‫بنام خداوند جان وخرد‬
‫نشر‪ :‬اندیشه رفیع‬
‫منونه سواالت آزمون جامع علوم اپيه پزشکي‬
‫‪3‬‬
‫مکانيسم اثر سم کزاز کداميک از موارد زير است؟‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫الف‪ -‬ممانعت از سنتز استيل کولين‬
‫ب‪ -‬تشديد آزادسازي گابا‬
‫ج‪ -‬تشديد آزاد سازي گليسين‬
‫د‪ -‬مهار نوروترانسيمتر هاي مهاري‬
‫‪ ‬اسفند ‪88‬‬
‫‪4‬‬
‫کدام نوروترانسميرت به وسيله سم کلسرتيديوم بوتولينوم به‬
‫طور اختصاصي مهار مي شود؟‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫الف‪ -‬استيل کولين‬
‫ب‪ -‬گليسين‬
‫ج‪ -‬گابا (گاما آمينوبوتيريک اسيد)‬
‫د‪ -‬گلوتامات‬
‫‪ ‬اسفند ‪85‬‬
‫‪5‬‬
‫فلج شل عضالين توسط کدام يک از کلسرتيديوم هاي زير به‬
‫وجود مي آيد؟‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫الف‪ -‬کلستريديوم بوتولينوم‬
‫ب‪ -‬کلستريديوم پرفرينجنس‬
‫ج‪ -‬کلستريديوم ديفيسيل‬
‫د‪ -‬کلستريديوم تتاني‬
‫‪ ‬شهريور ‪82‬‬
‫‪6‬‬
‫کدام سم ميکروي مانع آزاد شدن استيل کولني در حمل‬
‫اتصال عصب و عضله مي شود؟‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫الف‪ -‬توکسين آنتراسيس‬
‫ب‪ -‬توکسين شيگال‬
‫ج‪ -‬توکسين ‪ TssT‬استافيلوکوکوس‬
‫توکسين بوتولينوم‬
‫‪ ‬اسفند ‪81‬‬
‫‪7‬‬
‫کدام يک از سروتيپ هاي سم کلسرتيديوم بوتولينوم در‬
‫مسموميت غذايي انسان دخالت دارد؟‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫الف‪C1, C2, D -‬‬
‫ب‪G, F, H -‬‬
‫ج‪L1, L2, L3 -‬‬
‫‪A, B. E‬‬
‫‪ ‬شهريور ‪81‬‬
‫‪8‬‬
‫تريسموس‪ ،‬قفل شدن دهان و خنده شيطاين و به دنبال آن‬
‫انرسايي تنفسي در کدام بيماري زير ديده مي شود؟‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫الف‪ -‬کزاز‬
‫ب‪ -‬بوتوليسم‬
‫ج‪ -‬مننژيت‬
‫د‪ -‬سيفيليس مادرزادي‬
‫‪ ‬اسفند ‪79‬‬
‫‪9‬‬
‫کدام نوروترانسميرت به وسيله سم کلسرتيديوم بوتولينوم به‬
‫طور اختصاصي مهار مي شود؟‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫الف‪ -‬استيل کولين‬
‫ب‪ -‬گليسين‬
‫ج‪ -‬گابا (گاما آمينوبوتيريک اسيد)‬
‫د‪ -‬گلوتامات‬
‫‪ ‬اسفند ‪85‬‬
‫‪10‬‬
‫کدام نوروترانسميرت به وسيله سم کلسرتيديوم بوتولينوم به‬
‫طور اختصاصي مهار مي شود؟‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫الف‪ -‬استيل کولين‬
‫ب‪ -‬گليسين‬
‫ج‪ -‬گابا (گاما آمينوبوتيريک اسيد)‬
‫د‪ -‬گلوتامات‬
‫‪ ‬اسفند ‪85‬‬
‫‪11‬‬
Anaerobic Bacteria
Clostridia
Dr Alvandi
94
‫تقسيم بندي ارگانيسم ها از نظر نياز به‬
‫اكسيژن‬


Obligate (strict) Aerobic
Obligate (strict) Anaerobes
• Bacteria: Clostridia, Bacteriodes ...



Facultative Anaerobes
Microaerophilic organisms
Aerotolerant Anaerobes
Oxygen Toxicity


Oxygen is used by aerobic and
facultatively anaerobic organisms as its
strong oxidising ability makes it an
excellent electron acceptor
During the stepwise reduction of osygen,
which takes place in respiration tosic and
highly reactive intermediates are produced
reactive oxygen species (ROs).

Organisms that use O2 have developed defence
mechanisms to protect themselves from these
toxic forms of oxygen - enymes

Catalase: H2O2 + H2O2 => 2H2O + O2

Perosidase: H2O2 + NADH + H+ => 2H2O + NAD+

superoxide dismutase: O2- + O2- + 2H+ => H2O2
+ O2
Anaerobic Bacteria cont…
spore-forming:
rod, Gram (+)--- Clostridia
Nonspore-forming:
Rod, Gram (+)
Propionibacterium
Bifidobacterium
Lactobacillus
Eubacterium
Actinomyces
Rod, Gram (-)
Bacteroides
Fusobacterium
Campylobacter
Cocci, Gram (+)
Peptococcus
Peptostreptococcus
Cocci, Gram (-)
Veillonella
Clostridia
18
Clostridia: general characteristics


Gram-positive bacilli
some clostridia consistently stain gram-negative (Clostridium
ramosum, C. clostridioforme)
 Anaerobic

Most members are strict anaerobes

inability to reduce sulfate to sulfite


some are aerotolerant
some species are aerotolerant and can grow on agar media
exposed to air (Clostridium tertium, Clostridium histolyticum)
19
19
Clostridia: general characteristics


Forming endospore: ubiquitous
spores may not be observed in some species (C. perfringens,
C. ramosum)

Natural habitat: soil and intestinal tracts of animals and
humans

Very active metabolisms, ferment a variety of sugars, very
short generation times

Production of numerous histolytic tosins, enterotosins, and
neurotosins
20
Virulence Factors
 (1) ability to survive adverse environmental
conditions through spore formation
 (2) rapid growth in a nutritionally enriched,
oxygen-deprived environment
 (3) production of numerous histolytic
tosins, enterotoxins, and neurotoxins.
21
23
Clostridium tetani
24
25
Physiology and structure

small, motile, spore-forming bacillus

Produces round, terminal spores (drumstick)

Relatively inactive metabolically

Estremely sensitive to osygen tosicity

Difficult to grow

Ferments: proteins or amino acids

Produces: acetic acid, fatty acids
NH3, CO2, H2
26
Pathogenesis and Immunity
1- Tetanolysin
Tetanospasmin
151,000 Da
An oxygen-labile hemolysin
Clinical significance is unknown
serologically like: streptolysin o
C. perfringens
Listeria monocytogenes
2- Tetanospasmin
Heat-labile neurotoxin
Plasmid-encoded
A-B toxin
Responsible for clinical manifestations of tetanus
27
Tetanospasmin
B-chain; carbosyl-terminal portion binds to a specific sialic acid receptors
(e.g., polysialogangliosides) and adjacent glycoproteins
A-chain; a zinc endopeptidase
degrades synaptobrevin
Inhibition of GABA and Glycine neurotransmitters releasing
28
spastic paralysis
29
30
Pathogenesis and Immunity
Germination of spore
(1) necrotic tissue, (2) calcium salts, and (3) associated pyogenic
infections,
All of which aid establishment of low oxidation-reduction potential
31
Epidemiology

Ubiquitous; spores are found in most soils and can colonize
gastrointestinal tract of humans and animals

Exposure to spores is common, but disease is uncommon except
in underdeveloped countries

Disease does not induce immunity
It is estimated that more than 1 million cases occur worldwide,
with a mortality rate ranging from 30% to 50%. At least half
the deaths occur in neonates.
32
Clinical Diseases
Incubation period varies from a few days to weeks
Generalized tetanus
Cephalic
Localized
Neonatal
33
Clinical Diseases
Generalized tetanus
most
common form
 A stiff
neck, a tight jaw (trismus or lockjaw)

Facial muscle spasms (Risus sardonicus)

Difficulty swallowing, Febrile, irritability, heavy sweating

Cardiac arrhythmias. fluctuations in blood pressure, profound sweating

Back spasms (opisthotonos)
 In advanced stages; break bones, Respiratory complications are common
and death rates high
A soldier dying from tetanus. Painting by Charles Bell
Opisthotonos 34
(spastic paralysis of the back)34
Clinical Diseases
Localized tetanus

Involvement of muscles in area of primary injury

Infection may precede generalized disease

Favorable prognosis
35
Cephalic tetanus


primary site of infection is head
Prognosis is very poor
36
Neonatal tetanus
 Generalized disease in neonates

Mortality in infants exceeds 90%

Infection typically originates from umbilical stump
37
Laboratory Diagnosis

On basis of clinical presentation
 As
stated earlier, C. tetani is a common contaminant of wounds
and may be found in patients who do not develop tetanus
Hence, isolation of bacteria from a patient may not be diagnostic
38
Treatment, Prevention, and Control
1)
Treatment of tetanus : debridement of primary wound
2)
Use of metronidazole or penicillin
3)
Passive immunization with human tetanus immunoglobulin
4)
Vaccination with tetanus toxoid
(Three doses followed by booster doses every 10 years)
Penicillin, like tetanospasmin, inhibits GABA activity
39
Clostridium botulinum
40
‫موارد بوتوليسم در ايران‬
Physiology and structure
 A heterogeneous
group of Fastidious

Large, anaerobic Gram positive bacillus

spore forming

Neurotoxin; A-B toxin

seven antigenically distinct botulinum toxins (A to G)

Human disease is associated with types A, B, E, and F

Types C and D affect animals

Type G has not been linked to illness up to this date

Only one toxin is produced by most individual isolates
42
Physiology and structure
 Other species of clostridia produce botulinum toxins
 C. butyricum (type E toxin)
 C. baratii (type F toxin)
 Clostridium argentinense (type G toxin)
 Human disease
 Rarely associate with C. butyricum and C. baratii
 not definitively demonstrate with C. argentinense
43
Pathogenesis and Immunity
 A-B tosin
 light or A chain with zinc-endopeptidase activity
 heavy or B chain
 Nontoxic proteins protects neurotoxin during passage through




digestive tract
Botulinum toxin is absorbed from the gut and binds to receptors
of presynaptic membranes of motor neurons of the peripheral
nervous system and cranial nerves
Carbosyl-terminal portion of botulinum heavy chain binds
specific sialic acid receptors and glycoproteins on surface of
motor neurons and stimulates endocytosis of toxin molecule.
Botulinum endopeptidase inactivates proteins that regulate
release of acetylcholine
Clinical presentation of botulism is a flaccid paralysis.
44
Pathogenesis and Immunity

Toxin is very specific for cholinergic nerves

Preventing release of neurotransmitter acetylcholine

Blocks neurotransmission at peripheral cholinergic synapses
45
46
47
Epidemiology

Commonly isolated in soil and water samples throughout world
1) Classic or foodborne botulism
2) Infant botulism("floppy baby").
3) Wound botulism
4) Inhalation botulism (bioterrorism)
 Types A & B toxins; consumption of home canned foods
 Type E toxin with consumption of preserved fish
48
Clinical Diseases
Foodborne Botulism

Incubation 24-72 hours ; Patients become weak and dizzy
Initial signs include

Blurred vision with fixed dilated pupils; Ptosis (Drooping eyelids)

Dry mouth (indicative of anticholinergic effects of tosin)

Constipation; Abdominal pain; Afebrile; normal mentation

In progressive disease; Descending Flaccid paralysis
(Bilateral weakness of peripheral muscles)
49
Nystagmus
Foodborne Botulism
 Death is most commonly attributed to respiratory paralysis
 Complete recovery in patients often requires many months
to years, or until affected nerve endings regrow.
 Mortality
 70%
 has been reduced to 5% to 10% through use of better supportive
care, particularly in the management of respiratory
complications.
51
Clinical Diseases
Infant Botulism (most between 1 and 6 months)

It is caused by ingestion of spores
In absence of competitive bowel microbes
Lack of breast milk
Untreated natural honey, corn syrup and infant milk
powder

Antigenic variations types A/B

Disease typically affects infants (1 and 6 months)

symptoms are initially nonspecific

Constipation, weak cry, or "failure to thrive"

Mortality is very low (1% to 2%)
52
Clinical Diseases
Wound Botulism
Least common, but on rise
 Occurs when spores inoculate a wound and anaerobic

conditions allow germination and subsequent production
of toxin
 Associated with IV drug use , and medical equipment es.
catheters

Often misdiagnosed as other neurological syndromes
53
Laboratory Diagnosis
 First: Clinical diagnosis
 Foodborne botulism
 toxin activity in food or patient's serum, feces, or gastric fluid.
 Infant botulism
 toxin is detected in the infant's feces or serum or organism cultured
from feces.
 Wound botulism
 Toxin in patient's serum or wound or organism cultured from wound.
 No single test for food borne botulism has sensitivity greater than
60%; in contrast, toxin is detected in serum of more than 90% of
infants with botulism.
 Isolation of C. botulinum from specimens contaminated with other
organisms can be improved by heating the specimen for 10
minutes at 80° C to kill all non clostridial cells.
54
Laboratory Diagnosis
 Culture of heated specimen on nutritionally enriched anaerobic
media allows heat-resistant C. botulinum spores to germinate.
 Demonstration of toxin production (typically performed at
public health laboratories) must be done with a mouse bioassay.
 This procedure consists of preparation of two aliquots of isolate,
mising of one aliquot with antitoxin, and intraperitoneal
inoculation of each aliquot into mice.
 If antitoxin treatment protects mice, toxin activity is confirmed.
 samples of implicated food, stool specimen, and patient's serum
should also be tested for toxin activity.
55
Treatment, Prevention, and Control
1. Adequate ventilatory support
2. Elimination of organism from gastrointestinal tract through
judicious use of gastric lavage and metronidazole or penicillin
3. Use of trivalent botulinum antitoxin versus tosins A, B, & E
to bind toxin circulating in blood stream
Prevention:
 Preventing spore germination (by maintaining food in an acid pH or
storage at 4° C or colder),
 Destroying preformed tosin (all botulinum tosins are inactivated by heating
at 60° C to 100° C for 10 minutes)
56
 Children younger than 1 year should not eat honey
Questions???
57
Thanks for your
attention
58