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.     

Determination of capillary leakage due to recombinant interleukin-2 by means of noninvasive conductivity measurements

Summary One of the most common side effects of treatment with recombinant interleukin-2 (IL-2) is capillary leakage. Its genesis is not completely understood. The aim of the study was to determine whether capillary leakage can be monitored by means of a non-invasive conductivity technique and to study its starting point. Eight patients with advanced renal cell cancer were studied in a medium care section of the Department of Medical Oncology, University Hospital over 4 days during treatment sessions of continuous, intravenously administered IL-2 (mean dose of 15.6 × 10⁶ IU · m^–2 · day ^–1). The fluid shift from the intravascular to the extra- and intracellular compartments was monitored by means of noninvasive conductivity measurements. Changes in blood volume were calculated from serial erythrocyte counts. The clinical parameters of capillary leakage (oliguria, positive fluid balance, and gain in mass) were recorded. The mean gain in mass was 9% after 4 days of IL-2 treatment. The extracellular fluid volume increased significantly [46 (SD 23.2)%; P < 0.01], whereas the intracellular fluid volume did not change. The increase in blood volume (BV) amounted to 7% (P < 0.05). The decline in albumin concentration was significantly more than the increase in BV [38 (SD 4.3) %; P < 0.01], indicating capillary albumin leakage. The main changes were observed after the 2nd day of treatment. From this study, it is suggested that conductivity measurements are a suitable method to monitor capillary leakage induced by IL-2, and could be used to detect the exact onset and severity of this leakage. The leakage started within the first 24 h of treatment and was detected as a fluid shift from the intravascular to the extracellular space, while the intracellular compartment remained stable. These measurements could be useful during intervention studies with the aim of preventing this adverse effect of IL-2.     

The influence of Ringer's lactate and gelatin infusion on the internal fluid balance of healthy volunteers measured by a non-invasive conductivity technique

Eight healthy male volunteers received in random order at an interval of 1 week 2 litres of Ringer's lactate or 0.8 litre of gelatin (Gelofusine) over half an hour, after overnight fasting. At the end of the infusion period, blood volume and mean arterial pressure had increased significantly in both groups but the increase in blood volume was more pronounced with the colloid. Extracellular fluid volume increased significantly after Ringer's lactate, while a significant decrease was noticed after gelatin. A small decrease in intracellular fluid volume was noted after infusion of Gelofusine, whereas it did not change after infusion of Ringer's lactate. During the 30 min after infusion, blood volume decreased significantly after both treatments but after the colloid it remained higher than the initial value. During the post-infusion period, no significant changes in either intra- or extracellular volume were seen after either treatments. At the end of the study, urine production was significantly more after the Ringer's lactate. It can be concluded that infusion of 0.8 litre of gelatin results in a larger and longer lasting increase in blood volume than 2 litres of Ringer's lactate, probably due to mobilization of extracellular fluid volume. It also leads to extracellular fluid accumulation. The decrease in blood volume after infusion is caused by increased urine production, since no changes were seen in intra- and extracellular fluid volume during this period.     

Antibody Response to a T-Cell-Independent Antigen Is Preserved after Splenic Artery Embolization for Trauma

Splenic artery embolization (SAE) is increasingly being used as a nonoperative management strategy for patients with blunt splenic injury following trauma. The aim of this study was to assess the splenic function of patients who were embolized. A clinical study was performed, with splenic function assessed by examining the antibody response to polysaccharide antigens (pneumococcal 23-valent polysaccharide vaccine), B-cell subsets, and the presence of Howell-Jolly bodies (HJB). The data were compared to those obtained from splenectomized patients and healthy controls (HC) who had been included in a previously conducted study. A total of 30 patients were studied: 5 who had proximal SAE, 7 who had distal SAE, 8 who had a splenectomy, and 10 HC. The median vaccine-specific antibody response of the SAE patients (fold increase, 3.97) did not differ significantly from that of the HC (5.29; P = 0.90); however, the median response of the splenectomized patients (2.30) did differ (P = 0.003). In 2 of the proximally embolized patients and none of the distally embolized patients, the ratio of the IgG antibody level postvaccination compared to that prevaccination was <2. There were no significant differences in the absolute numbers of lymphocytes or B-cell subsets between the SAE patients and the HC. HJB were not observed in the SAE patients. The splenic immune function of embolized patients was preserved, and therefore routine vaccination appears not to be indicated. Although the median antibody responses did not differ between the patients who underwent proximal SAE and those who underwent distal SAE, 2 of the 5 proximally embolized patients had insufficient responses to vaccination, whereas none of the distally embolized patients exhibited an insufficient response. Further research should be done to confirm this finding.     

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.