Importance of Animal Studies

8/12/2019 Importance of Animal Studies

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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/


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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/


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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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Importance of Animal Studies