Raphael's request (was Re: Dr. Marjorie , please read)

[Guest guest]

Here you go, , the abstract you mentioned, followed by two

earlier ones by the same lab. They are all from 1996-97, which by

neuropeptide research standards was a long time ago. Based on the

common subject matter and time frame, I would guess all three are

different aspects of the same research.

To my reading, this is basic science research demonstrating the

mechanism by which UVB radiation (sunlight) causes erythema and

vasodilation (sunburn). The first study mentions application of a

topical NO inhibitor on human skin, but only to prove the mechanism

by which UVB induces sunburn, not as a treatment option (at least not

here).

According to these studies, the mechanism by which UVB radiation

causes erythema and vasodilation is related to several nitrogen

oxides, including increased levels of NO, among other mechanisms. No

direct reference to rosacea, although the study does implicate some

of the same players in sun-induced erythma that some believe may be

involved in rosacea-induced erythema.

ly, I found these challenging abstracts to get through, so I may

have missed something (or everything ).

Marjorie

Marjorie Lazoff, MD

-=-=-==

J Dermatol Sci 1997 May;15(1):23-35 Related Articles, Books, LinkOut

Inhibition of ultraviolet B-induced skin erythema by N-nitro-L-

arginine and N-monomethyl-L-arginine.

Deliconstantinos G, Villiotou V, Stavrides JC.

Department of Experimental Physiology, University of Athens Medical

School, Greece.

Ultraviolet B (UVB)-irradiated human keratinocytes and human

endothelial cells release nitrogen oxides, i.e. nitric oxide (NO). S-

nitrosothiols, hydroxylamine (H2NOH) as well as ammonia (NH3) formed

from L-arginine. Generation of these compounds was time and

concentration-dependent and decreased by both N-monomethyl-L-arginine

(L-NMMA) and N-nitro-L-arginine (L-NA). UVB radiation of the cells

resulted in a concomitant increase of soluble guanylate cyclase (sGC)

activity which was inhibited by L-NMMA and L-NA. S-nitrosothiols

formed during the irradiation of the cells directly increased

purified sGC activity by a mechanism characteristic of release of NO

from a carried molecule. UVB-irradiated cells promptly increased

thiobarbituric acid reacting substance (TBARS) (estimated as

malondialdehyde. MDA) production which were inhibited by

desferrioxamine. In in vivo experiments using guinea pigs subjected

to UVB radiation, a Protection Factor (PF) of 2.25 +/- 0.75 was

calculated when an emulsified cream formulation containing L-NMMA (1%

w/w) and L-NA (1% w/w) was applied to their skin. In human volunteers

subjected to UVB radiation, a dose-dependent increase of PF was

observed. When an emulsified cream formulation containing L-NMMA (1%

w/w) and L-NA (1% w/w) was applied to their skin the PF was 2.15 +/-

0.80: by increasing the concentration of L-NMMA (1% w/w) and L-NA (2%

w/w) the PF was 4.25 +/- 1.25. The present results indicate that UVB

radiation acts as a potent stimulator of human keratinocytes and

endothelial cells to release nitrogen oxides that may diffuse out of

the keratinocytes and endothelial cells, activating sGC in

neighboring smooth muscle cells. This may be a major part of the

integrated response of the skin leading to vasodilation and erythema.

PMID: 9186809 [PubMed - indexed for MEDLINE]

-=-=-=

Biochem J 1996 Dec 15;320 ( Pt 3):997-1003 Related Articles, Books,

LinkOut

Increase of particulate nitric oxide synthase activity and

peroxynitrite synthesis in UVB-irradiated keratinocyte membranes.

Deliconstantinos G, Villiotou V, Stavrides JC.

Department of Experimental Physiology, University of Athens Medical

School, Greece.

Here we demonstrate that human keratinocytes possess a

Ca2+/calmodulin-dependent particulate NO synthase that can be

activated to release NO after exposure to UVB radiation. UVB

irradiation (up to 20 mJ/cm2) of human keratinocyte plasma membranes

resulted in a dose-dependent increase in NO and L-[3H]citrulline

production that was inhibited by approx. 90% in the presence of N-

monomethyl-L-arginine (L-NMMA). In time-course experiments with UVB-

irradiated plasma membranes the changes in NO production were

followed by analogous changes in soluble guanylate cyclase (sGC)

activity. In reconstitution experiments, when particulate NO synthase

was added to purified sGC isolated from keratinocyte cytosol, a 4-

fold increase in cGMP was observed; the cGMP was increased by NO

synthesized after UVB irradiation (up to 20 mJ/cm2) of particulate NO

synthase. A 5-fold increase in superoxide (O2-) and a 7-fold increase

in NO formation followed by an 8-fold increase in peroxynitrite (ONOO-

) production by UVB (20 mJ/cm2)-irradiated keratinocyte microsomes

was observed. UVB radiation (20 mJ/cm2) decreased plasma membrane

lipid fluidity as indicated by steady-state fluorescence anisotropy.

Membrane fluidity changes were prevented by L-NMMA. Changes in

Arrhenius plots of particulate NO synthase in combination with

changes in its allosteric properties induced by UVB radiation are

consistent with a decreased fluidity of the lipid microenvironment of

the enzyme. The present studies provide important new clues to the

role of NO and ONOO- released by UVB-irradiated human keratinocytes

in skin erythema and inflammation.

PMID: 9003391 [PubMed - indexed for MEDLINE]

-=-=-=

Exp Physiol 1996 Nov;81(6):1021-33 Related Articles, Books, LinkOut

Nitric oxide and peroxynitrite released by ultraviolet B-irradiated

human endothelial cells are possibly involved in skin erythema and

inflammation.

Deliconstantinos G, Villiotou V, Stavrides JC.

Department of Experimental Physiology, University of Athens Medical

School, Greece.

In this study we attempted to demonstrate whether endothelial cell

nitric oxide synthase (eNOS) and xanthine oxidase (XO) could be

activated to release nitric oxide (NO) and peroxynitrite (ONOO-)

following exposure to ultraviolet B (UVB) radiation and to define

whether this light-induced response could be involved in the

pathogenesis of sunburn erythema and inflammation. Treatment of human

endothelial cells with UVB (290-320 nm) radiation (up to 100 mJ/cm2)

resulted in an increase of both NO and ONOO- release that was

inhibited by NG-monomethyl-L-arginine (L-NMMA). Treatment of cell

cytosol with various doses of UVB radiation (up to 20 mJ/cm2)

resulted in a threefold increase of XO activity that was inhibited

(approximately 90% by oxypurinol. In reconstitution experiments, when

purified eNOS was added to purified XO, an almost fourfold increase

in ONOO- production at 20 mj/cm2 UVB radiation was observed. UVB

radiation (100 mg/cm2) decreased cell membrane fluidity, indicating

changes in the physicochemical characteristics of the membranes. In

in vivo experiments, when human volunteers were subjected to UVB

light, a protection factor (PF) of 3.90 +/- 0.85 was calculated when

an emulsified cream formulation containing nitro-L-arginine (L-NA;

2%) and L-NMMA (2%) was applied to their skin. The present studies

indicate that UVB radiation acts as a potent stimulator of eNOS and

XO in human endothelial cells. The cytotoxic effects of NO and ONOO-

may be the main factors in the integrated response of the skin

leading to vasodilatation, the first key event of erythema production

and the inflammation process.

PMID: 8960707 [PubMed - indexed for MEDLINE]

> There is an interesting article available at PUBMED which gives the

> impression that there are many other scientists involved with NO

> inhibitors'research . The abstract is available for free .As I

don't

> know how to post it here I ask you to go there and if possible post

> it to the whole group .

> At PUBMED's web site , type in the doctor's names :

> Deliconstantinos G , Villiotou V , Stavrides JC .

> or type in the article's title :

> Inhibition of ultraviolet B-induced skin erithema by N-nitro-L-

> arginine and N-monomethyl-L-arginine .

>

> Thanks a lot for helping this group .

>