Recent advances in characterizing biological mechanisms underlying UV-induced wrinkles: a pivotal role of fibrobrast-derived elastase

In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Cumulative irradiation with ultraviolet (UV) B at suberythemal doses significantly reduces the elastic properties of the skin, resulting in the formation of wrinkles. In in vitro studies, we identified a paracrine pathway between keratinocytes and fibroblasts, which leads to wrinkle formation via the up-regulation of fibroblast elastases that degrade elastic fibers. UVB irradiation stimulates the activity of fibroblast elastases in animal skin. Scanning electron microscopy revealed that cumulative UVB irradiation elicits a marked alteration in the three-dimensional structure of elastic fibers, which is closely associated with the subsequent reduction in the elastic properties of the skin, resulting in wrinkle formation. Studies using anti-wrinkle treatments suggest a close relationship between the recovery of wrinkles and an improvement in the linearity of elastic fibers. Those studies also suggest a close correlation between the recovery in the linearity of elastic fibers and the improvement in skin elasticity. In a study using ovariectomized animals, we characterized the important role of elastase in their high vulnerability to UV-induced wrinkle formation. A synthetic inhibitor specific for fibroblast elastases significantly prevents wrinkle formation without reducing the elastic properties of the skin, accompanied by minor damage in elastic fibers. Finally, we identified an effective extract of Zingiber officinale (L.) Rose from a screen of many herb extracts, which has a safe and potent inhibitory activity against fibroblast elastases. Animal studies using the L. Rose extract revealed that it has significant preventive effects against UVB-induced wrinkle formation, which occur in concert with beneficial effects on skin elasticity. A 1-year clinical study on human facial skin to determine the efficacy of the L. Rose extract demonstrated that it inhibits the UV-induced decrease in skin elasticity and prevents or improves wrinkle formation in skin around the corner of the eye without changing the water content of the stratum corneum. Our long-term studies support our hypothesis for a mechanism of wrinkle formation in which cytokine expression is activated by UV irradiation and triggers dermal fibroblasts to increase the expression of elastase. That increase in elastase results in the deterioration of the three-dimensional architecture of elastic fibers, reducing skin elasticity and finally leading to the formation of wrinkles.     

All-trans retinoic acid promotes the repair of tortuosity of elastic fibres in rat skin

To elucidate the repair effects of all-trans retinoic acid (t-RA) on ultraviolet (UV)-induced tortuosity of elastic fibres in rat skin, the hind limbs of Sprague-Dawley rats were irradiated at a suberythemal dose of UV (three times/week for 6 weeks) and 0.025% t-RA in ethanol was applied topically five times/week for 6 weeks. The three-dimensional arrangement of elastic fibres with special reference to their linearity was quantified by image analysis using a scanning electron microscope following a combination of intravascular resin injection and selective digestion using formic acid. When t-RA was topically applied for 6 weeks on wrinkles formed by 6 weeks' exposure of the skin of rat hind limbs to UV radiation, the wrinkles disappeared to control levels, concomitant with an improvement in skin elasticity. The linearity of the elastic fibres was significantly (P < 0.01) increased compared with age-matched UV-irradiated controls. These findings suggest that the degeneration and deposition of elastic fibres accompanied by an increase in their linearity is involved in the process of wrinkle repair by topical application of t-RA.     

Ovariectomy is sufficient to accelerate spontaneous skin ageing and to stimulate ultraviolet irradiation-induced photoageing of murine skin

Background: Wrinkling and sagging of the skin during photoageing is physiologically associated with diminished elasticity, which can be attributed to increased fibroblast-derived elastase activity. This degrades the dermal elastic fibres needed to maintain the three-dimensional structure of the skin. We previously reported that ovariectomy accelerates ultraviolet (UV)B-induced wrinkle formation in rat hind limb skin by altering the three-dimensional structure of elastic fibres. OBJECTIVES: In this study, we used hairless mice to assess the effects of ovariectomy with or without chronic UVA or UVB radiation on sagging and wrinkling of skin, on the elasticity of skin, as well as on matrix metalloproteinase activities in the skin. METHODS: Ovariectomies or sham operations were performed on 6-week-old female ICR/HR hairless mice. RESULTS: Even in the ovariectomy group without UV irradiation, the skin elasticity was significantly decreased during the 3-13 weeks after ovariectomy, which was accompanied by a significant increase in elastase activity in the skin. After UVA or UVB irradiation, skin elasticity was significantly decreased to a greater extent in the ovariectomy group than in the sham operation group, and this was accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV in the skin. Consistent with the decreased skin elasticity, UVA irradiation for 12 weeks elicited more marked sagging in the ovariectomy group than in the sham operation group. UVB irradiation for 12 weeks also induced more marked wrinkle formation in the ovariectomy group than in the sham operation group. CONCLUSIONS: These results suggest that ovariectomy alone is sufficient to accelerate skin ageing and to increase UV sensitivity, which results in the further deterioration of the skin and photoageing, and may account for the accelerated skin ageing seen in postmenopausal women.     

Inhibition of ultraviolet-B-induced wrinkle formation by an elastase-inhibiting herbal extract: implication for the mechanism underlying elastase-associated wrinkles

BACKGROUND: Previously, we have demonstrated that fibroblast-derived elastase plays an essential role in the increased three-dimensional tortuosity of elastic fibers, contributing to the loss of skin elasticity in UV-B-exposed skin. This decrease in skin elasticity is closely associated with the formation of wrinkles induced by UV exposure. OBJECTIVE: To further clarify the role of elastase in the formation of wrinkles induced by UV exposure, we assessed the effects of an extract of Zingiber officinale (L.) Rose (which inhibits fibroblast-derived elastase) on the wrinkle formation induced by chronic UV-B irradiation. RESULTS: Topical application of an extract of Zingiber officinale (L.) Rose to rat or hairless mouse skin significantly inhibited the wrinkle formation induced by chronic UV-B irradiation at a suberythemal dose, which was accompanied by a significant prevention of the decrease in skin elasticity in both types of animal skin. In the rat hind limb skin, consistent with the inhibition of reduced skin elasticity, wrinkle prevention occurred concomitantly with a significant decrease in the curling and three-dimensional tortuosity of dermal elastic fibers. CONCLUSION: Our results indicate that herbal extracts with an ability to inhibit fibroblast-derived elastase may prove to be effective as anti-wrinkling agents, confirming the important role of elastase in UV-B-induced wrinkle formation.     

The formation of wrinkles caused by transition of keratin intermediate filaments after repetitive UVB exposure

It has been reported that the formation of wrinkles involves changes in the elastic properties of the dermis due to the denaturation of elastic fibers. Several studies have shown that the hydration condition of the stratum corneum is also important in wrinkle formation. It is, however, still unclear how the stratum corneum contributes to wrinkle formation. Here we investigated the relationship between the formation of wrinkles and changes in the physical properties and condition of the skin after repetitive ultraviolet B (UVB) irradiation of hairless mice (HR/ICR). Repetitive UVB irradiation caused wrinkles on the dorsal skin of the mice. The elasticity (E) of the stratum corneum of UVB-irradiated mice was significantly lower than that of age-matched control (unirradiated) mice. UVB exposure also caused a deterioration of the fibrous ultrastructure of keratin intermediate filaments (KIFs) in the skin. We conclude that the deterioration of KIFs in the stratum corneum caused by repetitive UVB irradiation decreases the elastic properties of the stratum corneum, resulting in the formation of wrinkles.     

Effects of all-trans retinoic acid on UVB-irradiated and non-irradiated hairless mouse skin.

The effects of all-trans retinoic acid (t-RA) on photodamaged and normal non-irradiated skin were examined in hairless mice (Skh:HR-1). After being exposed to increasing doses of UVB for 10 weeks (total dose = 1.4 J/cm2), the animals were then treated with 0.1% t-RA in ethanol (50 microliters, five times per week) for another 10 weeks. Several animals (the follow-up group) were further observed after the termination of the t-RA treatment to investigate if the t-RA effect was reversible. Wrinkle effacement induced by t-RA was compared with three other parameters: a) de novo collagen synthesis, b) width of the dermal repair zone, and c) epidermal thickening. Interestingly, t-RA did not stimulate collagen synthesis in animals not exposed to UVB. In the irradiated animals, the time course of wrinkle reduction correlated with the stimulation of collagen synthesis. After a synchronous initial lag phase of 4-6 weeks, the wrinkling decreased from the maximum grade of 4 to a mean grade of 1.3, whereas collagen synthesis was enhanced to 245% of the control at week 10 of t-RA treatment. In contrast, a similar lag phase was not observed for either the appearance of the dermal repair zone or epidermal thickening. In the follow-up group, upon termination of t-RA treatment, collagen synthesis returned to the control level. Wrinkle effacement and thickening of the dermal repair zone, however, did not regress, suggesting the anti-photoaging effect of t-RA was not reversible over this time frame. The correlation between the length of the lag phases for collagen synthesis and wrinkle reduction points to the possibility that collagen plays an important role in tRA-induced wrinkle effacement. Both parameters are thus important endpoints for investigating the mechanism of RA-induced repair of photodamaged skin.     

Selective inhibition of skin fibroblast elastase elicits a concentration-dependent prevention of ultraviolet B-induced wrinkle formation

We previously reported that wrinkle formation in the skin following long-term ultraviolet B irradiation is accompanied by decreases in skin elasticity and the curling of elastic fibers in the dermis. We further showed that wrinkles could be repaired by treatment with retinoic acid and that this was concomitant with the recovery of skin elasticity ascribed to the repair of damaged elastic fibers. Those studies suggested that decreasing the tortuosity of dermal elastic fibers is an important factor involved in inhibiting or repairing wrinkle formation. Therefore, it is of particular interest to determine whether the inhibition of elastase activity in vivo would prevent the damage of dermal elastic fibers and might abolish wrinkle formation associated with the loss of skin elasticity. Because the major elastase in the skin under noninflammatory conditions is skin fibroblast elastase, we used a specific inhibitor of that enzyme to assess its biologic role in wrinkle formation. The hind limb skins of Sprague-Dawley rats were irradiated with ultraviolet B at a suberythemal dose three times a week for 6 wk. During that period, 0.1-10.0 mM N-phenetylphosphonyl-leucyl-tryptophane, an inhibitor of skin fibroblast elastase, was applied topically five times a week. N-phenetylphosphonyl-leucyl-tryptophane application at concentrations of 0.1-1.0 mM abolished wrinkle formation in a concentration-dependent manner, with a peak for inhibition at 1.0 mM. This inhibition was accompanied by a continued low tortuosity of dermal elastic fibers and a maintenance of skin elasticity. Measurement of elastase activity after 6 wk of ultraviolet B irradiation demonstrated that whereas phosphoramidon-sensitive elastase activity was significantly enhanced in the ultraviolet B-exposed skin, there was no significant increase in that activity in the ultraviolet B-exposed, N-phenetylphosphonyl-leucyl-tryptophane-treated skin. These findings suggest that skin fibroblast elastase plays an essential part in the degeneration and/or tortuosity of elastic fibers induced by cumulative ultraviolet B irradiation.     

Epidermal changes caused by chronic low-dose UV irradiation induce wrinkle formation in hairless mouse

To investigate the effects of chronic low-dose UV irradiation on the skin, hairless mice were irradiated with a 1/3 minimal erythemal dose (MED) of UV. We examined the relationship between visible changes and skin damage in the dermis and epidermis. Hairless mice were irradiated with UVB (20 mJ/cm2) and UVA (14 J/cm2) three times a week for 10 weeks, followed by a 24-week non-irradiation period. Visible fine wrinkling was present after 4 weeks of irradiation, and the wrinkling progressively worsened throughout the period of irradiation. The wrinkles remained after irradiation was discontinued. In dermal components, no significant histological changes in the collagen fibers and elastic fibers were found, and the amount of hydroxyproline was also not changed. Thus, in the epidermis, there was a significant increase in the number of stratum corneum layers and the terminal-differentiation marker, filaggrin, positive cells. The intensity of staining for the differentiation marker, keratin 1, was reduced. These changes were accompanied by wrinkle formation, and remained after discontinuance of irradiation. These findings suggested that chronic low-dose UV irradiation induces structural and quantitative changes in the epidermis as a result of keratinization impairment, and that this damage in the epidermis is an important causative factor in wrinkle formation.     

Unusual wrinkle formation after temporary skin fixation followed by UVB irradiation in hairless mouse skin

Abstract Generally, many wrinkles form on the human face, and temporary wrinkles eventually become permanent. We evaluated the effects of temporary skin fixation on wrinkle formation after UVB irradiation using the back skin of hairless mice. In the group treated with UVB irradiation immediately after production using cyanoacrylate resin of an artificial groove parallel to the midline, wrinkles formed parallel to the midline, an uncommon direction for wrinkle formation in this mouse model. These wrinkles did not disappear even when the skin was stretched. No such changes were observed in the group in which only the temporary groove alone was produced without UVB irradiation. In 3-D surface parameter analysis, all roughness parameters in the group treated with UVB irradiation immediately after production of an artificial groove were significantly increased relative to the age-matched control group. In contrast, no differences were observed between the group in which only the temporary groove alone was produced without UVB irradiation and age-matched controls. The results of this study suggest that both a temporary groove in the skin and UVB irradiation are necessary for wrinkle formation in the back skin of hairless mice.     

Characteristics of skin wrinkling and dermal changes induced by repeated application of squalene monohydroperoxide to hairless mouse skin

We have studied the effect of squalene monohydroperoxides (Sq-OOH), initial products of UV-peroxidated squalene, on the skin of hairless mice. Repeated topical application of 10 mM Sq-OOH to hairless mice for 15 weeks induced definite skin wrinkling. When image analysis was used to compare wrinkle formation induced by ultraviolet B (UVB) irradiation and Sq-OOH treatment, the degree of wrinkling in exposed skin was seen to be similar. However, the characteristics of wrinkles induced by either method differed markedly with regard to direction and distribution. Biochemical analysis revealed a significant decrease in collagen content per unit area and mass in Sq-OOH-treated skin, whereas no changes per unit area and decrease in collagen per unit mass were observed in UVB-irradiated skin. As for glycosaminoglycan (GAG) content per unit area, significant increases were observed in both Sq-OOH-treated skin and UVB-irradiated skin. These changes were not induced by organic hydroperoxides such as TERT-butylhydroperoxide or cumene hydroperoxide treatment. Histological observation revealed epidermal hyperplasia and dermal alterations such as collagen degradation and GAG increases in Sq-OOH-treated skin. Histological changes induced by Sq-OOH were not as pronounced as those induced by UVB irradiation. These results clearly suggest that the wrinkling and changes in dermal collagen content induced by Sq-OOH are qualitatively different to those induced by UVB exposure. This may provide a useful model for the study of skin aging, particularly with regard to collagen content.     

Mechanics of wrinkle formation: micromechanical analysis of skin deformation during wrinkle formation in ultraviolet‐irradiated mice

Background/purpose: The mechanical aspects of wrinkle formation were studied in the dorsal skin of hairless mice. Methods: Wrinkles were induced by irradiating with ultraviolet (UV) B for 10 weeks, while observing skin deformation during wrinkle formation. Changes in skin dimensions were also observed during the specimen excision process. Wrinkle depth and interval were measured before and after removal of the cutaneous muscle layer. Local deformation of wrinkled skin during uniaxial stretch was also measured. Changes in curvature of skin specimens upon muscle layer removal were then observed to determine the force balance in skin layers. Results: The skin showed spontaneous contraction in response to UV irradiation. Wrinkled skin showed a marked decrease in the wrinkle depth and a slight increase in wrinkle interval following muscle layer removal, a peculiar mechanical response that cannot be explained by homogeneous deformation of the skin. This response was due to compressive deformations of dermal tissue caused by the muscle layer and concentrated at valleys of the wrinkles. Curvature measurements indicated that the muscle layer compressed the dermal tissue predominantly in the craniocaudal direction. Morphological observations showed that the wrinkles coincided with rows of pores and sulci cutis, where the structural stiffness of the horny layer was relatively low. The horny layer showed significant thickening. Conclusion: Taken together, we propose the following hypothetical mechanisms of wrinkle formation during UV irradiation: spontaneous contraction of the dermis while maintaining or increasing the epidermal area induces buckling of the epidermis into the dermis at mechanically weak lines, namely, the rows of pores and sulci cutis, and buckling may be amplified by the axial compression of the dermis by the muscle layer.     

Skin rejuvenating effects of chemical peeling: a study in photoaged hairless mice

Background Chemical peeling is a dermatologic treatment for skin aging. However, the mechanism by which the chemical peel achieves its results is not clear. We investigated the effects of chemical peeling and the mechanism of wrinkle reduction in photoaged hairless mice skin. Methods After inducing photoaged skin in hairless mice by repetitive ultraviolet‐B irradiation applied over 14 weeks, we applied trichloroacetic acid (TCA) 30%, TCA 50%, and phenol on areas of the same size on the backs of the mice. Punch biopsies were obtained 7, 14, 28, and 60 days after the procedure for histologic and immunohistochemical analyses. Results Histologic examination showed an increase in dermal thickness, collagen fibers, and elastic fibers in the dermis of intervention groups compared with control groups. These increases were maintained significantly for 60 days. Conclusions This study demonstrates that chemical peeling reduces wrinkles and regenerates skin by increasing dermal thickness and the amount of collagen and elastic fibers in photoaged skin.     

Retinoic acids promote the repair of the dermal damage and the effacement of wrinkles in the UVB-irradiated hairless mouse

Chronic irradiation of hairless mice with UVB leads to elastosis as evidenced by both histologic means and an increase in skin desmosine content. Treatment with topical all-trans- or 13-cis-retinoic acid causes dose-dependent increments in the area of the dermal "repair zone"; skin desmosine content increases during irradiation but does not change significantly after irradiation is discontinued and retinoic acid treatment commenced. During the course of the irradiation the animals develop permanent wrinkles on the exposed dorsal surface, which can be recorded in plastic impressions. The extent of wrinkling can be quantitated and it has been demonstrated that topically applied retinoic acids lead to the complete effacement of these surface features and that the process appears to be permanent.     

Change in ultraviolet (UV) transmission following the application of vaseline to non-irradiated and UVB-exposed split skin

BACKGROUND: Topical preparations such as emollients used in combination with phototherapy can interfere with such treatment. OBJECTIVES: This study was performed to investigate the impact of vaseline on the ultraviolet (UV) transmission of non-irradiated split skin and on split skin previously exposed to UVB radiation. METHODS: Split-skin specimens were obtained from 20 patients. In each case, one sample was taken from an area of non-irradiated skin, while the second was taken from an area that had been previously exposed to UVB. The transmission was spectrophotometrically measured with split skin placed in specially designed quartz glass cuvettes before and after the application of two different amounts of vaseline (2.5 and 17.5 mg cm-2). RESULTS: Application of vaseline to skin previously exposed to UVB caused significant (P < 0.0001) changes in UV transmission in certain wavelength ranges. In the UVA range, a greater increase in transmission was achieved with 2.5 mg cm-2 vaseline, whereas in the UVB range, a greater increase was achieved with 17.5 mg cm-2 vaseline. The thicker the layer of vaseline applied, the lower was the difference in transmission between non-irradiated split skin and UVB-exposed split skin. CONCLUSIONS: Application of the correct amount of vaseline can enhance transmission in either the UVA or UVB range, and would enable dose reduction during a course of phototherapy.     

Comparison of erbium:YAG and carbon dioxide lasers in resurfacing of facial rhytides

OBJECTIVE: To compare the efficacy, adverse effects, and histological findings of erbium:YAG (Er:YAG) and carbon dioxide (CO2) laser treatment in removing facial rhytides. DESIGN: An intervention study of 21 subjects with facial rhytides. All participants were followed up for 6 months. The end points of the study were wrinkle improvement and duration of adverse effects. SETTING: Academic referral center. SUBJECTS: Nineteen female and 2 male volunteers with skin type I to III and wrinkle class I to III participated in the study. INTERVENTION: In all subjects, 1 side of the face was treated with a CO2 laser and other side with an Er:YAG laser. Skin biopsies were performed in 6 subjects before treatment and immediately, 1 day, 2 days, and 6 months after treatment. Observations were recorded by subjects, investigators, and a blinded panel of experts. MAIN OUTCOME MEASURES: Improvement in wrinkles and severity and duration of adverse effects. RESULTS: The CO2 laser-treated side had relatively better wrinkle improvement when evaluating all subjects (P<.03). However, in subjects receiving more than 5 passes of Er:YAG laser, improvement scores were not significantly different from those for 2 to 3 passes of CO2 laser treatment. Posttreatment erythema was noted at 2 weeks in 14 subjects (67%) on the Er:YAG laser-treated side and 20 subjects (95%) on the CO2 laser-treated side. The frequency of erythema was significantly less after Er:YAG laser treatment at 2 (P=.001) and 8 (P=.03) weeks. Hypopigmentation was seen in 1 Er:YAG-treated (5%) and 9 CO2-treated (43%) sides (chi2, P<.05). Histological evaluation showed residual thermal damage of up to 50 microm on the Er:YAG-treated side and up to 200 microm on the CO2-treated side. CONCLUSIONS: Erbium:YAG laser is safe and effective in removing facial rhytides. Subjects treated with Er:YAG laser recover more quickly from the procedure than those receiving CO2 laser treatment.     

Extracellular matrix in cutaneous ageing: the effects of 0.1% copper–zinc malonate-containing cream on elastin biosynthesis

Abstract:  Cutaneous ageing, as visualized at the exposed areas of skin, reflects dramatic alterations in the structure and function of the extracellular matrix of connective tissues. Among them, the elastic fibre network, which is responsible for the physiological elasticity and resilience of normal skin, undergoes degradative changes leading to loss of functional elastic fibres. A potential strategy to counteract these degenerative changes entails topical application of a compound that may lead to regeneration of the elastic fibre network. In this study, we have evaluated the effects of a bi-metal, 0.1% copper–zinc malonate-containing cream that has been shown to efface wrinkles in clinical trials. An effect on elastin biosynthesis and elastic tissue accumulation in skin biopsies was observed in 21 female patients with photoaged facial skin, as measured at baseline and at 6 weeks of treatment. Histopathological evaluation revealed evidence of elastic fibre regeneration, including those extending perpendicularly towards the dermo-epidermal junction within the papillary dermis. Elastin biosynthesis, measured by semi-quantitative immunofluorescence with an antibody recognizing only the newly synthesized, uncrosslinked tropoelastin molecules, suggested statistically significant enhancement of elastin biosynthesis by the bi-metal compound when applied twice daily. Accumulation of elastic fibres was confirmed by assay of desmosine, an elastin-specific crosslink compound. These results suggest that the bi-metal, 0.1% copper–zinc malonate-containing cream has the propensity to increase elastin synthesis in human skin in vivo , and that regeneration of elastic fibres may contribute to wrinkle effacement in female patients with photoaged facial skin.     

Relationships between changes in mechanical properties of the skin, wrinkling, and destruction of dermal collagen fiber bundles caused by photoaging

BACKGROUND/PURPOSE: Long-term exposure to ultraviolet (UV) radiation induces various cutaneous changes that differ from those because of physiological aging, including structural destruction of dermal collagen fiber bundles (DCFBs), which comprise the major component of the dermis. Wrinkling, a representative change in skin surface associated with photoaging, is often seen at the corners of the eyes and in the space between the eyebrows. These are locations where the skin contracts repeatedly and routinely. Lowered resiliency to skin contraction induced by marked structural changes in DCFBs may represent one cause of photo-induced wrinkles. Using animal models of photoaging, changes in mechanical properties of the skin caused by UV irradiation were measured, and relationships between UV-induced changes were analyzed. METHODS: Animal models of photoaging were prepared by irradiating hairless mice with UVB light. Dorsal skin surface replicas of animals were taken using silicon rubber, and volume of wrinkles was calculated using an image analyzer. Stress of the skin against horizontal contraction was measured using a new device called the Resiliometer. Three-dimensional organization of dermal collagen structures in skin samples collected from the back of each animal was observed under scanning electron microscopy, and compactness of DCFBs was assessed from electron micrography. RESULTS: With time and therefore increasing UV dose, deep wrinkles formed on the backs of mice. Volume of wrinkles peaked at 8 weeks. All parameters obtained from Resiliometer measurements were increased by irradiation. DCFB structure was degraded in a radiation dose-dependent manner. DCFB grading was significantly correlated with each Resiliometer parameter. Significant correlations were also observed between each Resiliometer parameter and volume of wrinkles. CONCLUSION: Stress of the skin against horizontal contraction obtained using the Resiliometer changes following UV irradiation, correlating with photo-induced wrinkling and destruction of DCFBs. These results support the hypothesis that changed force of restitution to skin contraction induced by marked structural changes in DCFBs represents one cause of photo-induced wrinkles. The resiliometric parameter may offer a good indicator for monitoring the condition of DCFB structure, as changes in these would induce failure in restitution to skin contraction, leading to wrinkling.     

Sunscreens promote repair of ultraviolet radiation-induced dermal damage

Chronic UV irradiation profoundly damages the dermis of human and animal skin. These alterations were thought to be irreversible. Recently, we showed that substantial repair occurred in hairless mice after stopping UV exposure. A band of new connective tissue was laid down subepidermally. The present study focussed on whether repair would occur if animals were protected by sunscreens after dermal damage was induced and irradiation was continued. Albino hairless mice were exposed to Westinghouse FS20 sunlamps thrice weekly for 30 weeks. The daily dose of UV (UVB + UVA) was 0.17 J/cm2. Sunscreens of sun protection factors (SPF) 6 and 15 were applied after 10 and 20 weeks of irradiation. Biopsies were taken at 10, 20, 30, and 45 weeks of the experiment. With both sunscreens, especially SPF-15, previously damaged dermis was repaired during continued irradiation. Repair occurred in situ and, in severely damaged skin, in the novel form of subepidermal reconstruction zones of new connective tissue with parallel collagen bundles and a network of fine elastic fibers.     

From skin microrelief to wrinkles. An area ripe for investigation

Skin microrelief alters progressively with age. Wrinkles do not result from these changes but are superimposed upon them. Wrinkles result from structural changes in the epidermis, dermis and hypodermis. Four types of wrinkles can be recognized. Type 1 wrinkles are atrophic. Type 2 wrinkles are elastotic. Type 3 wrinkles are expressional. Type 4 wrinkles are gravitational. Each type of wrinkle is characterized by distinct microanatomical changes and each type of wrinkle develops in specific skin regions. Each is likely to respond differently to treatment. Skin microrelief and skin folds can be identified on histological examination. By contrast, only minimal dermal changes are found beneath permanent or reducible wrinkles compared with immediately adjacent skin. A series of objective and non-invasive methods is available to quantify the severity of wrinkling.     

Narrowband (TL-01) ultraviolet B phototherapy for pruritus in polycythaemia vera

BACKGROUND: There are several reports of the efficacy of broadband ultraviolet (UV) phototherapy in the treatment of pruritus associated with polycythaemia vera. OBJECTIVES: To evaluate whether narrowband (TL-01) UVB phototherapy is also effective in treating this condition. METHODS: Ten patients with pruritus associated with polycythaemia vera were treated with narrowband (TL-01) UVB phototherapy. The first irradiation dose was 2/3 of the minimal erythema dose; the treatment schedule consisted of three irradiation sessions per week, with dose increments of 10% each session for skin types I and II, and 15% for skin types III and IV. RESULTS: Patients reported a marked relief of symptoms after an average of six treatments (median cumulative dose 1851.52 mJ cm-2, range 1180.4-2468.4). A complete remission of the pruritus occurred within 2-10 weeks of treatment (median cumulative dose 5371.46 mJ cm-2, range 3271.2-7336.3) in eight of 10 patients. Two patients had only a partial and temporary relief of pruritus after two cycles of treatment and a cumulative dose of 3271.2 mJ cm-2. CONCLUSIONS: Narrowband UVB phototherapy is effective for treatment of pruritus associated with polycythaemia vera, and has the advantage of being less erythemogenic than broadband UVB.