Fujie Numano

Relationship between plasma insulin concentration and plasma remnant lipoprotein response to an oral fat load in patients with type 2 diabetes.

OBJECTIVES The goal of this study was to evaluate the relative effects of hyperglycemia and hyperinsulinemia on postprandial remnant lipoprotein (RLP) concentrations in newly diagnosed type 2 diabetics. BACKGROUND Increases in fasting RLP concentration have been described in type 2 diabetics, as well as in insulin-resistant nondiabetics. Given the atherogenicity of RLPs, we have extended these observations by assessing postprandial RLP concentrations and observing that hyperglycemia was necessary for the increase in RLP concentrations. METHODS Patients with type 2 diabetes were subdivided on the basis of their plasma insulin response to oral glucose into hyperinsulinemic (H-DM) and normoinsulinemic (N-DM) groups of 15 patients each. Plasma triglyceride (TG), RLP-TG and RLP cholesterol (RLP-C) concentrations were determined before and 2 and 4 h after an oral fat load in these patients and 10 control (CTL) subjects. RESULTS Plasma TG, RLP-TG and RLP-C concentrations peaked 2 h after the fat load in the CTL group, returning to baseline within 4 h. In contrast, concentrations of these variables increased throughout the 4-h study in both groups of patients with type 2 diabetes. Total integrated plasma RLP-TG and RLP-C responses above baseline after the oral fat load were significantly higher in the H-DM group compared with the CTL (p = 0.019 and 0.009, respectively) or N-DM (p = 0.026 and 0.029, respectively) groups. Post-heparin lipoprotein lipase activities and apo E phenotypes were similar in the H-DM and N-DM groups. CONCLUSIONS Remnant lipoprotein response to an oral fat load is significantly increased in hyperinsulinemic patients with type 2 diabetes. These changes may increase the risk of coronary heart disease in these individuals.

Microassay of cyclic nucleotides in vessel wall: I. Cyclic AMP

Abstract The levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in the aortic intima and media of man and other species were measured microbiochemically by Lowrys quantitative histochemical technique and Gilmans competitive protein binding assay. Rather high levels of cAMP were found in the intima of all species examined as compared with that in the media. The role of cAMP in intima is discussed in relation to atherogenesis.

Antiaggregative Aspirin Dosage at the Affected Vessel Wall

The present study, using patients with Thkayasus disease (pulseless disease), characterized by segmentally affected arterial lesions and stenotic conditions with a nonspecific inflammatory morbid condition, was designed to assess whether or not a low dose of aspirin can practically exert its preventive effect against the aggregation of platelets that have just passed along a rough-surfaced arterial wall. Twenty Japanese women with Takayasus disease were selected under the following criteria: (1) A unilateral upper extremity was angiographi cally confirmed to be affected with the disease, while the contralateral limb was almost normal. (2) Systolic blood pressure on the affected side was almost half that on the nonaffected side. (3) The patients showed neither a positive CRP nor an accentuated ESR. In these patients, mean plasma levels of TXB2 and 3 μM ADP-induced platelet aggregation in blood obtained from the affected side were 156.5±17.7 pg/ml, and 59.5 ±6.0%, respectively, which were significantly high as compared with 104.5±17.6 and 41.7±8.8%, respectively, in samples from the nonaffected side. Forty and eighty mg of aspirin per day administered to two randomly composed groups, respectively, showed an improvement in plate let aggregability and TXB2 levels on the nonaffected side. In the affected limbs, though 80 mg/day led to significant decreases in TXB2 levels (108.0 ±7.8 pg/ml, p < 0.05) and platelet aggregability (21.3±7.6%), the 40-mg regimen showed no significant reductions (134.6±9.4 pg/ml, 35.6±17.1%). Plasma levels of 6-keto PGF1α revealed no differences between 40- and 80-mg regimens, or between before and after treatment. These data suggest that a dosage of 80 mg of aspirin per day is effective for long-term treatment in preventing thrombus formation in surface-damaged blood vessels.

Effects of thromboxane A2 injection on the rabbit coronary artery: II. The production of infarcts in cholesterol-fed animals

Abstract The role of thromboxane A 2 (TXA 2 ) in ischemic heart disease was studied using atherosclerotic rabbits fed a diet of pellets containing 1% cholesterol for 3 months, with agematched rabbits as controls. Various combinations of 15–30 μg of prostaglandin H 2 (PGH 2 ) and 1–5 mg of microsome protein obtained from cow platelets were injected at the origin of the aortic arch through an indwelling catheter. With this method, plasma levels of thromboxane B 2 of femoral arterial blood were over 1000 pg/ml immediately after injection of 30 μg of PGH 2 and 5 mg of microsome. The normal control groups showed no ECG changes related to myocardial damage. On the contrary, all of the cholesterol-fed rabbits exhibited a typical ST elevation in II, III, a Vf , and/or precordial leads at 3–5 min after injection of the TXA 2 -generating mixture, as well as a decrease in blood pressure and heart rate. All of these rabbits died within 40 hr except one given a mixture of minimum doses of PGH 2 (15 μg) and cow platelet microsome (1 mg protein). In two rabbits, the Q wave was observed. Various irregular-sized ischemic areas were frequently noted in the left ventricle and/or septal walls of the heart in these cholesterol-fed rabbits, using hematoxylin-basic fuchsin-picric acid stain and stains for detection of phosphorylase, LDH, and SDH activities. Microthrombi were frequently detected in the small coronary vessels, mainly at the subendocardial area of the myocardium. Such findings were not evident in the control group. These data suggest a role for thromboxane A 2 in the damaged myocardium and an association with coronary atherosclerosis.

Antiplatelet Therapy for Atherosclerotic Disorders

Recent studies have revealed the important roles of platelets in atherogenesis via vascular injury. Our in vivo and in vitro studies clearly demonstrate that activated platelets directly inflict injury to vascular endothelial cells, which is associated with a decrease in intracellular cyclic AMP levels in vascular tissues. Antiplatelet therapy is clinically important not only for the prevention of thrombotic episodes but also for the prevention of vascular injury and atherosclerosis. A small dose of aspirin (80 mg) induces clinically hypoaggregativeness of platelets with concomitantly decreased levels of thromboxane A2 in plasma. Our clinical study involving more than 3 years of treatment with small doses of aspirin demonstrated favorable therapeutic effects characterized by hypoaggregation of platelets and increased levels of cAMP and 6-keto PGF1 alpha in plasma which will aid in the prevention of atherosclerosis.

Estrogen and hyperaggregability of platelets measured by the screen filtration pressure (SFP) method in Takayasu's disease.

Platelet aggregability in 10 females (32.2 ± 3.1 years) with Takayasu’s disease and 16 healthy males (31.7 ± 2.7 years) and 14 females (28.6 ± 2.8 years) was measured by the screen filtration pressure

PLASMA FREE FATTY ACID and ACUTE VASCULAR INJURY

One‐shot treatment of atherogenic substances, such as cholesterol, animal fat, adrenalin or cigarette smoking to animals induces “acute vascular injury” characterized histologically by swollen endothelial cells and edematous changes in subendothelial layer and upper part of media of aorta (Shimamoto et al., 1960), the cause of which is still unknown.

Treatment of Experimental and Human Atherosclerosis with Bradykinin-Antagonist, Pyridinolcarbamate: A Preliminary Report

At the beginning of this century there were three incurable lesions having dead spaces with an accumulation of dead subtances: gummatous in syphilis, caseous in tuberculosis, and atheromatous in atherosclerosis. The discovery of modern chemotherapeutic agents has enabled cures for the first two, but the problem of atherosclerosis remains to be solved.

PULMONARY FUNCTIONS IN TAKAYASU'S DISEASE

近年高安病における腕動脈病変が注員されている.われわれは45名の高安病患者につき肺シンチレ一ション検査を中心に膝病変を追求した.肺シンチ検査では33名(73%)に異常所見が認められ,内9名(20%)はlobar perfusion defect (PD) (1群), 14名(31%)はsegmental PD (II群)を示した,さらに,肺区域単位として病変が確認出来ない,いわゆるnansegmental PD (III群)を示した例が10名(22%)あり,異常所見が認められなかつたのは僅か12名(27%) (IV群)にすぎなかつた.この内8例にHssure signの存在を確認した.又,吸入肺シンチ, RIアンギオによりPDを示した区域での気管支動脈を介しての肺循環の存在を確認した.呼吸機能検査ではVC, %VC, %FVCは正常範囲内にあつたがMVV, %MVは低下, RV, RV/TLCの上昇が認められた.動脈血ガス分析ではPH7.44±0.01, Po2. 67.1±7.0mmHgと同年令域健康婦人値7.41±0.004, 90.9±3.0mmHgに比し有意の低値(P<0.01)が認められた.さらに血小板凝集能をscreen filtration pressure法にて測定すると肺シンチに異常所見のみられる3群では, 374±30mmHg (I), 413±38 (II), 371±37 (III)といずれも健康女子SFP値265±14mmHgに比し有意の高値を示し,血小板凝集能亢進機序の存在がうかがわれた.肺シソチで異常所見のないIV群は256±40mmHgで正常値内であつた.以上の検索より,自覚症状は少ないが高安病患者には肺動脈病変がかなり高頻度に出現していること,そしてその肺シンチの特徴的な所見およびSFP値の高値より肺病変の出現,進行に血栓が重要な役割を演じていることが示唆された.

Protective Effects of Iloprost Against Thromboxane-Induced Myocardial Infarction

The discovery of thromboxane A2 (TXA2) and prostacyclin, and the elucidation of their physiologic roles have brought new insights into atherogenesis and thrombogenesis [1–3]. In particular, the roles of these prostanoids in the pathogenesis of ischemic heart disease have recently been highlighted in relation to coronary thrombosis, vasospasm, and microcirculatory disturbances [4–7], and there has been much discussion regarding whether or not antiplatelet agents such as prostacyclin have preventive or curative effects in these conditions [8–11].