RESUMO
BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.
Assuntos
Corantes Fluorescentes , Verde de Indocianina/análogos & derivados , Venenos de Escorpião , Animais , Proteínas do Sistema Complemento/análise , Cães , Hipersensibilidade a Drogas/sangue , Feminino , Corantes Fluorescentes/farmacocinética , Corantes Fluorescentes/toxicidade , Células HEK293 , Histamina/sangue , Humanos , Verde de Indocianina/farmacocinética , Verde de Indocianina/toxicidade , Macaca fascicularis , Masculino , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Ratos Sprague-Dawley , Venenos de Escorpião/sangue , Venenos de Escorpião/farmacocinética , Venenos de Escorpião/toxicidadeRESUMO
This study developed a method to estimate added sugar content in consumer packaged goods (CPG) that can keep pace with the dynamic food system. A team including registered dietitians, a food scientist and programmers developed a batch-mode ingredient matching and linear programming (LP) approach to estimate the amount of each ingredient needed in a given product to produce a nutrient profile similar to that reported on its nutrition facts label (NFL). Added sugar content was estimated for 7021 products available in 2007-08 that contain sugar from ten beverage categories. Of these, flavored waters had the lowest added sugar amounts (4.3g/100g), while sweetened dairy and dairy alternative beverages had the smallest percentage of added sugars (65.6% of Total Sugars; 33.8% of Calories). Estimation validity was determined by comparing LP estimated values to NFL values, as well as in a small validation study. LP estimates appeared reasonable compared to NFL values for calories, carbohydrates and total sugars, and performed well in the validation test; however, further work is needed to obtain more definitive conclusions on the accuracy of added sugar estimates in CPGs. As nutrition labeling regulations evolve, this approach can be adapted to test for potential product-specific, category-level, and population-level implications.
RESUMO
BACKGROUND/OBJECTIVES: Heart failure (HF) is a condition of chronic exacerbations and injury resulting from an intricate relationship between biochemical and biological mechanisms. Inflammation can be a significant contributor in the pathophysiology of HF. Antioxidants may slow the progression of HF because of their ability to inhibit damaging inflammatory processes. The purpose of this study was to test a dietary intervention in patients with HF to assess the impact of lycopene on biomarkers of inflammation. SUBJECTS/METHODS: Forty participants with HF were randomly assigned to 1 of 2 groups: lycopene intervention and usual care. The lycopene intervention group received 29.4 mg of lycopene intake per day by drinking an 11.5 oz serving of V8 100% vegetable juice for 30 days. We obtained serum lycopene, uric acid, C-reactive protein (CRP), and b-type natriuretic peptide to determine the impact of the intervention. RESULTS: Plasma lycopene levels increased in the intervention group compared with the usual care group (0.51 µmol/L to 0.76 µmol/L, P = .002; 0.56 µmol/L to 0.58 µmol/L). C-reactive protein levels decreased significantly in the intervention group in women and but not in men (P = .04). The preintervention CRP level for women was 5.9 ± 3.7 mg/dL and for men was 2.2 ± 2.1 mg/dL. The postintervention CRP level for women was 4.5 ± 3.6 mg/dL and for men was 2.4 ± 2.1 mg/dL. CONCLUSIONS: These findings suggest that the antioxidants in a 30-day intervention of V8 juice affect CRP levels in a sample of female patients with HF.
Assuntos
Antioxidantes/uso terapêutico , Carotenoides/uso terapêutico , Insuficiência Cardíaca/dietoterapia , Idoso , Bebidas , Biomarcadores/sangue , Proteína C-Reativa/análise , Carotenoides/sangue , Feminino , Insuficiência Cardíaca/sangue , Humanos , Licopeno , Masculino , Peptídeo Natriurético Encefálico/sangue , Projetos Piloto , Fatores Sexuais , Ácido Úrico/sangueRESUMO
SCOPE: Broccoli sprouts are a rich source of glucosinolates, a group of phytochemicals that when hydrolyzed, are associated with cancer prevention. Our objectives were to investigate the metabolism, distribution, and interconversion of isothiocyanates (ITCs) in mice fed thermally processed broccoli sprout powders (BSPs) or the purified ITC sulforaphane. METHODS AND RESULTS: For 1 wk, mice were fed a control diet (n = 20) or one of four treatment diets (n = 10 each) containing nonheated BSP, 60°C mildly heated BSP, 5-min steamed BSP, or 3 mmol purified sulforaphane. Sulforaphane and erucin metabolite concentrations in skin, liver, kidney, bladder, lung, and plasma were quantified using HPLC-MS/MS. Thermal intensity of BSP processing had disparate effects on ITC metabolite concentrations upon consumption. Mild heating generally resulted in the greatest ITC metabolite concentrations in vivo, followed by the nonheated and steamed BSP diets. We observed interconversion between sulforaphane and erucin species or metabolites, and report that erucin is the favored form in liver, kidney, and bladder, even when only sulforaphane is consumed. CONCLUSION: ITC metabolites were distributed to all tissues analyzed, suggesting the potential for systemic benefits. We report for the first time tissue-dependent ratio of sulforaphane and erucin, though further investigation is warranted to assess biological activity of individual forms.