1080 lines
86 KiB
HTML
1080 lines
86 KiB
HTML
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<h1></h1>
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<p></p>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: large"
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><strong>Rosacea, inflammation, and aging:</strong> <strong>The inefficiency of stress</strong
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></span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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><em>Rosacea, or acne rosacea, has been defined as "vascular and follicular dilation involving the
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nose and contiguous portions of the cheeks . . ." that may involve persistent erythema with
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hyperplasia of sebaceous glands. </em><em><strong>Stedman's Medical Dictionary 23rd
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edition.</strong></em></span></span></span>
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</blockquote>
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<blockquote></blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Light-skinned people, especially women between the ages of 30 and 50, sometimes develop a
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persistent redness of their cheeks and nose. It may begin as a tendency to flush excessively,
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but the blood vessels can become chronically dilated. Similar processes occur in dark-skinned
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people less frequently.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The eyes are sometimes involved, with redness of the exposed areas (conjuctival hyperemia). New
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blood vessels develop in the area, and the flow of blood through the affected tissue is greatly
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increased. The tissues become thickened and fibrotic, with the multiplication of fibroblasts and
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the increased deposition of collagen.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The cornea normally receives its oxygen from the air, and its nutrients from the aqueous humor. As
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rosacea of the eye develops, the blood vessels surrounding the cornea become increasingly
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visible, and, especially on the inner (nasal) side of the eye, the vessels tend to enlarge and
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become tortuous. Rhinophyma, or potato nose, has been described as a late development of
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rosacea.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Too often, the medical reaction is to give the condition a name, and to distinguish its variants as
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if they were different problems, and then to use the most direct means to eliminate the problem
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they have defined.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>A typical attitude is that "Rosacea is an enigmatic disease with multiple exacerbations and
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remissions, and, unfortunately, treatment is directed toward symptomatic control rather than
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cure" (Randleman).</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Lasers or other radiation, caustic chemical abrasion, surgical planing and dermal shaves, and other
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forms of surgery may be used to destroy the superficial blood vessels, and to reduce the
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enlarged nose or other irregularities. A few decades ago, when rosacea was believed to be the
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result of a local infection, antibiotics were used to treat it, and some of them, including
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tetracycline, helped. It was discovered that some antibiotics have anti-inflammatory actions,
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apart from their germicidal effects, and now it is very common to prescribe the chronic use of
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tetracycline to suppress symptoms.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Rosacea, and the fibrotic changes associated with it (pingueculae and pterygia in the eyes,
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rhinophyma of the nose, etc.), are much more than "cosmetic" issues, involving the skin and eye
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surface. If the invasive proliferation of blood vessels can be prevented, it's important to do
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that, because, for example, pannus/neovascularization of the cornea can seriously impair
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vision. </span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>But possibly the strangest thing about the relationship of the medical profession to rosacea is
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that its essential features, invasive neovascularization and fibrotic growth, are of great
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interest when they occur elsewhere, and many physiological processes are known to regulate the
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growth of blood vessels and fibroblasts, but nearly all the attention given to rosacea and
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rhinophyma concerns control of symptoms for cosmetic effect. Rosacea is a physiological problem
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that deserves consideration in the light of all that's known about physiology and developmental
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biology.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The increased incidence of rosacea after the age of 30, and the fact that it occurs most commonly
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in the areas that are most exposed to sunlight (bald men sometimes develop it on the top of the
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head), indicate that aging and irritation are essential causes. Stress, irritation (such as
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produced by ultraviolet or ionizing radiation or free radicals), and aging are known to cause
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disorganized growth of fibrous and vascular tissues in various parts of the body. The occurrence
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of these processes at the surface, where the changes can be observed immediately, and without
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invasive procedures, should have aroused wide interest among those who study kidney disease,
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diabetes, and other degenerative diseases in which fibrosis and neovascularization play
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important roles.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>A localized stress or irritation at first produces vasodilation that increases the delivery of
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blood to the tissues, allowing them to compensate for the stress by producing more energy. Some
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of the agents that produce vasodilation also reduce oxygen consumption (nitric oxide, for
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example), helping to restore a normal oxygen tension to the tissue. Hypoxia itself (produced by
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factors other than irritation) can induce vasodilation, and if prolonged sufficiently, tends to
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produce neovascularization and fibrosis. </span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Sensitivity to the harmful effects of light can be increased by some drugs and by excess porphyrins
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produced in the body (and by the porphyrin precursor, delta-amino levulinic acid), leading to
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rosacea, so those factors should be considered, but too often alcohol (which can cause porphyrin
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to increase) is blamed for rosacea and rhinophyma, without justification. There are many ways in
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which poor health can increase light sensitivity. Some types of excitation produced by
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metabolites (or by the failure of inhibitory metabolites) can produce vasodilation, involving
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the release of nitric oxide (Cardenas, et al., 2000), setting off a series of potentially
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pathological reactions, including fibrosis. The nitric oxide increases glycolysis while lowering
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energy production. The excitatory metabolite glutamate, and nitric oxide, are both inhibited by
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aspirin (Moro, et al., 2000).</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>When blood flow in skin affected by rosacea was measured, circulation was 3 or 4 times higher than
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normal (Sibenge & Gawkrodger, 1992), and oxygen tension may be increased. An inability to
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extract oxygen from the blood, or to use it to produce energy, will produce the same hyperemia
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that would be produced by a lack of oxygen. These measurements suggest that mitochondrial
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defects would be the best place to look for a general cause of rosacea.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>When mitochondria are damaged, active cells produce increased amounts of lactic acid, even in the
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presence of adequate oxygen. Otto Warburg identified this kind of metabolism, aerobic
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glycolysis, as an essential feature of cancer, and showed that it could be produced by stress,
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ionizing radiation, carcinogenic toxins, and even by a simple oxygen deficiency. Other
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investigators around the same time showed that lactic acid produces vasodilation (for example,
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in the cornea), and more recently it has been shown to promote the development of fibrosis, and
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it has been called a "phlogogen," a promoter of inflammation. </span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Riboflavin, vitamin B2, is an essential component of the mitochondrial respiratory enzymes, and it
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is very easily destroyed by light (blue light and especially ultraviolet). When it is excited by
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high energy light, it can spread the damage to other components of the mitochondria, including
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the cytochromes and the polyunsaturated fatty acids. The other B vitamins are affected when
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riboflavin's actions are disturbed.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Vitamin K is also extremely light sensitive, and it interacts closely with coenzyme Q in regulating
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mitochondrial metabolism. For example, mitochondrial Complex-I, NADH-ubiquinone reductase, is
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probably the most easily damaged part of the mitochondrion, and it is protected by vitamin K.
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Vitamin E, coenzyme Q, and the polyunsaturated fatty acids are also light sensitive, and they
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are more susceptible to free radical damage when vitamin K is deficient.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Niacinamide, one of the B vitamins, provides energy to this mitochondrial system. Under stress and
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strong excitation, cells waste niacinamide-NADH, but niacinamide itself has a sedative
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antiexcitatory effect, and some of its actions resemble a hormone. Estrogen tends to interfere
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with the formation of niacin from tryptophan. Tryptophan, rather than forming the sedative
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niacin (pyridine carboxylic acid), can be directed toward formation of the excitatory quinolinic
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acid (pyridine dicarboxylic acid) by polyunsaturated fatty acids. Excitation must be in balance
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with a cell's energetic resources, and niacinamide can play multiple protective roles,
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decreasing excitation, increasing energy production, and stabilizing repair systems. The state
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of excitation and type of energy metabolism are crucial factors in governing cell functions and
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survival.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The polyunsaturated fatty acids, besides their interactions with estrogen and tryptophan
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metabolism, promote excitation and decrease energy production in several other ways. For
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example, they increase the excitatory effects of the glutamate pathways (Yu, et al., 1986;
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Nishikawa, 1994), and their breakdown products inhibit mitochondrial respiration (Humphries, et
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al., 1998; Picklo, et al., 1999; Lovell, et al., 2000).</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The excess excitation that produces nitric oxide and lactic acid lowers the energy production of
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vascular cells, possibly enough to lower their contractile ability (Geng, et al., 1992), causing
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vasodilation. When flushing is caused by a mismatch between energy supply and energy demand,
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caffeine can decrease the vasodilation (Eikvar & Kirkebøen, 1998), but when vasodilation is
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caused more physiologically by carbon dioxide, caffeine doesn't have that effect (Meno, et al.,
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2005). In a study in which drinking hot water or coffee was compared with drinking
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room-temperature coffee or caffeine, it was found that the hot liquids caused flushing, but cool
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coffee and caffeine didn't.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Caffeine increases cells' energy efficiency, and by opposing the effects of adenosine (secreted by
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cells that are stressed and energy-depleted), it can inhibit vasodilation, angioneogenesis
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(Merighi, et al., 2007; Ryzhov, et al., 2007), and fibrosis (Chan, et al., 2006). </span
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></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>One nearly ubiquitous source of inappropriate excitation and energy depletion is the endotoxin,
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bacterial lipopolysaccharides absorbed from the intestine (Wang and White, 1999). That this
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ubiquitous toxin has a role in rosacea is suggested by the observation that intestinal
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stimulation, to speed transit through the bowel, immediately relieved symptoms (Kendall, 2002).
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Increased cortisol (Simon, et al., 1998) and sepsis (Levy, 2007) interfere with mitochondrial
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energy production.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Simple nervous blushing or flushing is usually considered harmless, and when a person is
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overheated, the reddening of the skin has the function of facilitating heat loss, to restore a
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normal temperature. But even nerve-regulated flushing can involve a distinct interference with
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mitochondrial respiration, and can stimulate the overgrowth of blood vessels. </span></span
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></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Cancer's respiratory defect that Warburg identified, fermentation with lactic acid production even
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in the presence of adequate oxygen, was the result of some kind of injury to the mitochondria.
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He showed that one of the injuries that could produce aerobic glycolysis was a deficiency of
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riboflavin. He observed that tumors generally were anoxic, and that cancers typically appeared
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in the midst of tissue that was atrophying, and suggested that the cancer cells' survival was
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favored by their ability to live without oxygen. This may be relevant to the observations of
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many surgeons of a small cancer embedded in the fibrous tissue of large rhinophymas that have
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been removed.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The relatively high incidence of rosacea among women (some studies indicate that it may be 3 times
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as common in women as in men) isn't likely to be the result of greater sun exposure, so it's
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reasonable to look for hormonal causes.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>In old age, it's well recognized that men's estrogen level rises. But the estrogen industry has
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convinced women that their estrogen declines as they get older. It's common knowledge that aging
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rodents often go into "persistent estrus," and that their estrogen levels generally increase
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with age (Parkening, et al., 1978; Anisimov and Okulov, 1981). Several studies in women have
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shown that serum estrogen levels rise from the teens into the 40s (Musey, et al., 1987;
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Wilshire, et al., 1995; Santoro, et al., 1996).</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Other studies show that serum and tissue estrogen concentrations are not concordant, and that some
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tissues may contain several times as much estrogen as the serum (Jefcoate, et al., 2001). Local
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irritation increases tissue estrogen content.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The antiestrogens, especially progesterone, begin declining in the 30s, so that the rising estrogen
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has more effect on the tissues during those years. These are the years in which the incidence of
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rosacea rises suddenly. Rosacea develops later on average in men, whose estrogen levels rise
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significantly at later ages.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Estrogen's most immediate effect on cells is to alter their oxidative metabolism. It promotes the
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formation of lactic acid. In the long run, it increases the nutritional requirements for the B
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vitamins, as well as for other vitamins. It also increases the formation of aminolevulinic acid,
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a precursor of porphyrin, and increases the risk of excess porphyrin increasing light
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sensitivity. Both aminolevulinic acid and excess porphyrins are toxic to mitochondria, apart
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from their photosensitizing actions. Nitric oxide, glutamate, and cortisol all tend to be
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increased by estrogen.</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Veins and capillaries are highly sensitive to estrogen, and women are more likely than men to have
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varicose veins, spider veins, leaky capillaries, and other vascular problems besides
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rosacea. Estrogen can promote angioneogenesis by a variety of mechanisms, including nitric
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oxide (Johnson, et al., 2006). "Estrogens potentiate corticosteroid effects on the skin such as
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striae, telangiectasiae, and rosacea dermatitis" (Zaun, 1981). Early forms of oral
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contraceptives, high in estrogen, were found to increase acne rosacea more than three-fold
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(Prenen & Ledoux-Corbusier, 1971).</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Lactic acid, produced under the influence of estrogen, nitric oxide, or other problems of energy
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formation, besides causing vasodilation, also stimulates the growth of fibroblasts. Oxygen
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deprivation, or damage to mitochondria, will increase lactic acid formation, and so it will
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immediately cause vasodilation, and if the problem is prolonged, new blood vessels will grow,
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and fibrous connective tissue will increase. Estrogen stimulates collagen synthesis, and it has
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been associated with a variety of inflammatory and fibrotic conditions (for example, Cutolo, et
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al., 2003. Payne, et al., 2006, suggest the use of the anti-estrogen, tamoxifen, to treat
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rhinophyma.)</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The cornea normally contains more riboflavin even than the retina, which has a much higher rate of
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metabolism. When the cornea isn't able to get enough oxygen from the air for its needs (and if
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riboflavin is deficient, its need for oxygen is increased), surrounding blood vessels at first
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dilate in response to the diffusing lactic acid, to increase the blood supply to the edges of
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the cornea. If the problem is prolonged, the conjuctiva becomes chronically blood-shot,
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hyperemic, and larger more visible blood vessels grow, surrounding the cornea, or even invading
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the cornea. Many people, especially women, experienced problems of this sort from wearing
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contact lenses, especially when the lenses were made of materials very impermeable to oxygen
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(Dumbleton, et al., 2006).</span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>Sunlight, and mechanical obstruction of the cornea, produce very localized effects, but those local
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effects are more likely to be harmful when there is a systemic nutritional deficiency or excess
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of estrogen. When the systemic problem is very severe, the cheeks, nose, and eyes might not be
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the first tissues to experience a functional disturbance. </span></span></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>The mitochondrial inhibition produced by the action of the parasympathetic nervous system
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(occurring in simple blushing) can occur wherever those nerves act, and blood vessels in all
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parts of the body are responsive to the acetylcholine secreted by those nerves. Sleep typically
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involves a shift of dominance in the autonomic nervous system toward the parasympathetic nerves,
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with vasodilation. Nosebleeds, especially in children, commonly occur during sleep (Jarjour
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& Jarjour, 2005: high incidence in sleep, and association with migraine). </span></span
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></span>
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</blockquote>
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<blockquote>
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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: medium"
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>A 3 year-old child who had been having an average of 3 nosebleeds every day, during a nap and at
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night, for several months, also had an extreme behavior problem. He became angry and sometimes
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violent when he went a little longer than normal between meals. After an oral dose of about ten
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milligrams of riboflavin, he was able to sleep without having another recurrence of the
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nosebleeds, and his tantrums became rare. Apparently, the nerve-regulated vasodilation produced
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by sleep, combined with a riboflavin deficiency, had been enough to produce nosebleeds. The
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energy deficit resulting from a systemic riboflavin deficiency had probably been causing him to
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be abnormally sensitive to glycogen depletion, producing sudden anger. In another individual,
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the energy problem might have taken the form of a memory problem, or of a hemorrhage in the
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brain or other essential organ.</span></span></span>
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</blockquote>
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<blockquote>
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|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>A 37 year old slightly alcoholic man with a bright red nose and cheeks was an amateur fiction
|
|
writer, but he was having trouble with his memory for words, and for everyday events. Even
|
|
conversationally, he had to struggle for relatively familiar words. On the suggestion that
|
|
riboflavin might help his memory, by allowing his brain cells to use oxygen more efficiently, he
|
|
had his doctor give him an intravenous injection of B vitamins. When I saw him the next day, his
|
|
conversation was perfectly fluent, and he obviously had easy access to a good vocabulary. Just
|
|
as noticeable was the normal color of his nose and cheeks. For a week, he had a daily injection
|
|
of the B vitamins, and his nose color and vocabulary stayed normal. But on the weekend, after
|
|
not having the shots for two days, his nose and cheeks were again maraschino cherry red, and his
|
|
speech was halting, as he struggled for words. He forgot the whole episode, and neglected to
|
|
return to the doctor for more of the vitamin injections. Ten years later, he had developed a
|
|
medium-sized potato nose, and had his heart valves replaced. </span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>His vitamin requirements were apparently abnormally high. At first, the problems resulting from
|
|
damaged mitochondria seem mostly functional (flushing, mood, memory problems, etc.) and
|
|
variable, but chronically disturbed functions lead to structural, anatomical changes, as
|
|
prolonged stimulation alters tissue maintenance and growth.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Abram Hoffer, who had been treating schizophrenia and senile dementia with niacin, accidentally
|
|
discovered that it cured his bleeding gums. That led to its use to treat heart disease.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>The "orthomolecular" ideas of Hoffer and Linus Pauling were developed in a context of biochemistry
|
|
governed by genetics, molecular biology, in which the goal was to provide a chemical that was
|
|
lacking because of a genetic defect in metabolism. Their idea of using nutrients as drugs has
|
|
led to many unphysiological practices, in which an isolated nutrient is supposed to have a
|
|
drug-like action, and if in isolation it doesn't act like a drug, then it should be used only
|
|
according to the normal genetically determined nutritional requirement.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>But in reality, nutritional requirements are strongly influenced by history and present
|
|
circumstances. For example, when corneal mitochondria have been damaged by riboflavin
|
|
deficiency, they have been found to subsequently require more than the normal amount of the
|
|
vitamin to function properly. And the presence of a certain amount of one nutrient often
|
|
increases or decreases the amount of other nutrients needed.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>When the interactions among energy expenditure and energy production, and cellular activation and
|
|
cellular inhibition, are taken into account, then it's clear that any particular problem is
|
|
likely to have many causes and many factors that could contribute to a cure.</span></span></span
|
|
>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Lactate, glutamate, ammonium, nitric oxide, quinolinate, estrogen, histamine, aminolevulinate,
|
|
porphyrin, ultraviolet light, polyunsaturated fatty acids and endotoxin contribute to excitatory
|
|
and excitotoxic processes, vasodilation, angioneogenesis, and fibrosis. </span></span
|
|
></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Carbon dioxide, glycine, GABA, saturated fatty acids (for example, Nanji, et al., 1997), vitamin K,
|
|
coenzyme Q10, niacinamide, magnesium, red light, thyroid hormone, progesterone, testosterone,
|
|
and pregnenolone are factors that can be increased to protect against inappropriate cellular
|
|
excitation.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>All of the nutritional factors that participate in mitochondrial respiration contribute to
|
|
maintaining a balance between excessive excitation and protective inhibition. Riboflavin,
|
|
coenzyme Q10, vitamin K, niacinamide, thiamine, and selenium are the nutrients that most
|
|
directly relate to mitochondrial energy production. </span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Coffee is often avoided by people with rosacea, but it is a very good source of niacin and
|
|
magnesium, and caffeine has some of the same cell-protective functions as niacinamide.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>People suffering from rosacea have been found to be more likely than average to have suffered from
|
|
styes in childhood, to have varicose veins and spider veins, and to suffer from migraines and
|
|
depression. </span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Hypothyroidism has been identified as a factor in all of those. Good thyroid function is necessary
|
|
for resistance to bacterial infection, for regulation of blood sugar, neurotransmitters, and
|
|
hormones related to mood, and for the formation of progesterone. Progesterone regulates smooth
|
|
muscle tone, including the walls of veins, so that a deficiency allows veins to enlarge. It also
|
|
prevents overgrowth of fibrotic tissue, and in some contexts may inhibit angioneogenesis.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>GABA itself tends to raise body temperature (Ishiwata, et al., 2005), by controlling vasodilation,
|
|
and the factors such as progesterone which protect mitochondrial energy production are also
|
|
thermogenic, supporting the GABA system. Flushing, both by directly causing heat loss and by
|
|
reducing mitochondrial energy production, tends to lower body temperature.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>The sun-damaged areas in rosacea can be directly provided with some of the protective factors by
|
|
applying them topically. In the same way that topical lactate can cause vasodilation and
|
|
disturbed energy metabolism (Rendl, et al., 2001), topical niacinamide, progesterone, vitamin K,
|
|
and coenzyme Q10 can improve the metabolism and function of the local tissues. Riboflavin can
|
|
probably be useful when applied topically, but because of its extreme sensitivity to light, it
|
|
should usually be used only internally, unless the treated skin is covered to prevent exposure
|
|
to light. Topically applied caffeine, even after sun exposure, can reduce local tissue damage
|
|
(Koo, et al., 2007). Aspirin and saturated fats can also be protective when applied
|
|
topically.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Some of the benefit from antibiotics probably results from the reduced endotoxin stress when
|
|
intestinal bacteria are suppressed. However, antibiotics can kill the intestinal bacteria that
|
|
produce vitamin K, so it's important to include that in the diet when antibiotics are
|
|
used.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Some fibers, such as raw carrots, that are effective for lowering endotoxin absorption also contain
|
|
natural antibiotics, so regular use of carrots should be balanced by occasional supplementation
|
|
with vitamin K, or by occasionally eating liver or broccoli.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Abram Hoffer's research was instrumental in getting niacin recognized as a heart protective drug,
|
|
but nearly everyone who prescribes it does so to lower blood lipids. That wasn't Hoffer's
|
|
understanding of its function. He thought it acted directly on blood vessels to protect their
|
|
integrity. During his studies of its effects on heart disease, he saw that it also lowered
|
|
cancer mortality, and so began treating cancer patients with it, with considerable success, but
|
|
there was no medical cliché that could allow the profession to follow in that
|
|
direction. </span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>The arguments I have outlined for considering rosacea to be essentially a problem of metabolic
|
|
energy, and the mechanisms that I mention for restoring mitochondrial functions, might seem more
|
|
complex than Hoffer's orthomolecular views. However, this approach is actually much simpler
|
|
conceptually than any of the ideologies of drug treatment. It simply points out that certain
|
|
excitatory factors can interfere with energy production, and that there are opposing
|
|
"inhibitory" factors that can restore energy efficiency. Sometimes, using just one or two of the
|
|
factors can be curative.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
>Because mitochondrial respiration is very similar in every kind of tissue, a physiological view of
|
|
rosacea could incline us toward considering the effects of these metabolic factors in other
|
|
organs during stress and aging--what would the analogous condition of rosacea and rhinophyma be
|
|
in the brain, heart, liver, or kidney?</span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: medium"
|
|
><strong><h3>REFERENCES</h3></strong></span></span></span>
|
|
</blockquote>
|
|
<blockquote></blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Probl Endokrinol (Mosk), 1981 Mar-Apr, 27:2, 48-52. <strong>[Blood estradiol level and
|
|
G2-chalone content in the vaginal mucosa in rats of different ages]</strong> Anisimov
|
|
VN; Okulov VB "17 beta-Estradiol level was higher in the blood serum of rats aged 14 to 16
|
|
months with regular estral cycles during all the phases as compared to that in 3- to 4-month-old
|
|
female rats." </span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Invest Ophthalmol Vis Sci. 1991 Jun;32(7):1981-5. <strong>Analysis of flavins in ocular
|
|
tissues of the rabbit</strong>. Batey DW, Eckhert CD. Riboflavin is the precursor of flavin
|
|
mononucleotide (FMN) and flavin adenine dinucleotide (FAD), coenzymes required for the activity
|
|
of flavoenzymes involved in the transfer of electrons in oxidation-reduction reactions. Flavins
|
|
are light sensitive and rapidly degrade when exposed to light in the near ultraviolet and
|
|
visible wavelengths. Some of the byproducts of flavin photodegradation are toxic. A quantitative
|
|
survey of flavins in rabbit ocular tissues is reported. Adult male Dutch-Belt Rabbits were fed
|
|
purified diets containing 3, 30, or 300 mg riboflavin/kg for 1 month. A method of aqueous
|
|
extraction and high-performance liquid chromatography with fluorescence detection was used to
|
|
measure riboflavin, FMN, and FAD in cornea, lens cortex, lens nucleus, retina, and blood. The
|
|
retina contained the highest flavin concentration. In all tissues, the primary flavin was FAD
|
|
followed by FMN and riboflavin. The highest concentration of riboflavin occurred in the cornea
|
|
followed by the retina, lens cortex, and lens nucleus. A trend toward increasing concentrations
|
|
of riboflavin occurred in the retina and blood in response to excess dietary riboflavin, but the
|
|
concentration changes were not statistically significant. The highest concentration of FAD and
|
|
FMN occurred in the retina followed by the cornea and the lens cortex and nucleus. The relative
|
|
contribution of riboflavin, FMN, and FAD to the total flavin pool was markedly different in the
|
|
various tissues of the eye. The proportion of tissue flavins present as riboflavin decreased
|
|
from anterior to posterior. It was highest in the cornea followed by lens and retina. The
|
|
pattern of distribution for FMN was: cornea greater than retina greater than lens cortex and
|
|
nucleus.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Boll Ocul. 1955 Mar;34(3):157-70. <strong>[Clinical contribution on riboflavin deficiency of
|
|
the eye.]</strong> [Article in Italian] Bellomio S.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Eur J Pharmacol. 2006 Oct 10;547(1-3):184-91. <strong>Characterization of the antinociceptive
|
|
and anti-inflammatory activities of riboflavin in different experimental models.</strong
|
|
> Bertollo CM, Oliveira AC, Rocha LT, Costa KA, Nascimento EB Jr, Coelho MM.</span></span
|
|
></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Vestn Oftalmol. 1961 Nov-Dec;74:48-53. <strong>[The content of riboflavin and ascorbic acid in
|
|
the cornea in burns of the eye.]</strong> [Article in Russian] Blinova LI, Tsypin LM,
|
|
Sheinberg AI.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Neurochem. 2000 May;74(5):2041-8. <strong>Implication of glutamate in the expression of
|
|
inducible nitric oxide synthase after oxygen and glucose deprivation in rat forebrain
|
|
slices.</strong> Cardenas A, Moro MA, Hurtado O, Leza JC, Lorenzo P, Castrillo A,
|
|
Bodelon OG, Bosca L, Lizasoain I.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Br J Pharmacol. 2006 Aug;148(8):1144-55. <strong>Adenosine A(2A) receptors play a role in the
|
|
pathogenesis of hepatic cirrhosis.</strong> Chan ES, Montesinos MC, Fernandez P, Desai
|
|
A, Delano DL, Yee H, Reiss AB, Pillinger MH, Chen JF, Schwarzschild MA, Friedman SL, Cronstein
|
|
BN.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Clin Exp Rheumatol. 2003 Nov-Dec;21(6):687-90. <strong>New roles for estrogens in
|
|
rheumatoid arthritis.</strong>Cutolo M, Capellino S, Montagna P, Villaggio B, Sulli A,
|
|
Seriolo B, Straub RH. Sex hormones appear to play an important role as modulators of autoimmune
|
|
disease onset/perpetuation. Steroid hormones are implicated in the immune response, with
|
|
estrogens as enhancers at least of humoral immunity, and androgens and progesterone (and
|
|
glucocorticoids) as natural immune suppressors. Serum levels of estrogens have been found to be
|
|
normal in rheumatoid arthritis (RA) patients. Synovial fluid levels (SF) of proinflammatory
|
|
estrogens relative to androgens are significantly elevated in both male and female RA patients
|
|
as compared to controls, which is most probably due to an increase in local aromatase activity.
|
|
Thus, available steroid pre-hormones are rapidly converted to proinflammatory estrogens in the
|
|
synovial tissue in the presence of inflammatory cytokines (i.e. TNF alpha, IL-1, IL-6). The
|
|
increased estrogen concentrations observed in RA SF of both sexes are characterized mainly by
|
|
the hydroxylated forms, in particular 16 alpha-hydroxyestrone, showing a mitogenic stimulating
|
|
role. Indeed, recent studies by us indicate that 17-beta estradiol (E2) clearly enhanced the
|
|
expression of markers of cell growth and proliferation, whereas testosterone (T) induced an
|
|
increase in markers indicating DNA damage and apoptosis. In particular, our data further shows
|
|
that the enhancing role of estrogens on the immune/inflammatory response is exerted by
|
|
activating the NFkB complex. In conclusion, locally increased estrogens may exert activating
|
|
effects on synovial cell proliferation, including macrophages and fibroblasts, suggesting new
|
|
roles for estrogens in RA.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Tidsskr Nor Laegeforen. 1998 Mar 30;118(9):1390-5. <strong>[Receptor mediated effects of
|
|
adenosine and caffeine] </strong>[Article in Norwegian] Eikvar L, Kirkebøen KA.
|
|
"Adenosine consists of one ribose and one purine moiety and binds to specific receptors on cell
|
|
membranes. The receptors are coupled to G-proteins and additionally to various effector-systems.
|
|
When a mismatch occurs between energy supply and energy demand, adenosine is produced by the
|
|
catabolism of adenosine triphosphate. The metabolism of an organ is thereby coupled to the local
|
|
blood supply (metabolic vasodilation)."</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Arch Dermatol. 1988 Jan;124(1):72-9. <strong>Health effects of sunlight exposure in the United
|
|
States. Results from the first National Health and Nutrition Examination Survey,
|
|
1971-1974.</strong><hr /></span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Nippon Ganka Gakkai Zasshi. 1961 Dec 10;65:2439-44. <strong>[The effects of vitamin B2 group
|
|
on the corneal metabolism. I.]</strong> [Article in Japanese] Funatsu H, Motegi
|
|
T.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Cosmet Dermatol. 2004 Apr;3(2):88-93. <strong>Nicotinic acid/niacinamide and the
|
|
skin.</strong> Gehring W.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Circ Res. 1992 Nov;71(5):1268-76. <strong>Interferon-gamma and tumor necrosis factor synergize
|
|
to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth
|
|
muscle cells.</strong> Geng Y, Hansson GK, Holme E. "Nitric oxide (NO) is an important
|
|
signal substance in cell-cell communication and can induce relaxation of blood vessels by
|
|
activating guanylate cyclase in smooth muscle cells (SMCs)." "It was recently shown that SMCs
|
|
may themselves produce NO or an NO-related compound. We have studied NO production and its
|
|
effects on energy metabolism in cultured rat aortic smooth muscle cells. It was observed that
|
|
the cytokines, interferon-gamma and tumor necrosis factor-alpha, synergistically induced an
|
|
arginine-dependent production of NO in these cells. This was associated with an inhibition of
|
|
complex I (NADH: ubiquinone oxidoreductase) and complex II (succinate: ubiquinone
|
|
oxidoreductase) activities of the mitochondrial respiratory chain, suggesting that NO blocks
|
|
mitochondrial respiration in these cells. Lactate accumulated in the media of the cells,
|
|
implying an increased anaerobic glycolysis, but there was no reduction of viability. An
|
|
NO-dependent inhibition of mitochondrial respiration and a switch to anaerobic glycolysis would
|
|
reduce energy production of the SMCs. This would in turn reduce the contractile capacity of the
|
|
cell and might represent another NO-dependent vasodilatory mechanism."</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Q Bull Northwest Univ Med Sch. 1952;26(2):120-3. <strong>Riboflavin and the cornea.</strong
|
|
> Gordon OE.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Bull Soc Fr Dermatol Syphiligr. 1950 May-Jun;57(3):277-80. <strong>Cutaneous-mucosal
|
|
ariboflavinosis; rosacea of cornea and medio-facial seborrheic dermatitis.</strong
|
|
> Gougerot H, Grupper C, Plas G.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Br J Dermatol. 2005 Dec;153(6):1176-81. <strong>Comorbidity of rosacea and depression: an
|
|
analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory
|
|
Care Survey--Outpatient Department data collected by the U.S. National Center for Health
|
|
Statistics from 1995 to 2002.</strong> Gupta MA, Gupta AK, Chen SJ, Johnson AM.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Biochemistry. 1998 Nov 10;37(45):15835-41. <strong>Selective inactivation of
|
|
alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase: reaction of lipoic acid with
|
|
4-hydroxy-2-nonenal.</strong>Humphries KM, Szweda LI. "Previous research has established
|
|
that 4-hydroxy-2-nonenal (HNE), a highly toxic product of lipid peroxidation, is a potent
|
|
inhibitor of mitochondrial respiration. HNE exerts its effects on respiration by inhibiting
|
|
alpha-ketoglutarate dehydrogenase (KGDH). Because of the central role of KGDH in metabolism and
|
|
emerging evidence that free radicals contribute to mitochondrial dysfunction associated with
|
|
numerous diseases, it is of great interest to further characterize the mechanism of inhibition."
|
|
"These results therefore identify a potential mechanism whereby free radical production and
|
|
subsequent lipid peroxidation lead to specific modification of KGDH and PDH and inhibition of
|
|
NADH-linked mitochondrial respiration."</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Biochemistry. 1998 Jan 13;37(2):552-7. <strong>Inhibition of NADH-linked mitochondrial
|
|
respiration by 4-hydroxy-2-nonenal.</strong> Humphries KM, Yoo Y, Szweda LI. During the
|
|
progression of certain degenerative conditions, including myocardial ischemia-reperfusion
|
|
injury, mitochondria are a source of increased free-radical generation and exhibit declines in
|
|
respiratory function(s). It has therefore been suggested that oxidative damage to mitochondrial
|
|
components plays a critical role in the pathology of these processes. Polyunsaturated fatty
|
|
acids of membrane lipids are prime molecular targets of free-radical damage. A major product of
|
|
lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is highly cytotoxic and can readily react with
|
|
and damage protein. In this study, the effects of HNE on intact cardiac mitochondria were
|
|
investigated to gain insight into potential mechanisms by which free radicals mediate
|
|
mitochondrial dysfunction. Exposure of mitochondria to micromolar concentrations of HNE caused
|
|
rapid declines in NADH-linked but not succinate-linked state 3 and uncoupled respiration. The
|
|
activity of complex I was unaffected by HNE under the conditions of our experiments. Loss of
|
|
respiratory activity reflected the inability of HNE-treated mitochondria to meet NADH
|
|
demand during maximum rates of O2 consumption. HNE exerted its effects on intact mitochondria by
|
|
inactivating alpha-ketoglutarate dehydrogenase. These results therefore identify a potentially
|
|
important mechanism by which free radicals bring about declines in mitochondrial
|
|
respiration.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Tohoku J Exp Med. 1954 Dec 25;61(1):93-104. <strong>Contribution to the ocular manifestation
|
|
of riboflavin deficiency. </strong>Irinoda K, Sato S.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Brain Res. 2005 Jun 28;1048(1-2):32-40. <strong>Changes of body temperature and
|
|
thermoregulatory responses of freely moving rats during GABAergic pharmacological
|
|
stimulation to the preoptic area and anterior hypothalamus in several ambient
|
|
temperatures. </strong>Ishiwata T, Saito T, Hasegawa H, Yazawa T, Kotani Y, Otokawa M,
|
|
Aihara Y.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Pediatr Neurol. 2005 Aug;33(2):94-7. <strong>Migraine and recurrent epistaxis in
|
|
children. </strong>Jarjour IT, Jarjour LK.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Natl Cancer Inst Monogr 2000;(27):95-112. <strong>Tissue-specific synthesis and oxidative
|
|
metabolism of estrogens. </strong>Jefcoate CR, Liehr JG, Santen RJ, Sutter TR, Yager
|
|
JD, Yue W, Santner SJ, Tekmal R, Demers L, Pauley R, Naftolin F, Mor G, Berstein L "However,
|
|
breast cancer tissue E2 levels are 10-fold to 50-fold higher in postmenopausal women than
|
|
predicted from plasma levels."</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Endocrine. 2006 Dec;30(3):333-42. <strong>Effects of estradiol-17beta on expression of mRNA
|
|
for seven angiogenic factors and their receptors in the endometrium of ovariectomized (OVX)
|
|
ewes. </strong>Johnson ML, Grazul-Bilska AT, Redmer DA, Reynolds LP.</span></span
|
|
></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Clin Exp Dermatol. 2004 May;29(3):297-9. <strong>Remission of rosacea induced by reduction of
|
|
gut transit time.</strong> Kendall SN. Rosacea is a chronic disorder characterized by
|
|
hypersensitivity of the facial vasculature, presenting with intense flushing eventually leading
|
|
to chronic erythema and telangiectasia. Although the precise aetiology of rosacea is not known,
|
|
numerous associations with inflammatory gastrointestinal tract disorders have been reported.
|
|
Furthermore, substance P-immunoreactive neurones occur in considerably greater numbers in tissue
|
|
surrounding affected blood vessels suggesting involvement of neurogenic inflammation and
|
|
moreover plasma kallikrein-kinin activation is consistently found in patients. In this report, a
|
|
patient without digestive tract disease is described, who experienced complete remission of
|
|
rosacea symptoms following ingestion of a material intended to sweep through the digestive tract
|
|
and reduce transit time below 30 h. It is possible that intestinal bacteria are capable of
|
|
plasma kallikrein-kinin activation and that flushing symptoms and the development of other
|
|
characteristic features of rosacea result from frequent episodes of neurogenic inflammation
|
|
caused by bradykinin-induced hypersensitization of facial afferent neurones. The possible
|
|
relevance of this hypothesis to other conditions featuring afferent hypersensitivity, such as
|
|
fibromyalgia, is considered.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Br J Dermatol. 2007 May;156(5):957-64. <strong>Protection from photodamage by topical
|
|
application of caffeine after ultraviolet irradiation.</strong> Koo SW, Hirakawa
|
|
S, Fujii S, Kawasumi M, Nghiem P.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Medicina (B Aires) 1985;45(2):110-6. <strong>[Fibrosis and cirrhosis in the rabbit induced by
|
|
diethylstilbestrol and its inhibition with progesterone].</strong> [Article in Spanish]
|
|
Lanari A, de Kremer GH.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Free Radic Biol Med. 2000 Oct 15;29(8):714-20. <strong>Acrolein, a product of lipid
|
|
peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures.</strong
|
|
> Lovell MA, Xie C, Markesbery WR.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Cereb Blood Flow Metab. 2005 Jun;25(6):775-84. <strong>Effect of caffeine on cerebral blood
|
|
flow response to somatosensory stimulation.</strong> Meno JR, Nguyen TS, Jensen EM,
|
|
Alexander West G, Groysman L, Kung DK, Ngai AC, Britz GW, Winn HR. "Hypercarbic vasodilatation
|
|
was unaffected by either caffeine or theophylline."</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Mol Pharmacol. 2007 Aug;72(2):395-406. <strong>Caffeine inhibits adenosine-induced
|
|
accumulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and
|
|
interleukin-8 expression in hypoxic human colon cancer cells. </strong>Merighi S,
|
|
Benini A, Mirandola P, Gessi S, Varani K, Simioni C, Leung E, Maclennan S, Baraldi PG, Borea
|
|
PA.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Neuropharmacology. 2000 Apr 27;39(7):1309-18. <strong>Mechanisms of the neuroprotective effect
|
|
of aspirin after oxygen and glucose deprivation in rat forebrain slices.</strong> Moro
|
|
MA, De Alba J, Cardenas A, De Cristobal J, Leza JC, Lizasoain I, Diaz-Guerra MJ, Bosca L,
|
|
Lorenzo P.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Am J Obstet Gynecol 1987 Aug;157(2):312-317. <strong>Age-related changes in the female
|
|
hormonal environment during reproductive life. </strong>Musey VC, Collins DC, Musey PI,
|
|
Martino-Saltzman D, Preedy JR "We found that increased age during reproductive life is
|
|
accompanied by a significant rise in both basal and stimulated serum follicle-stimulating
|
|
hormone levels. This was accompanied by an increase in the serum level of estradiol-17 beta and
|
|
the urine levels of estradiol-17 beta and 17 beta-estradiol-17-glucosiduronate." "Serum levels
|
|
of dehydroepiandrosterone and dehydroepiandrosterone sulfate decreased with age, but serum
|
|
testosterone was unchanged."</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Hepatology. 1997 Dec;26(6):1538-45. <strong>Dietary saturated fatty acids down-regulate
|
|
cyclooxygenase-2 and tumor necrosis factor alfa and reverse fibrosis in alcohol-induced
|
|
liver disease in the rat.</strong> Nanji AA, Zakim D, Rahemtulla A, Daly T, Miao L,
|
|
Zhao S, Khwaja S, Tahan SR, Dannenberg AJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Physiol. 1994 Feb 15;475(1):83-93. <strong>Facilitatory effect of docosahexaenoic acid on
|
|
N-methyl-D-aspartate response in pyramidal neurones of rat cerebral cortex.</strong
|
|
> Nishikawa M, Kimura S, Akaike N. </span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Gerontol, 1978 Mar, 33:2, 191-6. <strong>Circulating plasma levels of pregnenolone,
|
|
progesterone, estrogen, luteinizing hormone, and follicle stimulating hormone in young and
|
|
aged C57BL/6 mice during various stages of pregnancy. </strong>Parkening TA; Lau IF;
|
|
Saksena SK; Chang MC.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Antioxid Redox Signal. 1999 Fall;1(3):255-84. <strong>4-Hydroxynonenal as a biological signal:
|
|
molecular basis and pathophysiological implications.</strong> Parola M, Bellomo G,
|
|
Robino G, Barrera G, Dianzani MU.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Ann Plast Surg. 2002 Jun;48(6):641-5. <strong>Further evidence for the role of fibrosis in the
|
|
pathobiology of rhinophyma. </strong>Payne WG, Wang X, Walusimbi M, Ko F, Wright TE,
|
|
Robson MC.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Ann Plast Surg. 2006 Mar;56(3):301-5. <strong>Down-regulating causes of fibrosis with
|
|
tamoxifen: a possible cellular/molecular approach to treat rhinophyma.</strong> Payne
|
|
WG, Ko F, Anspaugh S, Wheeler CK, Wright TE, Robson MC.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Neurochem Res. 1991 Sep;16(9):983-9. <strong>Release of arachidonic acid by NMDA-receptor
|
|
activation in the rat hippocampus.</strong> Pellerin L, Wolfe LS.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Neurochem. 1999 Apr;72(4):1617-24. <strong>4-Hydroxy-2(E)-nonenal inhibits CNS mitochondrial
|
|
respiration at multiple sites.</strong> Picklo MJ, Amarnath V, McIntyre JO, Graham DG,
|
|
Montine TJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Biochim Biophys Acta. 2001 Feb 14;1535(2):145-52. <strong>Acrolein inhibits respiration in
|
|
isolated brain mitochondria. </strong>Picklo MJ, Montine TJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Arch Belg Dermatol Syphiligr. 1971 Jul-Sep;27(3):253-8. <strong>[Hormonal contraception and
|
|
dermatology]</strong>Prenen M, Ledoux-Corbusier M. PIP: A group of 150 Belgian women aged
|
|
17-47 taking various oral contraceptives was compared with a control group of 400 with respect
|
|
to incidence of cholasma and piloseborrheic disorders. While taking pills, 10% of alopecia and
|
|
5.3% of juvenile acne cases were improved, but the following symptoms appeared: hypertrichosis
|
|
in 4%, alopecia in 14.6, juvenile acne in 16.6%, and rosaceous acne in 3.3%. The incidence of
|
|
these symptoms in the controls was cholasma .75%, hypertrichosis 5.25%, alopecia 11.5%, juvenile
|
|
acne 21%, and acne rosacea 1%. The pill seemed to aggravate cholasma and rosaceous acne or to
|
|
improve piloseborrheic symptoms, depending on whether the formulation was dominant in estrogen
|
|
or progestagen.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Ann Plast Surg. 2000 Nov;45(5):515-9. <strong>Overexpression of transforming growth factor
|
|
beta-2 and its receptor in rhinophyma: an alternative mechanism of pathobiology.</strong
|
|
> Pu LL, Smith PD, Payne WG, Kuhn MA, Wang X, Ko F, Robson MC. "These findings support the
|
|
authors' hypothesis that fibrosis may also play an important role in the pathobiology of
|
|
rhinophyma."</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<a href="http://www.emedicine.com/oph/topic115.htm" target="_blank"><span style="color: #1155cc"><span
|
|
style="font-family: georgia, times, serif"
|
|
><span style="font-size: xx-medium"><span style="font-style: normal"><span
|
|
style="font-weight: normal"
|
|
>www.emedicine.com/oph/topic115.htm</span></span></span></span></span></a>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
><span style="font-style: normal"><span style="font-weight: normal"
|
|
> Last Updated: May 14, 2007. Author: J Bradley Randleman, MD, Assistant Professor,
|
|
Department of Ophthalmology, Cornea, External Disease, and Refractive Surgery Section,
|
|
Emory University School of Medicine</span></span></span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Br J Dermatol. 2001 Jul;145(1):3-9. <strong>Topically applied lactic acid increases
|
|
spontaneous secretion of vascular endothelial growth factor by human reconstructed
|
|
epidermis.</strong> Rendl M, Mayer C, Weninger W, Tschachler E.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Nature. 1969 Aug 2;223(5205):516-7. <strong>Diminished responsiveness to thyroid hormone in
|
|
riboflavin-deficient rats.</strong> Rivlin RS, Wolf G.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Pharmacol Exp Ther. 2007 Feb;320(2):565-72. <strong>Role of adenosine receptors in the
|
|
regulation of angiogenic factors and neovascularization in hypoxia. </strong>Ryzhov S,
|
|
McCaleb JL, Goldstein AE, Biaggioni I, Feoktistov I.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Clin Endocrinol Metab 1996 Apr;81(4):1495-501, <strong>Characterization of reproductive
|
|
hormonal dynamics in the perimenopause. </strong><hr /></span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>J Am Acad Dermatol. 1992 Apr;26(4):590-3. <strong>Rosacea: a study of clinical patterns, blood
|
|
flow, and the role of Demodex folliculorum.</strong> Sibenge S, Gawkrodger DJ.</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
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style="font-size: xx-medium"
|
|
>Cesk Oftalmol. 1951;7(1):37-42. <strong>[Effect of vitamin B1 and B2 on diseases of the
|
|
cornea.]</strong> Simkova M.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>FEBS Lett. 1998 Sep 11;435(1):25-8. <strong>Glucocorticoids decrease cytochrome c oxidase
|
|
activity of isolated rat kidney mitochondria.</strong> Simon N, Jolliet P, Morin C,
|
|
Zini R, Urien S, Tillement JP. "The importance of mitochondria is rising as a target in
|
|
pathologic processes such as ischemia." "A regulation of cytochrome c oxidase activity by
|
|
glucocorticoids will be of particular interest in pathology involving metabolic insult."</span
|
|
></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Am J Ophthalmol. 1950 Jul;33(7):1127-36. <strong>The ocular manifestations of riboflavin
|
|
deficiency.</strong> Stern JJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Arch Ophthal. 1949 Oct;42(4):438-42. <strong>Conditioned corneal vascularity in riboflavin
|
|
deficiency; report of a case.</strong> Stern HJ.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Nippon Ganka Kiyo. 1962 Nov;13:489-94. <strong>[Variations of total vitamin B2 content in the
|
|
cornea, iris and ciliary body and the blood of rabbits in stress. (A preliminary
|
|
report)]</strong> [Article in Japanese] Taketani T.</span></span></span>
|
|
</blockquote>
|
|
<blockquote>
|
|
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
|
style="font-size: xx-medium"
|
|
>Free Radic Res. 1996 Jun;24(6):421-7. <strong>The effect of the lipid peroxidation product
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<p> </p>
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© Ray Peat Ph.D. 2013. All Rights Reserved. www.RayPeat.com
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