RESUMEN
Polyaromatic hydrocarbons (PAHs) are ubiquitous in the environment and food. The Joint FAO/WHO Expert Committee on Food Additives concluded 13 individual PAHs are carcinogenic and genotoxic in vitro and in vivo. Food is recognized as the main source of exposure to PAHs for adult non-smokers, which contributed to more than 90% of total exposure. In this study, 300 food samples were collected in Hong Kong, analysed the levels of 16 European Union priority PAHs, the dietary exposure to these PAHs by the local adult population from these food items, and the associated health risk. The most predominant detectable PAH was chrysene (CHR) (14.4%), followed by benzo[c]fluorene (11.2%), benzo[a]anthracene (BaA) (10.6%) and benzo[b]fluoranthene (BbFA) (7.8%). The dietary exposures for average consumers of benzo[a]pyrene (BaP) and PAH4 (sum of BaP, CHR, BaA and BbFA) were 0.13-0.90 and 1.4-4.2 ng/kg bw/day respectively for lower and upper bound approaches. Cereal and its products contributed more than 50% to BaP and PAH4 for average consumers in a lower-bound approach. The margin of exposure (MOE) approach was used to assess the health risks of consumers. The calculated MOE values for both BaP and PAH4 of the average and high consumers (90th percentile) were >50,000, indicating a low concern for the health of the Hong Kong population.
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Exposición Dietética , Contaminación de Alimentos , Hidrocarburos Policíclicos Aromáticos , Humanos , Hong Kong , Exposición Dietética/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Adulto , Contaminación de Alimentos/análisis , Masculino , Femenino , Persona de Mediana Edad , Adulto Joven , Benzo(a)pireno/análisis , Crisenos/análisis , FluorenosRESUMEN
Chromium occurs naturally in different oxidation states. Amongst them, hexavalent chromium is classified as both genotoxic and carcinogenic while trivalent chromium can be considered as an essential element. Therefore, speciation analysis is essential when conducting dietary exposure assessment. Several critical reviews have been published on chromium speciation analysis in foodstuffs in the last decade. However, a method that can account for species interconversion during the extraction procedure has not been reported in the reviews. In recent years, an online method using species-specific isotope dilution mass spectrometry has been developed for the simultaneous determination of trivalent and hexavalent chromium in foodstuffs. Apart from that, new methods based on offline analytical techniques, to analyse trivalent and hexavalent chromium separately, are still under development. Therefore, one of the objectives of this paper is to review these recently published analytical methods and assess whether they are fit for chromium speciation analysis in foodstuffs. Additionally, an objective is also to assess whether their limits of detection are sufficiently low for dietary exposure assessment with respect to the neoplastic effects of hexavalent chromium. Moreover, possible future research gaps are identified based on the current knowledge and existing literature.
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Cromo , Exposición Dietética , Análisis de los Alimentos , Contaminación de Alimentos , Cromo/análisis , Contaminación de Alimentos/análisis , Humanos , Exposición Dietética/análisis , Espectrometría de MasasRESUMEN
Dithiocarbamates (DTCs) belong to a group of compounds used as fungicides in food production and can be divided into three major groups. Since DTCs easily oxidise and hydrolyse in alkaline and acidic medium respectively, precautions have to be implemented during preparation/homogenisation and extraction of samples. As such, test samples are commonly prepared individually by cutting into small pieces just before the digestion of DTCs with a hot acid to give carbon disulphide (CS2) and the results are expressed as CS2 without any differentiation of individual DTCs. However, individual DTCs have different toxicological potencies whilst their metabolites are more toxic than the parent compound. Apart from the hot digestion method, chromatographic separation of three major groups of DTCs has been developed by a number of different researchers. This review provides a comprehensive examination of sample preparation, extraction, clean-up and chromatographic methods for the determination of individual DTCs and their more toxic metabolites in foodstuffs. Moreover, this review also studies on how dietary exposure of DTCs can be efficiently and effectively estimated using different methods of analysis.
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Disulfuro de Carbono , Fungicidas Industriales , Exposición Dietética/análisis , Alimentos , Fungicidas Industriales/análisis , Tiocarbamatos/análisisRESUMEN
ABSTRACT: Liver disease etiology and transplantation outcomes may vary by ethnicity. We aimed to determine if disparities exist in our province.We reviewed the provincial database for liver transplant referrals. We stratified cohorts by ethnicity and analyzed disease etiology and outcomes.Four thousand nine hundred sixteen referrals included 220 South Asians, 413 Asians, 235 First Nations (Indigenous), and 2725 Caucasians. Predominant etiologies by ethnicity included alcohol (27.4%) and primary sclerosing cholangitis (PSC) (8.8%) in South Asians, hepatitis B (45.5%) and malignancy (13.9%) in Asians, primary biliary cholangitis (PBC) (33.2%) and autoimmune hepatitis (AIH) (10.8%) in First Nations, and hepatitis C (35.9%) in Caucasians. First Nations had lowest rate of transplantation (30.6%, Pâ=â.01) and highest rate of waitlist death (10.6%, Pâ=â.03). Median time from referral to transplantation (268âdays) did not differ between ethnicities (Pâ=â.47). Likelihood of transplantation increased with lower body mass index (BMI) (hazard ratio [HR] 0.99, Pâ=â.03), higher model for end stage liver disease (MELD) (HR 1.02, Pâ<â.01), or fulminant liver failure (HR 9.47, Pâ<â.01). Median time from referral to ineligibility status was 170âdays, and shorter time was associated with increased MELD (HR 1.01, Pâ<â.01), increased age (HR 1.01, Pâ<â.01), fulminant liver failure (HR 2.56, Pâ<â.01) or South Asian ethnicity (HR 2.54, Pâ<â.01). Competing risks analysis revealed no differences in time to transplant (Pâ=â.66) or time to ineligibility (Pâ=â.91) but confirmed increased waitlist death for First Nations (Pâ=â.04).We have noted emerging trends such as alcohol related liver disease and PSC in South Asians. First Nations have increased autoimmune liver disease, lower transplantation rates and higher waitlist deaths. These data have significance for designing ethnicity specific interventions.
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Enfermedad Hepática en Estado Terminal/etnología , Enfermedad Hepática en Estado Terminal/etiología , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , Colombia Británica/epidemiología , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Socioeconómicos , Factores de Tiempo , Listas de Espera/mortalidadRESUMEN
Current liver transplantation societies recommend recipients with active coronavirus disease 2019 (COVID-19) be deferred from transplantation for at least 2 wks, have symptom resolution and at least 1 negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test.1 This approach does not address patients who require urgent transplantation and will otherwise die from liver failure. We report a successful orthotopic liver transplant (OLT) in a patient with active COVID-19 infection. This is only the second to be reported worldwide and the first in Canada.
RESUMEN
Colours, natural and synthetic, are substances which add or restore colour to a food after processing or storage. They are widely used by food manufacturers but may pose a potential risk to human health. Most food safety authorities set up regulations to limit the use of synthetic colours, and monitor their levels and consumption by the general public. Therefore, validated analytical methods are needed to fulfil this requirement. This review presents a comprehensive overview of various liquid chromatographic methods used for quantification of permitted synthetic colours in foods. Available analytical methods have been assessed for their fitness for purpose in terms of extraction, clean-up, liquid chromatographic separation, quantification and method performance. The advantages and disadvantages are given of available analytical methods for analysing 24 synthetic colours, permitted for use by different jurisdictions. Gaps in the knowledge and levels of validation are identified and recommendations made on further research to develop suitable methods for routine monitoring of these permitted synthetic colours.
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Cromatografía Liquida/métodos , Análisis de los Alimentos/métodos , Colorantes de Alimentos/química , HumanosRESUMEN
Cereals and feed contaminated with ergot alkaloids (EAs) have been of concern for several decades. Nowadays, analysis of EAs is focused on ergometrine, ergotamine, ergosine, ergocristine, ergocryptine (a mixture of α- and ß-isomers) and ergocornine and their related -inine epimers as listed in the European Commission Recommendation 2012/154/EU. Liquid chromatography with fluorescence detection has been used for quantification of EAs for decades whilst LC-MS has become the work-horse for quantification of EAs in the last decade. However, in LC-MS analysis matrix effects of different magnitudes exist for each EA epimer, especially ergometrine/ergometrinine, even after different clean-up procedures. This leads to an underestimation or overestimation of EAs levels. Moreover, isotopic labelled standards for EAs are still not available in the market. This review aims to provide background information on different analytical methods, discuss their advantages and disadvantages and possible advancement. Moreover, the method performance requirements to support forthcoming regulations are also discussed.
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Grano Comestible/química , Alcaloides de Claviceps/análisis , Contaminación de Alimentos/análisis , Toxinas Biológicas/análisis , Fraccionamiento Químico , Cromatografía Líquida de Alta Presión , Ergolinas/análisis , Ergotaminas/análisis , Humanos , Lípidos/química , Espectrometría de Fluorescencia , Espectrometría de Masas en TándemRESUMEN
4-Nonylphenol (4-NP) is a para-substituted phenolic compound comprising a straight or branched carbon chain group while branched 4-NP consists of 211 possible structural isomers. NP is recognised as an environmental pollutant and exists ubiquitously in both the environment and in food. 4-NP, especially branched 4-NP, has been shown to have the potential role of endocrine disruptor and xeno-oestrogen. Moreover, different NP isomers also exhibit different oestrogen-like activities. Recently, it was reported that the isomer-specific profile of 4-NP in foodstuffs varies greatly between and within food groups. Hence, risk assessment based on total branched 4-NP cannot reflect dietary risk. This study reviews the analytical methods applicable to conduct an isomer-specific analysis of 4-NP and its occurrence in foodstuffs. Lastly, research gaps are identified for future research.
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Exposición Dietética/análisis , Contaminantes Ambientales/análisis , Análisis de los Alimentos , Contaminación de Alimentos/análisis , Fenoles/análisis , Estructura MolecularRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remains unclear. We performed a systematic literature search of the PubMed, Cochrane and Embase databases in order to identify clinical trials and case-series reporting on the safety and efficacy of intraperitoneal chemotherapy in patients with PDAC-derived PM. Eight publications reporting on 85 patients were identified, using three different therapeutic strategies. First, 37 patients received cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for PDAC with PM. Grade 3 and 4 complications occurred in 37.8% of patients, without perioperative mortality. Median disease-free survival and overall survival (OS) rates varied from 4 to 36 months and 4 to 62 months, respectively. Secondly, 40 patients with resectable PDAC without PM received prophylactic HIPEC following pancreatic resection, with postoperative morbidity and mortality rates of 30% and 5%, and 5-year OS rates of 23-24%. Finally, eight patients with PDAC-derived peritoneal disease were converted to resectable disease after receiving neoadjuvant intraperitoneal chemotherapy and operated on with curative intent, achieving a median OS of 27.8 months. In conclusion, CRS with HIPEC for PDAC-derived PM appears to be safe, conferring the same postoperative morbidity and mortality as reported on non-pancreatic malignancies. In highly selected patients, it could be considered for short-term disease control. However, long-term survival remains poor. The addition of prophylactic HIPEC for resectable PDAC cannot be recommended.
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Carcinoma Ductal Pancreático/terapia , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias Pancreáticas/terapia , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Carcinoma Ductal Pancreático/mortalidad , Terapia Combinada , Humanos , Neoplasias Pancreáticas/mortalidadRESUMEN
The degree of organotin compounds (OTCs), including dibutyltin, tributyltin, triphenyltin and dioctyltin, contamination in seafood purchased in 2017 and 2018 from Hong Kong market was studied. Edible portions of 341 seafood samples, including fish, crustaceans and molluscs, were used for analysis by gas chromatograph coupled to an inductively coupled plasma mass spectrometry (GC-ICP/MS). The method detection limits and quantification limits of OTCs were below or equal to 0.25 and 1.0 µg Sn kg-1 respectively. Triphenyltin accounted for the majority amongst other OTCs and was detected in 53% of samples. In general, mean total OTCs levels of fish (24 µg Sn kg-1) were higher than crustaceans (14 µg Sn kg-1) and molluscs (15 µg Sn kg-1). The highest detected levels of triphenyltin, tributyltin, dibutyltin and dioctyltin were found to be 480, 24, 4.5 and 0.89 µg Sn kg-1 in a mangrove snapper, noodle fish, coral clam and giant grouper respectively.
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Compuestos Orgánicos de Estaño , Animales , Crustáceos , Peces , Hong Kong , Alimentos Marinos/análisisRESUMEN
Sterigmatocystin (STC) is a toxic and potentially carcinogenic fungal toxin found in a variety of food commodities. This study describes the development of an analytical method to determine STC in roasted coffee beans and black pepper using ultra performance liquid chromatography (UPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS). 13C18-STC was used as internal standard. STC was extracted with a mixture of acetonitrile/water, diluted with a buffer, followed by purification with a solid-phase extraction and an immunoaffinity column prior to the UPLC-MS/MS analysis. Two multiple reaction monitoring (MRM) transitions were employed, one for quantification and one for confirmation of STC. The UPLC-MS/MS analytical method was validated with respect to selectivity, linearity, sensitivity, accuracy, precision, recovery, and stability. Calibration curves were linear over a concentration range 25-2,500 pg mL-1 with correlation coefficients (r) > 0.998. The method limit of quantification for STC in roasted coffee beans and black pepper was 0.10 µg kg-1. The accuracy and precision of the analytical method were acceptable within 15% at all quality control levels. This method was suitable to determine STC levels because of its selectivity, precision, and accuracy. The method was successfully applied to roasted coffee beans and black pepper samples.
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Coffea/química , Contaminación de Alimentos/análisis , Piper nigrum/química , Esterigmatocistina/análisis , Cromatografía de Afinidad , Cromatografía Liquida/métodos , Semillas/química , Extracción en Fase Sólida , Espectrometría de Masas en Tándem/métodosRESUMEN
BACKGROUND: The aim of this study was to evaluate whether elderly patients undergoing elective hepatectomy experience increased morbidity/mortality and whether these outcomes could be mitigated by minimally invasive hepatectomy (MIH). METHODS: 15,612 patients from 2014 to 2017 were identified in the Hepatectomy Targeted Procedure Participant Use File of the American College of Surgeons National Surgical Quality Improvement Program. Multivariable logistic regression models were constructed to examine the effect of elderly status (age ≥ 75 years, N = 1769) on outcomes with a subgroup analysis of elderly only patients by open (OH) versus MIH (robotic, laparoscopic, and hybrid, N = 4044). Propensity score matching was conducted comparing the effect of MIH to OH in elderly patients to ensure that results are not the artifact of imbalance in baseline characteristics. RESULTS: Overall, elderly patients had increased risk for 30-day mortality, major morbidity, prolonged length of hospital stay, and discharge to destination other than home. In the elderly subgroup, MIH was associated with decreased major morbidity (OR 0.71, P = 0.031), invasive intervention (OR 0.61, P = 0.032), liver failure (OR 0.15, P = 0.011), bleeding (OR 0.46, P < 0.001), and prolonged length of stay (OR 0.46, P < 0.001). Propensity score-matched analyses successfully matched 4021 pairs of patients treated by MIH vs. OH, and logistic regression analyses on this matched sample found that MIH was associated with decreased major complications (OR 0.69, P = 0.023), liver failure (OR 0.14, P = 0.010), bile leak (OR 0.46, P = 0.009), bleeding requiring transfusion (OR 0.46, P < 0.001), prolonged length of stay (OR 0.46, P < 0.001), and discharge to destination other than home (OR 0.691, P = 0.035) compared to OH. CONCLUSION: MIH is associated with decreased risk of major morbidity, liver failure, bile leak, bleeding, prolonged length of stay, and discharge to destination other than home among elderly patients in this retrospective study. However, MIH in elderly patients does not protect against postoperative mortality.
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Hepatectomía/métodos , Laparoscopía/métodos , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Anciano , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Humanos , Tiempo de Internación , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Periodo Posoperatorio , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Timely surgical resection in patients with suspected or diagnosed pancreas adenocarcinoma is an essential part of care. We hypothesized that longer surgical wait time was associated with worse oncologic outcomes. METHODS: A retrospective cohort of patients (N = 144) with resectable pancreas adenocarcinoma was divided into four wait time groups (<4, 4-8, 8-12, and >12 weeks), defined from the time of diagnosis on cross-sectional imaging. Overall and recurrence-free survival were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. A higher rate of conversion to palliative bypass in patients waiting over 4 weeks was observed and further analyzed using post-hoc multivariate regression. RESULTS: On multivariable analysis, longer wait time was associated with improved overall (HR 0.49, 95% CI: 0.28-0.85) and recurrence-free survival (HR 0.29, 95% CI: 0.15-0.56) in >12 weeks compared to <4 weeks group. On post-hoc analysis, longer wait time over 8 weeks was positively associated with palliative bypass (OR 5.33, 95% CI: 1.32-27.88). CONCLUSION: Wait time over 8 weeks was associated with a higher rate of palliative bypass. There was an improvement in overall and recurrence-free survival in patients who waited over 12 weeks, likely due to selection bias.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/cirugía , Humanos , Páncreas , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Listas de EsperaRESUMEN
Suspected nontargeted pyrrolizidine alkaloids (PAs), without analytical reference standard, were observed and interfered with the determination of targeted PAs in complex food matrices, especially for spices samples. Selectivity and applicability of multiple reaction monitoring (MRM) transitions, multistage fragmentation (MS3), and MRM with differential ion mobility spectrometry (DMS) for eliminating false positive identifications were evaluated. Afterward, a selective and sensitive LC-MS/MS method for the determination of 15 PAs and 13 PA N-oxides in foodstuffs was developed. The sample preparation and cleanup are applicable to a wide range of foodstuffs, including cereal products, dairy products, meat, eggs, honey, tea infusion, and spices. Freezing-out of the raw extract and the water/acetonitrile washing steps in a solid phase extraction was found to efficiently remove complex matrices. The method was validated at 0.05 µg kg-1 for general food and 0.5 µg kg-1 for spices, with reference to the Eurachem Guide. The estimated limit of quantifications of different PAs was in the range of 0.010-0.087 µg kg-1 for general food and 0.04-0.76 µg kg-1 for spices. Isotopically labeled PAs were used as internal standards to correct the variation of PAs/PANs performance in different food commodities. Matrix effects observed in complex food matrices could be reduced by solvent dilution. Recoveries of PAs and PA N-oxides were all seen within 50-120%.
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Cromatografía Líquida de Alta Presión/métodos , Huevos/análisis , Miel/análisis , Carne/análisis , Alcaloides de Pirrolicidina/química , Especias/análisis , Espectrometría de Masas en Tándem/métodos , Animales , Pollos , Contaminación de Alimentos/análisis , PorcinosRESUMEN
Tributyltin and triphenyltin have been extensively applied in anti-fouling paints since the 1960s. Hence, organotin compounds (OTCs), especially butyltins and phenyltins, in seafood has been of concern for decades. Even though the "International Convention on the Control of Harmful Anti-Fouling Systems on Ships, 2001" entered into force internationally in 2008 and prohibited the use of OTCs in anti-fouling paints used on ships, the analysis of OTCs in seafood was not commonly included in routine monitoring programmes. Besides, species of triphenyltin, including triphenyltin hydroxide and acetate, have been used as pesticides and may accumulate in food. Moreover, the European Food Safety Agency established a group tolerable daily intake for tributyltin, dibutyltin, triphenyltin and dioctyltin in 2004 as they exert their immunotoxic effects by similar mode of action and potency. Therefore, suitable methods are needed to analyze butyl-, phenyl- and octyl-tins simultaneously in food without affecting their moieties. This review aims to provide background information in this area.
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Técnicas de Química Analítica/métodos , Contaminación de Alimentos/análisis , Compuestos Orgánicos de Estaño/química , Contaminantes Químicos del Agua/química , Técnicas de Química Analítica/instrumentación , Estructura Molecular , Pintura/análisisRESUMEN
This study determined the levels of pyrrolizidine alkaloids (PAs), including their respective N-oxides, in foodstuffs available in Hong Kong by liquid chromatography-electrospray ionisation tandem mass spectrometry. A total of 234 samples (48 food items) were collected randomly from a local market and analysed. About 50% of samples were found to contain detectable amount of PAs. Amongst the 48 food items, PAs were not detected in 11 food items, including barley flour, beef, cattle liver, pork, pig liver, chicken meat, chicken liver, milk, non-fermented tea, Melissa tea and linden tea. For those found to contain detectable PAs, the summed PA content ranged up to 11,000 µg kg-1. The highest sum of PA content among the 37 food items calculated with lower bound was cumin seed, then followed by oregano, tarragon and herbs de Provence with ranges of 2.5-11,000, 1.5-5100, 8.0-3300 and 18-1300 µg kg-1 respectively. Among the samples, the highest sum of PA content was detected in a cumin seed sample (11,000 µg kg-1), followed by an oregano (5100 µg kg-1), a tarragon (3300 µg kg-1) and a herbs de Provence (1300 µg kg-1). In general, the results of this study agreed well with other published results in peer-reviewed journals, except that the total PAs in honey and specific tea infusion in this study were comparatively lower.
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Contaminación de Alimentos/análisis , Óxidos/análisis , Alcaloides de Pirrolicidina/análisis , Alcaloides de Pirrolicidina/química , Cromatografía Liquida , Hong Kong , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
BACKGROUND: Metronomic chemotherapy has shown promising activity against solid tumors and is believed to act in an antiangiogenic manner. The current study describes and quantifies the therapeutic efficacy, and mode of activity, of metronomic gemcitabine and a dedicated antiangiogenic agent (DC101) in patient-derived xenografts of pancreatic cancer. METHODS: Two primary human pancreatic cancer xenograft lines were dosed metronomically with gemcitabine or DC101 weekly. Changes in tumor growth, vascular function, and metabolism over time were measured with magnetic resonance imaging, positron emission tomography, and immunofluorescence microscopy to determine the anti-tumor effects of the respective treatments. RESULTS: Tumors treated with metronomic gemcitabine were 10-fold smaller than those in the control and DC101 groups. Metronomic gemcitabine, but not DC101, reduced the tumors' avidity for glucose, proliferation, and apoptosis. Metronomic gemcitabine-treated tumors had higher perfusion rates and uniformly distributed blood flow within the tumor, whereas perfusion rates in DC101-treated tumors were lower and confined to the periphery. DC101 treatment reduced the tumor's vascular density, but did not change their function. In contrast, metronomic gemcitabine increased vessel density, improved tumor perfusion transiently, and decreased hypoxia. CONCLUSION: The aggregate data suggest that metronomic gemcitabine treatment affects both tumor vasculature and tumor cells continuously, and the overall effect is to significantly slow tumor growth. The observed increase in tumor perfusion induced by metronomic gemcitabine may be used as a therapeutic window for the administration of a second drug or radiation therapy. Non-invasive imaging could be used to detect early changes in tumor physiology before reductions in tumor volume were evident.
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Inhibidores de la Angiogénesis/uso terapéutico , Desoxicitidina/análogos & derivados , Neovascularización Patológica/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Administración Metronómica , Inhibidores de la Angiogénesis/farmacología , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Proliferación Celular/efectos de los fármacos , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Humanos , Masculino , Ratones SCID , Microvasos/efectos de los fármacos , Microvasos/patología , Necrosis , Neoplasias Pancreáticas/irrigación sanguínea , Neoplasias Pancreáticas/patología , Perfusión , GemcitabinaRESUMEN
AIM: The dose-response relationship between doxorubicin and superabsorbent drug-eluting microspheres has not been established. In this study, we investigated the relationships between dose and delivery parameters as they pertain to toxicity and response in surgically resectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Twenty-five patients with resectable HCC were randomly assigned and divided into four groups, each receiving either bland, 25 mg, 50 mg or 75 mg of doxorubicin loaded Super Absorbent Polymer microspheres, with 24 patients undergoing surgical resection. Response Evaluation and Criteria in Solid Tumors (RECIST) 1.0 and European Association for the Study of the Liver (EASL)-based volumetric response was performed at one month and surgical resection of the reference tumor was performed at two months. Adverse events were collected at regular intervals. RESULTS: Fifty-six percent of patients demonstrated complete response according to EASL criteria as opposed to 0% according to RECIST (v1.0) criteria. Residual tumor was identified in all groups (0 mg: 35%±28.5%; 25 mg: 42%±30.4%; 50 mg: 3.6%±3.3%; and 75 mg: 49.29%±32.6%. A total of 112 adverse events of grades 1-3 occurred (average 5.1 per patient), with no grade 4 or 5. No difference was noted between bland embolic and drug-loaded groups. Subset analysis did demonstrate a significantly increased degree of necrosis in the 50 mg-loaded group (p=0.018). Strong correlation existed between arterial phase Computer Tomography EASL-based response and histopathology (r=0.81; p<0.0001). All groups had residual tumor. CONCLUSION: Histology correlates strongly with one-month post-procedural imaging and response optimized at 50 mg of loading per vial. Adverse events were a reflection of embolization, with no relationship between loading dose or administered dose of doxorubicin.
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Antibióticos Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Doxorrubicina/administración & dosificación , Neoplasias Hepáticas/terapia , Anciano , Antibióticos Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Relación Dosis-Respuesta a Droga , Doxorrubicina/efectos adversos , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Microesferas , Persona de Mediana EdadRESUMEN
This paper reports the development of a method for the quantitative analysis of perfluorinated compounds (PFCs), including C6-C14 perfluorinated carboxylic acids (PFCAs) and C4-C12 perfluorinated sulfonates (PFSAs), in fish and fatty foods by ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) in which the UPLC was equipped a PFC Analysis Kit to eliminate background contamination. Rapid baseline separation was achieved for 17 PFCs within 12 min, and PFCs were well-resolved from potential interferences from taurodeoxycholic acid and branched isomers of PFCs. The method was validated according to Commission Regulation 2002/657/EC of the European Commission with matrices including salmon, beef, egg, and butter. Average spiked recoveries, measured at concentration levels of 0.02 (method limit of quantification (MLOQ)), 0.2, and 2 µg/kg, were in the range of 68-117% with relative standard deviations below 20%. Matrix effects were evaluated and found to be correctable by internal standardization, especially for short- and long-chained PFCs. Trueness was verified against two certified reference materials. The method has also been successfully applied to the analysis of more than 200 food samples of a risk assessment study.
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Mantequilla/análisis , Cromatografía Líquida de Alta Presión/métodos , Huevos/análisis , Contaminación de Alimentos/análisis , Hidrocarburos Fluorados/química , Carne/análisis , Espectrometría de Masas en Tándem/métodos , Animales , Bovinos , Peces , Límite de DetecciónRESUMEN
Exploiting the functionalization chemistry of graphene, long-range electrostatic and short-range covalent interactions were harnessed to produce multifunctional energetic materials through hierarchical self-assembly of nanoscale oxidizer and fuel into highly reactive macrostructures. Specifically, we report a methodology for directing the self-assembly of Al and Bi2O3 nanoparticles on functionalized graphene sheets (FGS) leading to the formation of nanocomposite structures in a colloidal suspension phase that ultimately condense into ultradense macrostructures. The mechanisms driving self-assembly were studied using a host of characterization techniques including zeta potential measurements, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), particle size analysis, micro-Raman spectroscopy, and electron microscopy. A remarkable enhancement in energy release from 739 ± 18 to 1421 ± 12 J/g was experimentally measured for the FGS self-assembled nanocomposites.