TRPV4 as a target for bladder overactivity

Several papers published in the last 2-3 years suggest that transient receptor potential vanilloid 4 (TRPV4) channels are candidates as mechanosensors in the urinary bladder (including human) and indicate that modulation (inhibition) of these channels could represent a novel therapy for overactive bladder and storage dysfunction. The effects of only agonists on the bladder have been described up to now, although some compounds endowed with antagonistic activity were reported in the last year. Therefore, it is to be hoped that the effects of these compounds in different models of bladder overactivity will be evaluated

Nutrición y fertilización de lúpulo : revisión conceptual y actualización sobre recomendaciones prácticas

Al igual que ocurre con muchas especies que se crían o se cultivan en la Patagonia (desde ovejas hasta guindos), el lúpulo en general es bastante rústico y puede crecer en ambientes subóptimos. La longevidad de la planta dependerá de la calidad del suelo, pudiendo variar desde unos pocos años hasta más de medio siglo. Al ser una especie muy particular por su forma de cultivo, con una dispersión geográfica acotada en relación a los pocos países del mundo que producen lúpulo a escala comercial, mucha gente de distintas localidades en Argentina se pregunta si podrá tener éxito al cultivar algunas plantas. Las experiencias demuestran que es altamente probable que la planta crezca y se desarrolle hasta alcanzar la floración en la mayoría de las regiones del país. Sin embargo, para llevar a cabo una producción comercial de lúpulo, con indicadores de rendimiento aceptables en volumen y en calidad, éste debe ser cultivado en forma intensiva en ambientes propicios, y tiene elevadas exigencias en materia de fertilidad del suelo.Estación Experimental Agropecuaria BarilocheFil: Testa, Hernán Rodolfo. Patagonia Lúpulos Andinos; ArgentinaFil: Cardozo, Andrea Gabriela. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estacion Experimental Agropecuaria Bariloche. Agencia de Extension Rural El Bolson; Argentin

Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions

BACKGROUND: Antimuscarinic agents are the most popular treatment for overactive bladder and their efficacy in man is well documented, producing decreased urinary frequency and an increase in bladder capacity. During cystometry in rats, however, the main effect reported after acute treatment with antimuscarinics is a decrease in peak micturition pressure together with little or no effect on bladder capacity. In the present experiments we studied the effects, in rats, of the two most widely used antimuscarinic drugs, namely oxybutynin and tolterodine, utilising several different cystometrographic conditions. The aim was to determine the experimental conditions required to reproduce the clinical pharmacological effects of antimuscarinic agents, as seen in humans, in particular their ability to increase bladder capacity. RESULTS: Intravenous or oral administration of tolterodine or oxybutynin in conscious rats utilized 1 day after catheter implantation and with saline infusion at constant rate of 0.1 ml/min, gave a dose-dependent decrease of micturition pressure (MP) with no significant change in bladder volume capacity (BVC). When the saline infusion rate into the bladder was decreased to 0.025 ml/min, the effect of oral oxybutynin was similar to that obtained with the higher infusion rate. Also, experiments were performed in rats in which bladders were infused with suramin (3 and 10 μM) in order to block the non-adrenergic, non-cholinergic component of bladder contraction. Under these conditions, oral administration of oxybutynin significantly reduced MP (as observed previously), but again BVC was not significantly changed. In conscious rats with bladders infused with diluted acetic acid, both tolterodine and oxybutynin administered at the same doses as in animals infused with saline, reduced MP, although the reduction appeared less marked, with no effect on BVC. In conscious rats utilized 5 days after catheter implantation, a situation where inflammation due to surgery is reduced, the effect of tolterodine (i.v.) and oxybutynin (p.o.) on MP was smaller and similar, respectively, to that observed in rats utilized 1 day after catheter implantation, but the increase of BVC was not statistically significant. In anesthetized rats, i.v. administration of oxybutynin again induced a significant decrease in MP, although it was of questionable relevance. Both BVC and threshold pressure were not significantly reduced. The number and amplitude of high frequency oscillations in MP were unmodified by treatment. Finally, in conscious obstructed rats, intravenous oxybutynin did not modify frequency and amplitude of non-voiding contractions or bladder capacity and micturition volume. CONCLUSION: Despite the different experimental conditions used, the only effect on cystometrographic parameters of oxybutynin and tolterodine in anesthetized and conscious rats was a decrease in MP, whereas BVC was hardly and non-significantly affected. Therefore, it is difficult to reproduce in rats the cystometrographic increase in BVC as observed in humans after chronic administration of antimuscarinic agents, whereas the acute effects seem more similar

The new calcium antagonist lercanidipine and its enantiomers affect major processes of atherogenesis in vitro: is calcium entry involved?

Atherosclerosis results from multiple factors and involves several mechanisms, including endothelial monocyte and smooth muscle cell (SMC) changes, cholesterol accumulation, plaque rupture and thromboembolism. Calcium ions play a role in the initial and chronic development of atherosclerotic lesions. Several studies in experimental animal models have demonstrated the potential direct antiatherosclerotic effects of calcium antagonists. In this study the antiatherogenic activity of lercanidipine, a new lipophilic, second-generation calcium antagonist, was investigated. Lercanidipine and its enantiomers inhibited the replication and migration of arterial myocytes in concentrations ranging from 10 to 50 microM. The antiproliferative effect of lercanidipine was dose dependent, with a potency similar to that of lacidipine and nifedipine, and was unrelated to the stereoselectivity of enantiomers to bind L-type calcium channels. Lercanidipine and its enantiomers (25 microM) decreased the serum-induced elevation of [Ca2+]i in SMC, with the (S)-enantiomer (69% inhibition) being 2.4-fold more active than the (R)-counterpart (29% inhibition). The studies performed with enantiomers of lercanidipine suggest that the observed effects are not related to the blockade of voltage-dependent Ca2+ channels and confirm, at least in vitro, the pharmacological potential of the compound to influence negatively the process of atherogenesis

The High-Level Interface Definitions in the ASTRI/CTA Mini Array Software System (MASS)

ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) is a Flagship Project funded by the Italian Ministry of Education, University and Research, and led by INAF, the Italian National Institute of Astrophysics. Within this framework, INAF is currently developing an end-to-end prototype, named ASTRI SST-2M, of a Small Size Dual-Mirror Telescope for the Cherenkov Telescope Array, CTA. A second goal of the project is the realization of the ASTRI/CTA mini-array, which will be composed of seven SST-2M telescopes placed at the CTA Southern Site. The ASTRI Mini Array Software System (MASS) is designed to support the ASTRI/CTA mini-array operations. MASS is being built on top of the ALMA Common Software (ACS) framework, which provides support for the implementation of distributed data acquisition and control systems, and functionality for log and alarm management, message driven communication and hardware devices management. The first version of the MASS system, which will comply with the CTA requirements and guidelines, will be tested on the ASTRI SST-2M prototype. In this contribution we present the interface definitions of the MASS high level components in charge of the ASTRI SST-2M observation scheduling, telescope control and monitoring, and data taking. Particular emphasis is given to their potential reuse for the ASTRI/CTA mini-array

The ASTRI mini-array software system (MASS) implementation: a proposal for the Cherenkov Telescope Array

The ASTRI mini-array, composed of nine small-size dual mirror (SST-2M) telescopes, has been proposed to be installed at the southern site of the Cherenkov Telescope Array (CTA), as a set of preproduction units of the CTA observatory. The ASTRI mini-array is a collaborative and international effort carried out by Italy, Brazil and South Africa and led by the Italian National Institute of Astrophysics, INAF. We present the main features of the current implementation of the Mini-Array Software System (MASS) now in use for the activities of the ASTRI SST-2M telescope prototype located at the INAF observing station on Mt. Etna, Italy and the characteristics that make it a prototype for the CTA control software system. CTA Data Management (CTADATA) and CTA Array Control and Data Acquisition (CTA-ACTL) requirements and guidelines as well as the ASTRI use cases were considered in the MASS design, most of its features are derived from the Atacama Large Millimeter/sub-millimeter Array Control software. The MASS will provide a set of tools to manage all onsite operations of the ASTRI mini-array in order to perform the observations specified in the short term schedule (including monitoring and controlling all the hardware components of each telescope and calibration device), to analyze the acquired data online and to store/retrieve all the data products to/from the onsite repository

A high-gain mushroom-shaped dielectric resonator antenna for wideband wireless applications

A high-gain mushroom-shaped dielectric resonator (DR) antenna for wideband wireless applications, featuring 65% fractional bandwidth, is proposed. The antenna consists of a low-permittivity hollow cylindrical DR provided with a top-mount spherical cap lens and a metal reflector, excited by means of coaxial probes. Suitable shaping of lens and reflector yields high gain (exceeding 14 dBi) and limited back radiation. The proposed antenna features a broadside radiation diagram with stable radiation patterns and wideband impedance matching. Its potential applications include access points for indoor/outdoor wireless multimedia systems as well as satellite terminal receivers. CST Microwave Studio, implementing a fullwave locally conformal finite integration technique, is employed to design and characterize the antenna, while the singularity expansion method is adopted to express the antenna response to arbitrary excitation waveforms. The numerical results concerning the antenna parameters are found to be in good agreement with the experimental measurements performed on an antenna prototyp