, Jiule; Xing, Wei; Wu, Dongmei; Chen, Jie; Pan, Liang; Sun, Jun; Xing, Shijun; Dai, Yongming

2015-01-01

To assess the feasibility of susceptibility-weighted imaging (SWI) while monitoring changes in renal oxygenation level after water loading. Thirty-two volunteers (age, 28.0 ± 2.2 years) were enrolled in this study. SWI and multi-echo gradient echo sequence-based T2(*) mapping were used to cover the kidney before and after water loading. Cortical and medullary parameters were measured using small regions of interest, and their relative changes due to water loading were calculated based on baseline and post-water loading data. An intraclass correlation coefficient analysis was used to assess inter-observer reliability of each parameter. A receiver operating characteristic curve analysis was conducted to compare the performance of the two methods for detecting renal oxygenation changes due to water loading. Both medullary phase and medullary T2(*) values increased after water loading (p < 0.001), although poor correlations were found between the phase changes and the T2(*) changes (p > 0.05). Interobserver reliability was excellent for the T2(*) values, good for SWI cortical phase values, and moderate for the SWI medullary phase values. The area under receiver operating characteristic curve of the SWI medullary phase values was 0.85 and was not different from the medullary T2(*) value (0.84). Susceptibility-weighted imaging enabled monitoring changes in the oxygenation level in the medulla after water loading, and may allow comparable feasibility to detect renal oxygenation level changes due to water loading compared with that of T2(*) mapping.

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.

Glutathione S-transferases in human renal cortex and neoplastic tissue: enzymatic activity, isoenzyme profile and immunohistochemical localization.

PubMed

Rodilla, V; Benzie, A A; Veitch, J M; Murray, G I; Rowe, J D; Hawksworth, G M

1998-05-01

1. Glutathione S-transferase (GST) activity in the cytosol of renal cortex and tumours from eight men and eight women was measured using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. GST activities ranged from 685 to 2192 nmol/min/mg protein in cortex (median 1213) and from non-detectable (minimum 45) to 2424 nmol/min/mg protein in tumours (median 469). The activities in the tumours were lower than those in the normal cortices (p < 0.05). 2. In men, the activity in the cortical cytosol was in all cases higher than that measured in the corresponding tumours (p < 0.05). In women, the difference in activity between cortices and tumours was not significantly different (p > 0.05). 3. The age of the patients ranged from 42 to 81 years (median 62) and was not found to play a role in the levels of GST activity observed in cortex or in renal tumours from either sex. 4. Immunoblotting and immunohistochemical studies confirmed that GST-alpha was the predominant form expressed both in normal cortex and tumour and probably accounted for most of the GST activity present in these samples. GST-mu and GST-phi were expressed in both tumours and normal cortex and, while in some cases the level of expression in the cortices was higher than that found in the tumours, the reverse was also observed. Within the GST-mu class, GST M1/M2 was only detected in one sample (tumour), which showed the highest overall expression of GST-mu. GSTM3 was the predominant isoenzyme of the mu class in normal and tumour tissue, whereas GTM4 and GSTM5 were not detected. 5. These differences could have functional significance where xenobiotics or cytotoxic drugs are specific substrates for the different classes of GSTs.

Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor angiomyolipoma on multiphasic multidetector computed tomography.

PubMed

Coy, Heidi; Young, Jonathan R; Douek, Michael L; Brown, Matthew S; Sayre, James; Raman, Steven S

2017-07-01

To evaluate the performance of a novel, quantitative computer-aided diagnostic (CAD) algorithm on four-phase multidetector computed tomography (MDCT) to detect peak lesion attenuation to enable differentiation of clear cell renal cell carcinoma (ccRCC) from chromophobe RCC (chRCC), papillary RCC (pRCC), oncocytoma, and fat-poor angiomyolipoma (fp-AML). We queried our clinical databases to obtain a cohort of histologically proven renal masses with preoperative MDCT with four phases [unenhanced (U), corticomedullary (CM), nephrographic (NP), and excretory (E)]. A whole lesion 3D contour was obtained in all four phases. The CAD algorithm determined a region of interest (ROI) of peak lesion attenuation within the 3D lesion contour. For comparison, a manual ROI was separately placed in the most enhancing portion of the lesion by visual inspection for a reference standard, and in uninvolved renal cortex. Relative lesion attenuation for both CAD and manual methods was obtained by normalizing the CAD peak lesion attenuation ROI (and the reference standard manually placed ROI) to uninvolved renal cortex with the formula [(peak lesion attenuation ROI - cortex ROI)/cortex ROI] × 100%. ROC analysis and area under the curve (AUC) were used to assess diagnostic performance. Bland-Altman analysis was used to compare peak ROI between CAD and manual method. The study cohort comprised 200 patients with 200 unique renal masses: 106 (53%) ccRCC, 32 (16%) oncocytomas, 18 (9%) chRCCs, 34 (17%) pRCCs, and 10 (5%) fp-AMLs. In the CM phase, CAD-derived ROI enabled characterization of ccRCC from chRCC, pRCC, oncocytoma, and fp-AML with AUCs of 0.850 (95% CI 0.732-0.968), 0.959 (95% CI 0.930-0.989), 0.792 (95% CI 0.716-0.869), and 0.825 (95% CI 0.703-0.948), respectively. On Bland-Altman analysis, there was excellent agreement of CAD and manual methods with mean differences between 14 and 26 HU in each phase. A novel, quantitative CAD algorithm enabled robust peak HU lesion detection

Prognostic Value of Quantitative Metabolic Metrics on Baseline Pre-Sunitinib FDG PET/CT in Advanced Renal Cell Carcinoma

PubMed Central

Minamimoto, Ryogo; Barkhodari, Amir; Harshman, Lauren; Srinivas, Sandy; Quon, Andrew

2016-01-01

Purpose The objective of this study was to prospectively evaluate various quantitative metrics on FDG PET/CT for monitoring sunitinib therapy and predicting prognosis in patients with metastatic renal cell cancer (mRCC). Methods Seventeen patients (mean age: 59.0 ± 11.6) prospectively underwent a baseline FDG PET/CT and interim PET/CT after 2 cycles (12 weeks) of sunitinib therapy. We measured the highest maximum standardized uptake value (SUVmax) of all identified lesions (highest SUVmax), sum of SUVmax with maximum six lesions (sum of SUVmax), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) from baseline PET/CT and interim PET/CT, and the % decrease in highest SUVmax of lesion (%Δ highest SUVmax), the % decrease in sum of SUVmax, the % decrease in TLG (%ΔTLG) and the % decrease in MTV (%ΔMTV) between baseline and interim PET/CT, and the imaging results were validated by clinical follow-up at 12 months after completion of therapy for progression free survival (PFS). Results At 12 month follow-up, 6/17 (35.3%) patients achieved PFS, while 11/17 (64.7%) patients were deemed to have progression of disease or recurrence within the previous 12 months. At baseline, PET/CT demonstrated metabolically active cancer in all cases. Using baseline PET/CT alone, all of the quantitative imaging metrics were predictive of PFS. Using interim PET/CT, the %Δ highest SUVmax, %Δ sum of SUVmax, and %ΔTLG were also predictive of PFS. Otherwise, interim PET/CT showed no significant difference between the two survival groups regardless of the quantitative metric utilized including MTV and TLG. Conclusions Quantitative metabolic measurements on baseline PET/CT appears to be predictive of PFS at 12 months post-therapy in patients scheduled to undergo sunitinib therapy for mRCC. Change between baseline and interim PET/CT also appeared to have prognostic value but otherwise interim PET/CT after 12 weeks of sunitinib did not appear to be predictive of PFS. PMID:27123976

Quantitative Live Imaging of Human Embryonic Stem Cell Derived Neural Rosettes Reveals Structure-Function Dynamics Coupled to Cortical Development.

PubMed

Ziv, Omer; Zaritsky, Assaf; Yaffe, Yakey; Mutukula, Naresh; Edri, Reuven; Elkabetz, Yechiel

2015-10-01

Neural stem cells (NSCs) are progenitor cells for brain development, where cellular spatial composition (cytoarchitecture) and dynamics are hypothesized to be linked to critical NSC capabilities. However, understanding cytoarchitectural dynamics of this process has been limited by the difficulty to quantitatively image brain development in vivo. Here, we study NSC dynamics within Neural Rosettes--highly organized multicellular structures derived from human pluripotent stem cells. Neural rosettes contain NSCs with strong epithelial polarity and are expected to perform apical-basal interkinetic nuclear migration (INM)--a hallmark of cortical radial glial cell development. We developed a quantitative live imaging framework to characterize INM dynamics within rosettes. We first show that the tendency of cells to follow the INM orientation--a phenomenon we referred to as radial organization, is associated with rosette size, presumably via mechanical constraints of the confining structure. Second, early forming rosettes, which are abundant with founder NSCs and correspond to the early proliferative developing cortex, show fast motions and enhanced radial organization. In contrast, later derived rosettes, which are characterized by reduced NSC capacity and elevated numbers of differentiated neurons, and thus correspond to neurogenesis mode in the developing cortex, exhibit slower motions and decreased radial organization. Third, later derived rosettes are characterized by temporal instability in INM measures, in agreement with progressive loss in rosette integrity at later developmental stages. Finally, molecular perturbations of INM by inhibition of actin or non-muscle myosin-II (NMII) reduced INM measures. Our framework enables quantification of cytoarchitecture NSC dynamics and may have implications in functional molecular studies, drug screening, and iPS cell-based platforms for disease modeling.

Laparoscopic partial nephrectomy for hilar tumors: oncologic and renal functional outcomes.

PubMed

George, Arvin K; Herati, Amin S; Rais-Bahrami, Soroush; Waingankar, Nikhil; Kavoussi, Louis R

2014-01-01

To present our experience with laparoscopic partial nephrectomy (LPN) for hilar tumors and evaluate intermediate oncologic and renal functional outcomes. A retrospective review of LPN cases performed in 488 patients was performed. Hilar lesions were defined as renal cortical tumors in direct physical contact with the renal artery, vein, or both, as identified on preoperative imaging and confirmed intraoperatively. The clinicopathologic parameters, perioperative course, complications, and oncologic and 6-month renal functional outcomes were analyzed. A total of 488 patients underwent LPN, of which 43 were hilar. The mean tumor size for hilar and nonhilar tumors was 3.6 cm and 3.1 cm, respectively. The mean operative time was shorter for hilar as compared with nonhilar tumors (129.1 minutes vs 141.8 minutes). Mean estimated blood loss was greater in LPN for hilar tumors (311.65 mL vs 298.4 mL). There were no statistically significant differences noted in any of the perioperative parameters investigated despite a higher nephrometry complexity score in the hilar group. Change in estimated glomerular filtration rate at 6 months showed a decrease of 10.9 mL/min and 8.8 mL/min for hilar and nonhilar tumors, respectively (P = NS). There was 1 recurrence detected in the hilar group, with a median follow-up of 41.6 months. In the hands of an experienced laparoscopist, LPN can safely be performed for hilar tumors, with preservation of perioperative outcomes and durable renal functional and oncologic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Visualizing and quantifying the in vivo structure and dynamics of the Arabidopsis cortical cytoskeleton using CLSM and VAEM.

PubMed

Rosero, Amparo; Zárský, Viktor; Cvrčková, Fatima

2014-01-01

The cortical microtubules, and to some extent also the actin meshwork, play a central role in the shaping of plant cells. Transgenic plants expressing fluorescent protein markers specifically tagging the two main cytoskeletal systems are available, allowing noninvasive in vivo studies. Advanced microscopy techniques, in particular confocal laser scanning microscopy (CLSM) and variable angle epifluorescence microscopy (VAEM), can be nowadays used for imaging the cortical cytoskeleton of living cells with unprecedented spatial and temporal resolution. With the aid of suitable computing techniques, quantitative information can be extracted from microscopic images and video sequences, providing insight into both architecture and dynamics of the cortical cytoskeleton.

Discovering Cortical Folding Patterns in Neonatal Cortical Surfaces Using Large-Scale Dataset

PubMed Central

Meng, Yu; Li, Gang; Wang, Li; Lin, Weili; Gilmore, John H.

2017-01-01

The cortical folding of the human brain is highly complex and variable across individuals. Mining the major patterns of cortical folding from modern large-scale neuroimaging datasets is of great importance in advancing techniques for neuroimaging analysis and understanding the inter-individual variations of cortical folding and its relationship with cognitive function and disorders. As the primary cortical folding is genetically influenced and has been established at term birth, neonates with the minimal exposure to the complicated postnatal environmental influence are the ideal candidates for understanding the major patterns of cortical folding. In this paper, for the first time, we propose a novel method for discovering the major patterns of cortical folding in a large-scale dataset of neonatal brain MR images (N = 677). In our method, first, cortical folding is characterized by the distribution of sulcal pits, which are the locally deepest points in cortical sulci. Because deep sulcal pits are genetically related, relatively consistent across individuals, and also stable during brain development, they are well suitable for representing and characterizing cortical folding. Then, the similarities between sulcal pit distributions of any two subjects are measured from spatial, geometrical, and topological points of view. Next, these different measurements are adaptively fused together using a similarity network fusion technique, to preserve their common information and also catch their complementary information. Finally, leveraging the fused similarity measurements, a hierarchical affinity propagation algorithm is used to group similar sulcal folding patterns together. The proposed method has been applied to 677 neonatal brains (the largest neonatal dataset to our knowledge) in the central sulcus, superior temporal sulcus, and cingulate sulcus, and revealed multiple distinct and meaningful folding patterns in each region. PMID:28229131

Renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions: findings on MRI and computed tomography imaging.

PubMed

Liu, Kefu; Xie, Ping; Peng, Weijun; Zhou, Zhengrong

2014-08-01

To retrospectively analyze MRI and computed tomographic (CT) findings from renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions (Xp11-RCC). Institutional review board permission was obtained to review patient medical records, and the requirement for informed consent was waved . The clinical and MRI/CT features of five cases with Xp11-RCC that were confirmed by pathology were analyzed retrospectively. The image characteristics included the lesion location and size, contribution of cystic and solid components, intratumoral necrosis or hemorrhage, invasion of perinephric tissue and renal sinus, lymphadenopathy, major venous or arterial vascular invasion, pattern of the tumor growth, intratumor calcification and lipids, homogeneity of SI on T2-weighted images, attenuation and SI of the mass with respect to the normal renal cortex on precontrast and contrasted CT/MRI images, tumor SIs, tumor attenuations and tumor-to-cortex indices, homogeneity of enhancement on the contrasted images. The mean age was 32 years (range, 15-47 years). Most patients (4/5) were women. All tumors showed a cortical location. The average tumor size was 9 cm (range, 4-18 cm). Four tumors comprised a predominantly solid lesion with focal necrosis, and one tumor comprised a solid lesion with significant necrosis. All tumors showed intertumor hemorrhage, infiltrative growth and invasion of the perirenal adipose/renal sinus. Four cases showed retroperitoneal lymphadenopathy, of which one case showed simultaneous mediastinal and supraclavicular lymphadenopathy. All tumors from four cases showed mild hyperintensity on T1-weighted MRI images, and three tumors showed hypointensity on T2-weighted MRI images relative to the renal cortex except for 1 tumor that showed significant hemorrhage and a relative hyperintensity. For 3 cases who were imaged with CT, two tumors imaged using nonenhanced CT images showed mild hyperdensity relative to the renal cortex. Calcification was noted in all

The impact of systemic cortical alterations on perception

NASA Astrophysics Data System (ADS)

Zhang, Zheng

2011-12-01

Perception is the process of transmitting and interpreting sensory information, and the primary somatosensory (SI) area in the human cortex is the main sensory receptive area for the sensation of touch. The elaborate neuroanatomical connectivity that subserves the neuronal communication between adjacent and near-adjacent regions within sensory cortex has been widely recognized to be essential to normal sensory function. As a result, systemic cortical alterations that impact the cortical regional interaction, as associated with many neurological disorders, are expected to have significant impact on sensory perception. Recently, our research group has developed a novel sensory diagnostic system that employs quantitative sensory testing methods and is able to non-invasively assess central nervous system healthy status. The intent of this study is to utilize quantitative sensory testing methods that were designed to generate discriminable perception to objectively and quantitatively assess the impacts of different conditions on human sensory information processing capacity. The correlation between human perceptions with observations from animal research enables a better understanding of the underlying neurophysiology of human perception. Additional findings on different subject populations provide valuable insight of the underlying mechanisms for the development and maintenance of different neurological diseases. During the course of the study, several protocols were designed and utilized. And this set of sensory-based perceptual metrics was employed to study the effects of different conditions (non-noxious thermal stimulation, chronic pain stage, and normal aging) on sensory perception. It was found that these conditions result in significant deviations of the subjects' tactile information processing capacities from normal values. Although the observed shift of sensory detection sensitivity could be a result of enhanced peripheral activity, the changes in the effects

Micromechanical modeling of elastic properties of cortical bone accounting for anisotropy of dense tissue.

PubMed

Salguero, Laura; Saadat, Fatemeh; Sevostianov, Igor

2014-10-17

The paper analyzes the connection between microstructure of the osteonal cortical bone and its overall elastic properties. The existing models either neglect anisotropy of the dense tissue or simplify cortical bone microstructure (accounting for Haversian canals only). These simplifications (related mostly to insufficient mathematical apparatus) complicate quantitative analysis of the effect of microstructural changes - produced by age, microgravity, or some diseases - on the overall mechanical performance of cortical bone. The present analysis fills this gap; it accounts for anisotropy of the dense tissue and uses realistic model of the porous microstructure. The approach is based on recent results of Sevostianov et al. (2005) and Saadat et al. (2012) on inhomogeneities in a transversely-isotropic material. Bone's microstructure is modeled according to books of Martin and Burr (1989), Currey (2002), and Fung (1993) and includes four main families of pores. The calculated elastic constants for porous cortical bone are in agreement with available experimental data. The influence of each of the pore types on the overall moduli is examined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparing the influence of crestal cortical bone and sinus floor cortical bone in posterior maxilla bi-cortical dental implantation: a three-dimensional finite element analysis.

PubMed

Yan, Xu; Zhang, Xinwen; Chi, Weichao; Ai, Hongjun; Wu, Lin

2015-05-01

This study aimed to compare the influence of alveolar ridge cortical bone and sinus floor cortical bone in sinus areabi-cortical dental implantation by means of 3D finite element analysis. Three-dimensional finite element (FE) models in a posterior maxillary region with sinus membrane and the same height of alveolar ridge of 10 mm were generated according to the anatomical data of the sinus area. They were either with fixed thickness of crestal cortical bone and variable thickness of sinus floor cortical bone or vice versa. Ten models were assumed to be under immediate loading or conventional loading. The standard implant model based on the Nobel Biocare implant system was created via computer-aided design software. All materials were assumed to be isotropic and linearly elastic. An inclined force of 129 N was applied. Von Mises stress mainly concentrated on the surface of crestal cortical bone around the implant neck. For all the models, both the axial and buccolingual resonance frequencies of conventional loading were higher than those of immediate loading; however, the difference is less than 5%. The results showed that bi-cortical implant in sinus area increased the stability of the implant, especially for immediately loading implantation. The thickness of both crestal cortical bone and sinus floor cortical bone influenced implant micromotion and stress distribution; however, crestal cortical bone may be more important than sinus floor cortical bone.

Low cortical iron and high entorhinal cortex volume promote cognitive functioning in the oldest-old.

PubMed

van Bergen, Jiri M G; Li, Xu; Quevenco, Frances C; Gietl, Anton F; Treyer, Valerie; Leh, Sandra E; Meyer, Rafael; Buck, Alfred; Kaufmann, Philipp A; Nitsch, Roger M; van Zijl, Peter C M; Hock, Christoph; Unschuld, Paul G

2018-04-01

The aging brain is characterized by an increased presence of neurodegenerative and vascular pathologies. However, there is substantial variation regarding the relationship between an individual's pathological burden and resulting cognitive impairment. To identify correlates of preserved cognitive functioning at highest age, the relationship between β-amyloid plaque load, presence of small vessel cerebrovascular disease (SVCD), iron-burden, and brain atrophy was investigated. Eighty cognitively unimpaired participants (44 oldest-old, aged 85-96 years; 36 younger-old, aged 55-80 years) were scanned by integrated positron emission tomography-magnetic resonance imaging for assessing beta regional amyloid plaque load (18F-flutemetamol), white matter hyperintensities as an indicator of SVCD (fluid-attenuated inversion recovery-magnetic resonance imaging), and iron load (quantitative susceptibility mapping). For the oldest-old group, lower cortical volume, increased β-amyloid plaque load, prevalence of SVCD, and lower cognitive performance in the normal range were found. However, compared to normal-old, cortical iron burden was lower in the oldest-old. Moreover, only in the oldest-old, entorhinal cortex volume positively correlated with β-amyloid plaque load. Our data thus indicate that the co-occurrence of aging-associated neuropathologies with reduced quantitative susceptibility mapping measures of cortical iron load constitutes a lower vulnerability to cognitive loss. Copyright © 2017 Elsevier Inc. All rights reserved.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

Evaluation of Renal Blood Flow and Oxygenation in CKD Using Magnetic Resonance Imaging.

PubMed

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

2015-09-01

Animal studies suggest that progression of chronic kidney disease (CKD) is related to renal hypoxia. With renal blood supply determining oxygen delivery and sodium absorption being the main contributor to oxygen consumption, we describe the relationship between renal oxygenation, renal artery blood flow, and sodium absorption in patients with CKD and healthy controls. Cross-sectional study. 62 stable patients with CKD stages 3 to 4 (mean age, 61±13 [SD] years) and 24 age- and sex-matched controls. CKD versus control status. Renal artery blood flow, tissue oxygenation (relative changes in deoxyhemoglobin concentration of the renal medulla [MR2*] and cortex [CR2*]), and sodium absorption. Renal artery blood flow was determined by phase-contrast magnetic resonance imaging (MRI); MR2* and CR2* were determined by blood oxygen level-dependent MRI. Ultrafiltered and reabsorbed sodium were determined from measured glomerular filtration rate (mGFR) and 24-hour urine collections. mGFR in patients was 37% that of controls (36±15 vs 97±23 mL/min/1.73 m(2); P < 0.001), and reabsorbed sodium was 37% that of controls (6.9 vs 19.1 mol/24 h; P < 0.001). Single-kidney patient renal artery blood flow was 72% that of controls (319 vs 443 mL/min; P < 0.001). Glomerular filtration fraction was 9% in patients and 18% in controls (P < 0.001). Patients and controls had similar CR2* (13.4 vs 13.3 s(-1)) and medullary MR2* (26.4 vs 26.5 s(-1)) values. Linear regression analysis demonstrated no associations between R2* and renal artery blood flow or sodium absorption. Increasing arterial blood oxygen tension by breathing 100% oxygen had very small effects on CR2*, but reduced MR2* in both groups. Only renal artery blood flow was determined and thus regional perfusion could not be related to CR2* or MR2*. In CKD, reductions of mGFR and reabsorbed sodium are more than double that of renal artery blood flow, whereas cortical and medullary oxygenation are within the range of healthy persons

A Circuit for Motor Cortical Modulation of Auditory Cortical Activity

PubMed Central

Nelson, Anders; Schneider, David M.; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan

2013-01-01

Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

PubMed Central

Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J.; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

2016-01-01

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

Injury to the Premature Cerebellum: Outcome is Related to Remote Cortical Development

PubMed Central

Limperopoulos, Catherine; Chilingaryan, Gevorg; Sullivan, Nancy; Guizard, Nicolas; Robertson, Richard L.; du Plessis, Adré J.

2014-01-01

Cerebellar injury is an important complication of preterm birth with far-reaching neuropsychiatric sequelae. We have previously shown a significant association between isolated injury to the premature cerebellum and subsequent impairment of regional volumetric growth in the contralateral cerebrum. In the current study, we examine the relationship between these remote regional impairments of cerebral volumetric growth and domain-specific functional deficits in these children. In 40 ex-preterm infants with isolated cerebellar injury, we performed neurodevelopmental evaluations and quantitative magnetic resonance imaging (MRI) studies at a mean age of 34 months. We measured cortical gray matter volumes in 8 parcellated regions of each cerebral hemisphere, as well as right and left cerebellar volumes. We show highly significant associations between early signs of autism and dorsolateral prefrontal cortex volume (P < 0.001); gross motor scores and sensorimotor cortical volumes (P < 0.001); and cognitive and expressive language scores and premotor and mid-temporal cortical volumes (P < 0.001). By multivariate analyses, each unit increase in the corresponding regional cerebral volume was associated with lower odds of abnormal outcome score, adjusted for age at MRI and contralateral cerebellar volume. This is the first report linking secondary impairment of remote cerebral cortical growth and functional disabilities in survivors of prematurity-related cerebellar brain injury. PMID:23146968

Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs

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

Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de

Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blotmore » analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. - Highlights: • Rab3A has a similar migration pattern to cortical granules in mouse oocytes. • Rab3A can be a

Phonetically Irregular Word Pronunciation and Cortical Thickness in the Adult Brain

PubMed Central

Blackmon, Karen; Barr, William B.; Kuzniecky, Ruben; DuBois, Jonathan; Carlson, Chad; Quinn, Brian T.; Blumberg, Mark; Halgren, Eric; Hagler, Donald J.; Mikhly, Mark; Devinsky, Orrin; McDonald, Carrie R.; Dale, Anders M.; Thesen, Thomas

2010-01-01

Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTAR), is associated with regional variations in cortical structure. A sample of 60 right-handed, neurologically intact individuals were administered the WTAR and underwent 3T volumetric MRI. Using quantitative, surface-based image analysis, cortical thickness was estimated at each vertex on the cortical mantle and correlated with WTAR scores while controlling for age. Higher scores on the WTAR were associated with thicker cortex in bilateral anterior superior temporal gyrus, bilateral angular gyrus/posterior superior temporal gyrus, and left hemisphere intraparietal sulcus. Higher scores were also associated with thinner cortex in left hemisphere posterior fusiform gyrus and central sulcus, bilateral inferior frontal gyrus, and right hemisphere lingual gyrus and supramarginal gyrus. These results suggest that the ability to correctly pronounce phonetically irregular words is associated with structural variations in cortical areas that are commonly activated in functional neuroimaging studies of word reading, including areas associated with grapheme-to–phonemic conversion. PMID:20302944

Predictive factors for renal failure and a control and treatment algorithm

PubMed Central

Cerqueira, Denise de Paula; Tavares, José Roberto; Machado, Regimar Carla

2014-01-01

Objectives to evaluate the renal function of patients in an intensive care unit, to identify the predisposing factors for the development of renal failure, and to develop an algorithm to help in the control of the disease. Method exploratory, descriptive, prospective study with a quantitative approach. Results a total of 30 patients (75.0%) were diagnosed with kidney failure and the main factors associated with this disease were: advanced age, systemic arterial hypertension, diabetes mellitus, lung diseases, and antibiotic use. Of these, 23 patients (76.6%) showed a reduction in creatinine clearance in the first 24 hours of hospitalization. Conclusion a decline in renal function was observed in a significant number of subjects, therefore, an algorithm was developed with the aim of helping in the control of renal failure in a practical and functional way. PMID:26107827

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.

[Pathologic changes and expression of Heme oxygenase-1 in paraquat-induced renal injury].

PubMed

Tian, Ying-ping; Liu, Fu-rong; Tong, Fei; Shi, Han-wen; Yao, Dong-qi

2009-08-01

To study the mechanism of paraquat-induced renal injury in rats. Adult healthy Sprague-Dawley (SD) rats (female and male in half) were randomly divided into two groups, the control group and the paraquat poisoned group. The rats in the paraquat poisoned group were treated with PQ (25 mg/kg) intraperitoneally while the rats in the control group were treated with the same dose of normal saline. Its histopathological change was observed and the expression of HO-1 and the mRNA expression of HO-1 were detected by RT-PCR at 3rd h, 6th h, 12th h, on 1st d, 2nd d, 3rd d and 5th d. (1) In the control group, the tissue structure was clear without edema, vacuolar degeneration, cloudy swelling and necrosis. In the paraquat poisoned group, there were obvious lesions in the renal tubule of cortical part, including cellular swelling, the narrow cannula, the mesenchymal congestion and edema. These pathologic changes gradually became more severe, reached the peak on the 1st day, and did not relieve until the end of this study; there was the karyopyknosis and the cyto-architecture disappeared in some severe cases; Some glomerulus and medulla were also involved. (2) In the control group, there was no or weak expression of HO-1 and HO-1 mRNA. At the 3rd hour, the expressions of HO-1 in the paraquat poisoned group were observed in the membrane and cytoplasm of renal tubular epithelial cell of cortical part. Immunohistochemistry score (IHS) in the paraquat poisoned group was higher than that in the control group (P<0.05), except the HIS of the 5th day. At the 3rd hour, the expression of HO-1 mRNA increased, reached the peak on the 1st day, and then decreased. The expression of HO-1 mRNA was (0.53 +/- 0.21), (0.55 +/- 0.31), (0.56 +/- 0.22), (0.64 +/- 0.14) and (0.43 +/- 0.25) at the time point other than on the 3rd and 5th day. It showed statistical difference between the paraquat poisoned group and the control group from the 3rd hour to the 2nd day (P<0.05). The mechanism of paraquat

Renal arteriography

MedlinePlus

Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... an artery by a blood clot Renal artery stenosis Renal cell cancer Angiomyolipomas (noncancerous tumors of the ...

High sensitive volumetric imaging of renal microcirculation in vivo using ultrahigh sensitive optical microangiography

NASA Astrophysics Data System (ADS)

Zhi, Zhongwei; Jung, Yeongri; Jia, Yali; An, Lin; Wang, Ruikang K.

2011-03-01

We present a non-invasive, label-free imaging technique called Ultrahigh Sensitive Optical Microangiography (UHSOMAG) for high sensitive volumetric imaging of renal microcirculation. The UHS-OMAG imaging system is based on spectral domain optical coherence tomography (SD-OCT), which uses a 47000 A-line scan rate CCD camera to perform an imaging speed of 150 frames per second that takes only ~7 seconds to acquire a 3D image. The technique, capable of measuring slow blood flow down to 4 um/s, is sensitive enough to image capillary networks, such as peritubular capillaries and glomerulus within renal cortex. We show superior performance of UHS-OMAG in providing depthresolved volumetric images of rich renal microcirculation. We monitored the dynamics of renal microvasculature during renal ischemia and reperfusion. Obvious reduction of renal microvascular density due to renal ischemia was visualized and quantitatively analyzed. This technique can be helpful for the assessment of chronic kidney disease (CKD) which relates to abnormal microvasculature.

Noncontact ultrasound imaging applied to cortical bone phantoms

PubMed Central

Bulman, J. B.; Ganezer, K. S.; Halcrow, P. W.; Neeson, Ian

2012-01-01

Purpose: The purpose of this paper was to take the first steps toward applying noncontact ultrasound (NCU) to the tasks of monitoring osteoporosis and quantitative ultrasound imaging (QUS) of cortical bone. The authors also focused on the advantages of NCU, such as its lack of reliance on a technologist to apply transducers and a layer of acoustical coupling gel, the ability of the transducers to operate autonomously as specified by preprogrammed software, and the likely reduction in statistical and systematic errors associated with the variability in the pressure applied by the clinician to the transmitting transducer that NCU might provide. The authors also undertook this study in order to find additional applications of NCU beyond its past limited usage in assessing the severity of third degree burns. Methods: A noncontact ultrasound imaging system using a pair of specially designed broadband, 1.5 MHz noncontact piezoelectric transducers and cortical bone phantoms, were used to determine bone mineral density (BMD), speed of sound (SOS), integrated response (IR), and ultrasonic transmittance. Air gaps of greater than 3 cm, two transmission and two reflection paths, and a digital signal processor were also used in the collection of data from phantoms of nominal mass densities that varied from 1.17 to 2.25 g/cm3 and in bone mineral density from 0 to 1.7 g/cm3. Results: Good correlations between known BMD and measured SOS, IR, and transmittance were obtained for all 17 phantoms, and methods for quantifying and minimizing sources of systematic errors were outlined. The BMD of the phantom sets extended through most of the in vivo range found in cortical bone. A total of 16–20 repeated measurements of the SOS, thickness, and IR for the phantom set that were conducted over a period of several months showed a small variation in the range of measurements of ±1%–2%. These NCU data were shown to be in agreement with similar results using contact ultrasound to be within

Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

PubMed

Bergner, R; Siegrist, B; Gretz, N; Pohlmeyer-Esch, G; Kränzlin, B

2015-09-01

A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Impact of Lesion Placement on Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation.

PubMed

Mahfoud, Felix; Tunev, Stefan; Ewen, Sebastian; Cremers, Bodo; Ruwart, Jennifer; Schulz-Jander, Daniel; Linz, Dominik; Davies, Justin; Kandzari, David E; Whitbourn, Robert; Böhm, Michael; Melder, Robert J

2015-10-20

Insufficient procedural efficacy has been proposed to explain nonresponse to renal denervation (RDN). The aim of this study was to examine the impact of different patterns of lesion placements on the efficacy and consistency of catheter-based radiofrequency RDN in pigs. The impact of increasing number of lesions versus location of RDN was investigated in a porcine model (Group 1; n = 51). The effect of treating the main artery, the branches, and the 2 combined was compared in Group 2 (n = 48). The durability of response and safety of combined treatment of the main artery plus branches was examined in Group 3 (n = 16). Renal norepinephrine (NE) tissue content and renal cortical axon density were assessed. Increasing the number of RF lesions (4, 8, and 12) in the main renal artery was not sufficient to yield a clear dose-response relationship on NE content and axon density. In contrast, targeted treatment of the renal artery branches or distal segment of the main renal artery resulted in markedly less variability of response and significantly greater reduction of both NE and axon density than conventional treatment of only the main renal artery. Combination treatment (main artery plus branches) produced the greatest change in renal NE and axon density with the least heterogeneity. The changes were durable through 28 days post-treatment. These data provide the rationale for investigation of an optimized approach for RDN in future clinical studies. This may have profound implications for the clinical application of RDN, as this approach may not only achieve greater reductions in sympathetic activity but also reduce treatment effect variability. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Comparison of gray matter volume and thickness for analysis of cortical changes in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Liu, Jiachao; Li, Ziyi; Chen, Kewei; Yao, Li; Wang, Zhiqun; Li, Kunchen; Guo, Xiaojuan

2011-03-01

Gray matter volume and cortical thickness are two indices of concern in brain structure magnetic resonance imaging research. Gray matter volume reflects mixed-measurement information of cerebral cortex, while cortical thickness reflects only the information of distance between inner surface and outer surface of cerebral cortex. Using Scaled Subprofile Modeling based on Principal Component Analysis (SSM_PCA) and Pearson's Correlation Analysis, this study further provided quantitative comparisons and depicted both global relevance and local relevance to comprehensively investigate morphometrical abnormalities in cerebral cortex in Alzheimer's disease (AD). Thirteen patients with AD and thirteen age- and gender-matched healthy controls were included in this study. Results showed that factor scores from the first 8 principal components accounted for ~53.38% of the total variance for gray matter volume, and ~50.18% for cortical thickness. Factor scores from the fifth principal component showed significant correlation. In addition, gray matter voxel-based volume was closely related to cortical thickness alterations in most cortical cortex, especially, in some typical abnormal brain regions such as insula and the parahippocampal gyrus in AD. These findings suggest that these two measurements are effective indices for understanding the neuropathology in AD. Studies using both gray matter volume and cortical thickness can separate the causes of the discrepancy, provide complementary information and carry out a comprehensive description of the morphological changes of brain structure.

Correlates of Trabecular and Cortical Volumetric Bone Mineral Density of the Radius and Tibia in Older Men: The Osteoporotic Fractures in Men Study

PubMed Central

Barbour, Kamil E; Zmuda, Joseph M; Strotmeyer, Elsa S; Horwitz, Mara J; Boudreau, Robert; Evans, Rhobert W; Ensrud, Kristine E; Petit, Moira A; Gordon, Christopher L; Cauley, Jane A

2010-01-01

Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of vBMD in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men aged 69 to 97 years and enrolled in the Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (−), caffeine intake (−), total calcium intake (+), nontrauma fracture (−), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (−), education (+), diabetes with thiazolidinedione (TZD) use (+), rheumatoid arthritis (+), using arms to stand from a chair (−), and antiandrogen use (−) were associated only with trabecular vBMD. Factors associated only with cortical vBMD included clinic site (−), androgen use (+), grip strength (+), past smoker (−), and time to complete five chair stands (−). Certain correlates of trabecular and cortical vBMD differed among older men. An ascertainment of potential risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men. © 2010 American Society for Bone and Mineral Research. PMID:20200975

Quantitative analysis of microtubule orientation in interdigitated leaf pavement cells

PubMed Central

Akita, Kae; Higaki, Takumi; Kutsuna, Natsumaro; Hasezawa, Seiichiro

2015-01-01

Leaf pavement cells are shaped like a jigsaw puzzle in most dicotyledon species. Molecular genetic studies have identified several genes required for pavement cells morphogenesis and proposed that microtubules play crucial roles in the interdigitation of pavement cells. In this study, we performed quantitative analysis of cortical microtubule orientation in leaf pavement cells in Arabidopsis thaliana. We captured confocal images of cortical microtubules in cotyledon leaf epidermis expressing GFP-tubulinβ and quantitatively evaluated the microtubule orientations relative to the pavement cell growth axis using original image processing techniques. Our results showed that microtubules kept parallel orientations to the growth axis during pavement cell growth. In addition, we showed that immersion treatment of seed cotyledons in solutions containing tubulin polymerization and depolymerization inhibitors decreased pavement cell complexity. Treatment with oryzalin and colchicine inhibited the symmetric division of guard mother cells. PMID:26039484

Quantitative analysis of microtubule orientation in interdigitated leaf pavement cells.

PubMed

Akita, Kae; Higaki, Takumi; Kutsuna, Natsumaro; Hasezawa, Seiichiro

2015-01-01

Leaf pavement cells are shaped like a jigsaw puzzle in most dicotyledon species. Molecular genetic studies have identified several genes required for pavement cells morphogenesis and proposed that microtubules play crucial roles in the interdigitation of pavement cells. In this study, we performed quantitative analysis of cortical microtubule orientation in leaf pavement cells in Arabidopsis thaliana. We captured confocal images of cortical microtubules in cotyledon leaf epidermis expressing GFP-tubulinβ and quantitatively evaluated the microtubule orientations relative to the pavement cell growth axis using original image processing techniques. Our results showed that microtubules kept parallel orientations to the growth axis during pavement cell growth. In addition, we showed that immersion treatment of seed cotyledons in solutions containing tubulin polymerization and depolymerization inhibitors decreased pavement cell complexity. Treatment with oryzalin and colchicine inhibited the symmetric division of guard mother cells.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

PubMed

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation.

PubMed

de Jong, Mark R; Hoogerwaard, Annemiek F; Gal, Pim; Adiyaman, Ahmet; Smit, Jaap Jan J; Delnoy, Peter Paul H M; Ramdat Misier, Anand R; van Hasselt, Boudewijn A A M; Heeg, Jan-Evert; le Polain de Waroux, Jean-Benoit; Lau, Elizabeth O Y; Staessen, Jan A; Persu, Alexandre; Elvan, Arif

2016-06-01

Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing. This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation-induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation-induced systolic blood pressure increase was blunted in the main renal arteries (Δ systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (Δ systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability. © 2016 American Heart Association, Inc.

Crowdsourcing Assessment of Surgeon Dissection of Renal Artery and Vein During Robotic Partial Nephrectomy: A Novel Approach for Quantitative Assessment of Surgical Performance.

PubMed

Powers, Mary K; Boonjindasup, Aaron; Pinsky, Michael; Dorsey, Philip; Maddox, Michael; Su, Li-Ming; Gettman, Matthew; Sundaram, Chandru P; Castle, Erik P; Lee, Jason Y; Lee, Benjamin R

2016-04-01

We sought to describe a methodology of crowdsourcing for obtaining quantitative performance ratings of surgeons performing renal artery and vein dissection of robotic partial nephrectomy (RPN). We sought to compare assessment of technical performance obtained from the crowdsourcers with that of surgical content experts (CE). Our hypothesis is that the crowd can score performances of renal hilar dissection comparably to surgical CE using the Global Evaluative Assessment of Robotic Skills (GEARS). A group of resident and attending robotic surgeons submitted a total of 14 video clips of RPN during hilar dissection. These videos were rated by both crowd and CE for technical skills performance using GEARS. A minimum of 3 CE and 30 Amazon Mechanical Turk crowdworkers evaluated each video with the GEARS scale. Within 13 days, we received ratings of all videos from all CE, and within 11.5 hours, we received 548 GEARS ratings from crowdworkers. Even though CE were exposed to a training module, internal consistency across videos of CE GEARS ratings remained low (ICC = 0.38). Despite this, we found that crowdworker GEARS ratings of videos were highly correlated with CE ratings at both the video level (R = 0.82, p < 0.001) and surgeon level (R = 0.84, p < 0.001). Similarly, crowdworker ratings of the renal artery dissection were highly correlated with expert assessments (R = 0.83, p < 0.001) for the unique surgery-specific assessment question. We conclude that crowdsourced assessment of qualitative performance ratings may be an alternative and/or adjunct to surgical experts' ratings and would provide a rapid scalable solution to triage technical skills.

Chemokine receptors and cortical interneuron dysfunction in schizophrenia.

PubMed

Volk, David W; Chitrapu, Anjani; Edelson, Jessica R; Lewis, David A

2015-09-01

Alterations in inhibitory (GABA) neurons, including deficiencies in the GABA synthesizing enzyme GAD67, in the prefrontal cortex in schizophrenia are pronounced in the subpopulations of neurons that contain the calcium-binding protein parvalbumin or the neuropeptide somatostatin. The presence of similar illness-related deficits in the transcription factor Lhx6, which regulates prenatal development of parvalbumin and somatostatin neurons, suggests that cortical GABA neuron dysfunction may be related to disturbances in utero. Since the chemokine receptors CXCR4 and CXCR7 guide the migration of cortical parvalbumin and somatostatin neurons from their birthplace in the medial ganglionic eminence to their final destination in the neocortex, we sought to determine whether altered CXCR4 and/or CXCR7 mRNA levels were associated with disturbances in GABA-related markers in schizophrenia. Quantitative PCR was used to quantify CXCR4 and CXCR7 mRNA levels in the prefrontal cortex of 62 schizophrenia and 62 healthy comparison subjects that were previously characterized for markers of parvalbumin and somatostatin neurons and in antipsychotic-exposed monkeys. We found elevated mRNA levels for CXCR7 (+29%; p<.0001) and CXCR4 (+14%, p=.052) in schizophrenia subjects but not in antipsychotic-exposed monkeys. CXCR7 mRNA levels were inversely correlated with mRNA levels for GAD67, parvalbumin, somatostatin, and Lhx6 in schizophrenia but not in healthy subjects. These findings suggest that higher mRNA levels for CXCR7, and possibly CXCR4, may represent a compensatory mechanism to sustain the migration and correct positioning of cortical parvalbumin and somatostatin neurons in the face of other insults that disrupt the prenatal development of cortical GABA neurons in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Cortical orofacial motor representation in Old World monkeys, great apes, and humans. I. Quantitative analysis of cytoarchitecture.

PubMed

Sherwood, Chet C; Holloway, Ralph L; Erwin, Joseph M; Schleicher, Axel; Zilles, Karl; Hof, Patrick R

2004-01-01

Social life in anthropoid primates is mediated by interindividual communication, involving movements of the orofacial muscles for the production of vocalization and gestural expression. Although phylogenetic diversity has been reported in the auditory and visual communication systems of primates, little is known about the comparative neuroanatomy that subserves orofacial movement. The current study reports results from quantitative image analysis of the region corresponding to orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens) using the Grey Level Index method. This cortical region has been implicated in the execution of skilled motor activities such as voluntary facial expression and human speech. Density profiles of the laminar distribution of Nissl-stained neuronal somata were acquired from high-resolution images to quantify cytoarchitectural patterns. Despite general similarity in these profiles across catarrhines, multivariate analysis showed that cytoarchitectural patterns of individuals were more similar within-species versus between-species. Compared to Old World monkeys, the orofacial representation of area 4 in great apes and humans was characterized by an increased relative thickness of layer III and overall lower cell volume densities, providing more neuropil space for interconnections. These phylogenetic differences in microstructure might provide an anatomical substrate for the evolution of greater volitional fine motor control of facial expressions in great apes and humans. Copyright 2004 S. Karger AG, Basel

30-Second bound and pore water concentration mapping of cortical bone using 2D UTE with optimized half-pulses.

PubMed

Manhard, Mary Kate; Harkins, Kevin D; Gochberg, Daniel F; Nyman, Jeffry S; Does, Mark D

2017-03-01

MRI of cortical bone has the potential to offer new information about fracture risk. Current methods are typically performed with 3D acquisitions, which suffer from long scan times and are generally limited to extremities. This work proposes using 2D UTE with half pulses for quantitatively mapping bound and pore water in cortical bone. Half-pulse 2D UTE methods were implemented on a 3T Philips Achieva scanner using an optimized slice-select gradient waveform, with preparation pulses to selectively image bound or pore water. The 2D methods were quantitatively compared with previously implemented 3D methods in the tibia in five volunteers. The mean difference between bound and pore water concentration acquired from 3D and 2D sequences was 0.6 and 0.9 mol 1 H/L bone (3 and 12%, respectively). While 2D pore water methods tended to slightly overestimate concentrations relative to 3D methods, differences were less than scan-rescan uncertainty and expected differences between healthy and fracture-prone bones. Quantitative bound and pore water concentration mapping in cortical bone can be accelerated by 2 orders of magnitude using 2D protocols with optimized half-pulse excitation. Magn Reson Med 77:945-950, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

[Ultrasonographic study of blood flow in the renal arteries of patients with arterial hypertension].

PubMed

Makarenko, E S; Dombrovskiĭ, V I; Nelasov, N Iu

2012-01-01

Vascular duplex ultrasound duplex with simultaneous ECG registration was made to estimate the quantitative and time parameters of blood flow in the renal arteries with grade 1-2 arterial hypertension. There were increases in vascular resistance indices and acceleration phase index and a reduction in systolic phase index. There were correlations of the time parameters of blood flow in the renal arteries with age and lipidogram values.

Neural control of renal function: role of renal alpha adrenoceptors.

PubMed

DiBona, G F

1985-01-01

Adrenoceptors of various subtypes mediate the renal functional responses to alterations in efferent renal sympathetic nerve activity, the neural component, and renal arterial plasma catecholamine concentrations, the humoral component, of the sympathoadrenergic nervous system. Under normal physiologic as well as hypertensive conditions, the influence of the renal sympathetic nerves predominates over that of circulating plasma catecholamines. In most mammalian species, increases in efferent renal sympathetic nerve activity elicit renal vasoconstrictor responses mediated predominantly by renal vascular alpha-1 adrenoceptors, increases in renin release mediated largely by renal juxtaglomerular granular cell beta-1 adrenoceptors with involvement of renal vascular alpha-1 adrenoceptors only when renal vasoconstriction occurs, and direct increases in renal tubular sodium and water reabsorption mediated predominantly by renal tubular alpha-1 adrenoceptors. In most mammalian species, alpha-2 adrenoceptors do not play a significant role in the renal vascular or renin release responses to renal sympathoadrenergic stimulation. Although renal tubular alpha-2 adrenoceptors do not mediate the increases in renal tubular sodium and water reabsorption produced by increases in efferent renal sympathetic nerve activity, they may be involved through their inhibitory effect on adenylate cyclase in modulating the response to other hormonal agents that influence renal tubular sodium and water reabsorption via stimulation of adenylate cyclase.

Differences in Non-Enzymatic Glycation and Collagen Crosslinks between Human Cortical and Cancellous Bone

PubMed Central

Karim, Lamya; Tang, Simon Y.; Sroga, Grażyna E.; Vashishth, Deepak

2015-01-01

Purpose Accumulation of collagen crosslinks (advanced glycation end products [AGEs]) produced by non-enzymatic glycation deteriorates bone's mechanical properties and fracture resistance. Although a single AGE, pentosidine, is commonly used as a representative marker, it is unclear whether it quantitatively reflects total fluorescent AGEs in bone. The goal of this study was to establish the relationship between pentosidine and total AGEs in cancellous and cortical bone. Methods Pentosidine and total AGEs were quantified in 170 human bone samples. Total fluorescent AGEs were measured in 28 additional cancellous and cortical bone specimens of the same apparent volume that were incubated in control or in vitro glycation solutions. Correlations between pentosidine and total AGEs and differences between cortical and cancellous groups were determined. Results Pentosidine was correlated with total AGEs in cancellous bone (r=0.53, p<0.0001) and weakly correlated in cortical bone (r=0.23, p<0.05). There was more pentosidine (p<0.01) and total AGEs (p<0.001) in cancellous than in cortical bone. The in vitro glycation sub-study showed that cancellous bone accumulated more AGEs than cortical bone (p<0.05). Conclusion The relationship between pentosidine and total AGEs and their magnitude of accumulation differed in cancellous and cortical bone of the same apparent volume, and were dependent on the surface-to-volume ratios of each sample. It is important to consider the bone types as two separate entities, and it is crucial to quantify total AGEs in addition to pentosidine to allow for more comprehensive analysis of the effects of non-enzymatic glycation in bone. PMID:23471564

Adaptive changes in renal mitochondrial redox status in diabetic nephropathy

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

Putt, David A.; Zhong, Qing; Lash, Lawrence H., E-mail: l.h.lash@wayne.edu

2012-01-15

Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox statusmore » in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter. �

Atherosclerotic renal artery stenosis: epidemiology, cardiovascular outcomes, and clinical prediction rules.

PubMed

Zoccali, Carmine; Mallamaci, Francesca; Finocchiaro, Pietro

2002-11-01

Atherosclerotic renal artery stenosis is the most common primary disease of the renal arteries, and it is associated with two major clinical syndromes, ischemic renal disease and hypertension. The prevalence of this disease in the population is undefined because there is no simple and reliable test that can be applied on a large scale. Renal artery involvement in patients with coronary heart disease and/or heart failure is frequent, and it may influence cardiovascular outcomes and survival in these patients. Suspecting renal arterial stenosis in patients with recurrent episodes of pulmonary edema is justified by observations showing that about one third of elderly patients with heart failure display atherosclerotic renal disease. Whether interventions aimed at restoring arterial patency may reduce the high mortality in patients with heart failure is still unclear because, to date, no prospective study has been carried out in these patients. Increased awareness of the need for cost containment has renewed the interest in clinical cues for suspecting renovascular hypertension. In this regard, the DRASTIC study constitutes an important attempt at validating clinical prediction rules. In this study, a clinical rule was derived that predicted renal artery stenosis as efficiently as renal scintigraphy (sensitivity: clinical rule, 65% versus scintigraphy, 72%; specificity: 87% versus 92%). When tested in a systematic and quantitative manner, clinical findings can perform as accurately as more complex tests in the detection of renal artery stenosis.

Cortical relapses in multiple sclerosis.

PubMed

Puthenparampil, Marco; Poggiali, Davide; Causin, Francesco; Rolma, Giuseppe; Rinaldi, Francesca; Perini, Paola; Gallo, Paolo

2016-08-01

Multiple sclerosis (MS) is a white and grey matter disease of the central nervous system (CNS). It is recognized that cortical damage (i.e. focal lesions and atrophy) plays a role in determining the accumulation of physical and cognitive disability that is observed in patients with progressive MS. To date, an association of cortical lesions with clinical relapses has not been described. We report clinical and magnetic resonance imaging (MRI) findings of five relapsing-remitting MS (RRMS) patients who had clinical relapses characterized by the acute appearance of cortical symptoms, due to the development of large, snake-like, cortical inflammatory lesions. Symptoms were: acute Wernicke's aphasia mimicking stroke; agraphia with acalculia, not associated to a motor deficit nor linguistic disturbance; hyposthenia of the left arm, followed by muscle twitching of the hand, spreading to arm and face; acute onset of left lower limb paroxysmal hypertonia; and temporal lobe status epilepticus, with psychotic symptoms. Cortical relapses may occur in MS. MRI examination in MS should include sequences, such as double inversion recovery (DIR) or phase sensitive inversion recovery (PSIR), that are aimed at visualizing cortical lesions, especially in the presence of symptoms of cortical dysfunction. Our observation further stresses and extends the clinical relevance of cortical pathology in MS. © The Author(s), 2015.

Brain regions associated with cognitive impairment in patients with Parkinson disease: quantitative analysis of cerebral blood flow using 123I iodoamphetamine SPECT.

PubMed

Hattori, Naoya; Yabe, Ichiro; Hirata, Kenji; Shiga, Tohru; Sakushima, Ken; Tsuji-Akimoto, Sachiko; Sasaki, Hidenao; Tamaki, Nagara

2013-05-01

Cognitive impairment is a representative neuropsychiatric presentation that accompanies Parkinson disease (PD). The purpose of this study was to localize the cerebral regions associated with cognitive impairment in patients with PD using quantitative SPECT. Thirty-two patients with PD (mean [SD] age, 75 [8] years; 25 women; Hoehn-Yahr scores from 2 to 5) underwent quantitative brain SPECT using 123I iodoamphetamine. Parametric images of regional cerebral blood flow (rCBF) were spatially normalized to the standard brain atlas. First, voxel-by-voxel comparison between patients with PD with versus without cognitive impairment was performed to visualize overall trend of regional differences. Next, the individual quantitative rCBF values were extracted in representative cortical regions using a standard region-of-interest template to compare the quantitative rCBF values. Patients with cognitive impairment showed trends of lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices in the voxel-by-voxel analyses. Region-of-interest-based analysis demonstrated significantly lower rCBF in the bilateral anterior cingulate cortices (right, 25.8 [5.5] vs 28.9 [5.7] mL per 100 g/min, P < 0.05; left, 25.8 [5.8] vs 29.1 [5.7] mL per 100 g/min, P < 0.05) associated with cognitive impairment. Patients with cognitive impairment showed lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices. The results suggested dysexecutive function as an underlining mechanism of cognitive impairment in patients with PD.

Advantages of cortical surface reconstruction using submillimeter 7 T MEMPRAGE.

PubMed

Zaretskaya, Natalia; Fischl, Bruce; Reuter, Martin; Renvall, Ville; Polimeni, Jonathan R

2018-01-15

Recent advances in MR technology have enabled increased spatial resolution for routine functional and anatomical imaging, which has created demand for software tools that are able to process these data. The availability of high-resolution data also raises the question of whether higher resolution leads to substantial gains in accuracy of quantitative morphometric neuroimaging procedures, in particular the cortical surface reconstruction and cortical thickness estimation. In this study we adapted the FreeSurfer cortical surface reconstruction pipeline to process structural data at native submillimeter resolution. We then quantified the differences in surface placement between meshes generated from (0.75 mm) 3 isotropic resolution data acquired in 39 volunteers and the same data downsampled to the conventional 1 mm 3 voxel size. We find that when processed at native resolution, cortex is estimated to be thinner in most areas, but thicker around the Cingulate and the Calcarine sulci as well as in the posterior bank of the Central sulcus. Thickness differences are driven by two kinds of effects. First, the gray-white surface is found closer to the white matter, especially in cortical areas with high myelin content, and thus low contrast, such as the Calcarine and the Central sulci, causing local increases in thickness estimates. Second, the gray-CSF surface is placed more interiorly, especially in the deep sulci, contributing to local decreases in thickness estimates. We suggest that both effects are due to reduced partial volume effects at higher spatial resolution. Submillimeter voxel sizes can therefore provide improved accuracy for measuring cortical thickness. Copyright © 2017 Elsevier Inc. All rights reserved.

A knowledge-guided active model method of cortical structure segmentation on pediatric MR images.

PubMed

Shan, Zuyao Y; Parra, Carlos; Ji, Qing; Jain, Jinesh; Reddick, Wilburn E

2006-10-01

To develop an automated method for quantification of cortical structures on pediatric MR images. A knowledge-guided active model (KAM) approach was proposed with a novel object function similar to the Gibbs free energy function. Triangular mesh models were transformed to images of a given subject by maximizing entropy, and then actively slithered to boundaries of structures by minimizing enthalpy. Volumetric results and image similarities of 10 different cortical structures segmented by KAM were compared with those traced manually. Furthermore, the segmentation performances of KAM and SPM2, (statistical parametric mapping, a MATLAB software package) were compared. The averaged volumetric agreements between KAM- and manually-defined structures (both 0.95 for structures in healthy children and children with medulloblastoma) were higher than the volumetric agreement for SPM2 (0.90 and 0.80, respectively). The similarity measurements (kappa) between KAM- and manually-defined structures (0.95 and 0.93, respectively) were higher than those for SPM2 (both 0.86). We have developed a novel automatic algorithm, KAM, for segmentation of cortical structures on MR images of pediatric patients. Our preliminary results indicated that when segmenting cortical structures, KAM was in better agreement with manually-delineated structures than SPM2. KAM can potentially be used to segment cortical structures for conformal radiation therapy planning and for quantitative evaluation of changes in disease or abnormality. Copyright (c) 2006 Wiley-Liss, Inc.

Despite similar reduction of blood pressure and renal ANG II and ET-1 levels aliskiren but not losartan normalizes albuminuria in hypertensive Ren-2 rats.

PubMed

Vanourková, Z; Kramer, H J; Husková, Z; Cervenka, L; Vanecková, I

2010-01-01

The relationship between angiotensin II (ANG II) and endothelin-1 (ET-1) is known to be complex; both peptides can initiate and potentiate the gene expression of each other. This pilot study investigated the effects of the AT(1) receptor blocker losartan or the direct renin inhibitor aliskiren on mean arterial pressure (MAP) and albuminuria and the renal ANG II and ET-1 levels. 3-month-old male Ren-2 transgenic rats (TGR) were treated either with losartan (5 mg kg(-1) day(-1)) or aliskiren (10 mg kg(-1) day(-1)) for 10 weeks. At the end of the experiment, rats were decapitated and cortical and papillary parts of kidneys were separated. Plasma and tissue ANG II levels were measured by RIA and tissue ET-1 concentrations by ELISA. In all four groups of animals ET-1 levels were lowest in renal cortex and more than 100-fold higher in the papilla. Cortical and papillary ET-1 concentrations in untreated TGR significantly exceeded those of control HanSD rats and were significantly depressed by both drugs. In both strains, papillary ANG II concentrations were moderately but significantly higher than cortical ANG II, TGR exhibited higher ANG II levels both in cortex and papilla as compared to control HanSD rats. Aliskiren and losartan at the doses used depressed similarly the levels of ANG II in cortex and papilla and reduced ET-1 significantly in the renal cortex and papilla below control levels in HanSD rats. Albuminuria, which was more than twice as high in TGR as in HanSD rats, was normalized with aliskiren and reduced by 28% with losartan, although MAP was reduced to a similar degree by both drugs. Despite similar reductions of MAP and renal ET-1 and ANG II levels aliskiren appears to be more effective than losartan, at the doses used, in reducing albuminuria in heterozygous hypertensive Ren-2 rats.

Effect of electrocardiogram interference on cortico-cortical connectivity analysis and a possible solution.

PubMed

Govindan, R B; Kota, Srinivas; Al-Shargabi, Tareq; Massaro, An N; Chang, Taeun; du Plessis, Adre

2016-09-01

Electroencephalogram (EEG) signals are often contaminated by the electrocardiogram (ECG) interference, which affects quantitative characterization of EEG. We propose null-coherence, a frequency-based approach, to attenuate the ECG interference in EEG using simultaneously recorded ECG as a reference signal. After validating the proposed approach using numerically simulated data, we apply this approach to EEG recorded from six newborns receiving therapeutic hypothermia for neonatal encephalopathy. We compare our approach with an independent component analysis (ICA), a previously proposed approach to attenuate ECG artifacts in the EEG signal. The power spectrum and the cortico-cortical connectivity of the ECG attenuated EEG was compared against the power spectrum and the cortico-cortical connectivity of the raw EEG. The null-coherence approach attenuated the ECG contamination without leaving any residual of the ECG in the EEG. We show that the null-coherence approach performs better than ICA in attenuating the ECG contamination without enhancing cortico-cortical connectivity. Our analysis suggests that using ICA to remove ECG contamination from the EEG suffers from redistribution problems, whereas the null-coherence approach does not. We show that both the null-coherence and ICA approaches attenuate the ECG contamination. However, the EEG obtained after ICA cleaning displayed higher cortico-cortical connectivity compared with that obtained using the null-coherence approach. This suggests that null-coherence is superior to ICA in attenuating the ECG interference in EEG for cortico-cortical connectivity analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Glomerular loss after arteriovenous and arterial clamping for renal warm ischemia in a swine model.

PubMed

Bechara, Gustavo Ruschi; Damasceno-Ferreira, José Aurelino; Abreu, Leonardo Albuquerque Dos Santos; Costa, Waldemar Silva; Sampaio, Francisco José Barcellos; Pereira-Sampaio, Marco Aurélio; Souza, Diogo Benchimol De

2016-11-01

To evaluate the glomerular loss after arteriovenous or arterial warm ischemia in a swine model. Twenty four pigs were divided into Group Sham (submitted to all surgical steps except the renal ischemia), Group AV (submitted to 30 minutes of warm ischemia by arteriovenous clamping of left kidney vessels), and Group A (submitted to 30 minutes of ischemia by arterial clamping). Right kidneys were used as controls. Weigh, volume, cortical volume, glomerular volumetric density (Vv[Glom]), volume-weighted glomerular volume (VWGV), and the total number of glomeruli were measured for each organ. Group AV showed a 24.5% reduction in its left kidney Vv[Glom] and a 25.4% reduction in the VWGV, when compared to the right kidney. Reductions were also observed when compared to kidneys of sham group. There was a reduction of 19.2% in the total number of glomeruli in AV kidneys. No difference was observed in any parameters analyzed on the left kidneys from group A. Renal warm ischemia of 30 minutes by arterial clamping did not caused significant glomerular damage, but arteriovenous clamping caused significant glomerular loss in a swine model. Clamping only the renal artery should be considered to minimize renal injury after partial nephrectomies.

Role of TGF-β in a mouse model of high turnover renal osteodystrophy.

PubMed

Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

2014-01-01

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck

Comparison of the CMV brite turbo assay and the digene hybrid capture CMV DNA (Version 2.0) assay for quantitation of cytomegalovirus in renal transplant recipients.

PubMed

Ho, S K; Li, F K; Lai, K N; Chan, T M

2000-10-01

We compared the CMV Brite Turbo Kit (BT) and the Digene Hybrid Capture CMV DNA (version 2.0) assay (HC2) in the quantitation of pp65 antigenemia and cytomegalovirus (CMV) DNA levels in immunosuppressed renal transplant recipients. Of 123 blood specimens collected from 24 renal transplant recipients, BT and HC2 assays detected 35 and 39 positive samples, respectively. The overall concordance rate between the two assays was 90%. Discordant results were observed at low levels of viremia, so that 8 samples were HC2 positive but BT negative and another 4 were BT positive but HC2 negative. There was good correlation (R(2) = 0.766; P<0.01) between the levels of CMV DNA and pp65 antigenemia in the 31 concordant positive samples. Correlation between results obtained with the two assays was confirmed by longitudinal studies for a patient who developed clinical CMV disease. HC2 may be more sensitive at low viremia levels and allow earlier detection of impending CMV disease. The BT assay offered the advantage of a rapid (2-h) turnaround time. We conclude that BT and HC2 assays have similar sensitivity and efficacy in the diagnosis and monitoring of CMV infection and disease in renal transplant recipients. While the HC2 assay would be appropriate for centers that handle a large number of samples, the BT test may be more suitable for small sample numbers or when results are needed urgently.

Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors

PubMed Central

Ballesteros-Yáñez, Inmaculada; Benavides-Piccione, Ruth; Bourgeois, Jean-Pierre; Changeux, Jean-Pierre; DeFelipe, Javier

2010-01-01

The neuronal nicotinic acetylcholine receptors (nAChRs) are allosteric membrane proteins involved in multiple cognitive processes, including attention, learning, and memory. The most abundant form of heterooligomeric nAChRs in the brain contains the β2- and α4- subunits and binds nicotinic agonists with high affinity. In the present study, we investigated in the mouse the consequences of the deletion of one of the nAChR components: the β2-subunit (β2−/−) on the microanatomy of cortical pyramidal cells. Using an intracellular injection method, complete basal dendritic arbors of 650 layer III pyramidal neurons were sampled from seven cortical fields, including primary sensory, motor, and associational areas, in both β2−/− and WT animals. We observed that the pyramidal cell phenotype shows significant quantitative differences among different cortical areas in mutant and WT mice. In WT mice, the density of dendritic spines was rather similar in all cortical fields, except in the prelimbic/infralimbic cortex, where it was significantly higher. In the absence of the β2-subunit, the most significant reduction in the density of spines took place in this high-order associational field. Our data suggest that the β2-subunit is involved in the dendritic morphogenesis of pyramidal neurons and, in particular, in the circuits that contribute to the high-order functional connectivity of the cerebral cortex. PMID:20534523

Alzheimer disease: Quantitative analysis of I-123-iodoamphetamine SPECT brain imaging

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

Hellman, R.S.; Tikofsky, R.S.; Collier, B.D.

1989-07-01

To enable a more quantitative diagnosis of senile dementia of the Alzheimer type (SDAT), the authors developed and tested a semiautomated method to define regions of interest (ROIs) to be used in quantitating results from single photon emission computed tomography (SPECT) of regional cerebral blood flow performed with N-isopropyl iodine-123-iodoamphetamine. SPECT/IMP imaging was performed in ten patients with probable SDAT and seven healthy subjects. Multiple ROIs were manually and semiautomatically generated, and uptake was quantitated for each ROI. Mean cortical activity was estimated as the average of the mean activity in 24 semiautomatically generated ROIs; mean cerebellar activity was determinedmore » from the mean activity in separate ROIs. A ratio of parietal to cerebellar activity less than 0.60 and a ratio of parietal to mean cortical activity less than 0.90 allowed correct categorization of nine of ten and eight of ten patients, respectively, with SDAT and all control subjects. The degree of diminished mental status observed in patients with SDAT correlated with both global and regional changes in IMP uptake.« less

[Study on the role of the tubule in renal vasoconstriction induced by cyclosporine].

PubMed

Camaño Páez, S; Lázaro Fernández, A; Callejas Martínez, R; Lázaro Manero, J A; Castilla Barba, M; Martín-Vasallo, P; Martínez Escandell, A; Tejedor Jorge, A

2008-01-01

Cyclosporine (CyA) has proved to induce cell apoptosis on cultured proximal tubule cells. However, there is no much data about the in vivo functional consequences of this injury or the long time observed CyA-induced renal vasoconstriction. In a swine model of subacute CyA nephrotoxicity (10 mg/ Kg. dx 15 days), we performed a right nephrectomy, followed by left renal artery, vein and ureter catheterisati8n. After inducing water diuresis, three clearance periods of 15 minutes were performed before and after a furosemide 1 mg/kg infusion. Plasma and urine electrolytes, blood gas, acid excretion, plasma renin activity and aldosterone concentration, GFR, RPF, RBF, intra-renal vascular resistances, glomerular filtration pressure, distal Cl- delivery, water clearance and TTKG were measured or estimated on 7 control and 7 treated animals. Right kidney was processed for NaKATPase activity and immunostaining. Treated animals presented detaching proximal cells, luminal blebbing and loss of tight junctions. Cortical but not medullar sodium pump was internalised and partially inactive. Treated animals showed much lower fractional excretions of Na+, with significantly higher distal fractional reabsorption of Cl. Distal shift in fluid load resulted in a significant rise in renal O2 consumption, and modifications in the global renal estequiometry of Na+ transport/O2 uptake. Several consequences followed this situation: preglomerular resistances increased 3 times with only minor changes in postglomerular resistances and renal blood and plasma flow were significantly reduced. Furosemide partially reversed these effects. A slight increase in fractional filtration prevented GFR differences to become statistically significant. subacute CyA treatment even al doses not modifying GFR, may cause proximal tubule Na+ transport impairment, resulting in increased rates of distal delivery and absorption of fluid load. Renal uptake of O2 may be increased and tubule glomerular feedback should be

Significant impact of R.E.N.A.L. nephrometry score on changes in postoperative renal function early after robot-assisted partial nephrectomy.

PubMed

Miyake, Hideaki; Furukawa, Junya; Hinata, Nobuyuki; Muramaki, Mototsugu; Tanaka, Kazushi; Fujisawa, Masato

2015-06-01

Our objective was to evaluate the significance of the R.E.N.A.L. nephrometry score (RNS)--developed to quantitatively evaluate the complexity of renal tumors in a reproducible manner--in perioperative and renal functional outcomes following robot-assisted partial nephrectomy (RAPN). This study assessed 48 consecutive patients with renal tumors who underwent RAPN. Preoperative RNS for each patient was calculated, and its impact on several parameters associated with perioperative outcomes, including postoperative renal function, was investigated with Spearman's rank correlation test. Mean RNS in the 48 patients was 6.8; of these 48 patients, 21 (43.7%), 24 (50.0%), and three (6.3%) were classified into low-, moderate-, and high-complexity groups, respectively. The RNS was significantly correlated with resected tumor weight and postoperative changes in estimated glomerular filtration rate (eGFR) at both 1 and 4 weeks--but not age, body mass index (BMI), preoperative eGFR, operative time, warm ischemia time, estimated blood loss, postoperative complications, or eGFR-- after RAPN. No component of the RNS (R: radius; E: exophytic/endophytic properties; N: nearness of tumor to the collecting system or sinus; A: anterior/posterior; L: location relative to polar lines) alone had a significant impact on postoperative changes in eGFR at 1 and 4 weeks, whereas resected tumor weight was significantly associated with the R and E subcategories. Measurement of total RNS is useful for predicting renal functional outcomes early after RAPN.

Renal abnormalities among HIV infected children at Muhimbili National Hospital (MNH)-Dar es Salaam, Tanzania.

PubMed

Fredrick, Francis; Francis, Joel M; Ruggajo, Paschal J; Maro, Eden E

2016-03-21

Human Immunodeficiency Virus infection is a multisystem disease that contributes to significant morbidity. Renal involvement is reported to be common among patients with HIV. This study was carried out to determine renal involvement using simple bedside tests combined with ultrasonography examination. We recruited 240 children from the HIV clinic at Muhimbili National Hospital. Data were collected using structured questionnaires and included demographic, clinical information, radiological tests; renal ultrasound and laboratory tests; serum creatinine, white blood cells, CD4+ counts and percent, urine for microalbuminuria and proteinuria. Microalbuminuria and proteinuria were present in 20.4 % and 7.1 % respectively. Significantly higher prevalence of microalbuminuria (p < 0.01) and proteinuria p < 0.01) were noted with low CD4 percent (<25 %). Lower mean CD4+ count were noted among children with microalbuminuria [937.4 ± 595.3 cells/μL vs 1164.7 ± 664.3 cell/μL, (p < 0.05)] and proteinuria [675.5 ± 352.3 cells/μL vs 1152 ± 662 cells/μL (p < 0.001)]. Fourteen (5.8 %) HIV infected children had estimated glomerular filtration rate (eGFR of 30-59) consistent with severe renal impairment. Increased cortical echogenicity was noted in 69/153 (39.2 %) of participants who had ultrasound examination. Microalbuminuria, proteinuria and renal dysfunction were noted to be prevalent among HIV infected children indicating the need to consider routine screening of renal complications in these children.

QUANTITATIVE PLUTONIUM MICRODISTRIBUTION IN BONE TISSUE OF VERTEBRA FROM A MAYAK WORKER

PubMed Central

Lyovkina, Yekaterina V.; Miller, Scott C.; Romanov, Sergey A.; Krahenbuhl, Melinda P.; Belosokhov, Maxim V.

2010-01-01

The purpose was to obtain quantitative data on plutonium microdistribution in different structural elements of human bone tissue for local dose assessment and dosimetric models validation. A sample of the thoracic vertebra was obtained from a former Mayak worker with a rather high plutonium burden. Additional information was obtained on occupational and exposure history, medical history, and measured plutonium content in organs. Plutonium was detected in bone sections from its fission tracks in polycarbonate film using neutron-induced autoradiography. Quantitative analysis of randomly selected microscopic fields on one of the autoradiographs was performed. Data included fission fragment tracks in different bone tissue and surface areas. Quantitative information on plutonium microdistribution in human bone tissue was obtained for the first time. From these data, quantitative relationship of plutonium decays in bone volume to decays on bone surface in cortical and trabecular fractions were defined as 2.0 and 0.4, correspondingly. The measured quantitative relationship of decays in bone volume to decays on bone surface does not coincide with recommended models for the cortical bone fraction by the International Commission on Radiological Protection. Biokinetic model parameters of extrapulmonary compartments might need to be adjusted after expansion of the data set on quantitative plutonium microdistribution in other bone types in human as well as other cases with different exposure patterns and types of plutonium. PMID:20838087

Low serum vitamin D is associated with higher cortical porosity in elderly men.

PubMed

Sundh, D; Mellström, D; Ljunggren, Ö; Karlsson, M K; Ohlsson, C; Nilsson, M; Nilsson, A G; Lorentzon, M

2016-11-01

Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L -1 ) or insufficiency [25-49 nmol L -1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L -1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized β = -0.110, R 2 = 1.1%, P = 0.024), area (β = 0.123, R 2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R 2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R 2 = 0.9%, P = 0.04). Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of

Multimodality Intra-Arterial Imaging Assessment of the Vascular Trauma Induced by Balloon-Based and Nonballoon-Based Renal Denervation Systems.

PubMed

Karanasos, Antonios; Van Mieghem, Nicolas; Bergmann, Martin W; Hartman, Eline; Ligthart, Jurgen; van der Heide, Elco; Heeger, Christian-H; Ouhlous, Mohamed; Zijlstra, Felix; Regar, Evelyn; Daemen, Joost

2015-07-01

Renal denervation is a new treatment considered for several possible indications. As new systems are introduced, the incidence of acute renal artery wall injury with relation to the denervation method is unknown. We investigated the acute repercussion of renal denervation on the renal arteries of patients treated with balloon-based and nonballoon-based denervation systems by quantitative angiography, intravascular ultrasound, and optical coherence tomography (OCT). Twenty-five patients (50 renal arteries) underwent bilateral renal denervation with 5 different systems, 3 of which balloon-based (Paradise [n=5], Oneshot [n=6], and Vessix V2 [n=5)]) and 2 nonballoon-based (Symplicity [n=6] and EnligHTN [n=3]). Analysis included quantitative angiography and morphometric intravascular ultrasound measurements pre and post procedure and assessment of vascular trauma (dissection, edema, or thrombus) by OCT after denervation. A significant reduction in lumen size by quantitative angiography and intravascular ultrasound was observed in nonballoon denervation but not in balloon denervation. By postdenervation OCT, dissection was seen in 14 arteries (32.6%). The percentage of frames with dissection was higher in balloon-based denervation catheters. Thrombus and edema were detected in 35 (81.4%) and 32 (74.4%) arteries, respectively. In arteries treated with balloon-based denervation that had dissection by OCT, the balloon/artery ratio was higher (1.24 [1.17-1.32] versus 1.10 [1.04-1.18]; P<0.01). A varying extent of vascular injury was observed after renal denervation in all systems; however, different patterns were identified in balloon-based and in nonballoon-based denervation systems. In balloon denervation, the presence of dissections by OCT was associated with a higher balloon/artery ratio. © 2015 American Heart Association, Inc.

Quantitative and Qualitative Analysis of Transient Fetal Compartments during Prenatal Human Brain Development

PubMed Central

Vasung, Lana; Lepage, Claude; Radoš, Milan; Pletikos, Mihovil; Goldman, Jennifer S.; Richiardi, Jonas; Raguž, Marina; Fischi-Gómez, Elda; Karama, Sherif; Huppi, Petra S.; Evans, Alan C.; Kostovic, Ivica

2016-01-01

The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13–40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the

LRP5 gene polymorphism and cortical bone.

PubMed

Lauretani, Fulvio; Cepollaro, Chiara; Bandinelli, Stefania; Cherubini, Antonio; Gozzini, Alessia; Masi, Laura; Falchetti, Alberto; Del Monte, Francesca; Carbonell-Sala, Silvia; Marini, Francesca; Tanini, Annalisa; Corsi, Anna Maria; Ceda, Gian Paolo; Brandi, Maria Luisa; Ferrucci, Luigi

2010-08-01

There is evidence that distinct genetic polymorphisms of LRP5 are associated with low Bone Mineral Density (BMD) and the risk of fracture. However, relationships between LRP5 polymorphisms and micro- and macro architectural bone characteristics assessed by pQCT have not been studied. The aim of the present study was to investigate the association of Ala1330Val and Val667Met polymorphisms in LRP5 gene with volumetric BMD (vBMD) and macro-architectural bone parameters in a population-based sample of men and women. We studied 959 participants of the InCHIANTI study (451 men and 508 women, age range: 21-94 yrs). Trabecular vBMD (vBMDt, mg/cm3), cortical vBMD (vBMDc, mg/cm3), cortical bone area (CBA, mm2) and cortical thickness (Ct.Th, mm) at the level of the tibia were assessed by peripheral quantitative computed tomography (pQCT). Ala1330Val and Val667Met genotypes were determined on genomic DNA by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In age-adjusted analyses both LRP 1330-valine and LRP 667-metionin variants were associated with lower vBMDt in men (p<0.05), and lower vBMDt (p<0.05), Ct.Th (p<0.05) and CBA (p<0.05) in women. After adjusting for multiple confounders, only the association of LRP5 1330-valine and 667-metionin with CBA remained statistically significant (p=0.04 and p=0.01, respectively) in women. These findings suggest that both Ala1330Val and Val667Met LRP5 polymorphisms may affect the determination of geometric bone parameters in women.

Assessment of renal perfusion with contrast-enhanced ultrasound: Preliminary results in early diabetic nephropathies.

PubMed

Dong, Yi; Wang, Wen-Ping; Lin, Pan; Fan, Peili; Mao, Feng

2016-01-01

We performed a prospective study to evaluate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion in patients suspected of early diabetic nephropathies (DN), with the estimated GFR (MDRD equation) as the gold standard. The study protocol was approved by the hospital review board; each patient gave written informed consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 ± 4.14 years) of clinical confirmed early DN patients. After intravenous bolus injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent, real time CEUS of renal cortex was performed successively using a 2-5 MHz convex probe. Time-intensity curves (TICs) and quantitative indexes were created with Qlab software. Receiver operating characteristic (ROC) curves were used to predict the diagnostic criteria of CEUS quantitative indexes, and their diagnostic efficiencies were compared with resistance index (RI) and peak systolic velocity (PSV) of renal segmental arteries by chi square test. Our control group included forty-five healthy volunteers. Difference was considered statistically significant with P <  0.05. Changes of area under curve (AUC), derived peak intensity (DPI) were statistically significant (P <  0.05). DPI less than 12 and AUC greater than 1400 had high utility in DN, with 71.7% and 67.3% sensitivity, 77.8% and 80.0% specificity. These results were significantly better than those obtained with RI and PSV which had no significant difference in early stage of DN (P > 0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.

Effect of renal denervation on dynamic autoregulation of renal blood flow.

PubMed

DiBona, Gerald F; Sawin, Linda L

2004-06-01

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

Renal Perfusion in Scleroderma Patients Assessed by Microbubble-Based Contrast-Enhanced Ultrasound

PubMed Central

Kleinert, Stefan; Roll, Petra; Baumgaertner, Christian; Himsel, Andrea; Mueller, Adelheid; Fleck, Martin; Feuchtenberger, Martin; Jenett, Manfred; Tony, Hans-Peter

2012-01-01

Objectives: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. Materials and Methodology: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE%A) were calculated for different ROIs. Results: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. Conclusion: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media. PMID:22670165

Determination of split renal function using dynamic CT-angiography: preliminary results.

PubMed

Helck, Andreas; Schönermarck, Ulf; Habicht, Antje; Notohamiprodjo, Mike; Stangl, Manfred; Klotz, Ernst; Nikolaou, Konstantin; la Fougère, Christian; Clevert, Dirk Andrè; Reiser, Maximilian; Becker, Christoph

2014-01-01

To determine the feasibility of a dynamic CT angiography-protocol with regard to simultaneous assessment of renal anatomy and function. 7 healthy potential kidney donors (58 ± 7 years) underwent a dynamic computed tomography angiography (CTA) using a 128-slice CT-scanner with continuous bi-directional table movement, allowing the coverage of a scan range of 18 cm within 1.75 sec. Twelve scans of the kidneys (n = 14) were acquired every 3.5 seconds with the aim to simultaneously obtain CTA and renal function data. Image quality was assessed quantitatively (HU-measurements) and qualitatively (grade 1-4, 1 = best). The glomerular filtration rate (GFR) was calculated by a modified Patlak method and compared with the split renal function obtained with renal scintigraphy. Mean maximum attenuation was 464 ± 58 HU, 435 ± 48 HU and 277 ± 29 HU in the aorta, renal arteries, and renal veins, respectively. The abdominal aorta and all renal vessels were depicted excellently (grade 1.0). The image quality score for cortex differentiation was 1.6 ± 0.49, for the renal parenchyma 2.4 ± 0.49. GFR obtained from dynamic CTA correlated well with renal scintigraphy with a correlation coefficient of r = 0.84; P = 0.0002 (n = 14). The average absolute deviation was 1.6 mL/min. The average effective dose was 8.96 mSv. Comprehensive assessment of renal anatomy and function is feasible using a single dynamic CT angiography examination. The proposed protocol may help to improve management in case of asymmetric kidney function as well as to simplify evaluation of potential living kidney donors.

Dynamic Positron Emission Tomography Imaging of Renal Clearable Gold Nanoparticles

PubMed Central

Chen, Feng; Goel, Shreya; Hernandez, Reinier; Graves, Stephen A.; Shi, Sixiang; Nickles, Robert J.; Cai, Weibo

2016-01-01

Optical imaging has been the primary imaging modality for nearly all of the renal clearable nanoparticles since 2007. Due to the tissue depth penetration limitation, providing accurate organ kinetics non-invasively has long been a huge challenge. Although a more quantitative imaging technique has been developed by labeling nanoparticles with single-photon emission computed tomography (SPECT) isotopes, the low temporal resolution of SPECT still limits its potential for visualizing the rapid dynamic process of renal clearable nanoparticles in vivo. Here, we report the dynamic positron emission tomography (PET) imaging of renal clearable gold (Au) nanoparticles by labeling them with copper-64 (64Cu) to form 64Cu-NOTA-Au-GSH. Systematic nanoparticle synthesis and characterizations were performed to demonstrate the efficient renal clearance of as-prepared nanoparticles. A rapid renal clearance of 64Cu-NOTA-Au-GSH was observed (>75 %ID at 24 h post-injection) with its elimination half-life calculated to be less than 6 min, over 130 times shorter than previously reported similar nanoparticles. Dynamic PET imaging not only addresses the current challenges in accurately and non-invasively acquiring the organ kinetics, but also potentially provides a highly useful tool for studying renal clearance mechanism of other ultra-small nanoparticles, as well as the diagnosis of kidney diseases in the near future. PMID:27062146

Increased resistance during jump exercise does not enhance cortical bone formation.

PubMed

Boudreaux, Ramon D; Swift, Joshua M; Gasier, Heath G; Wiggs, Michael P; Hogan, Harry A; Fluckey, James D; Bloomfield, Susan A

2014-01-01

This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. Sprague-Dawley rats (male, 6 months old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 wk. Load in the HRE group was progressively increased from 80 g added to a weighted vest (50 repetitions) to 410 g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions), with only a 30-g vest applied. Low- and high-load jump RE resulted in 6%-11% higher cortical bone mineral content and cortical bone area compared with controls, as determined by in vivo peripheral quantitative computed tomography measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (+11%) and cross-sectional moment of inertia (+20%) versus the CC group. The three-point bending to failure revealed a marked increase in tibial maximum force (25%-29%), stiffness (19%-22%), and energy to maximum force (35%-55%) and a reduction in elastic modulus (-11% to 14%) in both LRE and HRE compared with controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20%-30% higher periosteal mineralizing surface versus the CC group. Mineral apposition rate and bone formation rate were significantly greater in animals in the LRE group (27%, 39%) than those in the HRE group. These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared with overload training in skeletally mature rats.

Etiology and outcome of acute renal failure in pregnancy.

PubMed

Hassan, Irfana; Junejo, Abdul Manan; Dawani, Manohar Lal

2009-11-01

To determine the etiology and outcome of Acute Renal Failure (ARF) in pregnancy. A case series. Nephrology Department of the Jinnah Postgraduate Medical Centre, Karachi, from August 2007 to July 2008. Pregnant women who were healthy previously and had developed ARF, diagnosed on oliguria (urine output <400 ml/day) and mounting azotemia (serum creatinine > 2 mg%) were included in the study. Percutaneous renal biopsy was performed for delayed recovery, i.e. after three weeks. Patients were followed up for a period of 6 months. Percentages were calculated for qualitative variables i.e. causes of ARF, mortality, morbidity and outcome in form of complete recovery, partial recovery, demise and non-recovery. A total of 43 patients with pregnancy-related ARF were included in the study. The puerperal group comprised 36 patients (83.7%). Haemorrhage was the etiology for ARF in 25 (58.1%), antepartum haemorrhage APH in 8 (18.6%) and postpartum haemorrhage PPH in 16 (37.2%) of patients. In 12 (27.9%), puerperal sepsis was the etiological factor, while 4 (9.3%) patients had DIC on presentation. Pre-eclampsia, eclampsia and HELLP syndrome accounted for 5 (11.6%). While 1 (2.3%) was diagnosed with hemolytic uremic syndrome and another one was diagnosed as ARF secondary to hypotension produced by hyperemesis gravidarum. Renal biopsy was performed in 31 patients showing that 10 had acute cortical necrosis and 21 had acute tubular necrosis. Maternal mortality was 16.2% (n=7). Of the 36 (83.7%) surviving patients, 18 (41.4%) had complete recovery of renal function; 12 (27.9%) had partial recovery; and 6 (13.9%) required chronic dialysis. Pregnancy-related ARF was associated with poor outcome. Antepartum and postpartum haemorrhage were the most common cause of ARF in pregnancy.

Label-free imaging of cortical structures with multiphoton microscopy

NASA Astrophysics Data System (ADS)

Wang, Shu; Chen, Xiuqiang; Wu, Weilin; Chen, Zhida; Lin, Ruolan; Lin, Peihua; Wang, Xingfu; Fu, Yu Vincent; Chen, Jianxin

2017-02-01

Cortical structures in the central nervous system exhibit an ordered laminar organization. Defined cell layers are significant to our understanding of brain structure and function. In this work, multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF), which was applied for qualitatively visualizing the structure of cerebral and cerebellar cortex from the fresh, unfixed, and unstained specimen. MPM is able to effectively identify neurons and neurites in cerebral cortex, as well as glial cells, Purkinje cells, and granule cells in cerebellar cortex at subcellular resolution. In addition, the use of automated image processing algorithms can quantify the circularity of neurons and the density distribution of neurites based on the intrinsic nonlinear optical contrast, further providing quantitative characteristics for automatically analyzing the laminar structure of cortical structures. These results suggest that with the development of the feasibility of two-photon fiberscopes and microendoscope probes, the combined MPM and image analysis holds potential to provide supplementary information to augment the diagnostic accuracy of neuropathology and in vivo identification of various neurological illnesses in clinic.

Censoring distances based on labeled cortical distance maps in cortical morphometry.

PubMed

Ceyhan, Elvan; Nishino, Tomoyuki; Alexopolous, Dimitrios; Todd, Richard D; Botteron, Kelly N; Miller, Michael I; Ratnanather, J Tilak

2013-01-01

It has been demonstrated that shape differences in cortical structures may be manifested in neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM) which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM) voxels with respect to GM/white matter (WM) surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information contained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control (Ctrl) subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface) for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.

Cortical layers: Cyto-, myelo-, receptor- and synaptic architecture in human cortical areas.

PubMed

Palomero-Gallagher, Nicola; Zilles, Karl

2017-08-12

Cortical layers have classically been identified by their distinctive and prevailing cell types and sizes, as well as the packing densities of cell bodies or myelinated fibers. The densities of multiple receptors for classical neurotransmitters also vary across the depth of the cortical ribbon, and thus determine the neurochemical properties of cyto- and myeloarchitectonic layers. However, a systematic comparison of the correlations between these histologically definable layers and the laminar distribution of transmitter receptors is currently lacking. We here analyze the densities of 17 different receptors of various transmitter systems in the layers of eight cytoarchitectonically identified, functionally (motor, sensory, multimodal) and hierarchically (primary and secondary sensory, association) distinct areas of the human cerebral cortex. Maxima of receptor densities are found in different layers when comparing different cortical regions, i.e. laminar receptor densities demonstrate differences in receptorarchitecture between isocortical areas, notably between motor and primary sensory cortices, specifically the primary visual and somatosensory cortices, as well as between allocortical and isocortical areas. Moreover, considerable differences are found between cytoarchitectonical and receptor architectonical laminar patterns. Whereas the borders of cyto- and myeloarchitectonic layers are well comparable, the laminar profiles of receptor densities rarely coincide with the histologically defined borders of layers. Instead, highest densities of most receptors are found where the synaptic density is maximal, i.e. in the supragranular layers, particularly in layers II-III. The entorhinal cortex as an example of the allocortex shows a peculiar laminar organization, which largely deviates from that of all the other cortical areas analyzed here. Copyright © 2017. Published by Elsevier Inc.

Quantitative phase imaging of platelets in patients with chronic renal failure treated with hemodialysis

NASA Astrophysics Data System (ADS)

Vasilenko, Irina; Vlasova, Elizaveta; Metelin, Vladislav; Kardasheva, Ziver

2018-02-01

The development of robust non-invasive laboratory screening methods for early diagnosis on the out-patient basis seems quite relevant for practical medicine. It is known, that platelet is an original biosensor, a detector of early changes in hemostasis condition. The aim of this study was to assess a potential of the quantitative phase imaging (QPI) technique for real time evaluation the influence of low-molecular weight and unfractionated heparin on platelets in patients with the end-stage of chronic renal failure, who were treated with program hemodialysis (PHD). The main group consisted of 21 patients who were administered a low-molecular weight heparin for hypocoagulation during the procedure of hemodialysis. The control group (15 patients) received unfractionated heparin. Morphodensitometric state of living platelets we evaluated by QPI using computer phase-interference microscope MIM (Moscow, Russia). We analyzed the optical-geometrical parameters and the morphological features of living platelets which reflected the degree of their activation at the beginning of PHD (before administration of heparin), in 15 minutes after it and at the end of the procedure. The results allow us to conclude that the use of low-molecular weight heparin provides better ratio of efficacy/safety and causes a reduction of the platelet activation during the hemodialysis procedure. Practical implementation of QPI for clinical monitoring of platelets makes it possible to obtain important information on hemostasis cell. It opens new opportunities to assess the efficacy of treatment, as well as for early diagnosis of complications for disease.

Maternal separation diminishes α-adrenergic receptor density and function in renal vasculature from male Wistar-Kyoto rats.

PubMed

Loria, Analia S; Osborn, Jeffrey L

2017-07-01

Adult rats exposed to maternal separation (MatSep) are normotensive but display lower glomerular filtration rate and increased renal neuroadrenergic drive. The aim of this study was to determine the renal α-adrenergic receptor density and the renal vascular responsiveness to adrenergic stimulation in male rats exposed to MatSep. In addition, baroreflex sensitivity was assessed to determine a component of neural control of the vasculature. Using tissue collected from 4-mo-old MatSep and control rats, α 1 -adrenergic receptors (α 1 -ARs) were measured in renal cortex and isolated renal vasculature using receptor binding assay, and the α-AR subtype gene expression was determined by RT-PCR. Renal cortical α 1 -AR density was similar between MatSep and control tissues (B max = 44 ± 1 vs. 42 ± 2 fmol/mg protein, respectively); however, MatSep reduced α 1 -AR density in renal vasculature (B max = 47 ± 4 vs. 62 ± 4 fmol/mg protein, P < 0.05, respectively). In a separate group of rats, the pressor, bradycardic, and renal vascular constrictor responses to acute norepinephrine injection (NE, 0.03-0.25 μg/μl) were determined under anesthesia. Attenuated NE-induced renal vasoconstriction was observed in rats exposed to MatSep compared with control ( P < 0.05). A third group of rats was infused at steady state with the α 1 agonist phenylephrine (10 μg/min iv) and vasodilator sodium nitroprusside (5 μg/min iv). The difference between the change in heart rate/mean arterial pressure slopes was indicative of reduced baroreflex sensitivity in MatSep vs. control rats (-0.45 ± 0.04 vs. -0.95 ± 0.07 beats·min -1 ·mmHg -1 , P < 0.05). These data support the notion that reduced α-adrenergic receptor expression and function in the renal vasculature could develop secondary to MatSep-induced overactivation of the renal neuroadrenergic tone. Copyright © 2017 the American Physiological Society.

LOGISMOS-B for primates: primate cortical surface reconstruction and thickness measurement

NASA Astrophysics Data System (ADS)

Oguz, Ipek; Styner, Martin; Sanchez, Mar; Shi, Yundi; Sonka, Milan

2015-03-01

Cortical thickness and surface area are important morphological measures with implications for many psychiatric and neurological conditions. Automated segmentation and reconstruction of the cortical surface from 3D MRI scans is challenging due to the variable anatomy of the cortex and its highly complex geometry. While many methods exist for this task in the context of the human brain, these methods are typically not readily applicable to the primate brain. We propose an innovative approach based on our recently proposed human cortical reconstruction algorithm, LOGISMOS-B, and the Laplace-based thickness measurement method. Quantitative evaluation of our approach was performed based on a dataset of T1- and T2-weighted MRI scans from 12-month-old macaques where labeling by our anatomical experts was used as independent standard. In this dataset, LOGISMOS-B has an average signed surface error of 0.01 +/- 0.03mm and an unsigned surface error of 0.42 +/- 0.03mm over the whole brain. Excluding the rather problematic temporal pole region further improves unsigned surface distance to 0.34 +/- 0.03mm. This high level of accuracy reached by our algorithm even in this challenging developmental dataset illustrates its robustness and its potential for primate brain studies.

Correlation between differential renal function estimation using CT-based functional renal parenchymal volume and (99m)Tc - DTPA renal scan.

PubMed

Sarma, Debanga; Barua, Sasanka K; Rajeev, T P; Baruah, Saumar J

2012-10-01

Nuclear renal scan is currently the gold standard imaging study to determine differential renal function. We propose helical CT as single modality for both the anatomical and functional evaluation of kidney with impaired function. In the present study renal parenchymal volume is measured and percent total renal volume is used as a surrogate marker for differential renal function. The objective of this study is to correlate between differential renal function estimation using CT-based renal parenchymal volume measurement with differential renal function estimation using (99m)TC - DTPA renal scan. Twenty-one patients with unilateral obstructive uropathy were enrolled in this prospective comparative study. They were subjected to (99m)Tc - DTPA renal scan and 64 slice helical CT scan which estimates the renal volume depending on the reconstruction of arterial phase images followed by volume rendering and percent renal volume was calculated. Percent renal volume was correlated with percent renal function, as determined by nuclear renal scan using Pearson coefficient. RESULTS AND OBSERVATION: A strong correlation is observed between percent renal volume and percent renal function in obstructed units (r = 0.828, P < 0.001) as well as in nonobstructed units (r = 0.827, P < 0.001). There is a strong correlation between percent renal volume determined by CT scan and percent renal function determined by (99m)TC - DTPA renal scan both in obstructed and in normal units. CT-based percent renal volume can be used as a single radiological tests for both functional and anatomical assessment of impaired renal units.

Reduced cortical complexity in children with Prader-Willi Syndrome and its association with cognitive impairment and developmental delay.

PubMed

Lukoshe, Akvile; Hokken-Koelega, Anita C; van der Lugt, Aad; White, Tonya

2014-01-01

Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in

Renal BOLD-MRI relates to kidney function and activity of the renin-angiotensin-aldosterone system in hypertensive patients.

PubMed

Vink, Eva E; de Boer, Anneloes; Hoogduin, Hans J M; Voskuil, Michiel; Leiner, Tim; Bots, Michiel L; Joles, Jaap A; Blankestijn, Peter J

2015-03-01

The renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are key factors in the pathophysiology of hypertension. Renal hypoxia is the putative mechanism stimulating both systems. Blood oxygen level-dependent MRI (BOLD-MRI) provides a noninvasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the relation between blood pressure (BP) and kidney function with renal BOLD-MRI. Moreover, the relation between direct and indirect variables of the RAAS and sympathetic nervous system and renal BOLD-MRI was studied. Seventy-five hypertensive patients (38 men) were included. Antihypertensive medication was temporarily stopped. Patients collected urine during 24 h (sodium, catecholamines), blood samples were taken (creatinine, renin, aldosterone), a captopril challenge test was performed, and ambulatory BP was measured. Mean age was 58 (±11) years, day-time BP was 167 (±19)/102 (±16) mmHg, and estimated glomerular filtration rate was 75 (±18) ml/min per 1.73 m). In multivariable regression analysis, renal medullary R2*-values inversely related to estimated glomerular filtration rate (P = 0.02). Moreover, the BP-lowering effect of captopril positively related to cortical (P = 0.02) and medullary (P = 0.008) R2*-values, as well as to P90 (P = 0.02). In patients with hypertension, kidney function relates to medullary R2*-values. Activation of the RAAS is also positively related to the renal R2*-values.

Trade-off of cerebello-cortical and cortico-cortical functional networks for planning in 6-year-old children.

PubMed

Kipping, Judy A; Margulies, Daniel S; Eickhoff, Simon B; Lee, Annie; Qiu, Anqi

2018-08-01

Childhood is a critical period for the development of cognitive planning. There is a lack of knowledge on its neural mechanisms in children. This study aimed to examine cerebello-cortical and cortico-cortical functional connectivity in association with planning skills in 6-year-olds (n = 76). We identified the cerebello-cortical and cortico-cortical functional networks related to cognitive planning using activation likelihood estimation (ALE) meta-analysis on existing functional imaging studies on spatial planning, and data-driven independent component analysis (ICA) of children's resting-state functional MRI (rs-fMRI). We investigated associations of cerebello-cortical and cortico-cortical functional connectivity with planning ability in 6-year-olds, as assessed using the Stockings of Cambridge task. Long-range functional connectivity of two cerebellar networks (lobules VI and lateral VIIa) with the prefrontal and premotor cortex were greater in children with poorer planning ability. In contrast, cortico-cortical association networks were not associated with the performance of planning in children. These results highlighted the key contribution of the lateral cerebello-frontal functional connectivity, but not cortico-cortical association functional connectivity, for planning ability in 6-year-olds. Our results suggested that brain adaptation to the acquisition of planning ability during childhood is partially achieved through the engagement of the cerebello-cortical functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Longitudinal Assessment of Renal Perfusion and Oxygenation in Transplant Donor-Recipient Pairs Using Arterial Spin Labeling and Blood Oxygen Level-Dependent Magnetic Resonance Imaging.

PubMed

Niles, David J; Artz, Nathan S; Djamali, Arjang; Sadowski, Elizabeth A; Grist, Thomas M; Fain, Sean B

2016-02-01

The aims of this study were to assess renal function in kidney transplant recipients and their respective donors over 2 years using arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and to prospectively evaluate the effect of losartan on functional MRI measures in recipients. The study included 15 matched pairs of renal transplant donors and recipients. Arterial spin labeling and BOLD MRI of the kidneys were performed on donors before transplant surgery (baseline) and on both donors and recipients at 3 months, 1 year, and 2 years after transplant. After 3 months, 7 of the 15 recipients were prescribed 25 to 50 mg/d losartan for the remainder of the study. A linear mixed-effects model was used to evaluate perfusion, R2*, estimated glomerular filtration rate, and fractional excretion of sodium for changes across time or associated with losartan treatment. In donors, cortical perfusion in the remaining kidney decreased by 50 ± 19 mL/min per 100 g (11.8%) between baseline and 2 years (P < 0.05), while cortical R2* declined modestly by 0.7 ± 0.3 s-1 (5.6%; P < 0.05). In transplanted kidneys, cortical perfusion decreased markedly by 141 ± 21 mL/min per 100 g (34.2%) between baseline and 2 years (P < 0.001), while medullary R2* declined by 1.5 ± 0.8 s-1 (8.3%; P = 0.06). Single-kidney estimated glomerular filtration rate increased between baseline and 2 years by 17.7 ± 2.7 mL/min per 1.73 m (40.3%; P < 0.0001) in donors and to 14.6 ± 4.3 mL/min per 1.73 m (33.3%; P < 0.01) in recipients. Cortical perfusion at 1 and 2 years in recipients receiving 25 to 50 mg/d losartan was 62 ± 24 mL/min per 100 g higher than recipients not receiving the drug (P < 0.05). No significant effects of losartan were observed for any other markers of renal function. The results suggest an important role for noninvasive functional monitoring with ASL and BOLD MRI in kidney transplant recipients and donors, and they indicate a potentially

Sex differences in circulating and renal angiotensins of hypertensive mRen(2).Lewis but not normotensive Lewis rats

PubMed Central

Pendergrass, Karl D.; Pirro, Nancy T.; Westwood, Brian M.; Ferrario, Carlos M.; Brosnihan, K. Bridget; Chappell, Mark C.

2008-01-01

Sex differences in blood pressure are evident in experimental models and human subjects, yet the mechanisms underlying this disparity remain equivocal. The current study sought to define the extent of male-female differences in the circulating and tissue renin-angiotensin aldosterone systems (RAASs) of congenic mRen(2).Lewis and control Lewis rats. Male congenics exhibited higher systolic blood pressure than females [200 ± 4 vs. 146 ± 7 mmHg, P < 0.01] or Lewis males and females [113 ± 2 vs. 112 ± 2 mmHg, P > 0.05]. Plasma ANG II levels were twofold higher in male congenics [47 ± 3 vs. 19 ± 3 pM, P < 0.01] and fivefold higher than in male or female Lewis rats [6 ± 1 vs. 6 ± 1 pM]. ANG I levels were also highest in the males; however, plasma ANG-(1-7) was higher in female congenics. Male congenics exhibited greater circulating renin and angiotensin-converting enzyme (ACE) activities, as well as angiotensinogen, than female littermates. Renal cortical and medullary ANG II levels were also higher in the male congenics versus all the other groups; ANG I was lower in the males. Cortical ACE2 activity was higher in male congenics, yet neprilysin activity and protein were greater in the females, which may contribute to reduced renal levels of ANG II. These data reveal that sex differences in both the circulating and renal RAAS are apparent primarily in the hypertensive group. The enhanced activity of the RAAS in male congenics may contribute to the higher pressure and tissue injury evident in the strain. PMID:18456730

Spatial integration and cortical dynamics.

PubMed

Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

1996-01-23

Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells within each cortical area over distances of 6-8 mm. The relationship between horizontal connections and cortical functional architecture suggests a role in visual segmentation and spatial integration. The distribution of lateral interactions within striate cortex was visualized with optical recording, and their functional consequences were explored by using comparable stimuli in human psychophysical experiments and in recordings from alert monkeys. They may represent the substrate for perceptual phenomena such as illusory contours, surface fill-in, and contour saliency. The dynamic nature of receptive field properties and cortical architecture has been seen over time scales ranging from seconds to months. One can induce a remapping of the topography of visual cortex by making focal binocular retinal lesions. Shorter-term plasticity of cortical receptive fields was observed following brief periods of visual stimulation. The mechanisms involved entailed, for the short-term changes, altering the effectiveness of existing cortical connections, and for the long-term changes, sprouting of axon collaterals and synaptogenesis. The mutability of cortical function implies a continual process of calibration and normalization of the perception of visual attributes that is dependent on sensory experience throughout adulthood and might further represent the mechanism of perceptual learning.

Postpartum cortical blindness.

PubMed

Faiz, Shakeel Ahmed

2008-09-01

A 30-years-old third gravida with previous normal pregnancies and an unremarkable prenatal course had an emergency lower segment caesarean section at a periphery hospital for failure of labour to progress. She developed bilateral cortical blindness immediately after recovery from anesthesia due to cerebral angiopathy shown by CT and MR scan as cortical infarct cerebral angiopathy, which is a rare complication of a normal pregnancy.

Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury.

PubMed

Peters, Esther; Ergin, Bülent; Kandil, Asli; Gurel-Gurevin, Ebru; van Elsas, Andrea; Masereeuw, Rosalinde; Pickkers, Peter; Ince, Can

2016-12-15

Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n=18) were subjected to renal ischemia (30min) and reperfusion (I/R), or sham-operated. In a second model, rats (n=18) received a 30min infusion of lipopolysaccharide (LPS; 2.5mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000U/kg) was administered intravenously (15min before reperfusion, or 90min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension at late reperfusion were no longer significantly affected. RecAP did not influence I/R-induced effects on mean arterial pressure. During endotoxemia, recAP treatment did not modulate the LPS-induced changes in systemic hemodynamics and renal oxygenation. In both models, recAP did exert a clear renal protective anti-inflammatory effect, demonstrated by attenuated immunostaining of inflammatory, tubular injury and pro-apoptosis markers. Whether this renal protective effect is sufficient to improve outcome of patients suffering from sepsis-associated AKI is being investigated in a large clinical trial. Copyright © 2016. Published by Elsevier Inc.

Cortical thinning in cognitively normal elderly cohort of 60 to 89 year old from AIBL database and vulnerable brain areas

NASA Astrophysics Data System (ADS)

Lin, Zhongmin S.; Avinash, Gopal; Yan, Litao; McMillan, Kathryn

2014-03-01

Age-related cortical thinning has been studied by many researchers using quantitative MR images for the past three decades and vastly differing results have been reported. Although results have shown age-related cortical thickening in elderly cohort statistically in some brain regions under certain conditions, cortical thinning in elderly cohort requires further systematic investigation. This paper leverages our previously reported brain surface intensity model (BSIM)1 based technique to measure cortical thickness to study cortical changes due to normal aging. We measured cortical thickness of cognitively normal persons from 60 to 89 years old using Australian Imaging Biomarkers and Lifestyle Study (AIBL) data. MRI brains of 56 healthy people including 29 women and 27 men were selected. We measured average cortical thickness of each individual in eight brain regions: parietal, frontal, temporal, occipital, visual, sensory motor, medial frontal and medial parietal. Unlike the previous published studies, our results showed consistent age-related thinning of cerebral cortex in all brain regions. The parietal, medial frontal and medial parietal showed fastest thinning rates of 0.14, 0.12 and 0.10 mm/decade respectively while the visual region showed the slowest thinning rate of 0.05 mm/decade. In sensorimotor and parietal areas, women showed higher thinning (0.09 and 0.16 mm/decade) than men while in all other regions men showed higher thinning than women. We also created high resolution cortical thinning rate maps of the cohort and compared them to typical patterns of PET metabolic reduction of moderate AD and frontotemporal dementia (FTD). The results seemed to indicate vulnerable areas of cortical deterioration that may lead to brain dementia. These results validate our cortical thickness measurement technique by demonstrating the consistency of the cortical thinning and prediction of cortical deterioration trend with AIBL database.

Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients.

PubMed

Chen, Xiao; Zhu, Qingqiang; Li, Baoxin; Cui, Wenjing; Zhou, Hao; Duan, Na; Liu, Yongkang; Kundra, Vikas; Wang, Zhongqiu

2017-02-01

To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. • Xp11.2/TFE RCC was more prevalent in young women. • On unenhanced CT, Xp11.2/TFE RCC attenuation was greater than in renal parenchyma. • Xp111/2TFE RCC arises primarily from the renal medulla. • Xp11.2/TFE RCC enhancement was less than in the cortex on all phases. • Enhancement was greater than in the medulla in arterial and corticomedullary phase.

Is cortical bone hip? What determines cortical bone properties?

PubMed

Epstein, Sol

2007-07-01

Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal

LRP5 gene polymorphism and cortical bone

PubMed Central

Lauretani, Fulvio; Cepollaro, Chiara; Bandinelli, Stefania; Cherubini, Antonio; Gozzini, Alessia; Masi, Laura; Falchetti, Alberto; Del Monte, Francesca; Carbonell-Sala, Silvia; Marini, Francesca; Tanini, Annalisa; Corsi, Anna Maria; Ceda, Gian Paolo; Brandi, Maria Luisa; Ferrucci, Luigi

2016-01-01

Background and aims There is evidence that distinct genetic polymorphisms of LRP5 are associated with low Bone Mineral Density (BMD) and the risk of fracture. However, relationships between LRP5 polymorphisms and micro- and macro-architectural bone characteristics assessed by pQCT have not been studied. The aim of the present study was to investigate the association of Ala1330Val and Val667Met polymorphisms in LRP5 gene with volumetric BMD (vBMD) and macro-architectural bone parameters in a population-based sample of men and women. Methods We studied 959 participants of the InCHIANTI study (451 men and 508 women, age range: 21–94 yrs). Trabecular vBMD (vBMDt, mg/cm3), cortical vBMD (vBMDc, mg/cm3), cortical bone area (CBA, mm2) and cortical thickness (Ct.Th, mm) at the level of the tibia were assessed by peripheral quantitative computed tomography (pQCT). Ala1330Val and Val667Met genotypes were determined on genomic DNA by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results In age-adjusted analyses both LRP 1330-valine and LRP 667-metionin variants were associated with lower vBMDt in men (p<0.05), and lower vBMDt (p<0.05), Ct.Th (p<0.05) and CBA (p<0.05) in women. After adjusting for multiple confounders, only the association of LRP5 1330-valine and 667-metionin with CBA remained statistically significant (p=0.04 and p=0.01, respectively) in women. Conclusion These findings suggest that both Ala1330Val and Val667Met LRP5 polymorphisms may affect the determination of geometric bone parameters in women. PMID:21116122

Correlates of a single cortical action potential in the epidural EEG

PubMed Central

Teleńczuk, Bartosz; Baker, Stuart N; Kempter, Richard; Curio, Gabriel

2015-01-01

To identify the correlates of a single cortical action potential in surface EEG, we recorded simultaneously epidural EEG and single-unit activity in the primary somatosensory cortex of awake macaque monkeys. By averaging over EEG segments coincident with more than hundred thousand single spikes, we found short-lived (≈ 0.5 ms) triphasic EEG deflections dominated by high-frequency components > 800 Hz. The peak-to-peak amplitude of the grand-averaged spike correlate was 80 nV, which matched theoretical predictions, while single-neuron amplitudes ranged from 12 to 966 nV. Combining these estimates with post-stimulus-time histograms of single-unit responses to median-nerve stimulation allowed us to predict the shape of the evoked epidural EEG response and to estimate the number of contributing neurons. These findings establish spiking activity of cortical neurons as a primary building block of high-frequency epidural EEG, which thus can serve as a quantitative macroscopic marker of neuronal spikes. PMID:25554430

Increased Cortical Porosity in Type-2 Diabetic Postmenopausal Women with Fragility Fractures

PubMed Central

Patsch, Janina M.; Burghardt, Andrew J.; Yap, Samuel P.; Baum, Thomas; Schwartz, Ann V.; Joseph, Gabby B.; Link, Thomas M.

2012-01-01

The primary goal of this study was to assess peripheral bone microarchitecture and strength in diabetic postmenopausal women with fragility fractures (DMFx) and to compare them with diabetic women without fracture (DM). Secondary goals were to assess differences in non-diabetic women with (Fx) and without fragility fractures (Co) and in women with (DM) and without diabetes (Co). Eighty women (mean age 61.3±5.7 yrs) were recruited into these groups (n=20 per group). Participants underwent DXA and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal and distal radius and tibia. In the HR-pQCT images volumetric bone mineral density, cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro-finite element analysis (μFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p=0.009; +95.4%, p=0.020), relative porosity (+58.1%; p=0.005; +87.9%, p=0.011) and endocortical bone surface (+10.9%, p=0.031; +11.5%, 0.019) than DM. At the distal radius DMFx had 4.7-fold greater relative porosity (p=0.000) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p=0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius; +36.8%, p=0.035), and lower total and cortical BMD (ultradistal tibia: −12.6%, p=0.031; −6.8%, p=0.011) than DM. DMFx exhibited significantly higher pore-related deficits in stiffness, failure load and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing non-diabetic Fx and Co, we only found a non-significant trend with increase in pore volume (+38.9%, p=0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in

Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

PubMed Central

Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

2012-01-01

Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy

PubMed Central

Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J.; Yong, Keir X.X.; Paterson, Ross W.; Slattery, Catherine F.; Foulkes, Alexander J.M.; Rabinovici, Gil D.; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M.; Fox, Nick C.; Crutch, Sebastian J.

2016-01-01

Age at onset (AAO) has been shown to influence the phenotype of Alzheimer’s disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. PMID:27318138

Mechanisms of bee venom-induced acute renal failure.

PubMed

Grisotto, Luciana S D; Mendes, Glória E; Castro, Isac; Baptista, Maria A S F; Alves, Venancio A; Yu, Luis; Burdmann, Emmanuel A

2006-07-01

The spread of Africanized bees in the American continent has increased the number of severe envenomation after swarm attacks. Acute renal failure (ARF) is one of the major hazards in surviving patients. To assess the mechanisms of bee venom-induced ARF, rats were evaluated before, up to 70 min and 24h after 0.5mg/kg of venom injection. Control rats received saline. Bee venom caused an early and significant reduction in glomerular filtration rate (GFR, inulin clearance, 0.84+/-0.05 to 0.40+/-0.08 ml/min/100g, p<0.0001) and renal blood flow (RBF, laser Doppler flowmetry), which was more severe in the cortical (-72%) than in the medullary area (-48%), without systemic blood pressure decrease. Creatine phosphokinase, lactic dehydrogenase (LDH) and serum glutamic oxaloacetic transaminase increased significantly, pointing to rhabdomyolysis, whereas serum glutamic pyruvic transaminase and hematocrit remained stable. Twenty-four hours after venom, RBF recovered but GFR remained significantly impaired. Renal histology showed acute tubular injury and a massive tubular deposition of myoglobin. Venom was added to isolated rat proximal tubules (PT) suspension subjected to normoxia and hypoxia/reoxygenation (H/R) for direct nephrotoxicity evaluation. After 60 min of incubation, 0.1, 2 and 10 microg of venom induced significant increases in LDH release: 47%, 64% and 86%, respectively, vs. 21% in control PT while 2 microg of venom enhanced H/R injury (85% vs. 55%, p<0.01). These results indicate that vasoconstriction, direct nephrotoxicity and rhabdomyolysis are important mechanisms in the installation of bee venom-induced ARF that may occur even without hemolysis or hypotension.

Proposal for a biometrics of the cortical surface: a statistical method for relative surface distance metrics

NASA Astrophysics Data System (ADS)

Bookstein, Fred L.

1995-08-01

Recent advances in computational geometry have greatly extended the range of neuroanatomical questions that can be approached by rigorous quantitative methods. One of the major current challenges in this area is to describe the variability of human cortical surface form and its implications for individual differences in neurophysiological functioning. Existing techniques for representation of stochastically invaginated surfaces do not conduce to the necessary parametric statistical summaries. In this paper, following a hint from David Van Essen and Heather Drury, I sketch a statistical method customized for the constraints of this complex data type. Cortical surface form is represented by its Riemannian metric tensor and averaged according to parameters of a smooth averaged surface. Sulci are represented by integral trajectories of the smaller principal strains of this metric, and their statistics follow the statistics of that relative metric. The diagrams visualizing this tensor analysis look like alligator leather but summarize all aspects of cortical surface form in between the principal sulci, the reliable ones; no flattening is required.

Noncoding RNA Expression and Targeted Next-Generation Sequencing Distinguish Tubulocystic Renal Cell Carcinoma (TC-RCC) from Other Renal Neoplasms.

PubMed

Lawrie, Charles H; Armesto, María; Fernandez-Mercado, Marta; Arestín, María; Manterola, Lorea; Goicoechea, Ibai; Larrea, Erika; Caffarel, María M; Araujo, Angela M; Sole, Carla; Sperga, Maris; Alvarado-Cabrero, Isabel; Michal, Michal; Hes, Ondrej; López, José I

2018-01-01

Tubulocystic renal cell carcinoma (TC-RCC) is a rare recently described renal neoplasm characterized by gross, microscopic, and immunohistochemical differences from other renal tumor types and was recently classified as a distinct entity. However, this distinction remains controversial particularly because some genetic studies suggest a close relationship with papillary RCC (PRCC). The molecular basis of this disease remains largely unexplored. We therefore performed noncoding (nc) RNA/miRNA expression analysis and targeted next-generation sequencing mutational profiling on 13 TC-RCC cases (11 pure, two mixed TC-RCC/PRCC) and compared with other renal neoplasms. The expression profile of miRNAs and other ncRNAs in TC-RCC was distinct and validated 10 differentially expressed miRNAs by quantitative RT-PCR, including miR-155 and miR-34a, that were significantly down-regulated compared with PRCC cases (n = 22). With the use of targeted next-generation sequencing we identified mutations in 14 different genes, most frequently (>60% of TC-RCC cases) in ABL1 and PDFGRA genes. These mutations were present in <5% of clear cell RCC, PRCC, or chromophobe RCC cases (n > 600) of The Cancer Genome Atlas database. In summary, this study is by far the largest molecular study of TC-RCC cases and the first to investigate either ncRNA expression or their genomic profile. These results add molecular evidence that TC-RCC is indeed a distinct entity from PRCC and other renal neoplasms. Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Cortical language lateralization in right handed normal subjects using functional magnetic resonance imaging.

PubMed

Vikingstad, E M; George, K P; Johnson, A F; Cao, Y

2000-04-01

In 95% of right handed individuals the left hemisphere is dominant for speech and language function. The evidence for this is accumulated primarily from clinical populations. We investigated cortical topography of language function and lateralization in a sample of the right handed population using functional magnetic resonance imaging and two lexical-semantic paradigms. Activated cortical language networks were assessed topographically and quantitatively by using a lateralization index. As a group, we observed left hemispheric language dominance. Individually, the lateralization index varied continuously from left hemisphere dominant to bilateral representation. In males, language primarily lateralized to left, and in females, approximately half had left lateralization and the other half had bilateral representation. Our data indicate that a previous view of female bilateral hemispheric dominance for language (McGlone, 1980. Sex differences in human brain asymmetry: a critical survey. Behav Brain Sci 3:215-263; Shaywitz et al., 1995. Sex differences in the functional organization of the brain for language. Nature 373:607-609) simplifies the complexity of cortical language distribution in this population. Analysis of the distribution of the lateralization index in our study allowed us to make this difference in females apparent.

Visual cortical activity reflects faster accumulation of information from cortically blind fields

PubMed Central

Martin, Tim; Das, Anasuya; Huxlin, Krystel R.

2012-01-01

Brain responses (from functional magnetic resonance imaging) and components of information processing were investigated in nine cortically blind observers performing a global direction discrimination task. Three of these subjects had responses in perilesional cortex in response to blind field stimulation, whereas the others did not. We used the EZ-diffusion model of decision making to understand how cortically blind subjects make a perceptual decision on stimuli presented within their blind field. We found that these subjects had slower accumulation of information in their blind fields as compared with their good fields and to intact controls. Within cortically blind subjects, activity in perilesional tissue, V3A and hMT+ was associated with a faster accumulation of information for deciding direction of motion of stimuli presented in the blind field. This result suggests that the rate of information accumulation is a critical factor in the degree of impairment in cortical blindness and varies greatly among affected individuals. Retraining paradigms that seek to restore visual functions might benefit from focusing on increasing the rate of information accumulation. PMID:23169923

Cortical-basal ganglionic degeneration.

PubMed

Riley, D E; Lang, A E; Lewis, A; Resch, L; Ashby, P; Hornykiewicz, O; Black, S

1990-08-01

We report our experience with 15 patients believed to have cortical-basal ganglionic degeneration. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Characteristic manifestations include cortical sensory loss, focal reflex myoclonus, "alien limb" phenomena, apraxia, rigidity and akinesia, a postural-action tremor, limb dystonia, hyperreflexia, and postural instability. The asymmetry of symptoms and signs is often striking. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. Postmortem studies in 2 patients revealed the characteristic pathologic features of swollen, poorly staining (achromatic) neurons and degeneration of cerebral cortex and substantia nigra. Biochemical analysis of 1 brain showed a severe, diffuse loss of dopamine in the striatum. This condition is more frequent than previously believed, and the diagnosis can be predicted during life on the basis of clinical findings. However, as with other "degenerative" diseases of the nervous system, a definitive diagnosis of cortical-basal ganglionic degeneration requires confirmation by autopsy.

Renal perfusion scintiscan

MedlinePlus

... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

Effects of exercise and excitement on mesenteric and renal dynamics in conscious, unrestrained baboons

NASA Technical Reports Server (NTRS)

Vatner, S. F.

1978-01-01

Radiotelemetry was used to measure arterial pressure and mesenteric and renal blood flows from nine unrestrained, conscious baboons during periods of rest, moderate exercise, and extreme excitement. A description of the experiments hardware is presented, including artificial depressants phenylcyclidine hydrochloride, 0.5-1.0 mg/kg, and pentobarbital sodium, 15 mg/kg, and an ultrasonic telemetry flow meter. Results showed rising heart rate and arterial pressure coupled with a reduction of mesenteric and renal flows as the level of exercise was increased. These findings are compared with mesenteric and renal flows somewhat above control level, but relatively stable heart rate and arterial pressure, postprandially. Attention is given to a quantitative analysis of the experimental results.

Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type

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

Chalmers, D.T.; Dewar, D.; Graham, D.I.

1990-02-01

Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-(3H)aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. (3H)Kainate receptor binding was significantly increased bymore » approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-(3H)methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive (3H)glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. (3H)Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others.« less

[Effects of modified three-step procedure for anatrophic nephrolithotomy in the treatment of complex staghorn renal calculi].

PubMed

Yang, C L; Wang, W; Zhou, W E; Xue, Y P; Wang, B Q; Nie, H B; Hu, W L

2017-10-01

Objective: To investigate the effects of modified three-step procedure for anatrophic nephrolithotomy in the treatment of complex staghorn renal calculi. Methods: A total of 22 patients with complex staghorn renal calculi between June 2013 and June 2016 at Department of Urology in Guangzhou General Hospital of Guangzhou Military Command were retrospective analyzed. There were 13 males and 9 females, ranging from 35 to 62 years old with mean age of 47 years. There were 17 patients with dull pain, and 5 patients who were found through physical examinations. Kidney calculi located in left kidney in 15 patients, right kidney in 7 patients. All patients were treated with modified three-step procedure for anatrophic nephrolithotomy. The operation time, blood loss, time of intraoperative renal ischemia, and postoperative complications were recorded. Serum creatinine (Scr), blood urea nitrogen(BUN), β(2)-microglobulin(β(2)-MG), diseased side glomerular filtration rate(GFR) , and renal cortical thickness of the diseased kidney in preoperative and postoperative were compared. The clinical data were compared by paired sample t test between pre-operation and post-operation. Results: The calculi were completely removed in 22 patients, the mean operation time was 84 minutes (50 to 126 minutes), the mean time of intraoperative renal ischemia was 31 minutes (20 to 56 minutes), the mean blood loss was 246 ml (150 to 360 ml). There were no secondary bleeding or urinary fistula happened, the perinephric drainage tub was removed in 3 to 7 days postoperative, the mean hospitalization time was 7 days.Compared with the preoperative, the Scr ((172.7±21.3)μmol/L vs . (146.4±22.8)μmol/L, t =7.197, P =0.000), BUN ((9.2±1.8)mmol/L vs . (8.0±0.5)mmol/L, t =3.798, P =0.001) and β(2)-MG ((203.0±32.0)μg/L vs . (175.6±23.8)μg/L, t =5.009, P =0.000) in postoperative decreased, the diseased side GFR increased ((28.6±4.0) ml/min(31.8±3.3) ml/min, t =-3.521, P =0.002). There were no

[Quantitative determination of the main metabolites of acetylsalicylic acid/2nd communication: the concentrations of salicylic acid and its metabolites in patients with renal insufficiency (author's transl)].

PubMed

Daneels, R; Loew, D; Pütter, J

1975-07-01

Quantitative Determination of the Main Metabolites of Acetylsalicylic Acid / 2nd Communication: The concentrations of salicylic acid and its metabolies in patients with renal insufficiency 9 patients suffering from renal insufficiencies of varing degrees and treated regularly by hemodialysis were given 1.5 g Colfarit (microcapsulated acetyl salicylic acid) as a single dose. The concentrations of salicylic acid (SA), salicyluric acid (SU), further salicylic acid conjugates (SAC) and salicyluric acid conjugates (SUC) were determined in the blood plasma. Likewise urea and creatinine were determined. SA concentration decreased continually and, at the end of the trial (72 h after application), had vanished almost completely from the plasma of most patients. SU increased at first and decreased afterwards. With the exception of the dailysis time SAC and SUC increased during the trial. After 3 days the SUC level was more than 50% of total salicylate (SSS) in most patients. SSS (the sum of SA + SU + SAC + SUC) did not change very much before dialysis, but showed a rather high decrease during the first hours of dialysis. tafter dialysis the SSS levels rose again, apparently as a consequence of a redistribution and of the synthesis of conjugates with decreased tissue affinity. It could be shown that SSS in the blood plasma does not parallel SSS in the whole body. The interindividual variation of SA metabolism as well as the variation of the biological blank values was rather high. The results are discussed with regard to salicylate pharmacokinetics in renal insufficiency and to normal salicylate metabolism.

Limitations of commonly used internal controls for real-time RT-PCR analysis of renal epithelial-mesenchymal cell transition.

PubMed

Elberg, Gerard; Elberg, Dorit; Logan, Charlotte J; Chen, Lijuan; Turman, Martin A

2006-01-01

Progressive renal fibrotic disease is accompanied by the massive accumulation of myofibroblasts as defined by alpha smooth muscle actin (alphaSMA) expression. We quantitated gene expression using real-time RT-PCR analysis during conversion of primary cultured human renal tubular cells (RTC) to myofibroblasts after treatment with transforming growth factor-beta1 (TGF-beta1). We report herein the limitations of commonly used reference genes for mRNA quantitation. We determined the expression of alphaSMA and megakaryoblastic leukemia-1 (MKL1), a transcriptional regulator of alphaSMA, by quantitative real-time PCR using three common internal controls, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin A and 18S rRNA. Expression of GAPDH mRNA and cyclophilin A mRNA, and to a lesser extent, 18S rRNA levels varied over time in culture and with exposure to TGF-beta1. Thus, depending on which reference gene was used, TGF-beta1 appeared to have different effects on expression of MKL1 and alphaSMA. RTC converting to myofibroblasts in primary culture is a valuable system to study renal fibrosis in humans. However, variability in expression of reference genes with TGF-beta1 treatment illustrates the need to validate mRNA quantitation with multiple reference genes to provide accurate interpretation of fibrosis studies in the absence of a universal internal standard for mRNA expression. 2006 S. Karger AG, Basel.

[Renal physiology].

PubMed

Gueutin, Victor; Deray, Gilbert; Isnard-Bagnis, Corinne

2012-03-01

The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. The flow of plasma is filtered in the range of 120 mL/min, and depends on the systemic and renal hemodynamics which is subject to self-regulation. The original urine will then be modified in successive segments of the nephron. The proximal nephron is to lead the massive reabsorption of water and essential elements such as sodium, bicarbonates, amino-acids and glucose. The distal nephron includes the distal convoluted tubule, the connector tube and the collecting duct. Its role is to adapt the quality composition of urine to the needs of the body.

Communication and wiring in the cortical connectome

PubMed Central

Budd, Julian M. L.; Kisvárday, Zoltán F.

2012-01-01

In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimize communication there is a trade-off between spatial (construction) and temporal (routing) costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fiber tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for cortical wiring patterns

Cortical GABA markers identify a molecular subtype of psychotic and bipolar disorders.

PubMed

Volk, D W; Sampson, A R; Zhang, Y; Edelson, J R; Lewis, D A

2016-09-01

Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a 'low GABA marker' (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders. Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects. Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype. These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

Perceptual learning and adult cortical plasticity.

PubMed

Gilbert, Charles D; Li, Wu; Piech, Valentin

2009-06-15

The visual cortex retains the capacity for experience-dependent changes, or plasticity, of cortical function and cortical circuitry, throughout life. These changes constitute the mechanism of perceptual learning in normal visual experience and in recovery of function after CNS damage. Such plasticity can be seen at multiple stages in the visual pathway, including primary visual cortex. The manifestation of the functional changes associated with perceptual learning involve both long term modification of cortical circuits during the course of learning, and short term dynamics in the functional properties of cortical neurons. These dynamics are subject to top-down influences of attention, expectation and perceptual task. As a consequence, each cortical area is an adaptive processor, altering its function in accordance to immediate perceptual demands.

Basic visual function and cortical thickness patterns in posterior cortical atrophy.

PubMed

Lehmann, Manja; Barnes, Josephine; Ridgway, Gerard R; Wattam-Bell, John; Warrington, Elizabeth K; Fox, Nick C; Crutch, Sebastian J

2011-09-01

Posterior cortical atrophy (PCA) is characterized by a progressive decline in higher-visual object and space processing, but the extent to which these deficits are underpinned by basic visual impairments is unknown. This study aimed to assess basic and higher-order visual deficits in 21 PCA patients. Basic visual skills including form detection and discrimination, color discrimination, motion coherence, and point localization were measured, and associations and dissociations between specific basic visual functions and measures of higher-order object and space perception were identified. All participants showed impairment in at least one aspect of basic visual processing. However, a number of dissociations between basic visual skills indicated a heterogeneous pattern of visual impairment among the PCA patients. Furthermore, basic visual impairments were associated with particular higher-order object and space perception deficits, but not with nonvisual parietal tasks, suggesting the specific involvement of visual networks in PCA. Cortical thickness analysis revealed trends toward lower cortical thickness in occipitotemporal (ventral) and occipitoparietal (dorsal) regions in patients with visuoperceptual and visuospatial deficits, respectively. However, there was also a lot of overlap in their patterns of cortical thinning. These findings suggest that different presentations of PCA represent points in a continuum of phenotypical variation.

Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.

PubMed

Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Foulkes, Alexander J M; Rabinovici, Gil D; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M; Fox, Nick C; Crutch, Sebastian J

2016-08-01

Age at onset (AAO) has been shown to influence the phenotype of Alzheimer's disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cortical motor activity and reorganization following upper-limb amputation and subsequent targeted reinnervation.

PubMed

Chen, Albert; Yao, Jun; Kuiken, Todd; Dewald, Julius P A

2013-01-01

Previous studies have postulated that the amount of brain reorganization following peripheral injuries may be correlated with negative symptoms or consequences. However, it is unknown whether restoring effective limb function may then be associated with further changes in the expression of this reorganization. Recently, targeted reinnervation (TR), a surgical technique that restores a direct neural connection from amputated sensorimotor nerves to new peripheral targets such as muscle, has been successfully applied to upper-limb amputees. It has been shown to be effective in restoring both peripheral motor and sensory functions via the reinnervated nerves as soon as a few months after the surgery. However, it was unclear whether TR could also restore normal cortical motor representations for control of the missing limb. To answer this question, we used high-density electroencephalography (EEG) to localize cortical activity related to cued motor tasks generated by the intact and missing limb. Using a case study of 3 upper-limb amputees, 2 of whom went through pre and post-TR experiments, we present unique quantitative evidence for the re-mapping of motor representations for the missing limb closer to their original locations following TR. This provides evidence that an effective restoration of peripheral function from TR can be linked to the return of more normal cortical expression for the missing limb. Therefore, cortical mapping may be used as a potential guide for monitoring rehabilitation following peripheral injuries.

Effect of renal nerve stimulation on responsiveness of the rat renal vasculature.

PubMed

DiBona, Gerald F; Sawin, Linda L

2002-11-01

When the renal nerves are stimulated with sinusoidal stimuli over the frequency range 0.04-0.8 Hz, low (< or =0.4 Hz)- but not high (> or =0.4 Hz)-frequency oscillations appear in renal blood flow (RBF) and are proposed to increase responsiveness of the renal vasculature to stimuli. This hypothesis was tested in anesthetized rats in which RBF responses to intrarenal injection of norepinephrine and angiotensin and to reductions in renal arterial pressure (RAP) were determined during conventional rectangular pulse and sinusoidal renal nerve stimulation. Conventional rectangular pulse renal nerve stimulation decreased RBF at 2 Hz but not at 0.2 or 1.0 Hz. Sinusoidal renal nerve stimulation elicited low-frequency oscillations (< or =0.4 Hz) in RBF only when the basal carrier signal frequency produced renal vasoconstriction, i.e., at 5 Hz but not at 1 Hz. Regardless of whether renal vasoconstriction occurred, neither conventional rectangular pulse nor sinusoidal renal nerve stimulation altered renal vasoconstrictor responses to norepinephrine and angiotensin. The RBF response to reduction in RAP was altered by both conventional rectangular pulse and sinusoidal renal nerve stimulation only when renal vasoconstriction occurred: the decrease in RBF during reduced RAP was greater. Sinusoidal renal nerve stimulation with a renal vasoconstrictor carrier frequency results in a decrease in RBF with superimposed low-frequency oscillations. However, these low-frequency RBF oscillations do not alter renal vascular responsiveness to vasoconstrictor stimuli.

Reduced cortical activation in inferior frontal junction in Unverricht-Lundborg disease (EPM1) - A motor fMRI study.

PubMed

Könönen, Mervi; Danner, Nils; Koskenkorva, Päivi; Kälviäinen, Reetta; Hyppönen, Jelena; Mervaala, Esa; Karjalainen, Pasi; Vanninen, Ritva; Niskanen, Eini

2015-03-01

Unverricht-Lundborg disease (EPM1) is characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic seizures and ataxia. Several disease-related alterations in cortical structure and excitability have been associated with the motor symptoms of EPM1. This study aimed to elucidate possible alterations in cortical activation related to motor performance in EPM1. Fifteen EPM1-patients and 15 healthy volunteers matched for age and sex underwent motor functional MRI. Group differences in activations were evaluated in the primary and supplementary motor cortices and sensory cortical areas. Furthermore, in EPM1 patients, the quantitative fMRI parameters were correlated with the severity of the motor symptoms. The EPM1-patients exhibited decreased activation in the left inferior frontal junction (IFJ) during right hand voluntary motor task when compared with controls. In the quantitative analysis, EPM1-patients had significantly weaker activation than controls in the hand knob and supplementary motor areas (SMA). The volume of activation in M1 decreased with age and duration of disease in the patient group, whereas the volume increased with age in controls. Negative correlations were observed between fMRI parameters of SMA and disease duration or age in patients but not in controls. The weaker motor fMRI activation observed in EPM1 patients parallels previous neurophysiological findings and correlates with the motor symptoms of the disease. Thus, the observed decrease in IFJ activation in EPM1 patients may be associated with the difficulties in initiation or termination of motor execution, a typical clinical symptom in EPM1. The fMRI findings reflect the progressive nature of this disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of tempol and tempol plus catalase on intra-renal haemodynamics in spontaneously hypertensive stroke-prone (SHSP) and Wistar rats.

PubMed

Ahmeda, Ahmad F; Rae, Mark G; Al Otaibi, Mohammed F; Anweigi, Lamyia M; Johns, Edward J

2017-05-01

Vasoconstriction within the renal medulla contributes to the development of hypertension. This study investigated the role of reactive oxygen species (ROS) in regulating renal medullary and cortical blood perfusion (MBP and CBP respectively) in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar rats. CBP and MBP were measured using a laser-Doppler flow meter before and after intra-renal infusion of tempol, the superoxide dismutase (SOD) mimetic or tempol plus catalase, the hydrogen peroxide-degrading enzyme. Tempol infusion significantly elevated blood perfusion within the renal medulla (MBP) in both SHRSP (by 43 ± 7%, P < 0.001) and Wistar rats (by 17 ± 2%, P < 0.05) but the magnitude of the increase was significantly greater in the SHRSP (P < 0.01). When the enzyme catalase and tempol were co-infused, MBP was again significantly increased in SHRSP (by 57 ± 6%, P < 0.001) and Wistar rats (by 33 ± 6%, P < 0.001), with a significantly greater increase in perfusion being induced in the SHRSP relative to the Wistar rats (P < 0.01). Notably, this increase was significantly greater than in those animals infused with tempol alone (P < 0.01). These results suggest that ROS plays a proportionally greater role in reducing renal vascular compliance, particularly within the renal medulla, in normotensive and hypertensive animals, with effects being greater in the hypertensive animals. This supports the hypothesis that SHRSP renal vasculature might be subjected to elevated level of oxidative stress relative to normotensive animals.

Cortical Correlates of Fitts’ Law

PubMed Central

Ifft, Peter J.; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

2011-01-01

Fitts’ law describes the fundamental trade-off between movement accuracy and speed: it states that the duration of reaching movements is a function of target size (TS) and distance. While Fitts’ law has been extensively studied in ergonomics and has guided the design of human–computer interfaces, there have been few studies on its neuronal correlates. To elucidate sensorimotor cortical activity underlying Fitts’ law, we implanted two monkeys with multielectrode arrays in the primary motor (M1) and primary somatosensory (S1) cortices. The monkeys performed reaches with a joystick-controlled cursor toward targets of different size. The reaction time (RT), movement time, and movement velocity changed with TS, and M1 and S1 activity reflected these changes. Moreover, modifications of cortical activity could not be explained by changes of movement parameters alone, but required TS as an additional parameter. Neuronal representation of TS was especially prominent during the early RT period where it influenced the slope of the firing rate rise preceding movement initiation. During the movement period, cortical activity was correlated with movement velocity. Neural decoders were applied to simultaneously decode TS and motor parameters from cortical modulations. We suggest that sensorimotor cortex activity reflects the characteristics of both the movement and the target. Classifiers that extract these parameters from cortical ensembles could improve neuroprosthetic control. PMID:22275888

Diffusive oxygen shunting between vessels in the preglomerular renal vasculature: anatomic observations and computational modeling.

PubMed

Gardiner, Bruce S; Thompson, Sarah L; Ngo, Jennifer P; Smith, David W; Abdelkader, Amany; Broughton, Brad R S; Bertram, John F; Evans, Roger G

2012-09-01

To understand how geometric factors affect arterial-to-venous (AV) oxygen shunting, a mathematical model of diffusive oxygen transport in the renal cortex was developed. Preglomerular vascular geometry was investigated using light microscopy (providing vein shape, AV separation, and capillary density near arteries) and published micro-computed tomography (CT) data (providing vessel size and AV separation; Nordsletten DA, Blackett S, Bentley MD, Ritman EL, Smith NP. IUPS Physiome Project. http://www.physiome.org.nz/publications/nordsletten_blackett_ritman_bentley_smith_2005/folder_contents). A "U-shaped" relationship was observed between the arterial radius and the distance between the arterial and venous lumens. Veins were found to partially wrap around the artery more consistently for larger rather than smaller arteries. Intrarenal arteries were surrounded by an area of fibrous tissue, lacking capillaries, the thickness of which increased from ∼5 μm for the smallest arteries (<16-μm diameter) to ∼20 μm for the largest arteries (>200-μm diameter). Capillary density was greater near smaller arteries than larger arteries. No capillaries were observed between wrapped AV vessel pairs. The computational model comprised a single AV pair in cross section. Geometric parameters critical in renal oxygen transport were altered according to variations observed by CT and light microscopy. Lumen separation and wrapping of the vein around the artery were found to be the critical geometric factors determining the amount of oxygen shunted between AV pairs. AV oxygen shunting increases both as lumen separation decreases and as the degree of wrapping increases. The model also predicts that capillaries not only deliver oxygen, but can also remove oxygen from the cortical parenchyma close to an AV pair. Thus the presence of oxygen sinks (capillaries or tubules) near arteries would reduce the effectiveness of AV oxygen shunting. Collectively, these data suggest that AV oxygen

αvβ6 Integrin Regulates Renal Fibrosis and Inflammation in Alport Mouse

PubMed Central

Hahm, Kyungmin; Lukashev, Matvey E.; Luo, Yi; Yang, William J.; Dolinski, Brian M.; Weinreb, Paul H.; Simon, Kenneth J.; Chun Wang, Li; Leone, Diane R.; Lobb, Roy R.; McCrann, Donald J.; Allaire, Normand E.; Horan, Gerald S.; Fogo, Agnes; Kalluri, Raghu; Shield, Charles F.; Sheppard, Dean; Gardner, Humphrey A.; Violette, Shelia M.

2007-01-01

The transforming growth factor (TGF)-β-inducible integrin αvβ6 is preferentially expressed at sites of epithelial remodeling and has been shown to bind and activate latent precursor TGF-β. Herein, we show that αvβ6 is overexpressed in human kidney epithelium in membranous glomerulonephritis, diabetes mellitus, IgA nephropathy, Goodpasture’s syndrome, and Alport syndrome renal epithelium. To assess the potential regulatory role of αvβ6 in renal disease, we studied the effects of function-blocking αvβ6 monoclonal antibodies (mAbs) and genetic ablation of the β6 subunit on kidney fibrosis in Col4A3−/− mice, a mouse model of Alport syndrome. Expression of αvβ6 in Alport mouse kidneys was observed primarily in cortical tubular epithelial cells and in correlation with the progression of fibrosis. Treatment with αvβ6-blocking mAbs inhibited accumulation of activated fibroblasts and deposition of interstitial collagen matrix. Similar inhibition of renal fibrosis was observed in β6-deficient Alport mice. Transcript profiling of kidney tissues showed that αvβ6-blocking mAbs significantly inhibited disease-associated changes in expression of fibrotic and inflammatory mediators. Similar patterns of transcript modulation were produced with recombinant soluble TGF-β RII treatment, suggesting shared regulatory functions of αvβ6 and TGF-β. These findings demonstrate that αvβ6 can contribute to the regulation of renal fibrosis and suggest this integrin as a potential therapeutic target. PMID:17200187

Cortical Feedback Control of Olfactory Bulb Circuits

PubMed Central

Boyd, Alison M.; Sturgill, James F.; Poo, Cindy; Isaacson, Jeffry S.

2013-01-01

SUMMARY Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. PMID:23259951

Detection of Focal Cortical Dysplasia Lesions in MRI Using Textural Features

NASA Astrophysics Data System (ADS)

Loyek, Christian; Woermann, Friedrich G.; Nattkemper, Tim W.

Focal cortical dysplasia (FCD) is a frequent cause of medically refractory partial epilepsy. The visual identification of FCD lesions on magnetic resonance images (MRI) is a challenging task in standard radiological analysis. Quantitative image analysis which tries to assist in the diagnosis of FCD lesions is an active field of research. In this work we investigate the potential of different texture features, in order to explore to what extent they are suitable for detecting lesional tissue. As a result we can show first promising results based on segmentation and texture classification.

iRENEX: a clinically informed decision support system for the interpretation of ⁹⁹mTc-MAG3 scans to detect renal obstruction.

PubMed

Garcia, Ernest V; Taylor, Andrew; Folks, Russell; Manatunga, Daya; Halkar, Raghuveer; Savir-Baruch, Bital; Dubovsky, Eva

2012-09-01

Decision support systems for imaging analysis and interpretation are rapidly being developed and will have an increasing impact on the practice of medicine. RENEX is a renal expert system to assist physicians evaluate suspected obstruction in patients undergoing mercaptoacetyltriglycine (MAG3) renography. RENEX uses quantitative parameters extracted from the dynamic renal scan data using QuantEM™II and heuristic rules in the form of a knowledge base gleaned from experts to determine if a kidney is obstructed; however, RENEX does not have access to and could not consider the clinical information available to diagnosticians interpreting these studies. We designed and implemented a methodology to incorporate clinical information into RENEX, implemented motion detection and evaluated this new comprehensive system (iRENEX) in a pilot group of 51 renal patients. To reach a conclusion as to whether a kidney is obstructed, 56 new clinical rules were added to the previously reported 60 rules used to interpret quantitative MAG3 parameters. All the clinical rules were implemented after iRENEX reached a conclusion on obstruction based on the quantitative MAG3 parameters, and the evidence of obstruction was then modified by the new clinical rules. iRENEX consisted of a library to translate parameter values to certainty factors, a knowledge base with 116 heuristic interpretation rules, a forward chaining inference engine to determine obstruction and a justification engine. A clinical database was developed containing patient histories and imaging report data obtained from the hospital information system associated with the pertinent MAG3 studies. The system was fine-tuned and tested using a pilot group of 51 patients (21 men, mean age 58.2 ± 17.1 years, 100 kidneys) deemed by an expert panel to have 61 unobstructed and 39 obstructed kidneys. iRENEX, using only quantitative MAG3 data agreed with the expert panel in 87 % (34/39) of obstructed and 90 % (55/61) of

Reduced Cortical Complexity in Children with Prader-Willi Syndrome and Its Association with Cognitive Impairment and Developmental Delay

PubMed Central

Lukoshe, Akvile; Hokken-Koelega, Anita C.; van der Lugt, Aad; White, Tonya

2014-01-01

Background Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. Methods High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Results Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. Conclusions These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene

6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

PubMed

Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A

2016-06-01

Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evolution of bone disease after kidney transplantation: A prospective histomorphometric analysis of trabecular and cortical bone.

PubMed

Carvalho, Catarina; Magalhães, Juliana; Pereira, Luciano; Simões-Silva, Liliana; Castro-Ferreira, Inês; Frazão, João Miguel

2016-01-01

Post-transplant bone disease results from multiple factors, including previous bone and mineral metabolism disturbances and effects from transplant-related medications. Bone biopsy remains the gold-standard diagnostic tool. We aimed to prospectively evaluate trabecular and cortical bone by histomorphometry after kidney transplantation. Seven patients, willing to perform follow-up bone biopsy, were included in the study. Dual-X-ray absorptiometry and trans-iliac bone biopsy were performed within the first 2 months after renal transplantation and repeated after 2-5 years of follow-up. Follow-up biopsy revealed a significant decrease in osteoblast surface/bone surface (0.91 ± 0.81 to 0.47 ± 0.12%, P = 0.036), osteoblasts number/bone surface (0.45 (0.23, 0.94) to 0.00/mm(2) , P = 0.018) and erosion surface/bone surface (3.75 ± 2.02 to 2.22 ± 1.38%, P = 0.044). A decrease in trabecular number (3.55 (1.81, 2.89) to 1.55/mm (1.24, 2.06), P = 0.018) and increase in trabecular separation (351.65 ± 135.04 to 541.79 ± 151.91 μm, P = 0.024) in follow-up biopsy suggest loss in bone quantity. We found no significant differences in cortical analysis, except a reduction in external cortical osteonal eroded surface (5.76 (2.94, 13.97) to 3.29% (0.00, 6.67), P = 0.043). Correlations between bone histomorphometric and dual-X-ray absorptiometry parameters gave inconsistent results. The results show a reduction in bone activity, suggesting increased risk of adynamic bone and loss of bone volume. Cortical bone seems less affected by post-transplant biological changes in the first years after kidney transplantation. © 2015 Asian Pacific Society of Nephrology.

The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

PubMed Central

Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

2015-01-01

Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

Absolute quantification of regional renal blood flow in swine by dynamic contrast-enhanced magnetic resonance imaging using a blood pool contrast agent.

PubMed

Lüdemann, Lutz; Nafz, Benno; Elsner, Franz; Grosse-Siestrup, Christian; Meissler, Michael; Kaufels, Nicola; Rehbein, Hagen; Persson, Pontus B; Michaely, Henrik J; Lengsfeld, Philipp; Voth, Matthias; Gutberlet, Matthias

2009-03-01

To evaluate for the first time in an animal model the possibility of absolute regional quantification of renal medullary and cortical perfusion by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a blood pool contrast agent. A total of 18 adult female pigs (age, 16-22 weeks; body weight, 45-65 kg; no dietary restrictions) were investigated by DCE-MRI. Absolute renal blood flow (RBF) measured by an ultrasound transit time flow probe around the renal vein was used as the standard of reference. An inflatable stainless cuff placed around the renal artery near its origin from the abdominal aorta was used to reduce RBF to 60%, 40%, and 20% of the baseline flow. The last measurement was performed with the cuff fully reopened. Absolute RBF values during these 4 perfusion states were compared with the results of DCE-MRI performed on a 1.5-T scanner with an 8-channel phased-array surface coil. All scans were acquired in breath-hold technique in the coronal plane using a field of view of 460 mm.Each dynamic scan commenced with a set of five 3D T1-weighted gradient echo sequences with different flip angles (alpha = 2 degrees, 5 degrees, 10 degrees, 20 degrees, 30 degrees): TE, 0.88 milliseconds; TR, 2.65 milliseconds; slice thickness, 8.8 mm for 4 slices; acquisition matrix, 128 x 128; and acquisitions, 4. These data served to calculate 3D intrinsic longitudinal relaxation rate maps (R10) and magnetization (M0). Immediately after these images, the dynamic 3D T1-weighted gradient echo images were acquired with the same parameters and a constant alpha = 30 degrees, half Fourier, 1 acquisition, 64 frames, a time interval of 1.65 seconds between each frame, and a total duration of 105.6. Three milliliters of an albumin-binding blood pool contrast agent (0.25 mmol/mL gadofosveset trisodium, Vasovist, Bayer Schering Pharma AG, Berlin, Germany) was injected at a rate of 3 mL/s. Perfusion was calculated using the arterial input function from the aorta, which was

Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure

PubMed Central

Kähönen, Mika; Raitakari, Olli; Laaksonen, Marika; Sievänen, Harri; Viikari, Jorma; Lyytikäinen, Leo-Pekka; Mellström, Dan; Karlsson, Magnus; Ljunggren, Östen; Grundberg, Elin; Kemp, John P.; Sayers, Adrian; Nethander, Maria; Evans, David M.; Vandenput, Liesbeth; Tobias, Jon H.; Ohlsson, Claes

2013-01-01

Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10−14; LOC285735, rs271170, p = 2.7×10−12; OPG, rs7839059, p = 1.2×10−10; and ESR1/C6orf97, rs6909279, p = 1.1×10−9). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10−9). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60–0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.

PubMed

Fukushi, Ken; Hatakeyama, Shingo; Yamamoto, Hayato; Tobisawa, Yuki; Yoneyama, Tohru; Soma, Osamu; Matsumoto, Teppei; Hamano, Itsuto; Narita, Takuma; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Terayama, Yuriko; Funyu, Tomihisa; Ohyama, Chikara

2017-02-06

Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m 2 or <60 mL/min/1.73 m 2 , respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m 2 , and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy. This study

Tc-99m Ethylenedicysteine and Tc-99m Dimercaptosuccinic Acid Scintigraphy-Comparison of the Two for Detection of Scarring and Differential Cortical Function.

PubMed

Dharmalingam, Anitha; Pawar, Shwetal U; Parelkar, Sandesh V; Shetye, Suruchi S; Ghorpade, Mangala K; Tilve, Gundu H

2017-01-01

The differential cortical function obtained by Tc-99m EC is comparable to that of Tc-99m DMSA. However, identification of scars on Tc-99m EC images needs to be studied. The aim of the study is to evaluate role of Tc-99m EC for detection of scarring and differential cortical function by comparing with Tc-99m DMSA. Prospective observational study of recurrent UTI; minimum 6 weeks after acute episode; when urine examination is negative for pus cells. Forty-seven children with normal positioned kidneys underwent Tc-99m EC and DMSA scintigraphy. The DRF and cortical phase images of both studies in the same image matrix size were evaluated by two independent observers for scarring; Tc-99m DMSA was considered as the gold standard. MS Excel 2007 and GraphPad Instat V3.1 and ROC analysis. There was no significant difference in the detection of scarring using two studies with Cohen's kappa coefficient (κ) 0.932. The sensitivity and specificity of Tc-99m EC for detection of scarring was 98.75% and 99.15%, respectively. There was good agreement between the differential cortical function calculated using two studies. The summed Tc-99m EC images with an acceptable high image contrast allow detection of cortical scarring in patients with normal kidney positions. It is an excellent single-modality comprehensive investigational agent for renal parenchymal defects, function, and excretion evaluation with the added advantages of lower cost, convenience, and low radiation exposure to the child.

Pathology and diagnosis of renal non-AL amyloidosis.

PubMed

Sethi, Sanjeev; Theis, Jason D

2018-06-01

Renal amyloidosis is characterized by acellular Congo red positive deposits in the glomeruli, interstitium and/or arteries. Light chain restriction on immunofluorescence studies is present in AL-amyloidosis, the most common type of amyloidosis involving the kidney. The detection of Congo red positive deposits coupled with negative immunofluorescence studies is highly suggestive of non-AL amyloidosis. Some of the non-AL amyloidosis are common while others are relatively rare. The clinical features, laboratory and renal pathology findings are helpful in the diagnosis and typing of non-AL amyloidosis. Thus, ALECT2 amyloidosis is characterized by diffuse cortical interstitial amyloid deposits, AA amyloidosis shows vascular deposits in addition to the glomerular deposits, AFib amyloidosis is characterized by massive amyloid accumulation limited to the glomeruli resulting in the obliteration of glomerular architecture, AApoA1 and AApoAIV are characterized by large amyloid deposits restricted to the medulla, and AGel shows swirling patterns of amyloid fibrils on electron microscopy. While light microscopy is very helpful, accurate typing of non-AL amyloidosis then requires immunohistochemical or laser microdissection/mass spectrometry studies of the Congo red positive deposits. Immunohistochemical studies are available for some of the non-AL amyloidosis. On the other hand, mass spectrometry analysis is a one stop methodology for confirmation and typing of amyloidosis. The diagnosis and typing of amyloidosis by mass spectrometry is based on finding the signature amyloid peptides, apolipoprotein E and serum amyloid-P component, followed by detection of precursor amyloidogenic protein such as LECT2, fibrinogen-α, gelsolin, etc. To, summarize, non-AL amyloidosis is a group of amyloidosis with distinctive clinical, laboratory and renal pathology findings. Typing of the amyloidosis is best performed using mass spectrometry methodology. Accurate typing of non-AL amyloidosis is

Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages.

PubMed

Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert

2010-05-01

Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

Birth Order and Maternal Age for Reported Cases of Severe Prenatal Cortical Hyperostosis (Caffey–Silverman Disease)

PubMed

Engel, Rolf R; Cifuentes, Raul F

2017-07-01

The spectrum of prenatal cortical hyperostosis includes a mild phenotype that typically presents after 35 weeks of gestation, and a severe form that presents earlier. The skeletal and systemic manifestations of the severe phenotype remain unexplained. A review of reported cases indicates that older mothers and firstborn infants are overrepresented. This combination suggests decreased fertility. Fourteen years after the birth of the present case, his mother presented with renal failure from multiple myeloma raising the possibility that a maternal antibody may play a role in the etiology of severe prenatal Caffey disease. The present case report is also intended to alert clinicians to potential difficulties with tracheal intubation secondary to micrognathia from mandibular involvement during a critical growth period.

The role of the renal specialist nurse in prevention of renal failure.

PubMed

Hurst, J

2002-01-01

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury

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

Peters, Esther, E-mail: esther.peters@radboudumc.n

Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n = 18) were subjected to renal ischemia (30 min) and reperfusion (I/R), or sham-operated. In a second model, rats (n = 18) received a 30 minmore » infusion of lipopolysaccharide (LPS; 2.5 mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000 U/kg) was administered intravenously (15 min before reperfusion, or 90 min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension at late reperfusion were no longer significantly affected. RecAP did not influence I/R-induced effects on mean arterial pressure. During endotoxemia, recAP treatment did not modulate the LPS-induced changes in systemic hemodynamics and renal oxygenation. In both models, recAP did exert a clear renal protective anti-inflammatory effect, demonstrated by attenuated immunostaining of inflammatory, tubular injury and pro-apoptosis markers. Whether this renal protective effect is sufficient to improve outcome of patients suffering from sepsis-associated AKI is being investigated in a large clinical trial. - Highlights: • Human recombinant alkaline phosphatase (recAP) is a potential new therapy for sepsis-associated acute kidney injury (AKI). • RecAP can modulate renal oxygenation and hemodynamics immediately following I/R-induced AKI. • RecAP did not modulate endotoxemia-induced changes in systemic hemodynamics and renal oxygenation. • RecAP did exert a clear renal

Transarterial Embolization of a Renal Artery Aneurysm Concomitant With Renal Arteriovenous Fistula.

PubMed

Hongsakul, Keerati; Bannangkoon, Kittipitch; Boonsrirat, Ussanee; Kritpracha, Boonprasit

2018-01-01

Congenital renal artery aneurysm is uncommon. Moreover, renal artery aneurysm concomitant with a congenital renal arteriovenous fistula is extremely rare. Transarterial embolization is the first-line treatment for these conditions. We report a case of a patient with congenital renal artery aneurysm concomitant with a congenital renal arteriovenous fistula of the upper polar left renal artery which was successfully treated by transarterial embolization with coil, glue, and Amplatzer vascular plug.

Cortical feedback control of olfactory bulb circuits.

PubMed

Boyd, Alison M; Sturgill, James F; Poo, Cindy; Isaacson, Jeffry S

2012-12-20

Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. Copyright © 2012 Elsevier Inc. All rights reserved.

Neurochemical abnormalities in brains of renal failure patients treated by repeated hemodialysis.

PubMed

Perry, T L; Yong, V W; Kish, S J; Ito, M; Foulks, J G; Godolphin, W J; Sweeney, V P

1985-10-01

We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.

Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers.

PubMed

Pruijm, Menno; Hofmann, Lucie; Charollais-Thoenig, Julie; Forni, Valentina; Maillard, Marc; Coristine, Andrew; Stuber, Matthias; Burnier, Michel; Vogt, Bruno

2013-09-01

Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

PubMed

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats

NASA Technical Reports Server (NTRS)

Allen, Matthew R.; Bloomfield, Susan A.

2003-01-01

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.

Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

PubMed

El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

2016-03-01

The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

Rehabilitation-triggered cortical plasticity after stroke: in vivo imaging at multiple scales (Conference Presentation)

NASA Astrophysics Data System (ADS)

Allegra Mascaro, Anna Letizia; Conti, Emilia; Lai, Stefano; Spalletti, Cristina; Di Giovanna, Antonino Paolo; Alia, Claudia; Panarese, Alessandro; Sacconi, Leonardo; Micera, Silvestro; Caleo, Matteo; Pavone, Francesco S.

2017-02-01

Neurorehabilitation protocols based on the use of robotic devices provide a highly repeatable therapy and have recently shown promising clinical results. Little is known about how rehabilitation molds the brain to promote motor recovery of the affected limb. We used a custom-made robotic platform that provides quantitative assessment of forelimb function in a retraction test. Complementary imaging techniques allowed us to access to the multiple facets of robotic rehabilitation-induced cortical plasticity after unilateral photothrombotic stroke in mice Primary Motor Cortex (Caudal Forelimb Area - CFA). First, we analyzed structural features of vasculature and dendritic reshaping in the peri-infarct area with two-photon fluorescence microscopy. Longitudinal analysis of dendritic branches and spines of pyramidal neurons suggests that robotic rehabilitation promotes the stabilization of peri-infarct cortical excitatory circuits, which is not accompanied by consistent vascular reorganization towards pre-stroke conditions. To investigate if this structural stabilization was linked to functional remapping, we performed mesoscale wide-field imaging on GCaMP6 mice while performing the motor task on the robotic platform. We revealed temporal and spatial features of the motor-triggered cortical activation, shining new light on rehabilitation-induced functional remapping of the ipsilesional cortex. Finally, by using an all-optical approach that combines optogenetic activation of the contralesional hemisphere and wide-field functional imaging of peri-infarct area, we dissected the effect of robotic rehabilitation on inter-hemispheric cortico-cortical connectivity.

Multiple Renal Artery Pseudoaneurysms in Patients Undergoing Renal Artery Embolization Following Partial Nephrectomy: Correlation with RENAL Nephrometry Scores

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

Gupta, Nakul; Patel, Anish; Ensor, Joe

PurposeTo describe the incidence of multiple renal artery pseudoaneurysms (PSA) in patients referred for renal artery embolization following partial nephrectomy and to study its relationship to RENAL nephrometry scores.Materials and MethodsThe medical records of 25 patients referred for renal artery embolization after partial nephrectomy were retrospectively reviewed for the following parameters: size and number of tumors, RENAL nephrometry scores, angiographic abnormalities, technical and clinical outcomes, and estimated glomerular filtration rates (eGFRs) after embolization.ResultsTwenty-four patients had primary renal tumors, while 1 patient had a pancreatic tumor invading the kidney. Multiple tumors were resected in 4 patients. Most patients (92 %) were symptomatic,more » presenting with gross hematuria, flank pain, or both. Angiography revealed PSA with (n = 5) or without (n = 20) AV fistulae. Sixteen patients (64 %) had multiple PSA involving multiple renal vessels. Higher RENAL nephrometry scores were associated with an increasing likelihood of multiple PSA. Multiple vessels were embolized in 14 patients (56 %). Clinical success was achieved after one (n = 22) or two (n = 3) embolization sessions in all patients. Post-embolization eGFR values at different time points after embolization were not significantly different from the post-operative eGFR.ConclusionA majority of patients requiring renal artery embolization following partial nephrectomy have multiple pseudoaneurysms, often requiring selective embolization of multiple vessels. Higher RENAL nephrometry score is associated with an increasing likelihood of multiple pseudoaneurysms. We found transarterial embolization to be a safe and effective treatment option with no long-term adverse effect on renal function in all but one patient with a solitary kidney.« less

Multiparametric Quantitative Ultrasound Imaging in Assessment of Chronic Kidney Disease.

PubMed

Gao, Jing; Perlman, Alan; Kalache, Safa; Berman, Nathaniel; Seshan, Surya; Salvatore, Steven; Smith, Lindsey; Wehrli, Natasha; Waldron, Levi; Kodali, Hanish; Chevalier, James

2017-11-01

To evaluate the value of multiparametric quantitative ultrasound imaging in assessing chronic kidney disease (CKD) using kidney biopsy pathologic findings as reference standards. We prospectively measured multiparametric quantitative ultrasound markers with grayscale, spectral Doppler, and acoustic radiation force impulse imaging in 25 patients with CKD before kidney biopsy and 10 healthy volunteers. Based on all pathologic (glomerulosclerosis, interstitial fibrosis/tubular atrophy, arteriosclerosis, and edema) scores, the patients with CKD were classified into mild (no grade 3 and <2 of grade 2) and moderate to severe (at least 2 of grade 2 or 1 of grade 3) CKD groups. Multiparametric quantitative ultrasound parameters included kidney length, cortical thickness, pixel intensity, parenchymal shear wave velocity, intrarenal artery peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index. We tested the difference in quantitative ultrasound parameters among mild CKD, moderate to severe CKD, and healthy controls using analysis of variance, analyzed correlations of quantitative ultrasound parameters with pathologic scores and the estimated glomerular filtration rate (GFR) using Pearson correlation coefficients, and examined the diagnostic performance of quantitative ultrasound parameters in determining moderate CKD and an estimated GFR of less than 60 mL/min/1.73 m 2 using receiver operating characteristic curve analysis. There were significant differences in cortical thickness, pixel intensity, PSV, and EDV among the 3 groups (all P < .01). Among quantitative ultrasound parameters, the top areas under the receiver operating characteristic curves for PSV and EDV were 0.88 and 0.97, respectively, for determining pathologic moderate to severe CKD, and 0.76 and 0.86 for estimated GFR of less than 60 mL/min/1.73 m 2 . Moderate to good correlations were found for PSV, EDV, and pixel intensity with pathologic scores and estimated GFR. The

UK audit of analysis of quantitative parameters from renography data generated using a physical phantom.

PubMed

Nijran, Kuldip S; Houston, Alex S; Fleming, John S; Jarritt, Peter H; Heikkinen, Jari O; Skrypniuk, John V

2014-07-01

In this second UK audit of quantitative parameters obtained from renography, phantom simulations were used in cases in which the 'true' values could be estimated, allowing the accuracy of the parameters measured to be assessed. A renal physical phantom was used to generate a set of three phantom simulations (six kidney functions) acquired on three different gamma camera systems. A total of nine phantom simulations and three real patient studies were distributed to UK hospitals participating in the audit. Centres were asked to provide results for the following parameters: relative function and time-to-peak (whole kidney and cortical region). As with previous audits, a questionnaire collated information on methodology. Errors were assessed as the root mean square deviation from the true value. Sixty-one centres responded to the audit, with some hospitals providing multiple sets of results. Twenty-one centres provided a complete set of parameter measurements. Relative function and time-to-peak showed a reasonable degree of accuracy and precision in most UK centres. The overall average root mean squared deviation of the results for (i) the time-to-peak measurement for the whole kidney and (ii) the relative function measurement from the true value was 7.7 and 4.5%, respectively. These results showed a measure of consistency in the relative function and time-to-peak that was similar to the results reported in a previous renogram audit by our group. Analysis of audit data suggests a reasonable degree of accuracy in the quantification of renography function using relative function and time-to-peak measurements. However, it is reasonable to conclude that the objectives of the audit could not be fully realized because of the limitations of the mechanical phantom in providing true values for renal parameters.

Microarchitectural Deterioration of Cortical and Trabecular Bone: Differing Effects of Denosumab and Alendronate

PubMed Central

Seeman, Ego; Delmas, Pierre D; Hanley, David A; Sellmeyer, Deborah; Cheung, Angela M; Shane, Elizabeth; Kearns, Ann; Thomas, Thierry; Boyd, Steven K; Boutroy, Stephanie; Bogado, Cesar; Majumdar, Sharmila; Fan, Michelle; Libanati, Cesar; Zanchetta, Jose

2015-01-01

The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double-blind pilot study, 247 postmenopausal women were randomized to denosumab (60mg subcutaneous 6 monthly), alendronate (70mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C-telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to < .001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab. PMID:20222106

Mapping cortical hubs in tinnitus

PubMed Central

2009-01-01

Background Subjective tinnitus is the perception of a sound in the absence of any physical source. It has been shown that tinnitus is associated with hyperactivity of the auditory cortices. Accompanying this hyperactivity, changes in non-auditory brain structures have also been reported. However, there have been no studies on the long-range information flow between these regions. Results Using Magnetoencephalography, we investigated the long-range cortical networks of chronic tinnitus sufferers (n = 23) and healthy controls (n = 24) in the resting state. A beamforming technique was applied to reconstruct the brain activity at source level and the directed functional coupling between all voxels was analyzed by means of Partial Directed Coherence. Within a cortical network, hubs are brain structures that either influence a great number of other brain regions or that are influenced by a great number of other brain regions. By mapping the cortical hubs in tinnitus and controls we report fundamental group differences in the global networks, mainly in the gamma frequency range. The prefrontal cortex, the orbitofrontal cortex and the parieto-occipital region were core structures in this network. The information flow from the global network to the temporal cortex correlated positively with the strength of tinnitus distress. Conclusion With the present study we suggest that the hyperactivity of the temporal cortices in tinnitus is integrated in a global network of long-range cortical connectivity. Top-down influence from the global network on the temporal areas relates to the subjective strength of the tinnitus distress. PMID:19930625

Quantitative Ultrasound for Measuring Obstructive Severity in Children with Hydronephrosis.

PubMed

Cerrolaza, Juan J; Peters, Craig A; Martin, Aaron D; Myers, Emmarie; Safdar, Nabile; Linguraru, Marius George

2016-04-01

We define sonographic biomarkers for hydronephrotic renal units that can predict the necessity of diuretic nuclear renography. We selected a cohort of 50 consecutive patients with hydronephrosis of varying severity in whom 2-dimensional sonography and diuretic mercaptoacetyltriglycine renography had been performed. A total of 131 morphological parameters were computed using quantitative image analysis algorithms. Machine learning techniques were then applied to identify ultrasound based safety thresholds that agreed with the t½ for washout. A best fit model was then derived for each threshold level of t½ that would be clinically relevant at 20, 30 and 40 minutes. Receiver operating characteristic curve analysis was performed. Sensitivity, specificity and area under the receiver operating characteristic curve were determined. Improvement obtained by the quantitative imaging method compared to the Society for Fetal Urology grading system and the hydronephrosis index was statistically verified. For the 3 thresholds considered and at 100% sensitivity the specificities of the quantitative imaging method were 94%, 70% and 74%, respectively. Corresponding area under the receiver operating characteristic curve values were 0.98, 0.94 and 0.94, respectively. Improvement obtained by the quantitative imaging method over the Society for Fetal Urology grade and hydronephrosis index was statistically significant (p <0.05 in all cases). Quantitative imaging analysis of renal sonograms in children with hydronephrosis can identify thresholds of clinically significant washout times with 100% sensitivity to decrease the number of diuretic renograms in up to 62% of children. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Hypertensive renal disease: susceptibility and resistance in inbred hypertensive rat lines.

PubMed

Braun, Michael C; Herring, Stacy M; Gokul, Nisha; Monita, Monique; Bell, Rebecca; Hicks, M John; Wenderfer, Scott E; Doris, Peter A

2013-10-01

Spontaneously hypertensive rat (SHR) lines differ in their susceptibility to hypertensive end-organ disease and may provide an informative model of genetic risk of disease. Lines derived from the original SHR-B and SHR-C clades are highly resistant to hypertensive end-organ disease, whereas lines derived from the SHR-A clade were selected for stroke susceptibility and experience hypertensive renal disease. Here we characterize the temporal development of progressive renal injury in SHR-A3 animals consuming 0.3% sodium in the diet and drinking water. SHR-A3 rats demonstrate albuminuria, glomerular damage, tubulointerstitial injury, and renal fibrosis that emerge at 18 weeks of age and progress. Mortality of SHR-A3 animals was 50% at 40 weeks of age, and animals surviving to this age had reduced renal function. In contrast SHR-B2, which are 87% genetically identical to SHR-A3, are substantially protected from renal injury and demonstrate only moderate changes in albuminuria and renal histological injury over this time period. At 40 weeks of age, electron microscopy of the renal glomerulus revealed severe podocyte effacement in SHR-A3, but slit diaphragm architecture in SHR-B2 at this age was well preserved. Renal injury traits in the F1 and F2 progeny of an intercross between SHR-A3 and SHR-B2 were measured to determine heritability of renal injury in this model. Heritability of albuminuria, glomerular injury, and tubulointerstitial injury were estimated at 48.9, 66.5 and 58.6%, respectively. We assessed the relationship between blood pressure and renal injury measures in the F2 animals and found some correlation between these variables that explain up to 26% of the trait variation. Quantitative trait locus (QTL) mapping was performed using over 200 single nucleotide polymorphism markers distributed across the 13% of the genome that differs between these two closely related lines. Mapping of albuminuria, tubulointerstitial injury, and renal fibrosis failed to

The multislice CT findings of renal carcinoma associated with XP11.2 translocation/TFE gene fusion and collecting duct carcinoma.

PubMed

Zhu, Qing-Qiang; Wang, Zhong-Qiu; Zhu, Wen-Rong; Chen, Wen-Xin; Wu, Jing-Tao

2013-04-01

Renal cell carcinoma associated with Xp11.2 translocation and TFE gene fusion (Xp11.2/TFE RCC), and collecting duct carcinoma (CDC) are uncommon subtypes of renal cell carcinomas. To investigate the multislice CT (MSCT) characteristics of these two tumor types. Nine patients with Xp11.2/TFE RCC and 10 patients with CDC were studied retrospectively. MSCT was undertaken to investigate differences in tumor characteristics and enhancement patterns. All patients had single tumors centered in the renal medulla. Two patients with each tumor type had lymph node involvement and there was a single case of hepatic metastasis (Xp11.2/TFE RCC). The mean tumor diameter of Xp11.2/TFE RCC tumors was significantly larger than for CDC tumors. Two patients with Xp11.2/TFE RCC had cystic components as did eight patients with CDC (P < 0.05). Calcifications were present in six patients, each with CDC. Clear tumor boundaries were visible in two patients with CDC and in nine with Xp11.2/TFE RCC (P < 0.05). The density of Xp11.2/TFE RCC tumors was greater than that of CDC tumors, normal renal cortex, or medulla on unenhanced CT. Enhancement was higher with Xp11.2/TFE RCC than with CDC tumors during all phases. Xp11.2/TFE RCC enhancement was higher than in the renal medulla during cortical and medullary phase but lower than in normal renal medulla during the delayed phase. CDC tumor enhancement was lower than that for normal renal medulla during all enhanced phases. Both tumor types originated from the renal medulla. Distinguishing features included density on unenhanced CT, enhancement patterns, and capsule signs. Identifying these differences may aid diagnosis.

Effect of aldosterone on BK channel expression in mammalian cortical collecting duct

PubMed Central

Estilo, Genevieve; Liu, Wen; Pastor-Soler, Nuria; Mitchell, Phillip; Carattino, Marcelo D.; Kleyman, Thomas R.; Satlin, Lisa M.

2008-01-01

Apical large-conductance Ca2+-activated K+ (BK) channels in the cortical collecting duct (CCD) mediate flow-stimulated K+ secretion. Dietary K+ loading for 10–14 days leads to an increase in BK channel mRNA abundance, enhanced flow-stimulated K+ secretion in microperfused CCDs, and a redistribution of immunodetectable channels from an intracellular pool to the apical membrane (Najjar F, Zhou H, Morimoto T, Bruns JB, Li HS, Liu W, Kleyman TR, Satlin LM. Am J Physiol Renal Physiol 289: F922–F932, 2005). To test whether this adaptation was mediated by a K+-induced increase in aldosterone, New Zealand White rabbits were fed a low-Na+ (LS) or high-Na+ (HS) diet for 7–10 days to alter circulating levels of aldosterone but not serum K+ concentration. Single CCDs were isolated for quantitation of BK channel subunit (total, α-splice variants, β-isoforms) mRNA abundance by real-time PCR and measurement of net transepithelial Na+ (JNa) and K+ (JK) transport by microperfusion; kidneys were processed for immunolocalization of BK α-subunit by immunofluorescence microscopy. At the time of death, LS rabbits excreted no urinary Na+ and had higher circulating levels of aldosterone than HS animals. The relative abundance of BK α-, β2-, and β4-subunit mRNA and localization of immunodetectable α-subunit were similar in CCDs from LS and HS animals. In response to an increase in tubular flow rate from ∼1 to 5 nl·min−1·mm−1, the increase in JNa was greater in LS vs. HS rabbits, yet the flow-stimulated increase in JK was similar in both groups. These data suggest that aldosterone does not contribute to the regulation of BK channel expression/activity in response to dietary K+ loading. PMID:18579708

Cognitive Plasticity and Cortical Modules

PubMed Central

Mercado, Eduardo

2009-01-01

Some organisms learn to calculate, accumulate knowledge, and communicate in ways that others do not. What factors determine which intellectual abilities a particular species or individual can easily acquire? I propose that cognitive-skill learning capacity reflects (a) the availability of specialized cortical circuits, (b) the flexibility with which cortical activity is coordinated, and (c) the customizability of cortical networks. This framework can potentially account for differences in learning capacity across species, individuals, and developmental stages. Understanding the mechanisms that constrain cognitive plasticity is fundamental to developing new technologies and educational practices that maximize intellectual advancements. PMID:19750239

Cognitive Plasticity and Cortical Modules.

PubMed

Mercado, Eduardo

2009-06-01

Some organisms learn to calculate, accumulate knowledge, and communicate in ways that others do not. What factors determine which intellectual abilities a particular species or individual can easily acquire? I propose that cognitive-skill learning capacity reflects (a) the availability of specialized cortical circuits, (b) the flexibility with which cortical activity is coordinated, and (c) the customizability of cortical networks. This framework can potentially account for differences in learning capacity across species, individuals, and developmental stages. Understanding the mechanisms that constrain cognitive plasticity is fundamental to developing new technologies and educational practices that maximize intellectual advancements.

Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.

PubMed

Arata, Yukinobu; Hiroshima, Michio; Pack, Chan-Gi; Ramanujam, Ravikrishna; Motegi, Fumio; Nakazato, Kenichi; Shindo, Yuki; Wiseman, Paul W; Sawa, Hitoshi; Kobayashi, Tetsuya J; Brandão, Hugo B; Shibata, Tatsuo; Sako, Yasushi

2016-08-23

Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Quantitative comparison of cortical and deep grey matter in pathological subtypes of unilateral cerebral palsy.

PubMed

Scheck, Simon M; Pannek, Kerstin; Fiori, Simona; Boyd, Roslyn N; Rose, Stephen E

2014-10-01

The aim of this study was to quantify grey matter changes in children with unilateral cerebral palsy (UCP), differentiating between cortical or deep grey matter (CDGM) lesions, periventricular white matter (PWM) lesions, and unilateral and bilateral lesions. In a cross-sectional study we obtained high resolution structural magnetic resonance images from 72 children (41 males, 31 females, mean age 10y 9mo [SD 3y 1mo], range 5y 1mo-17y 1mo) with UCP (33 left, 39 right hemiplegia; Manual Ability Classification System level I n=29, II n=43; Gross Motor Function Classification System level I n=46, II n=26), and 19 children with typical development (CTD; eight males, 11 females, mean age 11y 2mo [SD 2y 7mo], range 7y 8mo-16y 4mo). Images were classified by lesion type and analyzed using voxel-based morphometry (VBM) and subcortical volumetric analysis. Deep grey matter volumes were not significantly different between children with CDGM and PWM lesions, with the thalamus, putamen, and globus pallidus being reduced unilaterally in both groups compared with CTD (p≤0.001). Children with CDGM lesions additionally showed widespread cortical changes involving all lobes using VBM (p<0.01). Children with bilateral lesions had reduced thalamus and putamen volumes bilaterally (p<0.001). The thalamic volume was reduced bilaterally in children with unilateral lesions (p=0.004). Lesions to the PWM cause secondary changes to the deep grey matter structures similar to primary changes seen in CDGM lesions. Despite having a unilateral phenotype, grey matter changes are observed bilaterally, even in children with unilateral lesions. © 2014 Mac Keith Press.

Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms

PubMed Central

Suh, Sooyeon; Kim, Hosung; Dang-Vu, Thien Thanh; Joo, Eunyeon; Shin, Chol

2016-01-01

Study Objectives: Recent studies have suggested that structural abnormalities in insomnia may be linked with alterations in the default-mode network (DMN). This study compared cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia (PI) and good sleepers (GS). Methods: The current study used a clinical subsample from the longitudinal community-based Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia symptoms (PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants underwent MRI acquisition. Based on literature review, we selected cortical regions corresponding to the DMN. A seed-based structural covariance analysis measured cortical thickness correlation between each seed region of the DMN and other cortical areas. Association of cortical thickness and covariance with sleep quality and neuropsychological assessments were further assessed. Results: Compared to GS, cortical thinning was found in PIS in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural connectivity between anterior and posterior regions of the DMN was observed in the PIS group. Decreased structural covariance within the DMN was associated with higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to poor performance in executive function in PIS. Conclusion: Disrupted structural covariance network in PIS might reflect malfunctioning of antero-posterior disconnection of the DMN during the wake to sleep transition that is commonly found during normal sleep. The observed structural network alteration may further implicate commonly observed sustained sleep difficulties and cognitive impairment in insomnia. Citation: Suh S, Kim H, Dang-Vu TT, Joo E, Shin C. Cortical thinning and altered cortico-cortical structural covariance of the default mode network in patients with

Atheroembolic renal disease

MedlinePlus

Renal disease - atheroembolic; Cholesterol embolization syndrome; Atheroemboli - renal; Atherosclerotic disease - renal ... disorder of the arteries. It occurs when fat, cholesterol, and other substances build up in the walls ...

Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.

PubMed

Ding, Hao; Jiang, Lei; Xu, Jing; Bai, Feng; Zhou, Yang; Yuan, Qi; Luo, Jing; Zen, Ke; Yang, Junwei

2017-09-01

Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. Copyright © 2017 the American Physiological Society.

Response of Quiescent Cerebral Cortical Astrocytes to Nanofibrillar Scaffold Properties

NASA Astrophysics Data System (ADS)

Ayres, Virginia; Mujdat Tiryaki, Volkan; Xie, Kan; Ahmed, Ijaz; Shreiber, David I.

2013-03-01

We present results of an investigation to examine the hypothesis that the extracellular environment can trigger specific signaling cascades with morphological consequences. Differences in the morphological responses of quiescent cerebral cortical astrocytes cultured on the nanofibrillar matrices versus poly-L-lysine functionalized glass and Aclar, and unfunctionalized Aclar surfaces were demonstrated using atomic force microscopy (AFM) and phalloidin staining of F-actin. The differences and similarities of the morphological responses were consistent with differences and similarities of the surface polarity and surface roughness of the four surfaces investigated in this work, characterized using contact angle and AFM measurements. The three-dimensional capability of AFM was also used to identify differences in cell spreading. An initial quantitative immunolabeling study further identified significant differences in the activation of the Rho GTPases: Cdc42, Rac1, and RhoA, which are upstream regulators of the observed morphological responses: filopodia, lamellipodia, and stress fiber formation. The results support the hypothesis that the extracellular environment can trigger preferential activation of members of the Rho GTPase family with demonstrable morphological consequences for cerebral cortical astrocytes. The support of NSF PHY-095776 is acknowledged.

Effects of Renal Denervation from the Intima and the Adventitia of Renal Arteries on Renal Sympathetic Nerve Activity in Dogs: A Comparative Study.

PubMed

Bai, Minfu; Yang, Chaokuan; Gao, Chuanyu; Wang, Xianpei; Liu, Hongzhi; Zhang, You; Liu, Jun; Wu, Jintao; Jian, Dongdong; Zhu, Lijie; Zhao, Wenli; Ma, Peiyao; Han, Yaqi

2015-01-01

This study was designed to observe the efficacy and safety of renal denervation from the inside and outside of renal arteries. Fourteen beagles were randomly divided into a control group (n = 4) and treatment group (n = 10). One renal artery in every beagle of the treatment group was randomly assigned to an intimal group (10 renal arteries) which underwent percutaneous renal denervation from the inside, and another renal artery was assigned to an adventitial group (10 renal arteries) which underwent renal denervation from the outside by laparotomy. Compared with the intimal group, the renal norepinephrine (NE) concentration in the adventitial group had significantly decreased (p = 0.003) at 3 months postsurgery. Renal artery HE staining showed that the perineurium from the adventitial group appeared thickened. Western blotting showed that renal tissue tyrosine hydroxylase (TH) protein expression in the adventitial group was significantly lower than that in the intimal group (p < 0.01) at 3 months postsurgery. There was a renal artery stenosis and a renal atrophy in the intimal group after 1 month of follow-up. The inhibitory effect on renal sympathetic nerve activity was more effective in the adventitial group than the intimal group, and renal denervation in the former group was safe. © 2015 S. Karger AG, Basel.

Renal cell carcinoma

MedlinePlus

Renal cancer; Kidney cancer; Hypernephroma; Adenocarcinoma of renal cells; Cancer - kidney ... 2016:chap 57. National Cancer Institute website. Renal cell cancer treatment (PDQ) - health professional version. February 23, 2018. ...

Can MR Measurement of Renal Artery Flow and Renal Volume Predict the Outcome of Percutaneous Transluminal Renal Angioplasty?

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

Binkert, Christoph A.; Debatin, Jorg F.; Schneider, Ernst

2001-07-15

Purpose: Predicting therapeutic benefit from percutaneous transluminal renal angioplasty (PTRA) in patients with renal artery stenosis (RAS) remains difficult. This study investigates whether magnetic resonance (MR)-based renal artery flow measurements relative to renal parenchymal volume can predict clinical outcome following PTRA.Methods: The data on 23 patients (13 men, 10 women; age range 47-82 years, mean age 64 years) were analyzed. The indication for treatment was hypertension (n = 18) or renal insufficiency (n = 5). Thirty-four cases of RAS were identified: bilateral disease was manifest in 11 and unilateral disease in 12 patients. The MR imaging protocol included a breath-hold,more » cardiac-gated cine phase-contrast sequence for renal flow measurement and a fast multiplanar spoiled gradient-echo sequence for renal volume measurement. MR measurements were performed on the day prior to and the day following PTRA. Clinical success was defined as (a) a reduction in diastolic blood pressure > 15% or (b) a reduction in serum creatinine > 20%. Kidneys were categorized as normal volume or low volume. A renal flow index (RFI) was calculated by dividing the renal flow (ml/min) by the renal volume (cm{sup 3}).Results: Clinical success was observed in 11 patients. Twelve patients did not benefit from angioplasty. Normal kidney volume was seen in 10 of 11 responders and in 8 of 12 nonresponders, resulting in a sensitivity of 91%, specificity of 33%, a positive predictive value (PPV) of 56% and a negative predictive value (NPV) of 80%. A RFI below a threshold of 1.5 ml/min/cm{sup 3} predicted successful outcome with 100% sensitivity, 33% specificity, 58% PPV, and 100% NPV. The combination of normal renal volume and a RFI below 1.5 ml/min/cm{sup 3} identified PTRA responders with a sensitivity of 91%, a specificity of 67%, a PPV of 71%, and a NPV of 89%. PTRA resulted in a greater increase in renal flow in responders compared with nonresponders (p < 0.001).Conclusion

Data integration in physiology using Bayes’ rule and minimum Bayes’ factors: deubiquitylating enzymes in the renal collecting duct

PubMed Central

Xue, Zhe; Chen, Jia-Xu; Zhao, Yue; Medvar, Barbara

2017-01-01

A major challenge in physiology is to exploit the many large-scale data sets available from “-omic” studies to seek answers to key physiological questions. In previous studies, Bayes’ theorem has been used for this purpose. This approach requires a means to map continuously distributed experimental data to probabilities (likelihood values) to derive posterior probabilities from the combination of prior probabilities and new data. Here, we introduce the use of minimum Bayes’ factors for this purpose and illustrate the approach by addressing a physiological question, “Which deubiquitylating enzymes (DUBs) encoded by mammalian genomes are most likely to regulate plasma membrane transport processes in renal cortical collecting duct principal cells?” To do this, we have created a comprehensive online database of 110 DUBs present in the mammalian genome (https://hpcwebapps.cit.nih.gov/ESBL/Database/DUBs/). We used Bayes’ theorem to integrate available information from large-scale data sets derived from proteomic and transcriptomic studies of renal collecting duct cells to rank the 110 known DUBs with regard to likelihood of interacting with and regulating transport processes. The top-ranked DUBs were OTUB1, USP14, PSMD7, PSMD14, USP7, USP9X, OTUD4, USP10, and UCHL5. Among these USP7, USP9X, OTUD4, and USP10 are known to be involved in endosomal trafficking and have potential roles in endosomal recycling of plasma membrane proteins in the mammalian cortical collecting duct. PMID:28039431

Data integration in physiology using Bayes' rule and minimum Bayes' factors: deubiquitylating enzymes in the renal collecting duct.

PubMed

Xue, Zhe; Chen, Jia-Xu; Zhao, Yue; Medvar, Barbara; Knepper, Mark A

2017-03-01

A major challenge in physiology is to exploit the many large-scale data sets available from "-omic" studies to seek answers to key physiological questions. In previous studies, Bayes' theorem has been used for this purpose. This approach requires a means to map continuously distributed experimental data to probabilities (likelihood values) to derive posterior probabilities from the combination of prior probabilities and new data. Here, we introduce the use of minimum Bayes' factors for this purpose and illustrate the approach by addressing a physiological question, "Which deubiquitylating enzymes (DUBs) encoded by mammalian genomes are most likely to regulate plasma membrane transport processes in renal cortical collecting duct principal cells?" To do this, we have created a comprehensive online database of 110 DUBs present in the mammalian genome (https://hpcwebapps.cit.nih.gov/ESBL/Database/DUBs/). We used Bayes' theorem to integrate available information from large-scale data sets derived from proteomic and transcriptomic studies of renal collecting duct cells to rank the 110 known DUBs with regard to likelihood of interacting with and regulating transport processes. The top-ranked DUBs were OTUB1, USP14, PSMD7, PSMD14, USP7, USP9X, OTUD4, USP10, and UCHL5. Among these USP7, USP9X, OTUD4, and USP10 are known to be involved in endosomal trafficking and have potential roles in endosomal recycling of plasma membrane proteins in the mammalian cortical collecting duct. Copyright © 2017 the American Physiological Society.

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Lack of passive transfer of renal tubulointerstitial disease by serum or monoclonal antibody specific for renal tubular antigens in the mouse.

PubMed

Evans, B D; Dilwith, R L; Balaban, S L; Rudofsky, U H

1988-01-01

Mice immunized with rabbit renal basement membranes form autoantibodies to their kidney glomerular and tubular basement membranes (GBM/TBM). Development of renal tubular disease (RTD) consists of deposition of autoantibodies along the GBM/TBM with the inter- and intratubular accumulation of lymphocytes and macrophages and destruction of the TBM. Transfer of this disease in mice with either serum or monoclonal antibodies, however, has been difficult to demonstrate and, therefore, attempts were made to confirm a report that RTD is passively transferred by anti-TBM autoantibodies. Using the revised protocol in this later report, we found that 12 weeks after transfer autoantibodies were deposited along the GBM and/or TBM of the recipients, yet RTD was not observed. Although qualitative and quantitative characteristics of the antibody may play a role in the pathogenesis in the murine model of RTD, we could not obtain evidence to support and confirm this study.

The protective effect of menhaden oil in the oxidative damage and renal necrosis due to dietary choline deficiency.

PubMed

Ossani, Georgina P; Repetto, Marisa G; Boveris, Alberto; Monserrat, Alberto J

2013-02-26

Weanling rats fed a choline-deficient diet develop kidney oxidative damage, tubular and cortical kidney necrosis, renal failure and animal death. The effect of dietary menhaden oil was assayed on the mentioned sequence correlating oxidative stress with renal structure and function. Rats were fed ad libitum 4 different diets: (a) a choline-deficient diet with corn oil and sunflower hydrogenated oil as a source of fatty acids; (b) the same diet supplemented with choline; (c) a choline-deficient diet with menhaden oil as a source of fatty acids; and (d) the previous diet supplemented with choline. Animals were sacrificed at days 0, 2, 4 and 7. The histopathological study of the kidneys showed that renal necrosis was only observed at day 7 in choline-deficient rats receiving the vegetable oil diet, simultaneously with increased creatinine plasma levels. Homogenate chemiluminescence (BOOH-initiated chemiluminescence) and phospholipid oxidation indicate the development of oxidative stress and damage in choline-deficient rats fed vegetable oils as well as the protective effect of menhaden oil. Rats fed with the fish oil diet showed that oxidative stress and damage develop later, as compared with vegetable oil, with no morphological damage during the experimental period.