Increased salt intake is associated with diabetes and characteristic dietary habits: a community-based cross-sectional study in Japan.

We investigated the association of salt intake with lifestyle-related diseases and also the association of habitually consumed foods with salt intake. A cross-sectional study was conducted using data from a baseline survey of 2,129 residents of Yonezawa city (980 males and 1,149 females), Yamagata prefecture. The residents were divided into three groups based on their estimated daily salt intake: low, medium, and high. In both genders, the prevalence of hypertension and diabetes increased in the order of high > medium > low salt intake (trend p<0.001). Similar trends were observed in the prevalence of hyperlipidemia in females and metabolic syndrome in males. The prevalence of diabetes in the high salt intake group was significantly higher than that in the control group (matched from the low and medium salt intake groups), even when confounding factors were excluded by propensity score matching (p<0.01). Network analysis showed that the low salt intake group had a greater tendency to habitually consume various vegetables than the high salt intake group. Our findings reveal that the prevalence of lifestyle-related diseases increased with higher salt intake. We speculate that a dietary shift to multiple vegetable consumption could have salt-lowering effects.

A Cross-Sectional Survey on the Association between Dental Health Conditions and University Personality Inventory Scores among University Students: A Single-Center Study in Japan.

This study examined the association between dental health conditions and scores on the University Personality Inventory (UPI) among university students in Japan. Participants were freshmen at Yamagata University between 2010 and 2019. Dental check-ups, including dental caries, periodontal disease, malocclusion, and temporomandibular disorders (TMD), and mental health screening using the UPI were performed; 12,433 students were included in the final analysis. A logistic regression analysis was performed to confirm the association between dental health conditions and >30 UPI scores, which indicate the need to consult mental health professionals. Overall, students who required treatment for TMD had a 3.165-fold higher risk of >30 UPI scores (OR = 3.165, 95% CI = 1.710−5.857). Periodontal disease and TMD in male participants (periodontal disease: OR = 1.329, 95% CI = 1.108−1.595; TMD: OR = 3.014, 95% CI = 1.107−8.204) and TMD in female participants (OR = 2.938, 95% CI = 1.340−6.445) were significant risk factors for >30 UPI scores. Students requiring treatment for TMD were at risk of obtaining >30 UPI scores. Although our study has several limitations, students with subjective symptoms (e.g., disturbance in opening the mouth) should take the UPI test or in some cases consult mental health professionals.

High Parity Is an Independent Risk Factor for Tooth Loss in Women: A Community-Based Takahata Study in Japan.

Risk factors for tooth loss have been widely examined previously. However, no previous study has comprehensively investigated the risk factors, including lifestyle-related specific factors (parity, oral health habits, and socioeconomic status), for fewer than 20 teeth among women in the general population in Japan. This cross-sectional study explored the association of these risk factors, especially parity, with having fewer than 20 teeth among Japanese women. A self-reported questionnaire including items on lifestyle-related risk factors (parity, oral health, diet [e.g., alcohol and sucrose consumption]) and socioeconomic status was sent by post to female residents (age ≥ 40 years) of Takahata town, Yamagata Prefecture, in 2005. Multivariate logistic regression analysis including 3,854 eligible participants was performed to investigate the association between various factors (including parity) and having fewer than 20 teeth. The results indicated that, compared with nulliparous women, women with two, three, and four completed pregnancies had 2.485-, 2.844-, and 4.305-fold increased risk of having fewer than 20 teeth, respectively. Our study is the largest-scale study of the general female population in Japan and the first study to comprehensively investigate risk factors (parity, oral health status, and socioeconomic status) for fewer than 20 teeth. We thus found that higher parity, especially, two or more, was independent risk factors for having less than 20 teeth among Japanese women. In conclusion, the present study emphasizes the importance of good oral health habits in women, especially, during pregnancy and in the postpartum period, to maintain 20 or more teeth.

Association between presence of 20 or more natural teeth and all-cause, cancer-related, and cardiovascular disease-related mortality: Yamagata (Takahata) prospective observational study.

BACKGROUND: Several studies have surveyed the relationship between the presence of ≥ 20 natural teeth and mortality. However, very few have evaluated this association over a long-term follow-up of more than ten years within a large population in Japan. This study aimed to prospectively confirm the associations between mortality and the presence of ≥ 20 natural teeth within a community-based population in Japan. METHODS: A prospective observational study including 2208 participants aged ≥ 40 years was conducted in Takahata Town, Japan, between May 2005 and December 2016. All participants answered a self-administered questionnaire to provide their background characteristics, including their number of teeth. The participants were classified into two categories based on their self-reported number of teeth (< 20 and ≥ 20 teeth). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional-hazards regression model to assess risk factors for all-cause, cancer-, and cardiovascular disease-related mortality. RESULTS: The total follow-up period was 131.4 ± 24.1 months (mean ± SD). After adjusting for covariates, the risk of all-cause mortality was significantly higher in the group with < 20 teeth than in those with ≥ 20 teeth (HR = 1.604, 95% CI 1.007-2.555, p = 0.047). However, the risk of cancer- and cardiovascular disease-related mortalities was not statistically significant between the two groups. CONCLUSION: In this study, participants with < 20 teeth had a significantly higher risk of all-cause mortality, although the difference was borderline significant. These results emphasize the importance of having ≥ 20 natural teeth for a healthy life expectancy.

Oxidative stress evaluation of skeletal muscle in ischemia-reperfusion injury using enhanced magnetic resonance imaging.

Acute extremity arterial occlusion requires prompt revascularization. Delayed revascularization induces ischemia-reperfusion injury in the skeletal muscle. Organ injury-induced oxidative stress is widely reported, and oxidative stress is heavily involved in ischemia-reperfusion injury. This study aimed to evaluate oxidative stress in ischemia-reperfusion rat models using 3-carbamoyl PROXYL enhanced magnetic resonance imaging (3-CP enhanced MRI). Ischemia-reperfusion injury was induced through clamping the right femoral artery in rats, with a 4-h ischemia time in all experiments. 3-CP enhanced MRI was performed to evaluate oxidative stress, and the rats were divided into 3 reperfusion time groups: 0.5, 2, and 24 h. Signal intensity was evaluated using 3-CP enhanced MRI and compared in the ischemia-reperfusion and intact limbs in the same rat. Furthermore, the effect of edaravone (radical scavenger) was evaluated in the 4-h ischemia-24-h reperfusion injury rat model. The signal intensity of the ischemia-reperfusion limb was significantly stronger than that of the intact limb, suggesting that oxidative stress was induced in the ischemia-reperfusion muscle. Edaravone administration reduced the oxidative stress in the ischemia-reperfusion limb. The signal intensity of the ischemia-reperfusion limb was stronger than that of the intact limb, presumably reflecting the oxidative stress in the former. 3-CP MRI examination shows promise for effective assessment of oxidative stress and may facilitate early diagnosis of ischemia-reperfusion injury.

In vivo analysis of redox status in organs - from bench to bedside.

Reactive oxygen species (ROS) such as superoxide, hydroxyl radical, and hydrogen peroxide play an important role in the maintenance of life. However, production of excessive ROS and/or deficiency of the antioxidant system lead to oxidative stress and cause a variety of diseases. In the present study, we used electron spin resonance (ESR) to detect ROS in vivo to clarify its roles in redox dynamics and organ damage. However, the limited permeability of microwaves and low anatomic resolution of ESR equipment made it difficult to apply clinically. Nitroxide is widely used as a sensitive redox sensor for in vivo ESR analysis. The unpaired electrons of nitroxide are known to cause the T1 relaxation time-shortening effect of water protons, creating magnetic resonance imaging (MRI) effects. The remarkable development of MRI has facilitated the spatiotemporal analysis of nitroxide, which was previously impossible. In a rat model, we have been able to image and analyze the process of nitroxide reduction using MRI. MRI using nitroxide as a contrast medium is considered to be clinically applicable for evaluation of organ redox, imaging of ROS (which cause organ damage), and evaluation of therapeutic effects. In this review, we describe current advances in the analysis of in vivo redox capacity in animals using ESR and MRI equipment. We consider that redox evaluation using MRI can contribute to advances in clinical medicine.

Risk factors for tooth loss in community-dwelling Japanese aged 40 years and older: the Yamagata (Takahata) study.

OBJECTIVES: The aim of the present study was to investigate comprehensively the risk factors, including some lifestyle-associated factors, oral health habits, and socioeconomic status, for having less than 20 teeth in cross-sectional study in the general population of Japan. MATERIALS AND METHODS: The survey population was the general population of individuals aged greater than or equal to 40 years in Takahata town, Japan in 2005. A postal survey with a self-administered questionnaire was distributed, and 7542 participants were entered into the final statistical analysis. The self-administered questionnaire contained items regarding some lifestyle-associated factors, oral health, and dietary intake, including alcohol and sucrose consumption. To confirm the independent association between the number of teeth and several parameters, a multivariate logistic regression analysis was used to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A low educational status, no dental check-ups, low frequency of brushing, older age, and smoking habit were independent risk factors for less than 20 teeth. A low educational status was a particularly significant risk factor for less than 20 teeth (OR = 1.352, 95% CI = 1.125-1.624). CONCLUSION: These results emphasize the importance of good oral health habits, such as frequent tooth brushing, routine dental check-ups, and no smoking, and indicate that more appropriate and compulsory education regarding oral health is needed to lessen the education level-derived differences in oral health. CLINICAL RELEVANCE: Poor oral health habits and low educational status are the independent risk factors for having less than 20 teeth.

Fewer teeth are a risk factor for being underweight in community-dwelling Japanese aged 40 years and older: The Yamagata (Takahata) Study.

OBJECTIVE: The aim of the present study was to investigate comprehensively, the risk factors for underweight in cross-sectional study in the general population of Japan. METHODS: The survey population was the general population of individuals aged >40 years in Takahata town, Japan in 2005. A postal survey in the form of a self-administered questionnaire was distributed, and 6084 individuals were entered into the final statistical analysis. The self-administered questionnaire contained items regarding lifestyle, oral health status, socio-economic status and dietary intake. To examine the independent relationships between an underweight status and several parameters, a multivariate logistic regression analysis was used to estimate adjusted odds ratios (ORs). RESULTS: The number of teeth, age, alcohol consumption, hypertension, spousal status, smoking habit, appetite, body weight at 20 years of age, habit of going out and physical activity were independently associated with an underweight status compared with the normal weight group. Individuals with fewer than 10 teeth were especially more likely to be underweight than individuals with more than 20 teeth (OR = 1.956, 95% CI = 1.261-3.035). CONCLUSION: This study showed an independent association between the number of teeth and an underweight status, indicating that fewer teeth can increase the risk of being underweight.

In vivo visualization of redox status by high-resolution whole body magnetic resonance imaging using nitroxide radicals.

Various diseases are known to be associated with an imbalance of the redox state, but in vivo detection of free radicals is difficult. The purpose of this study is to establish a method for in vivo visualization of redox status by high-resolution whole-body MRI using nitroxide radicals. A redox-sensitive nitroxide probe, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL), was administered to rats intravenously, and in vivo T1-weighted MRI was performed to virtually visualize the redox status of various organs. In experiments using phantoms, a linear relationship between the MRI signal and the carbamoyl-PROXYL concentration persisted up to 80 mM. Among the phantoms, a sample containing 1 mM carbamoyl-PROXYL was readily identifiable. After intravenous injection of carbamoyl-PROXYL, whole-body T1-weighted MRI of the rat provided clear images with good spatial and temporal resolution. The signal intensities of four selected organs (heart, liver, kidney, and intestine) were analyzed quantitatively. The carbamoyl-PROXYL signal peaked and gradually declined due to reduction after intravenous injection. Among the four organs, the organ-specific reduction rate of carbamoyl-PROXYL was highest in the heart, followed by (in order) the liver, kidney, and intestine, and statistical analysis showed that the inter-organ differences were significant. In conclusion, T1-weighted carbamoyl-PROXYL-enhanced MRI provides excellent spatial and temporal imaging of carbamoyl-PROXYL distribution. Furthermore, it provides important functional information pertaining to blood flow and tissue redox activity in individual organs. MRI in combination with carbamoyl-PROXYL has potential clinical application for evaluation of redox activity in whole organs.

Imaging of reactive oxygen species generated in vivo.

PURPOSE: We sought to image the biodistribution of reactive oxygen species (ROS) within the living body using an in vivo electron spin resonance (ESR) imaging system using a spin probe, 1-acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrroline (ACP) that produces ESR-detectable nitroxide upon reaction with ROS. METHODS: Acute hepatic injury was induced in mice by priming with heat-killed Corynebacterium parvum followed by injection of a low dose of lipopolysaccharide. ACP was administered intravenously and an in vivo ESR imaging system was used to visualize hepatic oxidative stress. RESULTS: In this immune-mediated hepatic injury model, significant oxidative stress was evident at 3 h after lipopolysaccharide administration before the onset of massive hepatic injury. ACP was administered intravenously at 3 h after lipopolysaccharide injection when significant hepatic oxidative stress had been observed, and the ESR imaging system detected a high signal for 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (carbamoyl-PROXYL), which had originated from the ACP-derived hydroxylamine and produced large amount of ROS within the living body. Using the ESR imaging system with ACP, we were able to visualize ROS in the abdomen before onset of hepatic injury. CONCLUSION: We have succeeded in visualizing ROS within the body before onset of organ damage, representing a significant development in imaging for toxic molecules.

A case of adult type 1 Gaucher disease complicated by temporal intestinal hemorrhage.

A 21-year-old man with a history of sudden rectal hemorrhage was referred to our hospital. Examination disclosed thrombocytopenia and hepatosplenomegaly. A liver biopsy specimen demonstrated Gaucher cells in Glisson's capsule. Additional investigations revealed a low level of leukocyte ß-glucosidase activity and common mutations of the glucocerebrosidase gene, L444P/D409H. We diagnosed the patient with Gaucher disease type 1. He underwent enzyme replacement therapy. Thrombocytopenia and hepatosplenomegaly improved at a rate of approximately 50 and 20%, respectively, within 6 months. This case suggests that we must pay attention to adult Gaucher disease as a differential diagnosis for cryptogenic thrombocytopenia.

(99m)Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C.

We describe a 62-year-old woman with advanced chronic hepatitis C who showed no response to low-dose long-term interferon-beta monotherapy (3 MU, three times a week). The interferon monotherapy was continued for 2 years and 9 months. Despite this lack of response to interferon, the patient's clinical course was good and liver function assessed by (99m)Tc-galactosyl human serum albumin single photon emission computed tomography ((99m)Tc-GSA SPECT) analysis improved significantly. Improvement of the data obtained by (99m)Tc-GSA SPECT analysis justified continuation of the treatment. (99m)Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C, despite a lack of reduction of the ALT level and HCV-RNA titer.

Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.

The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.

A case of monocular blindness as the initial presentation of hepatocellular carcinoma with skull metastasis.

A 52-year-old man suffering from monocular blindness, with light perception only, was admitted to our hospital. The symptom had begun as low vision and developed rapidly within 3 weeks into monocular blindness in the right eye, with no other systemic manifestations. Imaging examinations revealed multiple hepatocellular carcinomas in the cirrhotic liver, and tumors at the skull base and vertebra. A pathological and immunochemical study of specimens obtained by endoscopic transnasal tumor biopsy and laminectomy revealed them to be metastatic hepatocellular carcinomas (HCCs). Although the patient underwent radiation therapy and chemotherapy, he died 5 months after admission to our hospital. The cranial HCC, involving only the optic canal, may have disturbed the optic nerve in preference to the other cranial nerves. This is the first report of a HCC patient with monocular blindness as the initial presentation of the disease.

Enhanced expression of fibroblast growth factor 2 in bone marrow cells and its potential role in the differentiation of hepatic epithelial stem-like cells into the hepatocyte lineage.

The transplantation of bone marrow cells (BMCs) has been applied in liver regenerative cell therapy. However, details of the interaction between the transplanted BMCs and hepatic stem cells have not been elucidated. The aim of the present study was to investigate the interaction of BMCs with hepatic stem-like cells (HSLCs) and to determine the BMC factor that steers HSLC differentiation into the hepatocyte lineage. Both BMCs and HSLCs were obtained from an adult Sprague-Dawley rat, and a co-culture system was established. Cell proliferation was analyzed by a proliferation assay, and the differentiation of HSLCs into the hepatocyte lineage was evaluated by the detection of cellular mRNA for liver-specific proteins. DNA microarray analysis was applied to BMCs co-cultured with HSLCs to determine the genes upregulated by their interaction. The proliferation of HSLCs co-cultured with BMCs was significantly higher than that of HSLCs cultured alone, and the expression of mRNAs for both albumin and tryptophan-2,3-dioxygenase was detectable in the co-cultured HSLCs. DNA microarray analysis showed the upregulated expression of fibroblast growth factor 2 (FGF2) mRNA in BMCs co-cultured with HSLCs, and the expression of mRNAs for both albumin and tyrosine aminotransferase became detectable in HSLCs cultured with FGF2. Thus, BMCs stimulate both the proliferation of HSLCs and their differentiation into the hepatocyte lineage. FGF2 is one of the factors that is produced by the interacting BMCs and that stimulates this differentiation.

Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C.

The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B. The association between HCV NS3 protein polymorphism and virological response was analyzed in patients infected with group A (n = 28) and B (n = 40) isolates who had good adherence to both pegylated interferon and ribavirin administration (>95% of the scheduled dosage) for 48 weeks. A sustained virological response (SVR) representing successful HCV eradication occurred in 33 (49%) in the 68 patients. Of the 28 patients infected with the group A isolate, 18 (64%) were SVR, whereas of the 40 patients infected with the group B isolate only 15 (38%) were SVR. The proportion of virological responses differed significantly between the two groups (P < 0.05). These results suggest that polymorphism in the secondary structure of the HCV-1b NS3 amino-terminal region influences the virological response to pegylated interferon plus ribavirin therapy, and that virus grouping based on this polymorphism can contribute to prediction of the outcome of this therapy.

Relationship between alcohol consumption and serum adiponectin levels: the Takahata study--a cross-sectional study of a healthy Japanese population.

CONTEXT: The relationship between alcohol consumption and serum adiponectin levels has not been fully explored in an Asian population. OBJECTIVE: Our goal was to determine whether alcohol consumption is associated with a change in adiponectin levels in a healthy Japanese population. DESIGN: This was a cross-sectional study. SETTING: Subjects were recruited from participants in a health check-up program. PARTICIPANTS: This study included 2932 subjects (1306 men and 1626 women). MAIN OUTCOME MEASURES: The effects of total weekly or daily volume of ethanol intake on serum adiponectin levels were evaluated. In addition, the correlation of clinical traits with serum adiponectin levels was examined. A multivariate regression model was used to control for possible confounding factors. RESULTS: Alcohol consumption was weakly correlated with decreased serum adiponectin levels in men [Spearman's ordered correlation coefficient (rs=-0.141; P<0.001]; an even weaker correlation was seen in women (rs=-0.055; P=0.025). Multivariate analysis demonstrated that alcohol consumption was independently associated with hypoadiponectinemia. CONCLUSION: In contrast to reports from the United States and Europe among White and Black subjects, our study demonstrated an inverse association between alcohol intake and serum adiponectin levels in Asian subjects, suggesting ethnic differences in the effects of alcohol consumption on serum adiponectin levels.

Expression of the RNA-binding protein Musashi1 in adult liver stem-like cells.

AIM: Musashi1 is an RNA-binding protein that regulates the Notch signaling pathway in stem cells. Our previous study revealed that Musashi1 is expressed in early hepatocytes during liver development in the mouse. However, whether this unique protein is expressed with Notch signaling markers in adult liver stem-like cells remains unknown. METHODS: Established hepatic stem-like cells (HSLC), which were derived from adult Sprague-Dawley rats, were used for experiments in vitro. HSLC were differentiated into mature cells in terms of producing albumin when co-cultured with epidermal growth factor (EGF). The mRNA expression of Musashi1, Notch family (Notch1 and Notch2), Jagged1 and Hes1 was examined in HSLC before and after cell differentiation using polymerase chain reaction-based techniques. Protein expression of Musashi1 was examined in the HSLC and normal mature hepatocytes by immunofluorescence staining. RESULTS: The mRNA expression of Musashi1, Notch1, Jagged1 and Hes1 was detected in the original HSLC before culturing with EGF but not in primary cultured mature hepatocytes. The mRNA expression of Musashi1 and Hes1 was found to be downregulated in differentiated HSLC that produce albumin. Protein expression of Musashi1 was detectable in the original HSLC but not in both differentiated HSLC and mature hepatocytes. CONCLUSION: These findings demonstrate that the RNA-binding protein Musashi1 is expressed with Notch signaling markers in adult liver stem-like cells.

Association study between the -1021C/T polymorphism of the dopamine-beta-hydroxylase gene promoter and personality traits in healthy subjects.

Dopamine and norepinephrine are implicated in the characterization of personality traits. Dopamine-beta-hydroxylase (DBH) is the enzyme responsible for conversion of dopamine to norepinephrine, and thus plays an important role in controlling dispositions of these neurotransmitters. Previous studies have shown that the -1021C/T polymorphism of the DBH gene promoter influences plasma DBH activity. Therefore, we examined the association between the -1021C/T DBH polymorphism and personality traits in 627 Japanese healthy volunteers. The DBH genotypes were identified by a PCR-RFLP method, and personality traits were assessed by the Temperament and Character Inventory (TCI). In the two-factor analysis of covariance with the DBH genotype and sex as factors and with age as a covariate, there was no main effect of the DBH genotype on any TCI score, while the interaction between the factors was significant in harm avoidance. In the post hoc analysis, the group with the T allele predictive of lower DBH activity had higher scores of harm avoidance than that without the T allele in females (p=0.006), but not in males. The present study suggests that the -1021C/T DBH polymorphism affects the personality trait of harm avoidance in healthy females.