Tetanus Internalization

Raghuvanshi, R.S. et al., Improved Immune Response from Biodegradable Polymer Particles Entrapping Tetanus Toxoid by Use of Different Immunization Protocol and Adjuvants, International Journal of Pharmaceutics. 245, 109, 2002. 

Every adult, whether traveling or not, should be immunized with tetanus toxoid and should also be fully immunized against poliomyelitis, measles (for those bom after 1956), and diphtheria. In addition, every traveler must fulfill the immunization requirements of the health authorities of the countries to be visited. These are listed in Health Information for International Travel, available from the Superintendent of Documents, United States Government Printing Office, Washington, DC 20402. A useful website is http //www.cdc. gov/travel/vaccinat.htm. The Medical Letter on Drugs and Therapeutics also offers periodically updated recommendations for international travelers (see issue of April 15, 2002). Immunizations received in preparation for travel should be recorded on the International Certificate of Immunization. Note Smallpox vaccination is not recommended or required for travel in any country. 

Critchley DR, Nelson PG, Habig WH, Fishman PH (1985) Fate of tetanus toxin bound to the surface of primary neurons in culture evidence for rapid internalization. J Cell Biol... 

Deinhardt K, Berninghausen O, Willison HJ, Hopkins CR, Schiavo G (2006) Tetanus toxin is internalized by a sequential clathrin-dependent mechanism initiated within lipid microdomains and independent of epsinl. J Cell Biol 174 459-71 Dixon RW, Harris JB (1999) Nerve terminal damage by beta-bungarotoxin its clinical significance. Am J Pathol 154 447-55... 

Rossetto O, Seveso M, Caccin P, Schiavo G, Montecucco C (2001b) Tetanus and botulinum neurotoxins turning bad guys into good by research. Toxicon 39 27—41 Rossetto O, Morbiato L, Rossetto et al. 2006 Caccin P, Rigoni M, Montecucco C (2006) Presynaptic enzymatic neurotoxins. J Neurochem 97 1534—4 5 Roux S, Colasante C, Saint Clomcnt C, Barbier J, Curie T et al. (2005) Internalization of a GFP-tetanus toxin C-terminal fragment fusion protein at mature mouse neuromuscular junctions. Mol Cell Neurosci 30 572-82... 

Future important discoveries will be the identification of the neuron-specific receptors of CNTs and of the mode of internalization and membrane translocation of the neurotoxins. Another important line of research is aimed at finding specific inhibitors of these metallo-proteinases. Inhibitors which can cross the neuronal plasmalemma into the cytosol would be potential therapeutic agents in the treatment of tetanus and botulism. The modification of BoNTs to prolong their life time inside the NMJs would be an important research goal to improve the treatment of dystonias. The determination of the three-dimensional structure of these neurotoxins will greatly accelerate the research on these fronts. 

Mochida S, Poulain B, Weller U, Habermann E, Tauc L (1989) Light chain of tetanus toxin intracellularly inhibits acethylcholine release at neuro-neuronal synapses, and its internalization is mediated by heavy chain. In FEBS Lett. 253 47—51 Monk JR, Fernandez JM (1994) The exocytotic fusion pore and neurotransmitter release. In Neuron 12 707-16... 

They bind initially to ganglioside in the neuromuscular jimction, one subunit then being internalized as with the diphtheria toxin (Box 29-A). Botulinum toxins specifically enter motor neurons, while tetanus toxin is taken up via synaptic vesicle endocytosis by both peripheral and central neurons. Retrograde axonal transport carries the toxin into the central nervous system and across synaptic clefts into cholinergic intemeurons, which are poisoned. 

Actions and Uses.—Internally — In excessive doses, narcotic poison in medicinal doses, sedative, antispasmodic, and anodyne. Used in chronic cough, chorea, epilepsy, chronic vomiting, carditis, palpitation of the heart, rheumatism, and tetanus. 

Kodes of Application.—Internally —Diluted with water. In troublesome cough in horses, twenty minims of the acid with a drachm each of camphor and extract of belladonna, made into a ball with powdered liquorice or linseed meal, and given two or three times a day. To the dog, in obstinate vomiting, two grains of the add with ten grains of carbonate of soda and one ounce of water may be administered every hour. One drachm of the add with about a quart of water, employed slowly as an enema two or three times a day, lessens muscular contn ons in tetanus. Externally — To allay pain and irritation in chronic skin affections, especially in dogs, two to three drachms of the acid are mixed with a pint of distilled or rain water. 

Raghuvanshi RS, Katare YK, Lalwani K, Ali MM, Singh O, Panda AK. Improved immune response from biodegradable polymer particles entrapping tetanus toxoid by use of different immunization protocol and adjuvants. International Journal of Pharmaceutics. October 1,2002 245(1-2) 109-121. PubMed... 

Primary cultures of spinal cord represent a convenient and sensitive system to study mechanisms of neurotransmitters release [11,12]. Internalized neurotransmitters by spinal cord neurons in culture were released quantitatively in response to depolarization and Ca2+. This release is inhibited by tetanus toxin and bot-ulinum neurotoxins in a concentration- and time-dependent manner [13-17]. Therefore, this system serves as a suitable model to examine the efficacy of prospective BoNT countermeasures. Sheridan and Adler indicated that the evoked release of neurotransmitters, notably glycine, in this system was time-dependently increased [18]. In our studies, there was a pronounced time-dependent increase of the drug carrier separation from DDV, which paralleled an enhancement of transmitter release. 

Fourth, repetitive contraction is associated with pumping of external fluid fluxes around each sarcomere. These external fluid pulses, together with internal circulation of AS, provide for an effective metabolic exchange and heat dissipation, over and above the slow rates of diffusion and convection. Evidently, a relatively quick fatigue is felt under isometric tetanus. 

Botulinum neurotoxins (seven serotypes, A-G) are relatively large water soluble proteins (150 kDa) produced by the Clostridium botulinum. Each protein has two polypeptide chains (a 100 kDa heavy chain and a 50 kDa light chain) linked through a disulfide bond (Fig. 2). In the proposed mode of action of botulinum and tetanus neurotoxins (Simpson, 1986, 1989), the C-terminal half of the heavy chain binds to the nerve membrane leading to internalization of the neurotoxin in the nerve cell through endocytosis. Subsequently, the pH of the endosome is lowered causing the heavy chain to get integrated in the membrane... 

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