Synergistic effects of dopamine D2-like receptor antagonist sulpiride and beta-blocker propranolol on learning in the Carousel maze, a dry-land spatial navigation task

Spatial navigation attracts the attention of neuroscientists as an animal analogue of human declarative memory. The Carousel maze is a dry-land navigational paradigm, which proved to be useful in studying neurobiological substrates of learning. The task involves avoidance of a stable sector on a rotating arena and is highly dependent upon the hippocampus. The present study aims at testing hypothesis that sulpiride (a centrally-active dopamine D2-like receptor antagonist) and propranolol (a beta-blocker) impair spatial learning in the Carousel maze after combined systemic administration. These doses were previously shown to be subthreshold in this task. Results showed that both substances affected behavior and significantly potentiated their negative effects on spatial learning. This suggests central interaction of both types of receptors in influencing acquisition of this dynamic-environment task.     

Presence of Borrelia burgdorferi in endomyocardial biopsies in patients with new-onset unexplained dilated cardiomyopathy

Dilated cardiomyopathy (DCM) represents the third most common cause of heart failure and the most frequent cause of heart transplantation. Infectious, mostly viral, and autoimmune mechanisms, together with genetic abnormalities, have been reported as three major causes of DCM. We hypothesized that Lyme disease (LD), caused by spirochete Borrelia burgdorferi (Bb), might be an important cause of new-onset unexplained DCM in patients living in a highly endemic area for LD such as the Czech Republic. We performed endomyocardial biopsy (EMB) in 39 consecutive patients presenting with symptomatic unexplained left ventricular (LV) systolic dysfunction lasting no more than 12 months. In eight subjects (21%), Bb was detected in the EMB sample by polymerase chain reaction or by electron microscopy. None of these patients exhibited any form of atrioventricular block or other extracardiac manifestation of Bb infection. Serological testing identified IgG antibodies against Bb in only two cases and IgM antibodies in none. All affected patients were treated with intravenous ceftriaxone for 3 weeks. At 6 months follow-up, LV morphology and function as well as functional status of these patients significantly improved. In conclusion, Bb infection may represent an important cause of new-onset unexplained DCM in patients living in endemic regions such as the Czech Republic. Because the antibiotic treatment appears to be markedly effective and serological examination does not provide a tool for diagnosing the disease, EMB focused on the detection of Bb should be performed in all patients from endemic areas with new-onset unexplained DCM not responding to conventional therapy.     

Advances in surface EMG: recent progress in detection and processing techniques

This article is the first section of a review work structured in three parts and concerning a) advances in surface EMG detection and processing techniques, b) recent progress in surface EMG clinical research applications and, c) myoelectric control in neurorehabilitation. This article deals with the state of the art regarding a) the electrode-skin interface (equivalent circuits, skin treatment, conductive gels), b) signal detection modalities, spatial filters and front-end amplifiers, c) power line interference removal, separation of propagating and non-propagating potentials and removal of outliers from surface EMG signal maps, d) segmentation of surface EMG signal maps, e) decomposition of surface EMG into the constituent action potential trains, and f) relationship between surface EMG and force. The material is presented with an effort to fill gaps left by previous reviews and identify areas open for future research.     

Neurofilament ELISA validation

BackgroundNeurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance.MethodsThe UmanDiagnostics NF-light ®enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68 kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses.ResultsThe intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R = 0.60, p < 0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R = 0.98, p < 0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics.ConclusionThis multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.     

Decreased paraoxonase activity in critically ill patients with sepsis

Paraoxonase 1 is believed to play a role in preventing lipid oxidation and, thus, limiting production of proinflammatory mediators. Systemic inflammatory response in sepsis increases oxidative stress and decreases high-density lipoprotein (HDL) concentrations. The objective of this study was to investigate serum paraoxonase 1 activities in critically ill patients with sepsis and after recovery. Serum paraoxonase 1 arylesterase/paraoxonase activities, concentration of total cholesterol, HDL cholesterol (HDL-C) and serum C-reactive protein (CRP) in septic patients of a medical intensive care unit (n = 30) and age/sex-matched outpatient controls without sepsis (n = 30) were analyzed. Paired convalescent samples were also taken 1 week after recovery (n = 11). In septic patients, both arylesterase (88.3 ± 36.5 vs. 162.1 ± 44.8 kU/l, P < 0.001) and paraoxonase (75.2 ± 50.0 vs. 125.2 ± 69.4 U/l, P < 0.01) paraoxonase 1 activities decreased as compared to controls. Both activities normalized after recovery. Negative correlation was found between CRP and both arylesterase (r = −0.676, P < 0.001) and paraoxonase (r = −0.401, P < 0.01) as well as positive correlation between HDL-C and both arylesterase (r = 0.585, P < 0.001) and paraoxonase (r = 0.405, P < 0.01) paraoxonase 1 activities. The decreased activity of paraoxonase 1 in negative correlation with CRP offers a potentially useful marker of sepsis progress and recovery in critically ill patients.     

Putative mesenchymal stem cells isolated from adult human ovaries

Purpose

The purpose of this study was to show that healthy adult human ovaries can be a source of cells showing typical MSCs characteristics under in vitro conditions.

Methods and results

The cells, which were isolated from ovarian cortex tissue and named putative ovarian mesenchymal stem cells (PO-MSCs), were compared to bone marrow-derived MSCs (BM-MSCs) and to adult human dermal fibroblasts (HDFs). The results of a gene expression analysis using the Human Mesenchymal Stem Cell RT² Profiler™ PCR Array revealed that PO-MSCs were different than fibroblasts. They expressed most of the analyzed genes as BM-MSCs, although some genes were differentially expressed. However, the heterogeneity of PO-MSCs samples was revealed. The PO-MSCs expressed the characteristic genes related to MSCs, such as CD105, CD44, CD90, M-CAM, CD73 and VCAM1. In addition, the expression of markers CD44, CD90, M-CAM and STRO-1 was confirmed in PO-MSCs using immunocytochemistry. The PO-MSCs showed multipotent character, since they were able to differentiate into the cells of adipogenic, osteogenic, neural and pancreatic lineage.

Conclusions

Healthy adult human ovaries can harbour an interesting population of cells showing typical MSCs characteristics under in vitro conditions and for this reason we named these cells putative MSCs. These cells express genes encoding main MSCs markers and have an interesting differential potential. Based on these results, we propose PO-MSCs as a novel type of MSCs which share some similarities with BM-MSCs. Nevertheless they show distinct and specific characteristics and are not fibroblasts.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-014-0254-8) contains supplementary material, which is available to authorized users.