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1.
Mem Inst Oswaldo Cruz ; 113(10): e180311, 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30304087

RESUMO

BACKGROUND: Scedosporium apiospermum is a ubiquitous, emerging and multidrug-resistant fungal pathogen with still rather unknown virulence mechanisms. OBJECTIVES/METHODS: The cellular basis of the in vitro interaction between fungi and host cells/tissues is the determinant factor for the development of a successful in vivo infection. Herein, we evaluated the interaction of S. apiospermum conidia with lung epithelial (A549), lung fibroblast (MRC-5) and RAW 264.7 macrophages by light and scanning/transmission electron microscopy. FINDINGS: After 4 h of fungi-host cell contact, the percentage of infected mammalian cells and the number of fungi per infected cell was measured by light microscopy, and the following association indexes were calculated for A549, MRC-5 and macrophage cells: 73.2 ± 25.9, 69.7 ± 22.5 and 59.7 ± 11.1, respectively. Both conidia and germinated conidia were regularly observed interacting with the evaluated cells, with a higher prevalence of non-germinated conidia. Interestingly, nests of germinated conidia were evidenced at the surface of lung cells by scanning electron microscopy. Some germination projections and hyphae were seen penetrating/evading the mammalian cells. Furthermore, internalised conidia were seen within vacuoles as visualised by transmission electron microscopy. MAIN CONCLUSIONS: The present study contributes to a better understanding of S. apiospermum pathogenesis by demonstrating the first steps of the infection process of this opportunistic fungus.


Assuntos
Células Epiteliais/microbiologia , Pulmão/microbiologia , Macrófagos/microbiologia , Scedosporium/ultraestrutura , Esporos Fúngicos/ultraestrutura , Células Epiteliais/ultraestrutura , Humanos , Pulmão/ultraestrutura , Macrófagos/ultraestrutura , Microscopia Eletrônica de Varredura , Scedosporium/fisiologia , Esporos Fúngicos/fisiologia
2.
Regul Toxicol Pharmacol ; 91: 1-8, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28970106

RESUMO

The application of in silico methods is increasing on toxicological risk prediction for human and environmental health. This work aimed to evaluate the performance of three in silico freeware models (OSIRIS v.2.0, LAZAR, and Toxtree) on the prediction of carcinogenicity and mutagenicity of thirty-eight volatile organic compounds (VOC) related to chemical risk assessment for occupational exposure. Theoretical data were compared with assessments available in international databases. Confusion matrices and ROC curves were used to evaluate the sensitivity, specificity, and accuracy of each model. All three models (OSIRIS, LAZAR and Toxtree) were able to identify VOC with a potential carcinogenicity or mutagenicity risk for humans, however presenting differences concerning the specificity, sensitivity, and accuracy. The best predictive performances were found for OSIRIS and LAZAR for carcinogenicity and OSIRIS for mutagenicity, as these softwares presented a combination of negative predictive power and lower risk of false positives (high specificity) for those endpoints. The heterogeneity of results found with different softwares reinforce the importance of using a combination of in silico models to occupational toxicological risk assessment.


Assuntos
Carcinógenos/toxicidade , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Medição de Risco/métodos , Compostos Orgânicos Voláteis/toxicidade , Simulação por Computador , Bases de Dados Factuais , Humanos , Modelos Biológicos , Mutagênese/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Sensibilidade e Especificidade , Software
3.
J Contemp Dent Pract ; 16(8): 665-73, 2015 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-26423503

RESUMO

AIM: This study assessed the biocorrosive capacity of two bacteria: Desulfovibrio desulfuricans and Desulfovibrio fairfieldensis on endodontic files, as a preliminary step in the development of a biopharmaceutical, to facilitate the removal of endodontic file fragments from root canals. MATERIALS AND METHODS: In the first stage, the corrosive potential of the artificial saliva medium (ASM), modified Postgate E medium (MPEM), 2.5 % sodium hypochlorite (NaOCl) solution and white medium (WM), without the inoculation of bacteria was assessed by immersion assays. In the second stage, test samples were inoculated with the two species of sulphur-reducing bacteria (SRB) on ASM and modified artificial saliva medium (MASM). In the third stage, test samples were inoculated with the same species on MPEM, ASM and MASM. All test samples were viewed under an infinite focus Alicona microscope. RESULTS: No test sample became corroded when immersed only in media, without bacteria. With the exception of one test sample between those inoculated with bacteria in ASM and MASM, there was no evidence of corrosion. Fifty percent of the test samples demonstrated a greater intensity of biocorrosion when compared with the initial assays. CONCLUSION: Desulfovibrio desulfuricans and D. fairfieldensis are capable of promoting biocorrosion of the steel constituent of endodontic files. CLINICAL SIGNIFICANCE: This study describes the initial development of a biopharmaceutical to facilitate the removal of endodontic file fragments from root canals, which can be successfully implicated in endodontic therapy in order to avoiding parendodontic surgery or even tooth loss in such events.


Assuntos
Desulfovibrio/fisiologia , Endodontia/instrumentação , Preparo de Canal Radicular/instrumentação , Bactérias Redutoras de Enxofre/fisiologia , Corrosão , Desulfovibrio/classificação , Desulfovibrio/efeitos dos fármacos , Endodontia/métodos , Humanos , Preparo de Canal Radicular/métodos , Bactérias Redutoras de Enxofre/classificação , Bactérias Redutoras de Enxofre/efeitos dos fármacos
4.
Curr Microbiol ; 69(3): 357-64, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24807624

RESUMO

Bacterial multiresistance is a health problem worldwide that demands new antimicrobials for treating bacterial-related infections. In this study, we evaluated the antimicrobial activity and the theoretical toxicology profile of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazide derivatives against gram-positive and gram-negative bacteria clinical strains. On that purpose we determined the minimum inhibitory (MIC) and bactericidal (MBC) concentrations, the in vitro cytotoxicity, and in silico risk profiles, also comparing with antimicrobial agents of clinical use. Among the 16 derivatives analyzed, four nitrofurans (N-H-FUR-NO(2), N-Br-FUR-NO(2), N-F-FUR-NO(2), N-Cl-FUR-NO(2)) showed promising MIC and MBC values (MIC = MBC = 1-16 µg/mL). The experimental data revealed the potential of these derivatives, which were comparable to the current antimicrobials with similar bactericidal and bacteriostatic profiles. Therefore, these molecules may be feasible options to be explored for treating infections caused by multiresistant strains. Our in vitro and in silico toxicity reinforced these results as these derivatives presented low cytotoxicity against human macrophages and low theoretical risk profile for irritant and reproductive effects compared to the current antimicrobials (e.g., vancomycin and ciprofloxacin). The molecular modeling analysis also revealed positive values for their theoretical druglikeness and drugscore. The presence of a 5-nitro-2-furfur-2-yl group seems to be essential for the antimicrobial activity, which pointed these acylhydrazone derivatives as promising for designing more potent and safer compounds.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hidrazonas/farmacologia , Infecções Bacterianas/microbiologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Macrófagos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos
5.
Mem Inst Oswaldo Cruz ; 109(7): 940-3, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25410999

RESUMO

Endothelial dysfunction is a major component of the pathophysiology of septicaemic group B Streptococcus (GBS) infections. Although cytokines have been shown to activate human umbilical vein endothelial cells (HUVECs), the capacity of interferon (IFN)-γ to enhance the microbicidal activity of HUVECs against GBS has not been studied. We report that the viability of intracellular bacteria was reduced in HUVECs activated by IFN-γ. Enhanced fusion of lysosomes with bacteria-containing vacuoles was observed by acid phosphatase and the colocalisation of Rab-5, Rab-7 and lysosomal-associated membrane protein-1 with GBS in IFN-γ-activated HUVECs. IFN-γ resulted in an enhancement of the phagosome maturation process in HUVECs, improving the capacity to control the intracellular survival of GBS.


Assuntos
Anti-Infecciosos/farmacologia , Células Endoteliais da Veia Umbilical Humana/microbiologia , Interferon gama/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus agalactiae/efeitos dos fármacos , Fosfatase Ácida/metabolismo , Aderência Bacteriana/efeitos dos fármacos , Endocitose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lisossomos/efeitos dos fármacos , Fagossomos/efeitos dos fármacos , Cultura Primária de Células , Infecções Estreptocócicas/prevenção & controle , Análise de Sobrevida
6.
Curr Microbiol ; 62(5): 1349-54, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21225264

RESUMO

Herpes simplex virus is an important human pathogen responsible for a range of diseases from mild uncomplicated mucocutaneous infections to life-threatening ones. Currently, the emergence of Herpes simplex virus resistant strains increased the need for more effective and less cytotoxic drugs for Herpes treatment. In this work, we synthesized a series of oxoquinoline derivatives and experimentally evaluated the antiviral activity against acyclovir resistant HSV-1 strain as well as their cytotoxity profile. The most active compound (3b), named here as Fluoroxaq-3b, showed a promising profile with a better cytotoxicity profile than acyclovir. The theoretical analysis of the structure-activity relationship of these compounds revealed some stereoelectronic properties such as lower LUMO energy and lipophilicity, besides a higher polar surface area and number of hydrogen bond acceptor groups as important parameters for the antiviral activity. Fluoroxaq-3b showed a good oral theoretical bioavailability, according to Lipinski rule of five, with a promising profile for further in vivo analysis.


Assuntos
Antivirais/química , Antivirais/farmacologia , Herpes Simples/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Quinolonas/química , Quinolonas/farmacologia , Animais , Antivirais/síntese química , Linhagem Celular , Chlorocebus aethiops , Herpes Simples/tratamento farmacológico , Humanos , Quinolonas/síntese química , Relação Estrutura-Atividade , Células Vero
7.
Blood Coagul Fibrinolysis ; 32(6): 411-417, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397450

RESUMO

Leukocyte-platelet rich fibrin (PRF) is an autologous biomaterial formed by platelets, cytokines, growth factors and cells imprisoned on a fibrin mesh, produced according to Choukroun's protocol. The aim of the present article was to report the use of PRF, associated with a bone substitute, on the regenerative treatment of a large bone defect resulting from the enucleation of a paradental cyst involving the posterior mandible. The treatment resulted in the maintenance of the bone volume, and radiographic evaluation showed new bone formation after 40 days, suggesting an osteogenic and osteoinductive effect. Also, the current literature was reviewed.


Assuntos
Substitutos Ósseos/uso terapêutico , Cistos/terapia , Leucócitos/metabolismo , Traumatismos Mandibulares/terapia , Fibrina Rica em Plaquetas/metabolismo , Adolescente , Regeneração Óssea , Substitutos Ósseos/metabolismo , Feminino , Humanos , Traumatismos Mandibulares/metabolismo , Traumatismos Mandibulares/patologia
8.
Vet Parasitol Reg Stud Reports ; 23: 100523, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33678378

RESUMO

The cattle tick Rhipicephalus microplus is a significant problem for livestock, causing losses of billions of dollars per year. This work aimed to determine the chemical composition of essential oils obtained from Laurus nobilis and Copaifera officinalis and evaluate activity against engorged R. microplus females. Chemical composition analyzed by GC-MS revealed the presence of 39 components accounting for 95.38% of the oil in L. nobilis, the most abundant being 1,8-cineol (25.7%), trans-sabinene-hydrate (20.8%), and α-terpinil acetate (15.0%). Chemical analysis of C. officinalis oil identified 25 components corresponding to 80.5% of the total constituents, where the major compounds were ß-caryophyllene (21.1%), caryophyllene oxide (10.7%), and α-trans-bergamotene (9.3%). Adult immersion test (AIT) showed that L. nobilis essential oil at 5% or 10% caused 80.5% mortality of engorged females after 24 h and reached 96.9% and 100% mortality on the third day after treatment, respectively. While the essential oil from C. officinalis caused 84.7% mortality after six days at 10% and at 5%, achieved approximately 100% mortality rate at the end of the experiment (day 15). Both essential oils and the combination significantly inhibited egg-laying; however, the combination treatment showed higher effectiveness than the isolated oils at 2.5%. A possible synergic action of L. nobilis and C. officinalis against the cattle tick R. microplus is therefore suggested. The present work introduces a potential alternative for the development of a formulation environment-friendly (green pesticide) used to control cattle tick infestations.


Assuntos
Acaricidas , Óleos Voláteis , Óleos de Plantas , Rhipicephalus , Acaricidas/farmacologia , Animais , Feminino , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Rhipicephalus/efeitos dos fármacos
9.
J Conserv Dent ; 23(2): 196-200, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33384495

RESUMO

AIMS: This study determined the corrosion rate by mass loss caused by oral strains of sulphate-reducing bacteria (SRB) in Kerr endodontic files (KF), aiming the development of a biopharmaceutical that facilitates the removal of endodontic limb fragments from root canals. MATERIALS AND METHODS: Nine new KF were analyzed after immersion in the modified Postgate E culture medium inoculated with Desulfovibrio desulfuricans oral (84 days), Desulfovibrio fairfieldensis in the consortium (84 days) and environmental D. desulfuricans (119 days). RESULTS: Optical microscopy revealed corrosion suggestive areas in all files submitted to immersion in SRB cultures, presenting a statistical difference (P < 0.05) between the samples environmental D. desulfuricans and KF control and between oral D. desulfuricans and KF control. Epifluorescence microscopy revealed an active SRB biofilm over the entire metal surface of the KF, as evidenced by the SYTO® 9 fluorophore. CONCLUSION: SRB were capable of promoting biocorrosion in Kerr type endodontic files, but with low rate.

10.
Pharmaceutics ; 11(5)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31052360

RESUMO

Cutaneous leishmaniasis (CL) is a parasitic disease characterized by progressive skin sores. Currently, treatments for CL are limited to parenteral administration of the drug, which presents severe adverse effects and low cure rates. Therefore, this study aimed to develop poly(vinyl-alcohol) (PVA) hydrogels containing Amphotericin B (AmB) intended for topical treatment of CL. Hydrogels were evaluated in vitro for their potential to eliminate promastigote forms of Leishmania spp., to prevent secondary infections, to maintain appropriate healing conditions, and to offer suitable biocompatibility. AmB was incorporated into the system in its non-crystalline state, allowing it to swell more and faster than the system without the drug. Furthermore, the AmB release profile showed a continuous and controlled behavior following Higuchi´s kinetic model. AmB-loaded-PVA-hydrogels (PVA-AmB) also showed efficient antifungal and leishmanicidal activity, no cytotoxic potential for VERO cells, microbial impermeability and water vapor permeability compatible with the healthy skin's physiological needs. Indeed, these results revealed the potential of PVA-AmB to prevent secondary infections and to maintain a favorable environment for the healing process. Hence, these results suggest that PVA-AmB could be a suitable and efficient new therapeutic approach for the topical treatment of CL.

11.
Rev. CEFAC ; 25(5): e6823, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1521543

RESUMO

ABSTRACT Purpose: to assess the advancement in communicative intention and cognition in children with autism spectrum disorder after applying a personalized alternative communication method. Methods: patients had their communicative intention and cognition (Vineland-3) assessed before and after the intervention with 10 structured alternative communication sessions. The "Demystifying Alternative Communication" podcast was developed as supplementary material to this study. Student's t-test was used, setting the significance level at p < 0.05. Results: patients improved their communicative intention, with higher scores after the intervention, and no changes were found in relation to cognition. Conclusion: even though the patients' equivalent age was inferior to their real age in the communication subdomain assessment, they progressed in expressive communication, language, and writing.


RESUMO Objetivo: avaliar o avanço da intenção comunicativa e da cognição em crianças com Transtorno do Espectro Autista após a aplicação de metodologia personalizada de comunicação alternativa. Métodos: foram realizadas dez sessões estruturadas de comunicação alternativa e os pacientes foram avaliados antes e após a intervenção quanto a intenção comunicativa e cognição (Vineland-3). Como material suplementar deste trabalho, foi elaborado o podcast "Desmistificando a Comunicação Alternativa". Foi utilizado teste t-Student com o p <0,05 onsiderado significante. Resultados: os pacientes apresentaram melhoras quanto à intenção comunicativa, demonstrando maiores escores após a realização da intervenção. Conclusão: apesar de os pacientes apresentarem uma idade equivalente inferior à idade real na avaliação do subdomínio da comunicação, estes demonstraram avanços quanto às variáveis de comunicação expressiva, linguagem e escrita.

12.
J Comput Biol ; 25(12): 1285-1300, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30251882

RESUMO

In vitro experiments were conducted in this work to analyze the proliferation of tumor (DU-145) and normal (macrophage RAW 264.7) cells under the influence of a chemotherapeutic drug (doxorubicin). Approximate Bayesian Computation (ABC) was used to select among four competing models to represent the number of cells and to estimate the model parameters, based on the experimental data. For one case, the selected model was validated in a replicated experiment, through the solution of a state estimation problem with a particle filter algorithm, thus demonstrating the robustness of the ABC procedure used in this work.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Modelos Teóricos , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Camundongos , Células RAW 264.7
13.
Int J Dent ; 2018: 8303450, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29861730

RESUMO

AIM: This study describes the biofilm formation and the corrosive capacity of sulfate-reducing bacteria (SRB) on the metallic structure of used endodontic files. METHODS: Sulfate-reducing bacteria (SRB) (Desulfovibrio desulfuricans oral and Desulfovibrio fairfieldensis or D. desulfuricans environmental) were inoculated into the culture media (Postgate C culture medium or modified Postgate E culture medium). The biocorrosive potential of these bacteria will be an important component of a biopharmaceutical under development called BACCOR. Afterwards, four used endodontic files (UEFs) were separately inoculated into a specific culture media for 445 days at 30°C in an incubator. The four UEFs were placed in a scanning electron microscope (SEM) and analyzed by the energy-dispersive X-ray spectrometry (EDS). RESULTS: The confocal laser scanning microscopic images indicate the presence of biofilm in the four samples. The SEM and SEM-EDS revealed the presence of rough, irregular structures adhering along the metallic surface of the used endodontic files, suggesting a mature calcified biofilm with a high concentration of Ca, P, C, and S. CONCLUSION: The formation of SRB biofilms on used endodontic files shows characteristics that may contribute to the biocorrosion of these files, and the results may also provide complementary data for a biopharmaceutical, which is still under development to assist in the removal of fractured endodontic files inside root channels.

14.
Med Chem ; 14(3): 304-310, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28676004

RESUMO

BACKGROUND: Over the last few years, fungal infections have emerged as a worrisome global public health problem. Candidiasis is a disease caused by Candida species and has been a problem worldwide mainly for immunosuppressed patients. Lately, the resistant strains and side effects have been reported as important issues for treating Candidiasis, which have to be solved by identifying new drugs. OBJECTIVE: The goal of this work was to synthesize a series of 1,3-benzoxathiol-2-one derivatives, XYbenzo[ d][1,3]oxathiol-2-ones, and evaluate their antifungal activity against five Candida species. METHODS: In vitro antifungal screening test and minimum inhibitory concentration determination were performed according to CLSI protocols using ketoconazole as the reference drug. The cytotoxicity of the most active compounds was evaluated by hemolysis and MTT (Vero cells) assays. RESULTS: Compounds 2 (XY = 6-hydroxy-5-nitro, MIC = 4-32 µg/mL) and 7 (XY = 6-acetoxy-5-nitro, MIC =16-64 µg/mL) showed good results when compared with current antifungals in CLSI values (MIC = 0.04-250 µg/mL). These compounds exhibited a safer cytotoxicity as well as a lower hemolytic profile than ketoconazole. CONCLUSION: Overall, the in vitro results pointed to the potential of compounds 2 and 7 as new antifungal prototypes to be further explored.


Assuntos
Antifúngicos/farmacologia , Compostos Heterocíclicos com 2 Anéis/farmacologia , Lactonas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/toxicidade , Candida/efeitos dos fármacos , Cristalografia por Raios X , Compostos Heterocíclicos com 2 Anéis/síntese química , Compostos Heterocíclicos com 2 Anéis/química , Compostos Heterocíclicos com 2 Anéis/toxicidade , Lactonas/síntese química , Lactonas/química , Lactonas/toxicidade , Testes de Sensibilidade Microbiana , Estrutura Molecular
15.
Biochem Res Int ; 2017: 5342947, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29123924

RESUMO

The present research aimed to study the chemical composition and acaricidal activity of Citrus limonum and Piper nigrum essential oils against the cattle tick Rhipicephalus microplus. GC-MS analysis of C. limonum essential oil showed limonene (50.3%), ß-pinene (14.4%), and γ-terpinene (11.7%) as the major components; P. nigrum oil was mainly composed of ß-caryophyllene (26.2%), σ-ocymene (5.8%), and α-pinene (5.5%). Acaricide activity was evaluated at concentrations of 2.5, 5.0, and 10.0% (v/v) of each plant oil, as well as 1 : 1 combination of both oils (5% : 5%, 2.5% : 2.5%, and 1.25% : 1.25% each), by immersing engorged R. microplus females for one minute. The LC90 of oils from C. limonum, P. nigrum, and the combination were 4.9%, 14.8%, and 5.1%, respectively. C. limonum essential oil caused 100% mortality of engorged females at the highest concentration (10%). P. nigrum essential oil inhibited egg-laying by up to 96% in a concentration-dependent manner, suggesting it reduces tick fecundity. When combined, the oils presented toxicity as to C. limonum oil alone, but with stronger inhibition of oviposition (5% : 5%), indicating a possible additive effect against R. microplus. The present data provide support for further investigation of novel natural products to control bovine tick infestations.

16.
Anticancer Agents Med Chem ; 17(4): 483-490, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27481554

RESUMO

Cancer incidence represents an important public health problem worldwide. Nuclear factor kappa B (NF- κB) transcription factor plays a pivotal role in the regulation of genes that control various responses in eukaryotic cells, including proliferation and survival, cytoskeletal remodeling, cellular adhesion and apoptosis. Extensive studies have demonstrated the contribution of NF-κB transcription in the promotion and progression of several hematological malignancies and solid tumors, in which NF-κB constitutive activation and/or overexpression are common clinical features. Moreover, triggering the NF-κB pathway is already considered one of the important mechanisms of resistance development to chemotherapy and radiotherapy, indicating that the inhibition of this signaling cascade is a promising approach to enhancing efficacy and preventing acquired resistance in cancer treatment. In this review, research efforts dedicated to the identification of novel NF-κB signaling pathway inhibitors as promising anticancer drug candidates are described.


Assuntos
Antineoplásicos/farmacologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Neoplasias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/química , Glucocorticoides/farmacologia , Humanos , Quinase I-kappa B/antagonistas & inibidores , Neoplasias/genética , Neoplasias/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitinação/efeitos dos fármacos
17.
Dent Mater J ; 35(5): 762-768, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27725513

RESUMO

This study assessed the cell viability of the inoculation vehicle of BACCOR (a combination of sulfate-reducing bacteria plus a culture media for bacteria), a biopharmaceutical product under development for dental use as aid in fractured endodontic file removal from the root canal. Different culture media for bacteria were evaluated: modified Postgate E (MCP-E mod), Modified Postgate E without Agar-agar (MCP-E w/Ag), Postgate C with Agar-agar (MCP-C Ag) and Postgate C without Agar-agar (MCP-C w/Ag). Cytotoxicity was quantified by the MTT test, exposing L929 and Vero cell lines to the vehicles over 24 h. The exposure of L929 cell line to MCP-E w/Ag resulted in biocompatibility (52% cell viability), while the exposure of the Vero kidney line revealed only MCP-E mod as cytotoxic. When diluted, all the vehicles showed biocompatibility with both cell lines. MCP-E w/Ag was the vehicle chosen for BACCOR, because of its biocompatibility with the cells used.


Assuntos
Sobrevivência Celular , Endodontia , Bactérias Redutoras de Enxofre , Linhagem Celular , Meios de Cultura , Sulfatos
18.
Int J Mol Med ; 15(5): 859-63, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15806310

RESUMO

The molecular mechanisms underlying entry of group B Streptococci (GBS) into human endothelial cells are not yet fully understood. This study is centered on the triggering of signaling cascade in human umbilical vein endothelial cells (HUVEC) during their interaction with different GBS serotypes/strains (type III: 80340-vagina and 90356-CSF and type V: 88641-vagina and 90186-blood). We have shown that the analyzed microorganisms adhere to HUVEC, but only those of the strains 90356-CSF, 88641-vagina and 90186-blood presented intracellular viability. Activation of PKC directly increased F-actin content and organization into stress fibers, and increased intracellular viability of GBS-III microorganisms. PKA inhibitor seems to promote surveillance of GBS type V microorganisms within HUVEC. These studies indicate that different molecules present at the cell surface of the GBS might induce different responses to HUVEC, interfering with the recruitment of cortical actin filaments.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Células Endoteliais/microbiologia , Proteína Quinase C/fisiologia , Transdução de Sinais , Streptococcus agalactiae/patogenicidade , Actinas/metabolismo , Aderência Bacteriana , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/enzimologia , Humanos , Isoquinolinas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Esfingosina/farmacologia , Streptococcus agalactiae/fisiologia , Fibras de Estresse/metabolismo , Sulfonamidas/farmacologia , Veias Umbilicais/citologia
19.
Int J Mol Med ; 15(1): 153-7, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15583842

RESUMO

The mechanism by which group B Streptococcus (GBS) interacts with human cells and disrupts physiological processes is an intriguing area of investigation and continues to unfold. The aim of this study was to investigate the adherence and intracellular viability within endothelial ECV304 cells of GBS serotypes Ia, III and V isolates from patients and asymptomatic carriers. The GBS isolates from patients (GBS-Ia 90222-urine, GBS-III 90356-liquor and GBS-V 90186-blood strains) exhibited a more efficient adherence and survival mechanisms to endothelial cells than those from asymptomatic carriers (GBS-Ia 85147-oropharynx, GBS-III 80340 and GBS-V 88641-vagina strains), independent of bacterial serotypes. Treatment of endothelial ECV304 cells with EDTA demonstrated that Ca2+-dependent molecules modulated the adherence and internalization process of GBS-Ia and III to ECV304 cells. SDS-PAGE analysis of samples of biotinylated ECV304 extracts treated with GBS clinical isolates (urine 90222-Ia, liquor 90356-III and blood 90186-V strains) revealed fragments ranging from approximately 61 to approximately 179 kDa. Results of immunoassays with ECV304 membrane proteins showed that ICAM-1 molecules interacted only with GBS-III liquor 90356 strain while beta1 integrin interacted with GBS-III liquor 90356 and GBS-V blood 90186 invasive strains. Thus, the interaction between ICAM-1 and beta1-integrin seems an additional means by which GBS exploits host endothelial cells during infection. These findings add to the current understanding of the roles played by multiple receptor-ligand systems in the uptake and pathogenesis of GBS infection.


Assuntos
Endocitose , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Integrina beta1/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/fisiologia , Aderência Bacteriana/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ácido Edético/farmacologia , Humanos , Streptococcus agalactiae/isolamento & purificação
20.
Arq. odontol ; 55: 1-12, jan.-dez. 2019. ilus, tab
Artigo em Português | LILACS, BBO - odontologia (Brasil) | ID: biblio-1052824

RESUMO

Objetivo: Avaliar as alterações químicas presentes na superfície metálica de limas endodônticas fraturadas em canais radiculares, in vitro, após a inoculação intrarradicular de culturas de BRS de três cepas microbianas, Desulfovibrio desulfuricans (uma cepa oral e outra ambiental) e Desulfovibrio fairfieldensis. Métodos: foram analisadas 5 limas kerr #90, sendo uma Lima Kerr nova, sem tratamento, e as outras 4 limas fraturadas dentro de canais radiculares in vitro, com posterior inoculação de Desulfovibrio desulfuricans, cepa oral e ambiental, e Desulfovibrio fairfieldensis e um grupo controle sem inoculação bacteriana, por 477 dias. Os grupos foram analisados no modo EDS (Espectrometria de Energia Dispersiva de Raios-x) do microscópio eletrônico de varredura (FEI-Inspect-S50). Resultados:A presença do S, Cl e O foram relacionados ao processo biocorrosivo, assim como a redução dos elementos de liga nesta área. Conclusão:As análises no modo EDS demonstraram biocorrosão ao longo da superfície metálica das limas quando empregado o biofármaco BACCOR, nas três diferentes cepas empregadas, indicada pela redução dos elementos formadores da liga metálica, Fe, Ni e Cr, com a associação da presença de elementos indicadores de biocorrosão como O, Cl e S. (AU)


Aim:To evaluate the chemical alterations present on the metallic surface of root canal fractured endodontic files in vitro after the intraradicular inoculation of BRS cultures of three microbial strains, Desulfovibrio desulfuricans (one oral and one environmental strain), and Desulfovibrio fairfieldensis. Methods: Five kerr #90 files were analyzed, one new untreated Kerr file and the other 4 files fractured within root canals in vitro, with a subsequent inoculation of Desulfovibrio desulfuricans (oral and environmental strains), and Desulfovibrio fairfieldensis, as well as a control group without bacterial inoculation for 477 days. The groups were analyzed using the scanning electron microscope (FEI-Inspect-S50) EDS (X-ray Dispersive Energy Spectrometry) mode. Results:The presence of S, Cl, and O were related to the biocorrosive process, as well as the reduction of alloying elements in this area. Conclusion: The EDS mode analysis showed biocorrosion along the metallic surface of the files when the BACCOR biopharmaceutical was used in the three different strains employed in this study, indicated by the reduction of the alloying elements ­ Fe, Ni, and Cr ­ with the association of the presence of indicator elements of biocorrosion, such as O, Cl, and S. (AU)


Assuntos
Produtos Biológicos , Corrosão , Meios de Cultura , Ligas Dentárias , Instrumentos Odontológicos , Desulfovibrio desulfuricans , Cavidade Pulpar , Desulfovibrio , Técnicas In Vitro , Endodontia
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