The effects of hemocoagulase in injectable form(hemocoagulating enzymatic fraction of South American snake Botrops Jararaca venom provided by Ravizza) on the control of intraocular bleeding during vitreous surgery were evaluated in rabbit eyes. Intraocular infusion solution with hemocoagulase(1 NIH thrombin unit/100 ml BSS) significantly reduced the bleeding time to 33.2 +/- 9.7 seconds. Electroretinogram b-wave and electroretinogram c-wave showed no abnormality. Infusate with hemocoagulase appeared to be a favorite agent for the control of intraocular bleeding during viteous surgery.
Batroxobin* ; Bleeding Time ; Bothrops ; Hemorrhage* ; Snakes ; Thrombin ; Venoms

Multiple agents can cause anaphylaxis in a perioperative setting. Identifying the agent responsible is essential for avoiding future adverse reactions as well as to attenuate the progression of anaphylaxis. Being able to distinguish an anaphylactic reaction from an anaphylactoid reaction would help clarify the therapeutic and medicolegal issues. Anaphylaxis generally occurs after reexposure to a specific antigen and requires the release of proinflammatory mediators from mast cells and basophils. An increased concentration of mast cell tryptase is a highly sensitive indicator of anaphylactic reactions during anesthesia. Botropase(R) is a procoagulant hemocoagulase purified from venom of Bothrops jararaca, a Brazilian viper and in wide use in patients with high risk of bleeding. We report a case of suspected anaphylaxis to Botropase(R) in a 67 years old female patient undergoing segmental resection of the liver with elevated concentration of serum mast cell tryptase.
Aged ; Anaphylaxis* ; Anesthesia ; Basophils ; Batroxobin* ; Bothrops ; Female ; Hemorrhage ; Histamine ; Humans ; Liver ; Mast Cells* ; Tryptases* ; Venoms

The effects of hemocoagulase in injectable form (hemocoagulating enzymatic fraction of South American snake Bothrops jararaca venom provided by Ravizza) on the control of intraocular bleeding during vitreous surgery were evaluated in rabbit eyes. Intraocular infusion solution with hemocoagulase (1 NIH thrombin unit/100 ml of BSS plus) significantly reduced the bleeding time. Electroretinogram b-wave and electroretinogram c-wave showed no abnormality. Infusate with hemocoagulase (1 NIH thrombin unit/100 ml of BSS plus) is not toxic to retinal tissue and appeared to be a useful agent for the control of intraocular bleeding during vitreous surgery.
Animals ; Batroxobin/*administration & dosage ; Eye Hemorrhage/*prevention & control ; Injections ; Rabbits ; Serine Endopeptidases/*administration & dosage ; *Vitrectomy/adverse effects

OBJECTIVE: To compare the hemostatic effects of local packing of Nasopore combined with hemocoagulase injection and local packing of Nasopore combined with saline injection for postoperative management of functional endoscopic sinus surgery by a double-blind, randomized control clinical trial. METHOD: Sixty-eight cases of chronic sinusitis needed functional endoscopic sinus surgery were randomly divided into the experimental group of 40 cases and control group of 28 cases, respectively. For the experimental group, 1 U of hemocoagulase dissolved in 0.5 ml saline was injected into Nasopore which was packed into the nasal cavity after operation. For the control group, 0.5 ml of saline was injected. The postoperative bleeding of the two groups were scored by visual analogue scale. RESULT: There was statistically significant difference between the bleeding VAS scores assessed 6 hours and the ones assessed 1, 2 and 3 days after the operation in the control group (P < 0.05). There was the statistically significant difference between the bleeding VAS scores of experimental group and control group assessed 6 h after the operation (P < 0.05). CONCLUSION The hemocoagulase may improve the hemostatic effect of Nasopore 6 hours after the operation by combined injection with Nasopore as nasal cavity packing.
Bandages ; Batroxobin ; administration & dosage ; Double-Blind Method ; Endoscopy ; Epistaxis ; therapy ; Female ; Humans ; Injections ; Male ; Nasal Cavity ; surgery ; Treatment Outcome

To study the effect of batroxobin(DF-521) on atherosclerosis, we divided 50 Japanese big ear rabbits into control group and high-lipid group. After the atherosclerosis model was successfully established, the high-lipid rabbits were divided into 3 groups(placebo group, treatment group 1 and treatment group 2). Batroxobin was injected in the treatment groups, and saline was injected in placebo group and control group. Getting the aorta before, inter and after treatment, dyeing the lipid, endothelium, smooth muscle, collagen fibers of the vascular plaque(the elastic fibers are of autofluorescence), we observed them with the light microscope and laser scanning confocal microscope. From the results, we found that the atherosclerotic plaque in the treatment groups, tended to be static four weeks later, but there was no obvious difference between treatment group 1 and treatment group 2. These implied that batroxobin possessed the action of stabilizing the atherosclerotic plaque, but the dosage-effect was not clear and the principle needed more study.
Animals ; Arteriosclerosis ; drug therapy ; pathology ; Batroxobin ; therapeutic use ; Disease Models, Animal ; Female ; Fibrinolytic Agents ; therapeutic use ; Male ; Rabbits

OBJECTIVEA first report of 3 patients who developed hypofibrinogenemia due to long-term administration of hemocoagulase.

METHODSThe clinical data of three patients with hypofibrinogenemia due to long-term administration of hemocoagulase were analyzed, and the related literature was reviewed.

RESULTSCase 1, a two-year old girl, had liver traumatic rupture and then treated with massive transfusion and fibrinogen infusion in addition to intravenous recombinant factor VIIa (two times) and hemocoagulase (2 U/d). The liver wound bleeding was soon stopped. However, her plasma fibrinogen level decreased to 0.12 g/L after continuous administration of hemocoagulase for 18 days. Case 2, a three-year old boy, had liver traumatic rupture and was treated with surgical repair, and then received hemocoagulase (2 U/d). On the 8th day, a large amount of blood was found to exude from abdominal cavity drainage tube and indwelling venous catheter, and his fibrinogen dropped to 0.24 g/L. Case 3 was a 45 year-old man who underwent a total mandibular resection because of malignant tumor, and he was given hemocoagulase (4 U/d). A continuous blood oozing was noted from his operation incision, and his fibrinogen level decreased to 0.25 g/L. All the three patients'plasma fibrinogen levels and coagulation tests returned to normal ranges after discontinuation of hemocoagulase administration and supplement of fibrinogen, and the bleeding stopped in cases 2 and 3.

CONCLUSIONLong-term use of hemocoagulase could induce hypofibrinogenemia and severe bleeding.

Afibrinogenemia ; chemically induced ; Batroxobin ; administration & dosage ; adverse effects ; Blood Coagulation ; Child, Preschool ; Female ; Fibrinogen ; analysis ; Humans ; Male ; Middle Aged

BACKGROUNDBatroxobin (BX), a serine protease used in defibrinogenation and thrombolysis, also has an effect on c-fos gene and growth factor. This study attempted to determine the effects of BX on the proliferation of vascular smooth muscle cells (VSMCs) and calcium metabolism.

METHODSVSMCs were treated with BX at concentrations of 0.1, 0.3, or 1.0 mmol/L and cell numbers were determined at 0, 24, 48, and 72 hours. Intracellular calcium concentration ([Ca2+]i) was measured using direct fluorescence methods.

RESULTSBX was found to suppress proliferation of VSMCs in a dose-dependent fashion with inhibition rates of 18% and 31% by 48 and 72 hours, respectively. In addition, BX decreases basal [Ca2+]i significantly. The basal level in untreated cells was 162.7 +/- 33.8 nmol/L, and decreased to 131.5 +/- 27.7 nmol/L, 128.3 +/- 28.5 nmol/L, and 125.6 +/- 34.3 nmol/L with the three concentrations of BX, respectively. Noradrenaline (NE)-induced [Ca2+]i stimulation was also attenuated by BX (0.1 mmol/L BX, 20% +/- 8% inhibition; 0.3 mmol/L BX, 54% +/- 11% inhibition; 1.0 mmol/L BX, 62% +/- 15% inhibition). The ability of NE to stimulate [Ca2+]i was attenuated in cultures in Ca(2+)-free medium, as was the ability of BX to blunt NE-induced stimulation.

CONCLUSIONThese findings demonstrate that BX can effectively inhibit proliferation of VSMCs, probably by blocking the release and uptake of Ca2+, thus influencing [Ca2+]i.

Animals ; Batroxobin ; administration & dosage ; pharmacology ; Calcium ; metabolism ; Cell Division ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Rabbits

OBJECTIVETo investigate the interactive effects between batroxobin and low molecular weight heparin (LMWH) in reducing peri-operative blood loss and coagulation function in patients who undergone the total hip replacement surgery.

METHODS240 ASA I - III patients received 4 000 IU LMWH 12 hours preoperatively before undergoing the total hip replacement operation, were randomly divided into two groups:testing group (Group A, n = 120) and control group (Group B, n = 120) receiving 2 U batroxobin or 50 mg mannitol 10 minutes before incision respectively. Perioperative blood loss, postoperative 24 hours drainage and blood routine test, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were measured respectively. Deep vein thrombosis (DVT) were measured through color Doppler B-ultrasound 3 days after the operation.

RESULTSThe perioperative blood loss in Group A (422.64 ml) was less than that in Group B (667.67 ml) (P < 0.01) while red blood cell, hemoglobin, red blood cell volume and platelet were decreasing after operation in both groups but no significant difference was found between the two groups (P > 0.05). There were no drug-related adverse effects found in the two groups, neither the difference in hospitalization between the two groups (P > 0.05).

CONCLUSIONBatroxobin (2 U) could reduce the perioperative blood loss in patients with LMWH who had undergone the total hip replacement operation but did not show adverse effect on DVT.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; Batroxobin ; therapeutic use ; Blood Coagulation ; drug effects ; Hemorrhage ; prevention & control ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Middle Aged

This study was aimed to investigate the hemostatic effects of hemocoagulase agkistrodon (HCA) and its mechanism. The procoagulative and hemostatic effects of HCA were evaluated by using rabbit blood coagulatin time and mouse tail bleeding time; the mechanisms of HCA hemostatic effect were analyzed by using rabbit blood clot lysis and fibrinogen lysis. The results showed that HCA shortened the rabbit blood coagulation time and the mouse tail bleeding time significantly. The effects are nearly similar to that of positive control (reptilase). HCA also induced rabbit blood clot lysis and directly hydrolysed the alpha-chain of fibrinogen. It is concluded that HCA exert its hemostatic effects by hydrolysing the alpha-chain of fibrinogen, but it is not able to induce production of XIII factor.
Agkistrodon ; Animals ; Batroxobin ; isolation & purification ; pharmacology ; Bleeding Time ; Blood Coagulation ; drug effects ; Crotalid Venoms ; enzymology ; Fibrinogen ; metabolism ; Hemostatics ; pharmacology ; Mice ; Rabbits ; Random Allocation

AIMTo investigate the effect of iontophoresis on skin permeation of defibrase.

METHODSIontophoresis was carried out in side-by-side chambers, excised rat skin membrane (RSM) or human epidermis membrane (HEM). The effects of electrode polarity, permeation medium pH and ionic strength were evaluated.

RESULTSPermeation of defibrase caused by anodal iontophoresis was more effective [the apparent permeability coefficient was (1.2 +/- 0.4) x 10(-4) cm x h(-1)] than that of cathodal iontophoresis [(4.3 +/- 1.4) x 10(-5) cm x h(-1)]. The amount of permeated defibrase caused by anodal iontophoresis in pH 7.4 medium was (25 +/- 5) x 10(-14) mol x cm(-2), which was higher than that of in pH 6. 4 permeation medium [(15 +/- 4) x 10(-14) mol x cm(-2)].

CONCLUSIONIontophoresis could enhance skin permeation of defibrase. Electroosmotic flow effect played an important role.

Animals ; Batroxobin ; administration & dosage ; pharmacokinetics ; Epidermis ; metabolism ; Fibrinolytic Agents ; administration & dosage ; pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Iontophoresis ; Rats ; Rats, Wistar ; Skin Absorption