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Ultrasound-guided biopsy needle identification is a crucial step in clinical treatment planning, but remains challenging due to the difficulty in data acquisition that includes the ultrasound speckle interference pattern and the presence of strong linear anatomical structure. This paper introduces a real-time needle tracking method for visualizing 2D needle shapes and trajectory during interventions. Based on observations of the needle dynamics within a small fraction of dynamic ultrasound images, the current needle placement was estimated: (1) A subspace based background suppression technique was used to identify points representing possible needle locations using the consecutive dynamic frames in a sliding-window fashion. and (2) a Hough transform was then used to filter out false positives and fit the remaining points on the Hough space. Evaluation on datasets from 16 subjects demonstrated that the proposed method produced high-quality needle-only images, significantly reducing the mean trajectory error to 1.89°and the tip position error to 5.1 mm, outperforming temporal subtraction (2.65°and 14.3 mm) and Gabor filtering (2.94°and 13.8 mm). The attention-based U-Net achieved a comparable mean trajectory angle error of 1.82°but yielded a higher mean tip position error of 8.2 mm. Qualitative and quantitative analyses consistently indicated that the proposed method offers enhanced accuracy and robustness across subjects compared to competing methods. [ABSTRACT FROM AUTHOR]

Abstract Printed organic sensors are of significant importance owing to their simplicity, low cost, easy fabrication and solution processability. However, organic sensors often suffer from the drawback of performance degradation when exposed to ambient environment. In this study, polyvinyl alcohol (PVA) is used as the functional layer of a temperature sensor and is encapsulated by aluminum oxide (Al 2 O 3) deposited through spatial atmospheric atomic layer deposition system (SAALD). The encapsulating layer of Al 2 O 3 was pure, atomically thin and highly reliable. Fabricated organic temperature sensor is based on a conductive and uniform interdigitated pattern deposited on a flexible polyethylene naphthalate substrate through advanced printing technology of reverse offset. Thin film of PVA is used as the temperature sensitive functional layer deposited through electrohydrodynamic atomization followed by Al 2 O 3 encapsulation. The developed sensors were tested in the temperature range of 25 °C to 90 °C with relative humidity reaching up to 75% relative humidity. The obtained results exhibited that Al 2 O 3 encapsulation deposited through SAALD significantly enhanced the linearity, repeatability, endurance (50 cycles), retention (2 months) and lifetime of PVA based temperature sensor as compared with the non-encapsulated sensor hence, protecting the organic device from performance degradation. Highlights • Lifetime of organic temperature sensor has been enhanced through encapsulation. • Electrical, mechanical, chemical, and morphological characterizations are included. • The device is encapsulated with Al 2 O 3 thin film deposited through SAALD system. • Encapsulated sensor displayed better results than non-encapsulated sensor. • The obtained results were highly stable and reproducible. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Metabolic syndrome (MetS) is an independent risk factor for chronic kidney and cardiovascular diseases. However, few studies have examined the combined effects of MetS and renal insufficiency after acute myocardial infarction (AMI). We examined the effect of MetS on clinical outcomes in patients with AMI in the presence or absence of renal insufficiency. Methods: From November 2005 to September 2008, 11,462 patients with AMI were enrolled in the prospective Korean Acute Myocardial Infarction Registry. Participants were analyzed according to the presence or absence of MetS and renal insufficiency, defined by a low estimated glomerular filtration rate (eGFR). The primary endpoints were major adverse cardiac events (MACE), including a composite of all cause-of-death, myocardial infarction, target lesion revascularization, and coronary artery bypass graft during the 1-year follow-up period. Results: The prevalence of MetS was higher in AMI patients with low eGFR. In-hospital death and composite MACE were significantly higher in patients with MetS than in those without MetS in the presence of renal insufficiency. Multivariate analysis showed that old age, multi-vessel involvement, high levels of inflammation, diabetes and MetS were associated with 1-year composite MACE in patients with renal insufficiency. After adjusting for multiple covariates, the 1-year mortality rate was higher in patients with both MetS and renal insufficiency than in those with MetS without renal insufficiency or in individuals without MetS. Conclusion: MetS is associated with poor clinical outcomes and it increases the mortality in patients with AMI, especially in association with renal insufficiency. [Copyright &y& Elsevier]

Increased expression of atrial natriuretic peptide in the kidney of rats with bilateral ureteral obstruction. Background. Whether the postobstructive diuresis can be related to an altered regulation of local atrial natriuretic peptide (ANP) in the kidney was investigated. Methods. Three groups of rats had both of their ureters obstructed for 48 hours. The kidneys were taken without releasing the obstruction in one group [bilateral ureteral obstruction (BUO)]. The obstruction was released in the other two groups and the animals were kept for 4 and 24 hours thereafter to collect urinary data (BUR-4 and BUR-24, respectively). Plasma and urine ANP levels were measured by radioimmunoassay. The mRNA expression of ANP, natriuretic peptide receptor-A (NPR-A), and NPR-C was determined by reverse transcription-polymerase chain reaction. ANP receptors were also quantitated by in vitro autoradiography. The activity of guanylyl cyclase was determined by the amount of cGMP generated in response to ANP. Results. Urinary volume and sodium excretion increased in BUR-4, along with the ANP mRNA expression in the kidney and the urinary ANP excretion. The ANP excretion positively correlated with the urinary volume and sodium excretion. The mRNA expression of both NPR-A and NPR-C was decreased by BUO, the latter being far more prominently affected. The maximal binding capacity of radiolabeled ANP was decreased in the glomerulus and papilla in BUO. Not only the urinary parameters but also the mRNA expression of ANP, NPR-A, and NPR-C were comparable between BUR-24 and control rats. ANP-stimulated cGMP generation was reduced in the glomerulus and papilla in BUO animals, which was rapidly resumed following the release of the obstruction. Conclusions. Postobstructive diuresis may be due partially to an increased ANP activity in the kidney. [ABSTRACT FROM AUTHOR]

Functional thin film of strontium titanate/polyvinyl alcohol (SrTiO 3 -PVA) hybrid nanocomposite was sandwiched between silver (Ag) electrodes for the application of resistive random access memory (RRAM). Bottom Ag electrodes were patterned using high resolution reverse offset printing system while the hybrid composite thin film and the top Ag electrode were deposited through electro-hydrodynamic (EHD) atomization and EHD patterning respectively. RRAM behavior of SrTiO 3 memory device has not been reported on a flexible substrate due to its brittle nature therefore, in this study we have successfully evaluated its mechanical robustness by forming its nanocomposite with highly flexible PVA polymer. The fabricated device showed bipolar, rewritable and nonvolatile memory behavior at low operating voltage. The bistable resistive switching behavior had off/on ratio of ~30, retention time of 8.64 × 104 s and electrical endurance of 500 operating cycles. The device illustrated mechanical robustness when subjected to 500 bend cycles and varying bending diameters. Image 100539 • A flexible resistive memory device was fabricated using hybrid composite thin film. • SrTiO 3 +PVA thin film was deposited using EHDA spray deposition technique. • All-printed memory device exhibited improved electrical and mechanical endurance. • It showed bistable, rewritable, nonvolatile memory behavior at low working voltage. • The device showed excellent mechanical robustness when tested for 500 bend cycles. [ABSTRACT FROM AUTHOR]

The aim of the work described here was to determine the feasibility of using a novel biopsy needle detection technique that achieves high sensitivity and specificity in a trade-off of resolution, detectability and depth of imaging. The proposed needle detection method consists of a model-based image analysis, temporal needle projection and needle library matching: (i) Image analysis was formulated under the signal decomposition framework; (ii) temporal projection converted the time-resolved needle dynamics into a single image of the desired needle; and (iii) the enhanced needle structure was spatially refined by matching a long, straight linear object in the needle library. The efficacy was examined with respect to different needle visibility. Our method effectively eliminated confounding effects of the background tissue artifacts more robustly than conventional methods, thus improving needle visibility even with the low contrast between the needle and tissue. The improvement in needle structure further resulted in an improvement in estimation performance for the trajectory angle and tip position. Our three-step needle detection method can reliably detect needle position without the need for external devices, increasing the needle conspicuity and reducing motion sensitivity. [ABSTRACT FROM AUTHOR]

Polyethylene oxide (PEO) is a polymer hydrogel possessing ionic conductivity that varies with different percentage of absorbed water molecules and ions. This property makes it a good candidate to be used in humidity sensors’ active layers. The degree of crystallinity of PEO thin films decrease with increasing humidity that facilitates the ion conduction in the thin films, thus reducing the film impedance. In this research work, the humidity sensing properties of the thin films of semi-crystalline PEO have been investigated and the material is then modified to its amorphous dominant phase by heating the thin films beyond the melting point of the polymer. The slowly cooled resulting thin films had a waxy solid like appearance and showed an excellent response towards quantitative detection of relative humidity in the surrounding environment. The results show a roughly linear impedance versus relative humidity curve in the range of 0% RH to 90% RH with a very high maximum achieved sensitivity of ∼35 kΩ/%RH. The response and recovery times measured for the modified sensors were 2.8 s and 5.7 s respectively. The 30 day trial of stability readings showed a standard deviation of only 1%. The results prove thermally modified amorphous PEO thin films to be strong candidates for high end electronic relative humidity sensors. [ABSTRACT FROM AUTHOR]

Fabry disease (FD) is a rare X-linked lysosomal storage disorder that results from the deficient activity of the lysosomal enzyme α-galactosidase A (α-Gal A) enzyme. Kidney transplantation is an option for treating end-stage renal disease in patients with FD. However, only a few cases of kidney transplantation have been reported involving patients with FD and end-stage renal disease and cardiomyopathy after enzyme replacement therapy. A 53-year-old man who underwent peritoneal dialysis was referred to our department because his brother was diagnosed with FD. The diagnosis of FD was also confirmed in our patient on account of the reduced leukocyte α-Gal A enzyme activity and mutation in the α-galactosidase A gene (p.Arg301Gln). Though our patient had end-stage renal disease, he received enzyme replacement therapy with 1 mg/kg agalsidase-β every 2 weeks (Fabrazyme; Genzyme Co, Mass, USA) owing to markedly diffuse cardiac hypertrophy. Six years later, he underwent successful deceased-donor kidney transplantation. The post-transplantation course was uneventful, 4 months after transplantation. However, though he showed T-cell-mediated rejection on kidney biopsy, lamellar lysosomal inclusions were not present in vascular endothelial cells. After several months, a permanent pacemaker was inserted owing to a complete atrioventricular block; the patient died of sepsis and candidemia 1 year later. Deceased-donor kidney transplantation was successfully performed in an FD patient with sustained enzyme replacement therapy. However, owing to high cardiac morbidity and infection risks even after enzyme replacement therapy, close monitoring of these risks is essential for increasing patient survival after kidney transplantation. [ABSTRACT FROM AUTHOR]

In this work, a polymeric material poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) and a two dimensional material molybdenum disulfide (MoS 2 ) 2D nanoflakes have been employed as the active layers of two separate transducers on a single substrate for the detection of relative humidity. The portion with MoS 2 based active region showed high responsivity towards low humidity levels while PEDOT:PSS based portion responded well to high humidity levels. These two sensing portions were connected in a series combination to fabricate a single humidity sensing device capable to respond to a wide range of relative humidity with very high sensitivity. 2D MoS 2 nanoflakes were obtained by aqueous exfoliation of pristine MoS 2 . The transducer electrode pairs were fabricated using reverse offset printing technique on a piezoelectric LiNbO 3 substrate. The active thin film of MoS 2 flakes was deposited by Electrohydrodynamic atomization (EHDA) while the thin film of PEDOT:PSS was deposited by SAW-EHDA hybrid system. The fabricated sensor is capable of sensing relative humidity with high sensitivity (50 kΩ/%RH or 800 Hz/%RH) in a wide range of 0%RH–80%RH. The response and recovery times are also excellent with values of 0.5 s and 0.8 s respectively. This unique approach of combining multiple transducers in a single sensing device can lead to the development of high performance sensors and can solve the current limitations of single transducer based sensing devices. [ABSTRACT FROM AUTHOR]

Abstract: Macrophage-stimulating protein (MSP) and its receptor, recepteur d’origine nantais (RON), play an important role in cell proliferation and migration. We have investigated the role of MSP in hydrogen peroxide (H2O2)-induced renal tubular apoptosis. Human renal proximal tubular (HK-2) cells were incubated with H2O2 for 24h in the presence of different concentrations of MSP, and cell viability was measured by MTT assay. The protein expression of Bax, Bcl-2, caspase-3, mitogen-activated protein kinases (MAPKs), phosphatidylinositol-3-kinase (PI3K)/Akt, and nuclear factor-kappa B (NF-κB) was determined by semiquantitative immunoblotting. Apoptosis was assessed by flow cytometry analysis after HK-2 cells were stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. H2O2 treatment decreased cell viability in HK-2 cells; this was counteracted by MSP pretreatment. H2O2 treatment induced an increased ratio of Bax/Bcl-2, cleaved caspase-3, and the number of condensed nuclei, which was also counteracted by MSP. Flow cytometry analysis showed H2O2-induced apoptosis, and its prevention by MSP treatment. Increased protein expression of phospho-p38 MAPK was attenuated by MSP, while phospho-extracellular signal-regulated kinase and c-Jun-N-terminal kinase were not affected. H2O2 induced NF-κB activation and IκB-α degradation, but the increased nuclear NF-κB activation was counteracted by MSP or by a p38 MAPK inhibitor. H2O2 treatment decreased expression of phospho-PI3K and phospho-Akt, which was reversed by MSP pretreatment. These findings suggest that MSP attenuates H2O2-induced apoptosis in HK-2 cells by modulating the p38 and NF-κB, as well as PI3K/Akt, signaling pathways. [Copyright &y& Elsevier]

PAI-1 and CTGF are overexpressed in kidney diseases and cause fibrosis of the lungs, liver, and kidneys. We used a rat model of unilateral ureteral obstruction (UUO) to investigate whether 6-BIO, a glycogen synthase kinase-3β inhibitor, attenuated fibrosis by inhibiting PAI-1 and CTGF in vivo. Additionally, TGFβ-induced cellular fibrosis was observed in vitro using the human kidney proximal tubular epithelial cells (HK-2), and rat interstitial fibroblasts (NRK49F). Expression of fibrosis-related proteins and signaling molecules such as PAI-1, CTGF, TGFβ, αSMA, SMAD, and MAPK were determined in HK-2 and NRK49F cells using immunoblotting. To identify the transcription factors that regulate the expression of PAI-1 and CTGF the promoter activities of AP-1 and SP-1 were analyzed using luciferase assays. Confocal microscopy was used to observe the co-localization of AP-1 and SP-1 to PAI-1 and CTGF. Expression of PAI-1, CTGF, TGFβ, and α-SMA increased in UUO model as well as in TGFβ-treated HK-2 and NRK49F cells. Furthermore, UUO and TGFβ treatment induced the activation of P-SMAD2/3, SMAD4, P-ERK 1/2, P-P38, and P-JNK MAPK signaling pathways. PAI-1, CTGF, AP-1 and SP-1 promoter activity increased in response to TGFβ treatment. However, treatment with 6-BIO decreased the expression of proteins and signaling pathways associated with fibrosis in UUO model as well as in TGFβ-treated HK-2 and NRK49F cells. Moreover, 6-BIO treatment attenuated the expression of PAI-1 and CTGF as well as the promoter activities of AP-1 and SP-1, thereby regulating the SMAD and MAPK signaling pathways, and subsequently exerting anti-fibrotic effects on kidney cells. [Display omitted] • 6-BIO inhibits UUO- and TGFβ induced kidney fibrosis. • 6-Bio reduces PAI-1 and CTGF expression associated with kidney fibrosis. • 6-BIO regulates AP-1 and SP-1 transcription activity in kidney cells. [ABSTRACT FROM AUTHOR]

Limited information is available regarding the impact of acute kidney injury (AKI) during hospitalization on clinical outcomes after myocardial infarction (MI), and the effect of transient kidney injury (KI) on long-term mortality has not been validated. We retrospectively analyzed 2,289 patients diagnosed with MI. AKI patients were classified into a transient KI group and a persistent KI group based on serum creatinine levels at discharge. The end point of the study was 3-year mortality after MI. We included 2,110 patients of whom 237 patients (11%) developed AKI during hospitalization. Of these 237 patients, 154 (65%) had transient KI, and 83 (35%) had persistent KI. Multivariate analysis showed that age, left ventricular ejection fraction, estimated glomerular filtration rate on admission, and Killip class were significantly associated with developing AKI during hospitalization. The adjusted hazard ratios for 3-year mortality were 1.71 (95% confidence interval: 1.08e2.70) for AKI patients with transient KI and 2.21 (95% confidence interval: 1.34e3.64) for AKI patients with persistent KI, compared with no AKI. In conclusion, AKI was associated with an increased risk of death for patients who experienced MIs and survived during hospitalization. Although renal function had completely recovered in many AKI patients at discharge, these transient KI patients are also at a great risk of death after MI. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To determine the diagnostic accuracy of serum free light chain κ/λ ratio (rFLC) using extended renal reference (renal range rFLC) in multiple myeloma (MM) with renal insufficiency. Design and Methods: Patients who visited a nephrologist due to renal insufficiency (n=471) were enrolled. Serum FLC quantification, protein electrophoresis (PEP), and pathologic diagnosis were performed. Results: Renal range rFLC showed the highest sensitivity to differentiate MM from non-MM among four tests (conventional rFLC, s-PEP, u-PEP). In intact immoglobulin MM (IIMM), the sensitivity and specificity were lower for both rFLCs than for s-PEP. On the other hand, both rFLC showed higher sensitivity compared than PEPs in light chain MM (LCMM). Combined analysis (renal rFLC+s-PEP) increased the sensitivity for both IIMM and LCMM. Conclusions: Renal rFLC is a valuable screening tool in renal insufficiency patients suspected of having MM, especially for LCMM. Combined analysis (renal rFLC+s-PEP) improves the diagnostic accuracy for detecting MM in the setting of renal impairment. [Copyright &y& Elsevier]

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduce major adverse cardiac events (MACE) and mortality in patients with acute coronary syndrome. We investigated the effectiveness of statin therapy in reducing MACE in patients with acute myocardial infarction (AMI) and renal dysfunction (RD). In the present retrospective study of 12,853 patients with AMI, the patients were categorized into 4 groups: group I, statin therapy and no RD (estimated glomerular filtration rate ≥60 ml/min/1.73 m2); group II, neither statin therapy nor RD; group III, statin therapy and RD; group IV, no statin therapy but RD. The primary end points were death and complications during the hospital course. The secondary end points were MACE during 1 year of follow-up after AMI. Significant differences in the composite MACE during 12 months of follow-up were observed among the 4 groups (group I, 11.7%; group II, 19.0%; group III, 26.7%; and group IV, 45.5%; p <0.001). In a Cox proportional hazards model, mortality at 12 months increased stepwise from group II to IV compared to group I. Moreover, MACE-free survival in the severe RD group (estimated glomerular filtration rate <30 mL/min/1.73 m2) was also greater in the statin-treated group. In conclusion, statin therapy reduced MACE at 1 year of follow-up in patients with AMI regardless of RD. [Copyright &y& Elsevier]

Abstract: The present study was performed to examine whether paricalcitol may prevent the cisplatin-induced kidney injury. Furthermore, potential molecular mechanisms underlying the protective effect of paricalcitol were explored. Male Sprague–Dawley rats were treated with vehicle (n=12), cisplatin (n=12, 6mg/kg/day, i.p.), or cisplatin+paricalcitol (n=12, 0.2μg/kg/day, s.c.) for 4days. In another series of experiment, HK-2 cells were treated with cisplatin (50μM), with or without paricalcitol (0.2ng/ml). Paricalcitol counteracted the cisplatin-induced decline in renal function. Paricalcitol also suppressed the expression of TGF-β1, Smad signaling, and the subsequent epithelial-to-mesenchymal process in cisplatin-treated rats. The expression of P-p53 and p21 was increased in cisplatin-induced nephropathy. These changes were completely prevented or significantly attenuated with paricalcitol co-treatment. The expression of p27kip1 was increased in cisplatin-treated rats, which was, however, further augmented by the paricalcitol co-treatment. In HK-2 cells, cisplatin increased the expression of p-ERK1/2 and P-p38. Cisplatin also increased the expression of fibronectin and CTGF. Cisplatin increased the expression of pro-apoptotic markers. The expression of CDK2 and Cyclin E as well as that of PCNA was increased. These changes were completely prevented or significantly attenuated by the paricalcitol pretreatment. In contrast, cisplatin increased the expression of p27kip1, which was further augmented by the paricalcitol-pretreatment. These results suggest that paricalcitol may ameliorate cisplatin-induced renal injury by suppressing the fibrotic, apoptotic and proliferative factors. Its underlying mechanisms may include inhibition of TGF-β1, mitogen-activated protein kinase signaling, p53-induced apoptosis, and augmentation of p27kip1. [Copyright &y& Elsevier]

Abstract: Cisplatin is a chemotherapeutic agent used for treating solid tumors. However, nephrotoxicity is the dose-limiting factor in its clinical use. The present study was aimed to determine whether altered regulation of the local nitric oxide (NO) and natriuretic peptide (NP) systems is involved in the pathogenesis of cisplatin-induced nephropathy. Cisplatin (6mg/kg) was injected intraperitoneally into male Sprague–Dawley rats. The control group was not treated with cisplatin. Expression levels of nitric oxide synthase (NOS), nitrotyrosine, soluble guanylyl cyclase and neutral endopeptidase (NEP) in the kidneys were determined 4days after treatment by semiquantitative immunoblotting. mRNA expression of NPs and natriuretic peptide receptors (NPRs) was determined by real-time polymerase chain reaction. The activities of soluble and particulate guanylyl cyclase were determined by measuring the amount of cyclic 3′,5′-guanosine monophosphate (cGMP) generated in responses to sodium nitroprusside and atrial natriuretic peptide (ANP), respectively. In the test rats, creatinine clearance was decreased, while sodium and water excretion were increased. The expression of inducible NOS (iNOS) and nitrotyrosine was increased in the cortex/outer stripe of outer medullar and inner medullar, while that of endothelial and neuronal NOS was decreased in the inner medullar. Excretion of NO metabolites was increased in these rats. The catalytic activity of soluble guanyly cyclase was blunted in the papilla after cisplatin was administered. The mRNA expression of ANP, brain natriuretic peptide, and C-type natriuretic peptide was increased, while that of NPR-A and NPR-C were decreased in the test rats. The catalytic activity of soluble and particulate guanylyl cyclase in the papilla was blunted after cisplatin was administered. In conclusion, increased production of NO by iNOS may contribute to cytotoxic injury, resulting in cisplatin-induced nephropathy, while the up-regulation of renal natriuretic peptide synthesis together with the down-regulation of NEP and NPR-C may contribute to the natriuresis and diuresis seen in cisplatin-induced nephropathy. [Copyright &y& Elsevier]

Abstract: The present study was aimed to determine whether there is an altered role of local nitric oxide (NO) and atrial natriuretic peptide (ANP) systems in the kidney in association with the angiotensin (Ang) II-induced hypertension. Male Sprague–Dawley rats were used. Ang II (100ng·min−1·kg−1) was infused through entire time course. Thirteenth day after beginning the regimen, kidneys were taken. The protein expression of NO synthase (NOS) and nitrotyrosine was determined by semiquantitative immunoblotting. The mRNA expression of components of ANP system was determined by real-time polymerase chain reaction. The activities of soluble and particulate guanylyl cyclases were determined by the amount of cGMP generated in responses to sodium nitroprusside and ANP, respectively. There developed hypertension and decreased creatinine clearance in the experimental group. The protein expression of eNOS, nNOS and nitrotyrosine was increased in the cortex, while that of iNOS remained unaltered. The urinary excretion of NO increased in Ang II-induced hypertensive rats. The catalytic activity of soluble guanylyl cyclase was blunted in the glomerulus in Ang II-induced hypertensive rats. The mRNA expression of ANP was increased in Ang II-induced hypertensive rats. Neither the expression of NPR-A nor that of NPR-C was changed. The protein expression of neutral endopeptidase was decreased and the activity of particulate guanylyl cyclase was blunted in the glomerulus and papilla in Ang II-induced hypertensive rats. In conclusion, the synthesis of NO and ANP was increased in the kidney of Ang II-induced hypertension, while stimulated cGMP response was blunted. These results suggest desensitization of guanylyl cyclase in the kidney of Ang II-induced hypertensive rats, which may contribute to the associated renal vasoconstriction and hypertension. [Copyright &y& Elsevier]

Abstract: The present study was aimed to determine whether there is an altered role of local nitric oxide (NO), atrial natriuretic peptide (ANP) and cyclooxygenase (COX) systems in the kidney in association with the aldosterone escape. Male Sprague–Dawley rats were used. Aldosterone (200μg/day) was infused through entire time course. The control group was kept on a low sodium diet (0.02mEq/day), and the experimental group was supplied with a higher sodium diet (2.0mEq/day). Four days after beginning the regimen, the kidneys were taken. The protein expression of NO synthase (NOS) and COX isoforms was determined by semiquantitative immunoblotting. The mRNA expression of components of ANP system was determined by real-time polymerase chain reaction. The activities of soluble and particulate guanylyl cyclases were determined by the amount of cGMP generated in responses to sodium nitroprusside and ANP, respectively. There developed aldosterone escape in the experimental group. Accordingly, the renal content and the urinary excretion of NO increased. The expression of nNOS was increased in the inner medulla. Neither the expression of eNOS nor that of iNOS was changed. The expression and the catalytic activity of soluble guanylyl cyclase remained unaltered. The mRNA expression of ANP was increased. Neither the expression of NPR-A or NPR-C nor the activity of particulate guanylyl cyclase was altered in the papilla. The protein expression of COX-2 was increased in the inner medulla, while that of COX-1 remained unchanged. In conclusion, the upregulation of nNOS, ANP, and COX-2 may be causally related with the aldosterone escape. [Copyright &y& Elsevier]

Abstract: Although deoxycorticosterone acetate (DOCA)–salt hypertension is a volume dependent model of hypertension, it shows polyuria and natriuresis. It is expected that dysregulation of aquaporin water channels (AQPs) and sodium transporters associated with natriuretic peptide (NP) system may play an escape role in sodium retaining state. One week after left unilateral nephrectomy, rats were subcutaneously implanted with silastic DOCA (200 mg/kg) strips. Physiologic saline was supplied as a drinking water to all animals. 4 weeks after operation, the protein expression of AQPs, sodium transporters, and endopeptidase (NEP) was determined in the kidneys by semiquantitative immunoblotting and immunohistochemistry. The mRNA expression of NP system was determined by real-time polymerase chain reaction. The amount of urinary ANP excretion was measured by radioimmunoassay. In DOCA–salt rats, urine osmolality was decreased while urinary excretion of sodium was increased. The expression of AQP1-3 as well as that of α-1 subunit of Na,K–ATPase, NHE3, NKCC2 and NCC was decreased in the kidney. The mRNA expression of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) was increased in the kidney. The expression of NEP was decreased, and urinary ANP excretion was increased. Downregulation of AQPs and sodium transporters may contribute to mineralocorticoid escape in DOCA–salt hypertension. Increased expression of natriuretic peptides associated with downregulation of NEP may play a role in natriuresis. [Copyright &y& Elsevier]

Abstract: Sympathetic nervous system and atrial natriuretic peptide (ANP) system play fundamental roles in the regulation of cardiovascular functions. Overactivity of sympathetic nervous system can lead into cardiovascular diseases such as heart failure and hypertension. The present study aimed to define which adrenergic receptors (ARs) affect atrial contractility and ANP release and to determine their modification in renal hypertensive rat atria. An α1-AR agonist, cirazoline increased ANP release with positive inotropism. These α1-AR agonist-mediated responses were attenuated by the α1A-AR antagonist, but not by the α1B- or α1D-AR antagonist. An α2-AR agonist, guanabenz and clonidine increased ANP release with negative inotropism and decreased cAMP level. The order of potency for the increased ANP release was cirazoline≫phenylephrine=guanabenz≫clonidine. In contrast, a β-AR agonist, isoproterenol decreased ANP release with positive inotropism and these responses were blocked by the β1-AR antagonist but not by the β2-AR antagonist. The increased cAMP level by isoproterenol was suppressed by pretreatment with both β1- and β2-AR antagonists. In renal hypertensive rat atria, the effects of isoproterenol on atrial contractility, ANP release, and cAMP level were attenuated whereas the effect of cirazoline on ANP release was unaltered. Atrial β1-AR mRNA level but not α1A-AR mRNA level was decreased in renal hypertensive rats. These findings suggest that α1A- and β1-AR oppositely regulate atrial ANP release and that atrial β1-AR expression/function is impaired in renal hypertensive rats. [Copyright &y& Elsevier]

[Display omitted] ACE inhibitors or angiotensin II receptor blockers (ACEi/ARBs) have been a cornerstone of the management in kidney disease, but their use is often limited by undesired systemic effects, such as symptomatic hypotension. To minimize the extra-renal effects of ACEi/ARBs, we formulated hydrophobically modified glycol chitosan (HGC) nanomicelles releasing olmesartan (HGC-Olm) that specifically accumulated in the kidney, and investigated whether kidney-specific delivery of olmesartan by HGC nanomicelles could ameliorate organ damage in Col4a3 −/− mouse, a murine model of progressive chronic kidney disease mimicking human Alport syndrome. Ex vivo tracing demonstrated that intravenously injected HGC-Olm nanomicelles were specifically delivered to the kidney, with sustained release of olmesartan for more than 48 h. Contrary to the conventional delivery of olmesartan via oral route, injection of HGC-Olm nanomicelles did not alter blood pressure in Col4a3 −/− mice. Immunohistochemistry revealed that HGC nanomicelles were diffusely distributed from the cortex and glomeruli to the outer medulla, sparing the inner medulla. Phenotypic analysis showed that the attenuation of kidney fibrosis in the kidney of Col4a3 −/− mice by HGC-Olm nanomicelles was comparable to that noted with conventionally delivered olmesartan. Therefore, our results suggest that HGC-Olm nanomicelles could be a safe and effective alternative drug delivery system for kidney diseases. [ABSTRACT FROM AUTHOR]

• Hydrophobically modified glycol chitosan polymeric nanomicelles (HGC) loaded with hydrophobic drug tacrolimus (TAC). • Selective deposition of TAC into the kidney because of the in-built property of glycol chitosan to target the kidney. • Megalin receptor-mediated endocytosis is involved in the uptake and retention of HGC-TAC nanomicelles in the kidney. • Demonstrates the potential of HGC nanomicelles as a novel strategy to deliver drugs specifically to kidneys without any systemic toxicity. In this study, we propose the use of glycol chitosan for the targeted delivery of hydrophobic drugs such as tacrolimus (TAC) towards the kidney. We synthesized a hydrophobically modified glycol chitosan (HGC) polymeric nanomicelle followed by loading TAC resulting in TAC loaded HGC nanomicelles (HGC-TAC). The HGC-TAC nanomicelles displayed spherical morphology with superior drug loading content and encapsulation efficiency. in vitro and in vivo evaluations demonstrated that HGC-TAC nanomicelles are non toxic and delivered TAC preferentially to kidney while lowering the plasma concentrations. The therapeutic effects of HGC-TAC and unencapsulated ("bare") TAC on the kidneys showed that a single intravenous administration of HGC-TAC achieved a therapeutic efficacy comparable to that obtained from daily intraperitoneal injections of TAC for 14 days without any systemic side effects. Thus, HGC-TAC nanomicelles could be effectively used for delivery of TAC towards the kidney, highlighting its potential as a safe modality for renal-targeted delivery of therapeutics. [ABSTRACT FROM AUTHOR]

Vaspin is a protein present in human serum that can cause type-2 diabetes, obesity, and other cardiovascular diseases. We report fluorescent upconverting nanoparticles (UCNPs)-based lateral flow biosensor for ultrasensitive detection of Vaspin. A pair (primary and secondary) of cognate aptamers was used that has duo binding with Vaspin. UCNPs with a diameter of around 100 nm were used as a tag to label a detection probe (secondary aptamer). A primary aptamer (capture probe) was immobilized on the test zone. Sandwich type hybridization reactions among the conjugate probe, target Vaspin, and primary aptamer were performed on the lateral flow biosensor. In the presence of target Vaspin, UCNPs were captured on the test zone of the biosensor and the fluorescent intensity of the captured UCNPs was measured through a colorimetric app under NIR. Fluorescence intensity indicates the quantity of Vaspin present in the sample. A range of Vaspin concentration across 0.1–55 ng ml−1 with a Limit of detection (LOD) 39 pg ml−1 was tested through this UCNPs based LFSA with high sensitivity, reproducibility and repeatability, whereas it's actual range in human blood is from 0.1 to 7 ng ml−1. Therefore, this research provides a well-suited lateral flow strip with an ultrasensitive and low-cost approach for the early diagnosis of type-2 diabetes and this could be applied to any targets with a duo of aptamers generated. Schematic illustration of the configuration and measurement of the UCNPs based lateral flow aptasensor for VASPIN detection. Image 1 • A fluorescence based aptasensor was developed for quantitative detection of Vaspin. • Upconversion nanoparticles were utilized as highly sensitive signal label. • A covalent conjugate of secondary aptamer was developed as signaling probe, and detected in the nM range. • The sensor design is lateral flow based and can be applied for other targets if duo aptamers are available. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 69-year-old woman with polyuria and bilateral knee pain. The patient undergo abdominal computed tomography (CT) which reveals bilateral hydronephrosis. Magnetic resonance imaging shows diffuse irregular sclerotic changes involving the diaphysis and metaphysic. Immunohistochemistry discovered that biopsy samples were CD68(+), but S-100(-) and CD1a(-), which is a distinctive finding in Erdheim-Chester disease.

The article discusses a case of a 43-year-old man who was presented to a hospital with generalized skin pruriginous and papulonodular eruptions. It say that a skin biopsy was performed and found symptoms of hyperkeratosis, pseudo-epitheliomatous acanthosis, and vascular hyperplasia of the upper dermis that are characteristics of prurigo nodularis. It states that tapere 16 milligram (mg) dose of oral methylprednisolone, antibiotics, antihistamines, ad cyrotherapy was treated to the patient.