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Olfactory dysfunction and related nutritional risk in free-living, elderly women.

OBJECTIVE/DESIGN: To determine the nutritional risk associated with measured olfactory dysfunction in free-living, elderly women through analytic observational methods. Olfactory perception was measured orthonasally (odor: butanol threshold and odor identification) and retronasally (flavor: orange flavor threshold in sweetened gelatin). SETTING/SUBJECTS: Elderly women were recruited from New Haven, Conn, through posters and direct contact. Screening of 120 elderly women identified 80 with high personal functioning to participate (mean age = 76 +/- 6 years, range = 65 to 93 years). All data were collected in subjects' homes. MAIN OUTCOME MEASURES: Nutritional risk was assessed in several ways: food behavior questionnaire; food preference questionnaire; interviews based on the National Cancer Institute food frequency questionnaire; five nonconsecutive, 24-hour food records; and weight, height, waist, and hip measurements. STATISTICAL ANALYSES: Correlation and regression analyses determined the separate association between olfactory perception and nutrition variables. RESULTS: Nearly half of the women (37 of 80) had olfactory dysfunction. The following nutritional risk pattern was associated with lower olfactory perception: lower interest in food-related activities (eg, enjoying cooking, eating a wide variety of foods); lower preference for foods with predominant sour/bitter taste (eg, citrus fruits) or pungency (eg, horseradish); higher intake of sweets; less intake of low-fat milk products; and nutrient intake profile indicative of higher risk for cardiac disease. APPLICATIONS: Olfactory dysfunction may make it more difficult for elderly women to maintain a diet to control risk for chronic disease. Practitioners should target nutrition intervention to elderly women with measured or self rated difficulty in preventing odors or olfactory flavor. Capitalizing on primary-taste quality and texture may help to compensate for the loss of olfactory flavor perception.

Aged↗

The influence of chemical gustatory stimuli and oral anaesthesia on healthy human pharyngeal swallowing.

This study explored the effects of taste and oral anaesthesia on human sequential swallowing. Subjects were healthy adults (n = 42, mean age 28 years, 21 females), investigated by means of a water swallow test. Taste stimuli comprised quinine, glucose, citrus and saline solutions compared with neutral water. Oral anaesthesia comprised topical lidocaine at doses of 10, 20 and 40 mg and compared with placebo. Data were collected on swallowing speed (volume per second), inter-swallow interval and swallowing capacity (volume per swallow). Compared with water, glucose, citrus and saline reduced swallowing speed (10.94 +/- 0.89 versus 9.56 +/- 0.79, 9.33 +/- 1.19, 9.37 +/- 0.92 ml/s respectively, P < 0.05). Inter-swallow interval was increased only by quinine and saline (1.47 +/- 1.11 versus 2.13 +/- 0.34 and 1.92 +/- 0.31 s, P < 0.04). Swallowing capacity was only marginally increased by quinine (P = 0.0759). Compared with the placebo, only 40 mg of lidocaine altered swallowing, immediately reducing the swallowing speed (7.89 +/- 2.34 versus 10.11 +/- 3.26 ml/s, P < 0.05) and increasing inter-swallow interval (1.67 +/- 0.38 versus 1.45 +/- 0.29 s, P < 0.01) without affecting capacity. By 15 min all measures except sensory thresholds had returned to baseline values. Thus, swallowing function is highly influenced by chemosensory input, providing insight into how oral sensation regulates pharyngeal swallowing.

Administration, Oral↗

Temporal integration and reaction times in human smell.

A model description of intensity perception in human taste and smell developed earlier has now been verified experimentally to determine parameter values for odorants. The final objective is to quantify and understand odour-odour interaction phenomena in e.g., masking, deo-perfumes and flavour enhancement. Five types of olfactometer experiments were carried out, viz. determination of thresholds, determination of reaction times, scaling of perceived intensity after 5 sec stimulation, scaling of perceived intensity of a fixed concentration at variable duration, and measurement of intensity/time relationships. Four subjects were used and the odorants cineole, geraniol and hexane.

Acyclic Monoterpenes↗

A family of K+ channel ancillary subunits regulate taste sensitivity in Caenorhabditis elegans.

We have identified a family of ancillary subunits of K(+) channels in Caenorhabditis elegans. MPS-1 and its related members MPS-2, MPS-3, and MPS-4 are detected in the nervous system of the nematode. Electrophysiological analysis in ASE neurons and mammalian cells and epigenetic inactivation by double-stranded RNA interference (RNAi) in vivo show that each MPS can associate with and functionally endow the voltage-gated K(+) channel KVS-1. In the chemosensory neuron ADF, three different MPS subunits combine with KVS-1 to form both binary (MPS-1.KVS-1) and ternary (MPS-2.MPS-3.KVS-1) complexes. RNAi of mps-2, mps-3, or both, enhance the taste of the animal for sodium without altering the susceptibility to other attractants. When sodium is introduced in the test plate as background or as antagonist attractant, the nematode loses the ability to recognize a second attractant. Thus, it appears that the chemosensory apparatus of C. elegans uses sensory thresholds and that a voltage-gated K(+) channel is specifically required for this mechanism.

Amino Acid Sequence↗

Taste response in the facial nerve of the carp, Cyprinus carpio L.

The stimulating effect of taste substances on the external chemoreceptors of the carp, Cyprinus carpio L., was studied by recording the electrical activity from the facial taste fibers innervating the facial skin surface. The integrated responses from each whole nerve bundle of the trigemino-facial complex nerve revealed that gustatory receptors on the snout of the carp were extremely sensitive to salts, acids and the extract of silk worm pupae. Quinine-HCl and sucrose elicited relatively small responses. Responses occurred to several amino acids, and especially to betaine. The threshold concentration for both mono- and di-valent salts was estimated to be about 5 X 10-3 M and that for acids about 10-4 M. Single fiber analysis was performed on 77 preparations. According to responsiveness to the 4 basic chemicals, the fibers were classified into 5 types: type I, activated by one stimulus (22 fibers out of 77); type II by two (29); type III by three (11); type IV by four (13); and type V showing inhibition by quinine-HCl (2) as their notable feature. Single fibers responsive to several amino acids, and the worm extract were found, among which the last was the most effective stimulus as shown in the whole nerve experiments.

Animals↗

Responses of neurons in the primate taste cortex to the glutamate ion and to inosine 5'-monophosphate.

To investigate the neural encoding of glutamate taste in the primate, recordings were made from taste responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex taste area, with a small number in adjacent taste areas. First, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. The correlation between the responses to these two tastants was higher than between any other pair of tastants, which included glucose (sweet), sodium chloride (salty), HCl (sour), and quinine HCl (bitter). Accordingly, the responsiveness to glutamic acid clustered with the response to monosodium glutamate in a cluster analysis with this set of stimuli, and glutamic acid was close to sodium glutamate in a space created by multidimensional scaling. Second, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5'-monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Third, concentration response curves showed that concentrations of monosodium glutamate as low as 0.001 M were just above threshold for some of these neurons. Fourth, neurons have not yet been found in this cortical region that showed synergism of monosodium glutamate and the nucleotide inosine 5'-monophosphate: it was shown that mixtures of 0.0001 M inosine 5'-monophosphate with different concentrations (0.001, 0.01, and 0.1 M) of monosodium glutamate did not have a greater effect than the monosodium glutamate alone. Fifth, some neurons in the orbitofrontal region, which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioural satiety. In some cases this reduction was sensory-specific. These findings show that the taste neurons activated by monosodium glutamate can also be activated by other umami tastants, including glutamic acid and the nucleotide inosine 5'-monophosphate. The responses to these umami tastants were more similar to each other than to any of the other prototypical tastants, providing evidence that in this system umami is encoded differently from the other tastants. Moreover, the findings with these tastants provide additional evidence that the responses to monosodium glutamate are not due just to activation of a sodium taste channel.

Animals↗

Aversive stimulus properties of the 5-HT2C receptor agonist WAY 161503 in rats.

Serotonin2C (5-HT2C) receptors may influence motivation and reward through effects on the mesocorticolimbic dopamine (DA) system. Previous work from this laboratory indicated that 5-HT2C receptor stimulation does not induce place conditioning when animals are tested in a drug-free state, but does result in decreased locomotor activity and increased frequency thresholds for electrical self-stimulation of the ventral tegmental area (VTA). The present study was conducted to determine whether the 5-HT2C receptor agonist WAY 161503 may induce place conditioning in a state-dependent manner and also whether this compound will induce gustatory avoidance conditioning in the conditioned taste aversion (CTA) paradigm. The effects of the 5-HT2C receptor agonist WAY 161503 in the place conditioning and CTA (two-bottle choice test) paradigms were assessed in male Sprague-Dawley rats. Administration of WAY 161503 (3.0 mg/kg) induced a state-dependent conditioned place aversion and a CTA to saccharin. The differential state dependency of 5-HT2C receptor agonists' effects in place conditioning (state dependent) and CTA (non-state dependent) is consistent with the activation of different brain systems in these two paradigms. The state-dependent effects in place conditioning underscore the need to include controls for state dependency in studies of 5-HT receptor related compounds.

Amphetamine↗

Clinical evaluation and symptoms of chemosensory impairment: one thousand consecutive cases from the Nasal Dysfunction Clinic in San Diego.

BACKGROUND: The aim of this study was to measure olfactory impairment in patients with various etiologies using symptom ratings and psychophysical measures of olfactory function. METHODS: We performed a cross-sectional, population-based study at the Nasal Dysfunction Clinic of the University of California, San Diego (UCSD), Medical Center. One thousand consecutive patients presented to the UCSD Nasal Dysfunction Clinic for evaluation of chemosensory dysfunction. Olfactory impairment was assessed by odor threshold and odor identification and symptom scores were assessed by self-report. RESULTS: The degree of olfactory impairment was driven by diagnostic category, age, and gender. Postviral disturbance was more prevalent in women and among elderly people. Elderly people and patients under 20 years of age showed the highest incidence of head trauma. Overall, older patients had poorer thresholds. Men showed higher prevalence of olfactory loss secondary to inflammation and toxin exposure. Patients with inflammation scored better than patients with other diagnoses (i.e., congenital, head trauma, postviral, toxin exposure, and miscellaneous causes). Patients with congenital etiologies and head trauma had the poorest scores. Symptom ratings were significantly different depending on diagnostic category, age, and gender. Patients with inflammation rated the majority of symptoms as most bothersome. Patients with postviral diagnoses were most likely to report parosmias. Patients with head trauma rated taste and smell loss as significantly more severe than other patients. CONCLUSION: Evaluation of 1000 patients at the UCSD Nasal Dysfunction Clinic in San Diego revealed differential olfactory impairment and differential symptom complaints based on diagnostic category, age, and gender.

Adolescent↗

Effects of Ginkgo biloba on alertness and chemosensory function in healthy adults.

Ginkgo biloba is reported to enhance cognitive function in patients with selected neural disorders. Its effects in healthy, young adults are less well characterized. This work explored whether Ginkgo biloba could ameliorate decrements in alertness post-prandially and/or enhance chemosensory function. Both are functions that could be influenced by enhanced cerebral blood flow and neuronal metabolism, reported properties of the compound. A double-blind placebo-controlled study was conducted with 19 males and 20 females with a mean age of 23.6 +/- 5.4 years and mean weight of 70.0 +/- 1.9 kg. Participants were supplemented for 13 weeks with either Ginkgo biloba (mean dose 184.5 mg/d (range 130-234 mg/d)) or placebo and administered various alertness, performance, affective state and chemosensory tests at weeks 1, 5, 9 and 13. Participants did experience the post-prandial affective state decrement (i.e. post-lunch dip), but not the performance decrement. Performance on the chemosensory tests improved over the 13-week study. However, Ginkgo biloba was ineffective at alleviating the symptoms of the post-lunch dip or at enhancing taste and smell function.

Adolescent↗

Topographical differences in sweetness sensitivity in the peripheral gustatory system of adults and children.

The sensitivity of localised areas of the anterior tongue of adults and 8-year-old males to the sweetener sucrose was determined, using a two-alternative forced choice psychophysical procedure. Stimulation of 12 areas by 0.2125 M sucrose or water, using a filter paper technique, indicated that the children were significantly more sensitive to the sweetener at eight of the areas. Counts of papillae at each of the 12 areas showed that there were similar numbers for adults and children at eight areas, whilst at three of the areas that exhibited a higher sensitivity to sucrose, children had significantly more papillae. Since 8-year-old males are less sensitive to sucrose when the stimulus is given as a whole-mouth stimulus [12], it is proposed that the children's gustatory system may be unable to integrate the information available at the tongue as efficiently as adults, or that the threshold and stimulus-response functions of receptor cells are different in the two groups.

Adult↗

Sensory-directed identification of taste-active ellagitannins in American (Quercus alba L.) and European oak wood (Quercus robur L.) and quantitative analysis in bourbon whiskey and oak-matured red wines.

Aimed at increasing our knowledge on the sensory-active nonvolatiles migrating from oak wood into alcoholic beverages upon cooperaging, an aqueous ethanolic extract prepared from oak wood chips (Quercus alba L.) was screened for its key taste compounds by application of the taste dilution analysis. Purification of the compounds perceived with the highest sensory impacts, followed by liquid chromatography/mass spectrometry as well as one-dimensional and two-dimensional NMR experiments, revealed the ellagitannins vescalagin, castalagin, and grandinin, the roburins A-E, and 33-deoxy-33-carboxyvescalagin as the key molecules imparting an astringent oral sensation. To the best of our knowledge, 33-deoxy-33-carboxyvescalagin has as yet not been reported as a phytochemical in Q. alba L. In addition, the sensory activity of these ellagitannins was determined for the first time on the basis of their human threshold concentrations and dose/response functions. Furthermore, the ellagitannins have been quantitatively determined in extracts prepared from Q. alba L. and Quercus robur L., respectively, as well as in bourbon whiskey and oak-matured red wines, and the sensory contribution of the individual compounds has been evaluated for the first time on the basis of dose/activity considerations.

Alcoholic Beverages↗

Capsaicin and its effects on olfaction and trigeminal chemoreception.

Capsaicin injections severely reduced or eliminated nasal trigeminal responses to 3 odorants (Experiment 1). However, capsaicin treated animals exhibited no deficits in locating buried food, in odor avoidance learning, or in operant odor detection and discrimination (Experiments 2 and 3). In addition, capsaicin desensitization did not affect responsiveness to salty or sour, but may have raised rejection thresholds for bitter (Experiment 4). Finally, while desensitized animals rejected menthol solution, they consumed relatively more than controls, suggesting that capsaicin may have menthol sensitivity. The present results suggest that substance P-containing fibers mediate trigeminal responsiveness to odorants and irritants but that the loss of this responsiveness does not appreciably affect smell or taste, per se.

Animals↗

Membrane currents in taste cells of the rat fungiform papilla. Evidence for two types of Ca currents and inhibition of K currents by saccharin.

Taste buds were isolated from the fungiform papilla of the rat tongue and the receptor cells (TRCs) were patch clamped. Seals were obtained on the basolateral membrane of 281 TRCs, protruding from the intact taste buds or isolated by micro-dissection. In whole-cell configuration 72% of the cells had a TTX blockable transient Na inward current (mean peak amplitude 0.74 nA). All cells had outward K currents. Their activation was slower than for the Na current and a slow inactivation was also noticeable. The K currents were blocked by tetraethylammonium, Ba, and 4-aminopyridine, and were absent when the pipette contained Cs instead of K. With 100 mM Ba or 100 mM Ca in the bath, two types of inward current were observed. An L-type Ca current (ICaL) activated at -20 mV had a mean peak amplitude of 440 pA and inactivated very slowly. At 3 mM Ca the activation threshold of ICaL was near -40 mV. A transient T-type current (ICaT) activated at -50 mV had an average peak amplitude of 53 pA and inactivated with a time constant of 36 ms at -30 mV. ICaL was blocked more efficiently by Cd and D600 than ICaT. ICaT was blocked by 0.2 mM Ni and half blocked by 200 microM amiloride. In whole-cell voltage clamp, Na-saccharin caused (in 34% of 55 cells tested) a decrease in outward K currents by 21%, which may be expected to depolarize the TRCs. Also, Na-saccharin caused some taste cells to fire action potentials (on-cell, 7 out of 24 cells; whole-cell, 2 out of 38 cells responding to saccharin) of amplitudes sufficient to activate ICaL. Thus the action potentials will cause Ca inflow, which may trigger release of transmitter.

Action Potentials↗

A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition.

Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption "Zydis Selegiline". The aim of the first study was to compare the therapeutic efficacy of Zydis Selegiline (1.25 mg or 10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg) in patients with Parkinson's disease (PD) who were previously treated with conventional selegiline tablets as an adjunct to levodopa/dopamine agonist therapy. Patients were observed for 4 weeks to ensure that they were stable. Stable patients (n=197) were then randomised to continue with conventional selegiline tablets 10 mg (n=68), or to treatment with Zydis Selegiline 1.25 mg (n=64) or Zydis Selegiline 10 mg (n=62) for 12 weeks in this randomised, parallel group study. A further aim was to establish the acceptability of Zydis Selegiline compared with conventional selegiline tablets. Patient preference for Zydis Selegiline was also evaluated in a second study, a single-dose, randomised, two-way crossover study conducted in patients with PD (n=148). Patients were stratified by the presence or absence of swallowing and salivation problems and were randomised to either Zydis Selegiline 5 mg or a placebo fast-dissolving formulation. In a third study, the degree of potentiation of the tyramine pressor effect following Zydis Selegiline was compared with that following conventional selegiline tablets in healthy volunteers. A total of 24 healthy volunteers were randomised to receive Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg for 14-16 days in an open-label, randomised parallel group study. Both Zydis Selegiline (1.25 mg and 10 mg) treatments were shown to be therapeutically equivalent to conventional selegiline tablets 10 mg based on comparison of mean total Unified Parkinson's Disease Rating Scale (UPDRS) scores. Therapeutic equivalence was defined a priori as the 90% confidence interval (CI) for the difference in total UPDRS scores between groups to lie entirely within the range +/-5. The difference (90% CI) in mean adjusted total UPDRS between Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg was -2.50 (-4.84, -0.17), and for Zydis Selegiline 10 mg and conventional selegiline tablets 10 mg, 0.04 (-2.30, 2.38). For the motor subscores of the UPDRS, differences between adjusted means (90% CI) compared with the conventional selegiline tablets group were: Zydis Selegiline 1.25 mg, -2.14 (-3.94, -0.33) and Zydis Selegiline 10 mg, -0.90 (-2.70, +0.91). Patients who switched from conventional selegiline tablets to Zydis Selegiline 1.25 mg showed a slight improvement in UPDRS scores following 12 weeks of treatment (standard error of difference 1.039; p=0.01). In the single-dose crossover study, most (61%) patients liked Zydis Selegiline 5 mg; a significantly greater proportion than the null hypothesis of 50% (p<0.002). However, only 62 patients (46%) indicated that they liked the taste of Zydis Selegiline. Nevertheless, the proportion of patients who preferred Zydis Selegiline (65%) to their usual medication was significantly greater than the null hypothesis of 50% (p<0.001). Similar findings were demonstrated in the 12-week study where a higher proportion of patients who received up to 3 months of treatment indicated a preference for either Zydis Selegiline 1.25 mg (90%) or Zydis Selegiline 10 mg (86%) over conventional selegiline tablets 10 mg. More than 90% of patients found Zydis Selegiline easy to take, with 61% rating it as extremely easy. Most (81%) patients taking Zydis Selegiline 1.25 mg liked the taste compared with 45% taking Zydis Selegiline 5 mg (in the previous study). Zydis Selegiline did not potentiate the tyramine effect: a pressor effect was elicited after 400 mg tyramine both before and after 14 days of treatment with Zydis Selegiline 1.25 mg. In contrast, after 14 days treatment with conventional selegiline tablets 10 mg, the threshold dose required to elicit the tyramine pressor response was significantly (p<0.0001) reduced from 400 mg to 200 mg. In summary, Zydis Selegiline at doses of 1.25 mg and 10 mg was therapeutically equivalent to conventional selegiline tablets 10 mg. The Zydis Selegiline formulation was well-liked by all patients, with most preferring Zydis Selegiline 1.25 mg to their usual selegiline tablet. Furthermore, Zydis Selegiline was well tolerated and, unlike conventional selegiline tablets, appeared to retain specificity for inhibition of monoamine oxidase type B (MAO-B), since it did not potentiate the pressor response to tyramine.

Administration, Oral↗