OBJECTIVE: To explore the inhibitory effects of Nardostachys Jatamansi DC. volatile oil (NJVO) on psychological factors substance P (SP)/cortisol (CORT)-induced hyperpigmentation. METHODS: The model of psychologically-induced hyperpigmentation of B16F10 cells was created using SP (10 nmol/L) + CORT (10 µmol/L) for 72 h. The levels of melanin content, tyrosinase (TYR) activity using NaOH lysis and L-dihydroxyphenylalanine (L-DOPA) oxidation methods were assessed, respectively. The effect of NJVO on SP/CORT-induced normal human skin tissue pigmentation was detected by Masson staining. Protein expressions of tyrosinase-related protein 1 (TRP-1), tyrosinase-relative protein 2 (DCT), and microphthalmia-associated transcription factor were determined using Western blot. The melanosome number, maturation, and melanosomal structure changes were detected through transmission electron microscopy and immunofluorescence experiments. In vivo, zebrafish pigment content was evaluated in SP/CORT-induced zebrafish hyperpigmentation model. RESULTS: NJVO significantly reduced the melanin content (P<0.01) and inhibited tyrosinase activity (P<0.01), the pigmentation of the normal skin tissue in the NJVO group was significantly lower than that in the SP/CORT group (P<0.05). And NJVO considerably downregulated expressions of melanogenesis-related proteins (TYR, TRP-1, DCT) in cells (P<0.01). In addition, the number of melanosomes was decreased and the dentrites formation of B16F10 cells was inhibited after NJVO treatment (P<0.01). In vivo, NJVO significantly reduced the pigment content in the zebrafish body (P<0.01). CONCLUSION NJVO effectively reversed SP/CORT-induced hyperpigmentation by suppressing the activity and expression of TYR and TRPs and inhibiting melanosome maturation in mouse B16F10 melanoma cells.
Animals ; Hyperpigmentation/psychology* ; Zebrafish ; Oils, Volatile/therapeutic use* ; Melanins/metabolism* ; Humans ; Monophenol Monooxygenase/metabolism* ; Mice ; Nardostachys/chemistry* ; Substance P ; Hydrocortisone ; Skin Pigmentation/drug effects* ; Cell Line, Tumor ; Melanosomes/ultrastructure* ; Microphthalmia-Associated Transcription Factor/metabolism* ; Melanoma, Experimental ; Oxidoreductases/metabolism* ; Intramolecular Oxidoreductases/metabolism*

BACKGROUND: Melanin is detectable in various sense organs including the skin in animals. It has been reported that melanin adsorbs toxic elements such as mercury, cadmium, and lead. In this study, we investigated the adsorption of molybdenum, which is widely recognized as a toxic element, by melanin. METHODS: Molybdenum level of the mouse skin was measured by inductively coupled plasma mass spectrometry. The pigmentation level of murine skin was digitalized as the L* value by using a reflectance spectrophotometer. An in vitro adsorption assay was performed to confirm the interaction between molybdenum and melanin. RESULTS: Our analysis of hairless mice with different levels of skin pigmentation showed that the level of molybdenum increased with an increase in the level of skin pigmentation (L* value). Moreover, our analysis by Spearman's correlation coefficient test showed a strong correlation (r = - 0.9441, p < 0.0001) between L* value and molybdenum level. Our cell-free experiment using the Langmuir isotherm provided evidence for the adsorption of molybdenum by melanin. The maximum adsorption capacity of 1 mg of synthetic melanin for molybdenum was 131 μg in theory. CONCLUSION Our in vivo and in vitro results showed a new aspect of melanin as an adsorbent of molybdenum.
Adsorption ; Animals ; Melanins ; chemistry ; metabolism ; Mice ; Mice, Hairless ; Mice, Transgenic ; Molybdenum ; chemistry ; metabolism ; pharmacology ; Skin ; chemistry ; drug effects ; Skin Pigmentation ; drug effects ; Water Pollutants, Chemical ; chemistry ; metabolism ; pharmacology

PURPOSE: Patients treated with anticancer agents often experience a variety of treatment-related skin problems, which can impair their quality of life. MATERIALS AND METHODS: In this cross-sectional study, Dermatology Life Quality Index (DLQI) and clinical information were evaluated in patients under active anticancer treatment using a questionnaire survey and their medical records review. RESULTS: Of 375 evaluated subjects with anticancer therapy, 136 (36.27%) and 114 (30.40%) were treated for breast cancer and colorectal cancer, respectively. We found that women, breast cancer, targeted agent use, and longer duration of anticancer therapy were associated with higher dermatology-specific quality of life distraction. In addition, itching, dry skin, easy bruising, pigmentation, papulopustules on face, periungual inflammation, nail changes, and palmoplantar lesions were associated with significantly higher DLQI scores. Periungual inflammation and palmoplantar lesions scored the highest DLQI. CONCLUSION: We believe our findings can be helpful to clinicians in counseling and managing the patients undergoing anticancer therapy.
Antineoplastic Agents* ; Breast Neoplasms ; Colorectal Neoplasms ; Counseling ; Cross-Sectional Studies* ; Dermatology ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Inflammation ; Medical Records ; Pigmentation ; Pruritus ; Quality of Life* ; Skin*

Several chemical compounds can restore pigmentation in vitiligo through mechanisms that vary according to disease etiology. In the present study, we investigated the melanogenic activity of six structurally distinct compounds, namely, scopoletin, kaempferol, chrysin, vitamin D, piperine, and 6-benzylaminopurine. We determined their effectiveness, toxicity, and mechanism of action for stimulating pigmentation in B16F10 melanoma cells and in a zebrafish model. The melanogenic activity of 6-benzylaminopurine, the compound identified as the most potent, was further verified by measuring green fluorescent protein concentration in tyrp1 a: eGFP (tyrosinase-related protein 1) zebrafish and mitfa: eGFP (microphthalmia associated transcription factor) zebrafish and antioxidative activity. All the tested compounds were found to enhance melanogenesis responses both in vivo and in vitro at their respective optimal concentration by increasing melanin content and expression of TYR and MITF. 6-Benzyamino-purine showed the strongest re-pigmentation action at a concentration of 20 μmol·Lin vivo and 100 μmol·Lin vitro, and up-regulated the strong fluorescence expression of green fluorescent protein in tyrp1a: eGFP and mitfa: eGFP zebrafish in vitro. However, its relative anti-oxidative activity was found to be very low. Overall, our results indicated that 6-benzylaminopurine stimulated pigmentation through a direct mechanism, by increasing melanin content via positive regulation of tyrosinase activity in vitro, as well as up-regulating the expression of the green fluorescent protein in transgenic zebrafish in vivo.
Alkaloids ; chemistry ; pharmacology ; Animals ; Benzodioxoles ; chemistry ; pharmacology ; Benzyl Compounds ; chemistry ; pharmacology ; Cholecalciferol ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Humans ; Kaempferols ; chemistry ; pharmacology ; Melanins ; genetics ; metabolism ; Monophenol Monooxygenase ; genetics ; metabolism ; Pigmentation ; drug effects ; Piperidines ; chemistry ; pharmacology ; Polyunsaturated Alkamides ; chemistry ; pharmacology ; Purines ; chemistry ; pharmacology ; Scopoletin ; chemistry ; pharmacology ; Vitiligo ; drug therapy ; enzymology ; metabolism ; Zebrafish

An unusual grayish brown discoloration of the synovium was found during a knee arthroscopy of a 72-year-old man. He also had similar pigmentation affecting the skin on the legs, arms, hands, and face. It was found he had been taking 400 mg of amiodarone hydrochloride daily for last 7 years. Amiodarone is known to cause a slate grey pigmentation of skin and cornea, but we believe this is the first report of amiodarone-induced pigmentation of the synovium. The arthroscopist should be aware of the possibility of drug-related synovial pigmentation and include this in differential diagnosis.
Aged ; Amiodarone/*adverse effects/therapeutic use ; Anti-Arrhythmia Agents/*adverse effects/therapeutic use ; Arrhythmias, Cardiac/complications/drug therapy ; Arthroscopy ; Diagnosis, Differential ; Humans ; Knee Joint/surgery ; Male ; Pigmentation Disorders/*chemically induced/*diagnosis ; Skin/pathology ; Synovial Membrane/*pathology

OBJECTIVETo study the possibility of removal melanin granules from autogenic acellular dermal matrix of giant nevus tissue by H2O2 bleaching technique.

METHODSA total of 32 skin specimens (0.5 cm x 0.5 cm) from giant nevus tissue and 1 piece (0.5 cm x 0.5 cm) of normal skin were obtained from the surgical removal. One giant nevus tissue was chosen as control. The others and the normal skin tissue were treated with solution of 0.25% Dispase II for digestion for 24 hours under normal temperature to remove epidermis. Then each piece was immerged into solution of 0.5% Triton X-100 for digestion for 48 hours in normal temperature. One giant nevus tissue and the normal skin tissue were chosen as control. The others were immerged into solution of different concentrations of H2O2, treated under different temperature and lasting for different period. Lastly, all specimens were treated with HE staining, immunohistochemical staining, light microscopy and so on.

RESULTSAfter giant nevus tissues were treated with solution of 0.25% Dispase II and immerged into solution of 0.5% Triton X-100 in normal temperature, nevus cells and all other cellular components of pigmented nevus tissues can be effectively removed, there were the cavities left by removal of cells without any residual cell debris, but still remaining part of pigment. Then each specimen were immerged into solution of different concentrations of H2O2, under different temperature and lasting for different period which can remove residual melanin granules. In solution of 3% H2O2 for 36 h under 37 degrees C, can remove all the melanin particles, the content of collagen type I in the obtained specimen was not changed. Collagen fibers were uniform in thickness, regular in arrangement with no obvious degeneration.

CONCLUSIONSWith solution of 0.25% Dispase II and solution of 0.5% Triton X-100 in normal temperature, all cells in nevus tissue can be removed effectively. Further treatment with 3% H2O2 at 37 degrees C for 36 h can remove all the melanin particles, while collagen type I has no obvious change. The preparation of acellular dermal matrix of the giant nevus may possibly be applied as autologous tissue implant to repair tissue defects.

Acellular Dermis ; Endopeptidases ; pharmacology ; Epidermis ; Humans ; Hydrogen Peroxide ; pharmacology ; Melanins ; Nevus ; pathology ; Nevus, Pigmented ; pathology ; Octoxynol ; pharmacology ; Skin Lightening Preparations ; pharmacology ; Skin Neoplasms ; pathology ; Skin Pigmentation ; drug effects ; Skin Transplantation ; Surface-Active Agents ; pharmacology

The anti-melanogenesis effect of glyceollins was examined by melanin synthesis, tyrosinase activity assay in zebrafish embryos and in B16F10 melanoma cells. When developing zebrafish embryos were treated with glyceollins, pigmentation of the embryos, melanin synthesis and tyrosinase activity were all decreased compared with control zebrafish embryos. In situ expression of a pigment cell-specific gene, Sox10, was dramatically decreased by glyceollin treatment in the neural tubes of the trunk region of the embryos. Stem cell factor (SCF)/c-kit signaling pathways as well as expression of microphthalmia-associated transcription factor (MITF) were determined by western blot analysis. Glyceollins inhibited melanin synthesis, as well as the expression and activity of tyrosinase induced by SCF, in a dose-dependent manner in B16F10 melanoma cells. Pretreatment of B16F10 cells with glyceollins dose-dependently inhibited SCF-induced c-kit and Akt phosphorylation. Glyceollins significantly impaired the expression and activity of MITF. An additional inhibitory function of glyceollins was to effectively downregulate intracellular cyclic AMP levels stimulated by SCF in B16F10 cells. Glyceollins have a depigmentation/whitening activity in vitro and in vivo, and that this effect may be due to the inhibition of SCF-induced c-kit and tyrosinase activity through the blockade of downstream signaling pathway.
Animals ; Embryo, Nonmammalian/drug effects ; Melanins/*biosynthesis ; Melanoma, Experimental/metabolism/pathology ; Mice ; Monophenol Monooxygenase/metabolism ; Phosphorylation/drug effects ; Pigmentation/drug effects ; Proto-Oncogene Proteins c-kit/*metabolism ; Pterocarpans/chemistry/*pharmacology ; SOXE Transcription Factors/metabolism ; Sesquiterpenes/chemistry/*pharmacology ; Signal Transduction/*drug effects ; Soybeans/*chemistry ; Stem Cell Factor/*pharmacology ; Zebrafish/embryology/metabolism

Fixed drug eruption is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Levocetirizine is an active (R)-enatiomer of cetirizine and there have been a few reports of fixed drug eruption related to these antihistamines. We experienced a case of levocetirizine-induced fixed drug eruption and cross-reaction with other piperazine derivatives confirmed by patch test. A 73-year-old female patient presented with recurrent generalized itching, cutaneous bullae formation, rash and multiple pigmentation at fixed sites after taking drugs for common cold. She took bepotastine besilate (Talion®) and levocetirizine (Xyzal®) as antihistamine. She took acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®), dihydrocodeinebitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®) at the same time. Patch test was done with suspected drugs and the result was positive with levocetirizine. We additionally performed patch test for other antihistamines such as cetirizine, hydroxyzine, fexofenadine and loratadine. Piperazine derivatives (cetirizine and hydroxyzine) were positive, but piperidine derivatives (fexofenadine and loratadine) were negative to patch test. There was no adverse drug reaction when she was challenged with fexofenadine. We report a case of levocetirizine-induced fixed drug eruption confirmed by patch test. Cross-reactions were only observed in the piperazine derivatives and piperidine antihistamine was tolerant to the patient.
Acetaminophen ; Aged ; Carbon ; Cetirizine ; Chlorpheniramine ; Common Cold ; Drug Eruptions ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Female ; Guaifenesin ; Histamine Antagonists ; Humans ; Hydroxyzine ; Hypersensitivity ; Loratadine ; Magnesium ; Patch Tests ; Pigmentation ; Pruritus ; Pseudoephedrine ; Triprolidine

BACKGROUND: Minocycline-induced pigmentation of bone (black bone) is well described in tooth-bearing intra-oral bone, but is less known in periarticular bone in patients who have undergone total joint arthroplasty. On a retrospective basis, we investigated the short-term clinico-radiological results of total joint arthroplasties in which the patient developed minocycline-induced periarticular black bone. METHODS: We found 5 cases (0.08%), in 4 patients, of periarticular bone pigmentation revealed during total joint arthroplasties (2 hips, 2 knees, and 1 ankle) in our series of total joint surgeries (6,548 cases) over a 10-year time period in our 3 institutes. Their mean age was 56 years at surgery. All patients had received long-term minocycline treatment. Mean dosage and duration of minocycline was 160 mg/day and 2.2 years, respectively. Minocycline had been prescribed for reactive arthritis (one), rheumatoid arthritis (two) and late infection after total joint arthroplasty (two patients). Mean follow-up period was 3.4 years after the surgeries. RESULTS: All cases had black or brown pigmentation in the periarticular bones during the surgery. There was no pigmentation in the cartilage or soft tissues of the joints. The mean Japanese Orthopaedic Association (JOA) score or Japanese Society for Surgery of the Foot (JSSF) scale for rheumatoid arthritis foot and ankle joints at latest follow-up (case 1, 66; case 2, 87; case 3, 77; case 4, 77; case 5, 80) improved compared to those of pre-surgery (case 1, 47; case 2, 45; case 3, 55; case 4, 34; case 5, 55). No implant loosening was noted on radiographic examination during the follow-up period. No abnormal bone formation, bone necrosis, hemosiderin deposition, malignancy or metallic debris was found on histological examination. CONCLUSIONS: No clinico-radiological symptoms of total joint arthroplasties showed in the patients with minocycline-induced periariticular black bone in the short-term. Systemic minocycline treatment has the potential to induce significant black pigmentation of many tissues. In particular, minocycline-induced pigmentation of periarticular bone may be accelerated by inflammation due to rheumatic or pyogenic arthritis. Surgeons should recognize the risk of bone pigmentation in inflamed joints due to the systemic treatment of minocycline and explore its influence on periarticular bone and total joint arthroplasty in the long-term.
Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*adverse effects/therapeutic use ; Antibiotic Prophylaxis/adverse effects ; Arthritis/drug therapy/*pathology/prevention & control ; Arthroplasty, Replacement/*methods ; Bone and Bones/*drug effects/pathology ; Female ; Humans ; Male ; Middle Aged ; Minocycline/*adverse effects/therapeutic use ; Retrospective Studies ; Skin/pathology ; Skin Pigmentation

OBJECTIVETo study the effect of Gan-Pi regulatory needling (GPRN) in treating chloasma and its influences on female sex hormones, superoxide dismutase (SOD), lipid peroxide (LPO) and melanocyte-stimulating hormone (MSH).

METHODSNinety chloasma patients were equally randomized to three groups, the treatment group treated with GPRN, the control group treated with conventional Western medicine and the blank group untreated. Changes in the scores of skin lesion (area and color) and symptom, as well as blood levels of female sex hormones, MSH, SOD and LPO were observed and compared after 3 months of treatment.

RESULTSIn the treatment group, the scores of skin lesion area and color were reduced from 2.76 + or - 0.96 and 2.48 + or - 0.78 before treatment to 1.42 + or - 0.42 and 1.03 + or - 0.41 after treatment, respectively, while in the control group they were from 2.78 + or - 1.06 and 2.53 + or - 0.88 to 1.58 + or - 1.23 and 1.28 + or - 0.96, respectively, all showing significant changes (P<0.05); the scores were insignificantly changed in the blank group (P>0.05). At the same time, the score of symptoms in the treatment group significantly improved after treatment (P<0.05), significantly different from that of the other two groups. Comparison of female sex hormones among groups showed no significant differences either before or after treatment. The level of LPO decreased and SOD increased in both the treatment group and the control group significantly (all P<0.05), but significant lowering of MSH was only seen in the treatment group (P<0.05).

CONCLUSIONSGPRN can effectively lessen the size and lighten the color of chloasma, improve the accompanying symptoms in patients and decrease LPO and MSH levels and increase the SOD level, but will not affect the level of the female sex hormones.

Acupuncture Points ; Acupuncture Therapy ; adverse effects ; methods ; Administration, Topical ; Adult ; Ascorbic Acid ; administration & dosage ; Biomarkers ; blood ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Gonadal Steroid Hormones ; blood ; Humans ; Melanosis ; blood ; therapy ; Needles ; adverse effects ; Skin Pigmentation ; drug effects ; physiology ; Treatment Outcome ; Vitamin E ; administration & dosage ; Western World