Oral Health and Nutritional Intake in Community-Dwelling 90-Year-Old Japanese People: A Cross-Sectional Study.

INTRODUCTION: This study aimed to determine the relationship between dentition, mastication, salivation and nutritional intake in 90-year-old Japanese people. METHODS: This cross-sectional study included 84 participants (39 men and 45 women) aged 90 years. We used questionnaires to collect demographic information, smoking status, nutritional intake and higher-level functional capacity. Nutritional intake was assessed using the validated Brief-Type Self-Administered Diet History Questionnaire, and higher-level functional capacity was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) questionnaire. Oral examinations, masticatory performance tests, stimulated salivary flow rate (SSF) tests, blood tests, blood pressure tests and body mass index (BMI) assessments were conducted. Univariable and multivariable linear regression analyses were performed. RESULTS: Multivariable linear regression analyses adjusted for sex, education, TMIG-IC and BMI ≤20 kg/m2 showed that participants with masticatory performance <173 mg/dL had lower intake of folic acid and vitamin A than those with masticatory performance ≥173 mg/dL. SSF was positively associated with intake of vitamin A. The number of teeth was positively associated with the intake of ß-carotene. With smaller effect sizes, masticatory performance, SSF and number of teeth were also associated with the intake of various micronutrients and carbohydrates. CONCLUSION: Lower masticatory performance, lower SSF and fewer teeth were associated with a lower intake of several micronutrients, such as vitamin A, ß-carotene and folic acids, in Japanese individuals of advanced age. Oral health practitioners should pay careful attention to the nutritional intake of older people with poor mastication, dry mouth and severe tooth loss.

Identification of Two Dysfunctional Variants in the ABCG2 Urate Transporter Associated with Pediatric-Onset of Familial Hyperuricemia and Early-Onset Gout.

The ABCG2 gene is a well-established hyperuricemia/gout risk locus encoding a urate transporter that plays a crucial role in renal and intestinal urate excretion. Hitherto, p.Q141K-a common variant of ABCG2 exhibiting approximately one half the cellular function compared to the wild-type-has been reportedly associated with early-onset gout in some populations. However, compared with adult-onset gout, little clinical information is available regarding the association of other uricemia-associated genetic variations with early-onset gout; the latent involvement of ABCG2 in the development of this disease requires further evidence. We describe a representative case of familial pediatric-onset hyperuricemia and early-onset gout associated with a dysfunctional ABCG2, i.e., a clinical history of three generations of one Czech family with biochemical and molecular genetic findings. Hyperuricemia was defined as serum uric acid (SUA) concentrations 420 µmol/L for men or 360 µmol/L for women and children under 15 years on two measurements, performed at least four weeks apart. The proband was a 12-year-old girl of Roma ethnicity, whose SUA concentrations were 397-405 µmol/L. Sequencing analyses focusing on the coding region of ABCG2 identified two rare mutations-c.393G>T (p.M131I) and c.706C>T (p.R236X). Segregation analysis revealed a plausible link between these mutations and hyperuricemia and the gout phenotype in family relatives. Functional studies revealed that p.M131I and p.R236X were functionally deficient and null, respectively. Our findings illustrate why genetic factors affecting ABCG2 function should be routinely considered in clinical practice as part of a hyperuricemia/gout diagnosis, especially in pediatric-onset patients with a strong family history.

Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients.

OBJECTIVES: Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000-3000 years. METHODS: Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. RESULTS: In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10-8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients' gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. CONCLUSIONS: Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.

Orosensory deprivation alters taste-elicited c-Fos expression in the parabrachial nucleus of neonatal rats.

In the present study we examined the effects of neonatal orosensory deprivation on taste-elicited gustatory activity in the rat parabrachial nucleus (PBN) using the functional anatomical marker c-Fos. Animals in three groups (GG, GO and GM) received gastric cannula implantation surgery on postnatal day 9 (P9). Animals in the fourth group (MR) did not receive any surgery. GG rats were fed by infusion of artificial milk directly into the stomach. GO rats were fed by intraoral infusion of artificial milk. GM and MR rats were reared by their mother with free access to mother's milk, water and rat chow. Rats from all groups were similar in body weight and length by P21. On P21 rats in all groups were intraorally presented with 0.5M sucrose solution and the brains were extracted and processed for c-Fos immunohistochemistry. Taste-elicited c-Fos expression in both the gustatory waist area, and the external lateral subnucleus of the PBN in rats in the GG group was significantly more robust than in the other three groups. These findings suggest a substantial alteration in orosensory-evoked neuronal response in this nucleus, due to sensory or motor deprivation during a critical developmental stage.

Effect of hydrocotarnine on cytochrome P450 and P-glycoprotein.

The injectable form of oxycodone contains hydrocotarnine that is supposed to potentiate the analgesic effect of oxycodone with unknown mechanism(s). In this study, the effects of hydrocotarnine on the cytochrome P450 (CYP) and P-glycoprotein (P-gp) were investigated. Hydrocotarnine did not induce a significant change in the metabolic activities of CYP2C9, 2C19, and 2E1 in an in vitro study using human CYP recombinants. Although weak inhibitory effects were observed on CYP3A4 and 2D6, these interactions did not seem to be clinically relevant. Hydrocotarnine also did not cause a significant change in the ATPase activity of human P-gp membranes, suggesting that it is not an inhibitor of P-gp. Furthermore, mice were intraperitoneally injected with hydrocotarnine for 14 days and the mRNA levels of major CYP isozymes and P-gp in the liver and small intestine were determined by real-time RT-PCR. As a result, none of the mRNAs investigated showed a significant change in their levels by hydrocotarnine treatment. In conclusion, it is unlikely that the potentiation of oxycodone effect by hydrocotarnine involves its effect on CYP and P-gp. The findings also demonstrate that hydrocotarnine is unlikely to cause drug interactions via CYP or P-gp.