Distinctive Lipid Characteristics of Colorectal Cancer Revealed through Non-targeted Lipidomics Analysis of Tongue Coating.

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.

Negative prognostic behaviour of PD-L1 expression in tongue and larynx squamous cell carcinoma and its significant predictive power in combination with PD-1 expression on TILs.

BACKGROUND: Biomarkers that can predict outcome will improve the efficacy of treatment for HNSCC patients. In this regard, we retrospectively evaluated the prognostic effect of PD1, PD-L1, and CD45RO in tongue and larynx squamous cell carcinomas. METHODS: FFPE tissue blocks of 63 larynx and 40 tongue squamous cell carcinoma samples were selected, cut into 3 µm sections, and immunohistochemically stained for PD1, PD-L1, and CD45RO. The slides were evaluated by an expert pathologist, and results were analysed using Chi-square, univariate, and multivariable Cox regression methods. RESULTS: TC-PD-L1 expression (P = 0.001) and its expression intensity (P = 0.002) were significantly correlated with a higher percentage of PD-1 + tumor infiltrating lymphocytes. In univariate survival analysis, TC-PD-L1 and its expression intensity had a significant impact on both DFS (HR: 0.203; P = 0.003 and HR: 0.320; P = 0.005) and OS (HR: 0.147; P = 0.002 and HR: 0.322; P = 0.005). Based on the multivariate analysis, PD1 (DFS: HR: 3.202; P = 0.011, OS: HR: 2.671; P = 0.027) and TC-PD-L1 (DFS: HR: 0.174; P = 0.006, OS: HR: 0.189; P = 0.009) were found to be independent prognostic markers. In the second part, scoring systems were defined based on the expression status of PD1 and PD-L1. Patients with higher scores were expected to have longer DFS and OS. In multivariate analysis, the PD1/TC-PD-L1 (DFS: P = 0.001, OS: P = 0.003) scoring systems showed superior prognostic effects. Interestingly, at the highest levels of this score, none of the patients experienced recurrence or cancer-caused death. CONCLUSION: Collectively, this study suggests negative prognostic behaviour for TC-PD-L1 protein and introduces the PD-1/TC-PD-L1 scoring system as a strong prognostic marker in OS and DFS prediction of tongue and larynx HNSCC patients.

Profiling flavor characteristics of cold brew coffee with GC-MS, electronic nose and tongue: effect of roasting degrees and freeze-drying.

BACKGROUND: Roasting is an important process in the formation of coffee flavor characteristics, which determines the quality of coffee and consumer acceptance. However, the influence of roasting degree on the flavor characteristics of cold brew coffee has not been fully described. RESULTS: In the present study, the flavor characteristics of cold brew coffee with different roasting degrees were compared in detail by using chromatographic and electronic sensory approaches, and the flavor changes induced by freeze-drying were investigated. Pyrazine and heterocyclic compounds were the main aroma compounds in coffee, and gradually dominated with the increase of roasting. Pyridine was consistently present in cold brew coffees of different roasting degrees and showed significant gradient of quantity accumulation. Aroma compounds such as pyrazine, linalool and furfuryl acetate were the main contributors to coffee roasting, floral and fruity flavor. Freeze-drying preserved the fruity and floral aromas of medium-roasted cold brew coffee, whereas reducing the bitterness, astringency and acidity properties that are off-putting to consumers. CONCLUSION: The higher consumer acceptance and enjoyment in medium roast cold brew coffee may be related to its stronger floral and fruity aroma. The aroma profile qualities of freeze-drying processed medium roasted cold brewed coffee were more dominant and more suitable for freeze-drying processing than medium dark roasting. Application of freeze-drying for cold brew coffee will promote the convenience of drinking. The present study provides valuable technical guidance in improving the flavor and quality of cold brew coffee, and also promotes its commercialization process. © 2024 Society of Chemical Industry.

In situ oral lubrication and smoothness sensory perception influenced by tongue surface roughness.

BACKGROUND: The human tongue is important in the oral processing of food and in sensory perception. Tongue topography could influence delicate differences in sensory perception. It is hypothesized that tongue surface roughness could alter oral lubrication status and affect perception of smoothness. Fifteen participants with varying levels of tongue surface roughness were recruited and tested. Participants' in situ oral lubrication status without and after consumption of fluid food (milk with varying fat content and maltodextrin solutions with different shear viscosities) was measured. Participants' smoothness sensory scores were also recorded. RESULTS: The in situ friction coefficient (0.299-1.505) was significantly positively correlated with tongue-surface roughness (54.6-140.0 µm) in all types of test fluid samples across participants. Oral lubrication was significantly decreased when participants consumed the test fluid samples compared with no liquid food consumption, for all test fluid sample types (P < 0.05). No significant differences in in situ friction coefficient were found after participants consumed different test fluid samples, and this was mainly attributed to the limited quantities of fluid residuals in the oral cavity after expectoration. Participants whose tongue surface roughness differed did not exhibit significant differences in smoothness perception with different test fluid samples. CONCLUSION: Tongue surface roughness has a strong impact on in situ oral lubrication, and fluid food intake reduces in situ oral lubrication significantly. Saliva film and tongue surface roughness might play greater roles in oral lubrication and smoothness sensory perception if fluid is expectorated after consumption. The association between oral physiology and texture perception still needs further elucidation. © 2021 Society of Chemical Industry.

Circular RNA_0001742 has potential to predict advanced tumor stage and poor survival profiles in tongue squamous cell carcinoma management.

BACKGROUND: Circular RNA_0001742 (circ_0001742) has been reported to be upregulated in tongue squamous cell carcinoma (TSCC) tissues/cells and regulate TSCC cell proliferation, migration, and invasion. This study aimed to further investigate the clinical significance of circ_0001742 in TSCC management. METHODS: Totally, 146 TSCC patients underwent surgical treatment were reviewed. Their fresh-frozen tumor tissue and adjacent tissue were acquired for detecting circ_0001742 expression via reverse transcription-quantitative polymerase chain reaction. According to circ_0001742 expression in tumor tissue, all patients were classified as tumor circ_0001742 low (0%-50% percentile) and high (50%-100% percentile) patients, the latter were further divided into the tumor circ_0001742 high+ (50%-75% percentile), high++ (75%-90% percentile), and high+++ (90%-100% percentile) patients, respectively. RESULTS: Circ_0001742 expression was increased in TSCC tumor tissue compared with adjacent tissue, and it presented good value in discriminating tumor tissue from adjacent tissue (area under the curve (AUC): 0.870, 95% CI: 0.831-0.910). Tumor high circ_0001742 expression was associated with higher T stage, N stage, and TNM stage, but not age, gender, or pathological grade. Furthermore, OS was reduced in tumor circ_0001742 high patients compared with tumor circ_0001742 low patients; moreover, OS was the shortest in tumor circ_0001742 high+++ patients, followed by tumor circ_0001742 high++ patients and tumor circ_0001742 high+ patients, and the longest in tumor circ_0001742 low patients. In addition, multivariate Cox's regression analysis revealed that higher tumor circ_0001742 expression was an independent predictive factor for decreased OS. CONCLUSION: Circ_0001742 serves as a potential biomarker for advanced tumor stage and poor survival in TSCC patients.

Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival.

Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.

Obesity is associated with altered gene expression in human tastebuds.

BACKGROUND: The role of taste perception in the development and persistence of obesity is currently unclear due to conflicting results from psychophysical and other studies. No study to date has assessed whether there is an underlying fundamental difference in the physiology of taste tissue between lean and obese individuals. METHOD/SUBJECTS: We analysed the transcriptomic profile (RNA-seq) of human fungiform taste papillae biopsied from lean (n = 23) and obese (n = 13) Caucasian females (age range 18-55) to identify differences in gene expression. RESULTS: Obesity status was the major contributor to variance in global gene expression between individuals. A total of 62 genes had significantly different gene expression levels between lean and obese (P < 0.0002), with the specific taste associated genes phospholipase C beta 2 (PLCß2) and sonic hedge-hog (SHH) having significantly reduced expression in obese group. Genes associated with inflammation and immune response were the top enriched biological pathways differing between the lean and the obese groups. Analysis of a broader gene set having a twofold change in expression (2619 genes) identified three enriched theme groups (sensory perception, cell and synaptic signalling, and immune response). Further, analysis of taste associated genes identified a consistent reduction in the expression of taste-related genes (in particular reduced type II taste cell genes) in the obese compared to the lean group. CONCLUSION: The findings show obesity is associated with altered gene expression in tastebuds. Furthermore, the results suggest the tastebud microenvironment is distinctly different between lean and obese persons and, that changes in sensory gene expression contribute to this altered microenvironment. This research provides new evidence of a link between obesity and altered taste and in the future may help design strategies to combat obesity.

Histopathological evaluation of oral membranous substance in bedridden elderly persons without oral intake in Japan.

OBJECTIVES: The aim of this study was to clarify by histopathological examination the origin of oral membranous substances deposited on the palate, tongue, buccal mucosa and teeth. BACKGROUND: Several investigators have reported membranous substances deposited in the mouths of bedridden elderly persons requiring nursing care without oral intake. However, the precise nature and origin of the substances are poorly understood. METHODS: Sixty-nine specimens were taken from the oral cavity of bedridden patients, that is, the palate, dorsum of the tongue, the cheek and teeth. Sections were stained with haematoxylin and eosin stain, alcian-blue and periodic acid-Schiff stain (AB-PAS) and antibodies for pankeratin (AE1AE3) and leukocyte common antigen (LCA). RESULTS: All specimens showed a film-like nature coloured from tan to white, accompanied by a mucous substance. Histologically, specimens of all sites had a similar feature of the combination of basophilic amorphous and eosinophilic lamellar features. The basophilic substance was positive for AB-PAS, and PAS-positive glycogen granules were also noted in the lamellar structure. Immunochemistry revealed various degrees of pankeratin positive substance and LCA-positive inflammatory cell infiltration. CONCLUSION: The oral membranous substance was composed of keratin and mucin with inflammation. These results suggest that the deposition of the oral membranous substance is a pathological condition or oral mucositis caused by dry mouth.

Tannerella forsythia and coating color on the tongue dorsum, and fatty food liking associate with fat accumulation and insulin resistance in adult catch-up fat.

BACKGROUND/OBJECTIVES: We aimed to determine the alteration of Tannerella forsythia and coating color on the dorsal tongue, and fatty food liking in catch-up fat in adult (CUFA), as well as the probable associations between fat accumulation, insulin resistance (IR) and these changes. SUBJECTS/METHODS: T. forsythia on the tongue dorsum, fatty food liking, fat accumulation and insulin sensitivity were investigated in CUFA humans and rats, and tongue-coating color was observed in CUFA individuals. We further determined the changes of fatty food liking, fat accumulation and IR in T. forsythia-infected rodents by oral lavage. RESULTS: Increases in fat accumulation, IR, percentage of subjects with yellow tongue coating and that with T. forsythia detected were observed in CUFA individuals. Additionally, the fat ranking scores were significantly lower and the hedonic ratings of low-fat options of sampled food were lower, while the ratings of high-fat options were remarkably higher in CUFA subjects. Additionally, T. forsythia level elevated in CUFA rats, and fatty food liking, fat accumulation and IR increased in CUFA and T. forsythia-infected animals, with the increases in T. forsythia infection and fatty food liking preceding the occurrence of fat accumulation and IR. CONCLUSIONS: T. forsythia and yellow coating on the dorsal tongue and fatty food liking associate fat accumulation and IR in CUFA. Moreover, we tentatively put forward that T. forsythia, which is very important in yellow tongue-coating microbiota, and its consequent increases in fatty food liking, might be crucial in the development of fat accumulation and IR in CUFA.

Raman spectroscopic analysis of the molecular composition of oral cavity squamous cell carcinoma and healthy tongue tissue.

A Raman tissue spectrum is a quantitative representation of the overall molecular composition of that tissue. Raman spectra are often used as tissue fingerprints without further interpretation of the specific information that they contain about the tissue's molecular composition. In this study, we analyzed the differences in molecular composition between oral cavity squamous cell carcinoma (OCSCC) and healthy tissue structures in tongue, based on their Raman spectra. A total of 1087 histopathologically annotated spectra (142 OCSCC, 202 surface squamous epithelium, 61 muscle, 65 adipose tissue, 581 connective tissue, 26 gland, and 10 nerve) were obtained from Raman maps of 44 tongue samples from 21 patients. A characteristic, average spectrum of each tissue structure was fitted with a set of 55 pure-compound reference spectra, to define the best library of fit-spectra. Reference spectra represented proteins, lipids, nucleic acids, carbohydrates, amino acids and other miscellaneous molecules. A non-negative least-squares algorithm was used for fitting. Individual spectra per histopathological annotation were then fitted with this selected library in order to determine the molecular composition per tissue structure. The spectral contribution per chemical class was calculated. The results show that all characteristic tissue-type spectra could be fitted with a low residual of <4.82%. The content of carbohydrates, proteins and amino acids was the strongest discriminator between OCSCC and healthy tissue. The combination of carbohydrates, proteins and amino acids was used for a classification model of 'tumor' versus 'healthy tissue'. Validation of this model on an independent dataset showed a specificity of 93% at a sensitivity of 100%.

Suitability of E-tongue Sensors to Assess Taste-Masking of Pediatric Liquids by Different Beverages Considering Their Physico-chemical Properties.

Manipulation of liquid oral drugs by mixing them into foodstuff is a common procedure for taste-masking of OTC pharmaceuticals when administered to children. However, the taste-masking capability of such application media is not systematically evaluated, and recommendations for suitable media are hardly published. In this study, a sensor array of commercially available and self-developed electronic tongue sensors was employed to assess the taste-masking efficiency of eight different beverages (tap water, apple juice, carrot juice, fennel tea, fruit tea, milk, cocoa, and Alete meal to drink) on the OTC pharmaceuticals Ambroxol-ratiopharm®, Cetirizin AL, and Laxoberal® by multivariate data analysis. The Euclidean distances between each pure application medium and its corresponding drug mixture were used as an indicator for the taste-masking efficiency and correlated to the physico-chemical properties of the beverages. Thus, the pH value, the viscosity, as well as the fat and sugar content of the beverages were included, whereas only the viscosity appeared to be insignificant in all cases. The sugar content as well as the fat content and pH value emerged to be a significant variable in taste-masking efficiency for some of the tested drug products. It was shown that the applied electronic tongue sensors were capable to demonstrate the impact of the physico-chemical properties of the application media on their taste-masking capacity regardless of their non-selectivity towards these characteristics.

Reliability and validity of tongue color analysis in the prediction of symptom patterns in terms of East Asian Medicine.

OBJECTIVE: To examine whether color parameters of tongue inspection (TI) using a digital camera was reliable and valid, and to examine which color parameters serve as predictors of symptom patterns in terms of East Asian medicine (EAM). METHODS: Two hundred female subjects' tongue substances were photographed by a mega-pixel digital camera. Together with the photographs, the subjects were asked to complete Yin deficiency, Phlegm pattern, and Cold-Heat pattern questionnaires. Using three sets of digital imaging software, each digital image was exposure- and white balance-corrected, and finally L* (luminance), a* (red-green balance), and b* (yellow-blue balance) values of the tongues were calculated. To examine intra- and inter-rater reliabilities and criterion validity of the color analysis method, three raters were asked to calculate color parameters for 20 digital image samples. Finally, four hierarchical regression models were formed. RESULTS: Color parameters showed good or excellent reliability (0.627-0.887 for intra-class correlation coefficients) and significant criterion validity (0.523-0.718 for Spearman's correlation). In the hierarchical regression models, age was a significant predictor of Yin deficiency (ß = 0.192), and b* value of the tip of the tongue was a determinant predictor of Yin deficiency, Phlegm, and Heat patterns (ß = - 0.212, - 0.172, and - 0.163). Luminance (L*) was predictive of Yin deficiency (ß = -0.172) and Cold (ß = 0.173) pattern. CONCLUSION: Our results suggest that color analysis of the tongue using the L*a*b* system is reliable and valid, and that color parameters partially serve as symptom pattern predictors in EAM practice.

[Purple-bluish tongue is associated with platelet counts, and the recurrence of epithelial ovarian cancer].

OBJECTIVE: To evaluate the relationship between purple-bluish tongue and platelet counts, and further to examine their associations with the recurrence of epithelial ovarian cancer. METHODS: A total of 82 epithelial ovarian cancer patients were enrolled in this study. Cluster analysis was used for grouping patients' P(RGB) (Red-R; Green-G; Blue-B; Average percentage of RGB, P(RGB)) values. Receiver operating characteristic (ROC) curve was performed for detecting the diagnostic standard of purple-bluish tongue. Χ2 test was used to assess the relationship between purple-bluish tongue and platelet counts, and the recurrence of epithelial ovarian cancer. The perioperative (preoperative) platelet level was examined with tongue image and disease recurrence. RESULTS: Tongue images were classified into two groups basing on P(RGB) values of images by cluster analysis. The numbers of cases in cluster "1" (normal color tongue) was 16 and cluster "2" (purple-bluish tongue) was 66. Two groups of P(RGB) values, classified by cluster analysis, were significantly correlated with vision-based tongue color recognition (Kappa = 0.852, P < 0.001). ROC curve showed that the ratio of P(B) to P(R) had the highest diagnostic value. The sensitivity and the specificity of the ratio of P(B) to P(R) were 95.3% and 88.9% respectively and the optimal cut-off point was 0.71. Purple-bluish tongue was significantly correlated with increased platelet counts (P < 0.001). Both the increased platelet counts (P = 0.01) and purple-bluish tongue were associated with recurrence of epithelial ovarian cancer (P < 0.001). CONCLUSION: The ratio of P(B) to P(R) greater than 0.71 could serve as an indicator for purple-bluish tongue diagnosing used in symptom pattern identification in Traditional Chinese Medicine. Purple-bluish tongue, associated with increased platelet counts, was also closely correlated with the recurrence of epithelial ovarian cancer.

Why is the tongue of blue-tongued skinks blue? Reflectance of lingual surface and its consequences for visual perception by conspecifics and predators.

Blue-tongued skinks of the genus Tiliqua (Scincidae) are characterized by their large blue melanin-pigmented tongues, often displayed during open-mouth threats, when the animal feels endangered. It is not clear whether this unusual coloration is a direct anti-predation adaptation or it may rather serve intraspecific communication, as ultraviolet-blue color is a frequent visual signal in a number of lizard species. We used spectrophotometry and visual modeling to compare blue tongues of Tiliqua gigas with tongues and skin coloration of other lizard species, and to examine their appearance through the eyes of both the conspecifics and avian predators. Our results show that (1) the tongue coloration is probably not substantially influenced by the amount of melanin in the skin, (2) lingual and oral tissues are UV-reflective in general, with blue colored tongues having chromatic qualities similar to UV-blue skin patches of other lizard species, (3) UV-blue tongues are more conspicuous than pink tongues, especially in the visual model of conspecifics. We hypothesize that blue tongues may possibly serve as a semantic (honest) signal analogous to UV-blue skin patches of other lizard species due to greater UV-bias in the vision of diurnal lizards. Regarding the social behavior and high aggressiveness in Tiliqua and their relatives, such signal might serve, e.g., in intraspecific long-distance communication between conspecifics in order to avoid aggression, and its anti-predation effect may only be a secondary function (exaptation).

Expression of umami-taste-related genes in the tongue: a pilot study for genetic taste diagnosis.

OBJECTIVE: Expression of taste-related genes in the tongue was analysed to develop a technique for genetic diagnosis of umami taste disorders. MATERIALS AND METHODS: Tissue samples were collected from healthy volunteers by scraping the foliate papillae of the tongue. Immunocytochemistry staining of gustducin, a taste-cell-specific G protein, and gene expression analysis by real-time polymerase chain reaction of ß-actin, gustducin (GNAT3) and umami receptors (T1R1, T1R3 and mGluR1) were performed. Changes in umami receptor expression following application of umami substances onto the tongue were analysed. RESULTS: Gustducin-positive cells were observed in the samples, indicating the presence of taste cells. Gene expression of ß-actin, GNAT3, T1R1 and T1R3 was detected in all seven samples tested, while that of mGluR1 was detected in four samples. Sequence analysis by NCBI Blast showed that each polymerase chain reaction product had a 99% rate of identification of its target sequence. Stimulation of the tongue with monosodium glutamate significantly upregulated the gene expression levels of T1R1 and T1R3, indicating that this method can detect alterations in umami-related gene expression. CONCLUSION: Evaluation of the expression of the umami receptor genes, T1R1 and T1R3, in the tongue may be clinically useful for objective genetic diagnosis of umami taste disorders.

The association between objective tongue color and endoscopic findings: results from the Kyushu and Okinawa population study (KOPS).

BACKGROUND: The relation between tongue color and gastroesophageal disease is unclear. This study was done to investigate the associations between tongue color (TC), endoscopic findings, Helicobacter.pylori infection status, and serological atrophic gastritis (SAG). METHODS: The participants were 896 residents of Ishigaki Island, Okinawa, aged 28-86 years. The tongue was photographed, esophagogastroduodenoscopy was done, and serum antibody to H.pylori was measured. SAG was defined as a serum Pepsinogen (PG)Ilevel ≤70 ng/ml and a PGI/IIratio ≤3.0. TC was measured by the device-independent international commission on Illumination 1976 L*a*b* color space standards at four points: (1) edge, (2) posterior, (3) middle, and (4) apex. We also calculated the ratio of the tongue edge to the three other measured points to examine the association between the coating of the tongue and the endoscopic and laboratory findings. RESULTS: Participants were excluded who had two or more endoscopic findings (n = 315) or who had SAG without seropositivity to H.pylori (n = 33). The remaining 548 participants were divided into three groups: SAG and seropositive to H.pylori (n = 67), seropositive to H.pylori alone (n = 56), and without SAG and seronegative for H.pylori (n = 425). We divided 425 residents into a single endoscopic finding positive group (n = 207) and a negative group, which served as a control (n = 218). The most frequent single endoscopic finding was esophageal hernia (n = 110), followed by erosive esophagitis (n = 35) and erosive gastritis (EG) (n = 45). EH was significantly associated with TC (2b*/1b*) (P < 0.05). EG was significantly associated with TC (3a*, 3b*) (P < 0.05). Seropositivity to H.pylori was significantly associated with TC (3 L*, 3 L*/1 L*) (P < 0.05, <0.01), and seropositivity to both H.pylori and SAG was significantly associated with TC (3 L*/1 L*) (P < 0.05). Multivariate analysis extracted TC (3a*, 3b*) as an independent factor associated with a differential diagnosis of EG (Odds ratio (OR) 2.66 P = 0.008, OR 2.17 P = 0.045). CONCLUSIONS: The tongue body color of the middle area reflects acute change of gastric mucosa, such as erosive gastritis. Tongue diagnosis would be a useful, non-invasive screening tool for EG.

Design, development and in-vitro evaluation of diclofenac taste-masked orodispersible tablet formulations.

CONTEXT: Fast onset of action is prerequisite for acute pain medication. A palatable orodispersible medicine of diclofenac providing rapid analgesic effect should improve patient compliance and treatment. OBJECTIVE: In the present study, diclofenac taste-masked orodispersible tablets (ODTs) with fast release characteristics were developed. Different taste-masking approaches and formulation concepts were screened in vitro for candidate selection. MATERIALS AND METHODS: Diclofenac was used as free acid. Five taste-masked microgranule formulations were prepared by wet granulation and/or coating processes, and compressed to ODTs. Citric acid (pH-modifying agent) and Eudragit® E PO (amino methacrylate copolymer) were used as taste-masking agents. Evaluation criteria were (i) disintegration time, (ii) processability and (iii) in-vitro dissolution profiles in simulated saliva (pH 7.4, 5 mL, 3 min) and compendial pH-change media (paddle, 50 rpm). The prototypes were compared to reference ODTs (without taste-masking). Most suitable ODT prototypes were selected and further evaluated for taste-masking efficiency using an electronic tongue. RESULTS AND DISCUSSION: In simulated saliva, the drug was slower released from the prototypes (between 1.1% and 15.5%) than from reference ODTs (23.7%). Less dissolved particles are thus expected in vivo for taste perception. Two ODT prototypes showed fast and complete drug release in phosphate buffer. The formulation providing the most efficient taste-masking was selected guided by electronic tongue data. CONCLUSION: A novel palatable and fast acting diclofenac ODT formulation was successfully developed. Formulation design, development and in-vitro evaluation used in this study may serve as rational approach for manufacturing taste-masked orodispersible dosage forms.

Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10†years after liver transplantation.

OBJECTIVE: To elucidate the long-term effects of liver transplantation (LT) on familial amyloid polyneuropathy (FAP). METHODS: We investigated clinicopathological and biochemical characteristics of systemic tissues in four autopsied cases of FAP patients surviving more than 10 years after LT and seven autopsied cases without LT. For analysing the truncated form of transthyretin (TTR) in amyloid, we also employed specimens from additional 18 FAP patients. RESULTS: Several tissue sites such as the heart, tongue and spinal cord had moderate-to-severe amyloid deposits but other tissues showed no or mild amyloid deposition. Those findings seemed similar to those observed in senile systemic amyloidosis (SSA), a sporadic amyloidosis caused by wild-type (WT) TTR. Also, amyloid deposits in systemic tissue sites except for the spinal cord in patients after LT derived mostly from WT TTR secreted from the normal liver grafts. In addition, in non-transplantation patients, proportions of WT TTR seemed to be relatively high in those tissue sites in which patients after LT had severe amyloid deposition, which suggests that WT TTR tends to form amyloid in those tissue sites. Finally, although the truncation of TTR in amyloid deposits did not depend on undergoing LT, we elucidated the truncation of TTR occurred predominantly in patients from non-endemic areas of Japan, where FAP amyloidogenic TTR V30M patients are late onset and low penetrance, compared with patients from an endemic area of Japan. CONCLUSIONS: FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.

Age-related changes in rat genioglossus, geniohyoid and masseter muscles.

OBJECTIVES: The aim of this study was to elucidate age-related changes from adult to middle age in the contractile properties of the masseter, genioglossus and geniohyoid muscles of the rat. MATERIALS AND METHODS: We analysed the expressions of myosin heavy chain (MyHC) mRNAs and proteins as indicators of the contractile properties in these muscles obtained from rats at 6, 12, 18 and 24 months of age using real-time PCR and SDS-PAGE. RESULTS: We found no marked age-related changes in the expressions of MyHC mRNAs and proteins in rat masseter and geniohyoid muscles, suggesting that the biological ageing process does not affect contractile properties in these muscles. However, we found a decrease in the expression of MyHC IIb mRNA with ageing in the rat genioglossus muscle, suggesting that biological ageing process induces at least some fast-to-slow myofibre phenotype transition. CONCLUSION: The biological ageing process from adult to middle age appears to differentially affect different types of craniofacial muscles.

Expression and localization of aqua-glyceroporins AQP3 and AQP9 in rat oral epithelia.

Aquaporins (AQPs) are a family of small integral membrane proteins made up of 6 hydrophobic, a-helical, membrane-spanning domains surrounding a highly selective aqueous pore. AQP3, AQP7, and AQP9, termed aqua-glyceroporins, are known to be involved in the transport of water, glycerol, and other small molecules. In this study, we investigated the expression and localization of aqua-glyceroporins in rat oral stratified squamous epithelia of the palate, the buccal mucosa, the inferior aspect of the tongue, and the oral floor by using RT-PCR, immunofluorescence, and immunogold electron microscopy. AQP3 and AQP9 mRNAs were expressed in whole oral epithelium. Immunostaining for AQP3 was recognized in each type of epithelium. The results suggest that AQP3 synthesis begins predominantly in the cytoplasm of the basal cells. During the process of epithelial cell differentiation, AQP3 protein appears to accumulate and be transported to the plasma membrane, from where it is incorporated into the cornified or surface layers. The intracellular localization of AQP3 appears to correlate with the differentiation of keratinocytes, suggesting that it acts as an enhancer of the physiological permeability barrier together with membrane coating granules. The distribution pattern of AQP9 was limited to the marginal areas of the basal and suprabasal layers, which was different from that of AQP3. This difference in distribution between AQP3 and AQP9 suggests that AQP9 in rat oral epithelia acts as a channel by facilitating glycerol uptake from the blood through the endothelial cells of the capillary vessels to the oral stratified squamous epithelium. AQP3 and AQP9 facilitate both transcellular osmotic water flow and glycerol transport as pore-like passive transporters in the keratinocytes of oral epithelia, and may play a key role in not only hydration and the permeability barrier, but also cell proliferation, differentiation, migration, development, and wound healing by generating ATP.