In vitro studies of primary explosive blast loading on neurons

In a military setting, traumatic brain injury (TBI) is frequently caused by blast waves that can trigger a series of neuronal biochemical changes. Although many animal models have been used to study the effects of primary blast waves, elucidating the mechanisms of damage in a whole‐animal model is extremely complex. In vitro models of primary blast, which allow for the deconvolution of mechanisms, are relatively scarce. It is largely unknown how structural damage at the cellular level impacts the functional activity at variable time scales after the TBI event. A novel in vitro system was developed to probe the effects of explosive blast (ranging from ∼25 to 40 psi) on dissociated neurons. PC12 neurons were cultured on laminin‐coated substrates, submerged underwater, and subjected to single and multiple blasts in a controlled environment. Changes in cell membrane permeability, viability, and cell morphology were evaluated. Significant increases in axonal beading were observed in the injured cells. In addition, although cell death was minimal after a single insult, cell viability decreased significantly following repeated blast exposure. © 2015 Wiley Periodicals, Inc.     

Regenerative Endodontic Treatment or Mineral Trioxide Aggregate Apical Plug in Teeth with Necrotic Pulps and Open Apices: A Systematic Review and Meta-analysis

Introduction

A mineral trioxide aggregate (MTA) apical plug (MAP) and regenerative endodontic treatment (RET) have shown acceptable clinical outcomes. However, comparative studies are scarce. The aims of this study were to examine the level of evidence for both treatments, conduct a systematic review of the literature on MAP and RET, and run a meta-analysis on the survival and success rates of teeth treated with these procedures.

Single Miniplate Fixation for Mandibular Symphysis and Parasymphysis Fracture as a Viable Alternative to Conventional Plating Based on Champy’s Principles: A Prospective Comparative Clinical Study

To compare long term and short term outcomes of fixing mandibular symphysis and parasymphysis fractures with single mini plate and conventional fixation using two mini plates. Study design: in this prospective clinical comparative study, 30 patients with fracture in study region were randomly divided into two groups. Group A patients received single 2.5 mm titanium miniplate and Group B patients received two 2 mm titanium miniplates as per Champy's lines of osteosynthesis. Patients were followed up at intervals of 1, 12 and 24 weeks. Parameters assessed were: duration of surgery, fracture stabilization, paresthesia, occlusion and wound dehiscence. Statistically significant difference was observed in mean duration of surgery and wound dehiscence (P < 0.05). No significant difference was observed with respect to other parameters. Single 2.5 mm miniplate for mandibular symphysis and parasymphysis fractures is a time saving and cost effective technique with post-operative outcomes similar to conventional 2 plate fixation.     

Glutamate cycling may drive organic anion transport on the basal membrane of human placental syncytiotrophoblast

Key points

• The placenta removes waste products, drugs and environmental toxins from the fetal circulation and two of the transport proteins responsible for this are OAT4 and OATP2B1 localised to the basal membrane of placental syncytiotrophoblast.
• We provide evidence that OAT4 and OATP2B1 mediate glutamate efflux when expressed in Xenopus oocytes and that in the perfused placenta, bromosulphothalein (an OAT4 and OATP2B1 substrate) stimulates glutamate efflux.
• Furthermore the efflux of glutamate can only be seen in the presence of aspartate, which will block glutamate reuptake by the placenta, consistent with cycling of glutamate across the basal membrane.
• We propose that glutamate efflux down its transmembrane gradient drives placental uptake via OAT4 and OATP2B1 from the fetal circulation and that reuptake of glutamate maintains this driving gradient.

Abstract

The organic anion transporter OAT4 (SLC22A11) and organic anion transporting polypeptide OATP2B1 (SLCO2B1) are expressed in the basal membrane of the placental syncytiotrophoblast. These transporters mediate exchange whereby uptake of one organic anion is coupled to efflux of a counter‐ion. In placenta, these exchangers mediate placental uptake of substrates for oestrogen synthesis as well as clearing waste products and xenobiotics from the fetal circulation. However, the identity of the counter‐ion driving this transport in the placenta, and in other tissues, is unclear. While glutamate is not a known OAT4 or OATP2B1 substrate, we propose that its high intracellular concentration has the potential to drive accumulation of substrates from the fetal circulation. In the isolated perfused placenta, glutamate exchange was observed between the placenta and the fetal circulation. This exchange could not be explained by known glutamate exchangers. However, glutamate efflux was trans‐stimulated by an OAT4 and OATP2B1 substrate (bromosulphothalein). Exchange of glutamate for bromosulphothalein was only observed when glutamate reuptake was inhibited (by addition of aspartate). To determine if OAT4 and/or OATP2B1 mediate glutamate exchange, uptake and efflux of glutamate were investigated in Xenopus laevis oocytes. Our data demonstrate that in Xenopus oocytes expressing either OAT4 or OATP2B1 efflux of intracellular [¹⁴C]glutamate could be stimulated by conditions including extracellular glutamate (OAT4), estrone‐sulphate and bromosulphothalein (both OAT4 and OATP2B1) or pravastatin (OATP2B1). Cycling of glutamate across the placenta involving efflux via OAT4 and OATP2B1 and subsequent reuptake will drive placental uptake of organic anions from the fetal circulation.

Abbreviations

BM

basal membrane

BSP

bromosulphothalein

DHEAS

dehydroepiandrosterone‐3‐sulfate

OAT

organic anion transporter

OATP

organic anion transporting polypeptide

PAH

para‐aminohippuric acid

     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men

OBJECTIVES: We aimed to determine the relationship between carotid intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. The relationship between carotid IMT and brachial artery FMD has not been well studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial artery FMD in 1,578 middle-aged men without known cardiovascular disease and analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid IMT correlated with age, systolic blood pressure, body mass index, fasting glucose, total and low-density lipoprotein (LDL) cholesterol, and with the overall Framingham risk score (p < 0.001 for all), whereas impaired brachial artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No relationship was observed between carotid IMT and brachial artery FMD for the entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle-aged healthy men, there is no significant correlation between carotid IMT and brachial artery FMD. This finding suggests that these are unique, independent surrogates that measure different aspects and stages of early atherosclerosis. Further studies are needed to define their role in clinical research and in cardiovascular risk assessment.