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1.
Inflamm Res ; 73(6): 1019-1031, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38656426

RESUMO

OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.


Assuntos
Angiotensina I , Lipopolissacarídeos , Pulmão , Ovalbumina , Fragmentos de Peptídeos , Animais , Angiotensina I/uso terapêutico , Angiotensina I/farmacologia , Angiotensina I/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/imunologia , Ovalbumina/imunologia , Camundongos , Masculino , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Camundongos Endogâmicos BALB C , Inflamação/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Eosinofilia/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia
2.
Clin Oral Investig ; 25(6): 4069-4074, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33464418

RESUMO

OBJECTIVE: To explore the use of 3D intraoral scanner/image analysis for the detection and monitoring of simulated non-carious cervical lesions (NCCLs) in vitro. MATERIALS AND METHODS: A total of 288 NCCLs of different severities and simulated using a laboratorial model associating toothbrush stiffness (soft, medium, and hard) and toothpaste abrasivity (low, medium, high, and negative control) were analyzed. Dental impressions were taken from specimens before and after 35K and 65K brushing strokes, and then scanned with a CEREC Omnicam scanner. 3D models were analyzed for volumetric tooth loss. 3D optical profilometry was considered as the gold standard. Data were analyzed using ANOVA and Fisher's PLSD tests (alpha = 0.05), and agreement between methods by using intraclass correlation coefficient. RESULTS: Toothbrushes of hard and mid stiffness caused higher tooth loss than soft when associated with the highest abrasive, at 35K and 65K strokes (p < 0.001). Variation in slurry abrasivity led to differences in tooth loss (with control < low < medium < high, p < 0.0001) after both 35K and 65K strokes, regardless of the type of toothbrush used, except at 35K, wherein control = low (p = 0.55). 35K strokes caused less tooth loss than 65K for all abrasive slurries (p < 0.0001) except controls. The intraclass correlation coefficient for agreement between the test and gold standard methods was 0.85. CONCLUSIONS: Analysis of 3D images from intraoral scanner could detect and monitor NCCL progression, although this ability was limited on incipient lesions. Overall good agreement was found between the test method and optical profilometry. CLINICAL RELEVANCE: The suggested method may be applicable to detect and monitor NCCLs clinically.


Assuntos
Abrasão Dentária , Erosão Dentária , Humanos , Escovação Dentária , Cremes Dentais
3.
J Environ Manage ; 300: 113737, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536739

RESUMO

Persistent Organic Pollutants (POPs) have become a very serious issue for the environment because of their toxicity, resistance to conventional degradation mechanisms, and capacity to bioconcentrate, bioaccumulate and biomagnify. In this review article, the safety, regulatory, and remediation aspects of POPs including aromatic, chlorinated, pesticides, brominated, and fluorinated compounds, are discussed. Industrial and agricultural activities are identified as the main sources of these harmful chemicals, which are released to air, soil and water, impacting on social and economic development of society at a global scale. The main types of POPs are presented, illustrating their effects on wildlife and human beings, as well as the ways in which they contaminate the food chain. Some of the most promising and innovative technologies developed for the removal of POPs from water are discussed, contrasting their advantages and disadvantages with those of more conventional treatment processes. The promising methods presented in this work include bioremediation, advanced oxidation, ionizing radiation, and nanotechnology. Finally, some alternatives to define more efficient approaches to overcome the impacts that POPs cause in the hydric sources are pointed out. These alternatives include the formulation of policies, regulations and custom-made legislation for controlling the use of these pollutants.


Assuntos
Poluentes Ambientais , Praguicidas , Cadeia Alimentar , Humanos , Poluentes Orgânicos Persistentes , Praguicidas/análise , Solo
4.
Clin Sci (Lond) ; 127(2): 101-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24502705

RESUMO

Muscular dystrophies are a group of heterogeneous genetic disorders that cause progressive muscle weakness and wasting, dilated cardiomyopathy and early mortality. There are different types of muscular dystrophies with varying aetiologies but they all have a common hallmark of myofibre degeneration, atrophy and decreased mobility. Mutation in Sgcd (sarcoglycan-δ), a subunit of dystrophin glycoprotein complex, causes LGMD2F (limb girdle muscular dystrophy 2F). Previously, we have reported that Sgcd-deficient (Sgcd-/-) mice exhibit AngII (angiotensin II)-induced autonomic and skeletal muscle dysfunction at a young age, which contributes to onset of dilated cardiomyopathy and mortality at older ages. Two counter-regulatory RAS (renin-angiotensin system) pathways have been identified: deleterious actions of AngII acting on the AT1R (AngII type 1 receptor) compared with the protective actions of Ang-(1-7) [angiotensin-(1-7)] acting on the receptor Mas. We propose that the balance between the AngII/AT1R and Ang-(1-7)/Mas axes is disturbed in Sgcd-/- mice. Control C57BL/6J and Sgcd-/- mice were treated with Ang-(1-7) included in hydroxypropyl ß-cyclodextrin (in drinking water) for 8-9 weeks beginning at 3 weeks of age. Ang-(1-7) treatment restored the AngII/AT1R compared with Ang-(1-7)/Mas balance, decreased oxidative stress and fibrosis in skeletal muscle, increased locomotor activity, and prevented autonomic dysfunction without lowering blood pressure in Sgcd-/- mice. Our results suggest that correcting the early autonomic dysregulation by administering Ang-(1-7) or enhancing its endogenous production may provide a novel therapeutic approach in muscular dystrophy.


Assuntos
Angiotensina I/farmacologia , Atividade Motora/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Distrofias Musculares/tratamento farmacológico , Distrofias Musculares/metabolismo , Fragmentos de Peptídeos/farmacologia , Sarcoglicanas/metabolismo , Administração Oral , Animais , Distrofina/metabolismo , Fibrose/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofias Musculares/genética , Fenótipo , Sarcoglicanas/genética
5.
J Sex Med ; 10(10): 2430-42, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23890028

RESUMO

INTRODUCTION: The renin angiotensin system plays a crucial role in erectile function. It has been shown that elevated angiotensin-II levels contribute to the development of erectile dysfunction (ED). Oppositely, angiotensin-(1-7) (Ang-[1-7]) mediates penile erection by activation of receptor Mas. Recently, we have developed a formulation based on Ang-(1-7) inclusion in cyclodextrin (CyD) [Ang-(1-7)-CyD], which allows for the oral administration of Ang-(1-7). AIM: In the present study, we evaluated the effects of chronic treatment with Ang-(1-7)-CyD on penile fibrosis, oxidative stress, and endothelial function in hypercholesterolemic mice. METHODS: Apolipoprotein(Apo)E-/- mice fed a Western-type diet for 11 weeks received Ang-(1-7)-CyD or vehicle during the final 3 weeks. Collagen content and reactive oxygen species (ROS) production within the corpus cavernosum were evaluated by Sirius red and dihydroethidium staining, respectively. Protein expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH) subunits (p67-phox and p22-phox), and AT1 and Mas receptors in the penis was assessed by Western blotting. Nitric oxide (NO) production was measured by Griess assay in the mice serum. Cavernosal strips were mounted in an isometric organ bath to evaluate the endothelial function. MAIN OUTCOME MEASURES: The effect of Ang-(1-7)-CyD treatment on penile fibrosis, oxidative stress, and endothelial function in hypercholesterolemia-induced ED. RESULTS: Ang-(1-7)-CyD treatment reduced collagen content in the corpus cavernosum of ApoE-/- mice. This effect was associated with an attenuation of ROS production and a diminished expression of NADPH. Furthermore, Ang-(1-7)-CyD treatment augmented the expression of nNOS and eNOS in the penis and elevated vascular NO production. Importantly, these effects were accompanied by an improvement in cavernosal endothelial function. CONCLUSION: Long-term treatment with Ang-(1-7)-CyD reduces penile fibrosis associated with attenuation of oxidative stress. Additionally, cavernosal endothelial function in hypercholesterolemic mice was markedly improved. These results suggest that Ang-(1-7)-CyD might have significant therapeutic benefits for the treatment of erectile dysfunction.


Assuntos
Angiotensina I/administração & dosagem , Ciclodextrinas/administração & dosagem , Hipercolesterolemia/complicações , Impotência Vasculogênica/tratamento farmacológico , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Vasodilatadores/administração & dosagem , Administração Oral , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Colágeno/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Fibrose , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Hipercolesterolemia/fisiopatologia , Impotência Vasculogênica/etiologia , Impotência Vasculogênica/metabolismo , Impotência Vasculogênica/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pênis/irrigação sanguínea , Pênis/metabolismo , Pênis/fisiopatologia , Fosfoproteínas/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Vasodilatação/efeitos dos fármacos
6.
Pharmaceutics ; 15(7)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37514076

RESUMO

This study reports the fabrication of polymeric matrices through electrospinning using polymethyl methacrylate (PMMA) and poly(lactic-co-glycolic acid) (PLGA), biocompatible polymers commonly used in medical systems. These polymers were combined with an antibacterial drug, sulfadiazine sodium salt (SDS) or its supramolecular system formed with hydroxypropyl-ß-cyclodextrin (HPß/CD) at 1:1 molar ratio, aiming to assemble a transdermal drug delivery system. The formation of fibers was confirmed by scanning electron microscopy (SEM), and the fibers' surface properties were analyzed using contact angle and water vapor permeability techniques. Drug release tests and cell viability assays were performed to evaluate the potential toxicity of the material. SEM images demonstrated that the obtained fibers had nanoscale- and micrometer-scale diameters in PLGA and PMMA systems, respectively. The contact angle analyses indicated that, even in the presence of hydrophilic molecules (SDS and HPßCD), PMMA fibers exhibited hydrophobic characteristics, while PLGA fibers exhibited hydrophilic surface properties. These data were also confirmed by water vapor permeability analysis. The drug release profiles demonstrated a greater release of SDS in the PLGA system. Moreover, the presence of HPßCD improved the drug release in both polymeric systems and the cell viability in the PMMA SDS/HPßCD system. In terms of antibacterial activity, all membranes yielded positive outcomes; nevertheless, the PLGA SDS/HPßCD membrane exhibited the most remarkable results, with the lowest microbial load values. Additionally, the pseudo wound healing analysis demonstrated that the PLGA SDS/HPßCD fiber exhibited results similar to the control group. Consequently, these findings exemplify the substantial potential of the obtained materials for use in wound healing applications.

7.
Phys Chem Chem Phys ; 14(6): 1934-44, 2012 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-22234498

RESUMO

The size, shape and surface chemistry of nanoparticles play an important role in cellular interaction. Thus, the main objective of the present study was the determination of the ß-cyclodextrin (ß-CD) self-assembly thermodynamic parameters and its structure, aiming to use these assemblies as a possible controlled drug release system. Light scattering measurements led us to obtain the ß-CD's critical aggregation concentration (cac) values, and consequently the thermodynamic parameters of the ß-CD spontaneous self-assembly in aqueous solution: Δ(agg)G(o) = -16.31 kJ mol(-1), Δ(agg)H(o) = -26.48 kJ mol(-1) and TΔ(agg)S(o) = -10.53 kJ mol(-1) at 298.15 K. Size distribution of the self-assembled nanoparticles below and above cac was 1.5 nm and 60-120 nm, respectively. The number of ß-CD molecules per cluster and the second virial coefficient were identified through Debye's plot and molecular dynamic simulations proposed the three-fold assembly for this system below cac. Ampicillin (AMP) was used as a drug model in order to investigate the key role of the guest molecule in the self-assembly process and the ß-CD:AMP supramolecular system was studied in solution, aiming to determine the structure of the supramolecular aggregate. Results obtained in solution indicated that the ß-CD's cac was not affected by adding AMP. Moreover, different complex stoichiometries were identified by nuclear magnetic resonance and isothermal titration calorimetry experiments.


Assuntos
Ampicilina/química , beta-Ciclodextrinas/química , Calorimetria , Portadores de Fármacos/química , Luz , Simulação de Dinâmica Molecular , Nanopartículas/química , Espalhamento de Radiação , Termodinâmica , Fatores de Tempo , Água/química
9.
Beilstein J Org Chem ; 8: 1867-76, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23209524

RESUMO

Organic-inorganic magnetic hybrid materials (MHMs) combine a nonmagnetic and a magnetic component by means of electrostatic interactions or covalent bonds, and notable features can be achieved. Herein, we describe an application of a self-assembled material based on ferrite associated with ß-cyclodextrin (Fe-Ni/Zn/ßCD) at the nanoscale level. This MHM and pure ferrite (Fe-Ni/Zn) were used as an adsorbent system for Cr(3+) and Cr(2)O(7) (2-) ions in aqueous solutions. Prior to the adsorption studies, both ferrites were characterized in order to determine the particle size distribution, morphology and available binding sites on the surface of the materials. Microscopy analysis demonstrated that both ferrites present two different size domains, at the micro- and nanoscale level, with the latter being able to self-assemble into larger particles. Fe-Ni/Zn/ßCD presented smaller particles and a more homogeneous particle size distribution. Higher porosity for this MHM compared to Fe-Ni/Zn was observed by Brunauer-Emmett-Teller isotherms and positron-annihilation-lifetime spectroscopy. Based on the pKa values, potentiometric titrations demonstrated the presence of ßCD in the inorganic matrix, indicating that the lamellar structures verified by transmission electronic microscopy can be associated with ßCD assembled structures. Colloidal stability was inferred as a function of time at different pH values, indicating the sedimentation rate as a function of pH. Zeta potential measurements identified an amphoteric behavior for the Fe-Ni/Zn/ßCD, suggesting its better capability to remove ions (cations and anions) from aqueous solutions compared to that of Fe-Ni/Zn.

10.
Pharmaceutics ; 14(8)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35893812

RESUMO

Considered a simple and versatile technique, electrospinning has emerged as a technology for developing 3D materials for a wide range of applications [...].

11.
Biomed Pharmacother ; 146: 112249, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34972632

RESUMO

The emergence of many new viruses in recent times has resulted in a significant scientific challenge for discovering drugs and vaccines that effectively treat and prevent viral diseases. Nanotechnology has opened doors to prevent the spread of several diseases, including those caused by viruses. Polymer-hybrid nanodevices are a class of nanotechnology platforms for biomedical applications that present synergistic properties among their components, with improved performance compared to conventional forms of therapy. Considering the growing interest in this emerging field and the promising technological advantages of polymer-hybrid nanodevices, this work presents the current status of these systems in the context of prevention and treatment of viral diseases. A brief description of the different types of polymer-hybrid nanodevices highlighting some peculiar characteristics such as their composition, biodistribution, delivery of antigens, and overall immune responses in systemic tissues are discussed. Finally, the work presents the future trends for new nanotechnological hybrid materials based on polymers and perspectives for clinical use.


Assuntos
Antivirais/administração & dosagem , Nanopartículas/administração & dosagem , Nanotecnologia/tendências , Polímeros/administração & dosagem , Viroses/prevenção & controle , Animais , Antivirais/metabolismo , Sistemas de Liberação de Medicamentos , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/fisiologia , Nanopartículas/metabolismo , Polímeros/metabolismo , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia , Viroses/metabolismo
12.
Eur J Oral Sci ; 119 Suppl 1: 83-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22243232

RESUMO

Proteins in mineralized tissues provide a window to the past, and dental enamel is peculiar in being highly resistant to diagenesis and providing information on a very narrow window of time, such as the developing period; however, to date, complete proteins have not been extracted successfully from ancient teeth. In this work we tested the ability of a whole-crown micro-etch technique to obtain enamel protein samples from mature enamel of recently extracted (n = 2) and ancient (n = 2; ad 800 to 1100) third molars. Samples were analyzed using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry, and the resulting spectra were searched against the Swiss-Prot protein database using the Mascot software for protein identification. In our protocol, the separation of proteins in gel is not necessary. Successful identification of specific enamel proteins was obtained after whole-crown superficial enamel etching with 10% HCl. Most protein fragments recovered from dry teeth and mummy teeth contained amino-terminal amelogenin peptides. Only one peptide specific for the amelogenin X-isoform was identified. In conclusion, the reported techniques allowed the successful recovery of proteins specific to dental enamel from samples obtained in a very conservative manner, which may also be important in forensic and/or archeological science.


Assuntos
Proteínas do Esmalte Dentário/análise , Corrosão Dentária/métodos , Coroa do Dente/química , Amelogenina/análise , Bases de Dados de Proteínas , Proteínas do Esmalte Dentário/história , História Medieval , Humanos , Dente Molar/química , Paleodontologia/métodos , Mapeamento de Peptídeos/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Suécia
13.
ACS Appl Mater Interfaces ; 12(25): 28607-28615, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32463219

RESUMO

Herein, we present the light-induced synthesis and characterization of a La3+/spiropyran derivative complex (LaMC) and its application as a catalyst when incorporated into electrospun polycaprolactone (PCL) fibers. In addition to experimental methods, computational calculations were also essential to better understand the structure and electronic characteristics of LaMC. The LaMC complex was identified as a 10-coordinated structure with the La3+ ion coordinated by four oxygens from the phenolate and the carbonyl of the carboxyl acid group from both MC ligands and by six oxygens from three nitrate ligands. In addition, LaMC was capable of getting reversibly isomerized by UV or visible light cycling. All PCL fibers were successively obtained, and their morphologies, surface properties, and catalytic behavior were studied. Results showed that PCL/LaMC fibers were capable of catalyzing bis(2,4-dinitrophenyl)phosphate degradation efficiently. Complete hydrolysis was accomplished in only 1.5 days relative to the half-life time of 35 days for the uncatalyzed hydrolysis at pH 8.1 and 25 °C.

14.
J Am Chem Soc ; 130(26): 8426-36, 2008 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-18529008

RESUMO

The supramolecular interactions between Imipramine hydrochloride (IMI), a tricyclic antidepressant, and beta-cyclodextrin (betaCD) have been investigated by experimental techniques and theoretical calculations. The association between these molecules might be lead to a host/guest compound, in which the physical chemistry properties of the guest molecule, such as high solubility, can be decreased. These new properties acquired by the inclusion phenomena are important to develop a strategy for pharmaceutical formulation. Nuclear magnetic resonance and horizontal attenuated total reflectance provided relevant information on the complex stoichiometries and the sites of interactions between the host and guest molecules. Stoichiometries of 1:2, 1:1, and 2:1 betaCD/IMI have been detected in solution. Self-diffusion coefficient and dynamic light scattering analysis provided information on the self-aggregation of the complex. Also, isothermal titration calorimetry studies indicated the existence of equilibrium between different complexes in solution. In order to determine the preferred arrangement for the inclusion complex formed by the IMI molecule and betaCD, theoretical calculations were performed. Of all proposed supramolecular structures, the 2:1 betaCD/IMI complex was calculated to be the most energetically favorable, in both gas and aqueous phases. The calculations indicated that the intermolecular hydrogen bonds involving the hydroxyl groups of betaCD play a major role in stabilizing the supramolecular 2:1 structure, corroborating experimental findings.

15.
Int J Pharm ; 353(1-2): 160-9, 2008 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-18255241

RESUMO

In this work the complex formed between beta-cyclodextrin (betaCD) and fluoxetine (FLU) was investigated by experimental and computational methods. From Horizontal Attenuated Total Reflectance (HATR) was possible to verify a strong modification in the vibrational modes of betaCD and FLU, indicating interactions between them. The Nuclear Magnetic Resonance (NMR) experiments confirm these interactions through the change in chemical shifts in (1)H spectra, reduction in longitudinal relaxation times values, and the Nuclear Ouverhauser Effect confirm the inclusion of aromatic rings of FLU into the betaCD. The structures of the proposed inclusion compounds were optimized at PM3 semiempirical level of theory. In addition, single point calculations at the Density Functional Theory (DFT) level, using the Becke, Lee, Yang, and Parr functional and 6-31G(d,p) basis set, were used to determine the interaction energy for these structures. The DFT calculations identified the aromatic ring, which contains the CF(3) group as the most stable into the betaCD by an amount of, 11.7 kcal mol(-1), in the gas phase. Polarized continuum model, at the DFT level mentioned, was used to investigate the solvent effect, and the results corroborated the gas phase analysis. A high equilibrium constant (K approximately 6921+/-316) and the stoichiometry, 1:1, were obtained by Isothermal Titration Calorimetry (ITC) experiments.


Assuntos
Fluoxetina/química , beta-Ciclodextrinas/química , Fluoxetina/administração & dosagem , Espectroscopia de Ressonância Magnética , Refratometria , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , beta-Ciclodextrinas/administração & dosagem
16.
Int J Pharm ; 544(1): 203-212, 2018 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-29679752

RESUMO

Supramolecular structures based on cyclodextrins have been extensively used for drug delivery systems over decades. However, combining host and guest molecules in a pharmaceutical formulation is not a trivial process, being one of the majors concern the inclusion complex compatibility with other excipients presented in the final formulation. Herein, experimental and theoretical calculations were used to investigate the competition of sodium dodecyl sulfate (SDS) with atenolol (ATE) or losartan (LOS), antihypertensive drugs widely used in the treatment of hypertension. Our findings, using nuclear magnetic resonance and isothermal titrations calorimetry experiments and molecular dynamic simulations demonstrated that LOS remain included into CD cavity after excipient (SDS) addition, which was not verified for ATE ternary system, being the drug displaced by SDS molecule.


Assuntos
Anti-Hipertensivos/química , Atenolol/química , Losartan/química , Dodecilsulfato de Sódio/química , Tensoativos/química , beta-Ciclodextrinas/química , Espectroscopia de Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
17.
Peptides ; 28(11): 2199-210, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17904691

RESUMO

We report the complete sequence-specific hydrogen NMR assignments of vasoactive peptide angiotensin-(1-7) (Ang-(1-7)). Assignments of the majority of the resonances were accomplished by COSY, TOCSY, and ROESY peak coordinates at 400MHz and 600MHz. Long-side-chain amino acid spin system identification was facilitated by long-range coherence transfer experiments (TOCSY). Problems with overlapped resonance signals were solved by analysis of heteronuclear 2D experiments (HSQC and HMBC). Nuclear Overhauser effects (NOE) results were used to probe peptide conformation. We show that the inclusion of the angiotensin-(1-7) tyrosine residue is favored in inclusion complexes with beta-cyclodextrin. QM/MM simulations at the DFTB/UFF level confirm the experimental NMR findings and provide detailed structural information on these compounds in aqueous solution.


Assuntos
Angiotensina I/química , Espectroscopia de Ressonância Magnética/métodos , Fragmentos de Peptídeos/química , beta-Ciclodextrinas/química , Dicroísmo Circular , Ligação de Hidrogênio , Modelos Moleculares , Estrutura Molecular , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
18.
BioDrugs ; 20(5): 283-91, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17025375

RESUMO

BACKGROUND: Cyclodextrins are suitable drug delivery systems because of their ability to subtly modify the physical, chemical, and biological properties of guest molecules through labile interactions by formation of inclusion and/or association complexes. Plant cysteine proteinases from Caricaceae and Bromeliaceae are the subject of therapeutic interest, because of their anti-inflammatory, antitumoral, immunogenic, and wound-healing properties. METHODS: In this study, we analyzed the association between beta-cyclodextrin (betaCD) and fraction P1G10 containing the bioactive proteinases from Carica candamarcensis, and described the physicochemical nature of the solid-state self-assembled complexes by Fourier transform infrared (FTIR) spectroscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and nuclear magnetic resonance (NMR), as well as in solution by circular dichroism (CD), isothermal titration calorimetry (ITC), and amidase activity. RESULTS AND DISCUSSION: The physicochemical analyses suggest the formation of a complex between P1G10 and betaCD. Higher secondary interactions, namely hydrophobic interactions, hydrogen bonding and van der Waals forces were observed at higher P1G10 : betaCD mass ratios. These results provide evidence of the occurrence of strong solid-state supramolecular non-covalent interactions between P1G10 and betaCD. Microcalorimetric analysis demonstrates that complexation results in a favorable enthalpic contribution, as has already been described during formation of similar betaCD inclusion compounds. The amidase activity of the complex shows that the enzyme activity is not readily available at 24 hours after dissolution of the complex in aqueous buffer; the proteinase becomes biologically active by the second day and remains stable until day 16, when a gradual decrease occurs, with basal activity attained by day 29. CONCLUSION: The reported results underscore the potential for betaCDs as candidates for complexing cysteine proteinases, resulting in supramolecular arrays with sustained proteolytic activity.


Assuntos
Carica/química , Látex/química , Peptídeo Hidrolases/metabolismo , beta-Ciclodextrinas/química , Amidoidrolases/metabolismo , Calorimetria/métodos , Varredura Diferencial de Calorimetria , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios X , beta-Ciclodextrinas/metabolismo
19.
Environ Sci Pollut Res Int ; 23(21): 21475-21484, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27510160

RESUMO

The "lead line" was described by Henry Burton in 1840. Rodents are used as sentinels to monitor environmental pollution, but their teeth have not been used to determine lead. To determine whether lead deposits can be observed in the teeth of lead-exposed animals, since the gingival deposits known as "lead line" would likely have a correlate in the calcified tissue to which the gums are opposed during life. Male Wistar rats were exposed to lead in the drinking water (30 mg/L) since birth until 60 days-old. Molars and the incisors of each hemimandible were analyzed by scanning electron microscopy (SEM) on regular and backscattered electrons (BSE) mode. Elements were determined using electron dispersive spectroscopy (EDS). Clean cervical margins were observed on control teeth, as opposed to the findings of extensive deposits on lead-exposed animals, even in hemimandibles that had been exhumed after being buried for 90 days. BSE/EDS indicated that those deposits were an exogenous material compatible with lead sulfite. Presence of calcium, phosphorus, magnesium, carbon, lead, and oxygen is presented. Lead-exposed animals presented marked root resorption. The lead deposits characterized here for the first time show that the "lead line" seen in gums has a calcified tissue counterpart, that is detectable post-mortem even in animals exposed to a low dose of lead. This is likely a good method to detect undue lead exposure and will likely have wide application for pollution surveillance using sentinels.


Assuntos
Exposição Ambiental , Monitoramento Ambiental/métodos , Poluentes Ambientais/metabolismo , Chumbo/análise , Dente Molar/química , Animais , Masculino , Microscopia Eletrônica de Varredura , Dente Molar/ultraestrutura , Ratos , Ratos Wistar , Fatores de Tempo
20.
Mater Sci Eng C Mater Biol Appl ; 54: 252-61, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26046289

RESUMO

Herein, we used an electrospinning process to develop highly efficacious and hydrophobic coaxial nanofibers based on poly-cyclodextrin (polyCD) associated with poly(methacrylic acid) (PMAA) that combines polymeric and supramolecular features for modulating the release of the hydrophilic drug, propranolol hydrochloride (PROP). For this purpose, polyCD was synthesized and characterized, and its biocompatibility was assessed using fibroblast cytotoxicity tests. Moreover, the interactions between the guest PROP molecule and both polyCD and ßCD were found to be spontaneous. Subsequently, PROP was encapsulated in uniaxial and coaxial polyCD/PMAA nanofibers. A lower PROP burst effect (reduction of approximately 50%) and higher modulation were observed from the coaxial than from the uniaxial fibers. Thus, the coaxial nanofibers could potentially be a useful strategy for developing a controlled release system for hydrophilic molecules.


Assuntos
Celulose/química , Ciclodextrinas/química , Sistemas de Liberação de Medicamentos/métodos , Nanofibras/química , Ácidos Polimetacrílicos/química , Materiais Biocompatíveis/química , Células Cultivadas , Células Imobilizadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Gengiva/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão
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