Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
1.
Biochem Pharmacol ; : 116339, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38848781

RESUMEN

Sleep is a fundamental state for maintaining the organism homeostasis. Disruptions in sleep patterns predispose to the appearance of memory impairments and mental disorders, including depression. Recent pre-clinical studies have highlighted the antidepressant-like properties of the synthetic compound 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1). To further investigate the neuromodulatory effects of SeBZF1, this study aimed to assess its therapeutic efficacy in ameliorating neurobehavioral impairments induced by sleep deprivation (SD) in mice. For this purpose, a method known as multiple platforms over water was used to induce rapid eye movement (REM) SD. Two hours after acute SD (24 h), male Swiss mice received a single treatment of SeBZF1 (5 mg/kg, intragastric route) or fluoxetine (a positive control, 20 mg/kg, intraperitoneal route). Subsequently, behavioral tests were conducted to assess spontaneous motor function (open-field test), depressive-like behavior (tail suspension test), and memory deficits (Y-maze test). Brain structures were utilized to evaluate oxidative stress markers, monoamine oxidase (MAO) and acetylcholinesterase (AChE) activities. Our findings revealed that SD animals displayed depressive-like behavior and memory impairments, which were reverted by SeBZF1 and fluoxetine treatments. SeBZF1 also reverted the increase in lipoperoxidation levels and glutathione peroxidase activity in the pre-frontal cortex in mice exposed to SD. Besides, the increase in hippocampal AChE activity induced by SD was overturned by SeBZF1. Lastly, cortical MAO-B activity was reestablished by SeBZF1 in mice that underwent SD. Based on the main findings of this study, it can be inferred that the compound SeBZF1 reverses the neurobehavioral alterations induced by sleep deprivation in male Swiss mice.

2.
Epilepsy Behav ; 156: 109832, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38761450

RESUMEN

Crack cocaine is a highly addictive and potent stimulant drug. Animal studies have shown that the cholinergic system plays a role in neurotoxicity induced by cocaine or its active metabolites inhalation. Behavioral alterations associated with crack cocaine use include hyperactivity, depressed mood, and decreased seizure threshold. Here we evaluate the acetylcholinesterase (AChE) and reactive oxygen species (ROS) activity, behavioral profile, and the threshold for epileptic seizures in rats that received intrahippocampal pilocarpine (H-PILO) followed by exposure to crack cocaine (H-PILO + CRACK). Animals exposed to H-PILO + CRACK demonstrated increased severity and frequency of limbic seizures. The AChE activity was reduced in the groups exposed to crack cocaine alone (CRACK) and H-PILO + CRACK, whereas levels of ROS remained unchanged. In addition, crack cocaine exposure increased vertical locomotor activity, without changing water and sucrose intake. Short-term memory consolidation remained unchanged after H-PILO, H-PILO + CRACK, and CRACK administration. Overall, our data suggest that crack cocaine inhalation reduced the threshold for epileptic seizures in rats submitted to low doses of pilocarpine through the inhibition of AChE. Taken together, our findings can be useful in the development of effective strategies for preventing and treating the harmful effects of cocaine and crack cocaine on the central nervous system.

3.
J Dairy Sci ; 105(4): 3102-3112, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35094850

RESUMEN

We evaluated the effects of abomasal infusion of emulsifiers on fatty acid (FA) digestibility and milk production of lactating dairy cows. All emulsifiers examined were polysorbates, nonionic surfactants, consisting of a polyethoxylated sorbitan esterified with FA. The polysorbates tested in this study consisted of the same polyethoxylated sorbitan base but differed by the FA esterified to it. Eight rumen-cannulated multiparous cows (89 ± 13 d in milk) were assigned to a treatment sequence in 4 × 4 Latin squares with 18-d periods consisting of 7 d of washout and 11 d of infusion. Treatments were abomasal infusions of water only (CON) or 30 g/d of different emulsifiers as follows: polysorbate-C16:0 (T40), polysorbate-C18:0+C16:0 (T60), and polysorbate-C18:1 (T80). Emulsifiers were dissolved in water and delivered at 6-h intervals (total daily infusion was divided into 4 equal infusions per day). Cows were fed the same diet that contained (% diet dry matter) 32.1% neutral detergent fiber, 15.7% crude protein, 25.8% starch, and 3.32% FA (including 1.92% FA from a saturated FA supplement containing 34.2% C16:0 and 47.7% C18:0). The T80 treatment increased total FA digestibility compared with CON (5.40 percentage units) and T60 (3.90 percentage units) and tended to increase it compared with T40. Also, T40 tended to increase and T80 increased (4.80 percentage units) 16-carbon FA digestibility compared with CON. The T80 treatment increased 18-carbon FA digestibility compared with the other treatments. The T40 treatment tended to increase and T80 increased total FA absorption compared with CON (53 g/d) and T60 (52 g/d). Both T40 and T80 increased the absorption of 16-carbon FA compared with CON and T60. The T60 treatment did not differ from CON for any digestibility variable. Both T40 and T80 increased the yields of milk fat, 3.5% fat-corrected milk, and de novo, mixed, and preformed milk FA compared with CON. In conclusion, not all emulsifiers increased FA digestibility. Compared with CON, T80 increased the digestibility and absorption of total, 16-, and 18-carbon FA. The T40 treatment tended to increase and T80 increased total FA absorption and the yields of milk fat and 3.5% FCM compared with CON. Milk fat yield was increased by increases in de novo, mixed, and preformed milk FA. In our short-term infusion study, results suggest that the predominant FA present in the polysorbate affects its ability to improve FA digestibility. Overall, FA digestibility and absorption were improved the most when cows received the T80 treatment.


Asunto(s)
Ácidos Grasos , Leche , Alimentación Animal/análisis , Animales , Bovinos , Dieta/veterinaria , Suplementos Dietéticos , Digestión , Ácidos Grasos/metabolismo , Femenino , Lactancia , Leche/metabolismo , Ácido Palmítico/metabolismo
4.
Front Plant Sci ; 12: 748829, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34691125

RESUMEN

The population growth trend in recent decades has resulted in continuing efforts to guarantee food security in which leguminous plants, such as the common bean (Phaseolus vulgaris L.), play a particularly important role as they are relatively cheap and have high nutritional value. To meet this demand for food, the main target for genetic improvement programs is to increase productivity, which is a complex quantitative trait influenced by many component traits. This research aims to identify Quantitative Trait Nucleotides (QTNs) associated with productivity and its components using multi-locus genome-wide association studies. Ten morpho-agronomic traits [plant height (PH), first pod insertion height (FPIH), number of nodules (NN), pod length (PL), total number of pods per plant (NPP), number of locules per pod (LP), number of seeds per pod (SP), total seed weight per plant (TSW), 100-seed weight (W100), and grain yield (YLD)] were evaluated in four environments for 178 Mesoamerican common bean domesticated accessions belonging to the Brazilian Diversity Panel. In order to identify stable QTNs, only those identified by multiple methods (mrMLM, FASTmrMLM, pLARmEB, and ISIS EM-BLASSO) or in multiple environments were selected. Among the identified QTNs, 64 were detected at least thrice by different methods or in different environments, and 39 showed significant phenotypic differences between their corresponding alleles. The alleles that positively increased the corresponding traits, except PH (for which lower values are desired), were considered favorable alleles. The most influenced trait by the accumulation of favorable alleles was PH, showing a 51.7% reduction, while NN, TSW, YLD, FPIH, and NPP increased between 18 and 34%. Identifying QTNs in several environments (four environments and overall adjusted mean) and by multiple methods reinforces the reliability of the associations obtained and the importance of conducting these studies in multiple environments. Using these QTNs through molecular techniques for genetic improvement, such as marker-assisted selection or genomic selection, can be a strategy to increase common bean production.

5.
Psychopharmacology (Berl) ; 238(10): 3013-3024, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34312682

RESUMEN

RATIONALE: Depression is a psychiatric disorder that constitutes one of the leading causes of disability worldwide. 2-Phenyl-3-(phenylselanyl)benzofuran (SeBZF1) has been studied as a potential antidepressant drug, but its pharmacological action needs more investigation. OBJECTIVES AND METHODS: Our aim was to extend information about the antidepressant-like action of SeBZF1 using the mouse tail suspension test (TST). Initial experiments investigated the mechanisms involved in the acute antidepressant-like action of SeBZF1 in male Swiss mice. For this purpose, males received noradrenergic or dopaminergic receptor antagonists before acute SeBZF1 administration (50 mg/kg, per oral). In parallel, effects of combined treatment with SeBZF1 and bupropion at sub-effective doses (1 and 3 mg/kg, respectively) were tested. The next experiments were designed to determine the acute effects of SeBZF1 in females through a dose-response curve (5-50 mg/kg). Lastly, the efficacy of a 7-day repeated treatment with SeBZF1 (1 and 5 mg/kg) in mice of both sexes and its safety were evaluated. TST and the open-field test (OFT) were employed in all behavioral experiments. RESULTS: Pre-administration of dopaminergic antagonists (SCH23390, a selective D1R antagonist; sulpiride, a selective D2/D3R antagonist; and haloperidol, a non-selective antagonist), but not of adrenergic α1, α2, and ß-R antagonists, blocked the acute antidepressant-like effects of SeBZF1 in males. Co-administration of sub-effective doses of SeBZF1 and bupropion reduced the depressive phenotype. In addition, acute treatment with SeBZF1 at 50 mg/kg produced a reduction of female immobility. Finally, repeated treatment with SeBZF1 (1 and 5 mg/kg) was effective in causing antidepressant-like effects in both sexes. Locomotor activity, plasma transaminases, and urea levels remained unaltered after SeBZF1 exposure. CONCLUSION: Our findings provide evidence of the involvement of the dopaminergic system in the acutely antidepressant-like action of SeBZF1 in male mice and reveal the compound efficacy when acute or repeatedly administered in both sexes.


Asunto(s)
Antidepresivos , Benzofuranos , Animales , Antidepresivos/farmacología , Benzofuranos/farmacología , Depresión/tratamiento farmacológico , Dopamina , Antagonistas de Dopamina , Relación Dosis-Respuesta a Droga , Femenino , Suspensión Trasera , Masculino , Ratones , Natación
6.
Theor Appl Genet ; 134(9): 2795-2811, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34027567

RESUMEN

KEY MESSAGE: QTNs significantly associated to nine mineral content in grains of common bean were identified. The accumulation of favorable alleles was associated with a gradually increasing nutrient content in the grain. Biofortification is one of the strategies developed to address malnutrition in developing countries, the aim of which is to improve the nutritional content of crops. The common bean (Phaseolus vulgaris L.), a staple food in several African and Latin American countries, has excellent nutritional attributes and is considered a strong candidate for biofortification. The objective of this study was to identify genomic regions associated with nutritional content in common bean grains using 178 Mesoamerican accessions belonging to a Brazilian Diversity Panel (BDP) and 25,011 good-quality single nucleotide polymorphisms. The BDP was phenotyped in three environments for nine nutrients (phosphorus, potassium, calcium, magnesium, copper, manganese, sulfur, zinc, and iron) using four genome-wide association multi-locus methods. To obtain more accurate results, only quantitative trait nucleotides (QTNs) that showed repeatability (i.e., those detected at least twice using different methods or environments) were considered. Forty-eight QTNs detected for the nine minerals showed repeatability and were considered reliable. Pleiotropic QTNs and overlapping genomic regions surrounding the QTNs were identified, demonstrating the possible association between the deposition mechanisms of different nutrients in grains. The accumulation of favorable alleles in the same accession was associated with a gradually increasing nutrient content in the grain. The BDP proved to be a valuable source for association studies. The investigation of different methods and environments showed the reliability of markers associated with minerals. The loci identified in this study will potentially contribute to the improvement of Mesoamerican common beans, particularly carioca and black beans, the main groups consumed in Brazil.


Asunto(s)
Cromosomas de las Plantas/genética , Genoma de Planta , Minerales/metabolismo , Phaseolus/metabolismo , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Brasil , Mapeo Cromosómico/métodos , Estudio de Asociación del Genoma Completo , Minerales/análisis , Phaseolus/genética , Phaseolus/crecimiento & desarrollo
7.
PLoS One ; 16(4): e0249858, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33886606

RESUMEN

The common bean (Phaseolus vulgaris L.) is of great importance to the food and nutritional security of many populations, and exploitation of the crop's genetic diversity is essential for the success of breeding programs. Thus, the aim of the present study was to evaluate the genetic diversity of 215 common bean accessions, which included cultivars, obsolete cultivars, improved lines, and landraces using morpho-agronomic and biochemical traits, and amplified fragment length polymorphism markers (AFLP). Genetic parameters, box plots, Pearson's correlation analysis, and Ward's hierarchical clustering were used to analyze the data. The Jaccard similarity coefficient and neighbour-joining clustering method were used for molecular analysis. A wide variability among the accessions was observed for morpho-agronomic and biochemical traits. Selective accuracy (Ac) and broad-sense heritability (h2) values were high to intermediate for all traits, except seed yield. Ward's hierarchical clustering analysis generated six groups. AFLP analysis also revealed significant differences among the accessions. There was no correlation between the differences based on genetic markers and those based on morpho-agronomic and biochemical data, which indicates that both datasets are important for elucidating the differences among accessions. The results of the present study indicate great genetic diversity among the evaluated accessions.


Asunto(s)
Phaseolus/genética , Polimorfismo Genético , Producción de Cultivos/métodos , Phaseolus/crecimiento & desarrollo , Carácter Cuantitativo Heredable , Selección Artificial
8.
Sci Rep ; 11(1): 2964, 2021 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-33536468

RESUMEN

Brazil is the world's largest producer of common bean. Knowledge of the genetic diversity and relatedness of accessions adapted to Brazilian conditions is of great importance for the conservation of germplasm and for directing breeding programs aimed at the development of new cultivars. In this context, the objective of this study was to analyze the genetic diversity, population structure, and linkage disequilibrium (LD) of a diversity panel consisting of 219 common bean accessions, most of which belonging to the Mesoamerican gene pool. Genotyping by sequencing (GBS) of these accessions allowed the identification of 49,817 SNPs with minor allele frequency > 0.05. Of these, 17,149 and 12,876 were exclusive to the Mesoamerican and Andean pools, respectively, and 11,805 SNPs could differentiate the two gene pools. Further the separation according to the gene pool, bayesian analysis of the population structure showed a subdivision of the Mesoamerican accessions based on the origin and color of the seed tegument. LD analysis revealed the occurrence of long linkage blocks and low LD decay with physical distance between SNPs (LD half decay in 249 kb, corrected for population structure and relatedness). The GBS technique could effectively characterize the Brazilian common bean germplasms, and the diversity panel used in this study may be of great use in future genome-wide association studies.


Asunto(s)
Genoma de Planta , Phaseolus/genética , Fitomejoramiento/métodos , Selección Genética , Brasil , ADN de Plantas , Domesticación , Frecuencia de los Genes , Pool de Genes , Variación Genética , Estudio de Asociación del Genoma Completo , Técnicas de Genotipaje , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple
9.
Eur Neuropsychopharmacol ; 44: 34-50, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33454149

RESUMEN

Crack users suffer the effects of cocaine present in the drug and the action of other active compounds from its pyrolysis. An emergent fact is an increase in the number of pregnant crack cocaine users. Studies suggest that crack cocaine and its metabolites cross the placenta, promoting premature birth, fever, irritability, sweating, and seizures in the early months of life. In children, the effects of crack cocaine have been associated with cognitive deficits, difficulty in verbalization, aggressiveness, and depression, besides enhancing the susceptibility to epileptic seizures, including status epilepticus (SE) in adulthood. Therefore, we investigated the effect of maternal exposure to smoke crack cocaine on several behavioral parameters in the offspring during adulthood. A series of behavioral tests and intrahippocampal pilocarpine (H-PILO) microinjection at sub-convulsive and convulsive doses in a rat model demonstrated that exposure to crack cocaine during the embryonic period leads to anxiogenic-like behavior and long-term memory impairment in both genders and promotes depressive-like behavior in the female. Besides, crack cocaine offspring exposed to a sub-convulsive H-PILO dose showed higher susceptibility to SE, increased seizure frequency, and neurodegeneration, while animals that received a convulsive dose of H-PILO displayed no alteration in SE severity. Taken together, our data suggest that crack cocaine exposure during the gestational period leads to an increased predilection for anxiety and depression, long-term memory deficits, and reduction in the threshold for developing epileptic seizures associated with neuronal death, which predispose crack cocaine babies to develop neuropsychological disorders.


Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína Crack , Epilepsia , Estado Epiléptico , Animales , Ansiedad/inducido químicamente , Cocaína Crack/toxicidad , Femenino , Masculino , Trastornos de la Memoria/inducido químicamente , Pilocarpina/toxicidad , Embarazo , Ratas , Convulsiones/inducido químicamente
10.
PLoS One ; 15(9): e0239263, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32986739

RESUMEN

Mineral deficiency is worldwide one of the major problems associated with human health, and biofortification through breeding is considered an important strategy to improve the nutritional content of staple food in countries that face this problem. The assessment of genetic variability for seed nutrient contents is a first step in the development of a biofortified crop. From the germplasm bank IDR-IAPAR-EMATER, a set of 1,512 common bean accessions, consisting of local and commercial varieties and improved lines, was analyzed. High variability among the accessions was observed for all evaluated nutrient contents (P, K, Ca, Mg, Cu, Zn, Mn, Fe and S and protein). In the mean, the contents of the carioca and black market groups (Mesoamerican gene pool), were around 7% higher for the minerals Ca, Cu, Mn and Fe and between 2-4% higher for P, K, Mg and Zn than in the other groups with Mesoamerican and Andean common bean. Few differences were observed among the Mesoamerican accessions that belong to the carioca and black commercial groups. Wide variability was observed among the evaluated genotypes, and the concentrations of the best accessions exceeded the overall mean by 14-28%. Due to the high variability in the evaluated accessions, these results may contribute to the selection of promising parents for the establishment of mating blocks. The nutritional contents of many of the improved lines evaluated in this study were higher than those of the commercial cultivars, indicating the possibility of developing new biofortified cultivars.


Asunto(s)
Biofortificación , Phaseolus/química , Banco de Semillas , Semillas/química , Brasil , Cruzamiento , Genotipo , Humanos , Hierro/química , Minerales/química , Phaseolus/genética , Semillas/genética
11.
Artículo en Inglés | MEDLINE | ID: mdl-32371105

RESUMEN

Monoaminergic and oxidative dysfunctions have been reported to play a role in depression. The present study investigated the antioxidant potential as well as the antidepressant-like action of 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1) in male Swiss mice. Time and dose-response curves were analyzed with the forced swim (FST) and tail suspension (TST) tests, in which SeBZF1 elicited antidepressant-like effects. Serotonergic mechanisms were investigated in the TST. The pre-administration of WAY100635 (selective 5-HT1A receptor antagonist, 0.1 mg/kg, subcutaneous route), ketanserin (5-HT2A/2C receptor antagonist, 1 mg/kg, intraperitoneal route, i.p.), and chlorophenylalaninemethyl ester (p-CPA) (selective tryptophan hydroxylase inhibitor, 100 mg/kg, i.p., for 4 days), but not of ondansetron (selective 5-HT3 receptor antagonist, 1 mg/kg, i.p.), abolished the antidepressant-like action of SeBZF1 (50 mg/kg, intragastric route, i.g.). Co-administration of sub-effective doses of SeBZF1 (1 mg/kg, i.g.) and fluoxetine (5 mg/kg, i.p., selective serotonin reuptake inhibitor) was effective in producing anti-immobility effects in the TST, revealing a synergistic effect. Besides, p-CPA induced hippocampal oxidative stress, characterized by a reduction of total thiols and lipoperoxidation, which was reversed by SeBZF1 (50 mg/kg). The in vitro screening of the antioxidant action of SeBZF1 in brain tissue reinforced these results. Lastly, SeBZF1 did not cause systemic toxicity at a high dose (300 mg/kg). In summary, the present study demonstrated that SeBZF1 exerted antidepressant-like action in male mice which appears to be mediated by the serotonergic system. Moreover, SeBZF1 elicited in vitro antioxidant action in brain tissue, attenuated the hippocampal oxidative damage induced by 5-HT depletion in mice and showed no toxic signs.


Asunto(s)
Antidepresivos/farmacología , Antioxidantes/farmacología , Serotoninérgicos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Fluoxetina/farmacología , Ketanserina/farmacología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Actividad Motora , Ondansetrón/farmacología , Piperazinas/farmacología , Piridinas/farmacología , Antagonistas de la Serotonina/farmacología
12.
Sci Rep ; 8(1): 4857, 2018 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-29559670

RESUMEN

Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2α), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T. cruzi inside mammalian cells with an EC50 of 1-3 µM and a selectivity of 17-fold. I-17 also prevented replication of African trypanosomes (Trypanosoma brucei bloodstream and procyclic forms) at similar doses. It caused changes in the T. cruzi morphology, arrested parasite cell cycle in G1 phase, and promoted phosphorylation of eIF2α with a robust decrease in ribosome association with mRNA. The activity against T. brucei also implicates eIF2α phosphorylation, as replacement of WT-eIF2α with a non-phosphorylatable eIF2α, or knocking down eIF2 protein kinase-3 by RNAi increased resistance to I-17. Therefore, we demonstrate that eIF2α phosphorylation can be engaged to develop trypanosome-static agents in general, and particularly by interfering with activity of eIF2 kinases.


Asunto(s)
Proteínas Protozoarias/metabolismo , Trypanosoma brucei brucei/efectos de los fármacos , Trypanosoma brucei brucei/metabolismo , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/metabolismo , Urea/metabolismo , Urea/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Enfermedad de Chagas/microbiología , Factor 2 Eucariótico de Iniciación/metabolismo , Fase G1/efectos de los fármacos , Hemo/metabolismo , Humanos , Mioblastos/efectos de los fármacos , Mioblastos/parasitología , Pruebas de Sensibilidad Parasitaria , Fosforilación , Ratas , Urea/análogos & derivados , eIF-2 Quinasa/metabolismo
13.
Sci Rep, v. 8, 4857, mar. 2018
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2402

RESUMEN

Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2 alpha), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T. cruzi inside mammalian cells with an EC50 of 1-3 mu M and a selectivity of 17-fold. I-17 also prevented replication of African trypanosomes (Trypanosoma brucei bloodstream and procyclic forms) at similar doses. It caused changes in the T. cruzi morphology, arrested parasite cell cycle in G1 phase, and promoted phosphorylation of eIF2 alpha with a robust decrease in ribosome association with mRNA. The activity against T. brucei also implicates eIF2 alpha phosphorylation, as replacement of WT-eIF2 alpha with a non-phosphorylatable eIF2 alpha, or knocking down eIF2 protein kinase-3 by RNAi increased resistance to I-17. Therefore, we demonstrate that eIF2 alpha phosphorylation can be engaged to develop trypanosome-static agents in general, and particularly by interfering with activity of eIF2 kinases.

14.
Sci Rep ; 8: 4857, 2018.
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib14893

RESUMEN

Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2 alpha), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T. cruzi inside mammalian cells with an EC50 of 1-3 mu M and a selectivity of 17-fold. I-17 also prevented replication of African trypanosomes (Trypanosoma brucei bloodstream and procyclic forms) at similar doses. It caused changes in the T. cruzi morphology, arrested parasite cell cycle in G1 phase, and promoted phosphorylation of eIF2 alpha with a robust decrease in ribosome association with mRNA. The activity against T. brucei also implicates eIF2 alpha phosphorylation, as replacement of WT-eIF2 alpha with a non-phosphorylatable eIF2 alpha, or knocking down eIF2 protein kinase-3 by RNAi increased resistance to I-17. Therefore, we demonstrate that eIF2 alpha phosphorylation can be engaged to develop trypanosome-static agents in general, and particularly by interfering with activity of eIF2 kinases.

15.
PLoS One ; 12(11): e0188798, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29190665

RESUMEN

Common bean (Phaseolus vulgaris L.) is one of the most important legumes for human consumption and is a staple food in the diet of the population of some countries of Latin America, Africa and Asia. The distinction between cultivars is based predominantly on morphological descriptors, which proved inefficient for the differentiation of some cultivars. This study had the objective of describing, distinguishing and evaluating the agronomic potential of 39 common bean cultivars of the carioca and black grain groups registered for cultivation in Brazil, based on 49 morphoagronomic descriptors and microsatellite (simple sequence repeat -SSR) markers. The morphoagronomic traits of each commercial group were characterized in four environments. Thirty-seven SSR markers were used for the molecular description. The morphological data, analyzed by the Shanonon-Weaver index, detected low variability among cultivars for qualitative data. On the other hand, the estimates of variance analysis, relative importance of the traits and hierarchical grouping analysis applied to the quantitative variables showed that the descriptors related to plant morphology were the most important for the carioca group, and those related to seed morphology were determining for the black group. The genetic parameters estimated for SSR markers by hierarchical and Bayesian cluster analysis identified 116 alleles, with 33 and 30 polymorphic loci and 24 and 22 private alleles for the carioca and black groups, respectively. The combined use of morphoagronomic and molecular descriptors improves the distinguishability of cultivars, contributing in a more efficient way to breeding and to the protection of cultivars.


Asunto(s)
Phaseolus/clasificación , Teorema de Bayes , Análisis por Conglomerados , Repeticiones de Microsatélite/genética , Phaseolus/genética
16.
An. acad. bras. ciênc ; 89(4): 2945-2954, Oct.-Dec. 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-886833

RESUMEN

ABSTRACT Forty isolates of endophytic bacteria isolated from banana tree roots were assessed as to their capacity to solubilize phosphate in a solid culture medium supplemented with different inorganic and one organic source of phosphorus. The amount of phosphorus (P) in each liquid medium was quantified, and an indirect assessment of acid phosphatase activity was performed. All assays had a fully randomized design, with three repetitions. Approximately 67.5% of the 40 isolates assessed in solid medium solubilized phosphorus from tricalcium phosphate and 7.5% of the isolates solubilized phosphorus from soy lecithin; no isolates exhibited P solubilization capacity in medium supplemented with iron phosphate. Acid phosphatase activity was detected in 65% of the isolates; Aneurinibacillus sp. and Lysinibacillus sp. isolates presented with the best solubilization indexes. All of the assessed isolates exhibited a capacity to reduce the potential of hydrogen in liquid medium supplemented with tricalcium phosphate. Isolate EB. 78 (Bacillus sp.) exhibited P solubilization capacity in solid media when Ca3(PO4)2 and soy lecithin were used as P sources; this isolate significantly reduced the pH of the liquid medium and exhibited acid phosphatase activity. The results of the present study highlight isolates that exhibit variations in their capacity to solubilize P. These isolates should be used in future tests to assess their field performance.


Asunto(s)
Fosfatos/metabolismo , Bacterias/metabolismo , Biodegradación Ambiental , Musa/microbiología , Endófitos/fisiología , Bacterias/clasificación
17.
Injury ; 48 Suppl 4: S34-S40, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29145966

RESUMEN

BACKGROUND: The universal accepted strategy for treating high-energy tibial plateau fractures remains a topic of ongoing debate. The challenge for the practicing orthopaedic trauma surgeon is to provide anatomical articular fracture reduction, with successfully managing the complex soft-tissue injury that is commonly present at patient admission. The primary aim of the actual study was to evaluate the results of a staged protocol for the treatment of high-energy bicondylar tibial plateau fractures. The secondary aim was to describe the technique used for the definitive fixation of this complex fracture pattern. METHODS: Thirty patients with unstable high-energy closed bicondylar tibial plateau fractures (17 Schatzker V and 13 Schatzker VI) were managed. There were 24 men (80%) and six women (20%). All of them were skeletally mature with their age ranging from 19 to 67 years (mean of 33.1±3.4 years). Treatment involved a two-stage procedure with appropriate emergency care, preoperative planning, and definitive fixation. Initial treatment, named 'damage control on complex articular fracture elements', consisted on temporary bridging external fixation. Definitive treatment was delayed in a mean of 10 days (ranging from seven to 13 days) and was performed when the soft-tissue conditioning demonstrated either complete or almost complete remission of the inflammatory reaction due to the 'first hit'. Conventional implants were used in the 30 patients. All patients were evaluated clinically and radiographically. RESULTS: Twenty-six (86.7%) patients had a moderate level of activity, three (10%) patients had a very light level of activity, and one (3.3%) patient was unable to have any kind of work activity and is currently supported by the Brazilian Welfare. Using the visual analog scale mean pain score was 30 (ranging from 10 to 60); even the patient with the workers' compensation had no severe pain. All patients except three have no difficulty with stairs, giving way, locking, swelling, and squatting, but were unable to run. Three (10%) patients had problems with stairs and could not bend the operated knee more than 90°. One of them had a varus knee but no instability. Ninety percent of the patients were either very satisfied or somewhat satisfied with their outcome. The three dissatisfied patients suffered postoperative complications, most commonly wound infections. Four (13.4%) patients with former anatomical reduction had a residual articular step-off or diastasis of less than 3mm after fracture healing. All patients had no or mild arthrosis at the time of the last outpatient consultation. CONCLUSIONS: The two-staged procedure presented herein showed to be an effective strategy for managing bycondilar tibial plateau fractures. The protocol used for these complex traumatic injuries follows very well defined steps, which means acute stabilization with a linear bridging external fixation, adequate soft tissue handling, preoperative planning, and definitive surgical fixation after seven to 14 days. The model presents a more biological approach to optimizing functional outcome with an acceptable complication rate and minimal risk of loss of reduction in these high-energy tibial plateau fractures.


Asunto(s)
Fijación de Fractura , Curación de Fractura/fisiología , Fracturas Intraarticulares/cirugía , Traumatismos de la Rodilla/cirugía , Rango del Movimiento Articular/fisiología , Fracturas de la Tibia/cirugía , Adulto , Anciano , Protocolos Clínicos , Femenino , Estudios de Seguimiento , Humanos , Fracturas Intraarticulares/diagnóstico por imagen , Fracturas Intraarticulares/fisiopatología , Traumatismos de la Rodilla/diagnóstico por imagen , Traumatismos de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Satisfacción del Paciente/estadística & datos numéricos , Estudios Prospectivos , Recuperación de la Función , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
18.
Rev Bras Ortop ; 49(2): 202-5, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26229800

RESUMEN

Fixation of an osteochondral fracture after acute patellar dislocation is an infrequent form of treatment. Likewise, the location of this fragment in the lateral region of the lateral femoral condyle, functioning as a free body, is uncommon. The aim of this study was to present a case of osteochondral fracture of the patella at an unusual site, along with the therapy used and the clinical follow-up.


A fixação da fratura osteocondral após a luxação aguda da patela é um tratamento infrequente, bem como a localização desse fragmento na região lateral do côndilo femoral lateral que funciona como um corpo livre. O objetivo desta pesquisa foi apresentar um caso de fratura osteocondral da patela em sítio não usual, assim como a terapêutica adotada e o seguimento clínico.

19.
Rev Bras Ortop ; 49(4): 374-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26229830

RESUMEN

OBJECTIVES: to review radiographs of patients who suffered tendon tears of the knee extensor apparatus and observe alterations that might be factors predisposing toward this type of injury. METHODS: we retrospectively analyzed 60 cases of injury to the knee extensor mechanism that were treated surgically at the Miguel Couto Municipal Hospital between March 2004 and March 2011. Four patients were excluded due to poor quality of the examination. RESULTS: of the 56 patients evaluated, 23 were considered to be normal and 33 presented radiographic alterations. Among these, eight (24.3%) presented suprapatellar osteophytes alone; seven (21.2%), infrapatellar calcification; seven (21.2%), suprapatellar calcification; six (18.2%), supra- and infrapatellar osteophytes; and five (15.1%), infrapatellar osteophytes alone. CONCLUSION: radiographic alterations were frequently observed in patients with extensor mechanism tears.


OBJETIVOS: revisar radiografias de pacientes vítimas de rupturas tendinosas do aparelho extensor do joelho e observar alterações que possam ser um fator predisponente a esse tipo de lesão. MÉTODOS: analisamos, retrospectivamente, 60 lesões do mecanismo extensor do joelho, tratadas cirurgicamente no Hospital Municipal Miguel Couto, de março de 2004 a março de 2011, e quatro pacientes foram excluídos por má qualidade do exame. RESULTADOS: dos 56 pacientes avaliados, 23 foram considerados normais e 33 apresentaram alterações radiográficas, oito (24,3%) com presença de osteófito suprapatelar isolado, sete (21,2%) com calcificação infrapatelar, sete (21,2%) com calcificação suprapatelar, seis (18,2%) com osteófitos supra e infrapatelares e cinco (15,1%) com osteófito infrapatelar isolado. CONCLUSÃO: as alterações radiográficas foram frequentes em pacientes com ruptura do mecanismo extensor.

20.
Neurochem Int ; 60(4): 409-14, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22285151

RESUMEN

The present study was conducted to evaluate the effect of 2-phenylethynyl-butyltellurium (PEBT), an organotellurium compound, at doses of 5 and 10 mg/kg on memory, employing the step-down inhibitory avoidance task in mice. Moreover, the involvement of glutamate uptake and release in cerebral cortex and hippocampus of mice was investigated. A single oral administration (p.o.) of PEBT at the dose of 10 mg/kg 1h before training (acquisition), immediately after training (consolidation) or 1 h before the test session (retrieval) of the step-down inhibitory avoidance task increased the step-through latency time in comparison to the control mice. In the open-field test, no significant differences in the number of crossings and rearings were observed among groups. The [(3)H]glutamate uptake by cerebral cortex and hippocampal slices of mice was significantly inhibited after 1h of treatment with PEBT. After 24h of PEBT exposure, only the hippocampal [(3)H]glutamate uptake was inhibited. The [(3)H]glutamate release by cerebral cortex and hippocampal synaptosomes of mice was not altered. These results suggest that PEBT improved memory stages (acquisition, consolidation and retrieval) in the step-down inhibitory avoidance task in mice. The improvement of memory by PEBT seems most likely to be mediated through an interaction with the amino acid transporters of the glutamatergic system.


Asunto(s)
Memoria/efectos de los fármacos , Compuestos Organometálicos/farmacología , Administración Oral , Animales , Reacción de Prevención/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Masculino , Ratones , Compuestos Organometálicos/administración & dosificación
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...