Diagnosis and treatment of immunoglobulin G subclass deficiency in aschool-age child with recurrent wheezing

Differential diagnosis of recurrent wheezing in school-age children includes not only asthma but also immunodeficiency. Immunoglobulin G (IgG) subclass deficiency is deficiency of 1 or more IgG subclasses ( < 2 standard deviations below the mean for age). IgG subclass deficiency in children may be associated with frequent respiratory tract infection and wheezing. An 8-year-old female patient had recurrent respiratory tract infection and wheezing despite the use of inhaled corticosteroids after the first wheezing around 100 days of age. The results of chest radiography, high resolution computed tomography of the chest, and spirometry were normal. In methacholine challenge test, provocation concentration causing a 20% fall in forced expiratory volume in 1 second was 18.29 mg/mL. Her total IgG was within the normal limit on the immunologic evaluation, but the IgG3 and IgG4 levels were decreased. She was diagnosed with IgG3 and IgG4 subclass deficiency. After intravenous immunoglobulin G (IVIG) infusion every 4–6 weeks, the number of respiratory tract infection and wheezing, the doses of systemic corticosteroids, and duration of antibiotic therapy were reduced. This case suggests that even in pediatric patients, if there are frequent respiratory tract infection and poorly controlled asthma, IgG subclass deficiency is suspected and clinical symptoms can be alleviated through IVIG treatment.

Clinical characteristics of bronchiolitis obliterans without preceding severe lower respiratory tract infection

Purpose@#We investigated young children who developed bronchiolitis obliterans (BO) without preceding severe lower respiratory tract infection (LRTI). @*Methods@#Twenty patients referred for chronic respiratory symptoms and diagnosed with BO were enrolled and divided into 2 age groups: group 1 ( < 2 years, n = 12) and group 2 ( ≥ 2, < 6 years, n = 8). A diagnosis of BO was made based on clinical and radiologic findings: (1) persistent cough or abnormal breath sounds which were not responsive to any treatment for more than 6 weeks; and (2) mosaic perfusion on high-resolution computed tomography. None of the subjects had experienced LRTI since birth, and those who had any underlying problems were excluded. The clinical characteristics and disease course were examined retrospectively. @*Results@#Mean age of the patients was 6.8 months and 3.4 years in group 1 and 2, respectively. All patients presented with chronic cough and the most common type of cough was mixed (wet and dry), 67% in group 1 and 50% in group 2. Persistent stridor was the major respiratory sign in group 1 (67%), but 63% of group 2 patients showed no abnormal breath sounds. Chest x-ray finding was nonspecific in 75% each of both groups. The respiratory symptoms and signs resolved rapidly in most patients treated with pulse corticosteroid therapy. Bronchial hyperresponsiveness and decreased forced expiratory volume in 1 second were observed in 3 of group 2 children at age 6, during the follow-up. @*Conclusion@#Our study shows that BO could develop without preceding severe LRTI. It also suggests that BO should be considered in the infants with persistent stridor accompanied by chronic cough.

The effect of probiotics supplementation in postoperative cancer patients: a prospective pilot study

Purpose@#Microbiota manipulation through selected probiotics may be a promising tool to prevent cancer development as well as onset, to improve clinical efficacy for cancer treatments. The purpose of this study was to evaluate change in microbiota composition after-probiotics supplementation and assessed the efficacy of probiotics in improving quality of life (QOL) in postoperative cancer patients. @*Methods@#Stool samples were collected from 30 cancer patients from February to October 2020 before (group I) and after (group II) 8 weeks of probiotics supplementation. We performed 16S ribosomal RNA gene sequencing to evaluate differences in gut microbiota between groups by comparing gut microbiota diversity, overall composition, and taxonomic signature abundance. The health-related QOL was evaluated through the EORTC Quality of life Questionnaire Core 30 questionnaire. @*Results@#Statistically significant differences were noted in group II; increase of Shannon and Simpson index (P = 0.004 and P = 0.001), decrease of Bacteroidetes and Fusobacteria at the phylum level (P = 0.032 and P = 0.014, retrospectively), increased of beneficial bacteria such as Weissella (0.096% vs. 0.361%, P < 0.004), Lactococcus (0.023% vs. 0.16%, P < 0.001), and Catenibacterium (0.0% vs. 0.005%, P < 0.042) at the genus level. There was a significant improvement in sleep disturbance (P = 0.039) in group II. @*Conclusion@#Gut microbiota in cancer patients can be manipulated by specific probiotic strains, result in an altered microbiota. Microbiota modulation by probiotics can be considered as part of a supplement that helps to increase gut microbiota diversity and improve QOL in cancer patients after surgery.

Effect of overweight or obesity on lung function and asthma severity in prepubertal asthmatic children

Purpose@#Cluster analysis on pediatric asthma identifying a cluster characterized by obesity, females, and puberty showed that obesity is an independent risk factor for severe asthma in this cluster. In the present study, we aimed to investigate the effect of overweight/obesity on lung function and asthma severity in prepubertal asthmatic children. @*Methods@#One hundred fifty-five prepubertal children (aged 6–10) with asthma were enrolled and divided into 2 groups: the overweight/obese group (body mass index [BMI] ≥ 85th percentile, n = 44) and the normal BMI group ( < 85th percentile, n = 111). We reviewed their medical records and analyzed whether there were any differences in clinical features, lung function and degree of bronchial hyperresponsiveness (BHR) between the 2 groups. The clinical factors associated with asthma severity were also investigated. @*Results@#There was no difference in clinical features between the 2 groups. Pulmonary function tests showed that only forced vital capacity in 1 second/forced vital capacity (FEV1/FVC) was significantly lower in the overweight/obese group than in the normal BMI group (P = 0.032). There was no difference in dysanapsis and BHR between the 2 groups. There were significantly more children with moderate-to-severe asthma in the overweight/obese group compared to the normal BMI group (P = 0.018). In multivariate logistic regression analysis, overweight/obesity has been identified as an independent risk factor of affecting asthma severity (odds ratio, 2.44; P = 0.018), in addition to the already known risk factor, FEV1. @*Conclusion@#Our study showed that overweight/obese prepubertal asthmatic children had lower FEV1/FVC than those with normal BMI. It also suggests that overweight/obesity may be an independent risk factor for severe asthma before puberty.

Relationships between lung function and clinical findings in school-agesurvivors of preterm birth

Purpose@#Survivors of preterm birth are at high risk of chronic pulmonary disease. We examined lung function in the school-age children born preterm and investigated the relationship between lung function and clinical parameters. @*Methods@#Thirty children born preterm were enrolled and divided into 2 groups: 14 very preterm (< 32-week gestational age [GA]) and 16 moderate-to-late preterm (32- to 36-week GA). Pulmonary function tests (PFTs) were performed repeatedly during schoolage and PFT parameters were compared with age-matched controls. The relationship between PFT and clinical parameters was also studied. @*Results@#PFT parameters in the very preterm group were persistently reduced compared with age-matched controls (P< 0.05). Half of the children had been diagnosed with asthma at the visit for the first PFT. Seventy-seven percent of patients in the very preterm group had bronchial hyperresposiveness. Birth weight, duration of oxygen therapy and mechanical ventilation in the neonatal intensive care unit, and body weight at age 1 were associated with forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC), or forced expiratory flow between 25% and 75% of expired vital capacity (FEF 25%–75%) z-scores. Multiple regression analysis revealed that body weight at age 1 was an independent predictor of FEV 1 and FVC z-scores, and duration of oxygen therapy was independently associated with FEF 25%–75% z-scores (P< 0.01 for all). @*Conclusion@#No catch-up in lung function was observed in school-age children born very preterm. Lower body weight at age 1 might be an independent risk factor for reduced FEV 1 and FVC, whereas long-term oxygen therapy might be associated with reduced FEF 25%–75%

A Case of Neonatal Thyrotoxicosis with Cardiac Insufficiency

Neonatal thyrotoxicosis is rare and most of the cases are secondary to maternal Graves’ disease. It is usually transient, but can be associated with significant morbidity and mortality if not recognized promptly and treated adequately. Neonates born to mothers treated with antithyroid drugs or those who receive maternal thyroid blocking antibodies may exhibit normal thyroid function or even hypothyroidism at birth. Since there may not be any obvious symptoms of hyperthyroidism at birth, it may be overlooked. Therefore, such neonates should be evaluated properly and monitored regularly to prevent serious complications of hyperthyroidism. We report a case of a 21-day-old male infant who developed thyrotoxicosis with dyspnea, irritability, tachycardia, and cardiac insufficiency. He was born to a mother who was treated for Graves’ disease with antithyroid drugs during pregnancy. We have also discussed the importance of careful examination and monitoring to prevent the development of clinical hyperthyroidism.

A case of vitamin D hydroxylation-deficient rickets type 1A caused by 2 novel pathogenic variants in CYP27B1 gene

Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A, OMIM 264700) is a rare autosomal recessive inherited disorder. Pathogenic variants in the CYP27B1 gene lead to loss of 1α-hydroxylase activity. We report the case of a 22-month-old toddler who presented with growth retardation and delayed development. The patient exhibited the typical laboratory findings of VDDR1A, including hypocalcemia (calcium: 5.2 mg/dL), elevated serum level of alkaline phosphatase (2,600 U/L), elevated serum level of intact-parathyroid hormone (238 pg/mL), low 1,25(OH)₂D₃ level (11.2 pg/mL), and normal 25(OH)D₃ level (40.7 ng/mL). His height and weight were 76.5 cm and 9.5 kg, respectively (both <3rd percentile). The Bayley Scales of Infant and Toddler Development II indicated significantly delayed development (mental development index <50, psychomotor development index <50). The patient was a compound heterozygous for two novel pathogenic variants in the CYP27B1 gene: c.57_69del (p.Glu20Profs*2) and c.171dupG (p.Leu58Alafs*275), inherited from his mother and father, respectively. The patient showed remarkable improvement after treatment with calcitriol and calcium carbonate.

A novel compound heterozygous mutation in DNAH5 in a Korean neonate with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease affecting motile cilia. A female neonate was hospitalized with respiratory distress 72 hours after birth and showed concurrent situs inversus. She was identified to have compound heterozygous mutations in DNAH5: c.5647C>T, p.Arg1883Ter (nonsense mutation) and c.10810dupA, p.Ile3604AsnfsTer2 (frameshift mutation). Sanger sequencing confirmed that they were inherited from her father and mother, respectively, and she was diagnosed with PCD. The c.10810dupA is a novel DNAH5 mutation that has never been reported. To the best of our knowledge, this is the first report describing DNAH5 mutations in a Korean patient with PCD.

Association between the Nutritional Status at Birth and Need for Respiratory Support on the First Day of Life

PURPOSE: Nutritional markers, such as total protein, albumin, and vitamin D have been reportedly associated with neonatal outcomes. This study aimed to assess the correlation between nutritional markers at birth and the need for respiratory support on the first day of life. METHODS: This retrospective study included 94 newborns admitted to the neonatal intensive care unit of Kyungpook National University Children's Hospital between March and December 2017. We measured levels of nutritional markers, including serum total protein, albumin, ferritin, 25-hydroxyvitamin D (25-OHD), and prealbumin, from cord blood or blood sample within 24 hours after birth. Respiratory support was defined as the use of nasal continuous positive airway pressure, humidified high-flow nasal cannula, or mechanical ventilation on the first day of life. RESULTS: The mean gestational age and birth weight were 36.6±2.3 weeks and 2,714±575 g, respectively. Serum total protein, albumin, prealbumin, and ferritin levels at birth were significantly correlated with gestational age and birth weight. Total protein, albumin, ferritin, and 25-OHD levels were not correlated with the time to recover birth weight after adjusting for gestational age. Moreover, prealbumin levels at birth were significantly lower in small-for-gestational-age infants than in appropriate-for-gestational-age infants. The need for respiratory support on the first day of life decreased 0.058- and 0.001-fold for every 1 g/dL increase in serum total protein (95% confidence interval [CI], 0.004 to 0.833; P=0.036) and albumin (95% CI, 0.000 to 0.136; P=0.009) levels, respectively. CONCLUSION: Nutritional status at birth could be associated with the need for respiratory support on the first day of life, regardless of the Apgar score.

Increased procalcitonin level is a risk factor for prolonged fever in children with Mycoplasma pneumonia / 소아과

PURPOSE: Macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) is characterized by prolonged fever and radiological progression despite macrolide treatment. Few studies have examined serum procalcitonin (PCT) level in children with MPP. We aimed to investigate the association of acute inflammation markers including PCT with clinical parameters in children with MPP. METHODS: A total of 147 children were recruited. The diagnosis of MPP relied on serial measurement of IgM antibody against mycoplasma and/or polymerase chain reaction. We evaluated the relationships between C-reactive protein (CRP), PCT, and lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts, and clinical severity of the disease. We used multivariate logistic regression analysis to estimate the odds ratio for prolonged fever (>3 days after admission) and hospital stay (> 6 days), comparing quintiles 2–5 of the PCT levels with the lowest quintile. RESULTS: The serum PCT and CRP levels were higher in children with fever and hospital stay than in those with fever lasting ≤ 3 days after admission and hospital stay ≤ 6 days. CRP level was higher in segmental/lobar pneumonia than in bronchopneumonia. The LDH level and WBC counts were higher in children with fever lasting for >3 days before compared to those with fever lasting for ≤ 3 days. The highest quintile of PCT levels was associated with a significantly higher risk of prolonged fever and/or hospital stay than the lowest quintile. CONCLUSION: Serum PCT and CRP levels on admission day were associated with persistent fever and longer hospitalization in children with MPP.

Diagnostic value of peripheral blood immune profiling in colorectal cancer

PURPOSE: Little is known about the clinical value of peripheral blood immune profiling. Here, we aimed to identify colorectal cancer (CRC)-related peripheral blood immune cells and develop liquid biopsy-based immune profiling models for CRC diagnosis. METHODS: Peripheral blood from 131 preoperative patients with CRC and 174 healthy controls was analyzed by flow cytometry and automated hematology. CRC-related immune factors were identified by comparing the mean values of immune cell percentages and counts. Subsequently, CRC diagnostic algorithms were constructed using binary logistic regression. RESULTS: Significant differences were observed in percentages and counts of white blood cells, lymphocytes, neutrophils, regulatory T cells, and myeloid-derived suppressor cells (MDSCs) of patients and controls. The neutrophil/lymphocyte and Th1/Th2 ratios were also significantly different. Likewise, the percentages and counts of peripheral blood programed death 1, cytotoxic T lymphocyte antigen 4, B-and T-lymphocyte attenuator, and lymphocyte activation gene-3 were higher in patients with CRC. The binary logistic regression model included 12 variables, age, CD3+%, NK%, CD4+CD279+%, CD4+CD25+%, CD4+CD152+%, CD3+CD366+%, CD3+CD272+%, CD3+CD223+%, CD158b−CD314+CD3−CD56+%, Th2%, and MDSCs cells/µL, for the prediction of cancer. Results of retrospective and prospective evaluation of the area under the curve, sensitivity, and specificity were 0.980 and 0.940, 91.53% and 85.80%, and 93.50% and 86.20%, respectively. CONCLUSION: Peripheral blood immune profiling may be valuable in evaluating the immunity of CRC patients. Our liquid biopsy-based immune diagnostic method and its algorithms may serve as a novel tool for CRC diagnosis. Future largescale studies are needed for better characterization of its diagnostic value and potential for clinical application.

Acute Gastritis and Splenic Infarction Caused by Epstein-Barr Virus / 대한소아소화기영양학회지

Epstein-Barr virus (EBV) infection can be presented with various clinical manifestations and different levels of severity when infected. Infectious mononucleosis, which is most commonly caused by EBV infection in children and adolescents, is a clinical syndrome characterized by fatigue, malaise, fever, sore throat, and generalized lymphadenopathy. But rarely, patients with infectious mononucleosis may present with gastrointestinal symptoms and complicated by gastritis, splenic infarction, and splenic rupture. We encountered a 16-year-old girl who presented with fever, fatigue, and epigastric pain. Splenic infarction and EBV-associated gastritis were diagnosed by using esophagogastroduodenoscopy and abdominal computed tomography. Endoscopy revealed a generalized hyperemic nodular lesion in the stomach, and the biopsy findings were chronic gastritis with erosion and positive in situ hybridization for EBV. As splenic infarction and acute gastritis are rare in infectious mononucleosis and are prone to be overlooked, we must consider these complications when an infectious mononucleosis patient presents with gastrointestinal symptom.

Augmentation of respiratory muscle activities in preterm infants with feeding desaturation / 소아과

PURPOSE: Frequent desaturation due to immature incoordination of suck-swallow-breathing in preterm infants can influence multiple organs such as the heart, lungs, and brain, which can then affect growth and development. Most notably in preterm infants, feeding desaturation may even affect pulmonary function during gavage feeding. Because respiratory muscle activities may reflect the work required during respiration, we evaluated the differences in these activities between full-term and preterm infants with feeding desaturation, and investigated the correlations with clinical variables. METHODS: Nineteen preterm infants with feeding desaturation (group 1) and 19 age-matched full-term infants (group 2) were evaluated. Oromotor function was evaluated using video recording. The root-mean-squre (RMS) envelope of the electromyography signal was calculated to quantify the activities of muscles involved in respiration. The differences in RMS between both groups and the correlation with clinical variables including gestational age (GA), birth weight (BW), and Apgar scores (AS) at 1 and 5 minutes after birth were evaluated. RESULTS: The RMS values of the diaphragm (RMS-D) and rectus abdominis (RMS-R) were significantly greater in group 1 compared to group 2, and the 1- and 5-min AS were significantly lower in group 1 compared to group 2. RMS-D and RMS-R were inversely correlated with GA, BW, 1- and 5-min AS in all infants. CONCLUSION: This study showed that respiratory muscle activities were augmented during feeding in preterm infants compared to full-term infants. Additionally, respiratory muscle activities were inversely correlated with all clinical variables.

Prediction of pregnancy complication occurrence using fetal cardiac output assessments made by ultrasonography at 20 to 24 weeks of gestation

OBJECTIVE: To evaluate the importance of assessment of fetal cardiac output (CO) for the prediction of complications of pregnancy. METHODS: We evaluated 65 fetuses and all of them had a fetal cardiac scan at 20 to 24 weeks of pregnancy. To measure CO, diameters (d) of the left right ventricle outflow tract were measured just above the valves. Each left CO (LCO) and right CO (RCO) was derived using the following equation: CO = velocity time integral ×π× d²/4 × heart rate. Pregnancy complications included gestational hypertensive disorders, fetal growth restriction (FGR) and preterm birth (PTB) caused from preterm labor or preterm premature rupture of membrane (PPROM). RESULTS: There were 23 cases with one more pregnancy complication (FGR, 9; gestational hypertensive disorders, 8; PTB caused from PTB or PPROM, 12). The LCO was lower in complication group than in normal group (88±53 vs. 117±48 mL/min, P=0.028). The RCO to the LCO ratio (RCO/LCO) was higher in complication group (2.43±1.69 vs. 1.48±0.81, P=0.001). Regression analysis demonstrated that RCO/LCO was a significant predictor of pregnancy complication; Odds ratio was 7.76 (95% CI, 1.15 to 52.21; P=0.029). The area under the receiver-operating characteristic curve for prediction of pregnancy complications from LCO was 0.71. The diagnostic cut-off value of LCO was 80 mL/min. The area under the receiver-operating characteristic curve from RCO/LCO was 0.68 and cut-off value was 1.41. CONCLUSION: This study demonstrated that pregnancy complications can be suspected based on fetal CO assessments at a GA of 20 to 24 weeks.

Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis / 소아과

PURPOSE: Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes. METHODS: Primary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: All MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05). CONCLUSION: Pretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways.

Brain-Derived Neurotrophic Factor (BDNF) Exerts a Protective Effect via an Anti-Apoptotic Mechanism on Hypoxic-Ischemic Injury in the Rat Brain / 대한주산의학회잡지

PURPOSE: Perinatal hypoxic-ischemic (HI) brain injury remains a common cause of chronic handicapping conditions of cerebral palsy, mental retardation, learning disability, and epilepsy. HI brain injury induces cell death via either necrosis or apoptosis. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family. It plays key roles in survival, differentiation, and maintenance of neurons. This study was to investigate the neuroprotective effects of BDNF via the mechanisms of anti-apoptosis in HI brain injury by using cortical astrocyte and neuronal cell culture. METHODS: Cortical astrocytes culture of 1-day-old Sprague-Dawley (SD) rat pups and embryonic cortical neuronal cell culture of SD rats at 14-day gestation were done. The Normoxia group was prepared in 5% CO2 incubators and the Hypoxia group and Hypoxia+BDNF group (after treatment with BDNF for 24 hours) were placed in 1% O2 incubators (94% N2, 5% CO2) for 6 or 18 hours. The expression of Bcl-2 and Bax were assessed by real-time PCR and western blot. The caspase-3 activation was evaluated by caspase activity assay kit. RESULTS: In astrocyte and neuronal cell, the expressions of Bcl-2 in the hypoxia groups were reduced compared to the normoxia groups, whereas, those in the Hypoxia+BDNF groups were increased compared to the hypoxia groups. However, the expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were revealed reversely. In astrocyte, Hypoxia group for 6 hours was not significantly altered in Bcl-2, Bax expressions. CONCLUSION: BDNF neuroprotective effects on HI brain injury in neonatal rats may occur via anti-apoptotic mechanism.

Erratum: Developmental profiles of preschool children with delayed language development / 소아과

In this article, first author's name was misspelled unintentionally.

Attenuation of RANKL-induced Osteoclast Formation via p38-mediated NFATc1 Signaling Pathways by Extract of Euphorbia Lathyris L

BACKGROUND: Osteoclasts are the only cell type capable of breaking down bone matrix, and its excessive activation is responsible for the development of bone-destructive diseases. Euphorbia lathyris L. (ELL) is an herbal plant that belongs to the Euphorbiaceae family. This study investigated the effects of the methanol extract of the aerial part of ELL on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and signaling pathways. METHODS: Osteoclasts were formed by co-culturing mouse bone marrow with osteoblasts or by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL. Bone resorption assays were performed using dentine slices. The expression level of mRNA was analyzed by real-time polymerase chain reaction (PCR) or reverse transcription (RT)-PCR. Western blotting assays were performed to detect the expression or activation level of proteins. RESULTS: ELL inhibited RANKL-induced osteoclast formation without cytotoxicity. Furthermore, the RANKL-stimulated bone resorption was diminished by ELL. Mechanistically, ELL blocked the RANKL-triggered p38 mitogen-activated protein kinase (MAPK) phosphorylation, which resulted in the suppression of the expression of c-Fos and nuclear factor of activated T cells (NFATc1). In osteoblasts, ELL had little effect on the mRNA expression of RANKL and osteoprotegerin (OPG). CONCLUSIONS: The present data suggest that ELL has an inhibitory effect on osteoclast differentiation and function via downregulation of the p38/c-Fos/NFATc1 signaling pathways. Thus, ELL could be useful for the treatment of bone diseases associated with excessive bone resorption.

Bee Venom Exerts Neuroprotective Effects on Neuronal Cells and Astrocytes under Hypoxic Conditions Through MAPK Signaling Pathways

PURPOSE: Hypoxic-ischemic brain injuries influence the mechanisms of signal transduction, including mitogen-activated protein kinase (MAPK) that regulates gene expression through transcription factor activity. Several attempts have been made to use bee venom (BV) to treat neurological diseases. However, limited data are available for brain injuries such as neonatal hypoxic-ischemic encephalopathy (HIE) and neurodegenerative disorders. The purpose of this study was to investigate the neuroprotective effects of BV by determining the expression of activated MAPK pathways. METHODS: We examined activation and cell viability in hypoxia (1% O2, 5% CO2, 94% N2) in low glucose-treated (H+low G) neuronal cells and astrocytes in the presence and absence of BV. After they were subjected to hypoxic conditions and treated with low glucose, the cells were maintained for 0, 6, 15, and 24 h under normoxic conditions. RESULTS: Extracellular-signal-regulated kinases 1/2 (ERK1/2), p38 MAPK, and stress-activated protein kinases (SAPK)/Jun amino-terminal kinases (JNK) were activated in H+low G conditions. Particularly, phosphorylation of ERK1/2 was maximized 6 h after exposure to H+low G condition. BV specifically inhibited the phosphorylation of ERK1/2. However, BV had no effect on p38 MAPK or SAPK/JNK. In addition, BV improved neuronal cell and astrocytes viability following exposure to H+low G. CONCLUSION: ERK inactivation is known to mediate protective effects in hypoxic brain injury. Taken together, these results suggest that treatment with BV may be helpful in reducing hypoxic injury in neonatal HIE through the ERK signaling pathway.

Significance of total serum IgE in children with lower respiratory infections due to respiratory syncytial virus

PURPOSE: Respiratory syncytial virus (RSV) is known to induce Th2 immune response with increased IgE production. We investigated serum IgE levels in RSV bronchiolitis/pneumonia (RSV-LRI) in relation to disease severity. METHODS: One hundred seven children admitted with RSV-LRI were enrolled. The patients were divided into 2 groups according to serum IgE levels: the high IgE (n=39, more than 2 standard deviations from the mean levels for age-matched controls) and low IgE groups (n=68). We investigated if there were any differences in clinical and laboratory findings, and recurrence of wheezing between the 2 groups. The difference in IgE levels between severe (severity score≥3) and nonsevere groups was also studied. RESULTS: More frequent and prolonged fever was observed in the high IgE group than in the low IgE group (P<0.05). Patients showing severe symptoms or respiratory difficulties were more frequently seen in the high IgE group (P=0.01). There was no difference in parental allergy and atopic sensitization. The nearly same findings were observed in reanalysis of data from patients with the first RSV-LRI, but recurrence of wheezing was significantly higher in the high IgE group than in the low IgE group (P=0.04). Patients with high IgE levels were more frequently seen in severe patients than in nonsevere patients (P=0.01). CONCLUSION: Our study showed that children who presented with high serum IgE levels during RSV infections had more severe symptoms compared to those with low IgE levels. It suggests that measurement of total serum IgE levels might be helpful in evaluating disease severity and recurrent wheezing in children admitted with RSV-LRI.