Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy

Chronic kidney diseasemineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-?B ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy. (C) 2012 American Society for Bone and Mineral Research.

Carbon nanotubes modified with antimony nanoparticles: A novel material for electrochemical sensing

In this study, a novel material for the electrochemical determination of bisphenol A using a nanocomposite based on multi-walled carbon nanotubes modified with antimony nanoparticles has been investigated. The morphology, structure, and electrochemical performance of the nanocomposite electrodes were characterised by field emission gun scanning electron microscopy, energy-dispersive X-ray spectroscopy, and cyclic voltammetry. A scan rate study and electrochemical impedance spectroscopy showed that the bisphenol A oxidation product is adsorbed on nanocomposite electrode surface. Differential pulse voltammetry in phosphate buffer solution at pH 6, allowed the development of a method to determine bisphenol A levels in the range of 0.5-5.0 mu mol L-1, with a detection limit of 5.24 nmol L-1 (1.19 mu g L-1). (C) 2012 Elsevier Ltd. All rights reserved.

Enzymatic Solid-Phase Reactor Based on Silica Organofunctionalized with p-Phenylenediamine for Electrochemical Detection of Phenolic Compounds

A new biomaterial, based on silica organofunctionalized with p-phenylenediamine (p-PDA) and the enzyme peroxidase, was used in the development of an enzymatic solid-phase reactor. The analytical techniques used in the characterization showed that the organic ligand was incorporated into the silica matrix. Thus, the silica modified with p-PDA allowed the incorporation of peroxidase by the electrostatic interaction between the carboxylic groups present in the enzyme molecules and the amino groups attached to the silica. The enzymatic solid-phase reactor was used for chemical oxidation of phenols in 1, 4-benzoquinone that was then detected by chronoamperometry. The system allowed the analysis of hydroquinone with a detection limit of 83.6 nmol L-1. Thus, the new material has potential in the determination of phenolic compounds river water samples.

Characterization of Stability Region for General Autonomous Nonlinear Dynamical Systems

The existing characterization of stability regions was developed under the assumption that limit sets on the stability boundary are exclusively composed of hyperbolic equilibrium points and closed orbits. The characterizations derived in this technical note are a generalization of existing results in the theory of stability regions. A characterization of the stability boundary of general autonomous nonlinear dynamical systems is developed under the assumption that limit sets on the stability boundary are composed of a countable number of disjoint and indecomposable components, which can be equilibrium points, closed orbits, quasi-periodic solutions and even chaotic invariant sets.

Theoretical study of the absorption and nonradiative deactivation of 1-nitronaphthalene in the low-lying singlet and triplet excited states including methanol and ethanol solvent effects

The photophysics of the 1-nitronaphthalene molecular system, after the absorption transition to the first singlet excited state, is theoretically studied for investigating the ultrafast multiplicity change to the triplet manifold. The consecutive transient absorption spectra experimentally observed in this molecular system are also studied. To identify the electronic states involved in the nonradiative decay, the minimum energy path of the first singlet excited state is obtained using the complete active space self-consistent field//configurational second-order perturbation approach. A near degeneracy region was found between the first singlet and the second triplet excited states with large spin-orbit coupling between them. The intersystem crossing rate was also evaluated. To support the proposed deactivation model the transient absorption spectra observed in the experiments were also considered. For this, computer simulations using sequential quantum mechanic-molecular mechanic methodology was used to consider the solvent effect in the ground and excited states for proper comparison with the experimental results. The absorption transitions from the second triplet excited state in the relaxed geometry permit to describe the transient absorption band experimentally observed around 200 fs after the absorption transition. This indicates that the T-2 electronic state is populated through the intersystem crossing presented here. The two transient absorption bands experimentally observed between 2 and 45 ps after the absorption transition are described here as the T-1 -> T-3 and T-1 -> T-5 transitions, supporting that the intermediate triplet state (T-2) decays by internal conversion to T-1. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4738757]

Evaluation of the detection and quantification limits in electroanalysis using two popular methods: application in the case study of paraquat determination

In this work, the reduction reaction of paraquat herbicide was used to obtain analytical signals using electrochemical techniques of differential pulse voltammetry, square wave voltammetry and multiple square wave voltammetry. Analytes were prepared with laboratory purified water and natural water samples (from Mogi-Guacu River, SP). The electrochemical techniques were applied to 1.0 mol L-1 Na2SO4 solutions, at pH 5.5, and containing different concentrations of paraquat, in the range of 1 to 10 mu mol L-1, using a gold ultramicroelectrode. 5 replicate experiments were conducted and in each the mean value for peak currents obtained -0.70 V vs. Ag/AgCl yielded excellent linear relationships with pesticide concentrations. The slope values for the calibration plots (method sensitivity) were 4.06 x 10(-3), 1.07 x 10(-2) and 2.95 x 10(-2) A mol(-1) L for purified water by differential pulse voltammetry, square wave voltammetry and multiple square wave voltammetry, respectively. For river water samples, the slope values were 2.60 x 10(-3), 1.06 x 10(-2) and 3.35 x 10(-2) A mol(-1) L, respectively, showing a small interference from the natural matrix components in paraquat determinations. The detection limits for paraquat determinations were calculated by two distinct methodologies, i.e., as proposed by IUPAC and a statistical method. The values obtained with multiple square waves voltammetry were 0.002 and 0.12 mu mol L-1, respectively, for pure water electrolytes. The detection limit from IUPAC recommendations, when inserted in the calibration curve equation, an analytical signal (oxidation current) is smaller than the one experimentally observed for the blank solution under the same experimental conditions. This is inconsistent with the definition of detection limit, thus the IUPAC methodology requires further discussion. The same conclusion can be drawn by the analyses of detection limits obtained with the other techniques studied.

Nanogravimetric study of lead underpotential deposition on selenium thin films as a semiconductor alloy formation procedure

An electrochemical quartz crystal microbalance Au electrode modified with a Se thin film was used to investigate the electrochemical behavior of lead ad-atoms using underpotential deposition (UPD) conditions. A specific quasi-reversible process was observed during the reduction of Pb2+ on Se thin films in perchloric acid media. The charge density of Pb ad-atoms on Se thin film (46.86 mu C cm(-2)) suggests a recovery of 0.1 monolayers, which is in good agreement with EQCM data. The Se thin film can be successfully alloyed with Pb atoms that are deposited by chronoamperometry using time intervals large enough to allow for diffusion toward the inner Se phase. Linear sweep voltammetry combined with EQCM in perchloric acid was used to characterize the amount of Pb absorbed in the Se thin film. These findings offer a new strategy for alloy formation in semiconductor films using UPD as an effective tool to quantify the exact amount of the incorporated metal.

Facial Profile Evaluation of Isolated Pierre Robin Sequence

Objective: To evaluate numerically the facial profile of children with isolated Pierre Robin sequence (PRS) and to compare them with a control group that has no pathologies and exhibits regular and balanced facial growth, with no skeletal alterations. Patients: Eighty-three children aged 5 to 10 years (PRS group, n = 60; control group, n = 23) were selected. Setting: Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo (HRAC-USP). Children from the control group were taken from the program of Interceptive Orthodontics at HRAC-USP. Design: Angular and ratio analyses of the facial profiles in both groups were realized through digital photographs. The PRS group was subdivided into two groups-complete and incomplete-according to the sagittal extension of the cleft palate, to investigate the possible influence of cleft extension on the face. Results: The facial convexity angle and the facial inferior third angle were considerably higher in the PRS groups than in the control group and were not significantly different between PRS groups. Nasolabial angle did not differ between groups. Conclusion: The facial profile was more convex in individuals with PRS than in those with regular facial growth and with no pathology. The mandible was responsible for the convexity of the profile in PRS because of its lack off anterior projection. An important relationship between the extension of the cleft palate and alterations in facial profile in PRS was not observed.

Total Obturation of Velopharynx for Treatment of Velopharyngeal Hypodynamism: Case Report

A child with microdeletion at 22q11.21 was referred to a craniofacial center due to hypernasality, unintelligible speech, and bifid uvula. Velopharyngeal dysfunction remained after surgical repair of submucous cleft palate and speech therapy. A prosthetic-behavioral treatment approach involving total obturation of the velopharynx was successfully implemented for management of velopharyngeal hypodynamism.

The Role of Keratinized Mucosa in Peri-Implant Health

Objective: To evaluate the role of keratinized mucosa around dental implants, correlating with other clinical parameters related to the success of dental implants. Design: Cross-section. Setting: Institutional tertiary referral hospital. Patients: A total of 202 dental implants fixed in the cleft area of 109 patients with cleft lip and/or palate were evaluated. Interventions: The evaluated clinical parameters were probing depth and gingival and plaque indexes on the buccal surface (three sites). Main Outcome Measures: All clinical parameters were correlated with the width of keratinized mucosa around the implants. Results: The largest probing depths were detected when the width of keratinized mucosa was 2 mm or more, with a statistically significant difference between the means of the probing depth and keratinized mucosa width. Conclusion: Even though the present results suggest that peri-implant health can be observed in areas with keratinized mucosa width under 2 mm provided an adequate oral hygiene control is performed, longitudinal randomized studies are necessary to analyze the relationship between the width of keratinized mucosa and the health of peri-implant tissues.

Glass/PDMS hybrid microfluidic device integrating vertically aligned SWCNTs to ultrasensitive electrochemical determinations

This communication reports a promising platform for rapid, simple, direct, and ultrasensitive determination of serotonin. The method is related to integration of vertically aligned single-walled carbon nanotubes (SWCNTs) in electrochemical microfluidic devices. The required microfabrication protocol is simple and fast. In addition, the nanomaterial influenced remarkably the obtained limit-of-detection (LOD) values. Our system achieved a LOD of 0.2 nmol L-1 for serotonin, to the best of our knowledge one of the lowest values reported in the literature.

Alveolar Bone Morphology in Patients With Bilateral Complete Cleft Lip and Palate in the Mixed Dentition: Cone Beam Computed Tomography Evaluation

Objectives: To verify the thickness and level of alveolar bone around the teeth adjacent to the cleft by means of cone beam computed tomography (CBCT) in patients with complete bilateral cleft lip and palate prior to bone graft surgery and orthodontic intervention. Method: The sample comprised 10 patients with complete bilateral cleft lip and palate (five boys and five girls) in the mixed dentition. The mean age was 9.5 years, and all subjects showed a G3 interarch relationship according to the Bauru index. The thickness of alveolar bone surrounding the maxillary incisors and the maxillary canines was measured in CBCT axial section using the software iCAT Xoran System. The distance between the alveolar bone crest and the cement-enamel junction (CEJ) was measured in cross sections. Results: The tomography images showed a thin alveolar bone plate around teeth adjacent to clefts. No bone dehiscence was observed in teeth adjacent to clefts during the mixed dentition. A slight increase in the distance between the alveolar bone crest and the CEJ was observed in the mesial and lingual aspects of canines adjacent to cleft. Conclusion: In patients with BCLP in the mixed dentition, teeth adjacent to the alveolar cleft are covered by a thin alveolar bone plate. However, the level of alveolar bone crest around these teeth seems to be normal, and no bone dehiscence was identified at this age.

Six minute walk test Z score: Correlations with cystic fibrosis severity markers

Background: The six-minute-walk-test (6MWT) has been increasingly used in cystic fibrosis (CF) patients. However, few studies in children have correlated 6MWT with current parameters used to evaluate CF severity. Moreover, no study transformed the values of distance walked from meters into Z scores to avoid bias like age and gender, which are sources of 6MWT variability. Methods: A cross-sectional descriptive study was performed to analyze the correlations (Spearman) among forced expiratory volume in one second (FEV1), body mass index (BMI), chest radiography (CXR), chest tomography (CT), and 6MWT Z score (Z-6MWT). Clinically stable CF patients, aged 6-21 years, were included. Results: 34 patients, 14F/20M, mean age 12.1 +/- 4.0 years were studied. The mean Z-6MWT was -1.1 +/- 1.106. The following correlations versus Z-6MWT were found: FEV1 (r=0.59, r(2)=0.32, p=0.0002), BMI Z score (r=0.42, r(2)=0.17, p=0.013), CXR (r=0.34, r(2)=0.15, p=0.0472) and CT (r=-0.45, r(2)=0.23, p=0.0073). Conclusions: In conclusion there was a significant, but poor, correlation between the six minute walk test Z score and the cystic fibrosis severity markers currently in use. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Relationship Between Occlusion and Lisping in Children With Cleft Lip and Palate

Introduction: The literature suggests that individuals with history of cleft lip and palate who present with midfacial growth deficiency are at higher risk of presenting lisping. The relationship between distortions during production of linguoalveolar fricative sounds and the severity of malocclusion, however, has not been established for the population with cleft. Objective: To study the association between lisping and dental arch relationship. Methodology: Speech samples and dental arch casts were obtained from 106 children with operated unilateral cleft lip and palate (UCLP) during the stage of mixed dentition and before orthodontic treatment. Videotaped productions of the phrase/u saci saiw sedu/were rated by speech-language pathologists for the identification of lisping during [s]. Dental arch casts were rated by orthodontists using the Goslon Yardstick and the Five-Year Index to establish dental arch relationship. Results: Multiple logistic regression showed no significant association between lisping and dento-occlusal index (p = .802) and age (p = .662). Substantial interjudge agreement during auditory-perceptual ratings was found (kappa = .63). Almost perfect agreement was found between orthodontists while establishing the dental arch relationship (kappa = .81). Discussion: This study failed to reveal an association between lisping and dental arch relationship in children with operated UCLP. Multiple variables may play a role in determining occurrence of lisping, warranting further investigation.

BAY 41-2272, a soluble guanylate cyclase agonist, activates human mononuclear phagocytes

BACKGROUND AND PURPOSE Phagocyte function is critical for host defense against infections. Defects in phagocytic function lead to several primary immunodeficiencies characterized by early onset of recurrent and severe infections. In this work, we further investigated the effects of BAY 41-2272, a soluble guanylate cyclase (sGC) agonist, on the activation of human peripheral blood monocytes (PBM) and THP-1 cells. EXPERIMENTAL APPROACH THP-1 cells and PBM viability was evaluated by methylthiazoletetrazolium assay; reactive oxygen species production by lucigenin chemiluminescence; gene and protein expression of NAPDH oxidase components by qRT-PCR and Western blot analysis, respectively; phagocytosis and microbicidal activity by co-incubation, respectively, with zymosan and Escherichia coli; and cytokine release by elisa. KEY RESULTS BAY 41-2272, compared with the untreated group, increased spreading of monocytes by at least 35%, superoxide production by at least 50%, and gp91PHOX and p67PHOX gene expression 20 to 40 times, in both PBM and THP-1 cells. BAY 41-2272 also augmented phagocytosis of zymosan particles threefold compared with control, doubled microbicidal activity against E. coli and enhanced the release of TNF-a and IL-12p70 by both PBM and THP-1 cells. Finally, by inhibiting sGC with ODQ, we showed that BAY 41-2272-induced superoxide production and phagocytosis is not dependent exclusively on sGC activation. CONCLUSIONS AND IMPLICATIONS In addition to its ability to induce vasorelaxation and its potential application for therapy of vascular diseases, BAY 41-2272 was shown to activate human mononuclear phagocytes. Hence, it is a novel pro-inflammatory drug that may be useful for controlling infections in the immunocompromised host.