Elevation in Body Temperature to Fever Range Enhances and Prolongs Subsequent Responsiveness of Macrophages to Endotoxin Challenge

Macrophages are often considered the sentries in innate immunity, sounding early immunological alarms, a function which speeds the response to infection. Compared to the large volume of studies on regulation of macrophage function by pathogens or cytokines, relatively little attention has been devoted to the role of physical parameters such as temperature. Given that temperature is elevated during fever, a long-recognized cardinal feature of inflammation, it is possible that macrophage function is responsive to thermal signals. To explore this idea, we used LPS to model an aseptic endotoxin-induced inflammatory response in BALB/c mice and found that raising mouse body temperature by mild external heat treatment significantly enhances subsequent LPS-induced release of TNF-α into the peritoneal fluid. It also reprograms macrophages, resulting in sustained subsequent responsiveness to LPS, i.e., this treatment reduces “endotoxin tolerance” in vitro and in vivo. At the molecular level, elevating body temperature of mice results in a increase in LPS-induced downstream signaling including enhanced phosphorylation of IKK and IκB, NF-κB nuclear translocation and binding to the TNF-α promoter in macrophages upon secondary stimulation. Mild heat treatment also induces expression of HSP70 and use of HSP70 inhibitors (KNK437 or Pifithrin-µ) largely abrogates the ability of the thermal treatment to enhance TNF-α, suggesting that the induction of HSP70 is important for mediation of thermal effects on macrophage function. Collectively, these results support the idea that there has been integration between the evolution of body temperature regulation and macrophage function that could help to explain the known survival benefits of fever in organisms following infection

Polysaccharide peptide from Coriolus versicolor induces interleukin 6-related extension of endotoxin fever in rats

Purpose: Polysaccharide peptide (PSP) extracted from the Coriolus versicolor mushroom is frequently suggested as an adjunct to the chemo- or radiotherapy in cancer patients. In a previous study we showed that PSP induced a tumour necrosis factor-a (TNF-a)-dependent anapyrexia-like response in rats. Thus, PSP appears to be a factor which modifies a number of pathophysiological responses. Because of this, PSP is suggested as a potential adjuvant for cancer therapy during which cancer patients frequently contract microbial infections accompanied by fever. The aim of the present study was to investigate whether or not PSP can modulate the course of the fever in response to an antigen such as lipopolysaccharide (LPS). Materials and methods: Body temperature (Tb) of male Wistar rats was measured by biotelemetry. PSP was injected intraperitoneally (i.p.) at a dose of 100mgkg 1, 2 h before LPS administration (50 mgkg 1, i.p.). The levels of interleukin (IL)-6 and TNF-a in the plasma of rats were estimated 3 h and 14 h post-injection of PSP using a standard sandwich ELISA kit. Results: We report that i.p. pre-injection of PSP 2 h before LPS administration expanded the duration of endotoxin fever in rats. This phenomenon was accompanied by a significant elevation of the blood IL-6 level of rats both 3 h and 14 h post-injection of PSP. Pre-treatment i.p. of the rats with anti-IL-6 antibody (30 mg/rat) prevented the PSP-induced prolongation of endotoxin fever. Conclusions: Based on these data, we conclude that PSP modifies the LPS-induced fever in IL-6-related fashion

Trivial trauma and delayed rupture of a normal spleen: a case report

Although a majority of splenic ruptures present acutely with a known mechanism of injury, a minority of patients present days to weeks following trauma with a delayed rupture. Also uncommon is the atraumatic rupture, the vast majority of which occur in patients with underlying splenic pathology. A handful of cases of apparently spontaneous rupture of a normal spleen are reported; however, there is debate about whether these actually represent delayed ruptures following a history of trauma that is not elicited. Although a few cases of delayed rupture of the spleen following trivial trauma have been reported, the majority of these present evidence of an underlying disease process. We found only two such cases that documented a normal spleen and three cases where underlying splenic pathology was not reported. We review the literature and discuss the phenomenon of delayed rupture of the normal spleen following trivial trauma

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Body piercing and tattoos: a survey on young adults' knowledge of the risks and practices in body art

<p>Abstract</p> <p>Background</p> <p>The practice of tattooing and piercing has expanded in western society. In order to verify young adults' knowledge of the risk and practices related to body art, an investigation was conducted among freshmen of the University of Bari in the region of Apulia, Italy.</p> <p>Methods</p> <p>The study was carried out in the Academic Year 2009-2010 through an anonymous self-administered written questionnaire distributed to 1.656 freshmen enrolled in 17 Degree Courses.</p> <p>Results</p> <p>Of the 1.598 students included in the analysis, 78.3% believe it is risky to undergo piercing/tattoo practices. AIDS was indicated as a possible infection by 60.3% of freshmen, hepatitis C by 38.2%, tetanus by 34.3% and hepatitis B by 33.7% of the sample. 28.1% of freshmen were not aware that there are also non-infectious complications. 29% of the sample had at least one piercing or tattoo (this percentage does not include earlobe piercing in women). Of those with body art, the decision to undergo body art was made autonomously in 57.9% of the participants. 56.3% of freshmen undergoing body art had taken less than a month to decide. With regard to the reasons that led the sample to undergo body art, 28.4% were unable to explain it, 23.8% answered to improve their aesthetic aspect, 18.4% to distinguish themselves from others, 12.3% for fashion; 17.1% for other reasons. 25.4% of the sample declared that they had a piercing (79.8% female vs 20.2% male; ratio M/F 1:4.0). The average age for a first piercing was 15.3 years (range 10-27; SD ± 2.9). 9.6% of the sample declared that they have a tattoo (69.9% female vs 30.1% male; ratio M/F 1:2.3). The average age for a first tattoo was 17.5 years (range 10-26, SD ± 2.4).</p> <p>Conclusions</p> <p>Most of the freshmen knew about AIDS-related risks but not other potential risks. Body art is fairly common among young adults (especially women). The decision is often not shared with the family and is undertaken mostly without a specific reason or for the improvement of aesthetic aspect. Information about freshmen's knowledge, attitudes and practices could help in effective planning of health promotion strategies.</p

Differential Genetic Susceptibility to Child Risk at Birth in Predicting Observed Maternal Behavior

This study examined parenting as a function of child medical risks at birth and parental genotype (dopamine D4 receptor; DRD4). Our hypothesis was that the relation between child risks and later maternal sensitivity would depend on the presence/absence of a genetic variant in the mothers, thus revealing a gene by environment interaction (GXE). Risk at birth was defined by combining risk indices of children's gestational age at birth, birth weight, and admission to the neonatal intensive care unit. The DRD4-III 7-repeat allele was chosen as a relevant genotype as it was recently shown to moderate the effect of environmental stress on parental sensitivity. Mothers of 104 twin pairs provided DNA samples and were observed with their children in a laboratory play session when the children were 3.5 years old. Results indicate that higher levels of risk at birth were associated with less sensitive parenting only among mothers carrying the 7-repeat allele, but not among mothers carrying shorter alleles. Moreover, mothers who are carriers of the 7-repeat allele and whose children scored low on the risk index were observed to have the highest levels of sensitivity. These findings provide evidence for the interactive effects of genes and environment (in this study, children born at higher risk) on parenting, and are consistent with a genetic differential susceptibility model of parenting by demonstrating that some parents are inherently more susceptible to environmental influences, both good and bad, than are others

Data for improvement and clinical excellence: protocol for an audit with feedback intervention in long-term care

<p>Abstract</p> <p>Background</p> <p>There is considerable evidence about the effectiveness of audit coupled with feedback, although few audit with feedback interventions have been conducted in long-term care (LTC) settings to date. In general, the effects have been found to be modest at best, although in settings where there has been little history of audit and feedback, the effects may be greater, at least initially. The primary purpose of the Data for Improvement and Clinical Excellence (DICE) Long-Term Care project is to assess the effects of an audit with feedback intervention delivered monthly over 13 months in four LTC facilities. The research questions we addressed are:</p> <p indent="1">1. What effects do feedback reports have on processes and outcomes over time?</p> <p indent="1">2. How do different provider groups in LTC and home care respond to feedback reports based on data targeted at improving quality of care?</p> <p>Methods/design</p> <p>The research team conducting this study comprises researchers and decision makers in continuing care in the province of Alberta, Canada. The intervention consists of monthly feedback reports in nine LTC units in four facilities in Edmonton, Alberta. Data for the feedback reports comes from the Resident Assessment Instrument Minimum Data Set (RAI) version 2.0, a standardized instrument mandated for use in LTC facilities throughout Alberta. Feedback reports consist of one page, front and back, presenting both graphic and textual information. Reports are delivered to all staff working in the four LTC facilities. The primary evaluation uses a controlled interrupted time series design both adjusted and unadjusted for covariates. The concurrent process evaluation uses observation and self-report to assess uptake of the feedback reports. Following the project phase described in this protocol, a similar intervention will be conducted in home care settings in Alberta. Depending on project findings, if they are judged useful by decision makers participating in this research team, we plan dissemination and spread of the feedback report approach throughout Alberta.</p

Nothing a Hot Bath Won't Cure: Infection Rates of Amphibian Chytrid Fungus Correlate Negatively with Water Temperature under Natural Field Settings

Dramatic declines and extinctions of amphibian populations throughout the world have been associated with chytridiomycosis, an infectious disease caused by the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Previous studies indicated that Bd prevalence correlates with cooler temperatures in the field, and laboratory experiments have demonstrated that Bd ceases growth at temperatures above 28°C. Here we investigate how small-scale variations in water temperature correlate with Bd prevalence in the wild. We sampled 221 amphibians, including 201 lowland leopard frogs (Rana [Lithobates] yavapaiensis), from 12 sites in Arizona, USA, and tested them for Bd. Amphibians were encountered in microhabitats that exhibited a wide range of water temperatures (10–50°C), including several geothermal water sources. There was a strong inverse correlation between the water temperature in which lowland leopard frogs were captured and Bd prevalence, even after taking into account the influence of year, season, and host size. In locations where Bd was known to be present, the prevalence of Bd infections dropped from 75–100% in water <15°C, to less than 10% in water >30°C. A strong inverse correlation between Bd infection status and water temperature was also observed within sites. Our findings suggest that microhabitats where water temperatures exceed 30°C provide lowland leopard frogs with significant protection from Bd, which could have important implications for disease dynamics, as well as management applications