Analysis of Genetic Polymorphism of Bitter Taste Receptor TAS2R38 and TAS2R46, and Its Relationship with Eating and Drinking Habits in Japanese ToMMo Subjects.

Human type 2 taste receptor (TAS2R) genes encode bitter-taste receptors that are activated by various bitter ligands. It has been said that TAS2R38 may detect bitter substances and then suppress their intake by controlling gustatory or digestive responses. The major haplotypes of TAS2R38 involve three non-synonymous, closely-linked single-nucleotide polymorphisms (SNPs), leading to three amino acid substitutions (A49P, V262A and I296V) and resulting in a PAV or AVI allele. The allele frequency of AVI/PAV was 0.42/0.58 in this study. The genotype frequency distributions of TAS2R38 were 18.32%, 46.95% and 33.95% for AVI/AVI, AVI/PAV and PAV/PAV, respectively, and were in Hardy-Weinberg equilibrium. Five haplotype combinations of minor alleles were identified: AVI/AAV, AVI/AVV, AAI/PAV, AVI/PVV, AVI/AAI, with corresponding frequencies of 0.49%, 0.10%, 0.10%, 0.05%, 0.05%, respectively, in 2,047 Japanese Tohoku Medical Megabank Organization (ToMMo) subjects (2KJPN). The 16 subjects with these minor alleles were excluded from the questionnaire analysis, which found no significant differences among the major TAS2R38 genotypes (AVI/AVI, AVI/PAV and PAV/PAV) in the intake frequency of cruciferous vegetables or in the frequency of drinking alcohol. This result differs from previous data using American and European subjects. This is the first study to analyze the relationship between TAS2R38 genotype and the eating and drinking habits of Japanese subjects. It was also shown that there were no relationships at all between the genetic polymorphism of TAS2R46 and the phenotypes such as clinical BMI, eating and drinking habits among the 3 genotypes of TAS2R46 (∗/∗, ∗/W, W/W) at position W250∗ (∗stop codon).

Taste alterations in patients with breast cancer following chemotherapy: a cohort study.

BACKGROUND: Chemotherapy-induced taste and smell alterations in cancer patients are associated with multiple adverse effects, namely, malnutrition, weight loss, and a diminished quality of life. The aim of this prospective study was to identify the incidence of taste alterations following epirubicin and cyclophosphamide (EC) chemotherapy in patients with breast cancer without previous history of cancer or chemotherapy. METHODS: Forty-one patients undergoing EC chemotherapy for breast cancer at Tokai University Hospital were included. A subjective (questionnaire) and an objective (filter paper disk method) assessment for 5 basic tastes were administered on day 4 post-chemotherapy and immediately before the subsequent cycle of chemotherapy for each cycle, in addition to an olfactory evaluation and oral examination. The correlation between subjective and objective taste alterations and factors influencing these alterations were analyzed by statistical means. RESULTS: The mean incidence of subjective taste alteration on the 4th day after chemotherapy was 53%. In each of the 4 cycles, taste alterations decreased to about 9.0% immediately before the next cycle. A significant correlation between subjective and objective assessments was seen only for salty taste, suggesting important differences in subjective versus objective assessment outcomes. A multivariate analysis indicated that age and body surface area influenced taste alterations. CONCLUSIONS: EC chemotherapy induced taste alterations in more than 50% of patients, which decreased to less than 10% immediately before the next chemotherapy cycle. A combination of objective and subjective assessments is essential to evaluate taste alterations induced by EC chemotherapy. These could be used in routine clinical practice.

Effects and Mechanisms of Tastants on the Gustatory-Salivary Reflex in Human Minor Salivary Glands.

The effects and mechanisms of tastes on labial minor salivary gland (LMSG) secretion were investigated in 59 healthy individuals. Stimulation with each of the five basic tastes (i.e., sweet, salty, sour, bitter, and umami) onto the tongue induced LMSG secretion in a dose-dependent manner. Umami and sour tastes evoked greater secretion than did the other tastes. A synergistic effect of umami on LMSG secretion was recognized: a much greater increase in secretion was observed by a mixed solution of monosodium glutamate and inosine 5'-monophosphate than by each separate stimulation. Blood flow (BF) in the nearby labial mucosa also increased following stimulation by each taste except bitter. The BF change and LMSG secretion in each participant showed a significant positive correlation with all tastes, including bitter. Administration of cevimeline hydrochloride hydrate to the labial mucosa evoked a significant increase in both LMSG secretion and BF, while adrenaline, atropine, and pirenzepine decreased LMSG secretion and BF. The change in LMSG secretion and BF induced by each autonomic agent was significantly correlated in each participant. These results indicate that basic tastes can induce the gustatory-salivary reflex in human LMSGs and that parasympathetic regulation is involved in this mechanism.

Differences in Taste Perception and Spicy Preference: A Thai-Japanese Cross-cultural Study.

Taste perception is influenced by several factors. However, the relation between taste perception and food culture is unclear. This study compared taste thresholds between populations with different food culture, i.e. Thai and Japanese. A matched case-control study was conducted in 168 adults (84 for each; aged between 50 and 90 years). The age, sex, systemic disease, medication, smoking, xerostomia, and oral hygiene of both groups were not different. Recognition thresholds (RTs) of sweet, salty, sour, bitter, and umami were measured using filter paper disc (FPD). Detection taste thresholds were measured using electrogustometry. Spicy preference was measured by calibrated questionnaires. Higher RTs of all tastes and higher detection taste thresholds were found in Thai as compared to those of Japanese (P < 0.0001). Separate analyses of healthy and unhealthy persons confirmed the significant differences between 2 countries. The average thresholds for sweet, salty, sour, and bitter in Thai and Japanese were 4 and 2, respectively. The average threshold for umami in Thai and Japanese was 5 and 3, respectively. Moreover, Thai population had stronger preference for spicy food (P < 0.0001) with 70% mild- or moderate and 10% strong lovers, compared to over 90% non- or mild-spicy lovers in Japanese. In addition, 70% of Thai consumed spicy food weekly, whilst 80% of Japanese consumed it monthly. Our findings suggested that population with stronger spicy preference such as Thai had much poorer taste sensitivity and perception than that with milder preference like Japanese. Extensive international survey is needed to conclude the influence of food culture on taste perception.

Genotyping Analysis of Bitter-Taste Receptor Genes TAS2R38 and TAS2R46 in Japanese Patients with Gastrointestinal Cancers.

Type-2 bitter-taste receptors (TAS2Rs) are important for the evaluation of food quality and the nutritional control in animals. Mutations in some TAS2Rs including TAS2R38 are known to increase susceptibility to various diseases. However, the involvement of TAS2Rs in cancers has not been well understood. We conducted a pilot study by genotyping two TAS2R genes, TAS2R38 and TAS2R46, in Japanese cancer patients diagnosed with the following types of cancer: biliary tract cancer, hepatocellular carcinoma, pancreatic cancer, colorectal cancer and gastric cancer. We selected the two TAS2Rs because they carry virtually non-functional alleles in human populations. We found that cancer risk is not associated with any TAS2R46 genotypes since there were no significant differences in genotype frequencies between cancer patients and controls. On the other hand, we confirmed that phenylthiocarbamide (PTC) non-tasters homozygous (AVI/AVI) for TAS2R38 were more frequent among Japanese cancer patients than those among controls as suggested in a previous study. The AVI/AVI genotype was therefore considered to increases cancer risk. In contrast, we also found that homozygous (PAV/PAV) PTC tasters are less frequent among cancer patients, suggesting that the PAV/PAV is a cancer resistant genotype that decreases cancer risk. Genotype frequencies for heterozygous AVI/PAV genotype were not significantly different between the two groups. It is suggested that the risk and resistance of cancers is antagonistically controlled by the two TAS2R38 alleles, PAV and AVI, rather than by the AVI allele alone.

Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome.

Burning mouth syndrome is characterized by altered sensory qualities, namely tongue pain hypersensitivity. We found that the mRNA expression of Artemin (Artn) in the tongue mucosa of patients with burning mouth syndrome was significantly higher than that of control subjects, and we developed a mouse model of burning mouth syndrome by application of 2,4,6-trinitrobenzene sulfonic acid (TNBS) diluted with 50% ethanol to the dorsum of the tongue. TNBS treatment to the tongue induced persistent, week-long, noninflammatory tongue pain and a significant increase in Artn expression in the tongue mucosa and marked tongue heat hyperalgesia. Following TNBS treatment, the successive administration of the transient receptor potential vanilloid 1 (TRPV1) antagonist SB366791 or neutralizing anti-Artn antibody completely inhibited the heat hyperalgesia. The number of glial cell line-derived neurotrophic factor family receptor α3 (GFRα3)-positive and TRPV1-positive trigeminal ganglion (TG) neurons innervating the tongue significantly increased following TNBS treatment and was significantly reduced by successive administration of neutralizing anti-Artn antibody. The capsaicin-induced current in TG neurons innervating the tongue was enhanced following TNBS treatment and was inhibited by local administration of neutralizing anti-Artn antibody to the tongue. These results suggest that the overexpression of Artn in the TNBS-treated tongue increases the membrane excitability of TG neurons innervating the tongue by increasing TRPV1 sensitivity, which causes heat hyperalgesia. This model may be useful for the study of tongue pain hypersensitivity associated with burning mouth syndrome.

Development of an umami taste sensitivity test and its clinical use.

There is a close relationship between perception of umami, which has become recognized as the fifth taste, and the human physical condition. We have developed a clinical test for umami taste sensitivity using a filter paper disc with a range of six monosodium glutamate (MSG) concentrations. We recruited 28 patients with taste disorders (45-78 years) and 184 controls with no taste disorders (102 young [18-25 years] and 82 older [65-89 years] participants). Filter paper discs (5 mm dia.) were soaked in aqueous MSG solutions (1, 5, 10, 50, 100 and 200 mM), then placed on three oral sites innervated by different taste nerves. The lowest concentration participants correctly identified was defined as the recognition threshold (RT) for MSG. This test showed good reproducibility for inter- and intra-observer variability. We concluded that: (1) The RT of healthy controls differed at measurement sites innervated by different taste nerves; that is, the RT of the anterior tongue was higher than that of either the posterior tongue or the soft palate in both young and older individuals. (2) No significant difference in RT was found between young adults and older individuals at any measurement site. (3) The RT of patients with taste disorders was higher before treatment than that of the healthy controls at any measurement site. (4) The RT after treatment in these patients improved to the same level as that of the healthy controls. (5) The cutoff values of RT, showing the highest diagnostic accuracy (true positives + true negatives), were 200 mM MSG for AT and 50 mM MSG for PT and SP. The diagnostic accuracy at these cutoff values was 0.92, 0.87 and 0.86 for AT, PT and SP, respectively. Consequently, this umami taste sensitivity test is useful for discriminating between normal and abnormal umami taste sensations.

Diagnostic performance of labial minor salivary gland flow measurement for assessment of xerostomia.

OBJECTIVE: Minor salivary gland flow rate (MF) has been proposed as a key feature of xerostomia (subjective feeling of dry mouth). To assess its diagnostic performance, MF was compared in xerostomia and control subjects. DESIGN: Sixty-six subjects with xerostomia and 30 controls were enrolled. MF was measured in the lower labial mucosa using the iodine-starch filter paper method. Stimulated whole salivary flow rates were also measured using the gum test (stimulated-WF). RESULTS: Both labial-MF and stimulated-WF were significantly lower in xerostomia subjects than in controls. There was a positive correlation between labial-MF and stimulated-WF in control but not xerostomia subjects. In xerostomia subjects compared to controls, there was a significantly larger reduction in labial-MF than in stimulated-WF. Xerostomia was most accurately diagnosed using a labial-MF cutoff value of 0.25 µL/cm(2)/min. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy at this cutoff value were 1.00, 0.87, 0.93, 1.00, and 0.96, respectively. Compared to respective values of 0.64, 1.00, 1.00, 0.56, and 0.75 for stimulated-WF at the traditional cutoff of 1.0 mL/min, these data indicate the higher sensitivity, negative predictive value, and diagnostic accuracy of labial-MF. CONCLUSIONS: Xerostomia was more strongly related to reduction of labial-MF than to that of stimulated-WF. Xerostomia was most likely triggered at a labial-MF cut-off value of 0.25 µL/cm(2)/min based on results from the iodine-starch method.

Application of umami taste stimulation to remedy hypogeusia based on reflex salivation.

Enjoying taste should be one of the greatest pleasures in human life. However, aging is sometimes associated with decreased taste sensitivity, also known as hypogeusia. The loss of taste not only affects quality of life, but can also cause weight loss and health problems in the elderly. Our recent study has shown that 37% of test subjects over 65 years of age exhibited hypogeusia. Further, whole saliva secretion, including minor salivary secretion, was significantly decreased in elderly patients with gustatory impairment, but was normal in all elderly subjects with normal taste thresholds. These data indicate that hyposalivation is closely related to hypogeusia. Moreover, clinical studies have shown that treatment of hyposalivation diminishes hypogeusia, indicating that salivation is essential to maintain normal taste function. However, many medications for relief of dry mouth, such as parasympathomimetic (cholinomimetic) drugs, have serious adverse effects. Palpitation, sweating, nausea, diarrhea and dizziness have all been observed in elderly patients taking parasympathomimetic drugs. To circumvent this problem, glutamate, which produces umami taste, was demonstrated to increase salivary secretion and thereby improve hypogeusia by enhancing the gustatory-salivary reflex. Our data suggests that umami is an effective tool for the relief of hypogeusia without the side effects of parasympathomimetic drugs.

A case of multiple idiopathic external root resorption: a 6-year follow-up study.

Multiple idiopathic external root resorption of permanent teeth is a very infrequent phenomenon. This paper describes a case of multiple idiopathic external root resorption at cement-enamel junction in 21 of 25 teeth followed up for 6 years. In addition to clinical features and radiographs, we present results of histological and bacteriological examinations.

Possible application of transmitted laser light for the assessment of human pulp vitality. Part 2. Increased laser power for enhanced detection of pulpal blood flow.

The purpose of this study was to investigate the effect of an increase in laser power on the transmitted laser signals from vital and non-vital teeth, in the hope of achieving a better assessment of human pulp vitality with the transmitted laser-light flowmeter. The experiments were carried out on total of 61 vital teeth with no restoration (19 upper central incisors, 16 upper lateral incisors, 16 upper canines, and 10 first premolars) and five non-vital upper central incisors (the root canals of which were filled with gutta-percha) in 15 subjects aged 22-28 years. For use with transmitted laser light, the fibers within the probe of a conventional laser Doppler flowmeter (LDF) apparatus were used, one for transmitting light onto the labial surface, the other for receiving it at the palatal surface of the same tooth, as reported previously. Laser output power was set at the original 2 mW and also at 5, 7, and 10 mW. The number of vital teeth displaying a blood flow (BF) signal at each laser power setting was: 1) 12/19 central incisors at 2 mW, 19/19 at 5, 7, and 10 mW, 2) 19/19 lateral incisors at 2, 5, 7, and 10 mW, 3) 0/16 canines at 2 mW, but eight, 12, and 14 at 5, 7, and 10 mW, 4) 0/10 first premolars at 2, 5, 7, and 10 mW. Thus, an increase in laser power increased BF detection from the thicker teeth (but not from premolars). In addition, clearer BF signals synchronized with heart rate, and greater passive BF changes secondary to blood pressure (BP) changes were observed at higher laser settings. In non-vital teeth, no signals synchronized with heart rate or BP changes were observed, indicating that no BF signal of non-pulpal origin was ever monitored with this ballistic light even when the laser power was increased. These results indicate that high-powered transmitted laser light could be a useful tool both for monitoring pulpal BF and for the assessment of tooth-pulp vitality.