Inhibition of cAMP/PKA Pathway Protects Optic Nerve Head Astrocytes against Oxidative Stress by Akt/Bax Phosphorylation-Mediated Mfn1/2 Oligomerization.

Glaucoma is characterized by a progressive optic nerve degeneration and retinal ganglion cell loss, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role in glaucomatous neurodegeneration. Here, we investigate the impact of activation of cyclic adenosine 3',5'-monophosphate (cAMP)/protein kinase A (PKA) pathway on mitochondrial dynamics of ONH astrocytes exposed to oxidative stress. ONH astrocytes showed a significant loss of astrocytic processes in the glial lamina of glaucomatous DBA/2J mice, accompanied by basement membrane thickening and collagen deposition in blood vessels and axonal degeneration. Serial block-face scanning electron microscopy data analysis demonstrated that numbers of total and branched mitochondria were significantly increased in ONH astrocytes, while mitochondrial length and volume density were significantly decreased. We found that hydrogen peroxide- (H2O2-) induced oxidative stress compromised not only mitochondrial bioenergetics by reducing the basal and maximal respiration but also balance of mitochondrial dynamics by decreasing dynamin-related protein 1 (Drp1) protein expression in rat ONH astrocytes. In contrast, elevated cAMP by dibutyryl-cAMP (dbcAMP) or isobutylmethylxanthine treatment significantly increased Drp1 protein expression in ONH astrocytes. Elevated cAMP exacerbated the impairment of mitochondrial dynamics and reduction of cell viability to oxidative stress in ONH astrocytes by decreasing optic atrophy type 1 (OPA1), and mitofusin (Mfn)1/2 protein expression. Following combined treatment with H2O2 and dbcAMP, PKA inhibition restored mitochondrial dynamics by increasing mitochondrial length and decreasing mitochondrial number, and this promoted cell viability in ONH astrocytes. Also, PKA inhibition significantly promoted Akt/Bax phosphorylation and Mfn1/2 oligomerization in ONH astrocytes. These results suggest that modulation of the cAMP/PKA signaling pathway may have therapeutic potential by activating Akt/Bax phosphorylation and promoting Mfn1/2 oligomerization in glaucomatous ONH astrocytes

Tumor hypoxia and reoxygenation: the yin and yang for radiotherapy.

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of ‘reoxygenation’ phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because ‘reoxygenation’ is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn’t it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy. © 2016. The Korean Society for Radiation Oncology.11Yscopu

Retrieval of NO2 Column Amounts from Ground-Based Hyperspectral Imaging Sensor Measurements

Total column amounts of NO2 (TCN) were estimated from ground-based hyperspectral imaging sensor (HIS) measurements in a polluted urban area (Seoul, Korea) by applying the radiance ratio fitting method with five wavelength pairs from 400 to 460 nm. We quantified the uncertainty of the retrieved TCN based on several factors. The estimated TCN uncertainty was up to 0.09 Dobson unit (DU), equivalent to 2.687 ?? 1020 molecules m???2) given a 1?? error for the observation geometries, including the solar zenith angle, viewing zenith angle, and relative azimuth angle. About 0.1 DU (6.8%) was estimated for an aerosol optical depth (AOD) uncertainty of 0.01. In addition, the uncertainty due to the NO2 vertical profile was 14% to 22%. Compared with the co-located Pandora spectrophotometer measurements, the HIS captured the temporal variation of the TCN during the intensive observation period. The correlation between the TCN from the HIS and Pandora also showed good agreement, with a slight positive bias (bias: 0.6 DU, root mean square error: 0.7 DU)

Case report: A fatal case of myocardial infarction due to myocardial bridge and concomitant vasospasm: the role of stress gated SPECT

IntroductionAlthough most cases of myocardial bridge (MB) are clinically benign, sometimes it can be one of potential threats of myocardial infarction (MI) and life-threatening arrhythmia. In the present study, we present a case of ST-segment elevation MI caused by MB and concomitant vasospasm.Case PresentationA 52-year-old woman was brought to our tertiary hospital due to resuscitated cardiac arrest. Because the 12-lead electrocardiogram indicated ST-segment elevation MI, coronary angiogram was promptly commenced, which showed near-total occlusion at the middle portion of left anterior descending coronary artery (LAD). After intracoronary nitroglycerin administration, this occlusion was dramatically relieved, however, systolic compression at this site remained, indicative of myocardial bridge (MB). Intravascular ultrasound also showed eccentric compression with a “half-moon” sign, which is consistent with MB. Coronary computed tomography also showed a bridged coronary segment surrounded by myocardium at the middle portion of LAD. To assess the severity and extent of myocardial damages and ischemia, myocardial single photon emission computed tomography (SPECT) was additionally conducted, showing a moderate fixed perfusion defect around the cardiac apex, suggesting MI. After receiving optimal medical therapy, the patient's clinical symptoms and signs were improved then the patient was discharged from the hospital successfully and uneventfully.ConclusionWe demonstrated a case of MB-induced ST-segment elevation MI which was confirmed with its perfusion defects via myocardial perfusion SPECT. There have been proposed a number of diagnostic modalities to examine its anatomic and physiologic significance. Among them, myocardial perfusion SPECT can be available as one of useful modalities to evaluate the severity and extent of myocardial ischemia in patients with MB