Synthetic 3′,4′-Dihydroxyflavone Exerts Anti-Neuroinflammatory Effects in BV2 Microglia and a Mouse Model

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer’s disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3′,4′-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3′,4′-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin E2 and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. This indicates that the anti-inflammatory activities of 3′,4′-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and NF-κB signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3′,4′-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

Development of a simple and sensitive HPLC-MS/MS method for determination of diazepam in human plasma and its application to a bioequivalence study

We developed a simple, sensitive, and effective ultra-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method with an electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) and positive ion modes to determine diazepam concentrations in human plasma using voriconazole as an internal standard (IS). Diazepam and IS were detected at transition 285.2→193.1 and 350.2→127.1, respectively. After liquid-liquid extraction (LLE) using 1.2 ml of ethyl acetate:n-hexane (80:20, v/v), diazepam and IS were eluted on a Phenomenex Cadenza CD-C18 column (150 × 3.0 mm, 3 µm) with an isocratic mobile phase (10 mM ammonium acetate in water:methanol [5:95, v/v]) at a flow rate of 0.4 mL/min. The peak retention time was 2.32 min for diazepam and 2.01 min for IS, respectively. The lower limit of quantitation (LLOQ) was 0.5 ng/mL (S/N > 10) using 50 µL of plasma, and no interferences were observed in chromatograms. Our analytical method was fully validated and successfully applied to a bioequivalence study of two formulations of diazepam in healthy Korean volunteers.

A Nudix Hydrolase Protein, Ysa1, Regulates Oxidative Stress Response and Antifungal Drug Susceptibility in Cryptococcus neoformans

A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.

A Ferroxidase, Cfo1, Regulates Diverse Environmental Stress Responses of Cryptococcus neoformans through the HOG Pathway

The iron uptake and utilization pathways play a critical role in allowing human pathogens, including Cryptococcus neoformans, the causative agent of fatal meningoencephalitis, to survive within the mammalian body by competing with the host for iron. Here we show that the iron regulon is also required for diverse environmental stress responses and that in C. neoformans, it is regulated by the high-osmolarity glycerol response (HOG) pathway. Between CFO1 and CFO2, two ferroxidase genes in the iron regulon, CFO1 but not CFO2 was induced during oxidative and osmotic stress. Interestingly, we found that the HOG pathway repressed basal expression of both CFO1 and CFO2. Furthermore, when the HOG pathway was blocked, CFO2 also responded to oxidative and osmotic stress and the response of CFO1 was increased. We also established that CFO1 plays a major role in responding and adapting to diverse environmental stresses, including oxidative and genotoxic damage, osmotic fluctuations, heavy metal stress, and stress induced by cell membrane destabilizers. Therefore, our findings indicate that in C. neoformans, the iron uptake and utilization pathways are not only required for iron acquisition and survival, but also play a significant role in the environmental stress response through crosstalk with the HOG pathway.

Cytotoxicity and anti-inflammatory effects of root bark extracts of Acanthopanax henryi / 中国天然药物

AIM@#To investigate the cytotoxicity, anti-inflammatory activity, and action mechanism of root bark extracts of Acanthopanax henryi.@*METHOD@#The hot methanol extract of the root bark of A. henryi was subjected to XAD-4 column chromatography eluting with a gradient of methanol in water. The cytotoxicity and anti-inflammatory effects of the MeOH fractions were evaluated on the inhibition on lipopolysaccharide (LPS)-induced nitric oxide, prostaglandin E2, interleukin-1β, and interleukin-6 production in RAW 264.7 macrophages.@*RESULTS@#The 80% MeOH fraction was a better inhibitor of LPS-induced NO, PGE2, IL-1β, and IL-6 production, and expression of inducible nitric oxide synthase (iNOS) at the protein levels in a concentration-dependent manner.@*CONCLUSION@#The 80% MeOH fraction of A. henryi root bark has significant anti-inflammatory activity. This provides a pharmacological basis for clinical application for the treatment of inflammation.

Clear Cell Hidradenoma on the Palm

No abstract available.

Pedunculated Eccrine Porocarcinoma / 대한피부과학회지

Eccrine porocarcinoma is a rare, malignant skin tumor that originates from the eccrine sweat gland. This disease affects elderly people, primarily. It is clinically present in varied forms and the location is not related to sweat-gland distribution, which occurs on the lower limb, trunk, and head. Herein, we report a rare case of pedunculated eccrine porocarcinoma, which had developed on the flank of a 79-year-old woman.

Medical Concern for Colloidal Silver Supplementation: Argyria of the Nail and Face

No abstract available.

Medical Concern for Colloidal Silver Supplementation: Argyria of the Nail and Face

No abstract available.

An Effective Modality for Argyria Treatment: Q-Switched 1,064-nm Nd:YAG Laser

No abstract available.

A Clinicopathologic Study of 43 Cases of Poroid Neoplasms: A Single Center Study / 대한피부과학회지

BACKGROUND: Poroid neoplasms consist of classic poroma, hidroacanthoma simplex, dermal duct tumor, and poroid hidradenoma. Poroid neoplasms are not rare tumors in dermatology. However, studies of the clinicopathologic characteristics of poroid neoplasms in Korea are very limited. OBJECTIVE: To investigate the clinicopathologic characteristics of poroid neoplasms in Korea. METHODS: The clinicopathologic characteristics of forty three cases of poroid neoplasms were retrospectively analyzed. RESULTS: Poroid neoplasms were diagnosed mostly in the sixth decade, without sex predominance. The most common site was the lower extremities, followed by the head & neck, the trunk, the sole, the palm, and the upper extremities. All cases were observed as a solitary lesion. Papule or nodule shape, verrucous surface, and erythmatous color were most common characteristics of poroid neoplasms. The two cases showed sebaceous differentiation. Some cases showed melanin pigmentations in the lesions or perilesional basal layer. CONCLUSION: Our study will be a resourceful data of poroid neoplasms for dermatologists and pathologists.

Polypoid Basal Cell Carcinoma Mimicking Soft Fibroma / 대한피부과학회지

Basal cell carcinoma (BCC) is the most common malignant tumor of the skin and usually seen on hair-bearing skin that is frequently exposed to the sun, especially on the face. Polypoid BCC, which is thought to be a new variant, is distinguished from other histologic types by having a stalk and by restriction of the tumor aggregation to the pedunculated zone. We report a case of polypoid BCC in a 73-year old man who had a skin-colored pedunculated papule in the perianal area mimicking soft fibroma.

A Case of Celecoxib Induced Acute Generalized Exanthematous Pustulosis

Acute generalized exanthematous pustulosis (AGEP) is manifested by rapid development of many sterile, nonfollicular pustules on a background of edematous erythema. More than 90 percent of AGEP are induced by medication, mostly antibiotics. Drug patch test can be helpful in the diagnosis of AGEP. This paper reports the first case of celecoxib-induced AGEP confirmed by patch test in Korean literature.

Analysis of Dermatologic Consultations in Intensive Care Unit Patients / 대한피부과학회지

BACKGROUND: Due to the characteristics of the intensive care unit (ICU), with its focus on patient's vital functions, dermatological symptoms are frequently overlooked during admission. But, there are occasions when a dermatological opinion in the ICU can be of value. OBJECTIVE: The purposes of this study were to analyze the frequency and characteristics of dermatologic consultations in patients admitted to ICUs and also to compare the results to other reports regarding inpatient dermatologic consultation. METHODS: We analyzed the data of 437 ICU patients who were consulted at a Department of Dermatology between January 1, 2007 and December 31, 2010. The total number of male and female patients were 241 (55.1%) and 196 (44.9%) (M : F = 1.23 : 1). We retrospectively reviewed medical records and demographics, reason of dermatologic consultation and the diagnosis of the dermatoses. RESULTS: The percent of patients who were referred to the Department of Dermatology for consultation was 1.9%. The most frequent age group was the 7th decade of life and the highest incidence of seasonal distribution was summer. Patients admitted to the Department of Internal Medicine were the most frequently consulted group. The most common underlying disease was pulmonary disorders. The most common skin disorders were infectious diseases (28.8%), followed by eczema (15.8%) and drug eruption (11.4%). The main reasons for dermatologic consultations were dermatologic diseases or conditions (53.7%), skin lesions related to the treatment of underlying diseases (26.3%), skin lesions of systemic diseases (10.0%) and the dermatologic tests (6.1%). CONCLUSION: The characteristics of dermatologic consultation in the ICU may be quite different from those of inpatient dermatologic consultation. Collaboration between the intensive care physician and dermatologist can improve the quality of patient care in the ICU.

Acute Generalized Exanthematous Pustulosis Caused by Diltiazem

Acute generalized exanthematous pustulosis is clinically characterized by fever, pruritus and an acute pustular eruption. It can be described as having an abrupt onset and then spontaneous resolution occurs shortly after the start of symptoms, and there is usually only a single episode. Most cases have been triggered by the ingestion of drugs. Diltiazem hydrochloride is a calcium channel blocker that is commonly used for treating hypertension and angina. This drug was found to be the responsible agent in our current patient. There have been 9 such case reports in the English medical literature, yet this is the first such report in the Korean medical literature. We present the case of a 51-year-old male who experienced an acute generalized exanthematous pustulosis due to diltiazem hydrochloride and we review the relevant literature.

Gender Differences Associated with Pain Patterns and Psychological Variables in Chronic Musculoskeletal Pain Patients

OBJECTIVE: To investigate gender differences in pain patterns and psychological variables among patients with chronic musculoskeletal pain. METHOD: Thirty-five male and thirty-eight female patients who visited our outpatient clinic due to chronic musculoskeletal pain were evaluated using a questionnaire survey. Chronic musculoskeletal pain was defined as pain lasting longer than 6 months. Patients were evaluated with visual analogue scale (VAS), pain site, pain duration and frequency. Beck depression inventory, state-trait anxiety index, somatization scale of symptom checklist-revised, symptom interpretation questionnaire, and pain catastrophizing scale were checked for psychological variables. Correlations among each variable were evaluated statistically. RESULTS: Female patients with chronic musculoskeletal pain recorded higher scores on number of pain site, pain catastrophizing scale, rumination, magnification and catastrophic attribution than male patients (p<0.05). In female patients, VAS was correlated significantly with depression, static anxiety, somatization, catastrophizing thought. rumination, magnification, helpless, and catastrophic attribution. Pain frequency was correlated significantly with somatization, catastrophizing thought, rumination, and helpless. Number of pain site was correlated with somatization, catastrophizing thought, magnification, and helpless. The correlation between pain patterns and psychological variables was also observed in male patients, but statistically less significant than female patients. CONCLUSION: We found gender difference associated with pain patterns and psychological variables in chronic musculoskeletal pain patients. Consideration of psychological factors may be important for management in female patients with chronic musculoskeletal pain.

Comparison of the Effect of Three Types of Treatment on Plantar Fasciitis: Ultrasonographic Follow-up

OBJECTIVE: To compare effectiveness of corticosteroid injection, foot orthoses and oral anti-inflammatory medication for the management of the plantar fasciitis by sequential ultrasonographic follow-up. METHOD: Thirty-three patients with plantar fasciitis were assigned to one of 3 treatment groups. Twelve patients received steroid injection and ten were applied with custom-made foot orthoses and eleven received 4-week course of a non-steroidal anti-inflammatory medication. All patients of each group were instructed to perform self stretching exercise of the Achilles tendon and plantar fascia for the follow-up period. Ultrasonographic evaluation and clinical assessments were performed during 12 weeks; before treatment, every week during the first 8 weeks, and then every 2 weeks during the last 4 weeks. RESULTS: On ultrasonographic examination, fascial thickness decreased significantly in all three groups (p<0.05) but earlier and greater change was noticed in injection group (p<0.05). Hypoechoic lesions were observed less commonly after treatment in injection and orthoses groups (p<0.05). Pain was not significant different among three groups after two or three weeks of treatment. CONCLUSION: Corticosteroid injection showed earlier and greater effect on pain and ultrasonographic feature than other treatments. Although pain aspects of three groups were similar after 12 weeks of follow-up, improved ultrasonographic features were well preserved in injection and orthoses groups. Ultrasonographic feature that was mostly related to the symptom relief was the decrease in fascial thickness other than resolution of hypoechoic lesion.

Subungual Extraskeletal Chondroma / 대한피부과학회지

Extraskeletal chondroma is a relatively uncommon, benign soft tissue tumor that usually occurs adjacent to the periarticular tissues or tenosynovium, without any adhesion to the underlying bone. The most common site of occurrence is the hands, with more than 60% of all extraskeletal chondromas being located here. Histologically, it can resemble hyaline cartilage or chondrosarcoma of bone, which is more cellular. Whatever the histologic appearance is, the behavior is uniformly benign and it does not metastasize, therefore the recommended treatment is local excision. We report here on a case of subungual extraskeletal chondroma in a 22-year-old female who presented with a subungual nodule of the left big toe.

A Case of Hydroa Vacciniforme

Hydroa vacciniforme (HV) is a rare and chronic pediatric disorder that is characterized by photosensitivity and recurrent vesicles that heal with vacciniforme scarring. The pathogenesis of HV is unknown; no chromosome abnormality has been identified. HV patients have no abnormal laboratory results, so the diagnosis of HV is based on identifying the associated histological findings in a biopsy specimen and using repetitive ultraviolet phototesting to reproduce the characteristic vesicles on a patient's skin. Herein, we present a case of HV in a 7-year-old female who was diagnosed with HV according to histopathology and ultraviolet phototesting.

A Case of Pleomorphic Basal Cell Carcinoma with Alopecia Areata / 대한피부과학회지

Pleomorphic basal cell carcinoma (BCC) is a pathologic variant of BCC characterized by the presence of atypical appearing, mononuclear or multinucleated giant cells. The tumor usually presents as a nodule on the head or neck. We report a case of pleomorphic BCC with alopecia areata on the scalp in a 63-year-old woman. She had had a well circumscribed, black nodule on an alopecic patch for several months.