Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

<sec>
<title>Objective:</title>
n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on atherosclerosis. Although specific salutary actions have been reported, the detailed distribution of n-3 polyunsaturated fatty acids in plaque and their relevance in disease progression are unclear. Our aim was to assess the pharmacodynamics of EPA and DHA and their metabolites in atherosclerotic plaques.


</sec>
<sec>
<title>Approach and Results:</title>

Apolipoprotein E-deficient (Apoe
^−/−
) mice were fed a Western diet supplemented with EPA (1%, w/w) or DHA (1%, w/w) for 3 weeks. Imaging mass spectrometry analyses were performed in the aortic root and arch of the Apoe
^−/−
mice to evaluate the distribution of EPA, DHA, their metabolites and the lipids containing EPA or DHA in the plaques. Liquid chromatography-mass spectrometry and histological analysis were also performed. The intima-media thickness of atherosclerotic plaque decreased in plaques containing free EPA and EPAs attached with several lipids. EPA was distributed more densely in the thin-cap plaques than in the thick-cap plaques, while DHA was more evenly distributed. In the aortic root, the distribution of total EPA level and cholesteryl esters containing EPA followed a concentration gradient from the vascular endothelium to the media. In the aortic arch, free EPA and 12-hydroxy-EPA colocalized with M2 macrophage.



</sec>
<sec>
<title>Conclusions:</title>
Administered EPA tends to be incorporated from the vascular lumen side and preferentially taken into the thin-cap plaque.


</sec>

DOI： 10.1161/atvbaha.119.313093

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ajpath.2018.05.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Toxicologic Pathology  

<p> Patchy thickening and reddish discoloration of active hair growth areas of skin in rabbits are occasionally found, and this gross feature could affect precise evaluation when conducting a dermal irritation test. Since little is known about the mechanism of this phenomenon, we examined the dorsal skin of New Zealand White rabbits morphologically and immunohistochemically in order to identify the possible mechanism responsible for developing these skin changes in relation to the hair cycle. Skin samples from 4 rabbits were divided into three groups (5 samples/group) based on their macroscopic characteristics: a thickened skin, erythematous skin, and smooth skin group. Histomorphological examination revealed that the percentage of hair follicles in the anagen phase, hair follicle length, hair follicle area, and proliferating cell nuclear antigen-positive cells in the hair follicles were greater in the thickened skin and erythematous skin groups than in the smooth skin group. Unlike mice and rats, the dermis was nearly adjacent to the muscular layer with a thin hypodermis, and the whole lengths of hair follicles in the anagen phase were located in the dermis in the rabbit skin. These results suggest that large hair follicles in the anagen phase compressed the surrounding dermis; therefore, the skin was grossly raised and showed thickening. A higher number of CD31-positive blood vessels, suggesting the occurrence of angiogenesis, was observed around the hair follicles in the erythematous skin group, and they seemed to affect the reddish discoloration of skin noted grossly.</p>

DOI： 10.1293/tox.2017-0033

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Toxicologic Pathology  

DOI： 10.1293/tox.2015-0054

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Pharmaceutical Society of Japan  

The purpose of this study was to characterize the non-aqueous nanosuspension of a hydrophilic drug prepared by bead milling for cutaneous application. Riboflavin was used as the model hydrophilic drug. The non-aqueous nanosuspensions were prepared by grinding riboflavin with zirconia beads using eight non-aqueous bases. The mean particle size of riboflavin in the suspensions ranged from 206 to 469 nm, as determined by the dynamic light scattering method. Among the well-dispersed samples, riboflavin nanosuspension prepared in oleic acid was selected for evaluation of the drug permeability through rat skin. The cumulative amount and permeation rate of riboflavin from the nanosuspension were approximately three times higher than those for unprocessed riboflavin in oleic acid. Fluorescence imaging of the riboflavin nanosuspension suggested improved penetration of riboflavin into the stratum corneum. Furthermore, the addition of polysorbate 65 or polyglyceryl-6 polyricinoleate to the nanosuspension prepared in oleic acid markedly improved the riboflavin dispersibility. These results show that the preparation of a nanosuspension in a non-aqueous base by bead milling is one of the simple methods to improve the skin permeability of hydrophilic drugs.

DOI： 10.1248/cpb.c14-00641

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

SCOPE: It is increasingly accepted that chronic inflammation is a feature of obesity. Obesity-induced inflammation triggers enhanced recruitment of macrophages into the adipose tissue. Depending on their phenotype, macrophages can be designated either as pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages. We have therefore investigated the effects of taurine, a sulfated amino acid that is abundant in seafood, on obesity-related inflammation. METHODS AND RESULTS: In high-fat diet fed C57BL/6J mice, taurine treatment reduced the infiltration of macrophages and promoted an M2-like phenotype of macrophages in adipose tissues. In addition, taurine decreased the production of inflammatory cytokines, and suppressed the development of hyperglycemia in diet-induced obese mice. Moreover, in vitro experiments that involved bone marrow derived macrophages indicated that taurine treatment induced alternative M2 macrophage activation, and its chloride, taurine chloramines, inhibited classical M1 macrophage activation. CONCLUSION: Our findings indicate that taurine treatment attenuates the infiltration of adipose tissue by macrophages and modulates the phenotype of macrophages, which suggest that taurine is a valuable food constituent with a potential to attenuate chronic inflammation in adipose tissue and improve obesity-related insulin resistance.

DOI： 10.1002/mnfr.201300150

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.bbalip.2011.12.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The American Association of Immunologists  

DOI： 10.4049/jimmunol.1101537

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1600-0625.2011.01337.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Association for Laboratory Animal Science  

Sprague-Dawley (SD) rats are broadly used in preclinical studies for drug development, so a lot of information for the rats can be obtained especially from pharmacokinetic, pharmacological and toxicological studies. The purpose of this study was to clarify whether SD rat skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate, and flurbiprofen, through human skin and SD rat skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs through human skin and SD rat skin were determined, and their variations were evaluated. The inter-individual variations in SD rat skin permeability of the three model drugs were much lower than that in human skin permeability, although the permeation rates of the three model drugs through the SD rat skin were about twice those through human skin. In addition, no difference in the skin permeability coefficients of the three model drugs was obtained between fresh SD rat skin and frozen SD rat skin. The markedly smaller variation in the permeability through SD rat skin compared with that through human skin indicated that in vitro permeation studies using SD rat skin would be especially useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability.<br>

DOI： 10.1538/expanim.60.373

CiNii Books

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.exer.2011.04.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Pharmaceutical Society of Japan  

The purpose of this study was to evaluate the variations in the in vitro Yucatan micropig (YMP) skin permeabilities of drugs and to clarify whether YMP skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate and flurbiprofen, through YMP skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs were determined, and their variations were evaluated. The inter-individual variations in YMP skin permeability for the three model drugs were smaller than that in human skin permeability, and the permeation rates of the three model drugs through the YMP skin were approximately half that through human skin. In addition, the intra-individual variations in YMP skin permeability for nicorandil and flurbiprofen were much smaller than the inter-individual variations in YMP skin. The inter- and intra-regional variations in YMP skin permeability were very small. The markedly smaller variation in the permeability through YMP skin as compared with that through human skin indicated that in vitro permeation studies using YMP skin would be particularly useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability.

DOI： 10.1248/bpb.34.555

CiNii Books

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.vph.2010.07.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as well as severe aortic lesions with lipid droplets. An immunohistochemical study showed that the lesion consisted of mainly lipid-rich macrophages and T cells. Sixty-day taurine supplementation (1% in drinking tap water) to LAP quails fed high-cholesterol diet containing 1% cholesterol significantly reduced serum non-HDL cholesterol from 4,549 to 2,350 mg/dl. The serum triglyceride level also decreased after taurine supplementation from 703 to 392 mg/dl. Although the HDL cholesterol level significantly decreased due to the high-cholesterol diet, it recovered to the control level fed a regular diet in response to taurine. Bile acid production was stimulated and hepatic cholesterol was reduced by taurine supplementation. A quantitative analysis using aortic cross-sections showed that areas of oil-red O positive lipid accumulation significantly decreased by 74% after taurine supplementation. These results demonstrated the lipid-lowering and anti-atherosclerotic effects of taurine in a diet-induced hyperlipidemic LAP quail model. The prevention of atherosclerosis by taurine is mainly attributed to an improvement in the serum cholesterol and triglyceride levels, which may be related to changes in the hepatic cholesterol metabolism.

DOI： 10.1007/s00726-009-0247-6

PubMed

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Other Link： http://link.springer.com/article/10.1007/s00726-009-0247-6/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.brainres.2009.06.050

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Thoracic Society  

DOI： 10.1164/rccm.200806-905oc

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/jgm.1091

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1600-0625.2007.00548.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1365-2133.2007.07882.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ejphar.2007.01.080

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1600-0625.2006.00540.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.plefa.2006.11.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ejphar.2006.10.064

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1365-2133.2006.07636.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Clarivate Analytics (US)  

DOI： 10.1358/mf.2006.28.9.1037493

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.lfs.2006.09.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1600-0625.2006.00480.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1600-0625.2006.00438.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.str.0000217398.37075.07

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Pharmacological Society  

DOI： 10.1254/jphs.fp0050564

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Pharmacological Society  

DOI： 10.1254/jphs.fp0040574

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.lfs.2004.07.022

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/intimm/dxh151

CiNii Books

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

1. The effects of two naturally occurring substances, namely taurine and catechins, on serum cholesterol levels and on the progression of atherosclerotic lesions were evaluated using spontaneously hyperlipidaemic (SHL) mice as an animal model of atherogenesis. 2. Twelve weeks treatment of SHL mice with taurine (1% in drinking water) significantly elevated serum high-density lipoprotein-cholesterol (HDL-C) levels without affecting levels of low-density lipoprotein- and very low-density lipoprotein-cholesterol. In addition, taurine suppressed the development of atherosclerotic lesions by 29%, as determined by oil red O-stained areas in cross-sections of the aorta. 3. In contrast, 12 weeks treatment with a catechin mixture had no apparent effect on serum cholesterol levels and on the progression of atherosclerosis. 4. Serum levels of thiobarbituric acid-reactive substances, an index of oxidized substances, significantly decreased from 9.6 to 6.7 nmol/mL following taurine treatment. 5. We suggest that retardation of atherosclerosis by taurine in SHL mice may be related to decreases in oxidized substances and increases in serum HDL-C levels.

DOI： 10.1046/j.1440-1681.2003.03828.x

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/eji.200323455

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/s0006-8993(02)03611-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

While the hypocholesterolemic effects of taurine have extensively been studied using experimental animals, the anti-atherosclerotic effects of taurine have been given less attention. We examined the effect of taurine on atherosclerotic lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits. Treatment of WHHL rabbits with taurine (0.3% in drinking tap water) for 24 weeks decreased aortic lesions by 31%, estimated as intimal thickening. Taurine significantly decreased cholesteryl ester content of aortic arch, thoracic aorta, and abdominal aorta by 35, 43, and 54%, respectively. Concomitantly, activity of acyl-CoA:cholesterol acyltransferase (ACAT), an enzyme responsible for cholesterol esterification, was also significantly decreased. Immunohistochemical analysis revealed decreased macrophages in the intima of taurine-treated rabbits. Taurine had no apparent effect on blood pressure and serum cholesterol levels. Contents of thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, was reduced in serum and aorta by 29 and 50%, respectively, when taurine was ingested. In addition, LDL from taurine-treated rabbits was resistant to copper-induced oxidative modification. These results revealed that taurine prevents development of atherosclerosis and that the anti-atherosclerotic effects of taurine are independent of serum cholesterol levels. The anti-oxidant action of taurine may be involved in inhibiting atherosclerosis in these rabbits.

DOI： 10.1016/s0021-9150(01)00764-x

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1074/jbc.m110703200

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

DOI： 10.5551/jat1994.8.71

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/s0021-9150(00)00743-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Department of Anatomy Keio University School of Medicine  

DOI： 10.2535/ofaj1936.77.5_181

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s004410050817

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Other Link： http://link.springer.com/article/10.1007/s004410050817/fulltext.html

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/oxfordjournals.jmicro.a023495

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Department of Anatomy Keio University School of Medicine  

DOI： 10.2535/ofaj1936.73.4_161

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/bf00414178

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Other Link： http://link.springer.com/article/10.1007/BF00414178/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/bf00354784

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Other Link： http://link.springer.com/article/10.1007/BF00354784/fulltext.html

Event date： 2023.3

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