Spectrofluorimetric determination of sertraline in dosage forms and human plasma through derivatization with 9-fluorenylmethyl chloroformate

<p>Abstract</p> <p>Background</p> <p>Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. A survey of the literature reveals that most of the reported methods are either insufficiently sensitive or tedious and require highly sophisticated and dedicated instrumentation. The proposed method is considered to be specific for determination of SER in presence of its metabolite (deaminated form).</p> <p>Results</p> <p>A sensitive, simple and specific spectrofluorimetric method was developed for the determination of sertraline (SER) in pharmaceutical formulations and biological fluids. The method is based on its reaction with 9-fluorenylmethyl chloroformate (FMOC-Cl) in borate buffer of pH 8.0 to yield a highly fluorescent derivative peaking at 315 nm after excitation at 265 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence concentration plot was rectilinear over the range of 0.05-1.0 μg mL^-1with a lower detection limit of 5.34 × 10^-3μg mL^-1and limit of quantitation of 0.016 μg mL^-1.</p> <p>Conclusions</p> <p>The proposed method was successfully applied to the analysis of commercial tablets and the results obtained were in good agreement with those obtained using the reference method. Furthermore, the method was applied for the determination of SER in spiked and real human plasma. The mean % recovery (n = 3) was 94.33 ± 1.53 and 92.00 ± 2.65, respectively. A proposal of the reaction pathway was postulated.</p

Two-dimensional SDS-PAGE fractionation of biological samples for biomarker discovery

Two-dimensional electrophoresis is still a very valuable tool in proteomics, due to its reproducibility and its ability to analyze complete proteins. However, due to its sensitivity to dynamic range issues, its most suitable use in the frame of biomarker discovery is not on very complex fluids such as plasma, but rather on more proximal, simpler fluids such as CSF, urine, or secretome samples. Here, we describe the complete workflow for the analysis of such dilute samples by two-dimensional electrophoresis, starting from sample concentration, then the two-dimensional electrophoresis step per se, ending with the protein detection by fluorescence

Gel-type autologous chondrocyte (Chondron™) implantation for treatment of articular cartilage defects of the knee

<p>Abstract</p> <p>Background</p> <p>Gel-type autologous chondrocyte (Chondron™) implantations have been used for several years without using periosteum or membrane. This study involves evaluations of the clinical results of Chondron™ at many clinical centers at various time points during the postoperative patient follow-up.</p> <p>Methods</p> <p>Data from 98 patients with articular cartilage injury of the knee joint and who underwent Chondron™ implantation at ten Korean hospitals between January 2005 and November 2008, were included and were divided into two groups based on the patient follow-up period, i.e. 13~24-month follow-up and greater than 25-month follow-up. The telephone Knee Society Score obtained during telephone interviews with patients, was used as the evaluation tool.</p> <p>Results</p> <p>On the tKSS-A (telephone Knee Society Score-A), the score improved from 43.52 ± 20.20 to 89.71 ± 13.69 (P < 0.05), and on the tKSS-B (telephone Knee Society Score-B), the score improved from 50.66 ± 20.05 to 89.38 ± 15.76 (P < 0.05). The total improvement was from 94.18 ± 31.43 to 179.10 ± 24.69 (P < 0.05).</p> <p>Conclusion</p> <p>Gel-type autologous chondrocyte implantation for chondral knee defects appears to be a safe and effective method for both decreasing pain and improving knee function.</p

Old World Arenaviruses Enter the Host Cell via the Multivesicular Body and Depend on the Endosomal Sorting Complex Required for Transport

The highly pathogenic Old World arenavirus Lassa virus (LASV) and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) use α-dystroglycan as a cellular receptor and enter the host cell by an unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Upon internalization, the viruses are delivered to acidified endosomes in a Rab5-independent manner bypassing classical routes of incoming vesicular trafficking. Here we sought to identify cellular factors involved in the unusual and largely unknown entry pathway of LASV and LCMV. Cell entry of LASV and LCMV required microtubular transport to late endosomes, consistent with the low fusion pH of the viral envelope glycoproteins. Productive infection with recombinant LCMV expressing LASV envelope glycoprotein (rLCMV-LASVGP) and LCMV depended on phosphatidyl inositol 3-kinase (PI3K) as well as lysobisphosphatidic acid (LBPA), an unusual phospholipid that is involved in the formation of intraluminal vesicles (ILV) of the multivesicular body (MVB) of the late endosome. We provide evidence for a role of the endosomal sorting complex required for transport (ESCRT) in LASV and LCMV cell entry, in particular the ESCRT components Hrs, Tsg101, Vps22, and Vps24, as well as the ESCRT-associated ATPase Vps4 involved in fission of ILV. Productive infection with rLCMV-LASVGP and LCMV also critically depended on the ESCRT-associated protein Alix, which is implicated in membrane dynamics of the MVB/late endosomes. Our study identifies crucial cellular factors implicated in Old World arenavirus cell entry and indicates that LASV and LCMV invade the host cell passing via the MVB/late endosome. Our data further suggest that the virus-receptor complexes undergo sorting into ILV of the MVB mediated by the ESCRT, possibly using a pathway that may be linked to the cellular trafficking and degradation of the cellular receptor

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Observation of the black widow B1957+20 millisecond pulsar binary system with the MAGIC telescopes

B1957+20 is a millisecond pulsar located in a black-widow-type compact binary system with a low-mass stellar companion. The interaction of the pulsar wind with the companion star wind and/or the interstellar plasma is expected to create plausible conditions for acceleration of electrons to TeV energies and subsequent production of very high-energy gamma-rays in the inverse Compton process. We performed extensive observations with the Major Atmospheric Gamma Imaging Cherenkov Telescopes (MAGIC) telescopes of B1957+20. We interpret results in the framework of a few different models, namely emission from the vicinity of the millisecond pulsar, the interaction of the pulsar and stellar companion wind region or bow shock nebula. No significant steady very high-energy gamma-ray emission was found. We derived a 95 per cent confidence level upper limit of 3.0 x 10(-12) cm(-2) s(-1) on the average gamma-ray emission from the binary system above 200 GeV. The upper limits obtained with the MAGIC constrain, for the first time, different models of the high-energy emission in B1957+20. In particular, in the inner mixed wind nebula model with mono-energetic injection of electrons, the acceleration efficiency of electrons is constrained to be below similar to 2-10 per cent of the pulsar spin-down power. For the pulsar emission, the obtained upper limits for each emission peak are well above the exponential cut-off fits to the Fermi-LAT data, extrapolated to energies above 50 GeV. The MAGIC upper limits can rule out a simple power-law tail extension through the sub-TeV energy range for the main peak seen at radio frequencies

Observations of Sagittarius A* during the pericenter passage of the G2 object with MAGIC

Context. We present the results of a multi-year monitoring campaign of the Galactic center (GC) with the MAGIC telescopes. These observations were primarily motivated by reports that a putative gas cloud (G2) would be passing in close proximity to the super-massive black hole (SMBH), associated with Sagittarius A*, located at the center of our galaxy. This event was expected to give astronomers a unique chance to study the effect of in-falling matter on the broad-band emission of a SMBH.Aims. We search for potential flaring emission of very-high-energy (VHE; >= 100 GeV) gamma rays from the direction of the SMBH at the GC due to the passage of the G2 object. Using these data we also study the morphology of this complex region.Methods. We observed the GC region with the MAGIC Imaging Atmospheric Cherenkov Telescopes during the period 2012-2015, collecting 67 h of good-quality data. In addition to a search for variability in the flux and spectral shape of the GC gamma-ray source, we use a point-source subtraction technique to remove the known gamma-ray emitters located around the GC in order to reveal the TeV morphology of the extended emission inside that region.Results. No effect of the G2 object on the VHE gamma-ray emission from the GC was detected during the 4 yr observation campaign. We confirm previous measurements of the VHE spectrum of Sagittarius A*, and do not detect any significant variability of the emission from the source. Furthermore, the known VHE gamma-ray emitter at the location of the supernova remnant G0.9+0.1 was detected, as well as the recently discovered VHE source close to the GG radio arc

First multi-wavelength campaign on the gamma-ray-loud active galaxy IC 310

Context. The extragalactic very-high-energy gamma-ray sky is rich in blazars. These are jetted active galactic nuclei that are viewed at a small angle to the line-of-sight. Only a handful of objects viewed at a larger angle are so far known to emit above 100 GeV. Multi-wavelength studies of such objects up to the highest energies provide new insights into the particle and radiation processes of active galactic nuclei.Aims. We aim to report the results from the first multi-wavelength campaign observing the TeV detected nucleus of the active galaxy IC 310, whose jet is observed at a moderate viewing angle of 10 degrees-20 degrees.Methods. The multi-instrument campaign was conducted between 2012 November and 2013 January, and involved observations with MAGIC, Fermi, INTEGRAL, Swift, OVRO, MOJAVE and EVN. These observations were complemented with archival data from the AllWISE and 2MASS catalogs. A one-zone synchrotron self-Compton model was applied to describe the broadband spectral energy distribution.Results. IC 310 showed an extraordinary TeV flare at the beginning of the campaign, followed by a low, but still detectable TeV flux. Compared to previous measurements in this energy range, the spectral shape was found to be steeper during the low emission state. Simultaneous observations in the soft X-ray band showed an enhanced energy flux state and a harder-when-brighter spectral shape behavior. No strong correlated flux variability was found in other frequency regimes. The broadband spectral energy distribution obtained from these observations supports the hypothesis of a double-hump structure.Conclusions. The harder-when-brighter trend in the X-ray and VHE emission, observed for the first time during this campaign, is consistent with the behavior expected from a synchrotron self-Compton scenario. The contemporaneous broadband spectral energy distribution is well described with a one-zone synchrotron self-Compton model using parameters that are comparable to those found for other gamma-ray-emitting misaligned blazars