The Study on the Development of Atherosclerotic Lesions in the WHHL Rabbits : The Comparison of the Coronary and Aortic Atherosclerosis

粥状動脈硬化の発生過程において, その主要な細胞構成成分として平滑筋細胞, マクロファージが, 細胞外構成成分としてコラーゲンがあげられる。本研究では, WHHLウサギを用い冠動脈と大動脈の病変について, これらの構成成分を中心に進展度別にその細胞数や沈着量の比較検討を行った。初期病変においては, 冠動脈では平滑筋細胞の増殖が優位であり, 大動脈ではマクロファージの増殖が優位であった。また, 初期では, アポトーシスはほとんど認められなかったが, 進行期でアポトーシスの関与している可能性があった。コラーゲンは初期病変では, I型, III型, IV型を内膜全体に認めた。進行するにつれV型を全層にVI型を深層に認めた。コラーゲンの分布に冠動脈と大動脈では各段階で明らかな差は認めなかった。このことから粥状動脈硬化性病変の発生過程において冠動脈と大動脈では平滑筋細胞とマクロファージの役割に違いがあることが示唆された。すなわち初期に冠動脈では平滑筋細胞の増殖が優位であり, 大動脈ではマクロファージの増殖が優位であったが, 病変の進行と共に両者は似た像を呈したことから, 冠動脈と大動脈では初期に平滑筋細胞とマクロファージの役割に違いがあることが重要な点であると考えられた。The differences in development of atherosclerosis between coronary artery and aorta in Watanabe heritable hyperlipidemic rabbits were investigated by immunohistochemical stained method. The areas of the major lesional components, smooth muscle cells, macrophages, collagen fibers, and extracellular lipid deposits, were measured with a color image analyzer. In the atherosclerotic lesions of the WHHL rabbit, at the early atherosclerotic stages, the smooth muscle cells were predominant in the coronary lesion and the macrophages were predominant in the aortic lesion. As for both, it presented a resembling image with the progress of the lesions. PCNA, the cell growth indicator, was stained in smooth muscle cells and macrophages of atherosclerotic lesions of coronary artery and aorta. In aorta, collagen type I, III, IV, V were stained at the lesions in early stage, and collagen type VI was stained in deep phase with the progress of the lesions. As the progress of atherosclerotic lesions, the apoptotic cells were increased in the both atherosclerotic lesions. These results were suggested that there was a difference in the role of the smooth muscle cells and the macrophages at the coronary artery and the aorta in the process of the development of atherosclerotic lesions

Different Role of Macrophages and Vascular Smooth Muscle Cells in Atherosclerotic Lesions of Watanabe Heritable Hyperlipidemic (WHHL) Rabbit between Aorta and Coronary Artery

The WHHL rabbit is often used to investigate the pathogenesis of atherosclerosis. Here we elucidate differences in the pathogenesis of atherosclerosis in coronary arteries (CA) and aorta (AO) by comparing dynamic changes in the distribution of vascular smooth muscle cells (VSMCs), macrophages, collagen and extracellular deposit during atherosclerosis in WHHL rabbits. Sections of CA and AO were obtained at the early, transitional and advanced stages of atherosclerosis and stained with hematoxilin-eosin, elastica van Gieson, antibodies specific to the above components, antibody against proliferated cell nuclear antigen (PCNA) and TUNEL. The relative areas of VSMCs, macrophages, collagen fibers and lipid deposits were calculated. In the early-stage atherosclerosis, VSMCs were predominant in CA lesions, while macrophages were predominant in AO lesions. PCNA-positive VSMCs and macrophages were noted in early-stage atherosclerosis in CA and AO. Collagen type I, III-V fibers were present in early-stage lesions of the AO, while type VI increased in the deep layer during the progression of atherosclerosis. The proportion of apoptotic cells increased in CA and AO lesions with the progression in atherosclerosis. Our results showed differences in the distribution patterns of VSMCs and macrophages at various stages of atherosclerosis in CA and AO of WHHL rabbits

Effects of anti-malarial drugs on the electrocardiographic QT interval modelled in the isolated perfused guinea pig heart system

<p>Abstract</p> <p>Background</p> <p>Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart.</p> <p>Methods</p> <p>The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 μM), quinine (0.3 - 2.4 μM), halofantrine (0.1 - 2.0 μM) and mefloquine (0.1 - 2.0 μM). The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects.</p> <p>Results</p> <p>Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC₅₀values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine < quinine ≈ halofantrine.</p> <p>Conclusions</p> <p>In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity.</p

Evaluation of the Usefulness of a Simple Touch-panel Method for the Screening of Dementia

In clinical settings, Hasegawa's dementia scale, revised (HDS-R), and the mini-mental state examination (MMSE) are widely employed as simple mental function tests useful for the diagnosis of dementia. In recent years, for the early diagnosis of dementia, a simple computerized touch panel-type screening test (touch panel-type screening test), called the "forgetfulness consultation program" (Nihon Kohden Corp.), has been developed. We performed dementia screening using this touch panel-type screening test in 95 elderly subjects, and evaluated its usefulness in comparison with HDS-R or MMSE. The results of evaluation using the touch panel-type screening test were significantly correlated with those using HDS-R and MMSE in the elderly subjects. This touch panel-type screening test was not time-consuming (about 3 min) since it includes only a small number of test items. It could also be performed solely by the examinee, and so was free from examinerrelated bias. Therefore, this method may be very useful for the diagnosis of dementia and evaluation of its severity