Mammals are subject to colonization by an astronomical number of mutualistic and commensal microorganisms on their environmental exposed surfaces. These mutualistic species build up a complex community, called the indigenous microbiota, which aid their hosts in several physiological activities. In this review, we show that the transition between a non-colonized and a colonized state is associated with modification on the pattern of host inflammatory and behavioral responsiveness. There is a shift from innate anti-inflammatory cytokine production to efficient release of proinflammatory mediators and rapid mobilization of leukocytes upon infection or other stimuli. In addition, host responses to hypernociceptive and stressful stimuli are modulated by indigenous microbiota, partly due to the altered pattern of innate and acquired immune responsiveness of the non-colonized host. These altered responses ultimately lead to significant alteration in host behavior to environmental threats. Therefore, host colonization by indigenous microbiota modifies the way the host perceives and reacts to environmental stimuli, improving resilience of the entire host-microorganism consortium to environmental stresses.
Necrotizing enterocolitis is the leading cause of morbidity and mortality from gastrointestinal disease in premature infants and is characterized by initial feeding intolerance and abdominal distention followed by the rapid progression to coagulation necrosis of the intestine and death in many cases. Although the risk factors for NEC development remain well accepted, namely premature birth and formula feeding, the underlying mechanisms remain incompletely understood. Current thinking indicates that NEC develops in response to an abnormal interaction between the mucosal immune system of the premature host and an abnormal indigenous microflora, leading to an exaggerated mucosal inflammatory response and impaired mesenteric perfusion. In seeking to understand the molecular and cellular events leading to NEC, various animal models have been developed. However, the large number and variability between the available animal models and the unique characteristics of each has raised important questions regarding the validity of particular models for NEC research. In an attempt to provide some guidance to the growing community of NEC researchers, we now seek to review the key features of the major NEC models that have been developed in mammalian and nonmammalian species and to assess the advantages, disadvantage, challenges and major scientific discoveries yielded by each. A strategy for model validation is proposed, the principal models are compared, and future directions and challenges within the field of NEC research are explored.
Antifungal chemotherapy in weakened resistance is restricted to the following three substances: amphotericin B, 5-fluorocytosine and the azo dyes. The paper only discusses the therapy of indigenous iatrogenic fungal infections due to mycelial fungi (molds) and yeasts. The pathogenesis must be investigated in every case, since a healthy individual does not contract such a fungal infection. Prophylaxis would be more important than treatment of such complications. At the end of the paper, the therapy is summarized in a table. It is clearly seen from the table that the optimal modern therapy of systemic mycoses is a combination of 5-fluorocytosine in a normal dosage and amphotericin B at reduced dosage.
To examine the immunological impacts of polychlorinated biphenyls (PCBs) in an environmentally relevant way, we orally contaminated Arctic charr (Salvelinus alpinus) with Aroclor 1254. After contamination, fish were either fed (0 and 100 mg Aroclor 1254 kg(-1) fish wt) or fasted (0, 1, 10, and 100 mg kg(-1)) to mimic cycles of feeding-fasting experienced by Arctic animals. After four months, PCB concentrations in muscle were the same in fasted and fed fish; however, PCBs in kidneys of fed fish were 33 to 50% of those in fasted fish. Arctic charr were exposed to Aeromonas salmonicida, the bacteria responsible for furunculosis, by cohabitation with infected conspecifics. Fasted fish had a significant trend toward lower survival with higher dose of PCBs--from 68% in controls to 48% in treatment involving 100 mg kg(-1). Independent of PCB contamination, fed fish had the lowest survival; we attribute this to stress associated with establishing and maintaining feeding hierarchies. A significant decrease in the activity of lysozyme was observed in skin mucus, as was hemagglutination ability of a putative rhamnose lectin in fasted, but not in fed, PCB-treated fish. These results demonstrate the immunosuppressive effects of PCBs on Arctic charr, and they illustrate the importance of considering environmentally relevant nutritional status in ecotoxicological studies.
Inflammation is a key factor in the development of atherosclerotic coronary artery disease. It is promoted through the inflammasome, a molecular machine that produces IL (interleukin)-1? in response to cholesterol crystal accumulation in macrophages. The CARD8 (caspase recruitment domain 8) protein modulates this process by suppressing caspase 1 and the transcription factor NF-?B (nuclear factor ?B). The expression of CARD8 mRNA was examined in atherosclerotic vascular tissue and the impact on MI (myocardial infarction) of a polymorphism in the CARD8 gene determined. CARD8 mRNA was analysed by microarray of human atherosclerotic tissue and compared with transplant donor arterial tissue. Microarray analysis was performed for proximal genes associated with the rs2043211 locus in plaque. The CARD8 rs2043211 polymorphism was analysed by genotyping of two Swedish MI cohorts, FIA (First Myocardial Infarction in Northern Sweden) and SCARF (Stockholm Coronary Atherosclerosis Risk Factor). The CRP (C-reactive protein) level was measured in both cohorts, but the levels of the pro-inflammatory cytokines IL-1?, IL-18, TNF (tumour necrosis factor) and MCP-1 (monocyte chemoattractant protein) were measured in sera available from the SCARF cohort. CARD8 mRNA was highly expressed in atherosclerotic plaques compared with the expression in transplant donor vessel (P