Development of Hsp90 inhibitor to regulate cytokine storms in excessive delayed- and acute inflammation.

BACKGROUND: The surplus cytokines remaining after use in the early stages of the inflammatory response stimulate immune cells even after the response is over, causing a secondary inflammatory response and ultimately damaging the host, which is called a cytokine storm. Inhibiting heat shock protein 90 (Hsp90), which has recently been shown to play an important role in regulating inflammation in various cell types, may help control excessive inflammatory responses and cytokine storms. METHODS: We discovered an anti-inflammatory compound by measuring the inhibitory effect of CD86 expression on spleen DCs (sDCs) using the chemical compounds library of Hsp90 inhibitors. Subsequently, to select the hit compound, the production of cytokines and expression of surface molecules were measured on the bone marrow-derived DCs (BMDCs) and peritoneal macrophages. Then, we analyzed the response of antigen-specific Th1 cells. Finally, we confirmed the effect of the compound using acute lung injury (ALI) and delayed-type hypersensitivity (DTH) models. RESULTS: We identified Be01 as the hit compound, which reduced CD86 expression the most in sDCs. Treatment with Be01 decreased the production of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1ß) in BMDC and peritoneal macrophages stimulated by LPS. Under the DTH model, Be01 treatment reduced ear swelling and pro-inflammatory cytokines in the spleen. Similarly, Be01 treatment in the ALI model decreased neutrophil infiltration and lower levels of secreted cytokines (IL-6, TNF-α). CONCLUSIONS: Reduction of CD80 and CD86 expression on DCs by Be01 indicates reduced secondary inflammatory response by Th1 cells, and reduced release of pro-inflammatory cytokines by peritoneal macrophages may initially control the cytokine storm.

Accuracy of mandibular repositioning surgery using new technology: Computer-aided design and manufacturing customized surgical cutting guides and fixation plates.

INTRODUCTION: Recent 3-dimensional technology advancements have resulted in new techniques to improve the accuracy of intraoperative transfer. This study aimed to validate the accuracy of computer-aided design and manufacturing (CAD-CAM) customized surgical cutting guides and fixation plates on mandibular repositioning surgery performed in isolation or combined with simultaneous maxillary repositioning surgery. METHODS: Sixty patients who underwent mandibular advancement surgery by the same surgeon were retrospectively evaluated by 3-dimensional surface-based superimposition. A 3-point coordinate system (x, y, z) was used to identify the linear and angular discrepancies between the planned movements and actual outcomes. Wilcoxon rank sum test was used to compare the outcomes between the mandible-only and the bimaxillary surgery groups with significance at P <0.05. Pearson correlation coefficient compared planned mandible advancement to the outcome from advancement planned. The centroid, which represents the mandible as a single unit, was computed from 3 landmarks, and the discrepancies were evaluated by the root mean square error (RMSE) for clinical significance set at 2 mm for linear discrepancies and 4° for angular discrepancies. RESULTS: There was no statistically significant difference between the planned and actual position of the mandible in either group when considering absolute values of the differences. When considering raw directional data, a statistically significant difference was identified in the y-axis suggesting a tendency for under-advancement of the mandible in the bimaxillary group. The largest translational RMSE for the centroid was 0.77 mm in the sagittal dimension for the bimaxillary surgery group. The largest rotational RMSE for the centroid was 1.25° in the transverse dimension for the bimaxillary surgery group. Our results show that the precision and clinical feasibility of CAD-CAM customized surgical cutting guides and fixation plates on mandibular repositioning surgery is well within clinically acceptable parameters. CONCLUSION: Mandibular repositioning surgery can be performed predictably and accurately with the aid of CAD-CAM customized surgical cutting guides and fixation plates with or without maxillary surgery.

Stability of pre-orthodontic orthognathic surgery depending on mandibular surgical techniques: SSRO vs IVRO.

The aim of this retrospective cohort study was to evaluate the postoperative stability of sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) in pre-orthodontic orthognathic surgery (POGS) for skeletal Class III malocclusion. Thirty-seven patients (SSRO, n = 18; IVRO, n = 19) who underwent bimaxillary surgery were divided into two groups according to the type of surgery. During the postoperative period, there were no significant differences in anterior and superior movements of the mandible at point B between the two groups, but occlusal plane angle of the SSRO group significantly decreased more than that of the IVRO group (P = 0.003). Only the SSRO group showed a linear relationship between the amount of postoperative horizontal and vertical movements of the mandible (R(2) = 0.254; P = 0.033), indicating that the amount of postoperative upward movement of the mandible increased as the amount of postoperative forward movement increased (r = -0.504; P = 0.033). The mandible after SSRO in POGS rotated counterclockwise due to rigid fixation between two segments, whereas the mandible after IVRO without rigid fixation in POGS moved mainly in a superior direction. These differences must be considered before surgery to ensure postsurgical stability for patients with mandibular prognathism.

Discovery of Endocotyle incana and Spelotrema pseudogonotyla (Digenea: Microphallidae) from scolopacid migratory birds in Korea.

Migratory birds have been suspected as playing a central role in transmission of various trematodes, but few surveys have been undertaken in the Republic of Korea. In the present study, we describe new fauna of microphallid flukes in Korea. Two species of microphallids were found in the intestines of 2 migratory bird species, namely the red necked stints (Calidris ruficollis) and the terek sandpiper (Xenus cinereus), in a coastal area of Gunsan-si, Jeollabuk-do. The microphallids recovered from the latter were 451 µm in length and 217 µm in width, and the eggs were very small, 13 µm by 8 µm. They had the characteristic extracecal vitellaria intruding into the median posttesticular area, belonging to Endocotyle incana. Another microphallids were discovered from both migratory birds, 417 µm in length and 249 µm in width. The cirrus was projecting into the genital atrium in form of male papilla, and bounded by a muscular flap, termed pseudogonotyl. They were identified as Spelotrema pseudogonotyla in consideration of the distinctive male papilla and pseudogonotyl. Besides these flukes, Maritrema obstipum and Gynaecotyla squatarolae also were recovered. This paper is in fact the first report on the presence of Spelotrema and Endocotyle in Korea.