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Enantioselective syntheses and sensory properties of the 3-mercapto-2-methylpentanols.

3-Mercapto-2-methylpentanol, a new powerful flavor compound, exhibits two stereocenters giving rise to two pairs of diastereomers. To determine differences in the sensory properties, all four diastereomers and enantiomers were stereo- and enantioselectively synthesized. A highly diastereoselective aldol reaction using a chiral auxiliary was one of the key steps in the synthesis. Further derivatization yielded the enantiopure compounds. Odor thresholds in air and water were determined.

Models, Chemical↗

Taste perception in cirrhosis: its relationship to circulating micronutrients and food preferences.

Impairment of gustatory acuity may influence nutrient intake and hence nutritional status. The aim of this study was to evaluate gustatory acuity in patients with cirrhosis and its relationship to circulating concentrations of micronutrients, and food preferences. Gustatory evaluation was undertaken, using a rinsing technique, in 75 cirrhotic patients and 75 comparable healthy volunteers. Circulating concentrations of magnesium, zinc, vitamin A, and alpha- and beta-carotene were measured, and food preferences were assessed by questionnaire. The cirrhotic patients showed impaired gustatory function with significantly higher (less sensitive) median thresholds for detection of salt, sweet, and sour and for recognition of bitter, salt, sweet, and sour, together with a higher overall median gustatory score (P < .0001). Mean circulating concentrations of magnesium, zinc, vitamin A, and alpha- and beta-carotene were significantly lower in the patient population. Serum magnesium was significantly negatively associated with detection of salt (P = .02) and gustatory score (P = .02). Patients' subjective assessment of taste acuity did not correspond with objective measurements. Overall, no differences were observed in food preferences between the two groups, nor was any association found between food preferences and gustatory acuity. Patients with cirrhosis have impaired gustatory acuity that is associated with hypomagnesemia but apparently does not affect food selection.

Adult↗

Identification of the astringent taste compounds in black tea infusions by combining instrumental analysis and human bioresponse.

Application of taste dilution analyses on freshly prepared black tea infusions revealed neither the high molecular weight thearubigen-like polyphenols nor the catechins and theaflavins, but a series of 14 flavon-3-ol glycosides as the main contributors to the astringent taste perceived upon black tea consumption. Among these glycosides, the apigenin-8-C-[alpha-l-rhamnopyranosyl-(1-->2)-O-beta-d-glucopyranoside] was identified for the first time in tea infusions. Depending on the structure, the flavon-3-ol glycosides were found to induce a velvety and mouth-coating sensation at very low threshold concentrations, which were far below those of catechins or theaflavins; for example, the threshold of 0.001 micromol/L found for quercetin-3-O-[alpha-l-rhamnopyranosyl-(1-->6)-O-beta-d-glucopyranoside] is 190000, or 16000 times below the threshold determined for epigallocatechin gallate or theaflavin, respectively. Moreover, structure/activity considerations revealed that, besides the type of flavon-3-ol aglycon, the type and the sequence of the individual monosaccharides in the glycosidic chain are key drivers for astringency perception of flavon-3-ol glycosides.

Biflavonoids↗

Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.

Action Potentials↗

Recovery of olfactory function following closed head injury or infections of the upper respiratory tract.

OBJECTIVE: To investigate the outcome of olfactory function in patients with olfactory loss following infections of the upper respiratory tract (post-URTI) or head trauma. DESIGN: Retrospective patient-based study. SETTING: Smell and Taste Outpatient Clinic at a university hospital. PATIENTS: A total of 361 patients (228 women, 133 men) were included. MAIN OUTCOME MEASURES: Olfactory function was assessed using the "Sniffin' Sticks" test battery, which result in a threshold, discrimination, and identification score. The mean interval between first and last visit was 14 months. RESULTS: In comparing the overall threshold, discrimination, and identification scores between the last and first visit, olfactory function improved in 26% of the patients whereas it decreased in 6%. The cause of olfactory impairment had a significant effect on the recovery rate of olfactory function. Within the post-URTI group (n = 262), 32% of the patients improved, but in the posttraumatic group (n = 99) only 10% improved. In patients with post-URTI olfactory loss, a negative correlation was found between age and recovery of olfactory function. In general, the factor "sex" had no significant effect on recovery of smell function. CONCLUSIONS: To our knowledge, the series of patients presented herein is the largest in the literature to date in which standardized testing methods were used to assess the progression of impaired olfaction. It showed that the rate of improvement of olfactory function was significantly higher in patients with post-URTI dysosmia compared with patients with posttraumatic dysosmia. During an observation period of approximately 1 year, more than 30% of patients with post-URTI olfactory loss experienced improvement, whereas only 10% of patients with posttraumatic olfactory loss experienced improvement. Furthermore, age plays a significant role in the recovery of olfactory function.

Adolescent↗

Physiological satiety implications of gastrointestinal antiobesity surgery.

This manuscript reviews the known satiety signals and the impact of antiobesity surgery on these physiological satiety mechanisms. Satiety signals originate from the stomach and small bowel to stop eating behavior. Stomach signals (gastric distension) produce early satiety by releasing hypothalamic cholecystokinin (CCK). The intermeal interval is probably mediated by peripheral CCK released by a threshold level of intraluminal calories. Anti-obesity operations probably rely little on these physiological satiety signals. Gastric balloons and gastroplasty produce nonphysiological gastric distension whereas intestinal bypass causes malabsorption. Gastric bypass combines supramaximal gastric distension with taste aversion from dumping. Future physiological manipulation of the satiety cascade will lead to improve obesity intervention.

Humans↗

Method of evaluation of the bitterness of clarithromycin dry syrup.

The degree of bitterness of clarithromycin (CAM) dry syrup was evaluated using several methods. Using the inversion method, shaking method, and paddle method, a reasonable correlation between the bitter taste and the amount dissolved was not observed. A mini-column with inner diameter of 0.76 cm and height of 5 cm packed with CAM dry syrup was used for the release test. The release rate of CAM in test solution, which passed through the mini-column, was then measured to evaluate bitterness. The release rate of CAM in the release test using the mini-column correlated well with the results of a sensory test for the bitterness of CAM dry syrup. The dissolution rate constant, defined as the percentage of CAM dissolved from the unit void surface multiplied by the void volume, was inversely proportional to the linear velocity of the test solution. The critical factors affecting evaluation of bitterness were the void volume of the column and linear velocity of the test solution. The optimum linear velocity and void volume were 0.048-0.021 cm/min and 0.27-0.12 cm3, respectively. In addition, the threshold of bitterness of CAM dry syrup was defined as the concentration at which half of the volunteers recognized bitterness in the sensory test. This threshold was found to be 135 microg/ml using the mini-column.

Anti-Bacterial Agents↗

Association between regional idiopathic neuropathy and salivary involvement as the possible mechanism for oral sensory complaints.

UNLABELLED: The idiopathic sensorial disturbances of burning mouth syndrome (BMS), taste disturbances (dysgeusia), and dry mouth (xerostomia) have recently been recognized as one entity and given the generic name of oral sensorial complaints (OSC). However, not all patients with OSC complain of all three disturbances, and the underlying mechanism of OSC has not yet been elucidated. This study sought to determine whether OSC was associated with the alteration of oral sensory perception, salivary profile and/or personality traits. It examined 35 patients with OSC and 19 controls. Sensory perception was assessed by Quantitative Sensory Testing (QST) applied to the tongue, including thresholds for thermal sensations and pain, and the magnitude estimation of tonic suprathreshold heat pain stimuli. The salivary profile included flow rate and compositional analysis. Personality traits were examined by both state and trait anxiety and somatization scoring. Results showed significantly elevated thermal sensory thresholds and decreased pain scores for tonic heat pain. In addition, there was an increased level of somatization in the OSC group as compared to the control group (15.1 +/- 1.5 vs. 6.6 +/- 2.1, respectively; P = .003). Concomitantly, altered salivary composition (elevated Na, K, Cl, Ca, IgA, and amylase concentrations)-but not salivary flow rate reduction-was observed in those patients despite their complaints of oral dryness. All parameters were similar among the patients with OSC regardless of their type of complaint. Linear regression analysis revealed that an elevated warm sensory threshold was associated with higher levels of salivary K and Cl concentrations in the patients with OSC. These findings may be attributed to a regional small fiber idiopathic neuropathy affecting oral sensation and salivary secretion in OSC. Alternatively, a primary idiopathic salivary dysfunction might cause sensory neural dysfunction at the receptor level by changing the oral cavity milieu. PERSPECTIVE: Based on the salivary, psychophysical, and personality traits analysis currently presented, as well as on the available literature, we hypothesize that a comprehensive mechanism for OSC is based on a regional neuropathy, which is expressed by complaints of BMS, taste disturbances, and/or xerostomia. All are clearly distinguishable from similar conditions with established organic/therapeutic-related etiologies.

Adult↗

Sucrose-induced analgesia is related to sweet preferences in children but not adults.

The present study tested the hypothesis that the efficacy of sucrose in reducing pain during the Cold Pressor Test (CPT) was related to its hedonic value. To this aim, we determined the most preferred level of sucrose and the analgesic properties of 24% w/v sucrose during the CPT in 242, 5- to 10-year-old children and their mothers. Outcome measures included pain thresholds (the time at which discomfort was first indicated) and pain tolerance (the length of time the hand was kept in the cold water bath). Although children, as a group, preferred significantly higher sucrose concentrations than adults, there were individual differences that allowed us to group them on the basis of those who preferred sucrose concentrations below that used in the CPT (24% w/v) and those who preferred levels >or=24% w/v sucrose. Regardless of such groupings, sucrose was not an effective analgesic in adult women. Unlike adults, the more children liked sucrose, the better its efficacy as an analgesic. That is, children who preferred >or=24%w/v sucrose exhibited an increased latency to report pain and tolerated pain for significantly longer periods of time when sucrose was held in their mouths relative to water. This effect was more pronounced among normal weight when compared to overweight/at risk for overweight children. The role that dietary habits and individual differences contribute to the preferences for sweet taste and its physiological consequences in children is an important area for future research.

Administration, Oral↗

Norbinaltorphimine blocks the feeding but not the reinforcing effect of lateral hypothalamic electrical stimulation.

The role of central kappa opioid receptors in the regulation of feeding and reward was evaluated using electrical brain stimulation paradigms in combination with the selective kappa antagonist, norbinaltorphimine (nor-BNI). Lateral ventricular injection of 10.0 and 50.0 nmol doses of nor-BNI increased the lateral hypothalamic stimulation frequency threshold for eliciting feeding behavior but had no effect on threshold for self-stimulation in the absence of food. This result is identical to those previously reported for naloxone and antibodies to dynorphin A and suggests that opioid activity is associated with feeding behavior rather than the eliciting brain stimulation. A further similarity between naloxone, dynorphin antiserum, and nor-BNI is their preferential effect on feeding threshold values obtained later, rather than initially, in a post-injection test session. This pattern of threshold elevation is shown to differ from that of the appetite suppressants, amphetamine and phenylpropanolamine, which elevate threshold uniformly throughout a post-injection test. The signature pattern of threshold elevation produced by opioid antagonism is consistent with the hypothesis that opioid activity is involved in the maintenance rather than the initiation of feeding. Specifically, it is hypothesized that a dynorphin A/kappa receptor mechanism is triggered by food taste and sustains feeding behavior by facilitating incentive reward.

Animals↗

Investigating the actions of bupropion on dependence-related effects of nicotine in rats.

RATIONALE: The clinical success of the antidepressant bupropion, marketed as Zyban in smoking cessation, presents an ideal opportunity to unravel its mechanism of action utilising animal models of nicotine dependence. OBJECTIVE: The present experiments utilise bupropion as a reference compound to examine putative interactions with stimulus properties of nicotine in rats. METHODS AND RESULTS: In male hooded Lister rats, bupropion (10 and 30 mg/kg IP) administered 30 min prior to each intravenous nicotine (0.03 mg/kg per infusion) self-administration session failed to attenuate rates of nicotine intake. Moreover, following the large dose of bupropion, nicotine intake was enhanced and response rates remained elevated throughout the 28-day course of treatment. To examine interactions with subjective effects of nicotine, rats trained to discriminate nicotine (0.2 mg/kg SC) from vehicle were tested with bupropion (1, 3, 10 and 30 mg/kg IP). Bupropion pre-treatment failed to exert a "nicotine-like" action and also failed to attenuate the orderly dose-related discrimination function of nicotine (0.05-0.4 mg/kg SC) in rats. Using the conditioned taste aversion procedure to assess the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake, bupropion (3, 10 and 30 mg/kg IP) pre-treatment failed to modify the aversive effects produced by a threshold dose of nicotine (0.2 mg/kg SC). CONCLUSIONS: The results obtained with bupropion in these animal models of dependence suggest this antidepressant may not directly interact with stimulus properties of nicotine; rather its clinical efficacy may be exposed in animal models that are based upon chronic exposure to nicotine and upon abstinence effects.

Animals↗

Sensory threshold of off-flavors caused by proteolysis and lipolysis in milk.

The objective of this study was to determine the sensory threshold of off-flavor caused by lipolysis in 2% fat milk and to establish the relationship between increased proteolytic activity in milk and the detection of bitter off-flavor. Homogenized raw milk was held at room temperature for 100 min to allow the native milk lipase to release free fatty acids from the triglycerides. Low and high lipolysis pasteurized milk containing 2% fat were blended together in varying amounts to create a series of six milks with increasing free fatty acid (FFA) concentration for sensory evaluation. Sensory threshold for lipolysis in 2% fat milk was determined by ascending forced-choice procedure, with a series of triangle tests in four sessions with 25 panelists in each session. The group best estimated threshold was the geometric mean of the individual thresholds within each of four panel sessions. The geometric mean best estimated detection thresholds for off-flavors caused by lipolysis in 2% fat milk carried out by native milk lipases were 0.320, 0.322, 0.351, and 0.316 meq of FFA/kg milk for panels 1 to 4, respectively. One third of the panelists detected an off-flavor at or below 0.250 meq of FFA/kg milk. To establish the relationship between proteolysis and detection of off-flavor in pasteurized skim milk, 2800 ppm of CO2 were added to pasteurized skim milk, and it was stored for 27 d at 6 degrees C. Another portion of the same milk was frozen on d 1 at -40 degrees C for use as a low proteolysis portion of the same milk. Decrease in casein as a percentage of true protein (CN/TP) was used as an index of proteolysis. After 27 d at 6 degrees C the milk had a decrease in CN/TP of 4.76% and a standard plate count of 430 cfu/ml. The novel approach of storing milk at 6 degrees C for 27 d with added CO2 blocked microbial growth but allowed proteolytic degradation by milk enzymes to proceed. Before sensory analysis, CO2 was removed by vacuum from the high proteolysis milk and the low proteolysis milk was given the same heat and vacuum. Two triangle tests were performed to determine whether panelists could detect off-flavors caused by proteolysis in milk. The threshold detection of off-flavor in skim milk produced by the action of native milk proteases was less than a decrease of CN/TP of 4.76%, but this value is probably near the threshold.

Animals↗

Embryonic geniculate ganglion neurons in culture have neurotrophin-specific electrophysiological properties.

Geniculate ganglion neurons provide a major source of innervation to mammalian taste organs, including taste buds in the soft palate and in fungiform papillae on the anterior two thirds of the tongue. In and around the fungiform papillae, before taste buds form, neurotrophin mRNAs are expressed in selective spatial and temporal patterns. We hypothesized that neurotrophins would affect electrophysiological properties in embryonic geniculate neurons. Ganglia were explanted from rats at gestational day 16, when growing neurites have entered the papilla core, and maintained in culture with added brain-derived neurotrophic factor (BDNF), neurotrophin 4 (NT4), nerve growth factor (NGF) or neurotrophin 3 (NT3). Neuron survival with BDNF or NT4 was about 80%, whereas with NGF or NT3 less than 15% of neurons survived over 6 days in culture. Whole cell recordings from neurons in ganglion explants with each neurotrophin condition demonstrated distinctive neurophysiological properties related to specific neurotrophins. Geniculate neurons cultured with either BDNF or NT4 had similar passive-membrane and action potential properties, but these characteristics were significantly different from those of neurons cultured with NGF or NT3. NGF-maintained neurons had features of increased excitability including a higher resting membrane potential and a lower current threshold for the action potential. About 70% of neurons produced repetitive action potentials at threshold. Furthermore, compared with neurons cultured with other neurotrophins, a decreased proportion had an inflection on the falling phase of the action potential. NT3-maintained neurons had action potentials that were of relatively large amplitude and short duration, with steep rising and falling slopes. In addition, about 20% responded with a repetitive train of action potentials at threshold. In contrast, with BDNF or NT4 repetitive action potential trains were not observed. The data demonstrate different neurophysiological properties in developing geniculate ganglion neurons maintained with specific neurotrophins. Therefore, we suggest that neurotrophins might influence acquisition of distinctive neurophysiological properties in embryonic geniculate neurons that are fundamental to the formation of peripheral taste circuits and a functioning taste system.

Action Potentials↗

Taste responses to deuterium oxide.

Substitution of deuterium oxide (D2O) as the solvent in taste stimuli elicits neural responses which differ from ordinary water (H2O). Previous reports have shown that D2O is toxic to many animals and rats avoid drinking it when offered H2O simultaneously. In the current study, summated responses were recorded from the chorda tympani nerves of rats after NaCl, KCl, sucrose and quinine were applied to the tongue in solutions of either D2O or H2O. Both solvents were used as the adapting or rinse solution in separate series. On tongues adapted to H2O, D2O elicited mean responses which were equivalent to 29% of the response to 0.1 M NaCl. The threshold concentration of D2O in H2O was between 25% and 50%. Solutes in D2O yielded responses which were greater than corresponding solutions of H2O when adapting rinse was H2O. Adaptation to D2O diminished the responses to D2O solutions of NaCl, KCl and sucrose but not quinine. This observation suggests that some portion of the augmented response to stimuli in D2O is due to the solvent itself. The taste of water has been examined by both electrophysiological methods and by behavior, but none of the mechanisms espoused for its effect seem adequate to explain the response to D2O. Water structure at the interface between molecular components of the cell membrane and the bulk phase of the surrounding medium is considered as a locus for disparity in the taste responses to D2O and H2O in the rat.

Animals↗

A critical evaluation of the glycerol test in Meniere's disease.

From the literature it is apparent that the glycerol test is being used frequently to evaluate Meniere patients, with regard to the choice of treatment, and in particular to find those who are suitable for surgery with different decompressive procedures. In our previous investigations on such patients we found that they often are extremely good placebo responders and it was natural to evaluate how important such psychological factors would be for the outcome of the glycerol test. In a group of patients with typical objective and subjective symptoms of Meniere's disease, the glycerol test was applied twice to each patient. In one of the tests, the patient was told that we would expect hearing to improve. In the other test, where the actual amount of glycerol was the same, we had the solution prepared with a different taste, and the patient was informed that we now would expect the hearing to deteriorate. The sequence of the two tests was randomly chosen for each patient. Most frequently the patient would follow our instructions, i.e. obtained a poorer hearing threshold when instructed to, and vice versa. The results are discussed with a special view to the risk of selection of suggestion-sensitive patients by this test.

Adult↗