RESUMO
OBJECTIVES: This split-mouth study evaluated miRNA expression of tissues around implants with different surface treatments. MATERIAL AND METHODS: Each patient of the sample (five men and five women) received two implants (one control and one test) into an edentulous quadrant to support fixed partial dentures. The control implants (Osseotite) had a dual acid-etched (DAE) surface in the apical portion and a machined coronal part, test implants (Full Osseotite, FOSS) were completely DAE. Machined healing abutments were placed on control implants and DAE abutments on test ones. All implants were assigned codes for blinding. Standardized periapical radiographs were taken at baseline, 2 and 6 months, and 1 year after surgery. Plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were recorded at 3 and 6 weeks, and 2, 3, 6, and 12 months post-implant placement. After 3 months, a mini-invasive sample of soft tissue was collected from seven patients (four women and three men) for miRNA microarray analysis. RESULTS: Control implants showed greater bone resorption (BR) and lower PI: this was not statistically significant. No statistically significant differences in BOP and PD appeared. miRNA modulated by implant surfaces as well as by other clinical conditions has been identified. miRNA microarray analysis revealed that: (i) implant sites with low PI and absence of BOP had a miRNA expression profile similar to those with plaque and absence of BOP; sites with high PI and high BOP had a different profile. (ii) Implant sites with BOP presented similar profiles independently from implant surface. (iii) Implant sites with high PI and normal BR differed from others for miRNA expression profile. (iv) Implant sites with normal BR despite high BOP differed from others. This profile resembled that of FOSS implants. (v) Implant surface affected BR; groups having similar BR clusterized differently according to the implant type. CONCLUSIONS: DAE surfaces induced lower BR and more plaque accumulation: This did not affect the health of soft tissues. miRNA analysis indicated that soft tissue inflammation is more related to gene expression profile than to plaque or to implant surface. Specific miRNA profile can protect implant sites from bleeding and BR irrespective of plaque accumulation.
Assuntos
Implantes Dentários , Prótese Dentária Fixada por Implante , Periodonto/metabolismo , Titânio , Planejamento de Prótese Dentária , Feminino , Humanos , Masculino , MicroRNAs/biossíntese , Análise em Microsséries , Valor Preditivo dos Testes , Propriedades de Superfície , Resultado do TratamentoRESUMO
Mn has been found to self-assemble into atomic chains running perpendicular to the surface dimer reconstruction on Si(001). They differ from other atomic chains by a striking asymmetric appearance in filled state scanning tunneling microscopy (STM) images. This has prompted complicated structural models involving up to three Mn atoms per chain unit. Combining STM, atomic force microscopy, and density functional theory we find that a simple necklacelike chain of single Mn atoms reproduces all their prominent features, including their asymmetry not captured by current models. The upshot is a remarkably simpler structure for modeling the electronic and magnetic properties of Mn atom chains on Si(001).
RESUMO
Molecular mechanisms relating interferon-alpha (IFN-alpha) to brain damage have recently been identified in a microarray analysis of cerebrospinal fluid lymphocytes from patients with Aicardi-Goutières Syndrome (AGS). These findings demonstrate that the inhibition of angiogenesis and the activation of neurotoxic lymphocytes are the major pathogenic mechanisms involved in the brain damage consequent to elevated interferon-alpha levels. Our previous study demonstrated that cathepsin D, a lysosomal aspartyl endopeptidase, is the primary mediator of the neurotoxicity exerted by AGS lymphocytes. Cathepsin D is a potent pro-apoptotic, neurotoxic, and demyelinating protease if it is not properly inhibited by the activities of leukocystatins. In central nervous system white matter, demyelination results from cathepsin over-expression when not balanced by the expression of its inhibitors. In the present study, we used RNA interference to inhibit cathepsin D expression in AGS lymphocytes with the aim of decreasing the neurotoxicity of these cells. Peripheral blood lymphocytes collected from an AGS patient were immortalized and co-cultured with astrocytes in the presence of interferon alpha with or without cathepsin D RNA interference probes. Cathepsin D expression was measured by qPCR, and neurotoxicity was evaluated by microscopy. RNA interference inhibited cathepsin D over-production by 2.6-fold (P<0.01) in AGS lymphocytes cultured in the presence of interferon alpha. AGS lymphocytes treated using RNA interference exhibited a decreased ability to induce neurotoxicity in astrocytes. Such neurotoxicity results in the inhibition of astrocyte growth and the inhibition of the ability of astrocytes to construct web-like aggregates. These results suggest a new strategy for repairing AGS lymphocytes in vitro by inhibiting their ability to induce astrocyte damage and leukodystrophy.
Assuntos
Astrócitos/patologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/patologia , Catepsina D/antagonistas & inibidores , Linfócitos/imunologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Malformações do Sistema Nervoso/imunologia , Malformações do Sistema Nervoso/patologia , Astrócitos/imunologia , Catepsina D/genética , Linhagem Celular Tumoral , Humanos , Interferon-alfa/imunologia , Proteínas do Tecido Nervoso/genética , Interferência de RNA , RNA Interferente Pequeno/genéticaRESUMO
As the only nourishment and scavenging source for most of the anterior and posterior chamber tissues in the eye, the aqueous humor represents one of the target for glaucoma. The aim of this study is to investigate the yet unexplored relationship between aqueous humor protein content and open-angle glaucoma (POAG) pathogenesis. Aqueous humor was collected from 10 POAG patients (cases) and 14 senile cataract patients (controls), matched for age and gender, undergoing surgery for trabeculectomy and cataract, respectively. Protein samples were cyanine-labeled and hybridized with antibody microarrays. Microarray signals were revealed by laser scanner, quantified, and compared by statistical analyses. Total protein amounts were not significantly different in patients versus controls. Conversely, a proteome cluster significantly modified in patients as compared to controls was identified as highly predictive for disease status. Selected proteins underwent dramatic variation, which was correlated to pathogenetic events characterizing POAG, including oxidative damage, mitochondrial damage, neural degeneration, and apoptosis. The results obtained indicate that proteomic analysis of aqueous humor is a new tool for POAG diagnosis in the case of otherwise uncertain disease recognition. Furthermore, this study allows a better understanding of mechanisms involved in the pathogenesis of POAG, the main cause of irreversible blindness worldwide.
Assuntos
Humor Aquoso/química , Proteínas do Olho/química , Glaucoma de Ângulo Aberto/metabolismo , Proteoma/química , Proteômica/métodos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Casos e Controles , Análise por Conglomerados , Proteínas do Olho/classificação , Proteínas do Olho/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Análise Serial de Proteínas , Estatísticas não ParamétricasRESUMO
T cells are made tolerant only to those self-peptides that are presented in sufficient amounts by antigen-presenting cells. They ignore cryptic self-determinants, such as either those not generated by processing machinery or generated in insufficient amounts. It is anticipated that mechanisms that either change antigen processing or increase the yield of previously "invisible" peptides may be capable of inducing T cell priming and, if they are self-maintained, may sustain autoimmune diseases. Herein, we demonstrate for the first time a mechanism by which the gp120 human immunodeficiency virus-I, by downregulating plasma membrane CD4 and increasing its processing, unveils hidden CD4 epitopes, inducing an autoimmune-specific T cell response.
Assuntos
Antígenos CD/imunologia , Antígenos CD4/química , Antígenos CD4/imunologia , Proteína gp120 do Envelope de HIV/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Células Apresentadoras de Antígenos/imunologia , Antígenos CD/química , Antígenos CD/efeitos dos fármacos , Linfócitos B/imunologia , Antígenos CD4/efeitos dos fármacos , Células CHO , Células Clonais , Cricetinae , Humanos , Dados de Sequência Molecular , Proteínas Recombinantes/efeitos dos fármacos , Proteínas Recombinantes/imunologia , Linfócitos T/efeitos dos fármacos , TransfecçãoRESUMO
The fabrication and characterization of superconducting and ferromagnetic heterostructures is an open field due to the fundamental interest in the physics of the coexistence of these two competing orders and their possible applications in the spintronics industry. In this paper we present structural, electrical and magnetic characterization for the single La(0.7)Ca(0.3)MnO(3) (LCMO) thin layer, La(0.7)Ca(0.3)MnO(3)/YBa(2)Cu(3)O(7-x) (LCMO/YBCO) bilayers and the LCMO/YBCO/LCMO trilayers. In particular, we show a detailed magnetic characterization of the LCMO thin films by means of low temperature magnetic force microscopy. We discuss the different dynamics of the magnetic domains observed, depending on the substrate induced strain and on the film thickness.
RESUMO
The tuftsin retro-inverso analogue H-Thr psi[NHCO](R,S)Lys-Pro-Arg-OH was synthesized through a novel procedure for the high-yield incorporation of isolated retro-inverso bonds into peptide chains and the use of the new Meldrum's acid derivative (CH3)2C(OCO)2CH(CH2)4NHCOCF3 followed by its efficient coupling in solution to trimethylsilylated H-D-Thr(t-Bu)NH2. Closely related peptide impurities were eliminated both from the crude final peptide and the fully protected tetrapeptide amide precursor via ion-exchange and reversed-phase displacement chromatography, respectively. The tuftsin retro-inverso analogue proved to be completely resistant to enzymatic degradation in vitro, either against isolated aminopeptidases or human plasma proteolytic enzymes. When administered either orally or intravenously, it was significantly more active than normal tuftsin in increasing the number of specific antibody secreting cells in spleen of mice immunized with sheep erythrocytes. Furthermore, the analogue exerted an enhanced stimulatory effect on the cytotoxic activity of splenocytes against YAC-1 tumor cells. Finally, retro-inverso-tuftsin was about 10-fold more potent than the native peptide in reducing rat adjuvant arthritis. The resistance of the retro-inverso analogue to peptidases might explain the increased in vivo activities and allows its further immunopharmacological characterization.
Assuntos
Adjuvantes Imunológicos/síntese química , Tuftsina/análogos & derivados , Adjuvantes Imunológicos/metabolismo , Adjuvantes Imunológicos/farmacologia , Sequência de Aminoácidos , Animais , Formação de Anticorpos/efeitos dos fármacos , Artrite Experimental/terapia , Estabilidade de Medicamentos , Eritrócitos/imunologia , Feminino , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Dados de Sequência Molecular , Peptídeo Hidrolases/metabolismo , Ratos , Ratos Endogâmicos Lew , Ovinos , Tuftsina/síntese química , Tuftsina/metabolismo , Tuftsina/farmacologiaRESUMO
We used single photon emission tomography to study regional cerebral perfusion in patients with different forms of spinocerebellar degeneration: 6 patients with Friedreich's ataxia (FA), 6 with early-onset cerebellar ataxia with retained tendon reflexes (EOCA), 5 with autosomal dominant cerebellar ataxia type 1 (ADCA I) and 11 with idiopathic late-onset cerebellar ataxia (ILOCA). The results were related to clinical and magnetic resonance imaging (MRI) findings. Cerebellar hypoperfusion was constant in ADCA I and frequent in patients with other spinocerebellar degenerations. Brain stem hypoperfusion was constant in ADCA I, frequent in ILOCA patients with pontocerebellar atrophy and absent in FA and EOCA. FA and EOCA often showed a reduction in the parietotemporal cortex blood flow, which was not related to cortical atrophy. ILOCA patients had an asymmetric pattern in the temporal areas with decreased blood flow in the right side only. Caudate hypoperfusion was found in ADCA I patients. Cerebral atrophy did not account for changes in regional blood flow, which probably indicate early involvement of cerebral structures.
Assuntos
Circulação Cerebrovascular/fisiologia , Degenerações Espinocerebelares/fisiopatologia , Adulto , Idade de Início , Idoso , Estudos de Casos e Controles , Ataxia Cerebelar/genética , Ataxia Cerebelar/fisiopatologia , Feminino , Genes Dominantes , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mioclonia/fisiopatologia , Degenerações Espinocerebelares/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
An investigation was performed in order to evaluate the presence as polluting agents of chlorinated hydrocarbons in complex cosmetic matrices. Chlorinated pesticides, such as Dieldrin, alpha-Endosulfan, Heptachlor, alpha-Hexachlorocyclohexane (alpha-HCH), Lindane and polychlorinated biphenyls (PCBs) such as Aroclor 1254, were studied in two ingredients and in three finished commercial products. The analytical procedure consists of extraction, extract clean-up, separation of pesticides from PCBs, identification and measurement. Analysis was performed by gas chromatography with electron-capture detector, identity of pesticides and PCBs was assumed from retention times and quantification was based on peak-height measurements.
Assuntos
Cosméticos/análise , Inseticidas/análise , Bifenilos Policlorados/análise , Cromatografia Gasosa/métodos , Humanos , Inseticidas/farmacocinética , Absorção CutâneaRESUMO
The synthesis of omega-dialkylaminoalkyl ethers 3 by the reaction of some 5-(arylmethylene)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6- hydroxyimines as sodium salts with the appropriate omega-chloroalkyldialkylamine in DMF solution is described. Some aminoethers 3 showed strong platelet antiaggregating activity in vitro superior to that of acetylsalicylic acid, as well as weak antiarrhythmic activity in rats and moderate infiltration anesthesia in mice.
Assuntos
Compostos Bicíclicos com Pontes/síntese química , Iminas/síntese química , Inibidores da Agregação Plaquetária/síntese química , Anestésicos Locais/síntese química , Animais , Antiarrítmicos/síntese química , Pressão Sanguínea/efeitos dos fármacos , Compostos Bicíclicos com Pontes/farmacologia , Humanos , Iminas/farmacologia , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Camundongos , Ratos , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
The synthesis of some N,N-disubstituted 4-amino-3-phenyl-2H,5H-[1]benzothiopyrano [4,3-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-1-benzothiopyran-4-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a strong platelet antiaggregating activity in vitro, superior to that of acetylsalicylic acid.
Assuntos
Benzotiepinas/síntese química , Inibidores da Agregação Plaquetária/síntese química , Agregação Plaquetária/efeitos dos fármacos , Piranos/síntese química , Anestésicos Locais/síntese química , Animais , Antiarrítmicos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Anti-Hipertensivos/síntese química , Benzotiepinas/farmacologia , Fenômenos Químicos , Química , Humanos , Técnicas In Vitro , Camundongos , Piranos/farmacologia , RatosRESUMO
The synthesis of some N,N-disubstituted 4-amino-6,7,8,9-tetrahydro-3-phenylcyclohepta[b]pyran-2(5H)-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylenecycloheptanones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as weak local anesthetic, antiinflammatory and analgesic activities in mice and rats.
Assuntos
Inibidores da Agregação Plaquetária/síntese química , Piranos/síntese química , Analgésicos/síntese química , Analgésicos/farmacologia , Anestésicos Locais/síntese química , Anestésicos Locais/farmacologia , Animais , Antiarrítmicos/síntese química , Antiarrítmicos/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Fenômenos Químicos , Físico-Química , Humanos , Técnicas In Vitro , Camundongos , Inibidores da Agregação Plaquetária/farmacologia , Piranos/farmacologia , RatosRESUMO
The synthesis of some N,N-disubstituted 1-amino-2-phenyl-3H,12H-naphtho[1,2-b]pyrano[2,3-d]pyran-3-ones 4, by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-naphtho[1,2-b]pyran-4-ones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. Some compounds 4 showed antiarrhythmic and analgesic activities.
Assuntos
Antiarrítmicos/farmacologia , Naftóis/farmacologia , Antiarrítmicos/química , Estrutura Molecular , Naftóis/química , Medição da DorRESUMO
The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones (4a-f), by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo[b]thiophen-4(5)-ones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. A moderate local anaesthetic activity was observed in the title compounds, particularly in 4e.
Assuntos
Anestésicos Locais/síntese química , Benzopiranos/síntese química , Analgesia , Anestésicos Locais/química , Anestésicos Locais/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Camundongos , Ratos , Relação Estrutura-AtividadeRESUMO
The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3,8-diphenyl-2H-pyrano[2,3-f]quinazolin- 2-ones by the reaction of phenylchloroketene with a series of N,N-disubstituted (E)-6-aminomethylene-7,8-dihydro-2-phenylquinazolin-5(6H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The methylbenzylamino and diphenylamino derivatives showed platelet antiaggregating activity in vitro superior to that of acetylsalicylic acid. The 1-pyrrolidinyl derivative showed appreciable local anesthetic activity in mice, whereas the whole series of compounds exhibited weak antiinflammatory activity in rats.
Assuntos
Inibidores da Agregação Plaquetária/síntese química , Piranos/síntese química , Quinazolinas/síntese química , Anestésicos Locais/síntese química , Animais , Antiarrítmicos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Carragenina , Edema/induzido quimicamente , Edema/prevenção & controle , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Camundongos , Piranos/farmacologia , Quinazolinas/farmacologia , Ratos , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
The synthesis of some N,N-disubstituted 4-amino-5,6,7,8-tetrahydro-3,6- diphenyl-2H-1-benzopyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylene-4-phenylcyclohexanones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid and an appreciable antiarrhythmic activity, as well as weak anti-inflammatory and local anesthetic activities in rats and mice.
Assuntos
Benzopiranos/síntese química , Inibidores da Agregação Plaquetária/síntese química , Aconitina/farmacologia , Anestésicos Locais/síntese química , Anestésicos Locais/farmacologia , Animais , Antiarrítmicos/síntese química , Antiarrítmicos/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Benzopiranos/farmacologia , Carragenina , Cicloexanos/química , Edema/induzido quimicamente , Edema/prevenção & controle , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Camundongos , Inibidores da Agregação Plaquetária/farmacologia , Ratos , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-[1]benzothiepino [5,4-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzothiepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The 4-methylphenylamino derivative showed a local anesthetic activity in mice superior to that of lidocaine and the 4-morpholino derivative showed an antiarrhythmic activity in rats comparable to that of quinidine.
Assuntos
Anestésicos Locais/síntese química , Antiarrítmicos/síntese química , Benzotiepinas/síntese química , Piranos/síntese química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Hipertensivos/síntese química , Benzotiepinas/farmacologia , Fenômenos Químicos , Química , Espectroscopia de Ressonância Magnética , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Piranos/farmacologia , Ratos , Tempo de Reação/efeitos dos fármacos , Espectrofotometria Infravermelho , Trombina/farmacologiaRESUMO
The synthesis of some O-(2-dialkylaminoethyl)oximes of 5-[(4-methoxy- or 4-methylthiophenyl)methylene]-1,3,3-trimethyl-2-oxabicyclo[2.2.2] octan-6-ones 5 by reaction of the corresponding oximes as sodium salts with the appropriate 2-chloroethyldialkylamine in dry ethanol solution is described. Some aminoethers 5 showed appreciable hypotensive and antiarrhythmic activities in rats, as well as a weak platelet antiaggregating activity in vitro and a moderate infiltration anesthesia in mice.
Assuntos
Antiarrítmicos/síntese química , Anti-Hipertensivos/síntese química , Oximas/síntese química , Anestésicos Locais/síntese química , Anestésicos Locais/farmacologia , Animais , Antiarrítmicos/farmacologia , Anti-Hipertensivos/farmacologia , Humanos , Técnicas In Vitro , Camundongos , Oximas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , RatosRESUMO
The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-pyrano[3,2-d]-1-benzoxepin-2 -ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzoxepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a platelet antiaggregating activity in vitro slightly superior to that of acetylsalicylic acid, as well as weak local anesthetic and antiinflammatory activities in mice and rats, respectively.
Assuntos
Benzoxepinas/síntese química , Inibidores da Agregação Plaquetária/síntese química , Piranos/síntese química , Anestésicos Locais/síntese química , Animais , Antiarrítmicos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Benzoxepinas/farmacologia , Humanos , Técnicas In Vitro , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Piranos/farmacologia , RatosRESUMO
The synthesis of some N,N-disubstituted 4-amino-6,7-dihydro-3-phenylbenzo[6,7]cyclohepta[1,2-b]pyran-2(5H) -ones by reaction of phenylchloroketene with a series of N,N-disubstituted 6-aminomethylene-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as a weak local anesthetic activity in mice and antiinflammatory activity in rats.