BIOL 1080 Lecture Notes - Lecture 2: Neuropharmacology, Leptin, Anabolic Steroid
2 May 2018
School
Department
Course
Professor
Research models
•
Human studies -Clinical, Non-clinical
•
Evidence-based Medicine
•
Accountability of Disseminating Information
•
New Dimensions in Medicine and Healthcare
•
Outline:
Simulations with mathematic models/computer (in silico)
A.
In vitro (in glass) and ex-vivo (out of the living) models -
cell culture, isolated tissues/organs
B.
Short life cycle (~3 days)
!
Self fertilizes
!
Can be frozen, thawed and remains visible
!
Transparent -facilitates the study of cell
differentiation
!
Embryonic metabolism
□
Using a flourescent tag to follow
digestion of nutrient, synthesis of
proteins/cholesterol…etc
□
Examples:
!
Elegans (nematode) -40% genetic homology to
humans
○
Life cycle and development are very sensitive
to environmental conditions
!
Example: used in neuropharmacology research
to study effects of drugs and alcohol
!
Drosophilia Melanogaster (fruit fly) -65% genetic
homology to humans
○
Very social and intelligent
!
Often used to study lifestyle effects on
metabolism
!
Tend to take a "more severe approach" than
with humans
!
Not a good model for human infants
(nutrition, metabolism)
!
Some genetically modified rats, but not as
common as with mice (e.g. Zucker rats lack
leptin receptors and are obese)
!
Rats:
○
Popular due to ease of applying recombinant
DNA technology
!
Test the importance of a single protein
!
Takes longer to make mouse insulin
resistant on high fat diet
□
Less impairment of glucose
uptake in mice with HF diet
compared to rat
!
Mitochondria adapt less robustly
with training in the mouse
compared to rat
!
Muscle metabolism can differ
□
Used to study lifestyle effects on metabolism
(may have different results than rats)
!
Mice:
○
Piglets are best non-primate model for human
infant development and metabolism
!
Used to study organ transplants (xenografts)
!
Swine:
○
Closest model to represent the human but
costly and ethically controversial
!
There is very little primate research in Canada
(much more in US)
!
Human pathologies
□
Transplantation
□
Drug abuse, toxicology
□
Types of research:
!
Primates:
○
Animal Models -nematodes and fruit flies are used
extensively to study genetics
C.
Human SubjectsD.
Experimental Models:
Leptin administration is effective (e.g. improve insulin
sensitivity) in deficient cases (rare!)
•
More typical is an elevation of leptin, whichc implies
resistance
•
*Leptin Example:
No treatment given
○
Cannot prove cause and effect; only predict
associations/correlations
○
Epidemiological studies are the most common
○
Non-intervention Studies (non-clinical):
•
Clinical trial -any investigation involving
participants that evaluates the effects of one or more
health-related interventions or health outcomes
○
A medicinal treatment and a control
substance/placebo is given (i.e. an intervention)
○
Can be used to predict cause and effect
○
Double-bling clinical trials are the gold standard
○
All human subjects are volunteers
○
Tests on laboratory animals1.
Phase I Clinical Trial -is the drug safe for
humans?
2.
Phase II Clinical Trial -does the drug work
for its intended purpose?
3.
Phase III Clinical Trial -how does the drug
compare with other available treatments?
4.
Tests performed to test a new drug's safety:
○
Intervention Studies (clinical):
•
Human Studies:
*see slide
○
Cochrane Collaboration -generates systematic review of
primary literature
•
Cohort and case studies -no intervention
○
Randomized controlled trials (RCTs) -controlled
interventions, should be blinded
○
Systematic reviews -less available information, but
more relevance to clinical setting
○
Where information begins -includes ex vivo experiments
and animal models
•
Evidence Based Medicine
Not cause and effect
○
No dietary records
○
Majority of subjects were smokers and overweight
○
There have been a lot of criticisms of a study investigating
fish oil supplements causing prostate cancer
•
Half of the animals on the 5% protein diet died by
the end of the first year due to liver toxicity
○
Giving alfatoxin probably isnt the most
representative model for how humans get cancer
○
Another example: rodent study showing that a 20% casein
diet caused rats to get liver cancer when administered
aflatoxin
•
Accountability for Relaying Accurate Information
The application of modern evolutionary theory to
understanding health and disease
○
Is our modern diet unhealthy? Should we try
to mimic early diets?
!
We get very little physical exercise in modern
society, is this a signal that we're injured and
need to slow down metabolism and initiate
inflammatory response?
!
We all have a 'fight or flight' response for
survival. But what if there's no 'fight or flight'
follow through?
!
Examples:
○
Evolutionary MedicineA.
Healing-oriented medicine that takes account of the
whole person, including all lifestyle aspects
○
It emphasizes the therapeutic relationship between
practitioner and patient, is informed by evidence,
and makes use of all appropriate therapies
○
Integrative MedicineB.
Recognizing that human an animal health and
mental heath (via the human-animal bond
phenomenon) are inextricably linked
○
Seeks to promote, improve, and defend the health
and well-being of all species by enhancing
cooperation and collaboration between physicians,
veternarians, and other scientific health
professionals
○
Collective Medicine -Eco Health Medicine & One
Health/World/Medicine
C.
Viagra
!
Fertility drugs
!
Erythropoietin
!
Laser vision enhancement
!
Anabolic steroids
!
Liposuction
!
Botox
!
Cholinergic stimulants
□
Dopaminergics
□
Natural cmpds
□
Nootropics (brain enhancers)
!
Examples:
○
Enhancement Medicine D.
New Dimensions in Medical and Health Care Practice
Research in Medicine & Health
Wednesday,+ September+ 13,+2017
8:31+AM
Research models
•
Human studies -Clinical, Non-clinical
•
Evidence-based Medicine
•
Accountability of Disseminating Information
•
New Dimensions in Medicine and Healthcare
•
Outline:
Simulations with mathematic models/computer (in silico)A.
In vitro (in glass) and ex-vivo (out of the living) models -
cell culture, isolated tissues/organs
B.
Short life cycle (~3 days)
!
Self fertilizes
!
Can be frozen, thawed and remains visible
!
Transparent -facilitates the study of cell
differentiation
!
Embryonic metabolism
□
Using a flourescent tag to follow
digestion of nutrient, synthesis of
proteins/cholesterol…etc
□
Examples:
!
Elegans (nematode) -40% genetic homology to
humans
○
Life cycle and development are very sensitive
to environmental conditions
!
Example: used in neuropharmacology research
to study effects of drugs and alcohol
!
Drosophilia Melanogaster (fruit fly) -65% genetic
homology to humans
○
Very social and intelligent
!
Often used to study lifestyle effects on
metabolism
!
Tend to take a "more severe approach" than
with humans
!
Not a good model for human infants
(nutrition, metabolism)
!
Some genetically modified rats, but not as
common as with mice (e.g. Zucker rats lack
leptin receptors and are obese)
!
Rats:
○
Popular due to ease of applying recombinant
DNA technology
!
Test the importance of a single protein
!
Takes longer to make mouse insulin
resistant on high fat diet
□
Less impairment of glucose
uptake in mice with HF diet
compared to rat
!
Mitochondria adapt less robustly
with training in the mouse
compared to rat
!
Muscle metabolism can differ
□
Used to study lifestyle effects on metabolism
(may have different results than rats)
!
Mice:
○
Piglets are best non-primate model for human
infant development and metabolism
!
Used to study organ transplants (xenografts)
!
Swine:
○
Closest model to represent the human but
costly and ethically controversial
!
There is very little primate research in Canada
(much more in US)
!
Human pathologies
□
Transplantation
□
Drug abuse, toxicology
□
Types of research:
!
Primates:
○
Animal Models -nematodes and fruit flies are used
extensively to study genetics
C.
Human Subjects
D.
Experimental Models:
Leptin administration is effective (e.g. improve insulin
sensitivity) in deficient cases (rare!)
•
More typical is an elevation of leptin, whichc implies
resistance
•
*Leptin Example:
No treatment given
○
Cannot prove cause and effect; only predict
associations/correlations
○
Epidemiological studies are the most common
○
Non-intervention Studies (non-clinical):
•
Clinical trial -any investigation involving
participants that evaluates the effects of one or more
health-related interventions or health outcomes
○
A medicinal treatment and a control
substance/placebo is given (i.e. an intervention)
○
Can be used to predict cause and effect
○
Double-bling clinical trials are the gold standard
○
All human subjects are volunteers
○
Tests on laboratory animals1.
Phase I Clinical Trial -is the drug safe for
humans?
2.
Phase II Clinical Trial -does the drug work
for its intended purpose?
3.
Phase III Clinical Trial -how does the drug
compare with other available treatments?
4.
Tests performed to test a new drug's safety:
○
Intervention Studies (clinical):
•
Human Studies:
*see slide
○
Cochrane Collaboration -generates systematic review of
primary literature
•
Cohort and case studies -no intervention
○
Randomized controlled trials (RCTs) -controlled
interventions, should be blinded
○
Systematic reviews -less available information, but
more relevance to clinical setting
○
Where information begins -includes ex vivo experiments
and animal models
•
Evidence Based Medicine
Not cause and effect
○
No dietary records
○
Majority of subjects were smokers and overweight
○
There have been a lot of criticisms of a study investigating
fish oil supplements causing prostate cancer
•
Half of the animals on the 5% protein diet died by
the end of the first year due to liver toxicity
○
Giving alfatoxin probably isnt the most
representative model for how humans get cancer
○
Another example: rodent study showing that a 20% casein
diet caused rats to get liver cancer when administered
aflatoxin
•
Accountability for Relaying Accurate Information
The application of modern evolutionary theory to
understanding health and disease
○
Is our modern diet unhealthy? Should we try
to mimic early diets?
!
We get very little physical exercise in modern
society, is this a signal that we're injured and
need to slow down metabolism and initiate
inflammatory response?
!
We all have a 'fight or flight' response for
survival. But what if there's no 'fight or flight'
follow through?
!
Examples:
○
Evolutionary MedicineA.
Healing-oriented medicine that takes account of the
whole person, including all lifestyle aspects
○
It emphasizes the therapeutic relationship between
practitioner and patient, is informed by evidence,
and makes use of all appropriate therapies
○
Integrative MedicineB.
Recognizing that human an animal health and
mental heath (via the human-animal bond
phenomenon) are inextricably linked
○
Seeks to promote, improve, and defend the health
and well-being of all species by enhancing
cooperation and collaboration between physicians,
veternarians, and other scientific health
professionals
○
Collective Medicine -Eco Health Medicine & One
Health/World/Medicine
C.
Viagra
!
Fertility drugs
!
Erythropoietin
!
Laser vision enhancement
!
Anabolic steroids
!
Liposuction
!
Botox
!
Cholinergic stimulants
□
Dopaminergics
□
Natural cmpds
□
Nootropics (brain enhancers)
!
Examples:
○
Enhancement Medicine D.
New Dimensions in Medical and Health Care Practice
Research in Medicine & Health
Wednesday,+ September+ 13,+2017 8:31+AM
