Vessel regrowth and lasers (was Re: need help with ansers from laser doc.)..

[Guest guest]

> Personally, I think Photoderm is a mixed bag. I believe that the

> technology holds *huge* potential but that the majority of

operators

> are not / cannot become skilled enough in its usage. However, I

> *don't* think this is the fault of the operators -- I think it's

the

> fault of the machine at this stage in its development. I believe

> that over time, the machine (and others like it) will be able to

> calibrate autmatically to deliver optimum energy to the skin

(either

> via a feedback mechanism in the delivery head or a laser

thermometer

> instument which is attached to the head and can meausure the

> heating / cooling curve of the skin). I think that because of the

> unpredictable results of the machines, the makers have been

> reluctant in pushing for more independant trials.

, I think you've raised an interesting and important point. My

theoretical concerns are not only with the best method of zapping

vessels as you discussed above, but (even with ideal equipment and

practitioner) the short- and long-term consequences of zapping

vessels. It may well be that zapping vessels may not result in

permanent change in some or even most rosaceans, and that repeated

treatments will be needed. It's entirely possible that, with the

body's compensatory mechanisms, original or continued treatments may

make rosacea worse.

Does anyone know if IPL, V-beam, photoderm, etc selectively zap

arteries, or do they indiscrimently hit both arteries and veins?

Arteries are the cause of flushing, veins just passive recipients of

chronic flushing. But I don't know if selective zapping would cause

more or fewer problems in the long run. Lots of different factors to

consider -- blood flow, pressure gradients, angiogenesis, etc.

You know, , the more we all discuss this, the more convinced I

am that IPL and related treatments are so in their infancy. This is

really experimental stuff. I'm also reminded here of Rick's

insightful hammer/nail analogy. We know that laser treatments work

best for specific, visible skin conditions and imperfections. Using

laser-related technologies for anti-aging and rosacea is wholly

different. (Below you mention psoriasis, but I assume you're

referring to post-PUVA therapy, oral medication that is then

activated by UV light; I wasn't aware that angiogenesis is a problem

there.)

> One important thing that we've not been considering in this is

> vessel re-growth. After any injury to tissue / blood vessels, the

> body releases VEGF which can cause new vessel growth. Before Nase

> was injured, he commented a few times (I think this was on the BFS

> board) that after any vascular surgery, after the 1st 3-4

> treatments, VEGF production (and therefore angiogensis, re-growth

> and poor results) is high. After 3-4 treatments, he thought that

> VEGF production fell (whether this was a hypothesis or based on

> data, published or otherwise, I don't know). This is why Nase was

> so keen on the topical NO inhibitors: He hypothesised that used in

> conjunction with vascular laser / IPL treatments, they could be

> made *significantly* more effective (with little or no re-growth).

> Multiple published studies (Ormerod on Psoriasis comes to mind)

> have shown that topical NO inhibition *does* reduce VEGF

> production.

In searching for Ormerod, I came upon this new study from a top

cardiovascular research group. It seems to suggest that while NO

induces VEGF it does *not* induce VEGF-dependent neoangiogenesis,

just VEGF-dependent vascular permeability -- though frankly I don't

know if I got this right, since with my limited knowledge this was a

tough abstract for me to understand. Maybe someone else can get more

out of it? But if I'm reading this right, then theoretically topical

NOI might help stave off facial edema and inflammation, but not

flushing.

-=-=-=

Arterioscler Thromb Vasc Biol 2002 Jun 1;22(6):901-6

Divergence of angiogenic and vascular permeability signaling by VEGF:

inhibition of protein kinase C suppresses VEGF-induced angiogenesis,

but promotes VEGF-induced, NO-dependent vascular permeability.

Spyridopoulos I, Luedemann C, Chen D, Kearney M, Chen D, Murohara T,

Principe N, Isner JM, Losordo DW.

Department of Cardiovascular Research, St. 's Medical

Center, Boston, Mass 02135, USA.

Vascular endothelial growth factor (VEGF) promotes angiogenesis by a

variety of mechanisms including stimulation of endothelial cell

proliferation and migration and increasing vascular permeability.

Although its mitogenic activity is mediated primarily by the beta(2)-

isoforms of protein kinase C (PKC), little is known about the

signaling pathways transducing its other physiological properties.

Accordingly, we used a novel inhibitor molecule to examine the role

of PKC isoforms alpha and beta in mediating VEGF-induced angiogenesis

and vascular permeability. Because conventional inhibitors of PKC,

such as staurosporine or calphostin C, also inhibit a variety of

other protein kinases, we used a novel compound to specifically

inhibit PKC. A myristoylated peptide, which mimics the

pseudosubstrate motif of PKC-alpha and -beta subtypes, has been shown

to be a highly selective and cell-permeable inhibitor of PKC.

Blocking led, as expected, to abrogation of VEGF-induced endothelial

cell proliferation in vitro. In vivo, VEGF-induced angiogenesis was

impaired by myristoylated peptide. Surprisingly, selective inhibition

of PKC induced vascular permeability in vivo via a NO-dependent

mechanism. Moreover, PKC inhibition led to a 6.4-fold induction of NO

synthase (NOS) activity in endothelial cells. Our findings

demonstrate that activation of PKC is a major signaling pathway

required for VEGF-induced proliferation and angiogenesis, whereas

vascular permeability was enhanced by blocking PKC. Inhibition of

calcium-dependent PKC by itself led to induction of NOS. Although NOS

is a downstream target for VEGF-induced angiogenesis, its induction

by PKC inhibition was not sufficient to promote neovascularization.

These results reveal that angiogenesis and vascular permeability

induced by VEGF are mediated by mechanisms which ultimately diverge.

PMID: 12067896 [PubMed - indexed for MEDLINE]

-=-=-=

For those interested in it's more clinical aspects, here's a Web page

on angiogenesis from a society dedicated to its various

manifestations:

http://www.angio.org/understanding/understanding.html

Marjorie

Marjorie Lazoff, MD

[Guest guest]

> Personally, I think Photoderm is a mixed bag. I believe that the

> technology holds *huge* potential but that the majority of

operators

> are not / cannot become skilled enough in its usage. However, I

> *don't* think this is the fault of the operators -- I think it's

the

> fault of the machine at this stage in its development. I believe

> that over time, the machine (and others like it) will be able to

> calibrate autmatically to deliver optimum energy to the skin

(either

> via a feedback mechanism in the delivery head or a laser

thermometer

> instument which is attached to the head and can meausure the

> heating / cooling curve of the skin). I think that because of the

> unpredictable results of the machines, the makers have been

> reluctant in pushing for more independant trials.

, I think you've raised an interesting and important point. My

theoretical concerns are not only with the best method of zapping

vessels as you discussed above, but (even with ideal equipment and

practitioner) the short- and long-term consequences of zapping

vessels. It may well be that zapping vessels may not result in

permanent change in some or even most rosaceans, and that repeated

treatments will be needed. It's entirely possible that, with the

body's compensatory mechanisms, original or continued treatments may

make rosacea worse.

Does anyone know if IPL, V-beam, photoderm, etc selectively zap

arteries, or do they indiscrimently hit both arteries and veins?

Arteries are the cause of flushing, veins just passive recipients of

chronic flushing. But I don't know if selective zapping would cause

more or fewer problems in the long run. Lots of different factors to

consider -- blood flow, pressure gradients, angiogenesis, etc.

You know, , the more we all discuss this, the more convinced I

am that IPL and related treatments are so in their infancy. This is

really experimental stuff. I'm also reminded here of Rick's

insightful hammer/nail analogy. We know that laser treatments work

best for specific, visible skin conditions and imperfections. Using

laser-related technologies for anti-aging and rosacea is wholly

different. (Below you mention psoriasis, but I assume you're

referring to post-PUVA therapy, oral medication that is then

activated by UV light; I wasn't aware that angiogenesis is a problem

there.)

> One important thing that we've not been considering in this is

> vessel re-growth. After any injury to tissue / blood vessels, the

> body releases VEGF which can cause new vessel growth. Before Nase

> was injured, he commented a few times (I think this was on the BFS

> board) that after any vascular surgery, after the 1st 3-4

> treatments, VEGF production (and therefore angiogensis, re-growth

> and poor results) is high. After 3-4 treatments, he thought that

> VEGF production fell (whether this was a hypothesis or based on

> data, published or otherwise, I don't know). This is why Nase was

> so keen on the topical NO inhibitors: He hypothesised that used in

> conjunction with vascular laser / IPL treatments, they could be

> made *significantly* more effective (with little or no re-growth).

> Multiple published studies (Ormerod on Psoriasis comes to mind)

> have shown that topical NO inhibition *does* reduce VEGF

> production.

In searching for Ormerod, I came upon this new study from a top

cardiovascular research group. It seems to suggest that while NO

induces VEGF it does *not* induce VEGF-dependent neoangiogenesis,

just VEGF-dependent vascular permeability -- though frankly I don't

know if I got this right, since with my limited knowledge this was a

tough abstract for me to understand. Maybe someone else can get more

out of it? But if I'm reading this right, then theoretically topical

NOI might help stave off facial edema and inflammation, but not

flushing.

-=-=-=

Arterioscler Thromb Vasc Biol 2002 Jun 1;22(6):901-6

Divergence of angiogenic and vascular permeability signaling by VEGF:

inhibition of protein kinase C suppresses VEGF-induced angiogenesis,

but promotes VEGF-induced, NO-dependent vascular permeability.

Spyridopoulos I, Luedemann C, Chen D, Kearney M, Chen D, Murohara T,

Principe N, Isner JM, Losordo DW.

Department of Cardiovascular Research, St. 's Medical

Center, Boston, Mass 02135, USA.

Vascular endothelial growth factor (VEGF) promotes angiogenesis by a

variety of mechanisms including stimulation of endothelial cell

proliferation and migration and increasing vascular permeability.

Although its mitogenic activity is mediated primarily by the beta(2)-

isoforms of protein kinase C (PKC), little is known about the

signaling pathways transducing its other physiological properties.

Accordingly, we used a novel inhibitor molecule to examine the role

of PKC isoforms alpha and beta in mediating VEGF-induced angiogenesis

and vascular permeability. Because conventional inhibitors of PKC,

such as staurosporine or calphostin C, also inhibit a variety of

other protein kinases, we used a novel compound to specifically

inhibit PKC. A myristoylated peptide, which mimics the

pseudosubstrate motif of PKC-alpha and -beta subtypes, has been shown

to be a highly selective and cell-permeable inhibitor of PKC.

Blocking led, as expected, to abrogation of VEGF-induced endothelial

cell proliferation in vitro. In vivo, VEGF-induced angiogenesis was

impaired by myristoylated peptide. Surprisingly, selective inhibition

of PKC induced vascular permeability in vivo via a NO-dependent

mechanism. Moreover, PKC inhibition led to a 6.4-fold induction of NO

synthase (NOS) activity in endothelial cells. Our findings

demonstrate that activation of PKC is a major signaling pathway

required for VEGF-induced proliferation and angiogenesis, whereas

vascular permeability was enhanced by blocking PKC. Inhibition of

calcium-dependent PKC by itself led to induction of NOS. Although NOS

is a downstream target for VEGF-induced angiogenesis, its induction

by PKC inhibition was not sufficient to promote neovascularization.

These results reveal that angiogenesis and vascular permeability

induced by VEGF are mediated by mechanisms which ultimately diverge.

PMID: 12067896 [PubMed - indexed for MEDLINE]

-=-=-=

For those interested in it's more clinical aspects, here's a Web page

on angiogenesis from a society dedicated to its various

manifestations:

http://www.angio.org/understanding/understanding.html

Marjorie

Marjorie Lazoff, MD