Glutamine/Glutamate Metabolism Studied with Magnetic Resonance Spectroscopic Imaging for the Characterization of Adrenal Nodules and Masses

Purpose. To assess glutamine/glutamate (Glx) and lactate (Lac) metabolism using proton magnetic resonance spectroscopic imaging (1H-MRS) in order to differentiate between adrenal gland nodules and masses (adenomas, pheochromocytomas, carcinomas, and metastases). Materials and Methods. Institutional review board approval and informed consent were obtained. A total of 130 patients (47 men) with 132 adrenal nodules/masses were prospectively assessed (54 +/- 14.8 years). A multivoxel system was used with a two-dimensional point-resolved spectroscopy/chemical-shift imaging sequence. Spectroscopic data were interpreted by visual inspection and peak amplitudes of lipids (Lip), choline (Cho), creatine (Cr), Lac, and Glx. Lac/Cr and Glx/Cr were calculated. Glx/Cr was assessed in relation to lesion size. Results. Statistically significant differences were observed in Glx/Cr results between adenomas and pheochromocytomas (P < 0.05), however, with a low positive predictive value (PPV). Glx levels were directly proportional to lesion size in carcinomas. A cutoff point of 1.44 was established for the differentiation between carcinomas larger versus smaller than 4 cm, with 75% sensitivity, 100% specificity, 100% PPV, and 80% accuracy. Lac/Cr results showed no differences across lesions. A cutoff point of -6.5 for Lac/Cr was established for carcinoma diagnosis. Conclusion. Glx levels are directly proportional to lesion size in carcinomas. A cutoff point of -6.5 Lac/Cr differentiates carcinomas from noncarcinomas.Universidade Federal de São Paulo, Dept Diagnost Imaging, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Endocrinol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Urol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imaging, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Endocrinol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Urol, BR-04024002 São Paulo, BrazilWeb of Scienc

Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy

Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy.BackgroundProteinuria plays a central role in the progression of glomerular disease, and there is growing evidence suggesting that it may determine tubular cell activation with release of chemokines and fibrogenic factors, leading to interstitial inflammatory reaction. However, most studies on this subject have been performed in experimental models, and the experience in human kidney biopsies has been scarce. We analyzed the tissue sections of patients with idiopathic membranous nephropathy (IMN), a noninflammatory glomerular disease that may follow a progressive disease with heavy persistent proteinuria, interstitial cell infiltration, and decline of renal function.MethodsParaffin-embedded biopsy specimens from 25 patients with IMN (13 progressive and 12 nonprogressive) were retrospectively studied by immunohistochemistry [monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted chemokine (RANTES), osteopontin (OPN), platelet-derived growth factor-BB (PD-GF-BB)] and in situ hybridization [MCP-1, RANTES, PDGF-BB, transforming growth factor-β1 (TGF-β1)]. Moreover, we studied the presence of myofibroblasts, which were identified by the expression of α-smooth muscle actin (α-SMA), the monocytes/macrophages (CD68-positive cells), and T-cell infiltration (CD4+ and CD8+ cells). All of the patients were nephrotic and without treatment at time of the biopsy.ResultsA strong up-regulation of MCP-1, RANTES, and OPN expression was observed, mainly in tubular epithelial cells, with a significant major intensity in the progressive IMN patients. A strong correlation between the mRNA expression and the corresponding protein was noted. The presence of these chemokines and OPN was associated with interstitial cell infiltration. TGF-β and PDGF were also up-regulated, mainly in tubular epithelial cells, with a stronger expression in the progressive IMN, and an association with the presence of myofibroblasts was found.ConclusionsPatients with severe proteinuria and progressive IMN have an overexpression in tubular epithelial cells of the chemokines MCP-1, RANTES, and OPN and the profibrogenic cytokines PDGF-BB and TGF-β. Because this up-regulation was associated with an interstitial accumulation of mononuclear cells and an increase in myofibroblastic activity, it is suggested that those mediators are potential predictors of progression in IMN. Finally, based on experimental data and the findings of this article, we speculate that severe proteinuria is the main factor responsible for the up-regulation of these factors in tubular epithelial cells

Prevalência de anticorpos para o vírus da hepatite A em duas populações de diferente nível sócio-econômico de São Paulo, Brasil

To evaluate the prevalence of antibody against hepatitis A in two socioeconomically distinct populations of a developing country, 540 serum specimens from children and adults living in São Paulo, Brazil, were tested for IgG anti HAV by a commercial radioimunoassay (Havab, Abbott Laboratories). The prevalence of anti-HAV in low socioeconomic level subjects was 75.0% in children 2-11 years old and 100.0% in adults, whereas in middle socioeconomic level significantly lower prevalences were observed (40.3% in chidren 2-11 years old and 91.9% in adults). Voluntary blood donors of middle socioeconomic level showed a prevalence of 90.4%. These data suggest that hepatitis A infection remains a highly endemic disease in São Paulo, Brazil.Para avaliar a prevalência de anticorpos para o vírus da hepatite A em um país em desenvolvimento, os Autores analisaram 540 amostras de soro de crianças e adultos colhidas em São Paulo, pertencente a duas populações distintas sota o ponto de vista socio-econômico. Os anticorpos IgG anti-VHA foram testados através de radioimunoensaio disponível comercialmente (Havata, Laboratorios Abbott). A prevalência de anticorpos IgG anti-HVA no grupo de baixo nível socioeconómico foi de 75,0% em crianças de 2-11 anos e 100,0% nos adultos, enquanto que no grupo de nível socioeconómico médio observaram-se prevalências acentuadamente mais baixas (40,3% nas crianças de 2 a 11 anos e 91,9% nos adultos). Doadores de sangue voluntários, de nível sócio-econômico médio, apresentaram prevalência de anticorpos de 90,4°/o. Estes achados sugerem que a infecção pelo vírus da hepatite A continua sendo uma infecção altamente endêmica em São Paulo, Brasil

Renal angiotensin II up-regulation and myofibroblast activation in human membranous nephropathy

Renal angiotensin II up-regulation and myofibroblast activation in human membranous nephropathy.BackgroundThe molecular mechanisms of renal injury and fibrosis in proteinuric nephropathies are not completely elucidated but the renin-angiotensin system (RAS) is involved. Idiopathic membranous nephropathy (MN), a proteinuric disease, may progress to renal failure. Our aim was to investigate the localization of RAS components in MN and their correlation with profibrotic parameters and renal injury.MethodsRenal biopsies from 20 patients with MN (11 with progressive disease) were studied for the expression of RAS components [angiotensin-converting enzyme (ACE) and angiotensin II (Ang II)] by immunohistochemistry. Transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF)-BB were studied by by in situ hybridization, and myofibroblast transdifferentiation by α-smooth muscle actin (α-SMA) staining.ResultsACE immunostaining was elevated in tubular cells and appeared in interstitial cells colocalized in α-actin–positive cells in progressive disease. Elevated levels of Ang II were observed in tubules and infiltrating interstitial cells. TGF-β and PDGF mRNAs were up-regulated mainly in cortical tubular epithelial cells in progressive disease (P < 0.01) and correlated with the myofibroblast transdifferentiation (r = 0.8, P < 0.01 for TGF-β; r = 0.6, P < 0.01 for PDGF). Moreover, in serial sections of progressive cases, the ACE and Ang II over-expression was associated with the tubular expression of these pro-fibrogenic factors, and with the interstitial infiltration and myofibroblast activation.ConclusionIntrarenal RAS is selectively activated in progressive MN. De novo expression of ACE at sites of tubulointerstitial injury suggests that the in situ Ang II generation could participate in tubular TGF-β up-regulation, epithelial-myofibroblast transdifferentiation, and disease progression. These results suggest a novel role of Ang II in human tubulointerstitial injury

Non-monotonic behavior of weak-polyelectrolytes adsorption on a cationic surface: A Monte Carlo simulation study

In this work, the weak polyelectrolyte (PE) adsorption on a strong cationic surface is studied with constant pH Monte Carlo simulations using a coarse-grained model. When a large number of PE chains is added to the system, the PE adsorbed amount vs pH curve exhibits a non-monotonic behavior, with the appearance of a maximum close to the intrinsic pKa0-value of the PE titratable groups. The apparent pKa-value of the PE chains shows a non-trivial tendency depending on the pH-value and the surface coverage degree. In increasing the pH-value, the small anions that accompany the cationic surface are replaced by PE chains and small cations. For pH>pKa0+1, an evident charge reversion of surface is observed. These results are explained analyzing the interplay between the attractive and repulsion electrostatic interactions between the different components of the system (inter- and intra-charged monomers of PE chains, the strong cationic surface and small ions) and their effects on the PE chain ionization.Fil: Narambuena, Claudio Fabian. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - San Luis. Instituto de Fisica Aplicada "dr. Jorge Andres Zgrablich". Grupo Vinculado Bionanotecnologia y Sistemas Complejos | Universidad Nacional de San Luis. Facultad de Cs.fisico Matematicas y Naturales. Instituto de Fisica Aplicada "dr. Jorge Andres Zgrablich". Grupo Vinculado Bionanotecnologia y Sistemas Complejos. - Universidad Tecnologica Nacional. Facultad Reg.san Rafael. Grupo Vinculado Bionanotecnologia y Sistemas Complejos.; ArgentinaFil: Blanco, Pablo M.. Universidad de Barcelona. Facultad de Quimica. Instituto de Quimica Teorica y Computacional.; EspañaFil: Rodriguez, Adrian. Universidad Tecnológica Nacional. Facultad Reg. Neuquen; ArgentinaFil: Rodríguez, Diego E.. Universidad Tecnológica Nacional. Facultad Reg. Neuquen; ArgentinaFil: Madurga, Sergio. Universidad de Barcelona. Facultad de Quimica. Instituto de Quimica Teorica y Computacional.; EspañaFil: Garcés, José L.. Universidad de Barcelona. Facultad de Quimica. Instituto de Quimica Teorica y Computacional.; EspañaFil: Mas Pujadas, Francesc. Universidad de Barcelona. Facultad de Quimica. Instituto de Quimica Teorica y Computacional.; Españ

Efecto del Tratamiento de Alta Presión Hidrostática en Parámetros de Calidad y Vida Útil de Cerezas

El objetivo del trabajo consistió en estudiar la evolución de parámetros de calidad de cerezas (parámetros cromáticos, textura, pH, recuento de microorganismos) sometidas a tratamientos con alta presión hidrostática (APH) y posterior almacenamiento bajo refrigeración. Las cerezas fueron envasadas al vacío y sometidas a tres niveles de presión (200, 400 y 600 MPa), durante 5 minutos a 10°C, contrastándose con un control (0 MPa). Luego del tratamiento, fueron almacenadas en cámara de frío (4°C) durante 63 días, extrayéndose muestras en días preestablecidos. El color se vio afectado al inicio del almacenamiento, en todos los tratamientos,aunque no se observaron diferencias significativas al final del mismo. La textura se modificó significativamente en todos los tratamientos. El pH resultó más elevado en las cerezas sin tratar al final del almacenamiento. El tratamiento resultó efectivo en la inactivación de microorganismos

Chiral Teropyrenes: Synthesis, Structure, and Spectroscopic Studies

: We present the inaugural synthesis of a chiral teropyrene achieved through a four-fold alkyne benzannulation catalyzed by InCl3, resulting in good yields. The product underwent thorough characterization using FT-Raman and FT-IR spectroscopies, demonstrating a close agreement with calculated spectra. X-ray crystallographic analysis unveiled a notable twist in the molecule's backbone, with an end-to-end twist angle of 51°, consistent with computational predictions. Experimentally determined enantiomeric inversion barriers revealed a significant energy barrier of 23 kcal/mol, facilitating the isolation of enantiomers for analysis via circular dichroism (CD) and circularly polarized luminescence (CPL) spectroscopies. These findings mark significant strides in the synthesis and characterization of chiral teropyrenes, offering insights into their structural and spectroscopic properties

Methodology of umbilical cord stem cells obtention and their potential use in dentistry and hematology

Las posibles aplicaciones terapéuticas de las células madre estromales mesenquimales (MSC) han despertado un gran interés en el campo de la ingeniería biomédica como terapia regenerativa. Las MSC son células madre adultas multipotentes que poseen un alto potencial de diferenciación, baja inmunogenicidad, propiedades inmunomoduladoras y capacidad de expansión in vitro eficiente. Las células madre derivadas de cordón umbilical humano (hUC-MSC) pueden diferenciarse a otros tipos celulares y ser utilizadas con fines terapéuticos. En este trabajo mostramos la metodología a través de la cual obtuvimos hUC-MSC, con la finalidad de diferenciarlas dentro del linaje eritropoyético. Así mismo, evaluamos y discutimos el potencial de estas hUC-MSC, en la diferenciación osteoblástica y su aplicación en la práctica odontológica.The possible therapeutic applications of mesenchymal stromal stem cells (MSC) have aroused great interest in the field of biomedical engineering, such as regenerative therapy. MSC´s are multipotent adult stem cells that have a high potential for differentiation, low immunogenicity, immunomodulatory properties and efficient in vitro expandability. Stem cells derived from human umbilical cord (hUC-MSC) can be differentiated into other cell types and may be used for therapeutic purposes. In this work we show the methodology by which we obtained hUC-MSC, in order to differentiate them within the erythropoietic lineage. Likewise, we evaluate and discuss the potential of these hUC-MSC, in osteoblastic differentiation and its application in dental practice.Fil: García Sanmartino, Clara. Universidad Nacional de Cuyo. Facultad de OdontologíaFil: Carminati, Sergio Andrés . Universidad Nacional de Cuyo. Facultad de Ciencias MédicasFil: Aguilera, Milton Osmar. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histologia y Embriología Mendoza. "Dr. Mario H. Burgos"Fil: Moras, M.. Paris Diderot University (France). Integrated Biology of Red Blood CellsFil: Ostuni, M. A.. Paris Diderot University (France). Integrated Biology of Red Blood CellsFil: Fader Kaiser, Claudio. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histologia y Embriología Mendoza. "Dr. Mario H. Burgos

Design, Environmental and Sustainability Constraints of new African Observatories: The example of the Mozambique Radio Astronomy Observatory

The Mozambique Radio Astronomy Observatory (MRAO) will be a first milestone towards development of radioastronomy in Mozambique. Development of MRAO will constitute a preparation step towards participation in the upcoming Africa VLBI Network and the Square Kilometer Array project. The MRAO first antenna is planned to serve as a capacitation and training facility and will be installed after the conversion of a 7-meter telecom dish in South Africa. Therefore, this first radiotelescope design has to comply with local spectral and environmental constraints. Furthermore, power availability and long term sustainability with potential inclusion of solar power and control of Radio Frequency Interference are analyzed. Here we outline some of the design, environmental and power sustainability constraints.Comment: 5 pages, 3 Figures; Proceedings of the URSI BEJ Session 'Large Scale Science Projects: Europa-Africa Connects', IEEE Africon 2013 Conference Mauritius (9-12 Sep) 2013, Accepted for Publication at IEEE Xplorer, Nov 201

Role of charge regulation and fluctuations in the conformational and mechanical properties of weak flexible polyelectrolytes

This work addresses the role of charge regulation (CR) and the associated fluctuations in the conformational and mechanical properties of weak polyelectrolytes. Due to CR, changes in the pH-value modifies the average macromolecular charge and conformational equilibria. A second effect is that, for a given average charge per site, fluctuations can alter the intensity of the interactions by means of correlation between binding sites. We investigate both effects by means of Monte Carlo simulations at constant pH-value, so that the charge is a fluctuating quantity. Once the average charge per site is available, we turn off the fluctuations by assigning the same average charge to every site. A constant charge MC simulation is then performed. We make use of a model which accounts for the main fundamental aspects of a linear flexible polyelectrolyte that is, proton binding, angle internal rotation, bond stretching and bending. Steric excluded volume and differentiated treatment for short-range and long-range interactions are also included. This model can be regarded as a kind of 'minimal' in the sense that it contains a minimum number of parameters but still preserving the atomistic detail. It is shown that, if fluctuations are activated, gauche state bond probabilities increase and the persistence length decreases, so that the polymer becomes more folded. Macromolecular stretching is also analyzed in presence of CR (the charge depends on the applied force) and without CR (the charge is fixed to the value at zero force). The analysis of the low force scaling behavior concludes that Pincus exponent becomes pH-dependent. Both, with and without CR, a transition from 1/2 at high pH-values (phantom chain) to 3/5 at low pH-values (Pincus regime) is observed. Finally, the intermediate force stretching regime is investigated. It is found that CR induces a moderate influence in the force-extension curves and persistence length (which in this force regime becomes force-dependent). It is thus concluded that the effect of CR on the stretching curves is mainly due to the changes in the average charge at zero force. It is also found that, for the cases studied, the effect of steric excluded volume is almost irrelevant compared to electrostatic interactions