Effect of glutamate and blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome and pathohistology of the hippocampus after traumatic brain injury in rats.

BACKGROUND: Decreasing blood glutamate concentrations after traumatic brain injury accelerates brain-to-blood glutamate efflux, leading to improved neurologic outcomes. The authors hypothesize that treatment with blood glutamate scavengers should reduce neuronal cell loss, whereas administration of glutamate should worsen outcomes. The authors performed histologic studies of neuronal survival in the rat hippocampus after traumatic brain injury and treatment with blood glutamate scavengers. METHODS: Traumatic brain injury was induced on anesthetized male Sprague-Dawley rats by a standardized weight drop. Intravenous treatment groups included saline (control), oxaloacetate, pyruvate, and glutamate. Neurologic outcome was assessed using a Neurological Severity Score at 1 h, and 1, 2, 7, 14, 21, 28 days. Blood glutamate was determined at baseline and 90 min. Four weeks after traumatic brain injury, a histologic analysis of surviving neurons was performed. RESULTS: Oxaloacetate and pyruvate treatment groups demonstrated increased neuronal survival (oxaloacetate 2,200 ± 37, pyruvate 2,108 ± 137 vs. control 1,978 ± 46, P < 0.001, mean ± SD). Glutamate treatment revealed decreased neuronal survival (1,715 ± 48, P < 0.001). Treatment groups demonstrated favorable neurologic outcomes at 24 and 48 h (Neurological Severity Score at 24 and 48 h: 5.5 (1-8.25), 5 (1.75-7.25), P = 0.02 and 3(1-6.5), 4 (1.75-4.5), P = 0.027, median ± corresponding interquartile range). Blood glutamate concentrations were decreased in the oxaloacetate and pyruvate treatment groups. Administration of oxaloacetate and pyruvate was not shown to have any adverse effects. CONCLUSIONS: The authors demonstrate that the blood glutamate scavengers oxaloacetate and pyruvate provide neuroprotection after traumatic brain injury, expressed both by reduced neuronal loss in the hippocampus and improved neurologic outcomes. The findings of this study may bring about new therapeutic possibilities in a variety of clinical settings.

[Incidence of hospitalizations among chronic obstructive pulmonary disease (COPD) patients with anemia].

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by progressive exertional and resting dyspnea and is associated with major co-morbidities. Hemoglobin level disorders (anemia and polycythemia) prevalence among patients and the relationship between them and the clinical expression are still not characterized unequivocally. The main purpose of this work is to test the association between anemia and hospitalizations. The presence of such a link may promote the diagnosis and treatment aimed at the patient's hemoglobin levels. HYPOTHESIS: Anemia in patients with COPD is associated with an increased number of hospitalizations. METHODS: A retrospective cohort study analysis, conducted on a group of COPD patients (n = 333) followed in the Pulmonology Institute of the Soroka University Medical Center in the years 2003-2009. Demographic physiological and clinical characteristics were compared between anemic, polycythemic and normal hemoglobin patients. Using statistical models, we examined the relationship between the presence of anemia and clinical outcome. RESULTS: Anemia was found in 79 patients (24%) and polycythemia among seven patients (2%). No difference was found between the groups in terms of number of hospitalizations, number of hospitalization days and ventilator events. There was a higher rate of co-morbidities (such as heart failure, chronic kidney disease) among anemic patients. There were also lower values of BMI and lung function and a higher proportion of men among anemic patients. CONCLUSIONS: Anemia in patients with COPD was not associated with an increase in the number of severe exacerbations. More studies are needed to clarify the threshold of a hemoglobin level below which there is an increase in the rate of hospitalizations.

Pyruvate's blood glutamate scavenging activity contributes to the spectrum of its neuroprotective mechanisms in a rat model of stroke.

In previous studies, we have shown that by increasing the brain-to-blood glutamate efflux upon scavenging blood glutamate with either oxaloacetate or pyruvate, one achieves highly significant neuroprotection particularly in the context of traumatic brain injury. The current study examines, for the first time, how the blood glutamate scavenging properties of glutamate-pyruvate transaminase (GPT), alone or in combination with pyruvate, may contribute to the spectrum of its neuroprotective mechanisms and improve the outcome of rats exposed to brain ischemia, as they do after head trauma. Rats that were exposed to permanent middle cerebral artery occlusion (MCAO) and treated with intravenous 250 mg/kg pyruvate had a smaller volume of infarction and reduced brain edema, resulting in an improved neurological outcome and reduced mortality compared to control rats treated with saline. Intravenous pyruvate at the low dose of 31.3 mg/kg did not demonstrate any neuroprotection. However, when combined with 0.6 mg/kg of GPT there was a similar neuroprotection observed as seen with pyruvate at 250 mg/kg. Animals treated with 1.69 g/kg glutamate had a worse neurological outcome and a larger extent of brain edema. The decrease in mortality, infarcted brain volume and edema, as well as the improved neurological outcome following MCAO, was correlated with a decrease in blood glutamate levels. We therefore suggest that the blood glutamate scavenging activity of GPT and pyruvate contributes to the spectrum of their neuroprotective mechanisms and may serve as a new neuroprotective strategy for the treatment of ischemic stroke.

Snoring intensity and excessive daytime sleepiness in subjects without obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: Snoring and excessive daytime sleepiness (EDS) are major obstructive sleep apnea (OSA) symptoms. Snorers with apnea/hypopnea index < 5 are designated "simple snorers" and do not meet OSA criteria. This study aimed to explore a possible association between snoring intensity and EDS defined as Epworth Sleepiness Scale (ESS) scores ≥ 11 in non-OSA subjects. STUDY DESIGN: Prospective cohort study. METHODS: From a total of 2,225 subjects who underwent polysomnography (PSG), 307 simple snorers qualified for the study and were assessed for snoring intensity and ESS score. The correlation between PSG-based snoring intensity measurements and ESS score was evaluated. A prediction model for EDS was derived using multivariate logistic regression. RESULTS: Subjects with EDS tended to be male and of heavier body habitus. Although both genders exhibited similar snoring intensities, men had higher ESS scores than women. A strong linear correlation was demonstrated between the maximal snoring intensity and the ESS score. Maximal snoring sound and male gender were shown to be predictors of EDS, with odds ratios of 1.93 (95% confidence interval [CI]:1.63-2.26, P < .001) and 3.70 (95% CI: 1.29-12.5, P = .01), respectively. CONCLUSIONS: In a population of non-OSA subjects referred to a PSG study, snoring intensity was associated with EDS in both men and women. A positive linear correlation was observed between snoring intensities and ESS scores. Additional studies are needed to further consolidate the evidence regarding the implications of simple snoring for public health. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:1696-1701, 2016.