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[Effect of ligustrazine injection on vascular endothelial cell of the patients with arteriosclerosis obliterans].

OBJECTIVE: To study the effect of ligustrazine injection (LI) on vascular endothelial cell of the patients with arteriosclerosis obliterans (ASO) and explore the new pathway of investigating effective vascular protective agents in Chinese medicinal herbs. METHODS: Forty-six patients with ASO in the LI group treated by LI were observed, their circulating endothelial cells (CEC) were detected quantitatively before and after treatment. The results were compared with the CEC of 53 cases of healthy persons (control group) in the same period. RESULTS: In the LI group, the immediate cure rate was 45.7% (21 cases), markedly effective rate 36.9% (17 cases) and the effective rate 17.4% (8 cases). The CEC of patients before treatment was 4.39 +/- 1.76/0.9 microliter, which was significantly higher than that of the healthy persons (1.53 +/- 0.42/0.9 microliter). It could be reduced after treatment, along with the improvement of symptoms and signs, to 2.43 +/- 0.87/0.9 microliter, P < 0.01. CONCLUSION: LI in treating ASO not only displays extraordinary effect, but also has good effect in curing the damage of endothelial cells.

Aged↗

[Pathophysiology and diagnosis for arteriosclerosis obliterans].

Patients with arteriosclerosis obliterans, or peripheral arterial disease have been conventionally diagnosed and treated from only the viewpoint of peripheral arterial circulation. These concepts may have improved the quality of life for patients, but could not contribute the prognosis of life, because peripheral arterial disease is associated with an increased risk of the coronary disease and cerebrovascular disease. Intermittent claudication, the most common symptom of peripheral arterial disease, results from flow-reducing lesions in the arteries of the lower extremity that cause exercise-induced muscle ischemia. In order to evaluate intermittent claudication, many kinds of noninvasive diagnostic studies, including ABPI (ankle brachial pressure index) and the measurement of claudication distance, et al have been proposed. We have used the recovery time of the ischemic reaction at foot sole, plethysmography, thermography, laser doppler flowmetry, or NIRS (near-infrared spectroscopy) after walking test, rather than ABPI. These examinations will be superior to ABPI to evaluate effects after ergotherapy or pharmacotherapy for patients with intermittent claudication. Carotid artery sclerosis may be a good marker of systemic atherosclerosis. By our assessment of risk factors, the progression of atherosclerotic change in carotid artery was strongly correlated with two risk factors, such as smoking and systolic blood pressure. In the cholesterol analysis, Lp (a) was only high risk factor for atherosclerotic change of carotid artery. Recent technical advances, adequate evaluation of systemic atherosclerosis, and reduction of risk factors should improve the prognosis of patients with peripheral arterial disease.

Arteriosclerosis Obliterans↗

Enhanced expression of endothelin-A receptor in human transplant renal arteriosclerosis.

Transplant renal arteriosclerosis (TRA), characterized by concentric neointimal thickening, is one of the major causes of chronic rejection in human kidney transplantation. Endothelin-1 is known to be a powerful vasoconstrictor and a vascular smooth muscle cell mitogen. Previous experimental studies have shown that endothelin-A receptor (ET(A) receptor) is expressed selectively in vascular smooth muscle cells, and is the major mediator of endothelin-1-induced effects. However, ET(A) receptor expression in human renal allografts has not been reported. In this study, we immunohistochemically investigated the expression of ET(A) receptor in relation to the development of TRA, using nine human renal allografts removed due to rejection and ten normal kidneys as controls. In intrarenal arteries of normal kidneys, medial smooth muscle cells showed weak expression of ET(A) receptor. In intrarenal arteries with TRA of human renal allografts, increased expression of ET(A) receptor was found in medial smooth muscle cells, and distinct expression of ET(A) receptor was also detected in smooth muscle cells within the neointima. These results suggest that enhanced expression of ET(A) receptor may induce an increase in the local proliferative and vasoconstrictive effects of endothelin-1 in human renal allografts.

Arteriosclerosis↗

[Isolation of resisting thrombus and arteriosclerosis compounds in leaves of Salix matsudana].

In this paper, three compounds were isolated and identified from the leaves of Salix matsudana. They are apigenin-7-0-beta-D-glucopyranside(I), luteolin-7-0-beta-D-glucopyranside(II), compound III. Compound I and II are isolated firstly from Salix spp., compound III is found firstly in the world. Furthermore, study on effect of arachidonic acid metabolisin in rat platelets by them with radio-chromatography found that they can significantly inhibit the production of 12-HETE(12-hydroxy-5,8, 10,14-eicosatetraenoic acid), which can induce allergy and arteriosclerosis. The production of apigenin-7-0-beta-D-glucopyranside being hydrolyzed was apigenin, it can inhibit TXB2(thromoxane B2) which can induce platelet aggregation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

[Effect of sodium ferulate on leucocyte spontaneous activation and surface adhesion molecule expression in arteriosclerosis obliterans patients].

OBJECTIVE: To explore the effect of sodium ferulate (SF) on leucocyte spontaneous activation rate (LSAR) and the surface expression of adhesion molecule (SEAM) in patients with arteriosclerosis obliterans (ASO). METHODS: Forty-two patients with ASO were treated by SF, LSAR and SEAM in them were determined qualitatively before and after SF treatment, as well as in 36 healthy subjects for control. RESULTS: Therapeutic effect of SF in the treated 42 patients was short-term cured in 17 cases (40.5%), markedly effective in 21 (50%), effective in 2 (4.8%), ineffective in 2(4.8%), and the total effective rate being 95.2%. LSAR and SEAM in ASO patients before treatment was 14.84 +/- 7.54% and 47.94 +/- 13.48% respectively, which was obviously higher than 4.96 +/- 2.04% and 24.12 +/- 9.35% in healthy subjects (P < 0.01) respectively, but markedly reduced to 8.19 +/- 4.09% and 28.63 +/- 7.91% after SF treatment (P < 0.01). CONCLUSION: SF could not only obviously lower both LSAR and SEAM but also exert a good therapeutic effect on patients with ASO.

Adult↗

Peripheral macrohemodynamics in patients with lower limb arteriosclerosis obliterans and type II diabetes mellitus.

The paper presents characteristic features of lower limb atherosclerotic lesions in patients with diabetes mellitus: more prominent calcification of vascular wall (involving media), frequent involvement of distal vascular segments and a symmetry of lesions. Typical variants are shown in images obtained with duplex angioscanning. The authors conclude that there are no principal differences in the course of lower limb arteriosclerosis obliterans between diabetics and non-diabetics. Nevertheless some special features were mentioned, particularly in clinical manifestation of intermittent claudication that can be attributed to concurrent diabetic neuropathy. Difficulties in clinical interpretation of lower limb arterial insufficiency for patients with diabetes mellitus determine the necessity of obligatory examination of peripheral vasculature. The authors advocate the discrete subclinical stage of the disease with increased rate of vascular accidents. The data may be interesting for angiologists, vascular surgeons, endocrine legists and other medical professions.

Aged↗

[Transplantation of autologous peripheral blood stem cells for the treatment of lower limb arteriosclerosis obliterans].

OBJECTIVE: To evaluate the clinical efficacy of mobilized autologous peripheral blood stem cells (PBSC) transplantation in a 48 years old patient with lower limb arteriosclerosis obliterans (ASO). METHODS: rhG-CSF 600 micro g/d for 5 days to mobilize stem cells. On the fifth day, PBSC were collected with a Version 4 blood-cells separator. Three hours late, the PBSC were intramuscularly injected into the ischemic areas of the two lower limbs (3 x 10(9) cells per limb). The clinical and laboratory findings were monitored every week for 3 months. Forty-four days after the implantation, left lower limb with severe ASO was given an additional implantation of the same number of cells as the first time. RESULTS: The peripheral blood CD(34)(+) cells were increased from 0.18% to 0.75% after 5 days of rhG-CSF mobilization. Three months after the first stem cell transplantation, severe pain lameness, local cool-feeling and ulcer were improved, and ABI increased from 0.49, 0.69 to 0.50, 0.85, the amplitude of blood flow and laser Doppler blood perfusion were also significantly improved (P < 0.01). At the same time, digital subtraction angiographic scores for new collateral vessel formation were showed as + 3(rich). No related complication or adverse effect were observed during the 3-month observation. CONCLUSION: Transplantation of mobilized autologous PBSC might be a simple, safe, and effective method for the treatment of ASO.

Arteriosclerosis Obliterans↗

[Arteriosclerosis obliterans(ASO) in diabetic patients].

The major risk factors of arteriosclerosis obliterans(ASO) in diabetic patients are age, male gender, smoking, poor glycemic control, hypertension, and dyslipidemia. Thus, to prevent the development and progression of ASO, intensive intervention in the risk factors should be required. HOPE study reported that treatment of ACE-inhibitor in the patients with ASO for 5 years clearly decreased the relative risk for incidence of cardiovascular events comparing with the placebo group. Furthermore, UKPDS Group demonstrated that the adjusted odds ratios to the development of ASO for each 1% HbA1c increase and each 10 mmHg systolic blood pressure increase were respectively 1.28 and 1.25 from multivariate analysis. However, optimal levels of HbA1c and blood pressure for prevention of ASO still have not been suggested. Therefore, large-scale intervention trial in Japanese diabetic subjects should be needed.

Angiotensin-Converting Enzyme Inhibitors↗

Effects of low-density lipoprotein apheresis on plasma matrix metalloproteinase-9 and serum tissue inhibitor of metalloproteinase-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans.

Low density lipoprotein (LDL) apheresis provides both structural and physiologic improvement to the vascular wall. The purpose of this study was to determine whether LDL pheresis alters levels of plasma matrix metalloproteinase-9 (MMP-9) and serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). MMP-9 and TIMP-1 were measured in 30 healthy control subjects (Group A), 20 type 2 diabetic hemodialysis patients without obvious arteriosclerosis obliterans (ASO) (Group B), and 20 type 2 diabetic hemodialysis patients with ASO (Group C). Hemodialysis patients were dialyzed three times weekly with a bicarbonate dialysate. Twelve Group C patients underwent LDL apheresis once weekly for 10 weeks, and changes in plasma MMP-9 and serum TIMP-1 levels because of LDL apheresis were measured. LDL apheresis resulted in a significant decrease in total cholesterol and LDL cholesterol levels (p < 0.01). In addition, LDL apheresis improved clinical symptoms (including cold lower extremity, intermittent claudication, and leg pain) and diminished the size of ulcer/necrosis in all patients. Plasma MMP-9 levels were significantly higher in Group C (76.5 +/- 14.6 ng/ml) than in Group A (31.2 +/- 8.4 ng/ml, p < 0.001) or Group B (58.5 +/- 10.8 ng/ml, p < 0.05). Serum TIMP-1 levels were significantly higher in Group C (360.5 +/- 116.5 ng/ml) than in Group A (142.5 +/- 82.5 ng/ml, p < 0.001) or Group B (254.6 +/- 92.6 ng/ml, p < 0.05). Plasma MMP-9 and serum TIMP-1 levels decreased significantly after LDL apheresis (p < 0.05). However, these levels showed little change in the remaining eight Group C patients who did not undergo LDL apheresis. The data suggested that MMP-9 and TIMP-1 are associated with ASO and that LDL apheresis is effective in reducing plasma MMP-9 and TIMP-1 levels in type 2 diabetic hemodialysis patients with ASO.

Arteriosclerosis Obliterans↗

Protective effects of various calcium antagonists against experimental arteriosclerosis.

Arterial walls altered by sclerotic processes accumulate lipids (particularly cholesterol) and calcium. Whereas the accumulation of lipids has long been incriminated as the major pathogenic factor involved in arteriosclerosis, concomitant arterial calcium overload has been considered of secondary importance. Using various animal models and specific calcium antagonists as experimental tools, we have shown the crucial role of excessive calcium uptake into arterial walls in the pathogenesis of arteriosclerotic lesions. Anticalcinotic vasoprotection with calcium antagonists has been demonstrated using light and electron microscopy, radiocalcium uptake experiments and calcium analyses with atomic absorption spectroscopy. The new 1,4-dihydropyridine calcium antagonist amlodipine has been shown to inhibit calcium accumulation in the internal elastic membrane of abdominal arteries of NaCl-loaded salt-sensitive Dahl-S rats, and consequently also exerts protective effects against arteriosclerotic lesions, shown particularly in the distal mesenteric artery branches. Formation of human coronary plaques is marked by a substantial local uptake of calcium, whereas there is a large overlap in the mural cholesterol content of healthy coronary arteries and plaques. Experimental findings in animals and with human tissue indicate that calcium antagonists such as amlodipine may provide a new approach to the prophylaxis of coronary artery lesions.

Amlodipine↗

Arteriosclerosis in rat aortic allografts: dynamics of cell growth, apoptosis and expression of extracellular matrix proteins.

Transplant vasculopathy is a key factor behind the late loss of transplanted organs. Since effective treatment is still lacking, a further understanding of the pathology of this process is important. Here, a rat model of aortic allografts was used and analyzed by immunohistochemistry and biochemical tests. Infrarenal aortic segments were transplanted from F344 to Lewis rats and analysed after 1-12 weeks using isografts as controls. After 1 week, endothelial cells gradually disappeared at the graft lumen as shown by von Willebrand factor staining and cellular activation was detected in the adventitia and intima using cellular retinol-binding protein-1 as a marker. Subsequently, proliferating smooth muscle cells, lymphocytes and macrophages accumulated in the intima as indicated by the appearance of staining for cell- and proliferation-specific antigens (smooth muscle alpha-actin, CD45RC, ED1, cyclin D1 and proliferating cell nuclear antigen). After 4-8 weeks, TUNEL- and Fas-positive cells were observed in the media, denoting progressive apoptosis. In parallel, the developing neointima contained increased immunoreactivity for fibronectin and osteopontin. At the end of the observation period, an accumulation of macrophages and calcification was observed in the media and endothelial cells reappeared at the graft surface. The findings demonstrate major cellular and structural changes in the transplanted artery, including activation, proliferation and apoptosis of SMCs, and an altered composition of the extracellular matrix. Possibly, the observed changes in SMC phenotype, cell cycle and apoptosis during development of transplant arteriosclerosis are related to the expression of extracellular matrix proteins.

Animals↗

Dipyridamole thallium-201 scintigraphy in patients with arteriosclerosis obliterans. Increased accuracy in identifying cardiac risk.

Forty-eight preselected patients (pts) with arteriosclerosis obliterans were investigated by dipyridamole thallium scintigraphy (DTS). No correlation was found between the distribution of positive or negative exercise ECG testing (ExECG) and isotopic risk-scores (P > 0.1 in the chi-square test). We assessed cardiac ischaemia in 12 pts with insufficient ExECG. Although only 2 pts had documented previous myocardial infarction, 20 pts exhibited irreversible perfusion defect. Silent reversible or irreversible ischaemia was identified in 12 pts (25%). Seven pts would not have been diagnosed to have coronary artery disease (CAD) even by ExECG. In conclusion, DTS was found very useful in these cases. We support a stepwise cardiac risk stratification before major vascular surgery.

Adult↗

[Elastin and arteriosclerosis: determination and characterization of elastin peptides in blood].

During pathologies such as arteriosclerosis and emphysema, degradation of elastin by elastases occurs and elastin peptides are produced. In order to evaluate elastin degradation, measurements of elastin peptide concentration in human blood were carried out. According to elastin peptides used for obtention of antibodies and for ELISA, the measured values are different. Elastin peptides have several biological effects: they are chemotactic, modify ion fluxes and several intracellular mechanisms.

Arteriosclerosis↗

Advanced peripheral arteriosclerosis; a physiological approach to management.

When peripheral arteriosclerosis progresses to the stage where blood flow through both primary and collateral circulations is impaired seriously, arteriolar relaxants, physical therapeutic, pharmacological and surgical, may aggravate the nutritional deficit. Although tissue viability is maintained precariously, limited activity may be tolerated unless the delicate balance between blood supply and metabolic activity is upset by the vicious circle of rest pain and dependent edema. This vicious circle constitutes an immediate threat to the structural integrity of the limb. Rest pain must be controlled if the delicate balance between blood supply and metabolic activity is to be restored and the threat of amputation mitigated. Intravenous injections of procaine may be of value.

Amputation, Surgical↗

[Adenovirus mediate FGF receptor gene transfer inhibits accelerated graft arteriosclerosis in rat aortic transplants].

OBJECTIVE: To evaluate the efficacy of adenovirus mediated fibroblast growth factor (FGF) receptor gene transfer in inhibition of accelerated graft arteriosclerosis (AGA) in rat aorta transplantation model. METHODS: The PCR product of rat sFGFR-1 cDNA was cloned into pCMV1-flag vector, then flag-sFGFR was cloned into pAdvs6a to construct recombinant vector pAv3flag-sFGFR1. The abdominal aorta was injected with buffer containing 5 x 10(9) pfu Adv3-sFGFR-1 and then resected in 30 DA rats. A section of abdominal aorta was resected in 30 PVG rats and the abdominal aorta of DA rats was transplanted. Av3-Nall and normal saline of the same volume were injected into the abdominal aortae of and rats as experimental controls and blank controls. Six rats were killed 5, 30, 60, and 90 days after the operation respectively. The transplanted aorta was harvested. RT-PCR was performed to detect the expression of sFGFR-1 gene with pCMV-Flag-sFGFR1 cDNA as positive control and the abdominal aorta RNA of non-transfected rats as negative control. Immunohistochemistry and HE staning were used to detect the localization and expression of sFGFR-1, and the morphology and cytology of the transplanted vessels. RESULTS: A construct encoding the FGFR1 ectodomain produced secreted sFGFR1 protein, which bound [(125)I]FGF-2 with high affinity and specificity, and inhibited FGF-2 stimulated 3T3 fibroblast proliferation in vitro. Gene transfer of sFGFR1 into rat aortic grafts, using an adenoviral vector, resulted in expression of sFGFR1 protein in endothelium and adventitia. Neointimal formation 60 and 90 days after transplantation was inhibited (P = 0.013) in aortic allograft transduced with sFGFR1, compared to allograft transduced with Null virus and saline. CONCLUSION: FGFs play a causal role in the development of AGA in the rat aortic transplant model and postulate that targeted interruption of FGF function could similarly reduce neointimal formation in transplant setting.

Adenoviridae↗

[Principle of treatment of intermittent claudication due to arteriosclerosis obliterans--reconstruction or conservative treatment].

MATERIALS AND METHODS: Two hundred and one patients of arteriosclerosis obliterans (ASO) with intermittent claudication (IC) were studied. Improvement of IC, score of return to social life, change of life condition and prognosis were compared between the two groups of reconstructive and conservative treatment. RESULTS: Improvement of IC was seen in 88.0% of the patients in the group of reconstruction and only 30.4% in the conservative treatment group. In the reconstructive group, the score of return to social life improved from 2.10 to 1.31 and the score of life condition also improved from 2.71 to 1.66. However in the conservative treatment group these score showed no significant improvement. Moreover the long term mortality rate was lower in the treatment group of reconstruction. CONCLUSION: The arterial reconstruction for IC is significant for improving the quality of life and exerts a favorable effect on life prognosis.

Aged↗

[Doppler ultrasonography in arteriosclerosis of the lower extremities].

Arteriography, which requires resources and is not entirely without risk, has hitherto been a prerequisite for reconstructive surgery in cases of symptom-producing arteriosclerosis in the lower limbs. As an alternative, indirect Doppler ultrasonic examination has been employed but does not appear to be suitable in the clinical routine. On the basis of a review of the literature, it is suggested that, employing a combination of ultrasonic picture scanning and Doppler ultrasonic duplex scanning, it may be possible to diagnose significant solitary stenoses or short occlusions in the aorto-iliac segment and in the femoral artery but that this does not appear to be employable at present in cases of multiple lesions. Examination of the popliteal artery is still too unreliable and reasonably certain assessment of the crural arteries is not possible with the present technique. Duplex scanning can thus not replace arteriography as yet for examination of patients with ischaemia in the lower limbs.

Arteriosclerosis↗

[Therapeutic angiogenesis by autologous transplantation of bone-marrow cells in a patient with progressive limb ischemia due to arteriosclerosis obliterans: a case report].

A 78-year-old woman with arteriosclerosis obliterans was admitted with complaints of progressive ischemic change and resting pain of the left leg. She had severe ischemic limb in stage IV of the Fontaine classification. Angiography showed total occlusion of the three main arteries with poor collateral flow at the left crus. Autologous transplantation of bone-marrow mononuclear cell to her left leg was performed to achieve therapeutic angiogenesis. One month later, follow-up angiography showed excellent angiogenesis of collateral vessels at the left crus. Her pain was relieved and leg amputation was not necessary. Recently, the TACT study in Japan showed the efficacy of angiogenesis by autologous bone-marrow transplantation for peripheral artery disease. This case illustrates the efficacy of this therapy.

Aged↗