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PubMed1979

Alcohol consumption in male social drinkers as a function of situationally induced depressive affect and anxiety.

Forty male subjects were randomly assigned to one of two conditions designed to induce either positive (Incentive Gain Condition) or negative (Incentive Loss Condition) affective states. This procedure was validated by an analysis of pre and post manipulation scores on the Multiple Affect Adjective Check List. Following the incentive manipulation subjects participated in an ad-lib drinking situation (Alcohol Taste Rating Rask) believing that the experiment was concerned with the relationship between intelligence, taste sensitivity and alcohol preferences. Contrary to expectation the analysis revealed that more alcohol was consumed by subjects in the incentive gain condition, this effect being most pronounced in heavy social drinkers in the incentive loss and gain conditions. A second analysis demonstrated that significantly less alcohol was consumed by subjects who, prior to ad lib drinking, evinced greater degrees of depressive affect and anxiety. The discussion focuses on the implications of these findings for tension reduction models of alcoholism.

Adolescent↗
PubMed1992

Application of Fishbein and Ajzen's expectancy-value model to understanding fat intake.

A questionnaire on attitudes towards the consumption of food types (specified by verbal labels) which contribute highly to fat in the diet was completed by 240 subjects who were quota sampled for sex, age and social class. The person's attitude toward consumption was found to be a good predictor of reported consumption. Differences in responses were found between groups of subjects who were classified by sex, age and social class. In general, females, the lower age groups and the higher social class subjects were found to have lower consumption and more negative attitudes towards the food types included. Individual belief-evaluation products on taste and healthiness of the foods were more closely related to attitudes towards consumption than were other beliefs (e.g. on convenience and price).

Adolescent↗
PubMed1999

The nutrient-toxin dosage continuum in human evolution and modern health.

Recent findings support the long-recognized principle that nutritive and toxic effects of an ingested material depend not only on its nature but very much on its quantity. The well known observation that essential nutrients can be toxic at high dosages suggests that the same reversal of effect may be true of many substances that could be beneficial but not essential at low dosages (the phenomenon of hormesis). This has been demonstrated for many well known toxins. We suggest a mathematical model that describes these dosage effects as an expected result of the evolution of human metabolic and dietary adaptations for maximizing benefits and minimizing costs of the ingestion or other intake of any substance. Evolved mechanisms for achieving benefits may be unrelated to those for reducing costs. These evolutionary considerations suggest important consequences demonstrable by experimental or epidemiological studies. They also suggest ways in which our evolved dietary adaptations may be currently maladaptive, and individual development of taste preferences poorly calibrated by early experience in modern environments. The apparent reality of hormesis raises the possibility of counterproductive effects of current dosage recommendations and limits for nutrients and pollutants. We propose that some conceptual and factual problems are urgently in need of resolution. Fundamental to evolutionary biology is the tendency for organisms to become increasingly adapted to those environments to which they are most commonly exposed (Parsons 1990).

Adaptation, Physiological↗
PubMed2000

Nedocromil sodium vs. sodium cromoglycate for preventing exercise-induced bronchoconstriction in asthmatics.

BACKGROUND: Nedocromil sodium and sodium cromoglycate inhaled shortly before exercise appear to reduce the severity of exercise-induced bronchoconstriction. There is some debate over which drug may be more effective. OBJECTIVES: The objective of this review was to compare the effects on post-exercise lung function between prophylactic doses of nedocromil sodium (NSG) and sodium cromoglycate (SCG) in persons diagnosed with exercise-induced bronchoconstriction. SEARCH STRATEGY: Randomized controlled trials were identified from the Cochrane Airways Review Group Asthma Register which compiles searches of CINAHL, EMBASE, MEDLINE and CENTRAL, plus hand searches for trials in 20 journals. Bibliographies of relevant studies and review articles were searched and primary authors, content experts and manufacturers of drugs were contacted for additional relevant studies. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials comparing NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were eligible. Studies were included if: the participants, aged 6 or over, had a confirmed diagnosis of asthma with exercise-induced bronchoconstriction, were subjected to an exercise challenge sufficient to trigger bronchoconstriction, and the measures of lung function were reported as either changes in forced expiratory volume in one second or peak expiratory flow rate. DATA COLLECTION AND ANALYSIS: Data extraction and methodological quality assessments were conducted independently by two reviewers using standard forms and validated assessment criteria. In some cases results were extrapolated from graphs. Results from similar studies were pooled and reported as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CI) using the random effects model. MAIN RESULTS: Of the 92 citations retrieved from the original search, a total of 8 studies were included in this review (117 participants). No significant difference was noted between NCS and SCG with respect to the maximum percent decrease in FEV1 (WMD = -0.88; 95% CI: -4.50, 2.74), complete protection (i.e. maximum % fall FEV1 still =>10%); OR = 0.95; 95% CI: 0.50 to 1.8, clinical protection (i.e. < 50% improvement over placebo); OR = 0.71; 95% CI: 0.36 to 1.39; unpleasant taste (OR = 6.85; 95% CI: 0.77, 60.73), or sore throat (OR = 3.46; 95% CI: 0.32, 37.48). For these pooled comparisons, no statistically significant heterogeneity was identified. Subgroup analyses based on age, dosage of medications and timing of exercise post-inhalation were consistent with the overall pooled analyses. REVIEWER'S CONCLUSIONS: No significant differences were evident between the effect of NCS and SCG during the immediate post-exercise period in adults and children with EIB with regards to pulmonary function - specifically maximum percent decrease in FEV1, complete protection, clinical protection, or side effects.

Administration, Inhalation↗
PubMed2005

An evaluation of automated in silico ligand docking of amino acid ligands to Family C G-protein coupled receptors.

Family C G-protein coupled receptors (GPCRs) consist of the metabotropic glutamate receptors (mGluRs), the calcium-sensing receptor (CaSR), the T1R taste receptors, the GABA(B) receptor, the V2R pheromone receptors, and several chemosensory receptors. A common feature of Family C receptors is the presence of an amino acid binding pocket. The objective of this study was to evaluate the ability of the automatic docking program FlexX to predict the favored amino acid ligand at several Family C GPCRs. The docking process was optimized using the crystal structure of mGluR1 and the 20 amino acids were docked into homology models of the CaSR, the 5.24 chemosensory receptor, and the GPRC6A amino acid receptor. Under optimized docking conditions, glutamate was docked in the binding pocket of mGluR1 with a root mean square deviation of 1.56 angstroms from the co-crystallized glutamate structure and was ranked as the best ligand with a significantly better FlexX score compared to all other amino acids. Ligand docking to a homology model of the 5.24 receptor gave generally correct predictions of the favored amino acids, while the results obtained with models of GPRC6A and the CaSR showed that some of the favored amino acids at these receptors were correctly predicted, while a few other top scoring amino acids appeared to be false positives. We conclude that with certain caveats, FlexX can be successfully used to predict preferred ligands at Family C GPCRs.

Amino Acids↗
PubMed1999

Functional domains within the degenerin/epithelial sodium channel (Deg/ENaC) superfamily of ion channels.

Application of recombinant DNA technology and electrophysiology to the study of amiloride-sensitive Na+ channels has resulted in an enormous increase in the understanding of the structure-function relationships of these channels. Moreover, this knowledge has permitted the elucidation of the physiological roles of these ion channels in cellular processes as diverse as transepithelial salt and water movement, taste perception, volume regulation, nociception, neuronal function, mechanosensation, and even defaecation. Although members of this ever-growing superfamily of ion channels (the Deg/ENaC superfamily) share little amino acid identity, they are all organized similarly, namely, two short N- and C-termini, two short membrane-spanning segments, and a very large extracellular loop domain. In this brief Topical Review, we discuss the structural features of each domain of this Deg/ENaC superfamily and, using ENaC as a model, show how each domain relates to overall channel function.

Amino Acid Sequence↗
PubMed2004

Sonic hedgehog exerts distinct, stage-specific effects on tongue and taste papilla development.

Taste papillae are ectodermal specializations that serve to house and distribute the taste buds and their renewing cell populations in specific locations on the tongue. We previously showed that Sonic hedgehog (Shh) has a major role in regulating the number and spatial pattern of fungiform taste papillae on embryonic rat tongue, during a specific period of papilla formation from the prepapilla placode. Now we have immunolocalized the Shh protein and the Patched receptor protein (Ptc), and have tested potential roles for Shh in formation of the tongue, emergence of papilla placodes, development of papilla number and size, and maintenance of papillae after morphogenesis is advanced. Cultures of entire embryonic mandible or tongues from gestational days 12 to 18 [gestational or embryonic days (E)12-E18] were used, in which tongues and papillae develop with native spatial, temporal, and molecular characteristics. The Shh signaling pathway was disrupted with addition of cyclopamine, jervine, or the 5E1 blocking antibody. Shh and Ptc proteins are diffuse in prelingual tissue and early tongue swellings, and are progressively restricted to papilla placodes and then to regions of developing papillae. Ptc encircles the dense Shh immunoproduct in papillae at various stages. When the Shh signal is disrupted in cultures of E12 mandible, tongue formation is completely prevented. At later stages of tongue culture initiation, Shh signal disruption alters development of tongue shape (E13) and results in a repatterned fungiform papilla distribution that does not respect normally papilla-free tongue regions (E13-E14). Only a few hours of Shh signal disruption can irreversibly alter number and location of fungiform papillae on anterior tongue and elicit papilla formation on the intermolar eminence. However, once papillae are well formed (E16-E18), Shh apparently does not have a clear role in papilla maintenance, nor does the tongue retain competency to add fungiform papillae in atypical locations. Our data not only provide evidence for inductive and morphogenetic roles for Shh in tongue and fungiform papilla formation, but also suggest that Shh functions to maintain the interpapilla space and papilla-free lingual regions. We propose a model for Shh function at high concentration to form and maintain papillae and, at low concentration, to activate between-papilla genes that maintain a papilla-free epithelium.

Animals↗
PubMed2004

Artemin-like immunoreactivity in the zebrafish, Danio rerio.

Artemin is a member of the glial cell line-derived neurotrophic factor (GDNF) family. It is a neurotrophic factor that supports neurite migration and outgrowth and survival of the sympathetic and sensory nervous system. Artemin has been studied in human and murine tissues, but no study has been devoted to nonmammalian species. Zebrafish is a teleost fish belonging to the family Ciprinidae, which is becoming an important model species for genetic and developmental studies. Thus, the aim of the present investigation was to evaluate, by immunochemical and immunocytochemical analyses, the tissue distribution pattern of artemin in zebrafish. Different isoforms of artemin with corresponding different molecular weights were detected in the brain, muscle, testis, ovary, kidney, gut, and gills of zebrafish by Western blot analysis. Immunocytochemical analysis showed artemin-like immunoreactivity in different cell types: in glial cells and rare neurons of the central nervous system, taste buds, retina, neuromasts of the lateral line, dorsal root ganglia, sympathetic ganglia, gill epithelium, tubular kidney epithelium, gut epithelium and ganglia, pancreas, thyroid, hypothalamus, testis, and ovary. These results indicate a wide distribution of artemin-like immunoreactivity in adult zebrafish, related to the presence of different forms of artemin. These findings might suggest a complex maturation pattern of artemin, whose forms could also exert different roles in zebrafish tissues.

Animals↗
PubMed1984

Feeding rate and meal patterns in the laboratory rat.

Many manipulations used in the study of feeding (e.g., changes of food taste or texture, anorectic drugs) affect the rate of food consumption. Consequent changes in meal patterning might reflect either direct effects of the manipulation or alternatively might result from indirect effects of the changed rate of intake. In the experiment reported here a direct reduction in the permitted rate of food intake resulted in a clear reduction of meal size and an increase in meal frequency in rats. We explore the extent to which this finding is predicted by quantitative models of the regulation of food intake.

Animals↗
PubMed2000

Microvascular transplantation of the rat submandibular gland.

Xerostomia results from salivary gland irradiation during treatment of head and neck malignancies. In addition to having difficulty with speech and swallowing, these patients experience loss of taste, dental caries, and chronic fungal infections. The paired submandibular glands provide 70 percent of the normal salivary flow and are difficult to shield during radiation therapy. Another sicca condition, xerophthalmia, may result from facial nerve injury or other medical disorders and results in pain, corneal ulceration, and possible vision loss. Treatment options for xerostomia are limited, and management of xerophthalmia usually focuses on the eyelids, rather than the fundamental problem of inadequate secretory protection. In this study, a rat model for submandibular gland microvascular transplantation was developed to assess the feasibility of salivary tissue transfer. Sixteen rats underwent submandibular gland transplantation from the neck to the groin. Fourteen of these rats underwent microvascular anastomosis of the vascular pedicle. Ten glands were assessed for viability at 4 days after transplantation, and four glands were examined after 7, 10, 14, or 21 days. By gross and histologic examination, 93 percent of transplanted glands showed expected long-term viability after at least 4 postoperative days. Microvascular techniques were shown to be applicable to the transplantation of submandibular gland salivary tissue. This has not previously been shown in a rat model. It is possible that submandibular glands could be transplanted to the eye for treatment of xerophthalmia and out of the neck during irradiation of the head and neck, with subsequent replantation after treatment as a means of preventing permanent xerostomia.

Anastomosis, Surgical↗
PubMed1998

Behavioral detection of low concentrations of ethanol in milk in the preweanling rat.

Previous animal models testing infantile reactivity to ethanol (EtOH) in maternal milk used EtOH doses that vastly exceeded levels actually encountered in a mildly or moderately intoxicated dam. The present study assessed whether 12- and 16-day-old rats are capable of detecting EtOH in milk at levels actually recorded in an intoxicated dam. Experiment 1 determined representative levels of EtOH in maternal milk as a function of maternal intragastric administration of EtOH (0.5-3.0 g/kg). Experiment 2A assessed generalization of conditioned taste aversions accrued with a high level of EtOH (6%) in either water or milk vehicles towards lower, more representative EtOH levels obtained from Experiment 1. With body weight gain as the dependent measure, conditioned aversions to milk were evident with the milk vehicle, but there was no detection of EtOH at any level at either age. Detection of the high level of EtOH (6%) in milk, however, was observed by 16 day olds within an habituation paradigm (Exp. 2b) via cardiac and behavioral (locomotion, mouthing) indexes. In Experiment 3 application of Experiment 2's more sensitive, behavioral index to assess generalization of the conditioned taste aversions revealed detection of a lower, more representative concentration of EtOH (175 mg%) in milk in 16-day-old rats. Overall the results show that the unweaned rat is capable of detecting very low concentrations of EtOH in milk and can modify their behavior accordingly. The expression of this capability is not, however, homogeneous across different response indexes. In conjunction with prior research it is clear that the infant rat's perception of EtOH in milk, including the very low levels of EtOH found in maternal milk during mild or moderate intoxication, is a relevant experience for generating new responses towards EtOH.

Animals↗
PubMed2003

Structure of the metabotropic glutamate receptor.

In the twelve years since the molecular elucidation of the metabotropic glutamate receptor subtype 1, a class III family of G-protein-coupled receptors has emerged; members of this family include the calcium-sensing receptor, the GABA(B) receptor, some odorant receptors and some taste receptors. Atomic structures of the ligand-binding core of the original metabotropic glutamate receptor 1 obtained using X-ray crystallography provide a foundation for determining the initial receptor activation of this important family of G-protein-coupled receptors.

Animals↗
PubMed2002

Chemical characterization of the aroma of Grenache rosé wines: aroma extract dilution analysis, quantitative determination, and sensory reconstitution studies.

The aroma of a Grenache rosé wine from Calatayud (Zaragoza, Spain) has been elucidated following a strategy consisting of an aroma extract dilution analysis (AEDA), followed by the quantitative analysis of the main odorants and the determination of odor activities values (OAVs) and, finally, by a series of reconstitution and omission tests with synthetic aroma models. Thirty-eight aroma compounds were found in the AEDA study, 35 of which were identified. Twenty-one compounds were at concentrations higher than their corresponding odor thresholds. An aroma model prepared by mixing the 24 compounds with OAV > 0.5 in a synthetic wine showed a high qualitative similarity with the aroma of the rosé wine. The addition of compounds with OAV < 0.5 did not improve the model, whereas the aroma of a model containing only odorants with OAV > 10 was very different from that of the wine. Omission tests revealed that the most important odorant of this Grenache rosé wine was 3-mercapto-1-hexanol, with a deep impact on the wine fruity and citric notes. The synergic action of Furaneol and homofuraneol also had an important impact on wine aroma, particularly in its fruity and caramel notes. The omission of beta-damascenone, which had the second highest OAV, caused only a slight decrease on the intensity of the aroma model. Still weaker was the sensory effect caused by the omission of 10 other compounds, such as fatty acids and their ethyl esters, isoamyl acetate, and higher alcohols.

Chromatography, Gas↗
PubMed2006

Noncovalent cross-linking of casein by epigallocatechin gallate characterized by single molecule force microscopy.

Interaction of the tea polyphenol epigallocatechin gallate (EGCG) with beta-casein in milk affects the taste of tea and also affects the stability of the tea and the antioxidant ability of the EGCG. In addition, interaction of polyphenols with the chemically similar salivary proline-rich proteins is largely responsible for the astringency of tea and red wine. With the use of single molecule force microscopy, we demonstrate that the interaction of EGCG with a single casein molecule is multivalent and leads to reduction in the persistence length of casein as calculated using the wormlike chain model and a reduction in its radius of gyration. The extra force required to stretch casein in the presence of EGCG is largely entropic, suggesting that multivalent hydrophobic interactions cause a compaction of the casein micelle.

Caseins↗
PubMed2000

Moral hazard in physician prescription behavior.

I examine whether the choice made by physicians concerning what drug version--trade-name or generic--to prescribe is subject to moral hazard. I use a data set containing information on exactly what drug and what version was prescribed at a particular patient visit to the physician. The results indicate that physicians' habits and the tastes acquired by patients are important. However, costs also matter. Patients having to pay large sums out-of-pocket are less likely to have trade-name versions prescribed than patients getting most of their costs reimbursed. This indicates moral hazard.

Decision Making↗
PubMed2005

Fluctuations of dissolved organic matter in river used for drinking water and impacts on conventional treatment plant performance.

Natural organic matter (NOM) in drinking water supplies can provide precursors for disinfectant byproducts, molecules that impact taste and odors, compounds that influence the efficacy of treatment, and other compounds that are a source of energy and carbon for the regrowth of microorganisms during distribution. NOM, measured as dissolved organic carbon (DOC), was monitored daily in the White River and the Indiana-American water treatment plant over 22 months. Other parameters were either measured daily (UV-absorbance, alkalinity, color, temperature) or continuously (turbidity, pH, and discharge) and used with stepwise linear regressions to predict DOC concentrations. The predictive models were validated with monthly samples of the river water and treatment plant effluent taken over a 2-year period after the daily monitoring had ended. Biodegradable DOC (BDOC) concentrations were measured in the river water and plant effluent twice monthly for 18 months. The BDOC measurements, along with measurements of humic and carbohydrate constituents within the DOC and BDOC pools, revealed that carbohydrates were the organic fraction with the highest percent removal during treatment, followed by BDOC, humic substances, and refractory DOC.

Biodegradation, Environmental↗
PubMed1986

Cholecystokinin, diet palatability, and feeding regulation in rats.

Rats ate less food than normal on cyclic-ratio schedules following cholecystokinin and lithium chloride injections. Nevertheless, they defended this lower eating rate in the same way as under control conditions. The pattern of effects produced by cholecystokinin and lithium chloride resembled those following diet adulteration with citric acid and sucrose octa acetate and differed from the effects produced by increases in body weight. Cholecystokinin and lithium chloride injections also produced similar changes in the free-feeding patterns of non-deprived rats: Both meal size and intermeal intervals decreased in manner similar to the effects of citric acid and sucrose octa acetate adulteration. Interpreted in terms of a static regulatory model, these results suggest that cholecystokinin and lithium chloride suppress feeding by degrading the palatability of food, not by promoting satiety, discomfort, or illness.

Animals↗
PubMed1991

(Acyloxy)alkyl carbamate prodrugs of norfloxacin.

As a new prodrug approach to norfloxacin (NFLX) we prepared the acetoxyalkyl carbamates of the type NFLX-CO-OCHR-OAc by the reaction of sodium or mercuric acetate on NFLX alpha-chloroalkyl carbamates. These produrgs did not have the bitter taste of NFLX. In vitro, the acetoxyethyl carbamate exhibited activity only against Staphylococcus spp. and was inactive against Gram-negative organisms. However, in the presence of serum and intestinal homogenate, esterase-catalyzed hydrolysis of the ester bond in these modified carbamates led to a cascade reaction resulting in the rapid regeneration of NFLX. At high oral doses of the prodrug, the acetaldehyde produced as a side product in the breakdown of the promoiety caused a slight decrease in alcohol metabolism in a mouse model. The bioavailability of NFLX from the acetoxyethyl carbamate was lower compared to an equivalent dose of NFLX when given as an oral suspension in rhesus monkeys, presumably because of the lower aqueous solubility of the prodrug.

Animals↗