Direct angiotensin AT2 receptor stimulation using a novel AT2 receptor agonist, compound 21, evokes neuroprotection in conscious hypertensive rats

Background: In this study, the neuroprotective effect of a novel nonpeptide AT2R agonist, C21, was examined in a conscious model of stroke to verify a class effect of AT2R agonists as neuroprotective agents. Methods and Results: Spontaneously hypertensive rats (SHR) were pre-treated for 5 days prior to stroke with C21 alone or in combination with the AT2R antagonist PD123319. In a separate series of experiments C21 was administered in a series of 4 doses commencing 6 hours after stroke. A focal reperfusion model of ischemia was induced in conscious SHR by administering endothelin-1 to the middle cerebral artery (MCA). Motor coordination was assessed at 1 and 3 days after stroke and post mortem analyses of infarct volumes, microglia activation and neuronal survival were performed at 72 hours post MCA occlusion. When given prior to stroke, C21 dose dependently decreased infarct volume, which is consistent with the behavioural findings illustrating an improvement in motor deficit. During the pre-treatment protocol C21 was shown to enhance microglia activation, which are likely to be evoking protection by releasing brain derived neurotrophic factor. When drug administration was delayed until 6 hours after stroke, C21 still reduced brain injury. Conclusion: These results indicate that centrally administered C21 confers neuroprotection against stroke damage. This benefit is likely to involve various mechanisms, including microglial activation of endogenous repair and enhanced cerebroperfusion. Thus, we have confirmed the neuroprotective effect of AT2R stimulation using a nonpeptide compound which highlights the clinical potential of the AT2R agonists for future development

Chemical Looping Combustion and Chemical Looping with Oxygen Uncoupling Experiments in a Batch Reactor Using Spray-Dried CaMn1–xMxO3−δ (M = Ti, Fe, Mg) Particles as Oxygen Carriers

Chemical looping combustion and chemical looping with oxygen uncoupling (CLOU) with oxygen carrier particles consisting of CaMn1-xMxO3-delta (M = Ti, Fe, Mg) has been studied by consecutive oxidation and reduction experiments in a fluidized-bed batch reactor. The examined particles were produced by spray drying, and all did show a significant release of gas-phase oxygen to the inert atmosphere at 900 and 1000 degrees C. All particles also provided very high reactivity with syngas and methane. Some of the examined particles showed unfavorable fluidization characteristics, i.e., they formed dust during operation or showed agglomeration or defluidization tendencies. The crushing strength of the particles that formed dust was typically <1.2 N. The desired perovskite structure was detected in all samples by X-ray diffractometry. The materials that included iron and titanium had these elements incorporated in the perovskite structure, substituting manganese. When magnesium had been included, it was not incorporated into the crystal structure; instead, it was present as a separate phase of MgO. In addition to a perovskite phase, most samples also contained small amounts of marokite (CaMn2O4). Particles doped with MgO calcined at 1300 degrees C showed good fluidization behavior, as well as particularly high reactivity with fuel

Combined Oxides of Iron, Manganese and Silica as Oxygen Carriers for Chemical-Looping Combustion

Spray-dried particles with the chemical compositions of Fe0.66Mn1.33SiO3 and FeMnSiO3 have been examined as oxygen carrier materials for chemical-looping combustion. The performance of the materials was examined in oxygen release experiments and during fuel operation with natural gas and syngas. The experiments were carried out in a fluidized-bed chemical-looping reactor system designed for a thermal power of 300 W. The reactor system includes an air reactor and a fuel reactor, as well as loop seals and means for circulation of the oxygen carrier particles. Both materials were able to release gas phase oxygen in inert atmosphere at temperatures between 800-950°C, and with approximately equal oxygen concentrations. Fe0.66Mn1.33SiO3 provided higher conversion of natural gas as compared to FeMnSiO3 and the fuel conversion increased with temperature for both materials. During natural gas operation with Fe0.66Mn1.33SiO3 the conversion reached 100% at around 950°C with a fuel reactor inventory of 235 kg/MW. The fuel conversion was improved when the solids inventory was increased; this improvement could especially be observed for FeMnSiO3 as the fuel conversion was lower for this material. Fe0.66Mn1.33SiO3 provided higher fuel conversion than FeMnSiO3 also when syngas was used as fuel. The fuel conversion increased with temperature for both materials and full conversion was reached above 800°C with a fuel reactor inventory of 225 kg/MW for Fe0.66Mn1.33SiO3, while FeMnSiO3 was incapable of providing full conversion. A rather large elutriation of fines and a significant change in particle size distribution could be observed during operation for both materials. Both materials could work as oxygen carrier for chemical-looping with oxygen uncoupling. Fe0.66Mn1.33SiO3 would be preferred as it has higher conversion of both syngas and natural gas, but the attrition behavior of the material would need to be further investigated

Angiotensin II, a Neuropeptide at the Frontier between Endocrinology and Neuroscience: Is There a Link between the Angiotensin II Type 2 Receptor and Alzheimer’s Disease?

Amyloid-β peptide deposition, abnormal hyperphosphorylation of tau, as well as inflammation and vascular damage, are associated with the development of Alzheimer’s disease (AD). Angiotensin II (Ang II) is a peripheral hormone, as well as a neuropeptide, which binds two major receptors, namely the Ang II type 1 receptor (AT1R) and the type 2 receptor (AT2R). Activation of the AT2R counteracts most of the AT1R-mediated actions, promoting vasodilation, decreasing the expression of pro-inflammatory cytokines, both in the brain and in the cardiovascular system. There is evidence that treatment with AT1R blockers (ARBs) attenuates learning and memory deficits. Studies suggest that the therapeutic effects of ARBs may reflect this unopposed activation of the AT2R in addition to the inhibition of the AT1R. Within the context of AD, modulation of AT2R signaling could improve cognitive performance not only through its action on blood flow/brain microcirculation but also through more specific effects on neurons. This review summarizes the current state of knowledge and potential therapeutic relevance of central actions of this enigmatic receptor. In particular, we highlight the possibility that selective AT2R activation by non-peptide and highly selective agonists, acting on neuronal plasticity, could represent new pharmacological tools that may help improve impaired cognitive performance in AD and other neurological cognitive disorders

Oxygen-Carrier Development of Calcium Manganite–Based Materials with Perovskite Structure for Chemical-Looping Combustion of Methane

The present work is related to the upscaling of calcium manganite–based oxygen-carrier materials, which have a perovskite structure, both with respect to the use of inexpensive raw materials, i.e., instead of pure chemicals, and the upscaling of production to multitonne batches. Results are presented from the two different stages of material development, i.e., raw material selection and upscaling. The evaluation involves both operation in chemical-looping combustor units of 300 W and 10 kW, and material characterization. In the latter unit, the gas velocities in the riser and in the grid-jet zone of the gas distributor come close to gas velocities of industrial-scale units and, therefore, this unit is also used to assess particle lifetime. Results from the various chemical-looping combustion units and oxygen-carrier materials produced from various raw materials of both high and low purity show that very high degrees of fuel conversion can be reached while achieving very high oxygen-carrier lifetimes. The composition of the oxygen-carrier materials seems robust and flexible with respect to the precursors used in its manufacturing

Coping with chronic pain: In-depth interviews with children suffering from Juvenile Chronic Arthritis

This study examined from the perspective of children with Juvenile Chronic Arthritis, their experiences of coping with chronic pain in daily life. In-depth interviews were conducted with 22 children (6–17 years). The grounded theory method was applied for analysing the taped and transcribed interviews. Seven descriptive categories were grounded in the data, labelled (1) “controlling strategies”, (2) “avoidance strategies”, (3) “cognitive strategies”, (4) “compliance with the treatment”, (5) “seeking social support”, and (6) “recovering”. A core category was identified and labelled “making me different”. The children seem to be caught in a dilemma. In one way the chosen coping strategy reduces chronic pain and in another way the strategy increases stress and feelings of being different from non-disabled peers. Our results indicate the great importance of social support from the children's environment

Combining scanning haptic microscopy and fibre optic Raman spectroscopy for tissue characterization

The tactile resonance method (TRM) and Raman spectroscopy (RS) are promising for tissue characterization in vivo. Our goal is to combine these techniques into one instrument, to use TRM for swift scanning, and RS for increasing the diagnostic power. The aim of this study was to determine the classification accuracy, using support vector machines, for measurements on porcine tissue and also produce preliminary data on human prostate tissue. This was done by developing a new experimental set-up combining micro-scale TRM—scanning haptic microscopy (SHM)—for assessing stiffness on a micro-scale, with fibre optic RS measurements for assessing biochemical content. We compared the accuracy using SHM alone versus SHM combined with RS, for different degrees of tissue homogeneity. The cross-validation classification accuracy for healthy porcine tissue types using SHM alone was 65–81%, and when RS was added it increased to 81–87%. The accuracy for healthy and cancerous human tissue was 67–70% when only SHM was used, and increased to 72–77% for the combined measurements. This shows that the potential for swift and accurate classification of healthy and cancerous prostate tissue is high. This is promising for developing a tool for probing the surgical margins during prostate cancer surgery

NMR relaxation rates for the spin-1/2 Heisenberg chain

The spin-lattice relaxation rate $1/T_1$ and the spin echo decay rate $1/T_{2G}$ for the spin-$1\over 2$ antiferromagnetic Heisenberg chain are calculated using quantum Monte Carlo and maximum entropy analytic continuation. The results are compared with recent analytical calculations by Sachdev. If the nuclear hyperfine form factor $A_q$ is strongly peaked around $q=\pi$ the predicted low-temperature behavior [$1/T_1 \sim \ln{^{1/2}(1/T)}$, $1/T_{2G} \sim \ln{^{1/2}(1/T)}/\sqrt{T}$] extends up to temperatures as high as $T/J \approx 0.5$. If $A_q$ has significant weight for $q \approx 0$ there are large contributions from diffusive long-wavelength processes not taken into account in the theory, and very low temperatures are needed in order to observe the asymptotic $T \to 0$ forms.Comment: 9 pages, Revtex 3.0, 5 uuencoded ps figures To appear in Phys. Rev. B, Rapid Com