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1.
Cochrane Database Syst Rev ; (6): CD011322, 2016 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-27356090

RESUMO

BACKGROUND: Ovarian cancer is seventh most common cancer in women worldwide. Approximately 1.3% of women will be diagnosed with ovarian cancer at some point during their life time. The majority of tumours arise from surface of the ovary (epithelial). Two thirds of these women will present with advanced disease, requiring aggressive treatment, which includes debulking surgery (removal of as much disease as possible) and chemotherapy. However, most women (75%) with advanced epithelial ovarian cancer (EOC) will relapse following surgery and chemotherapy. Patients who relapse are treated with either platinum or non-platinum drugs and this is dependent on the platinum-sensitivity and platinum-free interval. These drug regimens are generally well-tolerated although there are potential severe side effects. New treatments that can be used to treat recurrence or prevent disease progression after first-line or subsequent chemotherapy are important, especially those with a low toxicity profile. Hormones such as luteinising hormone releasing hormone (LHRH) agonists have been used in the treatment of relapsed EOC. Some studies have shown objective remissions, while other studies have shown little or no benefit. Most small studies report a better side-effect profile for LHRH agonists when compared to standard chemotherapeutic agents used in EOC. OBJECTIVES: To compare the effectiveness and safety of luteinising hormone releasing hormone (LHRH) agonists with chemotherapeutic agents or placebo in relapsed epithelial ovarian cancer (EOC). SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group trials register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase up to January 2016. We also searched registers of clinical trials and abstracts of scientific meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared LHRH agonists with chemotherapeutic agents or placebo in relapsed EOC. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether relevant studies met the inclusion criteria, retrieved data and assessed risk of bias. MAIN RESULTS: Two studies, including 97 women, met our inclusion criteria: one assessed LHRH agonist (leuprorelin) use in relapsed (platinum-resistant and platinum-refractory) EOC in comparison with a chemotherapeutic agent (treosulfan) (Du Bois 2002); the other examined LHRH agonist (decapeptyl) versus a placebo (Currie 1994). Since both studies had different control groups, a meta-analysis was not possible.There may be little or no difference between treatment with leuprorelin or treosulfan in overall survival (OS) (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.58 to 1.67; very low-quality evidence) or progression-free survival (PFS) at six and 12 months (risk ratio (RR) 0.61, 95% CI 0.22 to 1.68, and RR 0.65, 95% CI 0.12 to 3.66; very low-quality evidence), respectively (Du Bois 2002). The duration of follow-up was 2.5 years and quality of life (QoL) was not reported in this study.Alopecia and fatigue were probably more common with treosulfan than leuprorelin (alopecia RR 0.32, 95% CI 0.12 to 0.91 (very low-quality evidence)). There may be little or no difference in other Grade 3/4 side effects: nausea and vomiting (RR 0.65, 95% CI 0.12 to 3.66 (very low-quality evidence)); neurotoxicity (RR 0.32, 95% CI 0.01 to 7.71 (very low-quality evidence)) and neutropenia (RR 0.97, 95% 0.06 to 14.97 (very low-quality evidence)),The Currie 1994 study, which compared decapeptyl treatment with placebo, reported mean PFS of 16 weeks verus 11.2 weeks, respectively. No relative effects measures or P value at a particular time point were reported. Overall survival (OS) and QoL outcomes were not reported. In addition, adverse events were only mentioned for the decapeptyl group.Adverse events were incompletely reported (no adverse events in decapeptyl group, but not reported for the placebo group). AUTHORS' CONCLUSIONS: Based on this review of two small RCTs, there is not enough evidence to comment on the safety and effectiveness of LHRH agonists in the treatment of platinum-refractory and platinum-resistant (relapsed) EOC. Overall, the quality of evidence for all outcomes (including OS, PFS, QoL and adverse events) is very low.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Bussulfano/análogos & derivados , Hormônio Liberador de Gonadotropina/agonistas , Leuprolida/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Bussulfano/uso terapêutico , Carcinoma Epitelial do Ovário , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Crit Rev Food Sci Nutr ; 54(7): 924-37, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24499071

RESUMO

Tea is the second most consumed beverage in the world after water and there are numerous reported health benefits as a result of consuming tea, such as reducing the risk of cardiovascular disease and many types of cancer. Thus, there is much interest in the chemical composition of teas, for example; defining components responsible for contributing to reported health benefits; defining quality characteristics such as product flavor; and monitoring for pesticide residues to comply with food safety import/export requirements. Covered in this review are some of the latest developments in mass spectrometry-based analytical techniques for measuring and characterizing low molecular weight components of tea, in particular primary and secondary metabolites. The methodology; more specifically the chromatography and detection mechanisms used in both targeted and non-targeted studies, and their main advantages and disadvantages are discussed. Finally, we comment on the latest techniques that are likely to have significant benefit to analysts in the future, not merely in the area of tea research, but in the analytical chemistry of low molecular weight compounds in general.


Assuntos
Espectrometria de Massas/métodos , Chá/química , Camellia sinensis/química , Cromatografia/métodos , Flavonoides/análise , Manipulação de Alimentos/métodos , Cromatografia Gasosa-Espectrometria de Massas , Promoção da Saúde , Peso Molecular , Resíduos de Praguicidas/análise , Paladar
3.
Vet Rec ; 193(1): 46, 2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37417497

RESUMO

A pioneer of veterinary radiology, she was a born teacher and a role model.

4.
Anal Chem ; 84(3): 1540-8, 2012 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-22145650

RESUMO

Fructans are polymeric carbohydrates, which play important roles as plant reserve carbohydrates and stress protectants, and are beneficial for human health and animal production. Fructans are formed by the addition of ß-d-fructofuranosyl units to sucrose, leading to very complex mixtures of 1-kestose based inulins, 6-kestose linked levans, and 6G-kestose derived neoseries inulins and levans in cool season grasses such as Lolium perenne. The identification of isomeric fructan oligomers in chromatographic analysis of crude plant extracts is often hampered by the lack of authentic standards, and unambiguous peak assignment usually requires time-consuming analyses of purified fructan oligomers. We have developed a LC-MS(n) method for the separation and detection of fructan isomers and present here evidence for specific MS(n) fragmentation patterns associated with ß 1-2 (inulins) and ß 2-6 (levans) fructans. LC-MS(n) analysis of (13)C labeled fructan oligomers produced by L. perenne fructosyltransferases expressed in yeast has enabled us to account for the observed fragmentation patterns in terms of preferential cleavage of the glycosidic bond between O- and fructose C2 in both inulins and levans and to differentiate reducing-end from nonreducing end cross ring cleavages in levans. We propose that higher order MS fragmentation patterns can be used to distinguish between the two major classes of fructan, i.e., inulins and levans, without the need for authentic standards.


Assuntos
Cromatografia Líquida de Alta Pressão , Frutanos/análise , Espectrometria de Massas , Oligossacarídeos/análise , Isótopos de Carbono/química , Hexosiltransferases/genética , Hexosiltransferases/metabolismo , Humanos , Inulina/análise , Isomerismo , Lolium/enzimologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
5.
Food Chem ; 134(3): 1616-23, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25005990

RESUMO

Tea is the second most consumed beverage in the world and its consumption has been associated with numerous potential health benefits. Factors such as fermentation methods, geographical origin and season can affect the primary and secondary metabolite composition of tea. In this study, a hydrophilic interaction liquid chromatography (HILIC) method coupled to high resolution mass spectrometry in both positive and negative ionisation modes was developed and optimised. The method when combined with principal component analysis to analyse three different types of tea, successfully distinguished samples into different categories, and provided evidence of the metabolites which differed between them. The accurate mass and high resolution attributes of the mass spectrometric data were utilised and relative quantification data were extracted post-data acquisition on 18 amino acids, showing significant differences in amino acid concentrations between tea types and countries. This study highlights the potential of HILIC chromatography combined with non-targeted mass spectrometric methods to provide a comprehensive understanding of polar metabolites in plant extracts.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Extratos Vegetais/química , Chá/química , Interações Hidrofóbicas e Hidrofílicas
6.
J Biomed Biotechnol ; 2011: 974701, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21188174

RESUMO

The interleukin-10-deficient (IL10(-/-)) mouse develops colon inflammation in response to normal intestinal microflora and has been used as a model of Crohn's disease. Short-Column LCMS metabolite profiling of urine from IL10(-/-) and wild-type (WT) mice was used, in two independent experiments, to identify mass spectral ions differing in intensity between these two genotypes. Three differential metabolites were identified as xanthurenic acid and as the glucuronides of xanthurenic acid and of α-CEHC (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman). The significance of several differential metabolites as potential biomarkers of colon inflammation was evaluated in an experiment which compared metabolite concentrations in IL10(-/-) and WT mice housed, either under conventional conditions and dosed with intestinal microflora, or maintained under specific pathogen-free (SPF) conditions. Concentrations of xanthurenic acid, α-CEHC glucuronide, and an unidentified metabolite m/z 495(-)/497(+) were associated with the degree of inflammation in IL10(-/-) mice and may prove useful as biomarkers of colon inflammation.


Assuntos
Colite/urina , Interleucina-10/genética , Animais , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Colite/genética , Glucuronídeos/química , Glucuronídeos/metabolismo , Interleucina-10/metabolismo , Íons/química , Íons/metabolismo , Masculino , Espectrometria de Massas , Metabolômica/métodos , Camundongos , Camundongos Transgênicos , Xanturenatos/química , Xanturenatos/metabolismo
7.
Anal Bioanal Chem ; 401(9): 2955-63, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21927982

RESUMO

The main water-soluble carbohydrates in temperate forage grasses are polymeric fructans. Fructans consist of fructose chains of various chain lengths attached to sucrose as a core molecule. In grasses, fructans are a complex mixture of a large number of isomeric oligomers with a degree of polymerisation ranging from 3 to >100. Accurate monitoring and unambiguous peak identification requires chromatographic separation coupled to mass spectrometry. The mass range of ion trap mass spectrometers is limited, and we show here how monitoring selected multiply charged ions can be used for the detection and quantification of individual isomers and oligomers of high mass, particularly those of high degree of polymerization (DP > 20) in complex plant extracts. Previously reported methods using linear ion traps with low mass resolution have been shown to be useful for the detection of fructans with a DP up to 49. Here, we report a method using high-resolution mass spectrometry (MS) using an Exactive Orbitrap MS which greatly improves the signal-to-noise ratio and allows the detection of fructans up to DP = 100. High-sugar (HS) Lolium perenne cultivars with high concentrations of these fructans have been shown to be of benefit to the pastoral agricultural industry because they improve rumen nitrogen use efficiency and reduce nitrous oxide emissions from pastures. We demonstrate with our method that these HS grasses not only contain increased amounts of fructans in leaf blades but also accumulate fructans with much higher DP compared to cultivars with normal sugar levels.


Assuntos
Cromatografia Líquida/métodos , Misturas Complexas/análise , Frutanos/análise , Lolium/química , Espectrometria de Massas/métodos , Extratos Vegetais/análise , Ração Animal , Animais , Bovinos , Misturas Complexas/química , Frutanos/isolamento & purificação , Isomerismo , Peso Molecular , Extratos Vegetais/química , Folhas de Planta/química , Polimerização , Razão Sinal-Ruído
8.
Br J Haematol ; 150(6): 674-8, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20629660

RESUMO

Paediatric recommendations for unfractionated heparin (UFH) management are extrapolated from adult trials, a practice that may contribute to the inferior UFH-related outcomes in children compared to adults. This is the first study to determine UFH concentration in a population of children and correlated UFH concentration with measures of UFH effect. Correlation coefficients between protamine titration (concentration) and activated partial thromboplastin time (APTT), anti- activated factor X (Xa) assay and thrombin clotting time (effect) were 0·59, 0·46 and 0·52 respectively. A protamine titration level of 0·2-0·4 iu/ml in children was not equivalent to an anti-Xa assay of 0·35-0·7 iu/ml but to an anti-Xa assay 0·17-0·85 iu/ml. In addition, use of the anti-Xa or protamine titration assays to establish an APTT therapeutic range resulted in upper limits of APTT ranges exceeding 200 s. Existing methods for determining therapeutic ranges for UFH in adult populations do not produce equivalent ranges in children. As a result, paediatric clinical guidelines that state a therapeutic range for UFH can be determined using a protamine titration assay of 0·2­0·4 iu/ml or an anti-Xa assay of 0·35-0·7 iu/ml are not based on appropriate evidence. There is an urgent need for change in our approach to the use of UFH in children.


Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Adolescente , Fatores Etários , Anticoagulantes/sangue , Anticoagulantes/uso terapêutico , Testes de Coagulação Sanguínea/métodos , Criança , Pré-Escolar , Esquema de Medicação , Fator Xa/imunologia , Feminino , Heparina/sangue , Heparina/uso terapêutico , Humanos , Lactente , Masculino , Tempo de Tromboplastina Parcial
9.
Br J Haematol ; 151(4): 376-80, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20880110

RESUMO

The impact of age upon therapeutic response to unfractionated heparin (UFH) in children is proposed to reflect quantitative and potentially qualitative differences in coagulation proteins across childhood. This study explores the UFH-dependent tissue factor pathway inhibitor (TFPI) release in children compared to previously published data in adults. Children <16 years of age undergoing cardiac angiography formed the population for this prospective cohort study. TFPI release was measured prior to (baseline) and at 15, 30, 45 and 120 min post-UFH dose. This study demonstrated that, whilst the immediate release of TFPI post-UFH was similar in children compared to adults, TFPI release in children remained increased and consistent for a significantly longer period post-UFH administration compared to adults. Plasma TFPI levels in children did not demonstrate an UFH concentration -dependent reduction, as has been previously reported in adults. The prolonged TFPI-mediated anticoagulant levels observed in children administered UFH may contribute to the increased rate of major bleeding reported in children compared to adults. Furthermore, we postulate that this sustained UFH-dependent increase in TFPI levels in children may influence the binding of UFH to competitive plasma proteins, such as those involved in the immunological response to UFH associated with heparin-induced thrombocytopenia.


Assuntos
Anticoagulantes/farmacologia , Heparina/farmacologia , Lipoproteínas/sangue , Adolescente , Envelhecimento/sangue , Anticoagulantes/administração & dosagem , Criança , Pré-Escolar , Angiografia Coronária , Relação Dose-Resposta a Droga , Feminino , Heparina/administração & dosagem , Humanos , Lactente , Masculino , Estudos Prospectivos , Protaminas/sangue
10.
Rapid Commun Mass Spectrom ; 23(15): 2253-63, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19551846

RESUMO

The identification of quantitative trait loci (QTL) for plant metabolites requires the quantitation of these metabolites across a large range of progeny. We developed a rapid metabolic profiling method using both untargeted and targeted direct infusion tandem mass spectrometry (DIMSMS) with a linear ion trap mass spectrometer yielding sufficient precision and accuracy for the quantification of a large number of metabolites in a high-throughput environment. The untargeted DIMSMS method uses top-down data-dependent fragmentation yielding MS(2) and MS(3) spectra. We have developed software tools to assess the structural homogeneity of the MS(2) and MS(3) spectra hence their utility for phenotyping and genetical metabolomics. In addition we used a targeted DIMS(MS) method for rapid quantitation of specific compounds. This method was compared with targeted LC/MS/MS methods for these compounds. The DIMSMS methods showed sufficient precision and accuracy for QTL discovery. We phenotyped 200 individual Lolium perenne genotypes from a mapping population harvested in two consecutive years. Computational and statistical analyses identified 246 nominal m/z bins with sufficient precision and homogeneity for QTL discovery. Comparison of the data for specific metabolites obtained by DIMSMS with the results from targeted LC/MS/MS analysis showed that quantitation by this metabolic profiling method is reasonably accurate. Of the top 100 MS(1) bins, 22 ions gave one or more reproducible QTL across the 2 years.


Assuntos
Lolium/genética , Lolium/metabolismo , Metabolômica/métodos , Locos de Características Quantitativas , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Íons/química , Lolium/química , Sensibilidade e Especificidade , Fatores de Tempo
11.
Thromb Res ; 120(3): 347-51, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17118432

RESUMO

INTRODUCTION: Anti-Factor Xa (Anti-Xa) assays specifically determine the anticoagulant activity of UFH by measuring the ability of heparin-bound Antithrombin (AT) to inhibit a single enzyme, Factor Xa (FXa). Recent improvements in the automation, cost-effectiveness and accessibility of the assay to clinicians, have resulted in the Anti-Xa assay becoming a part of daily clinical practice in many institutions. OBJECTIVES: We hypothesized that different Anti-Xa assays have different applicability for use in clinical settings, depending on the amount of UFH administered. This was investigated in a tertiary paediatric institution. MATERIALS AND METHODS: Samples were collected from children receiving Low-dose of UFH of at least 10 IU/kg/h, with or without a previous bolus of up to 25 IU/kg/h, within the previous 6 h in the PICU and HDU. High-dose UFH population consisted of children undergoing Cardiac Catheterization (CC), who received a bolus of UFH of 100 IU/kg body weight, 30 min prior to sampling. RESULTS AND CONCLUSIONS: The Anti-Xa activity for a given dose of UFH was found to vary significantly based on the Anti-Xa assay and the population being monitored. Our study suggests that the MODIFIED COMATIC Anti-Xa assay provides the best physiological measure of the UFH effect in children, as it does not introduce sources of error, such as exogenous AT, which may increase the measured ant Factor Xa activity, nor Dextran Sulphate which can displace plasma protein bound heparin and once again leading to falsely elevated assay results. Further studies that include assessment of clinical outcomes are required to confirm the applicability of use of this particular assay in monitoring UFH therapy.


Assuntos
Anticoagulantes/uso terapêutico , Inibidores do Fator Xa , Heparina de Baixo Peso Molecular/uso terapêutico , Anticoagulantes/sangue , Anticoagulantes/farmacologia , Testes de Coagulação Sanguínea/métodos , Testes de Coagulação Sanguínea/normas , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Heparina de Baixo Peso Molecular/sangue , Heparina de Baixo Peso Molecular/farmacologia , Humanos , Masculino , Kit de Reagentes para Diagnóstico/normas , Sensibilidade e Especificidade
12.
Clin Cancer Res ; 10(7): 2473-81, 2004 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15073127

RESUMO

PURPOSE: Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer. EXPERIMENTAL DESIGN: We performed a systematic review of ovarian tumors from 178 BRCA1 mutation carriers, 29 BRCA2 mutation carriers, and 235 controls with a similar age distribution. Tumors were evaluated by four pathologists blinded to mutation status. Both morphological features and immunochemical staining for p53 and HER2 were evaluated. RESULTS: Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas (odds ratio, 1.84; 95% confidence interval, 1.21-2.79) and unlikely to be borderline or mucinous tumors. Tumors in BRCA1 carriers were of higher grade (P < 0.0001), had a higher percentage solid component (P = 0.001), and were more likely to stain strongly for p53 (P = 0.018). The distribution of pathological features in BRCA2 carriers was similar to that in BRCA1 carriers. CONCLUSIONS: Use of pathological features can substantially improve the targeting of predictive genetic testing. Results also suggest that BRCA1 and BRCA2 tumors are relatively aggressive and may be expected to have poor prognosis, although this may be treatment dependent.


Assuntos
Proteína BRCA2/genética , Genes BRCA1 , Heterozigoto , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Análise Mutacional de DNA , Progressão da Doença , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Imunofenotipagem , Modelos Logísticos , Pessoa de Meia-Idade , Mutação , Razão de Chances , Neoplasias Ovarianas/metabolismo , Prognóstico , Receptor ErbB-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo
13.
Food Chem ; 151: 394-403, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24423549

RESUMO

Oolong tea is a semi-fermented tea that is partially oxidised during the manufacturing process to create a product unique in composition. In this study, we investigated the potential of non-targeted LC-MS with two complementary chromatographic modes to provide a "comprehensive and unbiased" view of biochemical compositional changes occurring during oolong tea manufacturing in New Zealand. Tea leaf samples from throughout the manufacturing/fermentation process during three different harvest periods (spring, summer and autumn) were analysed by four different LC-MS streams. Principal component analysis revealed the de-greening stage of the manufacturing process was responsible for major changes in the biochemical profile, with the methodology detecting changes in a wide range of metabolites of differing polarities, such as flavonoids, nucleosides and primeverosides. Changes during the fermentation phase of the manufacturing process were less marked, however significant increases in levels of free amino acids, a hydroxyjasmonic acid and related metabolites were observed.


Assuntos
Cromatografia Líquida/métodos , Flavonoides/análise , Espectrometria de Massas/métodos , Chá/química , Nova Zelândia
14.
Food Chem ; 141(3): 2060-5, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23870928

RESUMO

Factors such as fermentation methods, geographical origin and season can affect the biochemical composition of tea leaves (Camellia sinensis L.). In this study, the biochemical composition of oolong tea during the manufacturing and fermentation process was studied using a non-targeted method utilising ambient ionisation with a direct analysis in real time (DART) ion source and mass spectrometry (MS). Caffeine dominated the positive ionisation spectra throughout the manufacturing process, while the negative ion spectra collected during manufacturing were rich in ions likely to be surface lipids. Correlation analyses on the spectra revealed two volatile compounds tentatively identified as indole and geranic acid, along with ammonium and caffeine clusters/adducts with geranic acid that increased in concentration during the fermentation stages of the process. The tentative identifications were assigned using a combination of DART-ion-trap MS(n) and DART-accurate mass MS(1) and MS(2) on tea samples and standard compounds. This study highlights the potential of DART-MS to rapidly monitor the progress of complex manufacturing processes such as tea fermentation.


Assuntos
Camellia sinensis/química , Espectrometria de Massas/métodos , Folhas de Planta/química , Fermentação , Espectrometria de Massas/instrumentação
15.
FEBS Lett ; 586(16): 2563-9, 2012 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-22750140

RESUMO

Epichloë festucae Fl1 in association with Lolium perenne synthesizes a diverse range of indole-diterpene bioprotective metabolites, including lolitrem B, a potent tremorgen. The ltm genes responsible for the synthesis of these metabolites are organized in three clusters at a single sub-telomeric locus in the genome of E. festucae. Here we resolve the genetic basis for the remarkable indole-diterpene diversity observed in planta by analyzing products that accumulate in associations containing ltm deletion mutants of E. festucae and in cells of Penicillium paxilli containing copies of these genes under the control of a P. paxilli biosynthetic gene promoter. We propose a biosynthetic scheme to account for this metabolic diversity.


Assuntos
Regulação Fúngica da Expressão Gênica , Indóis/química , Família Multigênica , Micotoxinas/biossíntese , Poaceae/metabolismo , Cromatografia Líquida/métodos , Epichloe , Deleção de Genes , Alcaloides Indólicos , Espectrometria de Massas/métodos , Modelos Químicos , Modelos Genéticos , Micotoxinas/química , Penicillium/metabolismo , Poaceae/microbiologia , Regiões Promotoras Genéticas , Fatores de Tempo
16.
Thromb Haemost ; 103(5): 1085-90, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20174762

RESUMO

Previous studies investigating continuous unfractionated heparin (UFH) therapy report age-related differences in UFH response in children, as measured by APTT and anti-Xa assay. This study determined the age-related response following administration of a single UFH bolus of 75-100 IU/kg in children. Venous blood samples were collected from children (n=56) at 15, 30, 45 and 120 minutes post-UFH. Anti-Xa, anti-IIa, APTT, TCT and protamine titration were performed on all samples. Age-dependent differences in the effect and concentration of UFH were identified for the anti-Xa, anti-IIa and protamine titration assays, respectively. In addition, a trend suggesting a proportional increase in anti-Xa and anti-IIa-mediated UFH effect with age was evident. Logistic regression demonstrated an increase in protamine titration of 0.6 IU/ml for every year of age in samples collected 15 minutes post-UFH. UFH-mediated anti-IIa activity was reduced compared to anti-Xa activity across childhood, with a two-fold increase in anti-Xa to anti-IIa ratio in infants less than one year of age compared to teenagers in the setting of high UFH concentrations. This study demonstrates that the previously reported age-dependent response to UFH occurs in the context of an age-dependent serum concentration of UFH. The trend toward increased UFH serum concentration and anticoagulant activity with age may be related to short-term differences in UFH binding to coagulant and competitive plasma proteins in vivo.


Assuntos
Fatores Etários , Cálculos da Dosagem de Medicamento , Heparina/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Medicina Baseada em Evidências , Fator Xa/metabolismo , Feminino , Heparina/análogos & derivados , Heparina/sangue , Humanos , Lactente , Recém-Nascido , Masculino , Tempo de Tromboplastina Parcial/métodos , Guias de Prática Clínica como Assunto , Valores de Referência
17.
J Chem Ecol ; 32(8): 1797-816, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16900433

RESUMO

The proanthocyanidin (PA) chemistry of 12 Lotus species of previously unknown PA content was examined in comparison with agricultural cultivars of L. pedunculatus, L. corniculatus, and L. tenuis and a "creeping" selection of L. corniculatus. Herbage harvested in winter 2000 and again in spring had extractable PA concentrations, estimations of which varied between 0.2 and 10.9% of dry matter. The four novel Lotus spp. with the highest concentrations were selected for further evaluation together with the agricultural accessions. PA concentrations in herbage were estimated for individual plants harvested in spring 2001 and bulk samples harvested in summer 2002-2003. PA oligomer and polymer fractions were separated by Sephadex LH-20 chromatography from aqueous acetone PA extracts of herbage. The chemical characteristics of the fractions were examined by acid catalyzed degradation with benzyl mercaptan, (13)C nuclear magnetic resonance spectroscopy, electrospray ionization (ESI), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). A wide variation was found in the chemical composition, mean degree of polymerization (mDP), and polydispersity of PAs from Lotus spp. Fractions from L. americanus, L. corniculatus "creeping selection," and L. pedunculatus consisted predominantly of prodelphinidin (PD) units, whereas PA from L. angustissimus and L. corniculatus consisted predominantly of procyanidin (PC) units. An approximately equal composition in terms of PC and PD units was found in L. parviflorus and L. suaveolens. In L. angustissimus, epicatechin is dominant in both extender and terminal units. In all Lotus PA fractions, the 2,3-cis isomers (epicatechin or epigallocatechin) predominated. Only trace amounts of PA were extracted from L. tenuis. The mDP of the PA fractions ranged from 8 to 97, with high mDP found only for L. pedunculatus and L. americanus. In the ESI-MS and MALDI-TOF-MS of the L. angustissimus PA fraction, ions for homo-PC oligomers were dominant, whereas ions for hetero-oligomers predominated in the other Lotus spp. Ions indicative of A-type linkages were observed in the MS of L. americanus. The results are discussed in terms of possible relationships between the concentration and composition of the PAs of Lotus spp. and ecological factors.


Assuntos
Lotus/química , Proantocianidinas/química , Ecologia , Geografia , Estrutura Molecular , Proantocianidinas/análise , Especificidade da Espécie
18.
J Comput Assist Tomogr ; 26(5): 740-2, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12439308

RESUMO

Necrosis in pathologic specimens of ovarian cancer is well documented; however, computed tomography (CT) evidence of gaseous necrosis in the absence of fistulation with bowel has not yet been described. We report three cases of ovarian adenocarcinoma that on CT showed evidence of gross gaseous necrosis, mimicking a pelvic abscess.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Feminino , Gases , Humanos , Pessoa de Meia-Idade , Necrose
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