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Printable Handouts
Navigable Slide Index
- Introduction
- Skin - the largest organ of the human body
- Outer layer of the human skin
- Role of inherited vs. induced (tanning) skin colour
- The four races of men from the tomb of Sethos I
- Induction of de novo melanogenesis by the sun
- Enhanced pigmentation after sun exposure
- Vitiligo – loss of inherited skin and hair colour
- The burden of vitiligo
- Correct diagnosis via characteristic fluorescence
- Use of Wood’s light for differential diagnosis
- Vitiligo characteristics - inherited skin colour loss
- The cause of vitiligo is yet unknown
- Pathogenesis of vitiligo - several hypotheses
- Patients accumulate H2O2 in their epidermis
- Epidermal H2O2 measured in vivo by spectroscopy
- Exogenous H2O2 - sources
- Depigmentation after hydroquinone treatment
- Depigmentation after topical Q10 treatment
- Intrinsic H2O2 sources in epidermal cells
- Lipid peroxidation in epidermal cells
- H2O2-mediated stress
- Epidermal H2O2-mediated oxidation confirmed
- H2O2 affects 6BH4 biosynthesis and recycling
- H2O2 oxidises 6BH4 to 6-biopterin
- Direct effect of H2O2 on 6BH4 biosynthesis
- H2O2 inhibits phenylalanine hydroxylase activity
- Direct effect of H2O2 on 6BH4 recycling via PCD
- H2O2 affects 6BH4 recycling via PCD
- H2O2 affects epidermal POMC processing
- Cleavage of POMC by PC1 and 2/7B2
- Oxidation of α-MSH and β-endorphin by H2O2
- Oxidised α-MSH and β-endorphin lose functionality
- The role of the antioxidant defence machinery
- H2O2 deactivates epidermal antioxidant enzymes
- H2O2 decreases catalase protein expression
- H2O2 deactivates epidermal catalase in vitiligo
- Oxidation affects NADPH-binding of catalase
- Epidermal thioproteins - severely affected in vitiligo
- Oxidation affects methionine sulfoxide repair
- Repair of R&S methionine sulfoxide diastereomers
- Epidermal MSRA & MSRB activities decrease
- Structural modelling of MSRA
- Epidermal peroxinitrite production in vitiligo
- Epidermal peroxynitrite levels are high in vitiligo
- Evidence for increased S-nitrosylation in vitiligo
- H2O2/ONOO- accumulation leads to DNA damage
- DNA damage (8-oxyguanine) in the epidermis
- DNA damage (8-oxyguanine) in the plasma
- Epidermal H2O2 is transferred to the system
- Systemic oxidative stress in vitiligo
- H2O2 affects epidermal tryptophan metabolism
- The production of H2O2
- Consequences of epidermal tryptophan shortage
- Impaired epidermal T-cell response in vitiligo
- overproduction of H2O2, NO and ONOO- affects
- The paradox in vitiligo
- Epidermal p53 is up-regulated in vitiligo
- Increased p53 in epidermal cell extracts in vitiligo
- P53 upregulation via enhanced DNA binding
- What can be done for the patients
- Reducing epidermal H2O2 with PC-KUS
- Up-regulation of epidermal catalase expression
- Up-regulation of epidermal thioredoxin reductase
- H2O2 reduction increases β-endorphin expression
- H2O2 reduction increases α-MSH expression
- In summary - H2O2 has two sites
- From the bench to the bedside
- Reducing H2O2 by pro-pseudocatalase PC-KUS
- Repigmentation after epidermal H2O2 reduction (1)
- Repigmentation after epidermal H2O2 reduction (2)
- Repigmentation after epidermal H2O2 reduction (3)
- Repigmentation after epidermal H2O2 reduction (4)
- Repigmentation after epidermal H2O2 reduction (5)
- Repigmentation after epidermal H2O2 reduction (6)
- Skin colour does not influence repigmentation
- Epidermal H2O2 reduction effects
- Conclusions
- Vitiligo - the dilemma and the hope
- Turning white' by Lee Thomas
Topics Covered
- Role of inherited vs. induced (tanning) skin colour
- Enhanced pigmentation after sun exposure
- Vitiligo and its characteristics (inherited skin colour loss)
- Correct diagnosis of vitiligo via characteristic fluorescence
- Use of Wood’s light for differential diagnosis
- Cause and pathogenesis of vitiligo
- Oxidation and nitration of proteins and peptides in vitiligo and their effects
- DNA damage, T-cell response & p53 in vitiligo
- Treating vitiligo: Reducing oxidation and repigementation
Talk Citation
Schallreuter, K.U. (2014, November 4). Vitiligo: in vivo and in vitro evidence for epidermal ROS/RNS-mediated regulation / dysregulation [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 3, 2024, from https://doi.org/10.69645/DVDL9069.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Karin U Schallreuter has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Vitiligo: in vivo and in vitro evidence for epidermal ROS/RNS-mediated regulation / dysregulation
Published on November 4, 2014
37 min
A selection of talks on Clinical Practice
Transcript
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0:00
My topic
today is to speak about vitiligo.
And I'm going to present some
in vivo and in vitro evidence
of epidermal Reactive Oxygen
Species and Reactive Nitrogen
Species-mediated regulation
or dysregulation in this disease.
0:15
The vitiligo is affecting,
of course, mostly the skin.
And since the skin is the largest,
outer-most organ of the human body,
it has an approximate size
of 1.85 to 2 square meter.
It's responsible for the
protection of our human body
against many environmental stress;
for example, radicals, chemicals,
heat, cold, water, and so on.
So I'm going to explain on the next
slide how the layers of the skin
is actually composed, especially
about the epidermal part
of the skin.
0:52
The outermost layer is composed
of the epidermis and the dermis
and subcutis, as seen
in this slide here.
The majority of the epidermis
is constructed of keratinocytes.
This is the melanocytes
at the basement membrane.
One melanocyte is surrounded
by 36 keratinocytes
and forming the
so-called epidermal unit.
At the basement membrane, and
we have the stratum basale.
That's the proliferation
zone of the epidermis,
followed by the stratum spinosum
and then the stratum corneum.
And those are the parts we
are interested in right now.
1:29
Now our skin color, that
what we are born with,
we call it the inherited skin color.
And then of course, we can also
use tanning to adjust the skin
color by, for example,
solar exposure.
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