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2.
Chemosphere ; 209: 480-488, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29940531

RESUMO

There is significant current interest in the application of magnetic (magnetite or maghemite) nanoparticles functionalised with chelating agents for the environmental remediation of metal contaminated waters and solutions. Whilst there is a body of knowledge about the potential remediation efficacy of such engineered nanoparticles from studies involving synthetic solutions of single metals, there is relatively little data involving mixed-metal solutions and virtually no studies about nanoparticle performance in chemically complex environmental solutions representing those to which a scaled-up nanoremediation process might eventually be applied. Therefore, we investigated the ability of diethylenetriaminepentaacetic acid (DTPA)-functionalised, silica-coated maghemite nanoparticles to extract potentially toxic (Cd, Co, Cu) and "non-toxic" (Ca, Mg) metals from solution (initial [metal] = 10 mg L-1; pH range: 2-8) and to extract a wider range of elements (As, Ca, Cd, Co, Cr, Cu, Mg, Na, Pb, Zn) from leachate obtained from 10 different contaminated soils with variable initial pH, (semi-)metal and dissolved organic carbon (DOC) concentrations. The functionalised nanoparticles could extract the potentially toxic metals with high efficiency (in general >70%) from single metal solutions and with efficiencies that were either unaffected or reduced from the soil leachates. Kd values remained high (>500 L kg-1), even for the soil leachate extractions. Our findings show that DOC and relatively high concentrations of non-toxic elements do not necessarily reduce the efficiency of metal contaminant removal by DTPA-functionalised magnetic nanoparticles and thus demonstrate the remediation potential of such particles when added to chemically complex soil-derived contaminated solutions.


Assuntos
Recuperação e Remediação Ambiental , Nanopartículas de Magnetita/química , Metais Pesados/isolamento & purificação , Ácido Pentético/química , Poluentes do Solo/química , Solo/química , Poluentes do Solo/análise
3.
Chemosphere ; 183: 519-527, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28570895

RESUMO

The ability of diethylenetriaminepentaacetic acid (DTPA)-functionalised, silica-coated magnetic nanoparticles to adsorb Pb and Zn from single and bi-metallic metal solutions and from solutions containing dissolved organic carbon was assessed. In all experiments 10 mL solutions containing 10 mg of nanoparticles were used. For single metal solutions (10 mg L-1 Pb or Zn) at pH 2 to 8, extraction efficiencies were typically >70%. In bi-metallic experiments, examining the effect of a background of either Zn or Pb (0.025 mmol L-1) on the adsorption of variable concentrations (0-0.045 mmol L-1) of the other metal (Pb or Zn, respectively) adsorption was well modelled by linear isotherms (R2 > 0.60; p ≤ 0.001) and Pb was preferentially adsorbed relative to Zn. In dissolved organic carbon experiments, the presence of fulvic acid (0, 2.1 and 21 mg DOC L-1) reduced Pb and Zn adsorption from 0.01, 0.1 and 1.0 mmol L-1 solutions. However, even at 21 mg DOC L-1 fulvic acid, extraction efficiencies from 0.01 to 0.1 mmol L-1 solutions remained >80% (Pb) and >50% (Zn). Decreases in extraction efficiency were significant between initial metal concentrations of 0.1 and 1.0 mmol L-1 indicating that at metal loadings between c. 100 mg kg-1 and 300 mg kg-1 occupancy of adsorption sites began to limit further adsorption. The nanoparticles have the potential to perform effectively as metal adsorbents in systems containing more than one metal and dissolved organic carbon at a range of pH values.


Assuntos
Benzopiranos/química , Poluentes Ambientais/análise , Chumbo/análise , Nanopartículas de Magnetita/química , Ácido Pentético/química , Dióxido de Silício/química , Zinco/análise , Adsorção , Substâncias Húmicas , Concentração de Íons de Hidrogênio , Modelos Teóricos , Soluções , Propriedades de Superfície
4.
J Proteomics ; 134: 193-202, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26778141

RESUMO

Posttranslational modifications and proteolytic processing regulate almost all physiological processes. Dysregulation can potentially result in pathologic protein species causing diseases. Thus, tissue species proteomes of diseased individuals provide diagnostic information. Since the composition of tissue proteomes can rapidly change during tissue homogenization by the action of enzymes released from their compartments, disease specific protein species patterns can vanish. Recently, we described a novel, ultrafast and soft method for cold vaporization of tissue via desorption by impulsive vibrational excitation (DIVE) using a picosecond-infrared-laser (PIRL). Given that DIVE extraction may provide improved access to the original composition of protein species in tissues, we compared the proteome composition of tissue protein homogenates after DIVE homogenization with conventional homogenizations. A higher number of intact protein species was observed in DIVE homogenates. Due to the ultrafast transfer of proteins from tissues via gas phase into frozen condensates of the aerosols, intact protein species were exposed to a lesser extent to enzymatic degradation reactions compared with conventional protein extraction. In addition, total yield of the number of proteins is higher in DIVE homogenates, because they are very homogenous and contain almost no insoluble particles, allowing direct analysis with subsequent analytical methods without the necessity of centrifugation. BIOLOGICAL SIGNIFICANCE: Enzymatic protein modifications during tissue homogenization are responsible for changes of the in-vivo protein species composition. Cold vaporization of tissues by PIRL-DIVE is comparable with taking a snapshot at the time of the laser irradiation of the dynamic changes that occur continuously under in-vivo conditions. At that time point all biomolecules are transferred into an aerosol, which is immediately frozen.


Assuntos
Raios Infravermelhos , Lasers , Tonsila Palatina/química , Pâncreas/química , Proteômica , Manejo de Espécimes , Animais , Humanos , Camundongos , Proteômica/instrumentação , Proteômica/métodos , Ratos Wistar , Manejo de Espécimes/instrumentação , Manejo de Espécimes/métodos
5.
Br Poult Sci ; 56(6): 696-707, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26447759

RESUMO

Three experiments were conducted to evaluate the applicability of the Taguchi method (TM) and optimisation algorithms to optimise the branch chain amino acids (BCAA) requirements in 0 to 7 d broiler chicks. In the first experiment, the standardised digestible (SID) amino acids and apparent metabolisable energy (AME) values of maize, wheat and soya bean meal were evaluated. In the second experiment, three factors including leucine (Leu), isoleucine (Ile) and valine (Val), each at 4 levels, were selected, and an orthogonal array layout of L16 (4(3)) using TM was performed. After data collection, optimisation of average daily gain (ADG) and feed conversion ratio (FCR) were obtained using TM. The multiobjective genetic algorithm (MOGA) and random search algorithm (RSA) were also applied to predict the optimal combination of BCAA for broiler performance. In the third experiment, a growth study was conducted to evaluate the applicability of obtained optimum BCAA requirements data by TM, MOGA and RSA, and results were compared with those of birds fed with a diet formulated according to Ross 308 recommendations. In the second experiment, the TM resulted in 13.45 g/kg SID Leu, 8.5 g/kg SID Ile and 10.45 g/kg SID Val as optimum level for maximum ADG (21.57 g/bird/d) and minimum FCR (1.11 g feed/g gain) in 0- to 7-d-old broiler chickens. MOGA predicted the following combinations: SID Leu = 14.8, SID Ile = 9.1 and SID Val = 10.3 for maximum ADG (22.05) and minimum FCR (1.11). The optimisation using RSA predicted Leu = 16.0, Ile = 9.5 and Val = 10.2 for maximum ADG (22.67), and Leu = 15.5, Ile = 9.0 and Val = 10.4 to achieve minimum FCR (1.08). The validation experiment confirmed that TM, MOGA and RSA yielded optimum determination of dietary amino acid requirements and improved ADG and FCR as compared to Aviagen recommendations. However, based on the live animal validation trial, MOGA and RSA overpredicted the optimum requirement as compared to TM. In general, the results of these studies showed that the TM may be used to optimise nutrient requirements for poultry.


Assuntos
Criação de Animais Domésticos/métodos , Galinhas/fisiologia , Isoleucina/metabolismo , Leucina/metabolismo , Modelos Biológicos , Necessidades Nutricionais , Valina/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos/fisiologia , Dieta/veterinária , Suplementos Nutricionais/análise , Digestão/efeitos dos fármacos , Masculino , Glycine max/química , Triticum/química , Zea mays/química
6.
Haematologica ; 97(2): 251-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22058195

RESUMO

BACKGROUND: The t(9;22) translocation leads to the formation of the chimeric breakpoint cluster region/c-abl oncogene 1 (BCR/ABL) fusion gene on der22, the Philadelphia chromosome. The p185(BCR/ABL) or the p210(BCR/ABL) fusion proteins are encoded as a result of the translocation, depending on whether a "minor" or "major" breakpoint occurs, respectively. Both p185(BCR/ABL) and p210(BCR/ABL) exhibit constitutively activated ABL kinase activity. Through fusion to BCR the ABL kinase in p185(BCR/ABL) and p210(BCR/ABL) "escapes" the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. A novel class of compounds including GNF-2 restores allosteric inhibition of the kinase activity and the transformation potential of BCR/ABL. Here we investigated whether there are differences between p185(BCR/ABL) and p210(BCR/ABL) regarding their sensitivity towards allosteric inhibition by GNF-2 in models of Philadelphia chromosome-positive acute lymphatic leukemia. DESIGN AND METHODS: We investigated the anti-proliferative activity of GNF-2 in different Philadelphia chromosome-positive acute lymphatic leukemia models, such as cell lines, patient-derived long-term cultures and factor-dependent lymphatic Ba/F3 cells expressing either p185(BCR/ABL) or p210(BCR/ABL) and their resistance mutants. RESULTS: The inhibitory effects of GNF-2 differed constantly between p185(BCR/ABL) and p210(BCR/ABL) expressing cells. In all three Philadelphia chromosome-positive acute lymphatic leukemia models, p210(BCR/ABL)-transformed cells were more sensitive to GNF-2 than were p185BCR/ABL-positive cells. Similar results were obtained for p185(BCR/ABL) and the p210(BCR/ABL) harboring resistance mutations. CONCLUSIONS: Our data provide the first evidence of a differential response of p185(BCR/ABL)- and p210(BCR/ABL)- transformed cells to allosteric inhibition by GNF-2, which is of importance for the treatment of patients with Philadelphia chromosome-positive acute lymphatic leukemia.


Assuntos
Proteínas de Fusão bcr-abl/antagonistas & inibidores , Leucemia Mielogênica Crônica BCR-ABL Positiva , Pirimidinas/farmacologia , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/fisiologia , Linhagem Celular Tumoral , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Pirimidinas/uso terapêutico
7.
Int J Cancer ; 122(12): 2744-52, 2008 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-18366061

RESUMO

The BCR/ABL oncogene is responsible for the phenotype of Philadelphia chromosome-positive (Ph+) leukemia. BCR/ABL exhibits an aberrant ABL-tyrosine kinase activity. The treatment of advanced Ph+ leukemia with selective ABL-kinase inhibitors such as Imatinib, Nilotinib and Dasatinib is initially effective but rapidly followed by resistance mainly because of specific mutations in BCR/ABL. Tetramerization of ABL through the N-terminal coiled-coil region (CC) of BCR is essential for the ABL-kinase activation. Targeting the CC-domain forces BCR/ABL into a monomeric conformation reduces its kinase activity and increases the sensitivity for Imatinib. We show that (i) targeting the tetramerization by a peptide representing the Helix-2 of the CC efficiently reduced the autophosphorylation of both unmutated and mutated BCR/ABL; (ii) Helix-2 inhibited the transformation potential of BCR/ABL independently of the presence of mutations; and (iii) Helix-2 efficiently cooperated with Imatinib as revealed by their effects on the transformation potential and the factor-independence related to BCR/ABL with the exception of mutant T315I. These findings support earlier observations that BCR/ABL harboring the T315I mutation have a transformation potential that is at least partially independent of its kinase activity. These data provide evidence that the inhibition of tetramerization inhibits BCR/ABL-mediated transformation and can contribute to overcome Imatinib-resistance.


Assuntos
Antineoplásicos/farmacologia , Biopolímeros/química , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Mutação , Piperazinas/farmacologia , Pirimidinas/farmacologia , Sequência de Bases , Benzamidas , Linhagem Celular , Primers do DNA , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Mutagênese Sítio-Dirigida , Fosforilação
8.
Pak J Biol Sci ; 10(18): 3103-8, 2007 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19090106

RESUMO

In a 3 months experiment, the effects of three different kinds of food rations including culture rotifers, commercial food and the equal amount mixture of these two foods were studied on some growth specifications and survival of the whitefish (Coregonus lavaretus) fry. The initial average weight and length of the fry were 0.009 g and 4 mm, respectively. The period of experiment was among April to July 2003. The assessed characteristics variance analysis showed that the different food treatments caused very significant differences among the all averages (p < 0.01). Comparing the characteristics averages showed that during the first month of experiment, the best results of weight (0.029 g), total length (8.78 mm), specific growth rate (5.36%) and food efficiency (63.48%) were obtained in live food treatment, whereas the weakest averages of referred characteristics were observed in commercial food treatment. During the last month of experiment, some of the above results reversed so that the best averages of specific growth rate (3.73%) and food efficiency (44.3%) were observed in commercial food treatment. The results of this study showed that the use of rotifer as live food for fry has provided better survival rate than the other two treatments. However, this food could not provide the best results for the all measured characteristics in all of the experiment period, for the reason that during the third month of experiment period, using commercial food treatment which consist of more miscellaneous nutrient components, created better results for some fry's characteristics than the live food.


Assuntos
Ração Animal , Salmonidae/crescimento & desenvolvimento , Salmonidae/fisiologia , Criação de Animais Domésticos , Ciências da Nutrição Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ingestão de Energia , Metabolismo Energético , Pesqueiros , Fatores de Tempo
9.
Environ Pollut ; 122(2): 183-93, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12531306

RESUMO

Polecats (Mustela putorius) in Britain are currently expanding their range eastwards from Wales to reoccupy central and eastern areas of England. Second-generation anticoagulant rodenticides (SGARs), to which polecats are exposed by eating contaminated prey, are used more extensively in these central and eastern regions, leading to fears of increased exposure, and possible resultant mortality. We measured bromadiolone, difenacoum, flocoumafen and brodifacoum concentrations in the livers of 50 polecats from areas that included newly recolonised habitats and found that at least one SGAR was detected in the livers of 13 out of 37 (35.1%) male and 5 out of 13 (38.5%) female polecats. Difenacoum and bromadiolone were detected most frequently. We then combined these data with measurements on another 50 individuals from earlier studies to create a dataset for 100 polecats collected throughout the 1990s from across the whole of their current range. Using this dataset, we determined if there was any evidence that contamination in polecats had increased during the 1990s and whether animals from England were more contaminated than those from Wales, as might be expected given regional differences in the patterns of SGAR use. Overall, 31 of the 100 polecats analysed to date contained SGAR residues. The incidence was a little higher (40%) in animals that died between January and June and this probably better reflects the overall proportion of animals that are sub-lethally exposed. There was no statistically significant change during the 1990s in the proportion of polecats exposed to SGARs nor any evidence that greater use of SGARs in England resulted in more contamination of polecats. Contrary to expectation, the proportion of animals that contained difenacoum was marginally higher in Wales than elsewhere.


Assuntos
Anticoagulantes/análise , Furões/metabolismo , Resíduos de Praguicidas/análise , Rodenticidas/análise , 4-Hidroxicumarinas/análise , Animais , Feminino , Fígado/química , Masculino , Fatores de Tempo , Reino Unido
10.
Ophthalmic Physiol Opt ; 21(4): 262-7, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11430619

RESUMO

Optimal delivery of healthcare requires consideration of various costs. A foldable intraocular lens (IOL) is more expensive than an equivalent rigid IOL. However, surgical and post-operative costs may make a foldable IOL economically preferable. We compared the economic costs of cataract surgery plus implantation of a foldable IOL with implantation of a rigid IOL. Prospective audit of the clinical records of 82 pseudophakes; 39 implanted with a rigid IOL and 43 implanted with a foldable IOL by one surgeon. Average follow-up periods were 25 +/- 7 months and 23 +/- 5 months respectively. There was no difference between the two groups for the follow-up period (P = 0.55), number of post-operative complications (P = 0.25) or cost of post-operative visits (P = 0.83). The cost of single-use theatre equipment was greater for the rigid-IOL group (P= 0.0001). The total identified cost per patient was greater for the foldable-IOL group (P = 0.0001). Despite possible technical advantages, implantation of the foldable IOL did not provide an economic benefit, either in the initial cost or in the costs of post-operative care. Over the 2-year period, implanting with the rigid IOL cost, on average, Pound Sterling57 less per patient. Despite this economic difference, a cost-benefit analysis is required, since other factors may be more important.


Assuntos
Extração de Catarata/economia , Custos Hospitalares , Lentes Intraoculares/economia , Facoemulsificação/economia , Procedimentos Cirúrgicos Ambulatórios/economia , Extração de Catarata/métodos , Seguimentos , Humanos , Implante de Lente Intraocular/economia , Auditoria Médica , Complicações Pós-Operatórias , Estudos Prospectivos , Escócia
11.
Sci Total Environ ; 280(1-3): 45-54, 2001 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-11763272

RESUMO

The wolf Canis lupus is a major terrestrial predator in eastern Europe and, as a top carnivore, may be exposed to high concentrations of contaminants that are readily transferred through the food chain. Despite this, there are few published data on pollutant and pesticide levels in wolves. This study utilised tissues from animals legally killed by hunters for other reasons (animals were not killed for the purposes of this study) to carry out the only detailed investigation of contaminants in wolves in Europe and the first in animals from Eastern Europe. The livers of 58 wolves from the Tver and Smoliensk regions of northwest Russia (54 degrees N 31 degrees E to 57 degrees N 35 degrees E) were analysed for seven organochlorine pesticides, 24 PCB congeners, Aroclor 1254-matched summed PCBs (sigmaPCBs), total mercury, cadmium and lead. Cadmium, most of the organochlorine pesticides and many PCB congeners were not detectable in any of the wolves. Hexachlorobenzene, alpha-HCH, pp'DDE, PCB congeners 118, 138, 149 and 156 and lead were detected in up to 6% of livers. Dieldrin, PCB congeners 153, 170 and 180, sigmaPCBs and mercury were detected more frequently. Contaminant levels were generally low; maximum wet weight concentrations of any of the organochlorine pesticides, sigmaPCBs and mercury were less than 0.1, 1 and 0.25 microg g(-1), respectively. PCB congeners 153, 170 and 180 accounted for 41% of the sigmaPCBs. Dieldrin, sigmaPCBs and mercury concentrations did not vary significantly between males and females nor between adult and juvenile (< 12 months old) wolves apart from the sigmaPCB concentration, which was on average five times higher in adults than juveniles. Liver residues were generally below the level normally associated with adverse effects except for lead levels which exceeded the critical 5 microg g(-1) dry wt. concentration in three of the 58 animals examined.


Assuntos
Poluentes Ambientais/farmacocinética , Inseticidas/farmacocinética , Metais Pesados/farmacocinética , Bifenilos Policlorados/farmacocinética , Lobos , Fatores Etários , Animais , Monitoramento Ambiental , Poluentes Ambientais/análise , Feminino , Cadeia Alimentar , Inseticidas/análise , Fígado/química , Masculino , Metais Pesados/análise , Bifenilos Policlorados/análise , Federação Russa , Fatores Sexuais , Distribuição Tecidual
12.
Eye (Lond) ; 13 ( Pt 3a): 329-35, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10624427

RESUMO

PURPOSE: To examine post-operative visual outcomes when using micro-incision surgery and a three-piece, foldable acrylic intraocular lens (IOL) and when using small-incision surgery and a one-piece, rigid polymethyl-methacrylate (PMMA) IOL. METHODS: Phacoemulsification and IOL implantation was conducted by one surgeon on 86 subjects (aged 50-89 years) with cataracts. Of these subjects, 67 completed the study. Subjects were implanted either with a foldable IOL (n = 38) or a rigid IOL (n = 29). Best corrected Snellen visual acuity and contrast sensitivity (2-28 cycles/degree) were measured approximately 2 months post-operatively. Comparisons were made between the pseudophakic groups and an additional group of 28 age-matched, normal subjects (aged 58-81 years). Non-parametric (Kruskal-Wallis and Mann-Whitney U) as well as parametric (ANOVA and Pearson) statistics tests were used in the analysis of results. RESULTS: All pseudophakes had corrected visual acuity of 6/9 or better. There were no significant differences in visual acuity (Kruskal-Wallis, p = 0.61) or contrast sensitivity (ANOVA, p = 0.33) between the three groups. The mean residual refractive error of the foldable IOL group was hypermetropic in comparison with the rigid IOL group but not significant at the 99% level of probability (Mann-Whitney U, p = 0.02). There was no significant difference in astigmatism between the groups. CONCLUSIONS: Implanting a foldable acrylic IOL gave no post-operative benefit in visual acuity and contrast sensitivity to pseudophakes over a less expensive rigid PMMA IOL, within this post-operative period. This study did not provide a comparison between the two lenses regarding post-operative complications, in particular the important long-term complication of posterior capsular opacification (PCO). Until and if any particular advantage of a given IOL in reduced incidence of PCO is confirmed, it appears more economical to implant the conventional rigid PMMA IOL using small-incision surgery.


Assuntos
Sensibilidades de Contraste , Lentes Intraoculares , Pseudofacia/fisiopatologia , Acuidade Visual , Resinas Acrílicas , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Humanos , Pessoa de Meia-Idade , Polimetil Metacrilato , Período Pós-Operatório , Estudos Prospectivos , Pseudofacia/psicologia , Refração Ocular , Resultado do Tratamento
13.
Artigo em Inglês | MEDLINE | ID: mdl-9720101

RESUMO

The objective of this study was to assess whether bony landmarks used for the standard inferior alveolar nerve block can be used to accurately determine the position of the mandibular foramen and whether panoramic radiographs are appropriate for this purpose. A total of 11 landmarks from 79 panoramic radiographs and 70 corresponding cases of oblique (45-degree) cephalometric radiographs were examined. Ten measurements of the distance from each landmark to the mandibular foramen, as well as 6 ratios from these distances, were calculated from all radiographs. The results showed that the position of the mandibular foramen was highly individualistic and not consistently related to traditional clinical landmarks. Panoramic radiographs were as good as oblique cephalometric radiographs for the locating of the mandibular foramen. No age or gender correlations were found. It was concluded that the mandibular foramen can be localized in panoramic radiographs but that its relation to bony landmarks is highly variable.


Assuntos
Anestesia Dentária , Mandíbula/diagnóstico por imagem , Nervo Mandibular/diagnóstico por imagem , Bloqueio Nervoso , Adolescente , Adulto , Fatores Etários , Cefalometria/métodos , Criança , Feminino , Humanos , Masculino , Radiografia Panorâmica/métodos , Fatores Sexuais
14.
Can J Physiol Pharmacol ; 74(2): 150-6, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8723027

RESUMO

The objective of this study was to determine the effects of 5-fluorouracil (5FU) on the expression of individual cytochrome P450 (CYP) isozymes in rat liver at the catalytic activity and apoprotein levels. Male Fischer 344 rats (9 to 10) weeks old) received a single intraperitoneal injection of 5FU (120 mg/kg) or vehicle. Rats were euthanized 1, 2, 7, or 14 days following drug administration. Hepatic microsomes were isolated and used for determination of spectral CYP and heme content and steroid hydroxylation activity, and immunoblot analysis of CYP apoproteins. 5FU treatment did not alter the levels of total microsomal CYP and heme. The major male-specific CYP isozyme, CYP2C11, was downregulated by 5FU treatment, as revealed by a significant decrease in CYP2C11 immunoreactive protein and catalytic activity (progesterone 2 alpha-hydroxylase) levels at day 14. Members of the CYP3A subfamily also appeared to be modulated by 5FU treatment in a complex manner. Two days following 5FU exposure, CYP3A immunoreactive protein was increased compared with vehicle control; however, 7 days after treatment, both CYP3A immunoreactivity and catalytic activity (progesterone 6 beta-hydroxylase) were suppressed by 5FU. 5FU appears to modulate the expression of constitutive CYP isozymes in the liver of male rats. The modulation of the catalytic activity of CYP2C11 and CYP3A by 5FU appears to be due to changes in the expression of the corresponding proteins.


Assuntos
Antimetabólitos/farmacologia , Hidrocarboneto de Aril Hidroxilases , Sistema Enzimático do Citocromo P-450/metabolismo , Fluoruracila/farmacologia , Isoenzimas/metabolismo , Fígado/efeitos dos fármacos , Esteroide 16-alfa-Hidroxilase , Animais , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/análise , Família 2 do Citocromo P450 , Heme/metabolismo , Immunoblotting , Fígado/enzimologia , Masculino , Microssomos Hepáticos/enzimologia , Oxirredutases N-Desmetilantes/análise , Ratos , Ratos Endogâmicos F344 , Esteroide Hidroxilases/análise , Esteroide Hidroxilases/metabolismo , Fatores de Tempo
15.
Biofouling ; 10(1-3): 213-24, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-22115113

RESUMO

Two major problems associated with biofouling studies are the lack of broad scale testing and failure to use consistent standards among different assays or studies. To address these issues the activity of two biologically active natural products, elatol and deschloroelatol, isolated from the marine red alga Laurencia rigida, and three commonly used biocides, Nopcocide N-96™, Irgarol 1051™ and Sea-Nine 211™, was compared, in a broad spectrum of bioassays. The activity of the different compounds varied substantially among different bioassay tests. Elatol and deschloroelatol had a narrow range of activity with strongest effects against invertebrate larvae. Both compounds were highly toxic. However, neither compound had strong activity against marine bacteria or the common epiphyte Ulva lactuca. Irgarol 1051 also had a narrow range of activity, only affecting algal settlement strongly. Nopcocide N-96 and Sea-Nine 211 had moderate to strong activity across the spectrum of bioassays, viz. growth of marine bacteria (Vibrio fischeri, Serratia sp.), inhibition of settlement of macroalgae (Ulva lactuca), toxicity (Balanus amphitrite), and inhibition of settlement of invertebrate larvae (Balanus amphitrite, Bugula neritina). Based on the results it is proposed that Sea-Nine 211, because of its broad spectrum activity, be used as a standard for comparative assessments of the antifouling activity of marine natural products and analogues.

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