Bone morphogenetic protein-2 (BMP-2) is used to promote bone regeneration. However, the bone regeneration ability of BMP-2 relies heavily on the delivery vehicle. Previously, we have developed heparin-conjugated fibrin (HCF), a vehicle for long-term delivery of BMP-2 and demonstrated that long-term delivery of BMP-2 enhanced its osteogenic efficacy as compared to short-term delivery at an equivalent dose. The aim of this study was to compare the bone-forming ability of the BMP-2 delivered by HCF to that delivered by clinically utilized BMP-2 delivery vehicle collagen sponge. An in vitro release profile of BMP-2 showed that HCF released 80% of the loaded BMP-2 within 20 days, whereas collagen sponge released the same amount within the first 6 days. Moreover, the BMP-2 released from the HCF showed significantly higher alkaline phosphatase activity than the BMP-2 released from collagen sponge at 2 weeks in vitro. Various doses of BMP-2 were delivered with HCF or collagen sponge to mouse calvarial defects. Eight weeks after the treatment, bone regeneration was evaluated by computed tomography, histology, and histomorphometric analysis. The dose of BMP-2 delivered by HCF to achieve 100% bone formation in the defects was less than half of the BMP-2 dose delivered by collagen sponge to achieve a similar level of bone formation. Additionally, bone regenerated by the HCF-BMP-2 had higher bone density than bone regenerated by the collagen sponge-BMP-2. These data demonstrate that HCF as a BMP-2 delivery vehicle exerts better osteogenic ability of BMP-2 than collagen sponge, a clinically utilized delivery vehicle.
Alkaline Phosphatase/metabolism ; Animals ; Bone Density ; *Bone Morphogenetic Protein 2/administration & dosage/genetics ; Bone Regeneration/*genetics ; Cells, Cultured ; Collagen Type I/chemistry/metabolism ; *Fibrin/chemistry/metabolism ; *Gene Transfer Techniques ; *Heparin/chemistry/metabolism ; Mice ; Osteogenesis/genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of plasma cross-linked D-dimer (XDP) and neuron-specific enolase (NSE) on the infarct volume and neurological function deficit in patients with cerebral infarction (CI).

METHODSPlasma XDP and NSE levels were measured in 66 CI patients on the different days after onset and also in 46 normal individuals, and the changes in XDP and NSE levels were analyzed in the CI patients with different infarct volume and neurological function deficit scores.

RESULTSWithin 48 h following CI onset, plasma XDP and NSE levels increased significantly (P<0.01) and reached the highest levels on day 5 (P<0.001), recovering the normal level till day 18. Plasma XDP and NSE levels were significantly higher in patients with moderate to large infarct volume and in those with moderate to severe neurological deficits than in those with small infarct volume and mild neurological deficits (P<0.001).

CONCLUSIONIncrement of XDP and NSE levels is an important pathological process in CI in close relation to the infarct volume and neurological deficits. XDP and NSE may serve as reliable indices for early diagnosis and evaluation of CI.

Aged ; Biomarkers ; Cerebral Infarction ; blood ; pathology ; Cross-Linking Reagents ; chemistry ; Female ; Fibrin Fibrinogen Degradation Products ; chemistry ; metabolism ; Humans ; Male ; Middle Aged ; Phosphopyruvate Hydratase ; blood

OBJECTIVETo evaluate the effect of platelet-rich fibrin extract (PRFe) on proliferation and differentiation and F-actin cytoskeleton of osteoblasts.

METHODSThe experimental group used the α-minimum essential medium (α-MEM) containing PRFe (10% fetal bovine serum), and the control group used the α-MEM (10% fetal bovine serum). The number of the osteoblasts at 1st, 3rd, 5th d was detected by methyl thiazolyl tetrazolium (MTT) assay, and the differentiation of osteoblast at 1st, 3rd, 5th,7 th d detected by the activity of alkaline phosphatase (ALP).The alizarin red dye was used to observe the number of calcium nodus at 14th, 21st d. The F-actin cytoskeleton was evaluated by confocal laser scanning microscope(CLSM) at 3rd,6th,9th,12th h. The level of osteogenetic biomarkers osteocalcin (OCN) and core-binding factor α1(Cbfα1) at 3rd,7th d were quantified by real-time PCR.

RESULTSA significant increase of absorbance at 1st, 3rd, 5th d was showed in experimental group (0.336 ± 0.011, 0.571 ± 0.039, 0.787 ± 0.050) compared to control group (0.300 ± 0.021, 0.387 ± 0.040, 0.527 ± 0.034) (P < 0.05). The absorbance of experimental group at 1st, 3rd, 5th, 7th d (0.146 ± 0.014, 0.199 ± 0.017, 0.390 ± 0.020, 0.492 ± 0.019) was significantly higher than that of control group (0.115 ± 0.014, 0.145 ± 0.015, 0.190 ± 0.015, 0.230 ± 0.026) (P < 0.05). The integrated absorbance of the calcium nodus in experimental group at 14th, 21st d (22.119 ± 3.694, 31.528 ± 3.162) was significantly higher than in control group (8.498 ± 2.041, 15.162 ± 2.526) (P < 0.05). The Cbfα1 and OCN gene expression in experimental group was higher than in control group (P < 0.05).

CONCLUSIONSPRFe could enhance the proliferation and differentiation of osteoblasts and promote the spread of F-actin cytoskeleton.

Alkaline Phosphatase ; metabolism ; Animals ; Cell Differentiation ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Cytoskeleton ; drug effects ; Fibrin ; isolation & purification ; pharmacology ; Male ; Mice ; Osteoblasts ; cytology ; Osteocalcin ; metabolism ; Platelet-Rich Plasma ; chemistry ; Rats ; Rats, Sprague-Dawley

To investigate the effects of complex danshen solution and heparin on the changes of blood coagulation factors in rats with hemorrhagic shock, and to explore the therapy of coagulopathy by compound danshen solution, the rat model of hemorrhagic shock was set up, 40 SD rats were randomized into four groups: sham operation, shock, compound danshen solution and heparin groups, each group was composed of 10 SD rats. Plasma SFMC, TM, ATIII, D-D, t-PA, PAI levels and APTT were detected, incidences of bleeding complications between heparin and danshen group were compared. The results showed that plasma SFMC, D-D levels in shock group were higher but ATIII level in shock group was lower than that in sham operation group, compound danshen solution group and heparin group (P < 0.001), TM levels obviously increased in shock group and heparin group (P < 0.001). There was no significant difference between compound danshen solution and sham-operation groups. Plasma t-PA, D-D levels obviously increased after shock for 2 hours, PAI level reached the peak after shock for 4 hours, but t-PA decreased. After shock for 6 hours, plasma PAI descended, t-PA continually drop in, but PAI and D-D remained in higher levels. Plasma D-D level in heparin group was lower than that in shock group, t-PA level was higher than that in shock group, but there was no significant difference between in heparin and shock groups. Plasma t-PA, PAI and D-D levels in compound danshen solution group were lower than that in shock group. APTT of danshen group was lower than that of shock group and heparin group. Bleeding incidences was 30% in heparin group and 0% in danshen group, respectively. It is concluded that compound danshen solution may used to treat hypercoagulation and hyperfibrinolysis. In comparsion with heparin, danshen posses-ses advantages of safety with less bleeding complication and needs not tight monitor.
Animals ; Anticoagulants ; therapeutic use ; Blood Coagulation ; drug effects ; Blood Coagulation Factors ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Heparin ; therapeutic use ; Male ; Partial Thromboplastin Time ; Phytotherapy ; Plasminogen Activator Inhibitor 1 ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry ; Shock, Hemorrhagic ; blood ; drug therapy ; Thromboplastin ; metabolism ; Tissue Plasminogen Activator ; blood

OBJECTIVETo evaluate the effect of decoction for invigorating the kidney and improving blood circulation to thrombosis on rabbits blood stasis model.

METHODThirty rabbits were randomly divided into normal group, model group, heavy dose group, slight dose group and xue shuan ning group. Tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), fibrinogen (Fbg) and D-dimer (DD) were investigated after those rabbits had been treated. One was selected randomly from each group to observe pathological changes.

RESULTThere was significant difference in t-PA, PAI, Fbg and DD between normal group and other groups (P < 0.01). Among groups of heavy dose, slight dose, xue shuan ning and model, the statistical differences were significant, as well as among groups of heavy dose, slight dose and xue shuan ning (P < 0.05). However, there was no statistical difference between heavy dose group and slight dose group (P > 0.05). The pathological changes in model group were most serious, and those in xue shuan ning were less serious. There were slight pathological change in heavy dose group and light dose group.

CONCLUSIONModels were made successfully. Heavy dose group and slight dose group have stronger effect on thrombosis than xue shuan ning group.

Animals ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Kidney ; pathology ; Liver ; pathology ; Lung ; pathology ; Male ; Medicine, Chinese Traditional ; Plants, Medicinal ; chemistry ; Plasminogen Inactivators ; blood ; Rabbits ; Random Allocation ; Thrombosis ; blood ; pathology ; Tissue Plasminogen Activator ; blood

OBJECTIVETo evaluate the effect of decoction for invigorating the kidney and improving blood circulation to thrombosis and pathology on rabbit blood stasis model.

METHODThirty rabbits were ramdomly divided into normal group, model group, high dose group, low dose group and Xue Shuan Ning group. Tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), fibrinogen (Fbg) and D-dimer (DD) were investigated after those rabbits had been treated. One rot was solected randomly from each group to observe pathological changes.

RESULTThere were significant differences in t-PA, PAI, Fbg and DD between normal group and other groups is very obvious (P < 0.01) . Between groups of high dose low dose Xue Shuan Ning and model, the statistical differeces were significant, as well as between groups of high dose, low dose and Xue Shuan Ning groups (P < 0.05). However, there was no statistical difference between high dose group and high dose group (P > 0.05). The pathological changes in model group were most serious, those in Xue Shuan Ning were less serious. There were slight pathological changes in high dose group and low dose group.

CONCLUSIONModels ware made successfully. High dose group and low dose group have stronger effect on thrombosis than Xue Shuan Ning group.

Animals ; Blood Viscosity ; drug effects ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Hematocrit ; Male ; Plants, Medicinal ; chemistry ; Plasminogen Inactivators ; blood ; Rabbits ; Random Allocation ; Thrombosis ; blood ; pathology ; Tissue Plasminogen Activator ; blood

OBJECTIVETo investigate the effect of Shengmai Injection (SMI) on blood coagulation in patients with chronic heart failure (CHF).

METHODSSixty patients with CHF were randomly divided into two groups, the 30 patients in the treated group were treated with SMI plus conventional treatment of western medicine, and the 30 in the control group treated with conventional treatment alone. The changes of cardiac function were observed and levels of plasma P-selectin, von Willebrand's factor (vWF) and D-dimer were determined.

RESULTSThe total effective rate and the markedly effective rate in the treated group were higher than those in the control group respectively. The levels of P-selectin, vWF and D-dimer lowered in both groups significantly after treatment, but the effect of lowering was better in the treated group than that in the control group.

CONCLUSIONHypercoagulative state exist in patients with chronic heart failure. SMI could improve the state in patients, which may reduce the occurrence and developing of emboic events to certain extent.

Aged ; Aged, 80 and over ; Blood Coagulation ; drug effects ; Drug Combinations ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Heart Failure ; blood ; drug therapy ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; P-Selectin ; blood ; Panax ; chemistry ; Phytotherapy ; von Willebrand Factor ; metabolism

Effects of the effective components group of Xiaoshuantongluo formula (XECG) on rat acute blood stasis model were studied under the guidance of the concept of effective components group. Rat acute blood stasis model was induced by subcutaneous injection of epinephrine combined with ice water bath. Hemorheology indices such as whole blood viscosity, plasma viscosity, erythrocyte aggregation index and platelet aggregation rate; coagulation parameters including PT, APTT, TT and FIB; 6-keto-PGF1alpha, TXB2 and D-dimer levels were determined to evaluate the effects of XECG. The results showed that XECG significantly reduced ADP-induced platelet aggregation, but showed little influence on the whole blood viscosity, plasma viscosity and erythrocyte aggregation rate. XECG extended PT and TT slightly, but had no effects on APTT and FIB content. D-dimer levels significantly decreased after administration of XECG with a little decrease of TXB2, but the content of 6-keto-PGF1alpha did not change significantly. The results suggest that the role of XECG of anti-aggregation is more prominent.
6-Ketoprostaglandin F1 alpha ; blood ; Animals ; Blood Coagulation ; drug effects ; Blood Coagulation Disorders ; blood ; Blood Viscosity ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Erythrocyte Aggregation ; drug effects ; Fibrin Fibrinogen Degradation Products ; metabolism ; Hemorheology ; drug effects ; Male ; Partial Thromboplastin Time ; Plants, Medicinal ; chemistry ; Platelet Aggregation ; drug effects ; Prothrombin Time ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thrombin Time ; Thromboxane B2 ; blood