The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The β or β-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.
Animals ; Anticonvulsants/therapeutic use* ; Neurotoxins/pharmacology* ; Scorpion Venoms/pharmacology* ; Scorpions/chemistry* ; Voltage-Gated Sodium Channels

BACKGROUNDShoulder pain is a common complication of stroke. Bee venom acupuncture (BVA) is increasingly used in the treatment of post-stroke shoulder pain.

OBJECTIVETo summarize and evaluate evidence on the effectiveness of BVA in relieving shoulder pain after stroke.

SEARCH STRATEGYNine databases, namely MEDLINE, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), the Japan Science and Technology Information Aggregator, Electronic (J-STAGE), and four Korean medical databases, namely, the National Assembly Library, the Research Information Service System, the National Discovery for Science Leaders, and OASIS, were searched from their inception through August 2014 without language restrictions.

INCLUSION CRITERIARandomized controlled trials (RCTs) were included if BVA was used at acupoints as the sole treatment, or as an adjunct to other treatments, for shoulder pain after stroke.

DATA EXTRACTION AND ANALYSISTwo review authors independently selected trials for inclusion, assessed methodological quality and extracted data.

RESULTSA total of 138 potentially relevant articles were identified, 4 of which were RCTs that met our inclusion criteria. The quality of studies included was generally low, and a preponderance of positive results was demonstrated. All four trials reported favorable effects of BVA on shoulder pain after stroke. Two RCTs assessing the effects of BVA on post-stroke shoulder pain, as opposed to saline injections, were included in the meta-analysis. Pain was significantly lower for BVA than for saline injections (standardized mean difference on 10-cm visual analog scale: 1.46 cm, 95% CI=0.30-2.62, P=0.02, n=86) CONCLUSION: This review provided evidence suggesting that BVA is effective in relieving shoulder pain after stroke. However, further studies are needed to confirm the role of BVA in alleviating post-stroke shoulder pain. Future studies should be conducted with large samples and rigorous study designs.

Acupuncture Therapy ; methods ; Bee Venoms ; therapeutic use ; Humans ; Shoulder Pain ; therapy ; Treatment Outcome

To evaluate the effectiveness and safety of Huachansu in the treatment of cancer-related pain,four Chinese databases( CNKI,VIP,Wan Fang,Sino Med) and three English databases( Cochrane Library,Medline,PubMed) were systematically and comprehensively retrieved since the establishment of each database to October 2018. Randomized controlled trials( RCTs) for the treatment of cancer-related pain with Huachansu were screened out according to pre-established inclusion criteria and exclusion criteria. Rev Man5. 3 software was used for Meta-analysis. A total of 241 articles were retrieved,and finally 10 studies were included. The total sample size was 1 293,including 648 in the experimental group and 645 in the control group. The overall quality of the included studies was generally low. The results of Meta-analysis showed that Huachansu combined with Western medicine acesodynes was superior to the single use of Western medicine acesodynes in the treatment of short-term pain relief,improvement of quality of life and reduction of constipation,nausea and vomiting,dizziness,drowsiness,anorexia and other adverse reactions. And it also has the advantage of a shorter onset time and longer duration time of analgesia,but cannot reduce the incidence of dysuria. Based on the findings,Huachansu had a certain effect in the treatment of cancer-related pain,and a significant positive effect on the improvement of quality of life and the reduction of adverse reactions. No serious adverse reactions occurred. However,due to the small number of studies included,the low quality of the included studies,published biases and other restrictions,the evidence in this study has a low quality,and the conclusion shall be adopted with caution. The effectiveness and safety of Huachansu in the treatment of cancer-related pain remained to be further confirmed in the future with a well-designed,rigorous,and standardized report,with a large sample size,multiple centers,and sufficient follow-up time for randomized controlled trials.
Amphibian Venoms ; therapeutic use ; Cancer Pain ; drug therapy ; Humans ; Quality of Life ; Randomized Controlled Trials as Topic

OBJECTIVETo explore the clinical effect of Agkistrodon antithrombogenase (AAT) in the treatment of rheumatoid arthritis (RA) and its possible mechanism.

METHODSBesides the conventional non-steroid anti-inflammatory agents and disease-modifying anti-rheumatic drug, patients were treated supplementally with intravenous injection of AAT. The intracutaneous test showed allergic to AAT patients were treated with Salvia injection and taken as control group. Changes of related clinical indexes in the two groups were observed.

RESULTSAfter 3 weeks treatment, condition of patients in both groups were improved clinically in joint swollen index, joint tenderness index, morning stiffness time, pain assessment (VAS) and health assessment questionnaire (HAQ) on daily life activity as well as ESR level (P < 0.05 or P < 0.01), with the VAS, HAQ and fibrinogen levels more significantly improved than those of control (P < 0.05 or P < 0.01), and the total effective rate higher in the AAT treated group than those in the control group (P < 0.05).

CONCLUSIONAAT has good effect on easing clinical symptoms of RA possibly through anti-inflammation and improving the microcirculation with less toxic and adverse reaction, so is worthy of recommendation.

Adult ; Ancrod ; therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Crotalid Venoms ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVEAcne vulgaris is a chronic dermatologic problem with multiple factors involved in its pathogenesis. Alternative solutions to acne treatment were instigated by antibiotic resistance despite of its extensive use. Purified bee venom (PBV) has been proposed as a promising candidate for that purpose. The present study was designed to confirm the antibacterial effect of PBV and access the efficacy of cosmetics containing PBV in subjects with acne vulgaris.

METHODSThe skin bacterium Propionibacterium acnes was incubated with PBV at various concentrations and bacterial growth was evaluated using the colony forming unit (CFU) assay. The mechanism of PBV employed in killing P. acnes was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, a total of 12 subjects were randomized in a double-blind, controlled trial to receive either cosmetics containing PBV or cosmetics without PBV for two weeks. Evaluations included lesion counts and skin microorganism.

RESULTSPBV exhibited antimicrobial activity in a concentration-dependent manner, reducing the number of P. acnes CFU by approximately 6 logs at a concentration of 0.5 mg. When PBV concentration was higher than 1.0 mg, no P. acnes colonies were spotted on an agar. TEM and SEM of untreated P. acnes illustrated the normal pleomorphic structure, whereas the PBV-treated bacterium lost the integrity of surface architecture. Significant difference (P=0.027) in the grading levels based on numbers of lesion counts for inflammatory and noninflammatory was observed in favour of the PBV group compared with the control group. In terms of average decrement of skin microorganism, subjects receiving cosmetics containing PBV experienced a significant 57.5% decrease of adenosine triphosphate levels, whereas participants receiving cosmetics without PBV experienced a nonsignificant decrease of 4.7%.

CONCLUSIONThese results show that the in vitro actions of antimicrobial activity of PBV were translated in vivo. Cosmetics containing PBV provided a certain degree of efficacy in terms of lesion counts and skin microorganism concentration compared with cosmetics without PBV in subjects with acne vulgaris. PBV may be a good candidate compound for developing therapeutic drug for the treatment of acne vulgaris.

Acne Vulgaris ; drug therapy ; microbiology ; Adolescent ; Adult ; Anti-Infective Agents ; therapeutic use ; Bee Venoms ; therapeutic use ; Child ; Cosmetics ; Double-Blind Method ; Humans ; Propionibacterium acnes ; drug effects

Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer. Snake venom toxins contributed significantly to the treatment of many medical conditions. There are many published studies describing and elucidating the anti-cancer potential of snake venom. Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species. Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes, affecting the migration and proliferation of these cells. Some of substances found in the snake venom present a great potential as anti-tumor agent. In this review, we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.
Antineoplastic Agents ; analysis ; pharmacology ; therapeutic use ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Neoplasms ; therapy ; Snake Venoms ; analysis ; pharmacology ; therapeutic use

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 observe enhanced effects of polypeptide extract from scorpion venom (PESV) combined Rapamycin on autophagy of H22 hepatoma cells in mice and to explore its possible mechanism.

METHODSThe H22 hepatocarcinoma cell suspension was subcutaneously inoculated into 40 Kunming mice. Then tumor-bearing mice were randomly divided into four groups, i.e., the control group,the high dose PESV group, the low dose PESV group, and the combination group (high dose PESV + Rapamycin), 10 in each group. Mice in high and dose PESV groups were administered with 20 mg/kg and 10 mg/kg PESV respectively by gastrogavage. Mice in the combination group were administered with 2 mg/kg rapamycin and 20 mg/kg PESV by gastrogavage. The intervention lasted for 14 successive days. The tumor volume was measured once every other day, the tumor growth curve was drawn, and then the tumor inhibitory rate calculated. Pathological changes of the tumor tissue were observed by HE staining. Protein expression levels of mammal target of rapamycin (mTOR), UNC-51-like kinase-1 (ULK1), microtubule-associated protein1 light chain3 (MAPILC3A), and Beclin1 were detected by immunohistochemical assay.

RESULTSThe growth of H22 hepatoma transplantation tumor was inhibited in high and low dose PESV groups and the combination group (P < 0.05). And there was statistical difference in tumor weight and tumor volume between the combination group and high and low dose PESV groups (P < 0.05). There was no statistical difference in tumor weight or tumor volume between the high dose PESV group and the low dose PESV group (P > 0.05). lmmunohistochemical assay showed that the protein expression of mTOR was higher, but protein expressions of ULK1, MAP1LC3A, Beclin1 were lower in the control group than in the rest 3 groups (P < 0.05, P < 0.01). Compared with the high dose PESV group, protein expressions of ULK1, MAP1LC3A, and Beclin1 were obviously lower (P < 0.05).

CONCLUSIONPESV combined Rapamycin might inhibit the development of H22 hepatoma transplantation tumor in mice possibly through inhibiting the activity of mTOR, enhancing expressions of ULK1, MAP1LC3A, and Beclin1.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; therapeutic use ; Autophagy ; drug effects ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Liver Neoplasms ; Mice ; Neoplasm Transplantation ; Peptides ; Scorpion Venoms ; pharmacology ; therapeutic use ; Sirolimus ; pharmacology ; therapeutic use

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Standard therapeutic approaches provide modest improvement in the progression-free and overall survival, necessitating the investigation of novel therapies. We review the standard treatment options for GBM and evaluate the results obtained in clinical trials for promising novel approaches, including the inhibition of angiogenesis, targeted approaches against molecular pathways, immunotherapies, and local treatment with low voltage electric fields.
Adult ; Angiogenesis Inhibitors ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Bevacizumab ; Brain Neoplasms ; therapy ; Cancer Vaccines ; therapeutic use ; Electric Stimulation Therapy ; Glioblastoma ; therapy ; Humans ; Immunotherapy ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Snake Venoms ; therapeutic use ; Standard of Care ; Vaccines, Subunit ; therapeutic use

Snake bites are one among the under reported clinical emergencies from tropical countries. There are variations in clinical presentation of snake bites and its toxic features differ with the species and type of bite. There are lots of controversies in the treatment guidelines which often makes it difficult to manage. We report the case of a severe hemotoxic snake bite who presented to the outpatient service of our hospital with a trivial foot injury. Even though snakebites are familiar clinical situations for an emergency physician from tropics, we report this case as most are under reported. We also intend to emphasize the excellent outcome of appropriately diagnosed and treated cases of snake bite.
Adult ; Animals ; Anticoagulants ; toxicity ; Antivenins ; therapeutic use ; Blood Coagulation ; Humans ; Male ; Snake Bites ; blood ; drug therapy ; pathology ; Snake Venoms ; toxicity ; Viperidae