Chlorogenic Acid Prevents AMPA-Mediated Excitotoxicity in Optic Nerve Oligodendrocytes Through a PKC and Caspase-Dependent Pathways

In the CNS, including the optic nerve, oligodendrocytes play a critical role in the myelination of axons. Oligodendrocytes are exceptionally sensitive to insults to the CNS, such as injury, ischemia, or inflammation, which result in the loss of oligodendrocytes and myelin and eventually secondary axon degeneration. Oligodendrocytes are sensitive to excitotoxic insults mediated by overactivation of their AMPA ionotropic glutamate receptors. Phenolic compounds, which are widely distributed in fruits and vegetables, received the great attention of scientists due to their antioxidant activities and free radical scavenging abilities. Chlorogenic acid (CGA) has been demonstrated to possess potent neuroprotective activities against oxidative stress in various cellular models and pathological conditions. Hence, CGA protect against oxidative stress and excitotoxic insults mediated by AMPA receptors and that the protective mechanisms involve free radical scavenging, Ca²⁺ handling in the cytosol, and modulating antioxidant enzyme system. CGA was associated with the protein kinase A (PKC) signaling pathways transduction. Caspases and calpains have been studied as apoptotic mediators and cell death in this model of AMPA toxicity. Inhibitors of caspases initiators, caspases 1, 8, and 9, the upstream of caspase 3 effectors, have totally abrogated the protective activity of CGA. Inhibitors of calpains also totally abrogated the protective activity of CGA. In addition, a potential role for the CGA in inhibiting Bax in oligodendrocyte cell model undergoing AMPA is inducing excitotoxic death. Our results indicate that CGA exhibits a protective potential via antioxidant and apoptosis caspases and calpains dependent against AMPA-mediated excitotoxicity, and these finding indicate that CGA is able to be a good candidate for preventive approach for neurodegenerative disorders associated with loss and damage in oligodendrocytes and AMPA-mediated excitotoxicity.     

Recreational soccer training improves heart-rate variability indices and physical performance in untrained healthy adolescent

The aim of this study was to evaluate the effects of soccer training on short-term heart-rate variability, blood pressure, and physical fitness in untrained healthy adolescents. Twenty-two adolescent boys took part in this study: 11 boys were randomly assigned to participate in an 8-week soccer training and 11 boys served as a control group. Soccer exhibited significant increases in high-frequency power (difference 52.9%, P = 0.03, effect size: ES = 1.2), root mean squared of the standard deviation rMSSD (10.8%, P = 0.02, ES = 1), and a significant decrease in sympathetic activity LF (26.3%, P = 0.004, ES = 1.4). The control group showed an increase in rMSSD (9.4%, P = 0.05, ES = 1). The soccer group showed increases in estimated aerobic fitness (30.9%, P = 0.001, ES = 1.50) and 20-m sprint performance (4.1%, P = 0.004, ES = 0.8) with a trend to an improvement in horizontal jumping (3.8%, P = 0.15, ES = 0.8). In conclusion, soccer-based training improved measures of both physical fitness and autonomic function making soccer an effective training strategy for improving health-related fitness measures in untrained adolescents.     

Rare case of coronary to pulmonary vein fistula with coronary steal phenomenon

Coronary artery fistulas are abnormal connections between coronary artery territories and cardiac chambers or major vessels,most of them are congenital.Patients with coronary artery fistula can be asymptomatic or present with different symptoms like angina.Cardiac computed tomography(CT)is one of the best modalities for diagnosis.We present an elderly patient that presented with angina symptoms,non invasive stress test was positive for ischemic heart disease,coronary angiogram could not reveal any obstructive lesions,but an abnormal branch of the left descending coronary artery(LAD),cardiac CT showed fistula that connect left anterior descending coronary artery to left superior pulmonary vein.Our case is extremely rare as most of the reported cases were fistulas between LAD and pulmonary artery,but in our case the fistula between LAD and left superior pulmonary vein.In addition,our patients’symptoms resolved with anti-ischemic medical treatment without any surgical intervention.     

The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors

Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellular concentrations of Na⁺ and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation. Here we recorded astrocytes from juvenile rat neocortical slices and analyzed the consequences of elevated intracellular glutamate concentrations and of GS inhibition on the time course of synaptically evoked transporter current (STC). In slices from rats treated with methionine sulfoximine (MSO), a GS inhibitor, STC evoked by short burst of high frequency stimulation (HFS; 100 Hz for 100 ms) but not by low frequency stimulation (LFS; 0.1 Hz) was twice slower than STC evoked from saline injected rats. Same results were obtained for astrocytes recorded with pipette containing 3–10 mM glutamate and compared with cells recorded with 0 or1 mM glutamate in the patch pipette. We also showed that HFS elicited significantly larger NMDAR‐excitatory postsynaptic currents (EPSCs) with a stronger peri/extrasynaptic component in pyramidal cells from MSO‐treated compared with saline treated rats. Taken together our data demonstrate that the conversion of glutamate by GS is fundamental to ensure an efficient clearance of glutamate by EAATs and to prevent glutamate spillover. GLIA 2017;65:401–415     

Death by ‘ice’: fatal methamphetamine intoxication of a body packer case detected by postmortem computed tomography (PMCT) and validated by autopsy

Fatal acute methamphetamine (MA) poisoning in cases of internal drug trafficking is rarely described in the literature. This case study reports an MA ‘body packer’ who died from fatal methamphetamine intoxication due to leaking drug packages in the alimentary tract. The deceased was examined by postmortem computed tomography (PMCT), and the results were correlated to subsequent autopsy and toxicological findings. The deceased was arrested by the police when he was found disoriented in the city of Kuala Lumpur. He was transferred to the emergency department on suspicion of drug abuse. The initial drug screening was reactive for amphetamines. Shortly after admission to the hospital, he died despite rigorous resuscitation attempts. The postmortem plain chest and abdominal radiographs revealed multiple suspicious opacities in the gastrointestinal tract attributable to body packages. An unenhanced whole body PMCT revealed twenty-five drug packages, twenty-four in the stomach and one in the transverse colon. At least two were disintegrating, and therefore leaking. The autopsy findings were consistent with the PMCT results. Toxicology confirmed the diagnosis of fatal methamphetamine intoxication.