Lethal component of the Naja kaouthia venom had been purified and used as antigen for producing antiserum according to an immunization protocol aiming to be efficient in the production of high affinity antibodies. A strong response was observed on all six immunized horses and tolerance to the antigen did not occur. All antitoxin sera obtained protected against lethality due to the entire venom. The potential production of these six horses is estimated to 4,300 doses/year compared to the estimated national need of 4,800 doses/year for a population of 80 millions.
Neurotoxins ; serum

As a kind of neurotoxin causing muscle paralysis from Clostridium botulinum, the botulinum toxin A is currently used in different clinical aspects, especially in the facial cosmetic. Compared with the traditional surgical methods, the botulinum toxin injection is minimally invasive and safe, favored by more beauty seekers and with better efficacy. However, factors, such as injection dose, operation skills, and anatomical variation, may result in side effects during the operation, including poor injection experience and drug dispersion.
Botulinum Toxins, Type A ; Face ; Injections ; Neurotoxins

Animals ; Humans ; Neurotoxins ; toxicity ; Pesticides ; toxicity ; Pyrethrins ; toxicity ; Toxicology

There are at least three conserved protein folds shared by ion channel-targeted neurotoxins and antimicrobial defensins, including cysteine-stabilized α-helix and β-sheet fold (CSαβ), inhibitor cystine knot fold (ICK) and β-defensin fold (BDF). Based on a combined data of sequences, structures and functions, it has been proposed that these neurotoxins could originate from related ancient antimicrobial defensins by neofunctionalization. This provides an ideal system to study how a novel function emerged from a conserved structural scaffold during evolution. The elucidation of functional novelty of proteins not only has great significance in evolutionary biology but also will be helpful in guiding rational molecular design. This review describes recent progresses in origin of neurotoxins, focusing on the three conserved protein scaffolds.
Defensins ; chemistry ; Evolution, Molecular ; Neurotoxins ; chemistry ; Protein Structure, Secondary

BACKGROUND: The utilization of botulinum toxin has rapidly expanded into various aesthetic applications. Achieving success with the aesthetic use of neurotoxins depends on several factors, including an understanding of the anatomy, the methods of dilution and the injection technique. Any guidelines representing a consensus for aesthetic treatments using botulinum toxin type A (BTA) have not been published in Korea. OBJECTIVE: We wanted to provide consensus recommendations on the treatment of facial wrinkles and benign masseter hypertrophy using BTA in Korean patients. METHODS: A panel of experienced Korean dermatologists was convened to develop a clinical consensus. The clinical consensus was comprised of the recommendations of the panel and the guidelines on general issues, such as the reconstitution and handling of the BTA, the procedural considerations, the dosing and injection-site standardizations, and the prevention and treatment of unwanted effects. Specific recommendations were provided according to the area of treatment, including glabellar lines, horizontal forehead lines, lateral periorbital wrinkles and benign masseter hypertrophy. RESULTS: The recommended final concentration of BTA was 50 units/ml (5 units/0.1 ml) after reconstitution with physiologic saline. For glabellar lines, the members recommend three injection points (a total of 8 units). For forehead wrinkles, the members recommend nine injections in two rows into the frontalis with 1 unit/point. For crow's feet, the members recommend three injections per side (7 units/side) at the lateral part of the orbicularis oculi. For benign masseter hypertrophy, three injections per side (24~30 units/side) were recommended. CONCLUSION: These consensus recommendations will provide a framework for Korean dermatologists who wish to perform safe and efficacious injection of BTA for facial rejuvenation.
Botulinum Toxins ; Botulinum Toxins, Type A ; Consensus ; Foot ; Forehead ; Handling (Psychology) ; Humans ; Hypertrophy ; Korea ; Neurotoxins ; Rejuvenation

PURPOSE: The present study was designed to explore the potential of flunarizine for cisplatin induced painful uremic neuropathy in rats. METHODS: Cisplatin (2 mg/kg; i.p., for 5 consecutive days) was administered and renal uremic markers i.e., serum creatinine were estimated on days 4 and 25. Behavioral changes were assessed in terms of thermal hyperalgesia (hot plate, plantar, tail immersion, and tail flick tests at different time intervals). Biochemical analysis of total calcium, superoxide anion, DNA, and transketolase, and myeloperoxidase activity in tissue samples was also performed. Furthermore, flunarizine (100, 200, and 300 microM/kg; p.o., for 21 consecutive days) was administered to evaluate its potency on uremic neuropathy, and the results were compared with those for the carbamazepine-treated (30 mg/kg; p.o., for 21 consecutive days) groups. RESULTS: Flunarizine attenuated the cisplatin-induced uremic neuropathy, and the degree of behavioral and biochemical changes in serum and tissue samples in a dose dependent manner. The medium and high doses of flunarizine were shown to produce a significant effect on cisplatin induced painful uremic neuropathy. CONCLUSIONS: Our results indicate the potential of flunarizine for anti-oxidative, anti-inflammatory, and neuroprotective actions. Therefore, it may have use as a novel therapeutic agent for the management of painful uremic neuropathy.
Animals ; Calcium ; Cisplatin ; Creatinine ; DNA ; Flunarizine ; Hyperalgesia ; Immersion ; Neurotoxins ; Peroxidase ; Rats ; Superoxides ; Transketolase ; Uremia

Only a few case studies describe reversible parkinsonism after organophosphate poisoning and their brain imagings are found to be normal. However, we experienced chronic, irreversible parkinsonism by acute organophosphate poisoning with bilateral basal ganglia lesions found on a brain MRI. We suggest that brief, large amounts of organophosphate intoxication can produce irreversible parkinsonism according to individual susceptibility and further studies including the investigation of insecticides as an environmental factor of parkinsonism should be done using neuroimagings.
Basal Ganglia ; Brain ; Insecticides ; Magnetic Resonance Imaging ; Neurotoxins ; Organophosphate Poisoning ; Organophosphates ; Parkinsonian Disorders*

OBJECTIVEThis review discusses the current status and progress in studies on the roles of hydrogen sulfide (H(2)S) in regulation of neurotoxicity, neuroprotection, and neuromodulator, as well as its therapeutic potential for neurodegenerative disorders.

DATA SOURCESThe data used in this review were mainly from Medline and PubMed published in English from 2001 to August 2011. The search terms were "hydrogen sulfide", "neuron", and "neurodegenerative disorders".

STUDY SELECTIONArticles regarding the regulation of neuronal function, the protection against neuronal damage and neurological diseases, and their possible cellular and molecular mechanisms associated with H(2)S were selected.

RESULTSThe inhibited generation of endogenous H(2)S is implicated in 1-methy-4-phenylpyridinium ion, 6-OHDA, and homocysteine-triggered neurotoxicity. H(2)S elicits neuroprotection in Alzheimer's disease and Parkinson's disease models as well as protecting neurons against oxidative stress, ischemia, and hypoxia-induced neuronal death. H(2)S offers anti-oxidant, anti-inflammatory and anti-apoptotic effects, as well as activates ATP-sensitive potassium channels and cystic fibrosis transmembrane conductance regulator Cl- channels. H(2)S regulates the long-term potentiation (LTP) and GABAB receptors in the hippocampus, as well as intracellular calcium and pH homeostasis in neurons and glia cells.

CONCLUSIONSThese articles suggest that endogenous H(2)S may regulate the toxicity of neurotoxin. H(2)S not only acts as a neuroprotectant but also serves as a novel neuromodulator.

Animals ; Humans ; Hydrogen Sulfide ; metabolism ; Nervous System ; metabolism ; Neuroprotective Agents ; metabolism ; Neurotoxins ; metabolism ; Neurotransmitter Agents ; metabolism

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

Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.
Animals ; Channelopathies ; physiopathology ; Hippocampus ; drug effects ; Neurons ; drug effects ; Neurotoxins ; pharmacology ; Venoms ; chemistry ; Voltage-Gated Sodium Channel Blockers ; pharmacology