We present a sample of 38 intervening damped Lyman ... (DLA) systems identified towards 100 z > 3.5 quasars, observed during the XQ-100 survey. The XQ-100 DLA sample is combined with major DLA ...surveys in the literature. The final combined sample consists of 742 DLAs over a redshift range approximately 1.6 < z sub( abs) < 5.0. We develop a novel technique for computing ... as a continuous function of redshift, and we thoroughly assess and quantify the sources of error therein, including fitting errors and incomplete sampling of the high column density end of the column density distribution function. There is a statistically significant redshift evolution in ... ( greater than or equal to 3...) from z ~ 2 to z ~ 5. In order to make a complete assessment of the redshift evolution of ...HI, we combine our high-redshift DLA sample with absorption surveys at intermediate redshift and 21-cm emission line surveys of the local universe. Although ...DLAHI, and hence its redshift evolution, remains uncertain in the intermediate-redshift regime (0.1 < z sub( abs) < 1.6), we find that the combination of high-redshift data with 21-cm surveys of the local universe all yield a statistically significant evolution in ... from z ~ 0 to z ~ 5 ( greater than or equal to 3...). Despite its statistical significance, the magnitude of the evolution is small: a linear regression fit between ... and z yields a typical slope of ~0.17 x 10 super( -3), corresponding to a factor of ~4 decrease in ... between z = 5 and z = 0. (ProQuest: ... denotes formulae/symbols omitted.)
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The use of colloidal particles (CPs) in the transport of drugs is developing rapidly thanks to its effectiveness and biosafety, especially in the treatment of various types of cancer. ...In this study Rose Bengal/PLGA CPs synthesized by double emulsion (W/O/W) and by electrostatic adsorption (layer-by-layer), were characterized and evaluated as potential breast cancer treatment. CPs were evaluated in terms of size, zeta potential, drug release kinetics and cell viability inhibition efficacy with the triple negative breast cancer cell line HCC70. The results showed that both types of CPs can be an excellent alternative to conventional cancer treatment by taking advantage of the enhanced permeation and retention (EPR) effect, manifested by solid tumors; however, the double emulsion CPs showed more suitable delivery times of up to 60% within two days, while layer-by-layer showed fast release of 50% in 90 min. Both types of CPs were capable to decrease cell viability, which encourage us to further testing in in vivo models to prove their efficacy and feasible use in the treatment of triple negative breast cancer.
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•Chitosan surface nanolayer on PLGA NPs facilitate antibody conjugation.•Direct quantification of antibody/NP ratio was achieved by fluorescein-labeling of ...antibodies.•Anti-HER2/cisplatin/PLGA NPs inhibit ovarian cancer cell viability more efficiently than antibody-less NPs.•HER2 overexpressing cells internalize anti-HER2 labeled NPs faster and at higher degree.
The conventional treatment (cytoreduction combined with cisplatin/carboplatin and taxane drugs) of ovarian cancer has a high rate of failure and recurrence despite a favorable initial response. This lack of success is usually attributed to the development of multidrug resistance mechanisms by cancer cells and avoidance of the anti-growth effects of monoclonal targeted therapeutic antibodies. The disease, like other cancers, is characterized by the overexpression of molecular markers, including HER2 receptors. Preclinical and clinical studies with trastuzumab, a HER2-targeted therapeutic antibody, reveal a low improvement of the outcomes of HER2 positive ovarian cancer patients. Therefore, here, we propose a cisplatin-loaded, HER2 targeted poly(lactic-co-glycolic) nanoplatform, a system capable to escape the drug-efflux effect and to take advantage of the overexpressed HER2 receptors, using them as docks for targeted chemotherapy. The NP/trastuzumab ratio was determined after fluorescein labeling of antibodies and quantification of fluorescence in NPs. The system was also characterized in terms of size, zeta potential, drug release kinetics, cytotoxicity and cellular internalization in the epithelial ovarian cancer cell line SKOV-3, and compared with the HER2 negative breast cancer cell line HCC70. Our results show an increased cytotoxicity of NPs as compared to free cisplatin, and moreover, an enhanced internalization and cytotoxicity due to the bionfunctionalization of NPs with the monoclonal antibody.
Background and purpose:
Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of ...anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague‐Dawley (SD) rats after an injection of CDDP (5 mgkg‐1 body weight).
Experimental approach:
Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic‐related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed.
Key results:
CDDP significantly increased the levels of caspase‐3/7 activity and active caspase‐3 protein expression and caspase‐3 immunofluorescence staining, caspase‐9 activity, and Bax protein expression but decreased Bcl‐2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment.
Conclusions and implications:
These findings support the hypothesis that cisplatin‐related apoptosis evokes an intrinsic pathway of pro‐apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin‐induced ototoxicity.
British Journal of Pharmacology (2007) 152, 1012–1020; doi:10.1038/sj.bjp.0707405; published online 1 October 2007
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Breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer and, in terms of mortality, is the fifth leading cause with 684,996 new deaths (6.7% of all cancer-related ...deaths) and the highest mortality amongst all cancers (15.5%) in women. Selective estrogen-receptor modulators (SERMs) have been used for the last thirty years for estrogen receptor-positive (ER+) BC prevention and treatment. Tamoxifen (TAM), the most widely used SERM, is orally administered and its long-term oral administration has been associated to toxicity and adverse side effects. Endoxifen (EDX) is one of the known active metabolites of TAM, with an affinity to ERα 100 times higher than TAM. Furthermore, EDX has shown antiproliferative activity against the ER+ BC cell line MCF-7. Alternative administration routes that avoid the metabolic processing of TAM seem an appealing alternative to its oral administration. With this aim, we have prepared a polymeric gel-like solution of Pluronic® F127 as vehicle for topical administration of EDX. In order to shed light on the potential clinical use of this formulation, we have compared it with the standard pharmaceutical form, i.e. orally administered TAM. The biodistribution, antitumor efficacy and toxic effects of topical EDX and oral TAM were evaluated in ER+ tumor xenograft athymic nu/nu mouse models. The results showed a statistically significant antitumor effect and reduced toxicity of topical EDX as compared to oral TAM or empty F127 gel. This novel administration route of SERMs could also have a strong impact in the prevention of BC at early development stages and could help to ameliorate the mortality and morbidity related to this disease.
Gamma-ray bursts (GRBs) are powerful probes of early stars and galaxies, during and potentially even before the era of reionization. Although the number of GRBs identified at z 6 remains small, they ...provide a unique window on typical star-forming galaxies at that time, and thus are complementary to deep field observations. We report the identification of the optical drop-out afterglow of Swift GRB 120923A in near-infrared Gemini-North imaging, and derive a redshift of from Very Large Telescope/X-shooter spectroscopy. At this redshift the peak 15-150 keV luminosity of the burst was 3.2 × 1052 erg s−1, and in this sense it was a rather typical long-duration GRB in terms of rest frame luminosity. This burst was close to the Swift/Burst Alert Telescope detection threshold, and the X-ray and near-infrared afterglow were also faint. We present ground- and space-based follow-up observations spanning from X-ray to radio, and find that a standard external shock model with a constant-density circumburst environment of density n 4 × 10−2 cm−3 gives a good fit to the data. The near-infrared light curve exhibits a sharp break at t 3.4 days in the observer frame which, if interpreted as being due to a jet, corresponds to an opening angle of . The beaming-corrected γ-ray energy is then erg, while the beaming-corrected kinetic energy is lower, erg, suggesting that GRB 120923A was a comparatively low kinetic energy event. We discuss the implications of this event for our understanding of the high-redshift population of GRBs and their identification.
•Rhodamine discoloration by interaction with chabazite in dark and under sunlight.•The rhodamine discoloration is more efficient and faster under sunlight.•Sunlight promotes photo chemical reactions ...driven by chabazite to degrade rhodamine.•Discoloration percentage in dark is 85.3% and under sunlight 97.7%, at 360min.
Natural zeolite chabazite was studied for the discoloration of rhodamine 6G solutions in dark and under sunlight irradiation. The discoloration of rhodamine aqueous solutions containing chabazite was monitored by UV–vis absorption and photoluminescence spectroscopies and high-performance liquid chromatography measurements on aliquots of the rhodamine solutions. After the discoloration experiments the chabazite powders were collected, dried and analyzed by Fourier-Transform Infrared spectroscopy to obtain additional information about the discoloration process. The results show that chabazite produces the discoloration of the rhodamine solutions in both conditions, dark and under sunlight, with different discoloration mechanisms and rates. In dark, chabazite removes the rhodamine molecules from the solution by adsorption and cation exchange mechanisms. Under sunlight irradiation, additional photo induced mechanisms produce the degradation of the rhodamine molecules and a faster discoloration of the solution. The discoloration process followed a first order kinetics with rate constants of 4.9×10−3 and 1.2×10−2min−1 in dark and under sunlight conditions, respectively. It is proposed a mechanism for the photodegradation of rhodamine molecules under sunlight irradiation, where the role of chabazite is fundamental.
The short gamma-ray burst (GRB) 170817A was the first GRB associated with a gravitational-wave event. Due to the exceptionally low luminosity of the prompt γ-ray and the afterglow emission, the ...origin of both radiation components is highly debated. The most discussed models for the burst and the afterglow include a regular GRB jet seen off-axis and the emission from the cocoon encompassing a "choked" jet. Here, we report low radio frequency observations at 610 and 1390 MHz obtained with the Giant Metrewave Radio Telescope. Our observations span a range of ∼7 to ∼152 days after the burst. The afterglow started to emerge at these low frequencies about 60 days after the burst. The 1390 MHz light curve barely evolved between 60 and 150 days, but its evolution is also marginally consistent with an F ∝ t0.8 rise seen in higher frequencies. We model the radio data and archival X-ray, optical, and high-frequency radio data with models of top-hat and Gaussian structured GRB jets. We performed a Markov Chain Monte Carlo analysis of the structured-jet parameter space. Though highly degenerate, useful bounds on the posterior probability distributions can be obtained. Our bounds of the viewing angle are consistent with that inferred from the gravitational-wave signal. We estimate the energy budget in prompt emission to be an order of magnitude lower than that in the afterglow blast wave.
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