Isoflurane increases the uptake of glutamate in synaptosomes from rat cerebral cortex

We have studied the effect of increasing concentrations of isoflurane on high- and low-affinity uptake of L-glutamate using synaptosomes from rat cerebral cortex. In the high-affinity uptake range, 0.5% isoflurane had no effect on uptake velocity, while 1.5% and 3.0% isoflurane caused an increase in mean Vmax to 131 (SEM 54) and 210 (103)% of control, respectively. There was no significant change in the K(m) value. Vmax and K(m) values for low-affinity uptake of L-glutamate were unchanged by 1.5% isoflurane. These results provide evidence for an isoflurane- induced increase in high-affinity uptake of glutamate into presynaptic terminals. This effect may contribute to a reduction of transmitter in the synaptic cleft and thereby decreased excitatory synaptic transmission.      

Methylprednisolone treatment does not influence axonal regeneration or degeneration following optic nerve injury in the adult rat.

BACKGROUND: Methylprednisolone (MP) is often used to treat optic nerve injury. However, its effects in experimental crush injury have not been extensively evaluated. METHODS: Adult Sprague-Dawley rats were subjected to a standardized optic nerve crush injury. Animals were treated either with 30 mg/kg MP intravenous bolus followed by subcutaneous injections every 6 hours for 48 hours, or with a drug vehicle alone. RESULTS: The injury resulted in a partial loss of neuronal nuclei-labeled retinal neurons and a corresponding degeneration of axons distal to the injury. EDI-labeled macrophages accumulated at the site of lesion, phagocyting FJ-labeled axonal debris. Regenerative fibers expressing growth associated protein-43 were seen proximal to the lesion, but did not traverse the glial scar. Analysis of optic nerve function using visual evoked potentials showed typical signals in intact animals, which were abolished after injury in MP-treated and untreated animals. CONCLUSIONS: We did not detect any effects of MP on retinal cell survival, macrophage activity at the site of injury, axonal degeneration/regeneration, or visual function. These experimental results provide a physiologic underpinning for the lack of efficacy demonstrated in a large trial of MP treatment of clinical optic nerve injury.     

Core-peripheral temperature gradient in children: does it reflect clinically important changes in circulatory haemodynamics?

Following open heart surgery, changes in core and peripheral skin temperature and changes in the core-peripheral temperature gradient were measured in 10 children. These were correlated with changes in cardiac index, systemic vascular resistance index, mean arterial pressure and urinary output. During the study intervals, which lasted 1 h each, no changes in medical management were made. Using Spearman's rank correlation, only a change in central venous pressure was found to correlate with a change in the core-peripheral temperature gradient. We conclude that a change in the core-peripheral temperature will give valuable information about the patient's intravascular volume.     

Amino-acid release from human cerebral cortex during simulated ischaemia in vitro

Summary The aim of the present study was to investigate the release of amino-acids in human cerebral cortex during membrane depolarization and simulated ischaemia (energy deprivation). Superfluous tissue from temporal lobe resections for epilepsy was cut into 500 m thick slices and incubated in vitro. Membrane depolarization with 50 mM K⁺ caused a release of glutamate, aspartate, GABA and glycine, but not glutamine or leucine. The release of glutamate and GABA was Ca⁺⁺-dependent. Slices were exposed to simulated ischaemia (energy deprivation; ED) by combined glucose/oxygen deprivation. This caused a Ca⁺⁺-indepedent release of glutamate, aspartate, GABA, glycine, and taurine which started after 8 min, peaked at the end or shortly after the 27 min period of ED, and returned to control levels within 11 min following termination of ED. Preloaded D-[³H]aspartate was released both during K⁺-stimulation and ED. Release of D-[³H]aspartate during ED was delayed compared to glutamate supporting an initial phase of synaptic glutamate release. Uptake of L-[³H]glutamate was increased during the period of glutamate release, suggesting passive diffusion across the cell membrane or enhanced transport efficacy in cellular elements with functioning uptake mechanisms.     

A patenting perspective on human neutrophil elastase (HNE) inhibitors (2014-2018) and their therapeutic applications

Introduction: Human neutrophil elastase (HNE) is involved in a variety of serious chronic diseases, especially cardiopulmonary pathologies. For this reason, the regulation of HNE activity represents a promising therapeutic approach, which is evident by the development of a number of new and selective HNE inhibitors, both in the academic and pharmaceutical environments.

Areas covered: The present review analyzes and summarizes the patent literature regarding human neutrophil elastase inhibitors for the treatment of cardiopulmonary diseases over 2014–2018.

Expert opinion: HNE is an interesting and defined target to treat various inflammatory diseases, including a number of cardiopulmonary pathologies. The research in this field is quite active, and a number of HNE inhibitors are currently in various stages of clinical development. In addition, new opportunities for HNE inhibitor development stem from recent studies demonstrating the involvement of HNE in many other inflammatory pathologies, including rheumatoid arthritis, inflammatory bowel disease, skin diseases, and cancer. Furthermore, the development of dual HNE/proteinase 3 inhibitors is being pursued as an innovative approach for the treatment of neutrophilic inflammatory diseases. Thus, these new developments will likely stimulate new and increased interest in this important therapeutic target and for the development of novel and selective HNE inhibitors.     

The Influence of Autonomic Neuropathy on Mortality in Insulin-dependent Diabetes

Five-year survival was investigated in 506 randomly selectedpatients with insulin-dependent diabetes mellitus screened forautonomic neuropathy with a series of cardiac autonomic functiontests. Of the 484 diabetics traced, 44 (9 per cent) had died. The cumulative 5-year mortality rate was increased more thanfive-fold in those with autonomic neuropathy: 27 per cent vs.5 per cent in those with normal autonomic function. Discriminantanalysis of survivors and non-survivors showed that autonomicneuropathy was the most important independent predictor of death.Among those who died, autonomic neuropathy was associated withan increased frequency of retinopathy and peripheral neuropathyand a slightly lower frequency of macrovascular disease. Autonomicneuropathy was associated with an increased mortality rate fromrenal failure, but not from any other causes.     

室间隔缺损部分修补的大动脉调转术的护理配合

总结了5例室间隔缺损部分修补的大动脉调转术的护理配合经验。洗手护士熟悉手术方法及步骤，充分准备所需器械和缝线，熟练配合；巡回护士注意手术进展，按要求配置心血管活性药物，正确使用降温厦复温辅助设施，预见可能出现的问题并做好应急准备，才能确保手术顺利进行。     

Monitoring transfusionist practices: a strategy for improving transfusion safety

BACKGROUND: Data from New York State indicate that about 1 of every 33,000 red cell units transfused is ABO-incompatible with the recipient. National application of these data suggests that as many as 360 ABO-incompatible whole blood and red cell transfusions might occur annually in the United States. Phlebotomy and blood bank laboratory errors cause some of these ABO-incompatible transfusions, but the greatest number result either partially or solely from the failure of transfusionists to identify properly either a patient or the blood component a patient receives. STUDY DESIGN AND METHODS: A quality assessment/quality improvement (QA/QI), process is described that allowed for the direct oversight (monitoring) of transfusionists' practices and for the assessment of institutional policies for blood administration. RESULTS: At the beginning of the QA/QI process, monitoring of blood administration practices revealed that a variance from institutional blood administration policy occurred during 50 percent of blood and component transfusions. As a result of the QA/QI process, the percentage of transfusions with an associated variance from institutional policy dropped to nearly zero. CONCLUSION: The QA/QI process described in this report, or one similar to it, could improve transfusion safety and serve as a model for increased involvement by transfusion service medical directors in the oversight of transfusionists' practices.