The authors conducted two multicenter, randomized, double-blinded, controlled Phase III clinical trials to study the efficacy and safety of phentolamine mesylate (PM) in shortening the duration and ...burden of soft-tissue anesthesia. The study involved 484 subjects who received one of four commercially available local anesthetic solutions containing vasoconstrictors for restorative or scaling procedures.
On completion of the dental procedure, subjects randomly received a PM or a sham injection (an injection in which a needle does not penetrate the soft tissue) in the same site as the local anesthetic injection. The investigators measured the duration of soft-tissue anesthesia by using standardized lip- and tongue-tapping procedures every five minutes for five hours. They also evaluated functional measures and subject-perceived altered function, sensation, appearance and safety.
Median recovery times in the lower lip and tongue for subjects in the PM group were 70 minutes and 60 minutes, respectively. Median recovery times in the lower lip and tongue for subjects in the sham group were 155 minutes and 125 minutes, respectively. Upper lip median recovery times were 50 minutes for subjects in the PM group and 133 minutes for subjects in the sham group. These differences were significant (P < .0001). Recovery from actual functional deficits and subject-perceived altered function, sensation and appearance also showed significant differences between the PM and the sham groups.
PM was efficacious and safe in reducing the duration of local anesthetic- induced soft-tissue numbness and its associated functional deficits.
Clinicians can use PM to accelerate reversal of soft-tissue anesthesia and the associated functional deficits.
Clibadium surinamense L, popularly known as cunambi, is a native plant from the Northern region of Brazil illegally used for predatory fishing. Previous results from our laboratory have demonstrated ...that the oral treatment of mice with the ethanolic extract (EE) of the leaves of the plant induced generalized tonic–clonic seizures followed by death within 30
min. The aims of the present paper were to characterize the convulsant effect of the hexanic extract (HE) of the stems and leaves of
C. surinamense and, by bioguided purification, to identify the active principle and its mechanism of action. The leaves and stems were extracted with hexane (100
g/L) in Soxhlet for 36
h (yield of 2.4%), the solvent was evaporated and the powder dissolved in 1.5% saline/Tween 80. Male mice (30–35
g) treated with HE (22.5–360
mg/kg, p.o.) showed behavioral alterations consistent with CNS stimulation. The intensity and duration of the effect were proportional to the administered doses. The behavioral alterations, measured with a graded score of seizure severity, revealed that pretreatment with carbamazepine (30
mg/kg, i.p., 60
min) or phenytoin (50
mg/kg, i.p., 30
min) did not alter the HE convulsive effect. In contrast, phenobarbital (30
mg/kg, i.p., 60
min) or diazepam (2
mg/kg, i.p., 30
min) reduced the HE effect, increasing the ED
50 for clonic seizures from 64.4 to 89.8
mg/kg and 168.9
mg/kg, respectively. Purification of the HE in a silica gel column eluted with a hexane/ethyl acetate gradient yielded a single fraction with convulsant effect in which cunaniol acetate was identified by
1H NMR as the main active compound. These results indicated that inhibition of GABAergic transmission by cunaniol acetate might be responsible for the convulsant effects of
C. surinamense L in mice, but do not exclude a direct cunaniol action labilizing neuronal excitability.
AMIGA (Auger Muons and Infill for the Ground Array) is an upgrade of the Pierre Auger Observatory designed to extend its energy range of detection and to directly measure the muon content of the ...cosmic ray primary particle showers. The array will be formed by an infill of surface water-Cherenkov detectors associated with buried scintillation counters employed for muon counting. Each counter is composed of three scintillation modules, with a 10 m\(^2\) detection area per module. In this paper, a new generation of detectors, replacing the current multi-pixel photomultiplier tube (PMT) with silicon photo sensors (aka. SiPMs), is proposed. The selection of the new device and its front-end electronics is explained. A method to calibrate the counting system that ensures the performance of the detector is detailed. This method has the advantage of being able to be carried out in a remote place such as the one where the detectors are deployed. High efficiency results, i.e. 98 % efficiency for the highest tested overvoltage, combined with a low probability of accidental counting (\(\sim\)2 %), show a promising performance for this new system.
On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events ...were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within \(\pm 500\) s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.
We report a first measurement for ultra-high energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered ...simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the `ankle' at \(\lg(E/{\rm eV})=18.5-19.0\) differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass \(A > 4\). Scenarios such as the proton dip model, with almost pure compositions, are thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.
We present a search for ultra-relativistic magnetic monopoles with the Pierre Auger Observatory. Such particles, possibly a relic of phase transitions in the early universe, would deposit a large ...amount of energy along their path through the atmosphere, comparable to that of ultrahigh-energy cosmic rays (UHECRs). The air shower profile of a magnetic monopole can be effectively distinguished by the fluorescence detector from that of standard UHECRs. No candidate was found in the data collected between 2004 and 2012, with an expected background of less than 0.1 event from UHECRs. The corresponding 90% confidence level (C.L.) upper limits on the flux of ultra-relativistic magnetic monopoles range from \(10^{-19}\) (cm\(^{2}\) sr s)\(^{-1}\) for a Lorentz factor \(\gamma=10^9\) to \(2.5 \times10^{-21}\) (cm\(^{2}\) sr s)\(^{-1}\) for \(\gamma=10^{12}\). These results - the first obtained with a UHECR detector - improve previously published limits by up to an order of magnitude.
