BACKGROUND AND PURPOSE: Arginine esterase(Ancrod), a thrombin-like enzyme, purified from the venoms of Agkistrodon halys, has known to cleave fibrinopeptide A from the fibrinogen and lead to circulation of soluble noncross-linked "ancrodfibrin', which stimulates endogenous T-PA release.Many authors have suggested clinical applicability of this enzyme,but clinical studies on its fibrinolytic action has been insufficient.Thus we studied the influence of this enzyme on fibrinolytic activity in cerebral infarction. METHOD: We observed the change of euglobulin fibrinolytic activity, t-PA antigen, t-PA activity, fibrinopeptide A, fibrinogen, FDP and D-dimer, during 12 hours after a bolus intravenous administration of 0.25 unit of the arginine esterase to the 9 patients with cerebral infarction. RESULT:There was no change of the euglobulin fibrinolytic activity, fibrinopeptide A and t-PA Ag but there was significant increase in both t-PA activity and FDP, D-dimer and significant decrease in fibrinogen. CONCLUSION: Our result suggest that arginine esterase converts fibrinogen to a fibrin polymer which has a increased susceptibility to lysis by plasmirl This enzyme seems to amplify T-PA activity through the consequent increase in FT)P, because there is no increase in the euglobulin fibrinolytic activity, fibr'mopeptide A and t-PA Ag suggesting direct T-PA release. Arginine esterase, having action of effective defibrinogenation and safe fibrinolysis,could be used for the thrombus related disease.
Administration, Intravenous ; Agkistrodon ; Arginine ; Cerebral Infarction ; Fibrin ; Fibrinogen ; Fibrinopeptide A ; Humans ; Polymers ; Snake Venoms* ; Snakes* ; Thrombosis ; Venoms

Bee venom (Apis mellifera L. BV) has been used as a cosmetic ingredient for anti-ageing, anti-inflammatory and antibacterial functions. The aim of this study was to evaluate the acute toxicity after a single dermal administration of BV, BV was administered to 2 groups of Sprague-Dawley (SD) male and female rats (5 animals/group) at doses of 0 and 1,500 mg/kg body weight (BW). Mortality, clinical signs, body weight changes and gross findings were continually monitored for 15 days following the single dose. There were no unscheduled deaths in any groups during the study period. No BV related clinical signs and body weight changes were observed in any groups during the study period. There were no abnormal gross findings at necropsy on day 15 after the treatment. On the basis of the above results, it was concluded that there were no treatment-related effect on mortality, clinical signs, body weight changes and gross findings in SD rats treated with a single dermal dose of BV at dose of 1,500 mg/kg BW. Therefore, the approximate lethal dose of BV was considered to be over 1,500 mg/kg/day for both sexes of rats. BV may provide a developmental basis for a cosmetic ingredient or external application for topical uses.
Administration, Cutaneous ; Animals ; Bee Venoms ; Bees ; Body Weight ; Body Weight Changes ; Cosmetics ; Female ; Humans ; Male ; Rats

OBJECTIVETo study the preparation of Venenum Bufonis beta-cyclodextrin inclusion complexes.

METHODAn optimal condition was established by the uniform design. Under the optimal conditions the Venenum Bufonis beta-cyclodextrin inclusion complexes were prepared with 5 different methods.

RESULTThe ball grinding method was superior to other four methods. The bufadienolide inclusion rate of Venenum Bufonis beta-cyclodextrin prepared with ball grinding method was 85.42%.

CONCLUSIONBall grinding method is the best method for the preparation of Venenum Bufonis beta-cyclodextrin inclusion complexes.

Amphibian Venoms ; administration & dosage ; chemistry ; Animals ; Bufanolides ; Bufo bufo ; Cholenes ; analysis ; Cyclodextrins ; Drug Carriers ; Drug Stability ; Materia Medica ; administration & dosage ; chemistry ; Solubility ; Technology, Pharmaceutical ; methods ; beta-Cyclodextrins

Bee sting therapy is sometimes used for the treatment of chronic recalcitrant neuralgia and arthralgia in traditional Korean herbal medicine, but retained sting materials at the treatment site may induce granulomatous inflammation. Recently, dried honey bee venom (Apitoxin Inj, Guju Pharma. Co., Seoul, Korea) has been approved by the Korea Food and Drug Administration (KFDA) as an anti-inflammatory drug. The adverse events associated with dried honey bee venom injection include itching, edema, pain, headache, fever and myalgia, but foreign body granuloma caused by drug injection has not been previously reported. We herein report two interesting cases of foreign body granuloma induced by dried honey bee venom injection.
Arthralgia ; Bee Venoms ; Bees ; Bites and Stings ; Edema ; Fever ; Foreign Bodies ; Granuloma, Foreign-Body ; Headache ; Herbal Medicine ; Honey ; Inflammation ; Korea ; Neuralgia ; Pruritus ; United States Food and Drug Administration

Adult ; Female ; Hemofiltration ; Hemolysis ; drug effects ; Humans ; Male ; Methylprednisolone ; administration & dosage ; therapeutic use ; Middle Aged ; Plasma Exchange ; Treatment Outcome ; Wasp Venoms ; poisoning ; Young Adult

OBJECTIVETo elucidate the inhibitory effects of recombinant Chinese scorpion neurotoxin BmK IM on seizures induced by pentylenetetrazol (PTZ) and the possible mechanism.

METHODSAfter purifying recombinant BmK IM from an E. coli cell line, its toxicity (both LD50 and minimum lethal dose) on rats was determined. BmK IM was then microinjected into the CA3 region of the right hippocampus and its ability to inhibit the effects of an intraperitoneal injection of PTZ was assessed. The effects of BmK IM on the electrophysiological properties of isolated CA3 pyramidal neurons were then studied using whole-cell patch clamp techniques.

RESULTSBmK IM can significantly prolong the latent period of epileptic seizures, decrease the degree of seizures, and decrease the frequency of epileptiform discharges induced by PTZ. At the same time, 24h after injection of BmK IM into the hippocampal tissue, BmK IM significantly reduces the concentration of the neurotransmitter glutamate and alleviates PTZ-induced lesions in the hippocampus. Whole-cell patch clamp recordings indicate that BmK IM inhibits INa of rat hippocampal neurons in a dose-dependent manner. BmK IM significantly shifts the activation curve of INa in a positive direction, indicating that BmK IM enhances the threshold potential of INa.

CONCLUSIONSBmK IM has significant anti-epileptic properties, and may prove useful as a drug in the therapy of epilepsy. The inhibitory effects of BmK IM on seizures caused by pentylenetetrazol might depend on reductions in the release of presynaptic glutamate via the blocking of Na+ channels.

Animals ; Glutamine ; secretion ; Hippocampus ; drug effects ; Male ; Microinjections ; Pentylenetetrazole ; Peptides ; administration & dosage ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Scorpion Venoms ; administration & dosage ; therapeutic use ; Seizures ; chemically induced ; prevention & control ; Sodium Channels ; drug effects

OBJECTIVETo evaluate the inhibitory effect of total bufadienolides from toad venom against H22 tumor in mice and preliminarily analyze the structures of the metabolites in tissues.

METHODHPLC and LC-MS were used for analysis of the chemical composition of TBFs. High, middle and low dosages of TBFs were orally administered or intra-peritoneally injected to H22 tumor-bearing mice for thirteen days. The animals were killed and the tumors were stripped and weighed. The metabolites in the tissues such as heart, liver, spleen, lung and kidney, were analyzed by HPLC and LC-MS.

RESULTThe chemical composition of TBFs were identified by comparison of the retention times with those of reference substances, on-line UV spectra and MS data. Its main components are concerned with gamabufotalin, arenobufagin, bufotalin, resibufagin, cinobufotalin, bufalin, cinobufagin and resibufogenin. TBFs had no obvious influence on body weight of H-22 tumor-bearing mice orally administered and the inhibition rate against tumor were 14.76%, 16.38% and 10.32% for low (5 mg x kg(-1)), middle (10 mg x kg(-1)) and high dosage (20 mg x kg(-1)), respectively. The mice intra-peritoneally injected with middle and high-dose of TBFs gained body weight slower than the control mice on the 5th day and recovered on the 13th day. The inhibition rate against tumor were 17.30%, 19.80% and 40.95% for low (1.5 mg x kg(-1)), middle (3 mg x kg(-1)) and high dose (6 mg x kg(-1)), respectively. The inhibitory effect took on dose-dependent manner. Based on the HPLC analyses on heart, liver, spleen, lung and kidney, bufadienolides were found in the liver tissue and 11 compounds of them were tentatively identified by LC-DAD-MS.

CONCLUSIONTBFs by oral administration had no inhibitory effect against H22 tumor in mice, however, TBFs by intra-peritoneal injection displayed the significantly inhibitory effect, accompanying some toxicity for early duration of the study. The identification of bufadienolides in the liver provides a good basis for the further investigation of the metabolic pathways of TBFs in vivo.

Amphibian Venoms ; chemistry ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; metabolism ; Bufanolides ; administration & dosage ; metabolism ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; physiopathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Administration Routes ; Female ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Neoplasm Transplantation

AIMThe effect of a renewed SS-cream (RSSC) on the treatment of premature ejaculation (PE) was evaluated and compared with the original SS-cream (OSSC).

METHODSSixty male white New Zealand rabbits, weighing 2.5 kg-3.0 kg, were divided at random into 3 groups: the RSSC, OSSC and placebo groups. The spinal somatosensory evoked potential (SSEP) elicited by electric stimulation of the glans penis with disk electrode was investigated with an electrophysiograph (Poseidomn, Shanghai, China) before and 10, 30 and 60 min after drug or placebo application on the glans. The Onset and the N1 latencies and the amplitude of SSEP were recorded and analyzed.

RESULTSThere was no significant difference (P>0.05) in the mean Onset and N1 latency of SSEP among the 3 groups before drug application. Compared with the pre-application value, the mean Onset and N1 latencies in the RSSC and OSSC groups were significantly prolonged at 10, 30 and 60 min after treatment (P<0.05), while they were not significantly changed (P>0.05) in the placebo group. The mean Onset latency of RSSC at 10 and 30 min and that of OSSC at 30 min were significantly delayed (P<0.05) compared with the placebo group. The mean N1 latency of RSSC at 30 and 60 min and that of OSSC group at 30 min were also significantly delayed (P<0.05).

CONCLUSIONRSSC delays the latencies of SSEP, suggesting a local desensitizing effect on the sensory receptor of the glans penis dorsal nerve, which provides the potential for PE treatment. The desensitizing effect of RSSC is higher than that of OSSC.

Amphibian Venoms ; administration & dosage ; Animals ; Drug Combinations ; Ejaculation ; drug effects ; Electric Stimulation ; Evoked Potentials, Somatosensory ; drug effects ; Male ; Penis ; innervation ; Placebos ; Plant Extracts ; administration & dosage ; Rabbits ; Sexual Dysfunction, Physiological ; drug therapy

Recently the use of peptides in bee venom (PBV) for cancer therapy has attracted considerable attention. In this study, the sterically stabilized liposomal PBV (PBV-SL) was prepared using soybean phosphatidylcholine, cholesterol, and cholesterol-PEG-COOH. The humanized antihepatoma disulfide-stabilized Fv (hdscFv25) was coupled to sterically stabilized liposomes using the N-hydroxysuccinimide ester method. The hdscFv25-immunoliposomes (SIL[hdscFv25]) were immunoreactive as determined by ELISA assay. SIL[hdscFv25] showed higher tumor cells selectivity. PBV-SIL[hdscFv25] can kill SMMC-7721 cells in vitro with higher efficiency than non-targeted liposomes. Whereas cytotoxicties were compared for Hela cells, no significant differences was observed between PBV-SIL[hdscFv25] and PBV-SL. Sterically stabilized immunoliposomal peptides in bee venom could be one drug targeting delivery system.
Antineoplastic Agents ; administration & dosage ; pharmacology ; Bee Venoms ; chemistry ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cholesterol ; chemistry ; Drug Delivery Systems ; HeLa Cells ; Humans ; Immunoconjugates ; chemistry ; pharmacology ; Liposomes ; chemistry ; Liver Neoplasms ; pathology ; Melitten ; administration & dosage ; isolation & purification ; pharmacology ; Peptides ; administration & dosage ; isolation & purification ; pharmacology ; Recombinant Proteins ; administration & dosage ; pharmacology

OBJECTIVETo study the protective effects of naja naja atra venom (NNAV) in a rat model of diabetic nephropathy (DN).

METHODSThe rat diabetes model was induced by intraperitoneal injection of streptozotocin (STZ). Thirty-two model rats were randomly divided into one DN group (n=8) and three treatment groups (n=8 each) that received NNAV at doses of 30, 90, or 270 μg/(kg·day) via oral gavage, another eight rats as normal controls. After 12 weeks, all rats were sacrificed and the changes in serum and urine biological index levels were determined by colorimetric assay. Microalbumin (mALB), N-acetyl-β- glucosaminidase (NAG) and cystatin C (CysC) concentrations were measured by ELISA. Renal tissues were sliced for pathological and immunohistochemical observations.

RESULTSComparied with the DN group, serum glucose was decreased by 31.04%, total cholesterol 21.96%, triglyceride 23.78%, serum creatinine 19.83%, blood urea nitrogen 31.28%, urinary protein excretion 45.42%, mALB 10.42%, NAG 20.65%, CysC 19.57%, whereas albumin increased by 5.55%, high-density lipoprotein-cholesterol 59.09%, creatinine clearance 19.05% in the treatment group by NNAV administration at dose of 90 μg/(kg·day). NNAV also reduced the levels of malondialdehyde in serum (22.56%) and kidney tissue (9.79%), and increased superoxide dismutase concentration in serum (15%) and decreased it in renal tissue (8.85%). In addition, under light microscopy kidney structure was improved and glomerular hypertrophy decreased by 8.29%. As shown by immunohistochemistry, NNAV inhibited transforming growth factor-β1 by 6.70% and nuclear actor-κB by 5.15%.

CONCLUSIONNNAV improves biological indexes in DN, and it may exert renoprotective effects in rats with STZ-induced diabetes.

Animals ; Body Weight ; Diabetes Mellitus, Experimental ; complications ; Diabetic Nephropathies ; drug therapy ; pathology ; Dose-Response Relationship, Drug ; Elapid Venoms ; administration & dosage ; pharmacology ; Elapidae ; physiology ; Kidney ; drug effects ; pathology ; Male ; Malondialdehyde ; Organ Size ; Rats ; Rats, Wistar ; Superoxide Dismutase