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1.
Sci Total Environ ; 862: 160585, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36502990

RESUMO

eDNA metabarcoding is an emergent tool to inform aerobiome complexity, but few studies have applied this technology with real-world environmental pollen monitoring samples. Here we apply eDNA metabarcoding to assess seasonal and regional differences in the composition of airborne pollen from routine samples collected across successive years. Airborne pollen concentrations over two sampling periods were determined using a continuous flow volumetric impaction air sampler in sub-tropical (Mutdapilly and Rocklea) and temperate (Macquarie Park and Richmond), sites of Australia. eDNA metabarcoding was applied to daily pollen samples collected once per week using the rbcL amplicon. Composition and redundancy analysis of the sequence read counts were examined. The dominant pollen families were mostly consistent between consecutive years but there was some heterogeneity between sites and years for month of peak pollen release. Many more families were detected by eDNA than counted by light microscopy with 211 to 399 operational taxonomic units assigned to family per site from October to May. There were 216 unique and 119 taxa shared between subtropics (27°S) and temperate (33°S) latitudes, with, for example, Poaceae, Myrtaceae and Causurinaceae being shared, and Manihot, Vigna and Aristida being in subtropical, and Ceratodon and Cerastium being in temperate sites. Certain genera were observed within the same location and season over the two years; Chloris at Rocklea in autumn of 2017-18 (0.625, p ≤ 0.004) and 2018-19 (0.55, p ≤ 0.001), and Pinus and Plantago at Macquarie Park in summer of 2017-18 (0.58, p ≤ 0.001 and 0.53, p ≤ 0.003, respectively), and 2018-19 (0.8, p ≤ 0.003 and 0.8, p ≤ 0.003, respectively). eDNA metabarcoding is a powerful tool to survey the complexity of pollen aerobiology and distinguish spatial and temporal profiles of local pollen to a far deeper level than traditional counting methods. However, further research is required to optimise the metabarcode target to enable reliable detection of pollen to genus and species level.


Assuntos
Biodiversidade , Código de Barras de DNA Taxonômico , Monitoramento Ambiental , Pólen , Austrália , DNA Ambiental , Monitoramento Ambiental/métodos , Poaceae , Pólen/classificação , Pólen/genética
2.
Sci Total Environ ; 747: 141189, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-32799020

RESUMO

The importance of grass pollen to the global burden of allergic respiratory disease is well established but exposure to subtropical and temperate pollens is difficult to discern. Current monitoring of airborne pollen relies on light microscopy, limiting identification of taxa to family level. This informs seasonal fluctuations in pollen aerobiology but restricts analysis of aerobiological composition. We aimed to test the utility of DNA metabarcoding to identify specific taxa contributing to the aerobiome of environmental air samples, using routine pollen and spore monitoring equipment, as well as assess temporal variation of Poaceae pollen across an entire season. Airborne pollen concentrations were determined by light microscopy over two pollen seasons in the subtropical city of Brisbane (27°32'S, 153°00E), Australia. Thirty daily pollen samples were subjected to high throughput sequencing of the plastid rbcL amplicon. Amplicons corresponded to plants observed in the local biogeographical region with up to 3238 different operational taxonomic units (OTU) detected. The aerobiome sequencing data frequently identified pollen to genus levels with significant quantitative differences in aerobiome diversity between the months and seasons detected. Moreover, multiple peaks of Chloridoideae and Panicoideae pollen were evident over the collection period confirming these grasses as the dominant Poaceae pollen source across the season. Targeted high throughput sequencing of routinely collected airborne pollen samples appears to offer utility to track temporal changes in the aerobiome and shifts in pollen exposure. Precise identification of the composition and temporal distributions of airborne pollen is important for tracking biodiversity and for management of allergic respiratory disease.


Assuntos
Poaceae , Pólen , Alérgenos , Austrália , Cidades , Estações do Ano
3.
Foot Ankle Surg ; 26(3): 320-324, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31079958

RESUMO

BACKGROUND: Weightbearing images are important to the diagnosis of foot pathologies as are the three dimensional views available from CT and MRI. Standard three-dimensional imaging hardware, however, does not have a simple tool to obtain weightbearing images. The current research aimed to design, build and test a simple device to apply load in a horizontal bore imaging facility. METHODS: With the immediate need in hallux valgus studies, hallux valgus subjects were imaged using the new loading device, which could be easily transported and had no additional electronics. RESULTS: Testing showed that the usual angular measures of the foot (intermetatarsal and hallux valgus) replicated the results from the standard of care standing plain film results. With application of load, HV angle changed from 29.9° non-weightbearing to 32.2° weightbearing, while IM angle changed from nonweightbearing 15.8° to weightbearing 16.5°. CONCLUSION: The pedal-like device can provide weightbearing images in a horizontal bore MRI facility.


Assuntos
Hallux Valgus/diagnóstico , Imageamento por Ressonância Magnética/métodos , Suporte de Carga/fisiologia , Adulto , Idoso , Feminino , Hallux Valgus/fisiopatologia , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Posição Ortostática
5.
AJNR Am J Neuroradiol ; 38(5): 875-881, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28302608

RESUMO

BACKGROUND AND PURPOSE: The impact of deep cerebral veins on neurologic outcome after intravenous thrombolysis in patients with acute ischemic stroke is unclear. We investigated the relationship between the appearance of deep cerebral veins on susceptibility-weighted imaging and neurologic outcome in patients who underwent thrombolysis. MATERIALS AND METHODS: We retrospectively analyzed 109 consecutive patients with acute ischemic stroke who had pretreatment SWI and received intravenous thrombolysis within 6 hours. We calculated the signal difference ratio (defined as the relative difference in signal intensity between the ipsilateral and contralateral veins) of the thalamostriate vein, septal vein, and internal cerebral vein on pretreatment SWI. RESULTS: Only the signal difference ratio of the thalamostriate vein was significantly associated with poor outcome (3-month modified Rankin Scale score > 2, P = .008). The optimal threshold was relative hypointensity of the ipsilateral vein of >4.8% (sensitivity of 53.7% and specificity of 80.9%). We defined a signal difference ratio of the thalamostriate vein of ≥5% as an ipsilateral prominent thalamostriate vein. Patients with an ipsilateral prominent thalamostriate vein were more likely to have poor outcome (OR = 3.66; 95% CI, 1.25-10.68; P = .02) and a lower rate of successful reperfusion (reperfusion rate of ≥70%; OR = 0.35; 95% CI, 0.13-0.92; P = .03), compared with those without an ipsilateral prominent thalamostriate vein. However, patients with an ipsilateral prominent thalamostriate vein were still less likely to experience poor outcome when reperfusion was achieved compared with when reperfusion did not occur (80.0% versus 44.4%, P = .04). CONCLUSIONS: A pretreatment ipsilateral prominent thalamostriate vein was associated with reduced reperfusion after thrombolysis and poor outcome. More intensive reperfusion approaches may be required for patients with an ipsilateral prominent thalamostriate vein.


Assuntos
Veias Cerebrais/patologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Terapia Trombolítica , Idoso , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Veias Cerebrais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia Trombolítica/métodos , Resultado do Tratamento
6.
AJNR Am J Neuroradiol ; 35(9): 1683-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24742803

RESUMO

BACKGROUND AND PURPOSE: Collateral vessel status is strongly associated with clinical outcome in ischemic stroke but can be challenging to assess. The aim of this study was to develop a tomography perfusion source imaging-based assessment of collateral vessel status. MATERIALS AND METHODS: Consecutive patients with ischemic stroke who received intravenous thrombolysis or intra-arterial reperfusion therapy after CTP were retrospectively analyzed. In those with middle cerebral artery or internal carotid artery occlusion, CT perfusion source imaging was used to identify the relative filling time delay between the normal MCA Sylvian branches and those in the affected hemisphere. Receiver operating characteristic analysis and logistic regression were used to assess the association of the relative filling time delay with the 24-hour Alberta Stroke Program Early CT Score based on noncontrast CT and the 90-day modified Rankin Scale score. RESULTS: There were 217 patients treated in 2009-2011 who had CTP data, of whom 60 had MCA or ICA occlusion and 55 had 90-day mRS data. The intraclass correlation coefficient for relative filling time delay was 0.95. Relative filling time delay was correlated with 24-hour ASPECTS (Spearman ρ=-0.674; P<.001) and 90-day mRS score (ρ=0.516, P<.01). Increased relative filling time delay was associated with poor radiologic outcome (ASPECTS, 0-7) (area under the curve=0.79, P<.001) and poor functional outcome (mRS score, 3-6) (area under the curve=0.77, P=.001). In multivariate logistic regression, the association of longer relative filling time delay with poor outcome remained significant, independent of age, sex, and baseline National Institutes of Health Stroke Scale score. CONCLUSIONS: Relative filling time delay is a useful independent predictor of clinical outcome after ischemic stroke.


Assuntos
Encéfalo/irrigação sanguínea , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alberta , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Estados Unidos
7.
AJNR Am J Neuroradiol ; 35(4): 660-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24335541

RESUMO

BACKGROUND AND PURPOSE: More than half of patients with TIA/minor stroke have ischemic lesions on early DWI, which represent irreversibly damaged tissue. The presence and volume of DWI lesions predict early deterioration in this population. We aimed to study the rate and implications of DWI reversal in patients with TIA/minor stroke. MATERIALS AND METHODS: Patients with TIA/minor stroke were prospectively enrolled and imaged within 24 hours of onset. Patients were followed for 3 months with repeat MR imaging either at day 30 or 90. Baseline DWI/PWI and follow-up FLAIR final infarct volumes were measured. RESULTS: Of 418 patients included, 55.5% had DWI and 37% had PWI (time-to-peak of the impulse response ≥2 seconds' delay) lesions at baseline. The median time from symptom onset to baseline and follow-up imaging was 13.4 (interquartile range, 12.7) and 78.73 hours (interquartile range, 60.2), respectively. DWI reversal occurred in 5.7% of patients. The median DWI lesion volume was significantly smaller in those with reversal (0.26 mL, interquartile range = 0.58 mL) compared with those without (1.29 mL, interquartile range = 3.6 mL, P = .002); 72.7% of DWI reversal occurred in cortically based lesions. Concurrent tissue hypoperfusion (time-to-peak of the impulse response ≥2 seconds) was seen in 36.4% of those with DWI reversal versus 62.4% without (P = .08). DWI reversal occurred in 3.3% of patients with penumbral patterns (time-to-peak of the impulse response ≥6 seconds - DWI) > 0 and in 6.8% of those without penumbral patterns (P = .3). The severity of hypoperfusion, defined as greater prolongation of time-to-peak of the impulse response (≥2, ≥4, ≥6, ≥8 seconds), did not affect the likelihood of DWI reversal (linear trend, P = .147). No patient with DWI reversal had an mRS score of ≥2 at 90 days versus 18.2% of those without reversal (P = .02). CONCLUSIONS: DWI reversal is uncommon in patients with TIA/minor stroke and is more likely to occur in those with smaller baseline lesions. DWI reversal should not have a significant effect on the accuracy of penumbra definition.


Assuntos
Infarto Cerebral/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Ataque Isquêmico Transitório/patologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/patologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética/normas , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes
8.
Eur J Neurol ; 20(2): 281-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22900825

RESUMO

BACKGROUND AND PURPOSE: Absence of FLAIR hyperintensity within an acute infarct is associated with stroke onset <4.5 h. However, some patients rapidly develop FLAIR hyperintensity within this timeframe. We hypothesized that development of early infarct FLAIR hyperintensity would predict hemorrhagic transformation (HT) in patients treated with tissue plasminogen activator (tPA) < 4.5 h after onset. METHODS: Consecutive acute stroke patients treated with intravenous tPA <4.5 h after onset who had MRI before and 1 day after thrombolysis were included. Two raters (blind to HT) independently identified FLAIR hyperintensity with reference to the diffusion-weighted image (DWI) lesion. HT was assessed using T2* MRI at 24 h. Hemorrhagic infarction (HI) was defined as petechial HT without mass effect, and parenchymal hematoma (PH) as HT with mass effect. Multivariable logistic regression analysis for HT included FLAIR status, baseline National Institutes of Health Stroke Scale and DWI lesion volume, leukoaraiosis (Wahlund score), serum glucose and reperfusion. RESULTS: Of 109 patients, 33 (30%) had acute FLAIR hyperintensity. HT occurred in 17 patients (15.6%; 15 HI, 2 PH). HT was more common in FLAIR-positive patients than FLAIR-negative patients (33.3% vs. 9.2%, P = 0.009). Median time-to-scan and median time-to-thrombolysis did not differ significantly between patients with HT and without [97 IQR(68, 155) vs. 90 IQR(73, 119), P = 0.5; 120 IQR(99, 185) vs. 125 IQR(95, 150), P = 0.6, respectively]. In multivariable analysis, only FLAIR hyperintensity was independently associated with HT after thrombolysis (OR 18; 95% CI 2-175, P = 0.013). CONCLUSIONS: Early development of FLAIR hyperintensity within the area of diffusion restriction is associated with increased risk of HT after thrombolysis in acute stroke patients.


Assuntos
Hemorragia Cerebral/patologia , Acidente Vascular Cerebral/patologia , Idoso , Hemorragia Cerebral/complicações , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Leucoaraiose/complicações , Leucoaraiose/patologia , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Reperfusão/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico
9.
J Clin Neurosci ; 19(3): 360-3, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22245278

RESUMO

Thrombolysis trials have recruited few patients aged ≥80 years, which has led to uncertainty about the likely risk-to-benefit profile in the elderly. Leukoaraiosis (LA) has been associated with hemorrhagic transformation (HT) and increases with advanced age. We tested whether there were any independent associations between age, LA and HT. Consecutive patients treated with intravenous (IV) tissue plasminogen activator (tPA) were identified from a prospective database. LA on baseline CT scans was assessed by two independent raters using the modified Van Swieten Score (mVSS) (maximum score 8, severe >4). HT was assessed on routine 24 hour to 48 hour CT /MRI scans using the European Cooperative Acute Stroke Study criteria for hemorrhagic infarct (HI) or parenchymal hematoma (PH) and judged symptomatic by the treating neurologist as per Safe Implementation of Thrombolysis in Stroke criteria. There were 206 patients treated with IV tPA (mean age: 71.0 years; range: 24-92 years), of whom 65/206 (32%) were aged ≥80 years. Overall, HT occurred in 41/206 patients (20%), HI in 31, PH1 in four (one symptomatic) and PH2 in six (three symptomatic). Age was not associated with HT (any HT: odds ratio [OR]=1.01; 95% confidence interval [CI]=0.5-2.08; p=0.99; PH: OR=0.53; 95% CI=0.12-2.3; p=0.51). There was one patient with PH1 and one patient with PH2 in 65 patients ≥80 years, both asymptomatic. LA was present in 112/208 (54%), and severe in 16.5%. LA increased with age (p<0.001) but was not associated with PH (any LA: OR=0.83; 95% CI=0.25-2.8; p=0.99; severe LA: OR=0.54, 95% CI=0.09-3.5; p=0.99). Age ≥80 years or LA did not increase the risk of HT (including PH) after thrombolysis, although LA increased with age. Neither factor should exclude otherwise eligible patients from tPA treatment.


Assuntos
Idoso de 80 Anos ou mais/fisiologia , Hemorragia Cerebral/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/efeitos adversos , Adulto , Fatores Etários , Idoso , Isquemia Encefálica/complicações , Hemorragia Cerebral/epidemiologia , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/uso terapêutico , Humanos , Injeções Intravenosas , Leucoaraiose/patologia , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X , Adulto Jovem
10.
Lett Appl Microbiol ; 52(5): 506-13, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21332761

RESUMO

AIMS: Determine whether certain, natural phenolic compounds enhance activity of commercial antifungal drugs against yeast strains of Candida and Cryptococcus neoformans. METHODS AND RESULTS: Twelve natural phenolics were examined for fungicidal activity against nine reference strains of Candida and one of C. neoformans. Six compounds were selected for synergistic enhancement of antifungal drugs, amphotericin B (AMB), fluconazole (FLU) and itraconazole (ITR). Matrix assays of phenolic and drug combinations conducted against one reference strain, each, of Candida albicans and C. neoformans showed cinnamic and benzoic acids, thymol, and 2,3- and 2,5-dihydroxybenzaldehydes (-DBA) had synergistic interactions depending upon drug and yeast strain. 2,5-DBA was synergistic with almost all drug and strain combinations. Thymol was synergistic with all drugs against Ca. albicans and with AMB in C. neoformans. Combinations of benzoic acid or thymol with ITR showed highest synergistic activity. Of 36 combinations of natural product and drug tested, none were antagonistic. CONCLUSIONS: Relatively nontoxic natural products can synergistically enhance antifungal drug activity, in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: This is a proof-of-concept, having clinical implications. Natural chemosensitizing agents could lower dosages needed for effective chemotherapy of invasive mycoses. Further studies against clinical yeast strains and use of animal models are warranted.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Fenóis/farmacologia , Anfotericina B/farmacologia , Candida albicans/efeitos dos fármacos , Sinergismo Farmacológico , Fluconazol/farmacologia , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , Saccharomyces cerevisiae
11.
Neurology ; 75(12): 1040-7, 2010 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-20720188

RESUMO

OBJECTIVE: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. METHODS: EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. RESULTS: In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. CONCLUSIONS: True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Atrofia/tratamento farmacológico , Atrofia/patologia , Encéfalo/patologia , Isquemia Encefálica/patologia , Mapeamento Encefálico , Imagem de Difusão por Ressonância Magnética , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/patologia , Fatores de Tempo , Resultado do Tratamento
12.
Lett Appl Microbiol ; 51(2): 177-83, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20536709

RESUMO

AIM: To overcome fludioxonil resistance of Penicillium expansum, a mycotoxigenic fungal pathogen causing postharvest decay in apple, by using natural phenolic chemosensitizing agents. METHODS AND RESULTS: Fludioxonil-resistant mutants of P. expansum were co-treated with different oxidising and natural phenolic agents. Resistance was overcome by natural phenolic chemosensitizing agents targeting the oxidative stress-response pathway. These agents also augmented effectiveness of the fungicide, kresoxim-methyl. Results indicated that alkyl gallates target mitochondrial respiration and/or its antioxidation system. Fungal mitochondrial superoxide dismutase (Mn-SOD) plays a protective role against alkyl gallates. CONCLUSIONS: Natural chemosensitizing agents targeting the oxidative stress-response system, such as Mn-SOD, can synergize commercial fungicides. SIGNIFICANCE AND IMPACT OF THE STUDY: Redox-active compounds can serve as potent chemosensitizing agents to overcome resistance and lower effective dosages of fungicides. This can reduce costs with coincidental lowering of environmental and health risks.


Assuntos
Antifúngicos/farmacologia , Dioxóis/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Oxidantes/farmacologia , Estresse Oxidativo , Penicillium/efeitos dos fármacos , Fenóis/farmacologia , Pirróis/farmacologia , Interações Medicamentosas , Proteínas Fúngicas/metabolismo , Malus/microbiologia , Redes e Vias Metabólicas/efeitos dos fármacos , Metacrilatos/farmacologia , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Penicillium/isolamento & purificação , Fenilacetatos/farmacologia , Estrobilurinas , Superóxido Dismutase/metabolismo
13.
Lett Appl Microbiol ; 45(2): 134-41, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17651208

RESUMO

AIMS: Identify natural products that effectively target antioxidative signal transduction/stress response systems [i.e., mitogen-activated protein kinase (MAPK) pathway, mitochondrial superoxide dismutase (Mn-SOD)] of fungi. Enhance activity of strobilurin or fludioxonil with discovered compounds. METHODS AND RESULTS: Enhancement of antifungal activity of strobilurins, inhibitors of complex III of the mitochondrial respiratory chain, was tested using berberine hemisulfate and different phenolic compounds. The Saccharomyces cerevisiae sod2Delta, a deletion mutant lacking Mn-SOD gene, was highly sensitive to berberine and veratraldehyde. Functional complementation analysis verified these compounds target Mn-SOD. Activity of strobilurin (25-50 micromol l(-1)) was elevated on most aspergilli and Penicillium expansum by co-application with berberine or veratraldehyde (2-4 mmol l(-1)). These compounds also prevented Aspergillus fumigatus MAPK mutants (sakADelta and mpkCDelta) from escaping toxicity of fludioxonil (a phenylpyrrole fungicide potentiated by the MAPK pathway), a typical phenotype of fungal MAPK mutants. CONCLUSIONS: Strobilurin activity or prevention of fungal escape from fludioxonil toxicity can be enhanced by co-application of certain alkaloids or phenolics. SIGNIFICANCE AND IMPACT OF THE STUDY: Natural products can be used to target cellular stress response systems in fungal pathogens and serve as alternatives/additives to commercial antifungal agents.


Assuntos
Antifúngicos/farmacologia , Berberina/farmacologia , Fungos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/fisiologia , Dioxanos/farmacologia , Dioxóis/farmacologia , Sinergismo Farmacológico , Fungos/genética , Fungos/fisiologia , Resposta ao Choque Térmico , Metacrilatos/farmacologia , Testes de Sensibilidade Microbiana , Mutação , Estresse Oxidativo/genética , Pirróis/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/fisiologia , Transdução de Sinais/genética , Superóxido Dismutase/genética
14.
Food Addit Contam ; 24(4): 391-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17454112

RESUMO

The effects of four alkaloids on the biosynthesis of ochratoxin A (OTA), ochratoxin B (OTB) and citrinin were examined on four OTA-producing aspergilli: Aspergillus auricomus, A. sclerotiorum and two isolates of A. alliaceus. Piperine and piperlongumine, natural alkaloids of Piper longum, significantly inhibited OTA production at 0.001% (w/v) for all aspergilli examined. Piperine and piperlongumine affected the polyketide synthesis step of OTA production and inhibited production of citrinin. Curcumin, a constituent of tumeric, completely inhibited mycelial growth of A. alliaceus isolate 791 at 0.1% (w/v) and decreased OTA production by approximately 70% at 0.01% (w/v). Sesamin, a constituent of sesame oil, inhibited OTA and OTB production by 60 and 45%, respectively, at 0.1% (w/v), showing its effect was on chloroperoxidase and polyketide synthase activity. The potential advantage of these natural products to reduce ochratoxin contamination of agricultural commodities is discussed.


Assuntos
Alcaloides/farmacologia , Aspergillus/metabolismo , Micotoxinas/biossíntese , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Aspergillus/efeitos dos fármacos , Aspergillus/crescimento & desenvolvimento , Benzodioxóis/farmacologia , Carcinógenos/metabolismo , Citrinina/biossíntese , Meios de Cultura , Curcuma/química , Curcumina/farmacologia , Dioxolanos/farmacologia , Dioxóis/farmacologia , Contaminação de Alimentos/análise , Lignanas/farmacologia , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Ocratoxinas/biossíntese , Piper/química , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Óleo de Gergelim/química
15.
J Appl Microbiol ; 101(1): 181-9, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16834605

RESUMO

AIMS: The aim of this study was to show whether antioxidative response systems are potentially useful molecular targets for control of Aspergillus fumigatus and Aspergillus flavus. Selected phenolic agents are used in target-gene-based bioassays to determine their impact on mitochondrial respiration. METHODS AND RESULTS: Vanillyl acetone, vanillic acid, vanillin, cinnamic acid, veratraldehyde, m-coumaric acid (phenolic agents to which Saccharomyces cerevisiae sod2delta mutant showed sensitivity), carboxin (inhibits complex II of the mitochondrial respiratory chain), strobilurins/antimycin A (inhibits complex III of the mitochondrial respiratory chain) and fludioxonil/fenpiclonil [antifungals potentiated by mitogen-activated protein kinase (MAPK)] were examined in A. fumigatus, A. flavus and S. cerevisiae. Individual or combined application of phenolics with inhibitors of mitochondrial respiration showed some of the phenolics effectively inhibited fungal growth. Target-gene bioassays were performed using a sakAdelta (MAPK deletion) strain of A. fumigatus and a complementation analysis using the mitochondrial superoxide dismutase (Mn-SOD) gene (sodA) of A. flavus in the ortholog mutant, sod2delta, of S. cerevisiae. The results demonstrated that mitochondrial antioxidative stress system plays important roles in fungal response to antifungal agents tested. CONCLUSIONS: Antioxidative response systems of fungi can be an efficient molecular target of phenolics for pathogen control. Combined application of phenolics with inhibitors of mitochondrial respiration can effectively suppress the growth of fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Natural compounds that do not pose any significant medical or environmental risks could serve as useful alternatives or additives to conventional antifungals. Identifying the antioxidative response systems in other pathogens could improve methods for fungal control.


Assuntos
Antifúngicos/farmacologia , Aspergillus/metabolismo , Fenóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Aspergillus/efeitos dos fármacos , Aspergillus flavus/efeitos dos fármacos , Aspergillus flavus/metabolismo , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/metabolismo , Dioxóis/farmacologia , Expressão Gênica/efeitos dos fármacos , Guaiacol/análogos & derivados , Guaiacol/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Micologia/métodos , Oxirredução , Pirróis/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Superóxido Dismutase/genética
16.
Mycotoxin Res ; 22(1): 3-8, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23605494

RESUMO

It was initially shown that gallic acid, from hydrolysable tannins in the pelliele of walnut kernels, dramatically inhibits biosynthesis of aflatoxin byAspergillus flavus. The mechanism of this inhibition was found to take place upstream from the gene cluster, including the regulatory gene,aflR, involved in aflatoxin biosynthesis. Additional research using other antioxidant phenolics showed similar antiaflatoxigenic activity to gallic acid. Treatment ofA. flavus withtert-butyl hydroperoxide resulted in an almost doubling of aflatoxin biosynthesis compared to untreated samples. Thus, antioxidative response systems are potentially useful molecular targets for control ofA. flavus. A high throughput screening system was developed using yeast,Saccharomyces cerevisiae, as a model fungus. This screening provided an avenue to quickly identify fungal genes that were vulnerable to treatment by phenolic compounds. The assay also provided a means to quickly assess effects of combinations of phenolics and certain fungicides affecting mitochondrial respiration. For example, theS. cerevisiae sod2† mutant was highly sensitive to treatment by certain phenolics and strobilurins/antimycin A, fungicides which inhibit complex III of the mitochondrial respiratory chain. Verification of stress to this system in the target fungus,A. flavus, was shown through complementation analysis, wherein the mitochondrial superoxide dismutase (Mn-SOD) gene (sodA) ofA. flavus in the ortholog mutant,sod2†, ofS. cerevisiae, relieved phenolic-induced stress. Mitochondrial antioxidative stress systems play an important role in fungal response to antifungals. Combined treatment of fungi with phenolics and inhibitors of mitochondrial respiration can effectively suppress growth ofA. flavus in a synergistic fashion.

17.
Mycotoxin Res ; 22(1): 16-21, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23605496

RESUMO

Aflatoxins are the most toxic and carcinogenic naturally occurring mycotoxins. They are produced primarily byAspergillus flavus andA. parasiticus. In order to better understand the molecular mechanisms that control aflatoxin production, identification of genes usingA. flavus expressed sequence tags (ESTs) and microarrays is currently being performed. Sequencing and annotation ofA. flavus ESTs from a normalizedA. flavus cDNA library identified 7,218 unique EST sequences. Genes that are putatively involved in aflatoxin biosynthesis, regulation and signal transduction, fungal virulence or pathogenicity, stress response or antioxidation, and fungal development were identified from these ESTs. Microarrays containing over 5,000 uniqueA. flavus gene amplicons were constructed at The Institute for Genomic Research. Gene expression profiling under aflatoxin-producing and non-producing conditions using this microarray has identified hundreds of genes that are potentially involved in aflatoxin production. Further investigations on the functions of these genes by gene knockout experiments are underway. This research is expected to provide information for developing new strategies for controlling aflatoxin contamination of agricultural commodities.

18.
Ann Hum Biol ; 31(2): 213-27, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15204364

RESUMO

BACKGROUND: Population variation in the timing of reproductive maturation among boys has received relatively little attention. However, evidence that the timing of pubertal onset is related to measures of adiposity suggests that the onset of reproductive maturation among boys in populations with poor nutritional status will be delayed. AIM: This study seeks to determine the impact of nutritional status on the timing of reproductive maturation by comparing urban and rural boys in an African population. SUBJECTS AND METHODS: Subjects were 794 rural and urban Tonga boys from Zambia, ages 5-19. Onset of puberty was defined as testicular volume >3 mL, which was measured using Prader beads. Data on height, weight, triceps skinfolds, and dental development were also obtained. RESULTS: Onset of testicular growth was 11.2 years (95% CI 10.9-11.4) for urban boys and 12.4 (95% CI 12.1-12.9) years for rural boys. Completion of testicular growth was also earlier in the urban sample: 15.3 years (95% CI 15.0-5.6) versus 17.1 years (95% CI 15.6-25.2). Both onset and completion of testicular growth were significantly and positively related to height and arm muscle area. In addition, triceps skinfolds by residence interaction was a significant predictor of testicular maturity, indicating a stronger relationship between energetic status and testicular growth in the rural sample. CONCLUSION: Our results demonstrate that delayed onset and slow testicular development among rural Gwembe boys is related to poor nutritional status.


Assuntos
População Rural , Maturidade Sexual/fisiologia , População Urbana , Adolescente , Adulto , Composição Corporal/fisiologia , Criança , Pré-Escolar , Humanos , Masculino , Estado Nutricional , Zâmbia
19.
J Med Primatol ; 32(6): 320-4, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14641786

RESUMO

Morphometric and hormonal measures were collected from 21 captive savanna baboons (Papio cynocephalus) maintained at the Tulane National Primate Research Center in order to determine age-related patterns in leptin levels over the life course as well as their relationships to body composition and adrenal and gonadal steroids. Comparison of leptin levels between peri-pubertal, adolescent, young adult, and fully mature males show lower levels among adolescent as compared with young adult males (P = 0.05 by Kruskal-Wallis ANOVA). In addition, abdominal fat varied among age groups (P = 0.003 by Kruskal-Wallis ANOVA) with the peri-pubertal animals lower than the adolescents, young adults, and prime adults. However leptin was not related to any measure of body composition, including abdominal fat, or to adrenal hormones (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol) or gonadal hormones (testosterone and estradiol). Age-related changes in leptin appear similar to those reported for captive rhesus macaques, while the failure to find an association between leptin and abdominal fat is interestingly different. These results confirm elevated levels of leptin in captive baboons compared with their wild counterparts and suggest that they result from changes in fetal development.


Assuntos
Corticosteroides/metabolismo , Composição Corporal/fisiologia , Hormônios Gonadais/metabolismo , Leptina/metabolismo , Papio/fisiologia , Fatores Etários , Análise de Variância , Animais , Masculino , Papio/metabolismo
20.
Med Anthropol Q ; 15(3): 391-408, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11693038

RESUMO

This article examines the health complaints of settled and nomadic Ngisonyoka Turkana of northwest Kenya. Samples of 152 nomadic and 124 settled men, aged 14 and over, were surveyed about their health status. The general pattern of disease reported concurs with previous studies of health among Turkana; that is, the primary complaints are respiratory tract infections and eye infections. The settled Turkana reported more severe complaints and higher rates of infectious disease than the nomads, including a significantly higher frequency of cold with cough, eye infection, and chest infection. Although the settled males as a group had slightly higher body mass index and other measures of body fat than the nomadic group, none of these indicators of body composition were predictive of health complaints. Observed differences in health patterns are possibly related to differences in dietary composition, exposure to pathogens associated with population density and environmental pollution, physical activity patterns, and psychosocial stress.


Assuntos
Indicadores Básicos de Saúde , Migrantes/estatística & dados numéricos , Adolescente , Adulto , Idoso , Resfriado Comum/epidemiologia , Efeitos Psicossociais da Doença , Exposição Ambiental , Infecções Oculares/epidemiologia , Humanos , Quênia/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Infecções Respiratórias/epidemiologia , Sociologia Médica , Topografia Médica
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