Late brain alterations in sepsis‐survivor rats

Central nervous system (CNS) dysfunction secondary to sepsis is characterized by long‐term cognitive impairment. It was observed that oxidative damage, energetic metabolism impairment, and cytokine level alteration seen in early times in an animal model of sepsis may persist for up to 10 days and might be associated with cognitive damage. In order to understand these mechanisms, at least in part, we evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF), oxidative parameters, and energetic metabolism in the brain of rats at both 30 and 60 days after sepsis induction by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent CLP with “basic support” or were sham‐operated. Both 30 and 60 days after surgery, the CSF was collected and the animals were killed by decapitation. Then, the prefrontal cortex, hippocampus, striatum, and cortex were collected. Thirty days after surgery, an increase of IL‐6 level in the CSF; an increase in the thiobarbituric acid‐reactive species (TBARS) in prefrontal cortex and a decrease in hippocampus, striatum, and cortex; a decrease of carbonyl protein formation only in prefrontal cortex and an increase in striatum; and an increase in the complex IV activity only in hippocampus were observed. Sixty days after sepsis, an increase of TNF‐α level in the CSF; a decrease of TBARS only in hippocampus; an increase of carbonyl protein formation in striatum; and a decrease of complex I activity in prefrontal cortex, hippocampus, and striatum were observed. These findings may contribute to understanding the role of late cognitive impairment. Further studies may address how these findings interact during sepsis development and contribute to CNS dysfunction. Synapse 67:786–793, 2013. © 2013 Wiley Periodicals, Inc.     

Purinergic transmission and transglial signaling between neuron somata in the dorsal root ganglion

Most dorsal root ganglion neuronal somata (NS) are isolated from their neighbours by a satellite glial cell (SGC) sheath. However, some NS are associated in pairs, separated solely by the membrane septum of a common SGC to form a neuron–glial cell–neuron (NGlN) trimer. We reported that stimulation of one NS evokes a delayed, noisy and long‐duration inward current in both itself and its passive partner that was blocked by suramin, a general purinergic antagonist. Here we test the hypothesis that NGlN transmission involves purinergic activation of the SGC. Stimulation of the NS triggered a sustained current noise in the SGC. Block of transmission through the NGlN by reactive blue 2 or thapsigargin, a Ca²⁺ store‐depletion agent, implicated a Ca²⁺ store discharge‐linked P2Y receptor. P2Y2 was identified by simulation of the NGlN‐like transmission by puffing UTP onto the SGC and by immunocytochemical localization to the SGC membrane septum. Block of the UTP effect by BAPTA, an intracellular Ca²⁺ scavenger, supported the involvement of SGC Ca²⁺ stores in the signaling pathway. We infer that transmission through the NGlN trimer involves secretion of ATP from the NS and triggering of SGC Ca²⁺ store discharge via P2Y2 receptors. Presumably, cytoplasmic Ca²⁺ elevation leads to the release of an as‐yet unidentified second transmitter from the glial cell to complete transmission. Thus, the two NS of the NGlN trimer communicate via a ‘sandwich synapse’ transglial pathway, a novel signaling mechanism that may contribute to information transfer in other regions of the nervous system.     

A comparative study of lateral cephalograms and cone-beam computed tomographic images in upper airway assessment

The purpose of this study was to evaluate the accuracy of airway measurements from lateral cephalograms, cone-beam computed tomographic (CBCT) lateral reconstructions, and CBCT axial planes, as well as to correlate these findings with area measurements acquired with the latter imaging method. Landmarks were defined for the measurements of naso- and oropharynx of 30 patients (12 males and 18 females, mean age 17.5 years), for different planes, using linear antero-posterior measurements and the corresponding area. Analysis of variance showed significant differences in the linear measurements of the oropharynx between the two methods, although all measurements assessed corresponded to the respective areas. The linear measurements of the airway space obtained using the different techniques correlated positively with the respective area measurements, which demonstrate the reliability of the investigated techniques.     

The influence of composite resin restorations and lining on radiographic diagnosis and decision-making: an in vitro investigation

The objective of this study was to evaluate the influence of resin-based restorations on the interpretation of digital and conventional radiographic images and to correlate the proposed diagnosis with decision-making. Class II cavities were prepared in one of the proximal surfaces of extracted human molars. Teeth were divided into five groups (n = 10) according to the restoratives used: Natural Flow (NF) and Filtek Supreme (FS); Filtek Flow (FF) and FS; Tetric Flow (TF) and FS; Protect Liner F (PLF) and FS; and FS alone. Bitewing radiographs were taken using conventional and digital systems. Subjective analysis was performed for each surface: no restoration; restored teeth; or restored teeth with gap. Based on the given diagnosis, clinical conduct was then indicated. Material radiopacity was determined according to ISO 4049. A Fisher exact test evaluated the influence of the restoratives on the diagnosis. Means were compared using ANOVA and the Games-Howell test. A Friedman test was used to analyze the influence of the systems on the diagnosis, and a binomial test was used to analyze the association between the presence of gaps and the decision to replace the restoration (P = 0.05). For each system, TF+FS was significantly associated with a high percentage of correct diagnoses. The opposite was the case for PLF+FS, which differed from all other groups. Radiographic systems presented similar behaviors, except for NF+FS. Apart from PLF, adequate radiopacity was observed. Diagnosis was influenced by restorative materials, regardless of the radiographic system used. The low radiopacity of PLF led to a greater number of erroneous diagnoses. Moreover, the decision-making process was influenced strongly by the given diagnosis.     

Influence of antithymocyte globulin treatment of brain‐dead organ donor on inflammatory response in cardiac grafts: an experimental study in mice

The expression of proinflammatory cytokines in donor hearts after antithymocyte globulin (ATG) treatment given prior to organ removal was evaluated to analyze changes in inflammatory response. Adult female OF‐1 mice were randomized into brain death (BD) groups (BD Control, BD ATG) with or without treatment, and Controls (Control, ATG). BD induction was performed through gradual inflation of an intracranial positioned balloon catheter. At the end of a 6‐h observation period, ATG (1 mg/kg BW) was given intravenously. After 45 min, the donor hearts were removed. Proinflammatory markers IL‐2 and IL‐6 were examined using ELISA and immunohistochemistry staining. After single administration of ATG, the inflammatory reaction in the myocardium showed a significant reduction in IL‐2 expression (BD Control vs. BD ATG, P = 0.033). Our investigation showed expected increase in proinflammatory mediators after BD. This increase was abolished by single infusion of ATG, indicated by significant reduction in IL‐2 levels in the myocardium. We observed a reduction of IL‐6 deposition in media cells in ATG‐treated specimens. Further research is necessary to evaluate the role of ATG in donor management considering a potentially positive effect of ATG on IL‐2‐directed inflammatory response and possible reduction of IL‐6‐mediated vascular changes.     

Pure Erythroid Leukemia Mimicking Ewing Sarcoma/Primitive Neuroectodermal Tumor in an Infant

Pure erythroid leukemia (PEL) is a rare type of acute myeloid leukemia (AML) with a very aggressive clinical course. Presentation as a myeloid/erythroid sarcoma is exceedingly rare. We describe an infantile PEL presenting as a multifocal myeloid sarcoma, clinically and pathologically mimicking Ewing sarcoma/PNET family of tumors. The patient died 8 weeks after the initial presentation due to widespread disease. Our case shows that PEL needs to be considered in the differential diagnosis of small round blue cell tumors in infancy. A meticulous workup including immunohistochemistry, flow cytometry, molecular, and cytogenetic studies was required to reach the diagnosis.