MAFFEIS, CLAUDIO, ANGELO PIETROBELLI, ALESSANDRA GREZZANI, SILVIA PROVERA, AND LUCIANO TATÒ . Waist circumference and cardiovascular risk factors in prepubertal children. Obes Res. 2001;9: 179 -187. Objective: Intra-abdominal fat has been identified as being the most clinically relevant type of fat in humans. Therefore, an assessment of body-fat distribution could possibly identify subjects with the highest risk of adverse lipid profile and hypertension. Few data on the relationship between body-fat distribution and cardiovascular risk factors are available in children, especially before puberty. Research Methods and Procedures:This cross-sectional study was undertaken to explore the relationship between anthropometric variables, lipid concentrations, and blood pressure (BP) in a sample of 818 prepubertal children (ages 3 to 11 years) and to assess the clinical relevance of waist circumference in identifying prepubertal children with higher cardiovascular risk. Height, weight, triceps and subscapular skinfolds, waist circumference, and BP were measured. Plasma levels for triacylglycerol, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) were determined. Results: Females were fatter than males (5.8 [3.5] vs. 4.8 [3.3] kg of fat mass; p Ͻ 0.01). Males had higher HDL cholesterol and ApoA1/ApoB plasma concentrations than females (p Ͻ 0.001 and p Ͻ 0.01, respectively). Waist circumference had a higher correlation with systolic and diastolic BP (r ϭ 0.40 and 0.29, respectively; p Ͻ 0.001) than triceps (r ϭ 0.35 and 0.21, respectively; p Ͻ 0.001) and subscapular (r ϭ 0.28 and 0.16, respectively; p Ͻ 0.001) skinfolds and relative body weight (0.33 and 0.23, respectively; p Ͻ 0.001). Multivariate linear model analysis showed that ApoA1/ApoB, HDL cholesterol, total cholesterol/HDL cholesterol, and systolic as well as diastolic BP were significantly associated with waist circumference and triceps and subscapular skinfolds, independently of age, gender, and body mass index. Discussion: Waist circumference as well as subscapular and triceps skinfolds may be helpful parameters in identifying prepubertal children with an adverse blood-lipids profile and hypertension. However, waist circumference, which is easy to measure and more easily reproducible than skinfolds, may be considered in clinical practice. Children with a waist circumference greater than the 90th percentile are more likely to have multiple risk factors than children with a waist circumference that is less than or equal to the 90th percentile.

OBJECTIVE: The purpose of our study was to assess the relationship between nutrient intake, partitioning of food intake, parents' overweight and adiposity in a group of children. SUBJECTS: 530 7 ± 11-year-old children: 278 males, 252 females. METHODS: Energy intake, nutrient intake and percentage distribution of the intake of energy among the different meals were assessed by means of diet history. Body composition was obtained by measuring skinfold thickness. RESULTS: We identi®ed the relationship between the children's adiposity and their parents' body mass index (BMI) mother: r 0.12, P`0.01; father: r 0.13; P`0.01), carbohydrate (r 7 0.15, P`0.001) and fat intake (r 0.14, P`0.002), and the proportion of energy taken at dinner (r 0.1, P`0.05). A multiple regression analysis was run with a stepwise procedure using relative adiposity as the dependent variable and parents' BMI, dinner intake (percentage of energy intake), EIaBMR ratio (an index of energy intake validity), and sex (dummy variable) as independent variables. All the independent variables, except percentage of fat intake, were included in the ®nal model. The equation was able to explain % 19% (R 0.44, P`0.001) of inter-individual fat mass percentage variability. CONCLUSIONS: Diet composition did not contribute to explain the children's adiposity when the parents' overweight (BMI) was taken into account. However, the percentage distribution of the intake of energy among the different meals, particularly at dinner, contributed to explain inter-individual variance of fatness in children of both sexes.

In this paper, we report the metabolic and molecular changes in response to cold and drought induced in Osmyb4 transgenic Arabidopsis thaliana compared with the wildtype (WT). The rice Osmyb4 gene codes for a transcription factor (Myb4) induced by cold treatment and, in Arabidopsis transgenic plants, improves cold and freezing tolerance [Vannini C, Locatelli F, Bracale M, Magnani E, Marsoni M, Osnato M, Mattana M, Baldoni E, Coraggio I (2004) Plant J 37: 115-127].Here, we report the ability of Myb4 to induce also drought tolerance in Arabidopsis transgenic plants. By the use of nuclear magnetic resonance (NMR) and enzymatic assays, we showed that several compatible solutes (glucose, fructose, sucrose, proline, glycine betaine and sinapoyl malate) accumulate in higher amount in Osmyb4-overexpressing plants with respect to the WT, both under normal and stress conditions. Considering proline, we also found that in transgenic plants the levels of the mRNAs coding for D 1 -pyrroline-5-carboxylate synthase (EC not assigned) and for D 1 -pyrroline-5-carboxylate dehydrogenase (EC 1.5.1.12) were higher and lower, respectively. The constitutive activation of several stress-inducible pathways and different kinetics in the accumulation of several metabolites, in Myb4 transgenic plants, may represent an advantage to prepare plants to face the stress condition. Moreover, these results taken together suggest that Myb4 integrates the activation of multiple components of stress response.Abbreviations -LC-NMR, liquid chromatography-NMR; NMR, nuclear magnetic resonance; PAL, phenylalanine ammonia lyase; P5CDH, D 1 -pyrroline-5-carboxylate dehydrogenase; P5CS, D 1 -pyrroline-5-carboxylate synthase.

We have developed QUANTAS (QUANTification by Artificial Signal), which is a software-based protocol for concentration measurement by NMR. QUANTAS is an absolute intensity external standard method for quantification by NMR that compensates for various experimental parameters. It is applicable to all nuclei and modern spectrometers. QUANTAS is demonstrated here for (1)H and (19)F NMR, enabling heteronuclear integrals to be compared. It can be applied using fixed probe tuning, matching and pulse length, for samples with the same effective loading on the probe coil as the appropriate reference spectrum. Otherwise, an optimised tuning and matching approach is adopted for every sample together with explicit PULCON (PUlse Length-based CONcentration measurements) absolute intensity corrections.

A small series of aminobisphosphonates (N-BPs) structurally related to zoledronic acid was synthesized with the aim of improving activity toward activation of human gammadelta T cells and in turn their in vivo antitumor activity. The absence of the 1-OH moiety, together with the position and the different basicity of the nitrogen, appears crucial for antitumor activity. In comparison to zoledronic acid, compound 6a shows a greater ability to activate gammadelta T cells expression (100 times more) and a proapoptotic effect that is better than zoledronic acid. The potent activation of gammadelta T cells, in addition to evidence of the in vivo antitumor activity of 6a, suggests it may be a new potential drug candidate for cancer treatment.

A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes with high affinity and selectivity for the DA D(3) receptor and excellent pharmacokinetic profiles was recently reported. We also recently discussed the role of the linker associated with the triazole moiety. In this manuscript, we are reporting a detailed exploration of the region of the receptor interacting with the amine terminus of the scaffold wherein SAR and developability data associated with these novel templates was undertaken.

OBJECTIVE:The aim of this study was to identify in a group of 8-y-old prepubertal children the anthropometric parameter with the highest prediction power of overweight, measured 4 y later. SUBJECTS: One-hundred and twelve Caucasian children (54 males, 58 females), aged 8.7 AE 0.9 y, were studied. RESULTS: An analysis of the association between relative body mass index (BMI) at follow-up (%) and some indexes of adiposity like relative BMI (%), waist circumference, subscapular and triceps skinfolds, the sum of four skinfolds and percentage fat mass measured at baseline, showed that relative BMI (relBMI) at baseline had the highest association with relBMI at follow-up (r 0.77; P`0.001); waist circumference had a slightly lower signi®cant association with relBMI at follow-up (r 0.74; P`0.001). In a multiple regression analysis, waist circumference (adjusted for age) accounted for $ 64% of the variation of relBMI at follow-up (P`0.001). RelBMI measured at baseline accounted for $ 59% of the variation of relBMI at follow-up (P`0.001). Multiple logistic regression analysis included waist circumference, adjusted for age, mother's BMI and relBMI measured at baseline as independent variables in the ®nal equation. In particular, each centimeter increase of waist circumference at the age of 8 y doubled the risk of having a relBMI greater than 120% at the age of 12 y. CONCLUSION: The results of this study, the ®rst which has approached this investigation in children, showed that waist circumference measured at the age of 8 y, which is simple to perform and easy to reproduce, may be a promising index to assess adiposity as well as to predict overweight at puberty. International Journal of Obesity (2001) 25, 978 ± 983

In an effort to discover novel druglike NK(1) receptor antagonists a new series of suitably substituted C-phenylpiperazine derivatives was identified by an appropriate chemical exploration of related N-phenylpiperazine analogues, with the specific aim to maximize their in vitro affinity and optimize in parallel their pharmacokinetic profile. Among the compounds synthesized, 2-(S)-(4-fluoro-2-methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3,5-bis-trifluoromethylphenyl)ethyl]methylamide (vestipitant) was identified as one of the most in vitro potent and selective NK(1) receptor antagonists ever discovered, showing appropriate pharmacokinetic properties and in vivo activity. On the basis of its preclinical profile, this compound was selected as a drug candidate.