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Background Studies on the association between smoke haze (hereafter ‘haze’) and adverse health effects have increased in recent years due to extreme weather conditions and the increased occurrence of vegetation fires. The possible adverse health effects on under-five children (U5Y) is especially worrying due to their vulnerable condition. Despite continuous repetition of serious haze occurrence in Southeast Asia, epidemiological studies in this region remained scarce. Furthermore, no study had examined the association accounting for three important aspects (time lag, duration and intensity) concurrently. Objective This study aimed to examine the association between haze and U5Y mortality in Malaysia, considering time lag, duration and intensity of exposure. Methods We performed a time-stratified case-crossover study using a generalized additive model to examine the U5Y mortality related to haze in 12 districts in Malaysia, spanning from 2014 to 2016. A ‘haze day’ was characterized by intensity [based on concentrations of particulate matter (PM)] and duration (continuity of haze occurrence, up to 3 days). Results We observed the highest but non-significant odds ratios (ORs) of U5Y mortality at lag 4 of Intensity-3. Lag patterns revealed the possibility of higher acuteness at prolonged and intensified haze. Stratifying the districts by the 95th-percentile of PM distribution, the ‘low’ category demonstrated marginal positive association at Intensity-2 Duration-3 [OR: 1.210 (95% confidence interval: 1.000, 1.464)]. Conclusions We found a null association between haze and U5Y mortality. The different lag patterns of the association observed over different duration and intensity suggest consideration of these aspects in future studies.

A reduction in heart rate variability (HRV) is reportedly associated with an increased risk of cardiovascular mortality and morbidity. In previous studies, an inverse association was noted between HRV and particulate air pollution, but the sample populations were small and most consisted only of elderly individuals. We examined the association between 24-h HRV and fine particulate matter (PM2.5) in a large study population spanning 7 prefectures in Japan from April 2010 through March 2013. Meta-analysis was also performed. In total, 59,493 records of 24-h HRV for patients aged 20–90 years with symptoms/signs suggestive of heart disease were included in this analysis. Air pollution data were obtained from the National Institute for Environmental Studies. Regression models were used to examine the association between daily concentration of PM2.5 and HRV indices (e.g., standard deviation of normal-to-normal (SDNN), SD of average NN internals calculated over short periods (SDANN), very low frequency (VLF), and ultra-low frequency (ULF)). The model was adjusted for age, sex, temperature, and relative humidity. We examined the lagged association for single (up to lag3) and moving average (up to lag03). We found that decreases in HRV indices, especially for SDNN, SDANN, VLF, and ULF, were associated with PM2.5 in Hokkaido, Chiba, Tokyo, and Kanagawa. In contrast, there was no clear association between HRV with PM2.5 in Saitama and Aichi. Meta-analysis revealed significant decreases in SDNN, SDANN, VLF, and ULF were associated with PM2.5. Short-term exposure to PM2.5 was associated with lower 24-h HRV in patients with symptoms/signs suggestive of heart disease.

Background Although health effects of air pollutants are well documented in many countries especially in North America and Western Europe, few studies have been conducted in Thailand where pollution mix, weather conditions, and demographic characteristics are different. The present study aimed to investigate the effects of ambient air pollution on hospital admissions for cardiovascular and respiratory diseases in Bangkok, Thailand. Methods We obtained daily air pollution concentration (O3, NO2, SO2, PM10, and CO) and weather variable monitored in Bangkok from January 2006 to December 2014. Daily hospital admissions for cardiovascular and respiratory diseases were obtained from the National Health Security Office during the study period. A time-series analysis with generalized linear model was used to examine the effects of air pollution on hospital admissions by controlling for long-term trend and other potential confounders. The effect modification by age (0–14 years, 15–64 years, ≥65 years) and gender was also examined. Results An increase of 10 μg/m3 in O3, NO2, SO2, PM10, and 1 mg/m3 in CO at lag 0–1 day was associated with a 0.14% (95% CI: −0.34 to 0.63), 1.28% (0.87 to 1.69), 8.42% (6.16 to 10.74), 1.04% (0.68 to 1.41) and 6.69% (4.33 to 9.11) increase in cardiovascular admission, respectively; and 0.69% (95% CI: 0.18 to 1.21), 1.42% (0.98 to 1.85), 4.49% (2.22 to 6.80), 1.18% (0.79 to 1.57) and 7.69% (5.20 to 10.23) increase in respiratory admission, respectively. The elderly (≥65 years) seemed to be the most susceptible group to the effect of air pollution, whereas the effect estimate for male and female was not significantly different. Conclusions Results from this study contributed the evidence to support the effects of air pollution (O3, NO2, SO2, PM10, and CO) on hospital admissions for cardiovascular and respiratory diseases, which might be useful for public health intervention in Thailand.

Background Epidemiological studies based on mortality and crime data have indicated that short-term exposure to higher temperature increases the risk of suicide and violent crimes. However, there are few studies on non-fatal intentional injury, especially on non-fatal self-harm which is much more common than suicide. Objectives We aimed to clarify how short-term exposure to temperature is associated with emergency ambulance transport caused by intentional injuries including acts of self-harm and assault. Method We applied a time-stratified case-crossover design using a conditional quasi-Poisson regression model for each of the 46 prefectures. All temperatures were converted to percentile value for each prefecture, to account for the varied climate across Japan. A Distributed Lag Non-Linear Model was used to explore the temperature percentile and lag pattern. The prefecture-specific results were combined using a meta-analysis with the random effects model. Result Between 2012 and 2015, the number of acts of self-harm and assault across all 46 prefectures totaled 151,801 and 95,861, respectively. We found that as the temperature increased, the relative risk (RRs) for both self-harm and assault behaviors increased in a nearly linear manner. The pooled relative risk at the 99th percentile temperature for self-harm behavior was 1.11 (95% CI: 1.07, 1.15) compared with the risk at the 1st percentile temperature, and that for assault was 1.12 (95% CI: 1.08, 1.16) at lag 0. The RRs were highest at lag0 and less than 1 at lag7–20. Conclusion The present study found that short-term exposure to higher temperature promotes the risk of emergency ambulance transport due to acts of self-harm and assault. The lag pattern indicates a possible “displacement” effect. These results suggest that exposure to high temperatures may potentially function as a trigger for intentional injuries.

Numerous epidemiological studies have demonstrated that short-term exposure to ambient PM2.5 increases mortality and morbidity. Investigating the association using hourly ambient PM2.5 exposure may provide important insights, as current evidence is limited mostly to daily lag term. This study aimed to investigate the hourly association between ambient PM2.5 concentrations and all-cause emergency ambulance dispatches (EAD) in 11 cities in Japan. We used a time-stratified case-crossover design and examined the hourly lags of ambient PM2.5 up to 24 h (unconditional distributed lags and moving average lags) using a conditional Poisson regression model. A significant increase in all-cause EAD was observed at lag 0 h [relative risk (RR): 1.0037 (95% CI: 1.0000, 1.0074)] and all moving average lags. The highest RR was observed within the first 6 h (at lag 0–5 h) [RR: 1.0091 (95% CI: 1.0068, 1.0114)], with a slight ascending pattern. This was followed by a descending pattern at lags 0–11, 0–17, and 0–23 h, but significant positive RR was observed even at lag 0–23 h, when the lowest RR was observed [RR: 1.0072 (95% CI: 1.0044, 1.0100)]. Though similar pattern was observed among the elderly, a different pattern was observed among the children (gradually ascending pattern). We conclude that all-cause EAD could be triggered by ambient PM2.5 exposure with very short lags.

Exposure to fine particulate matter (PM2.5) is a potential aggravating factor for respiratory and allergic diseases. However, which PM2.5 sources are associated with such diseases remains unclear. This study aimed to investigate the association of PM2.5 sources with allergic and respiratory symptoms in schoolchildren. PM2.5 samples were collected in Fukuoka during the spring in 2014 and 2015. Asian dust was observed in 2014. Ion components, elemental components, and organic components were analyzed. Positive matrix factorization (PMF) was conducted to calculate PM2.5 concentrations from each source. Mixed logistic regression analysis with a random intercept for each schoolchild was performed to evaluate the association of components and sources with symptoms. Among 2317 schoolchildren, the mean prevalence was 28.9%, 23.6%, 11.2%, and 11.4% for lower respiratory, nasal, ocular, and skin symptoms, respectively. PMF identified the following six PM2.5 sources “Secondary sulfate and coal combustion”, “Secondary nitrate”, “Heavy oil combustion”, “Sea salt”, “Soil” and “Traffic emission”. An interquartile range of PM2.5 mass was associated with nasal (Odds ratios 1.08, 95% confidence interval [1.03, 1.13]), ocular (1.10, [1.04, 1.16]), and skin symptoms (1.13, [1.06, 1.20]). Among the source factors, “Heavy oil combustion” was significantly associated with nasal symptom (1.11, [1.05, 1.18]) while “Sea salt” was associated with nasal (1.06, [1.02, 1.11]) and skin (1.073, [1.01, 1.14]) symptoms. We found “Soil”, which might be affected by Asian dust, was associated with ocular (1.07, [1.03, 1.10]) and skin (1.05, [1.01, 1.08]) symptoms. Further studies in other seasons or places are needed to clarify the influence of PM2.5 sources on children's health.

Patients with cancer often experience general nutritional problems as the disease progresses. We aimed to examine if there is a need and demand for nutritional counselling among cancer outpatients, and explore relevant psychological factors pertaining to eating and nutrition. A survey was conducted among adult patients receiving outpatient chemotherapy at the Tokyo Medical and Dental University Hospital. The participants completed self-report questionnaires, which included questions on their nutritional state (Patient-Generated Subjective Global Assessment Short Form), experience of eating-related distress and quality of life (QOL) (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30). Of the 151 (median age, 66.5 years) participants, 42 had a demand for nutritional counselling. Patients’ experience of eating-related distress and demand for nutritional counselling were significantly associated, particularly in regard to ‘conflicts over food between patients and the people surrounding them’ (p = 0.005), ‘concerns about food’ (p = 0.007) and ‘self-motivated effect related to nutrition’ (p = 0.018). A significant association was also observed between the demand for nutritional counselling and global health status (p = 0.028), emotional functioning (p = 0.022), cognitive functioning (p = 0.028) and social functioning (p = 0.040) in terms of QOL. Patients with a low QOL tended to demand nutritional counselling. The demand for nutritional counselling was associated with QOL and eating-related distress. Therefore, medical staff caring for patients with cancer, such as attending physicians, dietitians, nurses, clinical psycho-oncologists, social workers and psychiatric oncologists, should collaborate and share information to provide nutritional counselling.

This study examined the relationship between neurobehavioral changes and alterations in gene expression profiles in the brains of mice exposed to different levels of Hg(0) during postnatal development. Neonatal mice were repeatedly exposed to mercury vapor (Hg(0)) at a concentration of 0.057 mg/m(3) (low level), which was close to the current threshold value (TLV), and 0.197 mg/m(3) (high level) for 24 hr until the 20(th) day postpartum. Behavioral responses were evaluated based on changes in locomotor activity in the open field test (OPF), learning ability in the passive avoidance response test (PA), and spatial learning ability in the Morris water maze (MM) at 12 weeks of age. No significant differences were observed in the three behavioral measurements between mice exposed to the low level of Hg(0) and control mice. On the other hand, total locomotive activity in mice exposed to the high level of Hg(0) was significantly decreased and central locomotion was reduced in the OPF task. Mercury concentrations were approximately 0.4 μg/g and 1.9 μg/g in the brains of mice exposed to the low and high levels of Hg(0), respectively. Genomic analysis revealed that the expression of 2 genes was up-regulated and 18 genes was down-regulated in the low-level exposure group, while the expression of 3 genes was up-regulated and 70 genes was down-regulated in the high-level exposure group. Similar alterations in the expression of seven genes, six down-regulated genes and one up-regulated gene, were observed in both groups. The results indicate that an increase in the number of altered genes in the brain may be involved in the emergence of neurobehavioral effects, which may be associated with the concentration of mercury in the brain. Moreover, some of the commonly altered genes following exposure to both concentrations of Hg(0) with and without neurobehavioral effects may be candidates as sensitive biomarker genes for assessing behavioral effects in the early stages of development.

We measured the levels of some biological metals: copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), and zinc (Zn) in the cerebrospinal fluid (CSF) in patients with neurodegenerative diseases (52 patients with amyotrophic lateral sclerosis (ALS)), 21 patients with Alzheimer's disease (AD), and 20 patients with Parkinson's disease (PD) by inductively coupled plasma mass spectrometry (ICP-MS). The diagnoses were additionally supported by neuroimaging techniques for AD and PD. In ALS, the levels of Mg (p

Point-of-purchase (POP) information at food stores could help promote healthy dietary habits. However, it has been difficult to evaluate the effects of such intervention on customers’ behavior. We objectively evaluated the usefulness of POP health information for vegetables in the modification of customers’ purchasing behavior by using the database of a point-of-sales (POS) system. Two supermarket stores belonging to the same chain were assigned as the intervention store (store I) and control store (store C). POP health information for vegetables was presented in store I for 60 days. The percent increase in daily sales of vegetables over the sales on the same date of the previous year was compared between the stores by using the database of the POS system, adjusting for the change in monthly visitors from the previous year (adjusted ∆sales). The adjusted ∆sales significantly increased during the intervention period (Spearman’s ρ = 0.258, P for trend = 0.006) at store I but did not increase at store C (ρ = −0.037, P for trend = 0.728). The growth of the mean adjusted ∆sales of total vegetables from 30 days before the intervention period through the latter half of the intervention period was estimated to be greater at store I than at store C by 18.7 percentage points (95% confidence interval 1.6–35.9). Health-related POP information for vegetables in supermarkets can encourage customers to purchase and, probably, consume vegetables.

Patients with marked calcification of the basal ganglia and cerebellum have traditionally been referred to as having Fahr's disease, but the nomenclature has been criticized for including heterogeneous etiology. We describe 3 patients with idiopathic bilateral striatopallidodentate calcinosis (IBSPDC). The patients were a 24-year-old man with mental deterioration, a 57-year-old man with parkinsonism and dementia, and a 76-year-old woman with dementia and mild parkinsonism. The former 2 patients showed severe calcification of the basal ganglia and cerebellum, and the latter patient showed severe calcification of the cerebellum. We found significantly increased levels of copper (Cu), zinc (Zn), iron (Fe) and magnesium (Mg), using inductively coupled plasma mass spectrometry in the CSF of all these 3 patients. The increased levels of Cu, Zn, Fe and Mg reflect the involvement of metabolism of several metals and/or metal-binding proteins during the progression of IBSPDC. More numerous patients with IBSPDC should be examined in other races to clarify the common mechanism of the disease and to investigate the specific treatment.

Short-term health effects of ambient PM2.5 have been established with numerous studies, but evidence in Asian countries is limited. This study aimed to investigate the short-term effects of PM2.5 on acute health outcomes, particularly all-cause, cardiovascular, respiratory, cerebrovascular and neuropsychological outcomes. We utilized daily emergency ambulance dispatches (EAD) data from eight Japanese cities (2007–2011). Statistical analyses included two stages: (1) City-level generalized linear model with Poisson distribution; (2) Random-effects meta-analysis in pooling city-specific effect estimates. Lag patterns were explored using (1) unconstrained-distributed lags (lag 0 to lag 7) and (2) average lags (lag: 0–1, 0–3, 0–5, 0–7). In all-cause EAD, significant increases were observed in both shorter lag (lag 0: 1.24% (95% CI: 0.92, 1.56)) and average lag 0–1 (0.64% (95% CI: 0.23, 1.06)). Increases of 1.88% and 1.48% in respiratory and neuropsychological EAD outcomes, respectively, were observed at lag 0 per 10 µg/m3 increase in PM2.5. While respiratory outcomes demonstrated significant average effects, no significant effect was observed for cardiovascular outcomes. Meanwhile, an inverse association was observed in cerebrovascular outcomes. In this study, we observed that effects of PM2.5 on all-cause, respiratory and neuropsychological EAD were acute, with average effects not exceeding 3 days prior to EAD onset.

Metallothioneins (MTs) are metal binding proteins and have four isoforms. MT-3, known as growth inhibitory factor (GIF), exists mainly in the central nervous system. It regulates zinc levels and exhibits a neuroprotective effect in the various types of brain diseases. However, the reports demonstrate that the relation between MT-3 and psychiatric disorder is still unknown. In the present study, the authors carried out behavioral tests on MT-3 knock-out (KO) mice. The duration of the MT-3 KO mice's social interactions were significantly shorter than that of the wild-type (WT) mice. The acoustic startle response of the MT-3 KO mice showed diminished prepulse inhibition (PPI) at all prepulse intensities. However, the locomotor activity tests of the MT-3 KO mice displayed normal circadian rhythm, activity, and habituation to a novel environment. In the novel object recognition test, the MT-3 KO mice exhibited normal memory. These findings indicate that abnormalities of psychological behavior were observed in the MT-3 KO mice. Further experiments will be needed to clarify the involvement of MT-3 in higher brain function.

Objective: To investigate whether childhood sports participation, particularly weight-bearing sports, has any effect on bone mineral content (BMC), areal bone mineral density (aBMD) and bone geometric characteristics in middle-aged postmenopausal women. Design/setting: In this cross-sectional comparison of two groups, 46 middle-aged women (mean age, 60.2 (SD 5.6) years; range, 52–73 years) were grouped according to sport participation during growth: weight-bearing sports, including high-impact weight-bearing activities; and low-impact non-weight-bearing sports or no participation. Main outcome measures: Dual energy X-ray absorptiometry (DXA)-measured BMC, aBMD in the lumbar spine and femur. Magnetic resonance imaging (MRI) determined bone geometric characteristics in the femur, such as femoral mid-diaphyseal cross-sectional area, periosteal and endosteal perimeters and maximum and minimum second moment of area. Results: Postmenopausal middle-aged women with participation in weight-bearing sports during junior high to high school (12–18 years old) displayed significantly greater BMC in both lumbar spine and femoral neck regions, and also significantly greater femoral mid-diaphyseal bone cross-sectional area, periosteal perimeter and maximum and minimum second moment of area than the non-weight-bearing sports group. Conclusions: Adolescent weight-bearing exercise exerts preservational effects on femoral mid-diaphyseal size and shape, while DXA-measured BMC effectively identified the same tendency. Weight-bearing exercise in youth affects bone, and these effects may be preserved as BMC, geometric and structural advantages even after 40 years.

目的：高齢者訪問看護の質指標（16領域483指標）開発の一部として，全国の訪問看護ステーションで働く看護師を対象に，指標に関する実践の自己評価や指標についての意見を調査した．方法：全国5,322カ所の訪問看護ステーションに10,644通の調査票を郵送し回答を得た．結果：回答は3,068通（29.7%）あった．全領域で平均7割程度の指標が実施していると回答されていた．指標への「はい（＝実施している）」という回答率は摂食・嚥下障害ケアや口腔ケアが低く，清潔ケア等が比較的高かった．情報収集，精神的支援，医師への報告など侵襲が少なく病棟でも一般的なケアは「はい」の回答率が高く，判断を伴うアセスメント，学習を要する特殊な技術の提供やケア実施後の評価は「はい」の回答率が低かった．全領域で「訪問看護で必要な項目が網羅されている」という意見が7割以上得られた．結論：開発中の訪問看護質指標では，指標ごと，領域ごとに実施率にある程度のばらつきがみられた．今回の結果を参考にしつつ質指標の開発を進めていきたい．

A large body of literature has demonstrated that the indices of particulate matter (PM) have adverse effects on human health, mostly using hospital-based data, such as hospital admission or emergen...

Hypoxia is an important modulator of endurance exercise‐induced oxidative adaptations in skeletal muscle. However, whether hypoxia affects resistance exercise‐induced muscle adaptations remains unknown. Here, we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resistance and endurance exercise training, including muscle cross‐sectional area (CSA), one‐repetition maximum (1RM), muscular endurance, and makers of mitochondrial biogenesis and angiogenesis, such as peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α), citrate synthase (CS) activity, nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), hypoxia‐inducible factor‐1 (HIF‐1), and capillary‐to‐fiber ratio. Sixteen healthy male subjects were randomly assigned to either a normoxic resistance training group (NRT, n =7) or a hypoxic (14.4% oxygen) resistance training group (HRT, n =9) and performed 8 weeks of resistance training. Blood and muscle biopsy samples were obtained before and after training. After training muscle CSA of the femoral region, 1RM for bench‐press and leg‐press, muscular endurance, and skeletal muscle VEGF protein levels significantly increased in both groups. The increase in muscular endurance was significantly higher in the HRT group. Plasma VEGF concentration and skeletal muscle capillary‐to‐fiber ratio were significantly higher in the HRT group than the NRT group following training. Our results suggest that, in addition to increases in muscle size and strength, HRT may also lead to increased muscular endurance and the promotion of angiogenesis in skeletal muscle., This study investigated the effect of resistance exercise training performed under systemic hypoxia or normoxia on biochemical and molecular muscular adaptations in healthy male subjects. Our findings demonstrate that resistance training under systemic hypoxia led not only muscle hypertrophy, but most interestingly, to a greater increase in muscular endurance. This increase in muscular endurance was potentially caused by the increased angiogenesis as determined by capillary‐to‐fiber ratio.

The effect of jump exercise on middle-aged osteopenic rats was investigated. Forty-two 9-mo-old female rats were either sham-operated (Sham) or ovariectomized (OVX). Three months after surgery, the rats were divided into the following groups: Sham sedentary, Sham exercised, OVX sedentary, and OVX exercised. Rats in the exercise groups jumped 10 times/day, 5 days/wk, for 8 wk, with a jumping height of 40 cm. Less than 1 min was required for the jump training. After the experiment, the right tibia and femur were dissected, and blood was obtained from each rat. OVX rats were observed to have increased body weights and decreased bone mass in their tibiae and femurs. Jump-exercised rats, on the other hand, had significantly increased tibial bone mass, strength, and cortical areas. The bone mass and strength of OVX exercised rats increased to approximately the same extent as Sham exercised rats, despite estrogen deficiency or osteopenia. Our data suggest that jump exercise has beneficial effects on lower limb bone mass, strength, bone mineral density, and morphometry in middle-aged osteopenic rats, as well as in Sham rats.

This study was designed to investigate the effect of high-impact and low-repetition jump training on bones in ovariectomized (OVX) rats. Forty female Wistar rats were sham-operated (sham) or OVX at the age of 11 weeks. The rats were divided randomly into the following four groups: sham-sedentary (SS; n = 10), sham-exercised (SE; n = 10), OVX-sedentary (OS; n = 10), and OVX-exercised (OE; n = 10). The rats started the jump training at the age of 12 weeks. The jump-training protocol was 10 times/day, 5 days/week and the jumping-height was 40 cm. After 8 weeks of training, the mass and breaking force in the tibia and ulna, cross-sectional areas of diaphysis in the tibia, and serum bone turnover markers were measured. The jump training significantly increased the fat-free dry weight, ash weight, and ultimate breaking force in the tibia. The rate of increase in these parameters was similar in both the sham and the OVX groups. On the other hand, in the ulna, there were no significant changes in the ultimate breaking force. The jump training significantly increased the periosteal perimeter and cortical area, although the increase in these parameters in OE compared with OS was lower than that in SE compared with SS. The jump training significantly increased serum osteocalcin in the OVX groups, as well as in the sham groups. These results suggest that high-impact and low-repetition training had beneficial effects on bone formation and bone biomechanical properties in OVX rats, as well as in sham rats.

DNA microarray containing 30,000 genes was used to monitor the transcriptional response of the neonatal brain after cadmium (Cd) exposure. C57BL/6J pregnant mice were exposed to Cd (10 ppm) during gestation and lactation via drinking water. In a comparison between the Cd-exposed neonatal brain and control, three genes including transferrin receptor (Tfrc) were up-regulated and one gene was down-regulated.

Background & Aims: Prostaglandins (PGs) have important roles in the regulation of gastric acid secretion. The aim of this study was to examine the possible presence of PG receptors on the gastric enterochromaffin-like (ECL) carcinoid of Mastomys natalensis , which might be a useful model of normal ECL cells. Methods: A [ 3 H]PGE 2 binding experiment was performed by using the ECL tumor membrane, and intracellular signal transduction was studied in the cells. In addition, Northern blot analysis using EP 2 and EP 3 receptor complementary DNAs was conducted. Results: [ 3 H]PGE 2 specifically bound to the tumor cell membrane, and the binding was displaced by various PGs with a potency order of PGE 1 = PGE 2 > enprostil >PGF 2α . Although PGE 1 and PGE 2 stimulated 5′-cyclic adenosine monophosphate (cAMP) production, neither PGF 2α nor enprostil had any effect. On the other hand, all of PGE 1 , PGE 2 , PGF 2α , and enprostil attenuated the forskolin-induced cAMP production. Moreover, enprostil inhibited histamine release induced by forskolin. However, on pertussis toxin treatment, PGE 2 paradoxically enhanced the forskolin-induced increase of cAMP production. Finally, the presence of EP 2 and EP 3 receptor messenger RNAs was confirmed by RNA blot analysis. Conclusions: The ECL carcinoid tumor cells of Mastomys seem to possess two subtypes of PGE receptor: EP 2 linked to cAMP production and EP 3 coupled with inhibitory guanosine 5′-triphosphate-binding proteins mediating the inhibition of cAMP production.

Dental amalgam is a source of exposure to elemental mercury vapor in the general population. The aim of this study was to elucidate the effect of elemental mercury vapor exposure from dental amalgam restorations on gene expression profiles. Out of 26,962 rat genes, mercury vapor was found to increase the expression of 1 gene (Atp1b3) and decrease the expression of 1 gene (Tap1) in the cerebrum, increase the expression of 1 gene (Dnaja2) in the cerebellum, increase the expression of 2 genes (Actb and Timm23) and decrease the expression of 1 gene (Spink3) in the liver, increase the expression of 2 genes (RT1-Bb and Mgat5) and decrease the expression of 6 genes (Tnfaip8, Rara, Slc2a4, Wdr12, Pias4 and Timm13) in the kidney.

Metallothioneins (MTs) are metal-binding proteins and have four isoforms. MT-III was, at first, found in the brains of patients with Alzheimer's disease. MT-III exists mainly in the central nervous system, and the main effects are thought to be anti-oxidative and regulate zinc levels. In some previous reports, MT-III exhibited neuroprotective effects in various pathological situations, but its detailed effects are still unclear. In the present study, we examined neuronal damage after a middle cerebral artery occlusion (MCAO) in MT-III knockout (KO) mice to elucidate the relationship between MT-III and cerebral infarction. There was no significant difference in cerebral infarction after 24-h permanent MCAO between the wild-type and MT-III KO mice. On the other hand, after 2-h MCAO and 22-h reperfusion, cerebral infarction in the MT-III KO mice was aggravated compared with the wild-type mice. Furthermore, fatal rate of MT-III KO mice increased from 3 days after MCAO, and neurological deficits at 5 and 7 days after MCAO of MT-III KO mice were worse than those of wild-type. We examined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and the immunostaining of an oxidative stress marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG), at 24 h after transient MCAO. In the penumbra lesion, the positive cell numbers in both staining assays were higher in the MT-III KO mice than those of the wild-type mice. These findings indicate that neuronal damage was aggravated by reperfusion injury in the MT-III KO mice compared with the wild-type mice, suggesting that MT-III plays anti-oxidative and neuroprotective roles in transient cerebral ischemia.

Disrupted-in-Schizophrenia 1 (DISC1) and its molecular cascade have been implicated in the pathophysiology of major psychoses. Previously, we identified pericentrin 2 (PCNT2) and DISC1-binding zinc finger protein (DBZ) as binding partners of DISC1; further, we observed elevated expression of PCNT2 in the postmortem brains and in the lymphocytes of bipolar disorder patients, compared to controls. Here, we examined the association of PCNT2 with schizophrenia in a case–control study of Japanese cohorts. We also examined the association of DBZ with schizophrenia and with bipolar disorder, and compared the mRNA levels of DBZ in the postmortem brains of schizophrenia, bipolar and control samples. DNA from 180 schizophrenia patients 201 controls were used for the association study of PCNT2 and DBZ with schizophrenia. Association of DBZ with bipolar disorder was examined in DNA from 238 bipolar patients and 240 age- and gender-matched controls. We observed significant allelic and genotypic associations of the PCNT2 SNPs, rs2249057, rs2268524, and rs2073380 (Ser/Arg) with schizophrenia; the association of rs2249057 (P = 0.002) withstand multiple testing correction. Several two SNP- and three SNP-haplotypes showed significant associations; the associations of haplotypes involving rs2249057 withstand multiple testing correction. No associations were observed for DBZ with schizophrenia or with bipolar disorder; further, there was no significant difference between the DBZ mRNA levels of control, schizophrenia and bipolar postmortem brains. We suggest a possible role of PCNT2 in the pathogenesis of schizophrenia. Abnormalities of PCNT2, the centrosomal protein essential for microtubule organization, may be suggested to lead to neurodevelopmental abnormalities. © 2009 Wiley-Liss, Inc.

We investigated the osteogenic responses to jump training and subsequent detraining in young and adult male rats to test the following hypotheses: 1) jump training has skeletal benefits; 2) these skeletal benefits are preserved with subsequent detraining throughout bone morphometric changes; and 3) there are no differences between young and adult rats during detraining in terms of the maintenance of exercise-induced changes. Twelve-week-old (young) and 44-wk-old (adult) rats were divided into the following four groups: young-sedentary, young-exercised, adult-sedentary, and adult-exercised. The exercised groups performed jump training (height = 40 cm, 10 jumps/day, 5 days/wk) for 8 wk followed by 24 wk of being sedentary. Tibial bone mineral content and bone mineral density in vivo significantly increased with jump training, and the effects were maintained after detraining in both the young and adult exercised groups, although the benefits of training became somewhat diminished. After 24 wk of detraining, the beneficial effects of training on bone mass and strength were preserved and associated with morphometric changes, such as periosteal perimeter, cortical area, and moment of inertia. There were no significant age-exercise interactions in such parameters, except for the periosteal perimeter. These results suggest that there are few differences in bone accommodation and maintenance by training and detraining between young and adult rats.

We investigated whether the effects of jump training on bone are preserved after a detraining period in female normal and estrogen-deficient rats. Forty-four 11-wk-old Wistar rats were divided into the following four groups: sham sedentary ( n = 12), sham exercised ( n = 11), ovariectomized sedentary ( n = 10), and ovariectomized exercised ( n = 11). An 8-wk exercise period was introduced in which the rats in the exercised groups were jumped 10 times/day, 5 days/wk. This was followed by 24 wk of detraining. At the end of the exercise period, the jump training significantly increased the bone mineral content of the tibia ( P < 0.001), measured by dual-energy X-ray absorptiometry. After the detraining period, the bone mineral content ( P < 0.01), strength ( P < 0.001), and cross-sectional widths ( P < 0.001) of the tibia in the exercised groups were still greater than in the sedentary groups, without significant surgery-exercise interactions, although bone stiffness in the fracture test ( P < 0.05) and bone area in the center-proximal region, as measured by dual-energy X-ray absorptiometry ( P < 0.05), showed significant surgery-exercise interactions. These findings suggest that the exercise effect on bone strength is preserved, accompanied by cross-sectional morphological changes, even under estrogen deficiency.

The frequency per week or day of high-impact, low-repetition jump exercise for osteogenic response was assessed by two experiments. In the first experiment, 48 11-week-old rats were randomly divided into five groups: a sedentary control (W0: n = 8), one exercise session per week (W1: n = 10), three exercise sessions per week (W3: n = 10), five exercise sessions per week (W5: n = 10), and seven exercise sessions per week (W7: n = 10). In the second experiment, 30 11-week-old rats were randomly divided into three groups: a sedentary control (D0: n = 10), one exercise session per day (D1: n = 10), and two exercise sessions per day (D2: n = 10). One exercise session consisted of 10 continuous jumps. After 8 weeks of the exercise period, the jump exercise increased the fat-free dry weight of the tibia in the W1 (7.5%, n.s.), W3 (12.6%, P < 0.01), W5 (12.0%, P < 0.01), and W7 (19.8%, P < 0.001) groups compared with the W0 group. The jump exercise also increased the fat-free dry weight in the D1 (12.0%, P < 0.001) and D2 (13.0%, P < 0.001) groups compared with the D0 group. These increases were accompanied by increased bone strength and cortical area at the mid-shaft. The results in the present study suggest that for bone gain, it is not always necessary to do high-impact exercise every day, although exercising every day does have the greatest effect. The results in this study also suggest that there is little additional benefit if bones are loaded by two separate exercise sessions daily.

Jump exercise in rats creates high-impact loading on lower limbs and results in the promotion of osteogenesis. Although we clarified that a few loadings per day could increase bone mass and strength within 8 weeks, we did not observe an osteogenic response at the onset of the training period. The purpose of this study was to clarify whether the bone formation rate measured by the double-label immunofluorescence method increases with a few loadings for a short period. Forty female Wistar rats, 10 weeks old, were divided into a control group and three exercise groups: the 10 jumps/day (10 J) group, 40 jumps/day (40 J) group, and 100 jumps/day (100 J) group. The exercise groups were trained on days 1, 3, and 5, the fluorescent labels were injected on days 5 and 12, and the experiment ended on day 16. The bone formation rates were greater in all exercise groups compared with the control group and were significantly greater in the 40 J and 100 J groups than in the 10 J group. These data show that only 10 repetitions/day loading promotes the osteogenic response within a short period from the onset of the training.

Background DISC1 has been suggested as a causative gene for psychoses in a large Scottish kindred. PCNT2 has recently been identified as an interacting partner of DISC1. In this study, we investigated the role of PCNT2 in bipolar disorder, by gene expression analysis and genetic association study. Methods By TaqMan real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), we examined the messenger RNA (mRNA) levels of PCNT2 in the postmortem prefrontal cortex of bipolar disorder ( n = 34), schizophrenia ( n = 31), and control subjects ( n = 32), obtained from Stanley Array Collection. We also compared the mRNA levels of PCNT2 in the peripheral blood lymphocytes of bipolar disorder ( n = 21), schizophrenia ( n = 21), depression ( n = 33), and control subjects ( n = 57). For the association study, 23 single nucleotide polymorphisms (SNPs) were analyzed in 285 bipolar disorder patients and 287 age-and gender-matched control subjects, all of Japanese origin. The genotypes were determined by TaqMan assay. Results Significantly higher expression of PCNT2 was observed in the brain samples of bipolar group, compared with the control ( p = .001) and schizophrenia ( p = .018) groups. In the peripheral blood lymphocytes also, a significantly higher expression of PCNT2 was observed in the bipolar group, compared with the control subjects ( p = .043). However, none of the SNPs analyzed in our study showed a significant association with bipolar disorder; a weak tendency toward association was observed for two intronic SNPs. Conclusions Our findings suggest that elevated levels of PCNT2 might be implicated in the pathophysiology of bipolar disorder.

Urinary excretion of human liver-type fatty acid-binding protein (hL-FABP), which is expressed in human proximal tubules and engaged in free fatty acid (FFA) metabolism, was reported to reflect the clinical prognosis of chronic kidney disease. Here we have investigated the pathophysiological significance of hL-FABP in a model of protein overload nephropathy. Because L-FABP is not expressed in the wild-type mice, we generated hL-FABP chromosomal gene transgenic (Tg) mice. Tg mice were intraperitoneally injected with bovine serum albumin (BSA) replete with FFAs (r-BSA group) or FFA-depleted BSA (d-BSA group). The r-BSA group developed significantly more severe tubulointerstitial damage than did the d-BSA group. Renal expression of the hL-FABP gene was more up-regulated, and urinary excretion of hL-FABP was significantly higher, in the r-BSA group than in the d-BSA group. Furthermore, compared with their wild-type littermates injected with r-BSA, the number of infiltrated macrophages was significantly attenuated in Tg mice injected with it on day 28. In patients with kidney disease (n = 50), urinary hL-FABP was correlated with both urinary protein and the severity of tubulointerstitial injury. In conclusion, our experimental model suggests that urinary excretion of hL-FABP reflects stresses, such as urinary protein overload, on the proximal tubules. The clinical observations support this hypothesis.

Prolonged loading repetitions can diminish the mechanosensitivity of bones, and increased intervals between loading might restore sensitivity. This study was designed to investigate the effects of intervals between loadings or bouts on osteogenic response. Forty female Fisher 344 rats aged 5 wk were divided into a control group and three exercise groups: 20 jumps in a single bout with a 3-s (S3) or 30-s (S30) jump interval, or 20 jumps in 2 bouts (10 × 2) separated by a 6-h interval with a 3-s jump interval (D3). After 8 wk of training, the bone masses per body weight of the femur and tibia were significantly greater in the three exercise groups than in the control group, and these values were also greater in S30 than in S3, although they were at the same level in D3 and S3. These data suggest that a longer interval (30 s) between individual loading had more effective anabolic effects on bone than a shorter interval (3 s).

The purpose of this study was to examine the role of muscarinic cholinergic and alpha2-adrenergic mechanisms in growth hormone (GH) secretion during exercise in humans. The GH responses induced during moderate-intensity exercise (using a cycle ergometer at 60% maximal oxygen uptake, VO2max, for 30 min) without treatment (control) and after the administration of a muscarinic cholinergic antagonist (atropine 1 mg) or after an alpha2-adrenergic antagonist (yohimbine 15 mg) were compared in seven healthy men. Although, serum GH concentration had increased significantly after exercise in the control experiment [mean peak GH concentration 52.64 (SEM 18.60) ng x ml(-1)], the increase was suppressed by the administration of either atropine [mean peak GH concentration 8.64 (SEM 7.47) ng x ml(-1)] or yohimbine [mean peak GH concentration 17.50 (SEM 7.89) ng x ml(-1)]. The area under the curve of serum GH concentration against time was significantly lower in the experiment using these drugs [with atropine, mean area 458 (SEM 409) ng x ml(-1) min], with yohimbine mean area 946 (SEM 435) ng x ml(-1) min] than in the control experiment [mean area 3135 (SEM 1098) ng x ml(-1) x min]. These results suggest that muscarinic cholinergic and alpha2-adrenergic mechanisms are involved in GH secretion during exercise in humans.

We previously cloned a cDNA for a mouse PGE receptor positively coupled to adenylate cyclase from mouse mastocytoma cells, and reported it as EP2 subtype of PGE receptor [Honda, A., Sugimoto, Y., Namba, T., Watabe, A., Irie, A., Negishi, M., Narumiya, S. and Ichikawa, A. (1993) J. Biol. Chem. 268, 7759–7762]. However, it is not sensitive to one of the EP2 agonists, butaprost. Recently another subtype of PGE receptor coupled to adenylate cyclase has been identified pharmacologically and named EP4. These findings have led us to examine whether the cloned receptor is the EP4 subtype. AH23848B, a selective EP4 antagonist, not only displaced the [3H]PGE2 binding to the cloned receptor but antagonized the PGE2-stimulated cAMP formation in the receptor. In contrast, EP2 specific agonists, butaprost and 19(R)OH-PGE2 neither bound to the receptor nor stimulated the cAMP formation. These results suggest that this receptor previously reported as ‘EP2’ subtype is identical to the pharmacologically defined EP4 subtype and not of EP2 subtype.

PURPOSE. Retinal photoreceptor damage is a common feature of ophthalmic disorders, such as age-related macular degeneration and retinitis pigmentosa. Oxidative stress has a key role in these diseases. Metallothioneins (MTs) are a family of cysteinerich proteins, and various physiologic functions have been reported, including protection against metal toxicity and antioxidative potency. We investigated the functional role of MT-III in light-induced retinal damage. METHODS. The expression of retinal MT-I, -II, and -III mRNA was evaluated by real-time reverse-transcription PCR in retina exposed to light. Retinal damage in MT-deficient mice was induced by exposure to white light at 16,000 lux for 3 hours after dark adaptation. Photoreceptor damage was evaluated histologically by measuring the thickness of the outer nuclear layer (ONL) 5 days after light exposure and by electroretinogram recording. In an in vitro experiment, the MT-III siRNAs were tested for their effects on light-induced mouse photoreceptor cell (661W) damage. RESULTS. The mRNAs of the MTs were increased significantly in murine retina after light exposure. The ONL in the MT-III‐ deficient mice was remarkably thinner compared to lightexposed wild-type (WT) mice, and a- and b-wave amplitudes were decreased; the damage induced in MT-I/-II‐deficient mice was comparable to that observed in WT mice. MT-III knockdown by siRNA in 661W exacerbated the cell damage and increased the production of reactive oxygen species in response to light exposure. CONCLUSIONS. These findings suggested that MT-III can help protect against light-induced retinal damage compared to MT-I/ II. Some of these effects may be exerted by its antioxidative potency. (Invest Ophthalmol Vis Sci. 2012;53:7896‐7903)

The hypothesis of the present study was that low-repetition and high-impact training of 10 maximum vertical jumps/day, 3 times/wk would be effective for improving bone mineral density (BMD) in ordinary young women. Thirty-six female college students, with mean age, height, and weight of 20.7 ± 0.7 yr, 158.9 ± 4.6 cm, and 50.4 ± 5.5 kg, respectively, were randomly divided into two groups: jump training and a control group. After the 6 mo of maximum vertical jumping exercise intervention, BMD in the femoral neck region significantly increased in the jump group from the baseline (0.984 ± 0.081 vs. 1.010 ± 0.080 mg/cm2; P < 0.01), although there was no significant change in the control group (0.985 ± 0.0143 vs. 0.974 ± 0.134 mg/cm2). And also lumbar spine (L2–4) BMD significantly increased in the jump training group from the baseline (0.991 ± 0.115 vs. 1.015 ± 0.113 mg/cm2; P < 0.01), whereas no significant change was observed in the control group (1.007 ± 0.113 vs. 1.013 ± 0.110 mg/cm2). No significant interactions were observed at other measurement sites, Ward's triangle, greater trochanter, and total hip BMD. Calcium intakes and accelometry-determined physical daily activity showed no significant difference between the two groups. From the results of the present study, low-repetition and high-impact jumps enhanced BMD at the specific bone sites in young women who had almost reached the age of peak bone mass.

We present herein transcriptional changes in mouse spinal cords in response to physical exercise on a treadmill using a DNA microarray. By 30-min exercise, the expression of 3 genes was enhanced and expression of 29 genes reduced. By continuous 2-week exercise (30-min exercise per day), the expression of 1 gene was enhanced and expression of 13 genes reduced.