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1.
ISME J ; 17(1): 59-69, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36202927

RESUMO

Microbial activity in the deep sea is cumulatively important for global elemental cycling yet is difficult to quantify and characterize due to low cell density and slow growth. Here, we investigated microbial activity off the California coast, 50-4000 m water depth, using sensitive single-cell measurements of stable-isotope uptake and nucleic acid sequencing. We observed the highest yet reported proportion of active cells in the bathypelagic (up to 78%) and calculated that deep-sea cells (200-4000 m) are responsible for up to 34% of total microbial biomass synthesis in the water column. More cells assimilated nitrogen derived from amino acids than ammonium, and at higher rates. Nitrogen was assimilated preferentially to carbon from amino acids in surface waters, while the reverse was true at depth. We introduce and apply the Gini coefficient, an established equality metric in economics, to quantify intracommunity heterogeneity in microbial anabolic activity. We found that heterogeneity increased with water depth, suggesting a minority of cells contribute disproportionately to total activity in the deep sea. This observation was supported by higher RNA/DNA ratios for low abundance taxa at depth. Intracommunity activity heterogeneity is a fundamental and rarely measured ecosystem parameter and may have implications for community function and resilience.


Assuntos
Carbono , Ecossistema , Carbono/metabolismo , Nitrogênio , Água , Aminoácidos , Água do Mar/química
2.
Sci Total Environ ; 838(Pt 1): 155830, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35561917

RESUMO

Plastic and microplastic debris is transported by ocean currents over long distances, reaching remote areas, far from its original source. In Polar Regions, microplastics (MPs) can come from local activities or be transported from lower latitudes, with the former being the likely and major source. Although historically Antarctica was considered isolated from the global ocean, there is recent evidence of materials and organisms being transported in and out of the Southern Ocean, despite its multi-front structure. During the austral summer of 2019, beach surveys were conducted on the NW coast of the Fildes Peninsula (King George Island). The beach was characterised, and the first 2 cm of sediment from 5 quadrants (50 × 50 cm) along 100 m of the highest strandline were collected. Large microplastics (LMPs) and mesoplastics (MesoPs) were isolated, counted, measured, weighed and classified by shape. Polymer composition was analysed by FTIR and ageing estimated by Carbonyl Index. We found 293 items of LMPs (188 items) and MesoPs (105 items), with a total average density (±SD) of 234.4 ± 166 items m-2. Foams (130.4 ± 76.3), fragments (58.4 ± 56.0) and pellets (44.0 ± 50.5) were the most abundant shapes. The main polymers found were polystyrene, polypropylene, and polyethylene. We found pellets among the MesoPs, being the first record for beaches in Antarctica. The presence of these primary MPs south of 62°S not only alerts about their possible direct consequences on Antarctic ecosystems, but also gives empirical evidence for the passive entry of plastic debris from lower latitudes through cross-frontal exchanges, providing new evidence of a global connectivity of the Southern Ocean. Despite increasing research, knowledge of plastics dynamics and their impact in the Southern Ocean and Antarctica is still limited but certainly necessary.


Assuntos
Plásticos , Poluentes Químicos da Água , Regiões Antárticas , Ecossistema , Monitoramento Ambiental , Microplásticos , Oceanos e Mares , Poluentes Químicos da Água/análise
3.
Poult Sci ; 101(1): 101505, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34818612

RESUMO

The present study was intended to answer 2 scientific hypotheses: 1) the quail species has a significant influence in quail breast meat composition; 2) the wild quail's meat presents healthier composition than their farmed counterparts. An analysis of the pectoral muscles of wild and captive common quails (Coturnix coturnix) and domestic quails (Coturnix japonica domestica) was performed. The content of fatty acids (FA), amino acids, total cholesterol, and vitamin E, some basic macro- and microminerals in the pectoral muscles of the 2 species of the genus Coturnix were analyzed. Regarding the quail species influence on meat composition, Japanese Quail (JQ) revealed better lipid composition, characterized by lower saturated FA (SFA; less 3.17 g/100 g of total fatty acids), higher polyunsaturated FA contents (PUFA; more 5.5 g/100 g of total fatty acids) and healthier polyunsaturated FA/saturated FA (P/S) and n-6/n-3 ratios and TI value (1.08, 9.54 and 0.60 vs. 0.76, 12.58, and 0.75, correspondingly). The absence of differences observed on amino acids partial sums and ratios reveals equality between species on protein nutritional quality. On the other hand, Common Quail (CQ) proved to be a better source of copper (0.181 mg/100 g of meat), iron (2.757 mg/100 g of meat), manganese (0.020 mg/100 g of meat), and zinc (0.093 mg/100 g of meat) than JQ. The comparison of farmed and wild specimens within CQ, showed that wild birds presented lower total cholesterol (less 8.32 mg/g of fresh meat) and total PUFA (less 4.26 g/100 g of total fatty acids), and higher n-3 PUFA contents (more 1.53 g/100 g of total fatty acids), which contributed to healthier P/S and n-6/n-3 ratios, but worst PI (1.60, 8.08, and 113.1 vs. 0.76, 12.58, and 100.8, respectively). The wild species revealed higher α-tocopherol content (2.40 vs. 1.49 µg/g of fresh meat. Differences observed on their mineral composition counterbalance each other. Under intensive production system and similar feeding and management conditions, the CQ develops better nutritional qualities than JQ. The comparison of wild and farmed species within CQ reveals more similarities than differences. Quail´s meat presents good nutritional quality and introduces variability to human's diet, which is much valued by consumers.


Assuntos
Galinhas , Coturnix , Animais , Lipídeos , Carne , Minerais , Codorniz
4.
Mol Phylogenet Evol ; 113: 76-83, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28487261

RESUMO

In the last few years high-throughput sequencing technologies have permitted significant advances in mammalian phylogenetic studies from a genomic perspective. However, these studies have been restricted to a sparse number of species with available reference genomes. Thus, several issues inside the eutherian mammals phylogeny remain unresolved. This may be due in part to limited taxon sampling, as taxonomic density is known to affect phylogenetic resolution. In this context, we present a protocol to increase taxon coverage using high-throughput sequencing data (RNA or DNA) generated for other biological studies and available in public databases. Following this procedure we addressed pending or controversial issues concerning the phylogenetic position of Dermoptera, Pholidota and Chiroptera, considering multiple and independent loci. Also for Chiroptera and Arctoidea we evaluated the relationships of the lineages that compose it. Although the maximum number of genes used is moderate (95), in some cases taxon coverage doubles that of previous related studies. Globally, all coalescent-based (STAR, MP-EST and ASTRAL) and concatenated (IQ-TREE and BEAST2) methods used for species tree reconstruction were consistent to each other and most of interrogated nodes received high statistical support.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mamíferos/classificação , Mamíferos/genética , Animais , Fases de Leitura Aberta/genética , Filogenia , Especificidade da Espécie
5.
Chemosphere ; 176: 81-88, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28259082

RESUMO

A study is made to evaluate the bioaccessibility of heavy metals in contaminated soils through a simple bioaccessibility extraction test (SBET), applied to the analysis of both the gastric and intestinal phases. Soils with high metal content of the Mapocho, Cachapoal, and Rancagua series were studied; they are located in suburban areas of large cities in the central valley of Chile. The bioaccessible concentrations of Cd, Cr, Cu, Ni, Pb, and Zn were related to the main physicochemical characteristics of the soils and to the chemical forms obtained by sequential extraction. The elements Cd, Cu, Ni, and Zn are distributed in the soils between the exchangeable fractions, bound to oxides, to organic matter, and in the residual fraction. On the other hand, Cr and Pb are found mainly in the fractions bound to organic matter and in the residual fraction. The three soils have a high Cu content, (640-2060 mg/kg), in the order Cachapoal > Rancagua > Mapocho. The SBET test allowed establishing a different bioaccessibility for the elements in the soil. Cu was notoriously bioaccessible in both the gastric and intestinal phases in the three soils, reaching more than 50% in the Cachapoal and Rancagua soils. The other elements, regardless of the soil, were bioaccessible only in one of the phases, more frequently in the gastric phase. The multiple correlation study indicates that the metal forms have a higher incidence than the soil's physicochemical factors on the extractability to evaluate the human oral bioaccessibility of the metals.


Assuntos
Monitoramento Ambiental/métodos , Poluição Ambiental/análise , Metais Pesados/análise , Poluentes do Solo/análise , Chile , Cidades , Absorção Gástrica , Humanos , Absorção Intestinal , Modelos Biológicos , Solo/química
6.
Rev Esp Anestesiol Reanim ; 59(1): 6-11, 2012 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-22429630

RESUMO

OBJECTIVES: To evaluate whether Levosimendan has any impact on peri-operative mortality in cardiac surgery. MATERIAL AND METHODS: A literature search was performed with the main purpose of looking for mortality in cardiac surgery. Data tabulated by both the fixed effects model and the random effects model were analysed based on the method by Peto. The statistical heterogeneity and inconsistency was estimated and quantified, as well as performing a sensitivity analysis to test the influence of individual studies on the overall result. All the calculations and statistical analyses were performed using the software; "Comprehensive Meta-Analysis" V2.0 and "StatsDirect statistical software" V 2.7.8. At the same time, possible publication bias was also determined. RESULTS: A total of 169 articles were found, from which 13 studies were finally included in the meta-analysis; 12 randomised and one of them retrospective with paired data. The global analysis showed that the use of levosimendan was associated with a significant reduction in postoperative mortality. CONCLUSIONS: The meta-analysis showed that the use of Levosimendan was associated with a reduction in mortality in patients subjected to cardiac surgery, although there is still no definitively clear evidence. Additional randomised and multicentre clinical studies, with a much larger number of patients are required, in which hospital mortality and mortality at 6 months are analysed as the primary outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Cardiotônicos/uso terapêutico , Hidrazonas/uso terapêutico , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Piridazinas/uso terapêutico , Vasodilatadores/uso terapêutico , Humanos , Simendana
7.
J Chromatogr A ; 1218(24): 3771-80, 2011 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-21546028

RESUMO

Allergic asthma represents an important public health issue with significant growth over the years, especially in the paediatric population. Exhaled breath is a non-invasive, easily performed and rapid method for obtaining samples from the lower respiratory tract. In the present manuscript, the metabolic volatile profiles of allergic asthma and control children were evaluated by headspace solid-phase microextraction combined with gas chromatography-quadrupole mass spectrometry (HS-SPME/GC-qMS). The lack of studies in breath of allergic asthmatic children by HS-SPME led to the development of an experimental design to optimize SPME parameters. To fulfil this objective, three important HS-SPME experimental parameters that influence the extraction efficiency, namely fibre coating, temperature and time extractions were considered. The selected conditions that promoted higher extraction efficiency corresponding to the higher GC peak areas and number of compounds were: DVB/CAR/PDMS coating fibre, 22 °C and 60 min as the extraction temperature and time, respectively. The suitability of two containers, 1L Tedlar® bags and BIOVOC®, for breath collection and intra-individual variability were also investigated. The developed methodology was then applied to the analysis of children exhaled breath with allergic asthma (35), from which 13 had also allergic rhinitis, and healthy control children (15), allowing to identify 44 volatiles distributed over the chemical families of alkanes (linear and ramified) ketones, aromatic hydrocarbons, aldehydes, acids, among others. Multivariate studies were performed by Partial Least Squares-Discriminant Analysis (PLS-DA) using a set of 28 selected metabolites and discrimination between allergic asthma and control children was attained with a classification rate of 88%. The allergic asthma paediatric population was characterized mainly by the compounds linked to oxidative stress, such as alkanes and aldehydes. Furthermore, more detailed information was achieved combining the volatile metabolic data, suggested by PLS-DA model, and clinical data.


Assuntos
Asma/metabolismo , Testes Respiratórios/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos/análise , Microextração em Fase Sólida/métodos , Adolescente , Análise de Variância , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Compostos Orgânicos/isolamento & purificação
9.
Vitae (Medellín) ; 16(2): 228-236, mayo-ago. 2009.
Artigo em Espanhol | LILACS | ID: lil-533873

RESUMO

En este estudio, se perfilan cromátograficamente sesenta y cinco (65) muestras decomisadas de clorhidrato de cocaína. Se les determina la pureza y se hace análisis cualitativo de adulterantes, diluyentes y solventes residuales ocluidos. En las muestras se detecta la presencia de tropacocaína, norcocaína, cis-cinnamoilcocaína, trans-cinnamoilcocaína, benzoilecgonina, así como de los adulterantes cafeína, fenacetina, levamisol e hidroxicina. En el análisis cuantitativo se encuentra que la pureza de cocaína más baja fue del 64.58% y la más alta del 95.83%. En cuanto a solventes residuales, se detectan 136 compuestos de esta naturaleza, algunos de los cuales fueron identificados preliminarmente. Los anteriores resultados aportan al conocimiento de la química forense y del potencial toxicológico de muestras de clorhidrato de cocaína producidas e incautadas en Colombia.


Assuntos
Cocaína , Cromatografia Gasosa , Perfil de Saúde
10.
J Agric Food Chem ; 56(16): 7339-46, 2008 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-18642844

RESUMO

The sorption-desorption of two different pesticides, linuron and metalaxyl, by woods was studied. Sorbent/solution ratio and sorption kinetics were also determined. Untreated wood and water, NaOH, HCl, and octadecyltrimethylammonium bromide (ODTMA) treated pine (softwood) and oak (hardwood) were used as sorbents. Linuron and metalaxyl were sorbed by untreated woods up to 80 and 40%, respectively, in a short time when the sorbent/solution ratio of 1:10 was used. Sorption of pesticides was significantly higher by pine, having higher lignin content, than by oak. Freundlich sorption constants (K(f)) were 96.2 and 74.4 (linuron) and 8.28 and 4.95 (metalaxyl) for untreated pine and oak woods and increased 1.04-2.35-fold (linuron) and 1.33-2.17-fold (metalaxyl) when woods were treated. The sorption was higher by HCl- and ODTMA-treated woods. Additionally, Freundlich desorption constants also indicated greater sorption irreversibility of both pesticides for treated woods than for untreated woods. The results revealed wood residues as a promising, low-cost, and environmentally friendly material to immobilize pesticides in soils, preventing water contamination. Wood treatments aimed at removing soluble wood extracts or at modifying wood chemical structure could increase their sorption capacity.


Assuntos
Alanina/análogos & derivados , Fungicidas Industriais/química , Herbicidas/química , Linurona/química , Madeira/química , Adsorção , Alanina/química , Alcanos/farmacologia , Ácido Clorídrico/farmacologia , Cinética , Pinus/química , Compostos de Amônio Quaternário/farmacologia , Quercus/química , Hidróxido de Sódio/farmacologia , Soluções , Poluição da Água/prevenção & controle , Madeira/efeitos dos fármacos
11.
Qual Life Res ; 17(2): 179-93, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18175207

RESUMO

OBJECTIVE: The purpose of this paper is to summarize the best evidence regarding the impact of providing patient-reported outcomes (PRO) information to health care professionals in daily clinical practice. METHODS: Systematic review of randomized clinical trials (Medline, Cochrane Library; reference lists of previous systematic reviews; and requests to authors and experts in the field). RESULTS: Out of 1,861 identified references published between 1978 and 2007, 34 articles corresponding to 28 original studies proved eligible. Most trials (19) were conducted in primary care settings performed in the USA (21) and assessed adult patients (25). Information provided to professionals included generic health status (10), mental health (14), and other (6). Most studies suffered from methodologic limitations, including analysis that did not correspond with the unit of allocation. In most trials, the impact of PRO was limited. Fifteen of 23 studies (65%) measuring process of care observed at least one significant result favoring the intervention, as did eight of 17 (47%) that measured outcomes of care. CONCLUSIONS: Methodological concerns limit the strength of inference regarding the impact of providing PRO information to clinicians. Results suggest great heterogeneity of impact; contexts and interventions that will yield important benefits remain to be clearly defined.


Assuntos
Satisfação do Paciente , Qualidade de Vida , Retroalimentação , Indicadores Básicos de Saúde , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Actas Urol Esp ; 31(5): 548-52, 2007 May.
Artigo em Espanhol | MEDLINE | ID: mdl-17711175

RESUMO

INTRODUCTION AND OBJECTIVES: To report one case of prostatic abscess and subdural empyema by Staphylococcus aureus. METHODS: We describe the case of a 51 year old male patient who was diagnosed of prostatic abscess and subdural empyema by Staphilococcus aureus. We use clinical presentation and physical exploration based on rectal digital examination, as diagnostic approach method. And computerized axial tomography and transrectal ultrasonography, which allows the guided needle drainage of the abscess, as diagnostic confirmation methods. RESULTS: The clinical picture resolved with the transrectal ultrasonography guided needle aspiration of the abscess and conservative treatment with antibiotics and urinary diversion. CONCLUSIONS: Prostatic abscess is an uncommon entity nowadays. Provided the great variety of symptoms, a great degree of clinical suspicion is needed for the diagnosis, and once it is got it, immediate aggressive treatment must be initiated. Transrectal ultrasonography allows not only the diagnosis, but also the drainage of the abscess. The culture of the obtained material identifies the etiological agent and the most specific antibiotic therapy.


Assuntos
Abscesso/complicações , Empiema Subdural/etiologia , Doenças Prostáticas/complicações , Infecções Estafilocócicas/complicações , Abscesso/diagnóstico , Abscesso/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Prostáticas/diagnóstico , Doenças Prostáticas/terapia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/terapia
13.
J Anim Breed Genet ; 124(4): 208-13, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17651323

RESUMO

In this study we applied equivalence testing methods to prove the absence of differences in genetic values of ewes with different PrP genotypes. In particular, the milk production genetic value equivalence of ARR ovine prion protein (PrP) genotypes was analysed. There is no scientific evidence implying that the performances and genetic values of different PrP genotypes will be different, but it is interesting to confirm that the performance of one genotype is indistinguishable from another before starting a genetic scrapie control programme. Genotyping was performed on 204 ewes from a Spanish population of Lacaune breed. Ewes were sampled from the lower and upper tails for the distribution of estimated breeding value (EBV) for standardized lactation. The conditional probability that the number of ARR alleles contained in the group of higher EBV was larger than that found in the group of lower EBV was found to be in the interval between the true value (1/2) and two different pre-specified bounds (0.1 and 0.2). The results evidence the equivalence of ARR PrP genotypes for milk production EBV, and lead to the conclusion that the average genetic values for milk production of Lacaune flocks considered will not be affected by the selection of ewe carriers of resistance scrapie alleles (p<0.05).


Assuntos
Cruzamento , Genótipo , Doenças Priônicas/genética , Príons/genética , Ovinos/genética , Animais , Feminino , Masculino
14.
Scanning ; 28(6): 327-32, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17181134

RESUMO

A new high (24%)-chromium alloy was experimentally manufactured by combining the particular chemical composition of various materials with the use of thermal treatments to produce pump impellers for the sugar industry. The alloy metal was tested in situ in a sugar medium and then evaluated by electrochemical measurements; the two former procedures were associated with a nontraditional method to assess the susceptibility and resistance to corrosion. Potentiostatic and atomic absorption measurements were carried out to characterize the degradation and damage morphology by scanning electron microscopy (SEM) observations. The trials proved a good performance for the new alloy in the sugar medium in spite of nonsignificant localized damages involving erosion-corrosion mechanisms and surface microcrackings of the material.

15.
Rev Med Liege ; 61(5-6): 488-93, 2006.
Artigo em Francês | MEDLINE | ID: mdl-16910280

RESUMO

The prescription of a pharmacological agent concludes most medical visits. The rational basis of drug prescription by the physician relies on numerous pharmacodynamic, pharmacokinetic, pragmatic and economic considerations. However, it is a pity to notice that one patient out of two does not strictly follow the pharmacological treatment as it was prescribed. This article analyses some problems of the patient-doctor relationship, which may reduce medication compliance, and provides practical advice for improving such a situation in order to enhance both efficacy and safety of drug prescribing.


Assuntos
Prescrições de Medicamentos/normas , Humanos , Relações Médico-Paciente , Guias de Prática Clínica como Assunto
16.
Hum Exp Toxicol ; 21(5): 263-7, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12141397

RESUMO

GM3 is a ganglioside that has been biochemically identified as dominating the cell surface of several human tumours, but is also found on human normal cells at much lower density. Since GM3 is widely distributed in essentially all types of animal cells, there is a conflict with the concepts of tumour-associated antigen, immunogen, and toxicity. We have designed a GM3-based cancer vaccine for the treatment of human breast and melanoma tumours. Prior to the Phase I clinical trial, we carried out a 12-month dose repeated toxicity study in five male Macaca fascicularis monkeys. Four male monkeys were treated with placebo in a similar way. During the study, no differences were observed between control and treated monkeys related to daily clinical observations (other than local damage) including rectal temperature, blood pressure, respiratory and cardiac rates, weight gain, biochemical and hematological parameters (with the exception of transitory pathological changes), and anti-DNA and anti-nuclear antibodies, although treated monkeys consistently developed both IgM- and IgG-specific anti-GM3 antibodies. Sixty per cent of treated monkeys developed moderate local reactions at the injection site, which disappeared without sequels. We concluded that this GM3 cancer vaccine overcame in monkeys the natural tolerance to GM3 ganglioside evidenced by a strong immune response, while the local reactions elicited-were transitory without apparent important systemic toxicity effects.


Assuntos
Vacinas Anticâncer/toxicidade , Gangliosídeo G(M3)/toxicidade , Macaca fascicularis , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antineoplásicos/imunologia , Peso Corporal/efeitos dos fármacos , Neoplasias da Mama/imunologia , Neoplasias da Mama/prevenção & controle , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Cães , Avaliação Pré-Clínica de Medicamentos , Gangliosídeo G(M3)/administração & dosagem , Gangliosídeo G(M3)/imunologia , Testes Hematológicos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Testes de Função Renal , Testes de Função Hepática , Masculino , Melanoma/imunologia , Melanoma/prevenção & controle , Proteolipídeos/administração & dosagem , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/prevenção & controle , Testes de Toxicidade
17.
Xenobiotica ; 32(2): 131-40, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11868969

RESUMO

1. 10,11-Dihydro-10-hydroxyimino-5H-dibenzo/b, f/azepine-5-carboxamide (BIA 2-024) is a new anti-epileptic drug similar to oxcarbazepine (OXC) in structure and efficacy, but with a preferred pharmacodynamic profile. It possesses high in vitro activity, but since oximes are usually metabolized to their corresponding ketones, it is important to know whether its is vivo potency is a result of acting as a prodrug of OXC or if it is acting on its own. 2. The drug was given orally to rats, mice and rabbits, the metabolites identified and pharmacokinetic profiles compared between those species. Furthermore, the pharmacokinetic profile of the main metabolite was established in the rat. The results were compared to in vitro metabolism studies with liver microsomes from different mammalian species and humans. 3. In an atypical reaction for oximes, BIA 2-024 in rats was rapidly (t(max) = 2h) metabolized to the non-active 10-nitro-derivative (BIA 2-254), whereas rabbits and particularly mice oxidized the oxime moiety to a much lower extent. BIA 2-254 was then transformed to OXC and subsequently to the 10-hydroxy derivative and other minor metabolites. 4. In vitro data showed a very similar cross-species behaviour as the in vivo results; human liver microsomes catalysed the oxidation of BIA 2-024 to the nitro metabolite only at a low rate, and the same was observed for the subsequent metabolism to OXC. 5. The results allow prediction of the in vivo metabolism of BIA 2-024 in humans, where this drug is most likely absorbed efficiently and excreted mainly as the parent compound with a relatively low hepatic clearance. With the exception of rat, BIA 2-024 does not act as a prodrug of OXC.


Assuntos
Anticonvulsivantes/metabolismo , Dibenzazepinas/metabolismo , Animais , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Encéfalo/metabolismo , Dibenzazepinas/sangue , Dibenzazepinas/farmacocinética , Feminino , Humanos , Fígado/metabolismo , Masculino , Camundongos , Coelhos , Ratos , Ratos Wistar , Especificidade da Espécie
19.
Eur J Pharmacol ; 420(1): 27-32, 2001 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-11412836

RESUMO

1-[3,4-Dihydroxy-5-nitrophenyl]-2-phenyl-ethanone (BIA 3-202) is a new long-acting catechol-O-methyltransferase (COMT) inhibitor with limited access to the brain. The present study evaluated the interference of BIA 3-202 upon levels of L-3,4-dihydroxyphenylalanine (L-DOPA) and metabolites in plasma (3-O-methyl-L-DOPA) and brain [3-O-methyl-L-DOPA, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] in rats orally treated with L-DOPA (20 mg/kg) plus benserazide (30 mg/kg). At different time points (1, 3 and 6 h) after the administration of BIA 3-202 (0, 3, 10 and 30 mg/kg) or L-DOPA plus benserazide, rats were sacrificed and the right striatum was quickly dissected out and stored for the assay of L-DOPA, 3-O-methyl-L-DOPA, dopamine and amine metabolites. Levels of L-DOPA, 3-O-methyl-L-DOPA, dopamine, DOPAC and HVA in the striatum in L-DOPA plus benserazide-treated rats were higher than in vehicle-treated rats. However, this increase in striatal L-DOPA, dopamine, DOPAC and HVA was, in a dose- and time-dependent manner, even higher (P<0.05) in rats given BIA 3-202 (3, 10 and 30 mg/kg). This effect was accompanied by a marked decrease in 3-O-methyl-L-DOPA levels in the striatum of L-DOPA plus benserazide-treated rats. Increases in levels of L-DOPA and decreases in 3-O-methyl-L-DOPA levels in plasma also accompanied the administration of BIA 3-202. BIA 3-202 did not significantly affect levels of DOPAC and HVA in the striatum in vehicle-treated rats. It is concluded that administration of BIA 3-202 enhances the availability of L-DOPA to the brain by reducing its O-methylation in the periphery, which may prove beneficial in parkinsonian patients treated with L-DOPA plus an aromatic amino acid decarboxylase inhibitor.


Assuntos
Acetofenonas/farmacologia , Encéfalo/efeitos dos fármacos , Inibidores de Catecol O-Metiltransferase , Inibidores Enzimáticos/farmacologia , Levodopa/farmacocinética , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Disponibilidade Biológica , Encéfalo/metabolismo , Catecol O-Metiltransferase/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/sangue , Di-Hidroxifenilalanina/metabolismo , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Ácido Homovanílico/metabolismo , Levodopa/sangue , Levodopa/metabolismo , Masculino , Metilação/efeitos dos fármacos , Ratos , Ratos Wistar , Fatores de Tempo , Tirosina/análogos & derivados
20.
Eur J Med Chem ; 36(3): 227-36, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11337101

RESUMO

A series of novel derivatives of oxcarbazepine (5), 10,11-dihydro-10-oxo-5H-dibenz/b,f/azepine-5-carboxamide was synthesised and evaluated for their anticonvulsant activity and sodium channel blocking properties. The oxime 8 was found to be the most active compound from this series, displaying greater potency than its geometric isomer 9 and exhibiting also the highest protective index value. Importantly, the metabolic profile of 8 differs from the already established dibenz/b,f/azepine-5-carboxamide drugs such as 1 and 5 which undergo rapid and complete conversion in vivo to several biologically active metabolites. In contrast 8 is metabolised to only a very minor extent leading to the conclusion that the observed anti-convulsant effect is solely attributable to 8. It is concluded that 8 may be as effective as 1 and 5 at controlling seizures and that the low toxicity and consequently high protective index should provide the compound with an improved side-effect profile.


Assuntos
Amidas/química , Amidas/síntese química , Anticonvulsivantes/síntese química , Anticonvulsivantes/farmacologia , Azepinas/síntese química , Azepinas/farmacologia , Animais , Anticonvulsivantes/farmacocinética , Azepinas/farmacocinética , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Carbamazepina/química , Carbamazepina/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Coelhos , Ratos , Ratos Wistar , Bloqueadores dos Canais de Sódio , Canais de Sódio/metabolismo , Especificidade da Espécie
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