Astrocytes derived from fetal neural progenitor cells as a novel source for therapeutic adenosine delivery

PurposeIntracerebral delivery of anti-epileptic compounds represents a novel strategy for the treatment of refractory epilepsy. Adenosine is a possible candidate for local delivery based on its proven anti-epileptic effects. Neural stem cells constitute an ideal cell source for intracerebral transplantation and long-term drug delivery. In order to develop a cell-based system for the long-term delivery of adenosine, we isolated neural progenitor cells from adenosine kinase deficient mice (Adk^?/?) and compared their differentiation potential and adenosine release properties with corresponding wild-type cells.MethodsFetal neural progenitor cells were isolated from the brains of Adk^?/? and C57BL/6 mice fetuses and expanded in vitro. Before and after neural differentiation, supernatants were collected and assayed for adenosine release using liquid chromatography–tandem mass spectrometry (LC–MS/MS).ResultsAdk^?/? cells secreted significantly more adenosine compared to wild-type cells at any time point of differentiation. Undifferentiated Adk^?/? cells secreted 137 ± 5 ng adenosine per 10⁵ cells during 24 h in culture, compared to 11 ± 1 ng released from corresponding wild-type cells. Adenosine release was maintained after differentiation as differentiated Adk^?/? cells continued to release significantly more adenosine per 24 h (47 ± 1 ng per 10⁵ cells) compared to wild-type cells (3 ± 0.2 ng per 10⁵ cells).ConclusionsFetal neural progenitor cells isolated from Adk^?/? mice – but not those from C57BL/6 mice – release amounts of adenosine considered to be of therapeutic relevance.     

Cognitive vulnerability in fear of flying: the role of anxiety sensitivity

Previous research has indicated that more than 50% of air travel passengers experience hypoxia above clinical threshold. This condition produces a number of aversive somatic sensations such as difficulty breathing, elevated heart rate, dizziness, etc. Because these symptoms closely resemble the somatic symptoms of anxiety, it is interesting to look into a possible relationship between hypoxia-related symptoms and fear of flying. More specifically, the aim of this study is to clarify the role of anxiety sensitivity as a cognitive vulnerability marker in this relationship. Anxiety sensitivity is the specific tendency to interpret bodily sensations as threatening or harmful. Our hypothesis is that anxiety sensitivity moderates the relationship between hypoxia-related symptoms and fear of flying. When people with high anxiety sensitivity fly and experience somatic symptoms, they will make threatening interpretations causing fear and as a possible consequence avoidance behaviour leading to flight anxiety. About 160 participants were asked to complete the Flight Anxiety Situations Questionnaire, the Flight Anxiety Modality Questionnaire and the Anxiety Sensitivity Index. Results of a moderator analysis indicated that the relationship between somatic sensations and in-flight anxiety is stronger for people with high anxiety sensitivity than for people with low anxiety sensitivity. So it seems that anxiety sensitivity does indeed function as a moderator between the experience of somatic sensations while flying and in-flight anxiety. Clinical implications are discussed, as well as suggestions for further research.     

ABUSE DURING PREGNANCY: CURRENT THEORY AND NEW CONTEXTUAL UNDERSTANDINGS

This study used Landenburger's theory, a process of leaving and recovering from an abusive relationship, as a framework to interview 35 pregnant women identified as being at high risk for abuse. Results are reported on 18 women who disclosed active abuse during the study. Landenburger's model was not a good fit. Our participants became trapped and endured violent relationships if they perceived this was the best situation for their unborn child. Additionally the chaos, instability, and lack of resources experienced by these women likely contributed to their inability to complete the four phases described by Landenburger's model for non-pregnant women     

Differentiation between mild cognitive impairment, Alzheimer's disease and depression by means of cued recall

BACKGROUND: Discriminating Alzheimer's disease (AD) and mild cognitive impairment (MCI) from depression is a challenge in psychogeriatric medicine. A study was set up to ascertain whether cued recall could be useful in differentiating early AD and MCI from depression among elderly individuals. METHOD: The Visual Association Test (VAT) and the Memory Impairment Screen-plus (MIS-plus) were administered together with the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale (GDS) to 40 MCI patients, 35 mild AD patients, 46 depressed patients and 52 healthy control subjects. RESULTS: A one-way analysis of variance (ANOVA) followed by post-hoc Scheffé tests showed that AD patients had significantly lower cued recall scores (i.e. combined VAT and MIS-plus scores) than MCI patients, who in turn had lower scores than depressed patients. The scores of depressed patients and controls were not significantly different. Discriminant analysis revealed that 94% of the AD patients and 96% of the depressed patients could be classified correctly by means of the GDS and the cued recall sores. Receiver operating characteristic (ROC) curves identified an optimal cut-off score of 8 (maximum score 12) for differentiating AD and MCI patients from depressed elderly patients and controls. Applying this cut-off, a sensitivity of 83% (58%) and a specificity of 85% (85%) was obtained when differentiating AD (MCI) from depression. CONCLUSIONS: Cued recall, operationalized by the combined scores of VAT and MIS-plus, is a useful method for differentiating AD patients from depressed individuals and healthy controls. Probably because of the great heterogeneity among MCI patients, the diagnostic power of cued recall decreases when applied to differentiate MCI from depression.     

Mechanical influence of the extrafusal muscle on the static behaviour of deefferented primary muscle spindle endings in cat

Summary In 16 anesthetized cats 24 afferents of deefferented primary muscle spindle endings from the extensor digitorum longus muscle (EDL) were functionally isolated and their sensitivity to static stretches was tested. Each spindle was carefully located within the EDL using direct focal stimulation. Muscle spindle endings with poor static length sensitivity of stretch were always found in the most peripheral parts of the muscle fibre bundles, near to the aponeurotic and tendineous insertions. Endings having good static sensitivity to stretch were exclusively found in more central portions of the muscle fibre bundles. Using a photographic method, the alterations in the distance between designated points on the muscle surface ware measured during maintained muscle stretch. Only medial portions were markedly extended, whereas little or no increases in length occurred in peripheral parts of the muscle fibre bundles.Quantitatively, a direct relationship was found between the lengthening of those muscle portions, in which the muscle spindles were localized, and the receptors' sensitivity to maintained stretch.Preliminary reports of some of the results were given at the 1. Wissenschaftliche Tagung der Deutschen Gesellschaft für medizinische Physik (Rieboldet al., 1970; Robrechtet al., 1970) and at the Muscle-Spindle Symposium of the Anatomical Society of Great Britain and Ireland, April 4–6, 1974, at the University of Durham (Henatschet al., 1974). The results were presented in more detail in Meyer-Lohmann's Habilitationsschrift (1972).Supported by a grant from the Deutsche Forschungsgemeinschaft (Schwer-punktprogramm Rezeptorphysiologie).     

Diversity, dispersion and inconsistency of reaction time measures: effects of age and task complexity

BACKGROUND AND AIMS: Performance variability of reaction time is regarded as an important parameter for cognitive functioning with aging. We investigated three types of variability, diversity (or variability between persons), dispersion (variability across trials within one task) and inconsistency (variability across testing occasions), while distinguishing between decision time and movement time and evaluating performance across comparable complexity levels. METHODS: A single stratified reaction time test based on tasks with increasing complexity was used to evaluate inter- and intra-performance variability of 27 older (age 75+/-5 years) and 27 younger (age 29+/-7 years) participants, subdividing reaction time into decision and movement components. RESULTS: There were consistent age and complexity differences for all variability types in our sample. When controlling for processing speed, which was slower in the older group, variability across age groups and task complexity tended to diminish and a more complex picture emerged. The elderly group showed a higher diversity of all reaction time measures, except for movement time, and a higher dispersion of decision time. Task complexity significantly affected the diversity of movement and overall reaction times and the dispersion of all reaction time measures, except for movement time. CONCLUSIONS: These results highlight the importance of variability in cognitive functioning; it may be an important phenomenon for study and a useful indicator for cognitive deterioration. The reaction time test we propose is easy to use and can be applied in clinical practice.     

Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients

Neurofibromatosis type 1 (NF1), the most common tumor-predisposing disorder in humans, is caused by defects in the NF1 tumor-suppressor gene. Comprehensive mutation analysis applying RNA-based techniques complemented with FISH analysis achieves mutation detection rates of approximately 95% in NF1 patients. The majority of mutations are minor lesions, and approximately 5% are total gene deletions. We found 13 single- and/or multiexon deletions/duplications out of 1,050 detected mutations using our RNA-based approach in a cohort of 1,100 NF1 patients and confirmed these changes using multiplex ligation-dependent probe amplification (MLPA). With MLPA, we found another 12 novel multiexon deletion/duplications in 55 NF1 patients for whom analysis with multiple assays had not revealed a NF1 mutation, including 50 previously analyzed comprehensively. The extent of the 22 deletions and 3 duplications varied greatly, and there was no clustering of breakpoints. We also evaluated the sensitivity of MLPA in identifying deletions in a mosaic state. Furthermore, we tested whether the MLPA P122 NF1 area assay could distinguish between type I deletions, with breakpoints in low-copy repeats (NF1-LCRs), and type II deletions, caused by aberrant recombination between the JJAZ gene and its pseudogene. Our study showed that intragenic deletions and/or duplications represent only approximately 2% of all NF1 mutations. Although MLPA did not substantially increase the mutation detection rate in NF1 patients, it was a useful first step in a comprehensive mutation analysis scheme to quickly pinpoint patients with single- or multiexon deletions/duplications as well as patients with a total gene deletion who will not need full sequencing of the complete coding region.