Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers

Aim - The aim of the study was to determine the potential for KV1 potassium channel blockers as inhibitors of human neoinitimal hyperplasia. Methods and results - Blood vessels were obtained from patients or mice and studied in culture. Reverse transcriptasepolymerase chain reaction and immunocytochemistry were used to detect gene expression. Whole-cell patch-clamp, intracellular calcium measurement, cell migration assays, and organ culture were used to assess channel function.  KV1.3 was unique among the  KV1 channels in showing preserved and up-regulated expression when the vascular smooth muscle cells switched to the proliferating phenotype. There was strong expression in neointimal formations. Voltage-dependent potassium current in proliferating cells was sensitive to three different blockers of  KV1.3 channels. Calcium entry was also inhibited. All three blockers reduced vascular smooth muscle cell migration and the effects were non-additive. One of the blockers (margatoxin) was highly potent, suppressing cell migration with an IC of 85 pM. Two of the blockers were tested in organ-cultured human vein samples and both inhibited neointimal hyperplasia. Conclusion - KV1.3 potassium channels are functional in proliferating mouse and human vascular smooth muscle cells and have positive effects on cell migration. Blockers of the channels may be useful as inhibitors of neointimal hyperplasia and other unwanted vascular remodelling events. © 2010 The Author.

Suppression of spatiotemporal chaos in the oscillatory CO oxidation on Pt(110) by focused laser light

Chemical turbulence in the oscillatory catalytic CO oxidation on Pt(110) is suppressed by means of focused laser light. The laser locally heats the platinum surface which leads to a local increase of the oscillation frequency, and to the formation of a pacemaker which emits target waves. These waves slowly entrain the medium and suppress the spatiotemporal chaos present in the absence of laser light. Our experimental results are confirmed by a detailed numerical analysis of one- and two-dimensional media using the Krischer-Eiswirth-Ertl model for CO oxidation on Pt110. Different control regimes are identified and the dispersion relation of the system is determined using the pacemaker as an externally tunable wave source.

High-power spectral bistability in a multi-section quantum-dot laser under continuous-wave or mode-locked operation

Wavelength bistability between 1245nm and 1295nm is demonstrated in a multi-section quantum-dot laser, controlled via the reverse bias on the saturable absorber. Continuous-wave or mode-locked regimes are achieved (output power up to 25mW and 17mW). © OSA/CLEO 2011.

Power pre-emphasis for suppression of FWM in coherent optical OFDM transmission

Four-wave-mixing (FWM) due to the fiber nonlinearity is a major limiting factor in coherent optical OFDM transmission. We propose to apply power pre-emphasis, i.e. to allocate the transmitted power nonuniformly among subcarriers in order to suppress the FWM impairment. The proposed technique was numerically investigated for both single channel 15.6 Gbs CO-OFDM transmissions and 7-channel WDM transmissions, showing that up to 1 dB improvement in the system's Qfactor can be achieved without considering sophisticated power loading algorithms developed for wireless communications. © 2014 Optical Society of America.

Suppression of nonlinear distortion in few-mode fibres using strong mode coupling

In this paper, we investigate the impact of linear mode coupling on the efficiency of intermodal four-wave mixing and on the group delay statistics in few-mode fibres. The investigation will include not only the weak or strong linear coupling regimes, but also the transition region between them, the intermediate coupling regime. This analysis will allow to assess the level of coupling strength require to suppress the nonlinear distortion in a few-mode fibre below the level of distortion for single-mode propagation without mode coupling.

Towards a gravitational wave observatory designer: sensitivity limits of spaceborne detectors

The most promising concept for low frequency (millihertz to hertz) gravitational wave observatories are laser interferometric detectors in space. It is usually assumed that the noise floor for such a detector is dominated by optical shot noise in the signal readout. For this to be true, a careful balance of mission parameters is crucial to keep all other parasitic disturbances below shot noise. We developed a web application that uses over 30 input parameters and considers many important technical noise sources and noise suppression techniques to derive a realistic position noise budget. It optimizes free parameters automatically and generates a detailed report on all individual noise contributions. Thus one can easily explore the entire parameter space and design a realistic gravitational wave observatory. In this document we describe the different parameters, present all underlying calculations, and compare the final observatory's sensitivity with astrophysical sources of gravitational waves. We use as an example parameters currently assumed to be likely applied to a space mission proposed to be launched in 2034 by the European Space Agency. The web application itself is publicly available on the Internet at http://spacegravity.org/designer. Future versions of the web application will incorporate the frequency dependence of different noise sources and include a more detailed model of the observatory's residual acceleration noise.

Impaired reverse cholesterol transport and hepatic steatosis contribute to pathogenesis of high fat dietinduced hyperlipidemia in murine models

Purpose: To investigate the pathogenesis of high fat diet (HFD)-induced hyperlipidemia (HLP) in mice, rats and hamsters and to comparatively evaluate their sensitivity to HFD. Methods: Mice, rats and hamsters were fed with high-fat diet formulation (HFD, n = 8) or a control diet (control, n = 8) for 4 weeks. Changes in body weight, relative liver weight, serum lipid profile, expressions of hepatic marker gene of lipid metabolism and liver morphology were observed in three hyperlipidemic models. Results: Elevated total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) levels and body weight were observed in all hyperlipidemic animals (p < 0.05), while hepatic steatosis was manifested in rat and hamster HLP models, and increased hepatic TC level was only seen (p < 0.05) in hamster HLP model. Suppression of HMG-CoA reductase and up-regulation of lipoproteinlipase were observed in all HFD groups. Hepatic gene expression of LDLR, CYP7A1, LCAT, SR-B1, and ApoA I, which are a response to reverse cholesterol transport (RCT), were inhibited by HFD in the three models. Among these models, simultaneous suppression of HMG-CR, LCAT, LDLR and SR-BI and elevated LPL were features of the hamster model. Conclusion: As the results show, impaired RCT and excessive fat accumulation are major contributors to pathogenesis of HFD-induced murine HLP. Thus, the hamster model is more appropriate for hyperlipidemia research.

Culturable Bacterial Diversity From A Feed Water Of A Reverse Osmosis System, Evaluation Of Biofilm Formation And Biocontrol Using Phages.

Biofilm formation on reverse osmosis (RO) systems represents a drawback in the application of this technology by different industries, including oil refineries. In RO systems the feed water maybe a source of microbial contamination and thus contributes for the formation of biofilm and consequent biofouling. In this study the planktonic culturable bacterial community was characterized from a feed water of a RO system and their capacities were evaluated to form biofilm in vitro. Bacterial motility and biofilm control were also analysed using phages. As results, diverse Protobacteria, Actinobacteria and Bacteroidetes were identified. Alphaproteobacteria was the predominant group and Brevundimonas, Pseudomonas and Mycobacterium the most abundant genera. Among the 30 isolates, 11 showed at least one type of motility and 11 were classified as good biofilm formers. Additionally, the influence of non-specific bacteriophage in the bacterial biofilms formed in vitro was investigated by action of phages enzymes or phage infection. The vB_AspP-UFV1 (Podoviridae) interfered in biofilm formation of most tested bacteria and may represent a good alternative in biofilm control. These findings provide important information about the bacterial community from the feed water of a RO system that may be used for the development of strategies for biofilm prevention and control in such systems.

Didanosine-loaded Chitosan Microspheres Optimized By Surface-response Methodology: A Modified Maximum Likelihood Classification" Approach Formulation For Reverse Transcriptase Inhibitors."

Didanosine-loaded chitosan microspheres were developed applying a surface-response methodology and using a modified Maximum Likelihood Classification. The operational conditions were optimized with the aim of maintaining the active form of didanosine (ddI), which is sensitive to acid pH, and to develop a modified and mucoadhesive formulation. The loading of the drug within the chitosan microspheres was carried out by ionotropic gelation technique with sodium tripolyphosphate (TPP) as cross-linking agent and magnesium hydroxide (Mg(OH)2) to assure the stability of ddI. The optimization conditions were set using a surface-response methodology and applying the Maximum Likelihood Classification, where the initial chitosan concentration, TPP and ddI concentration were set as the independent variables. The maximum ddI-loaded in microspheres (i.e. 1433mg of ddI/g chitosan), was obtained with 2% (w/v) chitosan and 10% TPP. The microspheres depicted an average diameter of 11.42μm and ddI was gradually released during 2h in simulated enteric fluid.

Physiological limitations in two sugarcane varieties under water suppression and after recovering

Increasing water scarcity and depleted water productivity in irrigated soils are inducing farmers to adopt improved varieties, such as those with high-capacity tolerance. The use of tolerant varieties of sugarcane might substantially avoid the decline of productivity under water deficit. This research aimed to evaluate the harmful effects of drought on the physiology of two sugarcane varieties (RB867515 and RB962962) during the initial development. Young plants were subjected to irrigation suspension until total stomata closure, and then rewatered. Significant reduction on stomatal conductance, transpiration, and net photosynthesis were observed. RB867515 showed a faster stomatal closure while RB962962 slowed the effects of drought on the gas exchanges parameters with a faster recovering after rewatering. Accumulation of carbohydrates, amino acids, proline, and protein in the leaves and roots of the stressed plants occurred in both varieties, substantially linked to reduction of the leaf water potential. Due to the severity of stress, this accumulation was not enough to maintain the cell turgor pressure, so relative water content was diminished. Water stress affected the contents of chlorophyll (a, b, and total) in both varieties, but not the levels of carotenoids. There was a significant reduction in dry matter under stress. In conclusion, RB962962 variety endured stressed conditions more than RB867515, since it slowed down the damaging effects of drought on the gas exchanges. In addition, RB962962 presented a faster recovery than RB867515, a feature that qualifies it as a variety capable of enduring short periods of drought without major losses in the initial stage of its development.

T-wave alternans: desempenho clínico, limitações, metodologias de análise

Reconhecer com precisão indivíduos com maior risco imediato de morte súbita cardíaca (MSC) ainda é uma questão em aberto. A natureza fortuita dos eventos cardiovasculares agudos não parece se adequar ao conhecido modelo de indução de taquicardia/fibrilação ventricular por um gatilho em sincronia a um substrato arritmogênico estático. Quanto ao mecanismo da MSC, uma instabilidade elétrica dinâmica explicaria melhor a raridade da associação simultânea de um gatilho certo a um substrato cardíaco apropriado. Diversos estudos tentaram medir essa instabilidade elétrica cardíaca (ou um equivalente válido) em uma sequência de batimentos cardíacos no ECG. Dentre os mecanismos possíveis podemos citar o prolongamento do QT, dispersão do QT, potenciais tardios, alternância de onda T ou T-wave alternans (TWA), e turbulência da frequência cardíaca. Este artigo se atém em particular ao papel da TWA no panorama atual da estratificação de risco cardíaco. Os achados sobre TWA ainda são heterogêneos, variando de um desempenho prognóstico muito bom até um quase nulo, dependendo da população clínica observada e protocolo clínico usado. Para preencher as atuais lacunas no conhecimento sobre TWA, profissionais médicos e pesquisadores devem explorar melhor as características técnicas das diversas tecnologias disponíveis para a avaliação de TWA e atentar ao fato de que os valores de TWA respondem a diversos outros fatores, além de medicamentos. Informações sobre mecanismos celulares e subcelulares da TWA estão fora do escopo deste artigo, mas são referenciados alguns dos principais trabalhos sobre este tópico, com o intuito de auxiliar no entendimento dos conceitos e fatos cobertos neste artigo.

Determination of 5-aminosalicylic acid in pharmaceutical formulations by square wave voltammetry at pencil graphite electrodes

An analytical method for the determination of the anti-inflammatory drug 5-aminosalicylic acid (5-ASA) in pharmaceutical formulations using square wave voltammetry at pencil graphite electrodes was developed. After the optimization of the experimental conditions, calibration curves were obtained in the linear concentration range from 9.78 × 10-7 to 7.25 × 10-5 mol L-1 resulting in a limit of detection of 2.12 ± 0.05 x 10-8 mol L-1. Statistical tests showed that the concentrations of 5-ASA in commercial tablets and enemas obtained with the proposed voltammetric method agreed with HPLC values at a 95% confidence level.

Brazilian offshore wave climate based on NWW3 reanalysis

This paper provides a description of the wave climate off the Brazilian coast based on an eleven-year time series (Jan/1997-Dec/2007) obtained from the NWW3 operational model hindcast reanalysis. Information about wave climate in Brazilian waters is very scarce and mainly based on occasional short-term observations, the present analysis being the first covering such temporal and spatial scales. To define the wave climate, six sectors were defined and analyzed along the Brazilian shelf-break: South (W1), Southeast (W2), Central (W3), East (W4), Northeast (W5) and North (W6). W1, W2 and W3 wave regimes are determined by the South Atlantic High (SAH) and the passage of synoptic cold fronts; W4, W5 and W6 are controlled by the Intertropical Convergence Zone (ITCZ) and its meridional oscillation. The most energetic waves are from the S, generated by the strong winds associated to the passage of cold fronts, which mainly affect the southern region. Wave power presents a decrease in energy levels from south to north, with its annual variation showing that the winter months are the most energetic in W1 to W4, while in W5 and W6 the most energetic conditions occur during the austral summer. The information presented here provides boundary conditions for studies related to coastal processes, fundamental for a better understanding of the Brazilian coastal zone.

Evaluation of left ventricular diastolic echocardiographic parameters in healthy dogs by pulsed-wave Doppler

Left ventricular diastolic dysfunction plays an important role on heart failure progression. In order to obtain additional reference values of left ventricular diastolic parameters and investigate influence of common variables, peak E wave (peak E), peak A wave (peak A), E/A ratio (E/A), E wave deceleration time (EDT) and isovolumic relaxation time (IRVT) were studied in 40 clinically healthy dogs, by pulsed wave Doppler. The following values were obtained: peak E = 0.747 ± 0.117 m/s, peak A = 0.487 ± 0.062 m/s, E/A = 1.533 ± 0.198, EDT = 88.7 ± 9.2 ms and IRVT = 0.080 ± 0.009 s. Some parameters were influenced by heart rate (peak E, peak A and IRVT), by age (peak A and E/A) and by body weight (TRIV). Gender influence was absent. Values obtained can be used as reference for canine specimens but its interpretation should consider on the influence of related variables.

Evaluation of Primary Resistance to HIV Entry Inhibitors Among Brazilian Patients Failing Reverse Transcriptase/Protease Inhibitors Treatment Reveal High Prevalence of Maraviroc Resistance-Related Mutations

Entry inhibitor is a new class of drugs that target the viral envelope protein. This region is variable; hence resistance to these drugs may be present before treatment. The aim of this study was to analyze the frequency of patients failing treatment with transcriptase reverse and protease inhibitors that would respond to the entry inhibitors Enfuvirtide, Maraviroc, and BMS-806. The study included 100 HIV-1 positive patients from one outpatient clinic in the city of Sao Paulo, for whom a genotype test was requested due to treatment failure. Proviral DNA was amplified and sequenced for regions of gp120 and gp41. A total of 80 could be sequenced and from those, 73 (91.3%), 5 (6.3%) and 2 (2.5%) were classified as subtype B, F, and recombinants (B/F and B/C), respectively. CXCR4 co-receptor use was predicted in 30% of the strains. Primary resistance to Enfuvirtide was found in 1.3%, following the AIDS Society consensus list, and 10% would be considered resistant if a broader criterion was used. Resistance to BMS-806 was higher; 6 (7.5%), and was associated to non-B strains. Strikingly, 27.5% of samples harbored one or more mutation among A316T, I323V, and S405A, which have been related to decreased susceptibility of Maraviroc; 15% of them among viruses predictive to be R5. A more common mutation was A316T, which was associated to the Brazilian B strain harboring the GWGR motif at the tip of V3 loop and their derivative sequences. These results may be impact guidelines for genotype testing and treatment in Brazil.