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A chemical polymorphism in a multitrophic setting: thyme monoterpene composition and food web structure.

We investigated the effects of chemical variation in thyme (Thymus vulgaris L.) on its interactions with competitors, herbivores, and herbivore predators. Four different thyme monoterpene phenotypes (chemotypes) were grown in a 4x2x2 factorial of chemotype, caging (sham half-cages vs. full cages), and competition (control vs. the grass Bromus madritensis L.). Cages reduced numbers of arthropod predators. Thyme-feeding aphids Aphis serpylli Koch passed through full cage walls to increase more than fourfold. As a result, freed from their predators, aphids had a large negative effect on thyme size and flowering. Similarly, competition from Bromus had a negative effect on thyme size and flowering. Individual effects of aphids and competition were nonadditive, however, and their combined effect was significantly less than that predicted by a multiplicative null model. Differential thyme sizes among chemotypes were not mediated by herbivores or competitors, but differential flowering was due to the effects of chemotype on aphids. We thus document differential selection by aphids among thyme chemotypes and the influence of Bromus on the strength of these negative effects of aphids.

Animal Feed↗

Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics.

This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and analyses of divergent and complex traits. This strain, derived by crossing the spontaneously hypertensive rat, SHR/Ola, with a Brown Norway congenic, BN-Lx, carrying polydactyly-luxate syndrome, is referred to as HXB/BXH. The RI strain set has been used for linkage and association studies to identify quantitative trait loci for numerous cardiovascular phenotypes, including arterial pressure, stress-elicited heart rate, and pressor response, and metabolic traits, including insulin resistance, dyslipidemia and glucose handling, and left ventricular hypertrophy. The strain's utility has been enhanced with development of a new framework marker-based map and strain distribution patterns of polymorphic markers. Quantitative trait loci for behavioral traits mapped include loci for startle motor response and habituation, anxiety and locomotion traits associated with elevated plus maze, and conditioned taste aversion. The polydactyly-luxate syndrome Lx mutation has allowed the study of alleles important to limb development and malformation phenotypes as well as teratogens. The RI strains have guided development of numerous congenic strains to test locus assignments and to study the effect of genetic background. Although these strains were originally developed to aid in studies of rat genetic hypertension and morphogenetic abnormalities, this rodent platform has been shown to be equally powerful for a wide spectrum of traits and endophenotypes. These strains provide a ready and available vehicle for many physiological and pharmacological studies.

Animals↗

Consumer concerns and expectations about novel food processing technologies: effects on product liking.

Eighty-eight consumers participated in a blind pre-test in which they rated their baseline preference for chocolate pudding, their liking of three tasted brands of chocolate pudding, and their level of concern for 20 different food processing and preservation technologies. All returned one month later and tasted the same puddings, but this time they were informed that they had been processed by one of several different novel or traditional food processing techniques. Different sub-groups were informed of the name of the process, the name plus a factual description of the process, or the name, the factual description, plus a benefit statement. Ratings of expected liking were obtained before and after viewing the samples, but before tasting them. Finally, subjects tasted and rated the products for actual liking and a sub-group rated their concern levels for the same 20 technologies rated in the pre-test. Pre-test results showed females to have significantly higher concern levels for all technologies. Individuals who had demonstrated a willingness to consume foods processed by one novel technology (irradiation) had lower concern ratings for all technologies. Ratings of concern were negatively correlated with expected liking for products believed to be processed by the technologies. Expected liking ratings were positively influenced by visual exposure to the product and by a safety and benefit statement. Linear regression of the change in product liking as a function of whether products were better or worse than expected supported an assimilation model of the effect of disconfirmed expectations on liking/disliking. Lastly, post-test concern levels for many of the technologies were reduced by participation in the study.

Adolescent↗

Development pharmaceutics of microbicide formulations. Part I: preformulation considerations and challenges.

Microbicides, the compounds and formulations that can prevent transmission of sexually transmitted diseases (STDs)/HIV are being pursued actively as a promising AIDS intervention. The drug development chain for a topical microbicide differs significantly from that of any systemic or topical compound/formulation regarding to time line, cost, activities, and milestones. This is in part because of the lack of standard in vitro models to assess efficacy, and complex ethical issues in clinical trials of microbicides. Several factors, including changes in the physiology of the cervix and vagina with age and menstrual cycle, intercourse, as well as leakage of the formulation from the vagina may affect their design, development, and performance. Selection and development of optimal microbicide delivery systems (gel/cream, pessary, film, tablet, foam, etc.), their inactive ingredients, manufacturing details, and packaging system are dependent on the properties of active drug, or their preformulation parameters (PP). The PP of the active drug substance needs to be evaluated in initial stages of drug discovery and development so that the most suitable delivery system can be selected. Some PP of microbicide agents include physical state, organoleptic properties (color, odor, appearance, taste, etc.), molecular weight, aqueous solubility, hygroscopicity, acidity/alkalinity, permeability and absorption characteristics, stability in solid/solution state, and inherent bioadhesiveness. Thus, a well-coordinated, planned, and implemented preformulation program can help in not only accelerating microbicide formulation development, but also to minimize unforeseen failures in subsequent stages of the development. The objective of this review is to highlight the significance of PP, suggesting a systematic preformulation program.

Administration, Intravaginal↗

Is chemosensory input essential for the rapid rejection of toxic foods?

Herbivorous insects often rapidly reject foods containing toxic plant compounds. While the functional significance of this rejection response is clear, the mechanistic basis is not. The role of peripheral chemoreceptors in the rapid rejection of toxic foods was examined using a model system consisting of nicotine and the tobacco hornworm (Manduca sexta), which is a pest of tobacco plants. When offered diets containing naturally occurring concentrations of nicotine, larvae initially fed readily, but abruptly stopped feeding within 30s. A high percentage of larvae also exhibited toxic responses mediated by the central nervous system (twitching and writhing) to the ingested nicotine within 30s, indicating that nicotine could have been absorbed within the same time as the rejection response. Two lines of evidence are provided against a role of peripheral chemoreceptors in this rapid rejection response. First, all mouthpart chemoreceptors were ablated from the larvae, and they were then subjected to feeding tests with diets containing either nicotine or a compound (caffeine) that is known to stimulate deterrent taste receptors in M. sexta. Whereas the ablations virtually eliminated the rejection response to caffeine, they had no measurable impact on the rejection response to nicotine. Second, sensory recordings from two important gustatory sensilla (the medial and lateral styloconica) failed to demonstrate a plausible role of sensory input from either sensillum in the rapid rejection of nicotine. The most parsimonious interpretation of these results is that the nicotine rejection response was mediated by a rapidly acting post-ingestive mechanism.

Animals↗

Is it possible to dissociate 'liking' and 'wanting' for foods in humans? A novel experimental procedure.

Berridge's model (e.g. [Berridge KC. Food reward: Brain substrates of wanting and liking. Neurosci Biobehav Rev 1996;20:1-25.; Berridge KC, Robinson T E. Parsing reward. Trends Neurosci 2003;26:507-513.; Berridge KC. Motivation concepts in behavioral neuroscience. Physiol Behav 2004;81:179-209]) outlines the brain substrates thought to mediate food reward with distinct 'liking' (hedonic/affective) and 'wanting' (incentive salience/motivation) components. Understanding the dual aspects of food reward could throw light on food choice, appetite control and overconsumption. The present study reports the development of a procedure to measure these processes in humans. A computer-based paradigm was used to assess 'liking' (through pleasantness ratings) and 'wanting' (through forced-choice photographic procedure) for foods that varied in fat (high or low) and taste (savoury or sweet). 60 participants completed the program when hungry and after an ad libitum meal. Findings indicate a state (hungry-satiated)-dependent, partial dissociation between 'liking' and 'wanting' for generic food categories. In the hungry state, participants 'wanted' high-fat savoury>low-fat savoury with no corresponding difference in 'liking', and 'liked' high-fat sweet>low-fat sweet but did not differ in 'wanting' for these foods. In the satiated state, participants 'liked', but did not 'want', high-fat savoury>low-fat savoury, and 'wanted' but did not 'like' low-fat sweet>high-fat sweet. More differences in 'liking' and 'wanting' were observed when hungry than when satiated. This procedure provides the first step in proof of concept that 'liking' and 'wanting' can be dissociated in humans and can be further developed for foods varying along different dimensions. Other experimental procedures may also be devised to separate 'liking' and 'wanting'.

Adolescent↗

Primary culture of gustatory receptor neurons from the blowfly, Phormia regina.

Flies provide a powerful model system for exploring signaling systems in gustatory receptor neurons (GRNs). To elucidate the cellular and molecular bases of these signaling systems, we sought to develop techniques to dissociate GRNs. We developed a primary culture of GRNs isolated from the labella of the blowfly, Phormia regina, 4-5 days after pupation. Dissected labella were treated with papain in a low Ca2+ saline solution and shaken in Leibovitz's L-15 medium supplemented with 20-hydroxyecdysone, L-ascorbic acid, and trehalose with a test tube mixer. Released cells were plated and kept at 29 degrees C in a medium containing fetal bovine serum. After a minimum of 2 days in culture, we observed survival or growth of bipolar cells with the characteristic morphology of GRNs. We also examined taste responsiveness by monitoring intracellular Ca2+ with a Ca2+-sensitive fluorescent dye, fluo-3. For some bipolar cells, application of sucrose, NaCl, or LiCl for 5-20 s transiently increased the intracellular Ca2+ levels in cell bodies for 20-30 s. The primary cell culture described here is useful for functional analysis of GRNs.

Animals↗

Anticipatory nausea in cancer patients receiving chemotherapy: classical conditioning etiology and therapeutical implications.

The delivery of cytotoxic drugs in cancer treatment is often accompanied by posttreatment side effects (e.g., nausea). Moreover, there is evidence that cancer patients are at risk to develop these side effects in anticipation of chemotherapy (i.e., anticipatory nausea [AN]). AN can be explained as the result of a classical conditioning process with the cytotoxic drug as the unconditioned stimulus (US). Stimuli paired with the US (e.g., smells, tastes) can become conditioned stimuli (CSs) eliciting AN as the conditioned response (CR). The present study was conducted to test whether AN shows characteristics of a CR. Fifty-five ambulatory cancer patients were asked to record nine kinds of physical symptoms (e.g., nausea, vomiting, sweating) on time-scheduled symptom lists: after an infusion (indicating posttreatment symptoms) and prior to their next infusion (indicating anticipatory symptoms). Each measurement period covered a maximum of 48 hours. AN was reported by ten patients (18.08%). Data revealed (a) a statistically significant association between posttreatment nausea and vomiting, respectively, and AN; (b) the occurrence of AN increased with drug emetogenity (i.e., US-intensity); and (c) the duration of AN increased with temporal proximity to the infusion. The results support the conditioning model. Thus, it is proposed to prevent AN by classical conditioning techniques (e.g., overshadowing).

Antineoplastic Combined Chemotherapy Protocols↗

Flavour retention and release from protein solutions.

This paper briefly presents the main results obtained up to now on protein-flavour binding and release in relation with flavour perception. Among the food proteins, beta-lactoglobulin is the most extensively studied for its binding properties, which involve both hydrophobic and hydrogen binding. Recent developments using molecular modelling and Quantitative Structure-Activity Relationship confirmed the existence of two different binding sites for flavour compounds on beta-lactoglobulin. During the aroma release process in the mouth, not only free aroma compounds are released but also those reversibly bound by the protein, pointing out the fact that flavour perception is only affected if strong binding occurs.

Benzaldehydes↗

The food-service industry, dietary guidelines and change.

The influence of the food-service industry on compliance with the Australian dietary guidelines was investigated through three separate methods of data collection and analysis: a telephone survey of 1683 randomly selected Brisbane residents; telephone interviews with 69 food-service-industry operators and 10 face-to-face interviews with key stakeholders in industry and government. Nearly 40 per cent of respondents had consumed foods prepared by the food-service industry at least once on the day before the interview, mainly from restaurants, cafes and takeaway shops, in the form of fast-food or snacks. Consumption of these foods declined with age. Those consuming foods prepared by the food-service industry ate significantly less fruit, vegetables and dairy food and were therefore less likely to comply with the dietary guidelines. Outcomes from interviews with operators in the food-service industry show that food choices offered to consumers were the result of a dynamic interaction between consumer demand and operators' own tastes and perceptions of food quality. Key informant interviews show that public health nutrition programs will have limited effect without supportive environmental changes in the food-service industry supply. An effective means of increasing the likelihood of compliance with the Australian dietary guidelines will be to encourage food suppliers in ways that address their core business concerns simultaneously with the goals of health professionals.

Adult↗

Flavor programming during infancy.

OBJECTIVE: Although individuals differ substantially in their flavor and food preferences, the source of such differences remains a mystery. The present experimental study was motivated by clinical observations that early experience with formulas establishes subsequent preferences. DESIGN: Infants whose parents had chosen to formula-feed them were randomized into 1 of 4 groups by the second week of life. One group was assigned to be fed a milk-based formula (Enfamil), whereas another was assigned to be fed (Nutramigen), a particularly unpleasant-tasting protein hydrolysate formula. The remaining groups were assigned to be fed Nutramigen for 3 months and Enfamil for 4 months; the timing of exposure differed between the groups. After 7 months of exposure, infants were videotaped on 3 separate days while feeding, in counterbalanced order, Enfamil, Nutramigen, and Alimentum, a novel hydrolysate formula. RESULTS: For each of the 4 interrelated measures of behavior (intake, duration of formula feeding, facial expressions, and mothers' judgments of infant acceptance), previous exposure to Nutramigen significantly enhanced subsequent acceptance of both Nutramigen and Alimentum. Seven months of exposure led to greater acceptance than did 3 months. CONCLUSIONS: The bases for clinical difficulties in introducing hydrolysate formulas during older infancy are clarified in this study. More broadly, variation in formula flavor provided a useful model for demonstrating experimentally the effects of long-term exposure differences on later acceptance. Such early variation, under more species-typical circumstances (eg, via exposure to different flavors in amniotic fluid and mothers' milk), may underlie individual differences in food acceptability throughout the life span.

Age Factors↗

An in vitro model for the study of the role of innervation in circumvallate papillae morphogenesis.

The following study was done to demonstrate the reliability of an in vitro model for use in the study of early events and the role of innervation in mouse circumvallate papillae development. Gestational day (gd)-11 fetuses were partially dissected to produce explants that included the mandibular, hyoid, third and fourth branchial arches and their ganglia. In ganglionectomized explants, the nodose ganglia and either the geniculate, petrosal or both ganglia were removed. Explants were cultivated in roller tube culture for 24, 48, 72, and 96 h of culture and examined for the presence of papillary structures. Innervation was verified by immunostaining for neural cell adhesion molecule (NCAM). In all control explants, circumvallate papillae had formed by 72 h in culture. These papillae were innervated by fibers originating in petrosal or nodose ganglia, although, in a small number, fibers from the geniculate also contributed. Circumvallate papillae also formed in some explants in which either the geniculate or petrosal ganglia had been removed. However, placodal structures failed to mature into papillary structures even by 96 h in explants in which both ganglia had been removed. Our results demonstrate that an in vitro model using branchial arch explants supports the morphogenesis of an epithelial placode through the formation of a definite papillary structure, the circumvallate papilla, with an integrated nerve. Our results also indicate that, whereas the initial stages in gustatory papillae formation, the formation of a placode, are nerve-independent, the maturation of the placodal structure to form a papilla requires the presence of an intact nerve.

Animals↗

Nitrogen sources and concentrations shape algal odor compounds: Key drivers of β-cyclocitral and β-ionone in water bodies of the lower Yangtze River.

Taste and odor (T&O) compounds derived from cyanobacterial blooms pose escalating threats to freshwater security worldwide, yet the drivers of specific T&O metabolites remain poorly constrained. Here, we investigated the dual effects of nitrogen (N) sources and concentrations on the production of β-cyclocitral and β-ionone, two algal-derived T&O compounds, through integrated field surveys (54 sites across lakes and rivers) in the eutrophic lower Yangtze River, China, and laboratory cultivation of typical cyanobacteria (Microcystis aeruginosa and Pseudanabaena cinerea). Our field data revealed that the concentrations of β-cyclocitral and β-ionone in lakes and rivers were not significantly different, but increased with the trophic level index. Redundancy analysis and Mantel analysis showed that Microcystis and Pseudanabaena were potentially dominant contributors to β-cyclocitral and β-ionone in the water column. Structural equation modeling and variation partitioning analysis showed that enhanced nitrate (NO3--N) significantly promoted the production of these compounds. Laboratory experiments demonstrated that inorganic N (NaNO₃) maximized total T&O yields by promoting algal biomass, whereas organic N (urea and glutamic acid) elevated the T&O production per unit biomass by 1.5- to 9.5-fold. Notably, Pseudanabaena exhibited a 2.3-fold higher β-ionone yield than Microcystis, with greater sensitivity to N concentrations. Our study highlights the critical role of nitrogen pollution, both source and concentration, in the production of T&O compounds by phytoplankton and provides reference data for managing T&O issues in rivers and shallow lakes.

Norisoprenoids↗

Clinical evaluation of nedocromil sodium in asthma.

The recognition that inflammatory events in the airways play a key role in the pathogenesis of asthma has led to a relentless search for pharmacological agents which modify these processes. Nedocromil sodium (Tilade) represents one such agent. Nedocromil sodium, when inhaled by patients with asthma (0.05-0.50% nebulized, 0.5-4.0 mg m.d.i.), has been shown to inhibit immediate bronchoconstriction provoked by challenges with allergen (10 studies), exercise (five studies), isocapnic hyperventilation, fog and sulphur dioxide (one study each) and adenosine (two studies). With these challenges, inhibition of bronchoconstriction exhibited dose-dependency up to 4 mg, with nedocromil sodium being up to four times more potent than sodium cromoglycate. When inhaled prior to allergen provocation, nedocromil sodium inhibited the late asthmatic reaction; when taken regularly during the pollen season, it attenuated the allergen-induced increase in non-specific bronchial responsiveness. The efficacy of nedocromil sodium (4 mg q.i.d.) in the treatment of clinical asthma was initially shown in four open studies and subsequently confirmed in nine double-blind, placebo-controlled 4-12 week studies on patients with seasonal and perennial asthma. Further clinical trials (eight studies) identified some difficulty in replacing inhaled corticosteroids with nedocromil sodium, especially if the corticosteroids were reduced rapidly (four studies). However, two studies have shown that nedocromil sodium produced further improvement in asthma symptoms when used in addition to bronchodilators and inhaled corticosteroids. Treatment with nedocromil sodium (4 mg q.i.d.) for up to 52 weeks demonstrated a progressive reduction in bronchodilator usage throughout the whole treatment period. During clinical assessment, nedocromil sodium was well tolerated, side-effects being unpleasant taste, nausea and headache. In most cases the adverse reactions were mild and transient, although in approximately 3% of patients they resulted in withdrawal from clinical trials. Thus, nedocromil sodium is a novel drug of proven efficacy in the treatment of asthma. Its position in the therapeutic armamentarium is likely to be as an adjunct to bronchodilators and inhaled steroids, to produce improvement in symptoms beyond that achieved with the already established drugs.

Adrenal Cortex Hormones↗

Topiramate improves health-related quality of life when used to prevent migraine.

OBJECTIVE: To assess changes in health-related quality of life (HRQoL) measures among patients receiving topiramate (TPM) 100 mg/d in two divided doses for migraine prevention in three randomized, double-blind, placebo-controlled, 26-week trials with similar protocols and study populations. BACKGROUND: Migraine substantially impairs HRQoL and work productivity before, during, and after attacks. Approximately 50% of patients with migraine could be recommended for preventive therapies, yet only 3% to 5% of patients receive them. TPM is an effective and generally well-tolerated migraine prophylactic (preventive) therapy for adults, as demonstrated in several randomized, double-blind, placebo-controlled trials. The most common adverse events in double-blind, placebo-controlled studies of TPM in migraine prevention are paresthesia, fatigue, anorexia, nausea, taste alteration, and diarrhea. DESIGN AND METHODS: The Migraine-Specific Questionnaire (MSQ, version 2.1) was used to assess the effect of TPM 100 mg/d on the functionality and HRQoL of randomized intent-to-treat (ITT) and study-completer populations pooled from three randomized, double-blind, placebo-controlled trials. MSQ scores (0 to 100, higher score indicates better functioning) were assessed for the following three domains: role restriction (examines the degree to which performance of daily activities is limited by migraine), role prevention (examines the degree to which performance of daily activities is interrupted by migraine), and emotional function (examines feelings of frustration and helplessness due to migraine). Between-group differences from baseline in mean MSQ domain scores for TPM 100 mg/d and placebo were compared using a mixed-effects model with piecewise linear regression. Effect sizes were calculated to estimate the magnitude of change in HRQoL that can be associated with TPM therapy. RESULTS: TPM 100 mg/d significantly improved all three MSQ domains compared with placebo for both the ITT (TPM, n = 372; placebo, n = 362) and study-completer (TPM, n = 220; placebo, n = 216) populations (P < .001 for all three domains, both populations). Effect sizes for TPM 100 mg/d varied from 0.40 to 0.78, indicating that the changes in MSQ scores for TPM 100 mg/d were moderate and may be clinically significant. CONCLUSION: TPM 100 mg/d has been shown to be effective in the prevention of migraine headache in adults. As the MSQ results from the three randomized, placebo-controlled trials indicate, HRQoL is significantly improved for up to 6 months following initiation of treatment.

Adolescent↗

The influence of sensitivity to reward on reactivity to alcohol-related cues.

AIMS: To investigate the role of sensitivity to reward in mediating social drinkers' reactivity to alcohol cues. DESIGN: A standard cue-reactivity paradigm was employed. Two groups of social drinkers (heavy and light) were assessed after exposure to the sight, smell and taste of a neutral cue (water) and then an alcohol cue (glass of beer). SETTING: Sessions were conducted in a laboratory based environment. PARTICIPANTS: Twenty heavy (12 males, eight females) and 18 light social drinkers (seven males, 11 females) were recruited; mean age was 23.6 years. MEASUREMENTS: The Card Arranging Reward Responsivity Objective Test (CARROT), assessing behavioural responsiveness to a monetary incentive; urge to drink; positive affect; and the BAS scales, assessing sensitivity to reward. FINDINGS: Heavy drinkers displayed a significant increase in responsivity to rewards (i.e. CARROT) and self-reported urge to drink, but not positive affect, after exposure to alcohol. For the heavy drinkers, heightened sensitivity to reward (i.e. BAS scales) was significantly related to cue-elicited urge to drink and positive affect. CONCLUSION: The results are consistent with a conditioned appetitive motivational model of alcohol use and suggest that Gray's theory of personality may be of some benefit in explaining variation in reactivity responses.

Adolescent↗

Adolescent enrichment partially reverses the social isolation syndrome.

Early environmental experience produces profound neural and behavioural effects. For example, animals reared in isolation show increased anxiety, neophobia, and poorer performance in learning and spatial memory tasks. We investigated whether later enrichment reverses some or all of the deficits induced by isolation rearing. Eighty-four male Long-Evans rats (21 days old) were reared under different conditions: enriched (group housed with toys), isolated (one rat/cage), standard (two rats/cage), isolated-enriched, enriched-isolated, isolated-standard, or enriched-standard. In the latter four conditions, animals were housed in the first environment until adolescence (66 days). Following the 90-day rearing period, all animals were assessed in a battery of behavioural tests and cortical thickness was measured postmortem. Isolation rearing led to significant differences in behavioural tests measuring anxiety, spatial learning, and locomotor activity; switching the rearing condition partially reversed these changes. Rearing condition did not affect pain thresholds in the tail flick test or aversive associative learning in the conditioned taste aversion test. Enriched rats had the thickest cortex; isolated rats the thinnest. None of the switch groups differed significantly from standard-reared rats in this measure. Taken together, these results provide novel and interesting information regarding the effects of pre- or post-adolescent enrichment experience on behavioural and neural expression of the social isolation syndrome.

Adolescent↗

Structure-function relationship of the TRP channel superfamily.

Transient receptor potential (TRP) channels are involved in the perception of a wide range of physical and chemical stimuli, including temperature and osmolarity changes, light, pain, touch, taste and pheromones, and in the initiation of cellular responses thereupon. Since the last decade, rapid progress has been made in the identification and characterization of new members of the TRP superfamily. They constitute a large superfamily of cation channels that are expressed in almost all cell types in both invertebrates and vertebrates. This review summarizes and discusses the current knowledge on the TRP protein structure and its impact on the regulation of the channel function.

Animals↗