Protective effect of hochuekkito, a Kampo prescription, against ultraviolet B irradiation-induced skin damage in hairless mice.

A Kampo prescriptions, hochuekkito (HET) has been utilized for treating functional conditions such as general fatigue, compromised state and gastrointestinal motility disorder. Recently, HET has attracted the attention of dermatologists because of its clinically positive effects in atopic dermatitis (AD) treatment. To explain this positive effect of HET, we examined its protective ability against oxidative skin stress using a murine model. The dorsal region of 8-week-old male HR-1 hairless mice, which were raised on a HET (0%, 2% and 10%) mixed diet, was irradiated once with 70 mJ/cm(2) of ultraviolet (UV)-B light. After 4 days, transepidermal water loss (TEWL) and stratum corneum water content (SCWC), were determined as a measure of degree of skin dysfunction. To estimate the amount of active oxygen generated, the stratum corneum catalase activity (SCCA) and stratum corneum carbonylated protein (SCCP) content in the tape-stripped stratum corneum samples were measured. We also measured the H(2) O(2) scavenging ability of HET, and analyzed the changes in the expression levels of several inflammation and oxidative stress-related genes in the skin of HET-fed mice. In control mice, exposure to UV-B led to significant increases in TEWL and SCCP and significant decreases in SCWC and SCCA. These UV-B-induced changes were reduced in mice administrated HET, and the reduction was HET dose-dependent. Our results suggested that HET offered a protective effect against UV-B-induced skin damage. We also found that HET had relatively low ability to scavenge H(2) O(2) , and expression level of cyclooxygenase-2 mRNA decreased in HET-fed mouse.

Intense pulsed light therapy for aberrant Mongolian spots.

BACKGROUND: Aberrant Mongolian spots (AMS) distal to the lumbosacral region are thought to be more likely to persist than typical sacral Mongolian spots. So far, Q-switched ruby laser (QSRL) has been the treatment of choice for AMS. Intense pulsed light (IPL) is obtained from flashlamp devices that emit wavelengths between 515 and 1200 nm. IPL has documented efficacy for the treatment of irregular pigmentation, telangiectasia, rough skin texture, rhytids, hair removal, and vascular lesions, with several filters being available that can be used to block shorter wavelengths from the skin. As far as we could determine, there have been no clinical and histological studies on the treatment of AMS with IPL. Accordingly, the aim of this study was to assess the clinical and histological efficacy of IPL for AMS. METHODS: Seven patients (4 males and 3 females) presenting from September 2008 to July 2009 were assessed. Their mean age was 2.0 years, ranging from 0 to 7 years. The IPL device used in this study was a Natulight (Lumenis Ltd., Tokyo, Japan). Photographs were taken of all patients with a high-resolution digital camera at baseline and 6 months after treatment. Skin biopsy specimens were taken from 1 patient (case 4) before, immediately after, and 6 months after treatment. RESULTS: According to the 7 family members of the patients, the outcome of IPL was graded as follows: excellent improvement in 1 (14%), good improvement in 4 (57%), and slight improvement in 2 (29%). All families would have liked to continue IPL treatment. Evaluation of the effect of treatment by a physician was less favorable, with excellent improvement in 1 (14%), good improvement in 2 (29%), and slight improvement in 4 (57%). Histopathologic examination of the pigmented region revealed the typical features of a Mongolian spot in the hematoxylin-eosin stained section. Immediately after IPL, there were no changes in the dermis. At 6 months after treatment, however, the number of melanocytes in the middle and upper dermis was obviously decreased. CONCLUSIONS: IPL is an effective method for the treatment of AMS.

Allergic contact dermatitis caused by gum rosin and wood rosin in Tako-no-Suidashi ointment.

Tako-no-Suidashi ointment (TSO) is an old Japanese over-the-counter drug, used for the drainage of infectious pustular disease, such as furuncles, carbuncles and infectious atheroma, although whether it works well or not is unknown. The ingredients of the TSO compound commonly include rapeseed oil, gum rosin, wood rosin, Japanese wax, paraffin, petrolatum, copper sulfate, Peru balsam, acetic acid, salicylic acid and trace amounts of Guinea green B. We report a case of contact dermatitis in a 38-year-old Japanese woman caused by TSO. The patient presented to our hospital with pruritic erythema on her left cheek. In order to remove a subcutaneous tumor, she had applied TSO 4 days prior to presentation. Clinical examination showed a well-demarcated exudative erythematous macule with yellowish crusts and scales on her left cheek. Patch testing showed a positive reaction to TSO (++), gum rosin (++) and wood rosin (++) at 72 h. As TSO includes highly allergenic material, caution should be made in applying this topical therapy.

Enhancement of anti-allergic effects mediated by the Kampo medicine Shoseiryuto (Xiao-Qing-Long-Tang in Chinese) with lysed Enterococcus faecalis FK-23 in mice.

Kampo is a traditional Japanese medicine originating from ancient Chinese medicine which included the administration of herbal prescription, lifestyle advice and acupuncture. Orally administered Kampo prescriptions are believed to be influenced by diet and intestinal microbiota. However, reports on the Kampo administration effects are still limited. Shoseiryuto (TJ-19), which has anti-allergic and anti-inflammatory properties, is a Kampo prescription used clinically for the treatment of allergic bronchial asthma. We examined whether Shoseiryuto administration is affected by a probiotic product, lysed Enterococcus faecalis FK-23 (LFK). BALB/c mice were sensitized with cedar pollen allergen, and the peritoneal accumulation of eosinophils was induced. During a sensitization period of 21 days, varying amounts of Shoseiryuto (and saline as a control) were administered to the mice. The accumulation of eosinophils was significantly reduced by 30 mg/day doses of Shoseiryuto but not by 3 or 9 mg/day doses. Similarly, 3 mg/day Shoseiryuto, 30 mg/day LFK, 3 mg/day of Shoseiryuto co-administered with 30 mg/day of LFK, and saline control were compared. A significant reduction in the accumulation of eosinophils was observed at 3 mg/day Shoseiryuto co-administered with 30 mg/day of LFK. These results suggest that Shoseiryuto-mediated anti-allergic effects are enhanced by the probiotic (LFK). Although not significant statistically, serum allergen-specific and total IgE levels in the treatment group exposed to the mixed agent (ie. Shoseiryuto and LFK) were generally lower than those receiving either one alone. The results indicate a synergistic effect of a Kampo medicine (Shoseiryuto, Xiao-Qing-Long-Tang in Chinese) and lysed Enterococcus faecalis FK-23 on allergic responses in mice.

Comparison of regional efficacy and complications in the treatment of aberrant Mongolian spots with the Q-switched ruby laser.

BACKGROUND AND OBJECTIVE: Aberrant Mongolian spots (AMS) distal from the lumbosacral region are said to be more apt to persist than the typical sacral AMS, so the Q-switched ruby laser (QSRL) has been the treatment of choice for AMS. However, so far as we could determine, there is no statistical analysis of the treatment of AMS. This paper shows statistical comparisons of the efficacy and complications in the treatment of AMS with QSRL. METHODS: Fifty-three patients (16 males and 37 females) with 57 AMS regions were treated with the QSRL from March 1999 to April 2007, and we divided the diseased areas into exposed regions that could not be concealed by clothing and non-exposed regions that could be concealed by clothing, and performed a statistical analysis. RESULTS: The results indicated that QSRL treatment of AMS in the exposed regions showed significantly improved coloration and caused less pigmentation when compared with the non-exposed regions. CONCLUSION: We concluded that QSRL treatment of AMS in the exposed regions is more effective than that of AMS in the non-exposed regions.

Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo (Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study.

Hochu-ekki-to is a traditional herbal (Kampo) medicine that has been shown to be effective for patients with Kikyo (delicate, easily fatigable, or hypersensitive) constitution. Previous case reports have suggested that this herbal drug was effective for a certain subgroup of patients with atopic dermatitis (AD). We aimed to evaluate the efficacy and safety of Hochu-ekki-to in the long-term management of Kikyo patients with AD. In this multicenter, double blind, randomized, placebo-controlled study, 91 Kikyo patients with AD were enrolled. Kikyo condition was evaluated by a questionnaire scoring system. All patients continued their ordinary treatments (topical steroids, topical tacrolimus, emollients or oral antihistamines) before and after their protocol entry. Hochu-ekki-to or placebo was orally administered twice daily for 24 weeks. The skin severity scores, total equivalent amount (TEA) of topical agents used for AD treatment, prominent efficacy (cases with skin severity score = 0 at the end of the study) rate and aggravated rate (more than 50% increase of TEA of topical agents from the beginning of the study) were monitored and evaluated. Seventy-seven out of 91 enrolled patients completed the 24-week treatment course (Hochu-ekki-to: n = 37, placebo: n = 40). The TEA of topical agents (steroids and/or tacrolimus) was significantly (P < 0.05) lower in the Hochu-ekki-to group than in the placebo group, although the overall skin severity scores were not statistically different. The prominent efficacy rate was 19% (7 of 37) in the Hochu-ekki-to group and 5% (2 of 40) in the placebo group (P = 0.06). The aggravated rate was significantly (P < 0.05) lower in the Hochu-ekki-to group (3%; 1 of 37) than in the placebo group (18%; 7 of 39). Only mild adverse events such as nausea and diarrhea were noted in both groups without statistical difference. This placebo-controlled study demonstrates that Hochu-ekki-to is a useful adjunct to conventional treatments for AD patients with Kikyo constitution. Use of Hochu-ekki-to significantly reduces the dose of topical steroids and/or tacrolimus used for AD treatment without aggravating AD.

Expression of damage-induced neuronal endopeptidase (DINE) mRNA in peri-infarct cortical and thalamic neurons following middle cerebral artery occlusion.

Damage-induced neuronal endopeptidase (DINE) is a unique nerve-injury associated molecule, which was recently identified in a peripheral nerve injury model. The aim of this study was to determine the expression profiles and distribution of DINE in adult rats after middle cerebral artery (MCA) occlusion. Focal cerebral ischemia induced late-onset and prolonged expression of DINE mRNA in the peri-infarct cortex and specific nuclei of thalamus. Double labeling using immunohistochemistry and in situ hybridization revealed that DINE mRNA was exclusively expressed in cells that were positive to a neuronal marker NeuN. Previously established knowledge on neuroanatomical fiber connection suggests that DINE mRNA was expressed in areas projecting their axons to or through the core region of the infarction. This unique expression profile was similar to that of activating transcription factor-3 (ATF-3), which is a marker of nerve-injured neuron. More than 98% of ATF-3 immunoreactive neurons simultaneously expressed DINE mRNA, suggesting that DINE expression is observed in injured neurons of CNS as well as PNS. Since DINE expression promotes antioxidant activity, our results suggest that DINE may act as a neuroprotective molecule in neurons under ischemic insult.

An Alternative Approach to Atopic Dermatitis: Part II-Summary of Cases and Discussion.

In the first part of this Review, we presented case-series where Kampo treatment was introduced for those atopic dermatitis (AD) patients who had failed with conventional therapy, in an attempt to prove that there exists a definite subgroup of AD patients for whom Kampo treatment is effective. In this second part, we will first provide the summary of the results for 140 AD patients we treated in 2000. The results suggest that Kampo treatment is effective for more than half of AD patients who fail with conventional therapy. In the Discussion, we will examine the evidential basis for conventional AD therapy and discuss how Kampo treatment should be integrated into the guidelines for AD therapy. We contend that Kampo treatment should be tried before systematic immunosuppressive agents are considered. As each Kampo treatment is highly individualized, it should be regarded more as 'art' than technology, and special care should be taken to assess its efficacy in clinical trial.

An Alternative Approach to Atopic Dermatitis: Part I-Case-Series Presentation.

Atopic dermatitis (AD) is a complex disease of obscure pathogenesis. A substantial portion of AD patients treated with conventional therapy become intractable after several cycles of recurrence. Over the last 20 years we have developed an alternative approach to treat many of these patients by diet and Kampo herbal medicine. However, as our approach is highly individualized and the Kampo formulae sometimes complicated, it is not easy to provide evidence to establish usefulness of this approach. In this Review, to demonstrate the effectiveness of the method of individualized Kampo therapy, results are presented for a series of patients who had failed with conventional therapy but were treated afterwards in our institution. Based on these data, we contend that there exist a definite subgroup of AD patients in whom conventional therapy fails, but the 'Diet and Kampo' approach succeeds, to heal. Therefore, this approach should be considered seriously as a second-line treatment for AD patients. In the Discussion, we review the evidential status of the current conventional strategies for AD treatment in general, and then specifically discuss the possibility of integrating Kampo regimens into it, taking our case-series presented here as evidential basis. We emphasize that Kampo therapy for AD is more 'art' than technology, for which expertise is an essential pre-requisite.

Superiority of water application to water sealing in burn wound healing.

BACKGROUND: Recently there have appeared on the market many external dressings for wound management. They all use water-sealing materials to maintain wounds in a moist state. However, in our daily clinical observations, a water-sealing material sometimes results in poor wound healing. Although a water-sealing material does in fact keep the wound moist, the quality of the water is far from that of the optimum extracellular fluid. METHODS: A second-degree burn wound was made in the rat by contact with a metal stick. Experiment 1 was to evaluate the influence of delayed primary wound treatment on burn-wound depth progression. We used a time lag procedure. Each group was treated with a water-sealing application (hydrocolloid sheet). Experiment 2 was to investigate the progression-preventing effect of normal saline on a burn allowed to dry for 3 hours, we compared a group that received a water sealing (non-moistening and incomplete moisture) dressing with one that received a water-supplying (moistening) dressing with using chi-square test. RESULTS: In the Experiment 1 (time lag and water sealing test), the early group showed quite normal wound healing at 7 days after onset. The slough was thin (about 10-20% of full dermal thickness). The delayed groups showed the poor healing characteristic. The slough was relatively thick (about 30-60% of full dermal thickness). Three hours' delay seemed to bring about poor healing. In the Experiment 2 (water application test), the moistening (water application) group showed relatively good healing after seven days. The slough was as thin as in the early group in the Experiment 1. The non-moistening group showed a poor healing process like the delayed group in the Experiment 1. For the moistening group, the healing percentage of 77.8% was significantly greater than the 41.3% observed in the non-moistening group (chi-square test, p < 0.05). CONCLUSIONS: All the materials in wound dressing are water-sealing. When the component water under the sheet is far from the extracellular fluid, these applications bring about poor healing. Delayed application and incomplete moisture should be corrected by external water-application.

An extract of the root of Lithospermun erythrorhison accelerates wound healing in diabetic mice.

Many people suffer from intractable bedsores, which sometimes develop because of chronic metabolic failure in patients. An extract of the root of Lithospermun erythrorhison (SK) has been reported to have an effect on wound healing. However, the effects of SK have not been studied in chronic wounds, such as bedsores. The healing-impaired diabetic (db/db) mouse is a good model for the investigation of clinical healing therapies. Therefore, we examined whether SK accelerates wound healing in db/db mice. Full-thickness round wounds of 6-mm diameter were created on the backs of mice. After applying SK, we covered the wound with a film dressing to keep it moist. At three weeks, wound closure was complete in SK-treated mice but not in controls. Capillary vessel number and collagen synthesis increased early in wound healing in SK-treated wounds. At this time, vascular endothelial growth factor (VEGF)-positive neutrophils had infiltrated the wound and the appearance of apoptotic fibroblasts and endothelial cells in the granulation tissue was more advanced than in the controls. Where the wound was covered with epithelium, there tended to be less infiltration of VEGF-positive cells and apoptotic cells. These results suggest that the inflammatory phase was shortened, and the proliferative and maturation phases were advanced by SK. It is known that SK also has antibacterial activity. Therefore, we conclude that SK is useful for wound healing in db/db mice, and could potentially help patients with intractable bedsores.