Asunto(s)

Epilepsia Mioclónica Juvenil , Femenino , Embarazo , Humanos , Epilepsia Mioclónica Juvenil/tratamiento farmacológico , Mujeres Embarazadas , Pirrolidinonas/uso terapéutico , Anticonvulsivantes/uso terapéutico , Resultado del Tratamiento

RESUMEN

BACKGROUND: In prior studies, HIV-1 BF recombinants with subtype F integrases failed to develop resistance to raltegravir through the Q148H mutational pathway. We aimed to determine the role of subtype-specific polymorphisms in integrase on drug susceptibility, viral replication and integration. METHODS: Integrase sequences were retrieved from the Los Alamos Database or obtained from the Garrahan HIV cohort. HIV-1 infectious molecular clones with or without Q148H (+ G140S) resistance mutations were constructed using integrases of subtype B (NL4-3) or F1(BF) ARMA159 and URTR23. Integrase chimeras were generated by reciprocal exchanges of a 200 bp fragment spanning amino acids 85-150 of the catalytic core domain (CCD) of NL4-3-Q148H and either ARMA159-Q148H or URTR23-Q148H. Viral infections were quantified by p24 ELISA and Alu-gag integration PCR assay. RESULTS: At least 18 different polymorphisms distinguish subtype B from F1(BF) recombinant integrases. In phenotypic experiments, p24 at Day 15 post-infection was high (105-106 pg/mL) for WT and NL4-3-Q148H; by contrast, it was low (102-104 pg/mL) for both F1(BF)-Q148H + G140S viruses, and undetectable for the Q148H mutants. Compared with WT viruses, integrated DNA was reduced by 5-fold for NL4-3-Q148H (P = 0.05), 9-fold for URTR23-Q148H (P = 0.01) and 16000-fold for ARMA159-Q148H (P = 0.01). Reciprocal exchange between B and F1(BF) of an integrase CCD region failed to rescue the replicative defect of F1(BF) integrase mutants. CONCLUSIONS: The functional impairment of Q148H in the context of subtype F integrases from BF recombinants explains the lack of selection of this pathway in vivo. Non-B polymorphisms external to the integrase CCD may influence the pathway to integrase strand transfer inhibitor resistance.

Asunto(s)

Infecciones por VIH , Inhibidores de Integrasa VIH , Integrasa de VIH , VIH-1 , Aminoácidos/uso terapéutico , Dominio Catalítico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Integrasa de VIH/metabolismo , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/uso terapéutico , VIH-1/genética , Humanos , Mutación , Pirrolidinonas/farmacología , Raltegravir Potásico/farmacología , Raltegravir Potásico/uso terapéutico

RESUMEN

Antimicrobial resistance is one of the current public health challenges to be solved. The World Health Organization (WHO) has urgently called for the development of strategies to expand the increasingly limited antimicrobial arsenal. The development of anti-virulence therapies is a viable option to counteract bacterial infections with the possibility of reducing the generation of resistance. Here we report on the chemical structures of pyrrolidones DEXT 1-4 (previously identified as furan derivatives) and their anti-virulence activity on Pseudomonas aeruginosa strains. DEXT 1-4 were shown to inhibit biofilm formation, swarming motility, and secretion of ExoU and ExoT effector proteins. Also, the anti-pathogenic property of DEXT-3 alone or in combination with furanone C-30 (quorum sensing inhibitor) or MBX-1641 (type III secretion system inhibitor) was analyzed in a model of necrosis induced by P. aeruginosa PA14. All treatments reduced necrosis; however, only the combination of C-30 50 µM with DEXT-3 100 µM showed significant inhibition of bacterial growth in the inoculation area and systemic dispersion. In conclusion, pyrrolidones DEXT 1-4 are chemical structures capable of reducing the pathogenicity of P. aeruginosa and with the potential for the development of anti-virulence combination therapies.

Asunto(s)

Antibacterianos , Furanos , Hidrocarburos Halogenados , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Pirrolidinonas , Sistemas de Secreción Tipo III/antagonistas & inhibidores , Animales , Antibacterianos/química , Antibacterianos/farmacología , Furanos/química , Furanos/farmacología , Humanos , Hidrocarburos Halogenados/química , Hidrocarburos Halogenados/farmacología , Ratones , Necrosis , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/metabolismo , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/patogenicidad , Pirrolidinonas/química , Pirrolidinonas/farmacología , Percepción de Quorum/efectos de los fármacos , Sistemas de Secreción Tipo III/metabolismo , Factores de Virulencia/metabolismo

RESUMEN

Lysophosphatidic acid (LPA) acts through the activation of G protein-coupled receptors, in a Ca2+-dependent manner. We show the effects of LPA on the plasma membrane Ca2+-ATPase (PMCA) from kidney proximal tubule cells. The Ca2+-ATPase activity was inhibited by nanomolar concentrations of LPA, with maximal inhibition (~50%) obtained with 20 nM LPA. This inhibitory action on PMCA activity was blocked by Ki16425, an antagonist for LPA receptors, indicating that this lipid acts via LPA1 and/or LPA3 receptor. This effect is PKC-dependent, since it is abolished by calphostin C and U73122, PKC, and PLC inhibitors, respectively. Furthermore, the addition of 10-8 M PMA, a well-known PKC activator, mimicked PMCA modulation by LPA. We also demonstrated that the PKC activation leads to an increase in PMCA phosphorylation. These results indicate that LPA triggers LPA1 and/or LPA3 receptors at the BLM, inducing PKC-dependent phosphorylation with further inhibition of PMCA. Thus, LPA is part of the regulatory lipid network present at the BLM and plays an important role in the regulation of intracellular Ca2+ concentration that may result in significant physiological alterations in other Ca2+-dependent events ascribed to the renal tissue.

Asunto(s)

Calcio/metabolismo , Membrana Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Lisofosfolípidos/farmacología , ATPasas Transportadoras de Calcio de la Membrana Plasmática/genética , Receptores del Ácido Lisofosfatídico/genética , Animales , Fraccionamiento Celular , Membrana Celular/metabolismo , Células Epiteliales/citología , Células Epiteliales/metabolismo , Estrenos/farmacología , Regulación de la Expresión Génica , Transporte Iónico/efectos de los fármacos , Isoxazoles/farmacología , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Naftalenos/farmacología , Fosforilación/efectos de los fármacos , ATPasas Transportadoras de Calcio de la Membrana Plasmática/antagonistas & inhibidores , ATPasas Transportadoras de Calcio de la Membrana Plasmática/metabolismo , Cultivo Primario de Células , Propionatos/farmacología , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Pirrolidinonas/farmacología , Receptores del Ácido Lisofosfatídico/antagonistas & inhibidores , Receptores del Ácido Lisofosfatídico/metabolismo , Transducción de Señal , Porcinos , Acetato de Tetradecanoilforbol/farmacología , Fosfolipasas de Tipo C/antagonistas & inhibidores , Fosfolipasas de Tipo C/genética , Fosfolipasas de Tipo C/metabolismo

RESUMEN

Allatotropin is a pleiotropic peptide originally characterized in insects. The existence of AT neuropeptide signaling was proposed in other invertebrates. In fact, we previously proposed the presence of an AT-like system regulating feeding behavior in Hydra sp. Even in insects, the information about the AT signaling pathway is incomplete. The aim of this study is to analyze the signaling cascade activated by AT in Hydra plagiodesmica using a pharmacological approach. The results show the involvement of Ca2+ and IP3 signaling in the transduction pathway of the peptide. Furthermore, we confirm the existence of a GPCR system involved in this pathway, that would be coupled to a Gq subfamily of Gα protein, which activates a PLC, inducing an increase in IP3 and cytosolic Ca2+. To the best of our knowledge, this work represents the first in vivo approach to study the overall signaling pathway and intracellular events involved in the myoregulatory effect of AT in Hydra sp.

Asunto(s)

Señalización del Calcio , Hydra/metabolismo , Hormonas de Insectos/metabolismo , Neuropéptidos/metabolismo , Orexinas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Estrenos/farmacología , Proteínas de Unión al GTP/metabolismo , Indoles/farmacología , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Maleimidas/farmacología , Meliteno/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Pirrolidinonas/farmacología , Fosfolipasas de Tipo C/antagonistas & inhibidores , Fosfolipasas de Tipo C/metabolismo

RESUMEN

INTRODUCTION: This study investigated the effect of a calcium hydroxide (CH) paste (CleaniCal®) containing N-2-methyl pyrrolidone (NMP) as a vehicle on Enterococcus faecalis (E. faecalis) biofilms compared with other products containing saline (Calasept Plus™) or propylene glycol (PG) (Calcipex II®). METHODOLOGY: Standardized bovine root canal specimens were used. The antibacterial effects were measured by colony-forming unit counting. The thickness of bacterial microcolonies and exopolysaccharides was assessed using confocal laser scanning microscopy. Morphological features of the biofilms were observed using field-emission scanning electron microscopy (FE-SEM). Bovine tooth blocks covered with nail polish were immersed into the vehicles and dispelling was observed. The data were analyzed using one-way analysis of variance and Tukey tests (p<0.05). RESULTS: CleaniCal® showed the highest antibacterial activity, followed by Calcipex II® (p<0.05). Moreover, NMP showed a higher antibacterial effect compared with PG (p<0.05). The thickness of bacteria and EPS in the CleaniCal® group was significantly lower than that of other materials tested (p<0.05). FE-SEM images showed the specimens treated with Calasept Plus™ were covered with biofilms, whereas the specimens treated with other medicaments were not. Notably, the specimen treated with CleaniCal® was cleaner than the one treated with Calcipex II®. Furthermore, the nail polish on the bovine tooth block immersed in NMP was completely dispelled. CONCLUSIONS: CleaniCal® performed better than Calasept Plus™ and Calcipex II® in the removal efficacy of E. faecalis biofilms. The results suggest the effect might be due to the potent dissolving effect of NMP on organic substances.

Asunto(s)

Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Hidróxido de Calcio/farmacología , Enterococcus faecalis/efectos de los fármacos , Pirrolidinonas/farmacología , Irrigantes del Conducto Radicular/farmacología , Análisis de Varianza , Animales , Cloruro de Calcio/química , Cloruro de Calcio/farmacología , Hidróxido de Calcio/química , Bovinos , Recuento de Colonia Microbiana , Combinación de Medicamentos , Ensayo de Materiales , Microscopía Confocal , Microscopía Electrónica de Rastreo , Cloruro de Potasio/química , Cloruro de Potasio/farmacología , Pirrolidinonas/química , Reproducibilidad de los Resultados , Irrigantes del Conducto Radicular/química , Bicarbonato de Sodio/química , Bicarbonato de Sodio/farmacología , Cloruro de Sodio/química , Cloruro de Sodio/farmacología , Estadísticas no Paramétricas

RESUMEN

Neryl butyrate is a constituent of volatile oils obtained from aromatic plants. Aliphatic organic compound analogues chemically close to neryl butyrate possess vasodilator properties in rat aorta. To evaluate whether neryl butyrate has relaxing properties, this study tested its effects on isolated rat aorta. Unlike the analogues, neryl butyrate did not show relaxant profile in aortic rings precontracted with phenylephrine, but induced a contraction when it stimulated aortic rings under resting tonus. The contractile effect augmented in endothelium-denuded aortic rings. Treatment of endothelium-intact preparations with the nitric oxide synthase inhibitor L-NAME or the guanylyl cyclase inhibitor ODQ also augmented the contractile effect of neryl butyrate. Such phenomenon was absent in the presence of the cyclooxygenase inhibitor indomethacin. Contractile responses decreased in the presence of verapamil, a L-type Ca2+ channel blocker, or when Ca2+ was removed from the extracellular solution. Antagonists of α-adrenergic receptors (prazosin and yohimbine), but not the thromboxane-prostanoid receptor seratrodast, reversed the contraction induced by neryl butyrate. The α1A selective antagonist RS-17053 antagonized the neryl butyrate-induced contraction. The contraction caused by neryl butyrate was decreased by inhibiting the phospholipase C or the rho-associated kinase with U-73122 or Y-27632, respectively. Injected intravenously to awake rats, neryl butyrate induced arterial hypotension and bradycardia. Decreased frequency was also present in isolated right atrium preparations. In conclusion, the contractile effects of neryl butyrate were inhibited by α-adrenergic antagonists, indicating the involvement of α-adrenoceptors in the mechanism of action. In vivo, neryl butyrate caused hypotension, suggesting that other systemic influence than vasoconstriction may occur.

Asunto(s)

Aorta Torácica/efectos de los fármacos , Butiratos/farmacología , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Agonistas alfa-Adrenérgicos/farmacología , Amidas/farmacología , Animales , Aorta Torácica/fisiología , Calcio/farmacología , Estrenos/farmacología , Atrios Cardíacos/efectos de los fármacos , Técnicas In Vitro , Masculino , Fenilefrina/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Pirrolidinonas/farmacología , Ratas Wistar

RESUMEN

Glyphosate (GLY)-dicamba (DIC) and GLY-flurochloridone (FLC) are herbicide mixtures which are widely used for treating fallow containing glyphosate resistant weeds. The aim of this study was to evaluate the acute toxic effects and the prevailing interactions on stage 36 tadpoles of the anuran species Rhinella arenarum when exposed to equitoxic and non-equitoxic combinations of these herbicide combinations. Experiments were realized using the following combinations of commercial formulations: 48% GLY-based Credit® + 57.71% DIC-based Banvel® and 48% GLY-based Credit® + 25% FLC-based Twin Pack Gold®. GLY-DIC and GLY-FLC equitoxic mixtures were assayed mixing each constituent with an equivalent individual toxicity able to induce the same lethality effect. After 96 h of exposure, GLY-DIC and GLY-FLC equitoxic mixtures presented toxic unit 50 values (TU50 96h) of 1.74 (confidence interval: 1.58-1.92) and 1.54 (confidence interval: 1.46-1.62) respectively, indicating the presence of a weak antagonistic interaction as TU values were greater than 1. For their part, most non-equitoxic combinations of GLY-DIC and GLY-FLC tested did not significantly differ from additivity, the only exception being when DIC and FLC were fixed at 0.33 TUs, where a weak antagonism was observed. Overall, results indicate that the toxicity of both GLY-DIC and GLY-FLC mixtures to R. arenarum tadpoles vary from additive to slightly antagonistic, depending on the proportion of constituting herbicide formulations present in the mixture.

Asunto(s)

Bufonidae , Dicamba/toxicidad , Glicina/análogos & derivados , Herbicidas/toxicidad , Larva/efectos de los fármacos , Animales , Anuros , Mezclas Complejas/toxicidad , Antagonismo de Drogas , Glicina/toxicidad , Pirrolidinonas/toxicidad , Glifosato

RESUMEN

Abstract This study investigated the effect of a calcium hydroxide (CH) paste (CleaniCal®) containing N-2-methyl pyrrolidone (NMP) as a vehicle on Enterococcus faecalis (E. faecalis) biofilms compared with other products containing saline (Calasept Plus™) or propylene glycol (PG) (Calcipex II®). Methodology Standardized bovine root canal specimens were used. The antibacterial effects were measured by colony-forming unit counting. The thickness of bacterial microcolonies and exopolysaccharides was assessed using confocal laser scanning microscopy. Morphological features of the biofilms were observed using field-emission scanning electron microscopy (FE-SEM). Bovine tooth blocks covered with nail polish were immersed into the vehicles and dispelling was observed. The data were analyzed using one-way analysis of variance and Tukey tests (p<0.05). Results CleaniCal® showed the highest antibacterial activity, followed by Calcipex II® (p<0.05). Moreover, NMP showed a higher antibacterial effect compared with PG (p<0.05). The thickness of bacteria and EPS in the CleaniCal® group was significantly lower than that of other materials tested (p<0.05). FE-SEM images showed the specimens treated with Calasept Plus™ were covered with biofilms, whereas the specimens treated with other medicaments were not. Notably, the specimen treated with CleaniCal® was cleaner than the one treated with Calcipex II®. Furthermore, the nail polish on the bovine tooth block immersed in NMP was completely dispelled. Conclusions CleaniCal® performed better than Calasept Plus™ and Calcipex II® in the removal efficacy of E. faecalis biofilms. The results suggest the effect might be due to the potent dissolving effect of NMP on organic substances.

Asunto(s)

Animales , Bovinos , Pirrolidinonas/farmacología , Irrigantes del Conducto Radicular/farmacología , Hidróxido de Calcio/farmacología , Enterococcus faecalis/efectos de los fármacos , Biopelículas/efectos de los fármacos , Antibacterianos/farmacología , Cloruro de Potasio/farmacología , Cloruro de Potasio/química , Pirrolidinonas/química , Irrigantes del Conducto Radicular/química , Ensayo de Materiales , Cloruro de Calcio/farmacología , Cloruro de Calcio/química , Hidróxido de Calcio/química , Microscopía Electrónica de Rastreo , Cloruro de Sodio/farmacología , Cloruro de Sodio/química , Recuento de Colonia Microbiana , Reproducibilidad de los Resultados , Análisis de Varianza , Bicarbonato de Sodio/farmacología , Bicarbonato de Sodio/química , Estadísticas no Paramétricas , Microscopía Confocal , Combinación de Medicamentos

RESUMEN

Human kallikreins 5 and 7 (KLK5 and KLK7) exhibit trypsin- and chymotrypsin-like activities and are involved in pathologies related to skin desquamation process. A series of new 3-acyltetramic acids were developed as a novel class of inhibitors of KLK5, KLK7 and trypsin enzymes. The nature and length of the acyl chain is crucial to the KLK5, KLK7 and trypsin inhibition activities, and the most potent compounds (but not the most selective) 2b, 2c and 2g showed low micromolar IC50 values. While very few of the compounds were selective for KLK5, the selective inhibition of trypsin against chymotrypsin was achieved. Our molecular modelling studies revealed that the double bond in 2g provided the best fit in the binding site of KLK5, while the hydrogen bonding interactions modulated the best fit of 2c in the binding site of KLK7 due to the hydrophobicity of the cavity.

Asunto(s)

Calicreínas/antagonistas & inhibidores , Pirrolidinonas/química , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Calicreínas/química , Modelos Moleculares , Simulación del Acoplamiento Molecular , Conformación Proteica , Relación Estructura-Actividad

RESUMEN

Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks. In this work we developed two different strategies for the synthesis of intermediates used on the synthesis of levetiracetam/brivaracetam and ethambutol. The results obtained show that methionine methyl ester can be continuously converted to the desired ethambutol intermediate by RANEY® Nickel dessulfurization/reduction strategy whereas levetiracetam/brivaracetam intermediates could be synthesized by both RANEY® Nickel (without H2) and Pd/C-H2 approach or by photochemical desulfurization.

Asunto(s)

Anticonvulsivantes/síntesis química , Anticonvulsivantes/farmacología , Antituberculosos/síntesis química , Antituberculosos/farmacología , Anticonvulsivantes/química , Antituberculosos/química , Técnicas de Química Sintética , Etambutol/síntesis química , Etambutol/química , Etambutol/farmacología , Levetiracetam/síntesis química , Levetiracetam/química , Levetiracetam/farmacología , Pirrolidinonas/síntesis química , Pirrolidinonas/química , Pirrolidinonas/farmacología , Estereoisomerismo , Azufre/química

RESUMEN

Phytoplankton blooms can cause acute effects on marine ecosystems due either to their production of endogenous toxins or to their enormous biomass leading to major impacts on local economies and public health. Despite years of effort, the causes of these Harmful Algal Blooms are still not fully understood. Our hypothesis is that bacteria that produce photoactive siderophores may provide a bioavailable source of iron for phytoplankton which could in turn stimulate algal growth and support bloom dynamics. Here we correlate iron concentrations, phytoplankton cell counts, bacterial cell abundance, and copy numbers for a photoactive siderophore vibrioferrin biosynthesis gene in water samples taken from 2017 cruises in the Gulf of California, and the Pacific Ocean off the coast of northern Baja California as well as during a multiyear sampling at Scripps Pier in San Diego, CA. We find that bacteria producing the photoactive siderophore vibrioferrin, make up a surprisingly high percentage of total bacteria in Pacific/Gulf of California coastal waters (up to 9%). Vibroferrin's unique properties and the widespread prevalence of its bacterial producers suggest that it may contribute significantly to generating bioavailability of iron via photoredox reactions.

Asunto(s)

Citratos/biosíntesis , Hierro/metabolismo , Marinobacter/química , Sideróforos/biosíntesis , California , Citratos/química , Hierro/química , Marinobacter/metabolismo , México , Pirrolidinonas/química , Sideróforos/química

RESUMEN

Artificial insemination with cooled semen is the most common practice in rabbit farms and any improvement on it helps to increase the efficiency and productivity of rabbit meat farms. Therefore, the aim of this study was to assess whether different cryoprotectant agents (CPA) as glycerol, N, N-Dimethylformamide (DMF) and N-Methyl-2-Pyrrolidone (NMP) can improve cooled rabbit sperm quality stored at 4ºC and 16ºC. Sperm samples were diluted with INRA 96® (Extender A), INRA 96® with 6% glycerol (Extender B) or 6% DMF (Extender C) or 6% NMP (Extender D) respectively and stored at 4ºC and 16ºC. Samples were then analysed at 4, 24, 48 and 72 hours after refrigeration by integrated sperm analysis system (ISAS®), eosin-nigrosin stain (vitality), hypo-osmotic swelling test (HOS test) and acrosome integrity test. Extender C showed higher percentage of motility, vitality and HOS test than extender B and D (p<0.05). Whereas sperm quality decreased over time (p<0.05), data showed that the addition of DMF kept the motility and sperm plasma membrane integrity after 24 hours of storage better than other diluents. These results suggest that the addition of DMF to INRA 96® exerts a protective effect on the membrane of spermatozoa improving seminal quality.

Asunto(s)

Masculino , Animales , Conejos , Conejos/fisiología , Dimetilformamida/análisis , Dimetilformamida/efectos adversos , Glicerol/análisis , Glicerol/efectos adversos , Pirrolidinonas/análisis , Semen/citología , Semen/química , Crioprotectores/análisis , Inseminación Artificial/veterinaria

RESUMEN

Artificial insemination with cooled semen is the most common practice in rabbit farms and any improvement on it helps to increase the efficiency and productivity of rabbit meat farms. Therefore, the aim of this study was to assess whether different cryoprotectant agents (CPA) as glycerol, N, N-Dimethylformamide (DMF) and N-Methyl-2-Pyrrolidone (NMP) can improve cooled rabbit sperm quality stored at 4ºC and 16ºC. Sperm samples were diluted with INRA 96® (Extender A), INRA 96® with 6% glycerol (Extender B) or 6% DMF (Extender C) or 6% NMP (Extender D) respectively and stored at 4ºC and 16ºC. Samples were then analysed at 4, 24, 48 and 72 hours after refrigeration by integrated sperm analysis system (ISAS®), eosin-nigrosin stain (vitality), hypo-osmotic swelling test (HOS test) and acrosome integrity test. Extender C showed higher percentage of motility, vitality and HOS test than extender B and D (p<0.05). Whereas sperm quality decreased over time (p<0.05), data showed that the addition of DMF kept the motility and sperm plasma membrane integrity after 24 hours of storage better than other diluents. These results suggest that the addition of DMF to INRA 96® exerts a protective effect on the membrane of spermatozoa improving seminal quality.(AU)

Asunto(s)

Animales , Masculino , Conejos , Conejos/fisiología , Semen/química , Semen/citología , Glicerol/efectos adversos , Glicerol/análisis , Dimetilformamida/efectos adversos , Dimetilformamida/análisis , Pirrolidinonas/análisis , Inseminación Artificial/veterinaria , Crioprotectores/análisis

RESUMEN

Many organisms use chemicals to deter enemies. Some spiders can modify the composition of their silk to deter predators from climbing onto their webs. The Malaysian golden orb-weaver Nephila antipodiana (Walckenaer) produces silk containing an alkaloid (2-pyrrolidinone) that functions as a defense against ant invasion-ants avoid silk containing this chemical. In the present study, we test the generality of ants' silk avoidance behavior in the field. We introduced three ant species to the orb webs of Nephila clavipes (Linnaeus) in the tropical rainforest of La Selva, Costa Rica. We found that predatory army ants (Eciton burchellii Westwood) as well as non-predatory leaf-cutting ants (Atta cephalotes Linnaeus and Acromyrmex volcanus Wheeler) avoided adult N. clavipes silk, suggesting that an additional species within genus Nephila may possess ant-deterring silk. Our field assay also suggests that silk avoidance behavior is found in multiple ant species.

Asunto(s)

Hormigas/fisiología , Conducta Animal , Pirrolidinonas/química , Seda/química , Arañas/química , Animales , Costa Rica , Femenino

RESUMEN

Polyaniline nanoparticles (PANI-NPs) were easily obtained applying the solvent displacement method by using N-methylpyrrolidone (NMP) as good solvent and water as poor solvent. Different polymers such as polyvinylpyrrolidone (PVP), chondroitin sulfate (ChS), polyvinyl alcohol (PVA), and polyacrylic acid (PAA) were used as stabilizers. Dynamic light scattering and scanning electron microscopy corroborated the size and morphology of the formed NPs. It was demonstrated that the size of nanoparticles could be controlled by setting the concentration of PANI in NMP, the NMP to water ratio, and the stabilizer's nature. The functionalization and fluorescence of NPs were checked by spectroscopic techniques. Since polyaniline show only weak intrinsic luminescence, fluorescent groups were linked to the polyaniline chains prior to the nanoparticle formation using a linker. Polyaniline chains were functionalized by nucleophilic addition of cysteamine trough the thiol group thereby incorporating pendant primary aliphatic amine groups to the polyaniline backbone. Then, dansyl chloride (DNS-Cl), which could act as an extrinsic chromophore, was conjugated to the amine pendant groups. Later, the functionalized polyaniline was used to produce nanoparticles by solvent displacement. The optical and functional properties of fluorescent nanoparticles (F-PANI-NPs) were determined. F-PANI-NPs in the conductive state (pH < 4) are able to absorb near infrared radiation (NIR) creating a photothermal effect in an aqueous medium. Thus, multifunctional nanoparticles are obtained. The application of NIR on a F-PANI-NPs dispersion in contact with Pseudomonas aeruginosa causes bacterial death. Therefore, the F-PANI-NPs could be tracked and applied to inhibit different diseases caused by pathogenic microorganisms and resistant to antibiotics as well as a new disinfection method to surgical materials.

Asunto(s)

Compuestos de Anilina/síntesis química , Bacterias/aislamiento & purificación , Viabilidad Microbiana , Nanopartículas/química , Tamaño de la Partícula , Fototerapia , Solventes/química , Compuestos de Anilina/química , Dispersión Dinámica de Luz , Hidrodinámica , Concentración de Iones de Hidrógeno , Nanopartículas/ultraestructura , Pirrolidinonas/química , Espectrometría de Fluorescencia , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura

RESUMEN

A fungal strain of Aspergillus niger was recovered from sediments collected in the Northeast coast of Brazil (Pecém's offshore port terminal). Cultivation in different growth media yielded a new ester furan derivative, 1, along with malformin A1, malformin C, cyclo (trans-4-hydroxy-L-Pro-L-Leu), cyclo (trans-4-hydroxy-L-Pro-L-Phe), cyclo (L-Pro-L-Leu), cyclo (L-Pro-L-Phe), pseurotin D, pseurotin A, chlovalicin, cyclo (L-Pro-L-Tyr) and cyclo (L-Pro-L-Val). Compound 1 was cytotoxic against HCT-116 cell line, showing IC50 = 2.9 µg/mL (CI 95% from 1.8 to 4.7 µg/mL).

Asunto(s)

Antineoplásicos/farmacología , Aspergillus niger/química , Antineoplásicos/química , Brasil , Ciclohexanonas/aislamiento & purificación , Ciclohexanonas/farmacología , Dipéptidos/aislamiento & purificación , Dipéptidos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Epoxi/aislamiento & purificación , Compuestos Epoxi/farmacología , Furanos/química , Sedimentos Geológicos/microbiología , Células HCT116 , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Péptidos Cíclicos/química , Péptidos Cíclicos/aislamiento & purificación , Péptidos Cíclicos/farmacología , Pirrolidinonas/aislamiento & purificación , Pirrolidinonas/farmacología

Asunto(s)

Aprobación de Drogas , Anticuerpos Monoclonales Humanizados/uso terapéutico , Quimioterapia/enfermería , Humanos , Insulina de Acción Prolongada/uso terapéutico , Piperazinas/uso terapéutico , Piperidinas/uso terapéutico , Polímeros/uso terapéutico , Pirrolidinonas/uso terapéutico , Estados Unidos , United States Food and Drug Administration , Urea/análogos & derivados , Urea/uso terapéutico

RESUMEN

CONTEXTO: Uma epilepsia é definida como uma condição neurológica caracterizada por convulsões epilépticas recorrentes. Uma convulsão epiléptica é a manifestação clínica de uma descarga anormal e excessiva de um conjunto de neurônios no cérebro. A epilepsia deve ser vista como um sintoma de uma doença neurológica subjacente e não como uma entidade isolada. TECNOLOGIA: Levetiracetam. PERGUNTA: Levetiracetam é eficaz e seguro para o tratamento epilepsia? EVIDÊNCIAS: Revisão sistemática com network meta-analyses comparou a tolerabilidade relativa de todos os antiepilépticos em monoterapia para todos os tipos de epilepsia, bem como a sua eficácia na monoterapia da epilepsia focal. Levetiracetam mostrou melhor resultado de eficácia para número de indivíduos livre de convulsão em comparação com fenobarbital e primidona, e para o desfecho descontinuação por ineficácia terapêutica em comparação com pregabalina e gabapentina. Levetiracetam apresentou pior perfil de tolerabilidade quando comparado com clobazam e lamotrigina e melhor perfil de tolerabilidade do que fenobarbital e primidona. Não houve diferenças estatisticamente significativas para eficácia e segurança entre levetiracetam e carbamazepina, fenitoína, valproato, etossuximida, topiramato e vigabrina. CONCLUSÕES: Os medicamentos clobazam e lamotrigina, são medicamentos disponibilizados pelo SUS, que não apresentaram diferenças estatisticamente significantes para eficácia quando comparados com o levetiracetam, mas apresentaram melhor perfil de segurança.

Asunto(s)

Humanos , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Pirrolidinonas/uso terapéutico , Análisis Costo-Beneficio , Evaluación de la Tecnología Biomédica , Resultado del Tratamiento

RESUMEN

A novel, efficient and enantioselective Heck-Matsuda desymmetrization of non-activated cyclopentene-fused spiro-pyrrolidinones was developed. The reaction provided the Heck products in good to excellent yields and selectivities and tolerated a variety of functional groups in arenediazonium tetrafluoroborates (12 examples) with respect to its electronics and substitution patterns. This methodology was successfully applied in the concise enantioselective total synthesis of VPC01091 (2b), a drug candidate for the treatment of multiple sclerosis.

Asunto(s)

Ciclopentanos/química , Pirrolidinonas/química , Receptores de Lisoesfingolípidos/metabolismo , Compuestos de Espiro/química , Técnicas de Química Sintética , Ciclopentanos/síntesis química , Ciclopentanos/metabolismo , Modelos Moleculares , Conformación Molecular , Estereoisomerismo