Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Med Res Rev ; 43(4): 717-774, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36757198

RESUMEN

Photodynamic therapy is an alternative treatment mainly for cancer but also for bacterial infections. This treatment dates back to 1900 when a German medical school graduate Oscar Raab found a photodynamic effect while doing research for his doctoral dissertation with Professor Hermann von Tappeiner. Unexpectedly, Raab revealed that the toxicity of acridine on paramecium depends on the intensity of light in his laboratory. Photodynamic therapy is therefore based on the administration of a photosensitizer with subsequent light irradiation within the absorption maxima of this substance followed by reactive oxygen species formation and finally cell death. Although this treatment is not a novelty, there is an endeavor for various modifications to the therapy. For example, selectivity and efficiency of the photosensitizer, as well as irradiation with various types of light sources are still being modified to improve final results of the photodynamic therapy. The main aim of this review is to summarize anticancer and antibacterial modifications, namely various compounds, approaches, and techniques, to enhance the effectiveness of photodynamic therapy.


Asunto(s)
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Neoplasias/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Muerte Celular , Especies Reactivas de Oxígeno/metabolismo
2.
Brain ; 145(5): 1624-1631, 2022 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-35148383

RESUMEN

The recent description of biallelic DNAJC30 variants in Leber hereditary optic neuropathy (LHON) and Leigh syndrome challenged the longstanding assumption for LHON to be exclusively maternally inherited and broadened the genetic spectrum of Leigh syndrome, the most frequent paediatric mitochondrial disease. Herein, we characterize 28 so far unreported individuals from 26 families carrying a homozygous DNAJC30 p.Tyr51Cys founder variant, 24 manifesting with LHON, two manifesting with Leigh syndrome, and two remaining asymptomatic. This collection of unreported variant carriers confirms sex-dependent incomplete penetrance of the homozygous variant given a significant male predominance of disease and the report of asymptomatic homozygous variant carriers. The autosomal recessive LHON patients demonstrate an earlier age of disease onset and a higher rate of idebenone-treated and spontaneous recovery of vision in comparison to reported figures for maternally inherited disease. Moreover, the report of two additional patients with childhood- or adult-onset Leigh syndrome further evidences the association of DNAJC30 with Leigh syndrome, previously only reported in a single childhood-onset case.


Asunto(s)
Enfermedad de Leigh , Atrofia Óptica Hereditaria de Leber , Adulto , Niño , ADN Mitocondrial/genética , Femenino , Humanos , Enfermedad de Leigh/genética , Masculino , Mutación/genética , Atrofias Ópticas Hereditarias , Atrofia Óptica Hereditaria de Leber/genética
3.
Altern Lab Anim ; 51(4): 224-248, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37377062

RESUMEN

Animal testing has been prohibited for the safety assessment of cosmetic ingredients or finished products. Thus, alternative non-animal methods, followed by confirmatory clinical studies on human volunteers, should be used as the sole legally acceptable approach within the EU. The safety assessment of cosmetic products requires the involvement of multiple scientific disciplines, including analytical chemistry and biomedicine, as well as in chemico, in vitro and in silico toxicology. Recent data suggest that fragrance components may exert multiple adverse biological effects, e.g. cytotoxicity, skin sensitisation, (photo)genotoxicity, mutagenicity, reprotoxicity and endocrine disruption. Therefore, a pilot study was conducted with selected samples of fragrance-based products, such as deodorant, eau de toilette and eau de parfum, with the aim of integrating results from a number of alternative non-animal methods suitable for the detection of the following toxicological endpoints: cytotoxicity (with 3T3 Balb/c fibroblasts); skin sensitisation potential (in chemico method, DPRA); skin sensitisation potential (LuSens in vitro method, based on human keratinocytes); genotoxicity potential (in vitro Comet assay with 3T3 Balb/c cells); and endocrine disruption (in vitro YES/YAS assay). The presence of twenty-four specific known allergens in the products was determined by using GC-MS/MS. The strategies for estimation of the NOAEL of a mixture of allergens, which were proposed by the Scientific Committee on Consumer Products in their 'Opinion on Tea tree oil' document and by the Norwegian Food Safety Authority in their 'Risk Profile of Tea tree oil' report, were used as models for the NOAEL estimation of the mixtures of allergens that were identified in the individual samples tested in this study.


Asunto(s)
Cosméticos , Perfumes , Aceite de Árbol de Té , Animales , Humanos , Perfumes/análisis , Espectrometría de Masas en Tándem , Cromatografía de Gases y Espectrometría de Masas , Proyectos Piloto , Cosméticos/toxicidad , Alérgenos/toxicidad , Alérgenos/análisis
4.
Int J Mol Sci ; 24(12)2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37373060

RESUMEN

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.


Asunto(s)
Rayos Ultravioleta , Ácido Urocánico , Humanos , Rayos Ultravioleta/efectos adversos , Ácido Urocánico/farmacología , Piel/metabolismo , Protectores Solares/farmacología
5.
Bioorg Chem ; 119: 105570, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34953323

RESUMEN

A small series of N-aryl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-amines was synthesized from easily accessible 1-phenyl-1H-pyrazol-3-ol via 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine and 7-iodo-4-methyl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine intermediates and their subsequent use in palladium catalyzed Buchwald-Hartwig cross-coupling reaction with various anilines. Majority of the compounds were not significantly cytotoxic to melanoma G361 cells in the dark up to 10 µM concentration, but their activity could be increased by irradiation with visible blue light (414 nm). The most active compound 10 possessed EC50 values of 3.5, 1.6 and 0.9 µM in cells irradiated with 1, 5 and 10 J/cm2, respectively. The treatment caused generation of reactive oxygen species in cells and extensive DNA damage, documented by the comet assay and by detection of phosphorylated histone H2A.X, followed by apoptotic cell death. Our results suggest that N-aryl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-amines could serve as a potential source of photosensitizing compounds with anticancer activities.


Asunto(s)
Antineoplásicos/farmacología , Melanoma/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Luz , Melanoma/metabolismo , Melanoma/patología , Estructura Molecular , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Relación Estructura-Actividad , Células Tumorales Cultivadas
6.
Int J Mol Sci ; 23(7)2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35408948

RESUMEN

Clinically approved photodynamic therapy (PDT) is a minimally invasive treatment procedure that uses three key components: photosensitization, a light source, and tissue oxygen. However, the photodynamic effect is limited by both the photophysical properties of photosensitizers as well as their low selectivity, leading to damage to adjacent normal tissue and/or inadequate biodistribution. Nanoparticles (NPs) represent a new option for PDT that can overcome most of the limitations of conventional photosensitizers and can also promote photosensitizer accumulation in target cells through enhanced permeation and retention effects. In this in vitro study, the photodynamic effect of TPP photosensitizers embedded in polystyrene nanoparticles was observed on the non-tumor NIH3T3 cell line and HeLa and G361 tumor cell lines. The efficacy was evaluated by viability assay, while reactive oxygen species production, changes in membrane mitochondrial potential, and morphological changes before and after treatment were imaged by atomic force microscopy. The tested nanoparticles with embedded TPP were found to become cytotoxic only after activation by blue light (414 nm) due to the production of reactive oxygen species. The photodynamic effect observed in this evaluation was significantly higher in both tumor lines than the effect observed in the non-tumor line, and the resulting phototoxicity depended on the concentration of photosensitizer and irradiation time.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Porfirinas , Animales , Línea Celular Tumoral , Humanos , Ratones , Células 3T3 NIH , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/metabolismo , Porfirinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Distribución Tisular
7.
Invest New Drugs ; 39(1): 89-97, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32833137

RESUMEN

Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS2) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS4). Fluorescence microscopy revealed their different localizations within the cells. ZnTPPS4 seems to be mostly limited to the cytosol and lysosomes, whereas ZnPcS2 is most likely predominantly attached to membrane structures, including plasmalemma and the mitochondrial membrane. Phototoxicity assays of PDT-treated cells carried out under different partial pressures of oxygen showed dose-dependent responses. Interestingly, ZnPcS2 was also photodynamically effective at a minimal level of oxygen, under a nitrogen atmosphere. On the other hand, hyperbaric oxygenation did not lead to a higher PDT efficiency of either photosensitizer. Although both photosensitizers can induce a significant drop in mitochondrial membrane potential, ZnPcS2 has a markedly higher effect on mitochondrial respiration that was completely blocked after two short light cycles. In conclusion, our observations suggest that PDT can be effective even in hypoxic conditions if a suitable sensitizer is chosen, such as ZnPcS2, which can inhibit mitochondrial respiration.


Asunto(s)
Indoles/farmacología , Metaloporfirinas/farmacología , Compuestos Organometálicos/farmacología , Oxígeno/farmacología , Fotoquimioterapia/métodos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Indoles/administración & dosificación , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Metaloporfirinas/administración & dosificación , Mitocondrias/efectos de los fármacos , Compuestos Organometálicos/administración & dosificación , Oxígeno/administración & dosificación , Presión Parcial , Fármacos Fotosensibilizantes/farmacología , Oxígeno Singlete/análisis
8.
J Sleep Res ; 30(2): e13051, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32524698

RESUMEN

Leber hereditary optic neuropathy and Dominant optic atrophy are associated with a selective loss of retinal ganglion cells (RGC). A subtype of RGC is responsible for light-dependent physiological processes. The aim of our study was to evaluate both subjective and objective sleep parameters in 36 (18 males; mean age 33.8 ± 16.7) symptomatic/asymptomatic subjects with Leber hereditary optic neuropathy and dominant optic atrophy. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS) and nocturnal polysomnography were used to assess sleep disturbances and sleep quality. The questionnaires indicated significantly worse sleep quality (PSQI > 5; average 7.7 ± 3.8) in 21 (70%) and excessive daytime sleepiness (ESS > 10; average 6.3 ± 5.8) in six (20%) individuals. Nocturnal polysomnography has not revealed any significant changes of sleep structure. Rapid eye movement (REM) sleep without atonia was observed in two patients with Leber hereditary optic neuropathy. Obstructive sleep apnea was noted in eight cases. No correlation between subjective and polysomnographic data and no differences between symptomatic and asymptomatic groups were observed. None of the subjects fulfilled criteria for a circadian sleep disorder. In both symptomatic and asymptomatic individuals, a subjective decrease of the quality of sleep and wakefulness was noted without any correlation on polysomnography.


Asunto(s)
Atrofia Óptica Hereditaria de Leber/patología , Enfermedades del Nervio Óptico/complicaciones , Polisomnografía/métodos , Adolescente , Adulto , Niño , ADN Mitocondrial/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
9.
BMC Pediatr ; 20(1): 41, 2020 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-31996177

RESUMEN

BACKGROUND: Maternally inherited complex I deficiencies due to mutations in MT-ND genes represent a heterogeneous group of multisystem mitochondrial disorders (MD) with a unfavourable prognosis. The aim of the study was to characterize the impact of the mutations in MT-ND genes, including the novel m.13091 T > C variant, on the course of the disease, and to analyse the activities of respiratory chain complexes, the amount of protein subunits, and the mitochondrial energy-generating system (MEGS) in available muscle biopsies and cultivated fibroblasts. METHODS: The respiratory chain complex activities were measured by spectrophotometry, MEGS were analysed using radiolabelled substrates, and protein amount by SDS-PAGE or BN-PAGE in muscle or fibroblasts. RESULTS: In our cohort of 106 unrelated families carrying different mtDNA mutations, we found heteroplasmic mutations in the genes MT-ND1, MT-ND3, and MT-ND5, including the novel variant m.13091 T > C, in 13 patients with MD from 12 families. First symptoms developed between early childhood and adolescence and progressed to multisystem disease with a phenotype of Leigh or MELAS syndromes. MRI revealed bilateral symmetrical involvement of deep grey matter typical of Leigh syndrome in 6 children, cortical/white matter stroke-like lesions suggesting MELAS syndrome in 3 patients, and a combination of cortico-subcortical lesions and grey matter involvement in 4 patients. MEGS indicated mitochondrial disturbances in all available muscle samples, as well as a significantly decreased oxidation of [1-14C] pyruvate in fibroblasts. Spectrophotometric analyses revealed a low activity of complex I and/or complex I + III in all muscle samples except one, but the activities in fibroblasts were mostly normal. No correlation was found between complex I activities and mtDNA mutation load, but higher levels of heteroplasmy were generally found in more severely affected patients. CONCLUSIONS: Maternally inherited complex I deficiencies were found in 11% of families with mitochondrial diseases in our region. Six patients manifested with Leigh, three with MELAS. The remaining four patients presented with an overlap between these two syndromes. MEGS, especially the oxidation of [1-14C] pyruvate in fibroblasts might serve as a sensitive indicator of functional impairment due to MT-ND mutations. Early onset of the disease and higher level of mtDNA heteroplasmy were associated with a worse prognosis.


Asunto(s)
ADN Mitocondrial , Complejo I de Transporte de Electrón/deficiencia , Enfermedad de Leigh/genética , Síndrome MELAS/genética , Enfermedades Mitocondriales/genética , Mutación , Adolescente , Adulto , Edad de Inicio , Biopsia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Células Cultivadas , Niño , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Músculo Esquelético/metabolismo
10.
Regul Toxicol Pharmacol ; 115: 104685, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32454236

RESUMEN

The aim of the study was toxicological testing of an innovative and efficient antimicrobial agent based on photoactive phthalocyanine (Pc) derivative. A promising Aluminium phthalocyanine (AlPc) with efficient and stable antimicrobial effects was subjected to a battery of toxicological tests to avoid local and systemic toxicity hazard. In compliance with the current European legislation restricting the use of experimental animals, the methods comprised exclusively in vitro procedures based on cellular and tissue models of human origin or mimicking human tissues. The battery of toxicological tests to identify local toxicity included skin corrosion/irritation, eye irritation, and phototoxicity. The basic systemic toxicity tests included acute toxicity, skin sensitization, genotoxicity, and endocrine disruption. The results showed that AlPc induced skin and eye irritation, exhibited borderline sensitization potential and mutagenic potential in one test strain of the Ames test, which was not confirmed in the chromosome aberration test. The AlPc was found to be phototoxic. The results from the cytotoxicity test designed for acute oral toxicity estimation were not conclusive, the acute toxicity potential has to be determined by conventional tests in vivo. Regarding endocrine disruption, no agonistic activity of the AlPc on human estrogen receptor α, nor human androgen receptor was observed. The skin penetration/absorption test revealed that the AlPc has not penetrated into the dermis and receptor fluid, confirming no risk of systemic exposure via the bloodstream.


Asunto(s)
Antiinfecciosos/toxicidad , Indoles/toxicidad , Irritantes/toxicidad , Animales , Antiinfecciosos/farmacocinética , Células Cultivadas , Embrión de Pollo , Membrana Corioalantoides/irrigación sanguínea , Membrana Corioalantoides/efectos de los fármacos , Daño del ADN , Receptor alfa de Estrógeno/metabolismo , Ojo/efectos de los fármacos , Humanos , Indoles/farmacocinética , Irritantes/farmacocinética , Isoindoles , Linfocitos/efectos de los fármacos , Ratones Endogámicos BALB C , Procesos Fotoquímicos , Receptores Androgénicos/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Absorción Cutánea , Porcinos , Pruebas de Toxicidad
11.
Arterioscler Thromb Vasc Biol ; 38(8): 1859-1867, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29903730

RESUMEN

Objective- The leukocyte heme-enzyme MPO (myeloperoxidase) exerts proinflammatory effects on the vascular system primarily linked to its catalytic properties. Recent studies have shown that MPO, depending on its cationic charge, mediates neutrophil recruitment and activation. Here, we further investigated MPO's extracatalytic properties and its effect on endothelial glycocalyx (EG) integrity. Approach and Results- In vivo staining of murine cremaster muscle vessels with Alcian Blue 8GX provided evidence of an MPO-dependent decrease in anionic charge of the EG. MPO binding to the glycocalyx was further characterized using Chinese hamster ovary cells and its glycosaminoglycan mutants-pgsA-745 (mutant Chinese hamster ovary cells lacking heparan sulfate and chondroitin sulfate glycosaminoglycan) and pgsD-677 (mutant Chinese hamster ovary cells lacking heparan sulfate glycosaminoglycan), which revealed heparan sulfate as the main mediator of MPO binding. Further, EG integrity was assessed in terms of thickness using intravital microscopy of murine cremaster muscle. A significant reduction in EG thickness was observed on infusion of catalytically active MPO, as well as mutant inactive MPO and cationic polymer polylysine. Similar effects were also observed in wild-type mice after a local inflammatory stimulus but not in MPO-knockout mice. The reduction in EG thickness was reversed after removal of vessel-bound MPO, suggesting a possible physical collapse of the EG. Last, experiments with in vivo neutrophil depletion revealed that MPO also induced neutrophil-mediated shedding of the EG core protein, Sdc1 (syndecan-1). Conclusions- These findings provide evidence that MPO, via ionic interaction with heparan sulfate side chains, can cause neutrophil-dependent Sdc1 shedding and collapse of the EG structure.


Asunto(s)
Músculos Abdominales/irrigación sanguínea , Células Endoteliales/efectos de los fármacos , Glicocálix/efectos de los fármacos , Peroxidasa/metabolismo , Animales , Células CHO , Cationes , Cricetulus , Células Endoteliales/metabolismo , Células Endoteliales/patología , Glicocálix/metabolismo , Glicocálix/patología , Proteoglicanos de Heparán Sulfato/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Activación Neutrófila , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Peroxidasa/deficiencia , Peroxidasa/genética , Peroxidasa/farmacología , Unión Proteica , Sindecano-1/metabolismo
12.
Neuro Endocrinol Lett ; 39(6): 441-453, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30796794

RESUMEN

OBJECTIVES: The purpose of this study was to determine toxicity of wastewater from hospitals in the Czech Republic using traditional and alternative toxicological methods. The pilot study comprised weekly dynamics of sewage ecotoxicity of treated wastewater from one hospital in two different seasons. A detailed investigation of wastewater ecotoxicity, genotoxicity and reprotoxicity followed in five different hospitals. METHODS: The seven following bioassays were used in this study: algal growth inhibition test (ISO 8692), Vibrio fischeri test (ISO 11348-2), Daphnia magna acute toxicity test (ISO 6341), Allium cepa assay, Ames test (OECD TG 471), Comet assay and YES/YAS assay. RESULTS: The wastewater ecotoxicity during one week showed no differences in separate working days, however, higher toxicity values were recorded in May compared to November. In the following study, samples from two of the five hospitals were classified as toxic, the others as non toxic. Genotoxicity has not been confirmed in any sample. In several cases, wastewater samples exhibited agonist activity to the estrogen and androgen receptors. CONCLUSION: The study demonstrated different levels of toxicity of treated hospital wastewater. Variable sensitivity of individual bioassays for tested wastewater samples was recognized. A more extensive study including proposal for improvement of hospital wastewater treatment within the Czech Republic can be recommended with the aim to decrease the discharge of toxic chemicals into the local sewage system and the environment.


Asunto(s)
Aguas Residuales/toxicidad , Contaminantes Químicos del Agua/toxicidad , Aliivibrio fischeri/fisiología , Animales , Bioensayo/métodos , Chlorophyceae/fisiología , Daphnia/fisiología , Hospitales , Eliminación de Residuos Sanitarios , Cebollas/fisiología , Proyectos Piloto , Aguas Residuales/análisis , Contaminantes Químicos del Agua/análisis
13.
Cent Eur J Public Health ; 24(3): 234-240, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27755863

RESUMEN

AIM: Natural or artificial substances have become an inseparable part of our lives. It is questionable whether adequate testing has been performed in order to ensure these substances do not pose a serious health risk. The principal aim of our research was to clarify the potential risk of adding essential oils to food, beverages and cosmetic products. METHODS: The toxicity of substances frequently employed in cosmetics, aromatherapy and food industry (bergamot oil, Litsea cubeba oil, orange oil, citral) were investigated using cell line NIH3T3 (mouse fibroblasts) with/without UV irradiation. The MTT assay was used to estimate the cell viability. Reactive oxygen species (ROS) which are products of a number of natural cellular processes such as oxygen metabolism and inflammation were measured to determine the extent of cellular stress. DNA damage caused by strand breaks was examined by comet assay. RESULTS: MTT test determined EC50 values for all tested substances, varying from 0.0023% v/v for bergamot oil to 0.018% v/v for citral. ROS production measurement showed that UV radiation induces oxidative stress to the cell resulting in higher ROS production compared to the control and non-irradiated samples. Comet assay revealed that both groups (UV, without UV) exert irreversible DNA damage resulting in a cell death. CONCLUSIONS: Our findings suggest that even low concentrations (lower than 0.0464% v/v) of orange oil can be considered as phototoxic (PIF value 8.2) and probably phototoxic for bergamot oil (PIF value 4.6). We also found significant changes in the cell viability, the ROS production and the DNA after the cells were exposed to the tested chemicals. Even though these substances are widely used as antioxidants it should be noted that they present a risk factor and their use in cosmetic and food products should be minimized.


Asunto(s)
Fibroblastos/efectos de los fármacos , Fibroblastos/efectos de la radiación , Litsea/toxicidad , Monoterpenos/toxicidad , Células 3T3 NIH/efectos de los fármacos , Células 3T3 NIH/efectos de la radiación , Aceites de Plantas/toxicidad , Rayos Ultravioleta , Monoterpenos Acíclicos , Animales , Ensayo Cometa , Daño del ADN , Dermatitis Fototóxica , Ratones , Estrés Oxidativo , Especies Reactivas de Oxígeno
14.
Lasers Surg Med ; 47(2): 196-202, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25663017

RESUMEN

BACKGROUND AND OBJECTIVE: The not quite rare occurrence of inaccurate clinical diagnoses of burns in early post-burn days leads to an inappropriate conservative treatment strategy, or unnecessary surgery. LDI (Laser Doppler Imaging) objectively evaluates skin blood circulation, which correlates with the depth of the burn and the length of healing. The aim of this work was to suggest cutoff values for detecting burns without healing potential within 3 weeks, which should have undergone surgery. METHOD: The burned area's average blood perfusion of 148 burns was measured on 115 patients, using the Laser Doppler Imager PIM III. A total of 268 measurements were performed from the one to the ninth post-burn day (PBD). The perfusion values were compared to the healing time or histology in the case of the surgical treatment. Cutoff values indicating surgery were investigated in various post-burn days; the ROC analysis was used. RESULTS: This work suggest statistically significant increasing cutoff values for indication to surgery (P = 0.05). From the third to the fifth day 148.5 perfusion units (PU), from the sixth to the seventh day 186.0 PU, from the eighth to the ninth PBD 269.5 PU. The cutoff value is not possible to establish until the second day. CONCLUSION: LDI is a useful method for wound healing prediction and an indication of the necessity of surgery. We have demonstrated that the diagnosis of the healing capacity of LDI needs to take into account the factor of time.


Asunto(s)
Quemaduras/diagnóstico , Quemaduras/cirugía , Flujometría por Láser-Doppler , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Factores de Tiempo , Tiempo de Tratamiento , Cicatrización de Heridas , Adulto Joven
15.
Dev Period Med ; 19(4): 441-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26982751

RESUMEN

Mitochondrial disorders (MD) represent a clinically, biochemically and genetically heterogeneous group of diseases associated with dysfunction of the oxidative phosphorylation system and pyruvate dehydrogenase complex. Our aim was to illustrate the most common clinical presentation of MD on the example of selected diseases and syndromes. The minimal prevalence of MD is estimated as 1 to 5,000. MD may manifest at any age since birth until late-adulthood with acute manifestation or as a chronic progressive disease. Virtually any organ may be impaired, but the organs with the highest energetic demands are most frequently involved, including brain, muscle, heart and liver. Some MD may manifest as a characteristic cluster of clinical features (e.g. MELAS syndrome, Kearns-Sayre syndrome). Diagnostics includes detailed history, the comprehensive clinical examination, results of specialized examinations (especially cardiology, visual fundus examination, brain imaging, EMG), laboratory testing of body fluids (lactate, aminoacids, organic acids), and analysis of bioptic samples of muscle, skin, and liver, eventually. Normal lactate level in blood does not exclude the possibility of MD. Although the aimed molecular genetic analyses may be indicated in some of mitochondrial diseases, the methods of next generation sequencing come into focus. Examples of treatment are arginine supplementation in MELAS syndrome, ketogenic diet in pyruvate oxidation disorders or quinone analogs in patients with LHON. Conclusion: The clinical suspicion of a mitochondrial disorder is often delayed, or the disease remains undiagnosed. The correct diagnosis and adequate treatment can improve prognosis of the patient. Access to genetic counseling is also of great importance.


Asunto(s)
Encéfalo/fisiopatología , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/fisiopatología , ADN Mitocondrial/análisis , Electroencefalografía , Humanos , Síndrome de Kearns-Sayre/diagnóstico , Síndrome de Kearns-Sayre/fisiopatología , Síndrome MELAS/diagnóstico , Síndrome MELAS/fisiopatología , Síndrome MERRF/diagnóstico , Síndrome MERRF/fisiopatología , Encefalomiopatías Mitocondriales/diagnóstico , Encefalomiopatías Mitocondriales/fisiopatología , Miopatías Mitocondriales/diagnóstico , Miopatías Mitocondriales/fisiopatología
16.
J Mol Cell Cardiol ; 74: 353-63, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24976018

RESUMEN

Myeloperoxidase (MPO) is a heme enzyme abundantly expressed in polymorphonuclear neutrophils. MPO is enzymatically capable of catalyzing the generation of reactive oxygen species (ROS) and the consumption of nitric oxide (NO). Thus MPO has both potent microbicidal and, upon binding to the vessel wall, pro-inflammatory properties. Interestingly, MPO - a highly cationic protein - has been shown to bind to both endothelial cells and leukocyte membranes. Given the anionic surface charge of red blood cells, we investigated binding of MPO to erythrocytes. Red blood cells (RBCs) derived from patients with elevated MPO plasma levels showed significantly higher amounts of MPO by flow cytometry and ELISA than healthy controls. Heparin-induced MPO-release from patient-derived RBCs was significantly increased compared to controls. Ex vivo experiments revealed dose and time dependency for MPO-RBC binding, and immunofluorescence staining as well as confocal microscopy localized MPO-RBC interaction to the erythrocyte plasma membrane. NO-consumption by RBC-membrane fragments (erythrocyte "ghosts") increased with incrementally greater concentrations of MPO during incubation, indicating preserved catalytic MPO activity. In vivo infusion of MPO-loaded RBCs into C57BL/6J mice increased local MPO tissue concentrations in liver, spleen, lung, and heart tissue as well as within the cardiac vasculature. Further, NO-dependent relaxation of aortic rings was altered by RBC bound-MPO and systemic vascular resistance significantly increased after infusion of MPO-loaded RBCs into mice. In summary, we find that MPO binds to RBC membranes in vitro and in vivo, is transported by RBCs to remote sites in mice, and affects endothelial function as well as systemic vascular resistance. RBCs may avidly bind circulating MPO, and act as carriers of this leukocyte-derived enzyme.


Asunto(s)
Síndrome Coronario Agudo/sangre , Eritrocitos/metabolismo , Insuficiencia Cardíaca/sangre , Peroxidasa/sangre , Síndrome Coronario Agudo/patología , Animales , Aorta/efectos de los fármacos , Transporte Biológico , Células Cultivadas , Endotelio Vascular/efectos de los fármacos , Eritrocitos/patología , Corazón/efectos de los fármacos , Insuficiencia Cardíaca/patología , Heparina/química , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacología , Técnicas de Cultivo de Órganos , Peroxidasa/farmacología , Unión Proteica , Técnicas de Cultivo de Tejidos , Resistencia Vascular/efectos de los fármacos
17.
Am J Respir Cell Mol Biol ; 51(1): 155-62, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24521348

RESUMEN

Pulmonary arterial hypertension (PAH) is characterized by adverse remodeling of pulmonary arteries. Although the origin of the disease and its underlying pathophysiology remain incompletely understood, inflammation has been identified as a central mediator of disease progression. Oxidative inflammatory conditions support the formation of electrophilic fatty acid nitroalkene derivatives, which exert potent anti-inflammatory effects. The current study investigated the role of 10-nitro-oleic acid (OA-NO2) in modulating the pathophysiology of PAH in mice. Mice were kept for 28 days under normoxic or hypoxic conditions, and OA-NO2 was infused subcutaneously. Right ventricular systolic pressure (RVPsys) was determined, and right ventricular and lung tissue was analyzed. The effect of OA-NO2 on cultured pulmonary artery smooth muscle cells (PASMCs) and macrophages was also investigated. Changes in RVPsys revealed increased pulmonary hypertension in mice on hypoxia, which was significantly decreased by OA-NO2 administration. Right ventricular hypertrophy and fibrosis were also attenuated by OA-NO2 treatment. The infiltration of macrophages and the generation of reactive oxygen species were elevated in lung tissue of mice on hypoxia and were diminished by OA-NO2 treatment. Moreover, OA-NO2 decreased superoxide production of activated macrophages and PASMCs in vitro. Vascular structural remodeling was also limited by OA-NO2. In support of these findings, proliferation and activation of extracellular signal-regulated kinases 1/2 in cultured PASMCs was less pronounced on application of OA-NO2.Our results show that the oleic acid nitroalkene derivative OA-NO2 attenuates hypoxia-induced pulmonary hypertension in mice. Thus, OA-NO2 represents a potential therapeutic agent for the treatment of PAH.


Asunto(s)
Modelos Animales de Enfermedad , Hipertensión Pulmonar/prevención & control , Hipertrofia Ventricular Derecha/prevención & control , Hipoxia/fisiopatología , Inflamación/prevención & control , Ácidos Oléicos/uso terapéutico , Animales , Western Blotting , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Cromatografía Líquida de Alta Presión , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipertensión Pulmonar Primaria Familiar , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipertrofia Ventricular Derecha/etiología , Hipertrofia Ventricular Derecha/patología , Inflamación/etiología , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Superóxidos/metabolismo
18.
Biochim Biophys Acta ; 1830(10): 4524-36, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23707661

RESUMEN

BACKGROUND: Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood. METHODS: We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested. RESULTS: MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed. CONCLUSIONS: Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins. GENERAL SIGNIFICANCE: Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins.


Asunto(s)
Proteínas de la Matriz Extracelular/metabolismo , Glicosaminoglicanos/metabolismo , Peroxidasa/metabolismo , Células Cultivadas , Colágeno Tipo IV/metabolismo , Dimerización , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Proteínas de la Matriz Extracelular/química , Fibronectinas/metabolismo , Humanos , Nitratos/metabolismo , Estrés Oxidativo , Unión Proteica , Tirosina/metabolismo
19.
Mediators Inflamm ; 2014: 694312, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24803742

RESUMEN

The glycocalyx of the endothelium is an intravascular compartment that creates a barrier between circulating blood and the vessel wall. The glycocalyx is suggested to play an important role in numerous physiological processes including the regulation of vascular permeability, the prevention of the margination of blood cells to the vessel wall, and the transmission of shear stress. Various theoretical models and experimental approaches provide data about changes to the structure and functions of the glycocalyx under various types of inflammatory conditions. These alterations are suggested to promote inflammatory processes in vessels and contribute to the pathogenesis of number of diseases. In this review we summarize current knowledge about the modulation of the glycocalyx under inflammatory conditions and the consequences for the course of inflammation in vessels. The structure and functions of endothelial glycocalyx are briefly discussed in the context of methodological approaches regarding the determination of endothelial glycocalyx and the uncertainty and challenges involved in glycocalyx structure determination. In addition, the modulation of glycocalyx structure under inflammatory conditions and the possible consequences for pathogenesis of selected diseases and medical conditions (in particular, diabetes, atherosclerosis, ischemia/reperfusion, and sepsis) are summarized. Finally, therapeutic strategies to ameliorate glycocalyx dysfunction suggested by various authors are discussed.


Asunto(s)
Glicocálix/metabolismo , Inflamación/metabolismo , Animales , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Glicocálix/patología , Humanos , Inflamación/patología
20.
Neuro Endocrinol Lett ; 35 Suppl 2: 133-40, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25638377

RESUMEN

BACKGROUND: The aim of this study was to compare human and animal skin irritation data with results of selected in vitro methods, including HET-CAM test, Neutral Red Release Assay, Neutral Red Uptake Assay and EpiOcular eye irritation test and with already existing data of eye irritation obtained from animal experiments. METHODS: Chemicals employed in previous skin irritation validation studies and commercially available cosmetic formulations were subjected to further testing using in vitro methods Neutral Red Release (NRR) assay, Neutral Red Uptake (NRU) assay, HET-CAM test and EpiOcular assay. RESULTS: The study revealed that skin irritants are not necessarily eye irritants; specifically volatile or solid materials may be misclassified. NRR assay provided false negative results in case of substances with fixative effect or not removable under standard washing procedure, emphasizing the role of microscopical evaluation as a crucial additional endpoint. Although overpredictive, HET-CAM test provided the lowest false negative rate. The most aggressive cosmetic formulation was correctly identified by EpiOcular assay, in accordance with NRU and NRR assays results, while HET-CAM test correctly identified the mildest formulation. CONCLUSIONS: Each of the in vitro methods is related to a specific endpoint of ocular irritation and provides only partial information on the mode of action of the tested material. Despite good reproducibility of individual in vitro assays, only the weight-of-evidence approach and results of multiple selected in vitro tests can allow for estimation of eye irritation hazard in vivo.


Asunto(s)
Cosméticos/toxicidad , Oftalmopatías/inducido químicamente , Irritantes/toxicidad , Enfermedades de la Piel/inducido químicamente , Animales , Humanos , Técnicas In Vitro
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA