The Endocannabinoid System in the Mediterranean Mussel Mytilus galloprovincialis: Possible Mediators of the Immune Activity?

Anandamide (AEA) is one of the best characterized members of the endocannabinoid family and its involvement in many pathophysiological processes has been well documented in vertebrates and invertebrates. Here, we report the biochemical and functional characterization of key elements of the endocannabinoid system in hemocytes isolated from the Mediterranean mussel Mytilus galloprovincialis. We also show the effects of exogenous AEA, as well as of capsaicin, on the cell ability to migrate and to activate the respiratory burst, upon in vitro stimulation of phagocytosis. Interestingly, our findings show that both AEA and capsaicin suppress the hemocyte response and that the use of selective antagonists of CB2 and TRPV1 receptors revert their inhibitory effects. Overall, present data support previous evidence on the presence of endocannabinoid signaling in mollusks and advance our knowledge about the evolutionary origins of this endogenous system and its role in the innate response of mollusks

Limitations to testing the equivalence principle with satellite laser ranging

Abstract We consider the possibility of testing the equivalence principle (EP) in the gravitational field of the Earth from the orbits of LAGEOS and LAGEOS II satellites, which are very accurately tracked from ground by laser ranging. The orbital elements that are affected by an EP violation and can be used to measure the corresponding dimensionless parameter ? are semimajor axis and argument of pericenter. We show that the best result is obtained from the semimajor axis, and it is limited-with all available ranging data to LAGEOS and LAGEOS II-to ? = 2 × 10-9, more than 3 orders of magnitude worse than experimental results provided by torsion balances. The experiment is limited because of the non uniformity of the gravitational field of the Earth and the error in the measurement of semimajor axis, precisely in the same way as they limit the measurement of the product GM of the Earth. A better use of the pericenter of LAGEOS II can be made if the data are analyzed searching for a new Yukawa-like interaction with a distance scale of one Earth radius. It is found that the pericenter of LAGEOS II is 3 orders of magnitude more sensitive to a composition dependent new interaction with this particular scale than it is to a composition dependent effect expressed by the ? parameter only. Nevertheless, the result is still a factor 500 worse than EP tests with torsion balances in the gravitational field of the Earth (i.e. at comparable distance), though a detailed data analysis has yet to be performed. While EP tests with satellite laser ranging are not competitive, laser ranging to the Moon has been able to provide a test of the EP almost 1 order of magnitude better than torsion balances. We show that this is due to the much greater distance of the test masses (the Earth and the Moon) from the primary body (the Sun) and the correspondingly smaller gradients of its gravity field. We therefore consider a similar new experiment involving the orbit of LAGEOS: testing LAGEOS and the Earth for an EP violation in the gravitational field of the Sun. We show that this test may be of interest, though it is a factor 300 less sensitive than in the case of the Moon due to the fact that LAGEOS is closer to the Earth than theMoon and consequently its orbit is less affected by the Sun. The limitations we have pointed out for laser ranging can be overcome by flying in low Earth orbit a spacecraft carrying concentric test masses of different composition with the capability, already demonstrated in ground laboratories, to accurately sense in situ any differential effects between them

Limitations to testing the equivalence principle with satellite laser ranging

Abstract We consider the possibility of testing the equivalence principle (EP) in the gravitational field of the Earth from the orbits of LAGEOS and LAGEOS II satellites, which are very accurately tracked from ground by laser ranging. The orbital elements that are affected by an EP violation and can be used to measure the corresponding dimensionless parameter ? are semimajor axis and argument of pericenter. We show that the best result is obtained from the semimajor axis, and it is limited-with all available ranging data to LAGEOS and LAGEOS II-to ? = 2 × 10-9, more than 3 orders of magnitude worse than experimental results provided by torsion balances. The experiment is limited because of the non uniformity of the gravitational field of the Earth and the error in the measurement of semimajor axis, precisely in the same way as they limit the measurement of the product GM of the Earth. A better use of the pericenter of LAGEOS II can be made if the data are analyzed searching for a new Yukawa-like interaction with a distance scale of one Earth radius. It is found that the pericenter of LAGEOS II is 3 orders of magnitude more sensitive to a composition dependent new interaction with this particular scale than it is to a composition dependent effect expressed by the ? parameter only. Nevertheless, the result is still a factor 500 worse than EP tests with torsion balances in the gravitational field of the Earth (i.e. at comparable distance), though a detailed data analysis has yet to be performed. While EP tests with satellite laser ranging are not competitive, laser ranging to the Moon has been able to provide a test of the EP almost 1 order of magnitude better than torsion balances. We show that this is due to the much greater distance of the test masses (the Earth and the Moon) from the primary body (the Sun) and the correspondingly smaller gradients of its gravity field. We therefore consider a similar new experiment involving the orbit of LAGEOS: testing LAGEOS and the Earth for an EP violation in the gravitational field of the Sun. We show that this test may be of interest, though it is a factor 300 less sensitive than in the case of the Moon due to the fact that LAGEOS is closer to the Earth than theMoon and consequently its orbit is less affected by the Sun. The limitations we have pointed out for laser ranging can be overcome by flying in low Earth orbit a spacecraft carrying concentric test masses of different composition with the capability, already demonstrated in ground laboratories, to accurately sense in situ any differential effects between them

Indomethacin-Dipalmitoylphosphatidylcholine Interaction. A Calorimetric Study of Drug Release from Poly(Lactide-co-glycolide) Microspheres into Multilamellar Vesicles.

A comparative study of indomethacin controlled release from poly(lactide-co-glycolide) (50:50, molecular weight 3000) (PLGA) microspheres loaded with two different amounts of drug (10.9 ± 1%, and 34.1 ± 1% w/w) and pure free indomethacin, considering the effects exerted by the drug on the thermotropic behavior of dipalmitoylphosphatidylcholine multilamellar vesicles, was carried out by differential scanning calorimetry (DSC). The release was monitored by comparing the effect exerted by the free indomethacin on lipid thermotropic behavior with that of the drug released by the microspheres and relating these effects to a lipid aqueous dispersion containing the molar ratio of drug able to cause it. By DSC measurements, the pure free indomethacin was found to be able to have a fluidifying effect on the model membrane, causing a shift toward lower values of the transitional temperature (Tm), characteristic of phospholipid liposomes, without variations in the enthalpic changes (ΔH). This shift was found to be modulated by the drug molar fraction with respect to the lipid concentration in the aqueous dispersion. Successively, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of unloaded and indometha-cin-loaded microspheres as well as free powdered indomethacin, and the Tm shifts of the lipid bilayer caused by the drug released from the polymeric system, as well as by the free drug, were compared with that caused by free drug increasing molar fractions dispersed directly on the membrane, employed as a calibration curve to obtain the fraction of drug released. This drug release model could be employed to determine the different kinetics involved in the drug transfer from the microspheres to a membrane. This in vitro study suggests that the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres. This calorimetric study shows that the PLGA microspheres are a good delivery system able to sustain drug release. Moreover, the DSC technique applied to the drug interaction with biomembranes constitutes a good tool for determining the drug release representing an innovative alternative in vitro model

Italian validation of the Penn Acoustic Neuroma Quality of Life Scale (PANQOL-It)

Objective: translate and validate the Penn Acoustic Neuroma Quality of Life Scale into Italian language (PANQOL-It). Methods: the instrument was translated and psychometric properties were subsequently assessed by administering the PANQOL-It to 124 outpatients together with the Depression Anxiety Stress Scale (DASS21) and the Understanding and Communicating domain of the World Health Organization Disability Assessment Schedule II (WHODAS II-D1). The internal consistency, test-retest reliability, construct and criterion-related validity were assessed. Results: Cronbach's alpha coefficient was 0.92 for the total score and ranged from 0.44 to 0.90 in the seven domains. Significant test-retest reliability was observed (intraclass-correlation = 0.75; p < 0.01). Moderate correlation was reported between facial dysfunction domain and objective facial involvement (p < 0.01). Moderate to strong correlations were observed between anxiety, general health domains and all subscales of the DASS21, and between WHODAS II-D1 and general health and energy domains (p < 0.01). These latter results indicated good construct and criterion-related validity respectively. Conclusions: PANQOL-It presented more than acceptable psychometric properties and its adoption is justified for both clinical and research purposes

EXPERIMENTAL VALIDATION OF A HIGH ACCURACY TEST OF THE EQUIVALENCE PRINCIPLE WITH THE SMALL SATELLITE "GALILEO GALILEI"

The small satellite "Galileo Galilei" (GG) has been designed to test the equivalence principle (EP) to 10-17 with a total mass at launch of 250 kg. The key instrument is a differential accelerometer made up of weakly coupled coaxial, concentric test cylinders rapidly spinning around the symmetry axis and sensitive in the plane perpendicular to it, lying at a small inclination from the orbit plane. The whole spacecraft spins around the same symmetry axis so as to be passively stabilized. The test masses are large (10 kg each, to reduce thermal noise), their coupling is very weak (for high sensitivity to differential effects), and rotation is fast (for high frequency modulation of the signal). A 1 g version of the accelerometer ("Galileo Galilei on the Ground" — GGG) has been built to the full scale — except for coupling, which cannot be as weak as in the absence of weight, and a motor to maintain rotation (not needed in space due to angular momentum conservation). GGG has proved: (i) high Q; (ii) auto-centering and long term stability; (iii) a sensitivity to EP testing which is close to the target sensitivity of the GG experiment provided that the physical properties of the experiment in space are going to be fully exploited

Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis

Genetic ablation of type-1 cannabinoid receptors (CB1Rs) exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS). To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles) had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT), in fact, showed more severe alterations of the retinal nerve fiber layer (RNFL) thickness and of the macular volume (MV) after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI) evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS

on a rapidly converging iterative algorithm for diode parameter extraction from a single iv curve

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