Cell type–dependent variation in paracrine potency determines therapeutic efficacy against neonatal hyperoxic lung injury

AbstractBackground aimsThe aim of this study was to determine the optimal cell type for transplantation to protect against neonatal hyperoxic lung injury. To this end, the in vitro and in vivo therapeutic efficacies and paracrine potencies of human umbilical cord blood–derived mesenchymal stromal cells (HUMs), human adipose tissue–derived mesenchymal stromal cells (HAMs) and human umbilical cord blood mononuclear cells (HMNs) were compared.MethodsHyperoxic injury was induced in vitro in A549 cells by challenge with H2O2. Alternatively, hyperoxic injury was induced in newborn Sprague-Dawley rats in vivo by exposure to hyperoxia (90% oxygen) for 14 days. HUMs, HAMs or HMNs (5 × 105 cells) were given intratracheally at postnatal day 5.ResultsHyperoxia-induced increases in in vitro cell death and in vivo impaired alveolarization were significantly attenuated in both the HUM and HAM groups but not in the HMN group. Hyperoxia impaired angiogenesis, increased the cell death and pulmonary macrophages and elevated inflammatory cytokine levels. These effects were significantly decreased in the HUM group but not in the HAM or HMN groups. The levels of human vascular endothelial growth factor and hepatocyte growth factor produced by donor cells were highest in HUM group, followed by HAM group and then HMN group.ConclusionsHUMs exhibited the best therapeutic efficacy and paracrine potency than HAMs or HMNs in protecting against neonatal hyperoxic lung injury. These cell type-dependent variations in therapeutic efficacy might be associated or mediated with the paracrine potency of the transplanted donor cells

Change of Femoral Anteversion Angle in Children With Intoeing Gait Measured by Three-Dimensional Computed Tomography Reconstruction: One-Year Follow-Up Study

ObjectiveTo evaluate femoral anteversion angle (FAA) change in children with intoeing gait depending on age, gender, and initial FAA using three-dimensional computed tomography (3D-CT).MethodsThe 3D-CT data acquired between 2006 and 2016 were retrospectively reviewed. Children 4 to 10 years of age with symptomatic intoeing gait with follow-up interval of at least 1 year without active treatment were enrolled. Subjects were divided into three groups based on age: group 1 (≥4 and <6 years), group 2 (≥6 and <8 years), and group 3 (≥8 and <10 years). Initial and follow-up FAAs were measured using 3D-CT. Mean changes in FAAs were calculated and compared.ResultsA total of 200 lower limbs of 100 children (48 males and 52 females, mean age of 6.1±1.6 years) were included. The mean follow-up period was 18.0±5.4 months. Average initial and follow-up FAA in children with intoeing gait was 31.1°±7.8° and 28.9°±8.2°, respectively. The initial FAA of group 1 was largest (33.5°±7.7°). Follow-up FAA of group 1 was significantly reduced to 28.7°±9.2° (p=0.000). FAA changes in groups 1, 2, and 3 were −6.5°±5.8°, −6.4°±5.1°, and −5.3°±4.0°, respectively. These changes of FAA were not significantly (p=0.355) different among the three age groups. However, FAA changes were higher (p=0.012) in females than those in males. In addition, FAA changes showed difference depending on initial FAA. When initial FAA was smaller than 30°, mean FAA change was −5.6°±4.9°. When initial FAA was more than 30°, mean FAA change was −6.8°±5.4° (p=0.019).ConclusionFAA initial in children with intoeing gait was the greatest in age group 1 (4–6 years). This group also showed significant FAA decrease at follow-up. FAA changes were greater when the child was a female, younger, and had greater initial FAA

Acute Cerebral Infarction Following Intravenous Glycoprotein IIb/IIIa Inhibitor for Acute Myocardial Infarction

Stroke is a rare but serious complication of acute myocardial infarction (AMI). Currently, glycoprotein (GP) IIb/IIIa inhibitor is used in clinical practice for acute coronary syndromes and percutaneous coronary interventions (PCIs). The incidence of stroke in patients receiving GP IIb/IIIa inhibitor during PCIs is very low. We report the case of a 47-year-old man who presented with AMI and suffered an acute cerebral infarction after infusion of a GP IIb/IIIa inhibitor following primary PCI

Increased phosphorylation of Ser473-Akt, Ser9-GSK-3beta and Ser133-CREB in the rat frontal cortex after MK-801 intraperitoneal injection

GSK-3beta is regarded as playing an important part in the pathogenesis of schizophrenia and the action of psychotomimetic agents. We observed phosphorylation of molecules associated with the GSK-3beta signalling pathway in the rat brain after MK-801 injection, which induces a schizophrenia-like state in humans. Ser9-GSK-3beta phosphorylation was increased after injection of 1 mg/kg MK-801 in the rat frontal cortex but not in the hippocampus or cerebellum. This increase peaked at 30 min and was maintained until 90 min after injection. The phosphorylation showed a dose-dependent increase up to 1 mg/kg MK-801, followed by a decrease at higher dosage. Furthermore, phosphorylation of Ser473-Akt and Ser133-CREB showed similar temporal, dose-dependent and regionally specific patterns with those of Ser9-GSK-3beta. However, phosphorylation of Dvl and Ser33-beta-catenin was not affected by MK-801. These results suggest that GSK-3beta phosphorylation by MK-801 may be associated with the Akt-GSK-3beta pathway rather than with the Wnt-Dvl-GSK3beta pathway

Polymeric tandem organic light-emitting diodes using a self-organized interfacial layer

The authors have demonstrated efficient polymeric tandem organic light-emitting diodes (OLEDs) with a self-organized interfacial layer, which was formed by differences in chemical surface energy. Hydrophilic poly(styrene sulfonate)-doped poly(3,4-ethylene dioxythiophene) (PEDOT:PSS) was spin coated onto the hydrophobic poly(9,9-dyoctilfluorene) (PFO) surface and a PEDOT:PSS bubble or dome was built as an interfacial layer. The barrier heights of PEDOT:PSS and PFO in the two-unit tandem OLED induced a charge accumulation at the interface in the heterojunction and thereby created exciton recombination at a much higher level than in the one-unit reference. This effect was confirmed in both the hole only and the electron only devices. (c) 2008 American Institute of Physicsopen8

Successful Treatment of Tracheal Stenosis with Slide Tracheoplasty after the Failure of Resection with End-to-End Anastomosis

The combined effects of inhaled irritant gases and heat in burn patients can result in the development of laryngotracheal strictures. Several factors could adversely affect the development of tracheal stenosis and cause the growth of granulation tissue. Yet the current treatment options for this condition are limited because of the paucity of case reports. We report here on a case of a patient who experienced recurrent upper tracheal stenosis after an inhalation injury. She displayed repetitive symptoms of stenosis even after several laryngomicrosurgeries and resection with end-to-end anastomosis. Finally, 5 yr after the burn injury, slide tracheoplasty was successfully performed and the postoperative check-up findings and the increased airway volume seen on imaging were all satisfactory

Expression of Matrix Metalloproteinases and Their Inhibitors in Squamous Cell Carcinoma of the Tonsil and Their Clinical Significance

ObjectivesTo investigate expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in squamous cell carcinoma of the tonsil and to correlate expression profiles with clinicopathological characteristics.MethodsParaffin blocks were obtained from 45 tonsil squamous cell carcinoma (SCC) patients, who underwent surgery as an initial treatment between 1994 and 2004, and from 20 normal controls. Expressions of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 were investigated immunohistochemically.ResultsThe expressions of MMPs (except MMP-2) and TIMPs were found to be significantly different in tonsil SCC and normal control tissues. Furthermore, MMP-13 expression was found to be correlated with tumor invasion (P=0.05), and the expressions of MMP-9 and TIMP-1 with nodal metastasis (P=0.048, 0.031). No relation was found between MMP or TIMP expression and recurrence. However, MMP-9 expression was found to be significantly associated with 5-year survival in tonsil SCC patients by multivariate analysis (hazard ratio, 3.853; P=0.013).ConclusionSignificant overexpressions of multiple MMPs and TIMPs were found in tonsil SCC tissues. Furthermore, our findings suggest that MMP-9 expression might be a useful prognostic factor

Uncontrolled Self-Medication with Venlafaxine in a Patient with Major Depressive Disorder

Antidepressants are known to have no significant ability to cause addiction. However, a recent study showed many individuals with mood disorders self-medicated with antidepressants to relieve symptoms. We report here a male physician, diagnosed five years ago with major depressive disorder, with insomnia, anxiousness, and chest heaviness. He began self-medicating with 150 mg of venlafaxine daily, without any monitoring. During his most recent severe depressive episode, he was taking up to 1,500 mg of venlafaxine daily. Without this medication, he experienced discontinuation syndrome, which included severe anxiety, chest heaviness, and breathing difficulty, and which he judged as indicating a more severely depressed state. He also experienced overdose symptoms, such as hypertension and tachycardia. He attempted suicide with drugs that he possessed. In conclusion, careful monitoring is needed when treating patients with venlafaxine, because its discontinuation syndrome is similar to symptoms of major depressive disorder, and suicidality may result from an overdose

The effects of repeated administrations of MK-801 on ERK and GSK-3beta signalling pathways in the rat frontal cortex

Repeated administrations of NMDA receptor antagonists induce behavioural changes which resemble the symptoms of schizophrenia in animals. ERK and GSK-3beta associated signalling pathways have been implicated in the pathogenesis of psychosis and in the action mechanisms of various psychotropic agents. Here, we observed the phosphorylations of ERK and GSK-3beta and related molecules in the rat frontal cortex after repeated intraperitoneal injections of MK-801, over periods of 1, 5, and 10 d. Repeated treatment with 0.5, 1, and 2 mg/kg MK-801 increased the phosphorylation levels of the MEK-ERK-p90RSK and Akt-GSK-3beta pathways and concomitantly and significantly increased CREB phosphorylation in the rat frontal cortex. However, single MK-801 treatment did not induce these significant changes. In addition, the immunoreactivities of HSP72, Bax, and PARP were not altered, which suggests that neuronal damage may not occur in the rat frontal cortex in response to chronic MK-801 treatment. These findings suggest that chronic exposure to MK-801 may induce pro-survival and anti-apoptotic activity without significant neuronal damage in the rat frontal cortex. Moreover, this adaptive change might be associated with the psychotomimetic action of MK-801