169 research outputs found

    Monge's transport problem in the Heisenberg group

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    We prove the existence of solutions to Monge transport problem between two compactly supported Borel probability measures in the Heisenberg group equipped with its Carnot-Caratheodory distance assuming that the initial measure is absolutely continuous with respect to the Haar measure of the group

    Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

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    he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

    Lateralized periodic discharges in insular status epilepticus: A case report of a periodic EEG pattern associated with ictal manifestation

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    Objective: Insular lobe seizures generally represent a misconceived ictal phenomenon characterized by specific neurological signs. Aphasia can be a rare presenting sign associated with insular lobe epilepsy which could be easily mistaken for a manifestation of other acute brain diseases. Method: We describe an insular status epilepticus (SE) characterized by sudden onset of language disturbance associated with hypersalivation and paraesthesia. A concomitant EEG recording showed the presence of Lateralized Periodic Discharges plus superimposed fast activity (LPDs + F). After an adequate acute endovenous anti-seizure treatment, a normalization of the EEG abnormalities with a complete resolution of all the neurological symptoms was achieved. Discussion: Language disturbances can be usually found in various pathological acute pictures involving the dominant frontal and temporal lobes. The presence of certain EEG pattern, could rise the suspect of aphasia as a critical manifestation. LPDs pattern is usually correlated with structural lesions. The association between LPDs and seizure is controversial but it seems to be more consistent when they are associated with “Plus modifiers” and with an high periodic frequency. Conclusion: Our case underlines the importance of considering focal SE in the differential diagnosis of patients presenting aphasia, even in the absence of previous history of epilepsy. We describe how LPDs can be associated with SE in a patient affected by a brain tumour, supporting the idea that some characteristic periodic patterns could be associated with seizure occurrence

    Weak formulation for singular diffusion equation with dynamic boundary condition

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    In this paper, we propose a weak formulation of the singular diffusion equation subject to the dynamic boundary condition. The weak formulation is based on a reformulation method by an evolution equation including the subdifferential of a governing convex energy. Under suitable assumptions, the principal results of this study are stated in forms of Main Theorems A and B, which are respectively to verify: the adequacy of the weak formulation; the common property between the weak solutions and those in regular problems of standard PDEs.Comment: 23 page

    Plant communities of Italy. The vegetation prodrome

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    The Vegetation Prodrome of Italy was promoted in 2012 by the Italian "Ministry of Environment, Land and Sea Protection", in collaboration with the "Italian Society of Botany", to provide a comprehensive and systematic catalogue and description of Italian plant communities. The Prodrome that is presented in this paper is the first full organic synthesis of the vegetation of Italy at the alliance syntaxonomic level. It fulfils several needs, the main one being a unified and comprehensive national framework that may make an important contribution to the definition of the European Vegetation Prodrome. Syntaxonomy, as well as taxonomy, is sometimes based on considerations that may in part diverge: several authors tend to favour models that are divisive or aggregative to a greater or lesser extent in terms of flora, biogeography and ecology. These different points of view stimulate the scientific debate and allow the adoption of a framework that is more widely supported. The Prodrome includes 75 classes, 2 subclasses, 175 orders, 6 suborders and 393 alliances. The classes were grouped into nine broad categories according to structural, physiognomic and synecological elements rather than to syntaxonomic criteria. The rank, full valid name, any synonymies and incorrect names are provided for each syntaxon. The short declaration highlights the physiognomy, synecology, syndynamics and distribution of the plant communities that belong to the syntaxon. The Prodrome of the Italian Vegetation is linked to the European Strategy for Biodiversity, the European Habitats Directive and the European Working Groups related to the ecosystems and their services. In addition to basic applications, the Prodrome can be used as a framework for scientific research related to the investigation of the relationships between plant communities and the environmental factors that influence their composition and distribution

    The prescribed mean curvature equation in weakly regular domains

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    We show that the characterization of existence and uniqueness up to vertical translations of solutions to the prescribed mean curvature equation, originally proved by Giusti in the smooth case, holds true for domains satisfying very mild regularity assumptions. Our results apply in particular to the non-parametric solutions of the capillary problem for perfectly wetting fluids in zero gravity. Among the essential tools used in the proofs, we mention a \textit{generalized Gauss-Green theorem} based on the construction of the weak normal trace of a vector field with bounded divergence, in the spirit of classical results due to Anzellotti, and a \textit{weak Young's law} for (Λ,r0)(\Lambda,r_{0})-minimizers of the perimeter.Comment: 23 pages, 1 figure --- The results on the weak normal trace of vector fields have been now extended and moved in a self-contained paper available at: arXiv:1708.0139

    Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation.

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    A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4- (methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies

    X-ray irradiated cultures of mouse cortical neural stem/progenitor cells recover cell viability and proliferation with dose-dependent kinetics

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    Exposure of the developing or adult brain to ionizing radiation (IR) can cause cognitive impairment and/ or brain cancer, by targeting neural stem/progenitor cells (NSPCs). IR effects on NSPCs include transient cell cycle arrest, permanent cell cycle exit/differentiation, or cell death, depending on the experimental conditions. In vivo studies suggest that brain age influences NSPC response to IR, but whether this is due to intrinsic NSPC changes or to niche environment modifications remains unclear. Here, we describe the dose-dependent, time-dependent effects of X-ray IR in NSPC cultures derived from the mouse foetal cerebral cortex. We show that, although cortical NSPCs are resistant to low/moderate IR doses, high level IR exposure causes cell death, accumulation of DNA double-strand breaks, activation of p53- related molecular pathways and cell cycle alterations. Irradiated NSPC cultures transiently upregulate differentiation markers, but recover control levels of proliferation, viability and gene expression in the second week post-irradiation. These results are consistent with previously described in vivo effects of IR in the developing mouse cortex, and distinct from those observed in adult NSPC niches or in vitro adult NSPC cultures, suggesting that intrinsic differences in NSPCs of different origins might determine, at least in part, their response to IR

    Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation.

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    A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new 1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies

    Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitrooxyalkyl ethers and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors

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    A series of 3-substituted 1,5-diarylpyrroles bearing a nitrooxyalkyl side chain linked to different spacers were designed. New classes of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as COX-2 selective inhibitors and NO donors were synthesized and are herein reported. By taking into account the metabolic conversion of nitrooxyalkyl ethers (9, 10) into corresponding alcohols, derivatives 17 and 18 were also studied. Nitrooxy derivatives showed NO-dependent vasorelaxing properties, while most of the compounds proved to be very potent and selective COX-2 inhibitors in in vitro experimental models. Further in vivo studies on compounds 9a,c and 17a highlighted good anti-inflammatory and antinociceptive activities. Compound 9c was able to inhibit glycosaminoglycan (GAG) release induced by interleukin-1β (IL-1β), showing cartilage protective properties. Finally, molecular modeling and (1)H- and (13)C-NMR studies performed on compounds 6c,d, 9c, and 10b allowed the right conformation of nitrooxyalkyl ester and ether side chain of these molecules within the COX-2 active site to be assessed
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