Effects of cupric chloride on coagulation in human plasma: role of fibrinogen.

INTRODUCTION: Copper poisoning is associated with severe multiorgan injury and potentially death if chelation therapy is not administered. Of interest, while important gastrointestinal and urinary tract hemorrhage is associated with copper poisoning, very little is known concerning the nature of copper induced coagulopathy. METHODS: Using thrombelastography, we assessed changes in coagulation kinetics in human plasma following exposure to copper concentrations encountered during poisoning. RESULTS: While time to commence coagulation was not compromised, both velocity of thrombus growth and final strength were diminished. This result was duplicated with one concentration of copper in factor XIII deficient plasma. This pattern of coagulation kinetic response was interpreted as copper mediated fibrinogen dysfunction, perhaps via oxidation of key fibrinogen disulfide bridges. Lastly, experiments wherein glutathione was added implicated copper generated radical oxygen species as one of the mechanisms responsible for compromised coagulation kinetics. CONCLUSIONS: While chelation therapy is the key to survival following copper poisoning, perhaps this and future investigations of how copper affects coagulation may provide insight into effective supportive therapy for patients with active bleeding.

Chemical constituents and coagulation activity of Agastache rugosa.

BACKGROUND: In the Chinese traditional medicine, plant of Agastache rugosa (Fisch. & C.A. Mey.) Kuntze (A. rugosa) has been used to treat nausea, vomiting and dispel damp. However, currently, few reports about the chemical constituents, especially the non-volatile components of A. rugosa are available. METHODS: Through separation with various column chromatographies to elucidate the chemical constituents of A. rugosa, the biological activities of the major constituents were investigated. The extracts and main constituents of A. rugosa were evaluated for their anticoagulant effects by assaying the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) in vitro. RESULTS: Seven known compounds (namely compounds 1-7) were isolated from the aerial parts of A. rugosa. They were identified as methyl hexadecanoate (1), ß-sitosterol (2), acacetin (3), ursolic acid (4), apigenin (5), protocatechuic acid (6) and tilianin (7), respectively. Compounds 1 and 6 were isolated from the genus Agastache for the first time, and compound 4 was obtained from the plants for the first time. The results showed that the extract of A. rugosa had a significant procoagulant activity by shortening the time of PT (P < 0.001) and increasing FIB content (P < 0.001), as compared with Vitamin K1. While its major constituents acacetin and tilianin exhibited significant anticoagulant activities by prolonging the times of PT, APTT, TT and reducing FIB content (P < 0.001), as compared with blank control group. CONCLUSIONS: The total extract of A. rugosa possessed significant procoagulant activity, while its main components, acacetin and tilianin possessed significant anticoagulant activities. Further investigation should be pursued to find out the bioactivity components responsible for the procoagulant action of the plant.

Phthalide Derivatives with Anticoagulation Activities from Angelica sinensis.

Two new phthalide derivatives, angesinenolides A and B (1 and 2), were isolated from the roots of Angelica sinensis. Their structures were elucidated using HRMS, NMR, and X-ray crystallographic data. Compound 1 is the first example of a phthalide trimer presumably formed through two [2+2] cycloaddition reactions. Compound 2 is a unique dimeric phthalide with a peroxy bridge between C-3a and C-6. Both phthalides were evaluated for in vitro anticoagulation activities. Compound 1 reduced the level of fibrinogen (FIB). Compound 2 significantly extended thrombin time and activated partial thromboplastin time, as well as markedly reduced the content of FIB.

Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.

Aptamers are nucleic acid based molecular recognition elements with a high potential for the theranostics. Some of the aptamers are under development for therapeutic applications as promising antithrombotic agents; and G-quadruplex DNA aptamers, which directly inhibit the thrombin activity, are among them. RA-36, the 31-meric DNA aptamer, consists of two thrombin binding pharmacophores joined with the thymine linker. It has been shown earlier that RA-36 directly inhibits thrombin in the reaction of fibrinogen hydrolysis, and also it inhibits plasma and blood coagulation. Studies of both inhibitory and anticoagulation effects had indicated rather high species specificity of the aptamer. Further R&D of RA-36 requires exploring its efficiency in vivo. Therefore the development of a robust and adequate animal model for effective physiological studies of aptamers is in high current demand. This work is devoted to in vivo study of the antithrombotic effect of RA-36 aptamer. A murine model of thrombosis has been applied to reveal a lag and even prevention of thrombus formation when RA-36 was intravenous bolus injected in high doses of 1.4-7.1 µmol/kg (14-70 mg/kg). A comparative study of RA-36 aptamer and bivalirudin reveals that both direct thrombin inhibitors have similar antithrombotic effects for the murine model of thrombosis; though in vitro bivalirudin has anticoagulation activity several times higher compared to RA-36. The results indicate that both RA-36 aptamer and bivalirudin are direct thrombin inhibitors of different potency, but possible interactions of the thrombin-inhibitor complex with other components of blood coagulation cascade level the physiological effects for both inhibitors.

Anti-platelet effects of olive oil extract: in vitro functional and proteomic studies.

PURPOSE: Platelets play a key role in haemostasis and wound healing, contributing to formation of vascular plugs. They are also involved in formation of atherosclerosic plaques. Some traditional diets, like the Mediterranean diet, are associated with a lower risk of cardiovascular disease. Components in these diets may have anti-platelet functions contributing to their health benefits. METHODS: We studied the effects of alperujo extract, an olive oil production waste product containing the majority of polyphenols found in olive fruits, through measurement of effects on platelet aggregation and activation in isolated human platelets, and through identification of changes in the platelet proteome. RESULTS: Alperujo extract (40 mg/L) significantly decreased in vitro ADP- (p = 0.002) and TRAP- (p = 0.02) induced platelet activation as measured by the flow cytometry using the antibody for p-selectin (CD62p), but it did not affect the conformation of the fibrinogen receptor as measured by flow cytometry using the antibodies for anti-fibrinogen, CD42a and CD42b. Alperujo extract (100 mg/L) inhibited both collagen- and TRAP-induced platelet aggregation by 5% (p < 0.05), and a combination of hydroxytyrosol and 3,4-dihydroxyphenylglycol were, at least partly, responsible for this effect. Proteomic analysis identified nine proteins that were differentially regulated by the alperujo extract upon ADP-induced platelet aggregation. These proteins represent important mechanisms that may underlie the anti-platelet effects of this extract: regulation of platelet structure and aggregation, coagulation and apoptosis, and signalling by integrin αIIb/ß3. CONCLUSIONS: Alperujo extract may protect against platelet activation, platelet adhesion and possibly have anti-inflammatory properties.

Effect of the combination of mannitol and ringer acetate or hydroxyethyl starch on whole blood coagulation in vitro.

Mannitol is administered to decrease the intracranial pressure and to improve surgical conditions during craniotomy. Simultaneously a crystalloid infusion is always given and sometimes hydroxyethyl starch (HES) is indicated for intravascular volume replacement. As normal coagulation profile is required during craniotomy, we aimed at determining the effect of mannitol with or without HES or Ringer acetate on blood coagulation in this randomized cross-over in vitro study. Blood samples were withdrawn from 10 volunteers. From whole blood we prepared 10 vol.% and 20 vol.% dilutions of mannitol (15% Mannitol) alone, mannitol and Ringer acetate, and mannitol and HES 130/0.4 (Voluven) at a ratio of 1:1. Blood samples were analyzed by modified thromboelastometry. Coagulation parameters: clotting time, clot formation time, and maximum clot firmness (MCF), were registered. Clot formation time was prolonged in all dilutions compared with control (P<0.05). MCF decreased in all dilutions compared with control (P<0.05). MCF in 20 vol.% dilution of mannitol with HES was lower than MCF in the corresponding dilution with Ringer acetate (P<0.05). Fibrinogen-dependent MCF in 10 vol.% dilution of mannitol with HES was lower than MCF in the corresponding dilution with Ringer acetate (P<0.05). We conclude that mannitol in combination with HES 130/0.4 impairs clot propagation and clot strength in vitro. Fibrin clot strength impairment is more pronounced when mannitol is combined with HES than Ringer acetate. Our findings indicate that HES in combination with mannitol should be avoided whenever a disturbance in hemostasis is suspected during craniotomy.

C-reactive protein and fibrinogen of bedridden older patients in a six-month vitamin D supplementation trial.

OBJECTIVE: To elucidate the association between vitamin D status, C-reactive protein (CRP) and fibrinogen. DESIGN: Secondary analysis of a randomised double-blind placebo controlled trial. SETTING: Four longterm care hospitals (1215 beds) in Helsinki, Finland. PARTICIPANTS: 218 long-term inpatients aged over 65 years. INTERVENTION: Eligible patients (n = 218) were randomized to receive 0 IU/d, 400 IU/d, or 1200 IU/d cholecalciferol for six months. METHODS: Plasma 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), high sensitive CRP, fibrinogen, amino-terminal propeptide of type I procollagen (PINP), and carboxy-terminal telopeptide of type I collagen (ICTP) were measured. RESULTS: The patients were aged (84.5 +/- 7.5 years), vitamin D deficient (25-OHD = 23 +/- 10 nmol/l), chronically bedridden and in stable general condition. The mean baseline CRP and fibrinogen were 10.86 mg/l (0.12 mg/l - 125.00 mg/l) and 4,7 g/l (2.3 g/l - 8.6 g/l), respectively. CRP correlated with ICTP (r = 0.217, p = 0.001), but not with vitamin D status. Supplementation significantly increased 25-OHD concentrations, but the changes in CRP and fibrinogen were insignificant and inconsistent. The post-trial CRP concentrations (0.23 mg/l -138.00 mg/l) correlated with ICTP (r = 0.156, p < 0.001), but no association was found with vitamin D status. The baseline and post-trial fibrinogen correlated with CRP, only. CONCLUSIONS: CRP concentrations are associated with bone turnover, but not with vitamin D status, and vitamin D supplementation has no major effect on CRP or fibrinogen concentrations in bedridden older patients.

Improving abnormal hemorheological parameters in ApoE-/- mice by Ilex kudingcha total saponins.

The aim of this study was to test the effects of Ilex kudingcha total saponins on hemorheology of ApoE-/- mice suffering from hypercholesterolemia induced by high-cholesterol diet. The mice were randomly divided into six groups: the control group, the high-cholesterol diet group, 50 mg/kg atorvastatin treatment group, 75, 150 and 300 mg/kg Ilex kudingcha saponins treatment groups, and all the drug treatment groups were fed with a high-cholesterol diet. After administration with saponins (150 mg/kg or more) and atorvastatin (50 mg/kg) for six weeks, the plasma total cholesterol (TC), whole blood viscosity (WBV), plasma viscosity (PV), and erythrocyte aggregation index (EAI) had a remarkable decrease compared with that of the high-cholesterol diet group, but the hematocrit (Hct) and erythrocyte deformation index (DI) had no significant changes. In addition, it is found that the improving effects of saponins on reducing plasma fibrinogen (Fg) levels and prolonging the blood coagulation times including activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). In conclusion, the Ilex kudingcha total saponins may have a significant therapy application of hypercholesterolemia and atherosclerosis by considering its actions on hemorheological characteristics.

Synthesis, structural studies and biological properties of new TBA analogues containing an acyclic nucleotide.

A new modified acyclic nucleoside, namely N(1)-(3-hydroxy-2-hydroxymethyl-2-methylpropyl)-thymidine, was synthesized and transformed into a building block useful for oligonucleotide (ON) automated synthesis. A series of modified thrombin binding aptamers (TBAs) in which the new acyclic nucleoside replaces, one at the time, the thymidine residues were then synthesized and characterized by UV, CD, MS, and (1)H NMR. The biological activity of the resulting TBAs was tested by Prothrombin Time assay (PT assay) and by purified fibrinogen clotting assay. From a structural point of view, nearly all the new TBA analogues show a similar behavior as the unmodified counterpart, being able to fold into a bimolecular or monomolecular quadruplex structure depending on the nature of monovalent cations (sodium or potassium) coordinated in the quadruplex core. From the comparison of structural and biological data, some important structure-activity relationships emerged, particularly when the modification involved the TT loops. In agreement with previous studies we found that the folding ability of TBA analogues is more affected by modifications involving positions 4 and 13, rather than positions 3 and 12. On the other hand, the highest anti-thrombin activities were detected for aptamers containing the modification at T13 or T12 positions, thus indicating that the effects produced by the introduction of the acyclic nucleoside on the biological activity are not tightly connected with structure stabilities. It is noteworthy that the modification at T7 produces an ON being more stable and active than the natural TBA.

Haemostatic actions of the folkloric medicinal plant extract Ankaferd Blood Stopper.

Ankaferd Blood Stopper (ABS), a standardized mixture of five plants, has been used historically as a haemostatic agent but its mechanism of action remains unknown. This study investigated the in vitro effects of ABS on haemostatic parameters. When added to plasma or serum, ABS induced the very rapid formation of a protein network and erythrocyte aggregation. The levels of coagulation factors II, V, VII, VIII, IX, X, XI, and XIII were not affected by ABS. Plasma fibrinogen activity and antigen levels were decreased following the addition of ABS, in parallel with the prolonged thrombin time. Total protein, albumin, and globulin levels decreased after the addition of ABS. Our findings suggest that ABS stimulates the formation of an encapsulated protein network that provides focal points for erythrocyte aggregation. ABS has the therapeutic potential to be used for the management of haemorrhage and this agent should be investigated further in clinical trials.

Effect of zinc supplementation on protein metabolism in late-middle-aged men: The Zenith study.

OBJECTIVE: Zinc (Zn) is an essential trace element that is a potent enhancer of protein metabolism due to its numerous roles in metabolic processes. Protein turnover decreases with age. We determined whether a Zn supplementation, which increases serum Zn concentration and Zn exchangeable pool mass, modifies whole-body protein turnover and albumin and fibrinogen synthesis rates in late-middle-aged men. METHODS: Three groups of 16 healthy subjects 55-70 y of age participated in a randomized, doubled-blinded, placebo-controlled intervention. Each group received 0, 15, or 30 mg/d of supplemental Zn for 6 mo. At the end of the supplementation period, each subject received an intravenous infusion of L-[1-13C] leucine to quantify whole-body leucine fluxes and synthesis rates of albumin and fibrinogen. RESULTS: In the placebo group, mean +/- SEM whole-body leucine fluxes to protein synthesis, to oxidation, and from protein degradation were 1.46 +/- 0.05, 0.40 +/- 0.01, and 1.73 +/- 0.06 micromol.kg(-1).min(-1), respectively. Zn supplementation did not significantly change whole-body leucine fluxes. In the placebo group, plasma concentration and fractional rate of protein synthesis were 45 +/- 1 g/L and 8.2 +/- 0.6%/d for albumin and 3.6 +/- 0.2 g/L and 16.7 +/- 1.3%/d for fibrinogen, respectively. Zn supplementation did not significantly change these parameters or the absolute rates of synthesis of these proteins. CONCLUSION: Increasing Zn supply does not modify whole-body protein metabolism and synthesis rates of albumin and fibrinogen in late-middle-aged men.

Comparative study on plant latex proteases and their involvement in hemostasis: a special emphasis on clot inducing and dissolving properties.

In the present study we compared the clot inducing and dissolving properties of Calotropis gigantea R. Br. (Asclepiadaceae), Synadenium grantii Hook. f. (Euphorbiaceae) and Wrightia tinctoria R. Br. (Apocynaceae) latex extracts. All the three latex extracts hydrolyzed casein, fibrinogen and crude fibrin dose-dependently. The proteolytic action on fibrinogen subunity was in the order of Aalpha > Bbeta > gamma. All extracts exhibited procoagulant activity as assayed by re-calcification time. However, thrombin like activity is restricted to C. gigantea. In addition, the extracts dose-dependently hydrolyzed blood and plasma clots. Furthermore, the hydrolyzing pattern of fibrin in the plasma clot was substantiated by SDS-PAGE. The extracts hydrolyzed all the subunits (alpha polymer, alpha-chains, gamma-gamma dimer and beta-chain) of fibrin efficiently. Both fibrinogenolytic and fibrinolytic activity potency of the extracts were in the order of C. gigantea > S. grantii > W. tinctoria. Among the three latices, C. gigantea is toxic with a minimum hemorrhagic dose (MHD) of > 75 microg, whereas S. grantii and W. tinctoria latex extracts were non-toxic and did not induce any hemorrhagic effect at the tested dose (> 200 microg). The proteolytic activity of C. gigantea latex extract on different substrates was inhibited by IAA. On the other hand, the proteolytic activities of S. grantii and W. tinctoria were inhibited by PMSF. Thus, this study provides the basis for the probable action of plant latex proteases to stop bleeding and effect wound healing as exploited in folk medicine.

Effect of Melothria maderaspatana leaf-tea consumption on blood pressure, lipid profile, anthropometry, fibrinogen, bilirubin, and albumin levels in patients with hypertension.

OBJECTIVE: To determine the effect of Melothria maderaspatana (Linn.) leaf-tea on blood pressure, plasma lipid profile, fibrinogen, albumin together with serum bilirubin and anthropometric measurements in volunteer participants with hypertension, because all these variables have been shown to influence vascular events. SUBJECTS AND DESIGN: A total of 50 subjects-25 (mean age of 58 +/- 9.0 years; 12 were women) with mild-to-moderate hypertension (systolic blood pressure [SBP] >or= 140 mm Hg; diastolic blood pressure [DBP] >or= 90 mm Hg) and 25 normotensives (mean age of 48 +/- 8.0 years; 11 women)-were selected for this study. Plasma lipid profile, fibrinogen, albumin, serum bilirubin, and anthropometric measurements were measured at baseline and after leaf-tea consumption by the patient with hypertension for 45 days. RESULTS: SBP and DBP gradually decreased and pulse rate decreased. The total cholesterol, low-density lipoprotein cholesterol and triglycerides, and phospholipids levels decreased significantly and high-density lipoprotein cholesterol and serum bilirubin levels increased after tea consumption in patients with hypertension. We also observed significant body weight loss and reduction in fibrinogen levels. There was no significant difference in plasma level of albumin. CONCLUSIONS: Thus, M. maderaspatana leaf-tea consumption gradually decreased BP and showed beneficial effects on blood lipid profile, fibrinogen, bilirubin, and body mass index in patients with hypertension.

Improving abnormal hemorheological parameters in aging guinea pigs by water-soluble extracts of Salvia miltiorrhiza Bunge.

Salvia miltiorrhiza Bunge, known as Danshen in Chinese traditional medicine is effective at promoting blood circulation and removing (or decreasing) blood stasis. In the present study, we selected aging, 24-month-old guinea pigs as the animal experimental models and fed them a diet containing 75, 100 or 150 mg/(kg day) of water-soluble extract components of Salvia miltiorrhiza Bunge (WSm) for 28 days, respectively, in order to evaluate the effects of WSm on their abnormal hemorheological parameters. The results showed that the blood biochemical parameters of the aging guinea pigs remained unaffected by orally given WSm compared to the controls, except that the fibrinogen levels of the group fed the high dose of WSm (150 mg/(kg day)) decreased. Aging guinea pigs fed a low dose of WSm (75 mg/(kg day)) showed no significant difference in hemorheological parameters. However, feeding of WSm at 100 mg/(kg day) (medium dose), significantly reduced erythrocyte membrane MDA levels, which probably increased erythrocyte deformability and decreased erythrocyte flow resistance, though no improvement in erythrocyte aggregation, blood viscosity, and blood viscoelasticity could be observed. Furthermore, when the dose reached 150 mg/(kg day) of WSm (high dose), a significant decrease in whole blood viscosity was observed at high, medium and low shear rates. Blood viscosity and viscoelasticity exhibited significant improvement in oscillatory measurements. Also, we found that the oxygen transport efficiency of whole blood increased.

[The effect of bamboo leaves extract on hemorheology of normal rats].

Sixty rats were randomly divides into six groups. Blood stasis model was set up by sc isoprenaline, and different dose of BLE (15 mg/kg, 30 mg/kg and 60 mg/kg) were iv. The effects of BLE on rat's blood viscosity, plasma viscosity, FIB, ESR, TK, electrophoresis times and HCT were measured by automatic analysis system. Sixty mice were randomly divided into six groups, and the serum cholesterol of the high cholesterol's mice was obtained by eyepit vein and measured. The results showed that BLE (15 mg/kg, 30 mg/kg and 60 mg/kg) could reduce blood viscosity, plasma viscosity, FIB, ESR, TK, HCT and increase the speed of electrophoresis time in blood adhesion model, and BLE (22.5 mg/kg, 45 mg/kg, 90 mg/kg) could significantly reduce serum cholesterol of the high cholesterol's mice.

In vitro effects of poly-N-acetyl glucosamine on the activation of platelets in platelet-rich plasma with and without red blood cells.

BACKGROUND: This study was performed to assess the effect of poly-N-acetyl glucosamine fiber slurry on plasma clotting proteins, platelets, and red blood cells in the clotting of the blood. METHODS: Citrate phosphate dextrose whole blood was stored at 22degreesC for 48 hours to prepare platelet-poor plasma, platelet-rich plasma (PRP), and PRP plus red blood cells with hematocrit values of 20%, 35%, and 45% with and without an equal volume of poly-N-acetyl glucosamine fibers (1 mg/mL 0.9% NaCl). RESULTS: Thromboelastogram data show that poly-N-acetyl glucosamine fibers (p-GlcNAc) significantly reduced the R time in platelet-poor plasma, PRP, and PRP supplemented with red blood cells. Poly-N-acetyl glucosamine fibers increased, but not significantly, Annexin V and factor X binding to platelets, platelet microparticles, and red blood cell Annexin V binding. Poly-N-acetyl glucosamine fibers increased the production of thromboxane B2 by PRP. CONCLUSION: Poly-N-acetyl glucosamine slurry activates platelets.

Effects of conventional and aggressive statin treatment on markers of endothelial function and inflammation.

BACKGROUND: Atherosclerosis is considered to be a chronic inflammatory disorder. Several large-scale clinical studies demonstrate that markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP), fibrinogen, and soluble CD40 ligand, are potent and independent predictors of vascular risk. HYPOTHESIS: The study was undertaken to investigate the effect of increasing the statin dose from conventional to aggressive treatment on lipids levels, inflammation, and endothelial function in patients with coronary artery disease (CAD). METHODS: We randomized 97 patients to either 20 mg simvastatin or 80 mg atorvastatin. Plasma levels of lipids, hsCRP, fibrinogen, soluble adhesion molecules, and nitric oxide-total were analyzed at baseline and after 6 months of treatment. RESULTS: Lipid values were significantly reduced in both treatment groups, but with significantly greater reduction in the aggressively treated group. Furthermore, aggressive statin treatment significantly decreased hsCRP and fibrinogen, while only small reductions were seen in the conventionally treated group, resulting in significant differences between the two treatment groups (p < 0.001). Nitric oxide-total increased significantly in both treatment groups, although the increase was more pronounced in the aggressively treated group (22.6 vs. 15.6%). CONCLUSION: Aggressive statin treatment significantly improved lipid status and reduced markers of inflammation and improved endothelial function compared with conventional treatment in patients with CAD. No interaction was observed, and high-dose treatment did not offer additional benefit compared with standard-dose treatment with respect to soluble adhesion molecules.

The effect of flax seed cultivars with differing content of alpha-linolenic acid and lignans on responses to mental stress.

BACKGROUND: Phytoestrogens offer a possible alternative to hormone replacement therapy. Flax seed contains large quantities of a phytoestrogen precursor, secoisolariciresinol diglucoside (SDG), as well as large quantities of alpha-linolenic acid; these factors may be protective against vascular disease. We have previously shown that the rise in blood pressure during mental stress is a strong predictor of atherosclerosis progression. METHODS: 35 postmenopausal women with vascular disease, 62 +/- 8 years of age, were treated in a random-sequence double-blind Latin square crossover study comparing three strains of flax seed: Flanders (low in lignan and high in alpha-linolenic acid), Linola 989 (high in lignan and low in alpha-linolenic acid) and AC Linora (intermediate in both lignan and alpha-linolenic acid). RESULTS: Compared to the pre-treatment baseline diet, all three strains of flax significantly reduced blood pressure during mental stress induced by a frustrating cognitive task (Stroop color-word interference task) (p = 0.004). Linola 989, the strain highest in lignan and lowest in alpha-linolenic acid, was associated with the least increase in peripheral resistance during stress, the greatest reduction in plasma cortisol during stress and the smallest increase in plasma fibrinogen during mental stress. CONCLUSION: Flax phytoestrogens ameliorate certain responses to stress and thus may afford protection against atherosclerosis; this hypothesis should be tested in clinical trials.

[The effect of yang xue qing nao granule on chronic cerebral ischemia].

OBJECTIVE: To study the effect of Yang Xue Qing Nao Granule (YXQNG) on the chronic cerebral ischemia (CCI). METHODS: 80 cases with CCI were divided randomly into treatment group (43 cases) and control group (37 cases). Each group was disposed with intravenous drops of energy mixture. Besides, treatment group was prescribed with YXQNG, control group received nimedipine plates. The whole therapeutic process of each group was 30 days. The vertibrobasal artery systolic end maximum flow rate (VBASEMFR) and blood rheology (BR) were tested before and after treatment. RESULTS: The total efficiency of treatment group was 90.70% (P < 0.05). The effect of treatment group on lowering blood viscosity and enhancing the cerebral blood flow rate was better than that of control group (P < 0.05). CONCLUSION: YXQNG can effectively treat CCI and improve the life quality of patients.