A comparative evaluation of functions for partitioning nitrogen and amino acid intake between maintenance and growth in broilers

The results from three types of study with broilers, namely nitrogen (N) balance, bioassays and growth experiments, provided the data used herein. Sets of data on N balance and protein accretion (bioassay studies) were used to assess the ability of the monomolecular equation to describe the relationship between (i) N balance and amino acid (AA) intake and (ii) protein accretion and AA intake. The model estimated the levels of isoleucine, lysine, valine, threonine, methionine, total sulphur AAs and tryptophan resulting in zero balance to be 58, 59, 80, 96, 23, 85 and 32 mg/kg live weight (LW)/day, respectively. These estimates show good agreement with those obtained in previous studies. For the growth experiments, four models, specifically re-parameterized for analysing energy balance data, were evaluated for their ability to determine crude protein (CP) intake at maintenance and efficiency of utilization of CP intake for producing gain. They were: a straight line, two equations representing diminishing returns behaviour (monomolecular and rectangular hyperbola) and one equation describing smooth sigmoidal behaviour with a fixed point of inflexion (Gompertz). The estimates of CP requirement for maintenance and efficiency of utilization of CP intake for producing gain varied from 5.4 to 5.9 g/kg LW/day and 0.60 to 0.76, respectively, depending on the models.

Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude

Amphiphilic chitosan-based polymers (M-w < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the degree of lipidic derivatization and molecular weight of the carbohydrate. The extent of drug incorporation by these novel micellar clusters is 1 order of magnitude higher than is seen with triblock copolymers, with molar polymer/drug ratios of 1:48 to 1:67. On intravenous injection, the pharmacodynamic activity of a carbohydrate propofol formulation is increased by 1 order of magnitude when compared to a commercial emulsion formulation, and on topical ocular application of a carbohydrate prednisolone formulation, initial drug aqueous humor levels are similar to those found with a 10-fold dose of prednisolone suspension.

Developing synthetic mucosa-mimetic hydrogels to replace animal experimentation in characterisation of mucoadhesive drug delivery systems

Mucosa-mimetic polymeric hydrogels have been developed to replace the use of animal tissues as substrates for characterising mucoadhesive properties of drug delivery systems.

The impact of obesity-related single nucleotide polymorphisms on appetite and energy intake: a pilot study

An increasing number of studies have reported a heritable component for the regulation of energy intake and eating behaviour, although the individual polymorphisms and their ‘effect size’ are not fully elucidated. The aim of the present study was to examine the relationship between specific SNP and appetite responses and energy intake in overweight men. In a randomised cross-over trial, forty overweight men (age 32 (sd 09) years; BMI 27 (sd 2) kg/m2) attended four sessions 1 week apart and received three isoenergetic and isovolumetric servings of dairy snacks or water (control) in random order. Appetite ratings were determined using visual analogue scales and energy intake at an ad libitum lunch was assessed 90 min after the dairy snacks. Individuals were genotyped for SNP in the fat mass and obesity-associated (FTO), leptin (LEP), leptin receptor (LEPR) genes and a variant near the melanocortin-4 receptor (MC4R) locus. The postprandial fullness rating over the full experiment following intake of the different snacks was 17·2 % (P= 0·026) lower in A carriers compared with TT homozygotes for rs9939609 (FTO, dominant) and 18·6 % (P= 0·020) lower in G carriers compared with AA homozygotes for rs7799039 (LEP, dominant). These observations indicate that FTO and LEP polymorphisms are related to the variation in the feeling of fullness and may play a role in the regulation of food intake. Further studies are required to confirm these initial observations and investigate the ‘penetrance’ of these genotypes in additional population subgroups.

Population based models of cortical drug response: insights from anaesthesia

A great explanatory gap lies between the molecular pharmacology of psychoactive agents and the neurophysiological changes they induce, as recorded by neuroimaging modalities. Causally relating the cellular actions of psychoactive compounds to their influence on population activity is experimentally challenging. Recent developments in the dynamical modelling of neural tissue have attempted to span this explanatory gap between microscopic targets and their macroscopic neurophysiological effects via a range of biologically plausible dynamical models of cortical tissue. Such theoretical models allow exploration of neural dynamics, in particular their modification by drug action. The ability to theoretically bridge scales is due to a biologically plausible averaging of cortical tissue properties. In the resulting macroscopic neural field, individual neurons need not be explicitly represented (as in neural networks). The following paper aims to provide a non-technical introduction to the mean field population modelling of drug action and its recent successes in modelling anaesthesia.

Influence of dietary protein intake and glycemic index on the association between TCF7L2 HapA and weight gain

BACKGROUND: Genetic polymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BMI. OBJECTIVE: The objective was to investigate whether TCF7L2 HapA is associated with weight development and whether such an association is modulated by protein intake or by the glycemic index (GI). DESIGN: The investigation was based on prospective data from 5 cohort studies nested within the European Prospective Investigation into Cancer and Nutrition. Weight change was followed up for a mean (±SD) of 6.8 ± 2.5 y. TCF7L2 rs7903146 and rs10885406 were successfully genotyped in 11,069 individuals and used to derive HapA. Multiple logistic and linear regression analysis was applied to test for the main effect of HapA and its interaction with dietary protein or GI. Analyses from the cohorts were combined by random-effects meta-analysis. RESULTS: HapA was associated neither with baseline BMI (0.03 ± 0.07 BMI units per allele; P = 0.6) nor with annual weight change (8.8 ± 11.7 g/y per allele; P = 0.5). However, a previously shown positive association between intake of protein, particularly of animal origin, and subsequent weight change in this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01). We showed that weight gain becomes independent of protein intake with an increasing number of HapA alleles. Substitution of protein with either fat or carbohydrates showed the same effects. No interaction with GI was observed. CONCLUSION: TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet.

Supporting visual assessment of food and nutrient intake in a clinical care setting

Monitoring nutritional intake is an important aspect of the care of older people, particularly for those at risk of malnutrition. Current practice for monitoring food intake relies on hand written food charts that have several inadequacies. We describe the design and validation of a tool for computer-assisted visual assessment of patient food and nutrient intake. To estimate food consumption, the application compares the pixels the user rubbed out against predefined graphical masks. Weight of food consumed is calculated as a percentage of pixels rubbed out against pixels in the mask. Results suggest that the application may be a useful tool for the conservative assessment of nutritional intake in hospitals.

Association between sucrose intake and risk of overweight and obesity in a prospective sub-cohort of EPIC-Norfolk

Objective: The objective of this study was to investigate associations between sugar intake and overweight using dietary biomarkers in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Design: Prospective cohort study Setting: European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) in the UK, recruitment between 1993 and 1997. Subjects: 1734 participants (39 – 77 years). Sucrose intake was assessed using 7-day diaries. Baseline spot urine samples were analysed for sucrose by GC-MS. Sucrose concentration adjusted by specific gravity was used as biomarker for intake. Regression analyses were used to investigate associations between sucrose intake and risk of BMI > 25 kg/m2 after three years of follow-up. Results: After three years of follow-up, mean BMI was 26.8 kg/m2. Self-reported sucrose intake was significantly positively associated with biomarker. Associations between biomarker and BMI were positive (β=0.25; 95% CI: 0.08; 0.43), while they were inverse when using self-reported dietary data (β=-1.40; 95% CI: -1.81; -0.99). Age- and sex-adjusted OR for BMI > 25 kg/m2 in participants in the fifth vs. first quintile was 1.54 (95% CI: 1.12; 2.12; pTrend=0.003,) when using biomarker and 0.56 (95% CI: 0.40; 0.77; pTrend<0.001) with self-reported dietary data. Conclusions: Our results suggest that sucrose measured by objective biomarker but not self-reported sucrose intake is positively associated with body mass index. Future studies should consider use of objective biomarkers of sucrose intake.

Online dietary intake estimation : reproducibility and validity of the Food4Me food frequency questionnaire against a 4-day weighed food record

Background: Advances in nutritional assessment are continuing to embrace developments in computer technology. The online Food4Me food frequency questionnaire (FFQ) was created as an electronic system for the collection of nutrient intake data. To ensure its accuracy in assessing both nutrient and food group intake, further validation against data obtained using a reliable, but independent, instrument and assessment of its reproducibility are required. Objective: The aim was to assess the reproducibility and validity of the Food4Me FFQ against a 4-day weighed food record (WFR). Methods: Reproducibility of the Food4Me FFQ was assessed using test-retest methodology by asking participants to complete the FFQ on 2 occasions 4 weeks apart. To assess the validity of the Food4Me FFQ against the 4-day WFR, half the participants were also asked to complete a 4-day WFR 1 week after the first administration of the Food4Me FFQ. Level of agreement between nutrient and food group intakes estimated by the repeated Food4Me FFQ and the Food4Me FFQ and 4-day WFR were evaluated using Bland-Altman methodology and classification into quartiles of daily intake. Crude unadjusted correlation coefficients were also calculated for nutrient and food group intakes. Results: In total, 100 people participated in the assessment of reproducibility (mean age 32, SD 12 years), and 49 of these (mean age 27, SD 8 years) also took part in the assessment of validity. Crude unadjusted correlations for repeated Food4Me FFQ ranged from .65 (vitamin D) to .90 (alcohol). The mean cross-classification into “exact agreement plus adjacent” was 92% for both nutrient and food group intakes, and Bland-Altman plots showed good agreement for energy-adjusted macronutrient intakes. Agreement between the Food4Me FFQ and 4-day WFR varied, with crude unadjusted correlations ranging from .23 (vitamin D) to .65 (protein, % total energy) for nutrient intakes and .11 (soups, sauces and miscellaneous foods) to .73 (yogurts) for food group intake. The mean cross-classification into “exact agreement plus adjacent” was 80% and 78% for nutrient and food group intake, respectively. There were no significant differences between energy intakes estimated using the Food4Me FFQ and 4-day WFR, and Bland-Altman plots showed good agreement for both energy and energy-controlled nutrient intakes. Conclusions: The results demonstrate that the online Food4Me FFQ is reproducible for assessing nutrient and food group intake and has moderate agreement with the 4-day WFR for assessing energy and energy-adjusted nutrient intakes. The Food4Me FFQ is a suitable online tool for assessing dietary intake in healthy adults.

Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial

Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (<35yrs) and 20 elderly (50-80yrs) healthy, male non- smokers consumed either a CF-containing drink (450mg CF) or nutrient-matched, CF-free control drink bi-daily for 14 days. The primary endpoint was endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints included cardiac output, vascular stiffness, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Following 2 weeks of CF intake, FMD improved in young (6.1±0.7% vs. 7.6±0.7%, p<0.001) and elderly (4.9±0.6% vs. 6.3±0.9%, p<0.001). Secondary outcomes demonstrated in both groups that CF intake decreased pulse wave velocity and lowered total peripheral resistance, increased arteriolar- and microvascular vasodilator capacity, red cell deformability, and diastolic blood pressure, while cardiac output remained affected. In the elderly, baseline systolic blood pressure was elevated, driven by an arterial stiffness-related augmentation. CF intake decreased aortic augmentation index (-9%), and thus systolic blood pressure (-7mmHg). (Clinicaltrials.gov:NCT01639781) CF intake reverses age-related burden of cardiovascular risk in healthy elderly, highlighting the potential of dietary flavanols to maintain cardiovascular health.

Synthesis of mucoadhesive thiol-bearing microgels from 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate: novel drug delivery systems for chemotherapeutic agents to the bladder

Thiol-bearing microgels have been synthesised from copolymerisation of 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate, and subsequent deprotection using sodium thiomethoxide. The concentration of thiol groups on these microgels could be tailored by use of different molar ratios of the two monomers. These thiol-bearing microgels were shown to adhere to ex vivo porcine urinary bladder, which was correlated with their level of thiolation. By simply mixing solutions of thiol-bearing microgels and doxorubicin, high levels of drug loading into the microgels could be achieved. Thiol-bearing microgels controlled the release of doxorubicin in a time-dependent manner over several hours. These doxorubicin-loaded thiol-bearing microgels could have application in the treatment of early-stage bladder cancers. The method used represents a new ‘bottom-up’ approach for the synthesis of novel mucoadhesive microgels.

Exploring the association of diary product intake with the fatty acids C15:0 and C17:0 measured from dried blood spots in a multi-population cohort: findings from the Food4Me study

Scope: The use of biomarkers in the objective assessment of dietary intake is a high priority in nutrition research. The aim of this study was to examine pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) as biomarkers of dairy foods intake. Methods and results: The data used in the present study were obtained as part of the Food4me Study. Estimates of C15:0 and C17:0 from dried blood spots and intakes of dairy from an FFQ were obtained from participants (n=1,180) across 7 countries. Regression analyses were used to explore associations of biomarkers with dairy intake levels and receiver operating characteristic (ROC) analyses were used to evaluate the fatty acids. Significant positive associations were found between C15:0 and total intakes of high-fat dairy products. C15:0 showed good ability to distinguish between low and high consumers of high-fat dairy products. Conclusion: C15:0 can be used as a biomarker of high-fat dairy intake and of specific high-fat dairy products. Both C15:0 and C17:0 performed poorly for total dairy intake highlighting the need for caution when using these in epidemiological studies.