Redox modification of cell signaling in the cardiovascular system

Oxidative stress is presumed to be involved in the pathogenesis of many diseases, including cardiovascular disease. However, oxidants are also generated in healthy cells, and increasing evidence suggests that they can act as signaling molecules. The intracellular reduction-oxidation (redox) status is tightly regulated by oxidant and antioxidant systems. Imbalance between them causes oxidative or reductive stress which triggers cellular damage or aberrant signaling, leading to dysregulation. In this review, we will briefly summarize the aspects of ROS generation and neutralization mechanisms in the cardiovascular system. ROS can regulate cell signaling through oxidation and reduction of specific amino acids within proteins. Structural changes during post-translational modification allow modification of protein activity which can result in altered cellular function. We will focus on the molecular basis of redox protein modification and how this regulatory mechanism affects signal transduction in the cardiovascular system. Finally, we will discuss some techniques applied to monitoring redox status and identifying redox-sensitive proteins in the heart. This article is part of a Special Section entitled "Post-translational Modification."     

Focal Lesion in Upper Part of Brachial Plexus can be Detected by Magnetic Cervical Motor Root Stimulation

BackgroundThe utilities of magnetic cervical motor root stimulation are well known for lesions in the lower part of the brachial plexus, but not for lesions in the other parts.ObjectiveThe aim of paper is to show the utilities of magnetic cervical motor root stimulation for lesions in the upper part of the brachial plexus.MethodsWe analyzed the brachial plexus using both electrical stimulation at Erb's point and magnetic cervical motor root stimulation in a patient with brachial plexopathy caused by tumor invasion.ResultsOn the fourth day after onset, magnetic cervical motor root stimulation revealed abnormal findings in the upper part of the brachial plexus. Two weeks after onset, needle electromyography supported the existence of the focal lesion.ConclusionMagnetic cervical motor root stimulation is useful in detecting abnormal findings in the upper part of the brachial plexus, even at the acute phase.     

Determinants of in-hospital death in patients with postinfarction ventricular septal perforation

Ventricular septal perforation (VSP) is a serious complication associated with acute myocardial infarction (MI). The purpose of this study was to investigate the determinants of in-hospital death in patients with postinfarction VSP. Between January 1990 and April 2010, we identified 37 patients from our hospital records. Univariate analysis and multivariate logistic regression analysis were performed to find the determinants of in-hospital death. In-hospital mortality was 35% (13/37 patients). History of hypertension (P = 0.03), percutaneous coronary intervention (P = 0.04), and preoperative percutaneous cardiopulmonary support (P = 0.04) were associated with in-hospital death, whereas history of hyperlipidemia was associated with in-hospital survival. The interval from MI to VSP in survivors was significantly longer than that in nonsurvivors (P < 0.01). In multivariate logistic regression analysis, a shorter interval from MI to VSP (odds ratio 0.57, 95% confidence interval 0.34-0.95, P = 0.03) was found to be an independent predictor of in-hospital death. In conclusion, in-hospital mortality was high in patients with postinfarction VSP. A shorter interval from MI to VSP was a significant independent predictor of in-hospital death.     

Donor–acceptor random regioregular π-conjugated copolymers based on poly(3-hexylthiophene) with unsymmetrical monothienoisoindigo units

Donor–acceptor π-conjugated random copolymers based on regioregular poly(3-hexylthiophene), rr-P3HT, with unsymmetrical monothienoisoindigo moieties were obtained by direct arylation polycondensation of 2-bromo-3-hexylthiophene with unsymmetrical monothienoisoindigo motifs under the optimized conditions [palladium-immobilized on thiol-modified silica gel with chloride counter anions, PITS-Cl (2.5 mol%), PivOH (1.0 equiv.), K₂CO₃ (3.0 equiv.), DMAc, 100 °C, 24 h]. Incorporation of unsymmetrical monothienoisoindigo electron-acceptor units into the polymers tuned their highest occupied and lowest unoccupied molecular orbital levels, which were close to those of the hole transport material (PEDOT) and electron transport material (PCBM), respectively, in thin-film organic solar cells. Alkyl chains of the unsymmetrical monothienoisoindigo units in the polymers tuned their macrostructural order, resulting in the observation of crystalline patterns and specific absorption peaks in thin films. An organic solar cell containing the most crystalline random copolymer showed an efficiency of 1.91%.

Donor–acceptor π-conjugated random copolymers based on regioregular poly(3-hexylthiophene) with unsymmetrical monothienoisoindigo moieties were obtained by direct arylation polycondensation.     

Synergistic anti-tumor efficacy by combination therapy of a self-assembled nanogel vaccine with an immune checkpoint anti-PD-1 antibody

Therapeutic strategies for cancer involving immune checkpoint inhibitors (ICIs) have been gaining widespread attention, but their efficacy remains limited. Thus, combination of ICI therapies with other therapeutic modalities may be required to improve their outcomes. In this study, we examined the improved efficacy of a CHP nanogel-based vaccine delivery system after combination with ICI therapy. For this, we evaluated the therapeutic efficacy of combining an anti-PD-1 antibody as an ICI with an OVA antigen-complexed CHP nanogel vaccine delivery system in a mouse E.G7-OVA tumor model. Mice were subcutaneously inoculated with E.G7-OVA tumor cells on one side of the back, and subcutaneously injected with OVA or the OVA/CHP nanogel vaccine on the other side of the back. Anti-PD-1 antibody was administered at defined intervals. Tumor volume, immune responses, and tumor-infiltrating cells were evaluated. Mice treated with OVA vaccine alone showed weak tumor suppression compared with untreated control mice. Mice receiving combined OVA/CHP nanogel vaccine and anti-PD-1 antibody therapy exhibited strong tumor growth suppression and markedly improved survival, suggesting that PD-1 signaling blockade by the anti-PD-1 antibody enhanced the anti-tumor efficacy of the OVA vaccine. Furthermore, tumor-infiltrating cells and immune responses were increased in the combined therapy group. No serious side effects were observed for any of the treatments. Taken together, the immune system activation induced by the CHP nanogel vaccine was synergistically enhanced by the anti-PD-1 antibody. The present findings suggest the potential for enhanced therapeutic efficacy by combining the CHP nanogel vaccine delivery system with ICI therapy for various cancer types.

Combination therapy of OVA/CHP nanogel vaccine with anti-PD-1 antibody synergistically improved anti-tumor effect and survival rate without side effects.     

Comparison of Pentax-AWS Airwayscope, Airtraq and Miller laryngoscope for tracheal intubation by novice doctors during infant cardiopulmonary resuscitation simulation: a randomized crossover trial

Recent guidelines for infant cardiopulmonary resuscitation emphasize that all rescuers should minimize interruption of chest compressions, even for endotracheal intubation. We compared the utility of the Pentax-AWS Airway Scope (AWS) with an infant-sized Intlock (AWS-I), Airtraq laryngoscope (ATQ) and Miller laryngoscope during chest compressions on an infant manikin. Twenty-three novice doctors performed tracheal intubation on an infant manikin using the AWS-I, ATQ and Miller laryngoscope, with or without chest compressions. In Miller laryngoscope trials, one participant failed to secure the airway without chest compressions, while nine failed with compressions (P < 0.05). In ATQ trials, none of the participants failed without compressions, while six failed with compressions (P < 0.05). In AWS-I trials, all participants succeeded regardless of chest compressions. Intubation time was significantly longer with chest compressions with the Miller laryngoscope and ATQ, but not with the AWS-I. The AWS-I is an effective device for endotracheal intubation during chest compressions in infant simulations managed by novice doctors.     

Cervical Lymph Node Dissection for Clinically Submucosal Carcinoma of the Thoracic Esophagus

Background

The purposes of this study were to clarify the risk factors for supraclavicular lymph node (SCLN) metastasis and the survival benefit from cervical lymph node (LN) dissections in patients with clinically submucosal (cT1b) carcinoma of the thoracic esophagus.

Methods

A total of 86 patients with this disease who underwent esophagectomy with 3-field lymph node dissection were retrospectively reviewed. Multivariate logistic regression and Cox proportional hazard model were used to identify the independent risk factors for SCLN metastasis and prognostic factors, respectively. An index calculated by multiplying the frequency of metastasis at nodal basin and the 5-year overall survival rate of patients with metastasis at that basin were used to assess the therapeutic outcomes.

Results

A total of 40 patients (47 %) were found to have pathological LN metastasis. Also, 13 patients (15 %) had cervical LN metastasis: 6 and 7 with carcinoma of the upper and mid-thoracic esophagus, respectively. SCLN metastasis was found in 6 patients (7 %); however, there was no independent risk factor for SCLN metastasis. The 5-year overall survival rate was 72.5 %. Cervical LN metastasis was an independent prognostic factor (p = .04; odds ratio 2.55; 95 % confidence interval 1.03–6.31); however, there was no significant difference in survival between patients with SCLN metastasis and those without (p = .06). The calculated index of estimated benefit from cervical LN dissections was 6.9, following upper mediastinal LN of 15.6 and perigastric LN of 8.3.

Conclusions

We could not identify risk factors to predict SCLN metastasis. Cervical LN dissection should not be omitted in patients with cT1b carcinoma, especially of the upper and mid-thoracic esophagus.