Thrombin Induced Apoptosis through Calcium-Mediated Activation of Cytosolic Phospholipase A2 in Intestinal Myofibroblasts

Thrombin is a serine protease that participates in a variety of biological signaling through protease-activated receptors. Intestinal myofibroblasts play central roles in maintaining intestinal homeostasis. In this study, we found that thrombin-induced apoptosis is mediated by the calcium-mediated activation of cytosolic phospholipase A2 in the CCD-18Co cell. Thrombin reduced cell viability by inducing apoptosis and proteinase-activated receptor-1 antagonist attenuated thrombin-induced cell death. Endogenous ceramide did not affect the cell viability itself, but a ceramide-mediated pathway was involved in thrombin-induced cell death. Thrombin increased intracellular calcium levels and cytosolic phospholipase A2 activity. The ceramide synthase inhibitor Fumonisin B 1, intracellular calcium chelator BAPTA-AM, and cytosolic phospholipase A2 inhibitor AACOCF 3 inhibited thrombin-induced cell death. Thrombin stimulated arachidonic acid release and reactive oxygen species generation, which was blocked by AACOCF 3, BAPTA-AM, and the antioxidant reagent Trolox. Taken together, thrombin triggered apoptosis through calcium-mediated activation of cytosolic phospholipase A2 in intestinal myofibroblasts.

Development of a Label-Free LC-MS/MS-Based Glucosylceramide Synthase Assay and Its Application to Inhibitors Screening for Ceramide-Related Diseases

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 588.6 → 264.4 for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625–160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.

Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells

Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that is widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, PQ has been reported to be an immunotoxic agrochemical compound. PQ was shown to decrease the number of macrophages in rats and suppress monocyte phagocytic activity in mice. However, the effect of PQ on macrophage cell viability remains unclear. In this study, we evaluated the cytotoxic effect of PQ on the mouse macrophage cell line, RAW264.7 and its possible mechanism of action. RAW264.7 cells were treated with PQ (0, 75, and 150 muM), and cellular apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS levels were determined. Morphological changes to the cell nucleus and cellular apoptosis were also evaluated by DAPI and Annexin V staining, respectively. In this study, PQ induced apoptotic cell death by dose-dependently decreasing MMP. Additionally, PQ increased the cleaved form of caspase-3, an apoptotic marker. In conclusion, PQ induces apoptosis in RAW264.7 cells through a ROS-mediated mitochondrial pathway. Thus, our study improves our knowledge of PQ-induced toxicity, and may give us a greater understanding of how PQ affects the immune system.

Basal Cell Carcinoma of the Umbilicus / 대한피부과학회지

Basal cell carcinoma (BCC) is the most common skin cancer in humans. It usually develops on sun-exposed areas of the head and neck but can occur anywhere on the body. The various clinical features include nodules, ulcers, bleeding, crust, or scale. Thus, it is important to distinguish BCC from other diseases with similar clinical features. The umbilicus is one of the sun-protected sites where BCC rarely develops. Herein, we describe 71-year-old woman with umbilical BCC initially misdiagnosed as pyoderma.

Multiple Epidermal Cysts in Lowe Syndrome

Lowe syndrome is a rare genetic disease that appears to cause various clinical symptoms involving the eye, nervous system, and kidney. While a mutation of the OCRL1 gene is known to be responsible for this syndrome, the exact pathophysiology remains unclear. Various multi-organ symptoms are characteristic of Lowe syndrome, but skin lesions have rarely been described. Recently, mechanisms for the association of Lowe syndrome and skin lesions have been proposed. We report this case of Lowe syndrome involving multiple epidermal cysts on the scalp in a 6-year-old male child.

Two Cases of Trichophyton rubrum Syndrome / 대한의진균학회지

Trychophyton (T.) rubrum is the most prevalent pathogen among causative fungi of dermatophytosis. Primary infection of T. rubrum can be spread by autoinoculation or other reason and some suggests this generalized infection can be a syndrome. We report two cases of T. rubrum syndrome. The first patient, a 43-year-old male, had a tinea pedis with tinea unguium, tinea corporis, tinea cruris, and tinea manus. The second patient, a 73-year-old female, had a tinea pedis with tinea unguium, tinea manus, tinea corporis, tinea capitis, and tinea faciale. Causative pathogens were T. rubrum.

Myxoid Neurofibroma in the Right Inguinal Area / 대한피부과학회지

Myxoid neurofibroma is a histological variant of neurofibroma and represent a conventional neurofibroma with extensive deposition of stromal mucin. Myxoid neurofibroma may present as a sporadic lesion or in the context of neurofibromatosis I. The most common locations of the myxoid neurofibroma are the face, shoulders, arms, periungual area and in the feet. To the best of our knowledge, location in an inguinal area has been rarely reported. We report a case of a 37-year-old man with a solitary myxoid neurofibroma in the right inguinal area.

A Case of the Giant and Hyperkeratotic Variant of Porokeratosis / 대한피부과학회지

We report here on a case of the giant and hyperkeratotic variant of porokeratosis. A 51-year-old man presented with a 30x20 cm sized extremely hyperkeratotic brownish verrucous plaque on his buttock. Histologic examination showed an increased number and size of the cornoid lamella, which displayed packed parakeratotic cells and the partial loss of the underlying granular layer. We diagnosed the patient with the giant and hyperkeratotic variant of porokeratosis on the basis of the clinical features and the characteristic histologic findings. Giant porokeratosis is a rare clinical condition among the several subtypes of porokeratosis, and the hyperkeratotic variant is an extremely rare clinical condition.

Analysis of Dermatologic Consultations in Rheumatologic Inpatients / 대한피부과학회지

BACKGROUND: Many different dermatologic manifestations can accompany a variety of systemic diseases such as rheumatic disorders. The number of patients who have skin lesions related to systemic diseases is steadily increasing. In such cases, dermatologic consultation can be important to diagnosis and treatment. OBJECTIVE: The purpose of this study was to analyze patterns of skin manifestations in rheumatic diseases. METHODS: We did an analysis of data for 192 inpatients who were referred by the department of rheumatology and consulted by the department of dermatology between May 1, 2005 and April 30, 2009. We retrospectively reviewed their medical records and noted age, sex, reasons for dermatologic consultation, diagnosis of the dermatoses and changed diagnosis after the consultation. RESULTS: The percent of patients who were referred by the department of rheumatology and consulted by the department of dermatology was 15.5% (192 consulted inpatients/1,242 rheumatologic inpatients). The most frequent age group was those in their 5th decade of life (23.0%) and the male to female ratio was 1:2.15. Consultations for dermatologic manifestations unrelated to systemic or rheumatic diseases were the most common reason for consultation (62.0%). Dermatoses related to systemic or rheumatic diseases were the 2nd most common reason of consultation (34.9%). Infectious diseases were the most common dermatoses (46 cases). There were 13 cases where there was a diagnosis of undetermined dermatoses and changed diagnosis after dermatologic consultation. CONCLUSION: Analysis of consultations from inpatients referred by the department of rheumatology to the department of dermatology indicates that there is a substantial number of patients that have skin manifestations of their rheumatic diseases.

Two Cases of Albright's Hereditary Osteodystrophy Occurring in Pseudopseudohypoparathyroidism / 대한피부과학회지

A 36 year-old man and his 6 month-old daughter presented with multiple, slightly depressed, skin-colored, hard nodules and plaques on the abdomen, back, and both extremities. They also showed abnormal physical appearance, including short stature and neck, round face, and short digits, which suggested Albright's hereditary osteodystrophy (AHO). Histopathologically, various sized bony spicules were present in the dermis. The laboratory results showed normal serum calcium, phosphorus and parathyroid hormone levels. On the basis of clinical, laboratory and histologic findings, we diagnosed these cases as Albright's hereditary osteodystrophy with cutaneous ossification occurring in pseudopseudohypoparathyroidism.

Two Cases of Albright's Hereditary Osteodystrophy Occurring in Pseudopseudohypoparathyroidism / 대한피부과학회지

A 36 year-old man and his 6 month-old daughter presented with multiple, slightly depressed, skin-colored, hard nodules and plaques on the abdomen, back, and both extremities. They also showed abnormal physical appearance, including short stature and neck, round face, and short digits, which suggested Albright's hereditary osteodystrophy (AHO). Histopathologically, various sized bony spicules were present in the dermis. The laboratory results showed normal serum calcium, phosphorus and parathyroid hormone levels. On the basis of clinical, laboratory and histologic findings, we diagnosed these cases as Albright's hereditary osteodystrophy with cutaneous ossification occurring in pseudopseudohypoparathyroidism.

A Case of Onychomycosis Caused by Fusarium verticillioides / 대한의진균학회지

Onychomycosis is caused by dermatophytes usually, but some species of non-dermatophytic molds and yeasts are also associated with invasion of nails. Fusarium (F.) verticillioides is a non-dermatophytic mold, which are common soil saprophytes. Onychomycosis due to Fusarium species almost always involves great toe nails and occurs infection easily in the presence of trauma, onychodystrophy and prior onychomycosis. We report a first case of onychomycosis caused by Fusarium verticillioides in a 48-year-old man. He presented with proximal white superficial onychomycosis for 3 months. Fungal culture showed whitish cottony colonies and microscopic examination of colonies showed microconidia in a chain from monophialide. We diagnosed onychomycosis caused by Fusarium verticillioides and treated by itraconazole 200 mg daily and 5% amorolfine nail lacquer for 3 months.

A Case of Unilateral Angiokeratoma of Fordyce with Varicocele / 대한피부과학회지

Angiokeratoma of Fordyce is a relatively common type of angiokeratoma that is characterized by small, multiple, purplish to dark red papules on the scrotum. Pathogenesis is unknown, but it has been suggested that increased venous pressure caused by varicocele, hernia or tumor of the epididymis can induce angiokeratoma of Fordyce. We report a case of unilateral angiokeratoma of Fordyce with varicocele in a 30 year-old man. He presented with approximatly 2 mm sized, purplish to dark red, and multiple hyperkeratotic papules on the left scrotum. The lesions were strictly limited to the left side of the scrotum and associated with varicocele on the same side. Histopathologically, hyperkeratosis, acanthosis with elongation of rete ridges and dilated papillary vessels are presented. Based on this clinical and histologic finding, we diagnosed this case as unilateral angiokeratoma of Fordyce with varicocele. The patient was treated with varicocelectomy for left varicocele and then cryotherapy for skin lesions.

A Case of Lymphocutaneous Sporotrichosis on the Infantile Face / 대한의진균학회지

Sporotrichosis is a chronic cutaneous fungal infection caused by Sporothrix (S.) schenckii. It is subdivided into three groups by clinical manifestation: lymphocutaneous, fixed cutaneous, disseminated sporotrichosis. Lymphocutaneous sporotrichosis is most common type and involves upper extremities usually. The incidence of lymphocutaneous sporotrichosis on the face is very low, especially in children. We report a case of lymphocutaneous sporotrichosis on face in a 10-month-old girl. The lesions represented linear three small erythematous papules on the right cheek. The fungal culture on Sabouraud's dextrose agar showed dark brown to black colored wrinkled colonies. The microscopic examination showed septated, branched mycelia and clustered conidia in slide culture of S. schenckii. The patient was treated with oral administration of potassium iodide and the lesions were cured completely.

A Case of Pthiriasis Occurring on the Scalp of an Adult / 대한피부과학회지

Pthiriasis is a sexually transmitted disease, and in most cases this is caused by Pthirus pubis (pubic or crab lice) that mainly infest the pubic hair of adults. Eyebrows, eyelashes and axillary hair are also relatively common sites of infestation, but the scalp is an uncommon site of manifestation, and especially in adults. We report here on a case of pthiriasis that was confined to the scalp, without involving any other parts of the body of a 55-year-old woman.

A Case of Pthiriasis Occurring on the Scalp of an Adult / 대한피부과학회지

Pthiriasis is a sexually transmitted disease, and in most cases this is caused by Pthirus pubis (pubic or crab lice) that mainly infest the pubic hair of adults. Eyebrows, eyelashes and axillary hair are also relatively common sites of infestation, but the scalp is an uncommon site of manifestation, and especially in adults. We report here on a case of pthiriasis that was confined to the scalp, without involving any other parts of the body of a 55-year-old woman.

A Case of Steatocystoma Simplex Involving the Scalp

Steatocystoma is a benign adnexal tumor originating from the pilosebaceous duct junction which can be classified into two groups (steatocystoma simplex and steatocystoma multiplex). Steatocystoma simplex, which presents as a solitary lesion, is very rare. Steatocystoma simplex occurs most commonly on the face and the case reported herein involving the scalp is extremely rare. A 49-year-old man presented for evaluation and treatment of a solitary papule on the right parietal scalp which had persisted for a period of 1 year. The histopathologic examination revealed a thin-walled cyst consisting of stratified squamous epithelium with hyaline cuticle that lacked a stratum granulosum. Based on clinical and histologic findings, we diagnosed this case as steatocystoma simplex of the scalp and report this rare case.

A Clinical Study of Colon Diseases of Old Age Based on Colonoscopic Finding

BACKGROUND: Recently, geriatric diseases become the matter of concern, and the neoplastic lesion of colon including polyp and cancer by the western-style diet is increasing. The aims of this study were to assess the relations between colon diseases, clinical manifestations and features of colonoscopic finding in elderly. METHODS: We retrospectively evaluated records of 764 patients underwent colonoscopy. Colonoscopic finding, each colon diseases and lower gastrointestinal symptoms were analyzed to compare between two groups, which are 416 elders aged over 65 and control of 348 adults aged from 25 to 65. RESULTS: Both two groups underwent colonoscopy showed lower abdominal pain is the most symptom of lower gastrointestinal symptoms. But, anaemia and bowel habit change were significantly high frequency in the elderly group while diarrhea appeared in the control group(p<0.05). Colon polyp and cancer were significantly increased frequency in the elderly group(p<0.05). Symptoms such as diarrhea and hematochezia were significantly high in case of colon polyp of elderly group(p<0.05). But in case of colon cancer, lower abdominal pain had significantly high in the control group compared with the elderly group who had various lower gastrointestinal symptoms such as constipation, diarrhea, hematochezia, bowel habit change(p<0.05). CONCLUSIONS: As people getting older, the incidence of colon polys and cancer is higher, and non-specific, various clinical manifestations are seen. Therefore, we think that seniors who have change in bowel habit, abdominal pain, hematochezia or constipation need colonoscopy increasingly and should pay attention to find neoplastic lesions.

Therapeutic Effects of Sclerotherapy of Venous Lake on the Lip / 대한피부과학회지

BACKGROUND: Although venous lake is asymptomatic, treatment is usually performed for cosmetic purposes or to prevent bleeding after trauma. The treatment is diverse and includes surgical excision, compression and cryotherapy. Above all, sclerotherapy is a useful and effective procedure for the treatment of venous lake on the lip. OBJECTIVE: This study was undertaken to assess the effectiveness and complications of the sclerotherapy of venous lake on the lip. METHODS: Fifteen lesions from eleven patients with venous lake on the lip were treated with sclerotherapy using sodium tetradecyl sulfate, detergent sclerosant. According to the size of lesions, the volume of infused solution was varied and the effectiveness of treatment was evaluated after four weeks. RESULTS: After a single treatment, fourteen of the fifteen lesions(93.3%) were cleared completely. The remaining lesion was treated one additional time. There were no reported complications during treatment. CONCLUSION: Sclerotherapy is highly effective and safe for the treatment of venous lake on the lip and may be a promising treatment option.

Clinical Analysis of Upper Gastrointestinal Diseases in Elderly Patients Underwent Esophagogastroduodenoscopy

Background: Recently the elderly people have increased in Korea. So, the interest of upper gastrointestinal diseases have increased. Our aim was to determine clinical characteristics of upper gastrointestinal diseases in the elderly patients underwent esophagogastroduodenoscopy. Methods: We investigated clinical characteristics of 1190 elderly patients aged 65 years or older and 952 controls aged 64 years or younger who underwent esophagogastrodu odenoscopy in Seonam University Hospital from Jan. 2000 to Dec. 2004. retrospecti vely. Only two main symptoms were included among symptoms of two or over. The endoscopic findings were in the same manner. Results: The average age were 73.9 (+/-7.25)-year-old in the elderly, and 47.2 (+/-11.32)-year-old in controls. The most common symptom was dyspepsia in the elderly and in controls. The most common endoscopic findings showed chronic atrophic gastritis in the elderly, and chronic erythematous & erosive gastritis in controls. 64% was positive in 424 cases performed rapid urease test in the elderly and 63% was positive in controls. The most common associated diseases was hypertension in both group. The history of Non-steroidal anti-inflammatory drugs and aspirins were 21% in the elderly, and 15% in controls. Conclusion: We found that dyspepsia was the most common symptom in the elderly and controls underwent esophagogastroduodenoscopy. The most common upper intestinal disease was chronic atrophic gastritis in the elderly. We recommend esophagogastroduodenoscopy for the elderly patients in regular interval because they may have vague and atypical symptoms or asymptom.