956 resultados para Inhibitors of P. falciparum bc1 complex
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Besides being considered the greatest pests of fruit growing, fruit flies constitute a large obstacle to the growth of the exportation of fresh fruit. Knowledge of the structure of fruit fly communities is of great importance to the bioecological studies of these insects, but there is a lack of information about the faunistic composition of fruit flies in Brazil. The objective of this work was to analysis the composition of the species of Anastrepha, in eleven mango orchards of the fruit growing complex Gaviao River, Bahia, Brazil. These studies were done in 2004 and 2005, in Anage, Caraibas and Belo Campo town, 23 McPhail traps, which collected 798 female fruit flies from the genus Anastrepha. The structure of these communities was evaluated in each orchard by means of faunistic indexes frequency, constancy, dominance, diversity and similarity. The number of species varied from four to eight in each orchard; and the following species was recorded: Anastrepha fraterculus (Wiedemann), Anastrepha obliqua (Macquart), Anastrepha dissimilis Stone, Anastrepha amita Zucchi, Anastrepha distincta Greene, Anastrepha pickeli Lima. Anastrepha sororcula Zucchi and Anastrepha zenildae Zucchi. The most frequent and dominant species were A. fraterculus and A. obliqua. The indexes of diversity varied from 1.01 to 1.62. In general, the similarity between orchards was high (above 55.0%). We observed the formation of groups, one constituted by Frutvale, Carlan, Santa Clara and Panorama orchards; another composed of Cofet, Campo Gaviao and Ouro Verde and a third group formed by Boa Vista orchard. Barra da Onca and Arruda are distinguished from other orchards.
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The crystal structures of five new non-electrophilic β-strand-templated thrombin active-site inhibitors have been determined bound to the enzyme. Four co-crystallize with hirugen and inhibitor isomorphously to produce thrombin-hirugen crystals (monoclinic, space group C2), while one co-crystallizes in the hexagonal system, space group P65. A 1,4-substituted cyclohexyl moiety is conserved at the P1 position of all the inhibitors, along with a fused hetero-bicyclic five- and six-membered ring that occupies the P2 site. Amino, amidino and aminoimidazole groups are attached to the cyclohexyl ring for recognition at the S1 specificity site, while benzylsulfonyl and diphenyl groups enhance the binding at the S3 subsite. The cyclohexyl groups at the P1 positions of three of the inhibitors appear to be in the energetically favored chair conformation, while the imidazole-substituted cyclohexyl rings are in a boat conformation. Somewhat unexpectedly, the two cyclohexyl-aminoimidazole groups bind differently in the specificity site; the unique binding of one is heretofore unreported. The other inhibitors generally mimic arginyl binding at S1. This group of inhibitors combines the nonelectrophilicity and selectivity of DAPA-like compounds and the more optimal binding features of the S1-S3 sites of thrombin for peptidic molecules, which results in highly potent (binding constants 12 nM-16 pM, one being 1.1 μM) and selective (ranging from 140 to 20 000 times more selective compared with trypsin) inhibitors of thrombin. The binding modes of these novel inhibitors are correlated with their binding constants, as is their selectivity, in order to provide further insight for the design of therapeutic antithrombotic agents that inhibit thrombin directly at the active site.
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We investigated the ABO genotypes and heterogeneity of the O alleles in Plasmodium falciparum-infected and non-infected individuals from the Brazilian Amazon region. Sample collection took place from May 2003 to August 2005, from P. falciparum malaria patients from four endemic regions of the Brazilian Amazon. The control group consisted of donors from four blood banks in the same areas. DNA was extracted using the Easy-DNA(TM) extraction kit. ABO genotyping was performed using PCR/RFLP. There was a high frequency of ABO*O01O01. ABO*AO01 was the second most frequent genotype, and the third most frequent genotype was ABO*BO01. There were low frequencies of the ABO*O01O02, ABO*AA, ABO*AB, ABO*BB, and ABO*O02O02 genotypes. We analyzed the alleles of the O phenotype; the O(1variant) allele was the most frequent, both in malaria and non-malaria groups; consequently, the homozygous genotype O(1)(v)O(1)(v) was the most frequently observed. There was no evidence of the homozygous O(2) allele. Significant differences were not detected in the frequency of individuals with the various alleles in the comparison of the malaria patients and the general population (blood donors).
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Turmeric oleoresin is a colorant prepared by solvent extraction of turmeric (Curcuma longa L.). Curcumin, the major pigment present in turmeric, has been described as a potent antioxidant, anti-inflammatory and anticarcinogenic agent. Turmeric pigments are lipid soluble and water insoluble and are sensitive to light, heat, oxygen and pH, which can be overcome by microencapsulation of turmeric oleoresin. The aim of this work was to investigate microencapsulation of turmeric oleoresin by complex coacervation using gelatin and gum Arabic as encapsulants and freeze-drying as the drying method. The coacervation process was studied by varying the concentration of biopolymer solution (2.5, 5.0 and 7.5%) and the core material: total encapsulant ratio (25, 50, 75 and 100%). Microcapsules were evaluated for encapsulation efficiency, morphology, solubility and stability to light. Encapsulation efficiency ranged from 49 to 73% and samples produced with 2.5% of wall material and 100% core: encapsulant ratio showed better stability to light. © 2012 Wiley Periodicals, Inc.
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In recent years, several studies have shown that concentrations of trace elements are altered in neoplastic breast tissues. However, the microenvironment and metabolic changes caused by tumors are complex and still not completely understood. Under this aspect, the combination of different techniques to investigate the role of trace elements in promoting and/or maintaining a tumor is interesting once the combination of information obtained by analytical techniques and immunohistochemical assays, associated with clinicopathological data, may allow a better metabolic understanding of trace elements in breast cancer. In this work, the role of the trace elements Ca, Fe, Cu and Zn in neoplastic breast tissues was investigated by X-ray fluorescence (XRF) techniques and immunohistochemical assays. We determined concentrations of Ca, Fe, Cu and Zn in normal and neoplastic breast tissues using energy dispersive XRF, and these values were used to set the positive or negative expression of elements in normal and neoplastic tissues. These expressions were correlated with the spatial distributions of trace elements (evaluated by micro-XRF) and with immunoexpression of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs and vascular endothelial growth factor. The results revealed that the expression of the trace elements Fe, Cu and vascular endothelial growth factor are related, indicating that higher levels of these elements can be associated with the angiogenic process in breast cancer. Also, associations between Ca, Zn and MMPs expression have been observed, possibly because of the fact that both metals are present in these proteins. © 2013 John Wiley & Sons, Ltd.
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Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical tests are still needed to corroborate the usefulness of using them in combination with other commonly used chemotherapeutic drugs. © 2013 Landes Bioscience.
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Inteins are coding sequences that are transcribed and translated with flanking sequences and then are excised by an autocatalytic process. There are two types of inteins in fungi, mini-inteins and full-length inteins, both of which present a splicing domain containing well-conserved amino acid sequences. Full-length inteins also present a homing endonuclease domain that makes the intein a mobile genetic element. These parasitic genetic elements are located in highly conserved genes and may allow for the differentiation of closely related species of the Candida parapsilosis (psilosis) complex. The correct identification of the three psilosis complex species C. parapsilosis, Candida metapsilosis, and Candida orthopsilosis is very important in the clinical setting for improving antifungal therapy and patient care. In this work, we analyzed inteins that are present in the vacuolar ATPase gene VMA and in the threonyl-tRNA synthetase gene ThrRS in 85 strains of the Candida psilosis complex (46 C. parapsilosis, 17 C. metapsilosis, and 22 C. orthopsilosis). Here, we describe an accessible and accurate technique based on a single PCR that is able to differentiate the psilosis complex based on the VMA intein. Although the ThrRS intein does not distinguish the three species of the psilosis complex by PCR product size, it can differentiate them by sequencing and phylogenetic analysis. Furthermore, this intein is unusually present as both mini- and full-length forms in C. orthopsilosis. Additional population studies should be performed to address whether this represents a common intraspecific variability or the presence of subspecies within C. orthopsilosis. Copyright © 2013, American Society for Microbiology. All Rights Reserved.
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Phylogenetic approaches based on mitochondrial DNA variation (fragments of Cyt B and 16S ribosomal RNA) have revealed Triatoma sherlocki as the most recent species addition to the Triatoma brasiliensis species complex; a monophyletic group which includes T. brasiliensis, Triatoma melanica, and Triatoma juazeirensis. T. sherlocki is the most differentiated among all species of this complex: it is unable to fly, possesses longer legs than the other members, and has reddish tonality in some parts of its exochorion. We question whether these species are reproductively compatible because of this pronounced morphological differentiation, and therefore, we present a series of cross breeding experiments that test compatibility between T. sherlocki and other members of the T. brasiliensis complex. We extended our analyses to include crosses between T. sherlocki and Triatoma lenti, because the latter has been suggested as a possible member of this complex. T. sherlocki male. ×. T. lenti female pairs failed to produce hybrids. All other crosses of T. sherlocki and members of T. brasiliensis species complex, as well as backcrosses, produced viable offspring through the third generation. This study stresses the importance of searching for the features that may isolate members of the T. brasiliensis species complex. © 2013 Elsevier B.V.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Periodontal disease (PD) is induced by a complex microbiota, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola (together called the red complex), which triggers intense inflammatory reaction. Down syndrome (DS) individuals demonstrate a high prevalence of PD compared with those who are otherwise chromosomally normal (euploids). This pilot study aimed to evaluate the effect of non-surgical periodontal treatment in DS chronic periodontitis patients on clinical and microbiological parameters. Patients with chronic periodontitis, 23 DS and 12 euploids (control group), were submitted to non-surgical mechanical periodontal treatment, followed by maintenance for 45 days. Clinical parameters after periodontal treatment were similar in diseased and healthy sites, independent of the genetic background. Diseased sites of DS and control patients harbored similar levels of P. gingivalis and T. forsythia at baseline, but significantly higher levels of T. denticola were found in DS patients. Increased levels of P. gingivalis at healthy sites were found in DS individuals. Non-surgical periodontal therapy decreased the levels of red complex microorganisms and improved the tested clinical parameters of diseased sites in both groups. However, the levels of red complex bacteria were higher in diseased sites of DS patients after the periodontal treatment. We conclude in this pilot study that, although the mechanical periodontal treatment seemed to be effective in DS subjects over a short-term period, the red complex bacteria levels did not decrease significantly in diseased sites, as occurred in controls. Therefore, for DS patients, it seems that the conventional non-surgical periodontal therapy should be improved by utilizing adjuvants to reduce the presence of periodontopathogens.
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Purpose: To verify the presence of Socransky Red Complex (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) and P. intermedia using polymerase chain reaction (PCR) in periodontally healthy pregnant women and pregnant women with periodontal disease, as well as its relation to arterial blood pressure and capillary glycaemia.Materials and Methods: This case control study included 86 pregnant women, including 50 pregnant women with healthy periodontium, 27 with gingivitis and 9 with periodontitis. Arterial blood pressure and glycaemia were evaluated and recorded. Clinical specimens from the gingival crevice or periodontal pockets were gathered with sterile absorbent paper cones. DNA extraction was accomplished using the Easy-DNA Kit test and the presence of bacteria was detected by PCR with primers and specific probes for each microorganism.Results: The arterial pressure of all pregnant women was found to be within normal levels and 51% presented with hyperglycaemia, these two variables were not associated with periodontal conditions and/or presence of microorganisms. Socransky Red Complex was not present in pregnant women with healthy periodontium; however, it was present in pregnant women with gingivitis (3.7%) and in a higher percentage of pregnant women with periodontitis (33.3%).Conclusion: Socransky Red Complex was found only in cases of periodontal diseases and is not related to blood pressure and/or high levels of blood glucose.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Sodium chloride intake was studied in rats submitted to different neurosurgical procedures. Intake decreased in animals submitted to bilateral destruction of the basolateral amygdaloid complex, and increased after the same animals were submitted to destruction of the anterior lateral hypothalamus, a procedure which is known to cause increased intake in intact rats. In the reverse experiment, where the anterior lateral hypothalamus was destroyed before the basolateral amygdaloid complex, the effect of increased sodium chloride intake induced by destruction of the hypothalamus overcame the decreased expected upon destruction of the amygdaloid complex. These results permit us to conclude that the hypothalamic areas which inhibit sodium chloride intake predominate over the stimulating areas of the amygdaloid complex in the control of sodium chloride intake. © 1981 ANKHO International Inc.
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The malaria parasite Plasmodium falciparum is able to synthesize de novo PLP (pyridoxal 5'-phosphate), the active form of vitamin B-6. In the present study, we have shown that the de novo synthesized PLP is used by the parasite to detoxify O-1(2) (singlet molecular oxygen), a highly destructive reactive oxygen species arising from haemoglobin digestion. The formation of O-1(2) and the response of the parasite were monitored by live-cell fluorescence microscopy, by transcription analysis and by determination of PLP levels in the parasite. Pull-down experiments of transgenic parasites overexpressing the vitamin B-6-biosynthetic enzymes PfPdx1 and PfPdx2 clearly demonstrated an interaction of the two proteins in vivo which results in an elevated PLP level from 12.5 mu M in wild-type parasites to 36.6 mu M in the PfPdx1/PfPdx2-overexpressing cells and thus to a higher tolerance towards O-1(2). In contrast, by applying the dominant-negative effect on the cellular level using inactive mutants of PfPdx1 and PfPdx2, P. falciparum becomes susceptible to O-1(2). Our results demonstrate clearly the crucial role of vitamin B-6 biosynthesis in the detoxification of O-1(2) in P falciparum. Besides the known role of PLP as a cofactor of many essential enzymes, this second important task of the vitamin B-6 de novo synthesis as antioxidant emphasizes the high potential of this pathway as a target of new anti-malarial drugs.