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Bilateral skin temperature, handedness, and the biofeedback control of skin temperature.

There are differences in physiological variables when they are recorded from the left and right side of the body simultaneously. In some cases, handedness has been found to have a significant relationship to bilateral differences. The present study examined the relationship between handedness and baseline heart rate and skin temperature, as well as bilateral differences in skin temperature during visual and auditory biofeedback. Subjects were 32 college females, 24 right-handed and 8 left-handed. Recordings of heart rate and skin temperature from both the dominant and the nondominant hand were made during baseline and during the 10-min experimental session while subjects attempted to warm their dominant hand. Both groups showed significantly increased skin temperature during the experimental session. No prominent bilateral differences in skin temperature were found. These results do not support bilateral differences as a generalizable construct.

Adult↗

Noninvasive procedure for in situ determination of skin surface aspartic proteinase activity in animals; implications for human skin.

The present study demonstrated a noninvasive procedure for in situ determination of stratum corneum aspartic proteinase in the living animal. A non-leaky well, containing [125I]S-carboxymethylated insulin B-chain (ICMI) as a substrate, was constructed on the shaved back of anesthetized guinea pigs and rats. The enzymatic activity was determined by measuring the radiolabeled trichloroacetic acid soluble material. We demonstrated pepstatin-sensitive proteinase activity bound to the skin surface indicating the involvement of aspartic proteinase(s) such as cathepsin D and/or E. Aged rats had about six fold lower activity than young animals. The proteinase activity was inhibited by the alkylating agent mechlorethamine and by the cosmetic propylene glycol. A similar procedure was carried out with intact human skin pieces obtained during plastic surgery. The activity was inhibited by antihuman cathepsin D antibodies. Cathepsin D was immunohistochemically localized in the corneal and granular layers of the epidermis. Skin surface aspartic proteinase/cathepsin D activity may serve as a marker for skin aging or for certain skin disorders leading to a new approach to their medical treatments.

Aging↗

Treatment of skin and skin structure infections in the patient at risk.

Infections of the skin and skin structures in patients at risk can be either primary or secondary. In the normal host, the most important primary dermal pathogens are the group A beta-hemolytic Streptococcus and Staphylococcus aureus. These organisms can spread rapidly and seed to distant sites. Secondary skin involvement occurs in several life-threatening bacteremic conditions in previously normal hosts, especially in those involving meningococci and S. aureus. In the compromised host, although the acute pyogenic bacteria just mentioned can be even more devastating, low grade pathogens or nonpathogenic members of the normal flora, or both, are commonly involved. Such organisms include gram-negative aerobic bacilli, a variety of anaerobes, several fungi, and the herpesviruses. Therapy of primary skin and skin structure infections invariably should include debridement along with antibiotic coverage. Debridement must be complete, opening all deep extensions of the primary infection and removing, to the extent possible, all foreign materials. In the normal host, antibiotic coverage must include a beta-lactamase-resistant antibiotic or vancomycin if beta-lactamase-resistant, antibiotic-resistant S. aureus could be involved. In the compromised host, signs of local inflammation may be reduced; yet, debridement must still be aggressive and antibiotic coverage broad. Neutropenic patients should be covered for Pseudomonas aeruginosa, requiring a combination of an antipseudomonal agent plus an aminoglycoside. Antifungal or antiviral therapy, or both, should be added in the severely compromised host in the proper setting, especially in patients not promptly responding to antibacterial measures. Attempts to enhance host defenses should be considered.

Anti-Bacterial Agents↗

Cool perfusion solutions for skin flaps: a new mixture of pharmacological agents which improves skin flap viability.

This study tested the hypotheses that perfusion of cooled skin flaps with established organ preservation solutions improves their viability and that this improvement can be further enhanced by pharmacological manipulation. Rabbit epigastric skin flaps were perfused with different solutions before explantation and stored at 8 degrees C for 6 days. In the first part of the experiment, flap viability was assessed 7 days after reperfusion of the flap via microvascular anastomoses. The different solutions were heparinised blood, University of Wisconsin solution, two of its modifications, EuroCollins solution and a pharmacological mixture containing phosphoenolpyruvate, desferrioxamine, nitrendipine, dextran 70 and a platelet-aggregating factor receptor antagonist (WEB 2170). In the second part, biochemical parameters of skin were measured at various reperfusion times. Adenosine triphosphate (ATP), reduced glutathione (GSH), myeloperoxidase (MPO) and tissue water were assayed at 0, 1, and 24 h after reperfusion. In addition, plasma thromboxane (TXB2) was measured at 0, 30 and 60 minutes after reperfusion. The viability of flaps perfused with the mixture (81%) was significantly higher than that of any of the other groups (39% for controls, 38% for EuroCollins, 13% for UW solution, 27% and 31% for its modifications). ATP levels after reperfusion were higher in the mixture group than in UW-perfused group. GSH levels in the mixture group were also higher than in the UW group, indicating higher level of protection against oxidative stress during reperfusion. There were no differences in MPO levels. Thromboxane levels associated with UW-perfused flaps were significantly higher than those associated with any other perfusion solution. In conclusion, perfusion of a mixture of pharmacological agents targeting specific aspects of ischaemia/reperfusion injury improved the viability of skin flaps stored in the cold for 6 days, whereas standard organ preservation solutions failed to affect significantly skin flap survival.

Adenosine↗

Monocytes accumulate on Rebuck skin window coverslips but not in skin chamber fluid. A comparative evaluation of two in vivo migration models.

Migration of leukocytes into an inflammatory site is an important step of host defense. The Rebuck skin window and the skin blister chamber technique allow study of the dynamics of the inflammation in vivo. The type of inflammation is basically different in each of these methods. Whereas the former technique provokes a late monocytic response, the latter technique provokes virtually no monocyte accumulation. the difference between these two types of inflammation has never been systematically studied. We describe a skin blister chamber technique with a novel multiwell device which allows the observation of cell accumulation under different conditions, i.e., in presence and in absence of a foreign body (coverslip). This method proved simple and reproducible with variability among volunteers exceeding variability of replicate chambers within a given subject. Furthermore, it confirms that no monocytes accumulate in blister chambers during the first 20 h of inflammation, whereas monocytes accumulate on skin window coverslips within the first 6 h of inflammation. Control experiments show that the continuous presence of the coverslip in the skin window is the critical element provoking accumulation of monocytes. A different degree of neutrophil degranulation in presence and absence, respectively, of a foreign body may be responsible for the different types of inflammatory response.

Adolescent↗

The ratio of lipidperoxides to superoxide dismutase activity in the skin lesions of patients with severe skin diseases: an accurate prognostic indicator.

We studied 35 patients with active inflammatory skin diseases, measuring the levels of lipidperoxides and of the oxygen radical scavenging enzyme superoxide dismutase (SOD) in biopsy specimens of skin lesions. Lipidperoxide levels were markedly elevated in all patients. In fifteen patients with disease that was severe and highly resistant to therapy, SOD activity was only slightly increased, in comparison with normal controls. In contrast, in the twenty patients with mild disease that responded well to therapy, SOD activity was markedly elevated. The ratio of lipidperoxide levels to SOD activity was thus an accurate prognostic indicator, being elevated only in the group not responding to treatment. These findings suggest that the severity of allergic inflammatory skin disease and/or the response to treatment may in part be governed by the degree to which the patient's SOD activity is up-regulated in response to the generation of tissue-damaging substances such as lipidperoxides. Interestingly, our studies revealed the SOD activities of both normal and inflamed skin to be unexpectedly high; our data suggest that SOD plays a critical role in protecting the skin from the effects of oxygen radicals and ultraviolet light.

Adolescent↗

New primary nonmelanoma skin cancer in patients with a history of squamous cell carcinoma of the skin. Implications and recommendations for follow-up.

BACKGROUND: Rational follow-up guidelines for skin cancer patients should be based on the risk of three separate events: cancer recurrence, cancer metastasis, and the development of subsequent skin cancers. However, currently no guidelines exist for follow-up of patients with squamous cell carcinoma of the skin (SCC), which take into account all three of these risks. OBJECTIVE: The purpose of this study is to establish rational minimum guidelines for follow-up of patients with SCC. To do this, we first must determine the risk of SCC patients for the development of subsequent skin cancers. Combining these data with previously published data on SCC recurrence and SCC metastasis, we then propose guidelines for follow-up of patients with SCC. METHODS: We followed up 101 SCC patients on a yearly basis for 5 years after treatment and recorded the date and site of subsequent nonmelanoma skin cancers (NMSCs). RESULTS: Thirty percent of SCC patients developed additional SCCs and 52% developed subsequent NMSCs within 5 years of therapy for their first SCC. Patients showing the highest risk of subsequent NMSC were those presenting with multiple SCC, SCC greater than 1 cm in diameter, SCC requiring more than 1 Mohs surgery layer to remove, or SCC occurring on the scalp, ear, nose, or extremities. One hundred percent of subsequent NMSCs were detected by the fourth year of follow-up; 54% of these occurred within the first year of follow-up. CONCLUSION: After combining our data with previously published studies of SCC recurrence and metastasis, we recommend that all patients with SCC be followed up for at least 4 years after treatment. Moreover, because most subsequent NMSCs, SCC recurrences, and SCC metastases developed early in the follow-up period, we recommend that patients be reexamined at least every 3 months during the first year of follow-up and every 6 months thereafter. It must be stressed that these are meant as minimum follow-up guidelines.

Carcinoma, Squamous Cell↗

Effect of constituents of burned skin and in vivo skin burning on the respiratory activity of rat liver mitochondria.

The formation of toxic substances in the skin, due to the influence of thermal energy, is supposed to be one possible mechanism responsible for the high mortality rate after severe burns covering large areas of the body surface. The effects of low-molecular-weight volatile substances (dry distillates) generated after burning mouse skin were investigated. They led to reductions of the respiratory activity of rat liver mitochondria. Among other substances carbon disulphide, methylethylketone and pyrrole were isolated and characterized using gas chromatography. All of them had strong uncoupling effects on mitochondrial respiration. In a second study respiratory measurements were made on mitochondria from rats with 20-30 per cent TBSA full skin thickness burns. A decreased respiratory control ratio and thus uncoupling of mitochondrial respiration was found on days 1, 2 and 5 postburn. The basal mitochondrial respiration was significantly decreased on day 5, which could be important for the mortality mentioned above. Finally after cross-transplantations rats having burned skin grafted showed a reduction of the RCR when compared with rats with the unburned graft. Thus it can be concluded that toxic substances must have been present in burned skin.

Animals↗

The source-skin distance measuring bridge: a method to avoid radiation teleangiectasia in the skin after interstitial therapy for breast cancer.

Inappropriate positioning of interstitial Iridium 192 implants, used as booster dose in the breast conserving treatment of mammary cancer, may cause disturbing teleangiectasia of the breast skin, when high radiation doses are delivered on the dermal blood vessels. Based on the localization of the vascular plexuses in human breast skin, and on the dose distribution around different types of interstitial implants, a method is described to avoid overlap between the high dose area of the implant and the blood vessels in the skin. The latter are demonstrated to run within the first 5 mm under the epiderm. For source lengths varying from 5 to 8 cm, simple mathematical relations exist between the maximal security margin (MSM) and intersource distance (E) for single plane implants (MSM = 0.4 (E + 1)), double plane square implants (MSM = 0.4 E) and double plane triangular implants (MSM = 0.4 (E - 1)). We developed a device to measure precisely the distance between the radioactive wires and the overlying skin, along the whole source trajectory. Using this method, the occurrence of teleangiectasia in the breast skin after interstitial implants with Ir 192 may be significantly reduced.

Brachytherapy↗

Early relationship environments: physiology of skin-to-skin contact for parents and their preterm infants.

Skin-to-skin care involves the mother placing her diaper-clad infant upright between her breasts in direct skin contact. The practice has evolved worldwide to be an intervention strategy in neonatal intensive care units for premature infants and their mothers. Few adverse outcomes have been noted in thermoregulation, cardiovascular changes, or behavioral organization. Findings have been positively related to better infant physiologic and neurobehavioral outcomes, maternal breastfeeding success, and positive attachment relationships. The early, intimate, and physiologically stabilizing benefits of skin-to-skin care provide for a new conceptualization of the optimal environment for preterm infants in intensive care.

Humans↗

The effect of skin permeation enhancers on the formation of porphyrins in mouse skin during topical application of the methyl ester of 5-aminolevulinic acid.

The influence of skin permeation enhancers, such as dimethyl sulphoxide (DMSO) and 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), Labrafac CC, Labrafil, Labrasol and Transcutol in a concentration of 10% (wt./wt.) on the formation of porphyrins in normal mouse skin from topical application of creams with methyl 5-aminolevulinate (MAL) was studied. The concentration of porphyrins in the mouse skin was determined by direct fluorescence measurements. The results show that studied permeation enhancers increase the formation of porphyrins, and therefore also the skin penetration 2% MAL whereas for 10% and 20% (wt./wt.) MAL concentrations only DMSO, HPE-101 and Labrafac CC increased the porphyrin formation. At all studied MAL concentrations DMSO gave the largest enhancing effect, similarly to that of HPE-101. This suggests that in 2-20% MAL creams HPE-101 may be substituted by Labrafac CC to reduce skin irritation induced by HPE-101 without impairing the porphyrin formation.

Administration, Topical↗

The role of UV induced lesions in skin carcinogenesis: an overview of oncogene and tumor suppressor gene modifications in xeroderma pigmentosum skin tumors.

Xeroderma pigmentosum (XP), a rare hereditary syndrome, is characterized by a hypersensitivity to solar irradiation due to a defect in nucleotide excision repair resulting in a predisposition to squamous and basal cell carcinomas as well as malignant melanomas appearing at a very early age. The mutator phenotype of XP cells is evident by the higher levels of UV specific modifications found in key regulatory genes in XP skin tumors compared to those in the same tumor types from the normal population. Thus, XP provides a unique model for the study of unrepaired DNA lesions, mutations and skin carcinogenesis. The high level of ras oncogene activation, Ink4a-Arf and p53 tumor suppressor gene modifications as well as alterations of the different partners of the mitogenic sonic hedgehog signaling pathway (patched, smoothened and sonic hedgehog), characterized in XP skin tumors have clearly demonstrated the major role of the UV component of sunlight in the development of skin tumors. The majority of the mutations are C to T or tandem CC to TT UV signature transitions, occurring at bipyrimidine sequences, the specific targets of UV induced lesions. These characteristics are also found in the same genes modified in sporadic skin cancers but with lower frequencies confirming the validity of studying the XP model. The knowledge gained by studying XP tumors has given us a greater perception of the contribution of genetic predisposition to cancer as well as the consequences of the many alterations which modulate the activities of different genes affecting crucial pathways vital for maintaining cell homeostasis.

Genes, Tumor Suppressor↗

[Diagnostic cost-effectiveness of the skin biopsy in inflammatory diseases of the skin].

INTRODUCTION: Inflammatory skin diseases are a very heterogeneous and extensive group of entities whose clinical and pathological diagnosis is difficult. In cases where the clinical diagnosis is doubtful, the histopathological study of one or more lesions can be of great help. The aim of our work is to compare the effectiveness of the histopathological diagnosis in inflammatory skin lesions according to the department performing the biopsy. MATERIAL AND METHODS: A retrospective study was carried out on the reports for pathological study requests and the histopathological reports from the year 2003 from the Pathology Department of Hospital Santa María del Rosell. In the reports for the pathological study requests, the following data was assessed: department performing the biopsy, whether or not the type of lesion was stated on the request form, location, evolution and clinical diagnosis. The histopathological diagnoses were reviewed by one of the authors and classified into two major groups: a) specific diagnoses and b) non-specific diagnoses. Five departments took part in performing biopsies on inflammatory skin lesions: Dermatology, General Surgery, Primary Care, Internal Medicine and Gynecology. To better compare the data, we have divided the departments into two groups: 1. Dermatology Department and 2. Non-dermatology departments. We performed a statistical analysis (proportion comparison) of the specific diagnoses between the two groups and among the specific diagnoses of the non-dermatology departments. RESULTS: The total number of inflammatory skin lesions studied was 97. The Dermatology Department performed 48 biopsies, and the non-dermatology departments performed 49. There was less clinical data in the reports sent by the non-dermatological departments than in those from the Dermatology Department. The pathologist made a specific diagnosis in 77 % of the biopsies performed by the Dermatology Department, compared to 41 % of the biopsies sent by the non-dermatology departments (p < 0.001). There are no statistically significant differences among the specific diagnoses made by the departments that make up the non-dermatology group. CONCLUSION: The histopathological diagnoses made in the biopsies sent from the Dermatology Department are more specific (77 %) than those made in the biopsies performed by the non-dermatology departments (41 %). Thus, biopsies on inflammatory skin lesions should be performed by the Dermatology Department so that diagnostic effectiveness is maximized, and in order to prevent delays and inappropriate treatments that might be harmful to the patient.

Biopsy↗

Temporal events in skin injury and the early adaptive responses in ultraviolet-irradiated mouse skin.

We examined the effects of ultraviolet (UV) radiation on the time course for induction of sunburn (apoptotic) cells and expression of proteins known to be associated with growth arrest and apoptosis in SKH-hr1 mouse skin. Mice were irradiated with a single dose (2.5 kJ/m(2)) of UV from Kodacel-filtered (290-400 nm) FS40 sunlamps and the skin tissues were analyzed at various times after irradiation for the presence of apoptotic cells and expression of p53, p21(Waf-1/Cip1), bcl-2, bax, and proliferating cell nuclear antigen. The results indicated that p53 expression was induced early in the epidermis, reaching maximum levels 12 hours after irradiaton, and p21(Waf-1/Cip1) expression in the epidermis peaked at 24 hours after irradiation. In contrast, UV radiation induced high levels of bax at 24 to 72 hours after irradiation with a concomitant decrease in bcl-2 expression. Coinciding with these changes, apoptotic cells began to appear 6 hours after irradiation and reached a maximum at 24 hours after irradiation. Interestingly, proliferating cell nuclear antigen expression, which was initially confined to the basal layer, became dispersed throughout the basal and suprabasal layers of the skin at 48 hours and paralleled marked hyperplasia. These results suggest that UV irradiation of mouse skin induces apoptosis mediated by the p53/p21/bax/bcl-2 pathway and that the dead cells are replaced by hyperproliferative cells, leading to epidermal hyperplasia. This implies that UV-induced apoptosis and hyperplasia are closely linked and tightly regulated and that dysregulation of these two events may lead to skin cancer development.

Adaptation, Physiological↗

Purification and characterization of antimicrobial and vasorelaxant peptides from skin extracts and skin secretions of the North American pig frog Rana grylio.

Eight peptides with differential growth-inhibitory activity against the gram-positive bacterium Staphylococcus aureus, the gram-negative bacterium Escherichia coli and the yeast, Candida albicans were isolated from an extract of the skin of the North American pig frog Rana grylio. The primary structures of these antimicrobial peptides were different from previously characterized antimicrobial peptides from Ranid frogs but on the basis of sequence similarities, the peptides may be classified as belonged to four previously characterized peptide families: the ranatuerin-1, ranatuerin-2 and ranalexin families, first identified in the North American bullfrog, Rana catesbeiana, and the temporin family first identified in the European common frog Rana temporaria. Peptides belonging to the brevinin-1, brevinin-2, esculentin-1, and esculentin-2 families, previously isolated from the skins of other species of Ranid frogs, were not identified in the extracts. The ranatuerin-1 and ranalexin peptides showed broadest spectrum of antimicrobial activity whereas the temporins were active only against S. aureus. Synthetic replicates of temporin-1Gb (SILPTIVSFLSKFL.NH(2)) and temporin-1Gd (FILPLIASFLSKFL.NH(2)) produced concentration-dependent relaxation of preconstricted vascular rings from the rat thoracic aorta (EC(50) = 2.4+/-0.1 microM for temporin-1Gb and 2.3+/-0.2 microM for temporin-1Gd). The antimicrobial peptides that were isolated in extracts of the skin R. grylio were present in the same molecular forms in electrically-stimulated skin secretions of the animal demonstrating that the peptides are stored in the granular glands of the skin in their fully processed forms.

Amino Acid Sequence↗

High-performance liquid chromatographic measurement of urocanic acid isomers and their ratios in naturally light-exposed skin and naturally shielded skin.

We have developed methods for sampling and extraction of trans-urocanic acid and cis-urocanic acid from human skin, and subsequent high-performance liquid chromatographic measurement of these isomers. Sampling involves applying cellophane adhesive tape to the skin for 10 s. Urocanic acid isomers were completely extracted by immersing the tape in KOH solution. The HPLC column was a Tosoh ODS 80TS (250x4.6 mm I.D., 7 microm average particle size) eluted with 20 mM potassium dihydrogenphosphate containing 1 g/l sodium heptanesulphonate (pH 3.7)-acetonitrile (93:7, v/v) at a flow-rate of 1.0 ml/min. The isomers were detected by UV absorbance at 264 nm. This technique was used to analyze the ratio of trans-urocanic acid/cis-urocanic acid on human skin at various sites on the body. It was found that the ratio was low in naturally light-exposed skin and high in naturally shielded skin.

Adult↗

Selective binding of colloidal gold-protein conjugates to secretory granules of granular skin glands and myelin sheaths in the skin of Xenopus laevis.

Colloidal gold-protein conjugates are widely used in immunoelectron microscopical studies as general "second antibody" markers. This report demonstrates that colloidal gold conjugated with goat anti-mouse immunoglobulin G (IgG), protein A, and bovine serum albumin (BSA) binds selectively to secretory granules of granular skin glands and myelin sheaths in the skin of Xenopus laevis. The gold labeling pattern was identical whether goat anti-mouse IgG, protein A, or BSA was used to stabilize the colloidal gold sols. Selective labeling over secretory granules of granular skin glands and myelin sheaths with colloidal gold alone was also observed. Such selective labeling could be prevented by increasing the ionic strength (elevation of NaCl content up to 30%) of the washing buffers and the diluent of the antibody. These results demonstrate that secretory granules of granular skin glands and myelin sheaths in the skin of X. laevis have affinity for colloidal gold-protein conjugates and may bind to the charged gold particles electrostatically.

Animals↗

Recruitment of cycling epidermal cells and expression of filaggrin, involucrin and tenascin in the margin of the active psoriatic plaque, in the uninvolved skin of psoriatic patients and in the normal healthy skin.

The peripheral changes in the uninvolved skin adjacent to the extending psoriatic lesions may represent early events. The sequence of these events remains controversial. In the present study we evaluated epidermal and dermal aspects of the margin of the progressive psoriatic plaque, the distant uninvolved skin and normal healthy skin, using immunohistochemistry with markers for keratinization, proliferation and connective tissue: filaggrin, involucrin, Ki-67 and tenascin. The results showed that: (i) processes in distant uninvolved skin were comparable with the observations in normal skin; (ii) in the margin zone of the spreading psoriatic lesion, following the increased appearance of tenascin, the transition into parakeratosis, abnormal expression of filaggrin, involucrin and recruitment of cycling epidermal cells, happened simultaneously. The simultaneous normalization of these epidermal processes might be a consequence of a signal which is simultaneously transduced to the basal and suprabasal cell layers of the epidermis. Based on the present results and earlier findings, we would like to propose a triple stage model for the development of the psoriatic lesion: Stage 1, involvement of the stroma; stage II, inflammatory infiltrate formation and penetration into the upper layers of the epidermis, with suprabasal expression of keratin 16; stage III, recruitment of cycling epidermal cells and abnormal terminal differentiation. Further studies are required on the regulation of tenascin expression, focusing on factors derived from the stroma affecting both recruitment of cycling epidermal cells, involucrin and filaggrin expression. An intermediate step in the dermo-epithelial interrelation is the inflammatory infiltrate, penetrating into the most superficial zone of the epidermis, and the suprabasal expression of keratin 16.

Adult↗