Validated UPLC-MS/MS method for the determination of tadalafil in human plasma and its application to a pharmacokinetic study

A simple, rapid, and reliable UPLC-MS/MS method was developed and validated for the determination of tadalafil in human plasma. The plasma samples were deproteinized with acetonitrile. Chromatographic separation was performed on a Shiseido C18 (100 × 2.1 mm, 2.7 µm) column with isocratic elution using 2.0 mM ammonium acetate and acetonitrile (55:45, v/v) with 0.1% formic acid at a flow rate of 0.7 mL/min. The total run time was 1 min per sample. The quantitative analysis was performed using multiple reaction monitoring at transition of m/z 390.4 → 268.3 for tadalafil and m/z 475.3 → 283.3 for sildenafil as an internal standard. The method was fully validated over a concentration range of 5–1,000 ng/mL with a lower quantification limit of 5 ng/mL. Intra- and inter-day precision (relative standard deviation, %RSD) were within 8.4% and accuracy (relative error, %RE) was lower than -3.2%. The developed and validated method was successfully applied to a pharmacokinetic study of tadalafil (20 mg) in Korean healthy male subjects (n = 12).

Changes in Etiologies and Clinical Characteristics of Operated Unilateral Sinus Diseases: Comparison Study between 2005 and 2015

BACKGROUND AND OBJECTIVES: A considerable proportion of sinus diseases is associated with a unilateral lesion. Unilateral paranasal pathological lesions require precise preoperative diagnosis and histopathological assessment. This study aimed to analyze the changes in etiologies and clinical characteristics of operated unilateral sinus diseases between 2005 and 2015. SUBJECTS AND METHODS: Two hundred eighteen operated cases with unilateral sinus disease in 2005 and 2015 were reviewed to retrospectively analyze the etiologies and clinical characteristics. RESULTS: In 2015 compared with 2005, the proportion of unilateral sinus disease and patient age were increased. The proportions of patients with allergic rhinitis and hypertension were significantly increased in 2015. The leading cause of unilateral sinus lesions was nasal polyp, followed by fungus, tumor, mucocele, anatomical variation, odontogenic sinusitis, and foreign body. This ranking did not change between 2005 and 2015. The number of patients with fungal sinusitis was significantly increased in 2015. The direction of nasal septal deviation had no statistically significant relation with unilateral sinus disease. CONCLUSION: This comparison study of unilateral sinus disease between 2005 and 2015 showed that the proportion of fungal sinusitis, patient age, and patients with underlying disease were increased.

Alternaria Induces Production of Thymic Stromal Lymphopoietin in Nasal Fibroblasts Through Toll-like Receptor 2

PURPOSE: Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease with markedly increased eosinophils, Th2-type lymphocytes, fibroblasts, and goblet cells. Fungi are commonly associated with airway inflammatory diseases, and thymic stromal lymphopoietin (TSLP) is important in the development of Th2 inflammatory responses. The aim of this study was to investigate the interaction between airborne fungi and nasal fibroblasts in TSLP mRNA and protein expression. METHODS: Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria and Aspergillus, respectively, for 48 hours, and TSLP mRNA and protein expressions were measured. The reverse transcriptase polymerase chain reaction was performed for the Toll-like receptor (TLR) mRNA expression of the nasal fibroblasts. To determine the role of TLR in the induction of TSLP, the fibroblasts were transfected with siRNA against TLR2 and TLR5. RESULTS: Alternaria induced TSLP mRNA and protein expression in both inferior turbinate and nasal polyp fibroblasts. The nasal polyp fibroblasts responded more strongly to the fungi. TLR2 and TLR5 mRNA expressions were significantly increased with fungal stimulation and TSLP production was significantly inhibited by siRNA against TLR2. CONCLUSIONS: The results of this study show that TSLP expression could be induced in nasal fibroblasts by exposure to Alternaria and that TLR2 may be involved in the process. The promotion of TSLP production in nasal fibroblasts by airborne fungi may facilitate the development or exacerbation of Th2-type nasal inflammation, especially in CRS with nasal polyps.

A Case of the Ex Utero Intrapartum Treatment Procedure for Fetal Giant Fourth Branchial Cleft Cyst / 대한이비인후과학회지

Large neck masses in the fetus can result in neonatal hypoxia with airway obstruction during a delivery. The ex-utero intrapartum treatment (EXIT) is a procedure that would be helpful in safely securing a fetal airway when the maternal-fetal circulation is being obstructed. Branchial cleft cyst (BCC) is a relatively common congenital malformation in the neck, however, the fourth BCC is very rare. Herein, we present a case of a giant fourth BCC, which was prenatally detected on ultrasound and safely surgically treated to secure an airway with EXIT procedure during the delivery.

The Effect of Omnaris(R) on the Inflammatory Reaction and Mucin Gene Expression from Nasal Polyp Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Glucocorticoids are a potent anti-inflammatory agent. The au-thors conducted this study to investigate the effect of Omnaris(R) on suppression of inflammation induction and mucin gene expression in nasal polyp epithelial cells. SUBJECTS AND METHOD: Primary nasal polyp epithelial cells were stimulated by 5 ug/mL of streptococcal enterotoxin B (SEB) and lipopolysaccharide (LPS). To determine the effects of Omnaris(R), cells were pretreated with 200, 100, 10, 1 ng/mL of Omnaris(R). The anti-inflammatory effect of epithelial cells were confirmed by measuring interleukin (IL)-6, IL-8, and granulocyte-macrophage colony stimulating factor (GM-CSF), and mucin gene expressions were determined by real time PCR for MUC4, MUC5AC, MUC5B, MUC8. RESULTS: SEB and LPS enhanced the production of IL-6, IL-8, and GM-CSF from nasal polyp epithelial cells. The increased cytokine levels were significantly suppressed by Omnaris(R) at 100 and 10 ng/mL. The expressions of MUC4, MUC5AC, MUC5B, MUC8 mRNA, and MUC4 mRNA were increased by SEB and LPS, respectively. The increased expression of these mucin genes were significantly suppressed by 100, 10, and 1 ng/mL of Omnaris(R). CONCLUSION: Omnaris(R) significantly suppressed the production of chemical mediators and mucin gene expression, which indicated that Omnaris(R) is effective in improving and treating inflammatory diseases in the nasal cavity.

Fatal pulmonary thromboembolism during total hip replacement under spinal anesthesia / 대한마취과학회지

No abstract available.

The effectiveness of L2 nerve root block for the management of patients who are suffering from chronic low back and referred pain / 대한마취과학회지

No abstract available.

Antitumor Effect of Dendritic Cell Pulsed with Tumor Cell Lysate Against Hepatic Metastases in Murine Model

PURPOSE: Activated bone marrow-derived dendritic cells (DCs) express high level of MHC class I and II molecules as well as intercellular adhesion molecule and B7, required for T cell activation. This study was designed to examine whether DCs pulsed with tumor lysates were capable of inducing tumor specific CTLs. METHODS: To generate mature DCs, bone marrow cells of female BALB/c mice were cultured in the presence of GM-CSF and IL-4. Mature DCs were idenfied by surface expression of MHC class II molecules and costimulatory molecules. By FACS analysis, it was found that most DCs highly expressed B7-1, B-7-2 and CD40 as well as MHC class II molecules. BAlB/c were immunized subcutaneously. Cytolytic activity was determined by chromium release assay using splenocytes harvested from immunized mice 7 days after the immunization, Cytolytic activity was measured against CT-26 and RAG tumor cells. In vivo protection experiment was performed. Mice were immunized subcutaneously wity DCs pulsed with CT-26 lysates (1x10(6) per mouse) and were challenged intrahepatically with wild type CT-26 (5x10(4) per mouse) two weeks following immunization. Three weeks after the challenge, animals were euthanized for identification of hepatic tumors. RESULTS: Lysis of CT-26 cells were significantly greater with the splenocytes from the immunized mice. Incidence and mean volume of hepatic cancer in the immunized group were 50% (5/10) and 78+/-22 mm3. These results were significantly different from those from control groups:100% (10/10) and 1014.5+/-667.8 mm3 in media treated group, 90% (9/10) and 855.5+/-270.6 mm3 in mice treated with irradiated CT-26, 100% (10/10) and 994 255 mm3 in the animals treated with DC alone. CONCLUSIONS: DCs pulsed with CT-26 lysates could successfully induce antitumor immunity in the BLAB/c against syngeneic CT-26 carcinoma cells. Pulsing method was so simple that neither genetic engineerings nor cellular fusion were not necessary. Even though the present study did not conduct survival experiments, it was thought that clinical application of DC-based immunotherapy could be expedited by pulsing of tumor lysate into the DCs.

Clinical Analysis of 62 patients with Rectovaginal Fistula

Rectovagianl fistula(RVF) is a congenital or acquired communication between the two epithelial-lined surface of the rectum and the vagina. We present our experience with 62 patients with RVF. There were various etiologies and repair methods of rectovaginal fistula. The purpose of this study was to retospectively review the clinical course of the patients we treated and to evaluate the efficacy of various treatment options. The mean age was 40.5 yr, The type of RVF was classified to one of two(simple and complex), according to their location, size and etiology. RVF was developed most commonly after radiotherapy due to cervical cancer(n=17), then after pelvic surgery due to malignancy(n=16), obstetric trauma after episiotomy at delivery(n=7), congenital malformation(n=4), inflammatory bowel disease(n=1), Bechet's disease(n=1), infections such as perianal fistula or abscess(n=2), direct invasion of carcinoma(n=3), after chemotherapy(n=1), and idiopathic(n=6). Three cases of them associated with rectovesicovaginal fistula. Surgical therapeutic option was divided to local repair, abdominal approach and tissue transposition by the type of RVF. Most simple RVFs were repaired with local approach through the vagina or rectum. Most complex RVFs were repaired through abdominal approach or tissue transposition. With an average follow up of 20 months, the treatment results were as follows: completely healed(n=36, 58.1%), persistent symptom(n=6, 9.7%), recurrence after repair(n=5, 8.1%), loss of search or death(n=15, 24.1%). Therefore we assist that the management of RVF depends on size, location, and cause. anal sphincter function and overall health status of the patient. Careful preoperative assessment of the fistula, surrounding tissues, and anal sphincter and exclusion of associated disease are essential. With through evaluation, thoughtful consideration of treatment options, and meticulous operative technique, patient can be assured of an optimal outcome.