scholarly journals Primary Cultures of Embryonic Chicken Neurons for Sensitive Cell-Based Assay of Botulinum Neurotoxin: Implications for Therapeutic Discovery

2007 ◽  
Vol 12 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Andrea M. Stahl ◽  
Gordon Ruthel ◽  
Edna Torres-Melendez ◽  
Tara A. Kenny ◽  
Rekha G. Panchal ◽  
...  
Keyword(s):  
Nervous System ◽  
Botulinum Toxin ◽  
Neutralizing Antibodies ◽  
Botulinum Neurotoxin ◽  
Potent Inhibitor ◽  
Primary Cultures ◽  
Embryonic Chick ◽  
Sensitive Cell ◽  
Botulinum Neurotoxin A ◽  
Therapeutic Compounds

Botulinum toxin is an exceedingly potent inhibitor of neurotransmission across the neuromuscular junction, causing flaccid paralysis and death. The potential for misuse of this deadly poison as a bioweapon has added a greater urgency to the search for effective therapeutics. The development of sensitive and efficient cell-based assays for the evaluation of toxin antagonists is crucial to the rapid and successful identification of therapeutic compounds. The authors evaluated the sensitivity of primary cultures from 4 distinct regions of the embryonic chick nervous system to botulinum neurotoxin A (BoNT/A) cleavage of synaptosomal-associated protein of 25 kD (SNAP-25). Although differences in sensitivity were apparent, SNAP-25 cleavage was detectable in neuronal cells from each of the 4 regions within 3 h at BoNT/A concentrations of 1 nM or lower. Co-incubation of chick neurons with BoNT/A and toxin-neutralizing antibodies inhibited SNAP-25 cleavage, demonstrating the utility of these cultures for the assay of BoNT/A antagonists. ( Journal of Biomolecular Screening 2007:370-377)

scholarly journals Botulinum Toxin Use in the Lower Urinary Tract

2007 ◽  
Vol 7 ◽  
pp. 808-817
Author(s):  
Shelby N. Morrisroe ◽  
Michael B. Chancellor
Keyword(s):  
Botulinum Toxin ◽  
Urinary Tract ◽  
Overactive Bladder ◽  
Lower Urinary Tract ◽  
Botulinum Neurotoxin ◽  
Botulinum Toxins ◽  
Muscle Paralysis ◽  
Botulinum Neurotoxin A ◽  
Beneficial Effects ◽  
Lower Urinary

Botulinum toxins are well known for their ability to disrupt neurotransmission and cause muscle paralysis. Recently, urologists have discovered their beneficial effects in patients with neurogenic and overactive bladder conditions. This review is intended to provide a quick overview for urologists of the structure, function, and clinical uses of botulinum neurotoxin A in the lower urinary tract.

The Use of Botulinum Toxin in Flap Surgery: A Review of the Literature

2019 ◽  
Vol 26 (4) ◽  
pp. 478-484 ◽  
Author(s):  
Francesco Segreto ◽  
Giovanni Francesco Marangi ◽  
Matteo Signoretti ◽  
Vito Cazzato ◽  
Riccardo Giorgino ◽  
...  
Keyword(s):  
Botulinum Toxin ◽  
Animal Models ◽  
Botulinum Neurotoxin ◽  
Vascular Complications ◽  
Vascular Anastomosis ◽  
Random Pattern ◽  
Injection Timing ◽  
Flap Surgery ◽  
Botulinum Neurotoxin A ◽  
Botulinum Neurotoxin B

Botulinum neurotoxin-A and botulinum neurotoxin-B have been shown to play a potential role in improving flap survival in animal models. The aim of this study is to review indications as well as to study injection timing, technique, and doses of botulinum neurotoxin-A and botulinum neurotoxin-B in animal models. Seventeen articles describe a total of 266 animals that underwent botulinum toxin injections before or during flap harvesting or vascular anastomosis procedure. All the studies demonstrated a beneficial effect of botulinum toxin administration in flap surgery or vascular anastomosis. Botulinum neurotoxin-A injection was shown to be a reliable approach in reducing vascular complications rate and increasing survival of flaps in animal models. The main conclusions drawn from the study include the following: perivascular injections targeting each vascular pedicle are preferred in cases of free flaps or axial flaps; subdermal injections are favorable in cases of random pattern skin flaps; and injections should be performed 7 days before flap elevation.

scholarly journals Mechanism and Priority of Botulinum Neurotoxin A versus Sacral Neuromodulation for Refractory Overactive Bladder: A Review

2021 ◽  
pp. 1-6
Author(s):  
Yanping Zhang ◽  
Fengping Ji ◽  
Erpeng Liu ◽  
Jian Guo Wen
Keyword(s):  
Nervous System ◽  
Overactive Bladder ◽  
Botulinum Neurotoxin ◽  
Sacral Neuromodulation ◽  
Order Effect ◽  
Poor Quality ◽  
Physical And Mental Health ◽  
Botulinum Neurotoxin A ◽  
Optimal Method ◽  
Advantages And Disadvantages

<b><i>Background:</i></b> The treatment of common overactive bladder (OAB) has reached a consensus, but there is not a clear answer to the treatment of refractory OAB (ROAB). ROAB is defined as nonresponsive to treatment with behavioural and oral therapies. The disease can influence the physical and mental health of patients, cause poor quality of life, and create an urgent socio-economic burden. With the advancement of medical treatment, the treatment of OAB has improved significantly in the last 2 decades, especially ROAB, by the usage of botulinum neurotoxin A (BoNT-A) and sacral neuromodulation (SNM). Many studies have demonstrated their effectiveness and safety. However, which therapy is the optimal method remains unclear for patients with ROAB, and the exact mechanism involved in the procedures is still unknown. <b><i>Summary:</i></b> This review is to clarify the mechanisms, advantages, and disadvantages of SNM and BoNT-A in treatment of ROAB, and determine whether there is an order effect of SNM and BoNT-A in managing ROAB. <b><i>Key Messages:</i></b> BoNT-A and SNM mainly act on the peripheral nervous system and central nervous system, respectively. But BoNT-A and SNM may partly act on the central and peripheral nervous systems, separately. SNM may be a better choice than BoNT-A in the long time. At the same time, BoNT-A and SNM can treat the ROAB as the first and next steps, and the sequence of both would not affect the effectiveness of each other.

Identification of novel inhibitors of botulinum neurotoxin A

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
C Yalamanchili ◽  
VK Manda ◽  
AG Chittiboyina ◽  
WA Harrell Jr ◽  
RP Webb ◽  
...  
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin A

Botulinumtoxin zur Behandlung von neuropathischen Schmerzen

2017 ◽  
Vol 36 (05) ◽  
pp. 315-323
Author(s):  
N. Üçeyler ◽  
C. Sommer
Keyword(s):  
Botulinum Neurotoxin ◽  
Neuropathische Schmerzen ◽  
Botulinum Neurotoxin A ◽  
Topische Therapien

ZusammenfassungDie Behandlung neuropathischer Schmerzen mit systemisch wirksamen oral verabreichten Pharmaka ist bei vielen Patienten wirksam, kann jedoch zu zentralnervösen unerwünschten Wirkungen wie Müdigkeit oder Schwindel führen. Daher sind in den letzten Jahren topische Therapien in das Zentrum der Aufmerksamkeit gerückt. Botulinumtoxin, etabliert in der Therapie von Dystonien und Spastik, wurde zunehmend bei Schmerzerkrankungen getestet, hierbei ist Botulinum-Neurotoxin A der am besten untersuchte Serotyp. Die häufigsten Indikationen waren Schmerzen im Trigeminusversorgungsbereich und periphere neuropathische Schmerzen. Bei den meisten Studien war Botulinum-Neurotoxin A Placebo deutlich überlegen. Präklinische Studien zum Wirkmechanismus erbrachten die Erkenntnis, dass neben dem erwarteten peripheren Effekt sehr wahrscheinlich auch eine zentrale Reduktion der Ausschüttung von exzitatorischen Neurotransmittern an der Wirkung beteiligt ist.

Acute and Persistent Infection of Human Neural Cell Lines by Human Coronavirus OC43

1999 ◽  
Vol 73 (4) ◽  
pp. 3338-3350 ◽  
Author(s):  
Nathalie Arbour ◽  
Geneviève Côté ◽  
Claude Lachance ◽  
Marc Tardieu ◽  
Neil R. Cashman ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Lines ◽  
Persistent Infection ◽  
Viral Antigen ◽  
Primary Cultures ◽  
Point Mutations ◽  
Neural Cell ◽  
Persistently Infected ◽  
Human Neural Cell ◽  
Neural Cell Lines

ABSTRACT Human coronaviruses (HuCV) are recognized respiratory pathogens. Data accumulated by different laboratories suggest their neurotropic potential. For example, primary cultures of human astrocytes and microglia were shown to be susceptible to an infection by the OC43 strain of HuCV (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800–806, 1997). We speculate that the neurotropism of HuCV will lead to persistence within the central nervous system, as was observed for murine coronaviruses. As a first step in the verification of our hypothesis, we have characterized the susceptibility of various human neural cell lines to infection by HuCV-OC43. Viral antigen, infectious virus progeny, and viral RNA were monitored during both acute and persistent infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK-N-SH, neuroglioma H4, oligodendrocytic MO3.13, and the CHME-5 immortalized fetal microglial cell lines, were all susceptible to an acute infection by HuCV-OC43. Viral antigen and RNA and release of infectious virions were observed during persistent HuCV-OC43 infections (∼130 days of culture) of U-87 MG, U-373 MG, MO3.13, and H4 cell lines. Nucleotide sequences of RNA encoding the putatively hypervariable viral S1 gene fragment obtained after 130 days of culture were compared to that of initial virus input. Point mutations leading to amino acid changes were observed in all persistently infected cell lines. Moreover, an in-frame deletion was also observed in persistently infected H4 cells. Some point mutations were observed in some molecular clones but not all, suggesting evolution of the viral population and the emergence of viral quasispecies during persistent infection of H4, U-87 MG, and MO3.13 cell lines. These results are consistent with the potential persistence of HuCV-OC43 in cells of the human nervous system, accompanied by the production of infectious virions and molecular variation of viral genomic RNA.

scholarly journals Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Changjiao Gan ◽  
Wenbo Luo ◽  
Yunzhou Yu ◽  
Zhouguang Jiao ◽  
Sha Li ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Clostridium Botulinum ◽  
Freeze Drying ◽  
Botulinum Neurotoxin ◽  
Secretory Iga ◽  
Immune Protection ◽  
Dry Powder ◽  
Botulinum Neurotoxin A ◽  
Spray Freeze Drying

AbstractBotulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

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