Anticancer peptides : prospective innovation in cancer therapy

© Springer International Publishing Switzerland 2016Current cancer treatments require improvements in selectivity and efficacy. Surgery, radiation, and chemotherapy approaches result in patient’s suffering over time due to the development of severe side-effects that simultaneously condition adherence to therapy. Biologically active peptides, in particular antimicrobial peptides (AMPs), are versatile molecules in terms of biological activities. The cytotoxic activities of several AMPs turn this group of molecules into an amazing pool of new templates for anticancer drug development. However, several unmet challenges limit application of peptides in cancer therapy. The mechanism(s) of action of the peptides need better description and understanding, and innovative targets have to be discovered and explored, facilitating drug design and development. In this chapter, we explore the natural occurring AMPs as potential new anticancer peptides (ACPs) for cancer prevention and treatment. Their modes of action, selectivity to tumor compared to normal cells, preferential targets, and applications, but also their weaknesses, are described and discussed.info:eu-repo/semantics/publishedVersio

Non-invasive hemodynamic evaluation by Doppler echocardiography

The approach for treating a hemodynamically unstable patient remains a diagnostic and therapeutic challenge. Stabilization of the patient should be rapid and effective, but there is not much room for error. This narrow window of intervention makes it necessary to use rapid and accurate hemodynamic evaluation methods. Echocardiography is the method of choice for the bedside evaluation of patients in circulatory shock. In fact, it was intensive care physicians who recognized the potential of Doppler echocardiography for the initial approach to patients in circulatory failure. An echocardiogram allows rapid anatomical and functional cardiac evaluation, which may include non-invasive hemodynamic evaluation using a Doppler study. Such an integrated study may provide data of extreme importance for understanding the mechanisms underlying the hemodynamic instability of the patient to allow the rapid institution of appropriate therapeutic measures. In the present article, we describe the most relevant echocardiographic findings using a practical approach for critical patients with hemodynamic instability.info:eu-repo/semantics/publishedVersio

From antimicrobial to anticancer peptides : a review

Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective, and more efficient drugs is evident. Even though ACPs are expected to be selective toward tumor cells without impairing the normal body physiological functions, the development of a selective ACP has been a challenge. It is not yet possible to predict antitumor activity based on ACPs structures. ACPs are unique molecules when compared to the actual chemotherapeutic arsenal available for cancer treatment and display a variety of modes of action which in some types of cancer seem to co-exist. Regardless the debate surrounding the definition of structure-activity relationships for ACPs, great effort has been invested in ACP design and the challenge of improving effective killing of tumor cells remains. As detailed studies on ACPs mechanisms of action are crucial for optimizing drug development, in this review we provide an overview of the literature concerning peptides' structure, modes of action, selectivity, and efficacy and also summarize some of the many ACPs studied and/or developed for targeting different solid and hematologic malignancies with special emphasis on the first group. Strategies described for drug development and for increasing peptide selectivity toward specific cells while reducing toxicity are also discussed.The authors thank Fundação para a Ciência e a Tecnologia (FCT- MEC, Portugal) for funding—PTDC/QUI-BIO/112929/2009. Diana Gaspar also acknowledges FCT for fellowship SFRH/BPD/ 73500/2010 and A. Salome Veiga for funding within the FCT Investigator Programme (IF/00803/2012

Lactobacillus crispatus as the etiological agent in cytolytic vaginosis

Introduction: Lactobacillus spp. dominate the vaginal niche but can also be involved in other vaginal dysbiosis, such as cytolytic vaginosis (CV), which remains poorly studied. It is characterized by a cryptic symptomatology, that often confounds the clinic. Goals: The aim of this work was to search for the etiological agent of CV, by studying the vaginal microbiome and metabolomics of women afflicted with this disease and compare it with women with other clinical diagnostic. Methods: Twenty-one vaginal washes have been collected from women attending a gynaecology consultation of a private clinic. The samples were categorized according with clinical diagnosis at the time of sampling (CV, 11; vulvovaginal candidosis, 8; Healthy, 2). The distribution of bacterial species, and their prevalence was assessed by next-generation sequencing of the 16S V4 region. In addition, total lactate D-lactic acid and L-lactic acid was quantified in all washes by a commercial kit, as well as lactate dehydrogenase (LDH) activity. Results: L. crispatus was dominant (>70%) in all CV samples. Lactate was increased in CV in comparison with other cases. The presence of D-lactic acid isomer was associated with presence of L. crispatus. LDH activity was increased in vaginal washes that tested positive for the presence of L. crispatus, however no direct association was found with CV cases. Discussion/Conclusions: The microbiome of women afflicted with CV was dominated in all cases by L. crispatus, contrarily with the results obtained for women diagnosed with other clinical symptomatology. In addition, the finding that an increase in D-lactic acid is associated with CV patients can be related to the role of L. crispatus in CV. The determination of LDH activity did not correlate exclusively with CV cases. On the other hand, D-lactic acid and total lactate quantification could be used as a valuable biomarker to diagnose this cryptic vaginal infection.info:eu-repo/semantics/publishedVersio

Stabilization of high-order solutions of the cubic Nonlinear Schrodinger Equation

In this paper we consider the stabilization of non-fundamental unstable stationary solutions of the cubic nonlinear Schrodinger equation. Specifically we study the stabilization of radially symmetric solutions with nodes and asymmetric complex stationary solutions. For the first ones we find partial stabilization similar to that recently found for vortex solutions while for the later ones stabilization does not seem possible

Performance evaluation of CFD codes in building energy and environmental analysis

Experimental studies in building energy usage and environmental analysis are very time consuming and expensive, and require sophisticated sensors and instrumentation techniques. So, there has been great interest in developing Computational Fluid Dynamics (CFD) computer codes to improve building design and HVAC systems. The majority of these CFD programs are based on the solution of Navier-Stokes equations, the energy equation, the mass and concentration equations as well as the transport equations for turbulent velocity and its scale. The aim of this study is to present the advantages, applicability and potentialities of CFD in building design. The advantages and the performance of (two) commercial CFD codes and an academic CFD code develop for this purpose are evaluated. The codes were applied to predict typical situations of the airflow in buildings and the predictions were compared with experimental results.info:eu-repo/semantics/publishedVersio

Dynamic modelling of refrigerated truck chambers

A refrigerated truck chamber is always under variable conditions. Not only weather changes but also loading and unloading processes can make the chamber behaviour dependent on time. A prediction of relevant properties distributions (velocity, temperature and relative humidity) in refrigerated chambers requires the simultaneous solution, by an iteration process, of the three-dimensional non-linear differential equations for the momentum and heat/mass transport. Basically, these two transport phenomena are coupled by the buoyancy force due to natural convection. However, especially for non-steady state thermal conditions, the high computations times become unattractive the simultaneous integration. For the majority of refrigerated truck chambers, in which the air flow is mainly dominated by forced convection, the equations can be decoupled and the two transport phenomena can be treated separately. Therefore, in the case of dynamic (transient) simulation, this strategy makes the problem much simpler and can strongly reduce the computation time. In this study the simulation method described here was applied in a case study modelling (steady and transient) and was validated by measurements taken from an experimental reduced-scale model.info:eu-repo/semantics/publishedVersio

Therapeutic plasma exchange in patients in a portuguese ICU

Purpose: The aim of this study is to characterize a Portuguese Intensive Care Unit experience in therapeutic plasma exchange in critically ill patients. Methods: We performed a retrospective analysis of the patients treated with therapeutic plasma exchange between 2000 and 2019. Data on patient characteristics, therapeutic plasma exchange prescription, adjuvant therapy used, adverse events and outcome under treatment were collected. Results: A total of 101 therapeutic plasma exchange procedures in 20 patients were studied. Mean number of therapeutic plasma exchange sessions per patient was 5.1±1.3. The most frequent indications to begin this treatment were myasthenia gravis (25.0%) and anti -neutrophil -cytoplasmic antibody -associated vasculitis (15.0%). There were 45.5% adverse events and the most frequent was hypotension (15.2%). 98% of the complications were mild -to -moderate. The outcome was favorable in 60.0% of patients. Conclusion: Therapeutic plasma exchange is an effective and safe therapy in many diseases that had high morbidity and mortality prior to the use of this technique.info:eu-repo/semantics/publishedVersio

Term Structure Models with Shot-noise Effects

This work proposes term structure models consisting of two parts: a part which can be represented in exponential quadratic form and a shot noise part. These term structure models allow for explicit expressions of various derivatives. In particular, they are very well suited for credit risk models. The goal of the paper is twofold. First, a number of key building blocks useful in term structure modelling are derived in closed-form. Second, these building blocks are applied to single and portfolio credit risk. This approach generalizes Duffie & Garleanu (2001) and is able to produce realistic default correlation and default clustering. We conclude with a specific model where all key building blocks are computed explicitly