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External manipulation of nanostructure in photoresponsive lipid depot matrix to control and predict drug release in vivo
No full textOn-demand drug delivery systems are highly promising to control the time-course of drug release and ultimately optimize drug concentration time profiles in patients. Lipid based lyotropic liquid crystalline mesophases have demonstrated exceptional responsiveness to external stimuli such as heat, pH and light. Our objective was to quantitatively characterize the time-course of light activated drug release from near infrared (NIR) activated photothermal systems using ex vivo and in vivo studies. Photoresponsive hybrid gold nanorod-liquid crystalline matrices were prepared and loaded into custom-made implants which were inserted into subcutaneous tissues in rats. Time resolved SAXS studies showed the abdomen to be the best site of implantation to achieve in vivo activation of the subcutaneous dose from by the NIR laser. External control of drug release was achieved via NIR laser light and plasma concentrations of the model drug were determined over time. Laser activation achieved a phase change of the photoresponsive formulations and thereby a considerable change in the rate of drug release. Population pharmacokinetic modeling of all results simultaneously revealed a two stage release process unique to these liquid crystalline matrices. The developed structural model was able to successfully describe also the results of our previous study in 2009 where a change in temperature was utilized to trigger subcutaneous drug release. Thus, modeling of the data proved to be a valuable analytical tool which provided a quantitative understanding of the time-course of drug release in vivo and will be essential in the development of these matrices as on-demand release systems. © 2016, Elsevier B.V
Retention and damage in 3C-β SiC irradiated with He and H ions.
No full text3C-β SiC was implanted with He and H ions using plasma immersion ion implantation (PIII). Regions of damage were created at various depths by applying a sample stage bias of 5 kV, 10 kV, 20 kV or 30 kV. Raman spectroscopy results indicate that He irradiation leads to more damage compared to H irradiation, as observed via increased disordered C and Si signals, as well as broadening of the SiC peaks. X-ray photoelectron spectroscopy (XPS) and near edge X-ray absorption fine structure spectroscopy (NEXAFS) results indicate significant change to the SiC structure and that surface oxidation has occurred following irradiation, with the degree of change varying dependent on impinging He fluence. The distributions of implanted species were measured using elastic recoil detection analysis. Despite the varying degree and depth of damage created in the SiC by the He ion irradiations, the retained H distribution was observed to not be affected by preceding He implantation. © 2015 Elsevier B.V
Elemental composition of ambient fine particles in urban schools : sources of children’s exposure
No full textCurrently, there is a limited understanding of the sources of ambient fine particles that contribute to the exposure of
children at urban schools. Since the size and chemical composition of airborne particle are key parameters for determining
the source as well as toxicity, PM1 particles (mass concentration of particles with an aerodynamic diameter less than 1 μm)
were collected at 24 urban schools in Brisbane, Australia and their elemental compositions determined. Based on the
elemental compositions four main sources were identified; secondary sulphates, biomass burning, vehicle and industrial
emissions. While secondary sulphates were likely to be a large contributing source by mass, industrial emissions accounted
for the most variation in trace metals in the PM1 that children were exposed to at the schools. PM1 concentrations at the
schools were compared to the elemental composition of the PM2.5 particles (mass concentration of particles with an
aerodynamic diameter less than 2.5 μm) from a previous study conducted at a suburban and roadside site in Brisbane. This
comparison suggested that the more toxic heavy metals (V, Cr, Ni, Cu, Zn and Pb), mostly from vehicle and industrial
emissions, were predominantly in the PM1 fraction. Thus, the results from this study points to PM1 as a potentially good
particle size fraction for investigating the health effects of airborne particles. Further work is required to confirm this
hypothesis. © 2014 Taiwan Association for Aerosol Researc
A new late Quaternary palaeohydrological record from the humid tropics of northeastern Australia
No full textHigh resolution X-ray fluorescence (XRF) is presented as a robust palaeoclimatic proxy, suitable for use on Late Pleistocene to Holocene sediments located in a volcanic crater on the Atherton Tableland in northeastern Queensland, Australia. The proxy allows identification of wet and dry shifts in a complex sedimentary sequence comprised of peat, gyttja, laminated organic rich muds and fine clastic silt-rich sediments. Significant correlation is found between the XRF record and other proxies including magnetic susceptibility, humification, grain size, macrocharcoal, δ13C and C/N and pollen.
Sixteen wetter periods are identified in the 37 ka sedimentary record for Bromfield Swamp. Three wetter periods commence in late Marine Isotope Stage 3, nine in the early glacial, one in the late de-glacial and four in Holocene. Nineteen drier periods are identified, four in late MIS 3, seven in the early glacial, one during the LGM, one in the late de-glacial period and six in the Holocene.
The XRF record for Bromfield Swamp is specifically used to identify periods of abrupt climate change. Marked changes in effective precipitation are detected at 32,690, 30,080, 24,660, 21,870, 11,880, 10,020, 9170 and 5120 cal. yr BP. The detection of these abrupt climate events may allow correlation with records from terrestrial sites across the Southern Hemisphere and potentially, the Northern Hemisphere. © 2016 Elsevier B.V
Impact of extraneous mispositioned events on motion-corrected brain SPECT images of freely moving animals
No full textPurpose: Single photon emission computed tomography (SPECT) brain imaging of freely moving small animals would allow a wide range of important neurological processes and behaviors to be studied, which are normally inhibited by anesthetic drugs or precluded due to the animal being restrained. While rigid body motion of the head can be tracked and accounted for in the reconstruction, activity in the torso may confound brain measurements, especially since motion of the torso is more complex (i.e., nonrigid) and not well correlated with that of the head. The authors investigated the impact of mispositioned events and attenuation due to the torso on the accuracy of motion corrected brain images of freely moving mice. Methods: Monte Carlo simulations of a realistic voxelized mouse phantom and a dual compartment phantom were performed. Each phantom comprised a target and an extraneous compartment which were able to move independently of each other. Motion correction was performed based on the known motion of the target compartment only. Two SPECT camera geometries were investigated: a rotating single head detector and a stationary full ring detector. The effects of motion, detector geometry, and energy of the emitted photons (hence, attenuation) on bias and noise in reconstructed brain regions were evaluated. Results: The authors observed two main sources of bias: (a) motion-related inconsistencies in the projection data and (b) the mismatch between attenuation and emission. Both effects are caused by the assumption that the orientation of the torso is difficult to track and model, and therefore cannot be conveniently corrected for. The motion induced bias in some regions was up to 12% when no attenuation effects were considered, while it reached 40% when also combined with attenuation related inconsistencies. The detector geometry (i.e., rotating vs full ring) has a big impact on the accuracy of the reconstructed images, with the full ring detector being more advantageous. Conclusions: Motion-induced inconsistencies in the projection data and attenuation/emission mismatch are the two main causes of bias in reconstructed brain images when there is complex motion. It appears that these two factors have a synergistic effect on the qualitative and quantitative accuracy of the reconstructed images. © 2014 American Association of Physicists in Medicine
Understanding the production and retention of in situ cosmogenic 14C in polar firn.
No full textRadiocarbon in CO2, CO and CH4 trapped in polar ice is of interest for dating of ice cores, studies of past solar activity and cosmic ray flux, as well as studies of the paleoatmospheric CH4 budget. The major difficulty with interpreting 14C measurements in ice cores stems from the fact that the measured 14C represents a combination of trapped paleoatmospheric 14C and 14C that is produced within the firn and ice lattice by secondary cosmic ray particles. This in situ cosmogenic 14C component in ice is at present poorly understood. Prior ice core 14C studies show conflicting results with regard to the retention of in situ cosmogenic 14C in polar firn and partitioning of this 14C among CO2, CO and CH4. Our study aims to comprehensively characterize the 14C of CO2, CO, and CH4 in both the air and the ice matrix throughout the firn column at Summit, Greenland. We will present preliminary measurements of 14C in Summit firn air and the firn matrix, along with initial interpretations with regard to in situ cosmogenic 14C retention. Preliminary results from firn air indicate a 14CO increase with depth in the lock-in zone resulting from in situ production by muons, as well as a lock-in zone 14CO2 bomb peak originating from nuclear testing in the late 1950s and early 1960s. A decrease in 14CH4 with depth is observed in the lock-in zone that is in agreement with observations of increasing atmospheric 14CH4 over the past several decades. We observe that only a small fraction of in-situ produced 14CO, 14CH4 and 14CO2 is retained in the firn matrix. Additionally, we describe progress in the development of a field-portable sublimation apparatus for extraction of CO2 from firn and ice for 14C measurements
Effects of typical and atypical antipsychotic drugs on rat brain muscarinic receptors
No full textQuantitative in vitro autoradiography was used to examine changes in muscarinic M1/M4 and M2/M4 receptors (targeted with [3H]pirenzepine and [3H]AF-DX384 respectively), in rats treated with the typical (haloperidol) and atypical (clozapine and olanzapine) antipsychotic medications for a period of 36 days. Rats were sacrificed at either 2 h or 48 h after the last drug administration to examine immediate effects as well as the effects at 48 h after drug withdrawal. Haloperidol significantly increased [3H]pirenzepine binding in the dentate gyrus (37%) and in the CA1 region of the hippocampus (34%) in animals sacrificed 2 h after the last drug administration compared to controls. Similarly, clozapine significantly increased [3H]pirenzepine binding in dentate gyrus (29%) in rats sacrificed 2 h after the last drug administration compared to controls. Haloperidol decreased [3H]AF-DX384 binding in the basolateral nucleus of the amygdala (20%) in the rats sacrificed 48 h after the last drug administration compared to controls. These findings suggest that muscarinic receptors and limbic brain regions such as hippocampus and amygdala might represent common targets that mediate beneficial clinical effects of antipsychotic drugs. © 2007 Springer Science+Business Media, LL
Crystal growth and electronic structure of low-temperature phase SrMgF4
No full textUsing the vertical Bridgman method, the single crystal of low temperature phase SrMgF4 is obtained. The crystal is in a very good optical quality with the size of 10×7×5 mm3. Detailed photoemission spectra of the element core levels are determined by a monochromatic AlKa (1486.6 eV) X-ray source. Moreover, the first-principles calculations are performed to investigate the electronic structure of SrMgF4. A good agreement between experimental and calculated results is achieved. It is demonstrated that almost all the electronic orbitals are strongly localized and the hybridization with the others is very small, but the Mg–F bonds covalency is relatively stronger than that of Sr–F bonds. © 2015 Elsevier B.V
Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation
No full textThe translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroinflammatory changes in a variety of CNS disorders. To date, only a few effective tools are available to explore TSPO by SPECT. We characterised here 6-chloro-2-(4'iodophenyl)-3-(N,N-diethyl) -imidazo[1,2-a]pyridine-3-acetamide or CLINDE in a rat model with different stages of excitotoxic lesion. Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of different amounts of quinolinic acid (75, 150 or 300 nmol). Six days later, two groups of rats (n = 5-6/group) were i.v. injected with [125I]-CLINDE (0.4 MBq); one group being pre-injected with PK11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography, in vitro autoradiography ([3H]-PK11195) and immunohistochemical studies (OX-42) were performed on brain sections. In the control group, [125I]-CLINDE binding was significantly higher (p < 0.001) in lesioned than that in intact side. This binding disappeared in rats pre-treated with PK11195 (p<0.001), showing specific binding of CLINDE to TSPO. Ex vivo and in vitro autoradiographic studies and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated microglia. Regression analysis yielded a positive relation between the ligand binding and the degree of neuroinflammation. These results demonstrate that CLINDE is suitable for TSPO in vivo SPECT imaging to explore their involvement in neurodegenerative disorders associated with microglial activation. © 2008 Springer International Publishin
Rainfall variability and temporal changes in the dead carbon fraction in an Indonesian speleothem
No full textThe number of speleothem-based paleoclimate records has increased significantly in recent
years. To assess the potential hydrological control on speleothem radiocarbon variability, we constructed a high-resolution dead carbon fraction (DCF) record from a speleothem from Flores,
Indonesia for two different periods, the Younger Dryas (YD) chronozone and the Last Millennium. A total of thirty-four 14C analyses were conducted on calcite extracted from U-Th dated stalagmite LR06-B1. To better characterise the paleoclimate and environmental changes, highresolution
stable-isotope (δ18O, δ13C) and trace-element (Mg/Ca, Sr/Ca) measurements were
also conducted along the same stalagmite sections.
Broad comparison of the DCF record with the hydrologically-controlled proxy data suggests that rainfall increases were matched by DCF increases. In line with a previous interpretation of DCF
variability for the same specimen, but during the interval 2.4-2.8 ka and the post-bomb period, we interpret the DCF during the YD and the Last Millennium to have been primarily controlled by limestone dissolution associated with changes in open- versus closed-system conditions, rather
than other potential factors such as kinetic fractionation and/or variations in the age-spectrum of soil organic matter above the cave. It then follows that more abundant monsoon rainfall in Flores resulted in the soil-karst system being in a more closed state, which inhibited carbon isotope
exchange between the karst-water dissolved inorganic carbon and soil-gas CO2, and ultimately led to a greater contribution of dead-carbon from the bedrock.
Our results indicate that DCF in tropical speleothems can be used as a proxy of past rainfall and consequently monsoon variability