Pharmacokinetics and antinociceptive effects of tramadol and its metabolite O-desmethyltramadol following intravenous administration in sheep

Although sheep are widely used as an experimental model for various surgical procedures there is a paucity of data on the pharmacokinetics and efficacy of analgesic drugs in this species. The aims of this study were to investigate the pharmacokinetics of intravenously (IV) administered tramadol and its active metabolite O-desmethyltramadol (M1) and to assess the mechanical antinociceptive effects in sheep. In a prospective, randomized, blinded study, six healthy adult sheep were given 4 and 6\u2009mg/kg tramadol and saline IV in a cross-over design with a 2-week wash-out period. At predetermined time points blood samples were collected and physiological parameters and mechanical nociceptive threshold (MNT) values were recorded. The analytical determination of tramadol and M1 was performed using high performance liquid chromatography. Pharmacokinetic parameters fitted a two- and a non-compartmental model for tramadol and M1, respectively. Normally distributed data were analysed by a repeated mixed linear model. Plasma concentration vs. time profiles of tramadol and M1 were similar after the two doses. Tramadol and M1 plasma levels decreased rapidly in the systemic circulation, with both undetectable after 6\u2009h following drug administration. Physiological parameters did not differ between groups; MNT values were not statistically significant between groups at any time point. It was concluded that although tramadol and M1 concentrations in plasma were above the human minimum analgesic concentration after both treatments, no mechanical antinociceptive effects of tramadol were reported. Further studies are warranted to assess the analgesic efficacy of tramadol in sheep

1-hypergroups of small sizes

In this paper, we show a new construction of hypergroups that, under appropriate conditions, are complete hypergroups or non-complete 1-hypergroups. Furthermore, we classify the 1-hypergroups of size 5 and 6 based on the partition induced by the fundamental relation \u3b2. Many of these hypergroups can be obtained using the aforesaid hypergroup construction

Estimating preferences for controlling beach erosion in Sicily

This study applied discrete-choice experiments to estimate preferences for a program aimed at reducing the retreatment of the sandy beach at "Lido di Noto", a renowned Sicilian bathing resort close to Noto (Italy). Econometric analysis of data was based on Multinomial Logit (MNL), Latent Class (LC) and Mixed Logit (MXL) models. Findings shown that users appreciated the advancement of the current coastline through nourishment, and negatively perceived the construction of emerged sea barriers. MXL and LC models revealed that preferences were heterogeneous

An XMM-Newton and INTEGRAL view on the hard state of EXO 1745-248 during its 2015 outburst

CONTEXT - Transient low-mass X-ray binaries (LMXBs) often show outbursts lasting typically a few-weeks and characterized by a high X-ray luminosity ($L_{x} \approx 10^{36}-10^{38}$ erg/sec), while for most of the time they are found in X-ray quiescence ($L_X\approx10^{31} -10^{33}$ erg/sec). EXO 1745-248 is one of them. AIMS - The broad-band coverage, and the sensitivity of instrument on board of {\xmm} and {\igr}, offers the opportunity to characterize the hard X-ray spectrum during {\exo} outburst. METHODS - In this paper we report on quasi-simultaneous {\xmm} and {\igr} observations of the X-ray transient {\exo} located in the globular cluster Terzan 5, performed ten days after the beginning of the outburst (on 2015 March 16th) shown by the source between March and June 2015. The source was caught in a hard state, emitting a 0.8-100 keV luminosity of $\simeq10^{37}$~{\lumcgs}. RESULTS - The spectral continuum was dominated by thermal Comptonization of seed photons with temperature $kT_{in}\simeq1.3$ keV, by a cloud with moderate optical depth $\tau\simeq2$ and electron temperature $kT_e\simeq 40$ keV. A weaker soft thermal component at temperature $kT_{th}\simeq0.6$--0.7 keV and compatible with a fraction of the neutron star radius was also detected. A rich emission line spectrum was observed by the EPIC-pn on-board {\xmm}; features at energies compatible with K-$\alpha$ transitions of ionized sulfur, argon, calcium and iron were detected, with a broadness compatible with either thermal Compton broadening or Doppler broadening in the inner parts of an accretion disk truncated at $20\pm6$ gravitational radii from the neutron star. Strikingly, at least one narrow emission line ascribed to neutral or mildly ionized iron is needed to model the prominent emission complex detected between 5.5 and 7.5 keV. (Abridged)Comment: 14 pages, 6 figure, 2 tables. Accepted for publication on A&A (21/03/2017

Tunable Short-Term Plasticity Response in Three-Terminal Organic Neuromorphic Devices

Reversibly tunable short-term plasticity (STP) of the channel current in organic neuromorphic devices is demonstrated with a three-terminal architecture. Electrolyte-gated organic transistors - EGOTs - are driven with square voltage pulses at the drain electrodes, while the gate bias enables the modulation of the amplitude and characteristic time scale of the depressive STP spiking response up to 1 order of magnitude. The gate potential sets the baseline and the steady-state current, preluding multilevel memory writing. The fine-tuning of the STP response, which is not possible with two-electrode organic neuromorphic devices, is reversible and does not imply chemical modifications of the active layer

Multifunctionally-doped PEDOT for organic electrochemical transistors

Organic Electrochemical Transistors (OECTs) are suitable for developing ultra-sensitive bioelectronic sensors. In the organic electrochemical transistors architecture, the source-drain channel is made of a conductive polymer film either cast from a formulated dispersion or electrodeposited from a monomer solution. The commercial poly(3,4-ethylenedioxidethiophene)/poly(styrene sulfonate) (PEDOT:PSS) water dispersion is the workhorse of organic bioelectronics for its high conductance, low impact and ease of processability. In this study, a hybrid organic electrochemical transistors channel fabrication strategy is presented, where electrochemical deposition of a PEDOT/X (with X indicating the counterion) is performed on a dispersion-cast PEDOT:PSS film. Six different counterions where used: X = PSS, Nafion, Hyaluronate, Dextran sulfate, Dexamethasone phosphate and tauroursodeoxycholic acid, each potentially endowing organic electrochemical transistors with additional functions such as ion exchange and pharmacological activity upon release of X. The PEDOT/X-PEDOT:PSS bilayers were characterized by means of electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and focused ion beam tomography combined with scanning electron microscopy (FIB-SEM). In addition, their respective organic electrochemical transistorss were characterized and compared to PEDOT:PSS organic electrochemical transistors. Our results show that the hybrid bilayer strategy is viable to fabricate multifunctional organic electrochemical transistorss with biologically-relevant function, thereby retaining the outstanding figures of merit of commercial PEDOT:PSS

Effects of atomic diffraction on the Collective Atomic Recoil Laser

We formulate a wave atom optics theory of the Collective Atomic Recoil Laser, where the atomic center-of-mass motion is treated quantum mechanically. By comparing the predictions of this theory with those of the ray atom optics theory, which treats the center-of-mass motion classically, we show that for the case of a far off-resonant pump laser the ray optics model fails to predict the linear response of the CARL when the temperature is of the order of the recoil temperature or less. This is due to the fact that in theis temperature regime one can no longer ignore the effects of matter-wave diffraction on the atomic center-of-mass motion.Comment: plain tex, 10 pages, 10 figure

Neutron star radius-To-mass ratio from partial accretion disk occultation as measured through fe kα line profiles

We present a new method to measure the radius-To-mass ratio (R/M) of weakly magnetic, disk-Accreting neutron stars by exploiting the occultation of parts of the inner disk by the star itself. This occultation imprints characteristic features on the X-ray line profile that are unique and are expected to be present in low-mass X-ray binary systems seen under inclinations higher than ∼65°. We analyze a Nuclear Spectroscopic Telescope Array observation of a good candidate system, 4U 1636-53, and find that X-ray spectra from current instrumentation are unlikely to single out the occultation features owing to insufficient signal-To-noise. Based on an extensive set of simulations we show that large-Area X-ray detectors of the future generation could measure R/M to ∼2 ÷ 3% precision over a range of inclinations. Such is the precision in radius determination required to derive tight constraints on the equation of state of ultradense matter and it represents the goal that other methods also aim to achieve in the future