Endogenous and Inhaled Nitric Oxide for the Treatment of Pulmonary Hypertension

Since the discovery of nitric oxide (NO) as a physiological substance produced in the endothelium, the impairment of endothelial NO production and reactivity of the pulmonary vasculature to NO have been described in animal models and patients with pulmonary hypertension (PH). The NO synthase-NO-cyclic guanosine monophosphate (cGMP) pathway is impaired in pulmonary arterial hypertension (PAH), pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Pioneering clinicians conceived that NO can be administered to the lung by inhalation and used this strategy to treat PH in humans and acute hypoxic PH in animal models. Inhaled NO (iNO) selectively decreases pulmonary arterial pressure with no changes in systemic arterial pressure. When iNO diffuses into the blood, it is converted to NO3−, thereby losing its vasodilatory effects. NO might then be recycled in hypoxic remote organs, where NO3− and NO2− are reduced to NO. In the present chapter, the metabolic fate of iNO, based on previous air pollution research in Japan, is discussed. Then, we describe recent clinical applications of iNO in pediatric patients with various diseases, including bronchopulmonary dysplasia (BPD), persistent PH of neonates, and congenital diaphragmatic hernia (CDH). We also summarize the role of iNO in the catheterization lab, including acute vasoreactivity testing to assess prognosis, indications for specific PH therapy, and operability of congenital heart disease

Dietary acrylamide intake and the risk of liver cancer: The japan public health center-based prospective study

Acrylamide has been studied for its carcinogenicity in experimental animals, causing tumors at several organ sites, and has been considered probably carcinogenic to humans as well. Given the small number of epidemiological studies that have been conducted, it is still uncertain whether the consumption of acrylamide is associated with liver cancer. Therefore, we investigated a study to determine the possible relationship between acrylamide intake and the risk of developing liver cancer in the Japanese population. A total of 85,305 participants, from the Japan Public Health Center-based Prospective Study, who provided a validated food-frequency questionnaire were enrolled between 1995 and 1998. During a median of 16.0 years follow-up, 744 new liver cancer cases were identified. Compared to the lowest tertile of acrylamide consumption (<4.8 μg/day), the multivariate hazard ratio (HR) for the highest tertile (≥7.6 μg/day) was 0.79 (95% confidence interval [CI] = 0.65-0.95) for liver cancer using multivariable model 1, adjusted for smoking status, body mass index (BMI), physical activity, medical history, and alcohol consumption; whereas the inverse relationship disappeared after additionally adjusting for coffee consumption in multivariable model 2 with HR of 1.08 (95% CI = 0.87-1.34) for the highest tertile. The effect of dietary acrylamide intake on the risk of liver cancer was not observed in the Japanese population.Zha, L.; Sobue, T.; Kitamura, T.; Kitamura, Y.; Ishihara, J.; Kotemori, A.; Liu, R.; Ikeda, S.; Sawada, N.; Iwasaki, M.; Tsugane, S.; JPHC Study Group, f.t. Dietary Acrylamide Intake and the Risk of Liver Cancer: The Japan Public Health Center-Based Prospective Study. Nutrients 2020, 12, 2503. https://doi.org/10.3390/nu1209250

Association of Vegetable, Fruit, and Okinawan Vegetable Consumption With Incident Stroke and Coronary Heart Disease

Background: Few studies have investigated the effects of Okinawan vegetable consumption on the risk of incident stroke and coronary heart disease. This study aimed to examine associations of vegetable, fruit, and Okinawan vegetable consumption with risk of incident stroke and coronary heart disease in the Japanese population of Okinawa.Methods: The study design was a prospective cohort study. During 1995–1998, a validated food frequency questionnaire was administered in two study areas to 16,498 participants aged 45–74 years. In 217,467 person-years of follow-up until the end of 2012, a total of 839 stroke cases and 197 coronary heart disease cases were identified.Results: No statistically significant association between total Okinawan vegetable consumption and risk of stroke and coronary heart disease was obtained: the multivariable adjusted hazard ratios for the highest versus lowest tertile of consumption were 1.09 (95% confidence interval, 0.93–1.29; P for trend = 0.289) in model 2. Total vegetable and fruit and specific Okinawan vegetable consumption were also not statistically significantly associated with risk of cardiovascular outcomes.Conclusions: This study demonstrated that consumption of total vegetable and fruit, total Okinawan vegetables, and specific Okinawan vegetables in Japanese residents of Okinawa was not associated with risk of incident stroke and coronary heart disease

Seaweed intake and risk of cardiovascular disease: the Japan Public Health Center–based Prospective (JPHC) Study

BackgroundThe minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established.ObjectivesWe examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease risk among a Japanese study population.MethodsWe surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40–69 y). Seaweed intake was determined by FFQ at baseline (1990–1994). Incidences of stroke and ischemic heart disease were ascertained until the end of 2009 (Cohort I) or 2012 (Cohort II). Sex-specific cardiovascular disease HRs (95% CIs) were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors.ResultsDuring 1,493,232 person-years of follow-up, 4777 strokes (2863 ischemic stroke, 1361 intraparenchymal hemorrhages, and 531 subarachnoid hemorrhages) and 1204 ischemic heart disease cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption compared with almost no consumption of seaweed were seen in ischemic heart disease [0.76 (0.58, 0.99); P-trend = 0.04] and total cardiovascular diseases [0.88 (0.78, 1.00); P-trend = 0.08]. Among women, such inverse associations were 0.56 (0.36, 0.85; P-trend = 0.006) for ischemic heart disease and 0.89 (0.76, 1.05; P-trend = 0.10) for total cardiovascular diseases. No significant associations were observed between seaweed intake and risk of total stroke or stroke types among either men or women.ConclusionsSeaweed intake was inversely associated with risk of ischemic heart disease

Dietary Inflammatory Index Is Associated With Inflammation in Japanese Men

Background: Dietary components are known to affect chronic low-grade inflammation status. The dietary inflammatory index (DII®) was developed to measure the potential impact of a diet on an individual\u27s inflammatory status, and it has been validated mainly in Western countries. Objective: This study aimed to examine the validity of the energy-adjusted DII (E-DIITM) using high-sensitivity C-reactive protein (hs-CRP) concentration in Japanese men and women. Methods: In total, 6,474 volunteers from a cancer-screening program (3,825 men and 2,649 women) completed a food frequency questionnaire (FFQ) and their hs-CRP concentrations were evaluated. E-DII scores were calculated on the basis of 30 food parameters derived from the FFQ. Higher E-DII scores reflect a greater pro-inflammatory potential of the diet. The associations between E-DII quartiles and hs-CRP concentration were assessed using regression models adjusted for age, body mass index, smoking status, and amount of physical activity. Results: Mean E-DII in men and women was + 0.62 ± 1.93 and −1.01 ± 2.25, respectively. The proportion of men and women who had hs-CRP concentration \u3e3 mg/L was 4.7 and 3.1%, respectively. A significant positive association was observed between E-DII score and hs-CRP concentration in men; geometric mean of hs-CRP concentration in the lowest and highest E-DII quartiles was 0.56 mg/L and 0.67 mg/L (Ptrend \u3c 0.01), respectively. The odds ratio (95% confidence interval) of having an elevated hs-CRP concentration (\u3e3 mg/L) was 1.72 (1.10–2.67) in the highest E-DII quartile (Ptrend = 0.03) in men. However, no association was observed between E-DII score and hs-CRP concentration in women, except in those not taking prescription medications. Conclusions: DII was associated with inflammation status in Japanese men, but the association was limited in Japanese women

BRCA1/2 Mutation Frequency is HIGH in Japanese Triple-Negative Breast Cancer Patients

Germline mutations of BRCA1/2 genes cause hereditary breast and/or ovarian cancer. However, whether guidelines like those of the National Comprehensive Cancer Network (NCCN) can suitably predict the likelihood of BRCA1/2 mutations in the Japanese population is unclear. Methods BRCA1/2 gene mutation frequencies were investigated in relation to parameters such as age, family history (FH), and breast cancer subtype using data collected from 922 Japanese breast cancer patients who underwent surgery between September 2010 and June 2013. BRCA1/2 mutations were present in 15 of 57 (26.3%) tested patients. The frequency of the mutations was not significantly related to age. Among the 180 patients who reported an FH of breast cancer, 11 of the 37 who were tested (29.7%) were positive for BRCA1/2 mutations. Of those with an FH of ovarian cancer (n = 34), seven of 12 patients tested (58.3%) were carriers of BRCA1/2 (P = 0.013). Six of these seven carriers were triple-negative breast cancer (TNBC) patients. In all, there were 97 TNBC patients, and the presence of the BRCA1/2 mutation in this subgroup was significantly greater than in non-TNBC patients, with 12 of 17 TNBC patients (70.5%) testing positive (P = 0.03). There were 59 TNBC patients < 60 years of age, and of the 16 (27.1%) who underwent BRCA1/2 genetic testing, 11 (68.8%) were found to have mutations in BRCA1/2. Among the TNBC patients, 29 also reported an FH of breast or ovarian cancer; of these, nine of the 13 tested (69.2%) were positive for a BRCA1/2 mutation. The data demonstrate that BRCA1/2 mutations are observed more frequently in TNBC patients, especially those < 60 years of age or in combination with an FH of breast and/or ovarian cancer, suggesting that some of the NCCN guidelines can adequately predict BRCA1/2 carriers in the Japanese population

Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires

Background: Although open-ended dietary assessment methods, such as weighed food records (WFRs), are generally considered to be comparable, differences between procedures may influence outcome when WFRs are conducted independently. In this paper, we assess the procedures of WFRs in two studies to describe their dietary assessment procedures and compare the subsequent outcomes. Methods: WFRs of 12 days (3 days for four seasons) were conducted as reference methods for intake data, in accordance with the study protocol, among a subsample of participants of two large cohort studies. We compared the WFR procedures descriptively. We also compared some dietary intake variables, such as the frequency of foods and dishes and contributing foods, to determine whether there were differences in the portion size distribution and intra- and inter-individual variation in nutrient intakes caused by the difference in procedures. Results: General procedures of the dietary records were conducted in accordance with the National Health and Nutrition Survey and were the same for both studies. Differences were seen in 1) selection of multiple days (non-consecutive days versus consecutive days); and 2) survey sheet recording method (individual versus family participation). However, the foods contributing to intake of energy and selected nutrients, the portion size distribution, and intra- and inter-individual variation in nutrient intakes were similar between the two studies. Conclusion: Our comparison of WFR procedures in two independent studies revealed several differences. Notwithstanding these procedural differences, however, the subsequent outcomes were similar