A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS method.

Fourteen compounds representing ester derivatives of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl) propanoic and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acids, expressing antiproliferative activity in vitro were examined. The objective of this study was to determinate their lipophilicity data, and also to ensure a mathematical model for prediction lipophilicity data of potential in vivo metabolites and new derivatives of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid, based on chromatographic parameters. Experimentally, lipophilicity data were obtained by a traditional shake flask procedure and an ultra-high performance liquid chromatographic tandem mass spectrometry (UHPLC-MS) method. A correlation between the partition coefficient n-octanol/water (logD7,4) and chromatographic data (CHI, 0), and also, between logD7,4 and retention time was investigated. A very good correlation (r2=0.8969) was found between lipophilicity parameters 0 and logD7,4 obtained using UHPLC-MS and shake flask methods: logD7,4 = (0.11±0.01)×0 + (1.25±0.20)×Nc - (9.19±1.18); statistical parameter F=47.84; significance of F = 3.74×10-6, Nc=number of C atoms between two amino groups (Nc=2 for 1,2-ethanediamine derivatives and Nc=3 for 1,3-propanediamine derivatives). The model predictivity power was determined by cross validation leave one out (LOO) technique, and expressed by the term Q2, was 0.89. The developed model has good predictivity power for prediction lipophilicity data of potential in vivo metabolites of the investigated compounds, such as novel 1,2-ethanediamine and 1,3-propanediamine N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. Also, the lipophilicity data obtained in the present study correlated with the antiproliferative activity of the investigated substances shown previously in in vitro studies.

Increased Bone Mineral Content During Rapid Weight Gain Therapy in Anorexia Nervosa.

Patients with anorexia nervosa (AN) are at high risk of reduced bone mass. Osteocalcin (OC), a bone formation marker, has been proposed to act as a link between bone and energy metabolism. We investigated how the 3 forms of OC respond during a 12-week intensive nutrition therapy in AN patients, in whom large changes in energy metabolism are expected.Twenty-two female AN patients, mean 20.9 years of age, with a starting mean body mass index (BMI) 15.5 kg/m2 (minimum-maximum) (13.4-17.3 kg/m2) completed the study. Biochemical markers, body composition, bone mass by DXA, and pQCT were assessed. Subjects gained in median 9.9 kg (5.5-17.0 kg), and BMI increased from median 15.4 kg/m2 (13.4-17.3 kg/m2) to 19.0 kg/m2 (16.2-20.6 kg/m2), p<0.0001. Fat mass increased from median 11.4% (4.4-24.8%) to 26.7% (16.9-39.8%). Total OC, carboxylated OC (cOC), undercarboxylated OC (ucOC), and bone-specific alkaline phosphatase (BALP) increased during the study period. No change was observed for the resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX). Total body bone mineral content (BMC) increased, but no changes were found for whole body or lumbar spine bone mineral density. Tibial trabecular density measured by pQCT decreased. Total OC, cOC, and ucOC were not associated with BMI, insulin or body composition parameters. This prospective study demonstrates that all 3 forms of OC (total OC, cOC, ucOC) increase during rapid weight gain. BALP increased while the resorption marker CTX was unchanged, which corroborate with the increased total body BMC.

Assessment of the contamination of riparian soil and vegetation by trace metals--A Danube River case study.

The aim of this study was to assess the spatial distribution of arsenic and heavy metals (Cd, Cr, Cu Hg, Ni, Pb and Zn) in a riparian area influenced by periodical flooding along a considerable stretch of the Danube River. This screening was undertaken on soil and plant samples collected from 43 sites along 2386 km of the river, collected during the international Joint Danube Survey 3 expedition (ICPDR, 2015). In addition, data on the concentration of these elements in river sediment was used in order to describe the relationship between sediment, riparian soil and riparian plants. A significant positive correlation (Spearman r, for p<0.05) was found for trace metal concentrations in river sediment and soil (r=0.817). A significant correlation between soil and plants (r=0.438) and sediment and plants (r=0.412) was also found for trace metal concentrations. Elevated levels of Cd, Cr, Cu, and Ni were found at certain sites along the Serbian stretch, while elevated concentrations of Hg were also detected in Hungary, of Pb along the Romanian stretch and of As along the Bulgarian stretch (the Lower Danube). These results point to the presence of naturally-occurring metals derived from ore deposits in the Danube River Basin and anthropogenic metals, released by mining and processing of metal ores and other industrial facilities, which are responsible for the entry of metals such as Cu, Ni and Zn. Our results also indicated toxic Cd and Zn levels in plant samples, measured at the Hercegsznato site (Middle Danube, Hungary), which highlighted these elements as a potential limiting factor for riparian vegetation in that area. The distribution of the analysed elements in plant material also indicates the species-specific accumulation of trace metals. Based on our results, the Lower and Middle Danube were found to be more polluted in terms of the analysed elements.

Validation of anthropometry and foot-to-foot bioelectrical resistance against a three-component model to assess total body fat in children: the IDEFICS study.

OBJECTIVE: To compare different field methods for estimating body fat mass with a reference value derived by a three-component (3C) model in pre-school and school children across Europe. DESIGN: Multicentre validation study. SUBJECTS: Seventy-eight preschool/school children aged 4-10 years from four different European countries. METHODS: A standard measurement protocol was carried out in all children by trained field workers. A 3C model was used as the reference method. The field methods included height and weight measurement, circumferences measured at four sites, skinfold measured at two-six sites and foot-to-foot bioelectrical resistance (BIA) via TANITA scales. RESULTS: With the exception of height and neck circumference, all single measurements were able to explain at least 74% of the fat-mass variance in the sample. In combination, circumference models were superior to skinfold models and height-weight models. The best predictions were given by trunk models (combining skinfold and circumference measurements) that explained 91% of the observed fat-mass variance. The optimal data-driven model for our sample includes hip circumference, triceps skinfold and total body mass minus resistance index, and explains 94% of the fat-mass variance with 2.44 kg fat mass limits of agreement. In all investigated models, prediction errors were associated with fat mass, although to a lesser degree in the investigated skinfold models, arm models and the data-driven models. CONCLUSION: When studying total body fat in childhood populations, anthropometric measurements will give biased estimations as compared to gold standard measurements. Nevertheless, our study shows that when combining circumference and skinfold measurements, estimations of fat mass can be obtained with a limit of agreement of 1.91 kg in normal weight children and of 2.94 kg in overweight or obese children.

Relation between bone mineral density, biological markers and anthropometric measures in 4-year-old children: a pilot study within the IDEFICS study.

OBJECTIVE: To investigate the relationship between bone mineral density (BMD), anthropometric characteristics, levels of biological markers for growth, bone turnover, insulin resistance and fat mass in 4-year-old Swedish children. METHODS: Descriptive study with 41 children (28 boys) who had anthropometric measurements and blood samples taken and heel dual-energy X-ray absorptiometry and laser (DXL) performed. The study participants were divided into groups of normal-weight (n=28) and overweight or obese (n=13) children. RESULTS: There was a significant difference in bone mineral content (BMC), BMD and bone mineral apparent density (BMAD) between overweight and normal-weight children. There was a significant positive correlation between BMC, BMD, BMAD and body mass index standard deviation scores (r=0.36, 0.34 and 0.29, P<0.01, respectively), waist circumference (r=0.32, 0.30, P<0.01 and r=0.26, P<0.05, respectively) and subscapular skinfold (r=0.26, 0.25 and 0.23, P<0.05, respectively). BMC and BMD correlated significantly with the sum of skinfold measures (r=0.25 and 0.23, P<0.05, respectively). Adiponectin was significantly inversely correlated with BMC, BMD and BMAD (r=-0.41, -0.40 and -0.41, P<0.01, respectively). Adiponectin was not correlated with skinfold measures. Multiple regression analysis revealed that adiponectin was an independent determinant of BMD, BMC and BMAD. CONCLUSION: To our knowledge, this is the first study investigating BMD assessed by heel-DXL in relation to anthropometry and metabolic markers in 4-year-old children. Adiponectin was significantly inversely correlated with bone mass parameters. Adiponectin may have an independent role in bone development and metabolism in young children.

The relationship between paediatric calcaneal quantitative ultrasound measurements and dual energy X-ray absorptiometry (DXA) and DXA with laser (DXL) as well as body composition.

BACKGROUND: Quantitative ultrasound (QUS) is a quick, non-invasive and inexpensive method to measure bone strength. Moreover, the device is portable, which makes it easy to be used in the field. In contrast to other bone measuring techniques, QUS does not use any ionised radiation. However, the validity of QUS in the measurement of bone health and the relationship between QUS output and body composition have not been assessed in very young children. OBJECTIVE: To investigate the relationship between paediatric calcaneal QUS and both dual-energy X-ray absorptiometry (DXA) and calcaneal DXA with laser (DXL) and body composition parameters. SUBJECTS: A total of 37 Belgian children (10 boys and 27 girls; 4 to 8 years old) underwent a calcaneal QUS as well as a DXA scan. A total of 24 Swedish children (15 boys and 9 girls; 3 to 5 years old) underwent a calcaneal QUS as well as a heel DXL scan. The height and weight of all children were measured. RESULTS: The QUS stiffness index (SI) was significantly negatively correlated with bone mineral density (BMD) of the total body (r=-0.370, P=0.02). No significant correlations were found between the SI and DXL results. In the total sample, the SI showed a significant positive correlation with body mass index (BMI) (r=0.298, P=0.02), even after correction for age, gender and centre. In the Belgian sample, the SI was also significantly positively correlated with total body fat mass content (r=0.416, P=0.01) and body fat percentage (r=0.566, P<0.01) obtained by whole-body DXA. CONCLUSION: The SI measured by QUS does not correlate significantly with BMD values measured by DXA or DXL in 3- to 8-year-old children. However, there is a significant positive correlation between SI and BMI and body fat %.

The IDEFICS validation study on field methods for assessing physical activity and body composition in children: design and data collection.

OBJECTIVE: To describe the design, measurements and fieldwork of the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) physical activity and body composition validation study, and to determine the potential and limitations of the data obtained. DESIGN: Multicentre validation study. SUBJECTS: A total of 98 children from four different European countries (age: 4-10 years). METHODS: An 8-day measurement protocol was carried out in all children using a collaborative protocol. Reference methods were the doubly labelled water method for physical activity, and a three- and a four-compartment model for body composition. Investigated field methods were accelerometers, a physical activity questionnaire and various anthropometric measurements. RESULTS: For the validation of physical activity field methods, it was possible to gather data from 83 to 89 children, laying the basis for age- and sex-specific results. The validation of body composition field methods is possible in 64-80 children and allows sex-specific analyses but has only limited statistical power in the youngest age group (<6 years). The amount of activity energy expenditure (AEE) varied between centres, sexes and age groups, with boys and older children having higher estimates of AEE. After normalisation of AEE by body weight, most group-specific differences diminished, except for country-specific differences. CONCLUSION: The IDEFICS validation study will allow age- and sex-specific investigation of questions pertaining to the validity of several field methods of body composition and physical activity, using established reference methods in four different European countries. From the participant analyses it can be concluded that the compliance for the investigated field methods was higher than that for the reference methods used in this validation study.