Mast cells are an effector cell that plays a pivotal role in type I hypersensitive immune responses. Mast cells exist in connective tissues, such as skin and mucosal tissue, and contain granules which contain bioactive substances such as histamine and heparin in cells. The granules of mast cells are secreted by antigen stimulation to cause the type I allergic hypersensitivity. In addition, stimulated by antigen, mast cells synthesize and secrete various eicosanoids and cytokines. While AT9283 is known to have anticancer effects, the therapeutic effect of AT9283 on allergic disorders is completely unknown. In this study, it was found that AT9283 reversibly inhibited antigen-IgE binding-induced degranulation in mast cells (IC50, approx. 0.58 μM) and suppressed the secretion of the inflammatory cytokines IL-4 (IC50, approx. 0.09 μM) and TNF-α (IC50, approx. 0.19 μM). For a mechanism of mast cell inhibition, while not inhibiting Syk phosphorylation, AT9283 suppressed the activation of LAT, a downstream substrate protein of Syk, in a dose-dependent manner. As expected, AT9283 also inhibited the activation of PLCγ1 and Akt, downstream signaling molecules of Syk/LAT, and MAP kinases such as JNK, Erk1/2, and P38. In an in vitro protein tyrosine kinase assay, AT9283 directly inhibited Syk activity. Next, AT9283 dose-dependently inhibited passive cutaneous anaphylaxis (PCA), an IgE-mediated allergic acute response, in mice (ED50, approx. 34 mg/kg, p.o.). These findings suggest that AT9283 has potential to use as a new drug for alleviating the symptoms of IgE-mediated allergic disorders.

Background: Acinetobacter baumannii infections cause high morbidity and mortality in intensive care unit (ICU) patients. However, there are limited data on the changes of longterm epidemiology of imipenem resistance in A. baumannii bacteremia among pediatric ICU (PICU) patients. Methods: A retrospective review was performed on patients with A. baumannii bacteremia in PICU of a tertiary teaching hospital from 2000 to 2016. Antimicrobial susceptibility tests, multilocus sequence typing (MLST), and polymerase chain reaction for antimicrobial resistance genes were performed for available isolates. Results: A. baumannii bacteremia occurred in 27 patients; imipenem-sensitive A. baumannii (ISAB, n = 10, 37%) and imipenem-resistant A. baumannii (IRAB, n = 17, 63%). There was a clear shift in the antibiogram of A. baumannii during the study period. From 2000 to 2003, all isolates were ISAB (n = 6). From 2005 to 2008, both IRAB (n = 5) and ISAB (n = 4) were isolated. However, from 2009, all isolates were IRAB (n = 12). Ten isolates were available for additional test and confirmed as IRAB. MLST analysis showed that among 10 isolates, sequence type 138 was predominant (n = 7). All 10 isolates were positive for OXA-23-like and OXA-51-like carbapenemase. Of 27 bacteremia patients, 11 were male (41%), the median age at bacteremia onset was 5.2 years (range, 0–18.6 years). In 33% (9/27) of patients, A. baumannii was isolated from tracheal aspirate prior to development of bacteremia (median, 8 days; range, 5–124 days). The overall case-fatality rate was 63% (17/27) within 28 days. There was no statistical difference in the case fatality rate between ISAB and IRAB groups (50% vs. 71%; P = 0.422). Conclusion IRAB bacteremia causes serious threat in patients in PICU. Proactive infection control measures and antimicrobial stewardship are crucial for managing IRAB infection in PICU.

Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.

Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.

Central venous stenosis is a relatively common complication in hemodialysis patients; however, jugular venous reflux (JVR) and increased intracranial pressure are rare, and associated progressive visual disturbance was reported in only a few cases. Here, we report a case of JVR with visual disturbance and increased intracranial pressure. Notably, the MRI was accompanied by a dilatation of the superior ophthalmic vein, which was mistaken for a cavernous sinus dural arteriovenous fistula (CSdAVF). The patient had JVR on time-of-flight MR angiography (TOF-MRA) and severe stenosis of the left brachiocephalic vein on conventional angiography. After balloon angioplasty for central venous stenosis, he was discharged after improvement of his visual disturbance. Although JVR due to central venous stenosis and CSdAVF might show similar symptoms, treatment plans are different. Therefore, it is important to distinguish radiologically based on a thorough review of MRI and TOF-MRA and confirm the central venous stenosis on cerebral angiography for the accurate diagnosis.

Purpose: As coronavirus disease 2019 pandemic has been prolonged, it became crucial to analyze the long-term impact of the pandemic on emergency department (ED) utilization for efficient use of emergency medicine resources. Methods: We reviewed the data of children (≤ 18 years) who visited the ED in Daejeon, Korea, from February 2019 through January 2021. This period was dichotomized by February 2020 into the reference and pandemic periods. The latter period was further divided into the early (February-August 2020) and late pandemic periods. Between the reference and pandemic periods, and between the early and late pandemic periods, we respectively compared proportions of children in all patients (including adults), age groups, high acuity (the Korean Triage and Acuity Scale 1-2), diagnostic codes, visits via ambulances, ED length of stay, and ED disposition. Results: Compared to the reference and early pandemic periods, the pandemic and late pandemic periods respectively showed changes as follows: proportion of children in all patients (from 29.8% to 19.0% and from 19.8% to 18.1%; all Ps < 0.001), children younger than 5 years (from 56.7% to 49.9% and from 52.1% to 47.4%; all Ps < 0.001), high acuity (from 12.0% to 7.8% [P < 0.001] and from 8.8% to 6.7% [P = 0.004]), “Injury, poisoning and certain other consequences of external causes (S00-T98; from 30.0% to 49.0% and from 48.3% to 49.8%),” and “Diseases of the respiratory system (J00-J99; from 29.6% to 10.3% and from 12.8% to 7.5%).” Increases in the visits via ambulances, ED length of stay, children undergoing intensive care unit hospitalization or death were noted only in comparison between the reference and pandemic periods. Conclusion A long-term impact of the pandemic on ED use may be a decrease in the proportion of young or ill children.

OBJECTIVES: Iodine deficiency causes multiple health problems. Previously we reported that 96% of high school students in Tuguegarao, Philippines had adequate iodine levels. However, iodine deficiency-associated problems remain among adults in the Philippines. Therefore, we evaluated iodine nutritional status and goiter prevalence among adults, including pregnant women, in Tuguegarao, Philippines. METHODS: A total of 245 adults, including 31 pregnant women, provided samples for urinary iodine analysis, and all pregnant women completed a questionnaire about iodine deficiency. RESULTS: The median urinary iodine level was 164.0 ± 138.4 µg/L; 38.4% of the participants were iodine deficient, according to the International Council for Control of Iodine Deficiency Disorders (ICCIDD) criteria. No severe iodine deficiency was observed. Among the 31 pregnant women, 24 (77.5%) fell into the iodine deficient category defined by a stricter World Health Organization (WHO) guideline, in which iodine deficiency is considered when urinary iodine levels are below 150 µg/L. Almost half (42%) of the pregnant women were unaware of the harmful effects of iodine deficiency on the human body and their fetus. CONCLUSIONS: Although iodine nutritional status in the Philippines has improved, iodine deficiency still exists among adults, especially among pregnant women. Therefore, our study strongly suggests that a better strategy should be established to monitor iodine nutritional status among adults continually, and to focus on populations susceptible to iodine deficiency, including pregnant women and women of reproductive age, to achieve the total elimination of iodine deficiency.
Adult* ; Female ; Fetus ; Goiter ; Human Body ; Humans ; Iodine* ; Nutritional Status* ; Philippines* ; Pregnant Women* ; Prevalence ; World Health Organization

BACKGROUND/OBJECTIVES: Benign prostatic hypertrophy (BPH) is a major cause of abnormal overgrowth of the prostate mainly in the elderly. Corni Fructus has been reported to be effective in the prevention and treatment of various diseases because of its strong antioxidant effect, but its efficacy against BPH is not yet known. This study was designed to evaluate the therapeutic efficacy of Corni Fructus water extract (CF) in testosterone-induced BPH rats. MATERIALS/METHODS: To induce BPH, rats were intraperitoneal injected with testosterone propionate (TP). Rats in the treatment group were orally administered with CF with TP injection, and finasteride, which is a selective inhibitor of 5α-reductase type 2, was used as a positive control. RESULTS: Our results showed that the increased prostate weight and histopathological changes in BPH model rats were suppressed by CF treatment. CF, similar to the finasteride-treated group, decreased the levels of testosterone and dihydrotestosterone by TP treatment in the serum, and it also reduced 5α-reductase expression and concentration in prostate tissue and serum, respectively. In addition, CF significantly blocked the expression of the androgen receptor (AR), AR co-activators, and proliferating cell nuclear antigen in BPH rats, and this blocking was associated with a decrease in prostate-specific antigen levels in serum and prostate tissue. CONCLUSIONS: These results suggest that CF may weaken the BPH status through the inactivation of at least 5α-reductase and AR activity and may be useful for the clinical treatment of BPH.
Aged ; Animals ; Antioxidants ; Cornus* ; Dihydrotestosterone ; Finasteride ; Humans ; Proliferating Cell Nuclear Antigen ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Rats* ; Receptors, Androgen* ; Testosterone ; Testosterone Propionate ; Water

PURPOSE: Chronic tophaceous gout is a painful and disabling inflammatory disease. Surgical treatment for chronic tophaceous gout is very difficult with many complications. This study evaluated the efficacy of shortening scarf osteotomy on the treatment of chronic tophaceous gout in the 1st metatarso-phalangeal (MTP) joint. MATERIALS AND METHODS: From January 2006 to December 2015, 14 patients (19 cases) who underwent axial shortening scarf osteotomy for chronic tophaceous gout were reviewed. All patients were male. The average age at the time of surgery was 59.6 years (42~66 years). The minimum follow-up was 24 months. Total removal of the tophi mass with the adhered medial capsule of the 1st MTP joint was attempted. Axial shortening scarf osteotomy was done on the 1st metatarsal shaft. The visual analogue scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score was assessed preoperatively and postoperatively. The range of motion (ROM) of the 1st MTP joint was also compared pre- and postoperatively. RESULTS: The average size of the extracted tophaceous mass was 32 mm. The mean amount of the length of metatarsal shortening was 4.9 mm. The mean ROM of the 1st MTP joint was improved from 30.4° to 62.3°. The mean AOFAS forefoot score improved from 51.4 to 86.6 points. The mean VAS for pain improved from 4.6 to 0.3 points. CONCLUSION: The axial shortening scarf osteotomy used on chronic tophaceous gout could reconstruct the 1st MTP joint with an improved ROM and was free of pain. Axial shortening scarf osteotomy is suggested as a useful and effective method for the treatment of chronic tophaceous gout.
Ankle ; Follow-Up Studies ; Foot ; Gout* ; Humans ; Joints* ; Male ; Metatarsal Bones ; Methods ; Osteotomy ; Range of Motion, Articular

BACKGROUND: We aimed to examine the factors that influence synovialization of the grafted tendon after double-bundle anterior cruciate ligament (ACL) reconstruction based on second-look arthroscopic findings. METHODS: Out of 205 knees that were treated between August 2008 and May 2016 with double-bundle ACL reconstruction using bio-absorbable cross-pins and Endobuttons for femoral tunnel fixation, we enrolled 65 knees (64 patients) that underwent second-look arthroscopy with hardware removal at 1 year postoperatively. Measured clinical outcomes included the Lysholm score and Tegner activity score that were evaluated preoperatively and during the final follow-up. We analyzed the relationship between synovial coverage and patient age, length of the preserved remnant tissue on the tibial side, type of bundle (anteromedial or posterolateral), type of graft (autograft or allograft), and time from injury to surgery. RESULTS: The area of synovial coverage showed a significant statistical correlation with patient age and the length of the preserved remnant tissue on the tibial side. The average synovial coverage was significantly better for the anteromedial bundle than for the posterolateral bundle, better for the autograft than for the allograft reconstruction, and better when treated in the acute stage than in the chronic stage. However, synovialization of grafted tendon did not correlate to clinical outcomes. CONCLUSIONS: While we were able to identify several factors influencing synovialization of the grafted tendon after double-bundle ACL reconstruction, including patient age, length of preserved remnant tissue of the torn ACL, type of bundle, type of graft, and time from injury to surgery, we found no evidence that increased synovialization improves clinical outcomes at 1 year postoperatively.
Allografts ; Anterior Cruciate Ligament Reconstruction* ; Anterior Cruciate Ligament* ; Arthroscopy ; Autografts ; Follow-Up Studies ; Humans ; Knee ; Lysholm Knee Score ; Tendons* ; Transplants*