3,280 research outputs found

    Effects of Gabaergic phenols on phospholipid bilayers as evaluated by 1H-NMR

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    The phenols propofol and thymol, and lately carvacrol, eugenol and chlorothymol, have been shown to act as positive allosteric modulators on GABAA receptor, which is the main inhibitory receptor of the central nervous system. GABAA receptor is an intrinsic membrane protein which activity may be affected by surface-active compounds and by physical changes in the membrane. Recently, we demonstrated that these phenols interacted with the lipid membrane phase, suggesting their anesthetic activity could be the combined result of their specific (with receptor proteins) as well as nonspecific (with surrounding lipid molecules) interaction modulating the supramolecular organization of the receptor environment. In the current study, by using 1H-NMR spectroscopy, we have investigated the effects of the insertion and the possible preferential location of the five phenol derivatives with GABAergic activity on EPC membranes. The results indicate that all compounds are able to insert in EPC phospholipid vesicles and to locate in the region between the polar group (choline molecule), the glycerol and the first atoms of the acyl chains, being the more lipophilic compounds (propofol and chlorothymol) that seem to prefer a deeper bilayer insertion. The location of the phenol molecules would reduce the repulsive forces among phospholipids head groups allowing closer molecular packing and finally diminishing the mobility of the hydrocarbon chains, as revealed by 1H spin relaxation times.Fil: Reiner, Gabriela de Las Nieves. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas. Universidad Nacional de C贸rdoba. Facultad de Ciencias Exactas, F铆sicas y Naturales. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas; Argentina. Universidade Estadual de Campinas; Brasil. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Fraceto, Leonardo Fernandes. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Paula, Eneida de. Universidade Estadual de Campinas; BrasilFil: Perillo, Maria Angelica. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas. Universidad Nacional de C贸rdoba. Facultad de Ciencias Exactas, F铆sicas y Naturales. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas; ArgentinaFil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas. Centro Cient铆fico Tecnol贸gico Conicet - C贸rdoba. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas. Universidad Nacional de C贸rdoba. Facultad de Ciencias Exactas, F铆sicas y Naturales. Instituto de Investigaciones Biol贸gicas y Tecnol贸gicas; Argentin

    Strong and Long-Lasting Antinociceptive and Anti-inflammatory Conjugate of Naturally Occurring Oleanolic Acid and Aspirin

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    The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7) and aspirin in dioxane. Analgesic effect of OAO-ASA (8) for the range of doses 0.3 鈥 300.0 mg/kg (p.o.) was performed in mice using a hot plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8) did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30.0 mg/kg. After its combined administration with morphine (MF, 5.0 mg/kg, s.c.) the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c.) did not affect the antinociceptive effect of OAO-ASA (8), therefore its opioid mechanism of action should be rather excluded. After combined administration with acetylsalicylic acid (ASA, 300.0 mg/kg, p.o.) in hot-plate test, the examined compound 8 enhanced the antinociceptive activity in significant way. It also shows that rather the whole molecule is responsible for the antinociceptive and anti-inflammatory effect of the tested compound 8, however it cannot be excluded that the summarizing effect is produced by ASA released from the compound 8 and the rest of triterpene derivative. The occurrence of tolerance for triterpenic derivative 8 was not observed, since the analgesic and anti-inflammatory effects after chronic administration of the conjugate OAO-ASA (8) was on the same level as after its single treatment. It seemed that the anti-inflammatory mechanism of action of OAO-ASA (8) is not simple, even its chronic administration lowered both blood concentration of IL-6 and mRNA IL-6 expression. However, the effects of the conjugate OAO-ASA (8) on TNF-伪 level and mRNA expression were opposite. Moreover, compound 8 did not change unequivocally mRNA TLR1, and TLR3 expression. Concluding, the obtained results regarding the antinociceptive and anti-inflammatory activity of new conjugate of oleanolic acid oxime and acetylsalicylic acid (OAO-ASA 8) are very interesting, but for explanation of its mechanism of action, more detailed studies are necessary

    Introgression Among Cultivated and Wild Grapevine in Tuscany

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    Wild grapevine, Vitis vinifera L. subsp. sylvestris (Gmelin, Hegi) is spontaneous to Europe and common in Tuscany. In this study, wild grapevines were identified in 22 populations from eight locations in Tuscan Maremma (Grosseto and Siena province). The plants were propagated by cuttings, collected in a vineyard, genotyped by nuclear simple sequence repeats (SSRs), chloroplast SSRs and single nucleotide polymorphisms (SNPs), and compared to locally cultivated varieties (Vitis vinifera L. subsp. sativa) and to non-vinifera and non-vitis genotypes. The identity analysis revealed that some individuals were redundant genotypes, suggesting natural vegetative propagation. In addition, four of the supposed V.v. sylvestris were in fact naturalized V.v. sativa. The majority of putative sylvestris genotypes had chlorotype A, while the remainder had chlorotype D, as the majority of Vitis vinifera subsp. sativa cultivated in Italy. Some of the recovered sylvestris genotypes appeared to be natural crosses with cultivated grapevine varieties in Tuscany, and their chlorotype suggests a higher pollen flow from sativa to the sylvestris genotypes than in the opposite direction. In addition, other genotypes appeared to be crosses within sylvestris, sylvestris-sativa or sylvestris-sylvestris siblings, or equivalent relationships. These relationships suggest a noticeably level of sexual reproductive activities among sylvestris and sylvestris-sativa genotypes. A cluster and structure analysis clearly differentiated the true sylvestris from the sativa, and the nonvinifera or non-vitis genotypes, and also highlighted a possible introgression of sylvestris into some Italian and French cultivated varieties. The results therefore suggest that, in addition to the primary ancient center of domestication from the Near East to Central Asia, the introgression among cultivated and wild grapevine occurred in other centers of diversification along the migration routes, contributing to the domestication processes, and suggesting that these processes are still ongoing despite the reduction in populations of sylvestris. The results also highlight that the GrapeReSeq 18K Vitis genotyping chip are suitable for non-vitis genotyping and that the range of SNPs heterozygosity in sylvestris appears to be up to 6% less and does not overlap the heterozygosity range of sativa genotypes

    Desarrollo de una aplicaci贸n web para la radicaci贸n y el control de problemas en la cl铆nica MAR CARIBE.

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    El departamento de Sistemas de la Cl铆nica Mar Caribe busca mejorar sus procesos en cuanto a la evaluaci贸n, asignaci贸n y respuesta de las solicitudes de soporte que realizan los usuarios de la empresa a Sistemas. La necesidad de mejora se debe a que en promedio, alrededor del 50% de las solicitudes que llegan al departamento de Sistemas no son resueltos de manera inmediata porque en ocasiones se acumulan con otros que estaban antes, o que se deja un servicio a medias y no se termina porque se tuvo que empezar otro que ten铆a m谩s prioridad, como estas razones y otras m谩s son las responsables de que no se completen algunas tareas y a ra铆z de esto se genere una molestia al usuario porque le toca volver a solicitar la ayuda. Debido a esto el departamento de Sistemas solicit贸 el desarrollo de una aplicaci贸n web que permita registrar y gestionar las solicitudes que lleguen al Departamento para controlar de mejor manera las prioridades que se le dan a las solicitudes y saber a qui茅n corresponden estas solicitudes, tener un historial de las peticiones que a煤n no se les ha dado respuesta y disponer de alertas en la aplicaci贸n que avisen acerca de los tickets que llevan un determinado n煤mero de d铆as sin cambiar su estado
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