Background and Purpose—: Several epidemiological studies have established an association between chronic kidney disease (CKD), based on estimated glomerular filtration rate (GFR), and risk of stroke. However, sex-specific evidence for the relationship between CKD and risk of stroke and its subtypes is still limited. Methods—: We conducted a prospective cohort study of 12 222 Japanese men and women age 40 to 69 years living in 4 communities under systematic surveillance of stroke incidence to determine the relationship between CKD and risk of stroke and its subtypes. Results—: During the 17-year follow-up, there were 566 strokes (327 ischemic and 186 hemorrhagic strokes). GFR was inversely associated with age- and community-adjusted risk of total stroke for both men and women. Compared with the reference group without CKD (GFR ≥60 mL/min per 1.73m ² ), the adjusted risks of total stroke for subjects with CKD (GFR <60 mL/min per 1.73m ² ) were 1.63 (1.22–2.17) for men and 1.51 (1.13–2.02) for women. Excess risk of stroke associated with CKD was identified primarily for hemorrhagic stroke among men and for ischemic stroke among women. After adjustment for traditional cardiovascular risk factors, associations remained statistically significant. When stratified by drinking status, excess risk of hemorrhagic stroke with CKD was confined to drinkers; adjusted risks were 4.18 (2.31–7.57) for men and 7.00 (1.92–25.56) for women. Conclusions—: CKD was associated with increased risk of hemorrhagic stroke for men, and of ischemic stroke for women. This sex difference may partly be explained by the difference in prevalence of drinkers between men and women.

Objective The hemoglobin levels and blood pressure has been reported in a few studies, and a positive association between the hemoglobin levels and the body mass index (BMI) status has also been documented. A higher BMI may therefore affect the association between the hemoglobin levels and hypertension. However, no published studies have examined this association in relation to the BMI status. The primary purpose of this study was to assess the association between the hemoglobin levels and hypertension in relation to the BMI status. Methods A cross-sectional study of 3,203 non-anemic subjects (1,191 men and 2,012 women, 30-79 years old) who were undergoing general health checkups was conducted. Results A positive association between the hemoglobin levels and hypertension was established for both men and women. For a one SD (standard deviation) increment in hemoglobin, the multivariable odds ratio (ORs) and 95% confidence interval (CIs) for hypertension were 1.21 (95%CI: 1.05-1.40) for men and 1.25 (95%CI: 1.13-1.39) for women. We also found that a significant association was confined to the participants with a BMI of <25 kg/m2. Among the participants with a BMI of <25 kg/m2, the multivariable ORs and 95% CIs for hypertension of a one SD increment in hemoglobin were 1.34 (95%CI: 1.12-1.60) for men and 1.31 (95%CI: 1.16-1.47) for women. Meanwhile, among those with a BMI of ≥25 kg/m2, the corresponding values were 1.01 (95%CI: 0.79-1.30) and 1.09 (95%CI: 0.87-1.37). Conclusion An independent positive association between the hemoglobin levels and the risk of hypertension was observed for both non-anemic Japanese men and women, confined to participants with a BMI of <25 kg/m2.

GPR52 is a Gs protein-coupled receptor that is predominantly expressed in the striatum and nucleus accumbens, and was recently proposed as a potential therapeutic target in schizophrenia. In the current study, we investigated the in vitro and in vivo pharmacological activities of a novel GPR52 agonist, 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzamide (FTBMT) functioned as a selective GPR52 agonist in vitro and in vivo, as demonstrated by the activation of cAMP signaling in striatal neurons. FTBMT inhibited MK-801-induced hyperactivity (an animal model for acute psychosis) without causing catalepsy in mice. The c-fos expression also revealed that FTBMT preferentially induced neuronal activation in the shell of the nucleus accumbens, compared with the striatum, thereby supporting its pharmacological profile. Furthermore, FTBMT improved recognition memory in a novel object recognition test and attenuated MK-801-induced working memory deficits in a radial arm maze test in rats. These procognitive effects were supported by the results of FTBMT-induced c-fos expression in brain regions related to cognition, including the medial prefrontal cortex, entorhinal cortex, and hippocampus. Taken together, these findings suggest that FTBMT shows antipsychotic and procognitive properties without causing catalepsy in rodents. Given its unique pharmacological profile, which differs from that of current antipsychotics, FTBMT may provide a new therapeutic option for the treatment of positive and cognitive symptoms of schizophrenia.

Background and Purpose— Although serum γ-glutamyltranspeptidase (GGT) levels have been associated with cardiovascular disease incidence, few studies have taken into account the effect of alcohol intake on GGT levels. In this study, we examined the relationship between GGT and stroke incidence according to drinking status. Methods— We conducted a prospective cohort study of Japanese women (N=6281) and men (N=3471) aged 40 to 69 years living in communities under systematic surveillance for stroke incidence. Results— During the 18-year follow-up, 202 (3.2%) women and 230 (6.6%) men had strokes. Serum GGT levels were positively associated with risk of total stroke for women but not men. The multivariable hazard ratios of total stroke for the highest quartile of GGT compared with the lowest quartile were 1.56 (95% CI, 1.01 to 2.39) for women and 1.37 (95% CI, 0.89 to 2.11) for men. Moreover, GGT was associated with total and ischemic stroke risks for never-drinking women. Conclusions— Serum GGT is associated with risk of total and ischemic strokes for Japanese women, especially never-drinkers.