Tramadol is an effective analgesic substance widely used in medical practice. Its therapeutic action have been mainly attributed to the activation of mu-opioid receptors as well as to the inhibition ...of neurotransmitter reuptake mechanisms and various voltage- and ligand-gated ion channels of the nociceptive system. As transient receptor potential vanilloid-1 (TRPV1, "the capsaicin receptor") has been shown to function as a central integrator molecule of pain sensation, our aim in the current study was to define the involvement of TRPV1 in the complex mechanism of action of tramadol.
To achieve these goals, we used single-cell Ca-imaging as well as fluorescent image plate reader assays on Chinese hamster ovary (CHO) cells heterologously over-expressing TRPV1.
We found that (1) tramadol, similar to the well-known TRPV1 agonist, capsaicin, significantly increased Ca(2+)(i) of TRPV1-CHO cells in a concentration-dependent fashion; (2) its effect was reversibly prevented by the TRPV1 antagonist capsazepine; (3) repeated application of tramadol resulted in marked tachyphylaxis; and (4) tramadol did not modify Ca(2+)(i) in control (empty vector expressing) CHO cells.
Collectively, these findings strongly support the intriguing and novel concept that tramadol acts as an agonist of TRPV1. Considering that activation of TRPV1 on sensory neurons is followed by a local release of vasoactive neuropeptides and a marked desensitization of the afferent fibers (hence termination of pain sensation), our findings may equally explain both the desired analgesic as well as the often-seen, yet "unexpected," local side effects (e.g., initiation of burning pain and erythema) of tramadol.
The aim of the present study was to compare the distribution of ion currents and the major underlying ion channel proteins in canine and human subepicardial (EPI) and midmyocardial (MID) ...left-ventricular muscle. Ion currents and action potentials were recorded from canine cardiomyocytes derived from the very superficial EPI and central MID regions of the left ventricle. Amplitude, duration and the maximum velocity of depolarization of the action potential were significantly greater in MID than EPI myocytes, whereas phase-1 repolarization was more pronounced in the EPI cells. Amplitudes of the transient outwards K+ current (29.5+/-1.5 vs. 19.0+/-2.3 pA/pF at +50 mV) and the slow component of the delayed rectifier K+ current (10.3+/-2.3 vs. 6.5+/-1.0 pA/pF at +50 mV) were significantly larger in EPI than in MID myocytes under whole-cell voltage-clamp conditions. The densities of the inwards rectifier K+ current, rapid delayed rectifier K+ current and L-type Ca2+ current were similar in both cell types. Expression of channel proteins in both canine and human ventricular myocardium was determined by Western blotting. In the canine heart, the expression of Kv4.3, Kv1.4, KChIP2 and KvLQT1 was significantly higher, and that of Nav1.5 and MinK much lower, in EPI than in MID. No significant EPI-MID differences were observed in the expression of the other channel proteins studied (Kir2.1, alpha1C, HERG and MiRP1). Similar results were obtained in human hearts, although the HERG was more abundant in the EPI than in the MID layer. In the canine heart, the EPI-MID differences in ion current densities were proportional to differences in channel protein expression. Except for the density of HERG, the pattern of EPI-MID distribution of ion-channel proteins was identical in canine and human ventricles.
We present a comparative study of absolute distances to a sample of very nearby, bright Type Ia supernovae (SNe) derived from high cadence, high signal-to-noise, multi-band photometric data. Our ...sample consists of four SNe: 2012cg, 2012ht, 2013dy and 2014J. We present new homogeneous, high-cadence photometric data in Johnson–Cousins BVRI and Sloan g′r′i′z′ bands taken from two sites (Piszkesteto and Baja, Hungary), and the light curves are analyzed with publicly available light curve fitters (MLCS2k2, SNooPy2 and SALT2.4). When comparing the best-fit parameters provided by the different codes, it is found that the distance moduli of moderately reddened SNe Ia agree within ≲0.2 mag, and the agreement is even better (≲0.1 mag) for the highest signal-to-noise BVRI data. For the highly reddened SN 2014J the dispersion of the inferred distance moduli is slightly higher. These SN-based distances are in good agreement with the Cepheid distances to their host galaxies. We conclude that the current state-of-the-art light curve fitters for Type Ia SNe can provide consistent absolute distance moduli having less than ∼0.1–0.2 mag uncertainty for nearby SNe. Still, there is room for future improvements to reach the desired ∼0.05 mag accuracy in the absolute distance modulus.
We have identified nearly a hundred close triply eclipsing hierarchical triple star systems from data taken with the space telescope TESS. These systems are noteworthy in that we can potentially ...determine their dynamical and astrophysical parameters with a high precision. In the present paper, we report the comprehensive study of seven new compact triply eclipsing triple star systems taken from this larger sample: TICs 133771812, 176713425, 185615681, 287756035, 321978218, 323486857, and 650024463. Most of the data for this study come from TESS observations, but two of them have Gaia measurements of their outer orbits, and we obtained supplemental radial velocity (RV) measurements for three of the systems. The eclipse timing variation curves extracted from the TESS data, the photometric light curves, the RV points, and the spectral energy distribution (SED) are combined in a complex photodynamical analysis to yield the stellar and orbital parameters of all seven systems. Four of the systems are quite compact with outer periods in the range of 41-56 days. All of the systems are substantially flat, with mutual inclination angles of < ~2 degrees. Including the systems reported in this work, we have now studied in considerable detail some 30 triply eclipsing triples with TESS, and are accumulating a meaningful census of these systems.
There is a growing number of peculiar events that cannot be assigned to any of the main supernova (SN) classes. SN 1987A and a handful of similar objects, thought to be explosive outcomes of blue ...supergiant stars, belong to them: while their spectra closely resemble those of H-rich (IIP) SNe, their light-curve (LC) evolution is very different. Here we present the detailed photometric and spectroscopic analysis of SN 2021aatd, a peculiar Type II explosion: while its early-time evolution resembles that of the slowly evolving, double-peaked SN 2020faa (however, at a lower luminosity scale), after \(\sim\)40 days, its LC shape becomes similar to that of SN 1987A-like explosions. Beyond comparing LCs, color curves, and spectra of SN 2021aatd to that of SNe 2020faa, 1987A, and of other objects, we compare the observed spectra with our own SYN++ models and with the outputs of published radiative transfer models. We also modeled the pseudo-bolometric LCs of SNe 2021aatd and 1987A assuming a two-component (core+shell) ejecta, and involving the rotational energy of a newborn magnetar in addition to radioactive decay. We find that both the photometric and spectroscopic evolution of SN 2021aatd can be well described with the explosion of a \(\sim\)15 \(M_\odot\) blue supergiant star. Nevertheless, SN 2021aatd shows higher temperatures and weaker Na ID and Ba II 6142 A lines than SN 1987A, which is reminiscent of rather to IIP-like atmospheres. With the applied two-component ejecta model (counting with both decay and magnetar energy), we can successfully describe the bolometric LC of SN 2021aatd, including the first \(\sim\)40-day long phase showing an excess compared to 87A-like SNe but being strikingly similar to that of the long-lived SN 2020faa. Nevertheless, finding a unified model that also explains the LCs of more luminous events (like SN 2020faa) is still a matter of concern.
EM Cygni: A study of its eclipse timings Csizmadia, Sz; Nagy, Zs; Borkovits, T. ...
Astronomische Nachrichten,
01/2008, Letnik:
329, Številka:
1
Journal Article
We report the discovery with \(TESS\) of a third set of eclipses from V994 Herculis (TIC 424508303), previously only known as a doubly-eclipsing system. The key implication of this discovery and our ...analyses is that V994 Her is the second fully-characterized (2+2) + 2 sextuple system, in which all three binaries eclipse. In this work, we use a combination of ground-based observations and \(TESS\) data to analyze the eclipses of binaries A and B in order to update the parameters of the inner quadruple's orbit (with a derived period of 1062 \(\pm\) 2d). The eclipses of binary C that were detected in the \(TESS\) data were also found in older ground-based observations, as well as in more recently obtained observations. The eclipse timing variations of all three pairs were studied in order to detect the mutual perturbations of their constituent stars, as well as those of the inner pairs in the (2+2) core. At the longest periods they arise from apsidal motion, which may help constraining parameters of the component stars' internal structure. We also discuss the relative proximity of the periods of binaries A and B to a 3:2 mean motion resonance. This work represents a step forward in the development of techniques to better understand and characterize multiple star systems, especially those with multiple eclipsing components.
In this work we report the independent discovery and analysis of nine new compact triply eclipsing triple star systems found with the TESS mission: TICs 47151245, 81525800, 99013269, 229785001, ...276162169, 280883908, 294803663, 332521671, and 356324779. Each of these nine systems exhibits distinct third-body eclipses where the third (`tertiary') star occults the inner eclipsing binary (EB), or vice versa. We utilize a photodynamical analysis of the TESS photometry, archival photometric data, TESS eclipse timing variations of the EBs, available archival spectral energy distribution curves (SED), and, in some cases, newly acquired radial velocity observations, to solve for the parameters of all three stars, as well as most of the orbital elements. From these analyses we find that the outer orbits of all nine systems are viewed nearly edge on (i.e., within \(\lesssim 4^\circ\)), and 6 of the systems are coplanar to within \(5^\circ\); the others have mutual inclination angles of \(20^\circ\), \(41^\circ\), and possibly \(179^\circ\) (i.e., a retrograde outer orbit). The outer orbital periods range from 47.8 days to 604 days, with eccentricities spanning 0.004 to 0.61. The masses of all 18 EB stars are in the range of 0.9-2.6 M\(_\odot\) and are mostly situated near the main sequence. By contrast, the masses and radii of the tertiary stars range from 1.4-2.8 M\(_\odot\) and 1.5-13 R\(_\odot\), respectively. We make use of the system parameters from these 9 systems, plus those from a comparable number of compact triply eclipsing triples published previously, to gain some statistical insight into their properties.
We present extensive ultraviolet (UV) and optical photometric and optical spectroscopic follow-up of supernova (SN)~2021gno by the "Precision Observations of Infant Supernova Explosions" (POISE) ...project, starting less than two days after the explosion. Given its intermediate luminosity, fast photometric evolution, and quick transition to the nebular phase with spectra dominated by Ca~II lines, SN~2021gno belongs to the small family of Calcium-rich transients. Moreover, it shows double-peaked light curves, a phenomenon shared with only four other Calcium-rich events. The projected distance from the center of the host galaxy is not as large as other objects in this family. The initial optical light-curve peaks coincide with a very quick decline of the UV flux, indicating a fast initial cooling phase. Through hydrodynamical modelling of the bolometric light curve and line velocity evolution, we found that the observations are compatible with the explosion of a highly-stripped massive star with an ejecta mass of \(0.8\,M_\odot\) and a \(^{56}\)Ni mass of \(0.024~M_{\odot}\). The initial cooling phase (first light curve peak) is explained by the presence of an extended circumstellar material comprising $\sim$$10^{-2}\,M_{\odot}\( with an extension of \)1100\,R_{\odot}$. We discuss if hydrogen features are present in both maximum-light and nebular spectra, and its implications in terms of the proposed progenitor scenarios for Calcium-rich transients.
The goal of the current study, conducted in freshly isolated thymocytes was (1) to investigate the possibility that the activation of poly(ADP-ribose) polymerase-1 (PARP-1) in an intact cell can be ...regulated by protein kinase C (PKC) mediated phosphorylation and (2) to examine the consequence of this regulatory mechanism in the context of cell death induced by the genotoxic agent. In cells stimulated by the PKC activating phorbol esters, DNA breakage was unaffected, PARP-1 was phosphorylated, 1-methyl-3-nitro-1-nitrosoguanidine-induced PARP activation and cell necrosis were suppressed, with all these effects attenuated by the PKC inhibitors GF109203X or Gö6976. Inhibition of cellular PARP activity by PKC-mediated phosphorylation may provide a plausible mechanism for the previously observed cytoprotective effects of PKC activators.
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