Saturday, July 07, 2007

organic tomatoes higher in quercetin and kaempferol

In a 10 year study highlighted by the BBC, organic tomatoes were found to contain twice the levels of flavonoids compared with commonly grown tomatoes.

Organic food 'better' for heart

Flavonoids have been shown to reduce high blood pressure, lowering the risk of heart disease and stroke.

Writing in the Journal of Agricultural and Food Chemistry, the team said nitrogen in the soil may be the key.

Dr Alyson Mitchell, a food chemist at the University of California, and colleagues measured the amount of two flavonoids - quercetin and kaempferol - in dried tomato samples that had been collected as part of a long-term study on agricultural methods.

...

Flavonoids have also been linked with reduced rates of some types of cancer and dementia.

The Food Standards Agency says there is some evidence that flavonoids can help to reduce the risk of cardiovascular disease and they are currently carrying out a study to look at the health benefits in more detail.

However, a spokesperson said there was no evidence that organic food was healthier.

"Our long-standing advice on organic food is there can be some nutrient differences but it doesn't mean it's necessarily better for you."

The RSRP Page on Quercetin tell us that, "Quercetin is an herbal COX and 5-LOX inhibitor that when taken as a supplement may be helpful in controlling inflammation". The role of Quercetin and other flavonoids in vascular function is an interesting area of study. Whilst there is no direct link yet to rosacea, general vascular health is definitely a good thing for rosacea sufferers.

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Wednesday, July 04, 2007

oracea plus metrogel, better than 100mg doxycycline plus metrogel ?

A clinical trial, sponsored by CollaGenex, is recruiting patients to see how Oracea compares to doxycycline (100mg once a day) when combined with metrogel 1%.

We can see from a Collagenex annual report that COL-101 was the name for Periostat MR, which then became Oracea.

Safety and Efficacy Study to Compare Two Rosacea Treatment Regimens

Purpose: To compare the safety and efficacy of two treatment regimens: 1) COL-101 and metronidazole gel 1%; 2) Doxycycline hyclate 100 mg and metronidazole gel 1%

Official Title: A Clinical Trial to Determine the Effects of COL-101 Administered Once Daily With Metronidazole Topical Gel, 1% Versus Doxycycline Hyclate 100 mg Administered Once Daily With Metronidazole Topical Gel, 1% in Patients With Moderate to Severe Rosacea

This trial follows on from a 2005 paper that studied the combination of periostat and metrogel. That study concluded that combining sub antibiotic dose doxycycline with metrogel 0.75% was better than metrogel on its own.

Combining a systemic antibiotic with metronidazole has been the mainstay of rosacea treatment for several years. What we are seeing here is updates to studies since the introduction of oracea and metrogel 1%.

Saturday, June 30, 2007

demodex mite bacteria causes the inflammation ?

This paper is proposing that a particular type of bacteria taken from a demodex mite, called Bacillus oleronius is capable of producing an inflammatory response. As the mite was isolated from a patient with papulopustular rosacea the tempting conclusion is that this bacteria has caused these rosacea symptoms. This part is of course not confirmed, just the fact that it is possible to isolate a bacteria that causes an inflammatory response in humans.

This paper looks to be the publication of a study mentioned in a 2004 press release from the National Rosacea Society - New Study Shows Role for Bacteria in Development of Rosacea Symptoms.

A study from February 2007 (also with NRS funding), mentioned in demodex bacteria - could that be the cause ?, tried a different approach to proving a link. Herer, Burroughs et.al. is suggesting that antibiotics actually affect the intraceluar bacteria in demodex mites - and that is the reason they work in rosacea - not their anti-inflammatory properties. 

So here is the abstract of the just-published paper.

Mite-related bacterial antigens stimulate inflammatory cells in rosacea.

Br J Dermatol., 2007 Jun 26, Lacey N, Delaney S, Kavanagh K, Powell FC .

Background: Patients with papulopustular rosacea have a higher density of Demodex folliculorum mites on their faces than normal subjects but the role, if any, of their mites in initiating inflammation is disputed. Selective antibiotics are effective in reducing the inflammatory changes of papulopustular rosacea, but their mode of action is unknown.

Objectives: To investigate whether a D. folliculorum-related bacterium was capable of expressing antigens that could stimulate an inflammatory immune response in patients with rosacea.

Methods: A bacterium (Bacillus oleronius) was isolated from a D. folliculorum mite extracted from the face of a patient with papulopustular rosacea, and was investigated further.

Results: This bacterium produced antigens capable of stimulating peripheral blood mononuclear cells proliferation in 16 of 22 (73%) patients with rosacea but only five of 17 (29%) control subjects (P = 0.0105). This antigenic preparation was fractionated into 70 subfractions and the proteins in each fraction were visualized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Western blot analysis revealed the presence of two antigenic proteins of size 62 and 83 kDa in fractions when probing with sera from patients with rosacea. No immunoreactivity to these proteins was recorded when probing with sera from control patients. Two-dimensional electrophoretic separation was used to isolate these proteins and matrix-assisted laser desorption/ionization time-of-flight analysis was employed to identify the relevant peptides. The 62-kDa immunoreactive protein shared amino acid sequence homology with an enzyme involved in carbohydrate metabolism and signal transduction while the 83-kDa protein was similar to bacterial heat shock proteins.

Conclusions: Antigenic proteins related to a bacterium (B. oleronius), isolated from a D. folliculorum mite, have the potential to stimulate an inflammatory response in patients with papulopustular rosacea.

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Wednesday, June 20, 2007

WP: Fashion & Beauty Article: Seeing Red

It is not very often than an online newspaper or news site features a half decent article about rosacea. This article from the Fashion & Beauty section of the Washington Post is reasonable for a mass audience paper. Rosacea is still a mystery to the population at large, so it is encouraging to see this sort of article.

SEEING RED

BY RACHEL HERSCHENFELD, M.D. - DERMATOLOGIST

Many of my patients call to make appointments because a spot on their skin has changed color or because they can't wait to get rid of their brown spots or white bumps. But the color they call most about is red, and it is usually because they've developed a red rash on their body or face.

For many of these patients, the issue is rosacea -- a common condition associated with pimples and redness on the face. Rosacea usually occurs in adults well after any acne has subsided, but it can cause at least as much embarrassment and frustration as acne does for teenagers. Part of the problem for many people is the mistaken stereotype that associates red noses with alcohol consumption. Although alcohol sometimes leads to flushing of the face, it is not the main cause of rosacea, and facial redness does not necessarily indicate an alcohol problem. Redness on the face is also difficult to camouflage, even with make-up.

[Read More]

The article goes on to mention the usual metronidazole & antibiotics, but also V-Beam and IPL.

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Monday, June 18, 2007

metrogel: how it gets into your skin

Two recently published papers look at the processes involved when you apply metrogel topically. The first abstract just tells us that they undertook some new ways of measuring metronidazole absorption, but doesn't reveal their results.

The second abstract suggests that a cream based metronidazole formulation (presumably metrocream, but could also include Noritate) had the greatest absorption when tested with human skin. They suggest that future research is needed to determine if indeed this makes any difference to rosacea symptoms.

Previously Rosacea News reported ;

metrogel, metrolotion, metrocream, noritate, once and twice per day - all the same same

"Despite quite a lot of activity in the marketing and development of the metronidazole treatments (lotion, cream, gel, generic equivalents, metrogel 1%, once per day, twice per day) this research suggests that the formulation and treatment frequency make little difference to the treatment outcome. So if you can tolerate one of the available formulations, there is likely marginal benefit from changing to another."

Metronidazole based treatments do seem to attract a lot of research, maybe even too much research given the marginal improvement that many rosacea sufferers experience from the metro triplets. Imagine if the research poured in metronidazole was directed to new, leading edge treatments.

As background, from `measuring niacinamide (vitamin B3) moisturizer and skin barrier': 

"Confocal Raman microspectroscopy (CRS), in contrast, is a new technique that combines the well attested method of Raman spectroscopy (the study of inelastic scattering of light, rather than its absorption) with confocal microscopy, allowing noninvasive, realtime, in vivo measures of molecular concentration profiles."


Follow-up of drug permeation through excised human skin with confocal Raman microspectroscopy. Eur Biophys J., 2007 Jun 13, Tfayli A, Piot O, Pitre F, Manfait M.

Skin is a multilayered organ which covers and protects the surface of human body by providing a barrier function against exogenous agents. Meanwhile, the efficacy of several topically applicated drugs is directly related to their penetration through the skin barrier. Several techniques are commonly used to evaluate the rate, the speed and the depth of penetration of these drugs, but few of them can provide real-time results. Therefore, the use of nondestructive and structurally informative techniques permits a real breakthrough in the investigations on skin penetration at a microscopic scale.

Confocal Raman microspectroscopy is a nondestructive and rapid technique which allows information to be obtained from deep layers under the skin surface, giving the possibility of a real-time tracking of the drug in the skin layers. The specific Raman signature of the drug enables its identification in the skin. In this study, we try to follow the penetration of Metronidazole, a drug produced by Galderma as a therapeutic agent for Rosacea treatment, through the skin. The first step was the spectral characterization of Metronidazole in the skin. Then micro-axial profiles were conducted to follow the penetration of the drug in the superficial layers, on excised human skin specimens. For more accurate information, transverse sections were cut from the skin and spectral images were conducted, giving information down to several millimeters deep. Moreover, the collected spectra permit us to follow the structural modifications, induced by the Metronidazole on the skin, by studying the changes in the spectral signature of the skin constituents.


Percutaneous absorption kinetics of topical metronidazole formulations in vitro in the human cadaver skin model, Adv Ther. 2007 Mar-Apr;24(2):239-46, Elewski BE

Topical formulations containing identical active agents are available in various vehicles and concentrations, which may affect percutaneous absorption. This study was undertaken to evaluate the in vitro percutaneous absorption pharmacokinetics of metronidazole in different vehicles and concentrations as the active agent in 6 topical formulations. Formulations were applied to sections from 3 cadaver skin donors, and percutaneous absorption of metronidazole was measured over a 48-h test period through the finite dose technique and the use of Franz diffusion cells. Metronidazole penetrates into and through human cadaver skin.

Data show the general ranking of delivery of similar concentrations of metronidazole according to vehicle as cream > lotion > gel. The 48-h penetration of metronidazole in the human cadaver skin model was greatest with cream formulations and lowest with gel formulations. These results reveal the importance of the vehicle selected for penetration of metronidazole into the skin. The relevant target zone in rosacea is the dermis because this is the area where inflammation takes place. Additional studies are warranted to examine absorption of metronidazole into the relevant target zone and the correlation of absorption with efficacy.

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