This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a noncompartmental method with Phoenix WinNonlin ® . A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (C max ) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795–0.9614) and 0.8630 (0.8472–0.8791) in the fasting study and 1.0926 (1.0102–1.1818) and 0.9998 (0.9675–1.0332) in the fed study, respectively. The time to reach C max of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow.

UI026 is an expectorant and antitussive agent which is a new combination of Pelargonium sidoides extract andCoptis extract. The bioactive compounds of Pelargonium sidoides and Coptis extracts were identified as epicatechin and berberine, respectively. This study evaluated the effect of food on the pharmacokinetics (PKs) and safety of UI026. A randomized, openlabel, single-dose, 2-treatment, parallel study in 12 healthy male subjects was performed. Subjects received a single oral dose of UI026 (27 mL of syrup) under a fed or fasted condition according to their randomly assigned treatment. Blood samples for the PK analysis were obtained up to 24 hours post-dose for berberine and 12 hours post-dose for epicatechin. The PK parameters were calculated by non-compartmental analysis. In the fed condition, the mean maximum plasma concentration (C max ) and mean area under the plasma concentrationtime curve from time zero to the last observed time point (AUC last ) for berberine were approximately 33% and 67% lower, respectively, compared with the fasted condition, both showing statistically significant difference. For epicatechin, the mean C max and mean AUC last were about 29% and 45% lower, respectively, compared to the fasting condition, neither of which showed a statistically significant difference. There were no drug-related adverse events. This finding suggests that food affects the systemic exposure and bioavailability of berberine and epicatechin.

Purpose: Papillary thyroid cancer (PTC) has a high incidence of BRAF V600E mutation. The purpose of this study was to evaluate the potential relationship between thyroiditis and BRAF V600E mutation status in patients with PTC. We investigated how a selective inhibitor of BRAF V600E PLX4032 affects the proliferation and inflammatory cytokine levels of thyroid cancer. Methods: Two thyroid cancer cell lines TPC1 and 8505C were treated with PLX4032, an analysis was done on cell growth, cell cycle, the degree of apoptosis, and levels of inflammatory cytokines. To identify the functional links of BRAF, we used the STRING database. Results: Docking results illustrated PLX4032 blocked the kinase activity by exclusively binding on the serine/threonine kinase domain. STRING results indicated BRAF is functionally linked to mitogen-activated protein kinase. Both cell lines showed a dose-dependent reduction in growth rate but had a different half maximal inhibitory concentration value for PLX4032. The reaction to PLX4032 was more sensitive in the 8505C cells than in the TPC1 cells. PLX4032 induced a G2/ M phase arrest in the TPC1 cells and G0/G1 in the 8505C cells. PLX4032 induced apoptosis only in the 8505C cells. With PLX4032, the TPC1 cells showed decreased levels of vascular endothelial growth factor, granulocyte-macrophage colonystimulating factor, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein 1, whereas the 8505C cells showed significantly decreased levels of IL-8, serpin E1/plasminogen activator inhibitor-1, and matrix metalloproteinase (MMP)-3. Conclusion PLX4032 was cytotoxic in both TPC1 and 8505C cells and induced apoptosis. In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAF V600E mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.

Background: Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. Results: PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. Conclusions In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.

Background: Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. Results: PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. Conclusions In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.

Objectives: . Endoscopic pituitary surgery usually requires a collaboration between neurosurgeons and ENT surgeons to achieve optimal outcomes. However, neurosurgeons occasionally perform these procedures alone without an ENT surgeon. In this study, postoperative sinonasal quality of life and olfactory function were compared in patients who underwent endoscopic pituitary surgery performed by a single neurosurgeon or by a collaborative team of a neurosurgeon and an ENT surgeon. Materials and Methods: . A retrospective review of prospectively collected data was performed. Patients who underwent endoscopic pituitary surgery for pituitary adenoma from January 2015 to April 2018 were included. The study patients were divided into two groups; patients in group 1 underwent surgery performed by a single neurosurgeon, while patients in group 2 received surgery performed by a collaborative team of surgeons. Olfaction was assessed using a subjective Likert scale, the Cross-Cultural Smell Identification Test (CC-SIT), and the butanol threshold test (BTT). In addition, patients answered the Sino-nasal Outcome Test (SNOT-22) questionnaire regarding sinonasal quality of life before and 3 months after surgery. Results: . This study included 152 patients (46 patients in group 1 and 106 patients in group 2). Significant differences were not observed between the two groups regarding age, sex, tumor size, or operation time. Although subjective olfaction was not significantly different before and after surgery, group 2 showed significantly better objective olfactory function based on the CC-SIT (8.44±3.00 vs. 9.84±1.40; P=0.012) and BTT (4.67±0.84 vs. 5.02±0.33; P=0.022) scores at 3 months after surgery. The SNOT-22 scores were not statistically significantly different between the two groups (P>0.05). Conclusion . In the present study, better olfactory outcomes were observed in patients who underwent surgery performed by a collaborative team of a neurosurgeon and an ENT surgeon. This result shows the need for collaboration between neurosurgeons and ENT surgeons in endoscopic pituitary surgery.

Abdominal aortic aneurysm (AAA) can be defined as an abnormal, progressive dilatation of the abdominal aorta, carrying a substantial risk for fatal aneurysmal rupture. Endovascular aneurysmal repair (EVAR) for AAA is a minimally invasive endovascular procedure that involves the placement of a bifurcated or tubular stent-graft over the AAA to exclude the aneurysm from arterial circulation. In contrast to open surgical repair, EVAR only requires a stab incision, shorter procedure time, and early recovery. Although EVAR seems to be an attractive solution with many advantages for AAA repair, there are detailed requirements and many important aspects should be understood before the procedure. In this comprehensive review, fundamental information regarding AAA and EVAR is presented.
Aneurysm ; Aorta, Abdominal ; Aortic Aneurysm, Abdominal ; Dilatation ; Endovascular Procedures ; Rupture

OBJECTIVE: To determine the accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade in patients with mucinous ovarian tumors. METHODS: This study included 1,032 patients with mucinous ovarian tumors who underwent frozen section diagnosis during surgery. Sensitivity, specificity, and diagnostic accuracy of frozen section diagnosis was calculated. Univariate and multivariate regression analyses were performed to determine factors associated with diagnosis upgrade in the final pathology report. RESULTS: The sensitivity and specificity of frozen section diagnosis were 99.1% (95% confidence interval [CI]=98%–99.6%) and 82.2% (95% CI=77.9%–85.7%), respectively, for benign mucinous tumors; 74.6% (95% CI=69.1%–79.4%) and 96.7% (95% CI=95.2%–97.8%), respectively, for mucinous borderline ovarian tumors; and 72.5% (95% CI=62.9%–80.3%) and 98.8% (95% CI=97.9%–99.3%), respectively, for invasive mucinous carcinomas. The multivariate analysis revealed that mixed tumor histology (odds ratio [OR]=2.8; 95% CI=1.3–6.3; p=0.012), tumor size >12 cm (OR=2.5; 95% CI=1.5–4.3; p=0.001), multilocular tumor (OR=2.9; 95% CI=1.4–6.0; p=0.006), and presence of a solid component in the tumor (OR=3.1; 95% CI=1.8–5.1; p<0.001) were independent risk factors for final pathological diagnosis upgrade. CONCLUSIONS: Mixed tumor histology, tumor size >12 cm, multilocular tumor, and presence of a solid component in the tumor were independent risk factors for final pathological diagnosis upgrade based on frozen section diagnosis.
Adenocarcinoma, Mucinous ; Diagnosis ; Frozen Sections ; Humans ; Mucins ; Multivariate Analysis ; Ovarian Neoplasms ; Pathology ; Risk Factors ; Sensitivity and Specificity

OBJECTIVE: To investigate the expression of androgen receptor (AR) and its correlation with disease status and survival outcome in uterine leiomyosarcoma with other hormone receptors. METHODS: The medical records and paraffin blocks of 42 patients were reviewed. The immunohistochemical expression of AR, estrogen receptor (ER), progesterone receptor (PR), gonadotropin releasing hormone (GnRH), and cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) were assessed using tissue microarray. RESULTS: In total, AR expression was observed in 11 patients (26.2%). International Federation of Gynecology and Obstetrics (FIGO) stage and AR were independent factors for disease-free survival (DFS) in multivariate regression analysis (odds ratio [OR]=5.8; 95% confidence interval [CI]=1.2–28.4 and OR=0.2; 95% CI=0.05–0.90; p=0.029 and 0.032, respectively). There were no deaths in the AR expression group, whereas the 5-year overall survival (OS) was 54.8% in the no expression group (p=0.014). Co-expression of ER and/or PR with AR was associated with significantly better 5-year DFS and OS than those with negative AR (72.7% vs. 28.6% and 100% vs. 64.3%; p=0.020 and 0.036, respectively). AR may be an independent prognostic marker regardless of ER/PR. CONCLUSION: AR can be a potential prognostic biomarker in uterine leiomyosarcoma.
Cytochrome P-450 Enzyme System ; Disease-Free Survival ; Estrogens ; Gonadotropin-Releasing Hormone ; Gynecology ; Humans ; Immunohistochemistry ; Leiomyosarcoma* ; Medical Records ; Obstetrics ; Paraffin ; Receptors, Androgen* ; Receptors, Progesterone

Multidetector CT (MDCT) gastrography has been regarded as a promising technique for the preoperative imaging of gastric cancer. It has the ability to produce various three-dimensional (3D) images. Because 3D reconstruction images are more effective and intuitive for recognizing abnormal changes in the gastric folds and subtle mucosal nodularity than two-dimensional images, 3D MDCT gastrography can enhance the detection rate of early gastric cancer, which, in turn, contributes to the improvement of the accuracy of preoperative tumor (T) staging. In addition, shaded surface display and tissue transition projection images provide a global view of the stomach, with the exact location of gastric cancer, which may replace the need for barium studies. In this article, we discuss technical factors in producing high-quality MDCT gastrographic images and present cases demonstrating the usefulness of MDCT gastrography for the detection and T staging of gastric cancer while emphasizing the significance of preoperative localization of gastric cancer in terms of surgical margin.
Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Neoplasm Staging ; Stomach Neoplasms/pathology/*radiography/surgery ; Tomography, X-Ray Computed