Agkistrodon acutus is a traditional Chinese herb medicine which has immunological regulation,anti-tumor,anti-inflammatory and analgesic effects,which is mainly used for the treatment of rheumatoid arthritis,ankylosing spondylitis,sjogren's syndrome and tumors. In order to excavate more important functional genes from A. acutus,the transcriptome of the venom gland was sequenced by the Illumina Hi Seq 4000,and 32 862 unigenes were assembled. Among them,26 589 unigenes were mapped to least one public database. 2 695 unigenes were annotated and assigned to 62 TF families,and 5 920 SSR loci were identified. The majority of mapped unigenes was from Protobothrops mucrosquamatus in the NR database,which revealed their closest homology. Three secretory phospholipase A_2 with different amino acid sequences showed similar spatial structures and all had well-conserved active sites. The 3 D structural models of C-type lectin showed conserved glycosylation binding sites( Asn45). This study will lay the foundation for the further study of the function of snake venom protein,and promoting the development and utilization of genome resources from A. acutus.
Agkistrodon/genetics* ; Animals ; Crotalid Venoms ; Gene Expression Profiling ; Snake Venoms/genetics* ; Snakes ; Transcriptome

The present study evaluated the effects of Androctonus amoreuxi scorpion venom, Cerastes cerastes snake venom and their mixture on prostate cancer cells (PC3). An MTT assay was used to determine the anti-proliferative effect of the venoms, while quantitative real time PCR was used to evaluate the expression of apoptosis-related genes (Bax and Bcl-2). Furthermore, colorimetric assays were used to measure the levels of malondialdehyde (MDA) and antioxidant enzymes. Our results show that the venoms significantly reduced PC3 cell viability in a dose-dependent manner. On the other hand, these venoms significantly decreased Bcl-2 gene expression. Additionally, C. cerastes venom significantly reduced Bax gene expression, while A. amoreuxi venom and a mixture of A. amoreuxi & C. cerastes venoms did not alter Bax expression. Consequently, these venoms significantly increased the Bax/Bcl-2 ratio and the oxidative stress biomarker MDA. Furthermore, these venoms also increased the activity levels of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Overall, the venoms have cytotoxic and anti-proliferative effects on PC3 cells.
Apoptosis ; Catalase ; Cell Survival ; Gene Expression ; Genes, bcl-2 ; Glutathione Peroxidase ; Glutathione Reductase ; Hand ; Humans* ; Malondialdehyde ; Oxidative Stress ; Prostate* ; Prostatic Neoplasms* ; Real-Time Polymerase Chain Reaction ; Scorpion Venoms ; Scorpions* ; Snake Venoms* ; Snakes* ; Superoxide Dismutase ; Venoms ; Viper Venoms ; Viperidae*

A 61 year-old male patient, plasma fibrinogen level was 2.98 g/L, endoscopic sinus surgery was performed under general anesthesia for polypoid of uncinate process with mycotic maxillary sinusitis. Hemocoagulase were given in pre- and post-operative for treatment. The patient was found postoperative drain blood continuously since 3 days after surgery, when the dose of hemocoagulase reach 26 KU, and fibrinogen determined in Plasma was 0.48 g/L. Coagulation returned to normal and nasal bleeding stopped after discontinuation of the hemocoagulase and supplement with fibrinogen.
Batroxobin ; adverse effects ; Blood Coagulation Disorders ; chemically induced ; Endoscopy ; adverse effects ; Fibrinogen ; analysis ; Humans ; Male ; Middle Aged ; Nasal Surgical Procedures ; adverse effects ; Paranasal Sinuses ; surgery

Sudden sensorineural hearing loss (SSNHL) is defined as a sensorineural hearing loss of at least 30 dB in 3 consecutive speech frequencies that occurred within the previous 3 days. In most cases the cause is not identified, although various infective, vascular, and miscellaneous causes have been proposed. It has a reported incidence of 5 to 20 per 100,000 patients per year. Many treatments are used, including corticosteroids, antiviral drugs, hemodilution agents, minerals, vitamins, herbal preparations, batroxobin, carbogen, and oxygen-based treatments. Intra-tympanic dexamethasone injection into the middle ear may be useful to SSNHL patients with profound hearing loss that is intractable to medical treatment or who also have diabetes mellitus. In SSNHL, early treatment with combined modalities that include steroid injection is generally recognized as the current best practice. The spontaneous recovery rates have been reported to be between 32-70%, and although various treatment protocols have been tried, only about half of patients completely recover, usually within 2 weeks. There is much to learn about pathogenesis of sudden sensorineural hearing loss, and more clinical trials are needed to establish evidence-based management.
Adrenal Cortex Hormones ; Antiviral Agents ; Batroxobin ; Clinical Protocols ; Dexamethasone ; Diabetes Mellitus ; Ear, Middle ; Hearing Loss ; Hearing Loss, Sensorineural* ; Hearing Loss, Sudden ; Hemodilution ; Humans ; Incidence ; Minerals ; Plant Preparations ; Practice Guidelines as Topic ; Steroids ; Vitamins

OBJECTIVETo investigate the effect of component I from agkistrodon acutus venomon (AAVC-I) the migration of human umbilical vein endothelial cells (HUVECs), and to elucidate the possible anti-angiogenic mechanism of AAVC-I.

METHODSThe effect of AAVC-I on the migration of HUVECs which was cultivated in vitro and treated with AAVC-1 at four concentrations: 0, 20, 40, 80 microg/ml, was observed by methods of scratch wound-healing and Transwell assay. The expression level of mRNA and protein of P-selectin and intercellular cell adhension molecule-I (ICAM-1) were examined by RT-PCR and Western blot assay.

RESULTSCompared with the blank group, the migration ability of HUVECs in each AAVE-I treated group was reduced in a dose-dependent manner, and the expression level of the mRNA and protein of P-selectin and ICAM-1 were decreased.

CONCLUSIONAAVC-I inhibits the migration of endothelial cell, which is acted by down-regulation of the expression content of mRNA and protein of P-selectin and ICAM-1.

Cell Movement ; drug effects ; Cells, Cultured ; Crotalid Venoms ; pharmacology ; Down-Regulation ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; P-Selectin ; metabolism ; RNA, Messenger

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

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

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

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.
Animals ; Area Under Curve ; Batroxobin ; administration & dosage ; blood ; pharmacokinetics ; pharmacology ; Dogs ; Enzyme-Linked Immunosorbent Assay ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Fibrinolytic Agents ; administration & dosage ; blood ; pharmacokinetics ; pharmacology ; Infusions, Intravenous ; Male ; Partial Thromboplastin Time ; Prothrombin Time ; Thrombin Time

To investigate the effects of component I from Agkistrodon acutus venom (AAVC-I) on the biological features of chronic myeloid leukemia cells, K562/A02 leukemia cells were cultured in the presence of AAVC-I (6.25 - 100 µg/ml) and the proliferation status was assayed by CCK-8 method. Morphological changes were observed by inversed microscope after Giemsa and Hochest 33258 staining, and cell apoptosis was detected by flow cytometry. Caspase 3 activity was tested by using Chromogenic Activity Assay Kit. The results showed that AAVC-I inhibited the growth of K562/A02 cells in time- and concentration-dependant manners, and the IC(50) at 48 h was 30.988 µg/ml. Giemsa and Hochest 33258 staining showed the typical apoptotic features in K562/A02 cells after induction with AAVC-I for 48 h. Flow cytometric analysis revealed that the percentage of the apoptotic cells reached from 0.88 up to 53.66 as the treated concentration was elevated from 0 to 50 µg/ml. Compared with the control group, the expression of caspase 3 in the tested group was enhanced in a dose-dependent manner (P < 0.05). It is concluded that AAVC-I can effectively inhibit the growth and promote apoptosis of K562/A02 cells. Elevated expression of caspase-3 may be attributed to the apoptosis of K562/A02 cells.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Proliferation ; drug effects ; Crotalid Venoms ; pharmacology ; Gene Expression Regulation, Leukemic ; Humans ; K562 Cells ; Leukemia ; metabolism ; pathology