Relationship between abdominal circumference and the incidence of hyperuricemia in the general Japanese population.

In this study, we aimed to separately evaluate the relationship between waist circumference and the incidence of hyperuricemia in men and women in the general Japanese population. We performed a population-based longitudinal study using data from the annual health examination of residents of Iki City, Japan. A total of 5567 participants without hyperuricemia at baseline were included in the analysis. The men and women were placed into groups according to the tertile of waist circumference. The outcome was incident hyperuricemia (uric acid > 416 µmol/L [7.0 mg/dL]). The relationship between waist circumference and the incidence of hyperuricemia was investigated using Cox proportional hazards models. During the follow-up period, hyperuricemia developed in 697 people (551 men and 146 women). The incidence (per 1000 person-years) of hyperuricemia increased with increasing waist circumference in the men (34.9 for tertile 1, 49.9 for tertile 2 and 63.3 for tertile 3; Ptrend < 0.001) and women (5.5 for tertile 1, 6.3 for tertile 2 and 11.9 for tertile 3; Ptrend < 0.001). Significant associations were identified after adjustment for potential confounders (men: Ptrend < 0.001; women: Ptrend = 0.014). In conclusion, both men and women with larger waist circumferences were at higher risks of subsequent hyperuricemia.

Involvement of dopamine D2 receptor signal transduction in the discriminative stimulus effects of the κ-opioid receptor agonist U-50,488H in rats.

We have reported previously that the inhibition of both dopaminergic and psychotomimetic/hallucinogenic components plays a role in the discriminative stimulus effects of U-50,488H. However, the mechanisms that underlie the discriminative stimulus effects of U-50,488H, and especially the component that plays a significant role, have not yet been clarified. The present study was designed to further investigate the mechanism(s) of the discriminative stimulus effects of the κ-opioid receptor agonist U-50,488H in rats that had been trained to discriminate between 3.0 mg/kg U-50,488H and saline. The dopamine D2 receptor antagonist sulpiride, but not the D1 receptor antagonist SCH23390, generalized to the discriminative stimulus effects of U-50,488H. The mood-stabilizing agents lithium chloride and valproic acid, which have attenuating effects on the Akt/GSK3 pathway, also partially generalized to the discriminative stimulus effects of U-50,488H. In contrast, the 5-HT-related compound racemic 3,4-methylenedioxymethamphetamine, the cannabinoid receptor agonist WIN55,212-2, and the µ-opioid receptor agonist morphine failed to generalize to the discriminative stimulus effects of U-50,488H. These results suggest that the inhibition of the dopaminergic activity mediated by the postsynaptic D2 receptor, followed by suppression of the Akt/GSK3 pathway may be critical for the induction of the discriminative stimulus effects induced by U-50,488H.

Involvement of serotonin receptor mechanisms in the discriminative stimulus effects of ketamine in rats.

We have demonstrated previously that the ketamine-induced discriminative stimulus effect is likely to reflect the phencyclidine-like psychotomimetic effects. Therefore, the present study was designed to investigate the effects of the antipsychotics and 5-HT2 receptor antagonist on the discriminative stimulus effects of ketamine in rats. While sulpiride did not attenuate the discriminative stimulus effects of ketamine, both clozapine and ketanserin attenuated those of ketamine, suggesting that the discriminative stimulus effects of ketamine are mediated by multiple receptors, especially the 5-HT2 receptor, but not the D2 receptor. Furthermore, our findings imply that atypical antipsychotics could be useful for the treatment of psychotomimetic effects induced by ketamine.

Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD).

OBJECTIVE: We aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population. SETTING: Population-based retrospective cohort study using annual health check-up data for residents of Iki City, Nagasaki Prefecture, Japan. PARTICIPANTS: A total of 5330 Japanese individuals (≥30 years old) without diabetes at baseline were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Serum ALT levels were determined using an enzymatic method and were classified into gender-specific quartile groups as follows: group 1 (3-16 U/L in men and 3-13 U/L in women), group 2 (17-21 U/L in men and 14-16 U/L in women), group 3 (22-29 U/L in men and 17-22 U/L in women) and group 4 (30-428 U/L in men and 23-268 U/L in women). The study outcome was the incidence of diabetes (fasting glucose ≥7.0 mmol/L, non-fasting glucose ≥11.1 mmol/L, glycated haemoglobin ≥6.5% or use of glucose-lowering therapies). RESULTS: After an average follow-up period of 5.0 years, 279 individuals developed diabetes. The incidence rate of diabetes increased with elevation of serum ALT levels (0.7% per 100 person-years in group 1, 0.9% in group 2, 0.9% in group 3 and 1.7% in group 4) (p<0.001 for trend). This association was significant after adjustment for other risk factors including age, sex, obesity, hypertension, dyslipidaemia, smoking, current daily alcohol intake and regular exercise (p<0.001 for trend). Comparable associations were observed between men and women (p=0.459 for interaction). CONCLUSION: Serum ALT levels were associated with future development of diabetes in the general Japanese population.

Association between pulse pressure and progression of chronic kidney disease.

The aim of this study was to investigate the association between pulse pressure (PP) and chronic kidney disease (CKD) progression among the general population in Japan. We conducted a population-based cohort study of the residents of Iki Island, Nagasaki, Japan, from 2008 to 2018. We identified 1042 participants who had CKD (estimated glomerular filtration rate(eGFR) < 60 mL/min/1.73 m2 or the presence of proteinuria) at baseline. Cox's proportional hazard model was used to evaluate the association between PP and progression of CKD. During a 4.66-year mean follow-up, there were 241 cases of CKD progression (incident rate: 49.8 per 1000 person-years). A significant increase existed in CKD progression per 10 mmHg of PP elevation, even when adjusted for confounding factors [adjusted hazard ratio 1.17 (1.06-1.29) p < 0.001]. Similar results were obtained even after dividing PP into quartiles [Q2: 1.14 (0.74-1.76), Q3: 1.35 (0.88-2.06), Q4: 1.87 (1.23-2.83) p = 0.003 for trend]. This trend did not change significantly irrespective of baseline systolic or diastolic blood pressures. PP remained a potential predictive marker, especially for eGFR decline. In conclusion, we found a significant association between PP and CKD progression. PP might be a potential predictive marker for CKD progression.

Synthesis of 2,3-disubstituted indenones by cobalt-catalyzed [3+2] annulation of o-methoxycarbonylphenylboronic acid with alkynes.

Treatment of alkynes with o-methoxycarbonylphenylboronic acid in the presence of a cobalt catalyst resulted in the corresponding 2,3-disubstituted indenones in good yields. Excellent regioselectivities were observed, when silyl aryl alkynes were used. The intermediate 3-silyl-2-aryl-substituted indenones were converted to 2,3-diaryl indenones by a three-step protocol involving C-Si bromination and Suzuki-Miyaura coupling reaction.