Regional expression and ultrastructural localization of EphA7 in the hippocampus and cerebellum of adult rat

EphA7 is expressed in the adult central nervous system (CNS), where its roles are yet poorly defined. We mapped its distribution using in situ hybridization (ISH) and immunohistochemistry (IHC) combined with light (LM) and electron microscopy (EM) in adult rat and mouse brain. The strongest ISH signal was in the hippocampal pyramidal and granule cell layers. Moderate levels were detected in habenula, striatum, amygdala, the cingulate, piriform and entorhinal cortex, and in cerebellum, notably the Purkinje cell layer. The IHC signal distribution was consistent with ISH results, with transport of the protein to processes, as exemplified in the hippocampal neuropil layers and weakly stained pyramidal cell layers. In contrast, in the cerebellum, the Purkinje cell bodies were the most strongly immunolabeled elements. EM localized the cell surface‐expression of EphA7 essentially in postsynaptic densities (PSDs) of dendritic spines and shafts, and on some astrocytic leaflets, in both hippocampus and cerebellum. Perikaryal and dendritic labeling was mostly intracellular, associated with the synthetic and trafficking machineries. Immunopositive vesicles were also observed in axons and axon terminals. Quantitative analysis in EM showed significant differences in the frequency of labeled elements between regions. Notably, labeled dendrites were ～3–5 times less frequent in cerebellum than in hippocampus, but they were individually endowed with ～10–40 times higher frequencies of PSDs, on their shafts and spines. The cell surface localization of EphA7, being preferentially in PSDs, and in perisynaptic astrocytic leaflets, provides morphologic evidence that EphA7 plays key roles in adult CNS synaptic maintenance, plasticity, or function. J. Comp. Neurol. 524:2462–2478, 2016. © 2016 Wiley Periodicals, Inc.     

Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus statement

Although surgical resection and liver transplantation are the only treatment modalities that enable prolonged survival in patients with hepatocellular carcinoma (HCC), the majority of HCC patients presents with advanced disease and do not undergo resective or ablative therapy. Transarterial chemoembolization (TACE) is indicated in intermediate/advanced stage unresectable HCC even in the setting of portal vein involvement (excluding main portal vein). Sorafenib has been shown to improve survival of patients with advanced HCC in two controlled randomized trials. Yttrium 90 is a safe microembolization treatment that can be used as an alternative to TACE in patients with advanced liver only disease or in case of portal vein thrombosis. External beam radiation can be helpful to provide local control in selected unresectable HCC. These different treatment modalities may be combined in the treatment strategy of HCC and also used as a bridge to resection or liver transplantation. Patients should undergo formal multidisciplinary evaluation prior to initiating any such treatment in order to individualize the best available options.     

Effect of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium on maximum tolerated dose and gastrointestinal symptoms following kidney transplantation

Despite the potential tolerability advantage of enteric-coated mycophenolate sodium (EC-MPS), no prospective, randomized trial has evaluated whether conversion from mycophenolate mofetil (MMF) to EC-MPS permits mycophenolic acid dose to be increased or gastrointestinal side-effects to be ameliorated. In a randomized, multicenter, open-label trial, kidney transplant recipients experiencing gastrointestinal side-effects either remained on MMF or switched to an equimolar dose of EC-MPS, adjusted 2 weeks subsequently to target the highest tolerated dose up to 1440 mg/day (EC-MPS) or 2000 mg/day (MMF). Patients were followed up to 12 weeks postrandomization. One hundred and thirty-four patients were randomized. The primary efficacy endpoint, the proportion of patients receiving a higher mycophenolic acid (MPA) dose at week 12 than at randomization, was significantly greater in the EC-MPS arm (32/68, 47.1%) than the MMF arm (10/61, 16.4%; P  < 0.001). At the final visit, 50.0% (34/68) of EC-MPS patients were receiving the maximum recommended dose versus 26.2% (16/61) of MMF patients ( P  = 0.007). Kidney transplant patients receiving reduced-dose MMF because of gastrointestinal side-effects can tolerate a significant increase in MPA dose after conversion to EC-MPS. Patient-reported gastrointestinal outcomes with higher doses of EC-MPS remained at least as good as in MMF-treated controls.     

Corelease of GABA/glycine in lamina-X of the spinal cord of neonatal rats

Spinal-cord slices from neonatal rats were used to record lamina-X neurons using the patch-clamp technique under whole cell recording configuration. Lamina-X surrounds the central canal of the spinal cord and contains sympathetic preganglionic neurons of the central autonomic nucleus. Miniature inhibitory postsynaptic currents were recorded in the presence of tetrodotoxin and kynurenic acid to block action potential-dependent transmitter release and glutamatergic transmissions, respectively. We recorded mixed gamma-amino-n-butyric acid/glycine miniature synaptic currents suggesting that gamma-amino-n-butyric acid and glycine can be coreleased from the same single synaptic vesicles, and that this corelease can be detected by the postsynaptic cell. In addition, acetylcholine can induce the release of gamma-amino-n-butyric acid/glycine by acting presynaptically at nicotinic receptors located on the gamma-amino-n-butyric acid ergic/glycinergic terminals.     

Gastrointestinal complications associated with hepatic arterial Yttrium-90 microsphere therapy

Hepatic arterial therapy with yttrium-90 microspheres exploits the avenue provided by the neoplastic microvasculature to deliver high-energy, low-penetrating therapeutic doses of radiation. Variant hepatic arterial anatomy, collateral vessels, and changes in flow dynamics during treatment can affect particle dispersion and lead to nontarget particle distribution and subsequent gastrointestinal morbidity. Awareness of these variances and techniques to prevent gastrointestinal tract microsphere delivery is essential in mitigating this serious complication. Our aim is to increase the understanding of the role of various imaging and preventative techniques in minimizing this undesired effect.     

A comparison of chemoembolization endpoints using angiographic versus transcatheter intraarterial perfusion/MR imaging monitoring

PURPOSE: Transcatheter arterial chemoembolization (TACE) is an established treatment for unresectable liver cancer. This study was conducted to test the hypothesis that angiographic endpoints during TACE are measurable and reproducible by comparing subjective angiographic versus objective magnetic resonance (MR) endpoints of TACE. MATERIALS AND METHODS: The study included 12 consecutive patients who presented for TACE for surgically unresectable HCC or progressive hepatic metastases despite chemotherapy. All procedures were performed with a dedicated imaging system. Angiographic series before and after TACE were reviewed independently by three board-certified interventional radiologists. A subjective angiographic chemoembolization endpoint (SACE) classification scheme, modified from an established angiographic grading system in the cardiology literature, was designed to assist in reproducibly classifying angiographic endpoints. Reproducibility in SACE classification level was compared among operators, and MR imaging perfusion reduction was compared with SACE levels for each observer. RESULTS: Twelve patients successfully underwent 15 separate TACE sessions. SACE levels ranged from I through IV. There was moderate agreement in SACE classification (kappa = 0.46 +/- 0.12). There was no correlation between SACE level and MR perfusion reduction (r = 0.16 for one operator and 0.02 for the other two). CONCLUSIONS: Angiographic endpoints during TACE vary widely, have moderate reproducibility among operators, and do not correlate with functional MR imaging perfusion endpoints. Future research should aim to determine ideal angiographic and functional MR imaging endpoints for TACE according to outcome measures such as imaging response, pathologic response, and survival.     

Effect of C-arm angiographic CT on transcatheter arterial chemoembolization of liver tumors

Rotational C-arm angiographic computed tomography (CT) with a flat-panel radiography unit permits three-dimensional (3D) reconstruction of soft tissues and blood vessels. The usefulness of this C-arm technique during transcatheter arterial chemoembolization (TACE) is unknown. The authors analyzed the role of the C-arm technique in 18 patients with unresectable liver tumors during TACE. The technique altered the catheter position anticipated by attending interventional radiologists in seven of the 18 patients (39%; 95% confidence interval [CI]: 20%, 61%) and improved the diagnostic confidence in the selected catheter position in 14 of the 18 patients (78%; 95% CI: 55%, 91%). The technique provides CT-like images that are useful to interventional radiologists during TACE.