TRPV1 in Salivary Gland Epithelial Cells Is Not Involved in Salivary Secretion via Transcellular Pathway

Transient receptor potential vanilloid subtype 1 (TRPV1) was originally found in sensory neurons. Recently, it has been reported that TRPV1 is expressed in salivary gland epithelial cells (SGEC). However, the physiological role of TRPV1 in salivary secretion remains to be elucidated. We found that TRPV1 is expressed in mouse and human submandibular glands (SMG) and HSG cells, originated from human submandibular gland ducts at both mRNA and protein levels. However, capsaicin (CAP), TRPV1 agonist, had little effect on intracellular free calcium concentration ([Ca2+]i) in these cells, although carbachol consistently increased [Ca2+]i. Exposure of cells to high temperature (>43degrees C) or acidic bath solution (pH5.4) did not increase [Ca2+]i, either. We further examined the role of TRPV1 in salivary secretion using TRPV1 knock-out mice. There was no significant difference in the pilocarpine (PILO)-induced salivary flow rate between wild-type and TRPV1 knock-out mice. Saliva flow rate also showed insignificant change in the mice treated with PILO plus CAP compared with that in mice treated with PILO alone. Taken together, our results suggest that although TRPV1 is expressed in SGEC, it appears not to play any direct roles in saliva secretion via transcellular pathway.

Role of LPA and the Hippo pathway on apoptosis in salivary gland epithelial cells

Lysophosphatidic acid (LPA) is a bioactive lysophospholipid involved in numerous physiological responses. However, the expression of LPA receptors and the role of the Hippo signaling pathway in epithelial cells have remained elusive. In this experiment, we studied the functional expression of LPA receptors and the associated signaling pathway using reverse transcriptase-PCR, microspectrofluorimetry, western blotting and immunocytochemistry in salivary gland epithelial cells. We found that LPA receptors are functionally expressed and involved in activating the Hippo pathway mediated by YAP/TAZ through Lats/Mob1 and RhoA/ROCK. Upregulation of YAP/TAZ-dependent target genes, including CTGF, ANKRD1 and CYR61, has also been observed in LPA-treated cells. In addition, based on data suggesting that tumor necrosis factor (TNF)-alpha induces cell apoptosis, LPA upregulates TNF-induced caspase-3 and cleaved Poly(ADP-ribose)polymerase (PARP). However, small interfering RNA treatment to Yes-associated protein (YAP) or transcriptional co-activator with a PDZ-binding motif (TAZ) significantly decreased TNF-alpha- and LPA-induced apoptosis, suggesting that YAP and TAZ modulate the apoptotic pathway in salivary epithelial cells.

Onychomycosis Due to Nondermatophytic Molds

BACKGROUND: Although there have been many studies about onychomycosis due to nondermatophytic molds (NDM), few studies about etiologic agents including NDM in onychomycosis have been reported in Korea. Objective: This study investigated onychomycosis due to NDM in the Gyeongju area of Korea. OBJECTIVE: This study investigated onychomycosis due to NDM in the Gyeongju area of Korea. METHODS: In the 10-year period from 1999~2009, we reviewed 59 patients with onychomycosis due to NDM. The etiologic agents were identified by cultures on Sabouraud's Dextrose agar with and without cycloheximide. In some cases, internal transcribed spacer sequence analysis was done. NDM isolated considered pathogens when the presence of fungal elements was identified by direct microscopy observation and in follow-up cultures yielding the same fungi. RESULTS: Onychomycosis due to NDM comprised 2.3% of all onychomycosis. Of the 59 patients with onychomycosis due to NDM, 84.7% were toenail onychomycosis and 15.3% were fingernail onychomycosis. The incidence rate was highest in the fifth decade (27.1%). The ratio of male to female patients was 1:1.6. The frequency of associated diseases, in descending order, was hypertension, diabetes mellitus, and cerebral hematoma. Distal and lateral subungual onychomycosis (86.4%) was the most common clinical type of onychomycosis. Aspergillus spp. was the most frequently isolated etiologic agent of onychomycosis due to NDM (83.0%). Other causative agents were Scopulariopsis brevicaulis (10.2%), Acremonium spp. (3.4%), Fusarium solani (1.7%), and Chaetomium globosum (1.7%). CONCLUSION: Because of the increase in onychomycosis due to NDM, we suggest the need of a careful mycological examination in patients with onychomycosis.

Onychomycosis Caused by Scopulariopsis brevicaulis: Report of Two Cases

Onychomycosis is usually caused by dermatophytes, but some nondermatophytic molds and yeasts are also associated with invasion of nails. Scopulariopsis brevicaulis is a nondermatophytic mold found in soil as a saprophyte. We report two cases of onychomycosis caused by S. brevicaulis in a 48-year-old male and a 79-year-old female. The two patients presented with a typical distal and lateral subungual onychomycosis. Direct microscopic examination of the potassium hydroxide preparation revealed fungal elements. From toenail lesions of the patients, brown colonies with powdery surface, which are a characteristic of S. brevicaulis, were cultured on two Sabouraud's dextrose agar plates. Three cultures taken from nail plates within a 2-week interval yielded similar findings. Numerous branched conidiophores with chains of rough walled, lemon-shaped conidia were observed in slide culture by light microscopy and scanning electron microscopy. The nucleotide sequences of the internal transcribed spacer for the two clinical isolates were identical to that of S. brevicaulis strain WM 04.498. To date, a total of 13 cases of S. brevicaulis onychomycosis including the two present cases have been reported in Korea. Mean age of the patients was 46.1 years, with a higher prevalence in males (69.2%). Toenail involvement was observed in all cases including a case involving both fingernail and toenail. The most frequent clinical presentation was distal and lateral subungual onychomycosis in 12 cases, while one case was proximal subungual onychomycosis.

Chromoblastomycosis Caused by Fonsecaea pedrosoi

We report herein a case of chromoblastomycosis caused by Fonsecaea (F.) pedrosoi in a 39-year-old male, who showed multiple, asymptomatic, scaly erythematous plaques on the left shin for 12 months. Histopathologically, chronic granulomatous inflammation and either sclerotic or muriform cells were observed. The fungal culture produced typical black colonies of F. pedrosoi. The DNA sequence of the internal transcribed spacer (ITS) region of the clinical sample was 100% match to that of F. pedrosoi IFM 47061 (GenBank accession number AB240943). The patient was treated with 200 mg of itraconazole daily, for 3 months. Skin lesions were improved. In Korea, only 9 cases of chromoblastomycosis, including this case, have been reported until now. The etiologic agent was F. pedrosoi in the majority of cases (6/9;67%). The incidence of chromoblastomycosis was slightly higher in female, and the upper limbs were more affected than the lower limbs in patients.

Epidemiologic Survey of Onychomycosis in Koreans: Multicenter Study / 대한의진균학회지

BACKGROUND: Although there have been many studies about onychomycosis, no study about Koreans in onychomycosis has been reported in Korea. OBJECTIVE: The purpose of this study was to investigate the onychomycosis in Koreans. METHODS: From April, 2009, to March, 2010, 1,893 patients with onychomycosis who visited the department of dermatology at 10 university hospitals were evaluated. RESULTS: Of 1,893 patients with onychomycosis, 93.8% were toenail onychomycosis, 2.2% fingernail onychomycosis, and 4.0% onychomycosis in both toenails and fingernails. Among the age groups, the incidence rate was highest over the sixties (35.6%). The ratio of male to female patients was 1.3:1. Distal and lateral subungual onychomycosis (80.3%) was the most common clinical type of onychomycosis. Combination therapy of oral terbinafine or itraconazole and topical amorolfine nail lacquer was most common in the treatment of onychomycosis. The most common reasons for combination therapy in onychomycosis were higher cure rate due to synergistic activity (40.2%), followed by shortened treatment duration (12.8%), patient compliance (12.3%), and prevention of recurrence and reinfection (1.7%). CONCLUSION: Because of the increase in onychomycosis, we suggest the need of standard treatment guidelines for Korean patients with onychomycosis.

Eczema-Like Tinea Incognito Occurring Leg / 대한의진균학회지

Tinea incognito is the dermatophytosis of atypical clinical presentation that induced by topical and systemic corticosteroid treatment or new class of topical non-steroidal agent such as tacrolimus or pimecrolimus. We report a case of eczema-like tinea incognito in a 15-year-old girl. The lesions were manifested by pruritic to tender, scaly well-demarcated erythematous macules and patches with pustules on the lateral side of right shin. She had been treated with topical corticosteroid and pimecrolimus for 6 months. Direct microscopic examination of the lesion was positive for hyphae and fungal culture revealed colonies of Trichophyton(T.) rubrum. Histopathologic examination of the skin lesion showed mild perivascular inflammation with presence of fungal hyphae in the horney layer of the epidermis. The patient was treated with 250 mg of terbinafine daily for 1 month and topical lanoconazole application. Skin lesions improved one month after the treatment, and no recurrence was observed.

Multiple Merkel Cell Carcinoma in a Vietnam Veteran Exposed to Agent Orange / 대한피부과학회지

Merkel cell carcinoma is a rare aggressive primary skin cancer which mostly occurs in the elderly on sun-exposed skin. It usually presents as a solitary dome-shaped red or purple nodule on the head, neck and extremities. The mortality rate is higher than the rate for malignant melanoma because its local recurrence is common. Agent Orange, an herbicide widely used as a defoliant in the Vietnam War, contains dioxin contaminants and can cause several dermatoses and skin cancers. We report a case of multiple Merkel cell carcinoma in a 65-year-old male with lesions on the head and neck, who had been exposed to Agent Orange during Vietnam War.

A Case of Kerion Celsi in an Adult Caused by Trichophyton mentagrophytes Probably Transmitted from Rabbit / 대한의진균학회지

Kerion celsi is a severe inflammatory type of tinea capitis that presents as an inflammatory, boggy plaque studded with broken hairs. It usually occurrs in children between the age of 4 and 14 years which is caused by zoophilic pathogens such as Microsporum(M.) canis, Trichophyton(T.) mentagrophytes, and T. verrucosum. Recently various mammals have become a pet in Korea and there has been increase in reports of dermatophytosis transmitted from these pets sporadically. We report a case of kerion celsi caused by T. mentagrophytes probably transmitted from rabbit in a 34-year-old adult male patient. The patient had localized, tender to mild pruritic, erythematous plaque with pustular nodules and irregular hair loss on the right temporal scalp for 2 months. Culture from a scalp lesion of patient on Sabouraud's dextrose agar showed typical T. mentagrophytes. He was treated with 250 mg of terbinafine daily for 12 weeks and short term therapy of low dose of prednisolone. He was cured without recurrence.

A Case of Rosacea-like Tinea Faciei Caused by Trichophyton rubrum / 대한의진균학회지

We report a case of rosacea-like tinea faciei in a 62-year-old female. The lesions were manifested by 2.0x2.0 cm and 2.0x2.0 cm-sized, two, pruritic, well-demarcated, erythematous macules on the nose and left ala nasi. Histopathologic examination of the skin lesion showed chronic dermal inflammation with presence of fungal hyphae in the honey layer of the epidermis. Fungal culture of the biopsy specimen grew out typical white cottony colonies of Trichophyton rubrum. The patient was treated with 250 mg of terbinafine daily for 1 month and topical lanoconazole application. Skin lesions improved one month after the treatment, and recurrence has not been observed.

A Case of Psoriasiform Tinea Corporis Caused by Microsporum canis / 대한의진균학회지

Tinea corporis is dermatophytosis of trunk and extremities except terminal hair present region. We report a case of psoriasiform tinea corporis in a 11-year-old girl. The lesions were showed multiple, pruritic, thick scaly erythematous macules and patches on the left forearm and trunk. She had been treated with topical and oral corticosteroid for 5 months. Direct microscopic examination and fungal culture were positive for hyphae and colonies of Microsporum canis. Histopathologic examination of the skin lesion revealed parakeratosis, psoriasiform epidermal hyperplasia and perivascular inflammatory infiltration in upper dermis with presence of fungal hyphae in stratum corneum. She was treated with 250mg of terbinafine daily and topical lanoconazole for 1 month. Skin lesions cured without recurrence.

Cutaneous Infection due to Mycobacterium fortuitum Originated from Soil / 대한피부과학회지

Mycobacterium (M.) fortuitum is a rapidly growing mycobacterium. It is classified as Runyon's group IV with M. abcessus and M. chelonae that are mostly found in water and soil. M. fortuitum infection usually occurs after trauma, surgery or procedures such as acupuncture that cause cutaneous or soft tissue manifestations. We report a case of cutaneous infection due to M. fortuitum in a 72-year-old woman with erythematous deep-seated nodules on her left hand. She inflicted a minor injury to her left hand in a farm. Culture from skin biopsy specimens on 3% Ogawa medium yielded bacterial colonies after 5 days. The microorganism was subsequently identified as M. fortuitum by PCR-restriction fragment length polymorphism analysis. The skin lesions were improved by antibiotic therapy with clarithromycin for 6 months.

Annular Syphilid Mimicking Tinea Corporis / 대한피부과학회지

Syphilid has been called the "great imitator" of skin disease, and it can have protean clinical manifestations and it may present with unusual lesions. Annular syphilid, which can mimic sarcoid, granuloma annulare, Sweet syndrome or tinea corporis, is a rare variant of syphilid. We report here on a case of annular syphilid that mimicked tinea corporis in a 29-year-old female who showed a three month history of multiple, pruritic, well-demarcated annular scaly erythematous patches with central clearing and an elevated border on the trunk and both upper extremities. Direct mycological examination and culture did not result in finding any fungal elements, and annular syphilid was confirmed according to the histopathologic and serologic findings. She and her boyfriend were treated with benzathine penicillin G, and the skin lesions disappeared completely.

A Case of Linear Porokeratosis on the Trunk / 대한피부과학회지

Porokeratosis is a genodermatosis that is characterized by abnormal epidermal keratinization with the histologic finding of a cornoid lamella. Linear porokeratosis is an uncommon variant that presents a characteristic linear nevoid distribution along the Blaschko's lines and linear porokeratosis has the highest potential for malignant degeneration of all the porokeratoses. Many treatment modalities have been used, but the treatment outcomes are variable and the treatments are poorly standardized. We report here on a case of linear porokeratosis in a 48-year-old female who showed localized, linear, brownish macules with a well-demarcated hyperkeratotic border on the left lower abdomen and back.

Seborrheic Dermatitis-like Norwegian Scabies on a Patient Living in an Eldercare Hospital / 대한피부과학회지

Norwegian scabies is a crusted rash that's caused by a massive infestation with the mite Sarcoptes scabiei. The characteristic skin lesions of this form are gross scaling and hyperkeratotic plaques, and especially on the hands, feet, face, nails and scalp with varying degrees of pruritus. It is often seen in the individuals with human immunodeficiency virus infection, the elderly, immunocompromised patients and institutionalized persons. We report here on a case of Norwegian scabies on an 86-year-old patient who was living in an eldercare hospital, and the patient presented with localized, pruritic, erythematous patches with thick yelolwish crusts on the scalp.

P2X7 Receptor-mediated Membrane Blebbing in Salivary Epithelial Cells

High concentrations of ATP induce membrane blebbing. However, the underlying mechanism involved in epithelial cells remains unclear. In this study, we investigated the role of the P2X7 receptor (P2X7R) in membrane blebbing using Par C5 cells. We stimulated the cells with 5 mM of ATP for 1~2 hrs and found the characteristics of membrane blebbing, a hallmark of apoptotic cell death. In addition, 500 micrometer Bz-ATP, a specific P2X7R agonist, induced membrane blebbing. However, 300 micrometer of Ox-ATP, a P2X7R antagonist, inhibited ATP-induced membrane blebbing, suggesting that ATP-induced membrane blebbing is mediated by P2X7R. We found that ATP-induced membrane blebbing was mediated by ROCK I activation and MLC phosphorylation, but not by caspase-3. Five mM of ATP evoked a biphasic [Ca2+]i response; a transient [Ca2+]i peak and sustained [Ca2+]i increase secondary to ATP-stimulated Ca2+ influx. These results suggest that P2X7R plays a role in membrane blebbing of the salivary gland epithelial cells.

Tinea Capitis due to Trichophyton verrucosum in a 6-month-old Infant / 대한의진균학회지

Tinea capitis is the most frequent manifestation of dermatophyte infection in children, but is rare in infants less than 1 year of age. Furthermore, Trichophyton(T.) verrucosum as a causative organisum of tinea capitis in infants is documented very rarely. We report a 6-month-old girl with tinea capitis caused by T. verrucosum. The lesion was manifested by round, 2.0x2.0 sized, fine scaly, well-difined erythematous patch on the occiput. Culture from the skin lesion of patient on Sabouraud's dextrose agar showed typical colony of T. verrucosum. The patient was treated with topical lanoconazole application for 1 month.

Ca2 -activated K Currents of Pancreatic Duct Cells in Guinea-pig

There are numerous studies on transepithelial transports in duct cells including Cl and/or HCO3. However, studies on transepithelial K transport of normal duct cells in exocrine glands are scarce. In the present study, we examined the characteristics of K currents in single duct cells isolated from guinea pig pancreas, using a whole-cell patch clamp technique. Both Cl and K conductance were found with KCl rich pipette solutions. When the bath solution was changed to low Cl, reversal potentials shifted to the negative side, 75 4 mV, suggesting that this current is dominantly selective to K. We then characterized this outward rectifying K current and examined its Ca2 dependency. The K currents were activated by intracellular Ca2. 100 nM or 500 nM Ca2 in pipette significantly (P< 0.05) increased outward currents (currents were normalized, 76.8 7.9 pA, n=4 or 107.9 35.5 pA, n=6) at 100 mV membrane potential, compared to those with 0 nM Ca2 in pipette (27.8 3.7 pA, n=6). We next examined whether this K current, recorded with 100 nM Ca2 in pipette, was inhibited by various inhibitors, including Ba2, TEA and iberiotoxin. The currents were inhibited by 40.4 % (n=3), 87.0 % (n=5) and 82.5 % (n=9) by 1 mM Ba2, 5 mM TEA and 100 nM iberiotoxin, respectively. Particularly, an almost complete inhibition of the current by 100 nM iberiotoxin further confirmed that this current was activated by intracellular Ca2. The K current may play a role in secretory process, since recycling of K is critical for the initiation and sustaining of Cl or HCO3 secretion in these cells.