53 research outputs found

    One-hit wonder: Late after burn injury, granulocytes can clear one bacterial infection but cannot control a subsequent infection

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    Objective: Burn injury induces an acute hyperactive immune response followed by a chronic immune dysregulation that leaves those afflicted susceptible to multiple secondary infections. Many murine models are able to recapitulate the acute immune response to burn injury, yet few models are able to recapitulate long-term immune suppression and thus chronic susceptibility to bacterial infections seen in burn patients. This has hindered the field, making evaluation of the mechanisms responsible for these susceptibilities difficult to study. Herein we describe a novel mouse model of burn injury that promotes chronic immune suppression allowing for susceptibility to primary and secondary infections and thus allows for the evaluation of associated mechanisms. Methods: C57Bl/6 mice receiving a full-thickness contact burn were infected with Pseudomonas aeruginosa 14 days (primary infection) and/or 17 days (secondary infection) after burn or sham injury. The survival, pulmonary and systemic bacterial load as well as frequency and function of innate immune cells (neutrophils and macrophages) were evaluated. Results: Following secondary infection, burn mice were less effective in clearance of bacteria compared to sham injured or burn mice following a primary infection. Following secondary infection both neutrophils and macrophages recruited to the airways exhibited reduced production of anti-bacterial reactive oxygen and nitrogen species and the pro-inflammatory cytokineIL-12 while macrophages demonstrated increased expression of the anti-inflammatory cytokine interleukin-10 compared to those from sham burned mice and/or burn mice receiving a primary infection. In addition the BALF from these mice contained significantly higher level so of the anti-inflammatory cytokine IL-4 compared to those from sham burned mice and/or burn mice receiving a primary infection. Conclusions: Burn-mediated protection from infection is transient, with a secondary infection inducing immune protection to collapse. Repeated infection leads to increased neutrophil and macrophage numbers in the lungs late after burn injury, with diminished innate immune cell function and an increased anti-inflammatory cytokine environment

    Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury

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    Smoke inhalation associated with structural fires, wildfires, or explosions leads to lung injury, for which innovative and clinically relevant animal models are needed to develop effective therapeutics. We have previously reported that damage-associated molecular patterns (DAMPs) and anti-inflammatory cytokines correlate with infectious complications in patients diagnosed with inhalational injury. In this study, we describe a novel and translational murine model of acute inhalational injury characterized by an accumulation of protein and neutrophils in the bronchoalveolar space, as well as histological evidence of tissue damage. Mice were anesthetized, and a cannula was placed in the trachea and exposed to smoldering plywood smoke three times for 2-min intervals in a smoke chamber. Here we demonstrate that this model recapitulates clinically relevant phenotypes, including early release of double-stranded DNA (dsDNA), IL-10, monocyte chemoattractant protein (MCP)-1, and CXCL1 along with neutrophilia early after injury, accompanied by subsequent susceptibility to opportunistic infection with Pseudomonas aeruginosa. Further investigation of the model, and in turn a reanalysis of patient samples, revealed a late release of the DAMP hyaluronic acid (HA) from the lung. Using nitric oxide synthase-deficient mice, we found that Nos2 was required for increases in IL-10, MCP-1, and HA following injury but not release of dsDNA, CXCL1 expression, early neutrophilia, or susceptibility to opportunistic infection. Depletion of CXCL1 attenuated early neutrophil recruitment, leading to decreased histopathology scores and improved bacterial clearance in this model of smoke inhalation. Together, these data highlight the potential therapeutic benefit of attenuating neutrophil recruitment in the first 24 h after injury in patients

    Characterization of the Basal and mTOR-Dependent Acute Pulmonary and Systemic Immune Response in a Murine Model of Combined Burn and Inhalation Injury

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    Severe burn injury leads to a cascade of local and systemic immune responses that trigger an extreme state of immune dysfunction, leaving the patient highly susceptible to acute and chronic infection. When combined with inhalation injury, burn patients have higher mortality and a greater chance of developing secondary respiratory complications including infection. No animal model of combined burn and inhalation injury (B+I) exists that accurately mirrors the human clinical picture, nor are there any effective immunotherapies or predictive models of the risk of immune dysfunction. Our earlier work showed that the mechanistic/mammalian target of rapamycin (mTOR) pathway is activated early after burn injury, and its chemical blockade at injury reduced subsequent chronic bacterial susceptibility. It is unclear if mTOR plays a role in the exacerbated immune dysfunction seen after B+I injury. We aimed to: (1) characterize a novel murine model of B+I injury, and (2) investigate the role of mTOR in the immune response after B+I injury. Pulmonary and systemic immune responses to B+I were characterized in the absence or presence of mTOR inhibition at the time of injury. Data describe a murine model of B+I with inhalation-specific immune phenotypes and implicate mTOR in the acute immune dysfunction observed

    Diet and lifestyle interventions in postpartum women in China: study design and rationale of a multicenter randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>"Doing the month", or "sitting month", is a traditional practice for postpartum women in China and other Asian countries, which includes some taboos against well-accepted healthy diet and lifestyles in general population. Previous studies have shown this practice may be associated with higher prevalence of postpartum problems. The current multicenter randomized controlled trial (RCT) aims to evaluate outcomes of diet and lifestyle interventions in Chinese postpartum women.</p> <p>Methods/Design</p> <p>The current multicenter RCT will be conducted in three representative areas in China, Shandong province, Hubei province and Guangdong province, which locate in northern, central and southern parts of China, respectively. Women who attend routine pregnancy diagnosis in hospitals or maternal healthcare centers will be invited to take part in this study. At least 800 women who meet our eligibility criteria will be recruited and randomly assigned to the intervention group (n > = 400) and the control group (n > = 400). A three-dimension comprehensive intervention strategy, which incorporates intervention measures simultaneously to individual postpartum woman, their family members and community environment, will be utilized to maximize the effectiveness of intervention. Regular visiting and follow-up will be done in both group; nutrition and health-related measurements will be assessed both before and after the intervention.</p> <p>Discussion</p> <p>To our knowledge, this current study is the first and largest multicenter RCT which focus on the effectiveness of diet and lifestyle intervention on reducing the incidence rate of postpartum diseases and improving health status in postpartum women. We hypothesize that the intervention will reduce the incidence rates of postpartum diseases and improve nutrition and health status due to a balanced diet and reasonable lifestyle in comparison with the control condition. If so, the results of our study will provide especially important evidence for changes in both the concept and action of traditional postpartum practice in China.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID NCT01039051.</p

    Traditional beliefs and practices in the postpartum period in Fujian Province, China: a qualitative study

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    <p>Abstract</p> <p>Background</p> <p><it>Zuo yuezi </it>is the month postpartum in China associated with a variety of traditional beliefs and practices. We explored the current status of <it>zuo yuezi </it>from social, cultural and western medical perspectives.</p> <p>Methods</p> <p>We interviewed family members (36) and health workers (8) in Fujian Province, selecting one rural and one rapidly developing urban county. We asked about their traditional beliefs and their behaviour postpartum. We used a framework approach to identify main themes. We categorised reported behaviour against their probable effects on health, drawing on Western standards.</p> <p>Results</p> <p>Respondents reported that <it>zuo yuezi </it>was commonly practiced in urban and rural families to help the mother regain her strength and protect her future health. <it>Zuo yuezi </it>included: dietary precautions, such as eating more food and avoiding cold food; behavioural precautions, such as staying inside the home, avoiding housework and limiting visitors; hygiene precautions, such as restricting bathing and dental hygiene; and practices associated with infant feeding, including supplementary feeding and giving honeysuckle herb to the infant. Respondents reported that the main reasons for adhering to these practices were respect for tradition, and following the advice of elders. Categorised against Western medical standards, several <it>zuo yuezi </it>practices are beneficial, including eating more, eating protein rich food, avoiding housework, and daily vulval and perineal hygiene. A few are potentially harmful, including giving honeysuckle herb, and avoiding dental hygiene. Some women reported giving infants supplementary feeds, although <it>zuo yuezi </it>emphasises breast feeding.</p> <p>Conclusion</p> <p><it>Zuo yuezi </it>is an important ritual in Fujian. In medical terms, most practices are beneficial, and could be used by health staff to promote health in this period. Further research on reported potentially harmful practices, such as supplements to breast feeding, is needed.</p
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