Although a Western diet has been identified as a risk factor for Crohn's disease (CD), there is still controversy surrounding the specific foods that may contribute to the development of the disease. ...In this study, we examined the association between food intake and the prevalence of CD in Japan, as Japanese patients with CD are known to have limited genetic involvement. We identified changes in food intake associated with an increase in the number of patients with CD by analyzing the per capita consumption of food types from 1981 to 2014. Additionally, we examined the association between CD prevalence and food intake in each prefecture. Finally, the relationship between food intake and estimated age at CD onset was also investigated. Between 1981 and 2014, we observed Increased consumption of meat, eggs, milk and dairy products, oil, and potatoes and decreased consumption of grains, beans, vegetables, fruit, fish, sugar, and seaweed. The annual incidence of CD increased by 1388% over the same period. We found that meat consumption was significantly associated with CD prevalence (β = 0.503, p = 0.0003), while a significant negative correlation was observed between CD prevalence and fruit and vegetable consumption (fruit, β = 0.464, p = 0.0012; vegetables, β = 0.404, p = 0.0023). Furthermore, we estimated that the peak consumption of more meat and less fruit and vegetables and the peak age of CD onset occurred within the age range of 20-24 years. Our study identified a clear correlation between the consumption of meat, fruits, and vegetables and the prevalence of CD in Japan. Additionally, we found an association between meat, fruit, and vegetable consumption and the age at CD onset.
Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D ...receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand.
Background The future burden of heart failure in Japan was projected to 2055 in order to prospectively estimate of the number of these patients. Methods and Results The statistics are based on ...prevalence data of left ventricular dysfunction (LVD) in Sado City using the Sado Heart Failure Study (2003) and population estimates from the Japanese National Institute of Population and Social Security Research Report (2006). The number of Japanese outpatients with LVD was 979,000 in 2005, and is predicted to increase gradually as the population ages, reaching 1.3 million by 2030. Conclusion LVD is expected to precipitate a future epidemic of heart failure in Japan. (Circ J 2008; 72: 489 - 491)
Background: Dyslipidemia, an important risk factor for cardiovascular disease, may be associated with atrial fibrillation (AF). Cross-sectional studies that have examined this association, however, ...have produced controversial results, and few longitudinal studies have been conducted. Methods and Results: Using annual health examinations in Japan, the association between lipid profile and the risk of new-onset AF was investigated in the general population. A total of 28,449 individuals who did not have AF at baseline were included in the study. During a follow-up of 4.5±2.7 years, 265 individuals (0.9%) developed AF. In multivariate models, low high-density lipoprotein (HDL) cholesterol was associated with the development of AF in women (hazard ratio HR, 2.86; 95% confidence interval CI: 1.49-5.50) but not in men (HR, 1.35; 95%CI: 0.77-2.38). Women had a 28% higher risk of AF with each 10% decrease in HDL cholesterol. Neither triglycerides nor lipid ratios were associated with AF. After excluding individuals with risk factors for AF, including those who were taking anti-hypertensive drugs, had diabetes, and structural heart disease, the association between low HDL cholesterol and AF remained significant in women. Conclusions: Low HDL cholesterol was associated with an increased risk of new-onset AF in women, but not in men. (Circ J 2011; 75: 2767-2774)
Hypertension is well known to increase atrial fibrillation (AF) and the development of AF is associated with atrial chamber remodeling. Although mineralocorticoid receptor (MR) inhibition provides ...cardiovascular protection, the role of MR on atrial structural remodeling and inducibility of AF in hypertension remains unclear. Here, we investigated roles of the MR on atrial structural remodeling and inducibility of AF in hypertensive rats by using MR antagonist eplerenone (EPL). Dahl salt-sensitive (DS) rats were fed a normal-salt or a high-salt (HS) diet from 7 weeks, and a non-antihypertensive dose of EPL or vehicle was administrated from 13 weeks, at which time myocytes hypertrophy, interstitial fibrosis in the atrium and AF inducibility had increased, until 20 weeks. There was no significant difference in systolic blood pressure between DS+HS (186 ± 4 mm Hg) and DS+HS+EPL (184 ± 5 mm Hg) at 20 weeks. Burst atrial pacing demonstrated decreased AF inducibility in DS+HS+EPL (0 of 10) compared with DS+HS (7 of 10). Fibrosis and myocytes hypertrophy in the atrium were decreased in DS+HS+EPL with the reduction of atrial inflammatory cytokines. These beneficial effects of EPL were associated with less atrial oxidative stress, as assessed by 4-hydroxy-2-nonenal staining, and reduced activation of the Rho GTPase Rac1 in the atrium. Thus, MR has important roles in atrial structural remodeling and AF inducibility in Dahl rats. The effects of MR are associated, at least in part, with activation of Rac1-oxidative stress/inflammatory axis.
Intestinal immunity has been closely associated with the pathogenesis and progression of renal diseases, a relationship known as the “gut–kidney axis.” To determine the association between ...immunoglobulin A nephropathy (IgAN) and Crohn’s disease (CD), a clinico-pathological study was performed on patients who had IgAN with CD (CD-IgAN) and without CD (NOS-IgAN). We enrolled 29 patients diagnosed with IgAN via renal biopsy at the Tokyo Yamate Medical Center from 2009 to 2017. The patients were divided into CD-IgAN (
n
= 18) and NOS-IgAN (
n
= 11) and evaluated for clinical and pathological findings. IgA subclasses and galactose-deficient IgA1 (Gd-IgA1) were examined via immunohistochemistry using formalin-fixed paraffin-embedded sections from renal biopsy. Our results showed no significant difference in the extent of mesangial IgA subclasses or Gd-IgA1 deposition according to the presence or absence of CD. Pathologically, however, those with CD-IgAN had remarkably higher percentage of global glomerulosclerosis and extent of interstitial fibrosis and tubular atrophy (IF/TA) compared to those with NOS-IgAN. Moreover, the extent of macrophage infiltration in the glomerulus and interstitium was significantly higher in CD-IgAN than in NOS-IgAN. Clinically, the CD-IgAN group had significantly worse responsiveness to steroid treatment compared to the NOS-IgAN group. In conclusion, the similar immunological characteristics of deposited IgA molecules in the glomeruli between the CD-IgAN and NOS-IgAN groups might suggest their etiological similarity. However, a renal pathology showing advanced glomerular and tubulointerstitial sclerosis accompanying increased macrophage infiltration and highly resistant clinical features in patients with CD-IgAN suggests that some pathophysiological factors in CD, including abnormal intestinal immunity, may promote and activate the inflammatory process in IgAN via undetermined mechanisms.
Angiotensin-converting enzyme-2 (ACE-2) is a homolog of ACE that preferentially forms angiotensin-(ANG)-1-7 from angiotensin II (ANG II). We investigated the cardioprotective effects of telmisartan, ...a well-known angiotensin receptor blockers (ARBs) against experimental autoimmune myocarditis (EAM). EAM was induced in Lewis rats by immunization with porcine cardiac myosin. The rats were divided into two groups and treated with telmisartan (10 mg/kg/day) or vehicle for 21 days. Myocardial functional parameters were significantly improved by treatment with telmisartan compared with vehicle-treated rats. Telmisartan lowered myocardial protein expressions of NADPH oxidase subunits 3-nitrotyrosine, p47phox, p67 phox, Nox-4 and superoxide production significantly than vehicle-treated rats. In contrast myocardial protein levels of ACE-2, ANG 1-7 mas receptor were upregulated in the telmisartan treated group compared with those of vehicle-treated rats. The myocardial protein expression levels of tumor necrosis factor receptor (TNFR)-associated factor (TRAF)-2, C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP) 78 were decreased in the telmisartan treated rats compared with those of vehicle-treated rats. In addition, telmisartan treatment significantly decreased the protein expression levels of phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, phospho-ERK and phospho (MAPK) activated protein kinase-2 than with those of vehicle-treated rats. Moreover, telmisartan significantly decreased the production of proinflammatory cytokines, myocardial apoptotic markers and caspase-3 positive cells compared with those of vehicle-treated rats. Therefore, we suggest that telmisartan was beneficial protection against heart failure in rats, at least in part by suppressing inflammation, oxidative stress, ER stress as well as signaling pathways through the modulation of ACE2/ANG1-7/Mas receptor axis.
A 59-year-old non-obese Japanese woman developed diabetes mellitus with a negative glutamic acid decarboxylase autoantibody (GADA) test result. Her hyperglycemia was initially well controlled by oral ...hypoglycemic agents; however, despite continued treatment the hyperglycemia gradually worsened. As she had endogenous insulin deficiency and tested positive for insulin autoantibody (IAA), insulin therapy was initiated. Few studies have investigated GADA-negative patients with slowly progressive type 1 diabetes mellitus (SPT1D). Our IAA-positive SPT1D patient progressed from the clinical onset of diabetes mellitus to starting insulin therapy relatively quickly (1.5 years), similarly to other previously reported non-obese patients with GADA-positive SPT1D.
Abstract Acute myocarditis is a non-ischemic inflammatory disease of the myocardium for which there is currently no specific treatment. We have previously shown that mesenchymal stem cells (MSC) can ...ameliorate heart injury during acute ischemia and in dilated cardiomyopathy; however, the therapeutic potential in acute myocarditis is unclear. In this study, we investigated the ability of MSC to attenuate myocardial injury and dysfunction during the acute phase of experimental myocarditis. Ten-week-old male Lewis rats were injected with porcine myosin to induce myocarditis. Cultured MSC (3 × 106 cells/rat) were injected intravenously 7 days after myosin injection. At 3 weeks, myosin injection resulted in severe inflammation and significant deterioration of cardiac function. MSC transplantation attenuated increases in CD68-positive inflammatory cells and monocyte chemoattractant protein-1 (MCP-1) expression in myocardium, and improved cardiac function in this model. Furthermore, myocardial capillary density was higher in myocarditis tissue, and was further increased by MSC transplantation. In vitro , cultured adult rat cardiomyocytes were injured in response to MCP-1, whereas this effect was attenuated by MSC-derived conditioned medium, suggesting cardioprotective effects of MSC acting in a paracrine manner. MSC transplantation attenuated myocardial injury and dysfunction in a rat model of acute myocarditis, at least in part through paracrine effects of MSC.
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