Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Toxicology UNC Fall 2023 > E2L1 Human Models In Vitro and In Vivo > Flashcards

E2L1 Human Models In Vitro and In Vivo Flashcards

1
Q

what is in vivo good for?

A

determining route of exposure effects, dose, species differences, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

who identified the need for the toxicology parallelogram?

A

Sorbels (1980)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the points on the toxicology parallelogram?

A

in vivo characterize toxic effects in animal experiments, assess hazards for the human, in vitro using target tissue, and in vitro from biopsies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the unofficial third arm of the toxicology parallelogram?

A

in silico (modeling to predict toxicity of compounds based on historical data)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is Thalidomide?

A

non-addictive, non-barbituate sedative used as an antiemetic (nausea reducer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what year was Thalidomide released and where was it most prevalently used?

A

1950s; Europe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what year was Thalidomide banned?

A

1961

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

why was Thalidomide banned?

A

discovered cases of birth defects affecting multiple body systems of approx. 10,000 plus cases around the world

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what was the first described case of species differences in drug reaction/response?

A

Thalidomide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

why did Thalidomide affect humans and not mice?

A

Mice are now known to be less sensitive to Thalidomide than other species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what could have prevented the Thalidomide disaster?

A

multi-species testing (rabbits, hamsters, chickens, fish, etc. have shown susceptibility to Thalidomide damage like humans)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is DGA?

A

Diglycolic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

where is DGA present?

A

in the US food supply as an indirect additive from the use of carboxymethyl cellulose (CMC) which is a binding agent in dietary supplements or a thickener

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how is DGA formed?

A

as a byproduct of CMC synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is DEG?

A

diethylene glycol; an active agent responsible for human renal toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

how are DEG and DGA connected?

A

DGA is a minor metabolite of DEG and is also a metabolic by-product of DEG– question is: is there toxicity with DGA?

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

how did we use the toxicology parallelogram to determine is there is toxicity with DGA?

A

two-pronged approach: in vivo safety study in rats and in vitro cellular testing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what were the results in the kidney cells of the two-pronged DGA study?

A
  • KIM-1 (kidney injury molecule 1) was elevated in both models (represents proximal tubule damage in vivo)
  • increased ROS production
  • decrease in cellular viability
  • dose-dependent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

based on the results of the two-pronged DGA study, is DGA a potential agent of toxicity and a human health hazard?

A

yes! they have now considerably limited the use of DGA in food supplies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are the 6 research design choices?

A
  1. in vitro
  2. cell/tissue cultures
  3. in silico
  4. model organisms
  5. healthy patients/volunteers
  6. populations/cohorts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is electrophoresis best used for?

A

size sorts proteins in gel; learn more about shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is electron microscope best used for?

A

look of compound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what are mass spec and crystallography best used for?

A

learning about the chemical composition and shape/size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what are the 7 methods to elucidate properties such as mass, shape, structure, color, kinetic, electric, and magnetic properties of chemicals and proteins in in vitro studies?

A
  1. electrophoresis
  2. hydrodynamics
  3. mass spec
  4. electron microscopy
  5. optical and vibrational spectroscopy
  6. NMR
  7. diffraction methods
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
what are the 4 different types of in vitro cell cultures?
1. human immortalized cell lines 2. co-culture 3. primary cell culture 4. organs-on-a-chip
26
what are immortalized cell lines?
- derived from a single common ancestral cell - have an indefinite lifespan
27
what are the pros and cons of immortalized cell lines?
PROS: - cost effective (can culture a bunch) - established protocol - good for figuring out simple mechanisms CONS: - lack of diversity - doesn't represent whole organism interactions - genetic drift changes - retention of disease characteristics from donor - majority are male-derived
28
what are examples of immortalized/stable cell lines?
- A549 -- lung - HepG2 -- liver - HEK-293 -- kidney - Calu1 -- lung - G-361 -- skin - BE(2)-M17 -- brain - COLO 205 -- colon - HeLa -- cervix
29
what is a case study example of immortalized/stable cell lines?
air pollution: feed cells from bottom and expose top to ozone which results in an uptick in IL6 and IL8 inflammatory gene expression
30
what are primary cell cultures?
cells taken from a direct organism; have a finite lifespan
31
what are the pros and cons of primary cell cultures?
PROS: - better mimics in vivo because coming from people - mimics donor genetics CONS: - labor and cost intensive - can die spontaneously - don't account for organ population - well to well variability
32
what is an example of primary cell culture?
bronchial epithelial cells: - pseudo-stratified somewhat similarly to in vivo - development of cilia at the top - develops mucus
33
what is a case study example of primary cell culture?
air pollution: - lungs are naturally exposed to particles, pathogens, gases, etc. which can influence lung function overall - culture primary cells at air-liquid interface, expose pollutants to air side - results in inflammation, cell injury, physical changes, etc.
34
what is a co-culture?
cultivation of multiple cell types
35
what are the pros and cons of a co-culture?
PROS: - cross-communication can be represented between different cell types CONS: - cross-communication between cell types that aren't cultured aren't represented - not a whole body representation - lack of tissue scaffolding/structure - results may differ from lab to lab (no standards)
36
what do cell types/tissues cultured together form?
"spheroids" AKA "organoids" which are mini-versions of the organ themselves; more representative of in vivo than cell type by itself or cells layered together
37
what is organ-on-a-chip?
multi co-culture of multiple cell types
38
what are the pros and cons of organ-on-a-chip?
PROS: - better mimics cell interactions - waste is removed by researchers which better represents the cells being fed from the body's food supply CONS: - extremely expensive - very hard to reproduce
39
what are the pros and cons of in silico?
PROS: - alternative to animal testing - low cost - allows mixtures assessment and selection of drugs/product development candidates CONS: - has to be fueled with data from in vivo and in vitro research - doesn't provide definitive assessments - historical data may not be able to capture functionality of newly created compounds
40
what are the pros and cons of model organisms?
PROS: - breed in large numbers - better models for ADME - easy to manage genomes - similar to humans - easy to manipulate embryos
41
what happens if we remove animal models from the equation?
we limit our research design choices
42
what are the two main human study designs?
- healthy human studies - diseased populations
43
what are healthy human studies commonly used for?
controlled exposures and drug safety trials
44
what are diseased populations commonly used for?
- drug efficacy trials - accidental or occupational exposures - case studies
45
what is a case study example of a healthy human study?
air pollution (at UNC): - healthy human walking on treadmill to induce deeper breathing is exposed to air pollution - increase in neutrophils after ozone exposure - decrease in FEV1 and FVC - increase in PMN (immune cells)
46
what is FEV1?
major markers of lung function
47
what is FVC?
marker of lung function
48
what are the pros and cons of human studies?
PROS: - immediate relevancy of results - no need to translate results - inter-individual differences - impactful CONS: - very costly - rely on participation - invasiveness and morality issues - participant reliability and retention - difficult to recruit participants
49
what are population cohorts commonly used in?
epidemiology
50
what are the three types of population cohort studies?
1. time-series analysis 2. cohort studies 3. panel studies
51
what are time-series analysis?
large datasets; short-term health effects with emphasis on mortality or hospital admission
52
what are cohort studies?
groups of people that share common characteristics; gold standard; extremely expensive and can last long!
53
what are panel studies?
smaller data sets that are limited to short-term effects
54
what is a case study example of population cohort studies?
air pollution (at Harvard): - showed association between particular matter (PM) and mortality - followed 8000 individuals in 6 different cities retrospectively over 15 years - association between least-to-most polluted city and mortality was found
55
what are the pros and cons of population cohort studies?
PROS: - can use existing data - large populations can be studied CONS: - seasonal variation - missing data points are common due to study compliance - difficult to establish cause and effect relationships - expensive - control for co-exposure is difficult
56
what are a few cases in biology where sex is not binary?
- sex chromosome disorders (XXY, XYY, Xnull, etc.) - hormonal disturbances (androgen insensitivity, etc.)
57
what triggered the SABV policy?
Ambien!
58
what was discovered after Ambien was released?
plasma concentrations in males decreases at a faster rate than in females; a lot of traffic accidents occurred after release where women still had Zolpidem in their system after 8 hours of taking
59
why do sex differences occur in pharmacokinetics?
biotransformation (cytochrome P450) enzyme expression differs by sex; there are quite a few cases where cyp enzymes are preferentially/differentially expressed by sex
60
what is "bikini medicine"?
clinical pharmacological studies viewed women's health only as the female organs men don't have
61
where did the "bikini medicine" assumption originate from?
many different places, but mostly the research pipeline
62
what evidence is there that the "bikini medicine" false assumptions originated from the research pipeline?
- most cell-based research is done in unspecified sex cells - animals that are used are males 80% of the time - men make up 67% of human trials - women make up 80% of healthcare decisions - women make up 51% of the population
63
what is sex omission?
the lack of reporting sex
64
what is sex bias?
favoring one sex over another
65
how did sex differences play into aripiprazole's effect on responsiveness to ozone exposure in 16HBE cells?
- nothing to note with aggregated cells - when cells were separated in male and female, the male response increased with aripiprazole and the female response decreased with addition of aripiprazole

Toxicology UNC Fall 2023 (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions