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Botulinumtoxin

L/O/G/O
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Contents
1 2 3 4 Introduction Tocicology Case Report Paper Reading

Introduction Family:
Clostridiaceae

Species:
Clostridium botulinum

Morphology:
Gram-positive G(+) Rod shaped bacterium Endospore

Introduction Environment:
obligate anaerobe 25~42 pH=5.7~8.0 animal protein commonly found in soil

Resistant:
Dry heating Moist heating Autoclave 180 5~15min 100 3~5hr 121 5min
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Introduction Botulinumtoxin
The most acutely toxic substance Neurotoxic protein

Type
Seven types of toxins A~G ABEF Human CD cows, birds, and other animals
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Introduction Structure
The toxin is a two-chain polypeptide with a 100-kDa heavy chain joined by a disulfide bond to a 50-kDa light chain

Toxin Produce
Nontoxic pre-toxin
In C. botulism

Release pre-toxin
After bacteria died

Become toxic
activated by trypsin

GI absorption
Cannot be destroyed by pepsin & gastric acid
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Pathogenesis mechanism
Botulinus toxin will bind the terminal nerve cell to enter the neuron, and have the autolysis phenomenon. Double S-bond of botulinus toxin will be broken, and the part of light chains will decompose SNARE protein.

B.D.F.G decompose VAMP A.C.E decompose SNAP-25 C decompose Syntaxin

Pathogenesis mechanism
SNARE protein is unable bind to the synapse, and the synapse can not fuse with nerve endings, causes preventing the release of acetylcholine results in paralysis of muscle Because botulinus toxin inhibits the release of acetylcholine but synthesis, therefore causes paralysis of muscles is reversal.
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Pathogenesis mechanism

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Clinical presentation

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Food botulism Wound botulism Infant botulism

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Food botulism Etiology


Infected food especially home-canned food

Symptom
Visual disturbance Flaccid paralysis Respiratory paralysis or cardiac arrest
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Food botulism
Incubation period
12~36 hrs Incubation period Toxicity

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Food botulism
Gastric lavage and lavement
eliminate the unclear substance

ABE antitoxin
in 1~24hr

Respiratory supporting therapy


avoid respiratory failure

cathartic
If constipation
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Food botulism

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Wound botulism Etiology


Uncommon Caused by infectious wound (sandsoilblack tar heroin) Produce toxin in anaerobe

Symptom
Same as food botulism

Incubation period
4~21 days
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Wound botulism
Debridement
Eliminate bacteria

Penicillin 3 million U
every 4 hrs

Avoid use Aminoglycoside & Clindamycin


Prevent NM blockade

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Wound botulism

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Wound botulism

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Infant botulism Etiology


In vivo multiplication C. botulism with production of neurotoxin within infant gut Honey

Symptom
Unobvious at beginning Flaccid paralysis Respiratory paralysis Sudden Infant Death Syndrome, SIDS

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Infant botulism Therapy


Supporting therapy Can not use antitoxin allergic Human botulism immune globulin (USA)

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Infant botulism

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Application Is the Botulinumtoxin safe for treatment?


Pure substance without bacteria Can not absorb into blood because it combines with muscle immediately

SAFE!!
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Application Therapy period


Maintain 3~6 months on average Different from peopledisease and injection site Gastroenterology Ophthalomology
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Use
Neurology Otolaryngology Dermatology

Application

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Case Report

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Case Report
A 60-year-old Atayal female who was brought to the hospital ate the meat her sister-in-law cured couple of days ago. Her symptoms are vomiting, nausea, drooping eyelids, slurred speech, swallowing difficulties and weakness in limbs. Doctors once thought that brain-stem stroke, myasthenia gravis, or neuropathy, but were unable to diagnose. Later she was transferred to neurology, after consultation, the toxicology collected her blood, stomach Abstraction and stool tests sent to the Department of Health, CDC. Testing completed, and finally to determine the patient is botulism.
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Case Report
Botulism treatment is injection of botulinum antitoxin. Patients with respiratory failure must be urgently given to respirator. Some other symptoms are used to support therapy. Baby is not suitable injection of anti-toxin, only the use of supportive therapy Because botulinum food poisoning cases are rare, together with their symptoms rather like neuropathy, clinical diagnosis is not easy. In particular, toxins often unevenly distributed, often result in error diagnosis.
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Paper Reading
S KHEMANI, R GOVENDER, A ARORA, P E OFLYNN, F M VAZ

Use of botulinum toxin in voice restoration after Laryngectomy (Review Article)


The Journal of Laryngology & Otology (2009), 123, 13081313.

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Whats laryngectomy? Why do it?


Removal of the larynx
Cancer Difficult to swallow

After that..

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Botulinum toxin to the pharyngoesophageal segment


Chemically denervate the pharyngeal musculature Prevent severe hypertonicity or spasm of the pharyngoesophageal segment Post-laryngectomy voice restoration
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Left: Videofluoroscopy showing hypertonic pharyngoesophageal segment. Right: Videofluoroscopy showing needle position for botulinum toxin injection (arrow).

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Mechanism

Preventing the release of acetylcholine at the neuromuscular junction.

Clean SNARE

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Result
Hoffman et al. Blitzer et al. Crary & Glowasky Zormeier et al Meleca et al. 8 6 5 7 5 45 U Botox 15-45 U Botox 25-35 U Botox 60-90 U Botox 60-80 U Botox 100 U Botox 500 U Botox ( ) 87.5% 100% 80% 87.5% 62.5 80% 87% (26%) 70% (40%)

23 Lewin et al. Ramachandran et al. 10 Hamaker & Blom Chone et al. 62 8

100 U Dysport 79% 1 89% 100 U Botox 100%

objective improvement in voice production occurred in between 70 and 100 per cent of cases.

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Result
Relax the hypertonic pharyngoesophageal segment. Prevent spasm of the pharyngoesophageal segment Most of all ! Help patients to improve their voice

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Conclusion
Seven type Foodwoundinfant botulism Plastic surgery Benefit to people

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THANKS FOR YOUR LISTENING


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