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1.
Molecules ; 27(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35011390

RESUMO

The conditions for determining the antioxidant properties of cyclitols (d-pinitol, l-quebrachitol, myo-, l-chiro-, and d-chiro-inositol), selected flavanones (hesperetin, naringenin, eriodictyol, and liquiritigenin) and glutathione by spectrophotometric methods-CUPRAC and with DPPH radical, and by a chromatographic method DPPH-UHPLC-UV, have been identified. Interactions of the tested compounds and their impact on the ox-red properties were investigated. The RSA (%) of the compounds tested was determined. Very low antioxidative properties of cyclitols, compared with flavanones and glutathione alone, were revealed. However, a significant increase in the determined antioxidative properties of glutathione by methyl-ether derivatives of cyclitols (d-pinitol and l-quebrachitol) was demonstrated for the first time. Thus, cyclitols seem to be a good candidate for creating drugs for the treatment of many diseases associated with reactive oxygen species (ROS) generation.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Ciclitóis/química , Ciclitóis/farmacologia , Relação Dose-Resposta a Droga , Flavanonas/química , Flavanonas/farmacologia , Sequestradores de Radicais Livres , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/química , Glutationa/farmacologia , Estrutura Molecular , Análise Espectral , Relação Estrutura-Atividade
2.
Int J Phytoremediation ; 21(11): 1090-1097, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31084361

RESUMO

The aim of the present work is to estimate remediation potential of Pistia stratiotes, its ability to uptake mesotrione (MES) - one of the most frequently used herbicides, and its main degradation products: 2-amino-4-methylsulfonyl benzoic acid (AMBA) and 4-methylsulfonyl-2-nitrobenzoic acid (MNBA). This research focuses on model experiments performed under laboratory conditions. The results show that Pistia stratiotes can uptake up to 75% of degradation products from 1 L of surface water samples polluted with 0.4 µg/L of each analyte during 7 days without significant phytotoxic effect. Under the same experimental conditions, the effectiveness of mesotrione sorption is in the range of 42-58%. The phytotoxicity of this compound is higher in comparison to its degradation products (decrease of chlorophyll concentration in plant tissues exposed to MES 27-32% vs 4-13% in case of exposition to AMBA and MNBA). The adequate nutrition of the plants is crucial to their well-being and thus the sorption of pollutants.


Assuntos
Araceae , Poluentes Químicos da Água , Biodegradação Ambiental , Cicloexanonas , Água
3.
Wiad Lek ; 72(8): 1586-1591, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32012513

RESUMO

A 66 year-old obese man, suffering from type 2 diabetes, high blood pressure, chronic nephropathy in stage 4, permanent atrial fibrillation accompanied by bradycardia was admitted to a cardiology ward with the signs and symptoms of acute right-sided heart failure. A standard therapy was used including combined diuretics therapy. In spite of the applied methods and pharmaceuticals, no significant reduction of the body weight neither improvement in cardiovascular capacity or renal parameters were observed. Due to the ineffectiveness of the standard combined pharmacotherapy applied in the case of the acute circulatory failure, the resistance to diuretics was recognized and as a result of the above, infusion of levosimendan was decided to be applied. This therapy resulted in rich diuresis, significant loss in body weight and considerable improvement in cardiovascular capacity which allowed to continue further diagnostics and appropriate invasive treatment. The article describes current knowledge on the place of levosimendan and its application in the treatment of an right-sided heart failure.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Piridazinas , Simendana/uso terapêutico , Idoso , Cardiotônicos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hidrazonas , Masculino
4.
Wiad Lek ; 72(1): 112-119, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-30796874

RESUMO

Heart failure appears in 2% of the adult population in Europe. One in five people aged 40 years will develop heart failure during their lifetime. Heart failure touch 20,000 people in the Opole province. Heart failure is the second, after acute coronary syndromes, urgent cause of admissions to the Clinic of Cardiology at the University Hospital in Opole. The paper presents the prognosis of hospitalization of patients with heart failure for the years 2015-2050 taking into account the processes of depopulation taking place in our region. The analysis makes it possible to predict that the age group particularly exposed to heart failure in the coming decades will be people who today belong to teenagers and young adults. The article presents current methods of treatment of heart failure. Improvement in the prognosis of patients with heart failure can occur through the implementation of the guidelines for treatment of heart failure recommended by the ESC. This goal is to be achieved by introducing the "Comprehensive care for patients with heart failure (KONS)" program in our country. The shift of the burden of care for patient with heart failure to outpatient unit will result in a significant reduction in the number of hospitalizations.


Assuntos
Cardiologia , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Polônia/epidemiologia , Prognóstico
5.
Wiad Lek ; 72(2): 284-290, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-30903789

RESUMO

Heart failure has accompanied mankind since the dawn of time. The first mentions of the disease, which today we describe as heart failure, come from ancient times. Epidemiology of symptomatic heart failure is well known , especially in Europe. Heart failure affects approximately 2% of the adult population in Europe. The article presents: definition, epidemiology and prognosis of patients with heart failure. The article presents current methods of pharmacotherapy and treatment of heart failure. An important element in the management of patients with heart failure is medical rehabilitation and the prevention of cardiovascular diseases, according to the ESC guidelines. The topic also discussed in the article is the analysis of socio-economic costs of heart failure. The article concludes that: heart failure is a medical problem, because despite the introduction of new treatment methods, it is a disease that is still characterized by poor prognosis; heart failure is an economic problem because its treatment is expensive and absorbs 2% of all costs of healthcare; heart failure is a social problem because it is a disorder affecting mainly elderly people, leading to a significant reduction in their ability to live independently, which results in their exclusion from social life.


Assuntos
Doenças Cardiovasculares , Europa (Continente) , Humanos , Prognóstico
6.
Biomed Chromatogr ; 30(4): 652-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26362402

RESUMO

A high-performance liquid chromatography method for simultaneous separation and determination of biogenic amines [dopamine, epinephrine, serotonin and its six metabolites (normetanephrine, metanephrine, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylglycol, homovanilic acid and 5-hydroxyindoloacetic acid)] with drugs from different therapeutically groups [analgesics (paracetamol, metamizol), diuretics (furosemide) and antibiotics (cefazolin, fluconazole)] was developed. A chromatographic column with pre-column with octadecylsilane phase (C18e ) and two detectors - diode array serial connected and fluorescence - was used. Gradient elution of mixture of acetate buffer (pH 4.66) and methanol as a mobile phase was applied. The limit of detection (LOD) of 8-10 ng/mL and limit of quantitation (LOQ) of 24-30 ng/mL for biogenic amines, as well as the LOD of 50-100 ng/mL and the LOQ of 150-300 ng/mL for drugs, were determined. The applied sample preparation method allowed recoveries of 93% for the biogenic amines and 92% for the drugs to be achieved. The developed procedure has been applied to simultaneous determination of the examined compounds in urine samples and could be used in clinical analysis.


Assuntos
Aminas Biogênicas/urina , Cromatografia Líquida de Alta Pressão/métodos , Preparações Farmacêuticas/urina , Humanos , Limite de Detecção , Silanos/química
7.
Biomed Chromatogr ; 29(1): 1-20, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25381720

RESUMO

In recent years demands on the amount of information that can be obtained from the analysis of a single sample have increased. For time and economic reasons it is necessary to examine at the same time larger number of compounds, and compounds from different groups. This can best be seen in such areas as clinical analysis. In many diseases, the best results for patients are obtained when treatment fits the individual characteristics of the patient. Dosage monitoring is important at the beginning of therapy and in the full process of treatment. In the treatment of many diseases biogenic amines (dopamine, serotonin) and methylxanthines (theophylline, theobromine, caffeine) play an important role. They are used as drugs separately or in combination with others to support and strengthen the action of other drugs - for example, the combination of caffeine and paracetamol. Vitamin supplementation may be also an integral part of the treatment process. Specification of complete sample preparation parameters for extraction of the above compounds from biological matrices has been reviewed. Particular attention was given to the preparation stage and extraction methods. This review provides universal guidance on establishing a common procedures across laboratories to facilitate the preparation and analysis of all discussed compounds.


Assuntos
Ácido Ascórbico/isolamento & purificação , Aminas Biogênicas/isolamento & purificação , Fracionamento Químico/métodos , Complexo Vitamínico B/isolamento & purificação , Xantinas/isolamento & purificação , Ácido Ascórbico/análise , Ácido Ascórbico/química , Aminas Biogênicas/análise , Aminas Biogênicas/química , Humanos , Modelos Moleculares , Complexo Vitamínico B/análise , Complexo Vitamínico B/química , Xantinas/análise , Xantinas/química
8.
Chemosphere ; 359: 142298, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38729438

RESUMO

Japanese radish (Raphanus sativus var. longipinnatus) plants grown under laboratory conditions were individually exposed to the same doses of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine, ATR) or its main degradation products: either 2-amino-4-chloro-6-isopropylamino-1,3,5-triazine (DEA) or 2-amino-4-chloro-6-ethylamino-1,3,5-triazine (DIA) or desethyl-desisopropyl-atrazine (DEDIA) or 4-(ethylamino)-2-hydroxy-6-(isopropylamino)-1,3,5-triazine (HA), respectively. One week after treatment in plants exposed to ATR, DIA, and DEA, their concentrations were 7.8 µg/g, 9.7 µg/g, and 14.5 µg/g, respectively, while those treated with DEDIA and HA did not contain these compounds. These results were correlated with plant amino acid profile obtained by suspect screening analysis and metabolomic "fingerprint" based on non-target analysis, obtained by liquid chromatography coupled with QTRAP triple quadrupole mass spectrometer. In all cases, both ATR and its by-products were found to interfere with the plant's amino acid profile and modify its metabolic "fingerprint". Therefore, we proved that the non-target metabolomics approach is an effective tool for investigating the hidden effects of pesticides and their transformation products, which is particularly important as these compounds may reduce the quality of edible plants.


Assuntos
Atrazina , Herbicidas , Metabolômica , Raphanus , Atrazina/toxicidade , Raphanus/efeitos dos fármacos , Raphanus/metabolismo , Herbicidas/toxicidade , Triazinas/toxicidade
9.
Pest Manag Sci ; 80(10): 4967-4979, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38829276

RESUMO

BACKGROUND: This study aims to obtain systematic understanding of the way by which pesticides are metabolized in plants and the influence of this process on plants' metabolism as this process has a key impact on plant-based food safety and quality. The research was conducted under field conditions, which enabled to capture metabolic processes taking place in plants grown under multihectare cultivation conditions. RESULTS: Research was conducted on three wheat varieties cultivated under field conditions and treated by commercially available preparations (fungicides, herbicides, insecticides, and growth regulator). Plant tissues with distinctions in roots, green parts, and ears were collected periodically during spring-summer vegetation period, harvested grains were also investigated. Sample extracts were examined by chromatographic techniques coupled with tandem mass spectrometry for: dissipation kinetics study, identification of pesticide metabolites, and fingerprint-based assessment of metabolic changes. CONCLUSION: Tissue type and wheat varieties influenced pesticide dissipation kinetics and resulting metabolites. Metabolic changes of plants were influenced by type of applied pesticide and its concentration in plants tissues. Despite differences in plant metabolic response to pesticide stress during cultivation, grain metabolomes of all investigated wheat varieties were statistically similar. 4-[cyclopropyl(hydroxy)methylidene]-3,5-dioxocyclo-hexanecarboxylic acid and trans-chrysantemic acid - metabolites of crop-applied trinexapac-ethyl and lambda-cyhalothrin, respectively, were identified in cereal grains. These compounds were not considered to be present in cereal grains up to now. The research was conducted under field conditions, enabling the measurement of metabolic processes taking place in plants grown under large-scale management conditions. © 2024 Society of Chemical Industry.


Assuntos
Praguicidas , Triticum , Triticum/metabolismo , Triticum/crescimento & desenvolvimento , Praguicidas/metabolismo , Biotransformação , Herbicidas/metabolismo
10.
J Clin Med ; 13(19)2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39407996

RESUMO

Background: Acute heart failure (AHF) is characterized by a complex pathophysiology. Aims: This study aimed to evaluate the usefulness of combined serial measurements of N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and growth differentiation factor 15 (GDF-15) for predicting long-term outcomes in patients with AHF. Methods: This study included 104 consecutive patients hospitalized due to AHF. The mean (SD) age was 65 (±15) years. Blood samples were collected on admission, at discharge, and at a 30-day follow-up visit. The primary composite endpoint was all-cause mortality or rehospitalization due to heart failure (HF) at 1-year follow-up. Results: During follow-up, the primary endpoint occurred in 31 persons. In the ROC analysis, the optimal cut-off values of GDF-15 for predicting the outcome were 5115.5 pg/mL on admission, 4145 pg/mL at discharge, and 4218.5 pg/mL at the 30-day visit. For NT-pro BNP, the optimal cut-off reached 6011 ng/L, 1250 ng/L, and 1456.5 ng/L, respectively. Patients with both GDF-15 and NT-pro BNP levels above the cut-off value had a higher risk of the primary composite endpoint than patients with only one or none of the biomarkers elevated at three time points. At the 30-day visit, the model combining NT-pro BNP and GDF-15 showed the highest predictive value for the primary composite endpoint (area under the curve, 0.75). Conclusions: Combined serial measurements of NT-pro BNP and GDF-15 outperform single measurements in outcome prediction at 1-year follow-up in patients with AHF. The repetitive combined model may serve as a useful risk assessment tool and facilitate decision-making during long-term observation.

11.
Postepy Hig Med Dosw (Online) ; 67: 695-9, 2013 Jul 24.
Artigo em Polonês | MEDLINE | ID: mdl-24018434

RESUMO

In recent years, the rapid development of scientific research led to the introduction of strategies based on new markers that allow for estimation of the latent disease period before the clinical symptoms of actual kidney failure are revealed. The experimental tests carried out on animals and cell lines derived from the proximal tubule have made possible the detection of genes that are induced early after hypoxia. The protein products of these genes can be considered as useful markers for the diagnosis of renal failure. The induction of gene KIM-1 (called Kidney Injury Molecule-1) results in the formation of protein that can be considered as a diagnostic marker. This work describes the data on the structure, biological function and importance of determining the concentrations of KIM-1 in the diagnosis of drug-induced toxicity and kidney damage.


Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/metabolismo , Glicoproteínas de Membrana/análise , Receptores Virais/análise , Injúria Renal Aguda/induzido quimicamente , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Linhagem Celular , Receptor Celular 1 do Vírus da Hepatite A , Túbulos Renais Proximais/química , Túbulos Renais Proximais/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Virais/metabolismo
12.
Sci Rep ; 13(1): 1473, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702867

RESUMO

Nitisinone (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, NTBC) is considered a potentially effective drug for the treatment of various metabolic diseases associated with disorders of L-tyrosine metabolism however, side-effects impede its widespread use. This work aimed to broaden the knowledge of the influence of NTBC and its metabolites 2-amino-4-(trifluoromethyl)benzoic acid (ATFA), 2-nitro-4-(trifluoromethyl)benzoic acid (NTFA), and cyclohexane-1,3-dione (CHD) on the catabolism of L-tyrosine and other endogenous compounds in Saccharomyces cerevisiae. Based on a targeted analysis performed by LC-ESI-MS/MS, based on multiple reaction monitoring, it was found that the dissipation kinetics of the parent compound and its metabolites are compatible with a first-order reaction mechanism. Moreover, it has been proven that formed NTBC metabolites, such as CHD, cause a decrease in L-tyrosine, L-tryptophan, and L-phenylalanine concentrations by about 34%, 59% and 51%, respectively, compared to the untreated model organism. The overall changes in the metabolism of yeast exposed to NTBC or its derivatives were evaluated by non-targeted analysis via LC-ESI-MS/MS in the ion trap scanning mode. Based on principal components analysis, a statistically significant similarity between metabolic responses of yeast treated with ATFA or NTFA was observed. These findings facilitate further studies investigating the influence of NTBC on the human body and the mechanism of its action.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase , Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/metabolismo , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Espectrometria de Massas em Tandem , Cicloexanonas/farmacologia , Cicloexanonas/uso terapêutico , Nitrobenzoatos/metabolismo , Metaboloma , Tirosina/metabolismo
13.
Sci Rep ; 13(1): 16822, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798340

RESUMO

Metabolic profiling offers huge potential to highlight markers and mechanisms in support of toxicology and pathology investigations during drug development. The main objective was to modify therapy with adamantane derivatives: amantadine and rimantadine, to increase their bioavailability and evaluate the influence of such therapy on drug metabolism using Saccharomyces cerevisiae as the model organism. In this study, the profile of endogenous metabolites of a model organism was measured and interpreted to provide an opportunity to investigate changes induced by treatment with amantadine and rimantadine. It was found that resveratrol supplementation synergistically enhanced the effects of amantadine treatment and increased rimantadine metabolism, potentially reducing side effects. The fingerprinting strategy was used as an efficient technique for qualitatively evaluating and monitoring changes in the profiles of endogenous components and their contents in a model organism. Chemometric tools were employed to find marker compounds that can be defined as characteristic indicators of a pharmacological response to a therapeutic intervention. An improved understanding of the mechanisms involved in drug effect and an increased ability to predict individual variations in the drug response of organisms will improve the treatment process and the development of new therapies.


Assuntos
Adamantano , Rimantadina , Rimantadina/efeitos adversos , Metabolismo Secundário , Amantadina/farmacologia , Taxa de Depuração Metabólica
14.
Sci Total Environ ; 875: 162709, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36907395

RESUMO

Pesticides that are absorbed by plants undergo biotransformation and might affect plant metabolic processes. The metabolisms of two cultivated wheat varieties, Fidelius and Tobak, treated with commercially available fungicides (fluodioxonil, fluxapyroxad, and triticonazole) and herbicides (diflufenican, florasulam, and penoxsulam) were studied under field conditions. The results provide novel insights regarding the effects of these pesticides on plant metabolic processes. Plants (roots and shoots) were sampled six times during the six-week experiment. Pesticides and pesticide metabolites were identified using GC-MS/MS, LC-MS/MS, and LC-HRMS, while root and shoot metabolic fingerprints were determined using non-targeted analysis. Fungicide dissipation kinetics were analyzed according to the quadratic mechanism (R2: 0.8522-0.9164) for Fidelius roots, and zero-order for Tobak roots (R2: 0.8455-0.9194); shoot dissipation kinetics were analyzed according to first-order (R2: 0.9593-0.9807) and quadratic (R2: 0.8415-0.9487) mechanisms for Fidelius and Tobak, respectively. The fungicide degradation kinetics were different compared to reported literature values, most likely due to differences in pesticide application methods. The following metabolites were respectively identified in shoot extracts of both wheat varieties for fluxapyroxad, triticonazole, and penoxsulam: 3-(difluoromethyl)-N-(3',4',5'-trifluorobiphenyl-2-yl)-1H pyrazole-4-carboxamide, 2-chloro-5-{(E)-[2-hydroxy-3,3-dimethyl-2-(1H-1,2,4-triazol-1-ylmethyl)-cyclopentylidene]-methyl}phenol, and N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-2,4-dihydroxy-6 (trifluoromethyl)benzene sulfonamide. Metabolite dissipation kinetics varied depending on the wheat variety. These compounds were more persistent than parent compounds. Despite having the same cultivation conditions, the two wheat varieties varied in their metabolic fingerprints. The study revealed that pesticide metabolism has a greater dependence on plant variety and method of administration compared to the physicochemical properties of the active substance. This highlights the necessity of conducting research on pesticide metabolism under field conditions.


Assuntos
Fungicidas Industriais , Resíduos de Praguicidas , Praguicidas , Praguicidas/análise , Triticum/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Fungicidas Industriais/análise , Plantas/metabolismo , Resíduos de Praguicidas/análise
15.
Environ Pollut ; 316(Pt 1): 120468, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36283473

RESUMO

A comprehensive approach was applied to evaluate the effects of pesticides on the metabolism of wheat (Triticum aestivum L). The application of commercially available pesticide formulations under field cultivation conditions provided a source of metabolic data unlimited by model conditions, representing a novel approach to study the effects of pesticides on edible plants. Gas and liquid chromatography coupled to tandem mass spectrometry were employed for targeted and non-targeted analysis of wheat roots and shoots sampled six times during the six-week experiment. The applied pesticides: prothioconazole, tebuconazole, fluoxastrobin, diflufenican, florasulam, and penoxulam were found at concentrations ranging 0.0070-25.20 mg/kg and 0.0020-2.2 mg/kg in the wheat roots and shoots, respectively. The following pesticide metabolites were identified in shoots: prothioconazole-desthio (prothioconazole metabolite), 5-(4-chlorophenyl)-2,2-dimethyl-3-(1,2,4-triazol-1-ylmethyl)pentane-1,3-diol (tebuconazole metabolite), and N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-2,4-dihydroxy-6-(trifluoromethyl)benzene sulphonamide (penoxulam metabolite). The metabolic fingerprints and profiles changed during the experiment, reflecting the cumulative response of wheat to both its growth environment and pesticides, as well as their metabolites. Approximately 15 days after the herbicide treatment no further changes in the plant metabolic profiles were observed, despite the presence of pesticide and their metabolites in both roots and shoots. This is the first study to combine the determination of pesticides and their metabolites plant tissues with the evaluation of plant metabolic responses under field conditions. This exhaustive approach contributes to broadening the knowledge of pesticide effects on edible plants, relevant to food safety.


Assuntos
Herbicidas , Praguicidas , Triticum/metabolismo , Praguicidas/metabolismo , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida , Herbicidas/metabolismo
16.
Biomater Adv ; 153: 213540, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37429048

RESUMO

Recurrent bacterial infections are a common cause of death for patients with cystic fibrosis and chronic obstructive pulmonary disease. Herein, we present the development of the degradable poly(sebacic acid) (PSA) microparticles loaded with different concentrations of azithromycin (AZ) as a potential powder formulation to deliver AZ locally to the lungs. We characterized microparticle size, morphology, zeta potential, encapsulation efficiency, interaction PSA with AZ and degradation profile in phosphate buffered saline (PBS). The antibacterial properties were evaluated using the Kirby-Bauer method against Staphylococcus aureus. Potential cytotoxicity was evaluated in BEAS-2B and A549 lung epithelial cells by the resazurin reduction assay and live/dead staining. The results show that microparticles are spherical and their size, being in the range of 1-5 µm, should be optimal for pulmonary delivery. The AZ encapsulation efficiency is nearly 100 % for all types of microparticles. The microparticles degradation rate is relatively fast - after 24 h their mass decreased by around 50 %. The antibacterial test showed that released AZ was able to successfully inhibit bacteria growth. The cytotoxicity test showed that the safe concentration of both unloaded and AZ-loaded microparticles was equal to 50 µg/ml. Thus, appropriate physicochemical properties, controlled degradation and drug release, cytocompatibility, and antibacterial behavior showed that our microparticles may be promising for the local treatment of lung infections.


Assuntos
Antibacterianos , Azitromicina , Humanos , Azitromicina/farmacologia , Azitromicina/química , Azitromicina/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Sistemas de Liberação de Medicamentos/métodos , Pulmão/metabolismo
17.
Postepy Hig Med Dosw (Online) ; 66: 603-8, 2012 Sep 10.
Artigo em Polonês | MEDLINE | ID: mdl-23001202

RESUMO

 The intensive studies carried out in many scientific laboratories and the efforts of numerous pharmaceutical companies have led to the development of drugs which are able to effectively inhibit HIV proliferation. At present, a number of antiretroviral agents with different mechanisms of action are available. Unfortunately, long-term use of antiretroviral drugs, however, does not remain indifferent to the patient and can cause significant side effects. In the present work, the antiretroviral drugs with a nephrotoxicity potential most commonly used in clinical practice are described. In the review attention has also been focused on the nephropathy resulting from the HIV infection alone and the influence of genetic factors on the occurrence of pathological changes in the kidney.


Assuntos
Antirretrovirais/efeitos adversos , Nefropatias/induzido quimicamente , Animais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Nefropatias/genética , Nefropatias/prevenção & controle
18.
Chemosphere ; 286(Pt 1): 131592, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34311397

RESUMO

Nitisinone (NTBC) is currently used for the treatment of tyrosinemia type 1, a rare disease. It also exhibits potential in the treatment of other orphan diseases as well as nervous system disorders - this is however limited by its side effects. In all living organisms, NTBC inhibits 4-hydroxyphenylpyruvate dioxygenase activity, thereby affecting l-tyrosine (L-TYR) catabolism, which results in the therapeutic effect. The NTBC metabolites formed in patient's body is one of the causes of its side effects. The influence of NTBC and its metabolites; 2-amino-4-(trifluoromethyl)benzoic acid, 2-nitro-4-(trifluoromethyl)benzoic acid, and cyclohexane-1,3-dione on L-TYR catabolism was investigated in Raphanus sativus var. longipinnatus. Based on targeted LC-MS/MS analysis the concentration of NTBC and its metabolites in exposed plant tissues was determined. Based on non-targeted LC-MS/MS analysis the concentrations of products of L-TYR catabolism: levodopa, epinephrine, norepinephrine, normetanephrine, dopamine, tyramine and vitamins C, B5 and B6, additionally leucine and valine were identified as influenced by the NTBC or its metabolites. NTBC and its metabolites influenced L-TYR catabolism differently. Particularly significant changes were found in the content of epinephrine and normetanephrine: in the plant tissues exposed to NTBC, an increase in the content of these neurotransmitters was found (+42%), whereas in the plant treated with 2-amino-4-(trifluoromethyl)benzoic acid or 2-nitro-4-(trifluoromethyl)benzoic acid a decrease in concentration (-39% and 55%, respectively) was observed. Cyclohexane-1,3-dione does not influence epinephrine and normetanephrine concentration. The conclusions of this study provide a platform for expanded research on the causes of side effects of NTBC treatment.


Assuntos
Nitrobenzoatos , Espectrometria de Massas em Tandem , Cromatografia Líquida , Cicloexanonas , Humanos , Tirosina
19.
Food Chem ; 356: 129680, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33819787

RESUMO

Liquid chromatography coupled with tandem mass spectrometry was employed for the detection of pesticides (thiamethoxam, lambda-cyhalothrin, deltamethrin, and metalaxyl) and their metabolites in Raphanus sativus var. longipinnatus exposed to these compounds under experimental conditions. Metalaxyl (0.008 mg/kg), metalaxyl acid (0.009 mg/kg), and (+)-trans-chrysanthemic acid (0.098 mg/kg) were identified in the plants exposed to the individual pesticides and their metabolites. Non-targeted analysis revealed the presence of thiamethoxam, lambda-cyhalothrin, and deltamethrin metabolites in plants exposed to these substances, despite the fact that the pesticide concentrations were below the analytical method's limit of quantification (0.005-0.006 mg/kg). Based on the non-targeted screening, non-specific (leucine and tyramine) and specific (epinephrine, dopamine, tryptamine, and serotonin) markers of plant exposure to the mentioned stress-inducing compounds were detected. These findings prove that non-targeted analysis is an indispensable tool for determining plants' exposure to pesticides, even when the parent compound has been completely metabolized.


Assuntos
Cromatografia Líquida de Alta Pressão , Metaboloma , Praguicidas/farmacologia , Raphanus/metabolismo , Espectrometria de Massas em Tandem , Epinefrina/análise , Epinefrina/isolamento & purificação , Leucina/análise , Leucina/isolamento & purificação , Nitrilas/farmacologia , Piretrinas/farmacologia , Raphanus/efeitos dos fármacos , Extração em Fase Sólida , Tiametoxam/farmacologia
20.
Food Chem ; 335: 127658, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32731124

RESUMO

Raphanus sativus var. longipinnatus, was exposed under experimental conditions to herbicides: rimsulfuron (RIM), administrated as (1) pure substance, (2) in commercially available formulation (RIMEL), (3) its degradation product: 4,6-dimethoxypyrimidin-2-amine (2ADP), (4) mesotrione (MES), (5) sulcotrione (SUL). Profiling and fingerprinting strategies, conducted by LC-MS/MS-FL, were employed to find markers of plant exposure to herbicide stress. The presence ofRIM metabolite in the tissues of plant exposed to this herbicide proved that it is necessary to determine both parent compound and its by-products to obtain reliable information on plant exposure to agrochemicals. A higher content of normetanephrine (NMN) (18-175%) and lower content of tyramine (TYR) (49-75%) and epinephrine (E) (75-83%) was observed in plant tissues exposed to RIM and 2ADP in comparison to blank sample. Therefore, NMN, TRY and E may be considered as markers of plant response to RIM. Non-target analysis enables to recognize the type of herbicide used during cultivation.


Assuntos
Herbicidas/toxicidade , Resíduos de Praguicidas/análise , Piridinas/toxicidade , Raphanus/química , Raphanus/efeitos dos fármacos , Sulfonamidas/toxicidade , Cromatografia Líquida , Cicloexanonas/farmacocinética , Cicloexanonas/toxicidade , Biomarcadores Ambientais , Epinefrina/análise , Mesilatos/farmacocinética , Mesilatos/toxicidade , Metaboloma , Normetanefrina/análise , Plantas Comestíveis/química , Plantas Comestíveis/efeitos dos fármacos , Piridinas/farmacocinética , Pirimidinas/toxicidade , Raphanus/metabolismo , Sulfonamidas/farmacocinética , Espectrometria de Massas em Tandem , Tiramina/análise
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