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Background and aims Nonalcoholic steatohepatitis (NASH) is linked to an increased risk of cardiovascular disease, regardless of the risk factors in metabolic syndrome. However, the intermediary factors between NASH and cardiovascular disease are still unknown. A previous study revealed that serum and hepatic bile acid (BA) levels are increased in some NASH patients. We aimed to examine whether NASH and cardiovascular disease were aggravated by BA using an animal model. Method and results From 10 to 18 weeks of age, SHRSP5/Dmcr rats divided into 3 groups were fed 3 types of high-fat and high-cholesterol (HFC) diets which were changed in the cholic acid (CA) concentration (0%, 2%, or 4%). The nitro oxide synthase inhibition (L-NAME) was administered intraperitoneally from 16 to 18 weeks of age. The 4% CA groups showed the worst LV dysfunction and myocardial fibrosis, and demonstrated severe hepatic fibrosis and lipid depositions. In addition, a large amount of lipid accumulation was observed in the aortas of the 4% CA group, and NFκB and VCAM-1 gene expression levels were increased. These findings were not seen in the 0% CA group. Conclusion In the SHRSP5/Dmcr rat model, NASH and cardiovascular disease were aggravated with increasing BAs concentrations in an HFC diet.

The non-alcoholic steatohepatitis (NASH) increases the cardiovascular risk regardless of risk factors in metabolic syndrome. The stroke-prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr), fed a high-fat and -cholesterol (HFC) diet and administered Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) presented NASH and cardiovascular disease. However, the intermediary factors between NASH and cardiovascular risk are still unknown. We investigated whether bile acids (BAs) play an intermediary role between NASH and cardiovascular disease in SHRSP5/Dmcr rats. SHRSP5/Dmcr rats divided into 2 groups were fed an SP (non-NASH group, n=7) or HFC diet (NASH group, n=10) for 8 weeks. L-NAME was administered intraperitoneally in the final 2 weeks. In the NASH group, total BA levels were increased in both serum and liver; they aggravated the endothelial dysfunction in aorta, which is the first step to atherosclerosis, and activated the gene expression levels of cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1) in coronary artery. In particular, the nuclear factor-kappa B (NFkB) was increased in the NASH group in the coronary endothelial cells activated by high BA levels. We demonstrated that liver BAs aggravated steatosis and fibrosis and serum BA accelerated arteriosclerosis and ischemic heart disease via the classical pathway of NFkB in the endothelial cells. BA metabolism disorder may be an intermediary factor between NASH and cardiovascular risk in SHRSP5/Dmcr rats.

Non‐alcoholic steatohepatitis (NASH) is linked to increased cardiovascular risk, independent of the broad spectrum of metabolic syndrome risk factors. Stroke‐prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr) fed a high‐fat and high‐cholesterol (HFC) diet developed hepatic lesions similar to those in human NASH pathology. These rats simultaneously developed lipid deposits in the mesenteric arteries, cardiac fibrosis, endothelial dysfunction and left ventricle (LV) diastolic dysfunction. However, the intermediary factors between NASH and cardiovascular disease are still unknown. We investigated whether NASH aggravates nitric oxide (NO) synthase inhibition‐induced arteriosclerosis in SHRSP5/Dmcr rats. Wistar Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 and fed the stroke‐prone (SP) or HFC diets for 8 weeks. To induce NO synthase inhibition, N(ω)‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME) mixed with drinking water was administered in the final 2 weeks. The NASH+L‐NAME group demonstrated the following characteristics related to arteriosclerosis and myocardial ischaemia: (a) LV systolic dysfunction with asynergy, (b) replacement fibrosis caused by the shedding of cardiomyocytes and (c) arterial lipid deposition and coronary occlusion secondary to endothelial dysfunction. These characteristics were not observed in the NASH or non‐NASH+L‐NAME groups. The SHRSP5/Dmcr rat model demonstrates that NASH significantly aggravates cardiovascular risk.

This paper analyzes the characteristics and effects of the Cape Town Convention, which provides legal protection for investors in relation to asset-based aircraft financing. Some countries lack credibility for investors, who believe that the protection level of creditor rights in the country differs before and after investment. This time inconsistency problem results in credit rationing. Airlines in such countries cannot access the credit market, particularly the international capital market. This paper first examines why developing countries have been suffering from a lack of credibility and from credit rationing, and then explores how the Convention resolves this problem. We focus on two devices: the white list system and the system of declarations. The former gives the contracting states incentive not to break the Convention. The latter is considered to promote the ratification of the Convention by potential contracting states. These devices enable the Convention to attract a number of states.

Japan has been engaged in providing technical training to improve the nursing care in developing countries, often by sending experts from Japan. This paper addresses the practical issues when such training is to be provided via live video using Internet. Three countries considered include, Mongolia, Nicaragua, and Sri Lanka. The paper discusses technical constraints and some practical solutions to overcome such constraints when conducting remote training via live streaming video connection from Japan, using Internet.1