Construction and application of an electrochemical sensor for paracetamol determination based on iron tetrapyridinoporphyrazine as a biomimetic catalyst of P450 enzyme

This work describes the construction and application of a biomimetic sensor for paracetamol determination in different samples . The sensor was prepared by modifying a glassy carbon electrode surface with a Nafion® membrane doped with FeTPyPz. The best performance of the sensor in 0.1 mol L-1 acetate buffer was at pH 3.6. Under these conditions, an oxidation potential of paracetamol was observed at 445 mV vs. Ag|AgCl. The sensor presented a linear response range between 4.0 and 420 µmol L-1, a sensitivity of 46.015 mA L mol-1 cm-2, quantification and detection limits of 4.0 µmol L-1 and 1.2 µmol L-1, respectively. A detailed investigation about its electrochemical behavior and selectivity was carried out. The results suggested that FeTPyPz presents catalytic properties similar to P450 enzyme for paracetamol oxidation. Finally, the sensor was applied for paracetamol determination in commercial drugs and for the monitoring of its degradation in an electrochemical batch reactor effluent.Descreve-se a construção e aplicação de um sensor biomimético para determinação de paracetamol em diversos tipos de amostras. O sensor foi construído modificando a superfície de um eletrodo de carbono vítreo com membrana de Nafion® dopada com tetrapiridinoporfirazina de ferro (FeTPyPz). Esse sensor apresentou melhor desempenho em tampão acetato 0,1 mol L-1 e pH 3,6. Nessas condições o potencial de oxidação do paracetamol foi de 445 mV vs. Ag|AgCl. O sensor apresentou uma faixa de resposta linear entre 4,0 e 420 µmol L-1, sensibilidade de 46,015 mA L mol-1 cm-2, limite de quantificação de 4,0 µmol L-1 e limite de detecção de 1,2 µmol L-1. Estudos eletroquímicos e de seletividade demonstraram a propriedade catalítica da FeTPyPz como sendo similares a da enzima P450 na oxidação do paracetamol. O sensor foi usado na determinação de paracetamol em formulações comerciais e no acompanhamento de sua degradação eletroquímica em efluentes provenientes de um reator em escala piloto.734743Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Genome And Secretome Analysis Of The Hemibiotrophic Fungal Pathogen, Moniliophthora Roreri, Which Causes Frosty Pod Rot Disease Of Cacao: Mechanisms Of The Biotrophic And Necrotrophic Phases

Background: The basidiomycete Moniliophthora roreri is the causal agent of Frosty pod rot (FPR) disease of cacao (Theobroma cacao), the source of chocolate, and FPR is one of the most destructive diseases of this important perennial crop in the Americas. This hemibiotroph infects only cacao pods and has an extended biotrophic phase lasting up to sixty days, culminating in plant necrosis and sporulation of the fungus without the formation of a basidiocarp.Results: We sequenced and assembled 52.3 Mb into 3,298 contigs that represent the M. roreri genome. Of the 17,920 predicted open reading frames (OFRs), 13,760 were validated by RNA-Seq. Using read count data from RNA sequencing of cacao pods at 30 and 60 days post infection, differential gene expression was estimated for the biotrophic and necrotrophic phases of this plant-pathogen interaction. The sequencing data were used to develop a genome based secretome for the infected pods. Of the 1,535 genes encoding putative secreted proteins, 1,355 were expressed in the biotrophic and necrotrophic phases. Analysis of the data revealed secretome gene expression that correlated with infection and intercellular growth in the biotrophic phase and invasive growth and plant cellular death in the necrotrophic phase.Conclusions: Genome sequencing and RNA-Seq was used to determine and validate the Moniliophthora roreri genome and secretome. High sequence identity between Moniliophthora roreri genes and Moniliophthora perniciosa genes supports the taxonomic relationship with Moniliophthora perniciosa and the relatedness of this fungus to other basidiomycetes. Analysis of RNA-Seq data from infected plant tissues revealed differentially expressed genes in the biotrophic and necrotrophic phases. 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Circulating biomarkers to assess cardiovascular function in critically ill

PURPOSE OF REVIEW: Circulatory shock is one of the most common reasons for ICU admission. Mortality rates in excess of 40% necessitate the rapid identification of high-risk patients, as well as the early assessment of effects of initiated treatments. There is an unmet medical need for circulating biomarkers that may improve patient stratification, predict responses to treatment interventions and may even be a target for novel therapies, enabling a better biological rationale to personalize therapy. RECENT FINDINGS: Apart from established biomarkers such as lactate, ScvO2 or NT-pro-BNP, novel biomarkers, including adrenomedullin, angiopoietins, angiotensin I/II ratios, renin and DPP3 show promise, as they are all associated with well defined, therapeutically addressable molecular pathways that are dysregulated during circulatory shock. Although some of the therapies related to these biomarkers are still in preclinical stages of development, they may represent personalized treatment opportunities for patients in circulatory shock. SUMMARY: From a molecular perspective, shock represents a highly heterologous syndrome, in which multiple unique pathways are dysregulated. Assessment of the status of these pathways with circulating biomarkers may provide a unique opportunity to detect specific phenotypes and implement personalized medicine in the treatment of circulatory shock

Promotion of vascular integrity in sepsis through modulation of bioactive adrenomedullin and dipeptidyl peptidase 3

Sepsis represents one of the major medical challenges of the 21st century. Despite substantial improvements in the knowledge on pathophysiological mechanisms, this has so far not translated into novel adjuvant treatment strategies for sepsis. In sepsis, both vascular tone and vascular integrity are compromised, and contribute to the development of shock, which is strongly related to the development of organ dysfunction and mortality. In this review, we focus on dipeptidyl peptidase 3 (DPP3) and adrenomedullin (ADM), two molecules that act on the vasculature and are involved in the pathophysiology of sepsis and septic shock. DPP3 is an ubiquitous cytosolic enzyme involved in the degradation of several important signalling molecules essential for regulation of vascular tone, including angiotensin II. ADM is a key hormone involved in the regulation of vascular tone and endothelial barrier function. Previous studies have shown that circulating concentrations of both DPP3 and ADM are independently associated with the development of organ failure and adverse outcome in sepsis. We now discuss new evidence illustrating that these molecules indeed represent two distinct pathways involved in the development of septic shock. Recently, both ADM-enhancing therapies aimed at improving endothelial barrier function and vascular tone and DPP3-blocking therapies aimed at restoring systemic angiotensin responses have been shown to improve outcome in various preclinical sepsis models. Given the current lack of effective adjuvant therapies in sepsis, additional research on the therapeutic application of these peptides in humans is highly warranted

Nonsurgical neovagina creation in congenital vaginal agenesis: a case report of movement-based dilator therapy

Objective: To report the use of progressive, high-frequency movement-based dilator therapy (MBDT) to create a neovagina in a patient with congenital vaginal agenesis. Design: Case report. Setting: Tertiary care military hospital. Patient(s): A 22-year-old woman with congenital vaginal agenesis. Intervention(s): Self-directed MBDT. Main Outcome Measure(s): Vaginal elongation by self-directed MBDT. Result(s): The patient achieved a 6.5-cm vaginal length after 6 pelvic health physical therapy sessions over a span of 4 months of progressive, high-frequency MBDT. Conclusion(s): Progressive, high-frequency MBDT should be considered as part of a first-line dilator therapy regimen for patients with congenital vaginal agenesis interested in creating a neovagina