6,452 research outputs found
In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine
BACKGROUND: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. Five species of Schistosoma are known to infect humans, out of which S. haematobium is the most prevalent, causing the chronic parasitic disease schistosomiasis that still represents a major problem of public health in many regions of the world and especially in tropical areas, leading to serious manifestations and mortality in developing countries. Since the 1970s, praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis, but concerns about relying on a single drug to treat millions of people, and the potential appearance of drug resistance, make identification of alternative schistosomiasis chemotherapies a high priority. Alkylphospholipid analogs (APLs), together with their prototypic molecule edelfosine (EDLF), are a family of synthetic antineoplastic compounds that show additional pharmacological actions, including antiparasitic activities against several protozoan parasites. METHODOLOGY/PRINCIPAL FINDINGS: We found APLs ranked edelfosine> perifosine> erucylphosphocholine> miltefosine for their in vitro schistosomicidal activity against adult S. mansoni worms. Edelfosine accumulated mainly in the worm tegument, and led to tegumental alterations, membrane permeabilization, motility impairment, blockade of male-female pairing as well as induction of apoptosis-like processes in cells in the close vicinity to the tegument. Edelfosine oral treatment also showed in vivo schistosomicidal activity and decreased significantly the egg burden in the liver, a key event in schistosomiasis. CONCLUSIONS/SIGNIFICANCE: Our data show that edelfosine is the most potent APL in killing S. mansoni adult worms in vitro. Edelfosine schistosomicidal activity seems to depend on its action on the tegumental structure, leading to tegumental damage, membrane permeabilization and apoptosis-like cell death. Oral administration of edelfosine diminished worm and egg burdens in S. mansoni-infected CD1 mice. Here we report that edelfosine showed promising antischistosomal properties in vitro and in vivo
Synthesis of a new chiral bis-arsine ligand based on natural carbohydrates
Transition-metal-catalyzed asymmetric allylic substitutions have become one of the most powerful tools for asymmetric C−C bond formation.1 Chiral diphosphine ligands have been some of the largest classes of ligands used in asymmetric substitutions.
Trost developed the chiral ligand, which played a crucial role in the improvement of Pdcatalyzed asymmetric substitutions.2 Based on the Trost modular ligand (TML) system 3 a family of ligands has been prepared. We recently reported the synthesis and application of the novel chiral bis-arsine ligand 2 derived from TML.http://blucherproceedings.com.br/articles/details/2323Fil: Parajón Puenzoa, Sol C. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina.Fil: Parajón Puenzoa, Sol C. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina.Fil: Parajón Puenzoa, Sol C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil: Parajón Puenzoa, Sol C. Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Hidratos de Carbonos; Argentina.Fil: Arata Badano, Joaquín. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina.Fil: Arata Badano, Joaquín. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina.Fil: Lopez Vidal, Martin G. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina.Fil: Lopez Vidal, Martin G. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina.Fil: Varela, Oscar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil: Varela, Oscar. Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Hidratos de Carbonos; Argentina.Fil: Martín, Sandra E. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina.Fil: Martín, Sandra E. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina.Química Orgánic
The Role of CagA Protein Signaling in Gastric Carcinogenesis — CagA Signaling in Gastric Carcinogenesis
Cholecystokinin in the central nervous system of the sea lamprey Petromyzon marinus: precursor identification and neuroanatomical relationships with other neuronal signalling systems
Cholecystokinin (CCK) is a neuropeptide that modulates processes such as digestion, satiety, and anxiety. CCK-type peptides have been characterized in jawed vertebrates and invertebrates, but little is known about CCK-type signalling in the most ancient group of vertebrates, the agnathans. Here, we have cloned and sequenced a cDNA encoding a sea lamprey (Petromyzon marinus L.) CCK-type precursor (PmCCK), which contains a CCK-type octapeptide sequence (PmCCK-8) that is highly similar to gnathostome CCKs. Using mRNA in situ hybridization, the distribution of PmCCK-expressing neurons was mapped in the CNS of P. marinus. This revealed PmCCK-expressing neurons in the hypothalamus, posterior tubercle, prethalamus, nucleus of the medial longitudinal fasciculus, midbrain tegmentum, isthmus, rhombencephalic reticular formation, and the putative nucleus of the solitary tract. Some PmCCK-expressing neuronal populations were only observed in adults, revealing important differences with larvae. We generated an antiserum to PmCCK-8 to enable immunohistochemical analysis of CCK expression, which revealed that GABA or glutamate, but not serotonin, tyrosine hydroxylase or neuropeptide Y, is co-expressed in some PmCCK-8-immunoreactive (ir) neurons. Importantly, this is the first demonstration of co-localization of GABA and CCK in neurons of a non-mammalian vertebrate. We also characterized extensive cholecystokinergic fibre systems of the CNS, including innervation of habenular subnuclei. A conspicuous PmCCK-8-ir tract ascending in the lateral rhombencephalon selectively innervates a glutamatergic population in the dorsal isthmic grey. Interestingly, this tract is reminiscent of the secondary gustatory/visceral tract of teleosts. In conclusion, this study provides important new information on the evolution of the cholecystokinergic system in vertebrates.</p
High Prevalence of Systemic Autoimmune Diseases in Patients with Menière's Disease
BACKGROUND: Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). METHODS AND FINDINGS: We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS: Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD
Limitaciones de la tomografia axial computada en la localizacion de quistes hidatidicos abdominales en pacientes con confirmacion inmunodiagnostica
The Large Aperture GRB Observatory
The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the
high energy (around 100 GeV) component of Gamma Ray Bursts, using the single
particle technique in arrays of Water Cherenkov Detectors (WCD) in high
mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela,
4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer
a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range.
The status of the Observatory and data collected from 2007 to date will be
presented.Comment: 4 pages, proceeding of 31st ICRC 200
Water Cherenkov Detectors response to a Gamma Ray Burst in the Large Aperture GRB Observatory
In order to characterise the behaviour of Water Cherenkov Detectors (WCD)
under a sudden increase of 1 GeV - 1 TeV background photons from a Gamma Ray
Burst (GRB), simulations were conducted and compared to data acquired by the
WCD of the Large Aperture GRB Observatory (LAGO). The LAGO operates arrays of
WCD at high altitude to detect GRBs using the single particle technique. The
LAGO sensitivity to GRBs is derived from the reported simulations of the gamma
initiated particle showers in the atmosphere and the WCD response to
secondaries.Comment: 5 pages, proceeding of the 31st ICRC 200
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