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PubMed2001

Surveillance of the gastrointestinal mucosa by sensory neurons.

A dense network of extrinsic and intrinsic sensory neurons supplies the gastrointestinal tract. Intrinsic sensory neurons provide the enteric nervous system with the kind of information that this brain of the gut requires for its autonomic control of digestion, whereas extrinsic afferents notify the brain about processes that are relevant to energy and fluid homeostasis and the sensation of discomfort and pain. The sensory repertoire of afferent neurons is extended by their responsiveness to mediators released from enteroendocrine and immune cells, which act like "taste buds" of the gut and serve as interface between the gastrointestinal lumen and the sensory nerve terminals in the lamina propria of the mucosa. Functional bowel disorders such as non-ulcer dyspepsia and irritable bowel syndrome are characterized by abdominal discomfort or pain in the absence of an identifiable organic cause. It is hypothesized with good reason that infection, inflammation or trauma causes sensory pathways to undergo profound phenotypic and functional alterations that outlast the acute insult. The pertinent changes involve an exaggerated sensitivity of the peripheral afferent nerve fibres as well as a distorted processing and representation of the incoming information in the brain. This concept identifies a number of receptors and ion channels that are selectively expressed by primary afferent neurons as important molecular targets at which to aim novel therapies for functional bowel disorders.

Colonic Diseases, Functional↗
PubMed1994

Elevated sweet taste pleasantness ratings in bulimia nervosa.

Recent studies suggest that some patients with bulimia nervosa may experience elevated pleasantness responses to sweet taste. This study explored possible associations between symptoms patterns and pleasantness ratings for sucrose solutions in bulimic patients. Subjects included 15 women meeting DSM III-R criteria for narrowly defined bulimia nervosa (no history of other eating disorder); five patients with current bulimia nervosa and a past history of anorexia nervosa; and 20 healthy age-matched female controls. Subjects ate a standardized breakfast prior to the morning study visit. Sucrose-water solutions (0% to 40% sucrose) were rated for sweetness intensity and pleasantness. Patients with narrowly defined bulimia nervosa showed significantly higher pleasantness ratings for 40% sucrose solutions than controls and patients with a history of anorexia nervosa. Pleasantness ratings were not significantly correlated with frequency of binge eating or purging behaviors. These results extend previous evidence for altered sweet taste pleasantness responses in bulimia nervosa, and for differences in eating-related behaviors between patients with narrowly defined bulimia nervosa vs. those with past anorexia nervosa.

Adult↗
PubMed2003

The discriminant validity of alcohol use disorder in well-functioning men with hazardous alcohol use.

The purpose of this study was to establish the discriminant validity of alcohol use disorder (AUD) diagnoses within a population of well-functioning male heavy drinkers. A group of 57 subjects with a consumption of at least 28 alcoholic units (AU)/week was recruited from wine-tasting clubs. Within this group, a comparison was made between those individuals who met the criteria of AUD and those who did not. We compared the subjective and objective health status and drinking habits of both groups. No significant differences were found between the individuals with AUD and those without AUD, or between individuals with alcohol dependence and those without AUD, except for their drinking pattern. These findings raise doubt of the discriminant validity of AUD diagnoses in well-educated heavy wine drinkers.

Adult↗
PubMed1990

Dopaminergic mechanism of imipramine action in an animal model of depression.

Rats, subjected chronically (10-12 weeks) to a variety of mild, unpredictable stressors, showed a decrease in their consumption of weak sucrose solutions; normal behavior was restored by chronic (5-9 weeks) treatment with the tricyclic antidepressant imipramine. Acute administration of the dopamine receptor antagonist pimozide or the specific dopamine D2 receptor antagonist raclopride had no effect in nonstressed animals and in vehicle-treated stressed animals, but both drugs selectively reversed the improvement of performance in imipramine-treated stressed animals. The 5HT antagonist metergoline increased sucrose consumption in all groups. The data suggest that the mechanism of action of imipramine in this model is an increase in functional activity at dopamine (DA) synapses.

Animals↗
PubMed2003

Pediatric drug formulations of sodium benzoate: II. Coated granules with a lipophilic binder.

Sodium benzoate is used as a therapeutic agent in the treatment of some rare disorders that predominantly affect children. In preliminary investigations, liquid and semi-solid formulations of sodium benzoate failed because children refuse the oral uptake due to the bad taste of the drug. Recently developed microcapsules with macrogol as a hydrophilic binder raise concern in high-dose treatment regimens because acceptable daily intake limits are exceeded. A novel microcapsule formulation was developed consisting of a lipophilic core with high sodium benzoate load and a saliva-resistant coating. A new powder quality of saturated triglycerides from plant origin was introduced which complies with the Ph. Eur. monograph 'Hard fat'. Sodium benzoate and the triglyceride were mixed and directly extruded at room temperature. The extrudates were spheronized and coated in a fluidized-bed process. The resulting coated granules are small-sized microcapsules and taste neutrally. They can be mixed with food before administration. As the amount of released sodium benzoate is negligible within the first minutes, children do not recognize the bad taste and accept the medication. Recently, sodium benzoate in this novel formulation has been designated by the European Community as an orphan drug in the treatment of non-ketotic hyperglycinemia.

Capsules↗
PubMed1998

Probing lymphocyte biology by genomic-scale gene expression analysis.

The identity and abundance of mRNA species within a cell dictate, to a large extent, the biological potential of that cell. Although posttranscriptional mechanisms modify protein expression in critical ways, cellular differentiation requires key changes in gene transcription, as evidenced by the potent phenotypes that result from disruption of transcription factor genes in mice. It is now possible to assess the mRNA profile of a cell globally using recently developed genomics techniques. This review focuses on the potential of cDNA microarrays to define gene expression in lymphoid cells, a field which is in its infancy. Examples of cellular activation genes and cytokine inducible genes discovered using this technology are presented but these represent only a taste of the fruit that this new technology will ultimately bear. Gene expression profiles should provide essential new insights into lymphocyte differentiation and activation, the pathogenesis of immune disorders, and the molecular abnormalities in lymphoid malignancies.

DNA, Complementary↗
PubMed1978

Hyperphagia.

Explore the source record for details and available documents.

Animals↗
PubMed2004

Clinical relevance of nasal polyps in individuals recruited from a general population-based study.

OBJECTIVE: To compare the clinical presentations of individuals with nasal polyps detected by endoscopy in a general population sample with those of patients with nasal polyp disease seeking medical attention. MATERIAL AND METHODS: A total of 38 individuals with nasal polyps from a population-based sample were compared with 38 matched controls and a third group consisting of 44 patients who presented to an outpatient clinic with symptoms and diagnosed nasal polyps Upper and lower airway symptoms were registered. Polyp size, peak nasal inspiratory flow (PNIF), olfactory function and health-related quality of life were measured. RESULTS: Compared with the individuals with nasal polyps in the population sample, patients actively seeking medical care for nasal polyposis experienced more symptoms of nasal blockage and an impaired sense of smell, and had more extensive polyps and reduced PNIF. There were equal frequencies of asthma symptoms in these two groups. Compared with the controls, the individuals with nasal polyps in the population sample had a greater frequency of asthma symptoms and aspirin intolerance and also experienced an impaired sense of smell. CONCLUSION: Nasal polyps alone, as seen occasionally, are indicative of airway disease involving the upper and lower respiratory tracts.

Adult↗
PubMed1995

Unawareness of smell loss in normal aging and Alzheimer's disease: discrepancy between self-reported and diagnosed smell sensitivity.

Awareness of loss in smell sensitivity was assessed in 80 normal elderly subjects, 80 patients with probable Alzheimer's disease (AD), and 80 patients with sinusitis by comparing measured smell sensitivity to questionnaire-based, self-reported sensitivity. Both AD patients and sinusitis patients had significantly poorer diagnosed smell sensitivity than the normal elderly. Both patient groups had thresholds which on average were about nine times more concentrated than those of the normal elderly. However, 74% of the AD patients and 77% of the normal elderly with smell loss reported normal smell sensitivity. In contrast, only 8% of the sinusitis patients with loss reported normal smell sensitivity.

Adolescent↗
PubMed2002

Lemon-flavored cod liver oil and a multivitamin-mineral supplement for the secondary prevention of otitis media in young children: pilot research.

We measured blood levels of fatty acids, vitamin A, and trace metals in children undergoing ambulatory surgery for placement of tympanostomy tubes and a comparison group having other ambulatory surgical procedures. We then performed a small, outpatient, secondary prevention study using nutritional supplements chosen on the basis of those blood levels. The study subjects had lower levels of red blood cell eicosapentaenoic acid (EPA) than did adult controls. Consistent with previous reports, the levels of vitamin A were < or = 40 microg/dL for 69% of our subjects, and the plasma selenium levels for children were lower than published values for adults. We then studied one otitis media (OM) season; 8 children (0.8 to 4.4 years of age) received 1 teaspoon of lemon-flavored cod liver oil (containing both EPA and vitamin A) and 1 half-tablet of a selenium-containing children's chewable multivitamin-mineral tablet per day. During this OM season, study subjects received antibiotics for OM for 12.3% +/- 13.4% (SD; p < .05) fewer days during supplementation than before supplementation. Larger, controlled trials are warranted to assess the utility of cod liver oil (of acceptable purity and taste) and a children's multivitamin-mineral preparation containing selenium, both for the prevention of OM and for the acceptance of delayed prescription of antibiotics for this disorder.

Acute Disease↗
PubMed1999

Drug addiction as a disorder of associative learning. Role of nucleus accumbens shell/extended amygdala dopamine.

Conventional reinforcers phasically stimulate dopamine transmission in the nucleus accumbens shell. This property undergoes one-trial habituation consistent with a role of nucleus accumbens shell dopamine in associative learning. Experimental studies with place- and taste-conditioning paradigms confirm this role. Addictive drugs share with conventional reinforcers the property of stimulating dopamine transmission in the nucleus accumbens shell. This response, however, undergoes one-trial habituation in the case of conventional reinforcers but not of drugs. Resistance to habituation allows drugs to repetitively activate dopamine transmission in the shell upon repeated self-administration. This process abnormally facilitates associative learning, leading to the attribution of excessive motivational value to discrete stimuli or contexts predictive of drug availability. Addiction is therefore the expression of the excessive control over behavior acquired by drug-related stimuli as a result of abnormal strenghtening of stimulus-drug contingencies by nondecremental drug-induced stimulation of dopamine transmission in the nucleus accumbens shell.

Amygdala↗
PubMedDate not supplied

Serum concentrations and urinary excretions of zinc in cirrhosis, nephrotic syndrome and renal insufficiency.

Serum zinc conentrations are decreased in patients with a variety of clinical disorders including cirrhosis, nephrotic syndrome and renal insufficiency. Urinary zinc excretions are increased in the first two disease states. Symptoms of acute zinc deficiency (anorexia, dysfunction of smell and taste and mental and cerebellar disturbances) and chronic zinc deficiency (growth retardation, anemia, testicular atrophy and impaired wound healing) are common in these patients. It remains unresolved whether these low serum zinc concentrations in these disease states are indicative of true symptomatic or asymptomatic zinc deficiency, or merely reflect a decrease in available zinc-binding proteins, as well over 90% of serum zinc is bound to protein in normal subjects. The correlation between serum zinc and albumin concentrations, reportedly the major zinc-binding protein, is unimpressive. Studies of serum and urine binding of added radiozinc65 using Sephadex G-200 gel column chromatography and polyacrylamide gel electrophoresis suggest most of the radiozinc is bound to a protein with a molecular weight near albumin (68,000). Polyacrylamide gel electrophoresis suggests this might be a prealbumin. The low serum zinc concentration in the patient with nephrotic syndrome does not appear to be due to loss of zinc bound to urinary protein.

Adult↗
PubMed2001

Morphology of the nerve endings in laryngeal mucosa of the horse.

To discuss the significance of laryngeal sensation on various disorders of the horse, we studied the morphological and topographical characteristics of sensory structures in the laryngeal mucosa using immunohistochemistry and immunoelectron microscopy. Various sensory structures, i.e. glomerular endings, taste buds and intraepithelial free nerve endings, were found in the laryngeal mucosa by immunohistochemistry for protein gene product 9.5 (PGP 9.5) and neurofilament 200kD (NF200). Glomerular nerve endings were distributed mainly in the epiglottic mucosa; some endings were also found in the arytenoid region arising from thick nerve fibres running through the subepithelial connective tissue. Some terminals directly contacted the epithelial cells. Taste buds were distributed in the epithelium of the epiglottis and aryepiglottic fold. In the whole mount preparation, the taste buds were supplied by the terminal branching of the thick nerve fibres. In some cases, the taste buds were arranged around the opening of the duct of the epiglottic glands. The intraepithelial free nerve endings were found to be immunoreactive for substance P (SP) and calcitonin gene-related peptide (CGRP). These nerve endings were surrounded by the polygonal stratified epithelial cells in the supraglottic region, and by the ciliated cells in the subglottic region. The density of the intraepithelial free nerve endings was highest in the corniculate process of the arytenoid region and lowest in the vocal cord mucosa. The densities of CGRP- and SP-immunoreactive nerve endings in the arytenoid region were (mean +/- s.d.) 30.6+/-12.0 and 10.0+/-4.9 per unit epithelial length (1 mm), respectively and in the vocal fold mucosa, 1.1+/-0.9 and 0.8+/-0.7, respectively. Approximately one half of the CGRP immunoreactive nerve endings were immunoreactive for SP, and most SP-immunoreactive nerve endings were also immunoreactive for CGRP. Well-developed subepithelial plexus with numerous intraepithelial fibres were observed in flat or round mucosal projections that existed on the corniculate process of the arytenoid region. In conclusion, the laryngeal mucosa of the horse seems to have morphology- and/or location-dependent sensory mechanisms against various endo-and exogenious stimuli.

Animals↗
PubMed2005

TRP channels as a newly emerging non-voltage-gated CA2+ entry channel superfamily.

It has long been known that many chemical and physical stimuli imposed on the cell from its exterior environments elicit a long-lasting Ca2+ influx through yet poorly elucidated transmembrane pathways distinct from voltage-gated and fast ligand-gated Ca2+ entry channels, thereby activating and modulating a variety of cellular functions. Recent progress in molecularly identifying these pathways, initiated from the discovery of Drosophila's visual transduction mutants transient receptor potential (TRP) proteins, has begun to reveal the presence of an enormous superfamily of non-voltage-gated Ca2+ channels. The mammalian members of TRP superfamily are (except for two members) Ca2+-permeable non-selective cation channels which are constitutively active or gated by a multitude of physicochemical stimuli such as receptor stimulation, phospholipids, oxidants, pheromones, cell volume change/shear stress, exogenous compounds affecting sensations, and changes in ambient temperature, acidity and osmolarity and cellular metabolic status. Owing to these diversities in activation and their broad distribution from brain to peripheral organs and tissues, TRP channels are now thought to be involved in divergent physiological functions including; pain and taste transductions; thermo- and mechano-sensations; regulation of mineral absorption/reabsorption; blood pressure, gut motility and airway responsiveness; cell proliferation/death, some of which seem tightly associated with specific genetic disorders. These features will render TRP channels the attractive novel molecular targets for future drug therapy. This paper briefly overviews the current knowledge available for these channels with a main interest in their possible linkage with in vivo function.

Animals↗
PubMed1977

Zinc metabolism in renal disease and renal control of zinc excretion.

Serum zinc concentrations are decreased in patients with a variety of clinical disorders including cirrhosis, nephrotic syndrome and renal insufficiency. Urinary zinc excretions are increased in the first two disease states. Symptoms of acute zinc deficiency (anorexia, dysfunction of smell and taste, and mental and cerebellar disturbances) and chronic zinc deficiency (growth retardation, anemia, testicular atrophy, and impaired wound healing) are common in these patients. It remains unresolved whether these disease states are indicative of true symptomatic or asymptomatic zinc deficiency or merely reflect a decrease in available zinc binding proteins. The low serum zinc concentrations and high urinary zinc excretions in patients with nephrotic syndrome do not appear to be due to loss of zinc bound to urinary proteins. Studies in dogs indicate increased serum and urine concentrations of certain amino acids(cysteine, histidine) greatly increase urinary zinc excretions. Studies are now underway to determine if the hyperzincuria and hypozincemia of cirrhosis, nephrotic syndrome and hyperalimentation can be explained by an increase in these urinary amino acids.

Animals↗