Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

Antipsychotic drugs have been used effectively for the treatment of schizophrenia symptoms, but they are often associated with metabolic side effects such as weight gain and endocrine disruptions. To investigate the possible mechanisms of antipsychotic-induced metabolic effects, we studied the impact of chronic administration of a typical antipsychotic drug (haloperidol) and an atypical antipsychotic (risperidone) to male rats on food intake, body weight, adiposity, and the circulating concentrations of hormones and metabolites that can influence energy homeostasis. Chronic (28 days) haloperidol administration had no effect on food intake, weight gain or adiposity in male rats, whereas risperidone treatment resulted in a transient reduction in food intake and significantly reduced body weight gain compared to vehicle-treated control rats. Whereas neither antipsychotic had any effect on serum lipid profiles, glucose tolerance or the circulating concentrations of hormones controlled by the hypothalamo-pituitary-thyroid (free T4), -adrenal (corticosterone), -somatotropic (IGF-1), or -gonadotropic axes (testosterone), haloperidol increased circulating insulin levels and risperidone increased serum glucagon levels. This finding suggests that haloperidol or risperidone induce distinct metabolic effects. Since metabolic disorders such as obesity and type 2 diabetes mellitus represent serious health issues, understanding antipsychotic-induced endocrine and metabolic effects may ultimately allow better control of these side effects

The Importance of Brain Banks for Molecular Neuropathological Research: The New South Wales Tissue Resource Centre Experience

New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders

Creativity in Hospitality Industry: Study of Hostels in St. Petersburg

The aim of this study is to explore dimensions of creativity in hostels managerial practices taking the example of St. Petersburg. Within the study 72 semi-structured interviews were conducted with owners and employees of hostels during October–November 2012. The findings of the study identify four main managerial activities as key elements of creativity in hostels. They are: targeted recruitment, segmentation of customers, organization of space, and organization of communications both with internal and external stakeholders

Antecedents and Consequences of Digital Entrepreneurial Ecosystems in the Interaction Process with Smart City Development

The nature of entrepreneurship and its developmental paths in the urban environment are extensively studied in the scientific literature. With a rising interest of scholars in the smart city phenomenon, the role entrepreneurship plays in the development of smart cities became a central topic in academia. However, there is a lack of discussion concerning the specific settings and characteristics of digital entrepreneurship in the smart city scenario. Nowadays, the concept of digital entrepreneurship is considered as a part of the digital entrepreneurial ecosystems (DEE) that provides an environment for effective entrepreneurial activities. Hence, the investigation on how DEE is interconnected with smart cities and how they both can contribute to their mutual development appears both timely and necessary. To reach this research objective, the authors, after giving a clear definition of each component of DEE based on an extensive literature review, consider its interconnection with the smart city model. The connection between the dimensions of a smart city and the structural constituents of DEE is also tracked, highlighting the contribution of each element to the development of a smart city. Through the creation of a comprehensive framework, the results of the paper show clearly that DEE is an inevitable part of a smart city environment. The research also covers the model of DEE engagement in smart city architecture

Region-specific Institutional Context for Citizen-driven Entrepreneurship in Smart Cities: Evidence from Rome and Berlin

During the last decades, the notion of smart cities emerges as one of the key concepts for improving urban areas and including citizens in entrepreneurship activities. The smart city concept should be considered as a multidimensional activity which is carefully balancing human, social, cultural, economic, environmental, and technological aspects to engage citizens to make urban change. The objective of this study is to question the role of citizen entrepreneurship in smart city development and analyse frameworks, strategic actions, and public policies which stipulate it. High levels of application of information and communication technologies (ICTs) and novel digital platforms enable numerous multiplicative benefits and allow the provision of innovative services, shifting our vocabulary to ’‘digital’ and ’‘smart’ services. With the proliferation of the concept of smart cities and disruptive digital tools, it is the entrepreneurs that stimulate the technological development of the cities to become smart. In this paper, the authors have analysed specific public policies that foster citizen entrepreneurship in Rome and Berlin smart cities concepts with the objectives of assessing types and depth of strategic actions that foster citizen-driven entrepreneurship and highlight the differences in frameworks and taxonomies in these two cities

Quality of radiology training and role of Royal Australian and New Zealand College of Radiology in supporting radiology trainees in NSW : results of the first radiology trainee survey

Introduction The Royal Australian and New Zealand College radiology training programme is a 5-year programme with a vast curriculum including reporting and research requirements. Undertaking training can be stressful for trainees who must balance their educational needs and work responsibilities. We undertook the first independent survey of New South Wales (NSW) radiology trainees to evaluate their perceptions about the quality of their training. Methods Focus groups with trainees from multiple NSW training sites were conducted to construct a survey which was then distributed to all NSW Radiology trainees (n = 118). Data from the survey were analysed, and factors correlating to the overall satisfaction with the programme were explored using Spearman's correlation. Results Survey response rate was 70.3%. Eighty-nine per cent of trainees were satisfied with their career choice, and 73% were satisfied with the training programme. Majority felt they had a good exposure to cases, modalities and access to resources to complete their training. Trainee satisfaction significantly correlated with a supportive work environment (r(s) = 0.83, P < 0.0001), which involved supportive consultants (r(s) = 0.75, P < 0.0001), good peer support (r(s) = 0.60, P < 0.0001) and their training site respecting work/life balance (r(s) = 0.62, P < 0.0001). As trainees progressed through the training programme, they became less satisfied, with trainees in years 3 and above being the most dissatisfied. Conclusion NSW radiology trainees are generally satisfied with their training programme and career choices. Trainee satisfaction correlated most strongly with supportive work environment, good consultant support, peer relationships and good work/life balance; satisfaction decreased for senior trainees

Behavioural effects of chronic haloperidol and risperidone treatment in rats

The therapeutic properties of typical antipsychotic drugs (APDs) such as haloperidol in schizophrenia treatment are mainly associated with their ability to block dopamine D2 receptors. This blockade is accompanied by side effects such as extrapyramidal symptoms (EPS). Atypical APDs such as risperidone have superior therapeutic efficacy possibly due to their activity at multiple receptors (in particular 5-HT2A receptors). Although the risk of EPS is significantly lower in atypical than in typical APDs, it is not negligible. To investigate and compare the behavioural profile and EPS-asssociated side effects of haloperidol and risperidone APD treatment we applied a multi-tiered, comprehensive behavioural phenotyping approach. Sprague-Dawley rats were treated chronically (28 days) with supratherapeutic EPS-inducing doses of haloperidol and risperidone using osmotic minipumps. Domains such as motor activity, exploration, memory, and anxiety were analysed together with EPS assessment (“early onset” vacuous chewing movements and catalepsy). Both APDs produced diminished motor activity and exploration, impaired working memory performances, and increased anxiety levels. These effects were more pronounced in haloperidol-treated animals. Chronic APD treatment also caused a time-course dependent elevation of EPS-like symptoms. Risperidone-treated animals showed a catalepsy-like phenotype, which differed to that of haloperidol-treated rats, indicating that processes other than the anticipated dopaminergic mechanisms are underlying this phenomenon. These EPS-related phenotypes are consistent with reported EPS-inducing D2 receptor occupancies of around 80%. Differences in the behavioural profile of haloperidol and risperidone, which were revealed by a comprehensive phenotyping strategy, are likely due to the unique receptor activation profiles of these APDs

Effects of chronic risperidone treatment on the striatal protein profiles in rats

Extrapyramidal symptoms (EPS) commonly occur as side effects of antipsychotic drugs (APDs) and are most likely to arise when the occupancy of dopamine D2 receptors in the striatum by these drugs exceeds 80%. We aimed to characterize changes in the protein expression profile in the striatum of rats after chronic (4 week) supra-therapeutic (EPS-inducing) treatment with risperidone (RIS), an atypical antipsychotic drug. Administration of RIS (2.1 mg/kg/day, via subcutaneous osmotic minipumps) induced significant vacuous chewing movements and catalepsy in male Sprague–Dawley rats over a 28-day treatment period compared with a vehicle (VEH) control group (n = 12) (Karl et al., unpublished observation). Using two-dimensional gel electrophoresis (2DE), total protein extracts from the rat brain striatum were separated and protein expression was analyzed by Phoretix 2D Expression and Image Beta V4.02 software followed by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). 2DE gels resolved up to 450 protein spots, presumably different proteins and/or their isoforms. There were 30 protein spots showing statistically significant different densities between the RIS- and VEH-treated groups. All 30 proteins were successfully identified by MALDI-TOF MS, 28 of these were divided into groups based on their known functions. These included metabolic, signaling, transport, protein metabolism, chaperone, DNA binding and cell cycle categories. We conclude that chronic risperidone treatment accompanied by an EPS-like behavioral phenotype results in alterations in the striatal protein profile possibly subsequent to blockade of dopaminergic systems. These results suggest that possible mechanisms involved in APD-induced EPS include metabolic dysfunction and oxidative stress

Cofilin and DNase I affect the conformation of the small domain of actin.

Cofilin binding induces an allosteric conformational change in subdomain 2 of actin, reducing the distance between probes attached to Gln-41 (subdomain 2) and Cys-374 (subdomain 1) from 34.4 to 31.4 A (pH 6.8) as demonstrated by fluorescence energy transfer spectroscopy. This effect was slightly less pronounced at pH 8.0. In contrast, binding of DNase I increased this distance (35.5 A), a change that was not pH-sensitive. Although DNase I-induced changes in the distance along the small domain of actin were modest, a significantly larger change (38.2 A) was observed when the ternary complex of cofilin-actin-DNase I was formed. Saturation binding of cofilin prevents pyrene fluorescence enhancement normally associated with actin polymerization. Changes in the emission and excitation spectra of pyrene-F actin in the presence of cofilin indicate that subdomain 1 (near Cys-374) assumes a G-like conformation. Thus, the enhancement of pyrene fluorescence does not correspond to the extent of actin polymerization in the presence of cofilin. The structural changes in G and F actin induced by these actin-binding proteins may be important for understanding the mechanism regulating the G-actin pool in cells