Histology + Basic Science Flashcards
(282 cards)
1
Q
What is the most common type of cancer in the UK?
A
Basal cell skin cancers
2
Q
Are basal cell skin cancers malignant or benign?
A
Malignant
but rarely metastasise
3
Q
Are melanomas malignant or benign?
A
Malignant
4
Q
Are squamous cell carcinomas malignant or benign?
A
Melignant
5
Q
what is the incidence trend of skin cancers?
A
increasing incidence
6
Q
what is the incidence trend of atopic dermatitis?
A
increasing incidence
7
Q
what is the incidence trend of venous leg ulceration?
A
staying the same
8
Q
why are venous leg ulcerations increasing in prevalence despite incidence being the same?
A
because people with the disease are living longer
9
Q
what is the definition of prevalence?
A
the total number of cases within the population at any one time
10
Q
what is the definition of incidence?
A
the number of new cases of a disease (as a percentage of the population over time)
11
Q
what type of cells make up the epidermis?
A
stratified squamous epithelium
12
Q
what type of tissue is the dermis?
A
connective tissue
13
Q
From what embryonic germ layer is the epidermis formed?
A
Ectoderm
14
Q
What is the name of the single layer which is formed from ectoderm cells and goes on to become epidermis?
A
Periderm
15
Q
From what embryonic germ layer is the dermis formed?
A
Mesoderm
16
Q
What is the name of pigment producing cells that reside in the epidermis?
A
Melanocytes
17
Q
Where do melanocytes come from?
A
Neural crest
18
Q
What is the name of the embryonic phase (days 7-10) where cellular organisation into germ layers occurs?
A
Gastrulation
19
Q
From what embryonic germ layer are endothelial linings formed?
A
Endoderm
20
Q
At 4 weeks of foetal development, what are the 3 layers of skin that are present?
A
Periderm
Basal layer
Dermis (corium)
21
Q
At 16 weeks of foetal development, what are the 5 layers of skin that are present?
A
Keratin layer Granular layer Prickle cell layer Basal layer Dermis
22
Q
What happens to the periderm as the foetus develops?
A
Gradual increase in layers of cells until keratin layer, granular layer and prickle cell layer are formed. The periderm casts off.
23
Q
What is the name of the developmental growth pattern of skin?
A
Blaschko’s lines
24
Q
What type of marks follow blaschko lines?
A
birth marks
25
what is the sub-cutis predominantly made of?
fat
26
what cells make up 95% of the epidermis?
keratinocytes
27
what is differentiation of a keratinocyte?
migration from basement membrane to keratin layer to be shed
28
what are the 4 defined layers of the epidermis?
keratin layer
granular layer
prickle cell layer
basal layer
29
What layer of the epidermis is noticeably thicker on the soles of feet and palms of hands?
keratin layer
30
what is epidermal turnover?
the rate of keratinocytes moving from the basement membrane to the keratin layer to be shed
31
compare epidermal turnover over of normal skin to the skin of a patient with psoriasis?
normal skin epidermal turnover: 28 days
psoriasis epidermal turnover: 45 days
32
what shape are the cells of the basal layer of the epidermis?
cuboidal
33
what shape are the cells of the prickle cell layer of the epidermis?
polyhedral
34
what adheres the cells of the prickle cell layer together?
desmosomes
| + intermediate filaments
35
what shape are the cells of the granular layer?
flattened cells
36
what phase in the life cycle of a keratinocyte happens in the granular layer?
keratinocytes start to die- cell nuclei is lost
37
what secretory organelles are released from keratinocytes in the granular layer?
odland bodies
| lamellar bodies
38
what layer of the epidermis is not present in psoriasis?
granular layer
39
what are corneocytes?
overlapping non-nucleated cell remnants (dead keratinocytes) which make up the keratin layer
40
what forms a tight waterproof barrier within the keratin layer of the epidermis?
the insoluble cornified envelope
+
lipids, flaggrin and involucrin proteins from granules secreted from keratinocytes in granular layer
41
What 3 main components are in the keratohyalin granules?
| from the keratinocytes in the granular layer
lipids
flaggrin
involucrin proteins
42
why does HPV commonly affect children below 6 years of age?
because corneocyte layer hasn't sealed properly yet so there is no effective barrier
43
Is oral masticatory mucosa keratinised or non-keratinised?
keratinised
44
Is oral lining mucosa keratinised or non-keratinised?
non-keratinised
45
What does a white area on mucosal surfaces (eg buccal mucosa) suggest?
thickened epithelial lining
46
What is lost when scar tissue is formed on epidermis?
appendages
47
Why are appendages lost in scar tissue?
fyboblasts try to repair skin with collagen tissue
48
what are the 3 main other cells (apart from keratinocytes) in the epidermis?)
melanocytes
langerhans cells
merkel cells
49
where are melanocytes located?
basal and suprabasal
50
what are melanocytes?
pigment producing dendritic cells
51
what are the organelles within melanocytes which produce melanin?
melanosomes
52
what is converted by melanosomes into melanin pigment?
tyrosine
53
what type of melanin is brown or black?
eumelanin
54
what type of melanin is red or yellow?
phaeomelanin
55
how are melanosomes (melanin granules) transferred to adjacent keratinocytes?
via dendrites
56
what does melanin pigment do once inside a keratinocyte?
forms a protective cap from UV light over nucleus
57
what organelle within the melanocyte is the origin of the melanosome membrane?
golgi apparatus membranes
58
why is there a loss of colour in vitiligo?
due to loss of melanocytes
59
what type of disease is vitiligo?
autoimmune
60
what type of disease is albinism?
genetic
61
what is the name of the syndrome where there is excess melanin-stimulating hormone produced by the pituitray?
Nelson's syndrome
62
what visual sign does Nelson's syndrome have?
tanned appearance
63
what is the name of a tumour of the melanocyte cell line?
(malignant) melanoma
64
where do Langerhans cells originate from?
bone marrow
65
where do Langerhans cells reside in the epidermis?
pricke cell layer
66
what type of cells are langerhans cells?
antigen presenting cells
67
what are the names of the tennis racket shaped organelles found in langerhans cells?
birbeck granules
68
what are merkel cells?
mechanoreceptors that directly synapse with free nerve endings
69
where do merkel cells reside in the epidermis?
basal layer
70
why can diabetes mellitus cause reduced/loss of feeling?
glycation (glucose tagging) of the myelin sheath which affects function of nerve
71
what are merkel cell cancers caused by?
viral infection
72
what is a pilosebaceous unit?
a hair follicle with an adjacent sebaceous gland
73
how does pigmentation of hair occur?
via melanocytes above dermal papilla
74
what is the beginning of a pilosebaceous unit in embryology?
hair bud
75
what are the 3 phases of hair growth?
anagen
catagen
telogen
76
what is the telogen phase also known as?
shedding phase
77
what happens to the dermal papilla n the catagen phase?
moves away from marix leaving an epithelial column
78
what is the anagen phase also known as?
growth phase
79
what is the catagen phase also known as?
resting phase
80
what does the hair matrix become in the telogen phase?
club hair
81
why in autoimmune disease such as alopecia, does the hair regrow as white/grey before colour returns?
hair regrows before melanisation occurs
82
In humans the telogen phase is asynchronus. What does this mean?
hairs all fall out at different times
83
what can commonly drive synchronisation of telogen phase and therefore cause hair loss?
psychosocial stress
84
what are the 3 patterns of male hair loss?
ventral
typical
anterior
85
compare nail growth in summer to winter?
faster nail growth in summer than in winter
86
where is the region of stem cells that become nails?
the nail matrix
| underneath the posterior nail fold
87
what are the 3 layers of the nail plate?
dorsal
intermediate
ventral
88
why is the luna white and the rest of the nail plate red?
luna is thicker, in the rest of the nail plate you can see the blood vessels underneath
89
why can trauma cause poorly shaped/crumbly nails?
permanently damages stem cells causing a differentiation defect
90
What anchors the epidermis to the dermis?
DE junctions
91
What are the names of the keratin filaments which stick the basal cells to the papillary dermis at the DE junction?
hemidesmosomes
92
What is epidermolysis bullosa?
an inherited disease of the DE junction which causes skin fragility
93
Name 3 acquired conditions caused by auto-antibodies to proteins in the skin?
pemphigus
bullous pemphigoid
dermatitis herpetiformis
94
what are the main cell types in the dermis?
```
fibroblasts
macrophages
mast cells
lymphocytes
langerhans cells
```
95
what are the main 2 fibres found in the dermis?
collagen (higher percentage)
| elastin
96
what is the function of collagen in the skin?
strengthening
97
what is the function of elastin in the skin?
elastic recoil to skin
98
what is the function of fibroblasts in the dermis?
secrete collagen
99
What is the name for physical urticaria?
| ie an exaggerated wealing tendency that occurs when skin is touched
dermographism
100
what cells degranulate to cause an urticarial response?
mast cells
101
what 2 main substances can increase wrinkling?
UV light
| smoking
102
what happens to the collagen during aging?
it becomes depleted
103
what happens to the DE junctions during aging?
DE junctions become flatter
104
compare the supply of the skin blood vessels to the metabolic demand?
supply is greater than demand
105
what is the name of a localised overgrowth of blood vessels?
angioma
106
what is the cause of a port wine stain?
an angioma of the face
| overgrowth of blood vessel population
107
what is the function of pacinian corpuscles?
pressure sensory free nerve endings
108
what is the function of meissner corpuscles?
vibration (light touch) sensory free nerve endings
109
what is the name of the inherited condition which causes an overgrowth of cutaneous nerve endings?
neurofibromatosis
110
what is the name of the benign tumour of cutaneous nerve endings?
neurofibromas
111
what are the 3 types of skin glands?
eccrine glands
sebaceous glands
apocrine glands
112
which skin glands sweat to cool you down?
eccrine glands
113
which skin glands secrete a feromone odour?
apocrine glands
114
when do apocrine glands start secreting?
puberty
115
what are the 2 main sites of apocrine glands?
axilla and groin
116
what is the of the structure formed by a sebaceous gland and a hair follicle?
pilosebaceous unit
117
where are the largest sebaceous glands found?
face and chest
118
when do sebaceous glands start secreting?
puberty
119
what are the 2 main functions of sebaceous glands?
1. control moisture loss
| 2. protection from bacterial and fungal infection
120
why do sebaceous glands protect the body from bacterial and fungal infection?
the sebum secreted creates a slight acidic environment
121
what hormone are the apocrine sweat glands dependent on?
androgens
122
which skin glands are the most involved in thermoregulation?
eccrine glands
123
what nervous system controls the secretions of eccrine glands?
sympathetic autonomic nervous system
124
where do sebaceous glands open onto?
hair follicles
125
where do eccrine glands open onto?
skin surface
126
what is the main cause of toxic epidermal necrolysis (acute skin failure)?
drugs
127
why does scale cause direct protein loss?
scale is made of keratin
128
what is a compound fracture?
a break in the bone AND bone exposed (direct break in skin)
129
where does vitamin D metabolism occur?
keratinocytes in the skin
130
what is the equation for vitamin D synthesis?
cholecalciferol --> vit D3
| using UV
131
what thyroid hormone is produced in the skin? (and from what hormone?)
T3
| T4 --> T3
132
what is crusted scabies?
scabies but with a much higher number of mites on the body than usual scabies
133
what failure is usually present in individuals who get crusted scabies?
immune system failure
134
what is tuberculoid leprosy?
a type of leprosy where you have few parasites but a huge immune response
135
what is the name of disseminated herpes simplex virus infection?
(widespread infection instead of localised cold sores)
eczema herpeticum
136
what type of tendency can cause eczema herpeticum to occur?
atopic tendency
137
Are langerhans cells innate or adaptive immunity?
innate immunity
138
What is the keratin layer made of?
corneocytes
139
what makes corneocytes?
terminal differentiation of keratinocytes
140
what 3 important structural proteins are found in the epidermis?
filaggrin
involucrin
keratin
141
What do keratinocytes produce that can directly kill pathogens?
anti-microbial peptides
142
what granules characterises langerhans cells?
birbeck granule
143
what T cells are mainly found in the epidermis?
CD8+ T cells4
| cytotoxic
144
what peptide produced by keratinocytes is found in a high level in psoriasis lesions?
anti-microbial pepitides
145
what type of helper T cells are associated with psoriasis?
Th1
| Th17
146
what type of helper T cells are associated with atopic dermatitis?
Th2
| Th17
147
where are T cells produced?
bone marrow
148
where are T cells sensitised?
thymus
149
what MHC class is found on the surface of almost all cells?
MHC-I
150
what type of T cells do MHC-I present antigens to?
cytotoxic T cells
151
what MHC class is found on professional antigen presenting cells?
MHC-II
152
what type of T cells do MHC-II present antigens to?
helper T cells
153
what mutation is associated with severe/early onset of atopic eczema?
mutation in fillagrin gene
154
what is the function of fillagrin?
bind to water molecules- water retention
| natural moisturiser
155
in vitiligo, what cells are being attacked by autoantibodies?
melanocytes
156
what antibodies mediate type 1 hypersensitivities?
IgE
157
what antibodies mediate Type 2 hypersensitivities?
IgM and IgG
158
what cell type mediates Type 4 hypersensitivities?
Th1 cells
159
what are the 2 types of fascia?
```
superficial fascia (subcutaneous tissue)
deep fascia
```
160
compare the connective tissue in superficial fasca to deep fascia?
superficial fascia:
loose connective tissue mixed with fat
deep fascia:
dense connective tissue
161
what is the name of the deep fascia that separates muscle compartments?
intermuscular septa
162
in which fascia do the cutaneous nerves and veins run?
superficial fascia
163
which artery of the forearm forms the deep palmar arch?
radial artery
164
which artery of the forearm forms the superficial palmar arch?
ulnar artery
165
what is the name of the network of veins seen on the dorsal aspect of the palms?
dorsal venous network
166
what vein drains blood from the lateral aspect of the forearm?
cephalic vein
167
what vein drains blood from the medial aspect of the forearm?
basilic vein
168
what are the names of any 2 veins which accompany an artery and eventually join?
venae comitantes
169
what connects the cephalic vein to the basilic vein?
median cubital vein
170
what artery runs into the anterior comparment oft he leg?
anterior tibial artery
171
what artery runs into the posterior compartment of the leg?
posterior tibial artery
172
what artery does the fibular artery bifurcate off of?
posterior tibial artery
173
what artery supplies the dorsal foot?
dorsal artery
174
what arteries supplies the plantar foot?
lateral plantar artery
| medial plantar artery
175
which plantar artery forms the plantar arch?
lateral plantar
176
what are deep veins of the leg?
popliteal vein
| femoral vein
177
what superficial vein drains directly into the femoral vein?
great saphenous vein
178
what superficial vein drains into the popliteal vein?
small saphenous vein
179
where does the great saphenous vein arise from?
dorsal venous arch
180
where does the small saphenous vein arise from?
dorsal venous arch
181
does the great saphenous vein run in front or behind the medial malleolus?
in front of
182
does the small saphenous vein run in front or behind the lateral malleolus?
behind
183
what aspect of the lower limb does the great saphenous vein run?
medial aspect of the lower limb
184
what aspect of the lower limb does the small saphenous vein run?
posterior midline of the lower limb
185
what is the name of the most common site of venous ulceration?
gaiter area
186
where is the gaiter area?
medial aspect of the distal lef
187
what is the route of the lymphatics in the upper limb?
cubital nodes
lateral axillary nodes
apical axillary nodes
188
in the limbs, what blood vessels do the lymphatics tend to follow?
veins
189
in the abdomen, what blood vessels do the lymphatics tend to follow?
arteries
190
where do the popliteal lymph nodes drain to?
superficial and deep inguinal nodes
191
What type of immunological reaction is pemphigus or pemphigoid?
```
type 2
(direct cell killing)
```
192
what type of immunological reaction is urticaria usually?
```
type 1
(IgE mediated)
```
193
what type of immunological reaction is erythema/rash usually?
```
type 4
(delayed type)
```
194
what type of immunological reaction is purpura usually?
```
type 3
(immune-complex mediated)
```
195
what is purpura?
red/purple spots that do not blanche
196
what is the cause of purpura?
bleeding under the skin
197
what happens to an allergic reaction when the dose of drug is decreased?
nothing
| not dose-dependent
198
what happens to a non-immunologial drug reaction when the dose of drug is decreased?
reaction is usually less
| dose-dependent
199
What is a morbiliform rash?
a rash which looks like measels
200
What is a pustular rash?
a rash with papules containin pus
201
What is a papulosquamous rash?
a rash with hyperkeratosis
202
is a high molecular weight drug or a low molecular weight drug more likely to be involved in drug eruptions?
high molecular weight
203
what is the most common type of cutaneous drug eruption?
exanthematous
| or maculopapular
204
what type of hypersensitivity is an exanthematous (maculopapular) rash?
```
type IV
(delayed type)
```
205
what is the usual onset of an exanthematous drug reaction?
4-21 days after first taking drug
206
what are the 6 indicators of a potential severe exanthematous drug eruption?
1. involvement of mucous membranes and face
2. facial oedema and erythema
3. widespread confluent erythema
4. fever (>38.5)
5. blisters, purpura, necrosis
6. SOB, wheeze
207
what happens in a non-immunological type 1 drug reaction? (eg urticaria)
direct release of inflammatory mediators from mast cells due to direct effect of drug
(not IgE mediated)
208
What do you see clinically on a patient with acute generalised exanthematous pustulosis? (AGEP)
extensive sheets of pustules
209
what is the usual cause of acute generalised exanthematous pustulosis? (AGEP)
drug eruption
210
What are the 4 main severe cutaneous adverse drug reactions?
1. Stevens-Johnson syndrome (SJS)
2. Toxic epidermal necrosis (TEN)
3. Drug reaction with eosinophilia and systemic symptoms (DRESS)
4. Acute generalised exanthematous pustulosis (AGEP)
211
What is a positive nikolsky sign?
gentle touching of the skin causes it to fall off
212
what is the nikolsky sign for pemphigus?
positive
213
what is the nikolsky sign for pemphigoid?
negative
214
what is the nikolsky sign for toxic epidermal nectosis?
positive
215
is phototoxicity an immunological or non-immunological drug reaction?
non-immunological
216
what are the 3 acute features of phototoxic drug reactions?
1. skin toxicity
2. systemic toxicity
3. photodegradation
217
what are the 3 chronic features of phototoxic drug reactions?
1. pigmentation
2. photoageing
3. photocarcinogenesis
218
What 2 requirements are needed for a phototoxic cutaneous drug reaction?
1. sufficient photo-reactive drug
| 2. appropriate wavelength of light
219
What is the mild form of polymorphic light eruption (PLE) commonly known as?
prickly heat
220
compare photo allergy and photoxicity in terms of immune sensitisation?
photo allergy requires immune sensitisation
| phototoxicity does not
221
compare photodermatose to photoaggravated dermatose?
photodermatose: condition caused by light
| photoaggravated dermatose: condition not cuased by light but can be made worse by it
222
What are porphyrias?
a group of conditions where there is a build up of porphyrin chemicals
223
What is the most common skin porphyria in Scotland?
porphyria cutanea tarda
| PCT
224
what is a porphyrin?
normal metabolites which are part of the haem metabolic pathway
225
what enzyme is defective in porphyria cutanea tarda?
uroporphyrinogen decarboxylase
226
what porphyrin builds up in porphyria cutanea tarda?
uroporphyrinogen III
227
where is the enzyme uroporphyrinogen decarboxylase made?
the liver
228
what is the typical presentation of porphyria cutanea tarda?
blistering and fragility
| also possible hyperpigmentation, hypertrichosis, solar urticaria, morphoea
229
what is hirtuism?
increased hair growth in male pattern
230
what is hypertrichosis?
increased hair growth generally
231
what is morphoea?
scarring process in the dermis
232
How do you investigate a possible porphyria cutanea tarda?
woods lamp using patients urine
233
what are the 4 main causes of porphyria cutanea tarda?
alcohol
viral hepatitis
oestrogens
haemochromatosis
all cause decreased uroporphyrinogen decarboxylase production in the liver
234
what porphyrin builds up in erythropoietic protoporphyria?
protoporphyrin IX
235
what enzyme is deficient in erythropoietic protoporphyria?
ferrochelatase
236
what vitamin do patients with porphyrias usually become deficient in?
vit D due to sun avoidance
237
compare signs and symptoms of erythropoietic protoporphyria?
no signs only symptoms (Severe prickly burning which lasts a few days)
although eventually scars appear
238
what is usually seen in a patient with a porphyria's full blood count?
```
reduced Hb (due to lack of haem)
--> anaemic
```
239
what is the management of porphyria cutanea tarda?
treatment of underlying condition
240
what is the management of erythropoietic protoporphyria?
visible light protection measures
241
what porphyrin builds up in acute intermittent porphyria?
porphobillinogen (PBG)
242
what enzyme is deficient in acute intermittent porphyria?
PBG deaminase
243
What is virulence?
the capacity of a microbe to cause damage to the host
244
What is adhesin?
a virulence factor which enables binding of the organism to host tissue
245
what is invasin?
a virulence factor which enables the organism to invade a host cell/tissue
246
what is impedin?
a virulence factor which enables the organism to avoid host defense mechanisms
247
what is aggressin?
a virulence factor which causes damage to the host directly
248
what is modulin?
a virulence factor which causes damage to the host indirectly
249
where is S. aureus usually carried by carriers?
```
anterior nares (in the nose)
perineum
```
250
what is haemolysin?
a virulence factor which breaks down clots
251
what adhesin increases the chance of a specific S. aureus strain being able to infect a joint?
collagen binding protein
252
what impedin, found in some strains of S. aureus is associated with severe skin infections?
Panton Valentine Leukocidin
253
compare PVL toxin percentage of hospital acquired MRSA strands to community acquired strands?
higher percentage of community acquired MRSA contain PVL than hospital acquired strands
254
what is refractory hypoxaemia?
oxygen is reduced but because the tissue is dead this cannot be improved by using an oxygen mask
255
What are superantigens?
antigens which causes immune system to respond with an inappropriate immune response that causes host damage
256
Why do superantigens cause a massive release of cytokines and an inappropriate immune response? (which leads to huge scale inflammation)
because they don't go through the normal reaction between receptor and presenting antigen
257
What superantigen found in S. aureus is associated with Toxic Shock Syndrome?
TSST-1
| toxic shock syndrome toxin 1
258
what are the 3 main skin infections caused by Strep pyogenes? (GAS)
impetigo
cellultis (erysipelas)
necrotising fasciitis
259
what is the lancefield system?
a system which serotypes the cell wall carbohydrate of a bacteria
260
what Strep infection has a lancefield classification of A?
Strep pyogenes
| GAS
261
what is celulitis?
skin infection of the dermis
| no necrosis
262
Why is there no bacteremia in S. aureus Toxic Shock Syndrome?
because the superantigen goes through the blood stream causing host destruction, the infection itself is localised
263
What acts as the brick and mortar in the brick and mortar model of the stratum corneum?
bricks- corneocytes
| mortar- intercellular lipids
264
what are the corneocytes held together by?
corneodesmosomes
265
what are the 2 entry routes of drug through the skin?
```
intercellular route (through intercellular lipids)
transcellular route (through corneocytes)
```
266
why is the intercellular route of drug entry through the skin highly tortuous?
it has to weave between the corneocytes
267
what is Fick's law?
```
J = Kp x Cv
J = Rate of Absorption (flux)
Kp = permeability coefficient
Cv = concenration of drug in vehicle
```
268
what is the best combination of drug and base to allow a good partition across the stratum corneum?
lipophilic drug in hydrophilic base
269
why does a lipophilic drug in a lipophilic base not allow a good partition across the stratum corneum?
lipophilic vehicle will retain the drug
270
what are excipents?
molecules which are included in the drug vehicle to increase solubility and enhance absorption
271
what are 2 ways to improve partitioning of the drug across the stratum corneum?
1. hydration of the skin by occlusion
| 2. addition of excipients
272
what receptors do glucocorticoids signal via?
nuclear receptors
273
how do glucocorticoids enter cells?
by diffusion across the plasma membrane
274
when glucorticoids are within the cytoplasm what do they combine with?
GRalpha molecules
275
what has to dissociate from the GRalpha molecules in order to let glucocorticoids combine?
inhibitory heat shock proteins
276
what allows the activated GRalpha receptor to translocate to the nucleus once it has binded with a glucocorticoid?
importins
277
what must form before the GRalphas can bind to glucorticoid response elements in the nucleus?
GRalpha monomers must become homodimers
278
where are glucocorticoid response elements found in genes?
in the promoter regions
279
what is the main disadvantage of subcutaneous administration?
injection volume limited
280
what is iontophoresis?
application of low voltage electrical pulses to the skin via a surface electrode in order to drive low molecular weight molecules of the same charge through the skin
281
what is electroporation?
very brief high voltage pulses which lead to pore formation in order to deliver hydrophilic and charged molecules into the skin
282
what is sonophoresis?
use of ultrasound to increase skin permeability
