Evaluation of skin phototoxicity of transdermally administered pharmaceuticals in Sprague-Dawley rats / 한국실험동물학회지

Some drugs cause phototoxicity in humans when exposed to light, thus there is a need for an in vivo phototoxicity test to evaluate them. However, an in vivo phototoxicity test method to evaluate this has not been established. This study aimed to establish an in vivo phototoxicity test method for transdermally administered drugs. For this, we evaluated the phototoxicity using Sprague-Dawley (SD) rats for transdermal administered drugs and we studied the appropriate UVA dose using 8-methoxypsalen, which is a well-known phototoxic drug. We found that a UVA dose of 15 J/cm2 was dose and time dependent response compared to other UVA doses. We performed the Minimum Erythema Dose (MED) test because UVB can cause skin irritation by itself and selected 0.01 J/cm2 as an appropriate dose of UVB. Using the selected UVA and UVB doses, we performed a phototoxicity study of 6 pharmaceutical drugs, which included phototoxic and non-phototoxic drugs. As a result of the phototoxicity test, 100% accuracy was obtained when compared with previous studies. In addition, we performed histopathology to confirm the new findings. We found that histopathology can be used as an additional indicator of phototoxicity test for transdermally administered drugs.

Evaluation of skin phototoxicity of transdermally administered pharmaceuticals in Sprague-Dawley rats / 한국실험동물학회지

Some drugs cause phototoxicity in humans when exposed to light, thus there is a need for an in vivo phototoxicity test to evaluate them. However, an in vivo phototoxicity test method to evaluate this has not been established. This study aimed to establish an in vivo phototoxicity test method for transdermally administered drugs. For this, we evaluated the phototoxicity using Sprague-Dawley (SD) rats for transdermal administered drugs and we studied the appropriate UVA dose using 8-methoxypsalen, which is a well-known phototoxic drug. We found that a UVA dose of 15 J/cm2 was dose and time dependent response compared to other UVA doses. We performed the Minimum Erythema Dose (MED) test because UVB can cause skin irritation by itself and selected 0.01 J/cm2 as an appropriate dose of UVB. Using the selected UVA and UVB doses, we performed a phototoxicity study of 6 pharmaceutical drugs, which included phototoxic and non-phototoxic drugs. As a result of the phototoxicity test, 100% accuracy was obtained when compared with previous studies. In addition, we performed histopathology to confirm the new findings. We found that histopathology can be used as an additional indicator of phototoxicity test for transdermally administered drugs.

Surgical Results of Limb Lengthening at the Femur, Tibia, and Humerus in Patients with Achondroplasia

BACKGROUND: Results of limb lengthening in patients with achondroplasia were previously reported in many studies. However, the reports of comparison among the three long bones (femur, tibia, and humerus) are rare, especially for the results of crossed lengthening (lengthening of one femur and contralateral tibia followed by that of the opposite side) for the lower limbs. The purpose of this study was to report the surgical results of a series of limb lengthening in achondroplastic or hypochondroplasia patients at our institution. METHODS: Fifteen patients (14 with achondroplasia and 1 with hypochondroplasia) underwent lower limb lengthening of the femur (n = 32) and tibia (n = 28), and 12 of them underwent crossed lengthening. Humeral lengthening was performed in 14 patients (n = 28). The mean age at the first operation was 11.7 years, and the mean follow-up duration was 66.7 months. The healing index, consolidation period index (duration of consolidation period/gained length), and other radiographic indices were analyzed. Limb length discrepancy and hip-knee-ankle alignment in lower limbs, and the occurrence of difficulties were assessed. RESULTS: The average gain in length for the femur, tibia, and humerus was 8.3 cm, 8.5 cm, and 7.4 cm, respectively. The mean healing index was 29.6 days/cm for the femur, 29.0 days/cm for the tibia, and 27.2 days/cm for the humerus. The mean consolidation period index was 14.7 days/cm for the humerus, which was significantly lower than that in the lower limb (17.3 days/cm for the femur and 17.8 days/cm for the tibia). Of the 12 who underwent crossed lengthening, five showed limb length discrepancy ≥ 1.0 cm. Among their 24 lower limbs, three showed valgus alignment ≥ 5° and one showed varus alignment ≥ 5°. Thirty-two pin site infections and three fractures were conservatively managed. Three femoral fractures, eight equinus deformities, and four cases with premature consolidation of the fibula were surgically treated. Obstacle and true complication related to humeral lengthening were not observed. CONCLUSIONS: Humeral lengthening was relatively effective and safe. Careful attention will be needed to avoid the occurrence of limb length discrepancy or malalignment in crossed lengthening.

Characterization of a Biflaviolin Synthase CYP158A3 from Streptomyces avermitilis and Its Role in the Biosynthesis of Secondary Metabolites

Streptomyces avermitilis produces clinically useful drugs such as avermectins and oligomycins. Its genome contains approximately 33 cytochrome P450 genes and they seem to play important roles in the biosynthesis of many secondary metabolites. The SAV_7130 gene from S. avermitilis encodes CYP158A3. The amino acid sequence of this enzyme has high similarity with that of CYP158A2, a biflaviolin synthase from S. coelicolor A3(2). Recombinant S. avermitilis CYP158A3 was heterologously expressed and purified. It exhibited the typical P450 Soret peak at 447 nm in the reduced CO-bound form. Type I binding spectral changes were observed when CYP158A3 was titrated with myristic acid; however, no oxidative product was formed. An analog of flaviolin, 2-hydroxynaphthoquinone (2-OH NQ) displayed similar type I binding upon titration with purified CYP158A3. It underwent an enzymatic reaction forming dimerized product. A homology model of CYP158A3 was superimposed with the structure of CYP158A2, and the majority of structural elements aligned. These results suggest that CYP158A3 might be an orthologue of biflaviolin synthase, catalyzing C-C coupling reactions during pigment biosynthesis in S. avermitilis.

New method for an evaluation of the esthetical improvements resulting from a mandibular angle reduction

OBJECTIVES: This paper proposes Han's ratio as an objective and quantitative comparative result obtained from pre and postoperative data in patients with a mandibular angle reduction. MATERIALS AND METHODS: Thirty patients, 12 men and 18 women, who visited the Department of Oral and Maxillofacial Surgery with the chief complaints of skeletal mandibular prognathism and prominent mandibular angle were selected. The subjects were classified into 3 groups according to the types of surgical procedures involved. Group A consisted of patients who underwent mandibular angle resection and mandibular setback. Group B was comprised of patients with mandibular angle resection, mandibular setback and genioplasty. Group C consisted of patients with mandibular angle resection, mandibular setback, Le Fort I osteotomy, and genioplasty. The landmarks placed in pre and postoperative frontal photographs were used to obtain the Han's ratio in each group. The Han's ratios were compared pre- and postoperation and according to the surgical techniques applied. RESULTS: Of the 3 groups who had undergone a mandibular angle resection, all showed a statistically significant increase in Han's ratio. On the other hand, there was no statistically significant difference based on the surgical techniques used. CONCLUSION: The ratio of the lateral lower face proposed in this study is a potential indicator of postoperative esthetic enhancement in mandibular angle reduction surgery.

A Case of Benign Meningioma Presented with Subdural Hemorrhage

Meningiomas are the most common benign intracranial tumors and make up 13-26% of all primary intracranial tumors. Clinical presentation of hemorrhage is rare in these tumors occurring in approximately 1.3% of cases and subdural hemorrhages are even more uncommon. The mechanism of hemorrhage is still unclear and may vary according to histologic type, location and the type of hemorrhage. We experienced a case of 61-year-old woman with a benign meningioma presenting as a subdural hemorrhage. She developed sudden onset of headache right after aggressively coughing. Her headache persisted for a week before she was admitted to the emergency room of National Cancer Center. She had a past medical history of ovarian cancer which had been treated and was allegedly recurrence-free for 2 years. At the time of admission, a headache was the only symptom and imaging studies showed a right frontal hemorrhagic subdural mass lesion accompanying an ipsilateral subdural hematoma. Elective surgery was performed and intraoperative findings revealed the hallmark characteristics of a meningioma with mixed stage diffuse subdural hematoma. Permanent pathology result determined it was a conventional meningioma (World Health Organization grade I). From this case, we discuss the rare presentation of subdural hemorrhage in meningioma and related points by reviewing the literature of previous studies.

Osteomyelitis in an Osteopathia Striata with Cranial Sclerosis Patient / 대한악안면성형재건외과학회지

Osteopathia striata with cranial sclerosis (OS-CS) is characterized by linear bone dysplasia at the long bone radiographically and sclerotic change at the cranium. The purpose of this case report is to study the symptoms and treatments of osteomyelitis in a patient with OS-CS. A 41-year-old patient had pus discharge from a fistula at the mental region and increase in radiolucencies with sequestra in panoramic radiograph images. Computed tomography (CT) as well as radiograph images for the whole skeleton were taken. The patient was diagnosed with OS-CS. Sequestrectomy and fistulectomy were performed. The patient recovered and no relapse occurred within six months after surgery. For diagnosis of OS-CS, CT and additional radiograph images for the whole skeleton are required. Because of the increased bone density, this patient is prone to relapse after sequestrectomy. Therefore, the surgeon must minimize trauma with the least incision and exfoliation, and preoperative antibiotics.

Undifferentiated Pleomorphic Sarcoma in Mandible / 대한악안면성형재건외과학회지

Undifferentiated pleomorphic sarcoma (UPS), previously known as malignant fibrous histiocytoma, occurs commonly in the soft tissues in adult, but is rare in the maxillofacial region. It consists of undifferentiated mesenchymal tumor cells resembling histiocytes and fibroblasts. The purpose of this article is to report a case of UPS in the mandible. A 44-year-old patient presented with a painful growing mass in the mandible of two months' duration. Computed tomography and positron emission tomography-computed tomography revealed an ill-defined heterogenous, hypermetabolic mass about 4 cm in size in the left mandible invading adjacent soft tissues. A left mandiblulectomy and reconstruction with a fibular free flap were performed. Immunohistochemical study gave a diagnosis of UPS. The patient was referred for adjuvant chemotherapy after surgical removal of the tumor.

The relation between idiopathic scoliosis and the frontal and lateral facial form / 대한치과교정학회지

OBJECTIVE: The purpose of this study was to evaluate the relation between idiopathic scoliosis and facial deformity in the horizontal, vertical, and anteroposterior planes. METHODS: A total of 123 female patients aged 14 years or older, who visited the Spine Clinic at the Department of Orthopedics, Korea University Guro Hospital for treatment of idiopathic scoliosis, were enrolled. Whole-spine anteroposterior and lateral radiographs were taken with the patient in a naturally erect position, and frontal and lateral cephalograms were taken in an erect position with the Frankfort horizontal line parallel to the floor. Scoliosis was classified according to the Cobb angle and Lenke classification of six curve types. Cephalometric tracing in all cases was carried out with V-Ceph 5.5 by the same orthodontist. The Kruskal-Wallis test was performed to determine whether any relation existed between each group of the idiopathic scoliosis classification and the cephalometric measurements of frontal and lateral cephalograms. RESULTS: The measurements did not reveal any significant association between the Cobb angle and cephalometric measurements and between the curve type based on the Lenke classification and cephalometric measurements. CONCLUSIONS: Based on the results of this study, no apparent relation was observed between the severity of scoliosis and facial form variations in idiopathic scoliosis patients.

p38 MAPK and ERK activation by 9-cis-retinoic acid induces chemokine receptors CCR1 and CCR2 expression in human monocytic THP-1 cells

9-cis-retinoic acid (9CRA) plays an important role in the immune response; this includes cytokine production and cell migration. We have previously demonstrated that 9CRA increases expression of chemokine receptors CCR1 and CCR2 in human monocytes. To better understand how 9CRA induces CCR1 and CCR2 expression, we examined the contribution of signaling proteins in human monocytic THP-1 cells. The mRNA and surface protein up-regulation of CCR1 and CCR2 in 9CRA-stimulated cells were weakly blocked by the pretreatment of SB202190, a p38 MAPK inhibitor, and PD98059, an upstream ERK inhibitor. Activation of p38 MAPK and ERK1/2 was induced in both a time and dose-dependent manner after 9CRA stimulation. Both p38 MAPK and ERK1/2 phosphorylation peaked at 2 h after a 100 nM 9CRA treatment. 9CRA increased calcium influx and chemotactic activity in response to CCR1-dependent chemokines, Lkn-1/CCL15, MIP-1alpha/CCL3, and RANTES/CCL5, and the CCR2-specific chemokine, MCP-1/CCL2. Both SB202190 and PD98059 pretreatment diminished the increased calcium mobilization and chemotactic ability due to 9CRA. SB202190 inhibited the expression and functional activities of CCR1 and CCR2 more effectively than did PD98059. Therefore, our results demonstrate that 9CRA transduces the signal through p38 MAPK and ERK1/2 for CCR1 and CCR2 up-regulation, and may regulate the pro-inflammatory process through the p38 MAPK and ERK-dependent signaling pathways.

Treatment of Cricopharyngeal Dysphagia with Shaker's Head Lift Exercise / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cricopharyngeal dysphagia refers to the dysfunction of the upper esophageal sphincter complex, which is composed of the cricopharyngeus, inferior pharyngeal constrictor and the upper segment of the cervical esophagus. Adequate relaxation of the cricopharyngeal muscle in conjunction with anterosuperior excursion of the larynx by suprahyoid muscles and propulsion of food bolus are prerequisite for normal swallow, mechanisms of which, if altered, may result in cricopharyngeal dysfunction. Head lift exercise, first described by Shaker, can be utilized in patients with cricopharyngeal dysphagia by strengthening the suprahyoid musculature and reducing the intrabolus pressure. The objective of this study was to introduce Shaker's head lift exercise in the treatment of cricopharyngeal dysphagia patients. SUBJECTS AND METHOD: Two patients suffering from cricopharyneal dysphagia after receiving skull base surgery were managed with Shaker's head lift exercise and the swallowing function was evaluated with videofluoroscopy. RESULTS: Both patients who had been taught how to perform head lift exercise showed improvement in swallowing function as observed with videofluoroscopy. Aspiration disappeared and both patients were able to take oral diet without the aid of gastrostomy tubes. CONCLUSION: Shaker's head lift exercise enabled oral feeding without aspiration in two patients. This demonstrates that Shaker's head lift exercise can be a promising noninvasive treatment modality in the treatment of cricopharyngeal dysphagia.

Clinical Evaluations of Sinonasal Infection in the Patients with Hematopoietic Stem Cell Transplantation / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: As a result of increasing the use of hematopoietic stem cell transplantation (HSCT) for hematologic malignancies and certain solid tumors, more patients have become susceptible to infection. Sinonasal infections in patients with HSCT frequently cause problems which are sometimes fatal. The purpose of this study is to determine the clinical features of sinonasal infections in the immunocompromised patients who received HSCT and to suggest a proper evaluation of these patients. MATERIALS AND METHOD: We reviewed retrospectively 1814 patients who had received HSCT in St. Mary's hospital from August 1995 to May 2003 to determine the clinical features of sinonasal infections in these patients and to analyze the correlation between sinonasal infection of pre- and post-HSCT. RESULTS: 403 patients (22.2%) had sinonasal infections. The infection occurred before HSCT in 206 patients (11.3%), whereas it occurred after HSCT in 197 patients (10.8%). Of 197 patients (27.4%) 54 had previously sinonasal infections. CONCLUSION: Sinonasal infection in the patients of pre-HSCT increased incidence of post-HSCT sinonasal infection. Early detection using endoscopic examination and sinus computed tomography scan as well as employing an aggressive combined treatment of medical and surgical modalities are essential for the treatment of sinonasal infections in the HSCT patients.

Diallyl Disulfide Inhibits Cytochrome c-Mediated Apoptosis in H2O2 Induced Death of Neuronal-differentiated PC12 Cells

BACKGROUND: The effects of diallyl disulfide (DADS), a garlic derived compound, on the viability and cell signaling- like the downstream signaling through cytochrome c, caspase-3, poly (ADP-ribose) polymerase (PARP) during an oxidative-stress induced injury were studied using H2O2 treated neuronal-differentiated PC12 cells by a nerve growth factor. METHODS: To evaluate the toxicity of the DADS itself, the viability of the differentiated PC12 cells treated with several concentrations of DADS was evaluated with 3, (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. To evaluate the protective effect of the low concentration of DADS from oxidative stress, the viability of the cells (DADS pretreated vs. not pretreated) was evaluated following the exposure to 100 micro M H2O2. Additionally, the expression of caspase-3, PARP, and cytochrome c was examined using western blot analyses. RESULTS: The viability was not affected at low concentrations of DADS, up to 20 micro M, but, over this concentration, it was decreased. Compared with the cells treated with only 100 micro M H2O2, the pretreatment with low concentrations of DADS before exposure to 100 micro M H2O2 increased the viability and induced the inhibition of caspase-3 activation, PARP cleavage, and cytochrome c release. CONCLUSIONS: These results show that low concentrations of DADS shows neuroprotective effects by affecting the downstream signaling through cytochrome c, caspase-3, and PARP pathway and may be a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury.

Clinical Effectiveness of Intraoperative Sentinel Node Biopsy in N0 Tongue Cancers: A Preliminary Report / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) seems to have the potential to change our attitude toward the surgical treatment of cN0-staged necks in the near future. If SLN localization can predict which patient requires a neck dissection, then such neck dissections may be avoided in patients with negative sentinel nodes, thus reducing the associated cosmetic deformities and shoulder dysfunction. The purpose of this study is to evaluate the feasibility and predictive ability of the SLN localization technique for patients with squamous cell carcinoma of the tongue. MATERIALS AND METHOD: We tried to localize the SLN with the lymphoscintigraphy preoperatively and the gamma probe intraoperatively, excised it, and performed frozen sections in 6 patients with lateral T1-T2, N0, and M0 squamous cell carcinoma of the tongue. In 3 of them, we performed supraomohyoid neck dissection. RESULTS: We localized the SLN in 6/6 with lymphoscintigraphy and 5/6 with gamma probe. The pathologic results of the frozen sections of SLN and neck dissection specimen were all negative, with the negative predictive value of SLNB being 100%. CONCLUSION: Our preliminary investigation shows that SLN localization is technically feasible in the head and neck surgery and is predictive of cervical metastasis.

A Case of Multiple Myeloma Involving Temporal Bone / 대한이비인후과학회지

Multiple myeloma (MM) is a systemic manifestation of plasma cell tumor. It shows anemia, bone pain and some pathologic fracture. MM is a relatively well known disease, but temporal bone involvement is very rare. In 1979, Lavine first reported the temporal bone involvement in MM. Since then, only a few cases of temporal involvement in MM were reported in literature. In Korea, temporal bone involvement in MM has not been reported yet. It is very difficult to diagnose MM of temporal bone in the early stage, since it presents general, nonspecific otologic symptoms and it is difficult to carry out pathological confirmation in the temporal bone. In most of reported cases, patients are already diagnosed with MM. when they are presented with MM of temporal bone. If MM is found in the temporal area, it is considered to be in the terminal stage of disease, but treatment for it is the same as that for the usual MM. We experienced a case with intractable otalgia and suddenly developed facial palsy, which was later confirmed to be a MM after a pathologic review and a systemic evaluation. We report this rare case with a review of literatures.