Late-onset interstitial nephritis in a patient with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms.

Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe hypersensitivity drug reaction affecting the skin and multiple internal organ systems. We report a 47-year-old man with DIHS/DRESS and comorbidities (fulminant type 1 diabetes mellitus, valsartan-induced photosensitivity, vitiligo and acute interstitial nephritis). Although acute interstitial nephritis usually appears in the early phase, his is a rare case of acute interstitial nephritis more than 2 years after the onset of DIHS/DRESS.

Effects of Cultivation Month and Genetic Background on Phenolic Content of Citrus tachibana Peel.

Species of the Citrus genus are known as rich sources of phenolic compounds. Peels of Citrus tachibana and Citrus unshiu are used in herbal formulations, sometimes in similar ways. In this study, we examined the effects of plant maturity and genetic background on the total phenolic contents and quantities of specific flavonoids in C. tachibana peel. In addition, we compared these values in C. tachibana and C. unshiu peels. The total phenolic contents and the contents of nobiletin, tangeretin, and hesperidin were higher in the extracts of the immature peel than in those of the mature peels of C. tachibana; moreover, the quantities of these compounds were also influenced by the genetic background of C. tachibana. In the extracts of C. unshiu peel, the contents of total phenolics, nobiletin, and tangeretin were lower than those of C. tachibana peel. However, the hesperidin content was higher in extracts of C. unshiu peel than those of C. tachibana peel. This study evaluated the phenolic and flavonoid contents of C. tachibana and C. unshiu in an effort to provide new insights into herbal medicines for further study and utilization.

Topical Application of Trisodium Ascorbyl 6-Palmitate 2-Phosphate Actively Supplies Ascorbate to Skin Cells in an Ascorbate Transporter-Independent Manner.

Ascorbic acid (AA) possesses multiple beneficial functions, such as regulating collagen biosynthesis and redox balance in the skin. AA derivatives have been developed to overcome this compound's high fragility and to assist with AA supplementation to the skin. However, how AA derivatives are transferred into cells and converted to AA in the skin remains unclear. In the present study, we showed that AA treatment failed to increase the cellular AA level in the presence of AA transporter inhibitors, indicating an AA transporter-dependent action. In contrast, torisodium ascorbyl 6-palmitate 2-phosphate (APPS) treatment significantly enhanced the cellular AA level in skin cells despite the presence of inhibitors. In ex vivo experiments, APPS treatment also increased the AA content in a human epidermis model. Interestingly, APPS was readily metabolized and converted to AA in keratinocyte lysates via an intrinsic mechanism. Furthermore, APPS markedly repressed the intracellular superoxide generation and promoted viability associated with an enhanced AA level in Sod1-deficient skin cells. These findings indicate that APPS effectively restores the AA level and normalizes the redox balance in skin cells in an AA transporter-independent manner. Topical treatment of APPS is a beneficial strategy for supplying AA and improving the physiology of damaged skin.

Evaluation of a newly-developed immunochromatography strip test for diagnosing dermatophytosis.

BACKGROUND: Traditionally, dermatophytosis, a common disease affecting millions of people world-wide, has been diagnosed by direct microscopy and fungal culture. The immunochromatography (ICG) strip test was recently developed. METHODS: We compared the performance of the ICG strip test for the detection of dermatophytes in samples from human skin and nails with direct microscopy. The 160 samples, consisting of 88 skin and 72 nail specimens, were subjected to direct microscopy study using a 20% KOH solution and to examination with the ICG strip test. Of 160 samples, 18 were examined by fungal culture using Sabouraud dextrose agar medium. RESULTS: We found that the overall sensitivity and specificity of the ICG test were 83.5% and 66.7%; they were 82.1% and 76.2% for the 88 skin and 85.4% and 58.3% for the 72 nail specimens, respectively. CONCLUSIONS: Our findings indicate that the efficacy of the ICG test is comparable to direct microscopy for the detection of dermatophytes. Performance of the assay was easy, and results were available quickly. We suggest that it is an effective tool for dermatophytosis screening.

Inhibition of immunological function mediated DNA damage of alveolar macrophages caused by cigarette smoke in mice.

Exposure to cigarette smoke impairs the pulmonary immune system, including alveolar macrophage function, although the mechanisms by which this occurs are not fully elucidated. This study investigates the effect of cigarette smoke exposure on the antigen-presenting activity of alveolar macrophages, which is required for antigen-specific response to T cells. C57BL/6 mice were exposed to cigarette smoke for 10 days using a Hamburg II smoking machine, and alveolar macrophages were obtained by bronchoalveolar lavage. The antigen-presenting activity of alveolar macrophages was significantly inhibited in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. Major histocompatibility complex class II cell surface molecule-positive cells, B7-1 molecule-positive cells, and interleukin-1beta messenger RNA gene expression in alveolar macrophages were significantly decreased in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. In contrast, DNA damage and generation of superoxide and hydrogen peroxide in alveolar macrophages were significantly increased by cigarette smoke exposure. These results suggest that inhibition of the antigen-presenting activity of alveolar macrophages may result from decreased expression of major histocompatibility complex class II and B7-1 molecules and interleukin-1beta messenger RNA gene expression following cigarette smoke exposure. Furthermore, inhibition of antigen presentation in alveolar macrophage may result from DNA damage induced by excessive amounts of reactive oxygen species being generated by alveolar macrophages following cigarette smoke exposure. These findings suggest that cigarette smoke impairs the immunological function of alveolar macrophages and, as a result, increases the risk for pulmonary infection.

Protection of human keratinocytes from UVB-induced inflammation using root extract of Lithospermum erythrorhizon.

UVB irradiation is an important inducer of biological changes in skin and can activate inflammatory reactions and apoptotic pathways, leading to skin damage. A root extract of Lithospermum erythrorhizon (SK), which has naphthoquinone pigments containing shikonin and shikonin derivatives, is known for its anti-inflammatory, anti-bacterial, and anti-tumor activity, and for its scavenging of reactive oxygen species. However, the effect of SK against UV damage is not clear. The aim of this study was to evaluate the efficacy of SK against UVB induced damage in normal human epidermal keratinocytes (NHEK). UVB-irradiated NHEK showed decreased cell viability, increased production of interleukin (IL)-1alpha, IL-6, IL-8, and tumor necrosis factor-alpha, and induced apoptosis. In an apoptosis pathway assay, UVB-irradiated NHEK showed increased caspase-3 activity, p53 and its phosphorylation at serine 15 compared with non-irradiated cells. All these effects induced by UVB irradiation were clearly inhibited by treatment with SK before and after UVB irradiation for 24 h. It is suggested that SK can protect epidermal cells against harmful effects of UVB irradiation and that SK treatment is probably beneficial for photoprotection of the skin.

The water-soluble extract of Illicium anisatum stimulates mouse vibrissae follicles in organ culture.

It is well known that reduced blood flow in the scalp is a cause of alopecia. We have shown previously that the extract of Illicium anisatum increases subcutaneous blood flow in mice. In the present study, we used an organ culture system to examine whether this extract promoted hair follicle elongation. B6C3HF1 mouse vibrissae follicles were cultured in serum-free medium for 7 days at 31 degrees C. Follicles treated with water-soluble (WS) extracts of the leaves, fruits and roots of Illicium anisatum or shikimic acid grew significantly longer than controls. In contrast, ethyl acetate-soluble (AS) extracts and n-hexane-soluble (HS) extracts of the leaves, fruits and roots of the plant inhibited hair follicles and shaft growth. Fractionation of the WS fruit extract showed that the number 1 and number 2 fractions possessed hair follicle elongation activity. GC/MS analysis revealed that the number 1 fraction contained shikimic acid, and that the number 2 fraction was a mixture of many components including glycosides and polysaccharides. Reverse transcription-polymerase chain reaction analysis demonstrated that shikimic acid also induced mRNA expression of insulin-like growth factor-1, keratinocyte growth factor, and vascular endothelial growth factor in the hair follicles. These results suggest that the WS extract of Illicium anisatum promotes hair growth and may be a useful additive in hair growth products.

Bacterial ceramides and sphingophospholipids induce apoptosis of human leukaemic cells.

The genus Sphingobacterium, whose members are Gram-negative non-fermentative rods, possesses ceramides and related sphingophospholipids (SPLs) with isoheptadecasphinganine and 2-hydroxy or non-hydroxy isopentadecanoic acid. This paper reports evidence that ceramides isolated from Sphingobacterium spiritivorum ATCC 33861 induce endonucleolytic DNA cleavage in human myeloid leukaemia HL-60 cells in vitro, which is the primary characteristic biochemical marker for apoptosis or programmed cell death. Ceramides and SPLs also induced DNA fragmentation and caspase-3 activation, followed by changes in morphology, such as alterations in the size of nuclei and cells, and cell cycle shortening. Apoptotic activity correlated with the ceramide structure. Ceramide with a 2-hydroxy fatty acid showed stronger apoptotic activity than ceramide with a non-hydroxy fatty acid. Furthermore, the major five SPLs (ceramide phosphorylethanolamine-1 and -2, ceramide phosphorylinositol-1 and -2, and ceramide phosphorylmannose-1) showed apoptosis-inducing activity in HL-60 cells, indicating that the ceramide moiety of the SPLs plays a crucial role as the intracellular second messenger but that their hydrophilicity is less important in this regard. The hydrophilic part of SPLs may play a role in other cellular response systems. The involvement of Fas antigen was implicated in the apoptotic event since Fas antigen expression was observed after 3 or 4 h stimulation of HL-60 cells with bacterial ceramides. However, a time-course study for caspase-3 activation indicated maximal activity at 1 h after stimulation with bacterial ceramides, suggesting that two (or possibly more) mechanisms of signal transduction, Fas-dependent and Fas-independent, may be involved. Fas antigen expression and caspase-3 activation by five kinds of SPLs were observed after 3 or 4 h. These results indicate that there is a difference in the response of HL-60 cells to bacterial ceramides and SPLs.

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.

Induction of apoptosis by Citrus paradisi essential oil in human leukemic (HL-60) cells.

Limonene is a primary component of citrus essential oils (EOs) and has been reported to induce apoptosis on tumor cells. Little is known about induction of apoptosis by citrus EOs. In this study, we examined induction of apoptosis by Citrus aurantium var. dulcis (sweet orange) EO, Citrus paradisi (grapefruit) EO and Citrus limon (lemon) EO. These EOs induced apoptosis in HL-60 cells and the apoptosis activities were related to the limonene content of the EOs. Moreover, sweet orange EO and grapefruit EO may contain components besides limonene that have apoptotic activity. To identify the components with apoptotic activity, grapefruit EO was fractionated using silica gel columns, and the components were analyzed by GC-MS. The n-hexane fraction contained limonene, and the dichloromethane fraction (DF) contained aldehyde compounds and nootkatone. Decanal, octanal and citral in the DF showed strong apoptotic activity, suggesting that the aldehyde compounds induced apoptosis strongly in HL-60 cells.