PIXE analysis in different stages of psoriatic skin

Elemental distribution in psoriatic skin varies with the functional state of the keratinocytes, e.g., electrolytes influence cell metabolism and cell proliferation, and trace elements play a crucial role in a great number of enzymes. Elemental distribution in pinpoint lesions, old plaques, and uninvolved skin of 5 psoriatic patients and 4 healthy controls was studied by means of PIXE (proton-induced x-ray emission) analysis. This technique allows the simultaneous detection of elements with an atomic number greater than or equal to 14 along the epidermis and dermis in freeze-dried skin biopsies. Trace elements such as Fe, Cu, and Zn were determined down to a level of 1 ppm. In comparison with uninvolved skin, concentrations of P and K were elevated in psoriatic epidermis. In addition, increased levels of K were correlated with the stage of the psoriatic lesion. Zinc concentrations were significantly elevated in pinpoint lesions. The Zn concentration profiles within the epidermis and upper dermis showed high correlation to the P concentration profiles. Iron levels were decreased in old psoriatic plaques, whereas Cu concentrations varied considerably. In comparison to the controls, Cl concentrations were markedly decreased in the dermis of involved and uninvolved psoriatic skin, whereas epidermal Cl levels were unaffected. As high K levels prevent the Ca-induced differentiation of keratinocytes, high K levels may be the cause of the high cell differentiation in psoriatic skin. Elevated DNA- and RNA-polymerases might be the cause of elevated Zn levels in pinpoint lesions.     

白癜风患者血清及皮损中某些酶及微量元素改变研究

本研究检测白癜风患者血清中超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、黄嘌呤氧化酶(XOD)活性,丙二醛(MDA)水平及血清、皮肤中锌(Zn)、铜(Cu)、硒(Se)、铁(Fe)含量。结果表明:患者血清中GSH-Px、SOD活性及Cu含量低于对照组(P<0.01),MDA、Fe含量高于对照组(P<0.01).皮损处Zn、Cu、Se或Fe含量分别低于或高于周围外观正常皮肤,治疗后血清SOD、GSH-Px活性增高、Cu、Fe含量显著降低(P<0.01)。提示:白癜风患者自由基防御系统中部分酶活性降低,Zn、Cu、Se缺乏。     

Evaluation of trace elements, calcium, and magnesium levels in the plasma and erythrocytes of patients with essential hyperhidrosis

Background Essential hyperhidrosis is a disease that expresses itself with excessive sweating in palmar, plantar, axillary, and craniofacial regions. The etiopathogenesis of the disease, which has particular importance because of leading to psychosocial morbidity, could have not been completely elucidated. In previous studies, it has been shown that oxidative stress might play a role in the pathogenesis. Aims Assessing the levels of trace elements such as Se, Zn, Cu, Fe, and Mg that have an important role in oxidative stress, as well as Ca and Mg that have an important role in membrane physiology, in patients with essential hyperhidrosis. Materials and methods Blood samples taken from the patient group with essential hyperhidrosis (42) and the control group (37) were separated into plasma and erythrocytes, and the levels of the bioelements were measured by use of ICP‐OES device. Results Erythrocyte levels of Se, Fe, Cu, Zn, Ca, and Mg were detected significantly higher in patients with essential hyperhidrosis. Furthermore, plasma levels of Cu, Ca, and Mg were significantly lower in patients with essential hyperhidrosis. Plasma levels of Se, Fe, and Zn showed no statistical difference between two groups. Dicussion It was thought that the high levels of Cu and Fe in erythrocytes may play a role in increased intracellular oxidative stress, whereas the increase in Se and Zn levels may be secondary to increased oxidative stress. Low extracellular concentrations of Ca and Mg raise the thought that they play a role either enhancing the membrane excitability of eccrine sweat glands or influencing the autonomic nerve system. Conclusion The levels of trace elements, which were determined to be different from the control group, may play a role in the pathogenesis of essential hyperhidrosis either in direct relation with or without oxidative mechanisms.     

Element concentrations in serum, erythrocytes, hair and urine of alopecia patients

The trace element concentrations of Se, Rb, Zn, Fe, Co, Cs, Mg, Ca, F, Cu, Cr and Ag in serum and of Se, Rb, Zn, Fe, Co and Cs in red cells of Finnish alopecia patients were determined. In addition the Cu and Zn content in 24 h urine and Cu, Zn, Cd, Cr and Se concentrations in the hair of these patients were studied. No differences in element concentrations of the samples mentioned above as compared to those of the normal population could be found. In addition, there was no tendency of excesses or deficiences of elements analysed in the samples. Statistically significant difference was found between the copper content of serum in alopecia areata and alopecia universalis patients and also between the copper content of serum in alopecia areata plus alopecia totalis and alopecia universalis patients. The selenium concentration in serum samples of a few patients was low, but this is in agreement with the fact that the selenium content in the Finnish population is low due to the scanty content of selenium in food.     

PIXE analysis in uninvolved skin of atopic patients and aged skin.

PIXE (proton-induced X-ray emission) analysis was used to determine the elemental distribution in normal-appearing skin of patients suffering from atopic eczema and in the skin of elderly people. With this technique, elements with atomic numbers greater than or equal to 14 can be detected simultaneously in cryosections of skin biopsies down to a concentration of 1 ppm. Compared with a control group, the epidermal concentrations of Zn and Cu, which are constituent parts of a variety of enzymes, were increased in uninvolved skin of patients with atopic eczema. An increased concentration of these two metals might indicate that even in the epidermis of clinically normal skin of atopic patients, the content of certain enzymes is increased. In the epidermis of elderly people the level of K was lower and that of Ca was higher than in the epidermis of a younger age group. The decreased K level may reflect a reduction of the intracellular volume in the epidermis of aged skin. As high Ca concentrations inhibit the proliferation of and promote the differentiation of keratinocytes, elevated Ca levels may be of importance for the age-associated decrease in epidermal turnover rate.     

Elemental analysis mirrors epidermal differentiation

Using a scanning nuclear microprobe, the distribution of elements and trace elements of skin cross sections of normal skin, non-lesional psoriatic skin and in dry atopic skin have been mapped. In non-lesional psoriatic skin and in dry atopic skin the epidermal Ca-gradient is higher than that of normal skin. In addition, abnormally high Fe and Zn levels were recorded in the stratum granulosum and corneum regions in the pathological skin. It is suggested that these findings correlate to an increased cell turnover in the basal cell layer of the psoriatic and atopic skins. The ratio of Ca/Zn in stratum corneum of paralesional psoriatic skin is approximately 8:1 compared to 12: 1 in normal skin and 15: 1 in atopic skin. This suggests that the differentiation process in paralesional psoriatic skin may actually be an example of disturbed programmed cell death.     

Analyses of Serum Copper and Zinc Levels and Copper/Zinc Ratios in Skin Diseases

With the objective of comprehending abnormal metabolisms of the essential metals of zinc (Zn) and copper (Cu) in three groups of skin diseases, skin cancer, inflammatory diseases, and non-inflammatory disease, we measured serum levels of Zn and Cu in 151 cases of various cutaneous manifestations and estimated the significance of the ratios between the two metals (Cu/Zn). The serum level of Zn was significantly decreased in cases of bullous pemphigoid, decubitus ulcer, and alopecia areata. The serum level of Cu was elevated in cases of psoriasis, decubitus ulcer, and skin cancer. We observed no elevation of serum Zn level or abnormally depressed serum Cu level. The Cu/Zn ratio showed significantly different values among these three groups of the diseases, suggesting the utility of measuring Cu/Zn ratios for differential diagnosis over that of determining the serum level of Zn or Cu alone. It was also demonstrated that, in each skin disease, the Cu/Zn ratio clearly reflects the severity of the progress.     

Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial

BACKGROUND: Adapalene is a synthetic retinoid with an established clinical efficacy against acne and good local tolerability. Its effectiveness in the treatment of photodamaged skin has not been studied. OBJECTIVE: We sought to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines. METHODS: In a prospective, 2-center, randomized, controlled, investigator-masked, parallel-group study, 90 patients with actinic keratoses and solar lentigines were treated daily with either adapalene gel (0.1% or 0.3%) or its vehicle gel for 4 weeks, followed by twice-daily applications, if tolerated, for up to 9 months. RESULTS: Of the 90 Caucasian patients (69 male, 21 female; mean age 63.1 years) who were enrolled into the study, 83 patients completed 9 months of treatment. With adapalene gel 0.1% and 0.3%, the mean number of actinic keratoses was reduced by 0.5 +/- 0.9 (mean +/- SE) and 2.5 +/- 0.9, respectively. Whereas, with the vehicle gel, there was an increase of 1.5 +/- 1.3 (P <.05). After 1 month of treatment, the patients who received adapalene had significant lightening of solar lentigines as compared with the patients who were treated with vehicle gel (P <.05). After 9 months, 57% and 59% of the patients had lighter lesions in the adapalene 0.1% and 0.3% groups, respectively, in comparison with only 36% in the vehicle group (P <.05). Histologic evaluations revealed improved cellular atypia and reduced epidermal melanin in adapalene-, as compared with vehicle-treated group. The differences, however, were not statistically significant. A retrospective evaluation of paired clinical photographs (before and after 9-month treatment) by 2 dermatologists who were treatment-blinded revealed significant improvement in wrinkles and other clinical features of photoaged skin with adapalene as compared with its vehicle. CONCLUSION: Adapalene gel 0.1% and 0.3% were well tolerated and improved actinic keratoses, solar lentigines, and other features of photodamaged skin.     

Intranuclear androgen concentrations in facial skin

The concentrations of 5 alpha-dihydrotestosterone (DHT) and testosterone were measured by radioimmunoassay (RIA) in the crude nuclear and cytoplasmic fractions of facial skin containing large sebaceous glands. The data obtained were compared with those obtained with specimens from non-target areas. The intranuclear levels of DHT and testosterone in facial skin were 0.03 +/- 0.3 pg/micrograms DNA and 0.35 +/- 0.03 pg/micrograms DNA, respectively levels in genital skin. By contrast, both androgens were below detection by RIA in non-target skin. There was no significant difference between men and women with respect to the intranuclear androgen levels in facial skin. These findings support the view that the sebaceous gland is a typical androgen target organ irrespective of sex.     

Trace element analyses in pseudoxanthoma elasticum

The dermis and sera of 11 patients with pseudoxanthoma elasticum (PXE) were analyzed by several techniques which test for the presence and quantity of trace elements (Fe, Ni, Co, Cu, Mn, Cr, Zn, Pb, Cd, Al, S, K, Cl, Ca and P). The investigative methods included 1) electron microscopic point X-ray microanalysis, 2) inductively coupled plasma atomic emission spectrophotometric analysis (ICP-AES), 3) X-ray diffraction analysis and/or 4) atomic absorption spectro-photometric analysis. 1) Among 7 specimens of dermis showing histological degeneration of the elastic fibers, 2 showed prominent levels of A1. In early degeneration of the elastic fibers, Ca was present in only small amounts; however, in more fully developed lesions, large quantities of both Ca and P were found, while Fe, Co, Ma and Zn were detected in trace amounts. 2) ICP-AES analysis confirmed large deposits of Al, Ca, and P in diseased dermis (Al: 32.1 ppm wet tissue); other elements were found in normal quantities. Al was not detected in the control dermis. 3) X-ray diffraction analysis suggested the pattern of hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂], which indicates that most of the Ca exists in a crystalline form. 4) Atomic absorption spectrophotometric analysis confirmed a large concentration of Al (11–21 μg/dl, mean=17.2; normal <10) in all test patient's sera. The combined analysis revealed an increased amount of Al in patient's sera as well as in the elastic fibers of the dermis at an early stage of this disease (PXE). These findings suggest a possible role for Al in the pathogenesis of PXE.     

Metals and arsenic in eye shadows

The regulations relating to cosmetic products give no limit values for toxic elements such as metals or arsenic occurring as impurities in cosmetic products. The present study of metals (lead, cobalt, nickel, chromium) and arsenic in eye shadows in 88 colors of 25 brands and 49 products provides a basis for assessing the safety of eye shadow. 66 out of 88 (75%) of the colors contained more than 5 ppm of at least one of the elements, and all 49 products contained more than one 1 ppm of at least 1 of the elements. In one color, the amount of all elements was less than 1 ppm. The highest levels of cobalt and nickel were 41 and 49 ppm, respectively. These levels were high enough to cause allergic symptoms in those previously sensitized. Furthermore, long-term exposure to such levels may probably sensitize. The concentrations of arsenic were extremely low, 2.3 ppm at most. The level of lead was less than 20 ppm in all products. Accordingly, the concentrations of arsenic and lead seemed to be safe. 9 colors had concentrations of water-soluble chromium exceeding 2 ppm, and a very high level, 318 ppm, was encountered in 1 case. The overall results indicate that eye-shadows probably have no significant systemic toxicological effects. The groups at greatest risk are those already sensitized to the allergenic elements. Such consumers will have difficulties in choosing suitable products, since these elements in the form of impurities are not declared in the list of ingredients. Manufacturers should demand certification that the raw materials they buy contain no toxic elements. Although some of the products studied were acceptable, many had excessive levels of the elements from the consumer's viewpoint.     

Electron microscopic microanalysis of prickle cell carcinoma, basaloma, malignant melanoma and normal skin

EMMA has been used in Dermatology since 10 years. In 1981, Fisher established the Cu/Zn index as a parameter for the prognosis of malignant melanoma. We tested the EMMA technique as a means to determine the Cu/Zn index in basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and normal skin. Our preliminary conclusions are: EMMA may be useful to determine the Cu/Zn index in skin tumors; it is possible to obtain useful data from tumors already fixed in paraffin; (c) the highest Cu/Zn index was found in normal skin, the lowest one in malignant melanoma.     

Acyclovir concentrations in the skin of humans after a single oral dose assessed by in vivo cutaneous microdialysis

BACKGROUND/PURPOSE: Acyclovir is a synthetic deoxyguanosine analogue used in the treatment of certain viral diseases. This drug is effective primarily against Herpes simplex virus, Varicella zoster virus and to a lesser extent against Epstein-Barr virus and cytomegalovirus. The aim of the study was to determine the acyclovir concentrations in plasma and skin (cutaneous microdialysate) and to compare its penetration into real (skin) and theoretical peripheral compartment after administration of a single 0.4 g oral dose. METHODS: To evaluate the skin concentrations of the examined agent in 10 healthy male volunteers linear microdialysis probes with 2 kDa molecular-weight cut-off were inserted intradermally and were perfused with Ringer solution up to 6 h after drug ingestion. RESULTS: The mean maximum acyclovir concentrations in the plasma, skin and theoretical peripheral compartment were 3.16+/-0.86, 0.94+/-0.34 and 1.85+/-0.69 micromol/L, respectively, and were achieved after 1.6+/-0.4, 2.4+/-0.3 and 3.7+/-0.7 h. The degree of penetration into the real (skin) and theoretical peripheral compartment was 0.36+/-0.15 and 0.74+/-0.12, respectively, and the differences were statistically significant. Similarly, also, the maximum concentration, time to maximum concentration and area under the concentration-time curve differed significantly between the plasma and skin as well as between the skin and the theoretical peripheral compartment. CONCLUSIONS: In selected cases skin concentrations should be determined rather than those in blood plasma when studying the distribution of orally administered drugs. Evaluation of acyclovir concentrations in the skin cannot be replaced by the calculation of the theoretical peripheral compartment.     

Substance P levels are decreased in lesional skin of atopic dermatitis

There is increasing evidence that neuropeptides (NP) such as substance P (SP) and vasoactive intestinal polypeptide (VIP) are involved in the pathogenesis of atopic dermatitis (AD). Vasoactive intestinal polypeptide levels were found to be significantly elevated in lesional skin of AD as compared to controls. We evaluated by radioimmunoassay the SP content in whole skin homogenates from chronic lichenified lesions of patients with AD. The levels of SP were significantly decreased in lesional skin from AD patients as compared to control skin (0.25 +/- 0.03 vs. 0.97 +/- 0.24 pmol/g tissue, p < 0.01). The diminished SP levels as opposed to increased VIP concentrations could be consistent with different roles of these NP as modulatory agents in the mechanisms associated with AD.     

Cutaneous manifestations of zinc deficiency in ethylic cirrhosis

Thirty-three patients with alcoholic cirrhosis (AC), selected on widely recognized criteria (16, 57), were investigated prospectively for cutaneous manifestations of zinc deficiency. The patients were divided into 3 groups: group A (n = 12): AC without skin lesions; group B (n = 12): AC with skin lesions responsive to a zinc-free topical treatment or resistant to enteral zinc sulfate intake; group C (n = 9): AC with skin lesions cured by oral zinc replacement therapy alone. The lesions observed in group C were studied microscopically. Data concerning zinc metabolism (Zn concentrations in plasma, red cells, urine and hair; alkaline phosphatase values), biochemical criteria of AC (plasma serum-albumin concentration, IgA/transferrin ratio) and a malabsorption test (xylosemia 120 min after oral absorption of D-xylose 25 g) were compared by the variance analysis method. A control group (D, n = 12) was used as reference. Few cases of cutaneous manifestations of zinc deficiency in AC patients have been published. In more than one half of the 15 or so we found in the literature, an aggravating factor (total parenteral nutrition, digestive tract surgery) had to be taken into account. In this prospective study 9 new cases in which AC was the only cause of zinc deficiency are reported. A clinical picture similar to acrodermatitis enteropathica with peribuccal bullous lesions was observed in only one patient. In all other cases the patients presented with a cracked and reticulated eczema on the extensor aspect of the limbs and (often erosive) in the perianal and genital regions. The eczema was associated with cheilitis, glossitis, stomatitis, alopecia and, seldom, ungual Beau's lines. Disorders of behaviour, diarrhoea and bouts of lever regressing under zinc replacement therapy were frequent. Histology was not very specific, except for the presence of necrotic areas in the stratum germinativum, sometimes associated with small subcorneal pustules containing altered polymorphonuclears. In every case, it was the rapid regression of symptoms under zinc sulfate treatment that confirmed the diagnosis. Plasma zinc concentrations were most significantly decreased in all AC groups as compared to controls (61.2 +/- 19.4 vs 97.8 +/- 10.4 micrograms/100 ml) and also in AC patients with skin manifestations of zinc deficiency as compared to the other AC patients (44.4 +/- 9.2 vs 66.5 +/- 18.8 micrograms/100 ml) table V). Changes in serum-albumin levels and in hepatocellular function were parallel to changes in plasma zinc concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Distribution to the skin of epinastine hydrochloride in atopic dermatitis patients

Although the pharmacological profiles and clinical efficacy of antihistamines for patients with atopic dermatitis (AD), one of the representative cutaneous pruritic diseases, have been well documented, the in vivo concentrations of antihistamines in human skin have previously been studied in less detail. In this randomized trial, the suction blister technique was applied to the measurement of the concentrations of epinastine hydrochloride in the extracellular water compartment in comparison with chlorpheniramine maleate in skin from AD patients. A total of 79 patients (mean age, 28.6 years) were randomly allocated to receive either 20 mg of epinastine or 6 mg of chlorpheniramine. Suction blisters were induced on both upper arms in all patients, and blister fluid was obtained for the measurement of concentrations of the 2 test agents by liquid chromatography-tandem mass spectrometry. Epinastine concentrations in 42 samples were 5.02-33.07 ng/mL (mean +/- SD, 14.08 +/- 10.51; median, 7.00), demonstrating that epinastine is distributed to the skin in high concentrations equal to the levels found in plasma and sufficient to exert its variety of pharmacological modes of action. In contrast, chlorpheniramine concentrations in all 37 samples were below the lower limit of quantification (< 0.5 ng/mL). Corresponding to these pharmacological results, a significant decrease of pruritus was observed in AD patients administered epinastine compared with chlorpheniramine. Hence epinastine is likely to be more effective clinically than chlorpheniramine in AD. This is the first report for the determination of in vivo local drug levels of antihistamines in the skin from AD patients.     

Distribution of ATPase-positive Langerhans cells in normal adult human skin

The distribution of ATPase-positive Langerhans cells (LC) was investigated in 117 specimens of normal adult human skin and mucosa taken from different areas of the body. Although there were significant variations in the numbers of LC in each area examined, skin from the face and neck contained the highest density of cells (976 +/- 30.93/mm2). The densities of LC in trunk skin (740 +/- 28.97/mm2), scalp (693 +/- 69.56/mm2) and arm or leg skin (640 +/- 40.95/mm2) were similar. Buccal mucosa had significantly fewer LC (567 +/- 42.94/mm2) than trunk skin, and sacrococcyx skin and palm and sole skin displayed the smallest number of these cells (267 +/- 56.14/mm2 and, 189 +/- 19.15/mm2 respectively). No ATPase-positive LC were detected in the centre of two corneal specimens.     

Comparative diffusion of fusidic acid, oxacillin, and pristinamycin in dermal interstitial fluid after repeated oral administration

OBJECTIVE: The aim of this study was to use the suction bullae technique to compare skin diffusion of 3 antibiotics commonly used for skin infections (fusidic acid, oxacillin, pristinamycin) and to estimate their potential activity at the site of skin infections. SUBJECTS AND METHODS: This comparative open study was conducted in 12 healthy volunteers using a repeated latin square experimental scheme. Antibiotic concentrations in serum and suction bullae fluid were measured by high performance liquid chromatography after 5.5 days of repeated oral administration of fusidic acid (1 g/d), oxacillin (2 g/d), and pristinamycin (2 g/d). RESULTS: Mean antibiotic concentrations in serum and interstitial fluid (suction bullae fluid) were highest for fusidic acid with a Cmax at 91.3 +/- 23.0 mg/l and 45.5 +/- 18.0 mg/l respectively (interstitial fluid/serum ratio=49 +/- 10 p. 100). For oxacillin, Cmax was 8.3 +/- 3.6 mg/l and 0.98 +/- 0.49 mg/l (ratio 13 +/- 5 p. 100). Pristinamycin concentrations were low with a Cmax at 0.51 +/- 0.40 and 0.26 +/- 0.15 mg/l (ratio 73 +/- 57 p. 100). Comparing the area under the interstitial fluid and the serum concentration-time curves showed that the best diffusion was obtained with pristinamycin (114 +/- 61 p. 100), followed by fusidic acid (57 +/- 13 p. 100) and oxacillin (48 +/- 25 p. 100). DISCUSSION: These data were used to calculate indicators of potential efficacy in the interstitial dermal fluid: inhibitor quotient (Cmax/MIC) and AUIC (ASC/MIC), indicator of the time antibiotic concentrations are maintained above the minimal inhibitor concentration (MIC). This showed that fusidic acid was potentially more active against all staphylococci. For streptococci, the observed interstitial concentrations of pristinamycin and of fusidic acid should theoretically inhibit streptococci A growth, but oxacillin was the most adapted antibiotic.     

Mitochondrial common deletion mutation and extrinsic skin ageing in German and Japanese women

The mitochondrial common deletion (CD) mutation is induced by oxidative stress. One main source of oxidative stress is the error-prone process of the respiratory chain located in the mitochondria. Another important source is the exposure to environmental factors, which further induces oxidative stress in the cells. For human skin, the primary damaging environmental factor is ultraviolet (UV) radiation, which is able to induce CD mutations and the characteristic extrinsic skin ageing signs. Traditionally, levels of UV exposure differ between German and Japanese populations, as tanned skin represents beauty and health in Western cultures, whereas photo-protected skin is considered ideal in Asia. We hypothesize that (i) this cultural-related UV exposure pattern might be reflected by CD concentrations in environmentally exposed skin and (ii) CD concentrations in environmentally exposed areas might be associated with the manifestation of extrinsic skin ageing. In this study, we determined the concentration of CD in skin from the neck (environmentally exposed area) and the buttock (environmentally protected area) of 22 German and 46 Japanese women between 30 and 70 years of age. We evaluated skin ageing signs by a validated clinical score, and exposure to environmental factors, such as UV exposure and smoking, was assessed using a questionnaire-based interview. Higher levels of CD were detected in neck skin than in buttock skin in both German and Japanese women. CD also increased with age in the neck skin. German women had higher CD concentrations in the neck skin than Japanese women. The CD concentrations in the buttock skin samples were similar in both populations. These findings suggest higher environmental UV exposure resulted in higher levels of CD in the skin of German women compared with Japanese women. However, only in Japanese women were the signs of extrinsic skin ageing associated with higher CD concentrations in the neck skin, in agreement with the hypothesis (ii). In German women, we did not find this latter association, which might be due to reaching a maximum level of CD, beyond which cells undergo negative selection and are lost to the population samples. In conclusion, under some conditions, there seems to be an association between the CD mutation concentration and extrinsic skin ageing, but this may be modified by cellular and tissue processes which affect the sampling rate for CD mutation concentrations and prevent a statistical association with extrinsic skin ageing.     

Isotretinoin in local treatment of acne and rosacea and animal experiment studies on isotretinoin and arotinoid

Fifteen patients with acne and 4 with rosacea were treated topically with 0.2% isotretinoin cream twice a day for 16 weeks. Inflammatory lesions responded better (30 +/- 22 versus 15 +/- 12) than non-inflammatory lesions (23 +/- 44 versus 17 +/- 24). Neither the "causal level" (123 +/- 85 versus 130 +/- 66 micrograms/cm2 nor the "replacement sum" (70 +/- 29 versus 77 +/- 30 micrograms/cm2) were changed (lipometer assay). In 150 adult male Syrian hamsters 1-2 drops of isotretinoin in concentrations varying from 0.3% to 0.001% and arotinoid ranging in concentration from 0.3% to 0.00001% in acetone were applied to the left ventral ear or the left flank organ twice a day (5/7 days) for 21 days. In higher concentrations there was a significant reduction in sebaceous gland size. Arotinoid, however, is extremely toxic. Even in concentrations as low as 0.00001% the animals showed severe side-effects within the 1st week.