Excitation of rat hippocampal interneurons via modulation of endogenous agonist activity at the α7 nicotinic ACh receptor

The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR) is prominently expressed in the hippocampus where it is thought to play a role in the regulation of cognitive function. In this study, we have investigated the effects of 5-hydroxyindole (5-HI), a positive modulator of the α7 nAChR, on GABAergic activity in hippocampal CA1 stratum radiatum interneurons in acute rat brain slices. Superfusion of 5-HI (100 μ m ) increased the mean frequency and amplitude of spontaneous IPSCs (sIPSCs). The potentiation was occluded by pretreatment of slices with: (1) a high concentration of the broad-spectrum agonist nicotine to desensitize the α7 receptor, (2) an α7 nAChR antagonist, and (3) tetrodotoxin to block action potential firing. These results indicate that facilitation by 5-HI was mediated by the α7 nAChR and required neuronal excitation. In contrast, 5-HI had no effect on sIPSCs recorded in hippocampal slices from younger animals, even though the expression of functional α7 nAChRs was confirmed by agonist application experiments. In these slices, 5-HI only enhanced sIPSCs after pretreatment with the acetylcholinesterase inhibitor Bw284c51. Taken together, our results suggest that 5-HI facilitates GABAergic transmission via excitation of the α7 nAChR, and that this effect requires the presence of the endogenous agonist ACh in the extracellular environment of the receptor.     

Setting targets: a three-stage model for determining priorities for health promotion

This paper describes a three-stage model for setting targets for health promotion. The model was developed in 1992 in response to the need to identify priority areas for health promotion for women in the Hunter Region of New South Wales. The approach enabled epidemiological data and views from the community to be synthesised and integrated with those of experts from health and social services (key informants), using a nominal group process. The reliability of the method was investigated by replicating the process with two groups of key informants. There was considerable commonality in the targets generated by the two groups. The process resulted in the identification of seven targets that reflected the concerns of the community and local experts as well as the health priorities suggested by local epidemiological data. The model used could be adapted for determining priorities in a wide range of health and health care settings, where available resources restrict the range of services or activities which can be offered. (Aust J Public Health 1995; 19: 263–9)     

Isolation of non-spore-forming anaerobic bacteria from patients with tuberculosis of the lungs and other diseases of the respiratory organs

The use of specific means in bacteriological examination for anaerobic microflora in patients with purulent inflammatory diseases of the lungs including ones developing in the presence of pulmonary tuberculosis was validated. Isolation of nonsporulating anaerobic bacteria in monocultures or as a component of polymicrobial associations was shown important for correct diagnosis and using of etiotropic therapy and respective therapeutic measures. This should enable to prevent or to limit development of severe destructive affections of the lungs.     

Evidence,education and multi-disciplinary integration are needed to embed exercise into lung cancer clinical care: A qualitative study involving physiotherapists

Aims: To explore physiotherapists perceptions regarding barriers and enablers to embedding exercise into routine lung cancer clinical care. Design: Qualitative study (content analysis). Eight physiotherapists working in the area of lung cancer at five hospitals participated. The focus group was conducted, transcribed verbatim and independently crosschecked. Thematic analysis was utilized. Results: The data generated four major themes: evidence justifying exercise; staffing and services; maximising the efficacy of interventions; and hospital culture. Physiotherapists perceived that barriers included lack of evidence, lack of physiotherapy time and funding, inconsistencies in patient access to outpatient exercise programs, lack of clear referral pathways, limited knowledge about exercise by the wider multi-disciplinary team, and poor culture of physical activity in the inpatient setting. Recommendations included developing a stronger evidence-base, establishing set patient pathways into exercise programs, re-allocating physiotherapy services to high-risk patients, and integrating/involving the multi-disciplinary team particularly through education and communication. Conclusion: This study has identified barriers to, and potential strategies for, the embedding of exercise into lung cancer clinical practice. Evidence, education and multi-disciplinary integration are viewed by physiotherapists as critical for success. A targeted gradual approach, by applying these strategies at defined stages across the lung cancer pathway, is recommended to facilitate future practice change.     

Dendritic cells process synthetic long peptides better than whole protein,improving antigen presentation and T‐cell activation

The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte‐derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4⁺ and CD8⁺ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome‐ and transporter associated with Ag processing‐dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD8⁺ T‐cell activation.     

A new hypothesis about hematopoietic Pbx-interaction protein (HPIP): Can it be a key factor in neurodegeneration in the post-menopausal period?

Neuronal degeneration in the post-menopausal term leads to cognitive symptoms such as anxiety, difficulty in concentrating, overreacting to minor upsets, quickly becoming irritated and forgetfulness in approximately 70–80% of all women around the world. These symptoms, which result from microtubule damage in the axon extensions of hippocampal neurons in during menopause, greatly reduce individuals’ life quality. Thus, an investigation of the estrogen receptor-signaling pathway–microtubule dynamic triangle and the possible links between them is important when it comes to explaining the possible mechanism of neurodegeneration. Hematopoietic Pbx-interaction protein (HPIP), a microtubule-binding protein, is a novel scaffolding protein. The detection of this protein on neurons represents the most important step in our hypothesis. The importance of the hypothesis is that it might provide important clues about the possible role of HPIP and its mechanism through in vivo and in vitro studies of estrogen receptors–microtubules and the HPIP triangle in terms of neuronal degeneration in the post-menopausal period.