Oral administration of the KATP channel opener diazoxide ameliorates disease progression in a murine model of multiple sclerosis

Background Multiple Sclerosis (MS) is an acquired inflammatory demyelinating disorder of the central nervous system (CNS) and is the leading cause of nontraumatic disability among young adults. Activated microglial cells are important effectors of demyelination and neurodegeneration, by secreting cytokines and others neurotoxic agents. Previous studies have demonstrated that microglia expresses ATP-sensitive potassium (KATP) channels and its pharmacological activation can provide neuroprotective and anti-inflammatory effects. In this study, we have examined the effect of oral administration of KATP channel opener diazoxide on induced experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Methods Anti-inflammatory effects of diazoxide were studied on lipopolysaccharide (LPS) and interferon gamma (IFNy)-activated microglial cells. EAE was induced in C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55). Mice were orally treated daily with diazoxide or vehicle for 15 days from the day of EAE symptom onset. Treatment starting at the same time as immunization was also assayed. Clinical signs of EAE were monitored and histological studies were performed to analyze tissue damage, demyelination, glial reactivity, axonal loss, neuronal preservation and lymphocyte infiltration. Results Diazoxide inhibited in vitro nitric oxide (NO), tumor necrosis factor alpha (TNF-¿) and interleukin-6 (IL-6) production and inducible nitric oxide synthase (iNOS) expression by activated microglia without affecting cyclooxygenase-2 (COX-2) expression and phagocytosis. Oral treatment of mice with diazoxide ameliorated EAE clinical signs but did not prevent disease. Histological analysis demonstrated that diazoxide elicited a significant reduction in myelin and axonal loss accompanied by a decrease in glial activation and neuronal damage. Diazoxide did not affect the number of infiltrating lymphocytes positive for CD3 and CD20 in the spinal cord. Conclusion Taken together, these results demonstrate novel actions of diazoxide as an anti-inflammatory agent, which might contribute to its beneficial effects on EAE through neuroprotection. Treatment with this widely used and well-tolerated drug may be a useful therapeutic intervention in ameliorating MS disease.

Reduction of symmetry in grandite solid solution

The results of a crystal structure refinement of an anisotropic grandite garnet specimen with composition Gro36-4 And63-6 are given. The structure obtained has orthorrombic symmetry (space group Fddd) and is compared with similar results obtained by other authors. In all cases the reduction of symmetry is due to the ordering of Fe3+ and Al in octahedral sites. Non cubic structures of grandites are discussed in connection with optical, morphological an grou-th features of these minerals.

Von Neumann-Morgenstern solution and convex descompositions of TU games

We study under which conditions the core of a game involved in a convex decomposition of another game turns out to be a stable set of the decomposed game. Some applications and numerical examples, including the remarkable Lucas¿ five player game with a unique stable set different from the core, are reckoning and analyzed.

Zenith angle distributions at Super-Kamiokande and SNO and the solution of the solar neutrino problem

We have performed a detailed study of the zenith angle dependence of the regeneration factor and distributions of events at SNO and SK for different solutions of the solar neutrino problem. In particular, we discuss the oscillatory behavior and the synchronization effect in the distribution for the LMA solution, the parametric peak for the LOW solution, etc. A physical interpretation of the effects is given. We suggest a new binning of events which emphasizes the distinctive features of the zenith angle distributions for the different solutions. We also find the correlations between the integrated day-night asymmetry and the rates of events in different zenith angle bins. The study of these correlations strengthens the identification power of the analysis.

A Rotating black ring solution in five dimensions

The vacuum Einstein equations in five dimensions are shown to admit a solution describing a stationary asymptotically flat spacetime regular on and outside an event horizon of topology S1S2. It describes a rotating black ring. This is the first example of a stationary asymptotically flat vacuum solution with an event horizon of nonspherical topology. The existence of this solution implies that the uniqueness theorems valid in four dimensions do not have simple five-dimensional generalizations. It is suggested that increasing the spin of a spherical black hole beyond a critical value results in a transition to a black ring, which can have an arbitrarily large angular momentum for a given mass.

Exact solution to the mean exit time problem for free inertial processes driven by Gaussian white noise

We obtain the exact analytical expression, up to a quadrature, for the mean exit time, T(x,v), of a free inertial process driven by Gaussian white noise from a region (0,L) in space. We obtain a completely explicit expression for T(x,0) and discuss the dependence of T(x,v) as a function of the size L of the region. We develop a new method that may be used to solve other exit time problems.

Continued fraction solution for the radiative transfer equation in three dimensions

Starting from the radiative transfer equation, we obtain an analytical solution for both the free propagator along one of the axes and an arbitrary phase function in the Fourier-Laplace domain. We also find the effective absorption parameter, which turns out to be very different from the one provided by the diffusion approximation. We finally present an analytical approximation procedure and obtain a differential equation that accurately reproduces the transport process. We test our approximations by means of simulations that use the Henyey-Greenstein phase function with very satisfactory results.

Solution to telegrapher's equation in the presence of reflecting and partly reflecting broundaries

We show that the reflecting boundary condition for a one-dimensional telegraphers equation is the same as that for the diffusion equation, in contrast to what is found for the absorbing boundary condition. The radiation boundary condition is found to have a quite complicated form. We also obtain exact solutions of the telegraphers equation in the presence of these boundaries.

Exact solution to the exit-time problem for an undamped free particle driven by Gaussian white noise

In a recent paper [Phys. Rev. Lett. 75, 189 (1995)] we have presented the exact analytical expression for the mean exit time, T(x,v), of a free inertial process driven by Gaussian white noise out of a region (0,L) in space. In this paper we give a detailed account of the method employed and present results on asymptotic properties and averages of T(x,v).

Strong coupling solution to Schrödinger Equation: the mixing of states

In this paper we give some ideas that can be useful to solve Schrödinger equations in the case when the Hamiltonian contains a large term. We obtain an expansion of the solution in reciprocal powers of the large coupling constant. The procedure followed consists in considering that the small part of the Hamiltonian engenders a motion adiabatic to the motion generated by the large part of the same.

Corpus Oral Dialectal (COD). Caràtula

Aquest document conté la imatge de la caràtula del CD "COD. Corpus Oral Dialectal". El COD és un component del Corpus de Català Contemporani de la Universitat de Barcelona (CCCUB), un arxiu de corpus de llengua catalana oral contemporània que ha estat confegit pel grup de recerca Grup d'Estudi de la Variació (GEV) amb la finalitat de contribuir a l'estudi de la variació dialectal, social i funcional en la llengua catalana. Aquest i altres materials del CCCUB són accessibles directament al Dipòsit Digital de la UB (http://diposit.ub.edu) o a través del web del CCCUB (http://www.ub.edu/cccub).

Some spectral properties of the canonical solution operator to $\bar\partial$ on weighted Fock spaces

We characterize the Schatten class membership of the canonical solution operator to $\overline{\partial}$ acting on $L^2(e^{-2\phi})$, where $\phi$ is a subharmonic function with $\Delta\phi$ a doubling measure. The obtained characterization is in terms of $\Delta\phi$. As part of our approach, we study Hankel operators with anti-analytic symbols acting on the corresponding Fock space of entire functions in $L^2(e^{-2\phi})$

Von Neumann-Morgenstern solution and convex descompositions of TU games

We study under which conditions the core of a game involved in a convex decomposition of another game turns out to be a stable set of the decomposed game. Some applications and numerical examples, including the remarkable Lucas¿ five player game with a unique stable set different from the core, are reckoning and analyzed.

In rats, oral oleoyl-DHEA is rapidly hydrolysed and converted to DHEA-sulphate

Background: Dehydroepiandrosterone (DHEA) released by adrenal glands may be converted to androgens and estrogens mainly in the gonadal, adipose, mammary, hepatic and nervous tissue. DHEA is also a key neurosteroid and has antiglucocorticoid activity. DHEA has been used for the treatment of a number of diseases, including obesity; its pharmacological effects depend on large oral doses, which effect rapidly wanes in part because of its short half-life in plasma. Since steroid hormone esters circulate for longer periods, we have studied here whether the administration of DHEA oleoyl ester may extend its pharmacologic availability by keeping high circulating levels. Results: Tritium-labelled oleoyl-DHEA was given to Wistar male and female rats by gastric tube. The kinetics of appearance of the label in plasma was unrelated to sex; the pattern being largely coincident with the levels of DHEA-sulfate only in females, and after 2 h undistinguishable from the results obtained using labelled DHEA gavages; in the short term, practically no lipophilic DHEA label was found in plasma. After 24 h only a small fraction of the label remained in the rat organs, with a different sex-related distribution pattern coincident for oleoyl- and free- DHEA gavages. The rapid conversion of oleoyl-DHEA into circulating DHEA-sulfate was investigated using stomach, liver and intestine homogenates; which hydrolysed oleoyl-DHEA optimally near pH 8. Duodenum and ileum contained the highest esterase activities. Pure hog pancreas cholesterol-esterase broke down oleoyl-DHEA at rates similar to those of oleoyl-cholesterol. The intestinal and liver esterases were differently activated by taurocholate and showed different pH-activity patterns than cholesterol esterase, suggesting that oleoyl-DHEA can be hydrolysed by a number of esterases in the lumen (e.g. cholesterol-esterase), in the intestinal wall and the liver. Conclusion: The esterase activities found may condition the pharmacological availability (and depot effect) of orally administered steroid hormone fatty acid esters such as oleoyl-DHEA. The oral administration of oleoyl-DHEA in order to extend DHEA plasma availability has not been proved effective, since the ester is rapidly hydrolysed, probably in the intestine itself, and mainly converted to DHEA-sulfate at least in females.