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1.
Entropy (Basel) ; 25(4)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37190409

RESUMO

In this work, a numerical analysis of three different flat plate solar collectors was conducted using their entropy generation rates. Specifically, the Computational Fluid Dynamics (CFD) technique was used to compare the detailed performance of conventional and zigzag tube geometries of flat plate solar collectors (FPCs) in terms of their entropy generation rates. The effects of fluid viscosity, heat transfer, and heat loss of the flat plate solar collectors were considered for the local and global entropy generation rate analyses. Variations on the inlet volumetric flow rate of the FPCs from 1.0 to 9.0 L/min were simulated under the average solar radiation for one year in the state of Guanajuato, Mexico. The results illustrate and discuss the temperatures, pressures, and global entropy generation rates for volumetric flow variations. The velocity, temperature, and pressure distributions and the maps of the local entropy generation rates inside the collectors are presented and analyzed for the case with a flow rate of 3.0 L/min. These results demonstrate that the zigzag geometries achieved higher outlet temperatures and greater entropy generation rates than the conventional geometry for all the volumetric flow rates considered.

2.
MethodsX ; 8: 101286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434806

RESUMO

Among natural freshwater pollutants, cyanotoxins, mycotoxins, and phytotoxins are the most important and less studied. Their identification in surface water is challenging especially cause of the lack of standards and established analytical parameters. Most target methods focus one or a single group of compounds with similar characteristics. Here we present an AIF fast method for the tentative identification of natural toxins in water. Respect to the previous method [1], it offers higher performances for the acquisition of unknown compounds at low levels for higher number of analytes. The key aspects of the method are: • The qualitative screening DIA-AIF workflow using Q Exactive Orbitrap. Both targeted and suspect screening bases have been combined with online databases and suspect list to retrieve candidates as suspect natural toxins and their metabolites or degradation products. • The in-silico analysis of mass spectrums allowed a fast structural characterization. • The workflow has been finally applied to real samples coming from the Czech Republic, Italy, and Spain allowing the determination of 17 suspect natural toxins, 4 of them confirmed. None toxin passed the limit of 1 µg/L taken from the legislation applied for microcystin LR and arbitrarily extended to all toxins.

3.
Clin Microbiol Infect ; 26(3): 383.e1-383.e7, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31288101

RESUMO

OBJECTIVE: To assess the performance of differential time to positivity (DTP) for the diagnosis of catheter-related bloodstream infections (CRBSI). METHODS: From all episodes of bloodstream infections (BSI) diagnosed during a 15-year period (2003-17) those in which a paired set of blood cultures drawn from a catheter and a peripheral vein were positive for the same microorganism and had a clinically and/or microbiologically defined source were selected. To assess diagnostic discrimination ability and accuracy of DTP for CRBSI, area under the receiver operating characteristic curves (AUC) and performance characteristics of a DTP ≥2 h were computed. RESULTS: A total of 512 BSI were included, of which 302 (59%) were CRBSI. Discrimination ability of DTP was low for Staphylococcus aureus (AUC 0.656 ± 0.06), coagulase-negative staphylococci (AUC 0.618 ± 0.081), enterococci (AUC 0.554 ± 0.117) and non-AmpC-producing Enterobacteriaceae (AUC 0.653 ± 0.053); moderate for Pseudomonas aeruginosa (AUC 0.841 ± 0.073), and high for AmpC-producing Enterobacteriaceae (AUC 0.944 ± 0.039). For the entire sample, DTP had a low-to-moderate discrimination ability (AUC 0.698 ± 0.024). A DTP ≥2 h has a low sensitivity for coagulase-negative staphylococci (60%) and very low for S. aureus (34%), enterococci (40%) and non-AmpC-producing Enterobacteriaceae (42%). A DTP cut-off of 1 h improved sensitivity (90%) for AmpC-producing Enterobacteriaceae. CONCLUSIONS: Differential time to positivity performs well for diagnosing CRBSI only when AmpC-producing Enterobacteriaceae and P. aeruginosa are involved. Performance is low for common Gram-positive organisms and non-AmpC-producing enteric bacilli; a negative test should not be used to rule out CRBSI due to these microorganisms. A DTP ≥1 h may improve accuracy for AmpC-producing Enterobacteriaceae, particularly Enterobacter spp.


Assuntos
Infecções Relacionadas a Cateter/diagnóstico , Testes Diagnósticos de Rotina , Sepse/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Infecções Relacionadas a Cateter/história , Cateterismo Venoso Central/efeitos adversos , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Gerenciamento Clínico , Feminino , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Sepse/epidemiologia , Sepse/etiologia , Sepse/história , Espanha/epidemiologia , Avaliação de Sintomas , Fatores de Tempo
4.
Clin Microbiol Infect ; 26(3): 345-350, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31295551

RESUMO

OBJECTIVES: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. METHODS: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. RESULTS: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and ß-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. CONCLUSIONS: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.


Assuntos
Farmacorresistência Bacteriana Múltipla , Neutropenia/complicações , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Idoso , Área Sob a Curva , Biomarcadores , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutropenia/diagnóstico , Neutropenia/epidemiologia , Razão de Chances , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Fatores de Risco , Sensibilidade e Especificidade , Espanha/epidemiologia
5.
Environ Res ; 179(Pt A): 108784, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606614

RESUMO

BACKGROUND AND OBJECTIVES: Despite the biological plausibility of the association between heavy metal exposure and mental health disorders, epidemiological evidence remains scarce. The objective was to estimate the association between heavy metals and metalloids in soil and the prevalence of mental disorders in the adult population of Spain. METHODS: Individual data came from the Spanish National Health Survey 2011-2012, 18,073 individuals residing in 1772 census sections. Mental health was measured with the 12-item General Health Questionnaire. The concentration estimates of heavy metal and metalloid levels in topsoil (upper soil horizon) came from the Geochemical Atlas of Spain based on 13,317 soil samples. Levels of lead (Pb), arsenic (As), cadmium (Cd) and manganese (Mn) were estimated in each census section by "ordinary Kriging". Odds ratios (OR) were calculated by multilevel logistic regression models. RESULTS: Compared with the lowest Pb concentration levels quartile, the OR for the second quartile was 1.29 (95%CI: 1.11-1.50), increasing progressively to 1.37 (95%CI: 1.17-1.60) and 1.51 (95%CI: 1.27-1.79) in the third and fourth quartiles, respectively. For As, the association was observed in the third and fourth quartiles: 1.21 (95%CI: 1.04-1.41) and 1.42 (95% CI: 1.21-1.65), respectively. Cd was associated also following a gradient from the second quartile: 1.34 (95%CI: 1.15-1.57) through the fourth: 1.84 (95%CI: 1.56-2.15). In contrast, Mn only showed a positive association at the second quartile. Additionally, individuals consuming vegetables > once a day the OR for the fourth quartile of Pb concentration, vs. the first, increased to 2.93 (95%CI: 1.97-4.36); similarly for As: 3.00 (95%CI: 2.08-4.31), and for Cd: 3.49 (95%CI: 2.33-5.22). CONCLUSIONS: Living in areas with a higher concentration of heavy metals and metalloids in soil was associated with an increased probability of having a mental disorder. These relationships were strengthened in individuals reporting consuming vegetables > once a day.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Saúde Mental/estatística & dados numéricos , Metais Pesados , Poluentes do Solo , Adulto , Cádmio , Monitoramento Ambiental , Humanos , Metaloides , Espanha/epidemiologia
6.
Clin Microbiol Infect ; 25(4): 447-453, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30096417

RESUMO

OBJECTIVES: We aimed to describe the current time-to-positivity (TTP) of blood cultures in individuals with onco-haematological diseases with febrile neutropenia. We assessed the probability of having a multidrug-resistant Gram-negative bacilli (MDR-GNB) bloodstream infection (BSI) 24 h after cultures were taken, to use this information for antibiotic de-escalation strategies. METHODS: BSI episodes were prospectively collected (2003-2017). When a patient experienced more than one BSI, only one episode was randomly chosen. Time elapsed from the beginning of incubation to a positive reading was observed; TTP was recorded when the first bottle had a positive result. RESULTS: Of the 850 patient-unique episodes, 323 (38%) occurred in acute leukaemia, 185 (21.8%) in non-Hodgkin's lymphoma and 144 (16.9%) in solid neoplasms. Coagulase-negative staphylococci (225; 26.5%), Escherichia coli (207; 26.1%), Pseudomonas aeruginosa (136; 16%), Enterococcus spp. (81; 9.5%) and Klebsiella pneumoniae (67; 7.9%), were the most frequent microorganisms isolated. MDR-GNB were documented in 126 (14.8%) episodes. Median TTP was 12 h (interquartile range 9-16.5 h). Within the first 24 h, 92.1% of blood cultures were positive (783/850). No MDR-GNB was positive over 24 h. Of the 67 (7.9%) episodes with a TTP ≥24 h, 25 (37.3%) occurred in patients who were already receiving active antibiotics against the isolated pathogen. Most common isolations with TTP ≥24 h were coagulase-negative staphylococci, candidaemia and a group of anaerobic GNB. CONCLUSIONS: Currently, the vast majority of BSI in individuals with onco-haematological diseases with febrile neutropenia have a TTP <24 h, including all episodes caused by MDR-GNB. Our results support reassessing empiric antibiotic treatment in neutropenic patients at 24 h, to apply antibiotic stewardship de-escalation strategies.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Bacteriemia/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/fisiologia , Neutropenia Febril/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Neoplasias/complicações , Idoso , Bacteriemia/sangue , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Hemocultura , Neutropenia Febril/sangue , Neutropenia Febril/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 204: 125-130, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-29920415

RESUMO

The photo-bleaching reaction of the chemical actinometer, Aberchrome 540™, is reported for the first time in a series of ionic liquids (ILs). This fulgide in its C-form undergoes an opening reaction to yield its E-form, when it is irradiated with UV light at wavelengths >400 nm. The magnitude of bleaching was monitored spectrophotometrically and their kinetics evaluated, obtaining first-order rate constants (kobs). The results obtained in different ILs suggest that changes in the rate constants (kobs) of the opening reaction of Aberchrome 540™ are mainly governed by weaker interactions such as coulombic (π* parameter) and Van der Waals interactions (δH2, parameter). In addition, the photochemical fatigue resistance was also studied in ILs media and compared with conventional solvents (benzene, toluene, etc.). In particular, we found that three different tendencies dependent on the ILs used exist. The first group of ILs where the reversibility of the fulgide is favored (for example, [Bmim][BF4], [Bmim][PF6] and [Bmim][OTf]), behaviour similar to conventional solvents. The second group corresponds to ILs where photo reversibility is partial; and finally, other group of ILs that prevented photo reversibility. It is proposed that depending on the ILs used, the stabilization of different forms of the fulgide can be controlled, thus resulting important in terms of choosing the appropriate ILs for a specific photochemical reaction.

8.
Springerplus ; 5(1): 1937, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27917336

RESUMO

BACKGROUND: Diets with increasing levels of energy were fed for 42 days to 200, 1-day old male broiler chickens to evaluate growth performance, carcass characteristics and chemical composition of meat. The study was performed in the subtropical area of northeastern Mexico. Treatments diets (T) for starter and finisher phases had apparent metabolizable energy (AME; kcal/kg) of: 2960 and 3040 (T1); 3000 and 3080 (T2); 3040 and 3120 (T3); 3080 and 3160 (T4), respectively. Within each of the growing phases the four treatment diets were formulated to contain similar levels of crude protein, amino acids, and other nutrients. In a completely randomized design, birds were allocated to the four treatments with five replicates (floor pens) of 10 birds each. The trial was divided in two phases (starter and finisher) of 21 days each (42 days total). RESULTS: Weight gain was not influenced by energy level; however, feed conversion efficiency was improved in the diets with 3040 and 3120 kcal/kg AME (T3; P < 0.05). There was no influence of treatment on total carcass weight or carcass cuts (P > 0.05). Meat from breast muscle had similar crude protein percentages among treatments; ether extract was higher in T1 than T4 (P < 0.05). The percentages of water, ether extract, ash and crude protein in thigh meat were not significantly different (P > 0.05) among treatments. CONCLUSIONS: For this study carried out in a dry tropical area, the moderate increase in dietary energy concentration (diet with 3040 and 3120 kcal/kg AME, T3) enhanced feed conversion efficiency of broiler chickens.

9.
Asian-Australas J Anim Sci ; 28(9): 1288-95, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26194225

RESUMO

In experiment 1, eighty crossbred steers (239±15 kg) were used in a 229-d experiment to evaluate the effects of increasing levels of enzymatically hydrolyzed yeast (EHY) cell wall in diets on growth performance feedlot cattle during periods of elevated ambient temperature. Treatments consisted of steam-flaked corn-based diets supplemented to provide 0, 1, 2, or 3 g EHY/hd/d. There were no effects on growth performance during the initial 139-d period. However, from d 139 to harvest, when 24-h temperature humidity index averaged 80, EHY increased dry matter intake (DMI) (linear effect, p<0.01) and average daily gain (ADG) (linear effect, p = 0.01). There were no treatment effects (p>0.10) on carcass characteristics. In experiment 2, four Holstein steers (292±5 kg) with cannulas in the rumen and proximal duodenum were used in a 4×4 Latin Square design experiment to evaluate treatments effects on characteristics of ruminal and total tract digestion in steers. There were no treatment effects (p>0.10) on ruminal pH, total volatile fatty acid, molar proportions of acetate, butyrate, or estimated methane production. Supplemental EHY decreased ruminal molar proportion of acetate (p = 0.08), increased molar proportion of propionate (p = 0.09), and decreased acetate:propionate molar ratio (p = 0.07) and estimated ruminal methane production (p = 0.09). It is concluded that supplemental EHY may enhance DMI and ADG of feedlot steers during periods of high ambient temperature. Supplemental EHY may also enhance ruminal fiber digestion and decrease ruminal acetate:propionate molar ratios in feedlot steers fed steam-flaked corn-based finishing diets.

10.
Vaccine ; 33(19): 2221-2227, 2015 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-25819711

RESUMO

INTRODUCTION: Although different epidemiological studies have assessed meningococcal C conjugate vaccine effectiveness within 1 and >1 year since vaccination, none of them evaluated long-term effectiveness. In order to assess if epidemiological data correlates with the findings described in seroprevalence studies we evaluated long-term vaccine effectiveness over time, up to 10 years since vaccination. METHODS: Cases targeted by vaccination programs and notified to the Spanish Surveillance System between 2001 and 2013 were included in the study. Vaccine effectiveness was estimated using the screening method. Relationship between vaccine effectiveness and time since vaccination was explored using point estimates, simple logistic regression or restricted cubic splines logistic regression model for all and for those vaccinated at <1, 1-11 and at 12-19 years of age. RESULTS: From 345 confirmed cases reported in the period and targeted by vaccination programs, 125 (36.23%) were vaccine failures. Proportion of vaccine failures decreased with age of vaccination: 63.97% at <1 year; 36.84% at 1-11 years; and 3.88% at 12-19 years. Using the best model for each group, vaccine effectiveness decreased from 99.12% to 90.85% (%change=-8.3%) for all; from 99.04% to 48.60% (%change=-50.9%) for those vaccinated at <1 years and from 99.45% to 90.18% (%change=-9.3%) for those vaccinated at 1-11 years after 10 years since vaccination. For those vaccinated at 12-19 years no changes were observed in vaccine effectiveness after 10 years (p=0.968). CONCLUSIONS: After 10 years, vaccine effectiveness decreased by 50% in those vaccinated at <1 year, while those vaccinated with one dose at 12-19 years showed no changes. Vaccine failures occurred early after vaccination and more frequently in those vaccinated at younger ages. Vaccination at ≥12 years seems to be related to a low number of vaccine failures and a higher and endurable protection over time.


Assuntos
Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo C/imunologia , Vacinação/métodos , Adolescente , Fatores Etários , Anticorpos Antibacterianos/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Infecções Meningocócicas/microbiologia , Estudos Soroepidemiológicos , Espanha , Fatores de Tempo , Vacinas Conjugadas/imunologia , Adulto Jovem
11.
J Cell Sci ; 128(1): 40-9, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25380826

RESUMO

By controlling HIFα hydroxylation and stability, the prolyl hydroxylase domain (PHD)-containing proteins are essential to the maintenance of oxygen homeostasis; therefore these enzymes are tightly regulated. Small ubiquitin-like modifier (SUMO) is a 10-kDa protein readily conjugated to lysine residues of the targeted proteins in a process termed SUMOylation. In this study, we introduce SUMO conjugation as a novel regulator of PHD3 (also known as EGLN3). PHD3 SUMOylation occurs at a cluster of four lysines at the C-terminal end of the protein. Furthermore, PHD3 SUMOylation by SUMO2 or SUMO3 contributes to PHD3-mediated repression of HIF1-dependent transcriptional activity. Interestingly, PHD3-SUMO conjugation does not affect PHD3 hydroxylase activity or HIF1α stability, providing new evidence for a dual role of PHD3 in HIF1 regulation. Moreover, we show that hypoxia modulates PHD3-SUMO conjugation and that this modification inversely correlates with HIF1 activation. PHD3 SUMOylation highlights a new and additional layer of regulation that is likely required to fine-tune HIF function.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Sumoilação/fisiologia , Transcrição Gênica/fisiologia , Ubiquitinas/metabolismo , Animais , Células COS , Chlorocebus aethiops , Células HEK293 , Células HeLa , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Estabilidade Proteica , Estrutura Terciária de Proteína , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Ubiquitinas/genética
12.
Biol Chem ; 394(4): 459-69, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23362194

RESUMO

By driving the primary transcriptional response, the hypoxia inducible factor (HIF) is a master player of the hypoxia-signaling cascade, activation of which is essential to maintain oxygen homeostasis. HIF is formed by the interaction of a constitutive HIF-1ß subunit with a HIF-α subunit tightly regulated through the concerted action of the prolyl hydroxylase domain containing proteins (PHDs) and factor inhibiting HIF. In well-oxygenated cells, HIF-α prolyl-hydroxylation by PHDs is the recognition signal for the binding of the ubiquitin E3 ligase pVHL, allowing protein poly-ubiquitination and degradation by the proteasome. Factor inhibiting HIF-mediated asparaginyl hydroxylation prevents interaction with the CBP/p300 coactivator and hence reduces HIF-dependent transcriptional activity. Upon low oxygen availability, HIF-α hydroxylation is blocked, resulting in protein stabilization and HIF complex activation. Post-translational modifications other than hydroxylation appear to be important in the cellular response to hypoxia. Small ubiquitin-like modifier (SUMO) is a 10 kDa protein readily conjugated to the lysine (K) residues of numerous cellular substrates in a sequential process termed SUMOylation. Recent data support the idea that a fine balance in SUMOylation/deSUMOylation is required for the adequate activation of the hypoxia-signaling cascade. In the present review, we will concentrate on the mechanisms of SUMOylation and its consequences in the cellular response to hypoxia.


Assuntos
Hipóxia/metabolismo , Transdução de Sinais/fisiologia , Sumoilação/fisiologia , Animais , Humanos , Hipóxia/enzimologia , Hipóxia/genética , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Transdução de Sinais/genética , Sumoilação/genética
13.
J Proteomics ; 78: 159-71, 2013 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-23178873

RESUMO

Pentachlorophenol (PCP) represents a critical concern worldwide due to its toxicity and recalcitrance to degradation. The capacity of Mucor plumbeus to transform PCP into several detoxification metabolites, including tetrachlorohydroquinone and several phase II conjugates, was observed by LC-HRMS. The data obtained support the degradation pathway proposed previously. PCP effects in M. plumbeus, an unsequenced species, were investigated using a proteomics approach (bidimensional gel electrophoresis followed by MALDI TOF/TOF analyses). The mycelial proteins identified in the differentially accumulated spots allowed the identification of PCP responsive proteins. The presence of PCP increased the energy demand, altered the cell wall architecture and cytoskeleton and induced a significant stress response. The latter was emphasised by the up-accumulation of protein species associated with defence mechanisms (e.g. HSP70 and cytochrome c peroxidase). Overall the data produced corroborate the capability of PCP to uncouple oxidative-phosphorylation in mitochondria. Importantly, one of the identified mycelial protein species, a NAD- and Zn-dependent ADH, is likely to be involved in PCP degradation. Amongst the fungal secretome analysed, no putative PCP degradative enzymes were detected. This work constitutes the first toxicoproteomic study involving a Zygomycota fungus and the very first concerning the effect of PCP in a fungal proteome.


Assuntos
Poluentes Ambientais/farmacologia , Proteínas Fúngicas/metabolismo , Mucor/metabolismo , Pentaclorofenol/farmacologia , Proteômica , Biotransformação/efeitos dos fármacos , Biotransformação/fisiologia , Poluentes Ambientais/metabolismo , Pentaclorofenol/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
15.
Rapid Commun Mass Spectrom ; 25(20): 3161-6, 2011 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-21953972

RESUMO

Benzophenone (BP) is one of the many contaminants reported as present in foodstuffs due to its migration from food packaging materials. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is acknowledged in the literature as the method of choice for this analysis. However, cases have been reported where the use of this methodology was insufficient to unambiguously confirm the presence of a contaminant. In previous work performed by the authors, the unequivocal identification of BP in packaged foods was not possible even when monitoring two m/z transitions (precursor ion - product ion), since ion ratio errors higher than 20% were obtained. In order to overcome this analytical problem a fast, sensitive and selective liquid chromatography/high-resolution mass spectrometry (LC/HRMS) methodology has been developed and applied to the analysis of BP in packaged foods. A direct comparison between LC/HRMS and LC/MS/MS data indicated better selectivity when working with LC/HRMS at a resolving power of 50,000 FWHM (full width at half maximum) than when monitoring two m/z transitions by LC/MS/MS. The resolving power used enabled the detection and identification of Harman as the compound impeding the confirmation of BP by LC-MS/MS. Similar quantitative results were obtained by an Orbitrap mass analyser (Exactive™) and a triple quadrupole mass analyser (TSQ Quantum Ultra AM™).


Assuntos
Benzofenonas/análise , Análise de Alimentos/métodos , Análise de Alimentos/normas , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas em Tandem/normas , Animais , Bebidas/análise , Bovinos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Embalagem de Alimentos , Alimentos Infantis/análise , Leite/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Leite de Soja/química
16.
J Biol Chem ; 285(24): 18217-24, 2010 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-20368331

RESUMO

Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor that activates the cellular response to hypoxia. The HIF1alpha subunit is constantly synthesized and degraded under normoxia, but degradation is rapidly inhibited when oxygen levels drop. Oxygen-dependent hydroxylation by prolyl-4-hydroxylases (PHD) mediates HIF1alpha proteasome degradation. Brain ischemia limits the availability not only of oxygen but also of glucose. We hypothesized that this circumstance could have a modulating effect on HIF. We assessed the separate involvement of oxygen and glucose in HIF1alpha regulation in differentiated neuroblastoma cells subjected to ischemia. We report higher transcriptional activity and HIF1alpha expression under oxygen deprivation in the presence of glucose (OD), than in its absence (oxygen and glucose deprivation, OGD). Unexpectedly, HIF1alpha was not degraded at reoxygenation after an episode of OGD. This was not due to impairment of proteasome function, but was associated with lower HIF1alpha hydroxylation. Krebs cycle metabolites fumarate and succinate are known inhibitors of PHD, while alpha-ketoglutarate is a co-substrate of the reaction. Lack of HIF1alpha degradation in the presence of oxygen was accompanied by a very low alpha-ketoglutarate/fumarate ratio. Furthermore, treatment with a fumarate analogue prevented HIF1alpha degradation under normoxia. In all, our data suggest that postischemic metabolic alterations in Krebs cycle metabolites impair HIF1alpha degradation in the presence of oxygen by decreasing its hydroxylation, and highlight the involvement of metabolic pathways in HIF1alpha regulation besides the well known effects of oxygen.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Oxigênio/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Prolina/química , Animais , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico , Fumaratos/química , Regulação da Expressão Gênica , Glucose/metabolismo , Humanos , Hidroxilação , Camundongos , Modelos Biológicos , Oxigênio/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Ácido Succínico/química
17.
Indian J Cancer ; 46(2): 120-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19346645

RESUMO

The role of surgery in the management of human gliomas has been controversial. The results from numerous neurosurgical series are inconsistent. The current adjuvant therapies have facilitated treatment of patients, and have rendered neurosurgical removal without morbidity or mortality more commonplace than ever before. Here, we investigated the role of surgery in the management of adults with low- and high-grade gliomas. Even though there is substantial evidence which claims that surgery per se has a role to play in extending patient survival, there is a paucity of randomized clinical trials on this subject, and little in the way of Class II data to support these claims. However, this should not divert patients away from surgery, because there may be additional benefits from a concerted effort to remove a tumor completely. At the present time, it seems best that clinicians continue to individualize patient treatment based on a myriad of factors that relate to the patient, the patient's tumor, and the known biology of the disease.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Glioma/mortalidade , Glioma/patologia , Humanos , Procedimentos Neurocirúrgicos , Taxa de Sobrevida
18.
Aliment Pharmacol Ther ; 28(4): 468-74, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18549464

RESUMO

BACKGROUND: There are few model networks to predict treatment outcome in viral hepatitis. AIM: To develop an easy bioinformatics platform based on algorithm decisions (Bayesian network) for a more efficient prediction of treatment response. METHODS: Totally 385 consecutive chronic hepatitis C (CHC) treated patients were included. More than 40 variables were analysed. Data from 308 patients were used to build the variable model network using DLIFE platform based on predictive graphical models. The prediction accuracy of the bioinformatics network was compared with the true data collected in a retrospective study. The model was then validated twice with external data from CHC patients treated in other hospitals. RESULTS: The accuracy of this bioinformatics network for treatment response in our 308 patients was 83.3%, which is higher than the accuracy obtained by physicians on the basis of study of clinical data and their own experience (50-65%). The receiver operator characteristic curve areas after validation with another cohort of patients were: 0.91 for sustained virological response, one for nonresponse, and 0.81 for relapse. DLIFE offered a diagnostic accuracy of 81.3%, which is a clear improvement compared with unassisted prognosis (50-65%). CONCLUSIONS: This bioinformatics platform (DLIFE) accurately predicts the outcome of CHC combination therapy, improving treatment decisions and reducing costs. This bioinformatics platform allows integrating widespread data sources and permits predicting the clinical outcome of a particular patient using a general predictive graphical model.


Assuntos
Antivirais/uso terapêutico , Biologia Computacional/métodos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Algoritmos , Biologia Computacional/economia , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Valor Preditivo dos Testes , Curva ROC , Proteínas Recombinantes , Reprodutibilidade dos Testes , Resultado do Tratamento
19.
J Chromatogr A ; 1159(1-2): 225-32, 2007 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-17383666

RESUMO

This paper shows the applicability of capillary electrophoresis (CE) coupled to mass spectrometry (MS) for the analysis of acrylamide (AA) in foodstuffs. In order to obtain an ionisable compound amenable to be analysed by CE, acrylamide was derivatised with 2-mercaptobenzoic acid. Spectra in positive and negative modes were studied in order to select the best ionisation mode and multistep tandem mass spectrometry was used to obtain structural information. Maximum signal was observed when negative mode was used and MS/MS and MS3 were selected for quantitation and confirmation, respectively. For the separation, a fused-silica capillary of 80 cm and 50 microm I.D. and 35 mM ammonium formate/ammonia solution at pH 10 as running electrolyte were used. The applicability of field amplified sample injection (FASI) in reversed polarity was evaluated in order to decrease detection limits. The developed FASI-CE-MS/MS method provided a detection limit of 8 ng g(-1) and good linearity (r=0.999) and precision (day-to-day lower than 15%). The method has been applied to the analysis of different representative food products and the results were compared with those obtained by LC-MS/MS.


Assuntos
Acrilamida/análise , Eletroforese Capilar/métodos , Monitoramento Ambiental/métodos , Análise de Alimentos/métodos , Contaminação de Alimentos/prevenção & controle , Espectrometria de Massas em Tandem/métodos , Acrilamida/química , Análise de Injeção de Fluxo/métodos , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Salicilatos/química , Sensibilidade e Especificidade , Solventes , Compostos de Sulfidrila/química , Volatilização
20.
Aliment Pharmacol Ther ; 25(7): 841-8, 2007 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-17373923

RESUMO

BACKGROUND: Hepatic venous pressure gradient (HVPG) has prognostic value in complications and survival of patients with liver cirrhosis. However, the relationship between HVPG and the outcome of acute alcoholic hepatitis (AAH), as well as the specific features of portal hypertension syndrome in this setting, have not been defined. AIMS: To evaluate the prognostic value of HVPG and to analyse the degree of portal hypertension and hyperdynamic circulation in patients with severe AAH. METHODS: Early measurements of HVPG were performed in 60 patients with severe AAH, and compared with the haemodynamic findings of 37 and 29 liver transplantation candidates with alcoholic or viral end-stage cirrhosis respectively. RESULTS: Twenty-three patients (38%) died during hospitalization. Portal hypertension and hyperdynamic circulation were more severe in AAH patients. HVPG was greater in non-survivors [26.9 (7.4) vs. 19.4 (5.2) mmHg, P < 0.001]. Only 4/31 (13%) patients with HVPG 22 (P < 0.001). Encephalopathy (OR 9.4; CI 1.4-64.8), Model for End-Stage Liver Disease (MELD) score > 25 (OR 7.4; CI 1.4-39.9) and HVPG > 22 mmHg (OR 6.7; CI 1.1-39.9) were independently associated to in-hospital mortality. CONCLUSIONS: Early measurement of HVPG provides important prognostic information on the short-term outcome of patients with severe AAH. In addition, MELD score also seems to be a strong prognostic factor in these patients.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hepatite Alcoólica/mortalidade , Hipertensão Portal/fisiopatologia , Cirrose Hepática/mortalidade , Pressão Venosa/fisiologia , Feminino , Veias Hepáticas , Mortalidade Hospitalar , Humanos , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Regressão , Índice de Gravidade de Doença , Taxa de Sobrevida
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