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1.
Artif Life ; 30(1): 16-27, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38358121

RESUMO

In the mid-20th century, two new scientific disciplines emerged forcefully: molecular biology and information-communication theory. At the beginning, cross-fertilization was so deep that the term genetic code was universally accepted for describing the meaning of triplets of mRNA (codons) as amino acids. However, today, such synergy has not taken advantage of the vertiginous advances in the two disciplines and presents more challenges than answers. These challenges not only are of great theoretical relevance but also represent unavoidable milestones for next-generation biology: from personalized genetic therapy and diagnosis to Artificial Life to the production of biologically active proteins. Moreover, the matter is intimately connected to a paradigm shift needed in theoretical biology, pioneered a long time ago, that requires combined contributions from disciplines well beyond the biological realm. The use of information as a conceptual metaphor needs to be turned into quantitative and predictive models that can be tested empirically and integrated in a unified view. Successfully achieving these tasks requires a wide multidisciplinary approach, including Artificial Life researchers, to address such an endeavour.


Assuntos
Biologia , Código Genético
2.
Artif Life ; 26(3): 315-326, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697160

RESUMO

Self-organizing precipitation processes, such as chemical gardens forming biomimetic micro- and nanotubular forms, have the potential to show us new fundamental science to explore, quantify, and understand nonequilibrium physicochemical systems, and shed light on the conditions for life's emergence. The physics and chemistry of these phenomena, due to the assembly of material architectures under a flux of ions, and their exploitation in applications, have recently been termed chemobrionics. Advances in understanding in this area require a combination of expertise in physics, chemistry, mathematical modeling, biology, and nanoengineering, as well as in complex systems and nonlinear and materials sciences, giving rise to this new synergistic discipline of chemobrionics.


Assuntos
Biologia , Biomimética , Química , Engenharia , Pesquisa Interdisciplinar , Origem da Vida , Física , Ciência dos Materiais , Modelos Teóricos , Nanoestruturas
4.
Exp Eye Res ; 147: 128-137, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27181227

RESUMO

In this study we tried to develop a new approach to suppress inflammation and neovascularization in the alkali-injured rabbit cornea. For this reason Cyclosporine A (CsA)-loaded electrospun nanofibers were transferred onto the ocular surface injured with alkali (0.25 N NaOH). Damaged corneas were divided into the following groups: untreated, treated with CsA eye drops, treated with nanofibers drug-free and treated with CsA-loaded nanofibers. Healthy rabbit corneas served as controls. Drug-free nanofibers and CsA-loaded nanofibers were transferred onto the damaged corneal surface immediately after the injury and sutured to conjunctiva. On day five after the injury the nanofibers were removed. The animals from all groups were sacrificed on day twelve after the injury. The extent of the inflammatory reaction and corneal healing were examined macroscopically, immunohistochemically and biochemically. The central corneal thickness was measured using an ultrasonic pachymeter. When compared with untreated injured corneas, injured corneas treated with drug-free nanofibers or injured corneas treated with CsA eye drops, the number of CD3-positive cells (T lymphocytes) and the production of pro-inflammatory cytokines were strongly reduced in corneas treated with CsA-loaded nanofibers, which was associated with the significantly decreased expression of matrix metalloproteinase 9, inducible nitric oxide synthase, vascular endothelial growth factor and active caspase-3. CsA-loaded nanofibers effectively suppressed corneal inflammation and corneal neovascularization. Central corneal thickness restored to levels before injury only in corneas treated with CsA-loaded nanofibers. Corneal transparency was highly restored in these corneas. It is suggested that the beneficial effect of CsA-loaded nanofibers was associated with the continuous release of CsA from nanofibers and continuous affection of damaged cornea by CsA. The suture of nanofibers to conjunctiva and the closed eyes contributed to beneficial corneal healing. This is in contrast to CsA eye drops, which are quickly washed from the ocular surface and the contact of CsA with the damaged cornea was limited. In conclusion, the approach with CsA-loaded nanofibers could represent an effective alternative mode of therapy for corneal chemical burns.


Assuntos
Álcalis/efeitos adversos , Queimaduras Químicas/tratamento farmacológico , Lesões da Córnea/induzido quimicamente , Ciclosporina/uso terapêutico , Queimaduras Oculares/tratamento farmacológico , Imunossupressores/uso terapêutico , Animais , Caspase 3/metabolismo , Lesões da Córnea/metabolismo , Lesões da Córnea/patologia , Neovascularização da Córnea/patologia , Ciclosporina/administração & dosagem , Modelos Animais de Doenças , Queimaduras Oculares/metabolismo , Queimaduras Oculares/patologia , Feminino , Imuno-Histoquímica , Nanofibras , Coelhos , Linfócitos T/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Langmuir ; 32(19): 4800-5, 2016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27116007

RESUMO

Pattern formation in far-from-equilibrium systems is observed in several disciplines including biology, geophysics, and reaction-diffusion chemistry, comprising both living and nonliving systems. We aim to study such nonequilibrium dynamics on the laboratory scale with materials of simple composition. We present a novel system based on a 1-decanol droplet placed in a solution of alkaline decanoate. Previously, we showed the short time scale behavior of this system, which included chemotaxis and maze solving. Here we explore long time scale dynamics of the system (several hours) when open to the environment. We observe dramatic morphological changes in the droplet including long tentacular structures, and we analyze the morphology of these structures at both the macroscopic and microscopic scales across a large range of initial conditions. Such reproducible morphological changes in simple droplets open a path to the exploration of shape-based effects in larger-scale pattern-formation studies.

6.
Langmuir ; 30(40): 11937-44, 2014 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-25215439

RESUMO

The chemotactic movement of decanol droplets in aqueous solutions of sodium decanoate in response to concentration gradients of NaCl has been investigated. Key parameters of the chemotactic response, namely the induction time and the migration velocity, have been evaluated as a function of the sodium decanoate concentration and the NaCl concentration gradient. The ability of the decanol droplets to migrate in concentration gradients has been demonstrated not only in a linear chemotactic assay but also in a topologically complex environment. Additionally, the ability to reverse the direction of movement repeatedly, to carry and release a chemically reactive cargo, to select a stronger concentration gradient from two options, and to initiate chemotaxis by an external temperature stimulus have been demonstrated.


Assuntos
Ácidos Decanoicos/química , Álcoois Graxos/química , Cloreto de Sódio/química , Cinética , Microscopia , Movimento (Física) , Tensão Superficial , Temperatura , Fatores de Tempo
7.
Exp Eye Res ; 116: 312-23, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24145108

RESUMO

The purpose of this study was to investigate whether rabbit bone marrow-derived mesenchymal stem cells (MSCs) effectively decrease alkali-induced oxidative stress in the rabbit cornea. The alkali (0.15 N NaOH) was applied on the corneas of the right eyes and then rinsed with tap water. In the first group of rabbits the injured corneas remained untreated. In the second group MSCs were applied on the injured corneal surface immediately after the injury and eyelids sutured for two days. Then the sutures were removed. In the third group nanofiber scaffolds seeded with MSCs (and in the fourth group nanofibers alone) were transferred onto the corneas immediately after the injury and the eyelids sutured. Two days later the eyelid sutures were removed together with the nanofiber scaffolds. The rabbits were sacrificed on days four, ten or fifteen after the injury, and the corneas were examined immunohistochemically, morphologically, for the central corneal thickness (taken as an index of corneal hydration) using an ultrasonic pachymeter and by real-time PCR. Results show that in untreated injured corneas the expression of malondialdehyde (MDA) and nitrotyrosine (NT) (important markers of lipid peroxidation and oxidative stress) appeared in the epithelium. The antioxidant aldehyde dehydrogenase 3A1 (ALDH3A1) decreased in the corneal epithelium, particularly in superficial parts, where apoptotic cell death (detected by active caspase-3) was high. (In control corneal epithelium MDA and NT are absent and ALDH3A1 highly present in all layers of the epithelium. Cell apoptosis are sporadic). In injured untreated cornea further corneal disturbances developed: The expressions of matrix metalloproteinase 9 (MMP9) and proinflammatory cytokines, were high. At the end of experiment (on day 15) the injured untreated corneas were vascularized and numerous inflammatory cells were present in the corneal stroma. Vascular endothelial growth factor (VEGF) expression and number of macrophages were high. The results obtained in injured corneas covered with nanofiber scaffolds alone (without MSCs) or in injured corneas treated with MSCs only (transferred without scaffolds) did not significantly differ from the results found in untreated injured corneas. In contrast, in the injured corneas treated with MSCs on nanofiber scaffolds, ALDH3A1 expression remained high in the epithelium (as in the control cornea) and positive expression of the other immunohistochemical markers employed was very low (MMP9) or absent (NT, MDA, proinflammatory cytokines), also similarly as in the control cornea. Corneal neovascularization and the infiltration of the corneal stroma with inflammatory cells were significantly suppressed in the injured corneas treated with MSCs compared to the untreated injured ones. The increased central corneal thickness together with corneal opalescency appearing after alkali injury returned to normal levels over the course of ten days only in the injured corneas treated with MSCs on nanofiber scaffolds. The expression of genes for the proinflammatory cytokines corresponded with their immunohistochemical expression. In conclusion, MSCs on nanofiber scaffolds protected the formation of toxic peroxynitrite (detected by NT residues), lowered apoptotic cell death and decreased matrix metalloproteinase and pro-inflammatory cytokine production. This resulted in reduced corneal inflammation as well as neovascularization and significantly accelerated corneal healing.


Assuntos
Queimaduras Químicas/cirurgia , Córnea/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Nanofibras/uso terapêutico , Estresse Oxidativo , Alicerces Teciduais , Álcalis/toxicidade , Animais , Queimaduras Químicas/patologia , Córnea/patologia , Lesões da Córnea , Modelos Animais de Doenças , Feminino , Coelhos , Cicatrização
8.
Graefes Arch Clin Exp Ophthalmol ; 249(8): 1185-94, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21494875

RESUMO

BACKGROUND: Trehalose, a nonreducing disaccharide of glucose, is synthesized as a stress response factor when cells are exposed to stressful conditions. In the cornea, oxidative stress plays the key role in the development of acute corneal inflammatory response to UVB rays, photokeratitis. We found previously that trehalose reduced UVB-induced oxidative effects on the formation of cytotoxic peroxynitrite, apoptotic corneal epithelial cell death and changes in corneal optics. The aim of the present study was to examine whether trehalose might inhibit UVB-mediated proinflammatory cytokine and matrix metalloproteinase induction and the development of an antioxidant/pro-oxidant imbalance in the corneal epithelium, changes found previously to be strongly involved in the acute corneal UVB-induced inflammation. The expression of heat shock protein 70 as a potential biomarker for corneal UVB-induced damage was also examined. METHODS: The corneas of New Zealand white rabbits were irradiated with UVB rays, 312 nm, daily dose of 0.5 J/cm(2) for 4 days. During the irradiation, trehalose drops were applied on the right eye and buffered saline on the left eye. One day after the end of irradiations, the animals were killed and the corneas examined immunohistochemically for the expression of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), pro-oxidant xanthine oxidoreductase/xanthine oxidase, proinflammatory cytokines (interleukin-6, interleukin-8), matrix metalloproteinase-9 and heat shock protein 70. RESULTS: After buffered saline treatment during UVB irradiation, an antioxidant/pro-oxidant imbalance appeared in the corneal epithelium: The expression of antioxidant enzymes was highly reduced, whereas the expression of pro-oxidant xanthine oxidase was increased. The pronounced expression of pro-inflammatory cytokines, matrix metalloproteinase and heat shock protein 70 was found in the UVB-irradiated corneal epithelium. Trehalose application significantly suppressed all the above-mentioned UVB-induced corneal disturbances. CONCLUSIONS: Trehalose favorably influenced the oxidative damage of the cornea caused by UVB rays. Trehalose suppressed proinflammatory cytokine induction. It is suggested that suppression of proinflammatory cytokines contributed strongly to reduced matrix metalloproteinase and xanthine oxidase expression in the UVB-irradiated corneal epithelium and to the decreased development of an antioxidant/pro-oxidant imbalance. The overexpression of heat shock protein 70 found in UVB-irradiated cornea after buffered saline treatment was reduced after trehalose application.


Assuntos
Citocinas/metabolismo , Epitélio Corneano/efeitos da radiação , Proteínas de Choque Térmico HSP70/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Oxirredutases/metabolismo , Lesões Experimentais por Radiação/tratamento farmacológico , Trealose/farmacologia , Animais , Antioxidantes , Biomarcadores/metabolismo , Epitélio Corneano/enzimologia , Feminino , Processamento de Imagem Assistida por Computador , Técnicas Imunoenzimáticas , Oxidantes , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Lesões Experimentais por Radiação/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Raios Ultravioleta/efeitos adversos
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 250: 119387, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33422883

RESUMO

The presented study is devoted to the investigation of the micellization-induced liquid-liquid fluctuations in sodium decanoate (NaD) aqueous solutions, based on the vibrational spectroscopic study of NaD and the determination of critical micelle concentration (CMC) of this system. At the same time, we focused on monitoring the effect of the addition of decanol to this system and changing its basic parameters from the point of view of CMC. CMC is an important parameter from a practical point of view and a characteristic feature of each micelle-forming compound. Upon analyzing the spectroscopic data we focus our attention mainly on the intensity and band position variations of both the symmetrical and antisymmetrical vibrational modes of CH2 groups situated in the high-frequency part of the spectrum. The study used normal (non-enhanced) Raman spectroscopy with excitation wavelength 785 nm, surface-enhanced Raman spectroscopy (SERS) on large-scaled gold-coated SERS-active substrates and infrared spectral measurements. The results of spectroscopic measurements were supported by tensiometry and potentiometry.

10.
Exp Eye Res ; 90(5): 583-90, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20153319

RESUMO

The aim of this study was to compare the presence and activity of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9 and 13 in human melted and cadaverous corneas. Twelve melted corneal specimens from three patients with rheumatoid arthritis, one patient with ocular cicatricial pemphigoid and one patient with melting attributed to spastic entropion and ten control corneal buttons were used. The presence of MMPs was detected using indirect enzyme immunohistochemistry. The active forms of MMP-2 and -9 and MMP-3 and -7 were examined by gelatin and casein zymography, respectively. The concentrations of active MMP-1 and -3 were measured using activity assays. Increased immunostaining intensity for MMP-1 and -9 was seen in the corneal epithelium and the anterior stroma of all, and for MMP-2, -3, -7 and -8 of almost all, melted corneas compared to the negative or slightly positive staining of the controls. The posterior stroma showed the presence of MMP-1, -2, -3 and -9 in almost all and of MMP-7 and -8 in half of all melted specimens. A markedly higher level of active MMP-2 was detected in six and active MMP-9 in all of eleven pathologic specimens compared to control specimens, using gelatin zymography. The proenzymes of MMP-3 and -7 and the MMP-7 intermediate cleavage product were detected only in melted corneas using casein zymography. Significantly increased MMP-1 and -3 activity was also found in the melted corneas using activity assays. The markedly increased immunostaining for MMP-1, -2, -3, -7, -8 and -9 as well as the elevated levels of the active forms of MMP-1, -2, -3 and -9 in melted corneal specimens from patients with various diagnoses suggest that although different stimuli may trigger the pathways that lead to the destruction of the extracellular matrix, these enzymes could play a subsequent role in this process.


Assuntos
Doenças da Córnea/enzimologia , Metaloproteinases da Matriz/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Doenças da Córnea/cirurgia , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Técnicas Imunoenzimáticas , Ceratoplastia Penetrante , Masculino , Pessoa de Meia-Idade , Penfigoide Mucomembranoso Benigno/complicações , Recidiva , Doadores de Tecidos , Adulto Jovem
11.
Graefes Arch Clin Exp Ophthalmol ; 248(12): 1749-56, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20596718

RESUMO

PURPOSE: Normal corneal hydration is necessary for the maintenance of corneal transparency. Damage of the corneal epithelium or endothelium by various external influences disturbs the mechanism by which the cornea maintains normal hydration and transparency. The cornea swells, and the corneal thickness increases, resulting in increased scatter and the development of corneal opacity. The transmission of light across the cornea is changed. The purpose of this study is to investigate spectrophotometrically the corneal light transmission under the influence of the various factors affecting the cornea. METHODS: We developed a spectrophotometric method to measure the light transmission across the cornea under the influence of various factors affecting the cornea, such as treatment with 0.9% NaCl, saline, or phosphate buffered saline (PBS), solutions employed as placebo eye drops (negative controls) in experimental studies, agents toxic to the cornea, such as diluted acids or alkalis. The method distinguishes between changes in corneal light transmission caused by altered corneal thickness (the level of hydration) and changes resulting from other corneal disturbances which in turn affect corneal light transmission. RESULTS: The results obtained show that the corneal light transmission is decreased following the application of toxic substances on the corneal surface. This decrease is highly dependent on the severity of the corneal injury evoked by individual noxes, and the resulting changes in corneal hydration and transparency. CONCLUSIONS: The influence of various influences applied to the cornea, manifested as changes in corneal light transmission, can be measured using our spectrophotometric method with a high degree of sensitivity.


Assuntos
Córnea/efeitos dos fármacos , Córnea/efeitos da radiação , Ácido Clorídrico/toxicidade , Luz , Hidróxido de Sódio/toxicidade , Animais , Edema da Córnea/induzido quimicamente , Coelhos , Espectrofotometria
12.
Oxid Med Cell Longev ; 2020: 7435260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655773

RESUMO

Corneal alkali burns are potentially blinding injuries. Alkali induces oxidative stress in corneas followed by excessive corneal inflammation, neovascularization, and untransparent scar formation. Molecular hydrogen (H2), a potent reactive oxygen species (ROS) scavenger, suppresses oxidative stress and enables corneal healing when applied on the corneal surface. The purpose of this study was to examine whether the H2 pretreatment of healthy corneas evokes a protective effect against corneal alkali-induced oxidative stress. Rabbit eyes were pretreated with a H2 solution or buffer solution, by drops onto the ocular surface, and the corneas were then burned with 0.25 M NaOH. The results obtained with immunohistochemistry and pachymetry showed that in the corneas of H2-pretreated eyes, slight oxidative stress appeared followed by an increased expression of antioxidant enzymes. When these corneas were postburned with alkali, the alkali-induced oxidative stress was suppressed. This was in contrast to postburned buffer-pretreated corneas, where the oxidative stress was strong. These corneas healed with scar formation and neovascularization, whereas corneas of H2-pretreated eyes healed with restoration of transparency in the majority of cases. Corneal neovascularization was strongly suppressed. Our results suggest that the corneal alkali-induced oxidative stress was reduced via the increased antioxidant capacity of corneal cells against reactive oxygen species (ROS). It is further suggested that the ability of H2 to induce the increase in antioxidant cell capacity is important for eye protection against various diseases or external influences associated with ROS production.


Assuntos
Álcalis/toxicidade , Antioxidantes/metabolismo , Queimaduras Químicas/tratamento farmacológico , Córnea/metabolismo , Queimaduras Oculares/tratamento farmacológico , Hidrogênio/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Animais , Queimaduras Químicas/metabolismo , Queimaduras Químicas/patologia , Córnea/irrigação sanguínea , Córnea/efeitos dos fármacos , Córnea/patologia , Neovascularização da Córnea/prevenção & controle , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/metabolismo , Queimaduras Oculares/patologia , Feminino , Hidrogênio/farmacologia , Coelhos , Espécies Reativas de Oxigênio/metabolismo , Cicatrização/efeitos dos fármacos
13.
Photochem Photobiol ; 85(3): 794-800, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19076313

RESUMO

The aim of the present paper was to examine the irradiation effect of two doses of UVA rays (365 nm) on the rabbit cornea and lens. Corneas of anesthetized adult albino rabbits were irradiated with UVA rays for 5 days (daily dose 1.01 J cm(-2) in one group of rabbits and daily dose 2.02 J cm(-2) in the second group of animals). The third day after the last irradiation, the rabbits were killed, and their eyes were employed for spectrophotometrical, biochemical and immunohistochemical investigations. Normal eyes served as controls. Absorption spectra of the whole corneal centers were recorded over the UV-VIS (visible) spectral range. Levels of antioxidant and prooxidant enzymes, nitric oxide synthases and nitric oxide (indirectly measured as nitrate concentration) were investigated in the cornea. Malondialdehyde, a byproduct of lipid peroxidation, was examined in the cornea and lens. The results show that the staining for endothelial nitric oxide synthase was more pronounced in corneas irradiated with the higher UVA dose. Otherwise, UVA rays at either dose did not significantly change corneal light absorption properties and did not cause statistically significant metabolic changes in the cornea or lens. In conclusion, UVA rays at the employed doses did not evoke harmful effects in the cornea or lens.


Assuntos
Córnea/efeitos da radiação , Cristalino/efeitos da radiação , Raios Ultravioleta , Animais , Relação Dose-Resposta à Radiação , Coelhos
14.
Histol Histopathol ; 34(6): 611-618, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30623968

RESUMO

Trehalose, a disaccharide of glucose, is a naturally occurring nontoxic and nonreducing bioactive sugar. Trehalose is synthetized by many organisms when cells are exposed to stressful conditions, including dehydration, heat, oxidation, hypoxia or even anoxia. Although trehalose is not synthesized by mammalian cells, it has recently been demonstrated to have a number of important properties that indicate its utility in humans. Trehalose enables wound healing by protecting cells, especially cell membranes, from oxidative injury and dessication. When the injured cornea is treated with trehalose, corneal inflammation, scar formation and corneal neovascularization are suppressed. In dry eye disease, trehalose decreased cell apoptosis and reduced oxidative, inflammatory and proteolytic activity at the ocular surface. In UVB irradiated cornea, trehalose suppressed photodamage evoked by UVB rays. It decreased the intracorneal inflammation and reduced corneal neovascularization. Trehalose prevented postoperative fibrous scar formation after ocular surgery, such as glaucoma filtration surgery. The non-toxicity of trehalose allows its administration in humans for extended periods and enables its use in various disease states.


Assuntos
Apoptose , Córnea/efeitos dos fármacos , Estresse Oxidativo , Trealose/farmacologia , Cicatrização , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Ensaios Clínicos como Assunto , Córnea/efeitos da radiação , Modelos Animais de Doenças , Síndromes do Olho Seco/tratamento farmacológico , Humanos , Oftalmologia , Coelhos , Trealose/química , Raios Ultravioleta
15.
Free Radic Res ; 53(3): 237-247, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30773939

RESUMO

Oxidative stress initiates, accompanies and contributes to the development of several human diseases and injuries, including ocular diseases. Reactive oxygen species (ROS) can generate oxidative stress via excessive ROS production and/or decreased physiologically occurring antioxidants. To replace these weakened antioxidants, substances with effective antioxidant properties are needed in order to suppress oxidative stress and enable healing. Molecular hydrogen (H2) is very suitable for this purpose due to its unique properties. H2 is the only antioxidant that crosses the blood-brain and blood-ocular barriers. It quickly penetrates through tissue due to its small molecular size and effectively removes ROS, mainly hydroxyl radicals and peroxynitrite. Apart from its antioxidant effects, H2 also displays anti-inflammatory, antiapoptotic, cytoprotective and mitohormetic properties. A significant advantage of H2 is its nontoxicity, even when applied at high concentrations. In this review, we present the results of studies utilising H2 in the treatment of ocular diseases involving oxidative stress. These results, obtained in experimental animals as well as in human clinical studies, show that the suppression of oxidative stress by H2 treatment leads to the prevention or improvement of ocular diseases. In severe degenerative diseases, H2 slows disease progression.


Assuntos
Oftalmopatias/tratamento farmacológico , Hidrogênio/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Oftalmopatias/patologia , Humanos , Hidrogênio/farmacologia
16.
J Pharm Sci ; 108(6): 2136-2142, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30721711

RESUMO

Many new therapeutic candidates and active pharmaceutical ingredients (APIs) are poorly soluble in an aqueous environment, resulting in their reduced bioavailability. A promising way of enhancing the release of an API and, thus, its bioavailability seems to be the use of liquid oil marbles (LOMs). An LOM system behaves as a solid form but consists of an oil droplet in which an already dissolved API is encapsulated by a powder. This study aims to optimize the oil/powder combination for the development of such systems. LOMs were successfully prepared for 15 oil/powder combinations, and the following properties were investigated: particle mass fraction, dissolution time, and mechanical stability. Furthermore, the release of API from both LOMs and LOMs encapsulated into gelatine capsules was studied.


Assuntos
Portadores de Fármacos/química , Composição de Medicamentos/métodos , Óleos/química , Água/química , Disponibilidade Biológica , Cápsulas , Química Farmacêutica , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Gelatina/química , Pós , Solubilidade , Fatores de Tempo
17.
Oxid Med Cell Longev ; 2019: 1857086, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31641422

RESUMO

Our previous research revealed that trehalose, a nonreducing disaccharide of glucose and an important stress responsive factor, proved to have anti-inflammatory, antiapoptotic, and particularly antioxidant properties in UVB-irradiated corneas. Trehalose reduced oxidative stress in corneas induced by UVB irradiation, by means of a decrease in the antioxidant/prooxidant imbalance in the corneal epithelium. In this study, we demonstrate that trehalose of 3% or 6% concentration in eye drops directly decreases oxidative stress in UVB-irradiated corneas, by removing the excessive amount of reactive oxygen species (ROS). Trehalose drops applied on corneas during UVB irradiation once daily for four days resulted in a reduction or even absence of the oxidative stress, DNA damage, and peroxynitrite formation (detected by nitrotyrosine residues), seen in buffer-treated corneas. Furthermore, trehalose treatment applied curatively after repeated irradiation for the subsequent fourteen days led to the renewal of corneal transparency and significant suppression or even absence of neovascularization. This was in contrast to buffer-treated irradiated corneas, where the intracorneal inflammation was developed and the untransparent corneas were vascularized. In conclusion, the treatment of UVB-irradiated corneas with trehalose eye drops removed the excessive amount of ROS in the corneal epithelium, leading to the suppression of oxidative stress and favorable corneal healing. The 6% trehalose showed a higher intensive antioxidant effect.


Assuntos
Córnea/patologia , Córnea/efeitos da radiação , Lesões da Córnea/tratamento farmacológico , Estresse Oxidativo , Trealose/uso terapêutico , Raios Ultravioleta , Cicatrização/efeitos dos fármacos , Animais , Córnea/efeitos dos fármacos , Dano ao DNA , Feminino , Interleucina-1beta/metabolismo , Queratinas/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Coelhos , Reepitelização/efeitos dos fármacos , Reepitelização/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Trealose/farmacologia , Tirosina/análogos & derivados , Tirosina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos da radiação
18.
Stem Cells Int ; 2019: 5909524, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30805009

RESUMO

The wide use of human multipotent mesenchymal stromal cells (MSCs) in clinical trials requires a full-scale safety and identity evaluation of the cellular product and subsequent transportation between research/medical centres. This necessitates the prolonged hypothermic storage of cells prior to application. The development of new, nontoxic, and efficient media, providing high viability and well-preserved therapeutic properties of MSCs during hypothermic storage, is highly relevant for a successful clinical outcome. In this study, a simple and effective trehalose-based solution was developed for the hypothermic storage of human bone marrow MSC suspensions for further clinical applications. Human bone marrow MSCs were stored at 4°C for 24, 48, and 72 hrs in the developed buffered trehalose solution and compared to several research and clinical grade media: Plasma-Lyte® 148, HypoThermosol® FRS, and Ringer's solution. After the storage, the preservation of viability, identity, and therapeutically associated properties of MSCs were assessed. The hypothermic storage of MSCs in the new buffered trehalose solution provided significantly higher MSC recovery rates and ability of cells for attachment and further proliferation, compared to Plasma-Lyte® 148 and Ringer's solution, and was comparable to research-grade HypoThermosol® FRS. There were no differences in the immunophenotype, osteogenic, and adipogenic differentiation and the immunomodulatory properties of MSCs after 72 hrs of cold storage in these solutions. The obtained results together with the confirmed therapeutic properties of trehalose previously described provide sufficient evidence that the developed trehalose medium can be applied as a low-cost and efficient solution for the hypothermic storage of MSC suspensions, with a high potential for translation into clinical practice.

19.
Biophys Chem ; 132(1): 9-17, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17988785

RESUMO

Starving cells of Dictyostelium discoideum undergo a developmental cycle where cAMP is autocatalytically produced and relayed from cell to cell, resulting in the propagation of excitation waves over a spatially extended population. Later on the homogeneous cell layer transforms into a pattern of cell streams directed perpendicular to the cAMP waves. Here we chemically influence aggregation competent cells by isopropylidenadenosin (IPA), an adenosine derivative. It can be assumed, that IPA acts via specific adenosine binding sites localized in the cellular membrane. We find, however, that pattern formation and cellular aggregation under the influence of IPA differ considerably compared to experiments with adenosine. In particular, our observations point towards an inhibitory effect on adenylate cyclase (ACA), the key enzyme in the autocatalytic production process of cAMP inside the cell. Our results suggest the existence of a direct coupling (via intracellular affection) or indirect coupling (via inhibition of cAMP binding) of the specific adenosine receptors to the regulatory circuit that controls cyclic intra- and extracellular cAMP concentration.


Assuntos
Adenosina/análogos & derivados , Inibidores de Adenilil Ciclases , Dictyostelium/efeitos dos fármacos , Adenosina/farmacologia , Animais , Agregação Celular/efeitos dos fármacos , AMP Cíclico/metabolismo , Dictyostelium/citologia , Dictyostelium/enzimologia
20.
Artif Life ; 24(1): 71-79, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29369709

RESUMO

Protocells are objects that mimic one or several functions of biological cells and may be embodied as solid particles, lipid vesicles, or droplets. Our work is based on using decanol droplets in an aqueous solution of sodium decanoate in the presence of salt. A decanol droplet under such conditions bears many qualitative similarities with living cells, such as the ability to move chemotactically, divide and fuse, or change its shape. This article focuses on the description of a shape-changing process induced by the evaporation of water from the decanoate solution. Under these conditions, the droplets perform complex shape changes, whereby the originally round decanol droplets grow into branching patterns and mimic the growth of appendages in bacteria or axon growth of neuronal cells. We report two outcomes: (i) the morphological changes are reversible, and (ii) multiple protocells avoid contact between each other during the morphological transformation. The importance of these morphological changes in the context of artificial life are discussed.


Assuntos
Células Artificiais/química , Ácidos Decanoicos/química , Álcoois Graxos/química , Gotículas Lipídicas/química , Biologia Sintética , Água/química
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