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991.
Aguiar AC Santos Rde M Figueiredo FJ Cortopassi WA Pimentel AS França TC Meneghetti MR Krettli AU 《PloS one》2012,7(5):e37259
Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation. 相似文献
992.
Ariel W. Guzmán-Franco Jorge Hernández-López Jhony N. Enríquez-Vara Raquel Alatorre-Rosas Fernando Tamayo-Mejía Laura D. Ortega-Arenas 《BioControl》2012,57(4):553-563
The white grub species Phyllophaga polyphylla and Anomala cincta (Coleoptera: Melolonthidae) are economically important species that affect many crops in Mexico. A series of experiments to study the pathogenic interaction between isolates of Beauveria bassiana and Metarhizium anisopliae and these two insect species were undertaken. First, the susceptibility of third instar P. polyphylla larvae to each of seven isolates representing both species of fungus was evaluated by dipping the insects in 1?×?108 conidia?ml?1 suspensions. A second study examined the differences in the susceptibility of P. polyphylla and A. cincta larvae to two selected isolates for each of the fungal species. Finally, the susceptibility of A. cincta larvae to one M. anisopliae isolate when incubated in soil collected from four different sites was assessed. No significant differences in proportion of infection of P. polyphylla larvae were observed amongst the fungal isolates tested and mortality due to fungal infection was never greater than 20% after 36?days incubation. Anomala cincta larvae were more susceptible than P. polyphylla larvae, with greater than 90% infection when inoculated with isolates of M. anisopliae whereas mortalities of only 20% where achieved against P. polyphylla larvae. The soil type in which A. cincta were incubated following inoculation with M. anisopliae affected their susceptibility to infection. The results demonstrated that there is a complex interaction amongst entomopathogenic fungi, white grub larvae and soil properties, and points to the need of further investigation of this system in order to optimize the efficacy of entomopathogenic fungi against these insect species. 相似文献
993.
Sampling collection for stable isotope analysis has traditionally involved the sacrifice of the animal. Seahorses (Hippocampus spp.) are listed as threatened by the Convention on International Trade in Endangered Species (http://www.cites.org) and consequently lethal sampling is undesirable. We evaluated the adequacy of dorsal fin tissue of adult seahorses Hippocampus guttulatus for stable isotope analysis as an alternative to lethal tissue sampling. Three seahorse tissues (dorsal fin, muscle, and liver) were analyzed for comparisons of δ15N and δ13C values. Similarities found between δ15N and δ13C values in dorsal fin and muscle tissue of H. guttulatus suggest that both tissues are adequate for stable isotope analysis to understand feeding ecology of seahorses. However, considering the threatened status of the species, dorsal fin tissue would be recommended in adult seahorses as a non-lethal sampling. The effect of lipid extraction on carbon and nitrogen stable isotope values was also evaluated in each seahorse tissues. Significant effects of lipids extraction did only occur for δ13C values in muscle and liver. It was found that lipid removal was not necessary to perform SIA in dorsal fin tissues. Due to the limited availability of fin tissue obtained from fin-clipping in seahorses, the relationship between the mass/surface of dorsal fin clip and stable isotope values was analyzed. δ15N and δ13C values in fin samples were found to be independent of the size of fin analyzed. According to our study, the use of fin-clipping sampling, with a minimum surface analyzed of 12.74?mm2, was found to be an adequate method for SIA in seahorses. 相似文献
994.
Gisele Pires de Mendon?a Dantas Diogo Meyer Raquel Godinho Nuno Ferrand Jo?o Stenghel Morgante 《Genetics and molecular biology》2012,35(4):874-885
Several phylogeographic studies of seabirds have documented low genetic diversity that has been attributed to bottleneck events or individual capacity for dispersal. Few studies have been done in seabirds on the Brazilian coast and all have shown low genetic differentiation on a wide geographic scale. The Kelp Gull is a common species with a wide distribution in the Southern Hemisphere. In this study, we used mitochondrial and nuclear markers to examine the genetic variability of Kelp Gull populations on the Brazilian coast and compared this variability with that of sub-Antarctic island populations of this species. Kelp Gulls showed extremely low genetic variability for mitochondrial markers (cytb and ATPase) and high diversity for a nuclear locus (intron 7 of the β-fibrinogen). The intraspecific evolutionary history of Kelp Gulls showed that the variability found in intron 7 of the β-fibrinogen gene was compatible with the variability expected under neutral evolution but suggested an increase in population size during the last 10,000 years. However, none of the markers revealed evidence of a bottleneck population. These findings indicate that the recent origin of Kelp Gulls is the main explanation for their nuclear diversity, although selective pressure on the mtDNA of this species cannot be discarded. 相似文献
995.
996.
Raquel F. Leal Cláudio S. R. Coy Lício A. Velloso Sushila Dalal Mariana Portovedo Viviane S. Rodrigues Andressa Coope Maria L. S. Ayrizono Jo?o J. Fagundes Marciane Milanski 《Cell and tissue research》2012,350(3):549-552
Crohn??s disease (CD) is a chronic intestinal disease with a multifactorial etiology. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected close to the affected intestinal area; however, there are few studies regarding autophagy and the hypertrophied mesenteric tissue in CD. To evaluate autophagy-related proteins in intestinal mucosae and mesenteric fat of patients with CD and controls, patients with ileocecal CD (CD Group) and with non-inflammatory disease (FC Group) selected for surgery were studied. Expression of LC3-II was determined by immunoblotting of protein extracts. In addition, beclin-1, LC3 and Atg16-L1 RNA levels were measured using RT-PCR. The expression of LC3-II was significantly lower in the mesenteric tissue and higher in intestinal mucosae of CD when compared to controls. However, mRNA expression of autophagy-related proteins was similar when comparing the mesenteric fat groups. These findings suggest a defect in autophagy activation in the mesenteric fat tissue of CD individuals, which could be involved in the maintenance of the inflammatory process. 相似文献
997.
Pires AL Pinho M Sena CM Seica R Leite-Moreira AF 《American journal of physiology. Heart and circulatory physiology》2012,302(5):H1131-H1137
Intermedin (IMD) is a novel vasoactive peptide from the calcitonin gene-related peptide (CGRP) implicated in cardiac regulation, yet the contractile effects of IMD remain controversial, since previous studies in vivo and isolated cardiomyocytes documented contradictory results. We hypothesized cardiac endothelial cells involvement in IMD modulation of cardiac function as an explanation for these opposing observations. With this in mind, we investigated the direct action of increasing concentrations of IMD (10(-8) to 10(-6)M) on myocardial performance parameters in rat left ventricular (LV) papillary muscles with and without endocardial endothelium (EE) and in presence of receptor antagonists and intracellular pathways inhibitors. In LV papillary muscles with intact EE, IMD induced a concentration-dependent negative inotropic action (%decrease relative to baseline, at IMD concentration of 10(-6)M, active tension of 14 ± 4%, and maximum velocity of tension rise of 10 ± 4%). These effects were blunted by EE removal, AM receptor antagonist (AM(22-52)), and CGRP receptor antagonist (CGRP(8-37)). Additionally, nitric oxide (NO) synthase inhibition with N(G)-nitro-l-arginine (l-NAME) in muscles with and without EE and guanylyl cyclase inhibition with {1H-[1,2,4]oxadiazole-[4,4-a]-quinoxalin-1-one} not only blunted the negative inotropic action of IMD but also unmasked IMD-positive inotropic effect dependent on CGRP receptor PKA activation. Western blot quantification of phosphorylated cardiac troponin I (P-cTnI) in IMD-treated papillary muscles revealed a significant increase in P-cTnI when compared with untreated muscles, while in l-NAME-pretreated papillary muscles IMD failed to increase P-cTnI. Finally, we found that stimulation of both EE and microvascular endothelial cells with IMD significantly increased NO production by 40 ± 3 and 38 ± 3%, respectively, suggesting the role of cardiac endothelial cells in NO production upon IMD stimulation. Our findings establish IMD negative inotropic effect in isolated myocardium due to NO/cGMP pathway activation with concomitant thin myofilament desensitization by increase in cTnI phosphorylation and provide a coherent explanation for the previously reported contradictory results. 相似文献
998.
The mechanisms underlying diabetic encephalopathy, are only partially understood. In this study, we try to address the mechanisms
of diabetes induced damage and whether docosahexaenoic acid (DHA) could attenuate the degenerative changes in diabetic hippocampus
in a rodent model of diabetes. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin. Animals were
divided into the following experimental groups: control rats; control animals treated with DHA; untreated diabetic rats; diabetic
rats treated with insulin; diabetic rats treated with DHA; diabetic rats treated with insulin and DHA. At the end of week
12, rats were killed and one of the hemispheres was cryosectioned and the other was dissected and hippocampi homogenized.
The number of bromodeoxyuridine positive cells in the hippocampus of diabetic rats was decreased, and the latency time to
find the platform in the Morris Water maze was significantly increased in the diabetic rats when compared to controls. No
changes where observed in the expression of p21 in the hippocampus of control and diabetic rats. Biochemical markers of oxidative
stress were altered in hippocampus of diabetic rats, and NFκB-positive cells were increased in the hippocampus of diabetic
rats when compared to controls. Treatment with DHA, or the combination of DHA with insulin, significantly restored to control
levels all the values mentioned above. Our findings confirm a pivotal role for oxidative stress as well as NF-κB, but not
p21, in diabetes-induced hippocampal impairments. Administration of DHA as well as insulin prevented the changes induced by
diabetes in hippocampus. 相似文献
999.
Paredes J Figueiredo J Albergaria A Oliveira P Carvalho J Ribeiro AS Caldeira J Costa AM Simões-Correia J Oliveira MJ Pinheiro H Pinho SS Mateus R Reis CA Leite M Fernandes MS Schmitt F Carneiro F Figueiredo C Oliveira C Seruca R 《Biochimica et biophysica acta》2012,1826(12):297-311
E-cadherin and P-cadherin are major contributors to cell-cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes during development, and in maintaining integrity and homeostasis in adult tissues. It is now generally accepted that alterations in these two molecules are observed during tumour progression of most carcinomas. Genetic or epigenetic alterations in E- and P-cadherin-encoding genes (CDH1 and CDH3, respectively), or alterations in their proteins expression, often result in tissue disorder, cellular de-differentiation, increased invasiveness of tumour cells and ultimately in metastasis. In this review, we will discuss the major properties of E- and P-cadherin molecules, its regulation in normal tissue, and their alterations and role in cancer, with a specific focus on gastric and breast cancer models. 相似文献
1000.
Teixeira GR Chuffa LG Martins OA Kremer R Pinheiro PF de Mello Júnior W Martinez M Martinez FE Domeniconi RF 《Tissue & cell》2012,44(1):47-53
Aquaporins (AQPs), notably AQP-1 and AQP-9, may contribute to reabsorption of fluid and solute across the epididymis. Ethanol is related to be a toxicant affecting directly or indirectly the epididymis and the sperm motility. This study examined the expression of AQP-1 and AQP-9 in adult epididymis of the UChA and UChB 10% (v/v) ethanol-preferring rats, focusing the ethanol-induced hormonal disturbances upon the regulation of these AQPs. Chronic ethanol intake significantly decreased body weight, while UChA and UChB rats displayed a marked loss of epididymal weights. Both ethanol-consuming animals had a severe reduction of testosterone levels, whereas LH and 17β-estradiol were unchanged. Throughout the epididymis, a strong reaction to AQP-1 was observed in myoid and endothelial cells of the UChB ethanol-preferring rats, differently from a moderate intensity in the initial segment of the UChA rats. In addition, AQP-9 showed a strong immunoreaction in the apical membrane of principal cells at initial segment. In cauda epididymis, the level of AQP-9 was reduced along the microvillus projections in both UChA and UChB rats compared to controls. We conclude that chronic ethanol consumption modulates the androgen levels, thereby modifying the expression pattern of AQP-1 and 9 in the epididymis. 相似文献