Understanding Solar Skin Elastosis-Cause and Treatment.

Photoageing, also called actinic ageing, is the main cause of prematurely aged skin. Our expertise in elastic fibers has led us to discover a process triggered in response to ultraviolet (UV) light and which upsets the balance of elastin fibers: there is too much elastin and insufficient lysyl oxidase (LOXL1) enzyme to form functional elastic fibers. This imbalance then leads to an accumulation of nonfunctional elastin, which forms aggregates. In addition to this imbalance, UV rays also induce elafin synthesis by fibroblasts. Known to be a marker of elastotic aggregates, elafin crystallizes the elastin fibers and stimulates the formation of aggregates that cannot be naturally eliminated by the skin. We developed a Hamamelis virginiana leaf extract that was able to restore both the balance between elastin and LOXL1 and to decrease the elafin synthesis to fight and correct the damage. This specific Hamamelis virginiana extract increased LOXL1 expression by twofold and decreased elafin synthesis. As a consequence, elastic fibers became functional and aggregates of unfunctional fibers decreased. The specific Hamamelis extract activity was confirmed in vivo with decreasing wrinkles and improving skin firmness.

Treatment of pseudoxanthoma elasticum-like papillary dermal elastolysis with nonablative fractional resurfacing laser resulting in clinical and histologic improvement in elastin and collagen.

OBJECTIVE: Pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-PDE) is a rare skin condition seen predominantly in elderly females. These asymptomatic lesions are brought to the dermatologist's attention due to patient's displeasure in their appearance. We report a case of a 28-year-old female with PXE-PDE on the right neck treated with nonablative fractional resurfacing (NAFR). CASE: The patient on examination had yellow-to-skin-colored papules that coalesced into a cobblestone-appearing plaque on her lateral neck. The area was treated with NAFR to improve texture and cosmesis. After three treatments, the patient noted at least a 50% improvement of appearance and texture in the affected skin. Adverse effects were mild without development of serious side effects, such as scarring and/or permanent dyspigmenation. CONCLUSION: Established therapies for elastin disorders like PXE-PDE have yielded unsatisfactory results by patient and clinician standards. Positive results with NAFR, illustrated in our PXE-PDE case, further provides a role for NAFR in elastin disorders.

Lower energy and pulse stacking. A safer alternative for skin tightening using fractional CO2 laser.

PURPOSE: To evaluate the effect of different energies and stacking in skin shrinkage. METHODS: Three decreasing settings of a fractional CO2 laser were applied to the abdomen of Twenty five Wistar rats divided into three groups. Group I (n=5) was histologically evaluated for microthermal zones dimensions. Groups II and III (n=10 each) were macroscopic evaluated with freeware ImageJ for area contraction immediately and after 30 and 60 days. RESULTS: No statistical significance was found within microthermal zone histological dimensions (Group I) in all settings studied. (Ablation depth: 76.90 to 97.18µm; Coagulation depth: 186.01 to 219.84 µm). In Group II, macroscopic evaluation showed that all settings cause significant immediate skin contraction. The highest setting cause significant more intense tightening effect initially, contracting skin area from 258.65 to 179.09 mm2. The same pattern was observed in Group III. At 30 and 60 days, the lowest setting significantly sustained contraction. CONCLUSION: Lower fractional CO2 laser energies associated to pulse stacking could cause consistent and long lasting tissue contraction in rats.

Lower energy and pulse stacking. A safer alternative for skin tightening using fractional CO2 laser

PURPOSE : To evaluate the effect of different energies and stacking in skin shrinkage. METHODS : Three decreasing settings of a fractional CO2 laser were applied to the abdomen of Twenty five Wistar rats divided into three groups. Group I (n=5) was histologically evaluated for microthermal zones dimensions. Groups II and III (n=10 each) were macroscopic evaluated with freeware ImageJ for area contraction immediately and after 30 and 60 days. RESULTS : No statistical significance was found within microthermal zone histological dimensions (Group I) in all settings studied. (Ablation depth: 76.90 to 97.18µm; Coagulation depth: 186.01 to 219.84 µm). In Group II, macroscopic evaluation showed that all settings cause significant immediate skin contraction. The highest setting cause significant more intense tightening effect initially, contracting skin area from 258.65 to 179.09 mm2. The same pattern was observed in Group III. At 30 and 60 days, the lowest setting significantly sustained contraction. CONCLUSION : Lower fractional CO2 laser energies associated to pulse stacking could cause consistent and long lasting tissue contraction in rats.

Evaluación de los efectos del LED en el tejido dérmico de ratones / The effect of application of red LED on the dermis of rats

Diodos Emisores de la Luz- Light Emitting Diodes (LED) son fuentes de luz que están siendo introducidos en los tratamientos del envejecimiento. El objetivo del estudio fue evaluar los efectos del LED rojo en la dermis de ratones wistar. Se trata de un estudio experimental controlado y randomizado, fueron utilizados 20 ratones wistar divididos en cinco grupos. Los grupos fueron: G1 en donde se aplicó 10 sesiones de diez minutos de fototerapia por LED. El G2 con 20 sesiones de 10minutos, el G3 con 10 sesiones de 20 minutos, el G4 con 20 sesiones de 20 minutos y el G5 fue el grupo control. Después de las aplicaciones se recolectó el material biológico de la zona, siendo realizado el análisis histológico de las áreas que recibieron las aplicaciones, sometiéndolas a las coloraciones de HE, tricómico de Masson y Verhoeef. Fue observada la presencia de micro vasos dérmicos con resultados significativos entre el G2 y el G5. Con relación a la presencia de mastocitos hubo resultados significativos entre el G1 y el G3. El análisis de las fibras elásticas presentó resultados significativos en los grupos G1, G2, G3, G4 en comparación al grupo control (G5). La evaluación de los efectos del LED en las fibras colágenos, los grupos tratados comparados al grupo control no presentaron ninguna diferencia significativa.

The Light-Emitting Diodes Light Emitting Diodes (LED) are a source of light wich are being introduced into the treatment of aging process. This study evaluate the effect of application of red LED on the dermis of Wistar rats. Twenty Wistar rats were used in this randomized controlled experimental study. Those rats were divided randomly into five groups. The G1 group underwent ten sessions of phototherapy by LED lasting ten minutes each. The G-2, 20 sessions of 10 minutes, the G-3, 20 minutes, the fourth group, 20 sessions of 20 minutes and the G-5 group was the control group. After the application, the biological material was collected and the histological analysis of the areas that suffered application were done, being subjected to HE staining, and Masson trichrome & Verhoeff. It was observed the presence of dermal microvascular, with significant results among G2 and G5 groups. Regarding the presence of mast cells, significant results were observed among G1 and G3 groups, however, that was not the case with the G5. By analyzing the elastic fibers, significant results were observed among G1, G2, G3, G4 groups, but the same results weren’t observed in the fifth group. Regarding the assessment of the effects of LED on the collagen fibers, the treated groups, when compared to the control group, showed no significant difference.

Luz intensa pulsada no fotoenvelhecimento: avaliação clínica, histopatológica e imuno-histoquímica / Intense pulsed light in photoaging: a clinical, histopathological and immunohistochemical evaluation

FUNDAMENTOS: A luz intensa pulsada tem sido muito utilizada no tratamento do fotoenvelhecimento sem completo conhecimento de seu mecanismo de ação. OBJETIVO: Estudar a ação da luz intensa pulsada no fotoenvelhecimento e na resposta imunológica cutânea por meio de estudo clínico, histopatológico, avaliando células de Langerhans (CD1), expressão da molécula de adesão intercelular, de linfócitos CD4 e CD8 e quantificação de colágeno e fibras elásticas. MÉTODOS: Um total de 26 pacientes, com idades entre 40 e 65 anos, com fototipos II a III de Fitzpatrick, foram tratadas do fotoenvelhecimento usando LIP, em 5 sessões, com intervalo mensal, durante o ano de 2006. Todas as pacientes foram submetidas à avaliação histológica e imuno-histoquímica 6 meses após o tratamento. RESULTADOS: Ao término do tratamento, houve melhora clínica em 76,92 por cento dos casos, estando relacionada ao aumento significante de fibras colágenas (51,33 por cento) e elásticas (44,13 por cento). O tratamento com luz intensa pulsada promoveu redução de linfócitos CD4 e não alterou a intensidade de linfócitos CD8. Além disso, promoveu aumento significante de pequenos vasos sanguíneos, não ectásicos, molécula de adesão intercelular positivos. CONCLUSÃO: O tratamento facial com luz intensa pulsada promoveu intensa melhora clínica que foi comprovada pelo estudo histopatológico da pele, constituindo boa opção de tratamento para o fotoenvelhecimento cutâneo, por ser técnica não- ablativa, segura e eficaz.

BACKGROUND: Intense pulsed light has been used in the treatment of photoaging without a full understanding of its mechanism of action. OBJECTIVE: To study the effect of intense pulsed light on photoaging and on the skin immune response by means of a clinical and histopathological study, evaluating Langerhans cells (CD1), expression of intercellular adhesion molecule, of CD4 and CD8 lymphocytes and quantification of collagen and elastic fibers. METHODS: In 2006 a total of 26 patients, aged 40 to 65 years, with phototypes II to III (Fitzpatrick scale), were treated for photoaging using intense pulsed light in five sessions with a monthly interval. All the patients were subjected to histological and immunohistochemical evaluation 6 months after treatment. RESULTS: At the end of the treatment clinical improvement was observed in 76.92 percent of cases. This improvement was associated to a significant increase of collagen (51.33 percent) and elastic (44.13 percent) fibers. Intense pulsed light treatment led to a reduction of CD4 lymphocytes and did not alter the amount of CD8 lymphocytes. It also led to a significant increase of small, nonectatic blood vessels, positive intercellular adhesion molecule. CONCLUSION: Facial treatment with intense pulsed light promoted major clinical improvement that was confirmed by histological examination of the skin. This technique is a good treatment option for skin photoaging because it is non-ablative, safe and effective.

Intense pulsed light in photoaging: a clinical, histopathological and immunohistochemical evaluation.

BACKGROUND: Intense pulsed light has been used in the treatment of photoaging without a full understanding of its mechanism of action. OBJECTIVE: To study the effect of intense pulsed light on photoaging and on the skin immune response by means of a clinical and histopathological study, evaluating Langerhans cells (CD1), expression of intercellular adhesion molecule, of CD4 and CD8 lymphocytes and quantification of collagen and elastic fibers. METHODS: In 2006 a total of 26 patients, aged 40 to 65 years, with phototypes II to III (Fitzpatrick scale), were treated for photoaging using intense pulsed light in five sessions with a monthly interval. All the patients were subjected to histological and immunohistochemical evaluation 6 months after treatment. RESULTS: At the end of the treatment clinical improvement was observed in 76.92% of cases. This improvement was associated to a significant increase of collagen (51.33%) and elastic (44.13%) fibers. Intense pulsed light treatment led to a reduction of CD4 lymphocytes and did not alter the amount of CD8 lymphocytes. It also led to a significant increase of small, nonectatic blood vessels, positive intercellular adhesion molecule. CONCLUSION: Facial treatment with intense pulsed light promoted major clinical improvement that was confirmed by histological examination of the skin. This technique is a good treatment option for skin photoaging because it is non-ablative, safe and effective.

The 308-nm excimer laser in the darkening of the white lines of striae alba.

OBJECTIVE: To evaluate the true efficacy of the 308-nm excimer laser for darkening striae alba using a modified approach. METHODS: Ten subjects were treated using the excimer laser on the white lines of striae, while the normal skin near to and between the lines was covered with zinc oxide cream. Assessment of efficacy was performed by colorimetric scores based on mexameter measurement and also digital photographs showing before-after laser therapy, which were compared by two independent dermatologists. RESULTS: The mexameter-based data analysis showed that the excimer laser was weakly effective in the repigmentation of the lines of striae. The analysis using before-after photographs showed that 80% of patients had a poor or moderate result. CONCLUSIONS: The results of this study showed the weakly positive effect of the 308-nm excimer laser in the repigmentation of striae alba; the splaying of pigment was a major side effect.

Bipolar fractional radiofrequency treatment induces neoelastogenesis and neocollagenesis.

BACKGROUND: We recently introduced Renesis, a novel minimally invasive radiofrequency (RF) device, for the treatment of human skin. The wound healing response post-fractional RF (FRF) treatment was examined in human subjects. STUDY DESIGN: The FRF system delivered RF energy directly within the dermis via 5 micro-needle electrode pairs. Tissue temperature was held at 72 degrees C for 4 seconds using an intelligent feedback system. The wound healing response was evaluated histologically and by RT-PCR up to 10 weeks post-RF treatment. Neoelastogenesis and the role of heat shock proteins (HSPs) were assessed by immunohistochemistry. RESULTS: FRF treatment generated a RF thermal zone (RFTZ) pattern in the reticular dermis that consisted of zones of denatured collagen separated by zones of spared dermis. RFTZs were observed through day 28 post-treatment but were replaced by new dermal tissue by 10 weeks. HSP72 expression rapidly diminished after day 2 while HSP47 expression increased progressively through 10 weeks. Reticular dermal volume, cellularity, hyaluronic acid, and elastin content increased. RT-PCR studies revealed an immediate increase in IL-1beta, TNF-alpha, and MMP-13 while MMP-1, HSP72, HSP47, and TGF-beta levels increased by 2 days. We also observed a marked induction of tropoelastin, fibrillin, as well as procollagens 1 and 3 by 28 days post-treatment. CONCLUSION: Our study revealed a vigorous wound healing response is initiated post-treatment, with progressive increase in inflammatory cell infiltration from day 2 through 10 weeks. An active dermal remodeling process driven by the collagen chaperone HSP47 led to complete replacement of RFTZs with new collagen by 10 weeks post-treatment. Furthermore, using both immunohistochemical and PCR studies, we successfully demonstrated for the first time evidence of profound neoelastogenesis following RF treatment of human skin. The combination of neoelastogenesis and neocollagenesis induced by treatment with the FRF system may provide a reliable treatment option for skin laxity and/or rhytids.

Skin rejuvenation in Asian skin: the analysis of clinical effects and basic mechanisms of intense pulsed light.

BACKGROUND: Skin aging consists of photoaging and intrinsic aging. It is characterized clinically not only by rhytides, but also by pigmentary alterations and facial telangiectasias. There continues to be a growing interest in the efficacy of intense pulsed light (IPL) devices in the treatment of skin aging, as well as further defining its mechanism of action. OBJECTIVES: The objective of this clinical trial was to evaluate the effects and the mechanism of action of an IPL by comparing clinical photographs and biopsy results before and after treatment. METHODS: A total of 58 patients were treated using a new IPL device. Clinical photographs were taken before treatment and compared to those taken 3 weeks after the treatment. Also, 4 cases had pathological analyses of tissues that were stained by haematoxylin-eosin and Uana orcein. Immunohistology of human collagen of types 1 and 3 and quantitative analyses of elastin and collagen were performed by a poly-functional digital image light microscope; a transmission electron microscope was used for 2 of the cases to look for additional changes. RESULTS: After 3 treatments, 62.1% of the patients showed improvement in wrinkles and skin texture. Pigmentation improved in 84.6% of the patients, and a reduction in telangiectasis was seen in 81.25% of the patients. Pathological examination showed that both type 1 and type 3 collagens increased following treatment, but elastin content decreased; however, the elastin fibers were arranged more neatly. In the transmission electron microscope study, the amount of fibroblast activity increased, the fibroblasts were more active, and there were more collagen fibers neatly rearranged within the stroma. CONCLUSION: Clinical and pathological studies demonstrated that the IPL was effective in improving wrinkles and skin texture. The mechanism of action may be through the increasing activity of the fibroblasts, hyperplasia of the fibroblasts, and rearrangement of both collagen and elastin within the stroma.

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.

[PUVA therapy: long-term degenerative effects. I. Histological changes observed after PUVA therapy]. / PUVA terapia: efectos degenerativos a largo plazo. I. Alteraciones histológicas observadas después de la PUVA terapia.

The authors studied PUVA induced histological alterations in a group of 7 patients compared with 6 control subjects of same age. The epidermal alterations were unprominent: a few necrotic keratinocytes and hyperpigmentation of basal layer melanocytes with a lentiginous pattern. Basement PAS positive membrane was in some cases desestructured, but this was reversible. In the papillary dermis there was homogenization and partial or total destruction of orceinophilic vertical fibers, these phenomena were also reversible. PUVA therapy induced aging of the skin which is dose related and depends also of the patients age. No phenomena of precancerous dysplasia were observed.

Photoaging. Manifestations, prevention, and treatment.

In recent years there has been a growing awareness that many of the so-called attributes of aging skin are, instead, a reflection of environmental assault upon exposed areas of the body. Of special import are the deleterious effects of solar radiation on dermal connective tissue, leading to the visible manifestations of photoaging. Often termed "premature aging," the salient features of the process are distinctly different from those found in normal intrinsic aging. In general, chronically irradiated skin is metabolically hyperactive with epidermal hyperplasia and neoplasia, increased production of elastic fibers, GAGs, accelerated breakdown and synthesis of collagen, and enhanced inflammatory processes. In contrast, protected aged skin is usually characterized by a slow decline in many of these components. Experimental studies with animal models have confirmed the notion that the shorter, more energetic portion of the ultraviolet spectrum (UVB) is responsible for the dermal connective tissue destruction observed in photoaged skin. More recently, it has been shown that UVA and infrared radiation contribute significantly to photoaging, producing, among other changes, severe elastosis. Because the three broad wavebands are inseparably linked in terrestrial sunlight, all are of concern in the photoaging of human skin. Photoaged skin has been thought to be irreversibly damaged. However, our findings indicate that destruction and repair go on simultaneously under continued assault by actinic radiation. The balance is shifted toward repair when the radiation stress is relieved. Both epidermis and dermis are capable of moderate self-restoration when exogenous injury ceases, either by avoidance of sunlight or by the use of broad-spectrum, high-SPF sunscreens. Repair of the dermis, characterized by broad regions of new collagen deposited subepidermally, can be pharmacologically enhanced by topical application of retinoic acid. Although early protection from sunlight, before severe photodamage occurs, is most desirable, it is deemed advisable to counsel even older persons with photoaged skin to adopt protective measures, thereby allowing repair processes to occur.