Nozomu Tamai

EFFECTS OF DEHYDROEPIANDROSTERONE ON MITOGEN-ACTIVATED PROTEIN KINASE IN HUMAN AORTIC SMOOTH MUSCLE CELLS

The objective of the present study was to determine whether dehydroepiandrosterone (DHEA) modifies growth factor-induced mitogen-activated protein kinase (MAPK) activation, based on our previous study demonstrating that DHEA attenuates fetal calf serum-induced proliferation in human male aortic smooth muscle cells (human male aortic SMCs). Human male aortic SMCs were used for this study. Platelet-derived growth factor-BB (PDGF-BB), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), but not insulin-like growth factor-1 (IGF-1), stimulated MAPK activity. Only MAPK activation induced by PDGF-BB was reduced by pretreatment with DHEA, although DHEA did not affect the MAPK activation induced by EGF or bFGF. The basal and PDGF-stimulated MAPK activity were decreased by two types of cyclic AMP (cAMP) elevating agents and increased by cAMP-dependent protein kinase (PKA) inhibitor in human male aortic SMCs, suggesting that cAMP regulates MAPK negatively. The intracellular cAMP was increased by PDGF-BB. The increase of cAMP by PDGF-BB was augmented by pretreatment with DHEA, although DHEA alone did not affect cAMP. Neither EGF nor bFGF affected cAMP with and without DHEA pretreatment. Secretion of PGE2 induced by PDGF was augmented by pretreatment with DHEA. Stimulatory effects of DHEA on the production of PGE2 and cAMP were partially canceled by aromatase inhibitor and completely canceled by indomethacin or selective inhibitor of cyclooxygenase-2. These results suggest that DHEA inhibited MAPK activation induced by PDGF-BB via PGE2 overproduction and subsequent cAMP-dependent pathway in human male aortic SMCs.

Resolution of Left Ventricular Thrombus Secondary to Tachycardia-Induced Heart Failure with Rivaroxaban

A 42-year-old man was admitted to our hospital because of lumbago and tachycardia-induced heart failure. Transthoracic echocardiography revealed impaired left ventricular function and a ball mass of thrombus in the left ventricle (LV). He was found to have systemic embolism in the spleen, kidneys, brain, and limbs. The patient was treated with limb thrombectomy followed by anticoagulation. Seven days after the direct factor Xa inhibitor, rivaroxaban, was initiated, transthoracic echocardiography was repeated, revealing disappearance of the LV thrombus without any clinical signs of cardiogenic embolism. His heart failure responded well and the LV wall motion had improved. This case suggests rivaroxaban has fibrinolytic effects on thrombi even in the LV.

Effects of vitamin C and vitamin E on plasma levels of lipid hydroperoxides and thiobarbituric acid reactive substance in humans

Abstract A study was conducted to investigate the effects of vitamin C and vitamin E on plasma levels of lipid hydroperoxides (LPO) and thio-barbituric acid reactive substance (TBARS) in human volunteers to identify the step in the lipid peroxidation cascade at which these vitamins act. Forty subjects (20 men and 20 women) were randomly assigned to receive either vitamin C or vitamin E. Twenty subjects received 500 mg of vitamin C daily for 4 weeks, and 20 subjects received 300 mg of vitamin E daily for 4 weeks. Blood samples were collected before and 4 weeks after vitamin treatment, in the morning, after the subjects had fasted for 12 hours. Plasma levels of LPO and TBARS were determined. Plasma levels of lipids, apolipoproteins, vitamin C, and vitamin E were also measured. Vitamin C significantly reduced plasma levels of LPO and TBARS. Vitamin E significantly increased plasma levels of LPO and significantly reduced plasma levels of TBARS. Plasma concentrations of vitamin C and vitamin E significantly increased after 4 weeks of vitamin treatment. There were no significant changes in the plasma levels of lipids except LPO, TBARS, and apolipoproteins. From these results, it was concluded that vitamin C reduced LPO and TBARS levels, and vitamin E increased LPO levels and reduced TBARS levels.

Strong synergistic anti-peroxidative effects of HDL3 and ascorbic acid against copper-catalyzed LDL peroxidation

The aim of this study was to investigate the effects of high density lipoprotein 3 (HDL3) and ascorbic acid (AsA) in combination on copper-catalyzed low density lipoprotein (LDL) peroxidation. LDL and HDL3 were isolated from sera of healthy volunteers. LDL protein, 200 microg/ml, was incubated in phosphate-buffered saline (PBS) containing 2.5 microM CuSO4 in the absence or presence of AsA, with HDL3 protein alone, or with coincubation of HDL3, 200 microg/ml, and AsA, 20 microg/ml, at 37 degrees C for up to 24 h. As a control, the same amount of control LDL protein was added to PBS. The protective effects of the HDL3 and AsA were examined by both electrophoresis and determination of the lipid hydroperoxide (LPO) level in each sample. The concentration of AsA was also measured in samples containing AsA. The coincubation of HDL3 and AsA exerts more powerful anti-peroxidative effects against copper-catalyzed LDL peroxidation, than either of these agents alone. In addition, AsA was retained in the media by the addition of HDL3. The findings suggest that there are strong synergistic anti-peroxidative effects of HDL3 and AsA and these two may act in concert in vivo to inhibit LDL peroxidation and thus exert an anti-atherosclerotic effect.

Ruptured plaque in a bare-metal stent 8 years after implantation—Comparison of IVUS and OCT findings

Optical coherence tomography (OCT) and intravascular ultrasound tomography (IVUS) findings in a patient with very late in-stent restenosis that was manifested as acute coronary syndrome 8 years after bare-metal stent implantation are presented. This case clearly shows the disruption of thin fibrous cap associated with a white thrombus by OCT. A superficial high signal with deep attenuation by OCT, composing more than half of the plaque, was expressed as heterogeneous tissue, mainly composed of echolucent lesion including outside the struts by IVUS. OCT was very useful, like it is for de novo vulnerable plaques, to evaluate vulnerable plaque that had formed in a previously implanted stent. On the other hand, tissue outside the stent struts could be visualized by IVUS. Combined use of OCT and IVUS was useful for understanding the plaque characteristics of ruptured vulnerable plaque that had formed in a previously implanted bare-metal stent even after stabilization of neointimal hyperplasia.

A case of idiopathic giant cell myocarditis with a past history of sarcoidosis

A 70-year-old woman with back pain and breathlessness was referred to our hospital for suspected myocardial infarction. Coronary angiogram was normal and endomyocardial biopsy showed inflammatory cell infiltrates consisting of eosinophils and multinucleated giant cells. The clinical course was hemodynamically fulminant, but steroid therapy improved the cardiac function. Interestingly, this patient had a past history of sarcoidosis. We diagnosed this case with idiopathic giant cell myocarditis (IGCM) from its clinical course. However, whether IGCM and cardiac sarcoidosis belong to the same histological entity has been debated. This case is important with respect to the pathogenic association between these two disorders. <Learning objective: Both idiopathic giant cell myocarditis and cardiac sarcoidosis are known to show multinucleated giant cell infiltration in the myocardium histologically. In particular, idiopathic giant cell myocarditis is a severe and fulminant disease, making its early diagnosis and treatment important. Although it is difficult to diagnose these diseases, endomyocardial biopsy is useful to decide the treatment strategy in such disorders that may assume a fulminant course.>.

Improvement in hyperchylomicronemia, transient deficiency in lipoprotein lipase and hepatic triglyceride lipase activity, and diabetes mellitus produced by pravastatin and bezafibrate: a case report

Abstract A 50-year-old Japanese woman with type IV hyperlipidemia was placed on a low-fat diet. This regimen was minimally effective, so lipid-lowering drugs (clinofibrate [600 mg/d] and niceritrol [750 mg/d]) were added. However, hypertriglyceridemia worsened and diabetes mellitus appeared. She then developed xanthomatous eruptions, type V hyperlipidemia, reduced postherapin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activity. She was admitted to the hospital, and previous drug therapy was stopped. Dietary control and administration of the antihyperlipidemic agents pravastatin (10 mg/d) and bazafibrate (400 mg/d) led to the gradual recovery of postheparin plasma LPL and HTGL activity, conversion of type V hyperlipidemia to type IV hyperlipidemia, the disappearance of xanthomatous eruptions, and concurrent improvement in diabetes mellitus.