RESUMEN
A 72-year-old man with a history of T1cN0M0 prostate adenocarcinoma and rising prostate-specific antigen underwent a fluciclovine PET/CT scan that showed high uptake in several para-aortic nodes, suspicious for prostate cancer. A right upper lobe single pulmonary nodule (SPN), demonstrated only mild uptake, which raised the suspicion for a lung primary. Subsequent FDG PET/CT showed high uptake in the SPN, revealing poorly differentiated adenocarcinoma at biopsy, but with no abnormal uptake in the para-aortic nodes. This case highlights the complementary potential of fluciclovine and FDG PET in patients with a history of prostate cancer biochemical recurrence and SPN.
Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/metabolismo , Ácidos Carboxílicos/metabolismo , Ciclobutanos/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Adenocarcinoma del Pulmón/patología , Anciano , Transporte Biológico , Humanos , Masculino , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Primarias Múltiples/patología , Neoplasias de la Próstata/patología , RecurrenciaRESUMEN
BACKGROUND: A survey on Fusarium species and moniliformin (MON) occurrence in sorghum grains collected from one of the main sorghum-producing areas of Argentina was conducted. Also, growth of F. thapsinum, one of the main sorghum pathogens, and MON production under different water activity (aw ) conditions on a sorghum-based medium were determined. RESULTS: Infection of sorghum grains by Fusarium species ranged from 82.5 to 99%; closely related species F. verticillioides, F. thapsinum and F. andiyazi were the most frequently recovered, followed by F. proliferatum and F. subglutinans. By sequencing a portion of the translation elongation factor-1α (TEF-1α) gene and by maximum parsimony analysis, F. verticillioides and closely related species were identified as F. thapsinum, F. andiyazi and F. verticillioides. Species within the F. graminearum species complex (FGSC) were isolated in high frequency. Maximum growth rates of 12 F. thapsinum strains were obtained at 0.995 aw . All evaluated strains were able to produce MON at all aw values tested, but MON production was higher at 0.995-0.982 aw . MON was detected in 41% of the samples at levels ranging from 363.2 to 914.2 µg kg-1 . CONCLUSION: This study provides new data on the occurrence of Fusarium species in sorghum grains destined for animal consumption in Argentina. The production of MON at different aw values showed that the toxin can be produced under field conditions. The risk to livestock exposed to daily low levels of MON associated with the toxin occurrence in the sorghum grains analyzed is unknown. © 2018 Society of Chemical Industry.
Asunto(s)
Alimentación Animal/análisis , Ciclobutanos/análisis , Fusarium/aislamiento & purificación , Micotoxinas/análisis , Sorghum/microbiología , Argentina , Ciclobutanos/metabolismo , Contaminación de Alimentos/análisis , Fusarium/clasificación , Fusarium/genética , Fusarium/crecimiento & desarrollo , Micotoxinas/metabolismo , Filogenia , Enfermedades de las Plantas/microbiología , Semillas/química , Semillas/microbiología , Sorghum/químicaRESUMEN
Zebrafish (Danio rerio) water tank (ZWT) approach was investigated as an alternative model for metabolism studies based on six different experiments with four model compounds. Sibutramine was applied for the multivariate optimization of ZWT conditions, also for the comparison of the metabolism among ZWT, humans and mice, beyond for the role of CYP2B6 in ZWT. After the optimization, 18 fish and 168 hours of experiments is the minimum requirement for a relevant panel of biotransformation products. A comparison among the species resulted in the observation of the same hydroxylated metabolites, with differences in metabolites concentration ratio. However, the ZWT allowed tuning of the conditions to obtain a specific metabolic profile, depending on the need. In addition, by utilizing CYP2B6 inhibition, a relevant ZWT pathway for the demethylation of drugs was determined. The stereospecificity of the ZWT metabolism was investigated using selegiline and no racemization or inversion transformations were observed. Moreover, the investigation of metabolism of cannabimimetics was performed using JWH-073 and the metabolites observed are the same described for humans, except for the hydroxylation at the indol group, which was explained by the absence of CYP2C9 orthologs in zebrafish. Finally, hexarelin was used as a model to evaluate studies by ZWT for drugs with low stability. As a result, hexarelin displays a very fast metabolization in ZWT conditions and all the metabolites described for human were observed in ZWT. Therefore, the appropriate conditions, merits, and relevant limitations to conduct ZWT experiments for the investigation of drug metabolism are described.
Asunto(s)
Preparaciones Farmacéuticas/metabolismo , Pez Cebra/metabolismo , Adulto , Animales , Antidepresivos/metabolismo , Antidepresivos/orina , Biotransformación , Ciclobutanos/metabolismo , Ciclobutanos/orina , Citocromo P-450 CYP2B6/metabolismo , Inhibidores del Citocromo P-450 CYP2B6/farmacología , Femenino , Humanos , Hidroxilación , Indoles/metabolismo , Indoles/orina , Masculino , Ratones , Modelos Animales , Naftalenos/metabolismo , Naftalenos/orina , Oligopéptidos/metabolismo , Oligopéptidos/orina , Preparaciones Farmacéuticas/orina , Selegilina/metabolismo , Selegilina/orina , Pez Cebra/orina , Proteínas de Pez Cebra/metabolismoRESUMEN
The effect of water activity (aw = 0.95, 0.98 and 0.995), temperature (15, 25 and 30°C), incubation time (7, 14, 21 and 28 days), and their interactions on growth and moniliformin (MON), beauvericin (BEA), fusaproliferin (FUS) and fumonisin B1 (FB1) production by two strains of Fusarium temperatum isolated from Argentinean maize were determined in vitro on sterile layers of maize grains. The results showed that there was a wide range of conditions for growth and mycotoxins production by F. temperatum. Both strains were found to grow faster with increasing aw and at 30°C. In relation to mycotoxin production, the two strains produced more FUS than the other mycotoxins regardless of aw or temperature evaluated (maximum = 50,000 µg g(-1)). For FUS, MON and BEA, the maximum levels were observed at 0.98 aw and 30°C (50,000, 5000 and 2000 µg g(-1) respectively). The lowest levels for these three mycotoxins were detected at 15°C and 0.95 aw (1700 and 100 µg g(-1) for FUS and MON respectively), and at 0.98 aw (400 µg g(-1) for BEA). The maximum levels of FB1 were produced at 15°C and 0.98 aw (1000 µg g(-1)). At all aw and temperatures combinations evaluated there was an increase in toxin concentrations with time incubation. The maximum levels were detected at 21 days. Statistical analyses of aw, temperature, incubation time, and the two- and three-way interactions between them showed significant effects on mycotoxins production by F. temperatum. For its versatility on growth and mycotoxin production, F. temperatum represents a toxicological risk for maize in the field and also during grain storage.
Asunto(s)
Microbiología de Alimentos , Fusarium/aislamiento & purificación , Zea mays/microbiología , Argentina , Ciclobutanos/análisis , Ciclobutanos/metabolismo , Depsipéptidos/análisis , Depsipéptidos/metabolismo , Fumonisinas/análisis , Fumonisinas/metabolismo , Fusarium/metabolismo , Temperatura , Terpenos/análisis , Terpenos/metabolismo , Factores de Tiempo , Agua/químicaRESUMEN
A method for identifying the metabolites of sibutramine 1-(4(chlorophenyl)-N,N-dimethyl-alpha-(2-methylpropyl))cyclobutanemethanamine) in urine, utilizing a double derivatization strategy, with N-methyl-N-(trimethylsilyl)-trifluoroacetamide and N-methyl-bis-(trifluoroacetamide), in gas chromatography/mass spectrometry is proposed. This methodology results in mass spectra with at least three fragments in abundance superior to 20%, attending the World Anti-Doping Agency identification criteria for qualitative assays. The characterization of the derivatives was obtained through two ionization modes: Chemical Ionization and Electron Impact ionization, both in full scan mode. Sibutramine was administered to 5 (five) volunteers and the excretion profile followed for 92h. Routine analytical, hydroxy-cyclobutane-bis-nor-sibutramine which becomes the more abundant metabolite in the first 10h and hydroxy-isopropyl-bis-nor-sibutramine which becomes the most abundant after 40h, were proposed for doping monitoring.
Asunto(s)
Ciclobutanos/orina , Fluoroacetatos , Compuestos de Trimetilsililo/orina , Acetamidas , Ciclobutanos/química , Ciclobutanos/metabolismo , Doping en los Deportes , Estabilidad de Medicamentos , Femenino , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ácido Trifluoroacético/orinaRESUMEN
Twenty-five samples of maize kernels collected at harvest time from geographically different corn fields in Peru, were examined for the occurrence of toxigenic Fusarium species. The most frequently recovered species were F. subglutinans (48%), F. moniliforme (46%), and F. equiseti (5%). Other Fusarium species isolated (up to 1%) included F. graminearum, F. acuminatum, F. solani, F. oxysporum, and F. culmorum. Assays of Fusarium culture extracts using Artemia salina larvae, showed F. subglutinans as one of the most toxigenic species, and its toxicity was mostly correlated to the capability to produce beauvericin (BEA). All eight tested isolates of F. subglutinans grown on autoclaved corn kernels produced BEA (from 50 to 250 mg/kg) as well as moniliformin (M) (from 70 to 270 mg/Kg). This is the first report on BEA and M production by maize isolates of F. subglutinans from South America.