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1.
J Mater Sci Mater Med ; 35(1): 14, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353746

RESUMO

In this study, poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with cannabidiol (CBD) were synthesized (PLGA@CBD microparticles) and embedded up to 10 wt% in a chondroitin sulfate/polyvinyl alcohol hydrogel matrix. In vitro chemical, physical, and biological assays were carried out to validate the potential use of the modified hydrogels as biomaterials. The microparticles had spherical morphology and a narrow range of size distribution. CBD encapsulation efficiency was around 52%, loading was approximately 50%. Microparticle addition to the hydrogels caused minor changes in their morphology, FTIR and thermal analyses confirmed these changes. Swelling degree and total porosity were reduced in the presence of microparticles, but similar hydrophilic and degradation in phosphate buffer solution behaviors were observed by all hydrogels. Rupture force and maximum strain at rupture were higher in the modified hydrogels, whereas modulus of elasticity was similar across all materials. Viability of primary human dental pulp cells up to 21 days was generally not influenced by the addition of PLGA@CBD microparticles. The control hydrogel showed no antimicrobial activity against Staphylococcus aureus, whereas hydrogels with 5% and 10% PLGA@CBD microparticles showed inhibition zones. In conclusion, the PLGA@CBD microparticles were fabricated and successfully embedded in a hydrogel matrix. Despite the hydrophobic nature of CBD, the physicochemical and morphological properties were generally similar for the hydrogels with and without the CBD-loaded microparticles. The data reported in this study suggested that this original biomaterial loaded with CBD oil has characteristics that could enable it to be used as a scaffold for tissue/cellular regeneration.


Assuntos
Canabidiol , Humanos , Porosidade , Materiais Biocompatíveis , Bioensaio , Hidrogéis
2.
Calcif Tissue Int ; 101(4): 341-354, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28612084

RESUMO

The aim of this study was to evaluate the morphological bone response in animal experiments by applying hydroxyapatite grafts in critical and non-critical size bone defects. Current report followed the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Animal experiments were selected by assessing repair of bone defects with hydroxyapatite as bone graft and with blood clot only as control. Eight articles were identified in specialized literature and included in the meta-analysis. Statistical analysis was carried out with a random-effect model (p = 0.05). Subgroup analyses were further performed to investigate bone repair in critical and non-critical bone defects. Comprehensive analysis of bone repair outcome showed a statistically significant difference between hydroxyapatite and blood clot control (p < 0.05). Subgroup analyses showed statistically significant difference for critical bone defects (p < 0.05). No statistically significant difference was reported in non-critical bone defects (p > 0.05). Although animal studies revealed a high risk of bias and results should be interpreted with caution, the literature suggests that non-critical bone defects may heal spontaneously and without the need of a bone graft. Conversely, when critical-size defects are present, the use of hydroxyapatite bone graft improves the bone repair process.


Assuntos
Substitutos Ósseos , Transplante Ósseo/métodos , Durapatita , Animais
3.
Bioorg Med Chem Lett ; 26(20): 5007-5008, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27623546

RESUMO

This article reports the in vitro antiplasmodial activity of two endoperoxides of the class 1,2-dioxetanes against Plasmodium falciparum: bis(adamantyl)-1,2-dioxetane and 3,3,4,4-tetramethyl-1,2-dioxetane. The results reveal that bis(adamantyl)-1,2-dioxetane displays substantial antiplasmodial activity, at least two orders of magnitude higher than that of artemisinin, while 3,3,4,4-tetramethyl-1,2-dioxetane is less active.


Assuntos
Antimaláricos/farmacologia , Compostos Heterocíclicos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/química , Hemólise/efeitos dos fármacos , Compostos Heterocíclicos/química , Compostos Heterocíclicos com 1 Anel
4.
Bioorg Med Chem Lett ; 25(16): 3311-3, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26077496

RESUMO

To find effective new candidate antimalarial drugs, bradykinin and its analogs were synthesized and tested for effectiveness against Plasmodium gallinaceum sporozoites and Plasmodium falciparum on erythrocytes. Among them, bradykinin and its P2 analog presented high activity against Plasmodium gallinaceum, but they degrade in plasma. On the other hand, RI-BbKI did not degrade and reached high activity. No analog was active against Plasmodium falciparum.


Assuntos
Antimaláricos/farmacologia , Bradicinina/farmacologia , Peptídeos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium gallinaceum/efeitos dos fármacos , Animais , Antimaláricos/síntese química , Antimaláricos/química , Bradicinina/química , Bradicinina/genética , Humanos , Peptídeos/síntese química , Peptídeos/química , Peptídeos/genética , Esporozoítos/efeitos dos fármacos
5.
Sci Rep ; 14(1): 4682, 2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409185

RESUMO

Malaria can have severe long-term effects. Even after treatment with antimalarial drugs eliminates the parasite, survivors of cerebral malaria may suffer from irreversible brain damage, leading to cognitive deficits. Angiotensin II, a natural human peptide hormone that regulates blood pressure, has been shown to be active against Plasmodium spp., the etiologic agent of malaria. Here, we tested two Ang II derivatives that do not elicit vasoconstriction in mice: VIPF, a linear tetrapeptide, which constitutes part of the hydrophobic portion of Ang II; and Ang II-SS, a disulfide-bridged derivative. The antiplasmodial potential of both peptides was evaluated with two mouse models: an experimental cerebral malaria model and a mouse model of non-cerebral malaria. The latter consisted of BALB/c mice infected with Plasmodium berghei ANKA. The peptides had no effect on mean blood pressure and significantly reduced parasitemia in both mouse models. Both peptides reduced the SHIRPA score, an assay used to assess murine health and behavior. However, only the constrained derivative (Ang II-SS), which was also resistant to proteolytic degradation, significantly increased mouse survival. Here, we show that synthetic peptides derived from Ang II are capable of conferring protection against severe manifestations of malaria in mouse models while overcoming the vasoconstrictive side effects of the parent peptide.


Assuntos
Antimaláricos , Malária Cerebral , Animais , Camundongos , Humanos , Malária Cerebral/tratamento farmacológico , Malária Cerebral/prevenção & controle , Malária Cerebral/parasitologia , Angiotensina II/farmacologia , Angiotensina II/uso terapêutico , Modelos Animais de Doenças , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Plasmodium berghei/fisiologia , Camundongos Endogâmicos C57BL
6.
J Pept Sci ; 19(9): 575-80, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23893516

RESUMO

Controlling the dissemination of malaria requires the development of new drugs against its etiological agent, a protozoan of the Plasmodium genus. Angiotensin II and its analog peptides exhibit activity against the development of immature and mature sporozoites of Plasmodium gallinaceum. In this study, we report the synthesis and characterization of angiotensin II linear and cyclic analogs with anti-plasmodium activity. The peptides were synthesized by a conventional solid-phase method on Merrifield's resin using the t-Boc strategy, purified by RP-HPLC and characterized by liquid chromatography/ESI (+) MS (LC-ESI(+)/MS), amino acid analysis, and capillary electrophoresis. Anti-plasmodium activity was measured in vitro by fluorescence microscopy using propidium iodine uptake as an indicator of cellular damage. The activities of the linear and cyclic peptides are not significantly different (p < 0.05). Kinetics studies indicate that the effects of these peptides on plasmodium viability overtime exhibit a sigmoidal profile and that the system stabilizes after a period of 1 h for all peptides examined. The results were rationalized by partial least-square analysis, assessing the position-wise contribution of each amino acid. The highest contribution of polar amino acids and a Lys residue proximal to the C-terminus, as well as that of hydrophobic amino acids in the N-terminus, suggests that the mechanism underlying the anti-malarial activity of these peptides is attributed to its amphiphilic character.


Assuntos
Angiotensina II/análogos & derivados , Angiotensina II/farmacologia , Antimaláricos/farmacologia , Plasmodium gallinaceum/efeitos dos fármacos , Sequência de Aminoácidos , Angiotensina II/química , Animais , Antimaláricos/química , Permeabilidade da Membrana Celular/efeitos dos fármacos , Galinhas , Avaliação Pré-Clínica de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Esporozoítos/efeitos dos fármacos
7.
Toxics ; 11(11)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37999563

RESUMO

Cosmetic residues have been found in water resources, especially trace elements of precursors, couplers, and pigments of hair dyes, which are indiscriminately disposed of in the sewage system. These contaminants are persistent, bioactive, and bioaccumulative, and may pose risks to living beings. Thus, the present study assessed the ecotoxicity of two types of effluents generated in beauty salons after the hair dyeing process. The toxicity of effluent derived from capillary washing with water, shampoo, and conditioner (complete effluent-CE) and effluent not associated with these products (dye effluent-DE) was evaluated by tests carried out with the aquatic organisms Artemia salina, Daphnia similis, and Danio rerio. The bioindicators were exposed to pure samples and different dilutions of both effluents. The results showed toxicity in D. similis (CE50 of 3.43% and 0.54% for CE and DE, respectively); A. salina (LC50 8.327% and 3.874% for CE and DE, respectively); and D. rerio (LC50 of 4.25-4.59% and 7.33-8.18% for CE and DE, respectively). Given these results, we can infer that hair dyes, even at low concentrations, have a high toxic potential for aquatic biota, as they induced deleterious effects in all tested bioindicators.

8.
J Mech Behav Biomed Mater ; 117: 104424, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33652234

RESUMO

The purpose of this study was two-fold: (i) to investigate whether the thermal treatment of direct dental resin composites (RCs) using microwave or autoclave heating cycles would modify the materials' strength as compared to the protocol without heating (control); and (ii) to compare the mechanical performance of direct and indirect RCs. Three RCs (from 3M ESPE) were tested: one indirect (Sinfony); and two direct materials (microhybrid - Filtek Z250; and nanofilled - Filtek Z350). Specimens from the direct RCs were prepared and randomly allocated into three groups according to the thermal treatment (n = 10): Control - no thermal treatment was performed; Microwave - the wet heating was performed using a microwave oven; and Autoclave - the wet heating was performed in an autoclave oven. The indirect RC was prepared following the instructions of the manufacturer. All materials were tested using flexural strength, elastic modulus, work of fracture (Wf), microhardness, and scanning electron microscopy (SEM) analyses. Data were analyzed with ANOVA and Tukey as well as Weibull analysis (α = 0.05). The thermal treatments tended to produce slight changes in the topography of direct RCs, especially by the autoclave' wet heating. Overall, the physico-mechanical properties changed after thermal treatment, although this effect was dependent on the type of RC and on the heating protocol. Sinfony showed the lowest modulus and hardness of the study, although it was the most compliant system (higher work of fracture). The load-deflection ability was also greater for the indirect RC. Reliability of the tested materials was similar among each other (p > 0.05). In conclusion, the alternative thermal treatments suggested here may significantly influence some aspects of the mechanical behavior of dental resin composites, with negative effects relying on both the chemical composition of the restorative material as well as on the wet heating protocol used. Clinicians should be aware of the possible effects that additional wet heating of direct resin composites using microwave or autoclave thermal protocols as performed here could have on the overall fracture and mechanical responses during loading circumstances.


Assuntos
Resinas Compostas , Materiais Dentários , Módulo de Elasticidade , Dureza , Teste de Materiais , Reprodutibilidade dos Testes , Estresse Mecânico , Propriedades de Superfície
9.
J Biomed Mater Res A ; 109(7): 1160-1172, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32985092

RESUMO

Novel poly(vinyl alcohol)/chondroitin sulfate (PVA/CS) composite hydrogels containing hydroxyapatite (HA) or Sr-doped HA (HASr) particles were synthesized by a freeze/thaw method and characterized aiming towards biomedical applications. HA and HASr were synthesized by a wet-precipitation method and added to the composite hydrogels in fractions up to 15 wt%. Physical-chemical characterizations of particles and hydrogels included scanning electron microscopy, energy-dispersive spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetry, porosity, compressive strength/elastic modulus, swelling degree, and cell viability. Particles were irregular in shape and appeared to have narrow size variation. The thermal behavior of composite hydrogels was altered compared to the control (bare) hydrogel. All hydrogels exhibited high porosity. HA/HASr particles reduced total porosity without reducing pore size. The mechanical strength was improved as the fraction of HA or HASr was increased. HASr particles led to a faster water uptake but did not interfere with the total hydrogel swelling capacity. In cell viability essay, increased cell growth (above 120%) was observed in all groups including the control hydrogel, suggesting a bioactive effect. In conclusion, PVA/CS hydrogels containing HA or HASr particles were successfully synthesized and showed promising morphological, mechanical, and swelling properties, which are particularly required for scaffolding.


Assuntos
Materiais Biocompatíveis/química , Sulfatos de Condroitina/química , Durapatita/química , Álcool de Polivinil/química , Estrôncio/química , Materiais Biocompatíveis/síntese química , Sulfatos de Condroitina/síntese química , Força Compressiva , Durapatita/síntese química , Módulo de Elasticidade , Álcool de Polivinil/síntese química , Porosidade , Termogravimetria
10.
Bioeng Transl Med ; 5(3): e10167, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33005737

RESUMO

The wasp venom-derived antimicrobial peptide polybia-CP has been previously shown to exhibit potent antimicrobial activity, but it is also highly toxic. Previously, using a physicochemical-guided peptide design strategy, we reversed its toxicity while preserving and even enhancing its antibacterial properties. Here, we report on several additional unanticipated biological properties of polybia-CP and derivatives, namely their ability to target Plasmodium sporozoites and cancer cells. We leverage a physicochemical-guided approach to identify features that operate as functional hotspots making these peptides viable antiplasmodial and anticancer agents. Helical content and net positive charge are identified as key structural and physicochemical determinants for antiplasmodial activity. In addition to helicity and net charge, hydrophobicity-related properties of polybia-CP and derivatives were found to be equally critical to target cancer cells. We demonstrate that by tuning these physicochemical parameters, it is possible to design synthetic peptides with enhanced submicromolar antiplasmodial potency and micromolar anticancer activity. This study reveals novel and previously undescribed functions for Polybia-CP and analogs. Additionally, we demonstrate that a physicochemical-guided rational design strategy can be used for identifying functional hotspots in peptide molecules and for tuning structure-function to generate novel and potent new-to-nature therapies.

11.
J Mater Chem B ; 8(47): 10797-10811, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33169763

RESUMO

Despite all the advances in adhesive dentistry, dental bonds are still fragile due to degradation events that start during application of adhesive agents and the inherent hydrolysis of resin-dentin bonds. Here, we combined two outstanding processing methods (electrospinning and cryomilling) to obtain bioactive (antimicrobial and anti-metalloproteinase) fiber-based fillers containing a potent matrix metalloproteinase (MMP) inhibitor (doxycycline, DOX). Poly(ε)caprolactone solutions containing different DOX amounts (0, 5, 25, and 50 wt%) were processed via electrospinning, resulting in non-toxic submicron fibers with antimicrobial activity against Streptococcus mutans and Lactobacillus. The fibers were embedded in a resin blend, light-cured, and cryomilled for the preparation of fiber-containing fillers, which were investigated with antibacterial and in situ gelatin zymography analyzes. The fillers containing 0, 25, and 50 wt% DOX-releasing fibers were added to aliquots of a two-step, etch-and-rinse dental adhesive system. Mechanical strength, hardness, degree of conversion (DC), water sorption and solubility, bond strength to dentin, and nanoleakage analyses were performed to characterize the physico-mechanical, biological, and bonding properties of the modified adhesives. Statistical analyses (ANOVA; Kruskal-Wallis) were used when appropriate to analyze the data (α = 0.05). DOX-releasing fibers were successfully obtained, showing proper morphological architecture, cytocompatibility, drug release ability, slow degradation profile, and antibacterial activity. Reduced metalloproteinases (MMP-2 and MMP-9) activity was observed only for the DOX-containing fillers, which have also demonstrated antibacterial properties against tested bacteria. Adhesive resins modified with DOX-containing fillers demonstrated greater DC and similar mechanical properties as compared to the fiber-free adhesive (unfilled control). Concerning bonding performance to dentin, the experimental adhesives showed similar immediate bond strengths to the control. After 12 months of water storage, the fiber-modified adhesives (except the group consisting of 50 wt% DOX-loaded fillers) demonstrated stable bonds to dentin. Nanoleakage was similar among all groups investigated. DOX-releasing fibers showed promising application in developing novel dentin adhesives with potential therapeutic properties and MMP inhibition ability; antibacterial activity against relevant oral pathogens, without jeopardizing the physico-mechanical characteristics; and bonding performance of the adhesive.


Assuntos
Antibacterianos/síntese química , Resinas Compostas/síntese química , Cimentos Dentários/síntese química , Desenvolvimento de Medicamentos/métodos , Inibidores de Metaloproteinases de Matriz/síntese química , Cimentos de Resina/síntese química , Doxiciclina/síntese química , Teste de Materiais/métodos , Resistência à Tração
12.
Eur J Oral Sci ; 117(1): 64-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19196320

RESUMO

This study evaluated the effect of different concentrations of 2-hydroxyethyl methacrylate (HEMA) on the inhibition of matrix metalloproteinase-2 (MMP-2) in vitro. Mouse gingival explants were cultured overnight in Dulbecco's modified Eagle's minimal essential medium, following which the expression of secreted enzymes was analyzed by gelatin zymography and the effects of different amounts of HEMA on enzyme activity were investigated. The gelatinolytic proteinases present in the conditioned media were characterized as being matrix metalloproteinases (MMPs) by means of specific chemical inhibition. The MMPs present in the conditioned media were identified, using immunoprecipitation, as MMP-2. Three major bands were detected in the zymographic assays and were characterized, according to their respective molecular weights, into the following forms of MMP-2: zymogene (72 kDa), intermediate (66 kDa), and active (62 kDa). All forms of MMP-2 were inhibited by HEMA in a dose-dependent manner, implying that MMP-2 may be inhibited by HEMA in vivo.


Assuntos
Cimentos Dentários/farmacologia , Gengiva/efeitos dos fármacos , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metacrilatos/farmacologia , Animais , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Gengiva/enzimologia , Metaloproteinase 2 da Matriz/metabolismo , Camundongos
13.
J Biomed Mater Res B Appl Biomater ; 106(3): 1358-1368, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28561919

RESUMO

To systematically review the literature to analyze the current trends and future perspectives of dental pulp capping materials through an analysis of scientific and technological data. This study is reported in accordance with the PRISMA Statement. Nine databases were screened: PubMed (MedLine), Lilacs, IBECS, BBO, Web of Science, Scopus, SciELO, Google Scholar, and The Cochrane Library. Additionally, the following patent applications were searched online in Questel Orbit (Paris, France), USPTO, EPO, JPO, INPI, and Patentscope databases. A total of 716 papers and 83 patents were included. Calcium hydroxide was the main type of material studied, especially for direct pulp capping, followed by MTA. Patents related to adhesives or resins increased from 1998 e 2008, while in the last years, a major increase was observed in bioactive materials (containing bioactive proteins), materials derived from MTA (calcium silicate, calcium phosphate and calcium aluminate-based cements) and MTA. It was possible to obtain a scientific and technological overview of pulp capping materials. MTA has shown favorable results in vital pulp therapy that seem to surpass the disadvantages of calcium hydroxide. Recent advances in bioactive materials and those derived from MTA have shown promising results that could improve biomaterials used in vital pulp treatments. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1358-1368, 2018.


Assuntos
Materiais Biocompatíveis , Materiais Dentários , Capeamento da Polpa Dentária/métodos , Capeamento da Polpa Dentária/tendências , Animais , Humanos
14.
Front Microbiol ; 9: 412, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29568291

RESUMO

Background: Macroalgae are sources of bioactive compounds due to the large number of secondary metabolites they synthesize. The Antarctica region is characterized by extreme weather conditions and abundant aggregations of macroalgae. However, current knowledge on their biodiversity and their potential for bio-prospecting is still fledging. This study evaluates the antimicrobial and cytotoxic activity of different extracts of four macroalgae (Cystosphaera jacquinotii, Iridaea cordata, Himantothallus grandifolius, and Pyropia endiviifolia) from the Antarctic region against cancer and non-cancer cell lines. Methods: The antimicrobial activity of macroalgae was evaluated by the broth microdilution method. Extracts were assessed against Staphylococcus aureus ATCC 19095, Enterococcus faecalis ATCC 4083, Escherichia coli ATCC29214, Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 62342, and the clinical isolates from the human oral cavity, namely, C. albicans (3), C. parapsilosis, C. glabrata, C. lipolytica, and C. famata. Cytotoxicity against human epidermoid carcinoma (A-431) and mouse embryonic fibroblast (NIH/3T3) cell lines was evaluated with MTT colorimetric assay. Results: An ethyl acetate extract of H. grandifolius showed noticeable antifungal activity against all fungal strains tested, including fluconazole-resistant samples. Cytotoxicity investigation with a cancer cell line revealed that the ethyl acetate extract of I. cordata was highly cytotoxic against A-431 cancer cell line, increasing the inhibitory ratio to 91.1 and 95.6% after 24 and 48 h exposure, respectively, for a concentration of 500 µg mL-1. Most of the algal extracts tested showed little or no cytotoxicity against fibroblasts. Conclusion: Data suggest that macroalgae extracts from Antarctica may represent a source of therapeutic agents. HIGHLIGHTS Different macroalgae samples from Antarctica were collected and the lyophilized biomass of each macroalgae was extracted sequentially with different solventsThe antimicrobial and anticancer potential of macroalgae extracts were evaluatedEthyl acetate extract of H. grandifolius showed noticeable antifungal activity against all the fungal strains tested, including fluconazole-resistant samplesEthyl acetate extract of I. cordata was highly cytotoxic against the A-431 cancer cell lineMost of the algal extracts tested showed little or no cytotoxicity against normal cell lines.

15.
J Dent Educ ; 79(8): 914-21, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26246529

RESUMO

The aim of this study was to review the effectiveness of methods used for teaching dental anatomy carving to dental students in operative dentistry as evaluated in published studies. This systematic review is described in accordance with the PRISMA statement. Two independent reviewers performed a systematic literature search of research published from January 1945 until May 2014. Seven databases were screened: MedLine (PubMed), Lilacs, IBECS, Web of Science, Scopus, SciELO, and The Cochrane Library. After removing duplicates, only studies using dental carving to assess the practical knowledge of anatomy were selected. The tabulated data were organized by title of article, names of authors, number of students assessed, assessment method, material used, groups tested, main results, and conclusions. The methodology quality was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Initially, 2,258 studies were identified in all databases. Five articles met the eligibility criteria and were included in this review. According to these studies, the geometric method, teaching step-by-step along with the teacher, and adjuvant methods such as the use of tutors and teaching through digital media with DVDs proved to be effective in improving learning. There is no standard technique that is widely accepted for the teaching of dental carving, nor is there an appropriately validated method of evaluation to verify whether the teaching methods used are effective for the acquisition of skills and expertise in dental anatomy by students.


Assuntos
Anatomia/educação , Dentística Operatória/educação , Educação em Odontologia , Destreza Motora/fisiologia , Ensino/métodos , Humanos , Escultura
16.
Chem Biol Drug Des ; 86(6): 1373-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26032859

RESUMO

The antimalarial activity of peroxides most likely originates from their interaction with iron(II) species located inside the malaria parasite, which forms destructive radical species through a Fenton-like mechanism. This article reports the first evaluation of the in vitro antimalarial activity of three peroxides of the class 1,2-dioxetanes against Plasmodium falciparum; the results reveal that the studied 3-methoxy-1,2-dioxetanes display significant antimalarial activity, at a similar level as artemisinin and also that their reactivity toward iron(II) correlate linearly with their antimalarial activity.


Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Peróxidos/química , Peróxidos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Artemisininas/farmacologia , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Hemólise/efeitos dos fármacos , Humanos , Técnicas In Vitro , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/patogenicidade
17.
Chem Biol Drug Des ; 85(2): 163-71, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24800635

RESUMO

Malaria is an infectious disease responsible for approximately one million deaths annually. The antimalarial effects of angiotensin II and its analogs against Plasmodium gallinaceum and P. falciparum have recently been reported. To evaluate antiplasmodial activity, we synthesized five angiotensin II-restricted analogs containing disulfide bridges. To accomplish this, peptides containing two inserted amino acid residues (cysteine) were synthesized by the Fmoc solid-phase method, purified by liquid chromatography, and characterized by mass spectrometry. Conformational studies were performed by circular dichroism. The results indicated that two of the analogs had higher antiplasmodium activity (92% and 98% activity) than angiotensin II (88% activity), measured by fluorescence microscopy. Results showed that the insertion position must be selected, to preserve the hydrophobic interactions between the non-polar residues, as this affects antiplasmodial activity. The circular dichroism studies suggested that the active analogs as well as the native angiotensin II adopt a ß-turn conformation in different solutions. This approach provided insight for understanding the effects of restricting the ring size and position on the bioactivity of angiotensin II and provides a new direction for the design of potential chemotherapeutic agents.


Assuntos
Angiotensina II/farmacologia , Antimaláricos/farmacologia , Galinhas/parasitologia , Malária Aviária/tratamento farmacológico , Peptídeos/farmacologia , Plasmodium gallinaceum/efeitos dos fármacos , Aedes , Sequência de Aminoácidos , Angiotensina II/análogos & derivados , Animais , Antimaláricos/química , Humanos , Malária Falciparum/tratamento farmacológico , Dados de Sequência Molecular , Peptídeos/química , Plasmodium falciparum/efeitos dos fármacos
18.
J Endod ; 40(4 Suppl): S33-40, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24698691

RESUMO

Emerging understanding about interactions between stem cells, scaffolds, and morphogenic factors has accelerated translational research in the field of dental pulp tissue engineering. Dental pulp stem cells constitute a subpopulation of cells endowed with self-renewal and multipotency. Dental pulp stem cells seeded in biodegradable scaffolds and exposed to dentin-derived morphogenic factors give rise to a pulplike tissue capable of generating new dentin. Notably, dentin-derived proteins are sufficient to induce dental pulp stem cell differentiation into odontoblasts. Ongoing work is focused on developing ways of mobilizing dentin-derived proteins and disinfecting the root canal of necrotic teeth without compromising the morphogenic potential of these signaling molecules. On the other hand, dentin by itself does not appear to be capable of inducing endothelial differentiation of dental pulp stem cells despite the well-known presence of angiogenic factors in dentin. This is particularly relevant in the context of dental pulp tissue engineering in full root canals in which access to blood supply is limited to the apical foramina. To address this challenge, scientists are looking at ways to use the scaffold as a controlled-release device for angiogenic factors. The aim of this article was to present and discuss current strategies to functionalize injectable scaffolds and customize them for dental pulp tissue engineering. The long-term goal of this work is to develop stem cell-based therapies that enable the engineering of functional dental pulps capable of generating new tubular dentin in humans.


Assuntos
Polpa Dentária/citologia , Células-Tronco/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Proteínas Angiogênicas/fisiologia , Diferenciação Celular/fisiologia , Dentina/fisiologia , Humanos , Células-Tronco Multipotentes/fisiologia , Odontoblastos/fisiologia , Proteínas/fisiologia , Transdução de Sinais/fisiologia
19.
Arch Oral Biol ; 59(9): 880-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24907517

RESUMO

The secretion of extracellular phospholipases and proteinases of Candida has been described as a relevant virulence factor in human infections. Aliphatic fatty acids have antimicrobial properties, but the mechanism by which they affect the virulence factors of microorganisms, such as Candida, is still unclear, and there are a few reports about their toxicity. The current study investigated the in vitro antifungal activity, exoenzyme production and cytotoxicity of some aliphatic fatty acids and their ester derivatives against the Candida species. The minimum inhibitory concentration and minimum fungicidal concentrations of aliphatic medium-chain fatty acids, methyl and ethyl esters were performed using the CLSI M27-A3 method and the cytotoxicity assay was performed according to ISO 10993-5. The influence of these compounds in the inhibition of the production of hydrolytic enzymes, phospholipases and proteinases by Candida was also investigated. Data analysis was performed using the one-way ANOVA method (p≤0.05). In relation to the MIC against Candida species, the fatty acid with the best result was Lauric acid, although its ester derivatives showed no activity. The inhibition of phospholipase production was more significant than the inhibition of proteinase production by Candida. Tested fatty acids revealed more than 80% cell viability in their MIC concentrations. Additionally, a cell viability of 100% was reported at concentrations of anti-enzymatic effect. Therefore, the potential use of these fatty acids could be the basis for more antimicrobial tests.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/enzimologia , Ésteres/farmacologia , Ácidos Graxos/farmacologia , Técnicas de Cultura de Células , Sobrevivência Celular , Fluconazol/farmacologia , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Peptídeo Hidrolases/metabolismo , Fosfolipases/metabolismo , Fatores de Virulência
20.
J Inorg Biochem ; 114: 1-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22687559

RESUMO

The octarepeat domain in cellular prion protein (PrP(C)) has attracted much attention over the last 10 years because of its importance in the complexation of copper with PrP(C). The aim of this research was to study the UV-vis spectra of a peptide similar to the 1-repeat of the octarepeat region in PrP(C) using experimental and theoretical approaches and to gain insight into the complexation of the PrP(C) octarepeat domain with copper(II) ions in solution. We found that the copper atom was responsible for the peptide conformation, which allows for charge transfers between its two terminal residues.


Assuntos
Complexos de Coordenação/química , Cobre/química , Fragmentos de Peptídeos/síntese química , Proteínas PrPC/química , Sítios de Ligação , Cátions Bivalentes , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Ligação Proteica , Estrutura Terciária de Proteína , Sequências Repetitivas de Aminoácidos , Análise Espectral , Eletricidade Estática
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