Nutrient recognition is one of the main physiological roles of the gustatory system. In mammals, it is well established that the taste of sodium salts is primarily mediated by sodium influx through the epithelial sodium channel. The epithelial sodium channel is a sodium-specific ion channel that is expressed across a wide range of transporting epithelia such as colon, kidney, and taste. In addition to its role as a salt taste receptor, sodium influx through the epithelial sodium channel is important systemically for maintaining sodium balance and blood pressure. Following our earlier work on the endocrine regulation of salt taste at the level of the epithelial sodium channel, we hypothesize that the epithelial sodium channel expressed in mouse taste receptor cells plays a central role in the restoration of salt and water balance. Using a multidisciplinary approach that includes patch clamp recording, functional sodium imaging, molecular biology, Western blotting, and behavioral assays, we have begun to investigate different mechanisms of the epithelial sodium channel regulation in the taste system. In the present study, we have demonstrated a number of mechanisms that regulate the epithelial sodium channel by both ions and/or hormones in mouse taste cells. In general, three new mechanisms of the epithelial sodium channel regulation were identified: (1) regulation of the epithelial sodium channel by chloride ions, (2) regulation of the epithelial sodium channel by insulin, and (3) alterations of the epithelial sodium channel function in diabetic taste cells. To test the relevance of one or more of these regulatory mechanisms in the animals' behavior, we used a variety of short-term behavioral assays. Interestingly, the results suggested that insulin regulates salt intake in rodents, which dovetails nicely with our functional and molecular findings. Consistent with insulin's physiological role in salt taste transduction, we investigated the modification of the epithelial sodium channel function during the onset of diabetes. Diabetic rodents displayed alterations in salt taste transduction via epithelial sodium channel from the gene level to the animals' behavior. These results are an example of how regulatory cues, like hormones, act on specific transduction elements to modulate the peripheral gustatory system.

The present experiment was conducted to determine the relationship between the human menstrual cycle and gustatory hedonic response. Hedonic response was defined as the perceived pleasantness or unpleasantness of a taste stimulus. Gender differences in taste hedonic have been observed; these may be due to differences in endocrine systems. Animal taste preferences are altered when reproductive hormonal status is experimentally manipulated. Previous researchers report that human females' hedonic responses to sucrose vary systematically with phase of menstrual cycle.

Indiana University-Purdue University Indianapolis (IUPUI) / Taste-and-Odor (T&O) occurrences are a worldwide problem and can locally have extensive socio-economic impacts in contaminated waterbodies. Tracing odorous compounds in surface waters or controlling the growth of producing organisms is particularly challenging. These approaches require the understanding of complex interactions between broad climate heterogeneity, large-scale physical processes such basin hydrology, lake/reservoir circulation, responses of aquatic ecosystems and communities. Eagle Creek Reservoir (ECR), a eutrophic water body, located in central Indiana experiences annual odorous outbreaks of variable durations and intensities that can impair its water quality. Two major compounds, 2-methylisoborneol and geosmin, have been identified as the main culprits occurring seasonally when the reservoir receives high discharges and nutrient loads from its main tributaries. Under these conditions, the growth of T&O-producing bacteria tends to take over other phytoplanktic organisms. Discrete samples collected within the water column during severe outbreaks in 2013 revealed that some bacterioplankton members belonging to Actinobacteria (Streptomyces) and Cyanobacteria (Planktothrix) were involved in the generation of T&O compounds. Most of this production occurred in the upper layers of the water column where higher abundances of key enzymes from MIB and geosmin metabolic pathways were detected. Application of a copper-based algaecide to curb the biosynthesis of bacterial metabolites led to geosmin production (linked to Cyanobacteria) being quickly terminated, whereas MIB levels (linked to Actinobacteria) lingered for several weeks after the algaecide treatment. Significant chemical differences in the association of these metabolites were measured in ECR. Geosmin was dominantly found cell-bound and settling after cellular death increases susceptibility to biodegradation in bottom sediments. MIB was mostly found dissolved making it less susceptible to biodegradation in bottom sediments. Genetic data identified Novosphingobium hassiacum and Sphingomonas oligophenolica (α- Proteobacteria) as potential degraders of geosmin and, four Flavobacterium species (Bacteroidetes) as potential MIB degraders. The role of Eagle Creek natural sediments in the removal of bacterial metabolites via chemical adsorption was also tested but was not proven efficient. Bacterial breakdown activity was demonstrated to be the major loss mechanism of MIB and geosmin.

京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第13205号 / 論農博第2863号 / 新制||農||1062(附属図書館) / 学位論文||H30||N5143(農学部図書室) / (主査)教授 松村 康生, 教授 奥本 裕, 教授 丸山 伸之 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Melt granulation is a versatile process that is underutilized in the pharmaceutical industry. Most pharmaceutical wet granulation and twin-screw extruders can be adapted for melt granulation. Twin-screw melt granulation (TSMG) is of interest since is a continuous process and allows for flexible process design and a high degree of control. TSMG can be used to produce formulations for oral immediate or sustained release. This research focuses on the use of TSMG to taste-mask APIs. Many APIs are bitter or unpleasant tasting. Taste-masking may be required, particularly for products intended for pediatric patients. Taste-masking has been achieved with many different techniques, but a simple, cost-effective method that can be applied to many different APIs is not currently available. A matrix encapsulation approach using continuous twin-screw melt granulation was attempted with three different APIs. The resulting granule properties, particularly particle size, are related to the granulation process parameters. Prediction of taste-masking based on in vitro assessments is challenging and generally clinical evaluation is required. A small-volume dissolution method was developed as a screening test the melt granules. It is not clear if this technique is predictive of clinical taste-masking performance, but it is expected to be an improvement over discrete sampling or typical quality control dissolution methods. The dissolution rate was estimated using the Noyes-Whitney equation and correlated to the mean granule particle size. From this, a simple model for time to a taste threshold could be used to define a design space around the granulation process. / Pharmaceutical Sciences

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