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  • 1
    Publication Date: 2018-05-22
    Description: Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts various vascular and cardioprotective functions and regulates immune function and inflammatory response at multiple levels. However, its role in inflammatory cardiovascular disorders is largely unknown. Myocarditis and atherosclerosis are two inflammatory and autoimmune cardiovascular diseases that cause important adverse circulatory events. In this study, we investigate the therapeutic effects of VIP in various well-established preclinical models of experimental autoimmune myocarditis and atherosclerosis. Intraperitoneal injection of VIP during the effector phase of experimental autoimmune myocarditis in susceptible BALB/c mice significantly reduced its prevalence, ameliorated signs of heart hypertrophy and injury, attenuated myocardial inflammatory infiltration, and avoided subsequent profibrotic cardiac remodeling. This effect was accompanied by a reduction of Th17-driven cardiomyogenic responses in peripheral lymphoid organs and in the levels of myocardial autoantibodies. In contrast, acute and chronic atherosclerosis was induced in apolipoprotein E–deficient mice fed a hyperlipidemic diet and subjected to partial carotid ligation. Systemic VIP treatment reduced the number and size of atherosclerotic plaques in carotid, aorta, and sinus in hypercholesterolemic mice. VIP reduced Th1-driven inflammatory responses and increased regulatory T cells in atherosclerotic arteries and their draining lymph nodes. VIP also regulated cholesterol efflux in macrophages and reduced the formation of foam cells and their presence in atherosclerotic plaques. Finally, VIP inhibited proliferation and migration of smooth muscle cells and neointima formation in a mouse model of complete carotid ligation. These findings encourage further studies aimed to assess whether VIP can be used as a pharmaceutical agent to treat heart inflammation and atherosclerosis.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Publication Date: 2015-06-25
    Description: An epidemic of Ebola virus disease of unprecedented scale has been ongoing for more than a year in West Africa. As of 29 April 2015, there have been 26,277 reported total cases (of which 14,895 have been laboratory confirmed) resulting in 10,899 deaths. The source of the outbreak was traced to the prefecture of Gueckedou in the forested region of southeastern Guinea. The virus later spread to the capital, Conakry, and to the neighbouring countries of Sierra Leone, Liberia, Nigeria, Senegal and Mali. In March 2014, when the first cases were detected in Conakry, the Institut Pasteur of Dakar, Senegal, deployed a mobile laboratory in Donka hospital to provide diagnostic services to the greater Conakry urban area and other regions of Guinea. Through this process we sampled 85 Ebola viruses (EBOV) from patients infected from July to November 2014, and report their full genome sequences here. Phylogenetic analysis reveals the sustained transmission of three distinct viral lineages co-circulating in Guinea, including the urban setting of Conakry and its surroundings. One lineage is unique to Guinea and closely related to the earliest sampled viruses of the epidemic. A second lineage contains viruses probably reintroduced from neighbouring Sierra Leone on multiple occasions, while a third lineage later spread from Guinea to Mali. Each lineage is defined by multiple mutations, including non-synonymous changes in the virion protein 35 (VP35), glycoprotein (GP) and RNA-dependent RNA polymerase (L) proteins. The viral GP is characterized by a glycosylation site modification and mutations in the mucin-like domain that could modify the outer shape of the virion. These data illustrate the ongoing ability of EBOV to develop lineage-specific and potentially phenotypically important variation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simon-Loriere, Etienne -- Faye, Ousmane -- Faye, Oumar -- Koivogui, Lamine -- Magassouba, Nfaly -- Keita, Sakoba -- Thiberge, Jean-Michel -- Diancourt, Laure -- Bouchier, Christiane -- Vandenbogaert, Matthias -- Caro, Valerie -- Fall, Gamou -- Buchmann, Jan P -- Matranga, Christan B -- Sabeti, Pardis C -- Manuguerra, Jean-Claude -- Holmes, Edward C -- Sall, Amadou A -- England -- Nature. 2015 Aug 6;524(7563):102-4. doi: 10.1038/nature14612. Epub 2015 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut Pasteur, Functional Genetics of Infectious Diseases Unit, 75724 Paris Cedex 15, France [2] CNRS URA3012, Paris 75015, France. ; Institut Pasteur de Dakar, Arbovirus and Viral Hemorrhagic Fever Unit, BP 220, Dakar, Senegal. ; Institut National de Sante Publique de Guinee, Conakry, Guinea. ; Projet de fievres hemorragiques de Guinee, Universite Gamal Abdel Nasser, BP 1147, Conakry, Guinea. ; Ministry of Health, BP 585 Conakry, Guinea. ; Institut Pasteur, Unite Environnement et Risques Infectieux, Cellule d'Intervention Biologique d'Urgence, 75724 Paris Cedex 15, France. ; Institut Pasteur, Genomic platform, 75724 Paris Cedex 15, France. ; Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia. ; Broad Institute, 75 Ames Street, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute, 75 Ames Street, Cambridge, Massachusetts 02142, USA [2] FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, 52 Oxford Street, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Topical application of clobetasol-17-propionate has been diffusely reported as an efficacious therapy in atrophic/erosive oral lichen planus (OLP), without exposing the patient to systemic side-effects. However, prolonged contact and respective topical effects on the oral mucosa should be avoided.Objectives  The aim of the present study was to evaluate efficacy and compliance of new lipid microspheres loaded with 0·025% of clobetasol propionate (formulation A) compared with a commonly used formulation (a sort of dispersion of a lipophilic ointment in a hydrophilic phase) with the same amount of drug (formulation B) in the topical treatment of OLP.Patients and methods  Fifty patients with symptomatic OLP were enrolled in a controlled single-blind phase IV clinical trial. After a dropout of five patients, a total of 45 patients [12 males and 33 females; mean age 61·1 years (± 12·3 SD; range 25–82)] were treated (17 with formulation A and 28 with formulation B, matched for gender and age; P 〉 0·2) with the same dosage regimen. At times T0, T1 and T2 we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0–100); (ii) clinical score; (iii) clinical resolution; and (iv) patient compliance. Statistical analysis was calculated using S-Plus 4.0 and SPSS 9.0 (Student's t-test, χ2, Kolmogorov–Smirnow, Friedman, Student–Newman–Keuls, Mann–Whitney U-test and Spearman tests).Results  Both formulations were found to be similar for parameters ii, iii and iv, although with a better general trend for formulation A; a significant difference was registered for formulation A in terms of a reduction in painful symptoms (parameter i) at time T2 (P = 0·02).Conclusions  Our results suggest that the new topical drug delivery system (formulation A) may enhance, at least in terms of symptom remission and compliance, the effectiveness of clobetasol propionate at a dose of 0·025% in OLP therapy.
    Type of Medium: Electronic Resource
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