RESUMO
Dental pulp is exposed to resin monomers leaching from capping materials. Toxic doses of the monomer, triethyleneglycol dimethacrylate (TEGDMA), impact cell growth, enhance inflammatory and oxidative stress responses, and lead to tissue necrosis. A therapeutic agent is required to rescue growth-arrested tissues by continuing their development and modulating the exacerbated responses. The functionality of N-Acetyl Cysteine (NAC) as a treatment was assessed by employing a 3D dental pulp microtissue platform. Immortalized and primary microtissues developed and matured in the extracellular matrix (ECM). TEGDMA was introduced at various concentrations. NAC was administered simultaneously with TEGDMA, before or after monomer addition during the development and after the maturation stages of the microtissue. Spatial growth was validated by confocal microscopy and image processing. Levels of inflammatory (COX2, NLRP3, IL-8) and oxidative stress (GSH, Nrf2) markers were quantified by immunoassays. NAC treatments, in parallel with TEGDMA challenge or post-challenge, resumed the growth of the underdeveloped microtissues and protected mature microtissues from deterioration. Growth recovery correlated with the alleviation of both responses by decreasing significantly the intracellular and extracellular levels of the markers. Our 3D/ECM-based dental pulp platform is an efficient tool for drug rescue screening. NAC supports compromised microtissues development, and immunomodulates and maintains the oxidative balance.
Assuntos
Acetilcisteína/farmacologia , Polpa Dentária/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Inflamação/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Resinas Compostas/farmacologia , Polpa Dentária/crescimento & desenvolvimento , Polpa Dentária/metabolismo , Avaliação Pré-Clínica de Medicamentos , Matriz Extracelular/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Interleucina-8/genética , Fator 2 Relacionado a NF-E2/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Estresse Oxidativo/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Ácidos Polimetacrílicos/farmacologiaRESUMO
Herein, thermo- and pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) copolymer-coated magnetic nanoparticles were synthesized via a green and rapid synthetic approach based on microwave irradiation. Firstly, a novel thermo- and pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) copolymer (Pec-g-PolyDMAEMA) was synthesized and then, Pec-g-PolyDMAEMA based magnetic nanoparticles (Pec-g-PolyDMAEMA@Fe3O4) were produced via microwave-assisted co-precipitation method. The thermo/pH/magnetic field multi-sensitive hybrid nanoparticle was characterized by techniques like TEM, VSM, FT-IR, and TGA/DSC. In vitro release studies of 5-Fluorouracil (FL) were carried out by altering the temperature (37 and 44°C), pH (5.5 and 7.4) and presence of an AMF. The FL release of Pec-g-PolyDMAEMA@Fe3O4@FL exhibited pH-sensitive behavior. They showed thermo/pH-sensitive FL release features with the greatest release of FL at 37°C (56%) than at 44°C (40%) and at pH of 7.4 (63%) than at pH of 5.5 (45%) within 48h. The FL release was also significantly increased (100%) with the presence of a 50 mT magnetic field. These results indicate that the developed Pec-g-PolyDMAEMA@Fe3O4 nanoparticles are promising in the application of multi-stimuli-sensitive delivery of drugs.
Assuntos
Materiais Revestidos Biocompatíveis , Portadores de Fármacos , Nanopartículas de Magnetita , Metacrilatos/química , Pectinas/química , Ácidos Polimetacrílicos/química , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/toxicidade , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/toxicidade , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Fluoruracila/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Campos Magnéticos , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/toxicidade , Camundongos , Transição de Fase , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/farmacologia , Ácidos Polimetacrílicos/toxicidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaRESUMO
Biodegradable polycaprolactone (PCL) has been widely applied as a scaffold material in tissue engineering. However, the PCL surface is hydrophobic and adsorbs nonspecific proteins. Some traditional antifouling modifications using hydrophilic moieties have been successful but inhibit cell adhesion, which is not ideal for tissue engineering. The PCL surface is modified with bioinspired zwitterionic poly[2-(methacryloyloxy)ethyl choline phosphate] (PMCP) via surface-initiated atom transfer radical polymerization to improve cell adhesion through the unique interaction between choline phosphate (CP, on PMCP) and phosphate choline (PC, on cell membranes). The hydrophilicity of the PCL surface is significantly enhanced after surface modification. The PCL-PMCP surface reduces nonspecific protein adsorption (e.g., up to 91.7% for bovine serum albumin) due to the zwitterionic property of PMCP. The adhesion and proliferation of bone marrow mesenchymal stem cells on the modified surface is remarkably improved, and osteogenic differentiation signs are detected, even without adding any osteogenesis-inducing supplements. Moreover, the PCL-PMCP films are more stable at the early stage of degradation. Therefore, the PMCP-functionalized PCL surface promotes cell adhesion and osteogenic differentiation, with an antifouling background, and exhibits great potential in tissue engineering.
Assuntos
Incrustação Biológica , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosforilcolina/análogos & derivados , Poliésteres/farmacologia , Ácidos Polimetacrílicos/farmacologia , Engenharia Tecidual , Adsorção , Animais , Animais Recém-Nascidos , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Fosforilcolina/síntese química , Fosforilcolina/farmacologia , Espectroscopia Fotoeletrônica , Poliésteres/síntese química , Ácidos Polimetacrílicos/síntese química , Ratos Sprague-Dawley , Propriedades de Superfície , Água/químicaRESUMO
Bacterial infections require special care since the indiscriminate use of antibiotics to treat them has been linked to the emergence of resistant strains. In this sense, phytoterapeutic alternatives such as curcumin and its nanocapsules have emerged as a promising supplement in optimizing availability of bioactives and reducing the development of antimicrobial resistance. Thus, the aim of this study was to verify the effects of pure and nanoencapsulated curcumin in the treatment of experimental listeriosis in gerbils regarding many aspects including antibacterial effect, antioxidant mechanisms involved and the energetic metabolism. Four groups were used containing 6 animals each: T0 (control), T1 (infected), T2 (infected and treated with free curcumin - dose of 30â¯mg/kg/day) and T3 (infected and treated with nanocapsules containing curcumin - a dose of 3â¯mg/kg/day). Treated animals received curcumin for 6 consecutive days starting 24â¯h after Listeria monocytogenes infection. All animals were euthanized on the 12th day after L. monocytogenes infection. Quantitative polymerase chain reaction (qPCR) identified L. monocytogenes DNA in the spleens of all animals of the T1 group, as well as T2 (2 out of 6) and T3 (5 out of 6). The weight of the spleens confirmed the infection, since it was larger in the T1 group, differing statistically from T0, and similarly to T2 and T3. Hepatic histopathological examination showed mild infiltration of neutrophils and macrophages, except for the T3 group (only 1/6). In the liver, the pyruvate kinase activity was higher in T1 and T2 compared to T0 and T3. The adenylate kinase activity did not differ between groups. The Na+/K+ATPase activity was lower in T1 group compared to T0 and T3. Lipoperoxidation was lower in the T3 group compared to groups T0, T1 and T2. The antioxidant capacity against peroxyl radicals was higher in T1, T2 and T3 groups compared to T0. In conclusion, free curcumin showed potent antibacterial effects; however, the nanoencapsulated form was able to minimize the effects caused by L. monocytogenes regarding tissue injury, changes on enzymes of the energetic metabolism, in addition to an antioxidant effect against lipoperoxidation.
Assuntos
Curcumina/administração & dosagem , Curcumina/uso terapêutico , Listeria monocytogenes/efeitos dos fármacos , Listeriose/tratamento farmacológico , Listeriose/veterinária , Nanocápsulas/química , Adenosina Trifosfatases , Adenilato Quinase/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/uso terapêutico , Antioxidantes/farmacologia , Curcumina/química , Suplementos Nutricionais , Modelos Animais de Doenças , Gerbillinae , Homeostase/efeitos dos fármacos , Inflamação , Peroxidação de Lipídeos/efeitos dos fármacos , Listeriose/microbiologia , Fígado/patologia , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Ácidos Polimetacrílicos/uso terapêutico , Piruvato Quinase/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , Baço/patologiaRESUMO
This works reports the synthesis and characterization of diallyl(5-(hydroxymethyl)-1,3-phenylene) dicarbonate (HMFBA) and 5-(hydroxymethyl)-1,3-phenylene bis(2-methylacrylate) (HMFBM) monomers and its evaluation as Bis-GMA eluents in the formulation of composite resins for dental use. The experimental materials formulated with HMFBA and HMFBM monomers presented flexural strength values similar to those of the control group formulated with Bis-GMA/TEGDMA. Regarding volumetric contraction percentage, the values obtained of experimental materials with HMFBA was 1.88% and for HMFBM was 4.15%, both lower than control resin (4.68%). In the case of double bond conversion, the resin formulated with HMFBA monomer exhibited a greater degree of conversion (87%). Besides, the DMA analyses proved that the values for Tg guarantee a good mechanical performance at body temperature. The new resins formulated with HMFBA and HMFBM monomers exhibit a cellular viability close to 100%, which indicates the absence of cytotoxicity towards fibroblastic cells.
Assuntos
Resinas Compostas , Fibroblastos/metabolismo , Teste de Materiais , Polietilenoglicóis , Ácidos Polimetacrílicos , Animais , Linhagem Celular , Resinas Compostas/química , Resinas Compostas/farmacologia , Avaliação Pré-Clínica de Medicamentos , Fibroblastos/citologia , Camundongos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologiaRESUMO
The objective of this study was to compare selective physical-mechanical properties, antibacterial effects and cytotoxicity of seven temporary restorative materials (TRM): five resin-based materials [Bioplic (B), Fill Magic Tempo (FM), Fermit inlay (F), Luxatemp LC (L) and Revotek LC (R)], and zinc oxide-eugenol cement (IRM) and glass ionomer cement (GIC) as the controls. Material and methods The physical-mechanical properties were evaluated by determining microleakage (ML), ultimate tensile strength (UTS) and Shore D hardness (SDH). In addition, the polymerization rate (Pr-1), depth of cure (DC), water sorption and solubility (WS/SL) were evaluated. The antimicrobial effects of the materials were assessed by biofilm accumulation of Streptococcus mutans (BT) and the direct contact test (DCT) by exposure to Enterococcus faecalis for 1 and 24 h, and cytotoxicity by MTT assay. The data were analyzed by ANOVA or Kruskall-Wallis tests, and a complementary post-hoc method (p<0.05). Results Group B, followed by FM and GIC had significantly lower percentages of microleakage in comparison with the other groups; Groups FM and L showed the highest WS, while Groups R and FM showed the significantly lowest SL values (p<0.05). Group R showed the statistically highest UTS mean and the lowest DC mean among all groups. Group F showed the lowest S. mutans biofilm accumulation (p=0.023). Only the Group L showed continued effect against E. faecalis after 1 h and 24 h in DCT. The L showed statistically lower viability cell when compared to the other groups. Conclusions These findings suggest the antibacterial effect of the temporary materials Fill Magic and Bioplic against S. mutans, while Luxatemp showed in vitro inhibition of S. mutans biofilm accumulation and E. faecalis growth. Regarding the cell viability test, Luxatemp was the most cytotoxic and Fill Magic was shown to be the least cytotoxic.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Resinas Compostas/química , Resinas Compostas/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Animais , Bis-Fenol A-Glicidil Metacrilato/química , Bis-Fenol A-Glicidil Metacrilato/farmacologia , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Infiltração Dentária , Restauração Dentária Temporária/métodos , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/farmacologia , Testes de Dureza , Teste de Materiais , Metilmetacrilatos/química , Metilmetacrilatos/farmacologia , Camundongos , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Reprodutibilidade dos Testes , Materiais Restauradores do Canal Radicular/química , Materiais Restauradores do Canal Radicular/farmacologia , Solubilidade , Resistência à Tração , Fatores de Tempo , Cimento de Óxido de Zinco e Eugenol/química , Cimento de Óxido de Zinco e Eugenol/farmacologiaRESUMO
Abstract The objective of this study was to compare selective physical-mechanical properties, antibacterial effects and cytotoxicity of seven temporary restorative materials (TRM): five resin-based materials [Bioplic (B), Fill Magic Tempo (FM), Fermit inlay (F), Luxatemp LC (L) and Revotek LC (R)], and zinc oxide-eugenol cement (IRM) and glass ionomer cement (GIC) as the controls. Material and methods The physical-mechanical properties were evaluated by determining microleakage (ML), ultimate tensile strength (UTS) and Shore D hardness (SDH). In addition, the polymerization rate (Pr-1), depth of cure (DC), water sorption and solubility (WS/SL) were evaluated. The antimicrobial effects of the materials were assessed by biofilm accumulation of Streptococcus mutans (BT) and the direct contact test (DCT) by exposure to Enterococcus faecalis for 1 and 24 h, and cytotoxicity by MTT assay. The data were analyzed by ANOVA or Kruskall-Wallis tests, and a complementary post-hoc method (p<0.05). Results Group B, followed by FM and GIC had significantly lower percentages of microleakage in comparison with the other groups; Groups FM and L showed the highest WS, while Groups R and FM showed the significantly lowest SL values (p<0.05). Group R showed the statistically highest UTS mean and the lowest DC mean among all groups. Group F showed the lowest S. mutans biofilm accumulation (p=0.023). Only the Group L showed continued effect against E. faecalis after 1 h and 24 h in DCT. The L showed statistically lower viability cell when compared to the other groups. Conclusions These findings suggest the antibacterial effect of the temporary materials Fill Magic and Bioplic against S. mutans, while Luxatemp showed in vitro inhibition of S. mutans biofilm accumulation and E. faecalis growth. Regarding the cell viability test, Luxatemp was the most cytotoxic and Fill Magic was shown to be the least cytotoxic.
Assuntos
Animais , Bovinos , Camundongos , Streptococcus mutans/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Resinas Compostas/farmacologia , Resinas Compostas/química , Fibroblastos/efeitos dos fármacos , Antibacterianos/sangue , Antibacterianos/farmacologia , Ácidos Polimetacrílicos/farmacologia , Ácidos Polimetacrílicos/química , Materiais Restauradores do Canal Radicular/farmacologia , Materiais Restauradores do Canal Radicular/química , Solubilidade , Resistência à Tração , Fatores de Tempo , Cimento de Óxido de Zinco e Eugenol/farmacologia , Cimento de Óxido de Zinco e Eugenol/química , Teste de Materiais , Sobrevivência Celular/efeitos dos fármacos , Reprodutibilidade dos Testes , Bis-Fenol A-Glicidil Metacrilato/farmacologia , Bis-Fenol A-Glicidil Metacrilato/química , Restauração Dentária Temporária/métodos , Cimentos de Ionômeros de Vidro/farmacologia , Cimentos de Ionômeros de Vidro/química , Testes de Dureza , Metilmetacrilatos/farmacologia , Metilmetacrilatos/químicaRESUMO
Novel "zwitterionic" gold nanorods (Au NRs) were constructed through a facile ligand exchange process between cetyltrimethylammonium bromide (CTAB)-Au NRs and the zwitterionic block polymer {poly(2-methacryloyloxyethyl phosohorylcholine)-b-poly(lipoic methacrylate) (pMPC-b-pLA)}. In vitro, they exhibited low dark cytotoxicity and a high therapeutic efficacy to cancer cells. Their blood circulation half-life in vivo (t1/2, â¼10 h) was 20-fold longer than that of CTAB-Au NRs (t1/2, <30 min). After intravenous administration, they accumulated in tumour sites via an enhanced permeability and retention (EPR) effect and enabled destruction of human xenograft tumours in mice after exposure of the tumour location to NIR laser irradiation at 808 nm. These studies showed that the "zwitterionic" Au NRs had low toxicity and high photothermal efficacy both in vitro and in vivo due to the suprahydrophilic, biocompatible zwitterionic polymer coating layer. They may have the potential to be a promising NIR PTT agent in the biomedical field.
Assuntos
Compostos de Cetrimônio/uso terapêutico , Ouro/uso terapêutico , Nanotubos , Neoplasias/terapia , Fosforilcolina/análogos & derivados , Ácidos Polimetacrílicos/uso terapêutico , Animais , Linhagem Celular Tumoral , Cetrimônio , Compostos de Cetrimônio/química , Compostos de Cetrimônio/farmacocinética , Compostos de Cetrimônio/farmacologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Humanos , Hipertermia Induzida/métodos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanotubos/análise , Nanotubos/química , Nanotubos/ultraestrutura , Neoplasias/patologia , Fosforilcolina/química , Fosforilcolina/farmacocinética , Fosforilcolina/farmacologia , Fosforilcolina/uso terapêutico , Fototerapia/métodos , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacocinética , Ácidos Polimetacrílicos/farmacologiaRESUMO
The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.
Assuntos
Antipsicóticos/farmacocinética , Risperidona/farmacocinética , Adesivo Transdérmico , Animais , Antipsicóticos/farmacologia , Disponibilidade Biológica , Feminino , Masculino , Camundongos , Olea , Óleo de Amendoim , Permeabilidade , Óleos de Plantas/farmacocinética , Óleos de Plantas/farmacologia , Ácidos Polimetacrílicos/farmacocinética , Ácidos Polimetacrílicos/farmacologia , Coelhos , Ratos , Ratos Wistar , Risperidona/farmacologia , Pele/efeitos dos fármacos , CerasRESUMO
Currently, colon-specific drug delivery systems have been investigated for drugs that can exert their bioactivities in the colon. In this study, Eudragit® S100 coated calcium pectinate microsphere, a pH-dependent and enzyme-dependent system, as colon-specific delivery carrier for curcumin was investigated. Curcumin-loaded calcium pectinate microspheres were prepared by emulsification-linkage method, and the preparation technology was optimised by uniform experimental design. The morphology of microspheres was observed under scanning electron microscopy. Interactions between drug and polymers were investigated with differential scanning calorimetry (DSC) and X-ray diffraction. In vitro drug release studies were performed in simulated colonic fluid in the presence of Pectinex Ultra SP-L or 1% (w/v) rat caecal content, and the results indicated that the release of curcumin was significantly increased in the presence of 1% (w/v) rat caecal contents. It could be concluded that Eudragit® S100 coated calcium pectinate microsphere was a potential carrier for colon delivery of curcumin.
Assuntos
Colo/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Pectinas/administração & dosagem , Ácidos Polimetacrílicos/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Varredura Diferencial de Calorimetria , Ceco/efeitos dos fármacos , Ceco/metabolismo , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Colo/metabolismo , Neoplasias do Colo/metabolismo , Curcumina/química , Curcumina/farmacologia , Microscopia Eletrônica de Varredura , Microesferas , Pectinas/química , Pectinas/farmacologia , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Ratos , Difração de Raios XRESUMO
Oxidized phospholipids (Ox-PLs) are generated in abundance at sites of inflammation. Recent studies have indicated that Ox-PLs may also exhibit anti-inflammatory activities. In this study, we investigated the beneficial effect of VB-201, a pure synthetic Ox-PL analog that we synthesized, on the development of a central nervous system (CNS) autoimmune inflammatory disease, in vivo. Oral administration of VB-201 ameliorated the severity of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) peptide MOG35-55, and restrained the encephalogenicity of MOG35-55-specific T-cells. Our data presents a novel prospect for the role of Ox-PL analogs in CNS inflammatory diseases.
Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Encefalite/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/prevenção & controle , Glicerilfosforilcolina/uso terapêutico , Animais , Células da Medula Óssea/efeitos dos fármacos , Bromodesoxiuridina/metabolismo , Antígenos CD4/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/metabolismo , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Modelos Animais de Doenças , Interações Medicamentosas , Encefalite/etiologia , Encefalite/imunologia , Encefalomielite Autoimune Experimental/complicações , Encefalomielite Autoimune Experimental/etiologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Fatores de Transcrição Forkhead/metabolismo , Adjuvante de Freund/efeitos adversos , Glicerilfosforilcolina/química , Glicerilfosforilcolina/farmacologia , Glicoproteínas/efeitos adversos , Ionomicina/farmacologia , Ionóforos/farmacologia , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Peptídeos/efeitos adversos , Toxina Pertussis/efeitos adversos , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Ácidos Polimetacrílicos/farmacologia , Índice de Gravidade de Doença , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fatores de TempoRESUMO
In the present investigation, pulsatile release beads were prepared by ionic gelation technique. Theophylline dual-cross-linked beads were prepared by dropping dispersed phase of theophylline, Delonix regia gum (DRG), and sodium alginate into the dispersion phase of different concentration of calcium chloride solution followed by aluminium chloride solution. The formulated beads were further coated by Eudragit L & S 100 in the ratio 1:2 w/w in order to achieve desired lag time. In vitro release study showed lag time of 57 h before release of theophylline from the formulated beads, which were found to be intact for 6 h. Thus, formulated dual cross-linked beads when administered at bed time may release theophylline when needed most for chronotherapeutics of early morning asthmatic attacks in chronic patients. In vivo radio imaging study carried out in New Zealand white strain rabbit confirms the findings of in vitro results.
Assuntos
Asma/tratamento farmacológico , Cronoterapia , Teofilina , Alginatos/química , Alginatos/farmacologia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Broncodilatadores/farmacologia , Química Farmacêutica , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Excipientes , Fabaceae/química , Ácido Glucurônico/química , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacologia , Humanos , Manose/química , Manose/farmacocinética , Microesferas , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Coelhos , Teofilina/farmacologiaRESUMO
The auditory mismatch negativity (MMN) event-related brain potential (ERP) reflects the storage of information in acoustic sensory memory. Thirteen patients with probable Alzheimer's disease (AD), 6 receiving treatment with the cholinesterase inhibitor (ChEI) tacrine (tetrahydroaminoacridine, THA) and 7 receiving no treatment, were administered 2 mg of nicotine polacrilex and placebo. MMNs were recorded with 1- and 3-s interstimulus intervals pre- and postplacebo/nicotine administration. In nontreated patients, amplitudes were decreased from pre- to postplacebo recordings but remained stable in THA-treated patients. Comparison of pre- and postnicotine MMNs found amplitude increases with nicotine in nontreated but not THA-treated patients. MMN latencies were shortened by nicotine in both treatment groups. These exploratory findings suggest that nicotine-improved strength of acoustic sensory memory traces and speed of acoustic sensory discrimination in AD are differentially affected by chronic ChEI treatment.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Inibidores da Colinesterase/uso terapêutico , Variação Contingente Negativa/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Nicotina/análogos & derivados , Nicotina/farmacologia , Ácidos Polimetacrílicos/farmacologia , Polivinil/farmacologia , Tacrina/uso terapêutico , Estimulação Acústica , Idoso , Estimulantes do Sistema Nervoso Central/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Processos Mentais/efeitos dos fármacos , Pessoa de Meia-Idade , Agonistas Nicotínicos/farmacologia , Tempo de Reação/efeitos dos fármacos , Dispositivos para o Abandono do Uso de TabacoRESUMO
PURPOSE: This study was designed to determine the usefulness of an established stable immortalized mouse odontoblast cell line (MO6-G3) for dental material biocompatibility testing. Using a standard toxicity assay based on cell respiratory activity, the response to MO6-G3 cells was compared to the mouse fibroblastic cell line, L929, presently used for dental materials testing. The dental resin monomer TEGDMA was used as the dental material for the assay. MATERIALS AND METHODS: Cell lines (1 x 10(3)/well) were plated in 96 well culture plates and grown in DMEM supplemented with 10% FCS, 100 units/ml each of penicillin and streptomycin, and 50 micrograms/ml ascorbic acid in an atmosphere of 95% air and 5% CO2. Cells were exposed to TEGDMA resin monomer covering a dose range of 1 x 10(-6) to 0.5 x 10(-3) M. Unexposed control cells, as well as cells exposed to the DMSO vehicle in which the TEGDMA was dissolved, were included in all assays. Cytotoxicity was evaluated by determining cell respiratory activity spectrophotometrically using the tetrazolium compound WST-1. RESULTS: Statistical analysis by ANOVA using Tukey's method for pair wise comparisons as the post hoc test indicated toxic effects of TEGDMA at 1 x 10(-5) M in the odontoblast cell line MO6-G3. By contrast, the monomer produced no toxic effects on the L929 fibroblast cell line after 24 hours of exposure, over the entire concentration range tested. Furthermore, MO6-G3 cells exposed to a concentration of 0.5 x 10(-3) M were unable to recover from the effects of the exposure 48 hours after removal of the resin. MO6-G3 cells exposed to 1 x 10(-4) and 0.5 x 10(-4) TEGDMA recovered 40-50% and 75-80% of control respiratory activity respectively, 48 hours after removal of the resin. Respiratory activity by L929 cells exposed to all TEGDMA concentrations tested was not different from the vehicle control 48 hours after removal of the resin.
Assuntos
Linhagem Celular/efeitos dos fármacos , Materiais Dentários/toxicidade , Polpa Dentária/citologia , Odontoblastos/efeitos dos fármacos , Testes de Toxicidade , Análise de Variância , Animais , Materiais Biocompatíveis/toxicidade , Respiração Celular/efeitos dos fármacos , Polpa Dentária/efeitos dos fármacos , Células L , Teste de Materiais/métodos , Camundongos , Odontoblastos/fisiologia , Polietilenoglicóis/farmacologia , Polietilenoglicóis/toxicidade , Ácidos Polimetacrílicos/farmacologia , Ácidos Polimetacrílicos/toxicidadeRESUMO
Without the use of highly effective dentinal adhesives, the cervical margins of tooth-colored adhesive inlays localized in dentin are poorly adapted. It was the purpose of this study to optimize these margins with the help of the Gluma-Clearfil combination. This goal was achieved, but the results indicated, that the success depended on the choice of the luting composite. Perfectly adapted cervical dentinal margins of tooth-colored adhesive inlays are achievable. For routine use, the system has to be simplified.