The concepts of quantum theory can be introduced into psychophysiology

Changes in the structural proteins and hydration during aging is responsible for altered skin morphologic and mechanical properties manifested as wrinkling, sagging, loss of elasticity, or apparent dryness. To gain insight into the age-related alterations in protein conformation and water structure, we obtained Raman spectra from the sun-protected buttock skin representing chronologic aging and the sun-exposed forearm skin representing combined effects of photoaging and chronologic aging. Ten aged individuals (five men, five women; age range 74-87) and 10 control young individuals (five men, five women; age range 22-29) entered the study. In the photoaged forearm skin the positions of protein-specific amide I, amide III, and CH stretching bands were shifted, suggesting increased protein folding. In contrast, major changes were seen only in the amide I peak in chronologically aged skin. The intensity of the 3250 cm(-1) OH stretching band was increased in photoaged skin (but not in chronologically aged skin) indicating an increased water content. R(v) representation of the low-frequency region of Raman spectra was applied to determine water structure. In the young skin and chronologically aged skin water was mostly present in the bound form. In the photoaged skin, however, an increase in intensity at 180 cm(-1) was noted, which reflects an increase in the not-protein bound water (tetrahedron water clusters). In conclusion, it seems that proteins in the photoaged skin are more compact and interact with water to limited degree. Impairment in protein hydration may add to the understanding of ultrastructural, mechanical, and biochemical changes in structural proteins in the aged skin.     

Echographic evaluation with image analysis of normal skin: variations according to age and sex

In order to identify and characterize the sonographic variations between different age groups, 48 subjects, 24 aged 27-30, and 24 over 60, were studied with a 20-MHz B scanner on six skin sites. Images were evaluated by the instrument's standard programme and by a new image analysis software package enabling the characterization of steady structures or transitory functional aspects of skin reactions, by highlighting areas in which the echo amplitudes are included within selected values, and by calculating their extension. Three bands were selected as intervals of interest, respectively, highlighting hyporeflecting parts of the dermis, tissue reflecting with intermediate amplitude values and hyperreflecting epidermis and dermis. This method was employed to assess skin thickness, demonstrating its decrease in elderly skin, to characterize and quantify the hypoechogenic subepidermal band appearing in the elderly at volar and dorsal forearm skin, and to evaluate echogenicity of the upper and lower dermis. Our data show that there is a great regional variation in the behaviour of ultrasound reflection of elderly skin in respect to the skin of young subjects. However, a general trend can be identified, consisting in a shift from low-intensity ultrasound echoes, characteristic in the dermis of young subjects, to intermediate or high reflection amplitudes, which are more frequent in elderly skin. Thus, the echographic method provides two parameters for the evaluation of skin aging.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fine structure of the retinal pigment epithelium of Oreochromis niloticus L. (Cichlidae; Teleostei) in light- and-dark adaptation

To examine pathological changes of melanocytes in photodamaged skin, we performed a comparative cytomorphometric analysis and a qualitative observation of melanocytes from sun-exposed and sun-protected facial skin at the electron microscopic level. The characteristic ultrastructural features of melanocytes in photodamaged skin included a statistically significant increase in their number, a marked nuclear heterogeneity, signs of cell activation, close apposition to photodamaged degenerate keratinocytes, degenerative changes represented by large intracytoplasmic vacuoles, and frequent direct contacts with Langerhans cells. Cytomorphometric analysis revealed significant decreases in cell and nuclear sizes, increases in cell and nuclear perimeters accompanied by irregular contours, and higher degrees of nuclear ellipticity in sun-exposed melanocytes. This study demonstrates that there are remarkable differences in the morphology of melanocytes between photoaged and intrinsically aged facial skin, and supports the concept that photoageing processes contribute to cytological alterations in melanocytes.     

A double-blind, placebo-controlled study of intranasal apomorphine spray as a rescue agent for off-states in Parkinson''s disease

Physico-chemical and morphologic parameters of skin layers and subcutaneous tissue in lymphedematous limb were studied in vivo using magnetic resonance imaging. High resolution images were obtained with a depth resolution of about 70 microm, using a specific surface gradient coil specially designed for skin imaging and connected to a standard whole-body imager at 1.5 T. Twenty-one patients with unilateral lower extremity lymphedema (11 primary and 10 secondary) were examined. Skin thickness, relaxation times, and relative proton density were calculated in lymphedematous limbs and in contralateral extremities. In diseased limbs, the average skin thickness (2.17 mm) was significantly larger (p = 1.5 x 10(-4)) than that of contralateral limb (1.14 mm). Major cutaneous alterations due to lymphedema took place in dermis. In lymphedematous dermis, the significant increase of relaxation time values could be due to a shift in the equilibrium of water inside this tissue in relation to the interactions between macromolecules and water molecules. In lymphedematous epidermis our results showed an increase in the number of free water protons. Information about water and fat distribution in lymphedema was also obtained using chemical shift weighted images. Our results demonstrated a water retention diffusely spread over the entire dermis, and an important fluid retention located in the interlobular spacing and beside the superficial fascia. Inside the subcutis, the mean thickness of the superficial fat lobules was increased more than that of the deep fat lobules. From all the various measurements we could not distinguish primary from secondary lymphedema.     

Clinical features of photodamaged human skin are associated with a reduction in collagen VII

Chronically sun-exposed or photodamaged human skin is characterized by a number of clinical features, including wrinkles. However, little is known about the molecular mechanisms that underlie these features. We investigated the hypothesis that the mechanism of wrinkle formation may involve loss of anchoring fibrils, composed mainly of collagen VII, which are important in maintaining dermal-epidermal junction integrity. Ten volunteers with moderate to severe photodamage of dorsal forearm skin were recruited to the study. Using immunohistochemistry, transmission electron microscopy and in situ hybridization, we compared collagen VII protein and mRNA content of photodamaged forearm skin with that of sun-protected hip and upper inner arm skin from the same subjects. Numbers of anchoring fibrils per linear microns of basement membrane (mean +/- SEM) were significantly lower in photodamaged skin (1.79 +/- 0.10) as compared with sun-protected hip (2.28 +/- 0.11) and upper inner arm skin (2.21 +/- 0.10) (P < 0.01), and similarly keratinocyte expression of collagen VII mRNA, quantitated as number of positively stained keratinocytes per high power field, was significantly reduced in photodamaged skin (6.3 +/- 2.5) as compared with sun-protected hip (20.0 +/- 5.6) and upper inner arm skin (17.7 +/- 4.9) (P < 0.001). Semiquantitative assessment of immunohistochemical staining for collagen VII showed a non-significant reduction in photodamaged skin as compared with sun-protected skin. We propose that reduced content of collagen VII in photodamaged skin contributes to wrinkle formation by weakening the bond between the dermis and epidermis.     

Photoageing-associated mitochondrial DNA length mutations in human skin

It has recently been suggested that mitochondrial DNA (mtDNA) mutations are important contributors to human ageing and degenerative diseases. Using PCR techniques, we demonstrated three types of mtDNA length mutations, a 4977 bp deletion, a 7436 bp deletion and tandem duplications, in normal human skin tissues. We found that these mutations started to appear in the third decade of life, and the age at which the mutations could be detected in sun-exposed skin was usually younger than in non-exposed skin. Moreover, the incidences of these deletions and tandem duplications of mtDNA in sun-exposed skin were all significantly higher than those in non-exposed skin (P < 0.05). The 4977 bp deletion was the most prevalant mtDNA mutation in human skin, and the 7436 bp deletion was the least frequent among the three types of mtDNA mutations examined. We first demonstrated the existence of tandem duplications with sizes of about 260 bp, 200 bp and 150 bp in the D-loop region of mtDNA in the skin of elderly individuals. Among the three tandem duplications, the 200-bp duplication was found to occur most frequently in ageing skin. The tandem duplications were found to coexist with either or both of the deletions in some elderly individuals. The frequency of occurrence of mtDNA deletions and tandem duplications in skin was found to increase in an age-dependent manner. However, the incidence of tandem duplications was not well correlated with the age of the subject.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of diurnal variation on the regional differences in sweating and skin blood flow during exercise

The aim of the present study was to examine changes in the control of heat-dissipation responses to exercise associated with the diurnal variation in core temperature from the viewpoint of the regional response patterns. We studied seven men during exercise on a cycle ergometer at 100 W for 40 min at 25 degrees C at 0630 (morning) 1630 (evening) hours on 2 separate days. Oesophageal temperature (T(oes)), local skin temperature, local sweating rate (msw) on the forehead, back, forearm and thigh, and skin blood flow by laser Doppler flowmeter (LDF) on the back and forearm were measured continuously. The T(oes) at rest was significantly higher in the evening than in the morning, the difference averaging approximately 0.4 degrees C (P < 0.05). The T(oes) thresholds for each site in msw and that for back in LDF were significantly different between the two times of day (P < 0.05). The change in T(oes) thresholds for sweating and vasodilatation for morning and evening were similar to T(oes) at rest. Although msw on the forehead was significantly higher in the morning than in the evening, msw on the back was significantly higher in the evening than in the morning (P < 0.05). Total local sweating rate (msw,tot) for each site during exercise was significantly higher on the forehead than on the forearm in the morning, and on the back than on the forearm in the evening, respectively (P < 0.05). The results would suggest that the diurnal variation of heat-dissipation responses to exercise is influenced not only by a central controlling mechanism but also by changes in the regional differences.     

Skin fold advancement flaps for closing large sternal and inguinal wounds in cats and dogs

Skin fold advancement flaps can be created from the elbow and flank folds to close large wounds in the pectoral and inguinal regions of cats and dogs, respectively. The attachments of the laterally facing (outer) and medially facing (inner) layers of the skin fold to the adjacent limb are divided to produce a U-shaped pedicle graft attached to the trunk. This mobilizes skin that can be advanced over large wounds involving the ventral chest or abdomen, or both. The use of skin fold advancement flaps enables direct closure of large skin defects without undue tension and without compromising the mobility of the adjacent limb.     

Expanded unilateral forehead flap (sail flap) for coverage of opposite forehead defect

This report details our experience with five patients who had skin defects of their forehead that were covered with an expanded unilateral forehead flap from the contralateral side that we call the sail flap. Skin expansion provides an ideal thin flap for the forehead aesthetic unit. The viability of the sail flap is sufficient through expansion, and it is available in suitable size and shape for the defect. The donor site is minimal and well accepted because the scar coincides with the hairline.     

Assessment of skin types, skin colours and cutaneous responses to ultraviolet radiation in an Asian population

Ninety normal individuals were included in this study on skin types, skin colours and cutaneous responses to ultraviolet radiation. Skin types were recorded using Fitzpatrick's classification, skin colours were measured using the Minolta Chromameter CR-300, and cutaneous responses to UV radiation were measured in terms of minimal erythema dose (MED) to UVA, UVB and the immediate pigment darkening dose to UVA (IPDDA). Skin colour measurements were taken from the right cheek to represent facultative skin colours, and from the buttock to represent constitutive skin colours. The colours measured were expressed by the L x a x b colour space. Skin types and some colour parameters (L and b from covered parts of body) correlated fairly well with the minimal erythema doses (MED) to UVA and UVB. Skin colour measurements are more objective than skin type assessment and could be better markers of photosensitivity. However, there is still considerable overlap in MEDs for persons with different skin colours, and further studies of these parameters are warranted. Our MEDs are higher than other reports on similar skin types and skin colours. This could be due to differences in methodology, genetic make-up or acclimatization from chronic sun exposure. This illustrates the importance of local controls for each institution dealing with photosensitive disorders.     

Composite resection and reconstruction for oral cavity and oropharynx cancer. A functional approach

Composite resection, the standard surgical approach for treating cancer of the oral cavity and oropharynx, results in considerable functional and cosmetic deformity, whether primary closure or flap reconstruction is employed. To minimize these problems, an alternate surgical approach has been developed. Essentials of the procedure include use of a non-lip-splitting visor flap for exposure and excision of the lesion, reconstruction with a skin or dermis graft formed into a pouch to fill dead space created by resection, and routine use of intermaxillary fixation for immobilization of the reconstructed area. In 16 patients undergoing this procedure, the approach had no adverse effect on short-term survival. Complication rate with skin and dermis graft reconstruction was acceptably low. Cosmetic improvement has been gratifying. Skin or dermis graft reconstruction has resulted in very satisfactory functional results in terms of tongue mobility, articulation, mastication, and swallowing.     

Facultative skin pigmentation in caucasians: an objective biological indicator of lifetime exposure to ultraviolet radiation?

To investigate age and gender trends in facultative and constitutive skin pigmentation we measured skin pigmentation non-invasively and objectively by skin reflectance spectroscopy in 653 caucasians (336 females and 317 males; mean age 38 years, range 0-85) who were not using artificial tanning devices. In all subjects, measurements were performed in the late winter and pre-spring period at five sites exposed to ultraviolet (UV) radiation: the forehead, the upper chest, the upper back and the lateral and medial aspects of the upper arm, and in UV-unexposed buttock skin. Constitutive pigmentation at the buttocks was highest in the first years of life and then decreased substantially during the first two decades of life (P < 0.01). After the age of 25 years, buttock pigmentation remained at a constant level (P = 0.20). There was no gender difference in constitutive pigmentation. Facultative skin pigmentation increased with age for all the measured sites with the highest levels found at the lateral aspect of the upper arm. Based on observations in this study we propose the idea of a 'sun exposure index' (SEI) for individuals, based on objective measurements of skin pigmentation. The SEI is calculated as the increase in facultative pigmentation above the constitutive level and is expressed as a percentage of the constitutive level. The SEI appeared to be related to cumulative lifetime UV exposure and may be used in epidemiological research as an objective estimate of UV exposure at different body sites in caucasians.     

Severe reversible cardiomyopathy associated with systemic vasculitis in primary Sj?gren''s syndrome

A dermal substitute was used for wound management and after early scar release on a 4-year-old child with mostly full thickness burns covering 60 per cent of the body surface. The biosynthetic material (INTEGRA Artificial Skin) consists of an upper silicone film and a lower layer of porous cross-linked collagen and chondroitin-6-sulfate as a template for dermal regeneration. Eight sheets each 4 x 10 in. were used to cover the patient's whole trunk after staged tangential necrectomy. In the third and fourth weeks following application the silicone layer was easily removed and the newly formed dermis covered with widely meshed, thin split-thickness autograft. Seven weeks after admission an early neck contracture was released and the skin defect also covered with INTEGRA Artificial Skin. Following the same principle, transplantation of the thin unmeshed autograft was performed successfully 3 weeks later. The good results regarding handling, final take, apparent initial scar reduction, and early recovery may favourably effect initial treatment and reconstruction planning after extensive full-thickness burn injuries.     

Idiopathic solitary neuroma of skin with unusual histologic changes

We report herein a case of idiopathic solitary neuroma with vascular proliferation and neurofibroma-like features. Clinically, the skin lesion was a 0.7 cm nodule without tenderness on the forearm. Histologically, there was vascular proliferation in the upper dermis, some neural structures among the proliferative vasculature in the mid dermis and large bundles of neural structures extending in various directions in the mid and deep dermis (resembling neurofibroma). Special stains, such as Masson's trichrome and Luxol fast blue, and immunohistochemical studies, including S-100 protein, neuron-specific enolase (NSE), vimentin, desmin, factor-VIII related antigen and epithelial membrane antigen (EMA), were added for this very rare case.     

Decreased p53 expression in chronically sun-exposed human skin after topical photoprotection

UV-induced DNA damage appears to play an essential role in skin carcinogenesis. Following acute UV irradiation, there is an overexpression of normal p53 protein in epidermal keratinocytes, representing a physiological response to DNA damage. Sun protection through topical sunscreens or clothing is believed to reduce the hazardous effects of UV irradiation and subsequently the risk of skin cancer. We have examined the effect of an SPF 15 topical sunscreen and blue denim fabric (SPF 1700) in chronically sun-exposed human skin after sun exposure during a normal summer. Skin biopsies from sun-protected and sun-exposed skin were compared with respect to immunohistochemically detectable p53. This method provides a model for assessing the significance of different degrees of UV protection under physiological conditions. Our results show a significant reduction of p53-positive cells in sun-protected skin as compared with sun-exposed skin. The reduction of p53-positive keratinocytes differed between topical sunscreen (33% reduction) and blue denim fabric (66% reduction). Interindividual variations were large, possibly because of variations in sun exposure. These variations also suggest that mechanisms determining UV damage at the cellular level are complex. The role of residual p53-positive keratinocytes after 2 months of total sun-protection (i.e., SPF 1700) is discussed.     

Urocanic acid isomers in patients with basal cell carcinoma and cutaneous malignant melanoma

Urocanic acid (UCA) is a major chromophore for ultraviolet (UV) radiation in the skin. On UV exposure, the naturally occurring trans-isomer converts to the cis-isomer in a dose-dependent manner. Accumulating evidence indicates that cis-UCA acts as an initiator of the UV-induced suppression of certain skin immune functions. This immunomodulation is recognized as an important factor in the development of skin cancer. In this study, pigmentation and UCA isomers were measured in 29 patients with previous basal cell carcinoma (BCC), 23 patients with previous cutaneous malignant melanoma (MM), and 32 healthy controls. Measurements were performed on UV-exposed (forehead, upper back) and UV non-exposed (buttock) skin. No significant differences in pigmentation percentage, total UCA concentration, relative (%) or absolute (nmol/cm2) cis-UCA concentration were observed between the groups in any of the body sites studied. The net production of cis-UCA after irradiation with a single test UV dose was evaluated. The relative production of cis-UCA following irradiation was significantly higher in both cancer groups when compared with the control group, while no significant difference was found between the BCC and the MM patients.     

Skin atrophy of the eyelid induced by topical ophthalmic corticosteroids

A case of eyelid skin atrophy caused by long-term application of topical ophthalmic corticosteroids for chronic uveitis is reported. Skin punch biopsy of the uveitic eye showed moderate atrophy of both epidermis and dermis (compared to normal skin on the other eye) resulting from a reduction in the three main fibrous components of the skin, namely type I and type III collagens, and elastic fibers. To our knowledge, this is the first report of skin atrophy in this association.     

Evidence for UV-associated activation of telomerase in human skin

Telomerase activation plays a crucial role in the immortalization of human cells and carcinogenesis; however, the temporal and pathophysiological aspects of the activation in vivo are poorly understood. We found telomerase activity not only in malignant tumors (91%) but also in most benign (60%) and premalignant (89%) skin tumors. This suggests the involvement of telomerase activation in a crucial biological step of human skin carcinogenesis. Because UV light is a major factor in skin carcinogenesis, we further examined telomerase activity in normal skin samples and in normal skin samples adjacent to benign, premalignant, and malignant skin lesions. Data for chronically sun-exposed body sites were compared with those for covered sites. Among normal skin samples, 39% (26 of 67) had telomerase activity, and this activity was unrelated to neighboring lesions but strongly associated with the level of sun exposure. Fifty-four % (21 of 39) of normal skin samples from chronically sun-exposed sites were telomerase-positive, compared with only 12% (3 of 26) of samples from covered sites. When we examined telomerase activity and CC to TT mutations at codons 247/8 of the p53 gene (which are considered to be UV specific) in the same normal skin samples, only 43% (7 of 16) of telomerase-positive normal skin samples at sun-exposed sites contained the p53 mutations, whereas all (7 of 7) of the samples with UV-specific p53 mutations showed telomerase activity (P = 0.019). These data suggest that telomerase activation is involved at an early stage of human skin carcinogenesis and that activation may precede the acquisition of UV-associated p53 mutations in the skin. Telomerase activity was also found in plucked hair follicles and enzymatically separated epidermis, which may be associated with the presence of stem cells in the skin.     

Increased dermal carotenoid levels assessed by noninvasive reflection spectrophotometry correlate with serum levels in women ingesting Betatene

beta-Carotene is being used as an oral sun protectant, and evidence indicates that carotenoids may protect human skin from light-induced lesions. However, limited information is available on the distribution and accumulation of beta-carotene in skin, especially with respect to various skin regions. With the use of reflection spectroscopy, we investigated the accumulation of total carotenoids in human skin after repeated supplementation of 12 women with beta-carotene from a natural source Betatene, an algal extract. After daily ingestion of 24 mg beta-carotene (in Betatene) for 12 wk, an increase in carotenoid skin levels was observed. Highest basal values were measured in skin of the forehead, palm of the hand and dorsal skin, with lower levels measured in skin of the arm and back of the hand. Upon treatment, increases in carotenoid skin levels were found in all areas as follows: 2.4-fold in forehead, 0.7-fold in dorsal skin, 2.2-fold in the palm of the hand, 17-fold on the back of the hand and 1.7-fold on the inside of the arm. After cessation of treatment, the carotenoid levels decreased in all skin areas. Serum beta-carotene levels were elevated upon treatment and correlated with carotenoid skin levels. Correlations for serum vs. skin from the palm of the hand (r = 0.94) and skin from the forehead (r = 0.89) were calculated, indicating that serum levels appeared to be a suitable indicator for carotenoid accumulation in specific regions of the skin. With doses of approximately 20-25 mg carotenoids/d, it is possible to raise dermal carotenoid levels.     

Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats

A 3-day monolithic polyacrylate adhesive dispersion type delivery system containing methadone was fabricated and in vitro permeation through hairless mouse and human cadaver skins was conducted. The effect of skin permeation enhancers was also investigated. Skin permeation rate across human cadaver skin was found to be lower than that of hairless mouse. Skin permeation profiles across both types of skins showed a membrane permeation controlled cumulative amount permeated (Q) versus time (t) relationship. Skin permeation rate was found to be dependent on both adhesive film thickness and loading dose of the drug in the matrix. Effective skin permeation rate across the hairless mouse skin was obtained from a patch with 1.5 mm thickness and 15% w/w loading dose. n-Decylmethyl sulfoxide and Azone were found to produce an effective skin permeation rate of methadone through human cadaver skin at a 5% w/w concentration. These initial studies demonstrated the feasibility of methadone administration through intact skin from a transdermal patch.