Hypoxia-inducible factor: role in cell survival in superoxide dismutase overexpressing mice after neonatal hypoxia-ischemia.

BackgroundSixty percent of infants with severe neonatal hypoxic-ischemic encephalopathy die, while most survivors have permanent disabilities. Treatment for neonatal hypoxic-ischemic encephalopathy is limited to therapeutic hypothermia, but it does not offer complete protection. Here, we investigated whether hypoxia-inducible factor (HIF) promotes cell survival and suggested neuroprotective strategies.PurposeHIF-1α-deficient mice have increased brain injury after neonatal hypoxia-ischemia (HI), and the role of HIF-2α in HI is not well characterized. Copper-zinc superoxide dismutase (SOD)1 overexpression is not beneficial in neonatal HI. The expression of HIF-1α and HIF-2α was measured in SOD1 overexpressing mice and compared to wild-type littermates to see if alteration in expression explains this lack of benefit.MethodsOn postnatal day 9, C57Bl/6 mice were subjected to HI, and protein expression was measured by western blotting in the ipsilateral cortex of wild-type and SOD1 overexpressing mice to quantify HIF-1α and HIF-2α. Spectrin expression was also measured to characterize the mechanism of cell death.ResultsHIF-1α protein expression did not significantly change after HI injury in the SOD1-overexpressing or wild-type mouse cortex. However, HIF-2α protein expression increased 30 minutes after HI injury in the wild-type and SOD1-overexpressing mouse cortex and decreased to baseline value at 24 hours after HI injury. Spectrin 145/150 expression did not significantly change after HI injury in the SOD1- overexpressing or wild-type mouse cortex. However, spectrin 120 expression increased in both wild-type and SOD1-overexpressing mouse at 4 hours after HI, which decreased by 24 hours, indicating a greater role of apoptotic cell death.ConclusionHIF-1α and HIF-2α may promote cell survival in neonatal HI in a cell-specific and regional fashion. Our findings suggest that early HIF-2α upregulation precedes apoptotic cell death and limits necrotic cell death. However, the influence of SOD was not clarified; it remains an intriguing factor in neonatal HI

Surfactant preparations for preterm infants with respiratory distress syndrome: past, present, and future

Following the first successful trial of surfactant replacement therapy for preterm infants with respiratory distress syndrome (RDS) by Fujiwara in 1980, several animal-derived natural surfactants and synthetic surfactants have been developed. Synthetic surfactants were designed to overcome limitations of natural surfactants such as cost, immune reactions, and infections elicited by animal proteins contained in natural surfactants. However, first-generation synthetic surfactants that are protein-free have failed to prove their superiority over natural surfactants because they lack surfactant protein (SP). Lucinactant, a second-generation synthetic surfactant containing the SP-B analog, was better or at least as effective as the natural surfactant, suggesting that lucinactant could act an alternative to natural surfactants. Lucinactant was approved by the U. S. Food and Drug Administration in March 2012 as the fifth surfactant to treat neonatal RDS. CHF5633, a second-generation synthetic surfactant containing SP-B and SP-C analogs, was effective and safe in a human multicenter cohort study for preterm infants. Many comparative studies of natural surfactants used worldwide have reported different efficacies for different preparations. However, these differences are believed to due to site variations, not actual differences. The more important thing than the composition of the surfactant in improving outcome is the timing and mode of administration of the surfactant. Novel synthetic surfactants containing synthetic phospholipid incorporated with SP-B and SP-C analogs will potentially represent alternatives to natural surfactants in the future, while improvement of treatment modalities with less-invasive or noninvasive methods of surfactant administration will be the most important task to be resolved

Erythropoietin Reduces Death and Neurodevelopmental Impairment in Neonatal Hypoxic-Ischemic Encephalopathy

Purpose Erythropoietin (EPO) is a promising neuroprotective drug. We investigated whether EPO has beneficial effects on neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy (HIE). Methods We retrospectively reviewed the data of 56 infants with HIE born at or after 35 weeks of gestation who were admitted to Inha University Hospital between 2012 and 2021. Patients were divided into two groups based on EPO use and compared. In the EPO group, patients were administered 1,000 U/kg of EPO on days 1, 2, 3, 5, and 7, starting within 24 hours after birth. The primary outcome was death or neurodevelopmental impairment (NDI) at the age of 12 months. Results EPO was administered to 38 infants, and 18 did not receive EPO. Only 37.5% of patients with HIE (21/56) and 60% of patients with moderate-to-severe HIE (21/35) received therapeutic hypothermia. Among all patients with HIE, death or NDI (21.1 % vs. 50.0%; odds ratio [OR], 0.09; 95% confidence interval [CI], 0.01 to 0.78; P=0.029) and brain injury on imaging (42.1% vs. 83.3%; OR, 0.16; 95% CI, 0.03 to 0.92; P=0.040) were significantly lower in the EPO group than in the control group. Among patients with moderate-to-severe HIE, brain injury on imaging (54.2% vs. 90.9%; OR, 0.04; 95% CI, 0.002 to 0.700; P=0.027) was significantly lower in the EPO group than in the control group. Conclusion EPO administration significantly reduced mortality and NDI in infants with HIE. EPO can be considered an adjunctive therapeutic agent for neonatal HIE

The First Korean Case of Cutaneous Lung Tissue Heterotopia

Cutaneous lung tissue heterotopia is a very rare disorder where mature lung tissues develop in the skin. This is only the second known report of cutaneous lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn infant had a hemangioma-like, freely movable mass connected to the anterior aspect of the sternal manubrium. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and branchial cleft cyst by histology and the location of the mass. We describe the clinical, radiologic, and pathologic findings of a cutaneous lung tissue heterotopia, the first reported in Korea

Erythropoietin Attenuates Brain Injury, Subventricular Zone Expansion, and Sensorimotor Deficits in Hypoxic-Ischemic Neonatal Rats

The aim of this study was to investigate the effect of erythropoietin (EPO) on histological brain injury, subventricular zone (SVZ) expansion, and sensorimotor function deficits induced by hypoxia-ischemia (HI) in newborn rat pups. Seven-day-old male rat pups were divided into six groups: normoxia control, normoxia EPO, hypoxia control, hypoxia EPO, HI control, and HI EPO group. Sham surgery or HI was performed in all animals. HI was induced by ligation of the right common carotid artery followed by 90 min of hypoxia with 8% oxygen. Recombinant human EPO 3 U/g or saline was administered intraperitoneally, immediately, at 24- and 48-hr after insult. At two weeks after insult, animals were challenged with cylinder-rearing test for evaluating forelimb asymmetry to determine sensorimotor function. All animals were then sacrificed for volumetric analysis of the cerebral hemispheres and the SVZ. The saline-treated HI rats showed marked asymmetry by preferential use of the non-impaired, ipsilateral paw in the cylinder-rearing test. Volumetric analysis of brains revealed significantly decreased preserved ipsilateral hemispheric volume and increased ipsilateral SVZ volume compared with the sham-operated animals. Treatment of EPO significantly improved forelimb asymmetry and preserved ipsilateral hemispheric volume along with decreased expansion of ipsilateral SVZ following HI compared to the saline-treated HI rats. These results support the use of EPO as a candidate drug for treatment of neonatal hypoxic-ischemic brain damage

LOWER EXTREMITY KINEMATICS OF SKI MOTION ON HILLS

This research study aimed to collect thre- dimensional joint angles of the lower extremity during a basic ski motion in order to provide more quantitative teaching guide-lines for ski instructors. Eleven infrared cameras were placed to cover the capture volume of three different stopping movements (e.g. “Pflug Fahren”) on hills. Six ski instructors participated in the test. Three trials of each stop were selected for comparison. Based on the results, skiers tended to use the edge of the ski and maintain a wider “V” shape at the shortest stop distance (e.g. 2m) compared to the other stops. Also, each skier had to invert the foot with a less flexed and more abducted knee and hip position as the stopping distance was decreased. This information will be useful for the development of more objective teaching guide-lines for beginner skiers

A case of de novo duplication of 15q24-q26.3

Distal duplication, or trisomy 15q, is an extremely rare chromosomal disorder characterized by prenatal and postnatal overgrowth, mental retardation, and craniofacial malformations. Additional abnormalities typically include an unusually short neck, malformations of the fingers and toes, scoliosis and skeletal malformations, genital abnormalities, particularly in affected males, and, in some cases, cardiac defects. The range and severity of symptoms and physical findings may vary from case to case, depending upon the length and location of the duplicated portion of chromosome 15q. Most reported cases of duplication of the long arm of chromosome 15 frequently have more than one segmental imbalance resulting from unbalanced translocations involving chromosome 15 and deletions in another chromosome, as well as other structural chromosomal abnormalities. We report a female newborn with a de novo duplication, 15q24-q26.3, showing intrauterine overgrowth, a narrow asymmetric face with down-slanting palpebral fissures, a large, prominent nose, and micrognathia, arachnodactyly, camptodactyly, congenital heart disease, hydronephrosis, and hydroureter. Chromosomal analysis showed a 46,XX,inv(9)(p12q13),dup(15)(q24q26.3). Array comparative genomic hybridization analysis revealed a gain of 42 clones on 15q24-q26.3. This case represents the only reported patient with a de novo 15q24-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component in Korea

Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Isolates Causing Invasive and Noninvasive Pneumococcal Diseases in Korea from 2008 to 2014

Introduction. Streptococcus pneumoniae is an important pathogen with high morbidity and mortality rates. The aim of this study was to evaluate the distribution of common serotypes and antimicrobial susceptibility of S. pneumoniae in Korea. Methods. A total of 378 pneumococcal isolates were collected from 2008 through 2014. We analyzed the serotype and antimicrobial susceptibility for both invasive and noninvasive isolates. Results. Over the 7 years, 3 (13.5%), 35 (10.8%), 19A (9.0%), 19F (6.6%), 6A (6.1%), and 34 (5.6%) were common serotypes/serogroups. The vaccine coverage rates of PCV7, PCV10, PCV13, and PPSV23 were 21.4%, 23.3%, 51.9%, and 62.4% in all periods. The proportions of serotypes 19A and 19F decreased and nonvaccine serotypes increased between 2008 and 2010 and 2011 and 2014. Of 378 S. pneumoniae isolates, 131 (34.7%) were multidrug resistant (MDR) and serotypes 19A and 19F were predominant. The resistance rate to levofloxacin was significantly increased (7.2%). Conclusion. We found changes of pneumococcal serotype and antimicrobial susceptibility during the 7 years after introduction of the first pneumococcal vaccine. It is important to continuously monitor pneumococcal serotypes and their susceptibilities