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Background:Abdominal obesity plays an important role in the development of insulin resistance, diabetes mellitus and atherosclerosis. The exact pathophysiological mechanisms are unclear but adipocyte dysfunction is thought to be crucial. Infections are associated with the development of atherosclerosis as well as diabetes. In this study we investigated whether adipocytes can be infected and whether this results in production of inflammatory cytokines relevant for the development of atherosclerosis and diabetes.Methods:Pre-adipocytes were cultured and differentiated into mature adipocytes in vitro. Adipocytes and pre-adipocytes were incubated with infective and heat-inactivated Chlamydia pneumoniae, cytomegalovirus (CMV), adenovirus (Ad) subtypes 2 and 36, influenza A and respiratory syncitial virus (RSV). After 48 h, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) were measured in supernatants.Results:Infection of adipocytes with Ad-36, CMV and RSV resulted in increased IL-6 production from 192±22 pg ml−1 (uninfected) to 1030±86 pg ml−1, 838±59 pg ml−1 and 1241±191 pg ml−1, respectively (all P<0.01 vs control). In addition, Ad-36 infection slightly reduced PAI production in adipocytes (285±26.8 ng ml−1 vs uninfected: 477±71.2 ng ml−1; P=0.05) and pre-adipocytes (709±43.3 ng ml−1 vs uninfected: 1071±71.8 ng ml−1; P<0.01). In contrast, human Ad type 2 did not exert any effect on IL-6 or PAI production. None of the microorganisms induced significant changes in adiponectin and/or TNF-α production.Conclusions:Adipocytes can be infected with several microorganisms in vitro. Infection of adipocytes with Ad-36, but not Ad-2 leads to increased production of IL-6 which might contribute to chronic low-grade inflammation, a process known to be involved in the development of cardiovascular diseases and type 2 diabetes.International Journal of Obesity (2008) 32, 892–901; doi:10.1038/ijo.2008.36; published online 18 March 2008 [ABSTRACT FROM AUTHOR]

Abstract Background There is increasing evidence that chronic inflammation plays a pivotal role in the development of atherosclerosis. Whether inflammation is the cause or consequence of vascular damage is unclear. Also, the source of inflammation is unknown, but may well be infection by Cytomegalovirus (CMV) or Chlamydia pneumoniae (C. pneumoniae ). Infection of the liver by CMV or C. pneumoniae may induce a general inflammatory reaction contributing to accelerated atherogenesis. In this study we investigated the production of interleukin-6 (IL-6), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) by hepatocytes after infection with CMV or C. pneumoniae . Methods HepG2 cell monolayers were grown to confluence in 48-well tissue culture plates. Hepatocytes were infected with 50 µL or 100 µL of suspension of CMV (102·70 TCID50 mL-1 ) and C. pneumoniae (104·75 TCID50 mL-1 ). The medium of the inoculated cells was collected every 24 h, from day 1 to day 4, for determination of IL-6, PAI-1 and fibrinogen concentrations. Results Fibrinogen production was increased significantly in a dose-dependent manner after infection with CMV (50 µL: P = 0·022 and 100 µL: P < 0·001) and C. pneumoniae (P = 0·012). Cytomegalovirus infection resulted in an increase of IL-6 production compared with uninfected cells (P = 0·048). Cytomegalovirus and C. pneumoniae infection did not result in a significantly increase of PAI-1 production by hepatocytes. Conclusion We conclude that in addition to direct vascular wall infection by C. pneumoniae and CMV, virus-related development of atherosclerosis might also be initiated by chronic liver infection and subsequent production of inflammatory and procoagulant mediators released in the circulation. This may be another pathophysiological link for the observed relation between infections and the development of atherosclerosis. [ABSTRACT FROM AUTHOR]

To develop and validate a prediction model for Clostridium difficile infection (CDI) in hospitalized patients treated with systemic antibiotics, we performed a case-cohort study in a tertiary (derivation) and secondary care hospital (validation). Cases had a positive Clostridium test and were treated with systemic antibiotics before suspicion of CDI. Controls were randomly selected from hospitalized patients treated with systemic antibiotics. Potential predictors were selected from the literature. Logistic regression was used to derive the model. Discrimination and calibration of the model were tested in internal and external validation. A total of 180 cases and 330 controls were included for derivation. Age >65 years, recent hospitalization, CDI history, malignancy, chronic renal failure, use of immunosuppressants, receipt of antibiotics before admission, nonsurgical admission, admission to the intensive care unit, gastric tube feeding, treatment with cephalosporins and presence of an underlying infection were independent predictors of CDI. The area under the receiver operating characteristic curve of the model in the derivation cohort was 0.84 (95% confidence interval 0.80-0.87), and was reduced to 0.81 after internal validation. In external validation, consisting of 97 cases and 417 controls, the model area under the curve was 0.81 (95% confidence interval 0.77-0.85) and model calibration was adequate (Brier score 0.004). A simplified risk score was derived. Using a cutoff of 7 points, the positive predictive value, sensitivity and specificity were 1.0%, 72% and 73%, respectively. In conclusion, a risk prediction model was developed and validated, with good discrimination and calibration, that can be used to target preventive interventions in patients with increased risk of CDI., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Obesity is associated with a chronic inflammatory state, and adipocyte dysfunction is thought to play a crucial role in this. Infection of adipose tissue may trigger the production of inflammatory cytokines, leading to increased recruitment of macrophages into adipose tissue, which in turn may exacerbate the inflammatory state in obesity. Low-grade inflammation was mimicked in an in vitro coculture model with human adipocytes and THP-1 monocytes. Adipocytes and monocytes were infected with adenovirus, cytomegalovirus (CMV), or influenza A virus. After 48 h, transinfection was evaluated and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, and plasminogen activator inhibitor 1 (PAI-1) were measured. IL-6 production was upregulated in cocultures of uninfected adipocytes and THP-1 macrophages in a THP-1 cell number-dependent fashion. IL-6 production by CMV-infected adipocytes was increased relative to that of uninfected adipocytes (P < 0.01). IL-6 production by CMV-infected cocultures was 16- to 37-fold higher than that of uninfected adipocytes (P < 0.001). IL-6 production in influenza A virus-infected cocultures was increased 12- to 20-fold (P < 0.05). Only CMV infection increased levels of PAI-1 in cocultures (fourfold; P < 0.05). Soluble factors produced by THP-1 macrophages rather than by adipocytes were responsible for the increased production of IL-6 in cocultures. Infection of cocultivated human adipocytes and THP-1 monocytes with CMV or influenza A virus led to increased production of IL-6 and PAI-1. Thus, infection of adipose tissue evokes an inflammatory response, leading to adipose tissue dysfunction and subsequent overproduction of IL-6 and PAI-1. This may further compound the atherogenic effects of obesity.

During summer and fall, enterovirus infections are responsible for a considerable proportion of hospitalizations of young infants. We prospectively studied the incidence of enterovirus infections via real-time polymerase chain reaction (PCR) in blood, feces, and cerebrospinal fluid samples from infants

Enterobacter cloacae is becoming an increasingly important nosocomial pathogen. Outbreaks of E. cloacae in intensive care units and burns units have been described frequently. In December 1999, a neonate with line sepsis was transferred from a university hospital to the neonatal unit of the Diakonessen Hospital. Blood culture yielded E. cloacae. An outbreak of E. cloacae was occurring in the university hospital at that time. In February 2000, a second neonate in our hospital developed line sepsis caused by E. cloacae. Direct measures taken included cohorting of infected children, disinfection of incubators, thermometers and wards, and screening patients. Of nine neonates, seven were colonized with E. cloacae. Despite these measures, the outbreak continued. Forty-one patients were screened; 15 were colonized. Environmental searches yielded E. cloacae in a sink and on two thermometers. Sixteen isolates were typed by arbitrarily primed PCR using four primers. All the patient isolates and the two isolates from thermometers were identical. The strain isolated from the sink was unrelated. Amplified fragment length polymorphism typing showed that the outbreak clone was identical to that in the university hospital. After the introduction of disposable thermometer covers, E. cloacae colonization slowly decreased., (Copyright 2002 The Hospital Infection Society.)