RESUMEN

BACKGROUND: Diagnostic performance based on x-ray breast imaging is subject to breast density. Although digital breast tomosynthesis (DBT) is reported to outperform conventional mammography in denser breasts, mass detection and malignancy characterization are often considered challenging yet. PURPOSE: As an improved diagnostic solution to the dense breast cases, we propose a dual-energy DBT imaging technique that enables breast compositional imaging at comparable scanning time and patient dose compared to the conventional single-energy DBT. METHODS: The proposed dual-energy DBT acquires projection data by alternating two different energy spectra. Then, we synthesize unmeasured projection data using a deep neural network that exploits the measured projection data and adjacent projection data obtained under the other x-ray energy spectrum. For material decomposition, we estimate partial path lengths of an x-ray through water, lipid, and protein from the measured and the synthesized projection data with the object thickness information. After material decomposition in the projection domain, we reconstruct material-selective DBT images. The deep neural network is trained with the numerical breast phantoms. A pork meat phantom is scanned with a prototype dual-energy DBT system to demonstrate the feasibility of the proposed imaging method. RESULTS: The developed deep neural network successfully synthesized missing projections. Material-selective images reconstructed from the synthesized data present comparable compositional contrast of the cancerous masses compared with those from the fully measured data. CONCLUSIONS: The proposed dual-energy DBT scheme is expected to substantially contribute to enhancing mass malignancy detection accuracy particularly in dense breasts.

Asunto(s)

Neoplasias de la Mama , Mamografía , Humanos , Femenino , Mamografía/métodos , Estudios de Factibilidad , Densidad de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Redes Neurales de la Computación , Fantasmas de Imagen , Intensificación de Imagen Radiográfica

RESUMEN

Diffuse optical tomography (DOT) is a non-invasive functional imaging modality that uses near-infrared (NIR) light to measure the oxygenation state and the concentration of hemoglobin. By complementarily using DOT with other anatomical imaging modalities, physicians can diagnose more accurately through additional functional image information. In breast imaging, diagnosis of dense breasts is often challenging because the bulky fibrous tissues may hinder the correct tumor characterization. In this work, we proposed a three-compartment-breast (3CB) decomposition-based prior-guided optical tomography for enhancing DOT image quality. We conjectured that the 3CB prior would lead to improvement of the spatial resolution and also of the contrast of the reconstructed tumor image, particularly for the dense breasts. We conducted a Monte-Carlo simulation to acquire dual-energy X-ray projections of a realistic 3D numerical breast phantom and performed digital breast tomosynthesis (DBT) for setting up a 3CB model. The 3CB prior was then used as a structural guide in DOT image reconstruction. The proposed method resulted in the higher spatial resolution of the recovered tumor even when the tumor is surrounded by the fibroglandular tissues compared with the typical two-composition-prior method or the standard Tikhonov regularization method.

RESUMEN

In this paper, we propose a method for compositing a synthetic mammogram (SM) from digital breast tomosynthesis (DBT) slice images. The method consists of four parts. The first part is image reconstruction of DBT from the acquired projection data by use of backprojection-filtration (BPF) algorithm with a low-frequency boosting scheme and a high-density object reduction technique embedded. Also, a few expectation-maximization (EM) iterations have been additively implemented on top of the BPF algorithm to prepare a separate volume image. The second is generating three kinds of intermediate SMs. A forward projection image and a linear structure weighted forward projection image were computed. A maximum intensity projection of the BPF reconstructed volume image was also generated. The third part is integrating three intermediate SMs. The last is the post-processing of the SM. We scanned two physical phantoms in a prototype DBT scanner, and we have evaluated the performance of the proposed method. We also performed a clinical data study by use of 30 patient data who went through both DBT and digital mammography (DM) scans. Three experienced radiologists have read the SMs generated by several component techniques and also read the DM of each patient, and evaluated the generated SMs. The experimental phantom study and the clinical reader study consistently demonstrated the usefulness of the proposed method.

Asunto(s)

Artefactos , Procesamiento de Imagen Asistido por Computador/métodos , Mamografía , Intensificación de Imagen Radiográfica/métodos , Algoritmos , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Fantasmas de Imagen , Relación Señal-Ruido

RESUMEN

Diffuse optical tomography (DOT) non-invasively measures the functional characteristics of breast lesions using near infrared light to probe tissue optical properties. This study aimed to evaluate a new digital breast tomosynthesis (DBT)/DOT fusion imaging technique and obtain preliminary data for breast cancer detection. Twenty-eight women were prospectively enrolled and underwent both DBT and DOT examinations. DBT/DOT fusion imaging was created after acquisition of both examinations. Two breast radiologists analyzed DBT and DOT images independently, and then finally evaluated the fusion images. The diagnostic performance of each reading session was compared and interobserver agreement was assessed. The technical success rate was 96.4%, with one failure due to an error during DOT data storage. Among the 27 women finally included in the analysis, 13 had breast cancer. The areas under the receiver operating characteristic curve (AUCs) for DBT were 0.783 and 0.854 for readers 1 and 2, respectively. DOT showed comparable diagnostic performance to DBT for both readers. The AUCs were significantly improved (P = 0.004) when the DBT/DOT fusion images were used. Interobserver agreements were highest for the DBT/DOT fusion images. In conclusion, this study suggests that DBT/DOT fusion imaging technique appears to be a promising tool for breast cancer diagnosis.

Asunto(s)

Neoplasias de la Mama/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Mamografía , Tomografía Óptica , Adulto , Femenino , Humanos , Persona de Mediana Edad

RESUMEN

Deep learning has been actively investigated for various applications such as image classification, computer vision, and regression tasks, and it has shown state-of-the-art performance. In diffuse optical tomography (DOT), the accurate estimation of the bulk optical properties of a medium is paramount because it directly affects the overall image quality. In this work, we exploit deep learning to propose a novel, to the best of our knowledge, convolutional neural network (CNN)-based approach to estimate the bulk optical properties of a highly scattering medium such as biological tissue in DOT. We validated the proposed method by using experimental, as well as, simulated data. For performance assessment, we compared the results of the proposed method with those of existing approaches. The results demonstrate that the proposed CNN-based approach for bulk optical property estimation outperforms existing methods in terms of estimation accuracy, with lower computation time.

Asunto(s)

Mama/diagnóstico por imagen , Aprendizaje Profundo , Tomografía Óptica/métodos , Simulación por Computador , Humanos , Procesamiento de Imagen Asistido por Computador , Luz , Modelos Teóricos , Dispersión de Radiación , Factores de Tiempo

RESUMEN

Diffuse optical tomography (DOT) has been investigated as an alternative imaging modality for breast cancer detection thanks to its excellent contrast to hemoglobin oxidization level. However, due to the complicated non-linear photon scattering physics and ill-posedness, the conventional reconstruction algorithms are sensitive to imaging parameters such as boundary conditions. To address this, here we propose a novel deep learning approach that learns non-linear photon scattering physics and obtains an accurate three dimensional (3D) distribution of optical anomalies. In contrast to the traditional black-box deep learning approaches, our deep network is designed to invert the Lippman-Schwinger integral equation using the recent mathematical theory of deep convolutional framelets. As an example of clinical relevance, we applied the method to our prototype DOT system. We show that our deep neural network, trained with only simulation data, can accurately recover the location of anomalies within biomimetic phantoms and live animals without the use of an exogenous contrast agent.

Asunto(s)

Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Óptica/métodos , Algoritmos , Animales , Línea Celular Tumoral , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/diagnóstico por imagen , Fantasmas de Imagen

RESUMEN

Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-ß1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form.

Asunto(s)

Anticuerpos Monoclonales/farmacología , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-met/agonistas , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Animales , Biomarcadores , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Fibrosis , Expresión Génica , Humanos , Inmunohistoquímica , Túbulos Renales Proximales/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/etiología

RESUMEN

OBJECTIVES: To compare the diagnostic performance and interpretation time of digital breast tomosynthesis (DBT) for both novice and experienced readers with and without using a computer-aided detection (CAD) system for concurrent read. METHODS: CAD system was developed for concurrent read in DBT interpretation. In this observer performance study, we used an enriched sample of 100 DBT cases including 70 with and 30 without breast cancers. Image interpretation was performed by four radiologists with different experience levels (two experienced and two novice). Each reader completed two reading sessions (at a minimum 2-month interval), once with and once without CAD. Three different rating scales were used to record each reader's interpretation. Reader performance with and without CAD was reported and compared for each radiologist. Reading time for each case was also recorded. RESULTS: Average area under the receiver operating characteristic curve values for BI-RADS scale on using CAD were 0.778 and 0.776 without using CAD, demonstrating no statistically significant differences. Results were consistent when the probability of malignancy and percentage probability of malignancy scales were used. Reading times per case were 72.07 s and 62.03 s (SD, 37.54 s vs 34.38 s) without and with CAD, respectively. The average difference in reading time on using CAD was a statistically significant decrease of 10.04 ± 1.85 s, providing 14% decrease in time. The time-reducing effect was consistently observed in both novice and experienced readers. CONCLUSION: DBT combined with CAD reduced interpretation time without diagnostic performance loss to novice and experienced readers. KEY POINTS: • The use of a concurrent DBT-CAD system shortened interpretation time. • The shortened interpretation time with DBT-CAD did not come at a cost to diagnostic performance to novice or experienced readers. • The concurrent DBT-CAD system improved the efficiency of DBT interpretation.

Asunto(s)

Neoplasias de la Mama/diagnóstico , Diagnóstico por Computador/instrumentación , Mamografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Diseño de Equipo , Femenino , Humanos , Persona de Mediana Edad , Curva ROC , Factores de Tiempo

RESUMEN

BACKGROUND: To compare the accuracy of mammography (MG), digital breast tomosynthesis (DBT), automated breast ultrasound (ABUS) and magnetic resonance imaging (MRI) for the assessment of residual tumor extent in breast cancer after neoadjuvant chemotherapy (NAC). METHODS: Fifty-one stage II-III breast cancer undergoing NAC were enrolled from March 2015 to December 2016. The longest diameter of residual tumor measured with MG, DBT, ABUS and MRI was compared with the pathologic tumor size. Statistical analysis was performed using intraclass correlation coefficients (ICC) and marginal homogeneity test. Receiver operating characteristics (ROC) analysis was used to evaluate the diagnostic performance for predicting pathologic complete response (pCR). RESULTS: MRI size correlated well with pathology (ICC = 0.83), significantly better than MG, DBT and ABUS size (ICC = 0.56, ICC = 0.63 and ICC = 0.55, respectively). The discrepancy between MRI and pathology was statistical different from that of MG and ABUS (p = 0.0231 and 0.0039, respectively), but not different from that of DBT (p = 0.5727). For predicting pCR, MRI and DBT had a better performance compared to MG and US (area under the ROC curve: 0.92, 0.84, 0.72, 0.75, respectively; p = 0.3749 for DBT, p = 0.0972 for MG and p = 0.0596 for ABUS, when MRI being reference). CONCLUSIONS: MRI and DBT allow more accurate assessment of tumor size compared to pathology compared with MG and ABUS. MRI and DBT outperform MG and ABUS in the prediction of pathologic complete response.

Asunto(s)

Neoplasias de la Mama/patología , Mamografía/métodos , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Neoplasia Residual , Estudios Prospectivos , Curva ROC , Ultrasonografía Mamaria/métodos

RESUMEN

Hepatocyte growth factor and its receptor cMet activate biological pathways necessary for repair and regeneration following kidney injury. Here, we evaluated the clinical role of urinary cMet as a prognostic biomarker in diabetic nephropathy (DN). A total of 218 patients with DN were enrolled in this study. We examined the association of urine cMet levels and long-term outcomes in patients with DN. The levels of urinary cMet were higher in patients with decreased renal function than in patients with relatively preserved renal function (5.25 ± 9.62 ng/ml versus 1.86 ± 4.77 ng/ml, P = 0.001). A fully adjusted model revealed that a urinary cMet cutoff of 2.9 ng/mL was associated with a hazard ratio for end-stage renal disease of 2.33 (95% confidence interval 1.19-4.57, P = 0.014). The addition of urinary cMet to serum creatinine and proteinuria provided the highest net reclassification improvement. We found that in primary cultured human glomerular endothelial cells, TGFß treatment induced fibrosis, and the protein expression levels of collagen I, collagen IV, fibronectin, and αSMA were decreased after administration of an agonistic cMet antibody. In conclusion, elevated levels of urinary cMet at the time of initial diagnosis could predict renal outcomes in patients with DN.

Asunto(s)

Nefropatías Diabéticas/orina , Proteínas Proto-Oncogénicas c-met/orina , Adulto , Anticuerpos/uso terapéutico , Biomarcadores/orina , Creatinina/orina , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/fisiopatología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Femenino , Fibrosis , Factor de Crecimiento de Hepatocito/farmacología , Factor de Crecimiento de Hepatocito/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Pruebas de Función Renal , Glomérulos Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-met/inmunología , Curva ROC , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/orina , Reproducibilidad de los Resultados , Solubilidad , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacos

RESUMEN

BACKGROUND AND OBJECTIVE: We propose a nipple detection algorithm for use with digital breast tomosynthesis (DBT) images. DBT images have been developed to overcome the weaknesses of 2D mammograms for denser breasts by providing 3D breast images. The nipple location acts as an invaluable landmark in DBT images for aligning the right and left breasts and describing the relative location of any existing lesions. METHODS: Nipples may be visible or invisible in a breast image, and therefore a nipple detection method must be able to detect the nipples for both cases. The detection method for visible nipples based on their shape is simple and highly efficient. However, it is difficult to detect invisible nipples because they do not have a prominent shape. Fibroglandular tissue in a breast is anatomically connected with the nipple. Thus, the nipple location can be detected by analyzing the location of such tissue. In this paper, we propose a method for detecting the location of both visible and invisible nipples using fibroglandular tissue and changes in the breast area. RESULTS: Our algorithm was applied to 138 DBT images, and its nipple detection accuracy was evaluated based on the mean Euclidean distance. The results indicate that our proposed method achieves a mean Euclidean distance of 3.10±2.58mm. CONCLUSIONS: The nipple location can be a very important piece of information in the process of a DBT image registration. This paper presents a method for the automatic nipple detection in a DBT image. The extracted nipple location plays an essential role in classifying any existing lesions and comparing both the right and left breasts. Thus, the proposed method can help with computer-aided detection for a more efficient DBT image analysis.

Asunto(s)

Neoplasias de la Mama/diagnóstico por imagen , Mama/diagnóstico por imagen , Mamografía/métodos , Intensificación de Imagen Radiográfica/métodos , Algoritmos , Mama/patología , Neoplasias de la Mama/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Pezones/diagnóstico por imagen , Reconocimiento de Normas Patrones Automatizadas , Reproducibilidad de los Resultados

RESUMEN

We propose computer-aided detection (CADe) algorithm for microcalcification (MC) clusters in reconstructed digital breast tomosynthesis (DBT) images. The algorithm consists of prescreening, MC detection, clustering, and false-positive (FP) reduction steps. The DBT images containing the MC-like objects were enhanced by a multiscale Hessian-based three-dimensional (3D) objectness response function and a connected-component segmentation method was applied to extract the cluster seed objects as potential clustering centers of MCs. Secondly, a signal-to-noise ratio (SNR) enhanced image was also generated to detect the individual MC candidates and prescreen the MC-like objects. Each cluster seed candidate was prescreened by counting neighboring individual MC candidates nearby the cluster seed object according to several microcalcification clustering criteria. As a second step, we introduced bounding boxes for the accepted seed candidate, clustered all the overlapping cubes, and examined. After the FP reduction step, the average number of FPs per case was estimated to be 2.47 per DBT volume with a sensitivity of 83.3%.

Asunto(s)

Mama/patología , Calcinosis/diagnóstico , Imagenología Tridimensional/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Algoritmos , Diseño Asistido por Computadora , Femenino , Humanos , Mamografía/métodos , Relación Señal-Ruido , Tomografía Computarizada por Rayos X/métodos

RESUMEN

PURPOSE: To evaluate interobserver agreement in full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in terms of both lesion detection and characterization, and to evaluate the cancer detection rate of standard two-view FFDM compared to various combinations of DBT. MATERIALS AND METHODS: Thirty-five women (mean age 59.7; range 50-80 years) with 37 breast cancers who underwent both two-view DBT and two-view FFDM were included. DBT images were obtained using an investigational prototype. We performed interobserver agreement analyses using kappa (k) statistics. The cancer detection rate of various combinations of DBT compared to standard two-view FFDM was estimated using a generalized estimation equation. RESULTS: There was fair to moderate agreement on detectability (k = 0.59-0.62) in both views of FFDM and DBT, while fair to substantial agreement was found for lesion location (k = 0.52-0.84) and fair to moderate agreement for lesion type (k = 0.46-0.70) and BI-RADS final assessment (k = 0.48-0.69). In generalized estimation equations, standard two-view FFDM was inferior to any combination of DBT. The detection rate ratio was significantly higher in the combined four views of DBT and FFDM compared to standard FFDM (p < 0.046). CONCLUSION: Our study showed good agreement in lesion detection and characterization between FFDM and DBT images. Our findings also demonstrated that combining DBT and FFDM is superior in detecting cancer compared to standard FFDM.

Asunto(s)

Neoplasias de la Mama/diagnóstico por imagen , Mamografía/métodos , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Variaciones Dependientes del Observador

RESUMEN

Digital breast tomosynthesis (DBT) is a recently developed system for three-dimensional imaging that offers the potential to reduce the false positives of mammography by preventing tissue overlap. Many qualitative evaluations of digital breast tomosynthesis were previously performed by using a phantom with an unrealistic model and with heterogeneous background and noise, which is not representative of real breasts. The purpose of the present work was to compare reconstruction algorithms for DBT by using various breast phantoms; validation was also performed by using patient images. DBT was performed by using a prototype unit that was optimized for very low exposures and rapid readout. Three algorithms were compared: a back-projection (BP) algorithm, a filtered BP (FBP) algorithm, and an iterative expectation maximization (EM) algorithm. To compare the algorithms, three types of breast phantoms (homogeneous background phantom, heterogeneous background phantom, and anthropomorphic breast phantom) were evaluated, and clinical images were also reconstructed by using the different reconstruction algorithms. The in-plane image quality was evaluated based on the line profile and the contrast-to-noise ratio (CNR), and out-of-plane artifacts were evaluated by means of the artifact spread function (ASF). Parenchymal texture features of contrast and homogeneity were computed based on reconstructed images of an anthropomorphic breast phantom. The clinical images were studied to validate the effect of reconstruction algorithms. The results showed that the CNRs of masses reconstructed by using the EM algorithm were slightly higher than those obtained by using the BP algorithm, whereas the FBP algorithm yielded much lower CNR due to its high fluctuations of background noise. The FBP algorithm provides the best conspicuity for larger calcifications by enhancing their contrast and sharpness more than the other algorithms; however, in the case of small-size and low-contrast microcalcifications, the FBP reduced detectability due to its increased noise. The EM algorithm yielded high conspicuity for both microcalcifications and masses and yielded better ASFs in terms of the full width at half maximum. The higher contrast and lower homogeneity in terms of texture analysis were shown in FBP algorithm than in other algorithms. The patient images using the EM algorithm resulted in high visibility of low-contrast mass with clear border. In this study, we compared three reconstruction algorithms by using various kinds of breast phantoms and patient cases. Future work using these algorithms and considering the type of the breast and the acquisition techniques used (e.g., angular range, dose distribution) should include the use of actual patients or patient-like phantoms to increase the potential for practical applications.

Asunto(s)

Algoritmos , Mama/anatomía & histología , Imagenología Tridimensional/métodos , Fantasmas de Imagen , Artefactos , Femenino , Humanos

RESUMEN

BACKGROUND: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is useful in diagnosing idiopathic membranous nephropathy (IMN). We investigated the clinical relevance of PLA2R-Ab enzyme-linked immunosorbent assay (ELISA) in patients with IMN. METHODS: We measured PLA2R-Ab with an ELISA kit from the serum of 160 patients with IMN (n = 93), secondary MN (n = 14) and other glomerulonephritis (n = 41) as well as healthy controls (n = 12) at the time of renal biopsy and investigated the correlation of titers of PLA2R-Ab with clinical parameters. RESULTS: PLA2R-Ab was positive in 41 of 93 patients (44.1%) with IMN. No samples from the patients with secondary MN and other glomerulonephritis or healthy controls were positive with the ELISA test. The PLA2R-Ab-positive patients showed severe disease activity and a low remission rate. The PLA2R-Ab titer positively correlated with proteinuria and was negatively associated with renal function and serum albumin. The patients with a high titer of PLA2R-Ab had significantly decreased remission rates. The cumulative probabilities of remission was significantly lower in patients with PLA2R-Ab (p = 0.01) and even so in patients with a high titer of PLA2R-Ab (p = 0.04). When we compared the ELISA titers with Western blot (WB) data of 43 patients who had been enrolled in our previous study, 18 and 30 patients were positive on ELISA (41.9%) and WB (69.8%), respectively. WB and ELISA had a concordance rate of 72.1% and were positively correlated (r = 0.590, p < 0.001). CONCLUSION: The presence, as well as a high titer, of PLA2R-Ab on ELISA was associated with poor prognosis of IMN. Assessment of PLA2R-Ab with ELISA is an easy and reliable tool for the diagnosis and guidance of therapeutic plans.

Asunto(s)

Glomerulonefritis Membranosa/inmunología , Receptores de Fosfolipasa A2/inmunología , Western Blotting , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Glomerulonefritis Membranosa/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico

RESUMEN

IL-1ß-secreting nucleotide-binding oligomerization domain protein 3 (NLRP3) inflammasomes play a pivotal role in triggering innate immune responses in metabolic disease. We investigated the role of soluble uric acid in NLRP3 inflammasome activation in macrophages to demonstrate the effect of systemic hyperuricemia on progressive kidney damage in type 2 diabetes. THP-1 cells, human acute monocytic leukemia cells, were cultured to obtain macrophages, and HK-2 cells, human renal proximal tubule cells, were cultured and stimulated with uric acid. In vivo, we designed four rat groups as follows: 1) Long-Evans Tokushima Otsuka (LETO); 2) Otsuka Long-Evans Tokushima Fatty (OLETF); 3) OLETF+high-fructose diet (HFD) for 16 wk; and 4) OLETF+HFD+allopurinol (10 mg/dl administered in the drinking water). Soluble uric acid stimulated NLRP3 inflammasomes to produce IL-1ß in macrophages. Uric acid-induced MitoSOX mediates NLRP3 activation and IL-1ß secretion. IL-1ß from macrophages activates NF-κB in cocultured proximal tubular cells. In vivo, intrarenal IL-1ß expression and macrophage infiltration increased in HFD-fed OLETF rats. Lowering the serum uric acid level resulted in improving the albuminuria, tubular injury, macrophage infiltration, and renal IL-1ß (60% of HFD-fed OLETF) independently of glycemic control. Direct activation of proximal tubular cells by uric acid resulted in (C-X-C motif) ligand 12 and high mobility group box-1 release and accelerated macrophage recruitment and the M1 phenotype. Taken together, these data support direct roles of hyperuricemia in activating NLRP3 inflammasomes in macrophages, promoting chemokine signaling in the proximal tubule and contributing to the progression of diabetic nephropathy through cross talk between macrophages and proximal tubular cells.

Asunto(s)

Proteínas Portadoras/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Hiperuricemia/complicaciones , Inflamasomas/metabolismo , Inflamación/etiología , Túbulos Renales Proximales/metabolismo , Macrófagos/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Ácido Úrico/metabolismo , Animales , Proteínas Portadoras/genética , Línea Celular , Quimiocina CXCL12/metabolismo , Técnicas de Cocultivo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/inmunología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/prevención & control , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Supresores de la Gota/farmacología , Proteína HMGB1/metabolismo , Humanos , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/inmunología , Hiperuricemia/metabolismo , Inflamasomas/genética , Inflamación/inmunología , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Interferencia de ARN , Ratas Endogámicas OLETF , Transducción de Señal , Factores de Tiempo , Transfección

RESUMEN

BACKGROUND: The plasma levels of cell-free DNA (cfDNA) are known to be elevated under inflammatory or apoptotic conditions. Increased cfDNA levels have been reported in hemodialysis (HD) patients. The aim of this study was to investigate the clinical significance of cfDNA in HD patients. METHODS: A total of 95 patients on HD were enrolled. We measured their predialysis cfDNA levels using real-time EIF2C1 gene sequence amplification and analyzed its association with certain clinical parameters. RESULTS: The mean plasma cfDNA level in the HD patients was 3,884 ± 407 GE/mL, and the mean plasma cfDNA level in the control group was 1,420 ± 121 GE/mL (P < 0.05). Diabetic patients showed higher plasma cfDNA levels compared with nondiabetic patients (P < 0.01). Patients with cardiovascular complications also showed higher plasma cfDNA levels compared with those without cardiovascular complication (P < 0.05). In univariable analysis, the cfDNA level was associated with 3-month mean systolic blood pressure (SBP), white blood cell, serum albumin, creatinine (Cr), normalized protein catabolic rate in HD patients. In diabetic patients, it was significantly correlated with SBP, hemoglobin A1c, and serum albumin. In multivariate analysis, SBP was the independent determinant for the cfDNA level. In diabetic patients, cfDNA level was independently associated with hemoglobin A1c and SBP. CONCLUSIONS: In patients with HD, cfDNA is elevated in diabetic patients and patients with cardiovascular diseases. Uncontrolled hypertension and poor glycemic control are independent determinants for the elevated cfDNA. Our data suggest that cfDNA might be a marker of vascular injury rather than proinflammatory condition in HD patients.

RESUMEN

This paper introduces a new approach for preparing magnetic colloidal suspensions with electrostatic repulsion between particles and polyelectrolyte surfactants. The surface charge of the iron oxide particles was positive in acidic aqueous conditions; however the surface charge of the colloid was negative in basic aqueous conditions due to the amphoteric property of Fe2O3. The long-term colloidal stability and particle distribution of the multivalent charged polymers, Poly(4-vinylbenzenesulfonate sodium salt) (PSS), Poly(acrylic acid) (PAA), and Poly(allylamine hydrochloride) (PAH) were compared with the monovalent surfactant sodium dodecyl sulfate (SDS). Both mono- and multivalent surfactant molecules showed good colloidal stability for extended periods of time. However, the particle distribution was dependent on the hydrophobicity of the surfactants' functional groups. Polyelectrolytes with a negatively charged functional group showed good long-term stability of particles and a narrow particle distribution regardless of the acid dissociation constant (pKa) of the polymer.

Asunto(s)

Coloides/química , Compuestos Férricos/química , Magnetismo , Nanopartículas del Metal/química , Polímeros/química , Dodecil Sulfato de Sodio/química , Tensoactivos/química , Electrólitos/química , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Electricidad Estática , Propiedades de Superficie

RESUMEN

PURPOSE: To evaluate the feasibility of iontophoresis and the combination effects with chemical enhancers on in vivo hypocalcemic effect of transbuccally delivered salmon calcitonin (sCT). METHODS: N-acetyl-L-cysteine (NAC), sodium deoxyglycocholate (SDGC), and ethanol were used as chemical enhancers; and 0.5 mA/cm(2) fixed electric current was employed as a physical enhancer. sCT hydrogel was applied to rabbit buccal mucosa, and blood samples were obtained via the central auricular artery. Blood calcium level was measured by calcium kit and the conformational changes of buccal mucosa were investigated with FT-IR spectroscopy. Hematoxylin/eosin staining was used for the histological evaluation of buccal mucosa. RESULTS: Iontophoresis groups except iontophoresis-NAC group showed significant hypocalcemic effect compared to negative control, in particular iontophoresis-SDGC combination group showed fast onset of action as well as sustained hypocalcemic effect (p < 0.05). FT-IR result demonstrated the reduction of buccal barrier function, and the histological study showed a decrease in buccal thickness as well as minor damage to the dermal-epidermal junctions in the enhancing method groups; however, the damaged tissues virtually recovered within 24 h after the removal of electrodes. CONCLUSIONS: Iontophoresis and combination with SDGC were found to be safe and potential strategies for transbuccal peptide delivery in vivo.

Asunto(s)

Calcitonina/administración & dosificación , Excipientes/administración & dosificación , Iontoforesis , Mucosa Bucal/efectos de los fármacos , Absorción por la Mucosa Oral/efectos de los fármacos , Acetilcisteína/administración & dosificación , Administración Bucal , Animales , Biomarcadores/sangre , Calcitonina/química , Calcitonina/farmacocinética , Calcitonina/toxicidad , Calcio/sangre , Química Farmacéutica , Regulación hacia Abajo , Etanol/administración & dosificación , Excipientes/química , Excipientes/toxicidad , Estudios de Factibilidad , Hidrogeles , Inyecciones Intravenosas , Masculino , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , Permeabilidad , Conejos , Espectroscopía Infrarroja por Transformada de Fourier , Tecnología Farmacéutica/métodos

RESUMEN

BACKGROUND: Diagnosing acute rejection (AR) in kidney transplant recipients typically requires an invasive kidney biopsy. A previous study has suggested that expression of five genes in peripheral blood can indicate the presence of AR in American pediatric kidney transplant recipients. This study aims to validate if these five genes are also useful to diagnose AR in Korean adult kidney transplant patients. METHODS: Blood samples were collected from 143 patients (39 biopsy-proven AR, 84 stable patients, and 20 other graft injuries) at an average of 9 months posttransplantation and performed real-time PCR for five-gene biomarkers (DUSP1, NKTR, MAPK9, PSEN1, and PBEF1). RESULTS: Patients with acute cellular rejection (ACR) had a significantly decreased level of MAPK9 and a significantly increased level of PSEN1 when compared with controls and also with patients with other graft injury (OGI). In multivariate logistic regression analysis, for discrimination between ACR and OGI, an excellent diagnostic accuracy was observed in the gene sets but five-gene set generated a higher AUC than two-gene set. With clinical variables combined to these gene sets, the diagnostic accuracy increased in both five-gene set and two-gene set. CONCLUSIONS: These results support the validity of 5 gene-set for the prediction of AR in Asian adult kidney transplant recipients and suggest the promising role of the peripheral blood gene test in the diagnosis of AR in kidney transplantation.

Asunto(s)

Rechazo de Injerto/diagnóstico , Trasplante de Riñón/efectos adversos , Insuficiencia Renal/sangre , Insuficiencia Renal/cirugía , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Biopsia , Pruebas Diagnósticas de Rutina , Femenino , Rechazo de Injerto/sangre , Antígenos HLA/metabolismo , Pruebas Hematológicas , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Proteína Quinasa 9 Activada por Mitógenos/metabolismo , Análisis Multivariante , Presenilina-1/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea