Inhibitor of apoptosis proteins, NAIP, cIAP1 and cIAP2 expression during macrophage differentiation and M1/M2 polarization

Monocytes and macrophages constitute the first line of defense of the immune system against external pathogens. Macrophages have a highly plastic phenotype depending on environmental conditions; the extremes of this phenotypic spectrum are a pro-inflammatory defensive role (M1 phenotype) and an anti-inflammatory tissue-repair one (M2 phenotype). The Inhibitor of Apoptosis (IAP) proteins have important roles in the regulation of several cellular processes, including innate and adaptive immunity. In this study we have analyzed the differential expression of the IAPs, NAIP, cIAP1 and cIAP2, during macrophage differentiation and polarization into M1 or M2. In polarized THP-1 cells and primary human macrophages, NAIP is abundantly expressed in M2 macrophages, while cIAP1 and cIAP2 show an inverse pattern of expression in polarized macrophages, with elevated expression levels of cIAP1 in M2 and cIAP2 preferentially expressed in M1. Interestingly, treatment with the IAP antagonist SMC-LCL161, induced the upregulation of NAIP in M2, the downregulation of cIAP1 in M1 and M2 and an induction of cIAP2 in M1 macrophages.This work was supported by Universidad de Granada, Plan Propio 2015;#P3B: FAM, VMC (http://investigacion.ugr.es/pages/planpropio/2015/ resoluciones/p3b_def_28072015); Universidad de Granada CEI BioTic;#CAEP2-84: VMC (http:// biotic.ugr.es/pages/resolucionprovisional enseaanzapractica22demayo/!); and Canadian nstitutes of Health Research;#231421, #318176, #361847: STB, ECL, RK (http://www.cihr-irsc.gc. ca/e/193.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Prospective observational cohort study of cerebrovascular CO2 reactivity in patients with inflammatory CNS diseases

The purpose of this study was to evaluate the significance of cerebrovascular CO(2) reactivity (CO(2) R) in the course and outcome of inflammatory central nervous system (CNS) diseases. Sixty-eight patients with inflammatory CNS diseases and 30 healthy volunteers were included in this prospective observational cohort study. The observational period was between January 2005 and May 2009. The CO(2) R was measured by transcranial Doppler (TCD) ultrasound using the breath-holding method. We compared patients with normal CO(2) R (breath-holding index [BHI(m)] ≥ 1.18 = BHI(N) group) with patients who showed impaired CO(2) R (BHI(m) < 1.18 = BHI(R) group). We also analyzed the association of impaired CO(2) R with the etiology, severity, and outcome of disease. When compared to the BHI(N) group, the patients from the BHI(R) group were older, had a heavier consciousness disturbance, experienced more frequent respiratory failure, and, subsequently, had worse outcomes. There were no fatalities among the 28 patients in the BHI(N) group. The comparison of subjects with bacterial and non-bacterial meningitis revealed no significant differences. The unfavorable outcome of disease (Glasgow Outcome Scale [GOS] score 1-3) was significantly more common in subjects with impaired CO(2) R (62.5% vs. 10.7%). Logistic regression analysis was performed in order to establish the prognostic value of BHI(m). The outcome variable was unfavorable outcome (GOS 1-3), while the independent variables were age, Glasgow Coma Scale (GCS) score, and BHI(m). The age and BHI(m) showed the strongest influence on disease outcome. A decrease of BHI(m) for each 0.1 unit increased the risk of unfavorable outcome by 17%. Our study emphasizes the importance of CO(2) R assessment in patients with inflammatory CNS diseases

Acute encephalopathy associated with Campylobacter jejuni enteritis

We present for the first time a case of acute encephalopathy in an adult patient induced by Campylobacter jejuni enteritis. Possible pathogenic mechanisms and importance of neuropsychological testing in the assessment of infection-related encephalopathy are discussed

Therapeutic hypothermia for severe adult Herpes simplex virus encephalitis

Despite antiviral treatment and advances in critical care, the Herpes simplex encephalitis (HSE) still has a poor outcome in a significant portion of patients. In severe cases of HSE, reduced carbon dioxide reactivity is usually present and these patients don't respond to the usual treatment of brain edema and intracranial hypertension. We present case series of patients with severe form of HSE treated with therapeutic hypothermia (TH) and describe in detail the indications, methods, and the rationale for its use. In this case series, patients presented with severely impaired consciousness and very high predicted death rate as measured by Glasgow coma scale and Acute Physiology and Chronic Health Evaluation (APACHE II) score respectively. According to our findings, TH in carefully selected patients with HSE holds promise as an adjunctive to the antiviral treatment

Dexamethasone for adult community-acquired bacterial meningitis: 20 years of experience in daily practice

The aim of the study was to assess adjunctive intravenous dexamethasone in adult community-acquired bacterial meningitis (BM) in daily practice. Analysis of consecutive patients (1990-2009) with acute community-acquired bacterial meningitis in a single centre in Zagreb, Croatia, N = 304. Adjusted relative risks [RR, dexamethasone vs. no dexamethasone (control)] of Glasgow Outcome Scale (GOS) = 1 (death) and GOS = 5 (full recovery) at discharge/end of specific treatment were estimated considering demographics; co-morbidity; BM pathogenesis and on-admission characteristics, and cerebrospinal fluid (CSF) inflammation markers; causative agent and antibiotic use. Two hundred forty (79%) patients had proven BM (43.1% Streptococcus pneumoniae, any other agent ≤ 8.2%). No independent effects of dexamethasone on GOS = 1 or GOS = 5 were observed in the entire cohort (dexamethasone n = 119, control n = 185; RR = 1.06, 95% CI 0.77-1.45 and RR = 0.99, CI 0.83-1.20, respectively), microbiologically proven disease (dexamethasone n = 104, control n = 136; RR = 0.97, CI 0.69-1.38 and RR = 1.03, CI 0.82-1.28), pneumococcal disease (dexamethasone n = 71, control n = 60; RR = 0.95, CI 0.53-1.70 and RR = 0.82, CI 0.57-1.18), and also in other BM, subgroups based on consciousness disturbance, CSF markers, prior use of antibiotics and timing of appropriate antibiotic treatment. CSF markers did not predict the outcomes. Conclusions: Our experience does not substantiate the reported benefits of adjunctive dexamethasone in adult BM. Socio-economic and methodological factors do not seem to explain this discrepancy. Empirical use of dexamethasone in this setting appears controversial

Incidence of neurological complications in patients with native-valve infective endocarditis and cerebral microembolism: an open cohort study

The objective of this open cohort study was to assess the association between neurological complications in patients with definite native-valve infective endocarditis (IE) and cerebral microembolism (MES). MES detection was performed with 1-h, bilateral middle cerebral arteries (MCA) insonation using a transcranial Doppler ultrasound (TCD) machine. Thirty patients with definite native-valve IE were stratified into 2 groups based upon the presence of MES. The most striking difference between the 2 groups of patients was the incidence of clinically evident neurological complications. Neurological complications of IE occurred in 10 (83.3%) patients with positive MES and in 6 (33.3%) MES-negative patients (p=0.021). Ischaemic stroke was the most common complication, occurring in 11 of 16 patients, followed by meningitis in 4 patients and cerebritis in 1 patient. There was a trend towards greater in-hospital mortality in patients with recorded MES than in the MES-negative, although this was not statistically significant (33.3% vs 16.6%; p=0.392). Our results reveal a significant association between MES and neurological complications in patients with native-valve IE. TCD is a promising tool in predicting individual patient risk for neurological complications of IE

Community-acquired bacterial meningitis in adults: antibiotic timing in disease course and outcome

OBJECTIVES: Despite improvements in diagnostic and therapeutic approach to adult patients with bacterial meningitis, the overall mortality rate is still high. The aim of this study was to evaluate antibiotic timing in the course and outcome of bacterial meningitis. ----- METHODS: Two hundred and eighty six patients with community-acquired bacterial meningitis aged 14 years and more were included in this retrospective cohort study. Observational period was between 1 January 1990 and 31 December 2004. To assess the association of antibiotic timing and disease outcome we analyzed three timing periods (according to the onset of disease, onset of consciousness disturbance and the time of admission to hospital). Analysis was also performed in a subgroup of culture positive meningitis in 176 patients with altered mental status. ----- RESULTS: Unfavorable outcome was found in 125 (43,7%) patients. In this group, the start of appropriate antibiotic treatment in relation to the onset of first symptoms and particularly to the onset of consciousness disturbance was significantly delayed (p = 0.018 and p < 0.001, respectively) compared to the favorable group. Logistic regression analysis in a subgroup of culture positive meningitis in patients with altered mental status revealed that early adequate antibiotic treatment related to the onset of overt signs of meningitis was independently associated with favorable outcome (OR = 11.19; 95% CI 4.37-32.57; p < 0.001). Advanced age, lower GCS and seizures (OR = 1.05, OR = 1.45 and OR = 3.65, respectively) were other risk factors of poor outcome. The presence of chronic diseases, pneumococcal etiology and clinical and laboratory variables which are indicators of disease severity (renal and/or liver dysfunction, hypotension and low cerebrospinal fluid glucose) were not confirmed as independent risk factors of poor outcome. ----- CONCLUSIONS: Our study emphasizes the importance of early and adequate antibiotic treatment in the management of bacterial meningitis which significantly enhances the chances for favorable outcome