Batroxobin can improve the efficacy of combination therapy for profound sudden sensorineural hearing loss greater than but not less than 100 dB HL.

OBJECTIVE: To investigate the effects of combination therapy with and without batroxobin, and the frequency of batroxobin use on the prognosis of profound sudden sensorineural hearing loss. METHODS: Hearing recovery in the batroxobin group (231 patients) and non-batroxobin group (56 patients) was compared. The correlation between the number of times batroxobin was used and hearing recovery was analysed. RESULTS: The decrease in hearing threshold and overall improvement rate in the batroxobin group with hearing loss exceeding 100 dB HL was significantly higher than that in the non-batroxobin group. There was no linear correlation between the number of times batroxobin was used and the overall improvement rate. Using batroxobin two to three times achieved a therapeutic effectiveness plateau. CONCLUSION: Batroxobin can improve the efficacy of combination therapy for profound sudden sensorineural hearing loss exceeding 100 dB HL, and using batroxobin two to three times yields the maximum overall improvement rate.

Slounase, a Batroxobin Containing Activated Factor X Effectively Enhances Hemostatic Clot Formation and Reducing Bleeding in Hypocoagulant Conditions in Mice.

Uncontrolled bleeding associated with trauma and surgery is the leading cause of preventable death. Batroxobin, a snake venom-derived thrombin-like serine protease, has been shown to clot fibrinogen by cleaving fibrinopeptide A in a manner distinctly different from thrombin, even in the presence of heparin. The biochemical properties of batroxobin and its effect on coagulation have been well characterized in vitro. However, the efficacy of batroxobin on hemostatic clot formation in vivo is not well studied due to the lack of reliable in vivo hemostasis models. Here, we studied the efficacy of batroxobin and slounase, a batroxobin containing activated factor X, on hemostatic clot composition and bleeding using intravital microcopy laser ablation hemostasis models in micro and macro vessels and liver puncture hemostasis models in normal and heparin-induced hypocoagulant mice. We found that prophylactic treatment in wild-type mice with batroxobin, slounase and activated factor X significantly enhanced platelet-rich fibrin clot formation following vascular injury. In heparin-treated mice, batroxobin treatment resulted in detectable fibrin formation and a modest increase in hemostatic clot size, while activated factor X had no effect. In contrast, slounase treatment significantly enhanced both platelet recruitment and fibrin formation, forming a stable clot and shortening bleeding time and blood loss in wild-type and heparin-treated hypocoagulant mice. Our data demonstrate that, while batroxobin enhances fibrin formation, slounase was able to enhance hemostasis in normal mice and restore hemostasis in hypocoagulant conditions via the enhancement of fibrin formation and platelet activation, indicating that slounase is more effective in controlling hemorrhage.

A Hyaluronan and Platelet-Rich Plasma Hydrogel for Mesenchymal Stem Cell Delivery in the Intervertebral Disc: An Organ Culture Study.

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 106 or 2 × 106 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 µL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.

Neuroprotective effects of Hemocoagulase Agkistrodon on experimental traumatic brain injury.

Traumatic brain injury (TBI) is the major cause of disability and mortality among young people and is associated with neurodegenerative diseases. However, the available clinical options have limited effectiveness. Here, we investigated the neuroprotective effect of Hemocoagulase Agkistrodon (HCA), a thrombin-like enzyme (TLE) isolated and purified from snake venom. Rats subjected to experimental TBI were administered a single dose of HCA or vehicle 10 min after injury. Neurological function was assessed with modified neurological severity score (mNSS). Brain edema were evaluated by measuring brain water content. Levels of hemoglobin and inflammatory cytokines were detected by Enzyme-linked immunosorbent assay (ELISA). In addition, assays including Evans blue extravasation, Western blot analysis and immunofluorescence staining were utilized to determined blood-brain barrier (BBB) integrity. Our results showed that HCA treatment ameliorated neurological deficits (p < 0.01), alleviated brain edema (p < 0.01) and hemorrhage (p < 0.01), decreased the production of the proinflammatory cytokines IL-1ß (p < 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.05), and increased the anti-inflammatory cytokine IL-10 at the contusion site (p < 0.01). Moreover, HCA administration reduced BBB disruption by regulating expression of tight junction proteins, including ZO-1, occludin and claudin-5 (ps < 0.01). Together, our results demonstrate that HCA might have therapeutic efficacy in acute TBI, suggesting a potential clinical application for mitigating the neuropathological damage associated with TBI.

A prospective comparison of four methods for preventing pacemaker pocket infections.

This study aims to evaluate four pacemaker pocket cleaning methods for preventing implantation-related infections. This single-center trial prospectively randomized 910 patients undergoing first-time pacemaker implantation or replacement into four pocket cleaning methods: hemocoagulase (group A, n = 228), gentamicin (group B, n = 228), hemocoagulase plus gentamicin (group C, n = 227), and normal saline (group D, n = 227). Before implanting the pacemaker battery, the pockets were cleaned with gauze presoaked in the respective cleaning solutions. Then, these patients were followed up to monitor the occurrence of infections for 1 month after implantation. Twelve implantation-related infections occurred in 910 patients (1.32%): four patients from group A (1.75%), three patients from group B (1.32%), two patients from group C (0.88%), and three patients from group D (1.32%) (P > .05). Furthermore, two patients developed bloodstream infections (0.22%), and both of these patients were associated with pocket infection (one patient was from group A, while the other patient was from group C, respectively). No cases of infective endocarditis occurred. The differences in the number of infections in these study groups were not statistically significant. The application of hemocoagulase, gentamicin, hemocoagulase plus gentamicin, or normal saline on the presoaked gauze before implantation was equally effective in preventing pocket-associated infections.

Use of thromboelastography to monitor effects of the hemocoagulase on the blood coagulation in patients after thoracic surgery.

BACKGROUND: Over the past few years, snake venom thrombin-like preparations which possess the advantages of low toxicity, fast onset, and long-lasting efficacy have been commonly used as hemostatic drugs in clinical surgery. However, recently, cases of hypofibrinogenemia and bleeding after using the hemocoagulase have been reported and cannot be ignored. Our study used thromboelastography (TEG) to monitor the hemocoagulase effects of blood coagulation status in patients after thoracic surgery. METHODS: Patients suffering thoracic surgery in the First Affiliated Hospital of Soochow University between June 2018 and June 2019 were selected and grouped based on the results of postoperative TEG. The patients with low coagulation index (CI) detected by the TEG were set as the low CI group, and randomly selected patients with normal CI were set as the control group and matched in gender, age, and disease type with patients in the low CI group. The general condition, disease type, preoperative blood coagulation routine, type of hemocoagulase used, postoperative blood coagulation status, and blood transfusion status of the two groups were separately analyzed. RESULTS: The preoperative fibrinogen (FIB) content in the low CI group was significantly lower than that in the control group (P<0.01). Of the 43 patients, 41 had no bleeding according to indicators like increased drainage. Two had a bleeding tendency, and were thus clinically discontinued from hemocoagulase and supplemented with FIB, fresh frozen plasma, and cryoprecipitate; their drainage volume was significantly reduced, and reexamination of TEG showed normal coagulation status. CONCLUSIONS: For patients with preoperative low FIB or a lower limit of normal value, hemocoagulase should be used with caution; after using this type of thrombin, applying TEG for the timely monitoring of a patient's coagulation status is optimally recommended.

Effects of batroxobin treatment on the survival of random skin flaps in rats.

OBJECTIVE: Batroxobin is a medicinal preparation extracted from the venom of the Fer-de-Lance snake, and is used to lower blood viscosity, promote blood fibrinogen decomposition, and inhibit thrombosis. This research is to investigate whether batroxobin can improve the survival of random skin flaps in a rat model. MATERIALS AND METHODS: Dorsal McFarlane flaps were harvested from 36 rats divided into two groups. Experimental group: Batroxobin was administered via the tail vein once daily. CONTROL GROUP: The same amount of normal saline was injected instead. On day 2, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured. On day 7, tissue slices were stained with haematoxylin and eosin. Expression of vascular endothelial growth factor (VEGF) was immunohistochemically evaluated. Microcirculatory flow was measured by laser Doppler flowmetry. Flap angiography, using the lead oxide-gelatin injection technique, was performed with the aid of a soft X-ray machine. RESULTS: The batroxobin group exhibited a greater mean flap survival area, a better microcirculatory flow, and higher-level expression of SOD and VEGF compared with the control group. However, the MDA level was significantly reduced. CONCLUSION: Batroxobin effectively improved the survival of random skin flaps.

The efficacy and safety of Batroxobin in combination with anticoagulation on cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is an uncommon subtype of stroke with highly variable clinical presentation. Although anticoagulation with heparin and/or warfarin remains the standard treatment for CVST, treatment failure is still common. This study aims to evaluate the safety and efficacy of Batroxobin in combination with anticoagulation on CVST control. In this retrospective study, a total of 61 CVST patients were enrolled and divided into Batroxobin (n = 23) and control (n = 38) groups. In addition to the same standard anticoagulation in control, patients in the treatment group received Batroxobin 5 BU intravenous infusion (10 BU for the first time) every other day, for a total of three infusions. A higher recanalization rate was found in Batroxobin group (adjusted OR [95% CI] of 2.5 [1.1-5.0], p = 0.028) compared to the control group, especially in patients with high levels of fibrinogen (adjusted OR [95% CI] of 4.7 [1.4-16.7], p = 0.015). Statistically significant differences between the two groups were seen regarding the levels of thrombin time, fibrinogen and D-dimer at each cut-off time point (all p < 0.01). Compared with baseline, NIHSS scores at discharge showed significant improvement in the Batroxobin group [0(0, 4.25)-5(2, 11), p = 0.036]. No significant difference in mRS scores was found between the two groups at discharge or at 6-month outpatient follow-up (all p > 0.05). Additionally, Batroxobin did not increase the risk of intracranial hemorrhage. We conclude that Batroxobin is a potentially safe and effective adjunct therapeutic agent promoting CVST recanalization especially in patients with high level of fibrinogen.

[Correlation between the changes of fibrinogen and the treatment effect of all-frequency sudden deafness].

Objective: To analyze the correlation between the changes of fibrinogen and the treatment effect of all-frequency sudden deafness, and to explore the individualized treatment strategy for the use of Batroxobin. Methods: Patients with all-frequency sudden deafness who were admitted to Department of Otorhinolaryngology, People's Hospital of Peking University, from January 2010 to September 2016 were selected. All patients were given standard treatment and regular use of Batroxobin. Value of fibrinogen on D1 (before treatment) / D3 / D7 (±1) and D14 (±2) were recorded, at the same time, the correlation between the changes of fibrinogen and prognosis of all-frequency sudden deafness by the audiograms of onset and after-treatment of all patients were analyzed. Independent t-test was used to analyze normal distributed measurement data and chi square linear trend test was used to analyze the curative effect of different fibrinogen groups. Results: A total of 148 patients were included, the outcomes were worst when the patient's fibrinogen was below 2 g/L or above 4 g/L before treatment, ineffective rate were both 50%. The fibrinogen was lowest when the treatment came to the third day. Normally, the patient's prognosis was best when this value waved between 0.7 and 0.9 g/L, with a total effective rate between 73.9% and 83.3%. The fibrinogen value of the 7th day was a good indicator of the outcome, and Fib7 value was significant lower in patients of effective group than ineffective ones ((1.25±0.37)g/L vs (1.38±0.35) g/L, t=-0.27, P=0.04). Patients found a best recovery when Fib7 was below 1 g/L, and the higher the Fib7 value, the higher the inefficiency (χ(2)=7.55, P=0.01). Batroxobin showed safety during the treatment and found no complications. Conclusion: The change of fibrinogen in the process of all-frequency sudden deafness is closely related to the curative effect.

The impact of hemocoagulase for improvement of coagulation and reduction of bleeding in fracture-related hip hemiarthroplasty geriatric patients: A prospective, single-blinded, randomized, controlled study.

BACKGROUND: Uncontrolled bleeding is associated with poor outcomes and mortality in geriatric patients undergoing hemiarthroplasty. Hemocoagulase agkistrodon is a hemocoagulative, anti-hemorrhagic enzyme complex from Deinagkistrodon acutus snake venom. This study aimed to investigate the efficacy of hemocoagulase agkistrodon on coagulation and bleeding outcomes in fracture-related hemiarthroplasty. PATIENTS AND METHODS: This was a prospective, single-blinded, randomized controlled trial carried out between October 2013 and September 2014 in 96 geriatric patients undergoing hemiarthroplasty for unilateral femoral neck fracture. Patients were administrated hemocoagulase agkistrodon (n=48) or normal saline (n=48). Intraoperative blood loss, transfusion volume and rate, and drainage were assessed. Hemoglobin (Hb) and coagulation parameters (prothrombin time [PT], thrombin time [TT], plasma fibrinogen [FIB], and activated partial thromboplastin time [aPTT]) were recorded preoperatively and 30min and 1, 3, and 5days after surgery. Complications were followed up for 4 weeks. RESULTS: Compared to controls, hemocoagulase patients exhibited lower intraoperative blood loss (P<0.01) and postoperative blood loss, total drainage, mean transfusion volume, and transfusion rates (all P<0.05), with lower aPTT at 30min (P<0.05). No significant differences in postoperative FIB were observed. Controls exhibited significantly higher PP and TT on day 1, and Hb on days 1, 3, and 5 (P<0.05). No serious complications were reported. CONCLUSIONS: Hemocoagulase reduced blood loss and transfusion in fracture-related hip hemiarthroplasty without increasing short-term adverse event rates. In geriatric populations, hemocoagulase could be used for limiting bleeding and related complications. TRIAL REGISTRATION: This trial is registered in the Chinese Clinical Trial Register (no. ChiCTR-TRC-14004379).

Functional improvement of hemostatic dressing by addition of recombinant batroxobin.

Although a number of natural materials have been used as hemostatic agents, many substances do not act quickly enough. Here, we created a novel dressings using collagen and chitosan with recombinant batroxobin (r-Bat) to promote faster and more effective hemostasis. We hypothesized that r-Bat would promote synergetic blood coagulation because it contains a blood coagulation active site different than those of collagen and chitosan. Our results suggest that each substances can maintain hemostatic properties while in the mixed dressings and that our novel hemostatic dressings promotes potent control of bleeding, as demonstrated by a whole blood assay and rat hemorrhage model. In a rat femoral artery model, the scaffold with a high r-Bat concentration more rapidly controlled excessive bleeding. This novel dressings has enormous possible for rapidly controlling bleeding and it improves upon the effect of collagen and chitosan used alone. Our novel r-Bat dressings is a possible candidate for improving preoperative care and displays promising properties as an absorbable agent in hemostasis. STATEMENT OF SIGNIFICANCE: Despite the excellent hemostatic properties of collagen and chitosan pads, they reported to brittle behavior and lack sufficient hemostatic effect within relevant time. Therefore, we created a novel pad using collagen and chitosan with recombinant batroxobin (r-Bat). r-Bat acts as a thrombin-like enzyme in the coagulation cascade. Specifically, r-Bat, in contrast to thrombin, only splits fibrinopeptide A off and does not influence other hemostatic factors or cells, which makes it clinically useful as a stable hemostatic agent. Also the materials in the pad have synergetic effect because they have different hemostatic mechanisms in the coagulation cascade. This report propose the novel hemostatic pad isreasonable that a great potential for excessive bleeding injury and improve effects of natural substance hemostatic pad.

Protective effects of batroxobin on a nigrostriatal pathway injury in mice.

Traumatic brain injury triggers a series of damaged processes, such as neuronal death and apoptosis, inflammation and scar formation, which contribute to evolution of brain injury. The present study investigated the neuroprotective effects of batroxobin, a drug widely used clinically for ischemia, in a nigrostriatal pathway injury model. Mice subjected to the nigrostriatal pathway injury were injected with batroxobin (30 BU/kg) or vehicle immediately after injury. The behavioral studies showed that batroxobin could improve the motor function in injured mice in long term. Batroxobin also reduced neuronal apoptosis and inflammation at the acute stage. Moreover, administration of batroxobin attenuated the scar formation and reduced the lesion size at 4 and 14days after brain injury. These results suggest that batroxobin has beneficial effects on the nigrostriatal pathway injury, indicating a potential clinical application.

Prognostic predictors of sudden sensorineural hearing loss in defibrinogenation therapy.

CONCLUSIONS: Defibrinogenation therapy rather than corticosteroids therapy should be chosen for patients specifically with profound hearing loss and with initial high fibrinogen. OBJECTIVES: Corticosteroids therapy is the standard treatment for sudden sensorineural hearing loss (SSNHL) and prognostic factors by this therapy were reported. Defibrinogenation therapy is one of the treatment options for SSNHL. Aims of this study were to identify prognostic factors and correlative markers with hearing improvement in treating SSNHL by defibrinogenation therapy. METHODS: During the early phase of the study, consecutive 61 patients were treated by defibrinogenation therapy with batroxobin (50 units), whereas corticosteroids (500 mg/day of hydrocortisone tapered by 9 days) were used for consecutive 64 patients during the late phase. Blood data that could predict a complete recovery were identified. Coagulation/fibrinolysis markers correlated with hearing improvement by defibrinogenation therapy were investigated. RESULTS: Although there were no overall differences in hearing improvement between the two therapies, recovery rate in profound hearing loss patients was better in defibrinogenation therapy. In patients who showed complete recovery, serum fibrinogen level before treatment was significantly higher in the defibrinogenation group than the corticosteroid group. Responses of several fibrinolysis markers to defibrinogenation therapy evaluated by post-/pre-values were negatively correlated with hearing improvement.

Bio-modulators in platelet-rich plasma: a comparison of the amounts in products from healthy donors and patients produced with three different techniques.

BACKGROUND: Platelet-rich plasma consists of platelets concentrated in a small volume of plasma and constitutes a reservoir of bio-modulators potentially useful in tissue repair. The amounts of bio-modulators detectable in platelet-rich plasma prepared with various commercial or "in house" methods have been reported, but virtually all the analyses described have been performed on platelet-rich plasma derived from healthy donors. Since leucocyte contamination is technically unavoidable, we investigated whether platelet-rich plasma prepared from patients could contain different amounts of bio-modulators because of a possible activated status of the leucocytes. MATERIALS AND METHODS: We evaluated platelet-rich plasma prepared with three different techniques (the commercial Vivostat and Biomet recover GPS II systems and an "in house" method) starting from whole blood from healthy donors and patients. Specifically, we compared the levels of sHLA-I, sFasL, platelet-derived growth factor, transforming growth factors-beta and vascular endothelial growth factor in the platelet-rich plasma releasates according to the method of preparation and to the immune system activation status of the subjects. RESULTS: With the exception of sHLA-I levels, no differences were found in the surrogate indices of lymphocyte activation between healthy donors and patients. No significant differences were found in sHLA-I, sFasL, platelet-derived growth factor, transforming growth factors-beta and vascular endothelial growth factor levels detectable in platelet-rich plasma produced with the three different methods in either healthy donors or patients. DISCUSSION: On the whole our findings indicate that the overall content of bio-modulators in autologous platelet-rich plasma is not influenced by T-lymphocyte activation status, at least in patients with uncomplicated femoral fractures. The amounts of sFasL and sHLA-I detected in all the platelet-rich plasma releasates studied were very small, far below the amounts detectable in all clinically available blood derivatives and absolutely insufficient to induce sHLA-I and/or sFasL mediated immunomodulation.

Hemocoagulase atrox reduces vascular modeling in rabbit carotid artery adventitia.

OBJECTIVE: This study aimed to compare the effects of hemocoagulase atrox and cauterization hemostasis on intimal hyperplasia and explore the effect of hemocoagulase atrox on vascular modeling in rabbit carotid artery adventitia. METHODS: A total of 27 rabbits were randomly divided into 3 groups (0d, 14d, 28d). They were anaesthetized using an intramuscular injection of phenobarbital sodium (1 ml/kg). The left and right common carotid arteries were exposed and capillary hemorrhaged after blunt dissection of the adventitia layers of common carotid arteries. Nine rabbits in each group were again randomly divided into 3 groups, in which animals were respectively treated with hemocoagulase (2 U/ml), cauterization (power = 40 w) and saline (as control). Groups of animals were euthanized at 0, 14 and 28 days after surgery. The samples were equally divided in the middle of the adventitia removal section to obtain equal parts for histologic, immunohistochemical and molecular biologic analysis. The vascular repair after adventitial stripping was observed by HE staining, Masson staining and transmission electron microscopy. The expression of carotid MCP-1, PCNA, TGF-ß1, α-SMA and VEGF were measured at different time points by RT-PCR and immunohistochemical staining. RESULTS: HE staining and Masson staining showed that hemocoagulase atrox had a significantly stronger effect on reducing intimal hyperplasia than the cauterization after 14 and 28 days. The results of RT-PCR showed that the expression of MCP-1, TGF-ß1, α-SMA and VEGF in hemocoagulase atrox-treated animals were lower than that of cauterization-treated animals. CONCLUSION: Our results suggested that hemocoagulase atrox as a topical hemostatic is safety and efficiently and it can accelerate adventitia restoration and decrease intimal proliferation.

[Pharmacodynamics and pharmacokinetics of batroxobin in Beagle dog].

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

Protective effects of Batroxobin on spinal cord injury in rats.

Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases destruction in the spinal cord, so measures to reduce secondary injury are needed. Our previous study demonstrated that, at the front of the expanding secondary injury in the spinal cord, there is an ischemic area in which many neurons can still be rescued. Therefore, enhancement of blood circulation in the cord may be helpful, and indeed, we found that a traditional Chinese medicine, shu-xue-tong, efficiently reduces the secondary injury. The aim of the present study was to investigate the effect of reducing fibrinogen with Batroxobin, a drug widely used clinically for ischemia, in rats with spinal cord contusion. We found that both 2 and 4 Batroxobin units (BU)/kg efficiently decreased the plasma fibrinogen, and 2 BU/kg significantly increased spinal blood flow, enhanced neuronal survival, mitigated astrocyte and microglia activation, and improved locomotor recovery. However, 4 BU/kg had no effect on the secondary spinal cord injury. These data suggest that Batroxobin has multiple beneficial effects on spinal cord injury, indicating a potential clinical application.

The effects of Batroxobin on the intimal hyperplasia of graft veins.

BACKGROUND: To investigate the effects of Batroxobin (BX) on the intimal hyperplasia of graft veins. METHODS: Twenty dogs were evenly divided into 2 groups. The femoral veins were grafted into the femoral artery by microsurgery, and the experimental group was treated with BX (0.1 BU/kg/48 hours). The serum level of endothelin-1 (ET-1) was detected 2 weeks after operation. Computer image analysis system was performed to calculate the cross-sectional area of neointima and media in the vein grafts 8 weeks after operation. Immunohistochemistry method was performed to identify proliferating cell nuclear antigen (PCNA) and c-Myc. RESULTS: The experimental group had a lower level of serum ET-1 than the control group (P < .01), and both intimal hyperplasia and media thickness of graft veins were reduced by BX in comparison with the control group (P < .05). C-Myc expression was higher in the control group than in the experimental group (P < .01). The PCNA expression in the experimental group was significantly lower than the control group (P < .05). CONCLUSIONS: These findings suggested that BX could inhibit intimal hyperplasia through suppressing cell proliferation activity.

Ultrastructural characteristics of fibrin clots from canine and feline platelet concentrates activated with calcium gluconate or calcium gluconate plus batroxobin.

BACKGROUND: The aim of this study was to use transmission electron microscopy to describe the ultrastructural characteristics of clots obtained from canine and feline platelet concentrates (PC) that had been activated with calcium gluconate (CG) or CG plus batroxobin (CGB). Platelets from fibrin clots were classified according their morphological changes. The area of the intercellular space (µm2), the area of the fibrin fibers (µm2), and the width of the fibrin fibers (µm) were determined for the dog clots. The platelet area (µm2), the area of fibrin fibers (µm2), the ratio of the minor and major axes of platelets, the ratio of the major and minor axes of platelets, and the number of α-granules found within platelets were measured for the cat clots. RESULTS: Cat platelets displayed full activation. Dog platelets displayed lysis with loss of normal architecture. In both species, a statistically significant difference was found (P < 0.01) between the fibrin fiber measurements in the PC clots activated with CG and CGB. CONCLUSIONS: The findings suggest that activation with CG caused platelet alpha granules to release their contents. In cats, fibrin production was greater when the PC was activated with CG. In dogs, activation with CG produced thick fibrin fibers.

The long road of research on snake venom serine proteinases.

It has long been recognized that snake venom serine proteinases (SVSPs) affect various physiological functions including blood coagulation, fibrinolysis, blood pressure and platelet aggregation. Therefore, SVSPs have been used as refined tools to study molecular mechanisms involved in the activation of key factors that control hemostasis and as therapeutic agents in various thrombotic and hemostatic conditions. The aim of this review is to highlight the state of our knowledge on the advances made in SVSP research since the 18th century. It includes the personal accounts of some distinguished scientists that addressed specific problems and contributed to advance the field.