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PubMed1999

Rotation-induced conditioned rejection in the taste reactivity test.

The taste reactivity test was used to evaluate the ability of motion sickness to produce conditioned rejection reactions, a putative measure of nausea in rats. Following three conditioning trials, rats displayed conditioned rejection reactions during an intraoral infusion of a rotation-paired saccharin solution. This is the first demonstration of conditioned rejection produced with a non-pharmacological emetic agent and provides support that the conditioned rejection reaction may serve as a rat model of nausea.

Animals↗
PubMed1987

Crystal and molecular structure of aspartame X HCl X 2H2O.

The crystal and molecular structure of the hydrochloride salt of the peptide sweetener aspartame (alpha-L-Asp-L-Phe methyl ester) has been determined at 120 K using 3877 reflections with I greater than 2.5 sigma I. Space group P2(1)2(1)2(1), cell dimensions a = 6.768(1), b = 9.796(1) and c = 26.520(3) A; final R factor 0.033. While the N-terminal L-Asp group in the structure of aspartame itself forms a six-membered ring with an intramolecular hydrogen bond between the carboxylate and the protonated amino terminus, the corresponding group in the hydrochloride adopts a completely different conformation with a weak intramolecular hydrogen bond between the carboxyl group and the N atom of the L-Phe residue. The L-Phe methyl ester moiety is rather similar in the two structures. Of the many possible conformations of aspartame, only one may be expected to function as a substrate at the receptor site for sweet taste, and a proposal is made for this active conformation.

Aspartame↗
PubMed1989

Relationships between sour and salt taste perception and selected subject attributes.

The relationships between perceived sour and salt taste intensity and selected subject attributes--taste/smell deficits, salt use, avoidance of salt/sour tasting foods, smoking, alcohol use, dentures, education, and prescription drug use--were investigated in 180 subjects (30 men and 30 women/age group: 20 to 29 years [young], 70 to 79 years [old], 80 to 99 years [very old]. Multiple regression analyses showed that the taste intensity estimates were significantly related to age, sex, stimulus concentration, self-reported taste/smell deficits, avoidance of salt/sour tasting foods, salt use, alcohol, smoking, education, and use of certain drugs (drugs for the treatment of arthritis, drugs acting on the gastrointestinal tract and heart system, and diuretics/drugs for the treatment of hypertension). The very old showed deficits in perception of the low suprathreshold tastant levels, with near normal perception of the high levels, whereas the old exhibited deficits at all levels. Wearing dentures was the only single variable not selected in any of the final regression models, due to the high prevalence and homogeneity in use of dentures in the elderly groups. Further work using a stratified sample and a large number of subjects is warranted to elucidate the influence of subject attributes on taste perception.

Acids↗
PubMed2003

Exopeptidases and their application to reduce bitterness in food: a review.

When exopeptidases catalyze hydrolysis of peptide bonds, the product(s) may have a less bitter taste, and the free amino acids or small peptides formed may function in food as pleasant-tasting flavor compounds or as flavor precursors. There are several classes of exopeptidase based on specificity for hydrolysis of synthetic substrates. Exopeptidases in food-stuff may be of natural origin or may be extrinsic, that is, produced by microorganisms or parasites. Exopeptidases used to modify foods are also becoming increasingly available in the industrial enzyme market. Exopeptidases contribute to a variety of quality changes in postharvest fruit, meats, and food fermentations. Foodstuff impacted by these enzymes during processing include cocoa, beer, aged and cured meat products, koji, fish sauce, ripened cheeses, and protein hydrolysates. An important role of exopeptidases in food is the hydrolysis of hydrophobic, bitter peptides. The relationship between peptide structure and sensory transduction/receptor models is discussed. Research on the use of exopeptidases to reduce bitterness is reviewed.

Exopeptidases↗
PubMed2005

Analyzing a bioterror attack on the food supply: the case of botulinum toxin in milk.

We developed a mathematical model of a cows-to-consumers supply chain associated with a single milk-processing facility that is the victim of a deliberate release of botulinum toxin. Because centralized storage and processing lead to substantial dilution of the toxin, a minimum amount of toxin is required for the release to do damage. Irreducible uncertainties regarding the dose-response curve prevent us from quantifying the minimum effective release. However, if terrorists can obtain enough toxin, and this may well be possible, then rapid distribution and consumption result in several hundred thousand poisoned individuals if detection from early symptomatics is not timely. Timely and specific in-process testing has the potential to eliminate the threat of this scenario at a cost of <1 cent per gallon and should be pursued aggressively. Investigation of improving the toxin inactivation rate of heat pasteurization without sacrificing taste or nutrition is warranted.

Animals↗
PubMed1996

Understanding the mechanism of sweet taste: synthesis of ultrapotent guanidinoacetic acid photoaffinity labeling reagents.

Azido-functionalized analogs of potently sweet guanidinoacetic acids have been synthesized for use as sweetener receptor photoaffinity labeling reagents. These compounds have been synthesized using readily available starting materials. One of the azido-labeled guanidinoacetic acids has been evaluated in an electrophysiological model in the Rhesus monkey. We found that the photoaffinity-labeling reagent caused irreversible inhibition in electrophysiological response to sweeteners upon exposure of the monkey tongue to a combination of the reagent and UV light.

Affinity Labels↗
PubMed2006

Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis rats.

RATIONALE: Application of the Fischer-Lewis genetic model of drug abuse to the study of alcohol's motivational properties has been limited. OBJECTIVES: To assess the aversive and rewarding effects of ethanol in Fischer and Lewis rats. MATERIALS AND METHODS: Fischer and Lewis rats underwent a four-trial combined conditioned taste aversion/conditioned place preference procedure (CTA/CPP; 0, 1, 1.25, or 1.5 g/kg IP ethanol). Others received 0, 1, or 1.5 g/kg followed by tail blood sampling at 15-, 60- and 180-min post-injection. In additional groups, hypothermia to 0, 1.5, and 3 g/kg was assessed before and 30- and 60-min post-injection. RESULTS: All alcohol-treated groups except low-dose Lewis acquired CTA after one trial. Fischer rats developed stronger CTAs than Lewis at 1.25 and 1.5 g/kg. Ethanol-induced reward in taste or place conditioning was not evident in either strain. Lewis animals showed overall higher peak blood alcohol concentrations, but hypothermia did not vary by strain. CONCLUSION: Compared to Fischer, Lewis rats are less sensitive to alcohol's aversive effects as assessed in the CTA paradigm. The behavioral differences observed are not due to hypothermia, but pharmacokinetic differences may contribute. These data underscore the importance of genetic factors and the aversive effects of initial drug exposures in modeling vulnerability to abuse. In addition to its application with other drugs, the Fischer-Lewis model may be useful for investigating the biobehavioral bases of alcohol abuse.

Alcohol Drinking↗
PubMed2002

Clinical assessment of retronasal olfactory function.

OBJECTIVES: To develop a test kit for the simple assessment of retronasal olfactory function and to compare orthonasal and retronasal olfactory function in healthy subjects and patients with olfactory disorders. DESIGN AND PATIENTS: We tested 230 individuals with normosmia, hyposmia, and anosmia using grocery-available powders. Initially, 30 different substances were investigated. Subjects identified each substance using a list with 4 verbal items (forced choice). After preliminary experiments, 20 items were selected according to the degree to which they were identified by normosmic and anosmic subjects. Orthonasal olfactory function was assessed psychophysically using "sniffin' sticks," which includes tests for odor identification, discrimination, and butanol odor thresholds. In addition, anosmia was confirmed electrophysiologically by means of olfactory-evoked potentials. RESULTS: In healthy subjects, there was a test-retest reliability correlation of r(27) = 0.76 for retronasal olfactory function, which is similar to other odor identification tests. Retronasal testing in normosmic subjects allowed for the discrimination of sex-related differences, with women scoring higher than men (P =.007), and the identification of a slight decrease with age (r(120) = -0.20; P =.03). Orthonasal and retronasal identification of odors was found to correlate (r(86) = 0.78; P<.001). Retronasal testing allowed for the discrimination between normosmia, hyposmia, and anosmia (P<.001). In addition, retronasal performance of anosmic patients appeared to improve with duration of anosmia (P =.03). No difference was found between patients with anosmia of different origin. CONCLUSION: Results of the present investigation indicate that the assessment of retronasal olfactory function is possible using oral stimulus presentation.

Adolescent↗
PubMed1975

Alterations in consummatory behavior of mice produced by dietary exposure to inorganic lead.

Mice suckled by mothers given tap water and by mothers given a 5 mg/ml lead acetate solution during lactation were given a choice between tap water and a lead acetate solution after lactation. All offspring demonstrated an immediate aversion to the lead acetate solution. The offspring from the mothers receiving lead acetate during lactation demonstrated a greater aversion to the lead acetate solution than did the offspring from mothers receiving tap water. In addition, the lead acetate offspring drank more total fluid (tap water plus lead acetate solution) after weaning than the control offspring. The results indicate both learned and unlearned changes in motivation for fluid following ingestion of lead via the mother's milk in infancy.

Animals↗
PubMed1987

Ethanol exposure as inducer of stable voluntary ethanol drinking in the male rat.

The effects of restricted 'Saturday night drinking' on voluntary ethanol intake was tested in male rats. During a treatment period of 57 weeks the animals (group B) could choose between ethanol and water for 24 h each week. After this period of choice they received ethanol (2.0 g/kg) i.v. Total weekly exposure was around 6-7 g/kg. Of two control groups, one was given i.p. injections of saline once a week (group A) and the other, in addition to saline injections, a continuous choice between ethanol (10%) and water as drinking fluid (group C). Weekly ethanol exposure was approximately 14 g/kg in group C. During a testing period of 46 weeks group A and C had continuous access to a choice between ethanol and water. After week 5 of the testing period concentrations of ethanol varied in 3-week intervals. For each tested concentration (5, 15, 20 and 25%) intake was calculated as g/kg per day based on the total period. For the reference concentration (10%) corresponding intake was calculated on 2 weeks prior to and 2 weeks after the tested concentration. In group B there was always a very strong correlation (r = 0.86-0.99) between intake of the different tested concentration and the corresponding reference concentration. This indicates that a strong individual preference for a defined daily dose of ethanol had developed in these rats. The corresponding relation was less developed in group C especially when higher concentrations of ethanol were tested. At the end of the testing period voluntary ethanol intake was slightly higher in group B and C when compared to group A. Analyses of blood ethanol levels at defined times during the testing period indicated an interrupted ethanol intake with occasionally substantial blood levels. Thus intermittent ethanol exposure can induce a voluntary ethanol drinking pattern in male rats which might be used as an animal model of alcoholism.

Alcohol Drinking↗
PubMed2002

Individual and environmental influences on adolescent eating behaviors.

Food choices of adolescents are not consistent with the Dietary Guidelines for Americans. Food intakes tend to be low in fruits, vegetables, and calcium-rich foods and high in fat. Skipping meals is also a concern among adolescents, especially girls. Factors influencing eating behaviors of adolescents need to be better understood to develop effective nutrition interventions to change eating behaviors. This article presents a conceptual model based on social cognitive theory and an ecological perspective for understanding factors that influence adolescent eating behaviors and food choices. In this model, adolescent eating behavior is conceptualized as a function of individual and environmental influences. Four levels of influence are described: individual or intrapersonal influences (eg, psychosocial, biological); social environmental or interpersonal (eg, family and peers); physical environmental or community settings (eg, schools, fast food outlets, convenience stores); and macrosystem or societal (eg, mass media, marketing and advertising, social and cultural norms).

Adolescent↗
PubMed1999

Delta-9-tetrahydrocannabinol interferes with the establishment and the expression of conditioned rejection reactions produced by cyclophosphamide: a rat model of nausea.

Reliable animal models of nausea are necessary to better understand the neurobiology of nausea and to assess treatment effectiveness. We present such a model based on conditioned rejection reactions in rats. Our results demonstrate that delta-9-tetrahydrocannabinol (THC), a treatment reported to reduce chemotherapy-induced nausea in humans, also reduces conditioned rejection reactions in rats. Rats were administered THC or vehicle prior to a pairing of saccharin solution with cyclophosphamide or saline during conditioning and/or prior to test. THC interfered with the establishment of cyclophosphamide-induced conditioned rejection during conditioning and with the expression of conditioned rejection during testing. Our results confirm that the conditioned rejection reaction in the rat is a useful animal model of nausea.

Animals↗
PubMed2006

Central gustatory processing in humans.

The purpose of this chapter is to provide a general overview of the central representation of gustatory information in the human brain. The anatomical pathways for the two primary animal models (rodent and nonhuman primate) are provided followed by the presumed human gustatory pathway. The section on the gustatory pathway describes what is known about how taste intensity, quality and affective value are represented in the human brain. The chapter concludes with a review of flavor processing.

Affect↗
PubMed2000

Oral paclitaxel and concurrent cyclosporin A: targeting clinically relevant systemic exposure to paclitaxel.

Oral paclitaxel is not inherently bioavailable because of the overexpression of P-glycoprotein by intestinal cells and the significant first-pass extraction by cytochrome P450-dependent processes. This study sought to simulate the toxicological and pharmacological profile of a clinically relevant schedule of paclitaxel administered on clinically relevant i.v. dosing schedules in patients with advanced solid malignancies using oral paclitaxel administered with cyclosporin A, an inhibitor of both P-glycoprotein and P450 CYP3A. Nine patients were treated with a single course of oral paclitaxel in its parenteral formulation at a paclitaxel dose level of 180, 360, or 540 mg. Cyclosporin A was administered at a dose of 5 mg/kg p.o. 1 h before and concurrently with oral paclitaxel. Blood sampling was performed to evaluate the pharmacokinetics of paclitaxel, 6-alpha-hydroxypaclitaxel, 3-p-hydroxypaclitaxel, and cyclosporin A. The pharmacokinetic behavior of paclitaxel was characterized using both compartmental and noncompartmental methods. Model-estimated parameters were used to simulate paclitaxel concentrations after once daily and twice daily oral administration of paclitaxel and cyclosporin A. Aside from an unpleasant taste, the oral regimen was well tolerated, and there were no grade 3 or 4 drug-related toxicities. The systemic exposure to paclitaxel, as assessed by maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) values, did not increase as the dose of paclitaxel was increased from 180 to 540 mg, and there was substantial interindividual variability (4-6-fold) at each dose level. Mean paclitaxel Cmax values approached plasma concentrations achieved with clinically relevant parenteral dose schedules, averaging 268+/-164 ng/ml. AUC values averaged 3306+/-1977 ng x h/ ml, which was significantly lower than AUC values achieved with clinically relevant i.v. paclitaxel dose schedules. However, computer simulations using pharmacokinetic parameters derived from the present study demonstrated that pharmacodynamically relevant steady-state plasma paclitaxel concentrations of at least 0.06 microM would be achieved after protracted once daily and twice daily dosing with oral paclitaxel and cyclosporin A. Paclitaxel metabolites were detectable in three patients, and the 6-alpha-hydroxypaclitaxel: paclitaxel and 3-p-hydroxypaclitaxel:paclitaxel AUC ratios averaged 0.63 and 0.86, respectively; these values were substantially higher than values reported in patients treated with i.v. paclitaxel. Oral paclitaxel was bioavailable in humans when administered in combination with oral cyclosporin A 5 mg/kg 1 h before and concurrently with paclitaxel treatment, and plasma paclitaxel concentrations achieved with this schedule were biologically relevant and approached concentrations attained with clinically relevant parenteral dose schedules. However, treatment of patients with oral paclitaxel using a single oral dose administration schedule failed to achieve sufficiently high systemic drug exposure and pharmacodynamic effects. In contrast, computer simulations demonstrated that clinically relevant pharmacodynamic effects are likely to be achieved with multiple once daily and twice daily oral paclitaxel-cyclosporin A dosing schedules.

Administration, Oral↗
PubMed2004

STG does not associate with psoriasis in the Swedish population.

Psoriasis is a chronic inflammatory skin disease that is known to have a strong genetic predisposition. Several psoriasis-susceptibility loci have been previously found through genomic scans. Of these, psoriasis-susceptibility region 1 (PSORS1) on chromosome 6p21 remains the most consistently identified region across populations with the highest association with disease. STG is a gene that was previously isolated from rhesus monkey taste buds, and its ortholog in humans was found to be part of the cluster of genes in PSORS1, which is telomeric to HLA-C. Upon characterization of STG, we identified several sequence variants and investigated their association with psoriasis in cases and controls from the Swedish population. None of these STG single-nucleotide polymorphisms were found to be significantly associated with psoriasis. However, HLA-Cw*0602 status was strongly associated with disease. STG expression was investigated in human tissues and found not to be restricted to taste buds, with signals also being detected in skin and tonsils.

Cell Line, Tumor↗
PubMed1989

Network thermodynamic model of rat lingual epithelium: effects of hyperosmotic NaCl.

A network thermodynamic model was developed to describe steady-state and transient ion flows (Na+, K+, and Cl-) and related electrical events in the rat lingual epithelium. The model, which uses only standard assumptions about topology and membrane ion transport processes from other tight epithelia, successfully simulates steady-state transepithelial electrical measurements seen in the in vitro rat dorsal lingual epithelium for a wide range (50-2,000 mM) of mucosal NaCl concentrations. It also simulates the intracellular depolarization and subsequent repolarization observed in situ in rat taste cells in response to a mucosal hyperosmotic NaCl stimulus. Because the intracellular potential has been identified with the receptor potential for gustation, the depolarization and repolarization may explain both the phasic and tonic components of taste nerve excitation in response to a salt stimulus. This study suggests that a better understanding of taste transduction may be gained by focusing more attention on the transport properties and mechanisms of lingual epithelia.

Animals↗