Transient sex-related changes in the mice hypothalamo–pituitary–adrenal (HPA) axis during the acute phase of the inflammatory process

The potential role of endogenous sex hormones in regulating hypothalamo–pituitary–adrenal (HPA) axis function was investigated after a single injection of endotoxin in adult (8 week old) BALB/c mice of both sexes. The effect of LPS on plasma ACTH, corticosterone (B), testosterone and oestradiol (E) levels and on anterior pituitary (AP) ACTH and adrenal B contents at different times after treatment was studied. The results indicate that: (a) basal B but not ACTH plasma levels were significantly higher in female than in male mice; (b) LPS significantly increased both ACTH and B plasma levels over the baseline 2 h after injection, both hormone levels being higher in female than in male mice; (c) although plasma ACTH concentrations recovered the basal value at 72 h after LPS in animals of both sexes, plasma B levels returned to the baseline only at 120 h after treatment; (d) E plasma levels significantly increased 2 h after LPS and returned to the baseline at 72 h post-treatment, in both sexes; (e) at 2 h after LPS, testosterone plasma levels significantly decreased in male mice and increased in female mice, recovering the baseline level at 120 and 72 h after LPS, respectively; (f) AP ACTH content was similar in both sexes in basal condition and it was significantly diminished 72 h post-treatment without sex difference; whereas AP ACTH returned to basal content 120 h after LPS in males, it remained significantly decreased in females; (g) basal adrenal B content was higher in female than in male mice, and it significantly increased in both sexes 2 h post-LPS, maintaining this sex difference. Whereas adrenal B returned to basal content 72 h after treatment in male mice, it remained significantly enhanced up to 120 h post-LPS in female animals. The data demonstrate the existence of a clear sexual dimorphism in basal condition and during the acute phase response as well as in the recovery of the HPA axis function shortly after infection

Scaling up the Planning Game: Collaboration Challenges in Large-Scale Agile Product Development

One of the benefits of agile is close collaboration of customer and developer. This ensures good commitment and excellent knowledge flows of information about priorities and efforts. However, it is unclear if this benefit can be leveraged at scale. Clearly, it is infeasible to use practices such as planning game with several agile teams in the room. In this paper, we investigate how a large-scale agile organization manages, what challenges exist, and which opportunities can be leveraged. We found challenges in three areas: (i) the abil-ity to estimate, prioritize, and plan; (ii) the context of planning with respect to working environment, team build-up, and team spirit; and (iii) the ceremonial agreement which promises to allow leveraging abilities in a given context

Depicting the smarter cities of the future: A systematic literature review & field study

Smart Cities have become one of the most interesting research topics for governments, businesses and researchers in the last few years. Being a Smart City implies a competitive edge compared to other cities in terms of economic growth, sustainability, human resources and governance. Therefore, more and more governments pursue this future vision and hop onto the Smart City `Bandwagon'. However, the development of Smart City solutions is faced with challenges since there is no clear definition for Smart Cities yet. This paper provides a review on what challenges arise when designing Smart City solutions to provide a complete overview of identified challenges. This paper carries out a systematic literature review of publications between 2008 and 2016 which will be compared with a field study on Smart City initiatives conducted by the municipality of Enschede to develop a requirements framework for these projects. This research is relevant to governments and businesses aiming to create Smart Cities and for researchers, who aim to enhance the concept of Smart Cities. This paper found eight sub-domains within the topic of Smart Cities and these are: Technical Infrastructure, Application Domains, System Integration, Data Processing, Governance & Management, Society & Citizens, Business Domain and Environmental Sustainability. The eight sub-domains are respectively divided in two types: technological and non-technological domains. By firstly identifying the challenges and their solutions within these sub-domains, this paper proposes a requirements framework in combination with a checklist of questions to provide guidance for promoters to conduct future initiatives

Requirements Prioritization Based on Benefit and Cost Prediction: An Agenda for Future Research

In early phases of the software cycle, requirements prioritization necessarily relies on the specified requirements and on predictions of benefit and cost of individual requirements. This paper presents results of a systematic review of literature, which investigates how existing methods approach the problem of requirements prioritization based on benefit and cost. From this review, it derives a set of under-researched issues which warrant future efforts and sketches an agenda for future research in this area

Cytokines stimulate the CRH but not the vasopressin neuronal system: evidence for a median eminence site of interleukin-6 action

Antigen-activated immune cells acutely release cytokines which, besides their effects on the immune system, increase hypothalamopituitary-adrenocortical (HPA) function to counteract the inflammatory process. The present study was designed to test, using in vitro paradigms, whether there exists a hypothalamic and/or a median eminence site of action, whereby different substances derived from the immune system could stimulate the CRH and/or the arginine-vasopressin (AVP) neuronal pathway. For this purpose, whole medial basal hypothalamus (containing the median eminence) were dissected from female rats and incubated in vitro with several concentrations of interleukin-1 (IL-1)beta, interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, thymosin fraction 5 (TF5) or bacterial lipopolysaccharide (LPS). After a 40-min incubation period, the amounts of CRH and AVP released into the incubation medium were measured by specific radioimmunoassays (RIAs). Additional experiments were carried out by superfusing isolated rat median eminence fragments with the different test substances; CRH and AVP released into the medium were also measured by RIAs. The results indicated that IL-1 beta (10(-11) to 10(-7) M), IL-6 (0.06 x 10(-10) to 0.4 x 10(-10) M), TNF-alpha (6 x 10(-9) to 6 x 10(-7) M) and TF5 (5-500 micrograms/ml) but not LPS (1-100 ng/ml) significantly enhanced hypothalamic CRH secretion above baseline in a concentration-related fashion. Additionally, superfusion experiments demonstrated that, among all test substances, only IL-6 possesses a direct and dose-dependent CRH-releasing activity at the median eminence level. Conversely, no preparation enhanced basal AVP release in either in vitro design.(ABSTRACT TRUNCATED AT 250 WORDS

Impaired hypothalamo-pituitary-adrenal axis function in Swiss nude athymic mice

Various evidence suggests a bidirectional circuit between the immune and neuroendocrine systems. Because of the well-known role of the thymus in the regulation of the immune function, we designed this study to determine whether the lack of thymus may affect hypothalamo-pituitary-adrenal (HPA) axis activity by using both in vivo and in vitro paradigms in Swiss nude (athymic) and BALB/c (normal) mice. Eight-week-old female mice of both strains were used to study: (a) the in vivo response of the HPA axis to various stress stimuli acting at either hypothalamic (ether vapor inhalation, insulin administration), pituitary (CRH injection) or adrenal (ACTH treatment) level and (b) the in vitro response of pituitary and adrenal cells to CRH and ACTH stimulation, respectively. The results indicate that: (1) basal plasma ACTH levels were significantly (p < 0.05) higher in Swiss nude than in BALB/c mice, whereas basal plasma corticosterone (B) concentrations were similar in both strains of mice; (2) the stress-induced release of ACTH and B in plasma were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice, regardless of the stimulus applied; (3) the in vitro pituitary response to CRH and the adrenal response to ACTH were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice, whereas (4) hypothalamic CRH and pituitary ACTH contents were similar in both strains, adrenal B concentration was significantly (p < 0.05) lower in athymic mice; in addition, the nude mice adrenal glands were larger than those of BALB/c animals, due to marked hypertrophy of the zona fasciculata.(ABSTRACT TRUNCATED AT 250 WORDS