Educação e diálogo na perspectiva de Freire

O diálogo, como um dos elementos principais na pedagogia de Freire, é abordado neste artigo em diferentes aspectos. Freire não teorizou, apenas, sobre o diálogo. Ele o praticou constantemente em sua trajetória e o expressou inclusive na elaboração de suas obras. Em mais de vinte livros, Freire aparece como co-autor, em diálogo com outros educadores. Quatro livros seus trazem no título o vocábulo “cartas”. Outros grandes pensadores, desde Sócrates e Platão, até Max Scheller e Mounier, praticaram o diálogo enquanto educadores, como também na elaboração de suas obras. O artigo situa historicamente Freire entre os grandes mestres do diálogo, definindo afinidades existentes, mas também as diferenças, sobretudo porque, como educador, inaugurou um novo paradigma epistemológico-pedagógico e político, enquanto constrói toda a sua obra através do diálogo preferencial com os “condenados da terra” (Fanon), com os excluídos, com os oprimidos, com os sujeitos históricos da “periferia”

New Perspective in HCV Clinical and Economical Management of the Current and Future Therapies

Hepatitis C virus (HCV) is a progressive disease that infects more than 185 million individuals worldwide and is associated with persistence of viral replication and ongoing necroinflammation and fibrosis. To date 20% of patients chronically infected with HCV progress to cirrhosis. Epidemiological studies demonstrate that the incidence of HCV is not well known, because acute infection is generally asymptomatic. The global prevalence is about 2.2% and there is a large degree of geographic variability. Before the 2011, the gold standard of therapy for the treatment of chronic hepatitis C (CHC) was based on the combination of pegylated Interferon (peg-IFN) and Ribavirin (RBV). However, several aspects related to safety profile limited their use in clinical practice. In the recent years, thanks to basic research on HCV structure and replicative cycle, it has been possible to develop direct acting antiviral drugs that have dramatically increased the viral clearance rate. Specifically, the advent of the triple therapy employing direct acting antivirals has dramatically increased the viral clearance rate, from less than 10%, with the initial regimen of IFN monotherapy, to more than 95% with the current therapy. Even though new medications for hepatitis C are effective disease modifiers and have the potential, in a long term perspective, to eradicate the pathology, the cost of new treatments are unlikely to be sustainable for the NHSs. The evidence documenting the effectiveness and tolerability of the new therapies for HCV and several pharmacoeconomic analysis, shows that despite the cost, the new treatments can be considered cost-effective in the long period. However, the health care systems are unable to compensate the height financial resources immediately needed for treating patients with the long terms savings that will be obtained from the eradication of HCV. Indeed, new pharmaceutical policy and a global commitment is required to improve strategies of treatment and price negotiation with pharmaceutical companies to move from a theoretical cost-effectiveness approach to a practical cost-sustainable reality

New technologies - new insights into the pathogenesis of hepatic encephalopathy

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which frequently accompanies acute or chronic liver disease. It is characterized by a variety of symptoms of different severity such as cognitive deficits and impaired motor functions. Currently, HE is seen as a consequence of a low grade cerebral oedema associated with the formation of cerebral oxidative stress and deranged cerebral oscillatory networks. However, the pathogenesis of HE is still incompletely understood as liver dysfunction triggers exceptionally complex metabolic derangements in the body which need to be investigated by appropriate technologies. This review summarizes technological approaches presented at the ISHEN conference 2014 in London which may help to gain new insights into the pathogenesis of HE. Dynamic in vivo13C nuclear magnetic resonance spectroscopy was performed to analyse effects of chronic liver failure in rats on brain energy metabolism. By using a genomics approach, microRNA expression changes were identified in plasma of animals with acute liver failure which may be involved in interorgan interactions and which may serve as organ-specific biomarkers for tissue damage during acute liver failure. Genomics were also applied to analyse glutaminase gene polymorphisms in patients with liver cirrhosis indicating that haplotype-dependent glutaminase activity is an important pathogenic factor in HE. Metabonomics represents a promising approach to better understand HE, by capturing the systems level metabolic changes associated with disease in individuals, and enabling monitoring of metabolic phenotypes in real time, over a time course and in response to treatment, to better inform clinical decision making. Targeted fluxomics allow the determination of metabolic reaction rates thereby discriminating metabolite level changes in HE in terms of production, consumption and clearance

Technical note: Preparation improvement of charred cadaveric viscera using sandison’s rehydrating solution for histological analysis

In forensic evaluation of charred corpses, internal detrimental signs may result as more significant of those observed during external examination and is often arduous to state if a victim was exposed to fire before or after death. When the histological analysis of the remaining internal viscera is necessary, the massive destruction caused by the lesion, the charring and the coarctation of the samples don't allow to give further information or to determine the remaining organic components of the viscera. This limit is determined by the intrinsic characteristics of this thermal lesivity of self-maintenance even after the exitus of the subject, worsening the initial detrimental framework. The Authors, with the purpose of improving the microscopic visualization of the samples collected from cadavers with peculiar deterioration, as in case of carbonization, suggest the use of a specific technical protocol based on the use of Sandison's rehydrating solution since the samples treated with this solution showed, at microscopic examination, a substantial histological-morphological improvement

Roughness of the plasma membrane as an independent morphological parameter to study RBCs: A quantitative atomic force microscopy investigation

AbstractA novel approach to the study of RBCs based on the collection of three-dimensional high-resolution AFM images and on the measure of the surface roughness of their plasma membrane is presented. The dependence of the roughness from several parameters of the imaging was investigated and a general rule for a trustful analysis and comparison has been suggested. The roughness of RBCs is a morphology-related parameter which has been shown to be characteristic of the single cells composing a sample, but independent of the overall geometric shape (discocyte or spherocyte) of the erythrocytes, thus providing extra-information with respect to a conventional morphology study. The use of the average roughness value as a label of a whole sample was tested on different kinds of samples. Analyzed data revealed that the quantitative roughness value does not change after treatment of RBCs with various commonly used fixation and staining methods while a drastic decrease occurs when studying cells with membrane–skeletal alteration both naturally occurring or artificially induced by chemical treatments. The present method provides a quantitative and powerful tool for a novel approach to the study of erythrocytes structure through an ultrastructural morphological analysis with the potential to give information, in a non-invasive way, on the RBCs function

Recombinant Alkaline Phosphatase Prevents Acute on Chronic Liver Failure

The lipopolysaccharide (LPS)– toll-like receptor-4 (TLR4) pathway plays an important role in liver failure. Recombinant alkaline phosphatase (recAP) deactivates LPS. The aim of this study was to determine whether recAP prevents the progression of acute and acute-on-chronic liver failure (ACLF). Eight groups of rats were studied 4-weeks after sham surgery or bile duct ligation and were injected with saline or LPS to mimic ACLF. Acute liver failure was induced with Galactosamine-LPS and in both models animals were treated with recAP prior to LPS administration. In the ACLF model, the severity of liver dysfunction and brain edema was attenuated by recAP, associated with reduction in cytokines, chemokines, liver cell death, and brain water. The activity of LPS was reduced by recAP. The treatment was not effective in acute liver failure. Hepatic TLR4 expression was reduced by recAP in ACLF but not acute liver failure. Increased sensitivity to endotoxins in cirrhosis is associated with upregulation of hepatic TLR4, which explains susceptibility to development of ACLF whereas acute liver failure is likely due to direct hepatoxicity. RecAP prevents multiple organ injury by reducing receptor expression and is a potential novel treatment option for prevention of ACLF but not acute liver failure

The HIV-1 Integrase Mutations Y143C/R Are an Alternative Pathway for Resistance to Raltegravir and Impact the Enzyme Functions

Resistance to HIV-1 integrase (IN) inhibitor raltegravir (RAL), is encoded by mutations in the IN region of the pol gene. The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure. Cloning analysis of the IN gene showed an independent selection of the mutations at loci 155 and 143. Characterization of the phenotypic evolution showed that the switch from N155H to Y143C/R was linked to an increase in resistance to RAL. Wild-type (WT) IN and IN with mutations Y143C or Y143R were assayed in vitro in 3′end-processing, strand transfer and concerted integration assays. Activities of mutants were moderately impaired for 3′end-processing and severely affected for strand transfer. Concerted integration assay demonstrated a decrease in mutant activities using an uncleaved substrate. With 3′end-processing assay, IC50 were 0.4 µM, 0.9 µM (FC = 2.25) and 1.2 µM (FC = 3) for WT, IN Y143C and IN Y143R, respectively. An FC of 2 was observed only for IN Y143R in the strand transfer assay. In concerted integration, integrases were less sensitive to RAL than in ST or 3′P but mutants were more resistant to RAL than WT

The role of RIPK1 mediated cell death in acute on chronic liver failure

Acute-on-chronic liver failure (ACLF) is characterized predominantly by non-apoptotic forms of hepatocyte cell death. Necroptosis is a form of programmed lytic cell death in which receptor interacting protein kinase (RIPK) 1, RIPK3 and phosphorylated mixed lineage kinase domain-like (pMLKL) are key components. This study was performed to determine the role of RIPK1 mediated cell death in ACLF. RIPK3 plasma levels and hepatic expression of RIPK1, RIPK3, and pMLKL were measured in healthy volunteers, stable patients with cirrhosis, and in hospitalized cirrhotic patients with acutely decompensated cirrhosis, with and without ACLF (AD). The role of necroptosis in ACLF was studied in two animal models of ACLF using inhibitors of RIPK1, necrostatin-1 (NEC-1) and SML2100 (RIPA56). Plasma RIPK3 levels predicted the risk of 28- and 90-day mortality (AUROC, 0.653 (95%CI 0.530–0.776), 0.696 (95%CI 0.593–0.799)] and also the progression of patients from no ACLF to ACLF [0.744 (95%CI 0.593–0.895)] and the results were validated in a 2nd patient cohort. This pattern was replicated in a rodent model of ACLF that was induced by administration of lipopolysaccharide (LPS) to bile-duct ligated rats and carbon tetrachloride-induced fibrosis mice administered galactosamine (CCL4/GalN). Suppression of caspase-8 activity in ACLF rodent model was observed suggesting a switch from caspase-dependent cell death to necroptosis. NEC-1 treatment prior to administration of LPS significantly reduced the severity of ACLF manifested by reduced liver, kidney, and brain injury mirrored by reduced hepatic and renal cell death. Similar hepato-protective effects were observed with RIPA56 in a murine model of ACLF induced by CCL4/GalN. These data demonstrate for the first time the importance of RIPK1 mediated cell death in human and rodent ACLF. Inhibition of RIPK1 is a potential novel therapeutic approach to prevent progression of susceptible patients from no ACLF to ACLF

Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study

Background & AimsIn acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure.MethodsPigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure.ResultsThe Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen.ConclusionsThe survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients