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To understand the need for animal studies
To know the advantages and disadvantages of animalstudies
To know which animals are routinely used for animal studies
Rules and ethics regarding animal research
Important animal studies in orthodontics
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Research is the corner stone for development in medical and
dental science
Scientists need to study natural situations to understand life
processes and to investigate how introducing a particularsubstance can change living systems.
There are several tiers of research and not all studies can be
carried out on human body due to safety and ethical concerns
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The processes in any organism are far more complicated than
just the sum of the individual parts.
It is difficult to replicate at the lab bench the complex
interactions.
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Animals and humans are very similar; we have the same organ
systems performing the same tasks in more or less the same way.
Animals suffer from diseases similar to humans; like cancers,TB, flu and asthma.
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YEAR MEDICAL ADVANCEMENT ANIMAL CREDITED
1796 Smallpox vaccine developed Cow
1881 Anthrax vaccine developed Sheep
1902 Lifecyle of Malaria discovered Pigeon
1921 Insulin discovered Dog, Fish
1933 Tetanus vaccine developed Horse
1939 Anticoagulants developed Cat
1954 Polio vaccine developed Mouse, Monkey
1956 Open-heart surgery & pacemakers
developed
Dog
1964 Cholesterol regulation discovered Rat
1982 Leprosy treatment developed Armadillo
1990 Organ transplant techniques
advanced
Dog, Pig, Sheep, Cow
1997 Prions discovered & characterized Hamster, Mouse
2000 Brain signal transduction discovered Sea Slug, Mouse, Rat
Foundation for Biomedical Research- 2003
http://www.fbresearch.org/http://www.fbresearch.org/8/12/2019 Importance of Animal Studies
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Each species in the animal kingdom is unique. But there are
both differences and similarities between animals and humans.
This is what comparative medicine is about: researchers use
both similarities and differences to gain insight into the many
complex human biological systems.
Researchers work with animal models that have biological
systems similar to that of a human.
For instance, swine and humans share similar cardiovascular and
skin systems.
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We share 95% of our genes with a mouse, making them an
effective model for the human body.
Organisms that look very different can be very similar
genetically.
Chimpanzees share 98.7% of their DNA with humans. Zebrafish
share 75 - 80% of their DNA with humans.
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The differences exhibited in a research model can also provide
great insights.
For instance, sharks rarely get cancer, cockroaches canregenerate damaged nerves, and some amphibians can regrow
lost limbs.
By studying these animals we may learn how they accomplishthese remarkable feats and apply the principles to human
medicine.
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Guinea pig
Zebra fish
ferret
rat
sheep
armadillo
pig
dog
rabbit
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Rats, mice and other rodent
81% Fish, amphibians, reptiles and
birds18%
Small mammals, mostly rabbitsand ferrets0.8%
Sheep, cows, pigs and other large
mammals0.4%
Dogs and cats0.12%
Primates, mainly macaque
monkeys
0.07%
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Study aspect animal
1. growth Mice
2. Genetics Mice
3. Histo-chemistry Rodents, dogs
4 Condylar changes rodents
5. Implants Dogs
6. Distraction osteogenesis Dog
7. Surgical procedures dog
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Areas of research
http://www.understandinganimalresearch.org.uk/how/areas-of-research/breeding-and-gm-mice/8/12/2019 Importance of Animal Studies
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Mice and rats are the most commonly used animals for geneticstudies.
They may be used in basic research to discover the function of a
particular gene in embryonic development (or the ageing of cells),
or in the study of diseases.
Genetically altered (GA)
Genetically modified (GM)
Transgenic
Knockout
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Genetically modified organisms as those which have been
genetically changed.
Genetically altered organisms include both GM organisms and
those carrying 'natural' mutations.
Transgenicrefers to a subtype of GM animals whose genomes
have been altered by the insertion of part of DNA from another
organism.
A knockoutanimal has had one or more genes inactivated or
silenced.
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Most accurate way to understand the effects of any substance or
procedure on a living body.
Easy to mimic interactions at organ system level.
Helps researchers find newer drugs and treatments
Human harm is reduced and human lives are saved but also
animal lives are saved because of animal testing.
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Animals may not have the exact same physiology as humans
but animal testing is accurate enough to test whether a substanceis even safe enough for human trials.
Studies requiring sacrifice can be performed
Alternative methods of testing do not simulate humans in the
same way
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- High cost :
The housing , feeding, carrying treatments, controlling the
environment, is very expensive.
Animals used for testing are usually obtained from specific
breeding facilities and come with a high price tag.
-Morality :
Animals have the right to live their own life; and we must not
meddle with them just because we can.
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-Necessity/validity :
It is not important enough to sacrifice an animal, like testing the
effect of cosmetics and household products.
-Usefulness :
Animals kept in unnatural conditions (a lab and not their naturalhabitat), or animals in pain or distress, are not giving rise to
accurate or consistent results.
Humans are quite different from other animals so the reaction of
the drug in the animals body versus the human body is different.
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Replacethe use of animals with alternative techniques.
Reducethe number of animals used to a minimum, to obtaininformation from fewer animals or more information from the
same number of animals.
Refinethe way experiments are carried out, to make sureanimals suffer as little as possible. This includes better housing
and improvements to procedures which minimize pain and
suffering and/or improve animal welfare.
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Guidelines have been laid down by the INDIAN NATIONAL SCIENCE
ACADEMY:
Animal experiments should be undertaken only after dueconsideration of their relevance for human or animal health.
The animals selected should be of an appropriate species and
quality.
Minimum number should be used to obtain scientifically and
statistically valid results.
Experiments on Animals ( Control and Supervision ) Rules, 1968
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Investigators should treat animals with kindness and avoid
discomfort, distress or pain.
Appropriate sedation, analgesia or anaesthesia must be given toavoid discomfort.
The best possible living condition should be provided to animals
used for research.
Care of animals should be under the supervision of a
veterinarian.
The experiment should not be performed for the purpose ofattaining or retaining manual skill.
In-vitro systems to replace or reduce the number of animals
should be used wherever possible.
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1. In vitro studies
2. Tests using cell or organ cultures rather than whole organisms
3. organisms such as worms or bacteria are used instead of
mammals.
4. Computer models to predict outcomes of testing.
However, each of these methods provides limited information that
applies to a very specific test situation and may not fully
anticipate the results in a complicated organism (such as humans)
with many interacting organ systems.
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Lei Sun; Meiqing Wang; Jianjun He; Lei Liu; Shuang Chen; Sven E. Widmalm
Angle Orthod. 2009;79:5153.
Twenty-four 8-week-old rats divided into a control group (left untreated)
and an experimental group where a non-balanced occlusion was created.
Elastic rubber bands, were inserted and 1 week later were replaced
by plastic material between the first and the second molars of the left
maxillary and the right mandibular dentitions to move the first molars
about 0.8 mm mesially.
This created and maintained a physiologically nonbalanced occlusion.
The animals were euthanized 8 weeks later, and the TMJ disc thickness was
measured histologically
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Results: The intermediate zone was thicker in the experimental group
than in the control group but no differences were found between
groups regarding the anterior and posterior bands.
There were no significantsex-related effects on this observation.
The results indicate that the intermediate zone of rat TMJ
disc has the ability to adapt to the alteration of the space between
condyle and fossa caused by occlusion changes.
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Yehya Ahmed Mostafa, Ahmed Mostafa Heider Mona Mohamed Salah Fayed,
Samah Mehanni, Nader Nabil ElBokle
Am J Orthod Dentofacial Orthop 2009;136:570-7
Aim:
(1) to identify the effect of the Corticotomy on orthodontic
tooth movement compared with the standard technique
(2) explore the histologic basis of the difference between
the 2 techniques.
Methods:
Six dogs, aged 6 to 9 months, were used in this study.
Extraction of the maxillary second premolar and miniscrew
placement were done bilaterally in the maxilla
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On the right side, the corticotomy was performed.
The first premolars were distalized against the miniscrews with
nickel-titanium coil springs on both sides.
One dog was killed each week after orthodontic force application.
Results:
The first premolar on the CF side moved significantlymore rapidly
(P \0.05). Histologic findingsshowed more active and extensivebone remodeling in the CF group.
Conclusions: The CF technique doubled the rate of orthodontic
tooth movement. The acceleration of tooth movement
associated with corticotomy is due to increased bone turnover andbased on a regional acceleratory phenomenon.
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Colin K. L. Ong, ; Laurence J. Walsh, ; Aart A. R. Taverne, Anne L. Symons,
(Angle Orthod 2000;70:118125.)
This study examined the effect of prednisolone on orthodontic
movement using an established rat model.
The corticosteroid treated group (N = 6) was administered prednisolone
(1 mg/kg) daily, for a 12-day; the control group (N = 6) receivedequivalent volumes of saline.
On day 12, an orthodontic appliance was placed which exerted 30 g of
mesial force to the maxillary first molar.
Animals were sacrificedon day 24 and tooth movement was measured.
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There were no significantdifferences in the magnitude of tooth movement
between the 2 groups.
steroid-treated rats displayed less root resorption on the compression side
and fewer TRAP-positive cells within the PDL space on the same side.
This suggests steroid treatment suppressed clastic activity.
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Angle Orthodontist, Vol 78, No 1, 2008
AIM :To associate the expressions of SOX9 and type II collagenduring growth in the synchondrosis with and without tensile stress in
order to understand the role of these factors in the growth of
cartilage in spheno-occipital synchondrosis.
Materials and Methods:
Sixty 1-day-old male BALB/c mice were divided into experimental
and control groups.
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Each group was subdivided again into fivedifferent time points
which were 6, 24, 48, 72, and 168 hours.
Each mouse was sacrificedusing an overdose of pentobarbitonesodium.
The synchondroses were aseptically removed and incubated in a
24-well plate with or without tensile stress in tissue culture.
Tissue sections were stained immunohistochemically to
quantitatively analyze the expression of SOX9 and type II collagen.
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Results: There was a statistically significantincrease of
57% in the expression of SOX9 between the experimental
and control groups at 24 hours, followed by a significant
increase of 44.4% in the expression of type II collagen at72 hours.
Conclusions: SOX9 may play an important role for early
differentiation of chondrocytes and increase the
expression of type II collagen, a major component of the
extracellular matrix, during the growth of cartilage in the
spheno-occipital synchondrosis.
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Angle Orthodontist, Vol 78, No 1, 2008
Objective:
The aim of this study is to examine the effect of gene therapy
(specificvascular growth inducting genes )on condylar growth bymeans of a morphological assessment.
Materials and Methods:
Ninety 35-day-old female rats were randomly divided into three
groups, which received any of the injections of recombinant adeno-
associated virus mediated vascular endothelial growth factor (rAAV-
VEGF), rAAV mediated enhanced green fluorescenceprotein (rAAV-
eGFP), or phosphate-buffered saline (PBS) into both mandibular
condyles.
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Each group of rats was sacrificedon the following experimental
days: 7, 14, 21, 30, and 60. Left halves of the mandibles were
isolated and digital pictures were obtained.
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Results:The length of condylar process as well as mandibular
length significantlyincreased on day 30 and continued to increase
until the end of the experiment.
The width of condyle increased significantlyfrom day 30 and lasted
to day 60.
Condylar length was found to be significantlylonger on day 60.
Conclusion: Gene therapy with VEGF stimulates condylar growth at
will. The rAAV-VEGF is an excellent candidate for future gene
therapy to induce mandibular growth
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A. Bakr M. Rabie, Zhihe Zhao, Gang Shen, Urban Hgg, Wayne Robinson
AIM:
To identify the sequence of cellular changes in the glenoid fossa
and to quantify the amount of bone formation in response to
mandibular advancement.
MATERIAL AND METHOD:
One hundred 35-day-old rats were randomly divided into 5experimental groups (15 rats each) and 5 control
groups (5 rats each).
Am J Orthod Dentofacial Orthop 2001;119:390-400
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In the experimental groups, functional appliances were used to
create continuous forward mandibular advancement.
The rats were killed after 3, 7, 14, 21, and 30 days. Sections werecut through the glenoid fossa in the parasagittal plane and stained
with periodic acid and Schiffs reagent for evaluation of bone
formation and with hematoxylin and eosin for observation of
cellular response.
RESULT:
In the control rats, bone formation decreased over time in all
regions.
In the experimental group, bone formation significantly increasedfrom day 7 to day 30. Day 21 marked the highest levels of bone
formation.
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CONCLUSION:
Mandibular protrusion resulted in the osteoprogenitor cells
being oriented in the direction of the pull of the posterior fibersof the disc and also resulted in a considerable increase
in bone formation in the glenoid fossa.
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Although research on animals is
an indispensible part of
medical/dental research;
indiscriminate use of animals
must be avoided.
Research carried out in
accordance with the principles
laid down by the governing
bodies can reduce the pain and
discomfort to animals.
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Anti-hypertensive medicines ACE inhibitor was developed due
to research into the Brazilian pit viper venom .
Animal research contributes to 70% of the Nobel prizes for
physiology and medicine.
Monkeys are used to develop and test HIV medicines because
the virus does not infect small animals like mice and rats.
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