Water is essential to life processes and has a number of significant functions. The ingredients of drinking water as well as nutrients in foodstuffs are now considered important to people's health. Deep-sea water in particular has started to receive attention for its rich inorganic nutrients such as Mg, Ca, and K 1,2) which are due mainly to less photosynthesis of plant plankton and much organic decomposition. In addition to the beneficial effects of these minerals on the cardiovascular system, unknown effects of some ultratrace elements or unknown substances in deep-sea water may be found in future. Some scientific evidences of therapeutic or preventive effects of deep-sea water have been reported recently. Deepsea water improved mineral imbalances and atopic eczema/ dermatitis syndrome in humans 2) and was effective in the prevention of hyperlipidemia and atherosclerosis in cholesterol-fed rabbits. 3,4) We expect that the continuous intake of deep-sea water could prevent hypertension as well as hypercholesterolemia, because investigators have revealed that oral supplementation of calcium 5,6) or magnesium 7,8) to hypertensive patients lowered blood pressure in addition to reducing the serum total cholesterol level. 7)Hypercholesterolemia and hypertension occur due to genetic as well as dietary factors. The Kurosawa and KusanagiHypercholesterolemic (KHC) rabbit is an animal model of spontaneous hypercholesterolemia (Type IIa) and atherosclerosis established by inbreeding a mutant of the Japanese White rabbit discovered by Japan Laboratory Animals, Inc. in 1985.9) The KHC rabbit is deficient in LDL-receptors in the liver and shows an abnormally increased LDL-cholesterol level without unusual deposits of fat in some organs.9) Atherosclerosis develops in the aortic arch and around bifurcations of the main branch arteries by the age of 3 months.9) We also reported previously that young adult KHC rabbits aged 10-12 months showed mild hypertension compared to agematched normal rabbits in addition to hypercholesterolemia, though atherosclerotic lesions were relatively in the earlystage. 10,11) The mild hypertension is thought to be independent of hypercholesterolemia.11) Intervention of either hypercholesterolemia or hypertension is considered to be inadequate to prevent progression of atherosclerosis and related cardiovascular events if hypertension and hypercholesterolemia coexist.12) Ca and Mg in deep-sea water could suppress absorption of cholesterol in the small intestine in cholesterol-fed rabbits, which might contribute to anti-hypercholesterolemic action of deep-sea water.3,4) Therefore, it is appropriate to use spontaneous hypercholesterolemic rabbits.In the present study, we investigated the effect of the intake of refined deep-sea water at a degree of hardness of 1000 for 6 months on hypercholesterolemia and mild hypertension in KHC rabbits aged 4 months, at which time atherosclerosis starts to occur in the ascending aorta and around orifices of branch arteries, by measuring serum and plasma biochemical par...

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In a previous study, we isolated the inhibitory peptide (P4 peptide, Gly-Phe-Hyp-Gly-Thr-Hyp-Gly-Leu-Hyp-Gly-Phe) for angiotensin I-converting enzyme (ACE) from chicken breast muscle extract possessing hypotensive activity for spontaneously hypertensive rats (SHRs). This study was performed to elucidate the peptide's action mechanisms of inhibiting ACE. Intravenous administration of synthetic P4 peptide resulted in significant drops in the blood pressures of SHRs. As Dixon plots indicate, the P4 peptide showed high affinity toward ACE (K(i) = 11.48 microM) and only 10% of the total amount of the P4 peptide was decomposed. The analyses of the relationship between the ACE inhibitory activity and structure of the P4 peptide clarified that Hyp-Gly-Leu-Hyp-Gly-Phe showed a stronger activity (IC50 = 10 microM) than the P4 peptide (IC50 = 46 microM). When Phe at the C-terminus of the P4 peptide was deleted, IC50 changed to 25000 microM, indicating that Phe at the C-terminus of the peptide is very important for ACE inhibitory activity.

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A rare case of reactive lymphoid hyperplasia (RLH) of the liver in a 75-year-old woman admitted to hospital for surgical treatment of gastric, caecal and colon carcinomas is described here. Two nodular lesions in the left and right lobes of the liver were clinically diagnosed as metastatic tumours by computed tomography of the abdomen. A demarcating grey-white mass of size 1.4 cm was observed in a partially resected liver specimen. On examining the lesion microscopically, it was found to be composed of hyperplastic lymphoid follicles, lymphocytes, plasma cells, other inflammatory cells and interlaced hyalinised fibrous tissues. In the portal tracts around the lesion, chronic inflammatory cell infiltrates were seen, but no interface hepatitis or lymphoid follicle was observed. No evidence of monoclonality was observed by immunohistochemistry for B and T cell markers, in situ hybridisation for k and l light chains, and polymerase chain reaction analysis of immunoglobulin heavy chains or T cell receptor b and c gene rearrangements. Bcl-2 immunoreactivity was not observed in the germinal centre. EpsteinBarr virus (EBV) antigen (latent membrane protein-1) and EBV-encoded small RNAs were not detected. A proliferation neither of myofibroblasts nor of cells positive for follicular dendritic cell markers was observed. RLH, formerly known as pseudolymphoma, has been reported of the liver in only 14 cases and is considered to be a differential diagnosis of small nodular lesions of the liver. That RLH has an inflammatory reactive nature, not a neoplastic disposition, and that EBV does not participate in the pathogenesis of RLH is supported by this case. P seudolymphoma was first defined in the lung by Saltzstein as a lymphocytic tumour associated with inflammation and with no evidence of systemic dissemination.1 Subsequently, these apparently benign tumours were shown to be clonal proliferative lesions that could possibly develop into lymphoma. The term reactive lymphoid hyperplasia (RLH) is used for true benign lymphocytic tumour-like lesions with polyclonal features. RLH has been reported in various organs, but there have been only 14 cases reported of RLH of the liver.2-13 Here, we report an additional case of RLH of the liver and review the literature. CASE REPORTA 75-year-old woman was admitted to hospital for surgical treatment of gastric, caecal and colon carcinomas. She had no fever. We observed no evidence of a predisposing factor for steatohepatitis, such as obesity, diabetes mellitus and hyperlipidaemia, and the patient had no history of intake of drugs that caused hepatitis. Laboratory data showed no leucocytosis and negative results for hepatitis B virus surface antigen, anti-hepatitis C virus antibodies, antinuclear antibodies and antimitochondrial antibodies. Immunoglobulin levels were within the normal range. On computed tomography of the abdomen, two similar nodular lesions in the left and right lobes of the liver were observed. Both tumours were preoperatively diagnosed to be metastatic. Distal gastrectomy...

Pulse wave velocity (PWV) has been used clinically as a direct measure of arterial stiffness. We investigated the inhibitory effects of defatted safflower seed extract (SSE) and serotonin derivatives (N-(p-coumaroyl)serotonin, N-feruloylserotonin; CS+FS), which are the active components in SSE, on hypercholesterolemia and atherosclerosis, using PWV in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. SSE and CS+FS were supplemented with a commercial diet containing 0.5% cholesterol for 8 weeks in male KHC rabbits, aged 2 months. Pulse waves were recorded at different aortic positions using two catheters with micromanometers under pentobarbital anesthesia. The atherosclerotic lesioned area in the aorta was significantly reduced in the SSE and CS+FS groups, without significant changes in serum cholesterol and triglyceride levels among the three groups after supplementation. Local PWV (LPWV) in the middle thoracic and distal abdominal aortas was significantly smaller in the SSE and CS+FS groups than in the control group. PWV in the entire aorta was also significantly lower in the SSE and CS+FS groups, compared with that in the control group. Pressure-strain elastic modulus, an index of wall distensibility, was significantly lower in the middle thoracic and middle abdominal aortas in the SSE and CS+FS groups than in the control group. Wall thickness was also significantly smaller in the middle thoracic aorta in the SSE and CS+FS groups compared with that in the control group. Serotonin derivatives inhibited the progress of atherosclerosis and ameliorated wall distensibility, which contributed, in part, to the lowering of LPWV. Serotonin derivatives may be beneficial in improving vascular distensibility and in reducing cardiovascular risk.

Postnatal changes in the rheological properties of the aortic wall were investigated in relation to morphological development of the wall in Sprague-Dawley (SD) rats at 3, 8 and 20 weeks old. The mechanical tensile characteristics of the longitudinal wall strip excised from the proximal thoracic aorta were assessed with stress-strain and stress-relaxation tests. Wall tension in the low and medium strain ranges was significantly lower in 3-week-old rats than in 8-week-old rats and in 8-week-old rats than in 20-week-old rats. Wall stress was significantly lower in 3-week-old rats than in 8- and 20-week-old rats mainly in the medium strain range, but was significantly greater in 3-week-old rats than in 8- and 20-week-old rats in the high strain range. The value of incremental elastic modulus at 3 weeks old was significantly smaller than that at 8 and 20 weeks old at a strain of 0.25 and significantly larger than that at 8 and 20 weeks old at a strain of 0.50. The value of relaxation strength at 5 min after the stretching was significantly greater at 3 weeks old than that at 8 and 20 weeks old. The wall was viscoelastic in the low and medium strain ranges at 3 weeks though large wall stress was generated in the high strain range. Histological investigation revealed that the smooth muscle layer, fine elastin fiber connecting thick elastin fibers and wall thickness were thin at 3 weeks old in comparison with those at 8 and 20 weeks old, though there was no significant difference in number of nuclei of the smooth muscle cells among the three age groups. Changes in the tensile characteristics of the wall reflected well those of the microstructure of the wall with growth. The rheological properties and microstructure of the aortic wall were close to maturation at 8 weeks in SD rats.