These results demonstrate that ET-1 evokes pruritic and nociceptive behaviors in the mouse cheek model. Both responses to ET-1 appear to be mediated via ET(A) receptors and subjected to limitation by simultaneous ET(B) receptor activation. Local endogenous opioids acting on μ-opioid receptors selectively modulate the pruritic response to ET-1, whereas histamine, possibly derived from mast cells and acting on H(1) receptors, contributes importantly to the nociceptive effect of ET-1 in this model.

Introduction: Considering the transformation process that has been occurring in pharmacy education and the urgent need to address social health needs, proposals of teaching methods for the development of competences and skills in patient-centered care have become an issue worth discussing. The study describes and discusses the method that has been used for developing of these competencies through experiential learning in a university pharmacy in Brazil. Educational Activity: The Teaching and Learning of Pharmacy Services (TLPS) method encompasses 2 components: theoretical-reflexive one (developing protocols covering the patient care process) and practical-reflexive one (using the protocols with real patients). TLPS connects the 2 components in a way to enable students to acquire and apply theoretical knowledge for a comprehensive assessment of the patients’ needs and understand how clinical reasoning and decision-making take place. The assessment process is performed, by the supervisor, which evaluates the behaviors necessary for good professional performance. Discussion: The active learning methodologies have been effectively used in the classroom as a way to stimulate critical thinking, problem-solving, and clinical reasoning. However, experiential learning is considered a central point in the learning process and essential for knowledge building. Thus, the method herein described is shown as an innovative tool to promote self-learning, consolidation and interrelation of the acquired knowledge, easier identification of patients’ needs, normalization of behaviors, and improvement in the quality of care.

In 2012, the first-generation protease inhibitors telaprevir (TVR) and boceprevir (BOC) were introduced in the Brazilian health system for treatment of chronic hepatitis C, after their approval by the National Committee for Health Technology Incorporation (CONITEC). However, these medicines were discontinued in 2015. The short period of use in therapy and their high cost require a discussion about the consequences for patients and for the health system of the early incorporation of new therapies. The article presents a qualitative analysis of the incorporation process of both medications in Brazil and the results of a multicenter study that included patients treated with BOC or TVR between January 2011 and December 2015 in five Brazilian cities. The study included 855 patients (BOC: n=247) and (TVR: n=608). The document analysis showed that CONITEC’s decision to incorporate BOC and TVR was based on results of phase III clinical trials that compared sustained virologic response (SVR) rates of patients treated with BOC and TVR with rates of those that received placebo. However, these studies included a low percentage of cirrhotic patients. The SVR rates observed in this multicenter study were worse than clinical trials pointed out (BOC: 45.6%; TVR: 51.8%), but similar to those achieved with previously adopted therapies. The discontinuation rate due to adverse events was (BOC: 15.4%; TVR: 12.7%). Based on these unsatisfactory results, the study brings a discussion that goes beyond the therapy outcomes, exploring the incorporation of these high-cost medicines and the related decision-making process, contributing to future decisions in medicine policies and in the treatment of chronic hepatitis C.

BACKGROUND Acute decompensation (AD) of cirrhosis is related to systemic inflammation and elevated circulating cytokines. In this context, biomarkers of inflammation, such as calprotectin, may be of prognostic value. AIM To evaluate serum calprotectin levels in patients hospitalized for complications of cirrhosis. METHODS This is a prospective cohort study that included 200 subjects hospitalized for complications of cirrhosis, 20 outpatients with stable cirrhosis, and 20 healthy controls. Serum calprotectin was measured by enzyme-linked immunosorbant assay. RESULTS Calprotectin levels were higher among groups with cirrhosis when compared to healthy controls. Higher median calprotectin was related to Child-Pugh C, ascites, and hepatic encephalopathy. Higher calprotectin was related to acute-on-chronic liver failure (ACLF) and infection in the bivariate, but not in multivariate analysis. Calprotectin was not associated with survival among patients with ACLF; however, in patients with AD without ACLF, higher calprotectin was associated with a lower 30-d survival, even after adjustment for chronic liver failure-consortium (CLIF-C) AD score. A high-risk group (CLIF-C AD score ≥ 60 and calprotectin ≥ 580 ng/mL) was identified, which had a 30-d survival (27.3%) similar to that of patients with grade 3 ACLF (23.3%). CONCLUSION Serum calprotectin is associated with prognosis in patients with AD without ACLF and may be useful in clinical practice to early identify patients with a very low short-term survival.

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