Benznidazole treatment attenuates liver NF-κB activity and MAPK in a cecal ligation and puncture model of sepsis

Recent studies have shown that Benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, modulates pro-inflammatory cytokines and nitric oxide (NO) release in activated macrophages by blocking NF-κB through inhibition of IKK in vitro. As so far, little is known about the mechanism by which BZL provokes the inhibition of inflammatory response in sepsis in vivo, we aimed to delineate the possible role of BZL as a modulator in liver inflammation in mice with sepsis induced by cecal ligation and puncture (CLP). Specifically, we analyzed leukocytes, liver production of TNF-α and NO and the intracellular pathways modulated by these mediators, including NF-κB and MAPKs, in the liver of mice 24 h post-CLP. Our results show that BZL reduces leukocytes in peripheral blood accompanied by an increase in peritoneal macrophages 24h after CLP. In the liver of these septic mice, BZL decreased expression of mRNA and protein for TNF-α and NOS-2 by inhibition of NF-κB and MAPK (p-38 and ERK). The body of evidence suggests that the immunomodulatory effects of BZL could act selectively, as it is able to decrease the systemic inflammatory reaction and the hepatic response but it can increase the number of cells in the site of infection.     

Face ethnicity and measurement reliability affect face recognition performance in developmental prosopagnosia: evidence from the Cambridge Face Memory Test-Australian

The Cambridge Face Memory Test (CFMT, Duchaine & Nakayama, 2006) provides a validated format for testing novel face learning and has been a crucial instrument in the diagnosis of developmental prosopagnosia. Yet, some individuals who report everyday face recognition symptoms consistent with prosopagnosia, and are impaired on famous face tasks, perform normally on the CFMT. Possible reasons include measurement error, CFMT assessment of memory only at short delays, and a face set whose ethnicity is matched to only some Caucasian groups. We develop the "CFMT-Australian" (CFMT-Aus), which complements the CFMT-original by using ethnicity better matched to a different European subpopulation. Results confirm reliability (.88) and validity (convergent, divergent using cars, inversion effects). We show that face ethnicity within a race has subtle but clear effects on face processing even in normal participants (includes cross-over interaction for face ethnicity by perceiver country of origin in distinctiveness ratings). We show that CFMT-Aus clarifies diagnosis of prosopagnosia in 6 previously ambiguous cases. In 3 cases, this appears due to the better ethnic match to prosopagnosics. We also show that face memory at short (<3-min), 20-min, and 24-hr delays taps overlapping processes in normal participants. There is some suggestion that a form of prosopagnosia may exist that is long delay only and/or reflects failure to benefit from face repetition.     

HIV-2 A-subtype gp125c₂-v₃-c₃ mutations and their association with CCR5 and CXCR4 tropism

The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and their cellular CD4-chemokine (CCR5/CXCR4) receptor complex. In this study, for the first time, the HIV-2 A-subtype gp125_C2-V3-C3 mutations and their tropism association were characterized by analyzing 149 HIV-2 sequences from the Los Alamos database. The analysis has strengthened the importance of C2-V3-C3 region as a determinant factor for co-receptor selection. Moreover, statistically significant correlations were observed between C2-V3-C3 mutations, and several correlated mutations were associated with CXCR4 and CCR5 co-receptor usage. A dendrogram showed two distinct clusters, with numerous associated mutations grouped, thus dividing CCR5- and CXCR4-tropic viruses. Fourteen X4-tropic virus mutations, all in V3 and C3 domains and forming highly significant subclusters, were found. Finally, R5 associations, two strong subclusters were observed, grouping several C2-V3-C3 mutated positions. These data indicate the possible contribution of C2-V3-C3 mutational patterns in regulating HIV-2 tropism.     

Regulation of biliary proliferation by neuroendocrine factors: implications for the pathogenesis of cholestatic liver diseases

The proliferation of cholangiocytes occurs during the progression of cholestatic liver diseases and is critical for the maintenance and/or restoration of biliary mass during bile duct damage. The ability of cholangiocytes to proliferate is important in many different human pathologic conditions. Recent studies have brought to light the concept that proliferating cholangiocytes serve as a unique neuroendocrine compartment in the liver. During extrahepatic cholestasis and other pathologic conditions that trigger ductular reaction, proliferating cholangiocytes acquire a neuroendocrine phenotype. Cholangiocytes have the capacity to secrete and respond to a variety of hormones, neuropeptides, and neurotransmitters, regulating their surrounding cell functions and proliferative activity. In this review, we discuss the regulation of cholangiocyte growth by neuroendocrine factors in animal models of cholestasis and liver injury, which includes a discussion of the acquisition of neuroendocrine phenotypes by proliferating cholangiocytes and how this relates to cholangiopathies. We also review what is currently known about the neuroendocrine phenotypes of cholangiocytes in human cholestatic liver diseases (ie, cholangiopathies) that are characterized by ductular reaction.     

Increased brain natriuretic peptide secretion is a marker of disease progression in nonobstructive hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is associated with increased plasma brain natriuretic peptide (BNP), but sequential plasma and myocardial BNP assessment in stable and dilated HCM has never been performed.Methods and ResultsForty consecutive HCM patients (42 ± 8 years, 25 males) underwent cardiac catheterization, angiography, and left ventricular (LV) endomyocardial biopsy. During follow-up (70.5 ± 6.7 months), 30 patients (Group 1) remained stable whereas 10 patients (Group 2) progressed to dilated phase. Group 2 patients underwent a second invasive study with LV biopsy. BNP plasma levels were measured at baseline and at follow-up in all patients. All biopsies were processed for histology and immunohistochemistry with anti-BNP antibodies. BNP plasma levels remained unchanged in Group 1, whereas it significantly increased in all Group 2 patients who exhibited an elevation of LV and right ventricular end-diastolic pressure. Immunohistochemistry showed an increase of BNP-positive myocytes in follow-up biopsies when compared with baseline (75.0 ± 15.0 % versus 29.8 ± 10.0 %; P = .005) with a significant correlation with LV end-diastolic pressure (r = 0.78, P < .001) and plasma BNP (r = 0.83, P < .001).ConclusionsProgression to end-stage of HCM is characterized by further increase of myocardial and plasma BNP. Serial assessment of plasma BNP may provide noninvasive recognition of hemodynamic deterioration, allowing prompt institution of heart failure therapy.     

The European Sero-Epidemiology Network 2: standardization of assay results for hepatitis B virus

The aim of the European Sero-Epidemiology Network 2 was to coordinate and standardize the serological surveillance of vaccine-preventable diseases in Europe. In this study, the standardization of hepatitis B virus (HBV) results is described. The 15 participating national laboratories tested a unique panel of 172 sera established by the Greek reference centre for HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs) and/or to the HBV core antigen (anti-HBc) by assay methods of their choice. Country-specific quantitative measurements for anti-HBs and anti-HBc were transformed into common units using standardization equations derived by regressing each country's panel results against the reference centre's results, thus adjusting for interassay and interlaboratory variability. For HBsAg, a qualitative analysis (positive/negative) showed at least 99% agreement with the reference laboratory for all countries. By combining these standardized and qualitative results for the markers mentioned earlier, it was possible to achieve comparable estimates of the proportion of the population susceptible to HBV, vaccinated against HBV, with a past HBV infection, and with a current infection or chronic carrier state. Standardization is a very important tool that allows for international serological comparisons to assess the current vaccination policies and the progress of HBV control in Europe.     

Are you always on my mind? A review of how face perception and attention interact

In this review we examine how attention is involved in detecting faces, recognizing facial identity and registering and discriminating between facial expressions of emotion. The first section examines whether these aspects of face perception are "automatic", in that they are especially rapid, non-conscious, mandatory and capacity-free. The second section discusses whether limited-capacity selective attention mechanisms are preferentially recruited by faces and facial expressions. Evidence from behavioral, neuropsychological, neuroimaging and psychophysiological studies from humans and single-unit recordings from primates is examined and the neural systems involved in processing faces, emotion and attention are highlighted. Avenues for further research are identified.     

Gestational treatment with methylazoxymethanol (MAM) that disrupts hippocampal-dependent memory does not alter behavioural response to cocaine

Schizophrenia is associated with increased rates of substance abuse that are thought to be the result of changes in cortical and mesolimbic dopamine activity. Previous work has shown that gestational methylazoxymethanol acetate (MAM) treatment induces increased mesolimbic dopamine activity when given around the time of embryonic day 17 (ED17), suggesting that MAM treatment may model some aspects of schizophrenia. Given that increased dopaminergic activity facilitates aspects of drug self-administration and reinstatement of drug seeking, the current experiments sought to assess cocaine self-administration in MAM treated animals. Experiment 1 examined the acquisition of cocaine self-administration in ED17 MAM and saline treated rats using a sub-threshold dose of cocaine. In experiment 2 ED17 MAM and saline treated animals were trained to self-administer cocaine and were then assessed under varying doses of cocaine (dose–response), followed by extinction and drug-induced reinstatement of responding. A subset of these animals was trained on a win-shift radial maze task, designed to detect impairments in hippocampal-dependent memory. In experiment 3, MAM and saline treated animals were assessed on a progressive ratio schedule of cocaine delivery. Finally, in experiment 4 MAM and saline treated animals were assessed on cocaine-induced locomotor activity across a range of doses of cocaine. MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed.