162 resultados para AK43-4934


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Objective: In recent years the use of anthraquinone laxatives, in particular senna, has been associated with damage to the intestinal epithelial layer and an increased risk of developing colorectal cancer. In the present study we evaluated the cytotoxicity of rhein, the active metabolite of senna, on human colon adenocarcinoma cells (Caco-2) and its effect on cell proliferation. Methods: Cytotoxicity studies were performed using MTT, NR and TEER assays whereas 3H-thymidine incorporation and western blot analysis were used to evaluate the effect of rhein on cell proliferation. Moreover, for genoprotection studies Comet assay and oxidative biomarkers measurement (malondialdehyde and reactive oxygen species) were used. Results: Rhein (0.1-10μg/ml) had no significant cytotoxic effect on proliferating and differentiated Caco-2 cells. Rhein (0.1 and 1 μg/ml) significantly reduced cell proliferation as well as MAP kinase activation; by contrast, at the high concentration (10μg/ml) rhein significantly increased cell proliferation and ERK phosphorylation. Moreover, rhein (0.1-10μg/ml) (i) did not adversely affect the integrity of tight junctions and hence epithelial barrier function, (ii) did not induce DNA damage rather it was able to reduce H2O2-induced DNA damage and (iii) significantly inhibited the increase in malondialdehyde and ROS levels induced by H2O2/Fe2+. Conclusions: Rhein, was devoid of cytotoxic and genotoxic effects in colon adenocarcinoma cells. Moreover, at concentrations present in the colon after a human therapeutic dosage of senna, rhein inhibited cell proliferation via a mechanism which seems to involve directly the MAP kinase pathway. Finally, rhein prevents the DNA damage probably via an anti-oxidant mechanism.

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Hydrogen sulfide (H(2)S) has recently been proposed as an endogenous mediator of inflammation and is present in human synovial fluid. This study determined whether primary human articular chondrocytes (HACs) and mesenchymal progenitor cells (MPCs) could synthesize H(2)S in response to pro-inflammatory cytokines relevant to human arthropathies, and to determine the cellular responses to endogenous and pharmacological H(2)S. HACs and MPCs were exposed to IL-1β, IL-6, TNF-α and lipopolysaccharide (LPS). The expression and enzymatic activity of the H(2)S synthesizing enzymes cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) were determined by Western blot and zinc-trap spectrophotometry, respectively. Cellular oxidative stress was induced by H(2)O(2), the peroxynitrite donor SIN-1 and 4-hydroxynonenal (4-HNE). Cell death was assessed by 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Mitochondrial membrane potential (DCm) was determined in situ by flow cytometry. Endogenous H(2) S synthesis was inhibited by siRNA-mediated knockdown of CSE and CBS and pharmacological inhibitors D,L-propargylglycine and aminoxyacetate, respectively. Exogenous H(2)S was generated using GYY4137. Under basal conditions HACs and MPCs expressed CBS and CSE and synthesized H(2)S in a CBS-dependent manner, whereas CSE expression and activity was induced by treatment of cells with IL-1β, TNF-α, IL-6 or LPS. Oxidative stress-induced cell death was significantly inhibited by GYY4137 treatment but increased by pharmacological inhibition of H(2)S synthesis or by CBS/CSE-siRNA treatment. These data suggest CSE is an inducible source of H(2)S in cultured HACs and MPCs. H(2)S may represent a novel endogenous mechanism of cytoprotection in the inflamed joint, suggesting a potential opportunity for therapeutic intervention.

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The hybrid Monte Carlo (HMC) method is a popular and rigorous method for sampling from a canonical ensemble. The HMC method is based on classical molecular dynamics simulations combined with a Metropolis acceptance criterion and a momentum resampling step. While the HMC method completely resamples the momentum after each Monte Carlo step, the generalized hybrid Monte Carlo (GHMC) method can be implemented with a partial momentum refreshment step. This property seems desirable for keeping some of the dynamic information throughout the sampling process similar to stochastic Langevin and Brownian dynamics simulations. It is, however, ultimate to the success of the GHMC method that the rejection rate in the molecular dynamics part is kept at a minimum. Otherwise an undesirable Zitterbewegung in the Monte Carlo samples is observed. In this paper, we describe a method to achieve very low rejection rates by using a modified energy, which is preserved to high-order along molecular dynamics trajectories. The modified energy is based on backward error results for symplectic time-stepping methods. The proposed generalized shadow hybrid Monte Carlo (GSHMC) method is applicable to NVT as well as NPT ensemble simulations.

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Several recent reports suggest that inflammatory signals play a decisive role in the self-renewal, migration and differentiation of multipotent neural stem cells (NSCs). NSCs are believed to be able to ameliorate the symptoms of several brain pathologies through proliferation, migration into the area of the lesion and either differentiation into the appropriate cell type or secretion of anti-inflammatory cytokines. Although NSCs have beneficial roles, current evidence indicates that brain tumours, such as astrogliomas or ependymomas are also caused by tumour-initiating cells with stem-like properties. However, little is known about the cellular and molecular processes potentially generating tumours from NSCs. Most pro-inflammatory conditions are considered to activate the transcription factor NF-kappaB in various cell types. Strong inductive effects of NF-kappaB on proliferation and migration of NSCs have been described. Moreover, NF-kappaB is constitutively active in most tumour cells described so far. Chronic inflammation is also known to initiate cancer. Thus, NF-kappaB might provide a novel mechanistic link between chronic inflammation, stem cells and cancer. This review discusses the apparently ambivalent role of NF-kappaB: physiological maintenance and repair of the brain via NSCs, and a potential role in tumour initiation. Furthermore, it reveals a possible mechanism of brain tumour formation based on inflammation and NF-kappaB activity in NSCs.

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Esta pesquisa investigou relações entre interesses vocacionais e o desenvolvimento psicossocial e de carreira na vida adulta. A tipologia de interesses vocacionais de J. Holland, hegemônica no campo da psicologia vocacional, considera a escolha da carreira como expressão direta da personalidade. O modelo propõe seis tipos de interesse ou fatores de personalidade vocacional: realista, investigativo, artístico, social, empreendedor e convencional. Holland sugeriu que as preferências vocacionais estão relacionadas à diferenças em capacidades e disposição para fazer transições de carreira. O mercado de trabalho atual requer profissionais adaptáveis e capazes de gerenciar as suas carreiras. Estes comportamentos podem ser descritos através dos conceitos de comprometimento e entrincheiramento de carreira. O comprometimento inclui a identificação com o trabalho e o planejamento da carreira. O entrincheiramento refere-se à imobilização do sujeito numa ocupação devido a falta de alternativas de carreira e ao medo da mudança. Adultos na meia-idade são propensos ao entrincheiramento devido a restrição de suas oportunidades de crescimento profissional neste período. É também nesta época que surgem as preocupações generativas. A generatividade significa o envolvimento do indivíduo com o bem-estar das próximas gerações e o seu desejo de ser lembrado na posteridade. Diferenças de personalidade têm sido associadas à adaptabilidade de carreira e à generatividade. Esta pesquisa investigou relações entre personalidades vocacionais, comportamentos de carreira e generatividade na vida adulta. Participaram do estudo 733 profissionais (415 homens e 318 mulheres) com idades entre 25 e 65 anos e com, no mínimo, 5 anos de carreira profissional. Os sujeitos responderam a medidas de interesses vocacionais, generatividade, comprometimento com a carreira e entrincheiramento na carreira. A generatividade correlacionou positivamente com o comprometimento e negativamente com o entrincheiramento. Tipos convencionais revelaram menor generatividade em comparação com artísticos, sociais e empreendedores. Na adultez média, tipos investigativos mostraram maior entrincheiramento do que empreendedores e realistas. Tipos empreendedores mostraram maior planejamento de carreira do que realistas e sociais. Os resultados indicaram que a adaptabilidade de carreira e a generatividade estão relacionadas a tipos de interesse vocacional, corroborando a importância de fatores de personalidade para o entendimento do desenvolvimento adulto. As implicações teóricas e práticas são discutidas. Palavras-chave: interesses vocacionais, generatividade, carreira.

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Trata do estudo da questão da terceirização com relação aos aspectos conjunturais do seu surgimento os novos modelos de relações do trabalho e relações industriais engendrado pelo modelo fordista de produção da questão estratégica e da prática da utilização da mesma pelas empresas brasileiras através da análise de pesquisa de campo

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Paracoccidioides brasiliensis is a fungal human pathogen with a wide distribution in Latin America. It causes paracoccidioidomycosis, the most widespread systemic mycosis in Latin America. Although gene expression in P. brasiliensis had been studied, little is known about the genome sequences expressed by this species during the infection process. To better understand the infection process, 4934 expressed sequence tags (ESTs) derived from a non-normalized cDNA library from P. brasiliensis (isolate Pb01) yeast-phase cells recovered from the livers of infected mice were annotated and clustered to a UniGene (clusters containing sequences that represent a unique gene) set with 1602 members. A large-scale comparative analysis was performed between the UniGene sequences of P. brasiliensis yeast-phase cells recovered from infected mice and a database constructed with sequences of the yeast-phase and mycelium transcriptome (isolate Pb01) (https://dna.biomol.unb.br/Pb/), as well as with all public ESTs available at GenBank, including sequences of the P. brasiliensis yeast-phase transcriptome (isolate Pb18) (http:// www.ncbi.nlm.nih.gov/). The focus was on the overexpressed and novel genes. From the total, 3184 ESTs (64.53%) were also present in the previously described transcriptome of yeast-form and mycelium cells obtained from in vitro cultures (https://dna.biomol.unb.br/Pb/) and of those, 1172 ESTs (23.75% of the described sequences) represented transcripts overexpressed during the infection process. Comparative analysis identified 1750 ESTs (35.47% of the total), comprising 649 UniGene sequences representing novel transcripts of P. brasiliensis, not previously described for this isolate or for other isolates in public databases. KEGG pathway mapping showed that the novel and overexpressed transcripts represented standard metabolic pathways, including glycolysis, amino acid biosynthesis, lipid and sterol metabolism. The unique and divergent representation of transcripts in the cDNA library of yeast cells recovered from infected mice suggests differential gene expression in response to the host milieu.

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The purpose of this study was to evaluate the effects of simvastatin on guided bone regeneration in the mandibles of ovariectomized rats, and to observe their blood cholesterol levels. Seventy female rats were divided into two groups: control and treated, both groups containing normal and ovariectomized rats. A month after ovariectomy a bone defect was created in the mandible, and was covered by a polytetrafluoroethylene membrane. The treated groups received simvastatin orally for 15 or 30 days. The rats were sacrificed 15, 30 or 60 days after surgery, at which time a blood sample was extracted for blood cholesterol level analysis and the mandible was extracted for densitometric, histological and morphometric analysis. All specimens underwent analysis of variance. The ovariectomized animals had higher cholesterol levels than the treated normal animals, and no significant difference was found between the different treatment periods and the sacrifice times. The densitometric, histological and morphometric analysis showed that the treated ovariectomized animals developed more new bone than the control ovariectomized rats, but no significant difference was observed between the treatment periods. It can be concluded that the deficiency of estrogen increased the level of blood cholesterol and that the simvastatin aided new bone formation in the ovariectomized animals.

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This pilot study evaluated, by culture testing, the effectiveness of lethal photosensitization for the microbiological treatment of peri-implantitis in dogs. Experimental peri-implantitis was induced by ligature placement for 2 months. Following ligature removal, plaque control was instituted by scrubbing with 0.12% chlorhexidine daily for 12 months. Subsequently, mucoperiosteal flaps were elevated for scaling the implant surface. Microbial samples were obtained with paper points before and after treatment of implant surfaces by means of 100 microg/ml toluidine blue O (TBO,) and were exposed, for 80 s, to light with a wavelength of 685 nm from a 50 mW GaAlAs diode laser. The mean initial and final bacterial counts were 7.22 +/- 0.20 and 6.84 +/- 0.44 CFU/ml, respectively for TVC (P < 0.0001); 6.19 +/- 0.45 and 3.14 +/- 3.29 CFU/ml for P. intermedia/nigrescens (P = 0.001); 5.98 +/- 0.38 and 1.69 +/- 2.90 CFU/ml for Fusobacterium spp. (P = 0.001); and 6.07 +/- 0.22 to 1.69 +/- 2.94 CFU/ml for beta-hemolytic Streptococcus (P = 0.0039). It may be concluded that lethal photosensitization resulted in a reduction of the bacterial count. Complete elimination of bacteria was achieved in some samples.

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The objective of this study was to assess the association between the levels of enzyme aspartate aminotransferase (AST) in gingival crevicular fluid (GCF) with the BANA hydrolysis microbiological test (Perioscan) and clinical periodontal diagnostic measurements, such as bleeding on probing, plaque index, gingival index, probing depth, and attachment level in patients with chronic periodontitis using an enzymatic test (PocketWatch). One hundred and forty-seven sites were evaluated in 22 patients with a probing depth of > or = 5 mm at selected sites. AST and BANA enzymatic tests were carried out, and clinical parameters recorded. Pearson's chi-square and Fisher's exact tests were used for statistical analysis. There was no statistical correlation between AST levels and any of the analyzed parameters. The lack of any association between the factors studied does not indicate, however, that the latter cannot be used in diagnosing the actual periodontal condition of patients and/or sites. However, more research should be carried out to evaluate the true relationship between AST and periodontal disease.

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Cleidocranial dysplasia (CCD) is a rare syndrome usually caused by an autosomal dominant gene, although 40% of cases of CCD appear spontaneously with no apparent genetic cause. This condition is characterized by several cranial malformations and underdevelopment, absence of the clavicles, and multiple supernumerary and impacted permanent teeth. The diagnosis of this condition is usually based on the presence of the main features (supernumerary teeth, partial or total absence of one or both the clavicles, and bony malformations) and on clinical and familial evidence. The bony and dental features of CCD may be visualized on radiographic images of the face and skull. Here, we present a familial case of CCD and discuss the importance of dental radiographs in diagnosis of the condition.

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The aim of this study was to evaluate the antimicrobial activity of different root-end filling materials - Sealer 26, Sealapex with zinc oxide, zinc oxide and eugenol, white and gray Portland cement, white and gray MTA-Angelus, and gray Pro Root MTA - against six different microorganism strains. The agar diffusion method was used. A base layer was made using Müller-Hinton agar (MH) and wells were formed by removing the agar. The materials were placed in the wells immediately after manipulation. The microorganisms used were: Micrococcus luteus (ATCC9341), Staphylococcus aureus (ATCC6538), Escherichia coli (ATCC10538), Pseudomonas aeruginosa (ATCC27853), Candida albicans (ATCC 10231), and Enterococcus faecalis (ATCC 10541). The plates were kept at room temperature for 2 h for prediffusion and then incubated at 37 degrees C for 24 h. Triphenyltetrazolium chloride 0.05% gel was added for optimization, and the zones of inhibition were measured. Data were subjected to the Kruskal-Wallis and Dunn tests at a 5% significance level. The results showed that all materials had antimicrobial activity against all the tested strains. Analysis of the efficacy of the materials against the microbial strains showed that Sealapex with zinc oxide, zinc oxide and eugenol and Sealer 26 created larger inhibition halos than the MTA-based and Portland cements (P < 0.05). On the basis of the methodology used, it may be concluded that all endodontic sealers, MTA-based and Portland cements evaluated in this study possess antimicrobial activity, particularly the endodontic sealers.

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A study was conducted to evaluate in vitro the effect of root surface conditioning with basic fibroblast growth factor (b-FGF) on morphology and proliferation of fibroblasts. Three experimental groups were used: non-treated, and treated with 50 microg or 125 microg b-FGF/ml. The dentin samples in each group were divided into subgroups according to the chemical treatment received before application of b-FGF: none, or conditioned with tetracycline-HCl or EDTA. After contact with b-FGF for 5 min, the samples were incubated for 24 h with 1 ml of culture medium containing 1 x 10(5) cells/ml plus 1 ml of culture medium alone. The samples were then subjected to routine preparation for SEM, and random fields were photographed. Three calibrated and blind examiners performed the assessment of morphology and density according to two index systems. Classification and regression trees indicated that the root surfaces treated with 125 microg b-FGF and previously conditioned with tetracycline-HCl or EDTA presented a morphology more suggestive of cellular adhesion and viability (P = 0.004). The density of fibroblasts on samples previously conditioned with EDTA, regardless of treatment with b-FGF, was significantly higher than in the other groups (P < 0.001). The present findings suggest that topical application of b-FGF has a positive influence on both the density and morphology of fibroblasts.

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Bone exostosis has long been described in the literature, appearing in most cases as a torus palatinus or mandibularis. These two variations are relatively common and affect approximately 30% of the world's population. Incidence is even higher when human skulls are examined post mortem, indicating that in some cases the exostosis is small and cannot be seen under the soft tissue. Removal of an exostosis is usually associated with the construction of a prothesis, but in rare cases such as the present, the lesion enlarges enough to affect speech and feeding. Few studies have reported the removal of such a large exostosis, and all were conducted in a hospital environment. In this case, complete removal was successfully conducted in an ambulatory clinic under local anesthesia.

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The potential for malignant transformation of oral lichen planus is still controversial. The expression of proteins related to cell proliferation and apoptosis in oral lichen planus and epithelial dysplasia was analyzed to evaluate the true potential for malignant transformation of this disease. Twenty-four cases of each lesion were subjected to the streptoavidin-biotin technique for identifying the immunohistochemical expression of PCNA, p53, bax, and bcl-2 proteins. Of the 24 cases of oral lichen planus, 14 (58.33%) were positive for PCNA, 10 (41.67%) for p53, 4 (16.67%) for bcl-2 and 12 (50%) for bax, whereas of the 24 cases of epithelial dysplasia, 20 (83.33%) were positive for PCNA, 10 (41.67%) for p53, 6 (25%) for bcl-2, and 20 (83.33%) for bax. Chi-squared test showed no statistically significant differences between the expression of p53 and bcl-2 in oral lichen planus and epithelial dysplasia, regardless of the grade (P > 0.05). However, the expression of PCNA and bax was significantly increased in epithelial dysplasia (P < 0.05). The results of this study showed that alterations in expression of these proteins are observed in oral lichen planus and epithelial dysplasia, suggesting the potential for malignant transformation in both lesions.