Dermal carbonyl modification is related to the yellowish color change of photo-aged Japanese facial skin.

BACKGROUND: The photo-aged facial skin is characterized by various unique features such as dark spots, wrinkles, and sagging. Elderly people, particularly Asians, tend to show a yellowish skin color change with photo-aging. However, there has been no analytical study conducted on this unique skin color change of the aged facial skin. OBJECTIVE: The purpose of the present study is to examine whether the carbonyl modification in the dermal protein is involved in the yellowish color change that occurs in the photo-aged skin. METHODS: Normal skin samples excised from the face, abdomen and buttock of variously aged Japanese were separated into the epidermal and the dermal portions. These skin samples were histologically examined for carbonyl modification. Moreover, an in vitro constructed dermis model composed of a contracted collagen gel was treated with acrolein or 4-hydroxynonenal. All these samples were also studied colorimetrically. RESULTS: The dermal samples obtained from the photo-aged facial skin exhibited an appearance of yellowish color, whereas neither the facial epidermis nor the dermis obtained from the abdomen or buttock showed such a yellowish discoloration. The upper layer of the dermis that revealed the yellowish color showed elastosis whose elastic fibers were found to colocalize with carbonyl protein as detected by a labeled hydrazide, as well as by an immunohistochemical examination using the antibody against acrolein adduct. Experimental induction of carbonyl modification in a dermis model in vitro by a long-term treatment with acrolein or 4-hydroxynonenal was found to show the appearance of the yellowish change which was also proven by an increase in b* value of colorimetry. It was more pronounced than that induced by glycation. CONCLUSION: Our present results strongly suggest that carbonyl modification of the dermal protein is involved in the production of the yellowish color change that is noted in the photo-aged facial skin.

Observation of dermal collagen fiber in wrinkled skin using polarization-resolved second-harmonic-generation microscopy.

Optical probe methods for in vivo assessments of cutaneous photoaging are necessary in fields such as anti-aging dermatology and skin cosmetic development. We investigated the relation between wrinkle direction and collagen orientation in ultraviolet-B-exposed (UVB-exposed) skin using polarization-resolved second-harmonic-generation (SHG) microscopy. A polarization anisotropic image of the SHG light indicated that wrinkle direction in UVB-exposed skin is predominantly parallel to the orientation of dermal collagen fibers. Furthermore, collagen orientation in post-UVB-exposed skin with few wrinkles changed from that of UVB-exposed wrinkled skin to that of no-UVB-exposed skin. The method proposed has the potential to become a powerful non-invasive tool for assessment of cutaneous photoaging.

Docetaxel, low-dose estramustine, and doxifluridine in hormone-refractory metastatic prostate cancer.

PURPOSE: Advanced prostate cancer, which is one of the most common cancers, usually progresses to hormone-refractory prostate cancer (HRPC). A recent randomized trial of treatment with docetaxel demonstrated improved survival for patients with HRPC. The combination of docetaxel and estramustine phosphate (estramustine) has been reported to be effective for HRPC. Low-dose estramustine suppresses the pituitary-gonadal axis. Docetaxel plus 5-fluoro-5'-deoxyuridine (5'-dFUrd) had supra-additive cytotoxic effects on HRPC cells consistent with the molecular mechanism. Therefore, we examined the efficacy of adding 5'-dFUrd on the chemotherapy regimen, which consist docetaxel and estramustine. METHODS: All of the HRPC patients were treated with estramustine 140 mg orally twice 5'-dFUrd 200 mg orally four times daily on days 1-21, and docetaxel 60 mg/m(2) was administered on day 1. We evaluated serum prostate-specific antigen (PSA) and measurable responses, the progression-free and overall survival, and the impact on adverse effects and the quality of life (QOL). RESULTS: Of 34 patients with a median age of 72.3 years, 73% showed PSA responses and 70% showed measurable responses. The median progression-free survival was 18.0 and 5.8 months for PSA responders and non-responders and the overall survival was 19.4 months, respectively. There were few serious adverse effects. Grade 3/4 neutropenia occurred in 32.4% of the patients, and was easily managed with granulocyte colony-stimulating factor (G-CSF) injection. There was no significant change in the overall QOL scores serially. CONCLUSIONS: This study shows that the combined regimen is tolerable and effective in Japanese HRPC patients.

Neurologic toxicity associated with interferon alpha therapy for renal cell carcinoma.

A 67-year-old man received interferon alpha (IFN alpha) therapy for lung metastases of renal cell carcinoma (RCC). Multiple pulmonary metastases disappeared completely. However, neurological toxicity was detected by magnetic resonance imaging (MRI) as abnormal brain lesions. After discontinuation of IFN alpha therapy, his neurological symptoms and abnormal lesions on MRI disappeared completely. Complete remission of RCC has continued, and results of neurological study have remained normal for 5 years after discontinuation of IFN alpha therapy.

Non-invasive visualization of melanin and melanocytes by reflectance-mode confocal microscopy.

In vivo visualization of epidermal melanin was performed by reflectance-mode confocal microscopy (RCM). Firstly, we examined the distribution of epidermal melanin in pigmented animals and compared with that of the human skin. Melanocytes in the skin of pigmented animals were found to accumulate a large amount of melanin that can be easily visualized because of its brightness. Their RCM images correlated well with the Fontana-Masson-stained sections for melanin. In contrast, in the human skin, typical dendritic melanocytes were hardly observed even in pigmented lesions, although supranuclear melanin caps were easily visible. These results suggested that human melanocytes rapidly transfer the produced melanin to keratinocytes and do not accumulate it. Secondly, to elucidate the production of melanin by human melanocytes, we evaluated the changes of melanin after a single ultraviolet (UV) exposure. The melanin-accumulating melanocytes were clearly visualized during the skin pigmentation process. The RCM images showed the brightness because of melanin gradually increased from day 4, then dendrite-elongated melanocytes appearing from day 8, and finally melanin caps formed from day 29. In conclusion, RCM successfully evidenced the difference in melanin distribution between the pigmented animals and humans, and the UV-induced pigmentation process in vivo as well.

Isolated renal tuberculosis following intravesical Bacillus Calmette-Guérin therapy for bladder cancer.

We present a case of isolated renal tuberculosis following bacillus Calmette-Guérin (BCG) therapy for bladder cancer. In the presurgical radiographic examination, we suspected an atypical renal cell carcinoma. According to the diagnosis of renal cell carcinoma, we performed a radical nephrectomy. The histological findings were tuberculosis-specific inflammatory changes and the patient received an antituberculous multiple drug therapy for a year. It is concluded that we should pay attention to the possibility of a renal tuberculosis granuloma in any patient who presented with subacute formed renal masses following BCG treatment before deciding on the strategy of the treatment of the renal masses, especially in patients who had received such a treatment which induced an immunocompromised state.

Effects of diabetes on nitric oxide-mediated relaxations in male rat corpus cavernosum smooth muscle.

INTRODUCTION: We evaluated the effects of diabetes on nitric oxide-mediated relaxations and nitric oxide synthase activity in male rat corpus cavernosum smooth muscles. METHODS: Eight-week-old male rats were assigned to three groups: control (injected with the vehicle), DM (diabetes mellitus, induced by injection with 65 mg/kg streptozotocin), and TES (testosterone, testosterone supplemented after induction of diabetes). After 8 weeks, corpus cavernosum smooth muscle strips were mounted in an organ bath for isometric tension recordings. Electrical field stimulation (EFS, 2-ms pulse duration, 0.3-20 Hz and 3 s train) was applied to the strips precontracted with 30 microM phenylephrine. The microdialysis probe was inserted into the strip, and Krebs-Henseleit solution was perfused into the probe. The dialysate during EFS was collected, and the amount of NO(-)(2)/NO(-)(3) (NOx) released in the dialysate was measured by the Greiss method. Sodium nitroprusside (0.1 nM to 10 mM) and carbachol (1 nM to 10 mM) were cumulatively added to the strips precontracted with 30 microM phenylephrine. RESULTS: EFS caused frequency-dependent relaxations and NOx releases of the strips. Pretreatment with N(omega)-nitro-L-arginine (100 microM) and tetrodotoxin (1 microM) completely inhibited the relaxations and NOx releases. The maximum relaxation was significantly greater in the DM group than in the control or TES group. The release of NOx was significantly greater in the DM group than in the control or TES group. Sodium nitroprusside, the endothelium-independent vasodilator, relaxed the tissues in all three groups. There were no significant differences among control, DM and TES groups in the maximum relaxation to sodium nitroprusside. CONCLUSION: The present data suggest that diabetes enhances nitric oxide synthase activity and nitric oxide-mediated relaxations in the male rat corpus cavernosum by the reduced testosterone level in the diabetic animals.

Effects of castration on nitric oxide-mediated relaxations in male rat corpus cavernosum smooth muscle.

BACKGROUND: The effects of castration on nitric oxide- mediated relaxations and nitric oxide synthase activity in male rat corpus cavernosum smooth muscles. METHODS: Eight-week-old male rats were assigned to two groups: control (sham operated) and castrated animals. After 8 weeks, corpus cavernosum smooth muscle strips were mounted in an organ bath for isometric tension recordings. Electrical field stimulation (EFS) was applied to the strips precontracted with 30 microM phenylephrine. The microdialysis probe was inserted into the strip, and Krebs-Henseleit solution was perfused into the probe. The dialysate during EFS and cholinergic stimulation was collected, and the amount of NO(-)(2)/NO(-)(3) (NOx) released in the dialysate was measured by the Greiss method. Sodium nitroprusside and carbachol were cumulatively added to the strips precontracted with 30 microM phenylephrine. RESULTS: EFS caused frequency-dependent relaxations and NOx releases in the strips. Pretreatment with N(omega)-nitro-L-arginine (100 microM) and tetrodotoxin (1 microM) completely inhibited relaxations and NOx releases. The maximum relaxation in the castration group was significantly greater than that in the control group. The release of NOx was significantly greater in the castration group than in the control group. Sodium nitroprusside relaxed the tissues in both groups similarly. Carbachol failed either to relax the tissue or to increase the amount of NOx production in the tissue. CONCLUSION: The present data suggest that castration enhances nitric oxide synthase activity and nitric oxide-mediated relaxations in the male rat corpus cavernosum.

Effect of exposure of human skin to a dry environment.

BACKGROUND/AIMS: Changes in the skin conditions after exposure to low humidity have been generally experienced in everyday life, but there have been few reports to approach it-especially in healthy skin. We have examined the effect of low humidity on healthy human skin by using noninvasive measurement devices. METHODS: Skin conditions on the ventral forearm and the cheek before and after 3 or 6 h exposure to low humidity were evaluated by measuring skin surface conductance, skin surface capacitance and transepidermal water loss. Skin surface replicas were also taken before and after exposure and analysed for roughness parameters--Ra (arithmetic mean roughness value), Rz (10-point height), Sm (mean value of the profile element) and VC1 (anisotropy of skin furrows). RESULTS: There was a significant decrease of water content of stratum corneum at both test sites from the time points 0 h to 3 h and 6 h (P < 0.01) and transepidermal water loss from the time point 0 h to 6 h (P < 0.05). Regarding the roughness parameters, a significant increase of Rz in the directions of 45 degrees/225 degrees and 90 degrees/270 degrees to the body axis and Sm in the directions of 0 degrees/180 degrees (P < 0.05) on the forearm and VC1 (P < 0.05) on the cheek. The parameter Rz also showed a tendency to increase in the directions of 45 degrees/225 degrees (P = 0.06) on the cheek. A specific pattern of the changes to be related to the Langer's lines in the surface morphology was observed. The changes of skin surface pattern in our experiment lead us to consider that exposure to low humidity even in such a short period would be related to inducing aggravation of skin texture and the formation of fine wrinkles. CONCLUSION: A short exposure of skin to a low-humidity environment induced changes in the moisture contents in the stratum corneum and skin surface pattern, which lead us to assume that a dry environment in our daily life would make fine wrinkles related to lack of water in the stratum corneum.