Deformity of the tear trough region, which can occur during the aging process, can result in dark shadows under the eyes and a fatigued appearance. Augmentation of the tear trough is challenging because of the thin skin and lack of fat in the region.

Adding volume to the tear trough region with a dermal filler is a nonsurgical procedure with minimal discomfort to the patient. Dermicol-P35 (Evolence; Ortho Dermatologics, Skillman, NJ) is a new, ribose crosslinked, highly purified, porcine-based collagen filler that does not require prior skin testing and has shown improved persistence compared with bovine collagen-based dermal fillers.

In this article, we present the clinical outcomes of patients who have received treatment with a novel ribose crosslinked porcine collagen dermal filler for the correction of tear trough deformity.



"Correction of tear trough deformity with novel porcine collagen dermal filler (Dermicol-P35)"
Aesthet Surg J. 2009 May-Jun; 29(3 Suppl): S9-S11Goldberg DJ (Hubmed.org)



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Estrogen deficiency may contribute to extracellular matrix turnover in skin. This has led previous authors to postulate that aged skin heals less efficiently when compared to younger skin. Also, cigarette smokers have been shown to heal less efficiently than nonsmokers.

Matrix metalloproteinase (MMP)-13, an enzyme that participates in the degradation of the extracellular matrix, has been implicated in physiologic aging and wound healing. This study investigates the effects of smoke exposure and estrogen deficiency on MMP-13 in young and aged female mouse skin.

Young and aged female C57Bl/6J mice were ovariectomized. They were then randomly administered either 17beta-estradiol (E2) or placebo pellets. Half the animals in each age group were further randomized to exposure to cigarette smoke for a period of 6 months. Smoking and estrogen deficiency increased MMP-13 protein and activity in aged skin.

The tissue inhibitors of metalloproteinases, which inhibit MMPs, activity was unchanged across all groups. E2 replacement decreased the actual level of MMP-13 protein and activity. We also found an increased collagen content and decreased ER receptor protein level in aged, smoke-exposed female mice.

Our experimental data show that tobacco smoke exposure and estrogen deficiency are additive risk factors for promoting increased activity of MMP-13 in aged skin. These findings suggest that MMP-13 functions as a mediator of smoke-induced skin injury in susceptible, aged experimental female mice.



"Estrogen Deficiency and Tobacco Smoke Exposure Promote Matrix Metalloproteinase-13 Activation in Skin of Aging B6 Mice"
Ann Plast Surg. 2009 Jul 13; Kassira N, Glassberg MK, Jones C, Pincus DJ, Elliot SJ, Fritz JR, Karl M, Thaller S (Hubmed.org)



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Recently, both clinical and bench research has begun to provide scientific validation for the use of certain botanical ingredients. Related findings regarding proposed biological mechanisms of action have translated into clinical practice.

Botanical compounds for which dermatologic and cosmetic applications have emerged include: olive oil, chamomile, colloidal oatmeal, oat kernal extract, feverfew, acai berry, coffee berry, curcumin, green tea, pomegranate, licorice, paper mulberry, arbutin, and soy. Many of these botanical sources offer biologically active components that require further in vitro and in vivo investigation in order for us to properly educate ourselves, and our patients, regarding over-the-counter products based on these ingredients.



"Natural ingredients in cosmetic dermatology
J Drugs Dermatol. 2009 Jun; 8(6 Suppl): s5-9Baumann L, Woolery-Lloyd H, Friedman A (Hubmed.org)



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The periorbital area is a key wrinkle-prone region, where the first signs of aging usually appear.

AIMS:
To demonstrate the ability of new anti-aging moisturizing products to improve overall smoothness and wrinkle depth appearance in the periorbital region via the Fast Optical in vivo Topometry of Human Skin (FOITS).

METHODS:
Two double-blind, randomized, controlled, split-face studies (n = 42, Study 1; n = 35, Study 2) were conducted in women 30-70 years old with moderate to distinct periorbital wrinkles. Subjects applied 0.5 g of individual products to half their face twice daily for 4 weeks. Four test products containing niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine were used and included a daytime SPF 30 lotion also containing antioxidants, a night cream, an eye cream also containing caffeine, and a wrinkle treatment containing retinyl propionate.

The wrinkle treatment was only tested in Study 2. The FOITS technique was used to measure changes in periorbital R(a) (mean roughness) and R(z) (average maximum roughness) at 2 and 4 weeks.

RESULTS:
In Study 1, the daytime SPF 30 lotion, night cream, and eye cream significantly improved crow's feet smoothness after 4 weeks relative to no treatment. After 4 weeks, the daytime SPF 30 lotion and night cream, but not the eye cream, were significantly better than no treatment at improving R(z).

In Study 2, the night cream, eye cream, and wrinkle treatment, but not the daytime SPF 30 lotion, significantly improved both R(a) and R(z) after 4 weeks. To increase power and precision of estimates, a meta-analysis was performed; the pooled data showed all three products were significantly better than no treatment at improving R(a) and R(z) after 4 weeks.

CONCLUSIONS:
Four weeks of treatment with these products was shown to improve the smoothness of periorbital skin and to reduce the apparent depth of larger wrinkles.


"Efficacy of anti-aging products for periorbital wrinkles as measured by 3-D imaging."
J Cosmet Dermatol. 2009 Sep; 8(3): 228-33Kaczvinsky JR, Griffiths CE, Schnicker MS, Li J


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Constipation is a common problem in children, and when it becomes chronic fecal impaction, overflow soiling and megarectum may develop. Children with chronic idiopathic constipation (IC) may not respond to conventional treatments of laxatives, enemas, and toilet training. The aims of the study were to evaluate the long-term outcome of transcutaneous needle-free injection of botulinum toxin (TNFBT) into the external anal sphincter (EAS) and to assess the extent of the toxin penetration into the sphincter.

METHOD:
Children were recruited if symptomatic with chronic constipation, soiling, painful defecation, and withholding behavior requiring disimpaction of stool and rectal biopsy under general anesthesia. A total dose of 200 U of botulinum toxin (BT) (Dysport; Ipsen Limited, Slough, United Kingdom) was injected transcutaneously into the EAS at 3 and 9-o'clock positions using J-tip needle-free syringes (National Medical Products Inc, Irvine, Calif).

The depth and width of toxin penetration was assessed by endosonography. Outcome was measured by a validated symptom severity (SS) score questionnaire. The total SS score ranged between 0 (best) and 65 (worst). The outcome was compared with 31 children in a comparable historical control group at 3 and 12-month follow-up.

RESULTS:
Sixteen children were recruited with median age of 6.11 (range, 3-14.85) years and median duration of symptoms of 3.9 years (1.6-11.5). On endosonography, the median depth and width of BT penetration was 8 (7-10) mm and 8 (6-10) mm, respectively. At 3-month follow-up, the median SS score improved in all children after TNFBT from 32.50 (5-57) to 7.50 (0-26) (Wilcoxon's P < .0001). There were significant improvements in symptoms of constipation, soiling, painful defecation, general health and behavior, and fecal impaction of rectum (P < .05). Anal fissures healed in all 4 children. The SS score in the control group improved from 33 (12-49) to 15 (0-40) (P < .0001). At 12-month follow-up, the improvement of SS score in TNFBT group was significantly more than the control group as follows: 4 (0-25) vs 15 (0-51), respectively (Mann-Whitney U P < .002).

Three patients had a second TNFBT injection for relapsed symptoms. There were no complications. The transcutaneous needle-free injection of botulinum toxin eliminates the risk of intravascular injection or needlestick injury. The transcutaneous needle-free injection of botulinum toxin also has other therapeutic applications including an alternative therapy to biofeedback training for dyssynergia of the EAS, treatment of muscle limb spasticity in cerebral palsy, and cosmetic treatment of overactive facial muscles and wrinkles and hyperhydrosis.

CONCLUSION:
Transcutaneous needle-free injection of botulinum toxin into the external anal sphincter is a novel and safe new treatment of chronic idiopathic constipation and anal fissure in children. A second injection may be required in 20% of patients.



"Transcutaneous needle-free injection of botulinum toxin: a novel treatment of childhood constipation and anal fissure"
J Pediatr Surg. 2009 Sep; 44(9): 1791-8Keshtgar AS, Ward HC, Clayden GS (Hubmed.org)



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Infraorbital dark circles refer to the conditions that present with darkness of the infraorbital eyelids. Although it is not a medical concern, it can be a cosmetic concern for a large number of individuals. Moreover, clear definition and possible causes have not been elucidated.

OBJECTIVE:
To review the possible causes and treatment options for infraorbital dark circles.

METHODS:
The article is based on a review of the medical literature and the author's clinical experience in treating infraorbital dark circles.

CONCLUSION:
Possible causative factors of infraorbital dark circles include excessive pigmentation, thin and translucent lower eyelid skin overlying the orbicularis oculi muscle, and shadowing due to skin laxity and tear trough, but because multiple factors cause infraorbital dark circles in the majority of patients, it is essential to identify the cause and choose the appropriate treatment according to the cause.



"Infraorbital dark circles: definition, causes, and treatment options"
Dermatol Surg. 2009 Aug; 35(8): 1163-71Roh MR, Chung KY (Hubmed.org)



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Primary human aging may be associated with augmented Rho-kinase (ROCK)-mediated contraction of vascular smooth muscle and ROCK-mediated inhibition of nitric oxide synthase (NOS). We hypothesized that the contribution of ROCK to reflex vasoconstriction (VC) is greater in aged skin.

Cutaneous VC was elicited by 1) whole-body cooling (Tsk=30.5 degrees C) and 2) local norepinephrine (NE) infusion (1x10(-6)M). Four microdialysis fibers were placed in the forearm skin of 8 young (Y) and 8 older (O) subjects for infusion of 1) Ringers solution (control), 2) 3 mM fasudil (ROCK inhibition), 3) 20 mM L-NAME (NOS inhibition), and 4) both ROCK + NOS inhibitors.

Red cell flux was measured by laser Doppler flowmetry (LDF) over each site. Cutaneous vascular conductance was calculated (CVC = LDF/MAP) and normalized to baseline CVC (%DeltaCVCbaseline). VC was reduced at the control site in O during cooling (Y: -34 +/- 3, O: -18 +/- 3 %DeltaCVCbaseline; P



"Reflex vasoconstriction in aged human skin increasingly relies on rho-kinase dependent mechanisms during whole-body cooling"
Am J Physiol Heart Circ Physiol. 2009 Aug 28; Lang JA, Jennings JD, Holowatz LA, Kenney WL (Hubmed.org)



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Massively parallel pyrosequencing of the small subunit (16S) ribosomal RNA gene has revealed that the extent of rare microbial populations in several environments, the 'rare biosphere', is orders of magnitude higher than previously thought.

One important caveat with this method is that sequencing error could artificially inflate diversity estimates. Although the per-base error of 16S rDNA amplicon pyrosequencing has been shown to be as good as or lower than Sanger sequencing, no direct assessments of pyrosequencing errors on diversity estimates have been reported.

Using only Escherichia coli MG1655 as a reference template, we find that 16S rDNA diversity is grossly overestimated unless relatively stringent read quality filtering and low clustering thresholds are applied. In particular, the common practice of removing reads with unresolved bases and anomalous read lengths is insufficient to ensure accurate estimates of microbial diversity.

Furthermore, common and reproducible homopolymer length errors can result in relatively abundant spurious phylotypes further confounding data interpretation. Thus, stringent quality-based trimming of 16S pyrotags and clustering thresholds no greater than 97% identity should be used to avoid overestimates of the rare biosphere.



"Wrinkles in the rare biosphere: pyrosequencing errors lead to artificial inflation of diversity estimates"
Environ Microbiol. 2009 Aug 27; Kunin V, Engelbrektson A, Ochman H, Hugenholtz P (Hubmed.org)



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The dermal degeneration accompanying photoaging is considered to promote skin roughness features such as wrinkles. Our previous study demonstrated that polarization-sensitive spectral domain optical coherence tomography (PS-SD-OCT) enabled noninvasive three-dimensional evaluation of the dermal degeneration of photoaged skin as a change in dermal birefringence, mainly due to collagenous structures.

Our purpose is to examine the relationship between dermal birefringence and elasticity and the skin morphology in the eye corner area using PS-SD-OCT. Nineteen healthy male subjects in their seventees were recruited as subjects. A transverse dermal birefringence map, automatically produced by the algorithm, did not show localized changes in the dermal birefringence in the part of the main horizontal wrinkle.

The averaged upper dermal birefringence, however, showed depth-dependent correlation with the parameters of skin roughness significantly, suggesting that solar elastosis is a major factor for the progress of wrinkles. Age-dependent parameters of skin elasticity measured with Cutometer did not correlate with the parameters.

These results suggest that the analysis of dermal birefringence using PS-SD-OCT enables the evaluation of photoaging-dependent upper dermal degeneration related to the change of skin roughness.



"Relationship between dermal birefringence and the skin surface roughness of photoaged human skin"
J Biomed Opt. 2009 Jul-Aug; 14(4): 044032Sakai S, Nakagawa N, Yamanari M, Miyazawa A, Yasuno Y, Matsumoto M (Hubmed.org)



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Int J Cosmet Sci. 2009 Sep 1; Dumont S, Cattuzzato L, Trouvé G, Chevrot N, Stoltz CSynopsis The mode of action of two cosmetic active ingredients (AIs), palmitoyl glycine (PG) and cocoyl alanine (CA) was studied with cDNA array experiments and quantitative PCR confirmations, which were performed on experimentally aged human fibroblasts. These preliminary studies revealed complementary profiles. Thus, specific supplementary investigations were then carried out for each AI. Protocols used were based either on in vitro models: (i) biochemical assays, (ii) monolayer cell culture (primary human fibroblasts and keratinocytes) and (iii) the model of capillary-like tube formation by human endothelial cells or on ex vivo models, i.e. topically treated skin explants and both immunohistochemical and Chromameter(TM) investigations. New prospects are proposed to fight out against skin aging. Indeed, PG and CA showed complementary properties and thus enabled a regulation or a restoration effect on main aging-associated disorders. Thus, they can not only act on tissue architecture, cell-cell interactions and extracellular matrix protection but also on inflammation, cell longevity, skin immune system protection, skin radiance and stem cell survey. Finally, a clinical trial performed on Caucasian women confirmed AI anti-wrinkle efficacy, which was superior to that of a market reference ingredient. In the future, complementary experiments enabling a better understanding of the aging-induced decline of epidermal stem cells would be of a great interest.

Plast Reconstr Surg. 2009 Sep; 124(3): 826-35McCluskey PD, Constantine FC, Thornton JFBACKGROUND: A full-thickness skin graft is generally not considered the ideal replacement for the thick, sebaceous skin of the nasal tip, ala, lower sidewalls, or dorsum. Instead, many clinicians prefer to reconstruct these defects with local or axial composite flaps that incorporate skin, subcutaneous tissue, and fat. METHODS: The authors conducted a retrospective analysis of 55 consecutive patients who underwent reconstruction of lower third nasal defects with full-thickness skin grafts between 2002 and 2007 performed by the senior author (J.F.T.). All of the patients in this review underwent skin cancer ablation by means of Mohs' micrographic surgery. RESULTS: Good aesthetic results, based on preoperative and postoperative photographic analysis of contour and pigmentation, have been achieved in both the recipient and donor sites in 52 of 55 patients. Three patients, all of whom were smokers, experienced loss of the skin graft requiring alternative reconstructive techniques. CONCLUSIONS: Under certain conditions, skin grafting of defects of the caudal third of the nose offers a viable reconstructive option that yields good contour and color match. Careful analysis of defect size, location, and depth and consideration of donor-site skin thickness and pigmentation are vital for accurate replacement of the thick, pitted, sebaceous skin of the caudal nose. An evolution in technique has revealed that the forehead donor skin often provides a more consistent color and contour match in such reconstructions. Secondary dermabrasion of the graft provides a critical step for obtaining final aesthetic contour and color.

J Cell Mol Med. 2009 Sep 1; Mimeault M, Batra SKRecent advances in skin-resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging may induce severe DNA damages and genomic instability in the skin-resident stem/progenitor cells and their progenies. These molecular events may result in the alterations in key signaling components controlling their self-renewal and/or regenerative capacities as well as the activation of tumor suppressor gene products that trigger their growth arrest and senescence or apoptotic death. The progressive decline in the regenerative functions and/or number of skin-resident adult stem/progenitor cells may cause diverse skin diseases with advancing age. Moreover, the photoaging, telomerase re-activation and occurrence of different oncogenic events in skin-resident adult stem/progenitor cells may also culminate in their malignant transformation into cancer stem/progenitor cells and skin cancer initiation and progression. Therefore, the anti-inflammatory and anti-oxidant treatments and stem cell-replacement and gene therapies as well as the molecular targeting of their malignant counterpart, skin cancer-initiating cells offer great promise to treat diverse skin disorders and cancers.

Aesthet Surg J. 2009 Jul-Aug; 29(4): 264-71Man DBACKGROUND: The telltale signs associated with facelift procedures, including tightening of the lower face (lateral sweep), visible scars, a distorted hairline, and the "pixie ear" deformity are grounds for concern among both patients and aesthetic surgeons. It is the author's belief that facelift results can be improved with correct positioning of the ears, so that these signs are reduced or eliminated altogether. OBJECTIVE: The purpose of this paper is to study the causes of ear deformity and describe the advantages of the author's technique for the prevention of ear deformities in facelift surgeries. METHODS: Between January 2005 and November 2007, the author performed facelifts on 106 patients using a technique that included autologous fat injections to improve facial volume, hidden incisions in and around the ear, and absorbable bidirectional barbed sutures. Patient charts and photographs were reviewed retrospectively. Pre- and postoperative angles were measured with respect to the ear and face and were documented to determine the degree of improvement or deformity. RESULTS: Significant improvement of the specified angles was noted in 70% of cases following facelift surgery; in these cases, the ear position was elevated. No change in ear position occurred in 10% of cases. Some distortion and lowering of the ear was seen in the remaining cases. CONCLUSIONS: Recognition of the effects of aging on the ear and the mechanisms leading to ear deformity associated with facelift procedures can aid in achieving improved aesthetic results. The advantages of the author's technique include shorter incisions, a diminished need to remove redundant skin, ear elevation, and a smoother repair with improved contour. Further investigation of long-term results is necessary.

Dermatol Surg. 2009 Aug 25; Marmur ES, Taylor SC, Grimes PE, Boyd CM, Porter JP, Yoo JYBACKGROUND Recently, the cosmetic market has seen an increase in the options for treatment for people with dark skin. OBJECTIVES This study evaluates the use of calcium hydroxylapatite (CaHA), a dermal filler indicated for the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs) in individuals with dark skin. METHODS This open-label, nonrandomized, prospective, five-center trial enrolled 100 patients aged 18 and older with Fitzpatrick skin types IV to VI. CaHA was injected subdermally with a 25- to 27-gauge needle. Participants received a range of 0.6 to 2.8 mL of CaHA and returned at 3 and 6 months to be assessed for keloid formation, hypertrophic scarring, and hyper- or hypopigmentation. If necessary, each subject was offered a touch-up at the conclusion of the 6-month visit. RESULTS No reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or other clinically significant adverse events were recorded. CONCLUSIONS People with dark skin injected subdermally with CaHA do not show signs of keloid formation, hypertrophic scarring, or hyper- or hypopigmentation. Because of this safety feature, as well as other characteristics of the product already shown in clinical literature, CaHA is an attractive dermal filler in this population. BioForm Medical, Inc. provided the products and equipment for this study. Drs. Marmur and Boyd are members of the Medical Education Faculty of Bioform.

Dermatol Surg. 2009 Aug 25; Marmur ES, Al Quran H, DE Sa Earp AP, Yoo JYBACKGROUND The process of skin aging is not limited to the face but involves every part of the body, including the hands. A common manifestation of aging of the hands is the loss of volume, which occurs as the skin loses its subcutaneous fat. Injectable dermal fillers have surfaced as a popular method to address such deficiencies. OBJECTIVES To report the use of calcium hydroxylapatite (CaHA) to address lost volume. METHODS Five female subjects with soft tissue deficiency of the dorsa of the hands were enrolled at Mount Sinai Medical Center. A solution of CaHA with 2% lidocaine in amounts of 0.3 to 1.0 mL was injected interdigitally at each of three to five insertion sites; the sites were massaged and molded up to three times to ensure an optimal cosmetic end point. Subjects were seen for a follow-up visit after 1, 4, 16, and 24 weeks. RESULTS With a single injection, all subjects reached their correction goals without requiring any touch-ups. At the 24-week visit, the subjects retained the filling effect, with no adverse events and high patient satisfaction. CONCLUSION CaHA, a new, easily injectable, safe dermal filler, has emerged as an excellent option for soft tissue augmentation in aging hands. BioForm Medical, Inc. provided the products and equipment for this study. Drs. Marmur and Boyd are members of the Medical Education Faculty of Bioform.

Clin Dermatol. 2009 Sep-Oct; 27(5): 479-84Singh RP, Agarwal RCosmeceuticals are used for nourishing and improving the appearance of the skin and are also documented as effective agents for treating various dermatologic conditions. Cosmeceutical preparations from herbal origin are most popular among consumers because these agents are mostly nontoxic and possess strong antioxidant activity. Because oxidative stress is one of the major mechanisms for skin aging and dermatologic conditions, phytochemicals with proven antioxidant activity, such as silibinin, could be useful for treating many dermatologic conditions as well as skin aging. Silibinin is a flavonolignan compound from Silybum marianum (milk thistle plant) that possesses strong antioxidant activity and also modulates many molecular changes caused by xenobiotics and ultraviolet radiation to protect the skin. This contribution reviews the evidence generated from laboratory studies to support the scientific rationale for the effective use of silibinin in cosmeceutical preparations.

Facial Plast Surg Clin North Am. 2009 Aug; 17(3): 469-487.e3Brenner MJ, Perro CAResidual disfigurement is a common problem for patients who have undergone skin cancer reconstruction. Restoring form and function in these patients is an artistic and technical endeavor. The efficacy of surgical scar revision, dermabrasion, chemical peels, and laser resurfacing is predicated upon the skin's innate ability to regenerate over time in response to mechanical, chemical, and thermal or ablative stresses. The patient and surgeon should be accepting of a process that is often gradual and may proceed in stages. Achieving proficiency with the secondary procedures for improving scars and local flaps may allow the motivated surgeon to mold an initially passable surgical result into an excellent one.

J Epidemiol. 2009 Aug 22; Asakura K, Nishiwaki Y, Milojevic A, Michikawa T, Kikuchi Y, Nakano M, Iwasawa S, Hillebrand G, Miyamoto K, Ono M, Kinjo Y, Akiba S, Takebayashi TBackground: The number of studies that use objective and quantitative methods to evaluate facial skin aging in elderly people is extremely limited, especially in Japan. Therefore, in this cross-sectional study we attempted to characterize the condition of facial skin (hyperpigmentation, pores, texture, and wrinkling) in Japanese adults aged 65 years or older by using objective and quantitative imaging methods. In addition, we aimed to identify lifestyle factors significantly associated with these visible signs of aging.Methods: The study subjects were 802 community-dwelling Japanese men and women aged at least 65 years and living in the town of Kurabuchi (Takasaki City, Gunma Prefecture, Japan), a mountain community with a population of approximately 4800. The facial skin condition of subjects was assessed quantitatively using a standardized facial imaging system and subsequent computer image analysis. Lifestyle information was collected using a structured questionnaire. The association between skin condition and lifestyle factors was examined using multivariable regression analysis.Results: Among women, the mean values for facial texture, hyperpigmentation, and pores were generally lower than those among age-matched men. There was no significant difference between sexes in the severity of facial wrinkling. Older age was associated with worse skin condition among women only. After adjusting for age, smoking status and topical sun protection were significantly associated with skin condition among both men and women.Conclusions: Our study revealed significant differences between sexes in the severity of hyperpigmentation, texture, and pores, but not wrinkling. Smoking status and topical sun protection were significantly associated with signs of visible skin aging in this study population.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 25-31Gilchrest BA, Eller MS, Yaar MUV-induced melanogenesis (tanning) and "premature aging" or photoaging result in large part from DNA damage. This article reviews data tying both phenomena to telomere-based DNA damage signaling and develops a conceptual framework in which both responses may be understood as cancer-avoidance protective mechanisms.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 25-31; doi:10.1038/jidsymp.2009.9.

J Appl Physiol. 2009 Aug 13; Hess KL, Wilson TE, Sauder CL, Gao Z, Ray CA, Monahan KDCardiovascular-related mortality peaks during cold winter months, particularly in older adults. Acute physiological responses, such as increases in blood pressure, in response to cold exposure may contribute to these associations. To determine if the blood pressure raising effect (pressor response) of acute non-hypothermic cold stress is greater with age we measured physiological responses to 20 minutes of skin surface cooling, via water-perfused suit, in 12 young (25+/-1 years old, mean+/-SE) and 12 older (65+/-2) adults. We found that skin surface cooling elicited a pressor response (P

Age (Dordr). 2009 Aug 21; Ford CT, Sherratt MJ, Griffiths CE, Watson REAging in human skin is the composite of time-dependent intrinsic aging plus photoaging induced by chronic exposure to ultraviolet radiation. Nuclear hormone receptors coordinate diverse processes including metabolic homeostasis. Liver X receptor beta (LXRbeta) is a close human homologue of daf-12, a regulator of nematode longevity. LXRbeta is positively regulated by sirtuin-1 and resveratrol, while LXRbeta-null mice show transcriptional profiles similar to those seen in aged human skin. In these studies, we examined LXRbeta expression in aged and photoaged human skin. Volunteers were recruited to assess intrinsic aging and photoaging. Epidermal LXRbeta mRNA was examined by in situ hybridization while protein was identified by immunofluorescence. No significant changes were observed in either LXRbeta mRNA or protein expression between young and aged volunteers (mRNA p = 0.90; protein p = 0.26). Similarly, LXRbeta protein expression was unaltered in photoaged skin (p = 0.75). Our data therefore suggest that, while not playing a major role in skin aging, robust cutaneous expression implies a fundamental role for LXRbeta in epidermal biology.

Gerontology. 2009 Aug 20; Kunz M, Mylius V, Schepelmann K, Lautenbacher SBackground: Both age and dementia have been shown to have an effect on nociception and pain processing. The question arises whether mild cognitive impairment (MCI), which is thought to be a transitional stage between normal ageing and dementia, is also associated with alterations in pain processing. Objective: The aim of the present study was to answer this question by investigating the impact of age and MCI on the pain response system. Methods: Forty young subjects, 45 cognitively unimpaired elderly subjects and 42 subjects with MCI were investigated by use of an experimental multi-method approach. The subjects were tested for their subjective (pain ratings), motor (RIII reflex), facial (Facial Action Coding System) and their autonomic (sympathetic skin response and evoked heart rate response) responses to noxious electrical stimulation of the nervus suralis. Results: We found significant group differences in the autonomic responses to noxious stimulation. The sympathetic skin response amplitude was significantly reduced in the cognitively unimpaired elderly subjects compared to younger subjects and to an even greater degree in subjects with MCI. The evoked heart rate response was reduced to a similar degree in both groups of aged subjects. Regression analyses within the two groups of the elderly subjects revealed that age and, in the MCI group, cognitive status were significant predictors of the decrease in autonomic responsiveness to noxious stimulation. Except for the autonomic parameters, no other pain parameter differed between the three groups. Conclusion: The pain response system appeared to be quite unaltered in MCI patients compared to cognitively unimpaired individuals of the same age. Only the sympathetic responsiveness qualified as an indicator of early aging effects as well as of pathophysiology associated with MCI, which both seemed to affect the pain system independently from each other.

An Bras Dermatol. 2009 Jul; 84(3): 263-9Montagner S, Costa AAs a result of the increase in life expectancy, the study of the organic process of aging has been stimulated. Skin ageing, which reflects the signs of time, is a time-dependent process of progressive deterioration that can be intensified by sun exposure, which is known as photoaging. The damage of radiation on various cell structures and on the skin results in molecular and morphological changes to these components. Many research studies are performed to try to minimize the effects of photoaging; however, the main strategy to manage it is still prevention, which will only be achieved once we learn about the mechanisms involved in the process.

Am J Med Genet A. 2009 Aug 13; Al-Dosari M, Alkuraya FSEffect of aging on decreased skin elasticity and bone mass is well known. Geroderma osteodysplastica (GO) is a very rare autosomal recessive disorder that recapitulates these two phenotypes at a much younger age. Using homozygosity mapping and linkage analysis in four Saudi families we have identified two mutations in SCYL1BP1, consistent with the very recent report by Hennies et al. [Hennies et al. (2008); Nat Genet 40: 1410-1412]. Interestingly, the missense mutation identified in our study is associated with an identical phenotype to that seen with the other null mutations including the other mutation in this study. Our study, therefore, supplements the limited available data on SCYL1BP1 and further establishes deficiency of this recently described golgin as the only known cause of GO. (c) 2009 Wiley-Liss, Inc.

Postgrad Med. 2001 Feb; 109(2 Suppl): 70-7Bonomo RAInfectious diseases in the institutionalized elderly are emerging as 1 of the major issues challenging physicians treating adult patients. The most common syndromes encountered are nursing home-acquired pneumonia, urinary tract infections, and skin and soft tissue infections. As a complicating factor, immunocompromised elderly patients are often infected with bacteria highly resistant to antibiotics. The use of broad-spectrum agents in the nursing home may be accelerating this process. Developing algorithms for appropriate treatment of nursing home-acquired infections, assessing the factors that encourage the development of resistance, and finding interventions that can stem these processes are urgent priorities. Important clinical research questions include determining how frequently elderly patients are colonized with multiresistant pathogens and how these pathogens disseminate in this population. The future possibility of altering the aging immune system still remains an elusive goal.

Pigment Cell Melanoma Res. 2009 Aug 4; Vanover JC, Spry ML, Hamilton L, Wakamatsu K, Ito S, D'Orazio JAAbstract The K14-SCF transgenic murine model of variant pigmentation is based on epidermal expression of stem cell factor (SCF) on the C57BL/6J background. In this system, constitutive expression of SCF by epidermal keratinocytes results in retention of melanocytes in the interfollicular basal layer and pigmentation of the epidermis itself. Here we extend this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci. In the presence of K14-Scf, tyrosinase-mutant animals (previously thought incapable of synthesizing melanin) exhibited progressive robust epidermal pigmentation with age in the ears and tails. Furthermore, K14-SCF Tyr(c2j/c2j) animals demonstrated tyrosinase expression and enzymatic activity, suggesting that the c2j Tyr defect can be rescued in part by SCF in the ears and tail. Lastly, UV sensitivity of K14-Scf congenic animals depended mainly on the amount of eumelanin present in the skin. These findings suggest that c-kit signaling can overcome the c2j Tyr mutation in the ears and tails of aging animals and that UV resistance depends on accumulation of epidermal eumelanin.

Braz Oral Res. 2009 Apr-Jun; 23(2): 144-8Mancuso DN, Goiato MC, dos Santos DMOne of the greatest challenges faced by buccomaxillofacial prosthetists is to reproduce the patient's exact skin color and provide adequate esthetics. To reach this objective, professionals must use materials with easy characterization and that maintain color over long periods of time. The objective of this study was, thus, to evaluate the color stability of two types of silicones, Silastic 732 and Silastic MDX4-4210. Twenty-four test specimens were made from each type of silicone and were divided into a colorless group and groups intrinsically pigmented with ceramics, cosmetics or iron oxide. The specimens were submitted to an accelerated system of aging for non-metallic materials. Readings were carried out initially and after periods corresponding to 163, 351, 692 and 1,000 hours of aging, using a reflection spectrophotometer analysis, and color alterations were calculated by the CIE L*a*b* system. The data were submitted to variance analysis and Tukey's test at a 5% level of probability. The results demonstrated that, irrespective of the period of time analyzed, all the materials underwent some type of chromatic alteration (DeltaE > 0). The test specimens made with Silastic 732 and MDX4-4210, without pigmentation, presented the lowest color alteration values after 1,000 hours of aging. Of the pigments, ceramic presented the lowest color alteration values and cosmetic powder presented the highest values. Thus, it may be concluded that the materials without the incorporation of pigments presented similar color alteration values, and did not differ statistically. The cosmetic powder used in this study was the pigment that most altered the color of the test specimens.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 8-14Kamenisch Y, Berneburg MProgeroid syndromes are a group of diseases characterized by signs of premature aging. These syndromes comprise diseases such as Werner syndrome, Bloom syndrome, Rothmund-Thomson syndrome, Hutchinson-Gilford syndrome, Fanconi anemia, and ataxia-telangiectasia, as well as xeroderma pigmentosum, trichothiodystrophy, and Cockayne syndrome. Clinical symptoms of premature aging are skin atrophy with loss of cutaneous elasticity, dysfunction of cutaneous appendices, degeneration of the central nervous system and an increased susceptibility for malignant tumors. Genetic defects in the repair of DNA damage can lead to progeroid syndromes, and it is becoming increasingly evident that direct DNA damage and indirect damage by highly reactive oxygen species play central roles in aging. The clinical signs of progeroid syndromes and the molecular aspects of UV (ultraviolet radiation)-induced oxidative stress in aging are discussed.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 8-14; doi:10.1038/jidsymp.2009.6.

J Drugs Dermatol. 2009 Aug; 8(8): 708-12Tanaka Y, Matsuo K, Yuzuriha SBACKGROUND: Infrared irradiation stimulates collagen production, but histological differences in its long-term effects on type I versus type III collagen and elastin in human tissue are unclear. OBJECTIVE: To investigate the effects of infrared irradiation. METHODS AND MATERIALS: In vivo human tissues in sun-protected and sun-exposed areas were irradiated with infrared. Histological samples were analyzed, and visual changes were assessed up to 90 days post-treatment. RESULTS: Infrared irradiation provided long-term increases in collagen and elastin levels on post-irradiation days 30, 60 and 90 compared to controls. Significant increases in type I collagen persisted until 30 and 60 days, and in sun-protected and exposed skin biopsies, respectively. Significant increases in type III collagen and elastin persisted until 90 days in both sun-protected and sun-exposed skin biopsies. CONCLUSION: Infrared irradiation provides safe and effective long-term stimulation of collagen I and III and elastin, which is beneficial for improving skin laxity and wrinkles.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 44-9Krutmann J, Schroeder PThe exact pathogenesis of photoaging of the skin is not yet known. Earlier, a number of molecular pathways explaining one or more characteristics of photoaged skin have been described, but a unifying mechanistic concept is still missing. Here we propose the "Defective Powerhouse Model of Premature Skin Aging", which reconciles most of the earlier conducted research as one concept. In this model, the persistence of UV radiation-induced mtDNA deletions or the infrared radiation-induced disturbance of the electron flow of the mitochondrial electron transport chain leads to inadequate energy production in dermal fibroblasts. As a consequence of this defective powerhouse, retrograde mitochondrial signaling pathways are triggered that then they transduce functional and structural alterations in the skin. This model, which is supported by a growing number of recent studies, is of direct clinical importance in preventing and treating photoaging in human skin.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 44-49; doi:10.1038/jidsymp.2009.1.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 15-9Cho S, Shin MH, Kim YK, Seo JE, Lee YM, Park CH, Chung JHSunlight damages human skin, resulting in a wrinkled appearance. Since natural sunlight is polychromatic, its ultimate effects on the human skin are the result of not only the action of each wavelength separately, but also interactions among the many wavelengths, including UV, visible light, and infrared (IR). In direct sunlight, the temperature of human skin rises to about 40 degrees C following the conversion of absorbed IR into heat. So far, our knowledge of the effects of IR radiation or heat on skin aging is limited. Recent work demonstrates that IR and heat exposure each induces cutaneous angiogenesis and inflammatory cellular infiltration, disrupts the dermal extracellular matrix by inducing matrix metalloproteinases, and alters dermal structural proteins, thereby adding to premature skin aging. This review provides a summary of current research on the effects of IR radiation and heat on aging in human skin in vivo.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 15-19; doi:10.1038/jidsymp.2009.7.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 20-4Quan T, Qin Z, Xia W, Shao Y, Voorhees JJ, Fisher GJUV radiation from the sun impacts skin health adversely through complex, multiple molecular pathways. Premature skin aging (photoaging) is among the most widely appreciated harmful effects of chronic exposure to solar UV radiation. Extensive damage to the dermal connective tissue is a hallmark of photoaged skin. Disruption of the normal architecture of skin connective tissue impairs skin function and causes it to look aged. UV irradiation induces expression of certain members of the matrix metalloproteinase (MMP) family, which degrade collagen and other extracellular matrix proteins that comprise the dermal connective tissue. Although the critical role of MMPs in photoaging is undeniable, important questions remain. This article summarizes our current understanding of the role of MMPs in the photoaging process and presents new data that (1) describe the expression and regulation by UV irradiation of all members of the MMP family in human skin in vivo and (2) quantify the relative contributions of epidermis and dermis to the expression of UV irradiation-induced MMPs in human skin in vivo.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 20-24; doi:10.1038/jidsymp.2009.8.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 2-7Amano SAging of sun-exposed skin is accelerated by three major environmental factors: UV radiation, dryness, and oxidation. UV radiation exposure is the most influential factor in skin aging (so-called photoaging). To find ways to protect against damage caused by UV exposure and to delay photoaging, we studied internal changes of sun-exposed skin compared with those of sun-protected skin. We found that the basement membrane (BM) at the dermal-epidermal junction (DEJ) of sun-exposed skin becomes damaged and multilayered and partly disrupted compared with that of sun-protected skin. BM plays important roles in maintaining a healthy epidermis and dermis, and repeated damage destabilizes the skin, accelerating the aging process. Matrix metalloproteinases (MMPs) and urinary plasminogen activator are increased in UV-irradiated skin. MMPs are detected in the cornified layer in sun-exposed skin, but not in sun-protected skin. Using skin-equivalent models, we found that MMPs and plasmin cause BM damage and that the reconstruction of BM is enhanced by inhibiting these proteinases, as well as by increasing the synthesis of BM components. Enhancement of BM repair mechanisms may be a useful strategy in retarding photoaging.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 2-7; doi:10.1038/jidsymp.2009.5.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 56-9Matsui MS, Hsia A, Miller JD, Hanneman K, Scull H, Cooper KD, Baron EThe association between ultraviolet radiation (UVR) exposure and both skin cancer and photo-aging is well documented. In addition to the conventional organic-chemical and physical-mineral type sunscreens, other non-sunscreen protective strategies have been developed. These include topically applied botanical extracts and other antioxidants as well as topical DNA repair enzymes. Standard terms of photoprotection such as sun protection factor (SPF) do not accurately reflect the photoprotection benefits of these materials. For example, in spite of minimal SPF, tea extract containing polyphenols such as (-)-epigallocatechin-3-gallate (EGCG) has been shown to protect against UV-induced DNA damage and immune suppression, in part through its ability to reduce oxidative stress and inhibit NF-kB. The addition of botanical antioxidants and vitamins C and E to a broad-spectrum sunscreen may further decrease UV-induced damage compared with sunscreen alone. These agents have been shown to enhance protection against UV-induced epidermal thickening, overexpression of MMP-1and MMP-9, and depletion of CD1a(+) Langerhans cells. Non-sunscreen materials such as botanical extracts, antioxidants, and DNA repair enzymes can contribute value when applied topically to human skin in vivo.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 56-59; doi:10.1038/jidsymp.2009.14.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 36-43Imokawa GIn clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Repetitive irradiation of animal skin with UVB radiation at suberythemal doses significantly reduces its elastic properties, resulting in the formation of wrinkles. Repetitive UVB irradiation elicits a marked alteration in the three-dimensional structure of elastic fibers, which is closely associated with a subsequent reduction in the elastic properties of the skin. Although UVB irradiation stimulates the activity of fibroblast elastases in the dermis, a synthetic inhibitor specific for fibroblast elastases prevents wrinkle formation. The close interrelationships among wrinkle formation, elastic properties, and elastic fiber linearity are revealed by the effects of different concentrations of the elastase inhibitor (R(2)>0.9), suggesting that enhanced elastase activity by dermal fibroblasts plays a pivotal role in the UVB wrinkling mechanism. In in vitro studies we identified a paracrine linkage between keratinocytes and fibroblasts that leads to wrinkle formation through the upregulation of fibroblast elastases. These studies support our hypothesis for a mechanism of wrinkle formation by which cytokine expression is activated in epidermal keratinocytes by UVB radiation and triggers dermal fibroblasts to increase their expression of elastase.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 36-43; doi:10.1038/jidsymp.2009.11.

J Investig Dermatol Symp Proc. 2009 Aug; 14(1): 53-5Morita A, Torii K, Maeda A, Yamaguchi YAlthough it is now widely recognized that tobacco smoke has negative effects on the skin, the molecular mechanisms underlying its skin-aging effects remain uncertain. Epidemiological studies indicate that tobacco smoking is a strong independent predictor of facial wrinkle formation and other aspects of premature skin aging. Recent in vivo studies in humans and mice provided the first direct evidence that tobacco smoke causes premature skin aging, and they have begun to reveal the molecular changes in the skin that occur in response to it. Water-soluble tobacco smoke extract, which predominantly produces oxidative stress when applied topically to cultured skin fibroblasts, impairs collagen biosynthesis. Matrix metalloproteinases, which degrade collagen, are induced dose-dependently by tobacco smoke extract as well as by other constituents that trigger the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor that mediates the toxicity of several environmental contaminants, including photoproducts in the body generated by UVB radiation. Tobacco smoke also contains many non-water-soluble constituents that activate the AhR pathway. Our most recent studies using hexane-soluble tobacco extract indicate that activation of the AhR pathway may play a role in the premature skin-aging effects of tobacco smoke exposure.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 53-55; doi:10.1038/jidsymp.2009.13.

Age (Dordr). 2009 Aug 11; Gonzales P, Rikke BAAging leads to a loss of thermoregulation that can be readily monitored in laboratory mice. However, it is unclear from previous studies-we provide a tabular summary of 15 articles-whether significant loss occurs by midlife ( approximately 15 months of age). In this study, we examined 34 females from 22 LSXSS strains starting at 4 and 8 months of age (17 mice per age group). We used transponders inserted just under the loose skin of the pelt and calibrated against rectal body temperature to measure temperatures quickly without restraint. We found that the mean body temperatures measured 5 months later (9 and 13 months of age) had dropped significantly below normal in both groups: 0.6 masculineC lower in the younger cohort and 1.0 masculineC lower in the older cohort. These drops were not associated with weight loss or signs of pathology. Notably, the loss of thermoregulation between 8 and 13 months of age also exhibited genetic variation that was highly significant (P = 0.004). Such variation is potentially a powerful tool for determining the cause of thermoregulatory loss with age and whether this loss predicts senescence changes later in life, including the force of mortality.

J Struct Biol. 2009 Aug 7; Youn HS, Shin TJSupramolecular assembly of collagen fibrils into collagen fiber and its distribution in fish scales of red seabream, Pagrus major, were investigated. By virtue of Zernike phase-contrast hard x-ray microscopy, it has been firstly observed that collagen fiber consists of helical substructures of collagen fibrils wrapped with incrustation. As it close to the scalar focus (that is, with aging), loosened- and deteriorated-helical assemblies started to be observed with loosing wrapping incrustation, indicative of the distortion of the basic helical assembly. Various distributions and packing arrangements of collagen fibers were observed dependent on subdivisions of fish scale. Freshly growing edge region of fish scale, embedded into fish skin, showed rarely patched and one directionally arranged collagen fibers, in which specifically triple helical assemblies of collagen fibrils were found. On the contrary, relatively aged region of the rostral field close to the scalar focus displayed randomly directed and densely packed collagen fibers, in which loosened- and deteriorated-helical assemblies of collagen fibrils were mostly found. Our results have demonstrated that hard x-ray microscope can be a powerful tool to study in-situ internal structure of biological specimens in an atmospheric pressure.

J Exp Med. 2009 Aug 10; Agius E, Lacy KE, Vukmanovic-Stejic M, Jagger AL, Papageorgiou AP, Hall S, Reed JR, Curnow SJ, Fuentes-Duculan J, Buckley CD, Salmon M, Taams LS, Krueger J, Greenwood J, Klein N, Rustin MH, Akbar ANImmunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4(+) T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-alpha secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-alpha after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging.

Forensic Sci Med Pathol. 2009 Aug 5; Gibson SJ, Scandrett CM, Solomon CJ, Maylin MI, Wilkinson CMA computer assisted method for altering the perceived age of a human face is presented. Our technique is based on calculating a trajectory or axis within a multi-dimensional space that captures the changes in large scale facial structure, shading and complexion associated with aging. Fine facial details associated with increasing age, such as wrinkles, are added to the aged face using a variation on a standard image processing technique called high boost filtering. The method is successfully applied to two-dimensional photographic images exhibiting uncontrolled variations in pose and illumination. Unlike our previous work on automated age progression, here the objective is to allow a certain degree of manual control over the process by the adjustment of three key progression-control-parameters. In the future this work may form the basis for a software tool to be used by forensic artists.

Cancer Biol Ther. 2009 Oct 6; 8(19): Li J, Chigurupati S, Agarwal R, Mughal MR, Mattson MP, Becker KG, Wood WH, Zhang Y, Morin PJClaudin proteins are frequently overexpressed in various tumors such as breast, prostate and ovarian cancer. While their functions in cancer have not been completely elucidated, roles in survival, adhesion and invasion have been suggested. In order to clarify the roles of claudins in ovarian cancer, we have performed gene expression profiling of ovarian surface epithelial cells overexpressing claudin-4 and compared the expression patterns to the parental, non-expressing cells. Claudin-4 expression leads to the differential expression of several genes, including many that have previously been implicated in angiogenesis. In particular, angiogenic cytokines, such as IL-8, were found elevated while genes of the angiostatic interferon pathway were found downregulated. In vitro assays show that claudin-4-expressing cells produce factors that can stimulate angiogenesis as measured by tube formation and migration in HUVEC cells. In addition, an in vivo mouse dorsal skinfold assay confirms that cells expressing claudin-4 secrete factors that can mediate angiogenesis in the dorsal skin of mice. Our data suggest a novel function for claudin-4 in cancer and provide an additional rationale for its common overexpression in human tumors.

Toxicol Ind Health. 2009 May; 25(4-5): 231-9Pavlou P, Rallis M, Deliconstantinos G, Papaioannou G, Grando SInhaled tobacco smoke comes in direct contact with few organs such as mouth, lungs, and stomach. Cigarette smoke (CS) in lungs has been extensively studied. However, limited data exist on its effect on skin, and there are no long-term experimental studies suggesting toxic effects on skin. Even though it is generally accepted that CS is among the main factors of skin aging, the number of experimental studies showing this aging effect is limited. We hereby studied the effect of long-term exposure to CS on the skin of hairless mice in combination with or without ultraviolet (UV) light. In addition, we investigated potential skin protection by a potent antioxidant namely procyanidine-rich French maritime pine bark extract (PBE) pycnogenol. Male and female hairless SKH-2 mice were exposed for 10 months to tobacco smoke and/or UV light in vivo, and their effects on skin were investigated. Some biophysical parameters such as development of erythema, transepidermal water loss (TEWL), and skin elasticity were measured. The results show that UV and CS may be acting synergistically, as shown by the enhanced TEWL, erythema values, epitheliomas, and squamous cell carcinomas (SCCs) observed, whereas PBE seems to protect skin against SCC.

Am J Pathol. 2009 Aug 6; Majora M, Wittkampf T, Schuermann B, Schneider M, Franke S, Grether-Beck S, Wilichowski E, Bernerd F, Schroeder P, Krutmann JDeletions within the mitochondrial DNA (mtDNA) are thought to contribute to extrinsic skin aging. To study the translation of mtDNA deletions into functional and structural changes in the skin, we seeded human skin fibroblasts into collagen gels to generate dermal equivalents. These cells were either derived from Kearns-Sayre syndrome (KSS) patients, who constitutively carry large amounts of the UV-inducible mitochondrial common deletion, or normal human volunteers. We found that KSS fibroblasts, in comparison with normal human fibroblasts, contracted the gels faster and more strongly, an effect that was dependent on reactive oxygen species. Gene expression and Western blot analysis revealed significant upregulation of lysyl oxidase (LOX) in KSS fibroblasts. Treatment with the specific LOX inhibitor beta-aminopropionitrile decreased the contraction difference between KSS and normal human fibroblast equivalents. Also, addition of the antioxidant N-tert-butyl-alpha-phenylnitrone reduced the contraction difference by inhibiting collagen gel contraction in KSS fibroblasts, and both beta-aminopropionitrile and N-tert-butyl-alpha-phenylnitrone diminished LOX activity. These data suggest a causal relationship between mtDNA deletions, reactive oxygen species production, and increased LOX activity that leads to increased contraction of collagen gels. Accordingly, increased LOX expression was also observed in vivo in photoaged human and mouse skin. Therefore, mtDNA deletions in human fibroblasts may lead to functional and structural alterations of the skin.

Toxicol Ind Health. 2009 May; 25(4-5): 241-7Valacchi G, Pecorelli A, Mencarelli M, Maioli E, Davis PBeta-carotene has been thought to protect against oxidative stress generated by ultraviolet radiation and thus prevents skin cancer and skin aging (Biesalski and Obermueller-Jevic, 2001). However, nothing is known about its potential effects against other environmental sources of oxidative stress such as ozone (O(3)) in skin. Intake of oral beta-carotene supplements before exposure to sunlight (and thus inevitably also to O(3)) has been recommended on a population-wide basis. However, although some studies have shown beta-carotene as providing skin protection as an antioxidant, other studies using skin cells in culture have shown that beta-carotene may have unexpected prooxidant properties (Obermüller-Jevic, et al., 2001). Given this, there is an ongoing debate regarding the protective or potentially harmful role(s) of beta-carotene in human skin. In this study, the effect of beta-carotene on ozone's effects on the skin of hairless mice was assessed. After feeding a diet supplemented with 0.5% beta-carotene for 1 month, mice were subjected to O(3) exposure (0.8 ppm 6 h/day; 7 days) and the induction of proinflammatory markers such as tumor necrosis factor-alpha (TNFalpha), macrophage inflammatory protein 2 (MIP2), and inducible nitric oxide synthase (iNOS), and markers of oxidative stress, heme-oxygenase-1 (HO-1), were quantitated. The data showed that beta-carotene downregulated the induction of TNFalpha, MIP2, iNOS, and HO-1 in response to O(3). We conclude that beta-carotene provides protection against O(3)-induced skin oxidative stress in vivo, which is consistent with a protective role for beta-carotene in the skin.

Wien Klin Wochenschr. 2009; 121(13-14): 431-9Pavicic T, Steckmeier S, Kerscher M, Korting HCAs well as for topically used dermatological agents, studies performed according to the rules of evidence-based medicine (EBM) are also needed for cosmetics. Although the concept of evidence-based cosmetics has been only partly developed so far, there are some agents and preparations available that can be considered as evidence-based. In this paper we present data from several studies that claim to have examined and demonstrated the efficacy of cosmetic preparations for the management of solar damage and aging skin as well as lentigo and melanosis according to EBM criteria. Certainly, further controlled studies are needed to cover the main application areas of dermocosmetics. Retinol and antioxidant agents such as vitamin C and coenzymes that positively act via several mechanisms on collagen biosynthesis can be considered evidence-based substances for the management of aging skin. According to the same criteria, the preventive effect of regularly applied dermocosmetic sun screens on the development of actinic keratosis could also be shown. Dermocosmetic sun screens should offer adequate protection against UV-B and UV-A light by combining compatible organic and/or non-organic UV-filters and at the same time be well tolerated. Furthermore, they may contain some additional agents such as antioxidants, DNA repair enzymes, dexpanthenol, glycerin or hamamelis distillate. In the treatment of melanosis, a substantial bleaching effect corresponding to that of 0.1% topical tretinoin can be achieved with 10% all-trans-retinol gel. Preparations containing urea, ammonium lactate or glycerol in different concentrations are considered the best characterized and most effective substances for the care of dry skin. However, the lack of controlled studies confirming the efficacy of dermocosmetic products as well as the superiority of the preparation incorporating the active agent over the corresponding base is a problem yet to be solved. Undoubtedly, the efficacy and the sustainability of the achieved effects have to be examined and proven accordingly to EBM criteria in further active cosmetic agents. Moreover, generally accepted guidelines for the examination of efficacy and tolerability of dermocosmetics have to be developed.

Skin Pharmacol Physiol. 2009 Jul 31; 22(4): 200-209Bellemère G, Stamatas GN, Bruère V, Bertin C, Issachar N, Oddos TThe antiaging efficacy of retinol (ROL) has been explored mainly clinically in photoprotected skin sites and for high doses of ROL (0.4-1.6%). The objective of the study was to demonstrate the antiaging action of a low and tolerable dose of ROL (0.1%) ex vivo by measuring the expression of cellular retinoic-acid-binding protein II (CRABP2) and heparin-binding epidermal growth factor (HBEGF) by a histological evaluation of the epidermis and in vivo by assessing major aging signs and performing three-dimensional profilometry and digital imaging during a 9-month double-blind placebo-controlled study involving 48 volunteers. Finally, epidermal cell proliferation was evaluated using tryptophan fluorescence spectroscopy. Our results demonstrate that 0.1% ROL induced CRABP2 and HBEGF gene expression and increased keratinocyte proliferation and epidermal thickness. In human volunteers, topical application of a ROL-containing product improved all major aging signs assessed in our study (wrinkles under the eyes, fine lines and tone evenness). Moreover, tryptophan fluorescence increased in the active-agent-treated group and not in the placebo-treated group, indicating that cell proliferation was accelerated in vivo. These data demonstrate that a product containing a low dose (0.1%) of ROL promotes keratinocyte proliferation ex vivo and in vivo, induces epidermal thickening ex vivo and alleviates skin aging signs, without any significant adverse reaction.

J Ethnopharmacol. 2009 Jul 18; Hsu MF, Chiang BHETHNOPHARMACOLOGICAL RELEVANCE: Radix astragali, a well-known Chinese herb, which has been traditionally used for skincare, and microbial fermentation is one of the conventional methods for processing Chinese herbs. AIM OF THE STUDY: This research studied the effects of non-fermented (HQNB) and fermented preparations (HQB) of Radix astragali on hyaluronic acid (HA) production in primary human skin cells. MATERIALS AND METHODS: HQB and HQNB were prepared and added to the cultures of primary human skin cells. Hyaluronic acid content was determined using ELISA. Real-time RT-PCR was used to evaluate hyaluronan synthase gene expression. The bioactive compounds were analyzed by HPLC. RESULTS: The growth-stimulating effect of HQNB on both of keratinocytes and fibroblasts were significantly higher than that of HQB. Conversely, HQB, but not HQNB significantly stimulated HA production in both cultured primary human epidermal keratinocytes and human dermal fibroblasts in dose-dependent manners. In addition, HQB markedly and dose-dependently increased the expression of hyaluronan synthase 3 and hyaluronan synthase 2 mRNA in HaCaT cells and human fibroblasts, respectively. Therefore, HQB might be a promising candidate for preventing the age-dependent loss of HA content in aged human skin, and its effect on the enhancement of HA synthesis in skin cells is highly related to its effect on the expression of hyaluronan synthase genes. The three major active isoflavonoids in Radix astragali were identified as ononin, calycosin, and formononetin. After fermentation, all of these three compounds in HQB were significantly reduced. However, HQB still had significantly higher enhancement effect on the production of HA than HQNB. It appeared that isoflavonoid aglycones or other metabolites, converted from their primary isoflavones during fermentation, might be responsible for the skincare functions found in this study. CONCLUSION: This study demonstrated the low toxicity and the stimulating effects of HQB on HA synthesis, and suggests that HQB may play a promising role in anti-aging cosmetic applications.

FASEB J. 2009 Jul 29; Salem MM, Shalbaf M, Gibbons NC, Chavan B, Thornton JM, Schallreuter KUVitiligo is characterized by a patchy loss of inherited skin color affecting approximately 0.5% of individuals of all races. Despite the absence of the protecting pigment and the overwhelming evidence for hydrogen peroxide (H2O2)-induced oxidative stress in the entire epidermis of these patients, there is neither increased photodamage/skin aging nor a higher incidence for sun-induced nonmelanoma skin cancer. Here we demonstrate for the first time increased DNA damage via 8-oxoguanine in the skin and plasma in association with epidermal up-regulated phosphorylated/acetylated p53 and high levels of the p53 antagonist p76(MDM2). Short-patch base-excision repair via hOgg1, APE1, and polymerasebeta DNA repair is up-regulated. Overexpression of Bcl-2 and low caspase 3 and cytochrome c levels argue against increased apoptosis in this disease. Moreover, we show the presence of high epidermal peroxynitrite (ONOO(-)) levels via nitrotyrosine together with high nitrated p53 levels. We demonstrate by EMSA that nitration of p53 by ONOO(-) (300x10(-6) M) abrogates DNA binding, while H2O2-oxidized p53 (10(-3) M) enhances DNA binding capacity and prevents ONOO(-)-induced abrogation of DNA binding. Taken together, we add a novel reactive oxygen species to the list of oxidative stress inducers in vitiligo. Moreover, we propose up-regulated wild-type p53 together with p76(MDM2) as major players in the control of DNA damage/repair and prevention of photodamage and nonmelanoma skin cancer in vitiligo.-Salem, M. M. A. E. L., Shalbaf, M., Gibbons, N. C. J., Chavan, B., Thornton, J. M., Schallreuter, K. U. Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage.

Consult Pharm. 2009 Jun; 24 Suppl B: 5-10Drab SROBJECTIVES: To identify the incidence and symptoms of type 2 diabetes in older adult patients, review appropriate glycemic targets for older adults with type 2 diabetes, and consider the rationale for managing hyperglycemia in this patient population. DATA SOURCES: Live symposium presentation based on clinical practice and research, medical literature, and studies published between January 1993 and November 2008 on managing diabetes in older adults, government statistics, and medical society guidelines. STUDY SELECTION: Thirty-five articles were identified from various data sources and were evaluated. The following search terms were used: Complications, Diabetes, Glucose Tolerance, Goals, Hyperglycemic Hyperosmolar Nonketotic Syndrome (HHNS), Long-term Care, Management, Obesity, Prevalence, Risk Factors, Screening, Senior, and Symptoms. All information deemed relevant to recognizing the rising impact of diabetes in seniors and its implications for management were included. DATA EXTRACTION: Data were extracted independently of the author by the librarians of the University of Pittsburgh. DATA SYNTHESIS: As a result of the aging of the U.S. population, the increasing prevalence of diabetes, and the considerable impact of this disease among older adults, it is only logical to assume that the number of older individuals with diabetes and its impact on older adults will continue to rise. Uncontrolled diabetes has significant risks in the elderly beyond the typical microvascular and macrovascular complications commonly associated with diabetes: cognitive impairment, depression, excessive skin problems, and an increased risk of falls. However, glycemic control reduces the development of these complications and can lead to improvements in dementia, memory, energy, physical activity, mood, and quality of life. CONCLUSION: Because many older adults may benefit from intensive, long-term glycemic control, consultant pharmacists should understand the importance of individualizing glycemic targets, management strategies, and pharmacotherapy in older adults.

J Drugs Dermatol. 2009 Jul; 8(7 Suppl): s3Weinkle SH, Tiesman JP

J Drugs Dermatol. 2009 Jul; 8(7 Suppl): s4-7Osborne R, Mullins LA, Jarrold BBGlobal gene expression profiling provides a useful means to identify key aspects of the skin aging process, and provides information to help develop new skin technologies. Important aspects of skin aging that can be addressed include skin hydration, barrier, matrix, pigmentation and antioxidant capacity. Human skin equivalent cultures allow topical application of test compounds, combinations and products to their stratum corneum surface and measurement of predictive biomarkers. Using this in vitro biomarker approach, it is possible to detect skin barrier enhancement in response to the compounds niacinamide and hexamidine, matrix effects to the peptides Pal-KT and Pal-KTTKS, and hydration and matrix responses to niacinamide and N-acetylglucosamine.

J Drugs Dermatol. 2009 Jul; 8(7 Suppl): s15-8Kaczvinsky JR, Grimes PESkin aging integrates the impact of extrinsic skin insults (e.g., ultraviolet [UV] light, etc.) with chronological, genetically programmed decreases in cellular function. A genomic study of aged skin highlighted the mechanistic importance of skin barrier function, exfoliation, control of reactive oxygen species and maintenance of extracellular matrix to the aging process. A set of topical products designed to address these mechanistic themes was developed and clinically tested. The individual products improved skin barrier function, hydration and skin turnover, as well as the smoothness and depth of periorbital wrinkles. Treatment with a regimen of these products improved the appearance of facial wrinkles after eight weeks. Changes in treated subjects' stratum corneum protein biomarker levels were consistent with the mechanistic pathways identified in the genomic work. Thus, leveraging a genomic understanding of skin aging led to the development of a clinically efficacious, aesthetically pleasing cosmetic regimen that improved the appearance of aged skin.

J Drugs Dermatol. 2009 Jul; 8(7 Suppl): s8-11Robinson MK, Binder RL, Griffiths CELike all tissues, the skin ages due to the passage of time (chronologic aging). However, skin is also exposed to external insults, such as sunlight. Aging due to chronic sun exposure (photoaging) is characterized clinically by wrinkling, dyspigmentation and other changes. Chronologic and photoaging of skin have been distinguished at the structural, cellular and molecular levels. However, many underlying mechanisms remain a mystery. Recent sequencing of the human genome and development of genome-wide microarray platforms now permit analysis of skin aging at the level of gene expression. Analysis of gene expression differences between young and older sun-protected and sun-exposed skin showed that photoaging produces many similar (but more severe) changes in gene expression versus chronologic aging. However, some changes are unique to one form of aging or the other. Bioinformatics tools also enable an integrated analysis of gene expression themes and pathways, which may provide new insights into the mechanisms of skin aging and possible interventions.

J Cosmet Laser Ther. 2009 Jul 22; 1-5Chiba C, Usui A, Hara H, Ishi YBackground: The long-pulse Nd:YAG laser is a versatile, effective and safe treatment modality for skin rejuvenation, in addition to the treatments of telangiectasia and laser hair removal. Objective: To evaluate the clinical efficacy and safety of a long-pulse Nd:YAG laser for skin rejuvenation in Japanese patients. Methods: A total of 19 female Japanese patients with Fitzpatrick skin types III or IV were treated for improving their wrinkles, skin texture, and skin laxity with a repetitive painting motion technique. Results: Of 19 patients, 10 showed good or superior results in their faces with minimal discomfort after two to seven treatments every 3-4 weeks. Improvement was also observed in wrinkles and skin laxity as well as skin texture and fine lines. An increase in the density of collagen fibers in the papillary dermis was observed histopathologically. Conclusion: The long-pulse Nd:YAG laser with a minimal down time technique should be considered as a treatment modality in Asian women. Further studies are necessary to determine more optimal treatment parameters, without compromising patients' comfort.

J Med Food. 2009 Jun; 12(3): 601-7Shim JS, Choi EJ, Lee CW, Kim HS, Hwang JKMatrix metalloproteinase (MMP)-1 is a superfamily of zinc-dependent endopeptidases that are capable of degrading all components of the extracellular matrix. Kaempferia pandurata extract (0.01-0.5 microg/mL) significantly reduced the expression of MMP-1 and induced the expression of type 1 procollagen at the protein and mRNA levels in a dose-dependent manner. Ultraviolet (UV)-induced MMP-1 initiates cleavage of fibrillar collagen. Once cleaved by MMP-1, collagen can be further degraded by elevated levels of MMP-3 and MMP-9. It was found that increased MMP-1 expression due to UV irradiation was mediated by activation of mitogen-activated protein kinases such as extracellular-regulated kinase (ERK), Jun N-terminal kinase (JNK), and p38 kinase. Treatment of K. pandurata extract in the range of 0.01-0.5 microg/mL inhibited the UV-induced phosphorylations of ERK, JNK, and p38, respectively. Moreover, inhibition of phosphorylated ERK, JNK, and p38 by K. pandurata extract resulted in decreased c-Fos expression and c-Jun phosphorylation induced by UV light. The results strongly suggest that K. pandurata is potentially useful for the prevention and treatment of skin aging.

Skin Res Technol. 2009 Aug; 15(3): 357-63Koehler MJ, Preller A, Kindler N, Elsner P, König K, Bückle R, Kaatz MBACKGROUND: Skin aging is accelerated by extrinsic factors, particularly actinic damage. Over the last decades, both clinical and pathological differences between intrinsic and actinic aging have been characterized. In this work, we aimed at quantifying skin aging by non-invasive in vivo methods. METHODS: Young healthy volunteers using indoor tanning facilities and aged people were compared with appropriate controls by measurements of skin elasticity with the Cutometer and the Reviscometer and by semi-quantitative evaluation of the dermal matrix composition by the multiphoton laser tomograph DermaInspect. RESULTS: We found differences between the sun-protected volar forearm and the dorsal side as well as between young and old test persons with all three methods. No significant differences were found between the skin of indoor-tanned test persons and control. Also, gender had no influence on the severity of skin aging. CONCLUSION: The most consistent results were obtained with the DermaInspect. The considerable inter-individual variation due to the cross-sectional design of the study may have disguised the factual skin damage caused by tanning beds.

Int J Cosmet Sci. 2009 Jul 17; Fujimura T, Sugata K, Haketa K, Hotta MSynopsis Visual scoring has been used to evaluate ethnic differences in skin wrinkling, but it is not sufficient to fully evaluate those differences in wrinkles. We examined whether both the roughness analysis of the skin and visual scoring are sufficient to characterize ethnic differences in wrinkles in Japanese, Chinese and German women. One hundred and five Japanese, 96 Chinese and 90 German age-matched women participated in this study. The severity of their wrinkles in the skin at two sites at the periphery of the eye was evaluated by visual scoring using a photoscale and by roughness values obtained from three-dimensional analysis of skin replicas. Slight but significant differences were scarcely observed between Japanese and Chinese women as well as between Japanese and German women at the same age group using the visual scoring method. However, significant and clearer differences among those ethnic groups were observed using the roughness analysis of skin replicas. Below the eye, significant differences among those ethnic groups were observed using both visual wrinkle scoring and roughness analysis. However, the extent of increased roughness values with age was relatively small compared with the increased wrinkle scores. These results show that roughness analysis is more sensitive than the visual scoring method when comparing ethnic differences in wrinkles. We conclude that roughness analysis of the skin is an important secondary evaluation criterion to visual scoring necessary to evaluate ethnic differences of wrinkles.

Skin Res Technol. 2009 Aug; 15(3): 306-13Querleux B, Baldeweck T, Diridollou S, de Rigal J, Huguet E, Leroy F, Holloway Barbosa VBACKGROUND: Ethnic differences in skin structural features have not been thoroughly investigated, and the few reported studies are contradictory. Thus, we have carried out a set of in vivo measurements on the skin of about 400 volunteers from various ethnic origins living in the same environment. METHODS: Female subjects were distributed into four ethnic groups: African Americans, Mexicans, Caucasians, and Chinese. Inter- and intra-ethnic skin structural differences, according to age and anatomic site, were investigated using three non-invasive skin-imaging methods: ultrasound (US) at 25 and 150 MHz, and optical coherence tomography (OCT). RESULTS: The thickness of the skin is higher on the cheek compared with the dorsal and ventral forearm, with no ethnic or age-related specificity. We confirm that the sub-epidermal non-echogenic band is a sensitive marker of skin aging, and reveal for the first time that it is less pronounced in African Americans. From OCT images, we bring out evidence that the thickness of the dermal-epidermal junction (DEJ) decreased with age, and was higher in African Americans than in Caucasians. Finally, by comparing US images at 150 MHz with OCT images, we show that papillary dermis thickness can be measured and appears to be quite constant irrespective of age or ethnic group. CONCLUSION: Our study confirms that skin imaging is very attractive to further our knowledge of the morphology of skin from various ethnic origins. Regarding age effects, quantitative parameters have shown that they would be delayed in African Americans compared with all other ethnic populations.