Polyamines: total daily intake in adolescents compared to the intake estimated from the Swedish Nutrition Recommendations Objectified (SNO)

Background: Dietary polyamines have been shown to give a significant contribution to the body pool of polyamines. Knowing the levels of polyamines (putrescine, spermidine, and spermine) in different foods and the contribution of daily food choice to polyamine intake is of interest, due to the association of these bioactive amines to health and disease. Objective: To estimate polyamine intake and food contribution to this intake in adolescents compared to a diet fulfilling the Swedish Nutrition Recommendations. Design: A cross-sectional study of dietary intake in adolescents and an ‘ideal diet’ (Swedish nutrition recommendations objectified [SNO]) list of foods was used to compute polyamine intake using a database of polyamine contents of foods. For polyamine intake estimation, 7-day weighed food records collected from 93 adolescents were entered into dietetic software (Dietist XP) including data on polyamine contents of foods. The content of polyamines in foods recommended according to SNO was entered in the same way. Results: The adolescents’ mean daily polyamine intake was 316±170 µmol/day, while the calculated contribution according to SNO was considerably higher with an average polyamine intake of 541 µmol/day. In both adolescent's intake and SNO, fruits contributed to almost half of the total polyamine intake. The reason why the intake among the adolescents was lower than the one calculated from SNO was mainly due to the low vegetable consumption in the adolescents group. Conclusions: The average daily total polyamine intake was similar to that previously reported in Europe. With an ‘ideal’ diet according to Swedish nutrition recommendations, the intake of this bioactive non-nutrient would be higher than that reported by our adolescents and also higher than that previously reported from Europe

Polyamines in foods: development of a food database

Background: Knowing the levels of polyamines (putrescine, spermidine, and spermine) in different foods is of interest due to the association of these bioactive nutrients to health and diseases. There is a lack of relevant information on their contents in foods. Objective: To develop a food polyamine database from published data by which polyamine intake and food contribution to this intake can be estimated, and to determine the levels of polyamines in Swedish dairy products. Design: Extensive literature search and laboratory analysis of selected Swedish dairy products. Polyamine contents in foods were collected using an extensive literature search of databases. Polyamines in different types of Swedish dairy products (milk with different fat percentages, yogurt, cheeses, and sour milk) were determined using high performance liquid chromatography (HPLC) equipped with a UV detector. Results: Fruits and cheese were the highest sources of putrescine, while vegetables and meat products were found to be rich in spermidine and spermine, respectively. The content of polyamines in cheese varied considerably between studies. In analyzed Swedish dairy products, matured cheese had the highest total polyamine contents with values of 52.3, 1.2, and 2.6 mg/kg for putrescine, spermidine, and spermine, respectively. Low fat milk had higher putrescine and spermidine, 1.2 and 1.0 mg/kg, respectively, than the other types of milk. Conclusions: The database aids other researchers in their quest for information regarding polyamine intake from foods. Connecting the polyamine contents in food with the Swedish Food Database allows for estimation of polyamine contents per portion

ZBED6, a Novel Transcription Factor Derived from a Domesticated DNA Transposon Regulates IGF2 Expression and Muscle Growth

This study identifies a previously uncharacterized protein, encoded by a domesticated DNA transposon, called ZBED6 that regulates the expression of the insulin-like growth factor 2 (IGF2) gene, and possibly numerous others, in all placental mammals including human

PopED: an extended, parallelized, nonlinear mixed effects models optimal design tool

Several developments have facilitated the practical application and increased the general use of optimal design for nonlinear mixed effects models. These developments include new methodology for utilizing advanced pharmacometric models, faster optimization algorithms and user friendly software tools. In this paper we present the extension of the optimal design software PopED, which incorporates many of these recent advances into an easily useable enhanced GUI. Furthermore, we present new solutions to problems related to the design of experiments such as: faster and more robust FIM calculations and optimizations, optimizing over cost/utility functions and diagnostic tools and plots to evaluate design performance. Examples for; (i) Group size optimization and efficiency translation, (ii) Cost/constraint optimization, (iii) Optimizations with different FIM approximations and (iv) optimization with parallel computing demonstrate the new features in PopED and underline the potential use of this tool when designing experiments. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs