Search results for "Locke"
showing 10 items of 332 documents
Extracellular site of action of phenylalkylamines on L-type calcium current in rat ventricular myocytes.
1995
The effects of the phenylalkylamines verapamil, gallopamil, and devapamil on L-type calcium currents (ICa) were studied in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. In particular, the question was addressed, whether the pharmacological binding sites for these drugs were located at the inner and/or at the outer surface of the cell membrane. Therefore, tertiary verapamil, gallopamil, and devapamil and their corresponding quaternary derivatives were applied either from the outside or the inside of the cell membrane. Extracellular application of verapamil, gallopamil and devapamil (each at 3 microM) reduced ICa to 16.1 +/- 8.6%, 11 +/- 8.9%, and 9.3 +/- 6%…
Dissipative rogue wave generation in multiple-pulsing mode-locked fiber laser
2013
Following the first experimental observation of a new mechanism leading to optical rogue wave (RW) formation briefly reported in Lecaplain et al (2012 Phys. Rev. Lett. 108 233901), we provide an extensive study of the experimental conditions under which these RWs can be detected. RWs originate from the nonlinear interactions of bunched chaotic pulses that propagate in a fiber laser cavity, and manifest as rare events of high optical intensity. The crucial influence of the electrical detection bandwidth is illustrated. We also clarify the observation of RWs with respect to other pulsating regimes, such as Q-switching instability, that also lead to L-shaped probability distribution functions.…
Aliskiren: Just a New Drug for Few Selected Patients or an Innovative Molecule Predestinated to Replace Arbs and Ace-Inhibitors?
2009
The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the pathophysiology of hypertension, diabetes mellitus, chronic kidney disease and chronic heart failure. Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEI) and angiotensin receptor blockers (ARBs) have gained wide clinical use for these indications. Despite progress, the morbidity and mortality of patients treated with ACEI or ARBs remain high. Aliskiren (Tekturna, Rasilez) is the first orally active inhibitor of renin approved for clinical use as an antihypertensive agent. The development program has established that at the licensed doses of 150 mg and 300 mg. Aliskiren is effective …
Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine
2015
Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissol…
Interacciones farmacológicas de los fármacos antihipertensivos
2005
A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. Hypertensive patients, mainly the more elderly ones, frequently present concomitant diseases that require the administration of several medicines which facilitates the appearance of interactions. The lack of effectiveness of the antihypertensive treatment is a relatively frequent fact that sometimes is due to interactions of antihypertensive drugs with other treatments. It is difficult to determine the incidence of interactions, but it is related to the number of drugs administered simultaneously. Between 37 and 60% of hospital-admis…
An attempt to enhance neurogenesis of mdx mice via aerobic exercise and myostatin inhibition
2013
Duchennen lihasdystrofia (DMD) on perinnöllinen sairaus, jonka esiintyvyys on noin 1/3600 poikavauvasta. Siihen liittyy lihasten heikkoutta, rappeutumista ja kognitiivista vajavaisuutta. Taudin aiheuttaa mutatoitunut geeni dystrophiini proteiinille. On esitetty, että kognitiivinen vajavaisuus johtuu taudin vaikutuksesta ehkäistä neurogeneesiä. Neurogeneesi on prosessi, joka jatkuvasti synnyttää uusia hermosoluja pääasiallisesti subventikulaari alueella ja hippokampuksen dentate gyruksella. Hoitoa ja parannusta tautiin tutkitaan yleensä mdx-hiirillä, joiden taudin etiologia on riittävän lähellä ihmisten tautia. Tämä tutkimus keskittyy pyrkimykseen vaikuttaa mdx-hiirten neurogeneesiin aerobis…
Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch
2015
[ES] Introducción y objetivos Se han implicado diversos mecanismos en la respuesta mecánica al estiramiento miocárdico, que incluyen la activación del intercambiador Na+/H+ por acciones autocrinas y paracrinas. Se estudia la participación de estos mecanismos en las respuestas electrofisiológicas al estiramiento agudo miocárdico mediante el análisis de los cambios inducidos con fármacos. Métodos Se analizan las modificaciones de la fibrilación ventricular inducidas por el estiramiento agudo miocárdico en corazones de conejo aislados y perfundidos utilizando electrodos múltiples epicárdicos y técnicas cartográficas. Se estudian 4 series: control (n = 9); durante la perfusión del antagonista d…
Synchronization techniques for power quality instruments
2004
The measurement of voltage characteristics in power systems requires the accurate estimation of the power supply frequency and signal synchronization, even in the presence of disturbances. The authors developed and tested two innovative techniques for instrument synchronization. The first is based on signal spectral analysis techniques performed by means of the Chirp-Z transform analysis. The second is a phase-locked loop (PLL) software based on a time-domain coordinate transformation and an innovative phase-detection technique. To evaluate how synchronization techniques are adversely affected by the application of a disturbing influence, experimental tests were carried out, taking into acc…
Wideband modeling of cascaded H-plane waveguide junctions using the generalised impedance matrix representation
2009
A strong interest in H-plane waveguide components composed of a large number of cascaded planar junctions is recently renewed. Therefore, the more efficient development of full-wave analysis tools of such devices is again receiving consideration, specially for its potential use within modern design tools. A novel technique for providing the wideband generalised impedance matrix representation of the inductive devices in the form of pole expansions, thus extracting the most expensive computations from the frequency loop is proposed. For such purpose, the whole device is first decomposed into simpler building blocks, i.e. planar junctions and uniform waveguides, which are modelled in terms of…
A Phase-Locked Loop for the Synchronization of Power Quality Instruments in the Presence of Stationary and Transient Disturbances
2007
Power quality instrumentation requires accurate fundamental frequency estimation and signal synchronization, even in the presence of both stationary and transient disturbances. In this paper, the authors present a synchronization technique for power quality instruments based on a single-phase software phase-locked loop (PLL), which is able to perform the synchronization, even in the presence of such disturbances. Moreover, PLL is able to detect the occurrence of a transient disturbance. To evaluate if and how the synchronization technique is adversely affected by the application of stationary and transient disturbing influences, appropriate testing conditions have been developed, taking int…