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The relationship between skin maturation and electrical skin impedance.

When performing electrophysiological testing, high electrical impedance values are sometimes found in neonates. Since excessive impedance can invalidate test results, a study was conducted to delineate the relationship between skin maturation and electrical skin impedance. This study investigated the skin impedance in 72 infants ranging from 196 to 640 days of age from conception. Regression analyses demonstrated a significant relationship between impedance and age, with the highest impedance centered around full-term gestation with values falling precipitously at time points on either side. Clinically, impedance values fall to normal levels at approximately four months following full-term gestation. Skin impedance values are low in premature infants, but rapidly increase as the age approaches that of full-term neonates. Low impedance values in premature infants are attributed to greater skin hydration which results from immature skin conditions such as 1) thinner epidermal layers particularly at the transitional and cornified layers; 2) more blood flow to the skin; and 3) higher percentage of water composition. These factors facilitate the diffusion of water vapor through the skin. As the physical barrier to skin water loss matures with gestational age, the skin impedance reaches a maximum value at full term neonatal age. After this peak, a statistically significant inverse relationship exists between electrical skin impedance and age in the first year of life. This drop in skin impedance is attributed to an increase in skin hydration as a result of the greater functional maturity of eccrine sweat glands.

Age Factors↗

Correlation of the expression of human telomerase subunits with telomerase activity in normal skin and skin tumors.

BACKGROUND: Telomerase activation is thought to be crucial for the continued growth or progression of cancer cells. Three major subunits of human telomerase, human telomerase RNA (hTR), telomerase-associated protein (TP1), and human telomerase catalytic subunit (hTERT) have been identified recently. In the current study, the expression of these telomerase subunits was examined in various human skin tumors and in normal skin samples, and the correlation of their expression with telomerase activity was evaluated. METHODS: Forty-five skin tumors, including benign, premalignant, and malignant tumors, and 19 samples of normal skin were analyzed by reverse transcriptase-polymerase chain reaction for the expression of telomerase subunits and by telomeric repeat amplification protocol assay for telomerase activity. RESULTS: TP1 expression was found in 43 of 45 skin tumors (95.6%) and in all normal skin samples analyzed. hTR expression was found in 42 of 45 skin tumors (93.3%) and in 18 of 19 normal skin samples (94.7%). In contrast, hTERT expression was detected in 33 of 45 skin tumors (73.3%) and in only 3 of 19 normal skin samples (15.8%). Telomerase activity was positive in 33 of 45 skin tumors (73.3%) and in 3 of 19 normal skin samples (15.8%). All together, 53 of 64 cases (82.8%) were concordant for both results (P < 0.001), i.e., telomerase activity positive and hTERT positive, or telomerase activity negative and hTERT negative. CONCLUSIONS: Activation of telomerase activity in skin tumors is strongly correlated with hTERT expression.

Catalytic Domain↗

Transdermal delivery of narcotic analgesics: comparative metabolism and permeability of human cadaver skin and hairless mouse skin.

The permeation of hairless mouse skin and human cadaver skin by narcotic analgesics was investigated to determine the interspecies variation. Permeability coefficients of morphine, fentanyl, and sufentanil across full-thickness hairless mouse skin were 1 order of magnitude higher than those found for human epidermis. The permeability coefficient of morphine for stripped hairless mouse skin was 500-fold higher than that for intact skin, showing the stratum corneum to be the principal barrier to its penetration. The permeability coefficient of fentanyl for stripped hairless mouse skin was also raised, but stripping caused an inappreciable increase in the permeation rate of sufentanil. The thick dermis of excised mouse skin obviously offered a significant resistance to the permeation of these lipophilic compounds. In comparison, the permeability coefficients of fentanyl and sufentanil through stripped cadaver epidermis (n > or = 25) were 67 and 37 higher than for intact human epidermis, respectively. The skin metabolism of the narcotics was investigated. No significant metabolic degradation of morphine, fentnayl, and sufentanil was observed in either fresh human cadaver skin or hairless mouse skin homogenates in the presence of NADPH cofactor, suggesting a low monooxygenase enzyme presence in skin. Moreover, no measurable glucuronidation of morphine took place in human skin or hairless mouse skin. Both processes proceeded rapidly in liver homogenates (mouse) under identical circumstances. It thus appears that these drugs pass through in intact form.

Administration, Cutaneous↗

Moist skin care can diminish acute radiation-induced skin toxicity.

BACKGROUND: Radiation treatment may induce acute skin reactions. There are several methods of managing them. Validity of these methods, however, is not sufficiently studied. We therefore investigated, whether moist skin care with 3% urea lotion will reduce acute radiation skin toxicity. PATIENTS AND METHODS: 88 patients with carcinomas of the head and neck undergoing radiotherapy with curative intent (mean total dose 60 Gy, range: 50-74 Gy) were evaluated weekly for acute skin reactions according to the RTOG-CTC score. In 63 patients, moist skin care with 3% urea lotion was performed. The control group consisted of 25 patients receiving conventional dry skin care. The incidence of grade I, II, and III reactions and the radiation dose at occurrence of a particular reaction were determined and statistically analyzed using the log-rank test. The dose-time relations of individual skin reactions are described. RESULTS: At some point of time during radiotherapy, all patients suffered from acute skin reactions grade I, > 90% from grade II reactions. 50% of patients receiving moist skin care experienced grade I reactions at 26 Gy as compared to 22 Gy in control patients (p = 0.03). Grade II reactions occurred at 51 Gy versus 34 Gy (p = 0.006). Further, 22% of the patients treated with moist skin care suffered from acute skin toxicity grade III as compared to 56% of the controls (p = 0.0007). CONCLUSION: Moist skin care with 3% urea lotion delays the occurrence and reduces the grade of acute skin reactions in percutaneously irradiated patients with head and neck tumors.

Amifostine↗

Evaluation of donor skin viability: fresh and cryopreserved skin using tetrazolioum salt assay.

Cell viability assessment in allograft skin is an essential step to ensure a supply of good quality allograft skin for clinical repair of wounds. It is widely recognised that 'take' of allografts is strongly influenced grafted by tissue viability. The aim of this study was to set-up storage protocols that maintain high viability of the allograft after harvest, treatment and storage. In this study, the viability of post-mortem allografts (n=350) harvested from 35 different donors, was investigated using the MTT salt assay. The conditions of preparation and storage of the allograft included: 1. Fresh skin samples (about 12, 30, and 60h after harvesting). 2. The same specimens (stored at 4 and 37 degrees C) tested for at least 1 month. 3. Samples after cryopreservation and thawing. 4. Thawed specimens tested daily for at least 6 days. Parallel histomorphological analysis performed, under each of these conditions, showed a correlation between changes in structure and changes in viability as measured by the MTT quantitative assay. The viability index (VI) of skin is expressed as the ratio between the optical density (O.D.) produced in the MTT assay by the skin sample and its weight in grams. The percentage viability index is the ratio of the VI of the fresh sample (considered as 100% viability) and the value of specimens from the same harvest batch after storage or cryopreservation. The results indicated that samples tested within 12-30h from harvesting have an average viability index of about 75 with little variation. Samples tested within 60h have an average viability index of 40, showing a viability decrease of about 50%. A protocol to treat skin within a maximum of 30h was, therefore, set-up. The data suggested that skin stored at 37 degrees C, undergoes a viability increase during the first 2 days after harvesting. However, the viability under these conditions then decreased very quickly. After 6 days of preservation at this temperature the samples were no longer viable (PVI = 0). The tissue structure started to become damaged after 3 days. On the other hand, skin stored at 4 degrees C, showed a very slow viability decrease. After 15 days, viability was still almost 25% of the fresh sample. The tissue architecture showed no signs of damage under these conditions until day 7 from harvesting. MTT analysis was performed on the specimens cryopreserved with DMSO at 10%. These measurements were compared to viability assessment of the same fresh skin samples (considered as 100%) that were analysed within 30h from harvesting. The average PVI of thawed skin was 54% of the fresh sample. This result demonstrates that the viability of cryopreserved skin is comparable to the viability of fresh skin stored at 4 degrees C for 4 days. The PVI of thawed skin samples decreased dramatically within 24h, and had reached 0% within 6 days.

Adolescent↗

Ultraviolet light induces expression of p53 and p21 in human skin: effect of sunscreen and constitutive p21 expression in skin appendages.

It has been suggested that p53 plays an important role in skin carcinogenesis. The p21 molecule acts as a downstream effector of wild-type p53 by enacting cell cycle arrest. We studied p53 and p21 expression in sun-exposed skin. Healthy volunteers were exposed to ultraviolet irradiation (UVA + UVB) in normal, previously non-sun-exposed skin, and skin biopsies were taken. Immunohistochemically detectable p53 and p21 were quantified, and the pattern of distribution was recorded. p53 was induced in epidermal cells 4 h after irradiation and returned to nearly normal levels after 120 h. Suprabasal cells showed a peak at 4 h, whereas basal cells peaked later, at 48 h. In epidermis, the expression of p21 was induced with a pattern that mirrored that of p53. In addition, p21 was induced in mesenchymal cells of the upper dermis, where there was no p53, suggesting an alternative pathway for p21 induction. Topical sunscreen and pigmentation (skin type 5) nearly eliminated UV-induced expression of p53 and p21. In contrast to the complete absence of p53 in skin never exposed to UV radiation, p21 reactivity was found in sharply demarcated areas of anagen hair follicles and sebaceous glands, as well as in scattered epidermal cells. The prevalence and distribution suggest a physiologic role of p21 in stopping the cell cycle in terminally differentiating skin epithelium. Archival skin material from the vicinity of skin lesions with variable sun exposure were also stained for p53. There was an increased "disperse" reactive staining pattern in skin samples excised in the summer as compared with less sunny seasons. Intensely stained p53 foci were detected as "compact bands" in morphologically normal epidermis, predominantly in sun-exposed areas of the skin, suggesting the existence of clonal proliferation of p53 mutated keratinocytes. These data show that p53 and p21 play a role in the human skin response to UV exposure and that p21 is implicated in the homeostasis of differentiating skin appendages.

Adult↗

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.

Adult↗

HIV-1 detection by nested PCR and viral culture in fresh or cryopreserved postmortem skin: potential implications for skin handling and allografting.

AIMS: To date, the risk relating to the handling or allografting of human immunodeficiency virus type 1 (HIV-1) infected postmortem skin remains hypothetical. While blood screening for HIV antibodies is still the key safety procedure to detect HIV infected cadavers, false negative results are a concern. Conversely, false positive results may hamper the collection of skin allografts. Accordingly, viral culture was used to clarify skin infectivity and the nested polymerase chain reaction (PCR) was used to assess the reliability of skin PCR testing. METHODS: Viral culture and nested PCR performed with gag and pol specific primers were investigated in cadaveric skin and blood from 12 HIV-1 infected patients. Samples were collected repeatedly between one and five days in seven patients. In most cases, analyses were performed on triplicate skin samples: fresh (n = 26); cryopreserved in 5% dimethylsulphoxide (n = 21), or cryopreserved in 30% glycerol (n = 26). RESULTS: HIV was isolated in two of 26 cultures of fresh skin specimens (8%), seven of 47 cryopreserved skin specimens (15%), and eight of 26 blood specimens (31%). The nested PCR detected HIV-1 in all skin samples (n = 73), regardless of the postmortem interval or cryopreservation. In blood, a positive signal was found in eight of 12 patients but two of them had discordant results on successive samples. CONCLUSIONS: These data suggest that nested PCR on postmortem skin samples can detect HIV more reliably than on blood. They also demonstrate the potential viral infectivity of fresh or stored skin postmortem samples in HIV infected patients. They underscore the need for caution during the handling of skin tissue from HIV infected cadavers and confirm the potential risk related to accidental allografting of HIV contaminated skin.

Acquired Immunodeficiency Syndrome↗

[Skin defect coverage with micro skin graft].

BACKGROUND: The aim of this study is to coverage of the large skin defect with microskin graft. METHODS: The wound coverage of the large skin defect may be difficult with auto skin graft. In these patients, split thickness skin graft may be used in a bloc shape or expanded skin graft shape and a stamp skin graft shape or expanded stamp skin graft shape. On the other hand, split thickness skin graft may be used as a micrograft shape after the mincing process, which reduces of the graft size in a few millimeters. In this study, 6 patients with skin defect was admitted in our clinic, and their skin defect was treated with micro skin graft. Expansion ratio was 1:15. RESULTS: Epithelialization on the wound surface was completed in 4 to 6 weeks and cobblestone appearance was observed after the wound coverage. CONCLUSION: Skin defect coverage with micrograft is an effective technique like the other skin graft coverage methods.

Adult↗

The effect of Cetaphil Gentle Skin Cleanser on the skin barrier of patients with rosacea.

A good skin care regimen is a critical part of rosacea treatment; however, care must be taken to choose nonirritating products because individuals with rosacea tend to have sensitive skin, and irritants can trigger a worsening of symptoms. This study examines the use of Cetaphil Gentle Skin Cleanser (a nonalkaline nonirritating cleanser) in patients with rosacea. To eliminate the confounding effects of various treatments, the cleanser was studied for a 2-week period in the absence of rosacea therapy following a 2-week washout period in patients with mild to moderate rosacea. During the washout period, patients were asked to cleanse twice daily with Dove Sensitive Skin Bar. During the 2-week study period, patients were monitored for skin barrier function through transepidermal water loss (TEWL) and corneometry; patients also were monitored for rosacea severity. Thirty patients were enrolled. No significant increase in TEWL was demonstrated at any point during the study, indicating that the gentle skin cleanser did not damage the skin barrier. Additionally, the cleanser was shown to maintain skin hydration. Furthermore, a post hoc statistical analysis suggests there was a significant reduction (P<.05) in investigator-assessed rosacea severity on the cheeks, forehead, and nose at the end of week 1 and on the cheeks, forehead, and chin at the end of week 2 compared with the end of the washout period (after 2 weeks of cleansing with Dove Sensitive Skin Bar). The mild nonirritating action of the gentle skin cleanser was supported by the lack of adverse events and the tolerability shown in the study. There were no increases in erythema, scaling, dryness, stinging, burning, or lack of smoothness in the skin during the 2-week study period, despite the fact that patients were not being treated for their rosacea during the study. These results indicate that Cetaphil Gentle Skin Cleanser may be a good choice for the cleansing part of a total rosacea skin care regimen.

Administration, Cutaneous↗

Percutaneous absorption of benzyl acetate through rat skin in vitro. 3. A comparison with human skin.

The comparative absorption of the fragrance and industrial compound, benzyl acetate, has been studied in rat and human skin, using shaved, full-thickness dorsal skin of male Fischer 344 rats and full-thickness human skin obtained from patients undergoing surgical resection. Penetration of the compound through rat and human skin was evaluated in vitro in flow-through diffusion cells following topical application of neat [methylene-14C] benzyl acetate (33.1 mg/cm2) to the epidermal surface and occlusion with a teflon cap, 2.9 cm above the skin surface. The absorption of benzyl acetate across rat skin was rapid and extensive, reaching 34.3 +/- 3.9% of the applied dose (11.3 +/- 1.3 mg/cm2) (mean +/- SD, n = 12) at 24 hr and 55.8 +/- 5.0% of the applied dose (18.5 +/- 1.7 mg/cm2) at 72 hr. The penetration of benzyl acetate was significantly (P < 0.05) less rapid and extensive through human skin, reaching 5.5 +/- 0.1% of the applied dose (1.8 +/- 0.0 mg/cm2) (mean +/- SD, n = 12) at 24 hr and 17.8 +/- 3.3% of the applied dose (5.9 +/- 1.1 mg/cm2) at 72 hr. The rate of penetration of benzyl acetate was greater through rat skin than through human tissue at all time points studied up to 72 hr. The maximum rate of skin penetration was 0.6 +/- 0.1 mg/cm2/hr and 0.1 +/- 0.0 mg/cm2/hr through rat and human skin, respectively. These data indicate that systemic exposure to benzyl acetate may occur after skin contact in humans. They also support the evidence from the literature that human skin is generally less permeable to xenobiotics than rat skin.

Animals↗

Disaccharide analysis of human skin glycosaminoglycans in sun-exposed and sun-protected skin of aged people.

The total amount of main disaccharide units of skin glycosaminoglycans was compared between sun-exposed (n = 12) and sun-protected skin (n = 14) of aged people using high performance liquid chromatography after labeling with 1-phenyl-3-methyl-5-pyrazolone. The total amount of main disaccharide units in sun-exposed skin was comparable to sun-protected skin presumably due to the diversity of individuals. Consequently, we compared sun-exposed skin with sun-protected skin in identical individuals (n = 6). The total amount of main disaccharide units in sun-exposed skin was significantly greater than that in sun-protected skin (P < 0.05). In addition, the ratio of delta Di-HA (hyaluronic acid, HA)/delta Di-4S (dermatan sulfate, DS) in sun-exposed skin showed a decreasing trend as compared with sun-protected skin in four of six individuals. These results are in agreement with our previous results obtained in animal experiments of photoaging, i.e., hairless mouse skin exposed to repeated UV irradiation showed an increase in total amount of main disaccharide units and a decrease in the ratio of delta Di-HA(HA)/delta Di-4S(DS). We could confirm similar changes in skin glycosaminoglycans both in human and murine photoaging supporting the appropriate rationale for using the hairless mouse as an animal model for photoaging. Again, disaccharide analysis should provide a useful method to examine the biochemical changes of skin glycosaminoglycans in human photoaging.

Aged↗

Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection.

Endogenous chromophores in human skin serve as photosensitizers involved in skin photocarcinogenesis and photoaging. Absorption of solar photons, particularly in the UVA region, induces the formation of photoexcited states of skin photosensitizers with subsequent generation of reactive oxygen species (ROS), organic free radicals and other toxic photoproducts that mediate skin photooxidative stress. The complexity of endogenous skin photosensitizers with regard to molecular structure, pathways of formation, mechanisms of action, and the diversity of relevant skin targets has hampered progress in this area of photobiology and most likely contributed to an underestimation of the importance of endogenous sensitizers in skin photodamage. Recently, UVA-fluorophores in extracellular matrix proteins formed posttranslationally as a consequence of enzymatic maturation or spontaneous chemical damage during chronological and actinic aging have been identified as an abundant source of light-driven ROS formation in skin upstream of photooxidative cellular stress. Importantly, sensitized skin cell photodamage by this bystander mechanism occurs after photoexcitation of sensitizers contained in skin structural proteins without direct cellular photon absorption thereby enhancing the potency and range of phototoxic UVA action in deeper layers of skin. The causative role of photoexcited states in skin photodamage suggests that direct molecular antagonism of photosensitization reactions using physical quenchers of photoexcited states offers a novel chemopreventive opportunity for skin photoprotection.

Chemoprevention↗

The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour.

BACKGROUND: One determining factor of skin colour is the distribution pattern of melanosomes within keratinocytes. Melanosomes in keratinocytes of light skin as in Caucasians are distributed as membrane-bound clusters, whereas the melanosomes in keratinocytes of dark skin as in African/American individuals tend to be larger and distributed individually. It has been shown that melanin content, melanin composition and the size of melanosomes in the human epidermis vary considerably with both ethnicity and chronic sun exposure. OBJECTIVES: To assess quantitatively the distribution pattern of melanosomes that have been transferred to keratinocytes in the photoprotected (volar forearm) skin from normal Asian individuals and to compare these data with those from light-skinned Caucasian and dark-skinned African/American individuals. METHODS: Electron microscopy was used. RESULTS: We have demonstrated that melanosomes within keratinocytes of Asian skin are distributed as a combination of individual and clustered melanosomes with a proportion of 62.6% vs. 37.4%, respectively. This contrasts with dark and light skin keratinocytes where melanosomes are predominantly individual (88.9%) and clustered (84.5%), respectively. Analysis of mean +/- SD melanosome size also revealed a progressive variation in size with ethnicity, melanosomes in dark skin being the largest (1.44 +/- 0.67 microm(2) x 10-2) followed in turn by those in Asian skin (1.36 +/- 0.15 microm(2) x 10-2) and Caucasian skin (0.94 +/- 0.48 microm(2) x 10-2). In addition, it was shown that the melanosomes that are individually distributed tend to have a larger size than the clustered melanosomes. CONCLUSIONS: The present data indicate that there may be a size gradient of melanosomes encompassing the global complexion coloration and that the melanosome distribution in keratinocytes of Asian skin is intermediate between that in light Caucasian and dark African/American skin.

Adolescent↗

Repeated ultraviolet exposure affords the same protection against DNA photodamage and erythema in human skin types II and IV but is associated with faster DNA repair in skin type IV.

We have investigated the photoprotective properties of induced pigmentation using erythema and epidermal DNA photodamage as endpoints. Previously unexposed buttock skin of 12 young, healthy adults (six skin type II and six skin type IV) was exposed daily (Monday to Friday) for 2 wk (days 1-12) with 0.65 minimal erythema dose of solar simulated radiation. Mean skin type IV minimal erythema dose was 1.8-fold greater than for skin type II. Compared to skin type II, solar simulated radiation treatments produced less erythema and more tanning in skin type IV. To assess DNA photodamage, biopsies were taken and prepared for paraffin sections that were stained with a monoclonal antibody for thymine dimers. Thymine dimers were quantified by image analysis. The single exposure data (0.65 and 2 minimal erythema dose) showed that DNA damage was related to physical dose (J per cm2) independent of skin type. Our data also showed that DNA photodamage accumulates in both skin types with repeated, suberythemal doses of solar simulated radiation. On day 12, there were more thymine dimers in skin type IV than skin type II, again indicating that physical rather than biologic dose determines the level of DNA damage. Comparisons on days 12 and 19, however, showed a much greater loss of thymine dimers in skin type IV, suggesting better thymine dimer repair. Protection factors for erythema and thymine dimers were calculated and shown to be about 2 in both skin types. This provides further indirect evidence that DNA is a chromophore for erythema, but also suggests that a tan may not be the major factor in natural photoprotection.

DNA Damage↗

Skin examinations and skin cancer prevention counseling by US physicians: a long way to go.

BACKGROUND: Nonmelanoma skin cancer and actinic keratoses may be partially preventable by physician counseling. OBJECTIVE: The purpose of this study was to assess the frequency of counseling for skin cancer prevention. METHODS: Data on skin cancer counseling and skin examinations were obtained from representative visits to outpatient physicians in the United States from the 1997 National Ambulatory Medical Care Survey. A limitation of the skin examination data is that the extent of the skin examination was not reported. RESULTS: Skin examinations occurred in 60 million (8.6%) of 703 million office visits, and skin cancer prevention counseling or education occurred in 12 million visits (1.5%). For patients younger than 20 years, such prevention counseling occurred in only 1.0% of 169 million visits. For those patients with a current or previous history of nonmelanoma or melanoma skin cancer or actinic keratosis (high-risk patients) identified by the treating physician, 2.8 million (35%) of 7.9 million patients received such counseling. In high-risk patients, dermatologists provided such counseling at 41% of visits, compared with 24% for general and family practice, 9.3% for otolaryngology, 13% for general surgery, and 7.7% for internal medicine. In such high-risk patients, skin examinations were performed at 78% of dermatology visits, 69% of otolarynogolgy visits, 36% of general surgery visits, and 27% of family physician visits. Capitation did not lead to greater primary preventive practices; skin cancer prevention counseling occurred in 4% of high-risk capitated patients compared with 38% of noncapitated patients. CONCLUSION: Physicians provide skin cancer prevention counseling or education at fewer than half of visits for high-risk patients. High-risk patients are likely to receive skin cancer prevention messages depending on the specialty of physician that they visit in roughly the following scheme: dermatologists>family physicians>all other specialties. Economic restraints within managed care systems may affect their "health maintenance" function.

Counseling↗

Transfollicular drug delivery: penetration of drugs through human scalp skin and comparison of penetration between scalp and abdominal skins in vitro.

In order to quantitatively investigate the importance of transfollicular pathway for drug delivery, drug penetration through human scalp skin was investigated using liquid formulations containing lipophilic and hydrophilic drugs in vitro. The penetration pathway for drugs through the scalp skin was examined using fluorescent probes. Additionally, the drug penetration through the scalp skin was compared with that via human abdominal skin to clarify the usefulness of intrafollicular delivery. Lipophilic melatonin (MT) and ketoprofen (KP) showed high permeabilities through the scalp skin, although the flux of KP was much higher. Absorption enhancers, N-methyl-2-pyrrolidone and isopropylmyristate, only slightly increased the fluxes. Hydrophilic fluorouracil (5FU) and acyclovir (ACV) penetrated through the scalp skin with relatively large fluxes. However, there was large variability in the fluxes of these drugs across scalp skin from different sources. When the relationship between the flux and hair follicle density was estimated, there was good correlation between the two (r = 0.651 for MT and r = 0.666 for ACV, P < 0.05). The histologic examination of the scalp skin, following application of the formulation with nile red or sodium fluorescein, indicated that the probes permeated into the junction of the internal and external root sheath of follicles and diffused into the dermis via the outer root sheath at the initial times. The penetration of nile red, a lipophilic probe, via the stratum corneum of scalp skin was later than that via the follicles. The permeation of MT and 5FU through the scalp skin was much higher than that via the abdominal skin, being 27 and 48 times as high as the abdominal skin, respectively. These results indicate that the drug delivery through the scalp skin will offer an available delivery means for drugs, particularly for hydrophilic drugs.

Abdomen↗

Percutaneous absorption and skin decontamination of PCBs: in vitro studies with human skin and in vivo studies in the rhesus monkey.

Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing.

Administration, Topical↗