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PRESENTATION ON CAT AS EXPERIMENTAL
ANIMAL MODEL
Under the guidance of
Dr. VGM Naidu.
Associate Professor ,
Pharmacology & toxicology.
M Tech. PhD
Presented by -
Miss.Pratiksha S. Raut and Ramya Sri
 CONTENTS
Aim of Experimental studies
Major Advances in Research that involves Animal Models
Animals used in clinical research are classified
Cruel Cat Experiment
CAT
Sources of Cats
Housing
Breeding colony and Management
Infectious Disease Exclusion and control
Application for various diseases
AIM OF EXPERIMENTAL STUDIES
a) To provide “SCIENTIFIC PROOF” of etiological or risk factors which
may permit the modification or control of those disease
b) To provide a method of “measuring the effectiveness and
efficiency of health service for the prevention ,to control and to
improve the health of the community
 MAJOR ADVANCES IN RESEARCH THAT INVOLVES
ANIMAL MODELS
1600’s – Functions of lungs ,measurement of Blood Pressure
1800’s – Vaccination ,Understanding of Infections diseases
1900’s – Antibodies , Hormones
1930’s – Nerve impulses ,Tumor virus -
1940’s – Embryonic development
1960’s – Monoclonal Antibodies , Liver Function
1970’s – Transplantation antigens , Brain functions , Discovery of
 Prostaglandins
1980’s – Development of Transgenic Animals
1990’s – Understanding Auto Immune Disorders ,In-vitro fertilization , Cloning
 Animals used in clinical studies are classified as-
Experimental Animals
Rodent Animal Models Non Rodent Animal Models
EX: Rat
Mice
Guinea pig
Hamster
EX: Rabbits
Monkey
Cat
Dog
EX: Frog
pigeon
Miscellaneous
Mammals
CRUEL CAT EXPERIMENT
“-----Orem multilates and kills animals as parts of the federal grant gravy train….for animals
who have no voice….Frankenstein lives……”
A_I_F.
“ I Found orem’s work among the most ghastly I have read. . .The gross insensitivity to the
animals used is a profound embarrassment to scientific community.”
SUZANNE CLIVER, D.V.M.
“cage too small….the size of the adult cat causes him not to turn and
move freely”.
U.S. DEPARTMENT
OF AGRICULTURE
CAT
-Of the 1,267,828 non-rodent animals used in research in the united state in 1997,only
26,091, or 2% were cats
-The domestic cat (Felis cattus ) is one of only a few mammals other than humans and mice for which extensive information has been generated on
its genome
-Since the turn of the century ,in Britain the cat has been the preeminentspecies for acute experiments
-These classicalinvestigationwere of great importancein elucidatingthe mode of action and regulation of the cellsand more recently of neuroendocrine
interrelationships
SOURCES OF CATS
A. Directories of source -The Institute for Laboratory Animal Research , The
American Association for laboratory science,- Animal care , U.S department of
agriculture division
B. Random source
C. Commercial purpose- Bred Colonies
D. Institutional Breeding Colonies
HOUSING
A. Caging Design and Operating Procedure
B. Animal Care Staff
C. Feline Social Behavior
D. Housing to Exclude Pathogens
E. Environmental Enrichment
BREEDING COLONY MANAGEMENT
A. Estrous Cycle and Mating
B. Pregnancy and Parturition
C. Infertility
D. Neonatal Care and Weaning
E. Nutrition and Feeding
-Commercial diets
-Energy Requirements
INFECTIOUS DISEASE EXCLUSION AND CONTROL
A. Preventive Medicines
B. Pathogen Control
C. Eliminating Parasites
D. Personnel Health Risks
i. Study of emotion
ii. Study of cardiac disease, spinal cord injury
iii. Study of Cataract surgery, glaucoma, lupus, diabetes,
spinabifida and more
iv. Cats have a distinct nictilating membrane used for
studying “Ganglionic drugs”
v. Cats have been used to study neurological problems
,such as Epilepsy, Deafness &Vision problems
vi. Studies on Aging
vii. The relatively long life Span Cats makes its possible to
observe the slower and more subtle effects of aging
Applications
REFRENCES
Brenda Griffin and Henry J. Baker
Guest Editor (s): James G. FoxMassachusetts Institute of Technology, Cambridge,
Massachusetts
Guest Editor (s): Lynn C. AndersonMerck Research Laboratories, Rahway, New Jersey
Guest Editor (s): Franklin M. LoewBecker College, Worcester, Massachusetts
Guest Editor (s): Fred W. QuimbyLaboratory Animal Research Center, Rockefeller
University, New York, New York
HAMSTER AS AN ANIMAL MODEL FOR RESEARCH
Under the guidance of
Dr .VGM Naidu,
Associate professor,
Department of Pharmacology and Toxicology,
MTech ,PhD.
Presented by
Ms.Mounisha bandakinda
MS.Anjana swathi
National Institute of pharmaceutical Education and Research GUWAHATI
Drugs, vital weapons in healthcare, are only used in therapeutics after being tested in the lab. In both
animals and humans, the roles of cells and organs are essentially the same. Many of the functions of
animal cells are similar to those of human cells. Humans are classified as animals biologically.
. Animals have also played an important role in the advancement of research; several new drug discoveries
have been made possible thanks to animal testing. So there are different types of Animal models are used in
Experimental study.
Animal models:
 RAT
 MICE
 RABBIT
 HAMSTER
 GUENIA PIG
 MONKEY
INTRODUCTION:
NIPER GUWHATI
Mesocricetus auratus is also known as the Syrian or Golden hamster. They belong to the family Cricetidae, to the
subfamily Cricetinae, to the genus Mesocricetus, and the species Mesocricetus auratus. When they burrow, play,
chew, and dig, the Syrian hamsters are mostly active at nighttime. Their nocturnal nature means that circadian
rhythms are perfect for learning.
HAMSTERS:
NIPER GUWHATI
TYPES OF HAMSTERS:
Based on Genus there are different types of Hamsters -
• Genus Cansumys
• Genus Allocricetulus:
•Mongolian hamster
•Eversmann's or Kazakh hamster
Genus Cricetulus:
•Tibetan dwarf or Ladak hamster
•Species C. barabensis, including "C. pseudogriseus" and "C. obscurus"—Chinese striped hamster, also called Chinese hamster;
striped dwarf hamster
•Genus Mesocricetus:
Golden hamsters Species- M. auratus-golden or Syrian hamster:-The Syrian hamster is an ideal small animal model to study the
disease caused by virus infection. Previous studies have shown that some human-specific viruses can also infect, replicate and cause similar
pathological alterations in Syrian hamsters.
•Genus Phodopus—dwarf hamsters:
Species P. campbelli—Campbell's dwarf hamster
Species P. roborovskii—Roborovski hamster
NIPER GUWHATI
Hamsters have unique physiological characteristics rendering them well-suited for biomedical research as experimental
model. They match beneficial traits of both smaller rodents and larger mammals that make them suitable for laboratory use,
such as availability, breeding ease, greater tissue proportions and the like. In experimental design, it is inevitable to select
laboratory animals of accurate age that can mimic the target human age in a specific research.
PHYSIOLOGICAL PARAMETERS:
Physiological and Reproductive data of Hamsters
NIPER GUWAHATI
• The effect of cage size and enrichment on core temperature :
Febrile response of the golden hamster
SENSITIVITY AND DEGREE OF PHYSIOLOGICAL RESPONSE:
• Different effects of acute and chronic immobilization stress.
• The photoperiodic response in Syrian hamster depends upon a melatonin-driven circadian
rhythm of sensitivity to melatonin .
• In the Syrian hamster, winter seasonal inhibition of reproduction occurs in response to decreasing day
length. This inhibitory response is modulated by nonphotic cues.
NIPER GUWAHATI
 The key to keeping your hamster healthy is a good diet and clean living conditions. Clean and
disinfect his cage at least once a week. Hamster's teeth grow continuously so provide him with
chews and gnaw sticks to wear down those dentures! Syrian Hamsters are susceptible to diarrhoea
known as wet tail.
 Give your hands a thorough wash with soap and water. ...
 Introduce your hand to the cage before touching your pet. ...
 Turn your palm up and wait for your hamster to crawl onto your hands. ...
 Keep your hands in the cage for the first few times you pick up your pet.
NIPER GUWAHATI
Among several possibilities for the administration of substances to Hamsters, the most common routes are
subcutaneous, intraperitoneal or intravenous and intra muscular injection.
ROUTE OF ADMINISTRATION :
Muscle tissue may also hold a larger volume of medication . The drug will be absorbed faster from the
intramuscular route because muscular tissue has rich blood supply.
Intra muscular route:
Subcutaneous injections are generally given under the loose skin of the back just behind and between
the shoulder blades, or on either side of the hamsters in the hip area.
Subcutaneous route:
NIPER GUWAHATI
Oral Route:
The oral route is economical, convenient, relatively safe, and some animals can be trained to cooperate
voluntarily, depending on the compound being administered
Intravenous administration:
The intravenous route of delivery is the most efficient means of delivering substances to animals because it
bypasses the need for solute absorption.
Administration to skin and muscle :
- Some substances can be administered directly to the skin surface (epicutaneous administration) for a
topical affect. The extent of absorption of materials through the skin and into the systemic circulation.
ROUTE OF ADMINISTRATION :
NIPER GUWAHATI
Hamsters are fun to watch
Hamsters are patient and curious animal and don't make noise
Hamster don't take up much space
Hamsters don't need walking don't mean a lot of work
No tax
DISADVANTGES :
Hamsters are active at night (from around 8 pm, but sometimes later)
Hamsters only live for 2-4 years
Hamsters are not suitable for cuddling quite delicate
Hamsters chew on cables (could mean extra costs)
ADVANTAGES:
NIPER GUWAHATI
The hamster is used frequently in IVF research among other research areas including oncology,
immunology and physiology. However, their unique reproductive system which include a continuous
4 day estrous cycle (the reproductive cycle of all non-higher primate mammals) and a very short
pregnancy period of 16 days.
DRUG ASSAY :
• Various infectious diseases
• Corona virus
• Cardiovascular disorders
• Diabetes mellitus
• Hypothermia research
Applicable to various diseases :
NIPER GUWAHATI
 Hamsters possess unique anatomical and physiological features, which make them desirable
research models. Unlike other commonly used laboratory rodents, hamsters possess a cheek
pouch, which can be easily everted and examined at both the gross and microscopic level.
WHY HAMSTERS PREFERRED IN RESEARCH :
 Hamsters, for many people, make excellent pets. They don't require a lot of attention, get enough
exercise running on their wheel, and are cute, cuddly, and pleasant to hold.
 Hamsters have special feature like nocturnal nature means that circadian rhythms are perfect for
learning in experimental pharmacology.
NIPER GUWAHATI
REFERENCES :
1.Bartlett P. P. The hamster handbook, in: Bartlett P. (Ed.), Barron’s Educational Series 2nd ed. Barron’s
Educational Series. 2015.
2.Blaha G. C. Reproductive senescence in the female golden hamster. The Anatomical Record.
1964;150:405-411
.
3.http://howmed.net/pharmacology/routes-drug-administration/--Routes.
4.https://www.karger.com/Article/FullText/516240.
5.https://www.researchgate.net/publication/349632243_ANIMAL_MODELS_OF_HUMAN_DISEASES_AND
_THEIR_SIGNIFICANCE_FOR_CLINICAL_STUDIES_OF_NEW_DRUGS.
6.ANIMAL MODELS OF HUMAN DISEASES AND THEIR SIGNIFICANCE FOR CLINICAL STUDIES OF NEW
DRUGS February 2021 Authors: parvova ,dhanchay.
THANK YOU !!
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
AN OVERVIEW ON GUINEA PIG
GUIDED BY
Dr. V.G.M. NAIDU
M.Tech, PhD
ASSOCIATE PROFESSOR
DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY
PRESENTED BY
SNEHASHIS KUNDU AND SUDIPTA NAYAK
M.S. (PHARM.), 1st SEMESTER
COURSE CODE: PC-530
12/12/2021 30
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
 SCIENTIFIC NAME & TAXONOMY
 INTRODUCTION
 PHYSICAL DESCRIPTION
 TYPES OF SPECIES & THEIR DESCRIPTION
 DRUG ASSAY & ROUTE OF ADMINISTRATION
 SENSITIVITY
 PHYSIOLOGICAL DATA AS PER CPCSEA GUIDELINE
 HAEMATOLOGICAL DATA AS PER CPCSEA GUIDELINE
 MINIMUM FLOOR AREA NEEDED AS PER CPCSEA GUIDELINE
 PROS & CONS
 APPLICATION
 WHY PREFERRED?
 CONCLUSION
 REFERENCES
CONTENTS
12/12/2021 31
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
SCIENTIFIC NAME: Cavia porcellus
TAXONOMY
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family : Caviidae
12/12/2021 32
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
INTRODUCTION:
 About 400 years ago, Guinea pig (Cavia porcellus) was introduced into Europe from
South America.
 Guinea pigs are domesticated species of rodent. Here rodent means mammals of the
order Rodentia, which are characterized by single pair of continuously growing
incisors in each of upper and lower jaw.
 Their gentle temperament and commercial availability make them useful as research
models.
 It is used as primary model to perform studies of anaphylaxis, asthma, gnotobiotics,
immunology, infectious and nutritional disease, and otology.
 Vitamin C was first discovered in guinea pigs in 1907. Like humans and unlike other
small laboratory animals, guinea pigs do not produce their own vitamin C and
instead must obtain this vitamin from their diet.
 Its serum contains asparaginase enzyme which having antileukemic action.
12/12/2021 33
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
PHYSICAL DESCRIPTION:
 The guinea pig has a stout, compact body and no tail. Common colours include white,
brown, black and combinations thereof.
 Guinea pig are large for rodents, measuring 20–40 cm from head to rump.
 Weight-weaning: 120gm.
 Adult male: 900-1000 gm and Female: 700-900 gm.
 Litter size: 2-5
 Life span: 4-5 years ( maximum 8 years).
12/12/2021 34
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
TYPES OF SPECIES & THEIR DESCRIPTION
Abyssinian Guinea pig Rough, wiry hair coat, hair made of rosettes, found in all colour and colour
combination.
American Guinea pig Most common bread, short, very glossy, fine hair, found in widely variety of
colour and colour combination.
Peruvian Guinea pig Long haired variety, hair length evenness and balanced are deciding feature,
lacks a tail.
Satin Guinea pig Fur is distinguishing feature, fine, dense, soft, luxurious and shiny.
Teddy Guinea pig Short hair, lies thick and close to the body.
Crested Guinea pig It also known as white crested, often look very similar to American guinea
pig but its having a crown of hair on top of their heads.
Silky Guinea pig Long hair, unlike Peruvian no long frontal sweep over head.
It sometimes called Sheltie.
12/12/2021 35
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
SEVEN MOST COMMON SPECIES OF GUINEA PIGS
American guinea pig Abyssinian guinea pig Teddy guinea pig Satin guinea pig
Crested guinea pig Silky guinea pig Peruvian guinea pig
12/12/2021 36
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
DRUG ASSAY & ROUTE OF ADMINISTRATION
DRUG NAME ROUTE OF ADMINISTRATION DOSE
Atropine Intramuscular 0.1-1.0 mg/kg
Ketamine Intramuscular 10-44 mg/kg
Midazolam Intramuscular 1-2 mg/kg
Diazepam Intramuscular 0.5-3.0 mg/kg
Ciprofloxacin Per os 5-20 mg/kg
Metronidazole Per os 25 mg/kg
Ketoconazole Per os 10-40 mg/kg
Ivermectin Subcutaneous 0.2-0.4 mg/kg
Vitamin C Per os, subcutaneous, Intramuscular 10-100 mg/kg
Epinephrine Intravenous 0.003 mg/kg
Cisapride Per os 0.1-0.5 mg/kg
Furosemide Per os, Subcutaneous 2-10 mg/kg
12/12/2021 37
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
SENSITIVITY:
 Guinea pigs are highly sensitive to histamine.
 Penicillin is 100-1000 times more toxic to the guinea pig than the mouse.
 Guinea pigs are also highly sensitive to dopamine because it causes fall in blood
pressure.
 They are very sensitive to loud noise.
 They are also sensitive to nickel contact.
12/12/2021 38
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
PHYSIOLOGICAL DATA AS PER CPCSEA GUIDELINE
 Rectal temperature: 37.6-38.9
 Normal respiration rate: 80 per minutes
 Gestation period: 59-72 days ( average: 63 days)
 First ovulation: 4-5 weeks
 First ejaculation: 8-10 weeks
 Cycle length: 15-17 days
 Implantation: 6-7 days ( post ovulation)
 Weaning age: 14-21 days
 Mating age: 12-30 weeks
 Urinary output(ml/100 gm) body weight: 4-9
 Daily fecal output (gm): 15-18
 Room temperature (F): 65-75
 Relative humidity of room(%): 45-55
 Daily feed intake (gm): 30-50
 Daily water intake (ml/100gm) body weight: 15
12/12/2021 39
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
HAEMATOLOGICAL DATA AS PER CPCSEA GUIDELINE
Total blood volume(ml/kg) body weight 75
Available blood volume(ml/kg) body
weight
35
RBC count(cells/ cu mm) 4.5-7
Hemoglobin (kg/100ml) 12.4
Blood plasma PH 7.3
WBC (x10^3 cells/microliter) 6-17
Platelets (x10^3 cells/ microliter) 250-850
12/12/2021 40
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
MINIMUM FLOOR AREA FOR GUINEA PIG AS PER CPCSEA GUIDELINE
WEIGHT(gm) FLOOR AREA/ANIMALE
(cm2)
CAGE HEIGHT
(cm2)
<350 387 18
>350 >= 651.4 18
12/12/2021 41
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
PROS OF GUINEA PIG
 Guinea pig live longer and healthy.
 They are docile in nature.
 Simple to move due to its small size.
 They are durable and warm.
 They do not occupy a lot of room.
 They are very affordable for a layman.
 They live more than different rodents.
CONS OF GUNIEA PIG
 Guinea pig can be really loud.
 They poop smells.
 They can cause allergies.
 They are effortless harmed.
 They are normally bashful.
12/12/2021 42
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
APPLICATIONS:
 Guinea pigs are employed for the evaluation of bronchodilator compounds against experimentally
induced asthma.
 They are widely used in immunology particularly in the studies of delayed hypersensitivity.
 They are employed in the study of local anesthetics as well as bioassay of digitalis.
 Its having sensitive cochlea are suitable for hearing experiments.
 Being docile in nature and more resistant to hypoxia than rats and mice, they are suitable for
experiments on oxygen consumption.
 It is a suitable host for mycobacterial infection, and is used in the study of tuberculosis.
 Being the only common laboratory animal which resembles man in that it requires exogenous vitamin
c, it is used in the study of ascorbic acid metabolism.
12/12/2021 43
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
WHY PREFERRED?
 They have many biological similarities to humans, beyond the simple fact that they are mammals,
which make them useful in many fields of research.
 Guinea pigs have contributed to 23 Nobel prizes for medicine with studies leading to the discovery of
Vitamin C, the tuberculosis bacterium, adrenaline, development of vaccines for diphtheria and
tuberculosis, replacement heart valves, blood transfusion, kidney dialysis,
antibiotics, anticoagulants and anti asthmatic drugs.
 Today, guinea pigs are still widely used in medical research, particularly in the study of respiratory,
nervous and immune systems.
 Guinea pigs have a similar hearing range to humans which makes them a useful model for
understanding how our ears work and how they can be repaired.
12/12/2021 44
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
CONCLUSION:
 The intent of this presentation is to highlight on the detail overview of guinea pig as
an experimental animal.
 We include its physical description, various species, sensitivity, physiological and
hematological data, pros and cons, as well as contribution in the field of drug
development.
 Besides, we also included the reasons for choosing guinea pig as an experimental
animal in the field of medical research.
12/12/2021 45
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
REFERENCES:
 Chakrabarty S., Nandi A., Mukhopadhyay C.K., Chatterjee I.B. Protective role of ascorbic acid
against lipid peroxidation and myocardial injury. Mol. Cell. Biol. 1992;111:41–47.
 Guide for the care and use of Laboratory Animals. DHEW publication Washington 1978.
 CPCSEA Guidelines. http://cpcsea.nic.in.
 Coates, M.E. Gnotobiotic animals in research: their uses and limitations. Lab. Anim. 9, 275–
282 (1975).
 Ghosh M.N, Vedasiromoni J.R. Fundamentals Of Experimental Pharmacology. 6th edition.
Kolkata. Hilton & Company Publisher: 2015.p.16-17.
 Medhi B, Prakash A. Practical Manual Of Experimental And Clinical Pharmacology. 1st edition.
New Delhi. Jaypee Brothers Medical Publishers Ltd: 2010.P.25-30.
12/12/2021 46
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)
12/12/2021 47
Horse as animal model
course code: PC-530
12-12-2021 1
Presented by:
Ujjawal Soni
Donker Chonzom
Department of pharmacology and
toxicology
Introduction:
• Horses are well –accepted , well –established and clinically relevant animal models for several human diseases, including
metabolic syndrome, asthma, musculoskeletal diseases, melanoma and autoimmune uveitis.
• More than 100 equine hereditable conditions may serve as models for human disorders, including inflammation, muscular
or fertility disorders, osteoarthritis and even depression.
• Horses are also used in biomedical procedures to produce bioactive compounds such as hormones, vaccines, anti-toxins
and anti-venoms.
• The anatomical and physiological differences between rodents and humans limits the comparative aspects of studies that
utilize rodents .
• Small rodent animals, specifically mouse and rat, are valuable for research into mechanisms of disease and fundamental
biology, but findings from such small animal models often do not translate into human clinical application.
• Due to translational challenges, showing the difference in bioavailability of pharmaceuticals between humans, primates,
dogs and rodents . Therefore, the European Medicines Agency (EMA), the USA Federal Food and Drug Administration
(FDA) and the International Society for Stem Cell Research (ISSCR) recommend the use of large animal models to
evaluate efficacy, durability, dose response, degradation and safety of advanced therapeutic medicinal products (ATMPs).
12-12-2021 49
Characteristic that are unique to the horse:
 Flight: • Primary Defense
• Most timid
• Must feel safe
Most Perceptive 5 senses
• Taste: likes salty and sweet, not medicinal
• Hearing: directional ears, keener than humans, mood indicator
• Smell: becomes familiar
• Touch: very sensitive, especially around head
• Sight: monocular and binocular
Limited color, Movement more important.
Large vision
Has to turn eye sideways to look at ground
12-12-2021 50
 Fast Learner
• Fastest of domestic species
• Learn in 3’s
• Learn from RELEASE of pressure
• Generalize learning: same in multiple location
 Memory
• Forgive but don’t forget
• Mules don’t forget or forgive
• Retention very
• Categorize – Fearful but doesn’t hurt them
• Do not stimulate the amygdala – Permanent – “No dust”
• Horses don’t rationalize – 2 sides - 2 horses
12-12-2021 51
Route of administration of drug :
 Intramuscular( IM) : needle is inserted at 90 degree to skin surface
Neck, Pectorals , Gluteal
 Subcutaneous (SC)
 Intravenous(IV) : Jugular groove
12-12-2021 52
Animal housing:
Horse require particular environments that accommodate their species-specific behaviours and physiology,
and ideal housing systems should provide fresh air and light, food and water, adequate space and
opportunities for exercise, conspecific social contact and general security.
Housing conditions horse housing facilities should include : 1.Adequate ventilation and lighting for
horses housed indoors or stabled.
Ventilation also helps horses and other large livestock to dissipate heat.
 Proper lighting helps to create a safe and comfortable environment for horses.
2. Bedding: The material used for bedding must be non-toxic and should provide effective drainage and
absorbency to minimize dampness on the bed floor and to reduce dust and ammonia in the air.
3. Feeding: Must have appropriate food materials and a sufficient food supply to feed their horses.
 Suitable foraging material for horses includes the aerial parts of pasture grasses, legumes and forbs.
Must also have an appropriate system in place to deliver food to horses.
Different feeding methods can be used to reduce and manage fouled food and cross-contamination
between horses.
12-12-2021 53
4. Water : Must have a sufficient water supply and an appropriate delivery system to accommodate their
horses.
A horse typically requires 20–70 l/d of water, depending on air temperature and humidity, body weight,
activity level and health10.
Maintain their hydration and water balance when water is provided intermittently.
5. Exercise: Opportunities for exercise are essential for the behavioural and physiological well being of
horses.
 Exercise promotes optimal musculoskeletal development in foals 33–35, and adult horses that are confined
for a long time without exercise can develop oedema and potentially impaired respiratory function.
12-12-2021 54
Advantages:
Largest of the model: Multiple large( critical size) defect and serial sampling possible
Functional correspondence of equine SDFT and human Achilles tendon
Thickness of knee cartilage is similar to the human
Clinical need- naturally occurring disease
Disadvantages :
Ethnical concerns- companion animals
Cost: special facilities needed for housing, surgery , imaging. Necropsy etc
Non-weight bearing postoperatively is not feasible
12-12-2021 55
Application:
Horse helped cure diphtheria and toxic bacillary dysentery by producing on large scale antiserum to the toxin
of bacteria.
Various human diseases can study in horse: example
Tendinopathy
Cartilage injuries and osteoarthritis
Asthma
 Short term memory testing in domestic horse
 Horse as model for understanding human innate immunity
Identification of biomarkers to monitor disease progression, and the effects of drug treatment on biomarker
are also being pursued.
Horse serum are used as an anti-venom, ex. When humans are bitten by snake ( Brazillian Bothrops or
crotales)
12-12-2021 56
Comparison of horse and mouse model for human disease:
Comments Horse Mouse
General :
• Body, organ , longevity closer to human less similar
Genetic :
• Genetic diversity
• Chromosome conservation with human
• Genome annotation
high
high
poor
low
low
high
Macrophage biology:
• CD14, CD16 monocyte observed in humans
• Response to LPS
detected
similar
not detected
less similar
Disease :
• Musculoskeletal disorders: osteoarthritis
• Asthma : COPD pathophysiology
• Human infectious disease
• Human mental and behavioural disorder
• Human metabolic disorder
common
similar
similar
similar
similar
less common
less similar
less similar
less similar
less similar
Therapeutic strategies :
• Translational application to human possible less possible
12-12-2021 57
Thank you….
12-12-2021 58
a
A MONKEYS AS
LABORATORY ANIMALS
Presented by
Ashitha Rajanan & Amal Jyothy Suresh
M.S (Pharm) 1st semester
Department of Pharmacology and
Regulatory Toxicology
59
Types of monkeys
Research areas
Why preferred ?
Advantages and Disadvantages
Conclusion
References
CONTENTS
Routes of Drug administration
Sensitivity and Drug testing
Introduction
60
INTRODUCTION
MONKEYS AS LABORATORY ANIMALS
 Human biology and disease can be studied in monkeys because they are very similar to humans;
biologically anatomically and physiologically.
 Most often used monkeys are; Cynomolgus macaques (Macaca fascicularis), Rhesus macaques
(macaca mulatta), Marmosets (Callithrix jacchus).
61
MACAQUES (macaca)
Cynomolgus macaques ( Macaca fascicularis)
The crab eating macaque also known as the long tailed macaque.
Common research primate (80%)
Native of Southeast Asia.
Smaller & less aggressive.
Rhesus macaques (Macaca mulatta)
Larger and more expensive to keep.
Easy to keep in captivity.
Extensively used in medical and biological research .
 wide availability and closeness to humans.
MARMOSETS (Callithrix)
Common marmoset ( Callithrix Jacchus)
Originated in Atlantic coastal forest in Northeast Brazil
Light weight arboreal monkeys.
Exhibit complex social behavior & cognitive functions that are similar to humans.
SQUIRREL MONKEY
• Common squirrel monkey [Saimiri sciureus] lives in the tropical forests of central and South
America.
• Mean body weight of adult squirrel monkey is less than 1kg.
• Easily adapt to laboratory housing.
• Used as a model for treatments in adult humans for colour blindness.
BABOONS
Baboons [Papio anubis] are ground dwelling and natives of Africa.
Life span about 45 years in captivity.
They have similar immune system as that of humans thus used as a model for vaccine
development.
PHYSIOLOGICAL DATA
A
Scientific name Macaca mullata
Order Primates
Body temperature 37-39 deg cel
Respiration rate 76-90/min
Heart rate Upto 180
beats/min
Blood pressure 130/100 mmHg
Blood volume 54ml/kg
A
Life span 30 years
Water
consumption
18.4 ml/Kg/day
Food
consumption
1-2.4 kg/day
Room
temperature
37-40 deg cel
Mating age 4-5 years
Gestation periods 165 days
Body weight About 5-6Kg
64
Accommodation &housing
 Monkeys should be housed in cages made up of steel or painted mild steel space.
 Permit freedom of movement and normal postural adjustments, and have a resting
place.
 Provide a comfortable environment , climbing structures.
 Provide easy access to food and water & adequate ventilation .
 Meet the biological needs of the animals, e.g., maintenance of body temperature,
urination, defecation, and reproduction . Temperature condition will vary from animal
to animal , Eg :for marmoset -<5deg cel , macaques->15deg cel
 Keep the animals dry and clean, consistent with species requirements .
 The height of the cage should be sufficient for the animals to stand erect with their feet
on the floor, whereas the minimum height of the cage for langurs has to be 90 cm.
65
ROUTES OF DRUG ADMINISTRATION
ORAL
• Most convenient
• Safe
• Drug mixed in
diet or other
food stuff
• Economical
INTRA
VENOUS
• 100%
bioavailability
• As bolus or
infusion
• Jugular,
cephalic,
femoral vein
INTRA
MUSCULAR
• Common
route for
larger
animals
• Small
volumes are
preferred
• Uniform and
rapid
absorption
66
SENSITIVITY AND DRUG TESTING
Drug testing-
 Determination of serum concentrations of penicillin ,doxycycline and ciprofloxacin in anthrax infected
monkeys.
 Studying of efficacy of psychostimulants like cocaine.
 More relevant data about the metabolites of cyclophosphamide and ifosamide from CSF of monkeys.
Olfactory
sensitivity
Sometimes more
than rat or dog
Vision
Squirrel monkeys
for vision studies
Ability to
hear
Sense of
touch
Monkeys as
smart as
toddlers [most
intelligent
monkey-capuchin]
67
RESEARCH AREAS
 African green monkeys and rhesus monkeys are suitable models than other animal models in
Covid 19 for studying the progression of disease.
 Monkey models are used in Neuroscience [Alzheimer’s to schizophrenia]
 Marmoset monkey models for Parkinson’s disease.
 Discovery of H56 vaccine from macaque models for tuberculosis.
 Similar visual system –Squirrel monkey model for colour blindness.
 Aotus monkeys are used for understanding malaria, screening antimalarial drugs and vaccine
development.
 Ovariectomized cynomolgus monkeys (Macaca fascicularis), baboons, langur such as used for
reproductive system research.
 Rhesus monkeys were used to design the first hepatitis E vaccine, hecolin. 68
SOME OTHER SCIENTIFIC ADVANTAGES
a
Polio
vaccine
Corneal
transplants
Yellow fever
vaccine
Mapping of
the heart
connections to
arteries
HIV model
Cancer
chemotherapy
69
ADVANTAGES DISADVANTAGES
Anatomical similarity
• Brain
• Eyes
Physiological similarity
• Immune system
• Reproductive system
Others
• Motor skills
• More similar metabolism
Ethical issues
Threatened species
Difficulty in maintenance
Housing changes cause
abnormal behaviour
Chances of zoonotic diseases
Experiments take several years
70
WHY PREFFERED ?
 The rodent lacks the pre fontal cortex specialisation that is found in monkeys and
humans.
 Due to the similarity in reproductive system between NHP female and human
female these are more pertinent species for study of reproductive effects.
 Regarding the ocular system, the retina of NHP and man show unique features that
not found in other mammal.
 NHP s are less susceptible to vomiting than dogs.
71
CONCLUSI N
 Genetical similarity of monkeys to humans make them particularly
suitable candidates for testing the safety of new drugs and studying of
variable diseases .
 But those similarities to humans also raise specific ethical questions
about their use for scientific experiments.
 However they play an indispensable role in the process of medical
research and development.
72
REFERENCE
 Leuner B, Kozorovitskiy Y, Gross CG, Gould E. Diminished adult neurogenesis in the marmoset brain
precedes old age. Proceedings of the National Academy of Sciences. 2007 Oct 23;104(43):17169-73.
 Mancuso K, Hauswirth WW, Li Q, Connor TB, Kuchenbecker JA, Mauck MC, Neitz J, Neitz M.
Gene therapy for red–green colour blindness in adult primates. Nature. 2009 Oct;461(7265):784-7.
 Wilcock GK, Esiri MM. Plaques, tangles and dementia: a quantitative study. Journal of the
neurological sciences. 1982 Nov 1;56(2-3):343-56.
 Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ. A primate model of
parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia
nigra by N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Proceedings of the National Academy of
Sciences. 1983 Jul 1;80(14):4546-50.
 Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, Bleicker T, Brünink S, Schneider
J, Schmidt ML, Mulders DG. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-
PCR. Eurosurveillance. 2020 Jan 23;25(3):2000045.
73
74
TOPIC :- MICE AS ANIMAL MODEL
COURSE CODE :- PC-530
DEPARTMENT :- PHARMACOLGOY & TOXICOLOGY
Presented by
Tejes Gholap & Avdhoot Kalambe
NIPER GUWAHATI
MICE
 Laboratory mice are usually of the species Mus Musculus. They are the most commonly
used mammalian research model and are used for research in genetics
,psychology,medicine and other scientific disciplines. Mice belong to
the Euarchontogrlires clade, which includes humans.
 Mice have been used in biomedical research since the 17th Century.
NIPER GUWAHATI
TYPES OF MICE
1) Non-obese diabetic (NOD) mice – Which develop diabetes mellitus type 1. for antidiabetic activity .
2) Knockout mice – For the purpose is to study the function of the gene's product or to simulate a human
disease
3) Oncomice - With an activated oncogene, so as to significantly increase the incidence of cancer.
4) Immunodeficient nude mice - lacking hair and a thymus - used for research in immunology and
transplantation.
5) Japanese waltzing mice - Which walk in a circular pattern due to a mutation adversely affecting their
inner ears.
6) Doogie mice - With enhanced NMDA receptor function, resulting in improved memory and learning,
7) Transgenic mice - With foreign genes inserted into their genome.
8) Murphy Roths large (MRL) mice - With unusual regenerative capacities.
NIPER GUWAHATI
AVAILABILITY
Strains Features Suppliers
C57BL / 6 Inberd black The jackson
laboratory
BALB/c Albino with
immunodeficient
Harlen
laboratory
CD -1 Outbred albino Taconic
bioscience
NIPER GUWAHATI
SENSITIVITY
Mice are sensitive to following paramaters –
1) To the light refluxes - Sensitive to bright lights and have poor eyesight.
2) To taste - Mice that can detect four of the five flavors that the buds recognize. Bitter, sweet, sour and umami .
3) To smell - Highly sensitive to Peppermint oil, cayenne pepper, pepper and cloves.
4) To drugs - Highly sensitive to drugs like acamprosate and baclofen.
Type of animal Sensitive to Example
Transgenic mice Cancer Colorectal cancer
Swiss albino Toxicology studies Barabiturate toxicity
Konckout mice To genetic disorder Thalassmia
Doogie mice Learning & memory Alzimer disease
Type of animal
Sensitive toe
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PROS & CRONS / ADVANTAGES &
DISADVANTAGES
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DRUG ASSAY
Following types of drugs are assayed by mice using as an animal model,
1)Antidiabetic drugs – eg .metformin etc.
2) NSAIDs – eg. Ibuprofen, indomethacin etc.
3) Analgesic – eg. Codain, Merperidone etc.
4) Antihypertensive drugs – eg. Reserpine , verapamil etc.
5) Anticancer drugs – eg. Vinca, taxens etc.
6) Others…..
NIPER GUWAHATI
HANDLING OF MICE
 A recommended method to pick up mice is to guide them into a handling tunnel, lift them inside
the tunnel and transport them to their destination. Gently tip animals from the tunnel
backwards, directly onto the surface or hand (a smooth plastic tunnel that the animals cannot
grip is best).
NIPER GUWAHATI
MAINTENANCE
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INFECTIONS PRON TO BE MICE
NIPER GUWAHATI
SITE OF ADMINISTRATION
1) Oral Route - The oral route is economical, convenient, relatively safe, and some
animals can be trained to cooperate voluntarily, depending on the compound being
administered
2) Intravenous administration - The intravenous route of delivery is the most
efficient means of delivering substances to animals because it bypasses the need for
solute absorption.
3) Administration to skin and muscle - Some substances can be
administered directly to the skin surface (epicutaneous administration) for a topical
affect. The extent of absorption of materials through the skin and into the systemic
circulation
Subcutaneous adminis- trations over the interscapular area are made as follows. The mouse is manually restrained and then placed on a
clean towel or solid surface. The needle is inserted under the skin of the interscapular area tented by the thumb and forefinger and the
substance then injected.
NIPER GUWAHATI
SUBCUTANEOUS ADMINISTRATION
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Oral administration
NIPER GUWAHATI
SITE OF ADMINISTRATION
4) Intraperitoneal Administration -Injection of substances into the peritoneal cavity is a common
technique in laboratory rodents but rarely is used in larger mammals and humans. Intraperitoneal injection is
used for small species for which intravenous access is challenging and it can be used to administer large
volumes of fluid safely
5) Intranasal, Intratracheal, and Inhalational Administration - In research settings, animals generally
are sedated or anesthetized47 for the intranasal and intratracheal routes of delivery, to minimize struggling and
sneezing.
6) Intramuscular Route - Administration of substances is a common parenteral route in large animals and
humans but often is avoided in smaller species because of the reduced muscle mass. Generally, intramuscular
injections result in uniform and rapid absorption of substances, because of the rich vascular supply. Smaller
volumes are administered intramuscularly
NIPER GUWAHATI
INTRAPERITONIAL ADMINISTRATION
NIPER GUWAHATI
APPLICATION FOR VARIOUS DISEASES
1)Diabetes mellitus – to check Antidiabtetic potential .
2) Cancer – eg.colon cancer ,Breast caner ,pancreatic cancer.etc
3) Hypertension – for antihypertensive activity
4) Analgesic activity
5) Immunogical disorders
6) ADIS
7) psoriasis
NIPER GUWAHATI
INSTRUMENTS USED FOR STUDY
1) Analgesiometer - The Hot Plate Analgesia Meter is used to evaluate thermal pain relfex due to footpad contact
with heated surface.
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2) ROTAROD –
Rotarod test is widely used to evaluate drug effects on motor coordination, balance and motor learning in rodents.
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EUTHANASIA
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WHY THEY ARE PREFERED ?
 Most of the mice and rats used in medical trials are inbred so they are almost identical
genetically helping to make the results of medical trials more uniform.
 Another reason they're used as models in medical testing is that their genetic, biological and
behavior characteristics closely resemble those of humans.
 The mouse genome is very similar to our own, making mouse genetic research particularly useful
for the study of human diseases. Mice are cost effective because they are cheap .
NIPER GUWAHATI
Thank You !!!
TITLE : USE OF DOG MODELS IN PRECLINICAL PHARMACOLOGY
SUBJECT CODE: PC-530
BY
ANKIT KUMAR & ANKANA GHOSH
Department of M.S(Pharm.) Pharmacology and
Toxicology
DATE :
It is unconscionable that dogs, the most popular companion animals in the country, are used as
research subjects in laboratories, but United States Department of Agriculture (USDA) reports show
that tens of thousands of dogs are used in research, testing, teaching, or experimentation in the U.S.
every year by research facilities, including hospitals, schools, diagnostic laboratories and private
firms in the pharmaceutical and biotechnology industries.
Although the number of dogs used in research has declined by 72% since their peak use in 1979,
Though many scientists have concluded that they are poor predictors of drug effects in the human body, still
they are used because regulatory authorities require that drugs be tested in both a rodent and a non-rodent
species for toxicity, and the latter is often dogs, due to their ready availability, as well as their trusting
and social nature, which makes them easy to handle.
Source: https://navs.org/
TYPES OF BREEDS USED IN PRECLINICAL STUDIES
The dealers from whom the dog models are being purchased, can be broadly differentiated in
two major classes based on the breeds sell, namely-
CLASS A Dealers
CLASS B Dealers
CLASS A DEALERS CLASS B DEALERS
Sells “purpose-bred” dogs specifically for research.
beagles, hounds and mongrel dogs
Sells “random source” dogs
raised the animals on their own premises to fulfill
orders of 33-60 pounds that are 6 to 12 months
old.
obtained from an animal shelter or dog pound
(a practice known as “pound seizure”), at auction,
or from any person who did not breed and raise
the dogs on their premises.
known vaccination history, preventative treatment for
parasites, known pedigree and improved
socialization
unverifiable health status, poorly-defined
temperament and unknown age.
they are expensive, costing over $700 per dog. less expensive
Image: Hound Image: Beagle
Generally beagles are most used bred of dogs for animal testing owing to their passive
nature and small size
What is pound seizure?
Pound seizure is the practice of releasing or selling cats and dogs in animal shelters to
laboratories and other facilities where they are used in biomedical research, product
development, testing and educational demonstrations. While a number of states no longer
allow this practice, many still do or leave it up to localities to decide.
ROUTE OF ADMINISTRATION OF DRUGS :-
 1.ORAL:-Dogs can take substances(drugs)in their food via pills or in some cases force feeding or
forced to inhale them.
 2.SUBCUTANEOUS INJECTION: Middle of the back or behind the shoulder. The needle should be
parallel to the skin.
 3.INTRAMUSCULAR INJECTION: At specific location of the dog skin ,syringe firstly prepared and
then needle is inserted between the angle of 45°-90°depending upon the location of the body area.
 4.RECTAL: It is less common and done by enema method.
 5.INTRAPEROTONEAL
 6 .INTRAVENOUS
ASSAY OF DRUGS :-DIURETICS (ACETAZOLAMIDE AND THEOPHYLLINE)
The screening of diuretics for clinical utility is a matter of practical importance.
Promising laboratory results often are not supported by subsequent clinical trials. Such differences
may arise from the fact that the final clinical evaluation is determined in patient with Congestive
Heart Failure, which is difficult to achieve in animals.
Materials and methods :
 Male mongrel dogs:- 20 dogs(Five dogs each for mersalyl, theophylline, acetazolamide and urea)
are anesthetized by dial urethane 70mg/kg,half of it being given intravenously and half to
intraperitonealy.Animals were hydrated using 0.9% saline solution with 20ml/kg by the rate of
10ml/kg/hour.
 Urinary bladder of the animal was exposed with the mild incision Over the lower part of abdomen.
 Both ureters were identified and cleared and cannulated over bladder using polyethylene tubing with
suitable size and length.
 Urine collected and volume recorded every 15 minutes
 Control observation made upto one and half to two hours after the saline drip was over.
 The drug is then injected and urine volume were collected for the further period of five hours.
 A detailed statistical analysis of results in dogs was done. Control readings are taken as concomitant
variable.
Results:
Comparing the effect of different drugs taken two at a time it was found that the effect due to mersalyl
differed significantly from the effects due to urea, theophylline or acetazolamide while later three drugs
did not differ significantly amongst themselves.
Action of mersalyl in dog was found to be significantly greater than that of urea, theophylline and
acetazolamide.
SENSITIVITY OF DOGS WITH THE DRUGS
 It was found that there is mutation in the gene of some breeds of dogs( like Collies,German
shepherd,shelties,Sheepdogs )in MDR1 gene and this abnormalities can lead to severe sensitivity
to many medication.
 The medication to which the dogs can react include common drugs such as ivermectin (used for
many parasite preventives and treatments),loperamide (used in kaopectate,Imodium and
Pepto).Other drugs are acepromazine,cyclosporine.
 The only way to know if this dog is sensitive to the drug is to test its DNA for the mutated MDR1 gene.
APPLICATIONS OF DOG MODELS
TYPES OF DISEASES BREEDS USED FOR TESTING
Non Hodgkin’s Lymphoma (NHL) Boxers and Golden Retrievers
Osteosarcoma(OSA) Heavy individuals having long bones like Great
Dane, Wolfhound, and Rottweiler are most
susceptible to OSA
Aging and Alzheimer’s Disease Beagle has been selected as the main breed
used for aging studies as its median lifespan is
12 to 14 years,
Endocrinopathies like pituitary dwarfism German Shepherd breed.
ADVANTAGES
Domesticated dogs are increasingly being identified as good models for a variety of
biomedical research fields as they have a number of unique advantages over other
commonly used experimental animals.
The dogs cohabitate with their owners, receive a good level care including highly-trained
healthcare. This offers valuable opportunities for researchers to examine complex
problems such as environmental contributions to diseases, aging and its effect on
disease susceptibility and progression, and the effects of long-term treatment
protocols.
Over the past several centuries, domestication and selective breeding of dogs has
resulted in nearly 400 distinct populations and thus the most naturally occurring genetic
diversity in any one species besides humans.
Careful breeding for trait selection has inadvertently resulted in breed-specific disease
susceptibilities and approximately 400 naturally-occurring, inherited diseases have
been identified in dogs which serves as very good model for research.
Finally, due to the rapid aging of dogs, there is a shorter duration for disease
development and progression. This is an enormous advantage in the context of drug
development as clinical trial study times are significantly reduced.
DISADVANTAGES
The genetic diversity is the main disadvantage of canine models as
there are breedspecific differences in physiology and metabolism,
especially idiosyncrasies in pharmacodynamics and pharmacokinetics,
which can introduce complications when interpreting or translating
results.
Dogs used in research in laboratory settings have been shown to display signs of
stress, fear and anxiety. While some dogs are able to adapt positively to stressors, other
dogs are unsuccessful and can develop disorders and dysfunctions that can adversely
affect their quality of life, in addition to significantly impacting the research in which the
animal is involved.
It has been noted that dogs often stop such behaviors when their handlers enter the
room, resulting in a serious underestimation of the true mental and physical condition of
dogs used in research in laboratory settings.
REFERENCE
 Field, G. and Jackson, T.A. The Laboratory Canine. CRC Press. Hasiwa, N., et al.
(2011) Critical Evaluation of the Use of Dogs in Biomedical Research and Testing in
Europe. 2007, ALTEX. Vol. 28, 4/11, p. 326-340
 Meunier, L.D. Selection, Acclimation, Training, and Preparation of Dogs for the
Research Setting, ILAR Journal, 2006 ,Vol 47, Number 4, p. 326-347.
 National Research Council. Scientific and Humane Issues in the Use of Random Source
Dogs and Cats in Research. Stafford, K.J, 2009 ,The Welfare of Dogs.
 Reeves PT , Roesch C., Raghnaill MN. How Drugs are Given in Animals. July 2016
THANK YOU
Experimental Pharmacology-PC 530
Animal Model:
Rat
(Rattus norvegicus)
By
Pallabi Panja (PC/2021-14/232)
Sitara Ghosh(PC/2021-14/233)
Department of Pharmacology & Toxicology
Introduction
 Animal models are indispensable in experimental
pharmacology to investigate dose-response relationship
and pharmacokinetics of different test substances.
 The commonly used laboratory animals are, Mice, Rat,
Guinea pig and Rabbits.
 Laboratory rats are the second most (after mice)
commonly used species in biomedical research.
 Well established strains of rats are used to study various
human diseases.
RAT (Rattus novergicus)
 The genus Rattus contain 66 species through laboratory rat is the
domesticated form of the species Rattus novergicus or the brown Norway
rat.
 Two most popular strains of rat in laboratory research are–
1. Wister rat 2. Sprague-Dawley rat
•Outbreed albino rat
•Developed in Wister Institute(1906)
•Wide head, long ears, tail length is less
than its body length
•Outbreed multipurpose breed developed
from Wistar rats
•Calm and easy to handle
•Narrower head and long tail
 Others strains includes –
(All of these are genetically modified )
Long Evans rats:
They are used as multipurpose model
organism, frequently in behavioral and
obesity research.
Zucker rats:
They are genetically modified rats
used to study obesity and
hypertension.
Biobreeding rats:
They are used as models to study
autoimmune type 1 diabetes.
Hairless rats:
They are used to study compromised
immune system and genetic kidney
diseases.
Biological Data:
Typical adult weight Male: 300-500 g, Females: 250-300 g
Life Span 2.5-3.5 years
Physiological Data:
Heart rate 300-500 beats/min
Respiration rate 65-180 /min
Daily Food intake 10-20 g
Routes of drug administration
1. Oral route 2. Subcutaneous route
3. Intraperitoneal route 4. Intramuscular route
Advantages
 Small size
 Greater sensitivity to most drugs
 Sturdy and can withstand long periods of experimentation
under anesthesia.
 Vomiting center is absent- oral administration of drug can be
done.
Disadvantages
 Vomiting centre absent. So emetics study is not possible
 Diffuse pancreas so not a good model for type I diabetic studies
 Do not have tonsil and gall bladder
Experimental uses
 Used in research of behavior, pharmacology, neurosciences,
physiology, immunogenetics, transplantation, cancer risk
assessment, cardiovascular diseases and aging.
 Study of analgesics and anticonvulsants.
 Bioassay of various hormones like insulin, oxytocin and
vasopressin.
 Study of estrous cycle, mating behavior and lactation.
 Chronic study.
 Gastric acid secretion.
 Hepatotoxicity studies.
 Study on mast cells.
 Toxicology studies.
 Rat brain tissue is extensively employed in radio-receptor
ligand studies.
 Various isolated tissues used are rat uterus, ileum, fundus strip,
vas deferens and anococcygeus muscle.
Why to choose Rats over mice?
 Rats share 90% of the genomes with humans, making them a suitable
research tool
 They are larger in size than mice, which makes handling, sampling and
performing procedures easier.
 For physiological studies, more responses and pathways are known.
 More accurately reflects human physiology than mice do.
 More suited for behavioral studies (learning and cognition).
 Sensitive to most drugs
 Can withstand long period of experimentation under anesthesia.
 Oral administration is possible as vomiting centre is absent.
References
1. Kemp, Robert. (2000). Handling and Restraint. 10.1016/B978-
012426400-7/50042-X.
2. Balagopalan, Devika & Hussain, Gazala & M M, Nidhin & Nambiar,
Sruthi. (2019). A review on experimental pharmacology. Journal of Drug
Delivery and Therapeutics. 9. 501-504. 10.22270/jddt.v9i1-s.2242.
3. Elizabeth C. Bryda. The Mighty Mouse: The Impact of Rodents on
Advances in Biomedical Research. Mo Med. 2013 May-Jun; 110(3):
207–211.
4. MATER METHODS 2012;2:113
Presentation on experimental animals
Topic: Rabbits (Oryctolagus cuniculus)
NAME: PREETHI K RAMAN & PRIYANSHA SINGH
INSTITUTE: NIPER GUWAHATI
DEPARTMENT: MS(PHARM) PHARMACOLOGY AND TOXICOLOGY
SUBJECT: EXPERIMENTAL PHARMACOLOGY
DATE:
Introduction
• What is animal experimentation?
• Animal experimentation is the use of animals in scientific
research
• usually in a laboratory, for the purpose of gaining new
biological knowledge or solving specific medical,
veterinary medical, dental, or biological problems.
Why should we use animal models
Mammalian animal models are useful to
investigate mechanisms of efficacy and toxicity because
of species similarities in pathways between animals
and humans. (i.e. :animals are phylogenetically similar
to humans)
Why be aware on selecting animals
model.
Because performing research in appropriate
animal, results should be approximate to what can be
expected in humans.
PARAMETERS TO BE NOTED BY THE ANIMAL
HOUSE IN-CHARGE FOR THE CARE OF ANIMALS
• Fluid
• Diet
• Cleanliness
• Litter
• Cages
• Labelling of the cages
• Ventilation
• Temperature and Humidity
• Handling
• Breeding
• Marking animals
• The detection of signs of disease in animals
Animals in use
The animals used as research models are divided into the following
two groups:
• Small animal category requiring local animal ethical committee
approval:
– Rats
– Mice
– Zebrafish
– Guinea pigs
– Rabbit (largest animal in this group)
• Large animal category requiring central animal ethical committee
approval in addition to the local ethical committee are:
– Dogs
– Goats
– Cats
– Primates
My topic : Rabbits ( Oryctolagus cuniculus)
Kingdom: Animalia
Phylum: Chordata
Class: Mammalia
Order: Lagomorpha
Family: Leporidae
• New Zealand White rabbits
(nickname: REW/NZ)
• large albino rabbits,
• Dutch Belted rabbits
are the most common breeds of
rabbits
Transgenic rabbits are also used
Commonly used:
New Zealand rabbits Dutch belted rabbits
Large albino rabbits
GFR rabbits(transgenic)
DETAILS
• Rectal temperature:38.7°C -39.1°C
• Normal respiratory rate:55/min
• Pulse rate:1.35/min
• Gestation period: 28-31 days
• Weaning age:6-8 weeks
• Mating age:6-9 months
• Litters: 4 yearly
• Weight:0.9-6.75 kg
• Gender is generally not a problem, but some investigators in
literature have preferred female sex as it is biologically the
stronger sex.
MAINTENANCE OF RABBITS IN THE ANIMAL HOUSE
• Newly arrived rabbits in the animal house should be quarantined for a
minimum of two weeks(serves as a period of adaptation to the
surroundings and the daily routine )
• examined for the most common diseases.
• easily infested with scabies, which is highly contagious and capable of
damaging the airways and predisposing to pneumonia.
• Adult rabbits , kept in individual mesh cages (0.90 × 0.60 × 0.45 m) hung
at a height of 0.8 cm from the ground so that excrement can fall out into
collecting trays.
• 12 to 14 hours of light are necessary for the colony's circadian biorhythms
Cages for rabbits to be used in experiments
 Cages are best made of galvanized iron.
 The minimum size for a medium sized rabbit is 2×2×1(1/2)ft.
 Young rabbits up to 3 months of age may be housed together but after that time sex
should be separated.
 From 8 -10 young rabbits may be kept together in pen similar to that used for guinea
pigs.
An image showing a sample cage for rabbits
• Fresh hay, oats and fresh vegetables (especially roots)
• Water (the most important constituent of its diet)
 Dehydration in rabbit is a very common serious condition that
needs immediate attention.
 Signs of dehydration can be detected by the skin on their body.
 The skin on the back of the rabbit's neck is raised upward until it is
stretched enough that is comfortable to the rabbit. If it snaps back
fast, the rabbit is healthy.
 The slower it takes for the skin to return, the more is the
dehydration. In such a case, one can hydrate them by giving
GatoradeR - mix the Gatorade half and half with water and feed
them with a dropper
• Pelleted diet 18 of Bruce and Parkers(1947) or
commercial breeders pellets are suitable
• Daily supply of 2.5 0z(72 gm) of a mixture of one part
oats and three parts bran may be fed as a slightly moist
mash
DIET
HANDLING
• Daily human contact reduces stress during handling.
• Gloves should always be worn when handling
• These animals can become nervous and inflict severe bites or
scratches from their powerful hind legs, if not properly handled and
restrained.
• Rabbits should never be handled by the ears because of a high
probability of causing cervical luxation and death.
• They should be held by grasping a large fold of loose skin over the
shoulders with one hand and either supporting or grasping the rear
feet with the other hand.
• Failing to support or hold onto the rear feet may result in the
animal kicking and trying to escape, which can cause severe spinal
injury or a broken back.
An image showing how rabbits are handled for experiments
Advantage and disadvantage
• ADVANTAGES OF RABBIT AS A MODEL ARE AS FOLLOWS
• very docile and non-aggressive and hence easy to handle and observe.
• Widely bred and very economical compared with the expense of larger
animals.
• Have short vital cycles (gestation, lactation, and puberty)
• It comes under the small animal category, hence easy ethical committee
clearance
• DISADVANTAGES:
• Fast and swift in nature
• Fragile body
• Vulnerable to animal prone/post operative diarrhea, GIT stasis, post
implantation fracture of fragile femur
INFECTIONS RABBITS ARE PRONE TO
• Coccidioisis (hepatic and intestinal)
• Pseudo tuberculosis
• Respiratory infections( Snuffles)
• Pneumococci
• Streptococci
• Intestinal infections( mucoid enteritis, Diarrhoea)
• Rabbit syphilis (Treponema cuniculi)
• Worms (cysticercus stage of dog tape worm,
Taenia pisiformis)
EXPERIMENTAL FEILDS
Lipid metabolism and atherosclerosis:
Atherosclerosis is a multifactorial disease and is one of the major
causes of mortality in Western societies. Rabbit models include normal
cholesterol-fed rabbits, spontaneous mutants for lipid metabolism
Cancer study:
Oncogene expressing transgenic rabbits, which developed lymphomas
and skin carcinoma were created and partially characterized. Those
animal models may be valuable for studying oncogenes and their
synergistic effects in tumor genesis. Furthermore they provide a model
for evaluating antitumor therapy
Eye research:
• surgical interventions including cataract removal, intraocular
lens insertion, corneal transplantation, laser refractive
procedures, glaucoma shunt implantation, and intravitreal
drug delivery.
Use of GFP rabbits
• GFP (green fluorescent protein) is a protein from Pacific
Ocean jellyfish which becomes green under UV light
• The observation of the GFP rabbit cells using a specific probe
(Cell-viZio, MKT) made it possible to obtain the precise
description of different tissues which appear green
• GFP rabbits are currently being used as models to study
cornea grafting. These rabbits made following the fate of the
green cells possible at different periods after cornea grafting
on normal rabbits
Anatomical and metabolic disorders
• Study of anti diabetics
• Surgically induced secondary osteoarthritis and osteotomy rabbit
models have also been created for in vivo gene therapy trials
• In the osteoarthritis model, the interleukin-1 receptor antagonist
gene was found to be effective in the prevention of osteoarthritis
progression In the osteotomy model the gene therapy vector
harbored the human BMP-6 gene and was shown to accelerate
healing
Alzheimer's disease
• rabbits have larger brains relative to the aforementioned species
allowing for greater flexibility in testing for cognitive impairment.
Transgenic rabbits as bioreactors
• Pharmaceutical proteins produced from transgenic rabbit milk
• The technology for using the mammary gland as a bioreactor has been
developed to the point that pharmaceuticals derived from the milk of
transgenic farm animals are currently in the advanced stages of clinical
trials.
Immunological studies:
• Sensitive to histamine.
• Available rabbit strains are naturally devoid of several immunoglobulin
loci. These animals, which received human immunoglobulin loci,
generate human polyclonal antibodies after classical immunization
• The rabbit appears to be particularly flexible in the preparation of
human antibodies
.
Cosmetic studies:
They are used in skin and eye irritation studies, such as the archaic
and painful Draize tests for cosmetics, personal care, household
products and other chemicals.
OTHER APPLICATIONS FOR RABBITS
AS EXPERIMENTAL ANIMALS
• Pyrogen testing of rabbits for parenterals (LAL & SHAMS test)
• Bioassay & screening of insulin, antidiabetic and curaremimetic drugs.
• Testing Topical agents as skin is sensitive
• Studies related to antifertility agents
• It has simple cardiac tissue free of connective tissue and hence is the animal
of choice for cardiac studies
• Screening embryotoxic agents and teratogens
• Rabbits also act as good models for preparation & extraction of antibodies
and serum.
SUMMARY
Rabbits are docile animals used as animal models
for pharmacological studies
Used in study of
• Atherosclerosis, osteoarthritis
• Oncological studies
• Eye research
• Immunological studies
• Anatomical and metabolical disorders
• Bioreactors
• Testing cosmetics and home applicants
Thank you

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Cat as Experimental Animal Model Research

  • 1. PRESENTATION ON CAT AS EXPERIMENTAL ANIMAL MODEL Under the guidance of Dr. VGM Naidu. Associate Professor , Pharmacology & toxicology. M Tech. PhD Presented by - Miss.Pratiksha S. Raut and Ramya Sri
  • 2.  CONTENTS Aim of Experimental studies Major Advances in Research that involves Animal Models Animals used in clinical research are classified Cruel Cat Experiment CAT Sources of Cats Housing Breeding colony and Management Infectious Disease Exclusion and control Application for various diseases
  • 3. AIM OF EXPERIMENTAL STUDIES a) To provide “SCIENTIFIC PROOF” of etiological or risk factors which may permit the modification or control of those disease b) To provide a method of “measuring the effectiveness and efficiency of health service for the prevention ,to control and to improve the health of the community
  • 4.  MAJOR ADVANCES IN RESEARCH THAT INVOLVES ANIMAL MODELS 1600’s – Functions of lungs ,measurement of Blood Pressure 1800’s – Vaccination ,Understanding of Infections diseases 1900’s – Antibodies , Hormones 1930’s – Nerve impulses ,Tumor virus - 1940’s – Embryonic development 1960’s – Monoclonal Antibodies , Liver Function 1970’s – Transplantation antigens , Brain functions , Discovery of  Prostaglandins 1980’s – Development of Transgenic Animals 1990’s – Understanding Auto Immune Disorders ,In-vitro fertilization , Cloning
  • 5.  Animals used in clinical studies are classified as- Experimental Animals Rodent Animal Models Non Rodent Animal Models EX: Rat Mice Guinea pig Hamster EX: Rabbits Monkey Cat Dog EX: Frog pigeon Miscellaneous Mammals
  • 6. CRUEL CAT EXPERIMENT “-----Orem multilates and kills animals as parts of the federal grant gravy train….for animals who have no voice….Frankenstein lives……” A_I_F. “ I Found orem’s work among the most ghastly I have read. . .The gross insensitivity to the animals used is a profound embarrassment to scientific community.” SUZANNE CLIVER, D.V.M.
  • 7. “cage too small….the size of the adult cat causes him not to turn and move freely”. U.S. DEPARTMENT OF AGRICULTURE
  • 8. CAT -Of the 1,267,828 non-rodent animals used in research in the united state in 1997,only 26,091, or 2% were cats -The domestic cat (Felis cattus ) is one of only a few mammals other than humans and mice for which extensive information has been generated on its genome -Since the turn of the century ,in Britain the cat has been the preeminentspecies for acute experiments -These classicalinvestigationwere of great importancein elucidatingthe mode of action and regulation of the cellsand more recently of neuroendocrine interrelationships
  • 9. SOURCES OF CATS A. Directories of source -The Institute for Laboratory Animal Research , The American Association for laboratory science,- Animal care , U.S department of agriculture division B. Random source C. Commercial purpose- Bred Colonies D. Institutional Breeding Colonies
  • 10. HOUSING A. Caging Design and Operating Procedure B. Animal Care Staff C. Feline Social Behavior D. Housing to Exclude Pathogens E. Environmental Enrichment
  • 11. BREEDING COLONY MANAGEMENT A. Estrous Cycle and Mating B. Pregnancy and Parturition C. Infertility D. Neonatal Care and Weaning E. Nutrition and Feeding -Commercial diets -Energy Requirements
  • 12. INFECTIOUS DISEASE EXCLUSION AND CONTROL A. Preventive Medicines B. Pathogen Control C. Eliminating Parasites D. Personnel Health Risks
  • 13. i. Study of emotion ii. Study of cardiac disease, spinal cord injury iii. Study of Cataract surgery, glaucoma, lupus, diabetes, spinabifida and more iv. Cats have a distinct nictilating membrane used for studying “Ganglionic drugs” v. Cats have been used to study neurological problems ,such as Epilepsy, Deafness &Vision problems vi. Studies on Aging vii. The relatively long life Span Cats makes its possible to observe the slower and more subtle effects of aging Applications
  • 14. REFRENCES Brenda Griffin and Henry J. Baker Guest Editor (s): James G. FoxMassachusetts Institute of Technology, Cambridge, Massachusetts Guest Editor (s): Lynn C. AndersonMerck Research Laboratories, Rahway, New Jersey Guest Editor (s): Franklin M. LoewBecker College, Worcester, Massachusetts Guest Editor (s): Fred W. QuimbyLaboratory Animal Research Center, Rockefeller University, New York, New York
  • 15.
  • 16. HAMSTER AS AN ANIMAL MODEL FOR RESEARCH Under the guidance of Dr .VGM Naidu, Associate professor, Department of Pharmacology and Toxicology, MTech ,PhD. Presented by Ms.Mounisha bandakinda MS.Anjana swathi National Institute of pharmaceutical Education and Research GUWAHATI
  • 17. Drugs, vital weapons in healthcare, are only used in therapeutics after being tested in the lab. In both animals and humans, the roles of cells and organs are essentially the same. Many of the functions of animal cells are similar to those of human cells. Humans are classified as animals biologically. . Animals have also played an important role in the advancement of research; several new drug discoveries have been made possible thanks to animal testing. So there are different types of Animal models are used in Experimental study. Animal models:  RAT  MICE  RABBIT  HAMSTER  GUENIA PIG  MONKEY INTRODUCTION: NIPER GUWHATI
  • 18. Mesocricetus auratus is also known as the Syrian or Golden hamster. They belong to the family Cricetidae, to the subfamily Cricetinae, to the genus Mesocricetus, and the species Mesocricetus auratus. When they burrow, play, chew, and dig, the Syrian hamsters are mostly active at nighttime. Their nocturnal nature means that circadian rhythms are perfect for learning. HAMSTERS: NIPER GUWHATI
  • 19. TYPES OF HAMSTERS: Based on Genus there are different types of Hamsters - • Genus Cansumys • Genus Allocricetulus: •Mongolian hamster •Eversmann's or Kazakh hamster Genus Cricetulus: •Tibetan dwarf or Ladak hamster •Species C. barabensis, including "C. pseudogriseus" and "C. obscurus"—Chinese striped hamster, also called Chinese hamster; striped dwarf hamster •Genus Mesocricetus: Golden hamsters Species- M. auratus-golden or Syrian hamster:-The Syrian hamster is an ideal small animal model to study the disease caused by virus infection. Previous studies have shown that some human-specific viruses can also infect, replicate and cause similar pathological alterations in Syrian hamsters. •Genus Phodopus—dwarf hamsters: Species P. campbelli—Campbell's dwarf hamster Species P. roborovskii—Roborovski hamster NIPER GUWHATI
  • 20. Hamsters have unique physiological characteristics rendering them well-suited for biomedical research as experimental model. They match beneficial traits of both smaller rodents and larger mammals that make them suitable for laboratory use, such as availability, breeding ease, greater tissue proportions and the like. In experimental design, it is inevitable to select laboratory animals of accurate age that can mimic the target human age in a specific research. PHYSIOLOGICAL PARAMETERS: Physiological and Reproductive data of Hamsters NIPER GUWAHATI
  • 21. • The effect of cage size and enrichment on core temperature : Febrile response of the golden hamster SENSITIVITY AND DEGREE OF PHYSIOLOGICAL RESPONSE: • Different effects of acute and chronic immobilization stress. • The photoperiodic response in Syrian hamster depends upon a melatonin-driven circadian rhythm of sensitivity to melatonin . • In the Syrian hamster, winter seasonal inhibition of reproduction occurs in response to decreasing day length. This inhibitory response is modulated by nonphotic cues. NIPER GUWAHATI
  • 22.  The key to keeping your hamster healthy is a good diet and clean living conditions. Clean and disinfect his cage at least once a week. Hamster's teeth grow continuously so provide him with chews and gnaw sticks to wear down those dentures! Syrian Hamsters are susceptible to diarrhoea known as wet tail.  Give your hands a thorough wash with soap and water. ...  Introduce your hand to the cage before touching your pet. ...  Turn your palm up and wait for your hamster to crawl onto your hands. ...  Keep your hands in the cage for the first few times you pick up your pet. NIPER GUWAHATI
  • 23. Among several possibilities for the administration of substances to Hamsters, the most common routes are subcutaneous, intraperitoneal or intravenous and intra muscular injection. ROUTE OF ADMINISTRATION : Muscle tissue may also hold a larger volume of medication . The drug will be absorbed faster from the intramuscular route because muscular tissue has rich blood supply. Intra muscular route: Subcutaneous injections are generally given under the loose skin of the back just behind and between the shoulder blades, or on either side of the hamsters in the hip area. Subcutaneous route: NIPER GUWAHATI
  • 24. Oral Route: The oral route is economical, convenient, relatively safe, and some animals can be trained to cooperate voluntarily, depending on the compound being administered Intravenous administration: The intravenous route of delivery is the most efficient means of delivering substances to animals because it bypasses the need for solute absorption. Administration to skin and muscle : - Some substances can be administered directly to the skin surface (epicutaneous administration) for a topical affect. The extent of absorption of materials through the skin and into the systemic circulation. ROUTE OF ADMINISTRATION : NIPER GUWAHATI
  • 25. Hamsters are fun to watch Hamsters are patient and curious animal and don't make noise Hamster don't take up much space Hamsters don't need walking don't mean a lot of work No tax DISADVANTGES : Hamsters are active at night (from around 8 pm, but sometimes later) Hamsters only live for 2-4 years Hamsters are not suitable for cuddling quite delicate Hamsters chew on cables (could mean extra costs) ADVANTAGES: NIPER GUWAHATI
  • 26. The hamster is used frequently in IVF research among other research areas including oncology, immunology and physiology. However, their unique reproductive system which include a continuous 4 day estrous cycle (the reproductive cycle of all non-higher primate mammals) and a very short pregnancy period of 16 days. DRUG ASSAY : • Various infectious diseases • Corona virus • Cardiovascular disorders • Diabetes mellitus • Hypothermia research Applicable to various diseases : NIPER GUWAHATI
  • 27.  Hamsters possess unique anatomical and physiological features, which make them desirable research models. Unlike other commonly used laboratory rodents, hamsters possess a cheek pouch, which can be easily everted and examined at both the gross and microscopic level. WHY HAMSTERS PREFERRED IN RESEARCH :  Hamsters, for many people, make excellent pets. They don't require a lot of attention, get enough exercise running on their wheel, and are cute, cuddly, and pleasant to hold.  Hamsters have special feature like nocturnal nature means that circadian rhythms are perfect for learning in experimental pharmacology. NIPER GUWAHATI
  • 28. REFERENCES : 1.Bartlett P. P. The hamster handbook, in: Bartlett P. (Ed.), Barron’s Educational Series 2nd ed. Barron’s Educational Series. 2015. 2.Blaha G. C. Reproductive senescence in the female golden hamster. The Anatomical Record. 1964;150:405-411 . 3.http://howmed.net/pharmacology/routes-drug-administration/--Routes. 4.https://www.karger.com/Article/FullText/516240. 5.https://www.researchgate.net/publication/349632243_ANIMAL_MODELS_OF_HUMAN_DISEASES_AND _THEIR_SIGNIFICANCE_FOR_CLINICAL_STUDIES_OF_NEW_DRUGS. 6.ANIMAL MODELS OF HUMAN DISEASES AND THEIR SIGNIFICANCE FOR CLINICAL STUDIES OF NEW DRUGS February 2021 Authors: parvova ,dhanchay.
  • 30. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) AN OVERVIEW ON GUINEA PIG GUIDED BY Dr. V.G.M. NAIDU M.Tech, PhD ASSOCIATE PROFESSOR DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY PRESENTED BY SNEHASHIS KUNDU AND SUDIPTA NAYAK M.S. (PHARM.), 1st SEMESTER COURSE CODE: PC-530 12/12/2021 30
  • 31. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G)  SCIENTIFIC NAME & TAXONOMY  INTRODUCTION  PHYSICAL DESCRIPTION  TYPES OF SPECIES & THEIR DESCRIPTION  DRUG ASSAY & ROUTE OF ADMINISTRATION  SENSITIVITY  PHYSIOLOGICAL DATA AS PER CPCSEA GUIDELINE  HAEMATOLOGICAL DATA AS PER CPCSEA GUIDELINE  MINIMUM FLOOR AREA NEEDED AS PER CPCSEA GUIDELINE  PROS & CONS  APPLICATION  WHY PREFERRED?  CONCLUSION  REFERENCES CONTENTS 12/12/2021 31
  • 32. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) SCIENTIFIC NAME: Cavia porcellus TAXONOMY Phylum: Chordata Class: Mammalia Order: Rodentia Family : Caviidae 12/12/2021 32
  • 33. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) INTRODUCTION:  About 400 years ago, Guinea pig (Cavia porcellus) was introduced into Europe from South America.  Guinea pigs are domesticated species of rodent. Here rodent means mammals of the order Rodentia, which are characterized by single pair of continuously growing incisors in each of upper and lower jaw.  Their gentle temperament and commercial availability make them useful as research models.  It is used as primary model to perform studies of anaphylaxis, asthma, gnotobiotics, immunology, infectious and nutritional disease, and otology.  Vitamin C was first discovered in guinea pigs in 1907. Like humans and unlike other small laboratory animals, guinea pigs do not produce their own vitamin C and instead must obtain this vitamin from their diet.  Its serum contains asparaginase enzyme which having antileukemic action. 12/12/2021 33
  • 34. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) PHYSICAL DESCRIPTION:  The guinea pig has a stout, compact body and no tail. Common colours include white, brown, black and combinations thereof.  Guinea pig are large for rodents, measuring 20–40 cm from head to rump.  Weight-weaning: 120gm.  Adult male: 900-1000 gm and Female: 700-900 gm.  Litter size: 2-5  Life span: 4-5 years ( maximum 8 years). 12/12/2021 34
  • 35. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) TYPES OF SPECIES & THEIR DESCRIPTION Abyssinian Guinea pig Rough, wiry hair coat, hair made of rosettes, found in all colour and colour combination. American Guinea pig Most common bread, short, very glossy, fine hair, found in widely variety of colour and colour combination. Peruvian Guinea pig Long haired variety, hair length evenness and balanced are deciding feature, lacks a tail. Satin Guinea pig Fur is distinguishing feature, fine, dense, soft, luxurious and shiny. Teddy Guinea pig Short hair, lies thick and close to the body. Crested Guinea pig It also known as white crested, often look very similar to American guinea pig but its having a crown of hair on top of their heads. Silky Guinea pig Long hair, unlike Peruvian no long frontal sweep over head. It sometimes called Sheltie. 12/12/2021 35
  • 36. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) SEVEN MOST COMMON SPECIES OF GUINEA PIGS American guinea pig Abyssinian guinea pig Teddy guinea pig Satin guinea pig Crested guinea pig Silky guinea pig Peruvian guinea pig 12/12/2021 36
  • 37. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) DRUG ASSAY & ROUTE OF ADMINISTRATION DRUG NAME ROUTE OF ADMINISTRATION DOSE Atropine Intramuscular 0.1-1.0 mg/kg Ketamine Intramuscular 10-44 mg/kg Midazolam Intramuscular 1-2 mg/kg Diazepam Intramuscular 0.5-3.0 mg/kg Ciprofloxacin Per os 5-20 mg/kg Metronidazole Per os 25 mg/kg Ketoconazole Per os 10-40 mg/kg Ivermectin Subcutaneous 0.2-0.4 mg/kg Vitamin C Per os, subcutaneous, Intramuscular 10-100 mg/kg Epinephrine Intravenous 0.003 mg/kg Cisapride Per os 0.1-0.5 mg/kg Furosemide Per os, Subcutaneous 2-10 mg/kg 12/12/2021 37
  • 38. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) SENSITIVITY:  Guinea pigs are highly sensitive to histamine.  Penicillin is 100-1000 times more toxic to the guinea pig than the mouse.  Guinea pigs are also highly sensitive to dopamine because it causes fall in blood pressure.  They are very sensitive to loud noise.  They are also sensitive to nickel contact. 12/12/2021 38
  • 39. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) PHYSIOLOGICAL DATA AS PER CPCSEA GUIDELINE  Rectal temperature: 37.6-38.9  Normal respiration rate: 80 per minutes  Gestation period: 59-72 days ( average: 63 days)  First ovulation: 4-5 weeks  First ejaculation: 8-10 weeks  Cycle length: 15-17 days  Implantation: 6-7 days ( post ovulation)  Weaning age: 14-21 days  Mating age: 12-30 weeks  Urinary output(ml/100 gm) body weight: 4-9  Daily fecal output (gm): 15-18  Room temperature (F): 65-75  Relative humidity of room(%): 45-55  Daily feed intake (gm): 30-50  Daily water intake (ml/100gm) body weight: 15 12/12/2021 39
  • 40. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) HAEMATOLOGICAL DATA AS PER CPCSEA GUIDELINE Total blood volume(ml/kg) body weight 75 Available blood volume(ml/kg) body weight 35 RBC count(cells/ cu mm) 4.5-7 Hemoglobin (kg/100ml) 12.4 Blood plasma PH 7.3 WBC (x10^3 cells/microliter) 6-17 Platelets (x10^3 cells/ microliter) 250-850 12/12/2021 40
  • 41. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) MINIMUM FLOOR AREA FOR GUINEA PIG AS PER CPCSEA GUIDELINE WEIGHT(gm) FLOOR AREA/ANIMALE (cm2) CAGE HEIGHT (cm2) <350 387 18 >350 >= 651.4 18 12/12/2021 41
  • 42. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) PROS OF GUINEA PIG  Guinea pig live longer and healthy.  They are docile in nature.  Simple to move due to its small size.  They are durable and warm.  They do not occupy a lot of room.  They are very affordable for a layman.  They live more than different rodents. CONS OF GUNIEA PIG  Guinea pig can be really loud.  They poop smells.  They can cause allergies.  They are effortless harmed.  They are normally bashful. 12/12/2021 42
  • 43. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) APPLICATIONS:  Guinea pigs are employed for the evaluation of bronchodilator compounds against experimentally induced asthma.  They are widely used in immunology particularly in the studies of delayed hypersensitivity.  They are employed in the study of local anesthetics as well as bioassay of digitalis.  Its having sensitive cochlea are suitable for hearing experiments.  Being docile in nature and more resistant to hypoxia than rats and mice, they are suitable for experiments on oxygen consumption.  It is a suitable host for mycobacterial infection, and is used in the study of tuberculosis.  Being the only common laboratory animal which resembles man in that it requires exogenous vitamin c, it is used in the study of ascorbic acid metabolism. 12/12/2021 43
  • 44. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) WHY PREFERRED?  They have many biological similarities to humans, beyond the simple fact that they are mammals, which make them useful in many fields of research.  Guinea pigs have contributed to 23 Nobel prizes for medicine with studies leading to the discovery of Vitamin C, the tuberculosis bacterium, adrenaline, development of vaccines for diphtheria and tuberculosis, replacement heart valves, blood transfusion, kidney dialysis, antibiotics, anticoagulants and anti asthmatic drugs.  Today, guinea pigs are still widely used in medical research, particularly in the study of respiratory, nervous and immune systems.  Guinea pigs have a similar hearing range to humans which makes them a useful model for understanding how our ears work and how they can be repaired. 12/12/2021 44
  • 45. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) CONCLUSION:  The intent of this presentation is to highlight on the detail overview of guinea pig as an experimental animal.  We include its physical description, various species, sensitivity, physiological and hematological data, pros and cons, as well as contribution in the field of drug development.  Besides, we also included the reasons for choosing guinea pig as an experimental animal in the field of medical research. 12/12/2021 45
  • 46. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) REFERENCES:  Chakrabarty S., Nandi A., Mukhopadhyay C.K., Chatterjee I.B. Protective role of ascorbic acid against lipid peroxidation and myocardial injury. Mol. Cell. Biol. 1992;111:41–47.  Guide for the care and use of Laboratory Animals. DHEW publication Washington 1978.  CPCSEA Guidelines. http://cpcsea.nic.in.  Coates, M.E. Gnotobiotic animals in research: their uses and limitations. Lab. Anim. 9, 275– 282 (1975).  Ghosh M.N, Vedasiromoni J.R. Fundamentals Of Experimental Pharmacology. 6th edition. Kolkata. Hilton & Company Publisher: 2015.p.16-17.  Medhi B, Prakash A. Practical Manual Of Experimental And Clinical Pharmacology. 1st edition. New Delhi. Jaypee Brothers Medical Publishers Ltd: 2010.P.25-30. 12/12/2021 46
  • 47. NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, GUWAHATI (NIPER-G) 12/12/2021 47
  • 48. Horse as animal model course code: PC-530 12-12-2021 1 Presented by: Ujjawal Soni Donker Chonzom Department of pharmacology and toxicology
  • 49. Introduction: • Horses are well –accepted , well –established and clinically relevant animal models for several human diseases, including metabolic syndrome, asthma, musculoskeletal diseases, melanoma and autoimmune uveitis. • More than 100 equine hereditable conditions may serve as models for human disorders, including inflammation, muscular or fertility disorders, osteoarthritis and even depression. • Horses are also used in biomedical procedures to produce bioactive compounds such as hormones, vaccines, anti-toxins and anti-venoms. • The anatomical and physiological differences between rodents and humans limits the comparative aspects of studies that utilize rodents . • Small rodent animals, specifically mouse and rat, are valuable for research into mechanisms of disease and fundamental biology, but findings from such small animal models often do not translate into human clinical application. • Due to translational challenges, showing the difference in bioavailability of pharmaceuticals between humans, primates, dogs and rodents . Therefore, the European Medicines Agency (EMA), the USA Federal Food and Drug Administration (FDA) and the International Society for Stem Cell Research (ISSCR) recommend the use of large animal models to evaluate efficacy, durability, dose response, degradation and safety of advanced therapeutic medicinal products (ATMPs). 12-12-2021 49
  • 50. Characteristic that are unique to the horse:  Flight: • Primary Defense • Most timid • Must feel safe Most Perceptive 5 senses • Taste: likes salty and sweet, not medicinal • Hearing: directional ears, keener than humans, mood indicator • Smell: becomes familiar • Touch: very sensitive, especially around head • Sight: monocular and binocular Limited color, Movement more important. Large vision Has to turn eye sideways to look at ground 12-12-2021 50
  • 51.  Fast Learner • Fastest of domestic species • Learn in 3’s • Learn from RELEASE of pressure • Generalize learning: same in multiple location  Memory • Forgive but don’t forget • Mules don’t forget or forgive • Retention very • Categorize – Fearful but doesn’t hurt them • Do not stimulate the amygdala – Permanent – “No dust” • Horses don’t rationalize – 2 sides - 2 horses 12-12-2021 51
  • 52. Route of administration of drug :  Intramuscular( IM) : needle is inserted at 90 degree to skin surface Neck, Pectorals , Gluteal  Subcutaneous (SC)  Intravenous(IV) : Jugular groove 12-12-2021 52
  • 53. Animal housing: Horse require particular environments that accommodate their species-specific behaviours and physiology, and ideal housing systems should provide fresh air and light, food and water, adequate space and opportunities for exercise, conspecific social contact and general security. Housing conditions horse housing facilities should include : 1.Adequate ventilation and lighting for horses housed indoors or stabled. Ventilation also helps horses and other large livestock to dissipate heat.  Proper lighting helps to create a safe and comfortable environment for horses. 2. Bedding: The material used for bedding must be non-toxic and should provide effective drainage and absorbency to minimize dampness on the bed floor and to reduce dust and ammonia in the air. 3. Feeding: Must have appropriate food materials and a sufficient food supply to feed their horses.  Suitable foraging material for horses includes the aerial parts of pasture grasses, legumes and forbs. Must also have an appropriate system in place to deliver food to horses. Different feeding methods can be used to reduce and manage fouled food and cross-contamination between horses. 12-12-2021 53
  • 54. 4. Water : Must have a sufficient water supply and an appropriate delivery system to accommodate their horses. A horse typically requires 20–70 l/d of water, depending on air temperature and humidity, body weight, activity level and health10. Maintain their hydration and water balance when water is provided intermittently. 5. Exercise: Opportunities for exercise are essential for the behavioural and physiological well being of horses.  Exercise promotes optimal musculoskeletal development in foals 33–35, and adult horses that are confined for a long time without exercise can develop oedema and potentially impaired respiratory function. 12-12-2021 54
  • 55. Advantages: Largest of the model: Multiple large( critical size) defect and serial sampling possible Functional correspondence of equine SDFT and human Achilles tendon Thickness of knee cartilage is similar to the human Clinical need- naturally occurring disease Disadvantages : Ethnical concerns- companion animals Cost: special facilities needed for housing, surgery , imaging. Necropsy etc Non-weight bearing postoperatively is not feasible 12-12-2021 55
  • 56. Application: Horse helped cure diphtheria and toxic bacillary dysentery by producing on large scale antiserum to the toxin of bacteria. Various human diseases can study in horse: example Tendinopathy Cartilage injuries and osteoarthritis Asthma  Short term memory testing in domestic horse  Horse as model for understanding human innate immunity Identification of biomarkers to monitor disease progression, and the effects of drug treatment on biomarker are also being pursued. Horse serum are used as an anti-venom, ex. When humans are bitten by snake ( Brazillian Bothrops or crotales) 12-12-2021 56
  • 57. Comparison of horse and mouse model for human disease: Comments Horse Mouse General : • Body, organ , longevity closer to human less similar Genetic : • Genetic diversity • Chromosome conservation with human • Genome annotation high high poor low low high Macrophage biology: • CD14, CD16 monocyte observed in humans • Response to LPS detected similar not detected less similar Disease : • Musculoskeletal disorders: osteoarthritis • Asthma : COPD pathophysiology • Human infectious disease • Human mental and behavioural disorder • Human metabolic disorder common similar similar similar similar less common less similar less similar less similar less similar Therapeutic strategies : • Translational application to human possible less possible 12-12-2021 57
  • 59. a A MONKEYS AS LABORATORY ANIMALS Presented by Ashitha Rajanan & Amal Jyothy Suresh M.S (Pharm) 1st semester Department of Pharmacology and Regulatory Toxicology 59
  • 60. Types of monkeys Research areas Why preferred ? Advantages and Disadvantages Conclusion References CONTENTS Routes of Drug administration Sensitivity and Drug testing Introduction 60
  • 61. INTRODUCTION MONKEYS AS LABORATORY ANIMALS  Human biology and disease can be studied in monkeys because they are very similar to humans; biologically anatomically and physiologically.  Most often used monkeys are; Cynomolgus macaques (Macaca fascicularis), Rhesus macaques (macaca mulatta), Marmosets (Callithrix jacchus). 61
  • 62. MACAQUES (macaca) Cynomolgus macaques ( Macaca fascicularis) The crab eating macaque also known as the long tailed macaque. Common research primate (80%) Native of Southeast Asia. Smaller & less aggressive. Rhesus macaques (Macaca mulatta) Larger and more expensive to keep. Easy to keep in captivity. Extensively used in medical and biological research .  wide availability and closeness to humans.
  • 63. MARMOSETS (Callithrix) Common marmoset ( Callithrix Jacchus) Originated in Atlantic coastal forest in Northeast Brazil Light weight arboreal monkeys. Exhibit complex social behavior & cognitive functions that are similar to humans. SQUIRREL MONKEY • Common squirrel monkey [Saimiri sciureus] lives in the tropical forests of central and South America. • Mean body weight of adult squirrel monkey is less than 1kg. • Easily adapt to laboratory housing. • Used as a model for treatments in adult humans for colour blindness. BABOONS Baboons [Papio anubis] are ground dwelling and natives of Africa. Life span about 45 years in captivity. They have similar immune system as that of humans thus used as a model for vaccine development.
  • 64. PHYSIOLOGICAL DATA A Scientific name Macaca mullata Order Primates Body temperature 37-39 deg cel Respiration rate 76-90/min Heart rate Upto 180 beats/min Blood pressure 130/100 mmHg Blood volume 54ml/kg A Life span 30 years Water consumption 18.4 ml/Kg/day Food consumption 1-2.4 kg/day Room temperature 37-40 deg cel Mating age 4-5 years Gestation periods 165 days Body weight About 5-6Kg 64
  • 65. Accommodation &housing  Monkeys should be housed in cages made up of steel or painted mild steel space.  Permit freedom of movement and normal postural adjustments, and have a resting place.  Provide a comfortable environment , climbing structures.  Provide easy access to food and water & adequate ventilation .  Meet the biological needs of the animals, e.g., maintenance of body temperature, urination, defecation, and reproduction . Temperature condition will vary from animal to animal , Eg :for marmoset -<5deg cel , macaques->15deg cel  Keep the animals dry and clean, consistent with species requirements .  The height of the cage should be sufficient for the animals to stand erect with their feet on the floor, whereas the minimum height of the cage for langurs has to be 90 cm. 65
  • 66. ROUTES OF DRUG ADMINISTRATION ORAL • Most convenient • Safe • Drug mixed in diet or other food stuff • Economical INTRA VENOUS • 100% bioavailability • As bolus or infusion • Jugular, cephalic, femoral vein INTRA MUSCULAR • Common route for larger animals • Small volumes are preferred • Uniform and rapid absorption 66
  • 67. SENSITIVITY AND DRUG TESTING Drug testing-  Determination of serum concentrations of penicillin ,doxycycline and ciprofloxacin in anthrax infected monkeys.  Studying of efficacy of psychostimulants like cocaine.  More relevant data about the metabolites of cyclophosphamide and ifosamide from CSF of monkeys. Olfactory sensitivity Sometimes more than rat or dog Vision Squirrel monkeys for vision studies Ability to hear Sense of touch Monkeys as smart as toddlers [most intelligent monkey-capuchin] 67
  • 68. RESEARCH AREAS  African green monkeys and rhesus monkeys are suitable models than other animal models in Covid 19 for studying the progression of disease.  Monkey models are used in Neuroscience [Alzheimer’s to schizophrenia]  Marmoset monkey models for Parkinson’s disease.  Discovery of H56 vaccine from macaque models for tuberculosis.  Similar visual system –Squirrel monkey model for colour blindness.  Aotus monkeys are used for understanding malaria, screening antimalarial drugs and vaccine development.  Ovariectomized cynomolgus monkeys (Macaca fascicularis), baboons, langur such as used for reproductive system research.  Rhesus monkeys were used to design the first hepatitis E vaccine, hecolin. 68
  • 69. SOME OTHER SCIENTIFIC ADVANTAGES a Polio vaccine Corneal transplants Yellow fever vaccine Mapping of the heart connections to arteries HIV model Cancer chemotherapy 69
  • 70. ADVANTAGES DISADVANTAGES Anatomical similarity • Brain • Eyes Physiological similarity • Immune system • Reproductive system Others • Motor skills • More similar metabolism Ethical issues Threatened species Difficulty in maintenance Housing changes cause abnormal behaviour Chances of zoonotic diseases Experiments take several years 70
  • 71. WHY PREFFERED ?  The rodent lacks the pre fontal cortex specialisation that is found in monkeys and humans.  Due to the similarity in reproductive system between NHP female and human female these are more pertinent species for study of reproductive effects.  Regarding the ocular system, the retina of NHP and man show unique features that not found in other mammal.  NHP s are less susceptible to vomiting than dogs. 71
  • 72. CONCLUSI N  Genetical similarity of monkeys to humans make them particularly suitable candidates for testing the safety of new drugs and studying of variable diseases .  But those similarities to humans also raise specific ethical questions about their use for scientific experiments.  However they play an indispensable role in the process of medical research and development. 72
  • 73. REFERENCE  Leuner B, Kozorovitskiy Y, Gross CG, Gould E. Diminished adult neurogenesis in the marmoset brain precedes old age. Proceedings of the National Academy of Sciences. 2007 Oct 23;104(43):17169-73.  Mancuso K, Hauswirth WW, Li Q, Connor TB, Kuchenbecker JA, Mauck MC, Neitz J, Neitz M. Gene therapy for red–green colour blindness in adult primates. Nature. 2009 Oct;461(7265):784-7.  Wilcock GK, Esiri MM. Plaques, tangles and dementia: a quantitative study. Journal of the neurological sciences. 1982 Nov 1;56(2-3):343-56.  Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Proceedings of the National Academy of Sciences. 1983 Jul 1;80(14):4546-50.  Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, Bleicker T, Brünink S, Schneider J, Schmidt ML, Mulders DG. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT- PCR. Eurosurveillance. 2020 Jan 23;25(3):2000045. 73
  • 74. 74
  • 75. TOPIC :- MICE AS ANIMAL MODEL COURSE CODE :- PC-530 DEPARTMENT :- PHARMACOLGOY & TOXICOLOGY Presented by Tejes Gholap & Avdhoot Kalambe
  • 76. NIPER GUWAHATI MICE  Laboratory mice are usually of the species Mus Musculus. They are the most commonly used mammalian research model and are used for research in genetics ,psychology,medicine and other scientific disciplines. Mice belong to the Euarchontogrlires clade, which includes humans.  Mice have been used in biomedical research since the 17th Century.
  • 77. NIPER GUWAHATI TYPES OF MICE 1) Non-obese diabetic (NOD) mice – Which develop diabetes mellitus type 1. for antidiabetic activity . 2) Knockout mice – For the purpose is to study the function of the gene's product or to simulate a human disease 3) Oncomice - With an activated oncogene, so as to significantly increase the incidence of cancer. 4) Immunodeficient nude mice - lacking hair and a thymus - used for research in immunology and transplantation. 5) Japanese waltzing mice - Which walk in a circular pattern due to a mutation adversely affecting their inner ears. 6) Doogie mice - With enhanced NMDA receptor function, resulting in improved memory and learning, 7) Transgenic mice - With foreign genes inserted into their genome. 8) Murphy Roths large (MRL) mice - With unusual regenerative capacities.
  • 78. NIPER GUWAHATI AVAILABILITY Strains Features Suppliers C57BL / 6 Inberd black The jackson laboratory BALB/c Albino with immunodeficient Harlen laboratory CD -1 Outbred albino Taconic bioscience
  • 79. NIPER GUWAHATI SENSITIVITY Mice are sensitive to following paramaters – 1) To the light refluxes - Sensitive to bright lights and have poor eyesight. 2) To taste - Mice that can detect four of the five flavors that the buds recognize. Bitter, sweet, sour and umami . 3) To smell - Highly sensitive to Peppermint oil, cayenne pepper, pepper and cloves. 4) To drugs - Highly sensitive to drugs like acamprosate and baclofen. Type of animal Sensitive to Example Transgenic mice Cancer Colorectal cancer Swiss albino Toxicology studies Barabiturate toxicity Konckout mice To genetic disorder Thalassmia Doogie mice Learning & memory Alzimer disease Type of animal Sensitive toe
  • 80. NIPER GUWAHATI PROS & CRONS / ADVANTAGES & DISADVANTAGES
  • 81. NIPER GUWAHATI DRUG ASSAY Following types of drugs are assayed by mice using as an animal model, 1)Antidiabetic drugs – eg .metformin etc. 2) NSAIDs – eg. Ibuprofen, indomethacin etc. 3) Analgesic – eg. Codain, Merperidone etc. 4) Antihypertensive drugs – eg. Reserpine , verapamil etc. 5) Anticancer drugs – eg. Vinca, taxens etc. 6) Others…..
  • 82. NIPER GUWAHATI HANDLING OF MICE  A recommended method to pick up mice is to guide them into a handling tunnel, lift them inside the tunnel and transport them to their destination. Gently tip animals from the tunnel backwards, directly onto the surface or hand (a smooth plastic tunnel that the animals cannot grip is best).
  • 85. NIPER GUWAHATI SITE OF ADMINISTRATION 1) Oral Route - The oral route is economical, convenient, relatively safe, and some animals can be trained to cooperate voluntarily, depending on the compound being administered 2) Intravenous administration - The intravenous route of delivery is the most efficient means of delivering substances to animals because it bypasses the need for solute absorption. 3) Administration to skin and muscle - Some substances can be administered directly to the skin surface (epicutaneous administration) for a topical affect. The extent of absorption of materials through the skin and into the systemic circulation
  • 86. Subcutaneous adminis- trations over the interscapular area are made as follows. The mouse is manually restrained and then placed on a clean towel or solid surface. The needle is inserted under the skin of the interscapular area tented by the thumb and forefinger and the substance then injected. NIPER GUWAHATI SUBCUTANEOUS ADMINISTRATION
  • 88. NIPER GUWAHATI SITE OF ADMINISTRATION 4) Intraperitoneal Administration -Injection of substances into the peritoneal cavity is a common technique in laboratory rodents but rarely is used in larger mammals and humans. Intraperitoneal injection is used for small species for which intravenous access is challenging and it can be used to administer large volumes of fluid safely 5) Intranasal, Intratracheal, and Inhalational Administration - In research settings, animals generally are sedated or anesthetized47 for the intranasal and intratracheal routes of delivery, to minimize struggling and sneezing. 6) Intramuscular Route - Administration of substances is a common parenteral route in large animals and humans but often is avoided in smaller species because of the reduced muscle mass. Generally, intramuscular injections result in uniform and rapid absorption of substances, because of the rich vascular supply. Smaller volumes are administered intramuscularly
  • 90. NIPER GUWAHATI APPLICATION FOR VARIOUS DISEASES 1)Diabetes mellitus – to check Antidiabtetic potential . 2) Cancer – eg.colon cancer ,Breast caner ,pancreatic cancer.etc 3) Hypertension – for antihypertensive activity 4) Analgesic activity 5) Immunogical disorders 6) ADIS 7) psoriasis
  • 91. NIPER GUWAHATI INSTRUMENTS USED FOR STUDY 1) Analgesiometer - The Hot Plate Analgesia Meter is used to evaluate thermal pain relfex due to footpad contact with heated surface.
  • 92. NIPER GUWAHATI 2) ROTAROD – Rotarod test is widely used to evaluate drug effects on motor coordination, balance and motor learning in rodents.
  • 94. NIPER GUWAHATI WHY THEY ARE PREFERED ?  Most of the mice and rats used in medical trials are inbred so they are almost identical genetically helping to make the results of medical trials more uniform.  Another reason they're used as models in medical testing is that their genetic, biological and behavior characteristics closely resemble those of humans.  The mouse genome is very similar to our own, making mouse genetic research particularly useful for the study of human diseases. Mice are cost effective because they are cheap .
  • 96. TITLE : USE OF DOG MODELS IN PRECLINICAL PHARMACOLOGY SUBJECT CODE: PC-530 BY ANKIT KUMAR & ANKANA GHOSH Department of M.S(Pharm.) Pharmacology and Toxicology DATE :
  • 97. It is unconscionable that dogs, the most popular companion animals in the country, are used as research subjects in laboratories, but United States Department of Agriculture (USDA) reports show that tens of thousands of dogs are used in research, testing, teaching, or experimentation in the U.S. every year by research facilities, including hospitals, schools, diagnostic laboratories and private firms in the pharmaceutical and biotechnology industries. Although the number of dogs used in research has declined by 72% since their peak use in 1979,
  • 98. Though many scientists have concluded that they are poor predictors of drug effects in the human body, still they are used because regulatory authorities require that drugs be tested in both a rodent and a non-rodent species for toxicity, and the latter is often dogs, due to their ready availability, as well as their trusting and social nature, which makes them easy to handle. Source: https://navs.org/
  • 99.
  • 100. TYPES OF BREEDS USED IN PRECLINICAL STUDIES The dealers from whom the dog models are being purchased, can be broadly differentiated in two major classes based on the breeds sell, namely- CLASS A Dealers CLASS B Dealers CLASS A DEALERS CLASS B DEALERS Sells “purpose-bred” dogs specifically for research. beagles, hounds and mongrel dogs Sells “random source” dogs raised the animals on their own premises to fulfill orders of 33-60 pounds that are 6 to 12 months old. obtained from an animal shelter or dog pound (a practice known as “pound seizure”), at auction, or from any person who did not breed and raise the dogs on their premises. known vaccination history, preventative treatment for parasites, known pedigree and improved socialization unverifiable health status, poorly-defined temperament and unknown age. they are expensive, costing over $700 per dog. less expensive
  • 101. Image: Hound Image: Beagle Generally beagles are most used bred of dogs for animal testing owing to their passive nature and small size What is pound seizure? Pound seizure is the practice of releasing or selling cats and dogs in animal shelters to laboratories and other facilities where they are used in biomedical research, product development, testing and educational demonstrations. While a number of states no longer allow this practice, many still do or leave it up to localities to decide.
  • 102. ROUTE OF ADMINISTRATION OF DRUGS :-  1.ORAL:-Dogs can take substances(drugs)in their food via pills or in some cases force feeding or forced to inhale them.  2.SUBCUTANEOUS INJECTION: Middle of the back or behind the shoulder. The needle should be parallel to the skin.  3.INTRAMUSCULAR INJECTION: At specific location of the dog skin ,syringe firstly prepared and then needle is inserted between the angle of 45°-90°depending upon the location of the body area.  4.RECTAL: It is less common and done by enema method.  5.INTRAPEROTONEAL  6 .INTRAVENOUS
  • 103. ASSAY OF DRUGS :-DIURETICS (ACETAZOLAMIDE AND THEOPHYLLINE) The screening of diuretics for clinical utility is a matter of practical importance. Promising laboratory results often are not supported by subsequent clinical trials. Such differences may arise from the fact that the final clinical evaluation is determined in patient with Congestive Heart Failure, which is difficult to achieve in animals. Materials and methods :  Male mongrel dogs:- 20 dogs(Five dogs each for mersalyl, theophylline, acetazolamide and urea) are anesthetized by dial urethane 70mg/kg,half of it being given intravenously and half to intraperitonealy.Animals were hydrated using 0.9% saline solution with 20ml/kg by the rate of 10ml/kg/hour.  Urinary bladder of the animal was exposed with the mild incision Over the lower part of abdomen.
  • 104.  Both ureters were identified and cleared and cannulated over bladder using polyethylene tubing with suitable size and length.  Urine collected and volume recorded every 15 minutes  Control observation made upto one and half to two hours after the saline drip was over.  The drug is then injected and urine volume were collected for the further period of five hours.  A detailed statistical analysis of results in dogs was done. Control readings are taken as concomitant variable. Results: Comparing the effect of different drugs taken two at a time it was found that the effect due to mersalyl differed significantly from the effects due to urea, theophylline or acetazolamide while later three drugs did not differ significantly amongst themselves. Action of mersalyl in dog was found to be significantly greater than that of urea, theophylline and acetazolamide.
  • 105. SENSITIVITY OF DOGS WITH THE DRUGS  It was found that there is mutation in the gene of some breeds of dogs( like Collies,German shepherd,shelties,Sheepdogs )in MDR1 gene and this abnormalities can lead to severe sensitivity to many medication.  The medication to which the dogs can react include common drugs such as ivermectin (used for many parasite preventives and treatments),loperamide (used in kaopectate,Imodium and Pepto).Other drugs are acepromazine,cyclosporine.  The only way to know if this dog is sensitive to the drug is to test its DNA for the mutated MDR1 gene.
  • 106. APPLICATIONS OF DOG MODELS TYPES OF DISEASES BREEDS USED FOR TESTING Non Hodgkin’s Lymphoma (NHL) Boxers and Golden Retrievers Osteosarcoma(OSA) Heavy individuals having long bones like Great Dane, Wolfhound, and Rottweiler are most susceptible to OSA Aging and Alzheimer’s Disease Beagle has been selected as the main breed used for aging studies as its median lifespan is 12 to 14 years, Endocrinopathies like pituitary dwarfism German Shepherd breed.
  • 107. ADVANTAGES Domesticated dogs are increasingly being identified as good models for a variety of biomedical research fields as they have a number of unique advantages over other commonly used experimental animals. The dogs cohabitate with their owners, receive a good level care including highly-trained healthcare. This offers valuable opportunities for researchers to examine complex problems such as environmental contributions to diseases, aging and its effect on disease susceptibility and progression, and the effects of long-term treatment protocols. Over the past several centuries, domestication and selective breeding of dogs has resulted in nearly 400 distinct populations and thus the most naturally occurring genetic diversity in any one species besides humans.
  • 108. Careful breeding for trait selection has inadvertently resulted in breed-specific disease susceptibilities and approximately 400 naturally-occurring, inherited diseases have been identified in dogs which serves as very good model for research. Finally, due to the rapid aging of dogs, there is a shorter duration for disease development and progression. This is an enormous advantage in the context of drug development as clinical trial study times are significantly reduced. DISADVANTAGES The genetic diversity is the main disadvantage of canine models as there are breedspecific differences in physiology and metabolism, especially idiosyncrasies in pharmacodynamics and pharmacokinetics, which can introduce complications when interpreting or translating results.
  • 109. Dogs used in research in laboratory settings have been shown to display signs of stress, fear and anxiety. While some dogs are able to adapt positively to stressors, other dogs are unsuccessful and can develop disorders and dysfunctions that can adversely affect their quality of life, in addition to significantly impacting the research in which the animal is involved. It has been noted that dogs often stop such behaviors when their handlers enter the room, resulting in a serious underestimation of the true mental and physical condition of dogs used in research in laboratory settings.
  • 110. REFERENCE  Field, G. and Jackson, T.A. The Laboratory Canine. CRC Press. Hasiwa, N., et al. (2011) Critical Evaluation of the Use of Dogs in Biomedical Research and Testing in Europe. 2007, ALTEX. Vol. 28, 4/11, p. 326-340  Meunier, L.D. Selection, Acclimation, Training, and Preparation of Dogs for the Research Setting, ILAR Journal, 2006 ,Vol 47, Number 4, p. 326-347.  National Research Council. Scientific and Humane Issues in the Use of Random Source Dogs and Cats in Research. Stafford, K.J, 2009 ,The Welfare of Dogs.  Reeves PT , Roesch C., Raghnaill MN. How Drugs are Given in Animals. July 2016
  • 112. Experimental Pharmacology-PC 530 Animal Model: Rat (Rattus norvegicus) By Pallabi Panja (PC/2021-14/232) Sitara Ghosh(PC/2021-14/233) Department of Pharmacology & Toxicology
  • 113. Introduction  Animal models are indispensable in experimental pharmacology to investigate dose-response relationship and pharmacokinetics of different test substances.  The commonly used laboratory animals are, Mice, Rat, Guinea pig and Rabbits.  Laboratory rats are the second most (after mice) commonly used species in biomedical research.  Well established strains of rats are used to study various human diseases.
  • 114. RAT (Rattus novergicus)  The genus Rattus contain 66 species through laboratory rat is the domesticated form of the species Rattus novergicus or the brown Norway rat.  Two most popular strains of rat in laboratory research are– 1. Wister rat 2. Sprague-Dawley rat •Outbreed albino rat •Developed in Wister Institute(1906) •Wide head, long ears, tail length is less than its body length •Outbreed multipurpose breed developed from Wistar rats •Calm and easy to handle •Narrower head and long tail
  • 115.  Others strains includes – (All of these are genetically modified ) Long Evans rats: They are used as multipurpose model organism, frequently in behavioral and obesity research. Zucker rats: They are genetically modified rats used to study obesity and hypertension.
  • 116. Biobreeding rats: They are used as models to study autoimmune type 1 diabetes. Hairless rats: They are used to study compromised immune system and genetic kidney diseases.
  • 117. Biological Data: Typical adult weight Male: 300-500 g, Females: 250-300 g Life Span 2.5-3.5 years Physiological Data: Heart rate 300-500 beats/min Respiration rate 65-180 /min Daily Food intake 10-20 g
  • 118. Routes of drug administration 1. Oral route 2. Subcutaneous route
  • 119. 3. Intraperitoneal route 4. Intramuscular route
  • 120. Advantages  Small size  Greater sensitivity to most drugs  Sturdy and can withstand long periods of experimentation under anesthesia.  Vomiting center is absent- oral administration of drug can be done.
  • 121. Disadvantages  Vomiting centre absent. So emetics study is not possible  Diffuse pancreas so not a good model for type I diabetic studies  Do not have tonsil and gall bladder
  • 122. Experimental uses  Used in research of behavior, pharmacology, neurosciences, physiology, immunogenetics, transplantation, cancer risk assessment, cardiovascular diseases and aging.  Study of analgesics and anticonvulsants.  Bioassay of various hormones like insulin, oxytocin and vasopressin.  Study of estrous cycle, mating behavior and lactation.
  • 123.  Chronic study.  Gastric acid secretion.  Hepatotoxicity studies.  Study on mast cells.  Toxicology studies.  Rat brain tissue is extensively employed in radio-receptor ligand studies.  Various isolated tissues used are rat uterus, ileum, fundus strip, vas deferens and anococcygeus muscle.
  • 124. Why to choose Rats over mice?  Rats share 90% of the genomes with humans, making them a suitable research tool  They are larger in size than mice, which makes handling, sampling and performing procedures easier.  For physiological studies, more responses and pathways are known.  More accurately reflects human physiology than mice do.  More suited for behavioral studies (learning and cognition).  Sensitive to most drugs  Can withstand long period of experimentation under anesthesia.  Oral administration is possible as vomiting centre is absent.
  • 125. References 1. Kemp, Robert. (2000). Handling and Restraint. 10.1016/B978- 012426400-7/50042-X. 2. Balagopalan, Devika & Hussain, Gazala & M M, Nidhin & Nambiar, Sruthi. (2019). A review on experimental pharmacology. Journal of Drug Delivery and Therapeutics. 9. 501-504. 10.22270/jddt.v9i1-s.2242. 3. Elizabeth C. Bryda. The Mighty Mouse: The Impact of Rodents on Advances in Biomedical Research. Mo Med. 2013 May-Jun; 110(3): 207–211. 4. MATER METHODS 2012;2:113
  • 126.
  • 127. Presentation on experimental animals Topic: Rabbits (Oryctolagus cuniculus) NAME: PREETHI K RAMAN & PRIYANSHA SINGH INSTITUTE: NIPER GUWAHATI DEPARTMENT: MS(PHARM) PHARMACOLOGY AND TOXICOLOGY SUBJECT: EXPERIMENTAL PHARMACOLOGY DATE:
  • 128. Introduction • What is animal experimentation? • Animal experimentation is the use of animals in scientific research • usually in a laboratory, for the purpose of gaining new biological knowledge or solving specific medical, veterinary medical, dental, or biological problems.
  • 129. Why should we use animal models Mammalian animal models are useful to investigate mechanisms of efficacy and toxicity because of species similarities in pathways between animals and humans. (i.e. :animals are phylogenetically similar to humans) Why be aware on selecting animals model. Because performing research in appropriate animal, results should be approximate to what can be expected in humans.
  • 130. PARAMETERS TO BE NOTED BY THE ANIMAL HOUSE IN-CHARGE FOR THE CARE OF ANIMALS • Fluid • Diet • Cleanliness • Litter • Cages • Labelling of the cages • Ventilation • Temperature and Humidity • Handling • Breeding • Marking animals • The detection of signs of disease in animals
  • 131. Animals in use The animals used as research models are divided into the following two groups: • Small animal category requiring local animal ethical committee approval: – Rats – Mice – Zebrafish – Guinea pigs – Rabbit (largest animal in this group) • Large animal category requiring central animal ethical committee approval in addition to the local ethical committee are: – Dogs – Goats – Cats – Primates
  • 132. My topic : Rabbits ( Oryctolagus cuniculus) Kingdom: Animalia Phylum: Chordata Class: Mammalia Order: Lagomorpha Family: Leporidae • New Zealand White rabbits (nickname: REW/NZ) • large albino rabbits, • Dutch Belted rabbits are the most common breeds of rabbits Transgenic rabbits are also used Commonly used:
  • 133. New Zealand rabbits Dutch belted rabbits Large albino rabbits GFR rabbits(transgenic)
  • 134. DETAILS • Rectal temperature:38.7°C -39.1°C • Normal respiratory rate:55/min • Pulse rate:1.35/min • Gestation period: 28-31 days • Weaning age:6-8 weeks • Mating age:6-9 months • Litters: 4 yearly • Weight:0.9-6.75 kg • Gender is generally not a problem, but some investigators in literature have preferred female sex as it is biologically the stronger sex.
  • 135. MAINTENANCE OF RABBITS IN THE ANIMAL HOUSE • Newly arrived rabbits in the animal house should be quarantined for a minimum of two weeks(serves as a period of adaptation to the surroundings and the daily routine ) • examined for the most common diseases. • easily infested with scabies, which is highly contagious and capable of damaging the airways and predisposing to pneumonia. • Adult rabbits , kept in individual mesh cages (0.90 × 0.60 × 0.45 m) hung at a height of 0.8 cm from the ground so that excrement can fall out into collecting trays. • 12 to 14 hours of light are necessary for the colony's circadian biorhythms
  • 136. Cages for rabbits to be used in experiments  Cages are best made of galvanized iron.  The minimum size for a medium sized rabbit is 2×2×1(1/2)ft.  Young rabbits up to 3 months of age may be housed together but after that time sex should be separated.  From 8 -10 young rabbits may be kept together in pen similar to that used for guinea pigs. An image showing a sample cage for rabbits
  • 137. • Fresh hay, oats and fresh vegetables (especially roots) • Water (the most important constituent of its diet)  Dehydration in rabbit is a very common serious condition that needs immediate attention.  Signs of dehydration can be detected by the skin on their body.  The skin on the back of the rabbit's neck is raised upward until it is stretched enough that is comfortable to the rabbit. If it snaps back fast, the rabbit is healthy.  The slower it takes for the skin to return, the more is the dehydration. In such a case, one can hydrate them by giving GatoradeR - mix the Gatorade half and half with water and feed them with a dropper • Pelleted diet 18 of Bruce and Parkers(1947) or commercial breeders pellets are suitable • Daily supply of 2.5 0z(72 gm) of a mixture of one part oats and three parts bran may be fed as a slightly moist mash DIET
  • 138. HANDLING • Daily human contact reduces stress during handling. • Gloves should always be worn when handling • These animals can become nervous and inflict severe bites or scratches from their powerful hind legs, if not properly handled and restrained. • Rabbits should never be handled by the ears because of a high probability of causing cervical luxation and death. • They should be held by grasping a large fold of loose skin over the shoulders with one hand and either supporting or grasping the rear feet with the other hand. • Failing to support or hold onto the rear feet may result in the animal kicking and trying to escape, which can cause severe spinal injury or a broken back.
  • 139. An image showing how rabbits are handled for experiments
  • 140. Advantage and disadvantage • ADVANTAGES OF RABBIT AS A MODEL ARE AS FOLLOWS • very docile and non-aggressive and hence easy to handle and observe. • Widely bred and very economical compared with the expense of larger animals. • Have short vital cycles (gestation, lactation, and puberty) • It comes under the small animal category, hence easy ethical committee clearance • DISADVANTAGES: • Fast and swift in nature • Fragile body • Vulnerable to animal prone/post operative diarrhea, GIT stasis, post implantation fracture of fragile femur
  • 141. INFECTIONS RABBITS ARE PRONE TO • Coccidioisis (hepatic and intestinal) • Pseudo tuberculosis • Respiratory infections( Snuffles) • Pneumococci • Streptococci • Intestinal infections( mucoid enteritis, Diarrhoea) • Rabbit syphilis (Treponema cuniculi) • Worms (cysticercus stage of dog tape worm, Taenia pisiformis)
  • 142. EXPERIMENTAL FEILDS Lipid metabolism and atherosclerosis: Atherosclerosis is a multifactorial disease and is one of the major causes of mortality in Western societies. Rabbit models include normal cholesterol-fed rabbits, spontaneous mutants for lipid metabolism Cancer study: Oncogene expressing transgenic rabbits, which developed lymphomas and skin carcinoma were created and partially characterized. Those animal models may be valuable for studying oncogenes and their synergistic effects in tumor genesis. Furthermore they provide a model for evaluating antitumor therapy
  • 143. Eye research: • surgical interventions including cataract removal, intraocular lens insertion, corneal transplantation, laser refractive procedures, glaucoma shunt implantation, and intravitreal drug delivery. Use of GFP rabbits • GFP (green fluorescent protein) is a protein from Pacific Ocean jellyfish which becomes green under UV light • The observation of the GFP rabbit cells using a specific probe (Cell-viZio, MKT) made it possible to obtain the precise description of different tissues which appear green • GFP rabbits are currently being used as models to study cornea grafting. These rabbits made following the fate of the green cells possible at different periods after cornea grafting on normal rabbits
  • 144. Anatomical and metabolic disorders • Study of anti diabetics • Surgically induced secondary osteoarthritis and osteotomy rabbit models have also been created for in vivo gene therapy trials • In the osteoarthritis model, the interleukin-1 receptor antagonist gene was found to be effective in the prevention of osteoarthritis progression In the osteotomy model the gene therapy vector harbored the human BMP-6 gene and was shown to accelerate healing Alzheimer's disease • rabbits have larger brains relative to the aforementioned species allowing for greater flexibility in testing for cognitive impairment.
  • 145. Transgenic rabbits as bioreactors • Pharmaceutical proteins produced from transgenic rabbit milk • The technology for using the mammary gland as a bioreactor has been developed to the point that pharmaceuticals derived from the milk of transgenic farm animals are currently in the advanced stages of clinical trials. Immunological studies: • Sensitive to histamine. • Available rabbit strains are naturally devoid of several immunoglobulin loci. These animals, which received human immunoglobulin loci, generate human polyclonal antibodies after classical immunization • The rabbit appears to be particularly flexible in the preparation of human antibodies . Cosmetic studies: They are used in skin and eye irritation studies, such as the archaic and painful Draize tests for cosmetics, personal care, household products and other chemicals.
  • 146. OTHER APPLICATIONS FOR RABBITS AS EXPERIMENTAL ANIMALS • Pyrogen testing of rabbits for parenterals (LAL & SHAMS test) • Bioassay & screening of insulin, antidiabetic and curaremimetic drugs. • Testing Topical agents as skin is sensitive • Studies related to antifertility agents • It has simple cardiac tissue free of connective tissue and hence is the animal of choice for cardiac studies • Screening embryotoxic agents and teratogens • Rabbits also act as good models for preparation & extraction of antibodies and serum.
  • 147. SUMMARY Rabbits are docile animals used as animal models for pharmacological studies Used in study of • Atherosclerosis, osteoarthritis • Oncological studies • Eye research • Immunological studies • Anatomical and metabolical disorders • Bioreactors • Testing cosmetics and home applicants
  • 148.