Baby's first bites: a randomized controlled trial to assess the effects of vegetable-exposure and sensitive feeding on vegetable acceptance, eating behavior and weight gain in infants and toddlers.

BACKGROUND: The start of complementary feeding in infancy plays an essential role in promoting healthy eating habits. Evidence shows that it is important what infants are offered during this first introduction of solid foods: e.g. starting exclusively with vegetables is more successful for vegetable acceptance than starting with fruits. How infants are introduced to solid foods also matters: if parents are sensitive and responsive to infant cues during feeding, this may promote self-regulation of energy intake and a healthy weight. However, the effectiveness of the what and the how of complementary feeding has never been experimentally tested in the same study. In the current project the what and how (and their combination) are tested in one study to determine their relative importance for fostering vegetable acceptance and self-regulation of energy intake in infants. METHODS: A four-arm randomized controlled trial (Baby's First Bites (BFB)) was designed for 240 first-time Dutch mothers and their infants, 60 per arm. In this trial, we compare the effectiveness of (a) a vegetable-exposure intervention focusing on the what in complementary feeding; (b) a sensitive feeding intervention focusing on the how in complementary feeding, (c) a combined intervention focusing on the what and how in complementary feeding; (d) an attention-control group. All mothers participate in five sessions spread over the first year of eating solid foods (child age 4-16 months). Primary outcomes are vegetable consumption, vegetable liking and self-regulation of energy intake. Secondary outcomes are child eating behaviors, child anthropometrics and maternal feeding behavior. Outcomes are assessed before, during and directly after the interventions (child age 18 months), and when children are 24 and 36 months old. DISCUSSION: The outcomes are expected to assess the impact of the interventions and provide new insights into the mechanisms underlying the development of vegetable acceptance, self-regulation and healthy eating patterns in infants and toddlers, as well as the prevention of overweight. The results may be used to improve current dietary advice given to parents of their young children on complementary feeding. TRIAL REGISTRATION: The trial was retrospectively registered during inclusion of participants at the Netherlands National Trial Register (identifier NTR6572 ) and at ClinicalTrials.gov ( NCT03348176 ). Protocol issue date: 1 April 2018; version number 1.

Development of a new in-home testing method to assess infant food liking.

The objective of this study was to develop a new elaborate method to evaluate infants' liking of foods that could be applied at home and to compare the results of this elaborate method with those of a basic method. Mothers of infants aged 4 to 7 (n = 44) and 12-15 months (n = 46) participated in this study. For the basic method, mothers were asked to assess their infant's global liking at the end of a meal. Then, for the elaborate method, mothers received detailed instructions on how to feed their infant, how infants might express like/dislike and when to stop the meal. During the first nine spoons, they were asked to report the presence/absence of positive and negative behaviours after each spoon, and the infant's initial liking was reported after each triplet of spoons. They also assessed their infant's global liking at the end of the meal. Both methods were applied using three commercial familiar baby foods adapted to each age range. In 4-7-month-olds, the elaborate method showed a significant difference across products for liking, whereas the basic method did not show any difference. In 12-15-month-olds, the elaborate method showed more differences across products for liking than the basic method. In both age groups, negative behaviours, despite being less frequently reported, provided better liking discrimination than positive behaviours. In conclusion, the elaborate method produced better product liking discrimination than the basic method by focusing maternal attention on infants' eating behaviours since the first spoons.

A step-by-step introduction to vegetables at the beginning of complementary feeding. The effects of early and repeated exposure.

Breastfeeding (BF) is associated with willingness to accept vegetables. This may be due to the variety of flavours delivered via breast milk. Some mothers add vegetables to milk during complementary feeding (CF) to enhance acceptance. The present study tested a step-by-step exposure to vegetables in milk then rice during CF, on intake and liking of vegetables. Just before CF, enrolled mothers were randomised to an intervention (IG, n = 18; 6 BF) or control group (CG, n = 18; 6 BF). IG infants received 12 daily exposures to vegetable puree added to milk (days 1-12), then 12 × 2 daily exposures to vegetable puree added to rice at home (days 13-24). Plain milk and rice were given to CG. Then both received 11 daily exposures to vegetable puree. Intake was weighed and liking rated on days 25-26 and 33-35 after the start of CF in the laboratory, supplemented by the same data recorded at home. Vegetables were rotated daily (carrots, green beans, spinach, broccoli). Intake, liking and pace of eating were greater for IG than CG infants. Intake and liking of carrots were greater than green beans. However, at 6m then 18m follow up, vegetable (carrot > green beans) but not group differences were observed. Mothers reported appreciation of the structure and guidance of this systematic approach. Early exposure to vegetables in a step-by-step method could be included in CF guidelines and longer term benefits assessed by extending the exposure period.

Complementary feeding and "donner les bases du goût" (providing the foundation of taste). A qualitative approach to understand weaning practices, attitudes and experiences by French mothers.

Complementary feeding (CF) practices vary within and across cultures but have been investigated only to a very limited extent. It is however important to understand CF practices and how they differ, as CF sets the foundation for children's later food choices. The present study was set out to examine practices, attitudes and experiences of CF including the introduction of vegetables amongst French mothers (n=18, 25-39 years). Thematic analysis of transcribed focus groups and interviews revealed the perceived importance of the weaning period, as a critical milestone for infants' development but with a sense of "now or never" for introducing new tastes including vegetables. Flavour exposure and taste discovery during weaning were identified as the beginning of a "taste journey", in which educating the palate with a variety of different foods was considered important for children's later eating habits. Weaning was described as emotional and complex, a transition period in which the baby makes progress away from milk towards the family diet and which goes beyond mere nutrition. Advice was sought from official sources, but adapted to the needs of infants. In agreement with earlier observations of French adults, pleasure and taste development were considered of primary importance. In particular, French mothers believed complementary feeding lay the foundations of taste early in life.

Feeding infants and young children. From guidelines to practice-conclusions and future directions.

Infant feeding is a challenging and intricate process. Food intake is shaped by prior experience of flavours derived from the maternal diet in utero and via human milk, by ongoing experience of foods eaten during the first years of life including the variety, types and frequency of foods offered. The ways in which parents interact with their children including the way foods are presented, the emotional context they cultivate and the feeding practices they use can influence their children's eating habits, either positively or negatively. There is a mismatch between what government guidelines advise parents in relation to the "when, what and how" to feed children including during the weaning period and what parents actually do. Acquisition of food preferences and the establishment of eating habits in the early years form part of an ongoing, complex developmental process, however there is a gap between experimental evidence on best practice in infant feeding and what parents receive as advice about feeding. It is timely, therefore, to translate these findings into solutions for parents. Practical support for infant feeding should be evidence based, parent-focused and contingent on the needs of the developing child since infant feeding sets the foundation of healthy eating habits for life.

Stability of thiols in an aqueous process flavoring.

The flavor stability of an aqueous solution of a savory model process flavoring based on ribose and cysteine was investigated during accelerated storage at 50 degrees C. Of the three sulfur-containing flavor-impact components investigated, 2-methyl-3-furanthiol was found to be the least stable (59% decrease/24 h), and it was followed by 2-furfurylthiol (28% decrease/24 h), 2-mercapto-3-butanone (14% decrease/24 h), and 2,5-dimethyl-4-hydroxy-3(2H)-furanone (max. 10% decrease/24 h). Both cysteine and ribose were found to affect the stability of various flavor compounds. A mechanism for the instability of 2-methyl-3-furanthiol is proposed, and was confirmed by H-D exchange experiments.

Characterization of different commercial soybean peroxidase preparations and use of the enzyme for N-demethylation of methyl N-methylanthranilate To produce the food flavor methylanthranilate.

The potential of different peroxidase preparations for the N-demethylation of methyl N-methylanthranilate to produce the food flavor methylanthranilate (MA) was investigated. All tested peroxidase preparations were able to catalyze the N-dealkylation. The tested soybean preparations vary widely with respect to their heme content. Furthermore, the operational stability of purified soybean peroxidase (SP) is at least 25-fold lower than that of horseradish peroxidase and only 5-fold higher than that of microperoxidase 8. Thus, the presence of a large protein chain around a porphyrin cofactor in a peroxidase is, by itself, insufficient to explain the observed differences in operational stability. Despite its relatively low operational stability, SP proved to be the most efficient biocatalyst for the production of MA with high yield and purity, especially observed at the high temperature and low pH values at which SP appeared to be optimally active.

Antimalarial activity of Tanzanian plants and their active constituents: the genus Uvaria.

Petroleum ether, dichloromethane, and methanol extracts of leaves, stem, and root bark of nine Uvaria species: U. dependens, U. faulknerae, U. kirkii, U. leptocladon, U. lucida ssp. lucida, Uvaria sp. (Pande)k U scheffleri, and U. tanzaniae were tested for their in vitro activity against the multidrug resistant K1 strain of Plasmodium falciparum. The IC50 values of the extracts varied between 5 and 500 micrograms/ml. The most active extracts were obtained from the stem and root bark of U. lucida ssp. lucida and Uvaria sp. (Pande) and the root bark of U. scheffleri, all of which had IC50 values between 5 and 9 micrograms/ml. Among the compounds isolated, uvaretin, diuvaretin, and (8',9'-dihydroxy)-3-farnesylindole were the most active (IC50 = 3.49, 4.20, and 2.86 micrograms/ml, respectively).

Antimalarial activity of Tanzanian medicinal plants.

Tanzanian medicinal plants were extracted and tested for in vitro antimalarial activity, using the multidrug resistant K1 strain of Plasmodium falciparum. Of 49 plants investigated, extracts of three plants were found to have an IC50 between 5-10 micrograms/ml, extracts of 18 other plants showed an IC50 between 10 and 50 micrograms/ml, all others were less active. The three most active extracts were obtained from the tubers of Cyperus rotundus L. (Cyperaceae), the rootbark of Hoslundia opposita Vahl. (Labiatae), and the rootbark of Lantana camara L. (Verbenaceae).

Antimalarial compounds containing an alpha,beta-unsaturated carbonyl moiety from Tanzanian medicinal plants.

Pure compounds were isolated from plant extracts with antimalarial activity. The extracts were obtained from the tubers of Cyperus rotundus L. (Cyperaceae), the rootbark of Zanthoxylum gilletii (De Wild) Waterm. (Rutaceae), and the rootbark of Margaritaria discoidea (Baill.) Webster (Euphorbiaceae). The most active compounds included (IC50 within brackets): alpha-cyperone (1) (5.5 micrograms/ml), N-isobutyldeca-2,4-dienamide (2) (5.4 micrograms/ml), and securinine (3) (5.4 micrograms/ml). A mixture of autoxidation products of beta-selinene was found to be the most active antimalarial substances obtained from C. rotundus (5.6 micrograms/ml.

Analysis of doxorubicin, 4'-epidoxorubicin, and their metabolites by liquid chromatography.

An analytical method based on isocratic HPLC separation and fluorescence detection was developed to allow for sensitive and specific analysis of anthracyclines and their metabolites in plasma and urine. The method is particularly advantageous when comparing the metabolism and/or pharmacokinetics of analogues, such as doxorubicin [(8S, 10S)-10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)- oxy]-8-glycolyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-meth- oxy-5,12-naphthacenedione] (1) and 4'-epidoxorubicin (2), since both drugs and their metabolites can be analyzed under identical conditions. The analytical properties of 1, 2, and eight metabolites were studied in plasma, serum, buffer solution, and urine. The detection limit in plasma was 4 X 10(-8) M for the glucuronides, 7 X 10(-9) M for the glycosides, and 1 X 10(-9) M for the aglycones. In plasma, 1, 2, doxorubicinol (3), 4'-epidoxorubicinol (4), doxorubicinone (5), and doxorubicinol aglycone (6) showed a linear concentration-response relationship from their detection limit up to 5 X 10(-6) M. A linear calibration graph for plasma samples was also obtained for 7-deoxydoxorubicinone (7) and 7-deoxydoxorubicinol (8); however, these compounds had a significantly lower upper limit (5 X 10(-7) M). Urine samples were acidified to pH 2.5 and analyzed by HPLC without further purification. A linear calibration curve was obtained in the clinically relevant range. The detection limit in urine was approximately 5 X 10(-8) M. Plasma and urine of two patients who had received 4'-epidoxorubicin by iv bolus injection were analyzed.

Handling of biological samples in the determination of the anti-neoplastic drug mitomycin C.

A study to ascertain suitable conditions for handling biological samples from patients, treated with the antibiotic mitomycin C (MMC), with the objective of improving the accuracy and reliability of the determination is described. Situations frequently occurring in medical practice are simulated to optimize procedures for reliable and reproducible sampling, sample treatment and determination of MMC. Continuation of drug partitioning in whole blood after sampling can be prevented by immediate cooling in ice before the separation of plasma from cells. The adjustment of the pH of urine samples is shown to be particularly important since a low urinary pH causes decomposition of MMC; moreover, it may decrease extraction recovery. Furthermore, long-term exposure of samples to daylight induces drug decomposition. Frozen storage of plasma and urine samples for periods greater than 3 weeks is to be avoided as this results in a considerable drop in MMC concentration. Repeated cycles of freezing and thawing are shown to have no effect upon the analytical results (6 cycles tested). The analysis of extracts of biological samples may take place up to at least 24 h after their preparation without measurable loss of analyte.

Pharmacokinetics of carminomycin in man: biweekly schedule vs single dose every three weeks.

Carminomycin was administered to five patients at a dose of 7.5 mg/m2 twice weekly. Plasma and urine samples were obtained during two subsequent 72-hr periods following drug administration, and assayed for carminomycin (C) and carminomycinol (Col) by HPLC with fluorescence detection. Distribution of carminomycin was rapid and drug levels decreased below the detection limit (5 X 10(-9)M) within 24 hr. Carminomycinol appeared very quickly and surpassed carminomycin levels in 10 min-4 hr, disappearing very slowly, with a half-life of 40-98 hr. No major differences in pharmacokinetic behavior were found when comparing the five patients in this study with patients who received 18 mg/m2, as described in a previous report. After the second dose of carminomycin in the 7.5 mg/m2 twice weekly schedule, however, carminomycin pharmacokinetics were found to be altered in comparison with the first dose, the most pronounced difference being an increase in the t1/2 for Col from 65 +/- 28 to 173 +/- 81 hr.

Metabolism of 4'-modified analogs of doxorubicin. unique glucuronidation pathway for 4'-epidoxorubicin.

The metabolism of doxorubicin (A), 4'-epidoxorubicin (E) and 4'-deoxydoxorubicin (D) was studied in vitro by incubating the analogs with rat liver subcellular fractions and in vivo by chromatographic analysis of human urine. Metabolites were identified by high-pressure liquid chromatography, fluorescence spectroscopy and enzymatic conversion. Human urine contained unchanged drug as well as the corresponding alcohol metabolites in all cases; however, urine of patients who received E also contained two glucuronides which could not be detected in the urine of patients who received A or D. We have identified these glucuronides as 4'-epidoxorubicin glucuronide (E-Glu) and 4'-epidoxorubicinol glucuronide (Eol-Glu). It was concluded that the glucuronide moiety is linked to the daunosamine sugar at the C4'-OH position. A hypothesis is proposed that this glucuronidation pathway may explain the differences in pharmacokinetics and toxicity between E and A. Rat liver microsomes were found to convert all three drugs to the 7-deoxyaglycones at the same rate. Rat liver 100,000 g supernatant was found to be capable of converting these drugs to their respective alcohol metabolites, doxorubicinol (Aol) being formed somewhat slower than 4'-epidoxorubicinol (Eol) and 4'-deoxydoxorubicinol (Dol).

Pharmacokinetics of 4'-epi-doxorubicin in man.

The pharmacokinetics of 4'-epi-doxorubicin (4'-epi-adriamycin, 4'-epi-DX) in man can be described by a three-compartment model with a rapid distribution phase and a very long elimination phase. Urine excretion amounts to a total of about 11% of the administered dose during 48 h after drug administration, and less than 1% during the following 48 h. In plasma 4'-epi-doxorubicin is rapidly converted to five metabolites (4'-epi-doxorubicinol, aglycones and glucuronides), the concentration of the aglycones sometimes exceeding that of 4'-epi-DX. In urine only three metabolites were found in addition to the parent drug; they were identified as 4'-epi-doxorubicinol (EOH), 4'-epi-doxorubicin-glucuronide (E-Glu) and 4'-epi-doxorubicinol-glucuronide (EOH-Glu). Comparison of the pharmacokinetics and metabolic profiles of 4'-epi-DX and doxorubicin (DX) in man revealed that 4'-epi-DX eliminates faster than DX.