STUDY - Technical - New Dacian's Medicine
Photosensitivity
and Other Skin Reactions to Light (1)
Translation Draft
Sunlight is the most visible and obvious source of comfort in the environment. This natural inclination towards the sun has the beneficial results of heat and vitamin D synthesis, but can also produce pathological consequences. Few effects due to sun exposure have been identified outside of skin exposure, but skin exposure to sunlight can trigger immunosuppressive responses and genetic changes that may be relevant to the pathogenicity of nonmelanomic skin cancers and may infections, e.g. herpes simplex.
The sun's energy comprises a wide range of radiation, from ionizing radiation to ultra-long radio waves with very low photonical energy. Thus, the emission spectrum is displayed on new orders of magnitude, but the one that reaches the earth's surface is narrow and limited to ultraviolet (UV) components, visible light and portions of infrared. The stopping point at the short end of the UV is about 290 nm, because the stratospheric ozone consists of ionizing radiation with a wavelength of less than 100 nm and absorbs solar energy between 120 and 310 nm, thus preventing the penetration to the earth's surface of short wavelengths, higher energy and potentially more dangerous solar radiation.
Indeed, concern for the destruction of the ozone layer by chlorofluorocarbons released into the atmosphere has led to international agreements to reduce the production of these chemicals. Solar flow measurements indicate that there is a 20-fold regional variation in the amount of energy at 300 nm that reaches the earth's surface. This variability is related to the seasonal effects, the path of transmission of sunlight through ozone and air, altitude (increase of 4% for every 300 m altitude), latitude (increased intensity with decreased latitude) and the amount of clouds, fog and pollution.
Major components of the otobiological action spectrum include UV wavelengths and visible between 290 and 700 nm. In addition, wavelengths beyond 700 nm in infrared cause mostly heat, but skin warming can increase the biological response to UV spectrum wavelengths and visible. The UV spectrum is arbitrarily divided into three mar segments (A, B and C) comprising wavelengths between 10 and 400 nm. UV-C consists of wavelengths between 10 and 290 nm and does not reach the ground due to their absorption by atmospheric ozone.
These wavelengths are not a cause of photosensitivity, except for occupational environments where artificial sources of this energy are used, for example, for germicide effects. UV-B swells between 290 and 320 nm. This portion of the photobiological action spectrum is most effective in producing redness or erythema of the human skin and is therefore sometimes called the "spectrum of sunburn". UV-A represents those wavelengths between 320 and 400 nm (UV. A1 between 340-400 nm and UV-A2 between 320 and 340 nm) and are about a thousand times less effective in producing skin hyperemia than UV-B.
The visible wavelengths between 400 and 700 nm comprise the well-known white light, which when passed through a prism turns out to be composed of different colours, comprising violet, indigo, blue, green, yellow, orange and red. The energy contained in photons in the visible spectrum is not usually capable of damage to human skin in the absence of a photosensitizing chemical. Energy absorption is decisive for the appearance of photosensitivity. Thus, the absorption spectrum of a molecule is defined by the range of wavelengths absorbed by it, while the spectrum of action for an effect of incident radiation is defined by the range of wavelengths that provoke the response.
Photosensitivity occurs when a photon-absorbing chemical (chromophor) present in the skin absorbs incident energy, becomes aroused and transfers the energy absorbed to different structures or to oxygen. The energy absorbed must be dissipated by processes comprising heat, fluorescence and phosphorescence. It is important to point out that absorption spectra and action spectra should not be superposable, but there must be overlap at some point to produce photosensitivity.
Now, a few things about skin structure and function. Exposure of the skin to the sun allows the absorption of wavelengths and the transmission of others. Essentially, human skin is a sandwich made up of two distinct compartments, the dermis and epidermis, separated by a basal membrane. The epidermis is a squamous layered epithelium, comprising on the surface the corneal layer (a compact membrane rich in proteins and lipids), the granular layer, the spinous layer and the basal cell layer. The basal cell layer contains a heterogeneous population of cells, some of which migrate upwards in the process of terminal differentiation leading to the expression of specific keratin genes and the formation of the corneal layer.
Epidermal cells are resident keratocytes and melanocytes and immigrant cells, comprising immunologically active cells Langerhans, lymphocytes, polymorphonuclear leukocytes, monocytes and macrophages, making the epidermis a major component of the immune system. Branches of the sensitive nerve endings also reach this compartment.
The second major component of the skin is the dermis, which is relatively stretched and less densely populated by cells, including fibroblas, endothelial cells inside dermal vessels and mastocytes. Tissue macrophages and rarely distributed inflammatory cells are also present. All these cells exist inside an extracellular matrix of collagen, elastin and glycosaminoglycans. Unlike the epidermis, the rich vascularization of the dermis allows it to play an important role in temperature regulation.
Let's see what's with ultraviolet radiation (UVR) and skin... The epidermis and dermis contain several chromophores capable of interacting with the incident solar energy. These interactions include reflection, refraction, absorption and transmission. The corneal layer is a major impediment to UV-B transmission and less than 10% of the incident wavelengths in this region penetrate the basal membrane. Approximately 3% of radiation below 300 nm, 20% of radiation below 360 nm and 33% of short visible radiation reaches the basal cellular layer of untanned human skin. Proteins and nucleic acids absorb intensely from the short UV-B range. In contrast, UV-A 1 and 2 penetrate the epidermis effectively to reach the dermis, where they probably produce changes in structural and matrix proteins, which contribute to the aging appearance of skin chronically exposed to the sun, especially in individuals with light skin.
One of the consequences of UV-B absorption by DNA is the production of pyridimine dimers. These structural changes can be repaired by mechanisms that lead to the recognition, excision and restoration of the normal base sequence. Effective repair of these structural aberrations is crucial because individuals with poor DNA repair have an increased risk of developing skin cancer. For example, patients with xeroderma pigmentosum, a recessive autosomal condition, are characterized by diminished repair, to varying degrees, of UV-induced photoproducts and their skin may develop, in the first two weeks of life, the xerotic appearance of photosenescence, as well as bazo and spinocellular carcinomas and melanomas.
Now, a few things about chromophores and skin optics. Chromophores are endogenous or exogenous chemical compounds that can absorb physical energy. Endogenous chromophores of the skin are of two types: 1. chemicals that are normally present, including nucleic acids, proteins, lipids and 7-dehydrocholesterol, the precursor of vitamin D and 2. Sum chemicals are porphyrins, synthesized elsewhere in the body, which circulate in the bloodstream and diffuse into the skin. Normally only traces of porphyrins are present in the skin, but in diseases called porphyries, increased amounts of porphyrins are released into circulation and transported to the skin, where they absorb the incidental energy both in the Soret band, around 400 nm (short visible spectrum), and to a lesser extent, in the red portion of the visible spectrum (580 - 660 nm). This leads to structural skin lesions, which can manifest as erythema, edema, hives or bubble formation.
In the end of this post I will present a few things about the acute effects of sun exposure. The immediate skin consequences of sun exposure include sunburn and vitamin D synthesis. Sunburn is a very common condition of human skin caused by exposure to UV radiation. In general, an individual's ability to tolerate sunlight is inversely proportional to his or her melanic pigmentation. Melanin is a complex polymer of tyrosine, which functions as an effective neutral density filter with wide absorption in the UV portion of the solar spectrum. Melanin is synthesized into specialized epidermal dendritic cells called melanocytes and is stored in melanosomes, which are transferred through dendritic extensions into keratocytes, where they provide photoprotection.
Sun-induced melanogenesis is a result of increased tyrosine sabroadsis activity in melanocytes, which in turn may be due to a combined release of eicosanoid and endotelin-1. Tolerance to sun exposure is based on the effectiveness of the epidermal melanic unit and can usually be certified in anamnesis by two questions: 1. do you experience burns after sun exposure? and 2. tan after sun exposure?. From the answers to these questions it is usually possible to divide the population into six skin types, ranging from type I (always burns appear, never tanned) to type VI (never burn, always tan).
There are two general theories about the pathogenesis of the solar burn reaction. First, the latency phase over time after skin exposure and the appearance of visible erythema (usually 4-12 hours) suggests the existence of an epidermal chromatophorus that causes delayed production and/ or the release of one(s) vasoactive mediator(s) or cytokines that diffuse to dermal vessels to cause vasodilation. Indeed, UV radiation stimulates the release of a large number of pro-inflammatory cytokines and nitrous oxide by keratinocytes.
Secondly, it is possible that the small amount of incidental UV-B (10% or less) that penetrates to the dermis can be absorbed directly by the endothelial cells in the vessels, thus directly producing vasodilation (but the problem is still unresolved). The spectrum of action for sunburn erythema includes UV-B and UV-A radiation. Shorter UV-B photons are at least a thousand times more effective than longer UV-B and UV-A photons in challenging response. However, UV-A can contribute to sunburn erythema at noon, when there are far more UV-A than UV-B.
The mechanism of the lesion remains incomplete, but the spectrum of action for UV-B erythema closely resembles the absorption spectrum for DNA after adjustments for the absorption of incident energy by the corneal layer. Apoptotic keratinocytes (so-called solar burn cells) are histologically visible within the first hour of exposure and are maximum within the first 24 hours. UV-A are less effective than UV-B in producing solar burn cells. Mastocytes can release mediators of inflammation after exposure to UV-A and UV-B increase histamine levels in human skin suction bubbles, which return to normal after 24 hours (before visible erythema disappears). Prostaglandin E2 increases to about 150% at 24 hours from the control level and then decreases. Because prostaglandins cause both pain and erythema when injected intradermally, their presence in suction bubbles after exposure to UV-B suggests a role in UV-B erythema.
There may be an age-related decline in the amount of detectable inflammatory mediators in human skin after UV-B irradiation. UV-A erythema induces few solar burn epidermal cells, but vascular endothelial lesions are larger than for UV-B. In addition, there are three elevated levels of arachidonic acid and prostaglandins D2, E2 and I2, which peak in 5-9 hours and then decrease before the appearance of maximum erythema. Despite evidence of the role of prostaglandins for both UV-B and UV-A irradiated skin, the administration of non-steroidal anti-inflammatory drugs is more effective in reducing UV-B-produced erythema than UV-A. UV-B also induces within a few hours of exposure.
From the point of view of vitamin D photochemistry, skin exposure to UV-B causes the photolysis of provitamin D3 (7-dehydrocholesterol) from the epidermis to previtamin D3, which is then subjected to temperature-dependent isomerization to form the hormone-vitamin D3 stable. This compound then diffuses into dermal vascularization and into the systemic circuit, where it is converted into the functional hormone 1,25-dihydroxy-vitamin D3. Vitamin D metabolites in circulation or those produced in the skin themselves can increase epidermal differentiation signals. Aging substantially decreases the ability of human skin to synthesize vitamin D3. This, along with the widely recommended use of UV-B-filtered sunscreens, has led to concern that vitamin D deficiency could become a significant problem in the elderly. Indeed, studies have shown that the use of sunscreen creams can hinder the production of vitamin D3 in human skin.
And I'm done for today... Posting number 200 (two hundred).
Sunlight is the most visible and obvious source of comfort in the environment. This natural inclination towards the sun has the beneficial results of heat and vitamin D synthesis, but can also produce pathological consequences. Few effects due to sun exposure have been identified outside of skin exposure, but skin exposure to sunlight can trigger immunosuppressive responses and genetic changes that may be relevant to the pathogenicity of nonmelanomic skin cancers and may infections, e.g. herpes simplex.
The sun's energy comprises a wide range of radiation, from ionizing radiation to ultra-long radio waves with very low photonical energy. Thus, the emission spectrum is displayed on new orders of magnitude, but the one that reaches the earth's surface is narrow and limited to ultraviolet (UV) components, visible light and portions of infrared. The stopping point at the short end of the UV is about 290 nm, because the stratospheric ozone consists of ionizing radiation with a wavelength of less than 100 nm and absorbs solar energy between 120 and 310 nm, thus preventing the penetration to the earth's surface of short wavelengths, higher energy and potentially more dangerous solar radiation.
Indeed, concern for the destruction of the ozone layer by chlorofluorocarbons released into the atmosphere has led to international agreements to reduce the production of these chemicals. Solar flow measurements indicate that there is a 20-fold regional variation in the amount of energy at 300 nm that reaches the earth's surface. This variability is related to the seasonal effects, the path of transmission of sunlight through ozone and air, altitude (increase of 4% for every 300 m altitude), latitude (increased intensity with decreased latitude) and the amount of clouds, fog and pollution.
Major components of the otobiological action spectrum include UV wavelengths and visible between 290 and 700 nm. In addition, wavelengths beyond 700 nm in infrared cause mostly heat, but skin warming can increase the biological response to UV spectrum wavelengths and visible. The UV spectrum is arbitrarily divided into three mar segments (A, B and C) comprising wavelengths between 10 and 400 nm. UV-C consists of wavelengths between 10 and 290 nm and does not reach the ground due to their absorption by atmospheric ozone.
These wavelengths are not a cause of photosensitivity, except for occupational environments where artificial sources of this energy are used, for example, for germicide effects. UV-B swells between 290 and 320 nm. This portion of the photobiological action spectrum is most effective in producing redness or erythema of the human skin and is therefore sometimes called the "spectrum of sunburn". UV-A represents those wavelengths between 320 and 400 nm (UV. A1 between 340-400 nm and UV-A2 between 320 and 340 nm) and are about a thousand times less effective in producing skin hyperemia than UV-B.
The visible wavelengths between 400 and 700 nm comprise the well-known white light, which when passed through a prism turns out to be composed of different colours, comprising violet, indigo, blue, green, yellow, orange and red. The energy contained in photons in the visible spectrum is not usually capable of damage to human skin in the absence of a photosensitizing chemical. Energy absorption is decisive for the appearance of photosensitivity. Thus, the absorption spectrum of a molecule is defined by the range of wavelengths absorbed by it, while the spectrum of action for an effect of incident radiation is defined by the range of wavelengths that provoke the response.
Photosensitivity occurs when a photon-absorbing chemical (chromophor) present in the skin absorbs incident energy, becomes aroused and transfers the energy absorbed to different structures or to oxygen. The energy absorbed must be dissipated by processes comprising heat, fluorescence and phosphorescence. It is important to point out that absorption spectra and action spectra should not be superposable, but there must be overlap at some point to produce photosensitivity.
Now, a few things about skin structure and function. Exposure of the skin to the sun allows the absorption of wavelengths and the transmission of others. Essentially, human skin is a sandwich made up of two distinct compartments, the dermis and epidermis, separated by a basal membrane. The epidermis is a squamous layered epithelium, comprising on the surface the corneal layer (a compact membrane rich in proteins and lipids), the granular layer, the spinous layer and the basal cell layer. The basal cell layer contains a heterogeneous population of cells, some of which migrate upwards in the process of terminal differentiation leading to the expression of specific keratin genes and the formation of the corneal layer.
Epidermal cells are resident keratocytes and melanocytes and immigrant cells, comprising immunologically active cells Langerhans, lymphocytes, polymorphonuclear leukocytes, monocytes and macrophages, making the epidermis a major component of the immune system. Branches of the sensitive nerve endings also reach this compartment.
The second major component of the skin is the dermis, which is relatively stretched and less densely populated by cells, including fibroblas, endothelial cells inside dermal vessels and mastocytes. Tissue macrophages and rarely distributed inflammatory cells are also present. All these cells exist inside an extracellular matrix of collagen, elastin and glycosaminoglycans. Unlike the epidermis, the rich vascularization of the dermis allows it to play an important role in temperature regulation.
Let's see what's with ultraviolet radiation (UVR) and skin... The epidermis and dermis contain several chromophores capable of interacting with the incident solar energy. These interactions include reflection, refraction, absorption and transmission. The corneal layer is a major impediment to UV-B transmission and less than 10% of the incident wavelengths in this region penetrate the basal membrane. Approximately 3% of radiation below 300 nm, 20% of radiation below 360 nm and 33% of short visible radiation reaches the basal cellular layer of untanned human skin. Proteins and nucleic acids absorb intensely from the short UV-B range. In contrast, UV-A 1 and 2 penetrate the epidermis effectively to reach the dermis, where they probably produce changes in structural and matrix proteins, which contribute to the aging appearance of skin chronically exposed to the sun, especially in individuals with light skin.
One of the consequences of UV-B absorption by DNA is the production of pyridimine dimers. These structural changes can be repaired by mechanisms that lead to the recognition, excision and restoration of the normal base sequence. Effective repair of these structural aberrations is crucial because individuals with poor DNA repair have an increased risk of developing skin cancer. For example, patients with xeroderma pigmentosum, a recessive autosomal condition, are characterized by diminished repair, to varying degrees, of UV-induced photoproducts and their skin may develop, in the first two weeks of life, the xerotic appearance of photosenescence, as well as bazo and spinocellular carcinomas and melanomas.
Now, a few things about chromophores and skin optics. Chromophores are endogenous or exogenous chemical compounds that can absorb physical energy. Endogenous chromophores of the skin are of two types: 1. chemicals that are normally present, including nucleic acids, proteins, lipids and 7-dehydrocholesterol, the precursor of vitamin D and 2. Sum chemicals are porphyrins, synthesized elsewhere in the body, which circulate in the bloodstream and diffuse into the skin. Normally only traces of porphyrins are present in the skin, but in diseases called porphyries, increased amounts of porphyrins are released into circulation and transported to the skin, where they absorb the incidental energy both in the Soret band, around 400 nm (short visible spectrum), and to a lesser extent, in the red portion of the visible spectrum (580 - 660 nm). This leads to structural skin lesions, which can manifest as erythema, edema, hives or bubble formation.
In the end of this post I will present a few things about the acute effects of sun exposure. The immediate skin consequences of sun exposure include sunburn and vitamin D synthesis. Sunburn is a very common condition of human skin caused by exposure to UV radiation. In general, an individual's ability to tolerate sunlight is inversely proportional to his or her melanic pigmentation. Melanin is a complex polymer of tyrosine, which functions as an effective neutral density filter with wide absorption in the UV portion of the solar spectrum. Melanin is synthesized into specialized epidermal dendritic cells called melanocytes and is stored in melanosomes, which are transferred through dendritic extensions into keratocytes, where they provide photoprotection.
Sun-induced melanogenesis is a result of increased tyrosine sabroadsis activity in melanocytes, which in turn may be due to a combined release of eicosanoid and endotelin-1. Tolerance to sun exposure is based on the effectiveness of the epidermal melanic unit and can usually be certified in anamnesis by two questions: 1. do you experience burns after sun exposure? and 2. tan after sun exposure?. From the answers to these questions it is usually possible to divide the population into six skin types, ranging from type I (always burns appear, never tanned) to type VI (never burn, always tan).
There are two general theories about the pathogenesis of the solar burn reaction. First, the latency phase over time after skin exposure and the appearance of visible erythema (usually 4-12 hours) suggests the existence of an epidermal chromatophorus that causes delayed production and/ or the release of one(s) vasoactive mediator(s) or cytokines that diffuse to dermal vessels to cause vasodilation. Indeed, UV radiation stimulates the release of a large number of pro-inflammatory cytokines and nitrous oxide by keratinocytes.
Secondly, it is possible that the small amount of incidental UV-B (10% or less) that penetrates to the dermis can be absorbed directly by the endothelial cells in the vessels, thus directly producing vasodilation (but the problem is still unresolved). The spectrum of action for sunburn erythema includes UV-B and UV-A radiation. Shorter UV-B photons are at least a thousand times more effective than longer UV-B and UV-A photons in challenging response. However, UV-A can contribute to sunburn erythema at noon, when there are far more UV-A than UV-B.
The mechanism of the lesion remains incomplete, but the spectrum of action for UV-B erythema closely resembles the absorption spectrum for DNA after adjustments for the absorption of incident energy by the corneal layer. Apoptotic keratinocytes (so-called solar burn cells) are histologically visible within the first hour of exposure and are maximum within the first 24 hours. UV-A are less effective than UV-B in producing solar burn cells. Mastocytes can release mediators of inflammation after exposure to UV-A and UV-B increase histamine levels in human skin suction bubbles, which return to normal after 24 hours (before visible erythema disappears). Prostaglandin E2 increases to about 150% at 24 hours from the control level and then decreases. Because prostaglandins cause both pain and erythema when injected intradermally, their presence in suction bubbles after exposure to UV-B suggests a role in UV-B erythema.
There may be an age-related decline in the amount of detectable inflammatory mediators in human skin after UV-B irradiation. UV-A erythema induces few solar burn epidermal cells, but vascular endothelial lesions are larger than for UV-B. In addition, there are three elevated levels of arachidonic acid and prostaglandins D2, E2 and I2, which peak in 5-9 hours and then decrease before the appearance of maximum erythema. Despite evidence of the role of prostaglandins for both UV-B and UV-A irradiated skin, the administration of non-steroidal anti-inflammatory drugs is more effective in reducing UV-B-produced erythema than UV-A. UV-B also induces within a few hours of exposure.
From the point of view of vitamin D photochemistry, skin exposure to UV-B causes the photolysis of provitamin D3 (7-dehydrocholesterol) from the epidermis to previtamin D3, which is then subjected to temperature-dependent isomerization to form the hormone-vitamin D3 stable. This compound then diffuses into dermal vascularization and into the systemic circuit, where it is converted into the functional hormone 1,25-dihydroxy-vitamin D3. Vitamin D metabolites in circulation or those produced in the skin themselves can increase epidermal differentiation signals. Aging substantially decreases the ability of human skin to synthesize vitamin D3. This, along with the widely recommended use of UV-B-filtered sunscreens, has led to concern that vitamin D deficiency could become a significant problem in the elderly. Indeed, studies have shown that the use of sunscreen creams can hinder the production of vitamin D3 in human skin.
And I'm done for today... Posting number 200 (two hundred).
Have a good day!
Dorin, Merticaru