Publications by authors named "Filipa Santos"

46 Publications

Low-grade serous epithelial ovarian cancer: a comprehensive review and update for radiologists.

Insights Imaging 2021 May 11;12(1):60. Epub 2021 May 11.

Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal.

Low-grade serous carcinoma (LGSC) is an infrequent subtype of ovarian cancer, corresponding to 5% of epithelial neoplasms. This subtype of ovarian carcinoma characteristically has molecular features, pathogenesis, clinical behaviour, sensitivity to chemotherapy, and prognosis distinct to high-grade serous carcinoma (HGSC). Knowing the difference between LGSC and other ovarian serous tumours is vital to guide clinical management, which currently is only possible histologically. However, imaging can provide several clues that allow differentiating LGSC from other tumours and enable precise staging and follow-up of ovarian cancer treatment. Characteristically, LGSC appears as mixed lesions with variable papillary projections and solid components, usually in different proportions from those detected in serous borderline tumour and HGSC. Calcified extracellular bodies, known as psammoma bodies, are also a common feature of LGSC, frequently detectable within lymphadenopathies and metastases associated with this type of tumour. In addition, the characterisation of magnetic resonance imaging enhancement also plays an essential role in calculating the probability of malignancy of these lesions. As such, in this review, we discuss and update the distinct radiological modalities features and the clinicopathologic characteristics of LGSC to allow radiologists to be familiarised with them and to narrow the differential diagnosis when facing this type of tumour.
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http://dx.doi.org/10.1186/s13244-021-01004-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113429PMC
May 2021

Molecular Dynamics Studies of Therapeutic Liquid Mixtures and Their Binding to Mycobacteria.

Front Pharmacol 2021 20;12:626735. Epub 2021 Apr 20.

Red Glead Discovery AB, Lund, Sweden.

Tuberculosis is an highly contagious disease still considered by the WHO as one of most infectious diseases worldwide. The therapeutic approach, used to prevent and treat tuberculosis targets the complex, comprises a combination of drugs administrated for long periods of time, which, in many cases, could cause several adverse effects and, consequently, low compliance of the patient to the treatment and drug-resistance. Therefore, therapeutic liquid mixtures formulated with anti-tuberculosis drugs and/or adjuvants in tuberculosis therapy are an interesting approach to prevent toxic effects and resistance to anti-tuberculosis drugs. The herein formulated therapeutic liquid mixtures, including ethambutol, arginine, citric acid and water under different molar ratios, were studied through a molecular dynamics approach to understand how ethambutol and arginine could be stabilized by the presence of citric acid and/or water in the mixture. To gain insights on how the uptake of these mixtures into the mycobacteria cell may occur and how a mycobacterial ABC transporter could contribute to this transport, multiple simultaneous ligand docking was performed. Interactions between citric acid and ethambutol involving the carboxyl and hydroxyl groups of citric acid with the amines of ethambutol were identified as the most critical ones. Water molecules present in the mixture provides the necessary network of hydrogen bonds that stabilize the mixture. Molecular docking additionally provided an interesting hypothesis on how the different mixture components may favor binding of ethambutol to an ABC importer. The data presented in this work helps to better understand these mixtures as well as to provide cues on the mechanisms that allow them to cross the mycobacterial cell membrane.
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http://dx.doi.org/10.3389/fphar.2021.626735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096353PMC
April 2021

Unravelling the nature of citric acid:L-arginine:water mixtures: the bifunctional role of water.

Phys Chem Chem Phys 2021 Jan;23(2):1706-1717

Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, TU Dortmund, 44227 Dortmund, Germany.

The use of water as a component of deep eutectic systems (DES) has raised some questions regarding its influence on the nature of the mixture. Does it form a DES or an aqueous solution and what is the role of water? In this work, the nature of citric acid:l-arginine:water mixtures was explored through phase equilibria studies and spectroscopic analysis. In a first step, PC-SAFT was validated as a predictive tool to model the water influence on the solid liquid equilibria (SLE) of the DES reline using the individual-component approach. Hence, activity coefficients in the ternary systems citric acid:l-arginine:water and respective binary combinations were studied and compared using ePC-SAFT. It was observed that the water-free mixtures citric acid:l-arginine showed positive deviation from Raoult's law, while upon addition of water strong negative deviation from Raoult's law was found, yielding melting depressions around 100 K. Besides these strong interactions, pH was found to become acidic (pH = 3.5) upon water addition, which yields the formation of charged species ([H2Cit]- and [l-arg]+). Thus, the increased interactions between the molecules upon water addition might be caused by several mechanisms such as hydrogen bonding or ionic forces, both being induced by water. For further investigation, the liquid mixtures citric acid:l-arginine:water were studied by FTIR and NMR spectroscopy. FTIR spectra disproved a possible solubility enhancement caused by salt formation between citric acid and l-arginine, while NMR spectra supported the formation of a hydrogen bonding network different from the binary systems citric acid:water and l-arginine:water. Either being a DES or other type of non-ideal solution, the liquefaction of the studied systems is certainly caused by a water-mediator effect based on the formation of charged species and cross interactions between the mixture constituents.
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http://dx.doi.org/10.1039/d0cp04992aDOI Listing
January 2021

Sphingolipid-enriched domains in fungi.

FEBS Lett 2020 11;594(22):3698-3718

Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Portugal.

Plasma membrane carries out multiple physiological functions that require its dynamic and tightly regulated organization into specialized domains of different size, stability, and lipid/protein composition. Sphingolipids are a group of lipids in which the plasma membrane is particularly enriched, thus being crucial for its structure and function. A specific type of sphingolipid-enriched plasma membrane domains, where ergosterol is depleted and lipids are tightly packed in a rigid gel phase, has recently been found in several fungal species, including yeasts and moulds. After presenting the main biophysical features of gel domains and the experimental method for their detection in the fungal plasma membrane, we review these sphingolipid-enriched gel domains and illustrate their importance to both unicellular and multicellular fungi. First, the biophysical properties of the fungal sphingolipid-enriched domains will be analysed taking into consideration the plasma membrane sphingolipidome. Next, their possible biological roles will be summarized, including their relations with plasma membrane compartments and involvement in stress responses. Moreover, since the plasma membrane is a target for several antifungal compounds, a biophysical connection between sphingolipid-enriched domains and antifungal action will be explored.
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http://dx.doi.org/10.1002/1873-3468.13986DOI Listing
November 2020

Organic Salts Based on Isoniazid Drug: Synthesis, Bioavailability and Cytotoxicity Studies.

Pharmaceutics 2020 Oct 10;12(10). Epub 2020 Oct 10.

LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.

Tuberculosis is one of the ten causes of morbidity and mortality worldwide caused by complex. Some of the anti-tuberculosis drugs used in clinic studies, despite being effective for the treatment of tuberculosis, present serious adverse effects as well as poor bioavailability, stability, and drug-resistance problems. Thus, it is important to develop approaches that could provide shorter drug regimens, preventing drug resistance, toxicity of the antibiotics, and improve their bioavailability. Herein, we reported the use of organic salts based on the isoniazid drug, which can act as an organic cation combined with suitable organic anions such as alkylsulfonate-based (mesylate, R or S-Camphorsulfonate), carboxylate-based (glycolate, vanylate) and sacharinate. The synthesis, characterization, and cytotoxicity studies comparing with the original isoniazid drug have been performed. The possibility to explore dicationic salts seems promising in order to improve original bioavailability, and promote the elimination of polymorphic forms as well as higher stability, which are relevant characteristics that the pharmaceutical industry pursues.
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http://dx.doi.org/10.3390/pharmaceutics12100952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600673PMC
October 2020

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

JAMA 2020 10;324(13):1317-1329

School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).

Main Outcomes And Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.

Conclusions And Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.
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http://dx.doi.org/10.1001/jama.2020.17022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489418PMC
October 2020

Biophysical Analysis of Lipid Domains in Mammalian and Yeast Membranes by Fluorescence Spectroscopy.

Methods Mol Biol 2021 ;2187:247-269

Centro de Química e Bioquímica, Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal.

The use of steady-state and time-resolved fluorescence spectroscopy to study sterol and sphingolipid-enriched lipid domains as diverse as the ones found in mammalian and fungal membranes is herein described. We first address how to prepare liposomes that mimic raft-containing membranes of mammalian cells and how to use fluorescence spectroscopy to characterize the biophysical properties of these membrane model systems. We further illustrate the application of Förster resonance energy transfer (FRET) to study nanodomain reorganization upon interaction with small bioactive molecules, phenolic acids, an important group of phytochemical compounds. This methodology overcomes the resolution limits of conventional fluorescence microscopy allowing for the identification and characterization of lipid domains at the nanoscale.We continue by showing how to use fluorescence spectroscopy in the biophysical analysis of more complex biological systems, namely the plasma membrane of Saccharomyces cerevisiae yeast cells and the necessary adaptations to the filamentous fungus Neurospora crassa , evaluating the global order of the membrane, sphingolipid-enriched domains rigidity and abundance, and ergosterol-dependent properties.
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http://dx.doi.org/10.1007/978-1-0716-0814-2_14DOI Listing
March 2021

Yeast Sphingolipid-Enriched Domains and Membrane Compartments in the Absence of Mannosyldiinositolphosphorylceramide.

Biomolecules 2020 06 6;10(6). Epub 2020 Jun 6.

Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal.

The relevance of mannosyldiinositolphosphorylceramide [M(IP)C] synthesis, the terminal complex sphingolipid class in the yeast , for the lateral organization of the plasma membrane, and in particular for sphingolipid-enriched gel-like domains, was investigated by fluorescence spectroscopy and microscopy. We also addressed how changing the complex sphingolipid profile in the plasma membrane could influence the membrane compartments (MC) containing either the arginine/ H symporter Can1p (MCC) or the proton ATPase Pma1p (MCP). To achieve these goals, wild-type () and Δ cells, which are unable to synthesize M(IP)C accumulating mannosylinositolphosphorylceramide (MIPC), were compared. Living cells, isolated plasma membrane and giant unilamellar vesicles reconstituted from plasma membrane lipids were labelled with various fluorescent membrane probes that report the presence and organization of distinct lipid domains, global order, and dielectric properties. Can1p and Pma1p were tagged with GFP and mRFP, respectively, in both yeast strains, to evaluate their lateral organization using confocal fluorescence intensity and fluorescence lifetime imaging. The results show that deletion strongly affects the rigidity of gel-like domains but not their relative abundance, whereas no significant alterations could be perceived in ergosterolenriched domains. Moreover, in these cells lacking M(IP)C, a clear alteration in Pma1p membrane distribution, but no significant changes in Can1p distribution, were observed. Thus, this work reinforces the notion that sphingolipid-enriched domains distinct from ergosterol-enriched regions are present in the plasma membrane and suggests that M(IP)C is important for a proper hydrophobic chain packing of sphingolipids in the gel-like domains of cells. Furthermore, our results strongly support the involvement of sphingolipid domains in the formation and stability of the MCP, possibly being enriched in this compartment.
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http://dx.doi.org/10.3390/biom10060871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356636PMC
June 2020

Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience.

J Neurooncol 2020 Apr 27;147(2):459-463. Epub 2020 Feb 27.

Pediatric Neuro-Oncology Unit, Pediatrics Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal.

Background: Plexiform neurofibromas (PN) are the most frequent tumors associated with Neurofibromatosis type 1 (NF-1). PN can cause significant complications, including pain, functional impairment, and disfigurement. There is no efficient medical treatment and, surgical resection of large PN is frequently infeasible. Selumetinib (AZD6244/ARRY-142886) is a mitogen-activated protein kinase enzyme (MEK1/2) inhibitor and works by targeting the MAPK pathway. It is an investigational treatment option for inoperable symptomatic PN associated with NF-1. Herein, we describe a single institutional experience with selumetinib for inoperable PN in NF-1.

Methods: Case series study of demographics, clinical, baseline characteristics, treatment effect, and follow-up of consecutive genetically confirmed NF1 patients with inoperable PN associated with significant or potential significant morbidity treated with selumetinib (April 2018 to April 2019).

Results: Nineteen patients were treated with selumetinib. Predominant target locations were head and neck (31.6%, 6/19), chest (26.3%, 5/19) and pelvis (21%, 4/19) and the most important comorbidities were disfigurement (47.4%, 9/19) and pain (26.3%, 5/19). The mean follow-up time was 223 days (range 35-420 days). All but one had sustained clinical improvement, mainly in the first 60-90 days of treatment. In one patient, the treatment was suspended after 168 days (lack of clear benefit and left ventricular ejection fraction drop). There were no adverse effects leading to treatment suspension.

Conclusions: In the first observational study of selumetinib for NF-1 associated PN we showed that the drug was associated with clinical and radiological improvement. Our study also confirms the safety described in the clinical trials.
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http://dx.doi.org/10.1007/s11060-020-03443-6DOI Listing
April 2020

Recurrent midgut volvulus in an adult patient - The case for pexy? A case report and review of the literature.

Int J Surg Case Rep 2020 27;66:91-95. Epub 2019 Nov 27.

Department of General Surgery - Hospital Garcia de Orta, Avenida Torrado da Silva, 2805-267 Almada, Portugal; Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.

Introduction: Intestinal malrotation is a rare condition, with an incidence estimated between 0,2 to 1%. Most cases are diagnosed and treated during childhood. Adult presentations are rare and most adults present with chronic nonspecific complaints. Midgut volvulus is the most feared complication of intestinal malrotation, far more common among the pediatric than the adult population. Presentation in adulthood with a midgut volvulus accounts for a minority of these patients (15%). The Ladd procedure is the standard surgical management of midgut volvulus and intestinal malrotation. Most evidence on the outcomes of the Ladd procedure originates from studies on pediatric population and the recurrence among children who have had a Ladd procedure is low (2-7%).

Presentation Of Case: We report an exceedingly rare case of a patient who presented in adulthood with a midgut volvulus and less than two years after undergoing Ladd procedure presented with a recurrence of the midgut volvulus. The recurrent midgut volvulus was successfully treated by a fixation procedure (cecopexy and duodenopexy).

Conclusion: Reports of midgut volvulus in adult patients are scarce and reports of recurrence even scarcer hence the rate of recurrence among adult patients has yet to be determined. The recurrence rate in some of the available adult series is much higher than the rate reported among children. Should the rate of recurrence among adult patients prove higher, it poses the question of whether the Ladd procedure should be modified to include bowel fixation when performed in adults.
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http://dx.doi.org/10.1016/j.ijscr.2019.11.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906706PMC
November 2019

Chronic pancreatitis in children: treat like an adult?

BMJ Case Rep 2019 Nov 21;12(11). Epub 2019 Nov 21.

Centro de Gastroenterologia, Hospital CUF Infante Santo, Lisboa, Portugal.

A 15-year-old boy with a medical background of obesity, familial hyperlipidemia and acute recurrent pancreatitis, presented to emergency department reporting a 3-day course of periumbilical abdominal pain and nausea. Pain was noticed on epigastric palpation. Laboratory evaluation revealed leucocytosis, neutrophilia and pancreatic enzymes elevation more than three times the upper limit of normal. An acute recurrence of pancreatitis was diagnosed, was admitted to the hospital, being discharged after 5 days. Four days after, he was readmitted because of symptoms recurrence. Elevation of transaminases, gamma-glutamyltransferase (GGT) and direct bilirubin were noticed. Pancreatic enzymes still elevated but lower than in the previous episode. An endoscopic ultrasound revealed a Wirsung with a cephalic stricture and diffuse structural abnormalities suggestive of chronic pancreatitis. The patients was submitted to endotherapy with several sessions of endoscopic retrograde cholangiopancreatography including stenting and pancreatoscopy with marked clinical and imaging improvement. A genetic variant was identified.
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http://dx.doi.org/10.1136/bcr-2019-231714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887479PMC
November 2019

Preparation of Binary and Ternary Deep Eutectic Systems.

J Vis Exp 2019 10 31(152). Epub 2019 Oct 31.

LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa;

The preparation of deep eutectic systems (DES) is a priori a simple procedure. By definition, two or more components are mixed together at a given molar ratio to form a DES. However, from our experience in the laboratory, there is a need to standardize the procedure to prepare, characterize and report the methodologies followed by different researchers, so that the results published can be reproduced. In this work, we test different approaches reported in the literature to prepare eutectic systems and evaluated the importance of water in the successful preparation of liquid systems at room temperature. These published eutectic systems were composed of citric acid, glucose, sucrose, malic acid, β-alanine, L-tartaric acid and betaine and not all of preparation methods described could be reproduced. However, in some cases, it was possible to reproduce the systems described, with the inclusion of water as a third component of the eutectic mixture.
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http://dx.doi.org/10.3791/60326DOI Listing
October 2019

New diphenylphosphane derivatives of ketoconazole are promising antifungal agents.

Sci Rep 2019 11 7;9(1):16214. Epub 2019 Nov 7.

Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal.

Four new derivatives of ketoconazole (Ke) were synthesized: diphenylphosphane (KeP), and phosphane chalcogenides: oxide (KeOP), sulphide (KeSP) and selenide (KeSeP). These compounds proved to be promising antifungal compounds towards Saccharomyces cerevisiae and Candida albicans, especially in synergy with fluconazole. Simulations of docking to the cytochrome P450 14α-demethylase (azoles' primary molecular target) proved that the new Ke derivatives are capable of inhibiting this enzyme by binding to the active site. Cytotoxicity towards hACSs (human adipose-derived stromal cells) of the individual compounds was studied and the IC values were higher than the MIC for C. albicans and S. cerevisiae. KeP and KeOP increased the level of the p21 gene transcript but did not change the level of p53 gene transcript, a major regulator of apoptosis, and decreased the mitochondrial membrane potential. Taken together, the results advocate that the new ketoconazole derivatives have a similar mechanism of action and block the lanosterol 14α-demethylase and thus inhibit the production of ergosterol in C. albicans membranes.
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http://dx.doi.org/10.1038/s41598-019-52525-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838151PMC
November 2019

Deltamethrin impact in a cabbage planted soil: Degradation and effect on microbial community structure.

Chemosphere 2019 Apr 6;220:1179-1186. Epub 2019 Jan 6.

REQUIMTE/LAQV-GRAQ, Instituto Superior de Engenharia do Porto, Politécnico do Porto, Rua Dr. António Bernardino de Almeida, 431, 4200-072 Porto, Portugal. Electronic address:

Synthetic pyrethroids (SPs) are one of the most common pesticides used worldwide. Their use has greatly increased in the last decades and its' continuous application lead to added pesticides concentration in soil. Consequently, SPs may enter the food chain, affecting the environment and human health. The degradation over time of the pyrethroid pesticide deltamethrin applied to cabbages was monitored. The evolution was followed both on cabbages and the surrounding soils, and the soil microbial community characterized by next-generation sequencing of the 16S rRNA gene. The main shift in the microbial community structure was observed during the first 30 days after pesticides' application. The modification in the microbial community composition, where an increased abundance of Nocardioides sp. and Sphingomonas sp. were observed, was correlated respectively with the conversions of deltamethrin and its metabolite, 3-phenoxybenzoic acid (3-PBA). Although deltamethrin was not found in any of the tested samples (soil and cabbage) after 180 days, it caused an environmental impact much further than the 7 days security interval. These findings suggest that deltamethrin application can disturb soil microbial community and that natural biodegradation can have an important part in pesticides soil decontamination.
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http://dx.doi.org/10.1016/j.chemosphere.2019.01.004DOI Listing
April 2019

Light-Induced Protein Clustering for Optogenetic Interference and Protein Interaction Analysis in S2 Cells.

Biomolecules 2019 02 12;9(2). Epub 2019 Feb 12.

Epithelial Polarity and Cell Division, i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.

Schneider 2 (S2) cells are a simple and powerful system commonly used in cell biology because they are well suited for high resolution microscopy and RNAi-mediated depletion. However, understanding dynamic processes, such as cell division, also requires methodology to interfere with protein function with high spatiotemporal control. In this research study, we report the adaptation of an optogenetic tool to S2 cells. Light-activated reversible inhibition by assembled trap (LARIAT) relies on the rapid light-dependent heterodimerization between cryptochrome 2 (CRY2) and cryptochrome-interacting bHLH 1 (CIB1) to form large protein clusters. An anti-green fluorescent protein (GFP) nanobody fused with CRY2 allows this method to quickly trap any GFP-tagged protein in these light-induced protein clusters. We evaluated clustering kinetics in response to light for different LARIAT modules, and showed the ability of GFP-LARIAT to inactivate the mitotic protein Mps1 and to disrupt the membrane localization of the polarity regulator Lethal Giant Larvae (Lgl). Moreover, we validated light-induced co-clustering assays to assess protein-protein interactions in S2 cells. In conclusion, GFP-based LARIAT is a versatile tool to answer different biological questions, since it enables probing of dynamic processes and protein-protein interactions with high spatiotemporal resolution in S2 cells.
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http://dx.doi.org/10.3390/biom9020061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406598PMC
February 2019

Topic platelet gel application in chronic diabetic foot ulcers.

Diabetes Metab Syndr 2019 Jan - Feb;13(1):644-647. Epub 2018 Nov 17.

Diabetic Foot Multidisciplinary Unit, Centro Hospitalar Universitário do Porto, Porto, Portugal.

In this observational study performed during 45 months we evaluated patients with chronic and recalcitrant diabetic ulcers who were treated with homologous platelet gel.

Methods: platelet gels were obtained from homologous platelet concentrates that were aliquoted and freezed, being then activated with calcium gluconate and applied in the ulcer after cleaning and debridement. We evaluated patient's comorbidities, wound characteristics (size, tissue, inflammatory signs, pain), number and time of treatment as well as outcome (classified as complete epithelialization; partial improvement- 50% reduction in wound size or pain relief; no evolution).

Results: Fifty-two patients (42 males, 10 females), with a median age of 65 years (range 43-85) were proposed for platelet gel. The following associated comorbidities were observed: hypertension (n = 41), dyslipidemia (n = 29), polyneuropathy (n = 30), peripheral arteriopathy (n = 32), retinopathy (n = 21), nephropathy (n = 15), cardiac ischemic disease (n = 14), obesity (n = 9). Thirty-eight patients presented with 3 or more associated comorbidities. The more frequent ulcer locations were sole of the foot (n = 13) and heel (n = 10). The median number of applications was 16, during 8.5 weeks. Nineteen patients (44%) achieved complete healing, 3 patients (7%) had a partial response and 21 (49%) had no progression. We did not observe a statistically significant relationship between patient age and response nor between number of comorbidities and response. We observed a more favorable evolution in patients with good compliance and good glycemic control.

Conclusion: Platelet gel is an effective therapeutic alternative, provided compliance and effective metabolic control are ensured.
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http://dx.doi.org/10.1016/j.dsx.2018.11.032DOI Listing
May 2019

Acacia, cherry and oak wood chips used for a short aging period of rosé wines: effects on general phenolic parameters, volatile composition and sensory profile.

J Sci Food Agric 2019 May 2;99(7):3588-3603. Epub 2019 Mar 2.

LEAF - Linking Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, Universidade de Lisboa, Lisboa, Portugal.

Background: There is a restricted knowledge about the potential impact of the use of different wood chip species on the rosé wine aging process. Thus, the aim of this work was to evaluate the general phenolic parameters, aroma composition and sensory profile of rosé wines during a short maturation (20 aging days) in contact with wood chips from oak, acacia and cherry. In addition, the different wood chips were added to a rosé wine without a previous clarification process (unfined wine) and to a rosé wine submitted to a clarification process (fined wine).

Results: For the brief maturation time considered, the use of different wood chips induced a tendency for an increase of phenolic content, in particular for unfined rosé wine aged in contact with acacia chips. For volatile composition, the differentiation was clearer for aldehyde compounds group. Regarding sensorial overall appreciation the panel test preferred the unfined rosé wine aged in contact with acacia wood chips.

Conclusions: The results show that, in general, the use of different wood chip species (acacia, cherry and oak) for a brief maturation time of rosé wines could play an important role in rosé wine characteristics, in particular in their phenolic composition. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.9580DOI Listing
May 2019

Biodegradation of enrofloxacin by microbial consortia obtained from rhizosediments of two estuarine plants.

J Environ Manage 2019 Feb 15;231:1145-1153. Epub 2018 Nov 15.

Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal. Electronic address:

This study aimed to investigate the potential of microbial communities from the rhizosediment of two plants - Phragmites australis and Juncus maritimus - occurring in an estuarine area subjected to a high anthropogenic impact, to biodegrade ENR, a commonly used veterinary antibiotic. An enrichment process with 1 mgL of ENR was conducted during ca. 9 months, using acetate as a co-substrate. After this, the enriched microbial consortia were challenged with higher ENR concentrations of 2 and 3 mgL. Microbial cultures enriched with 1 mgL of ENR were capable of biodegrading this antibiotic, though not completely. By the end of the enrichment phase, microbial cultures were defluorinating an average of 50% of the ENR supplemented. Higher ENR concentrations led to lower biodegradation performances, suggesting a possible toxic/inhibitory effect in the microbial cultures. Phylogenetic identification of the microorganisms isolated from microbial cultures enriched with ENR revealed a high taxonomical diversity, with microorganisms belonging mainly to Proteobacteria and Bacteroidetes phyla. Assemblage of the obtained isolated strains (according to the enriched cultures from which they were isolated) revealed that the resulting consortia were also capable of degrading ENR, indicating that the main microbial players in the biodegradation of this antibiotic were isolated. These consortia also showed to be more robust to degrade higher concentrations of ENR than the corresponding enriched cultures. This study shows that microorganisms derived from rhizosediments of the selected plants, exhibit capacity to biodegrade ENR, though not completely for the concentrations tested, and may be further explored for the development of bioremediation strategies for the treatment of this antibiotic.
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http://dx.doi.org/10.1016/j.jenvman.2018.11.022DOI Listing
February 2019

Removal of veterinary antibiotics in constructed wetland microcosms - Response of bacterial communities.

Ecotoxicol Environ Saf 2019 Mar 29;169:894-901. Epub 2018 Nov 29.

CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal.

This study aimed to evaluate the response of bacteria, in terms of microbial community structure, from constructed wetland (CW) microcosms exposed to two veterinary antibiotics, enrofloxacin (ENR) and ceftiofur (CEF), alone or in a mixture, identifying which bacterial groups were dominant in CWs substrate during livestock wastewater treatment. Wastewater, not-doped or doped with ENR and/or CEF (100 µg/L each), was treated during 18 one-week cycles. Systems showed removal percentages > 85% for the added antibiotics, showing also high removal percentages for nutrients and organic matter and confirming CWs systems were working properly. However, both time of exposure and presence of antibiotics influenced significantly CWs substrate bacterial community structure. Pyrosequencing results showed bacterial communities were dominated by phyla Proteobacteria (38-48%), Firmicutes (20-27%), Bacteroidetes (12-15%) and Actinobacteria (4-9%), and that their relative abundance was clearly affected by the presence of the antibiotics. Results suggest the applicability of CWs for the removal of veterinary antibiotics from livestock wastewaters and provide new knowledge about the bacteria within the system, which can potentially be involved in removal processes. This information could in the future be used to improve CWs removal rates of pharmaceuticals from livestock wastewaters.
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http://dx.doi.org/10.1016/j.ecoenv.2018.11.078DOI Listing
March 2019

Properties of Therapeutic Deep Eutectic Solvents of l-Arginine and Ethambutol for Tuberculosis Treatment.

Molecules 2018 Dec 24;24(1). Epub 2018 Dec 24.

LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.

The treatment for tuberculosis infection usually involves a prolonged regimen of multiple antibacterial drugs, which might lead to various secondary effects. For preventing drug resistance and side-effects of anti-tuberculosis drugs, new methods for improving the bioavailability of APIs were investigated. The strategy proposed consists of the preparation of therapeutic deep eutectic solvents (THEDES), that incorporate l-arginine and ethambutol. The eutectic mixtures were prepared by mixing the components at a certain molar ratio, until a clear liquid solution was formed. The prepared mixtures were characterized by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and nuclear magnetic resonance spectroscopy (¹H and C-NMR). The solubility and permeability of the drugs when they are in the THEDES form was evaluated at 37 °C, in phosphate buffered saline (PBS). Solubility studies showed an increase of the solubility of ethambutol when incorporated in the eutectic system. The cytotoxicity was evaluated using a model cell line (Caco-2), comparing the cytotoxicity of the API incorporated in the eutectic system. We observed that the cell viability in the THEDES was affected by the presence of citric acid, and higher cytotoxicity values were observed. Nonetheless, these findings do not compromise the possibility to use these systems as new delivery systems for ethambutol and arginine.
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http://dx.doi.org/10.3390/molecules24010055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337512PMC
December 2018

Changes in the Biophysical Properties of the Cell Membrane Are Involved in the Response of to Staurosporine.

Front Physiol 2018 11;9:1375. Epub 2018 Oct 11.

Departamento de Química e Bioquímica, Faculdade de Ciências, Centro de Química e Bioquímica, Universidade de Lisbon, Campo Grande, Lisbon, Portugal.

is a non-pathogenic filamentous fungus widely used as a multicellular eukaryotic model. Recently, the biophysical properties of the plasma membrane of conidia were thoroughly characterized. They evolve during conidial germination at a speed that depends on culture conditions, suggesting an important association between membrane remodeling and the intense membrane biogenesis that takes place during the germinative process. Staurosporine (STS) is a drug used to induce programmed cell death in various organisms. In , STS up-regulates the expression of the ABC transporter ABC-3, which localizes at the plasma membrane and pumps STS out. To understand the role of plasma membrane biophysical properties in the fungal drug response, was subjected to STS treatment during early and late conidial development stages. Following 1 h treatment with STS, there is an increase in the abundance of the more ordered, sphingolipid-enriched, domains in the plasma membrane of conidia. This leads to higher fluidity in other membrane regions. The global order of the membrane remains thus practically unchanged. Significant changes in sphingolipid-enriched domains were also observed after 15 min challenge with STS, but they were essentially opposite to those verified for the 1 h treatment, suggesting different types of drug responses. STS effects on membrane properties that are more dependent on ergosterol levels also depend on the developmental stage. There were no alterations on 2 h-grown cells, clearly contrasting to what happens at longer growth times. In this case, the differences were more marked for longer STS treatment, and rationalized considering that the drug prevents the increase in the ergosterol/glycerophospholipid ratio that normally takes place at the late conidial stage/transition to the mycelial stage. This could be perceived as a drug-induced development arrest after 5 h growth, involving ergosterol, and pointing to a role of lipid rafts possibly related with an up-regulated expression of the ABC-3 transporter. Overall, our results suggest the involvement of membrane ordered domains in the response mechanisms to STS in .
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http://dx.doi.org/10.3389/fphys.2018.01375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193110PMC
October 2018

Fine-needle aspiration features of extraskeletal myxoid chondrosarcoma: A study of cytological and molecular features.

Diagn Cytopathol 2018 Nov 24;46(11):950-957. Epub 2018 Oct 24.

Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal.

Background: Extraskeletal myxoid chondrosarcoma (EMC) is a tumor of uncertain differentiation. Few data are available regarding its cytomorphological features in fine-needle aspiration (FNA). Specific cytogenetic alterations involving the NR4A3 gene are found in EMC and can be identified in FNA samples.

Methods: We retrospectively reviewed 14 FNAs performed in 11 patients with an EMC; 10 FNAs were performed preoperatively on primary tumors; 2 were performed on recurrences and 2 were performed on metastasis. Cytological features were compared with histological findings. Immunohistochemistry (IHC) and molecular studies were performed both in FNA and histological specimens.

Results: A preoperative cytological diagnosis of EMC was rendered in eight FNAs performed in newly diagnosed tumors and in recurrent/metastatic cases. A descriptive diagnosis of a myxoid neoplasm was made in the remaining two cases. Smears were moderately hypercellular, composed of plasmocytoid to fusiform cells, with scant, pale cytoplasm, bland nuclei and inconspicuous nucleoli, dispersed as cords, strands and occasionally with a lace-like pattern, in an abundant chondromyxoid matrix. IHC performed showed focal positivity for S100 and NSE. Fluorescence in situ hybridization technique performed in three FNA specimens showed EWSR1 gene rearrangements in all, concomitant with NR4A3 gene rearrangement in one case. Histological specimens showed typical features of EMC and NR4A3 gene rearrangements were found in all cases tested.

Conclusion: FNA cytology is a reliable method to perform a preoperative diagnosis of EMC regarding its cytomorphological and molecular features. Main differential diagnoses include myoepithelial tumors of soft tissue, myxoid liposarcoma and myxofibrosarcoma. Ancillary studies are helpful when coupled with cytomorphology evaluation.
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http://dx.doi.org/10.1002/dc.24028DOI Listing
November 2018

Exploitation of new chalcones and 4H-chromenes as agents for cancer treatment.

Eur J Med Chem 2018 Sep 26;157:101-114. Epub 2018 Jul 26.

Department of Chemistry, University of Minho, Campus of Gualtar, Braga, Portugal. Electronic address:

Chalcone and chromene derivatives were synthesized in good yield through simple and effective reactions using innocuous solvents such as water and ethanol and high yielding aldol condensations. Generally, the reactions were performed at room temperature, leading to the isolation of highly pure compounds. These compounds were tested on breast cancer cells (MCF-7 and Hs578T) and breast non-neoplastic cells (MCF-10A). After determination of IC value, specific assays were performed to analyze the potential of these compounds, and those bearing halogenated substituents presented enhanced activity comparing to methoxyl or methyl groups. More specifically, the bromine atom was often present in the bioactive molecules that proceeded to the final assays and showed to be promising candidates for further studies. The selected chromene acted as a cell migration inhibitory agent and triggered regulated cell death associated with G/M cell-arrest and microtubule destabilization. For chalcones, the results suggest an anti-proliferative activity. Also, results for combination-therapy potentiated the antitumor effect of doxorubicin and reduced cytotoxicity in MCF-10A cells.
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http://dx.doi.org/10.1016/j.ejmech.2018.07.058DOI Listing
September 2018

Prepubertal gynaecomastia in a boy with Peutz-Jeghers syndrome: managing the aromatase overexpression.

J Pediatr Endocrinol Metab 2018 Oct;31(10):1149-1154

Paediatric Endocrinology Unit, Hospital Dona Estefânia - Centro Hospitalar Lisboa Central, Lisboa, Portugal.

Background Gynaecomastia, although rarely related to testicular tumours, in boys with Peutz-Jeghers syndrome (PJS) usually occurs due to large-cell calcifying Sertoli cell tumour (LCCSCT). Case presentation A 4-year-old boy, with a genetic diagnosis of PJS, presented gynaecomastia since the age of 2, associated with increased height velocity (HV). He exhibited bilateral breast enlargement (Tanner-B4) and a testicular volume of 4 mL. Testicular ultrasound revealed multifocal microcalcifications in both testicles. A laboratory evaluation showed undetectable gonadotrophins, testosterone and oestrogen and inhibin A of 4.6 pg/mL (0.9-1.7). The boy was subjected to therapy with anastrozole. In the last follow-up, 2 years after the start of therapy, he experienced a less tense Tanner-B2 and a decrease in HV; serum inhibin A had become negative. Conclusions This is one of the most precocious PJS-related gynaecomastia treated with aromatase inhibitors (AIs) reported in the literature. Oestrogen levels, although under the detection limit, may be sufficient to stimulate breast tissue/growth plates. Inhibin A is a good marker of LCCSCT and an indicator of response to AIs.
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http://dx.doi.org/10.1515/jpem-2017-0455DOI Listing
October 2018

Metastatic Endocervical Adenocarcinoma in a Mature Cystic Teratoma: A Case of a Tumor-to-Tumor Metastasis.

Int J Gynecol Pathol 2018 Nov;37(6):559-563

Anatomic Pathology Service (F.S., A.F.) Radiology Service (J.P.C.) Gynecology Service (A.C.), Portuguese Institute of Oncology (IPOLFG) NOVA Medical School, NOVA University of Lisbon (C.O.) CEDOC, Nova Medical School, NOVA University of Lisbon (A.F.), Lisbon, Portugal.

Tumor-to-tumor metastasis is a rare phenomenon defined as a metastasis in a histologically distinct tumor. We report an unusual case of a 51-yr-old woman who presented with a cervical, bleeding lesion diagnosed as a poorly differentiated adenocarcinoma, HPV18+. Imaging studies revealed an unresectable cervical carcinoma with an associated left ovarian multicystic teratoma. A suspicious solid nodule within the teratoma was also reported. Bilateral salpingo-oophorectomy was performed before the cervical tumor was treated. Pathologic findings showed a multicystic tumor measuring 110×40×30 mm with an area of adenocarcinoma, morphologically similar to the cervical neoplasm. The immunoprofile obtained in the malignant ovarian component (p16+, carcinogenic embryonic antigen+, vimentin-, estrogen receptor-) was similar to the one in the cervix. Moreover, both lesions harbored HPV18. These findings confirmed the presence of a metastatic cervical adenocarcinoma in a mature cystic teratoma. In the differential diagnosis, both somatic malignant transformation of the mature cystic teratomas and the presence of a "collision tumor" were considered and are discussed in this case report.
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http://dx.doi.org/10.1097/PGP.0000000000000457DOI Listing
November 2018

S-Nitrosylation of Ras Mediates Nitric Oxide-Dependent Post-Injury Neurogenesis in a Seizure Model.

Antioxid Redox Signal 2018 Jan 7;28(1):15-30. Epub 2017 Aug 7.

1 Centre for Biomedical Research (CBMR), University of Algarve , Faro, Portugal .

Aims: Nitric oxide (NO) is involved in the upregulation of endogenous neurogenesis in the subventricular zone and in the hippocampus after injury. One of the main neurogenic pathways activated by NO is the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway, downstream of the epidermal growth factor receptor. However, the mechanism by which NO stimulates cell proliferation through activation of the ERK/MAPK pathway remains unknown, although p21Ras seems to be one of the earliest targets of NO. Here, we aimed at studying the possible neurogenic action of NO by post-translational modification of p21Ras as a relevant target for early neurogenic events promoted by NO in neural stem cells (NSCs).

Results: We show that NO caused S-nitrosylation (SNO) of p21Ras in Cys118, which triggered downstream activation of the ERK/MAPK pathway and proliferation of NSC. Moreover, in cells overexpressing a mutant Ras in which Cys118 was replaced by a serine-C118S-, cells were insensitive to NO, and no increase in SNO, in ERK phosphorylation, or in cell proliferation was observed. We also show that, after seizures, in the presence of NO derived from inducible nitric oxide synthase, there was an increase in p21Ras cysteine modification that was concomitant with the previously described stimulation of proliferation in the dentate gyrus.

Innovation: Our work identifies p21Ras and its SNO as an early target of NO during signaling events that lead to NSC proliferation and neurogenesis.

Conclusion: Our data highlight Ras SNO as an early event leading to NSC proliferation, and they may provide a target for NO-induced stimulation of neurogenesis with implications for brain repair. Antioxid. Redox Signal. 28, 15-30.
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http://dx.doi.org/10.1089/ars.2016.6858DOI Listing
January 2018

Phototriggered release of tetrapeptide AAPV from coumarinyl and pyrenyl cages.

Amino Acids 2017 06 10;49(6):1077-1088. Epub 2017 Mar 10.

Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.

Ala-Ala-Pro-Val (AAPV) is a bioactive tetrapeptide that inhibits human neutrophil elastase, an enzyme involved in skin chronic inflammatory diseases like psoriasis. Caged derivatives of this peptide were prepared by proper N- and C-terminal derivatisation through a carbamate or ester linkage, respectively, with two photoactive moieties, namely 7-methoxycoumarin-2-ylmethyl and pyren-2-ylmethyl groups. These groups were chosen to assess the influence of the photosensitive group and the type of linkage in the controlled photo release of the active molecule. The caged peptides were irradiated at selected wavelengths of irradiation (254, 300, and 350 nm), and the photolytic process was monitored by HPLC-UV. The results established the applicability of the tested photoactive groups for the release of AAPV, especially for the derivative bearing the carbamate-linked pyrenylmethyl group, which displayed the shortest irradiation times for the release at the various wavelengths of irradiation (ca. 4 min at 254 nm, 8 min at 300 nm and 46 min at 350 nm).
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http://dx.doi.org/10.1007/s00726-017-2405-6DOI Listing
June 2017

[Pain Intensity and Time to Death of Cancer Patients Referred to Palliative Care].

Acta Med Port 2016 Nov 30;29(11):694-701. Epub 2016 Nov 30.

Cuidados Paliativos. Institutos de Investigação de Bruyere e Ottawa. Universidade de Ottawa. Ottawa. Canadá.

Introduction: Pain is a common symptom experienced by cancer patients, especially in those with advanced disease. Our aim was to describe pain intensity in advanced cancer patients, referred to the palliative care unit, the factors underlying moderate to severe pain and its prognostic values.

Material And Methods: This was a prospective observational study. All patients with mestastatic solid tumors and with no specific oncologic treatment were included. Pain intensity was accessed using the pain scale from Edmonton Symptom Assessment Scale, rated from 0 to 10 on a numerical scale, where zero = no pain and 10 = worst possible pain.

Results: Between October 2012 and June 2015, a total of 301 patients participated in the study. The median age was 69 years, (37 - 94); most of the patients were men (57%) and 64.8% had a performance status of 3/4. About 42% reported pain severity ≥ 4 and 74% were medicated with opioids. Multivariate analysis indicated a correlation between performance status and reported pain (OR: 1.7; IC 95%: 1.0 - 2.7; p = 0.045). Median overall survival was 37 days (IC 95%: 28 - 46). Patients reporting moderate to severe pain (pain severity ≥ 4) had a median survival of 29 days (IC 95%: 21 - 37), comparing with those who had no or moderate pain with median survival of 49 days (IC 95%: 35 - 63) (p = 0.022).

Discussion: The performance status was associated with more intense pain. The performance status, hospitalization, intra-abdominal metastization and opioid analgesia were associated with shorter time to death in advanced cancer patients referred to palliative care.

Conclusion: Cancer pain continues to be a major clinical problem in advanced cancer patients.
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http://dx.doi.org/10.20344/amp.7557DOI Listing
November 2016

Cytokeratin immunoprofile of primary and metastatic adenoid cystic carcinoma of salivary glands: a report of two cases.

Autops Case Rep 2016 Oct-Dec;6(4):57-63. Epub 2016 Dec 30.

Department of Stomatology - Dental School - Universidade de São Paulo, São Paulo/SP - Brazil .

Distant metastases from salivary gland tumors are considered infrequent: the incidence of distant metastases ranges from 24% to 61% according to different histotypes and to the site of the primary mass. The most common site of distant metastases due to salivary gland malignancies is the lung. From the pathology point of view, cytokeratins (CK) are important differentiation markers in salivary gland tumors, which are often used for the diagnostic process. Their employment also may be useful to identify and confirm the diagnosis of their distant metastases. We report the expression of CK in two cases of primary and metastatic adenoid cystic carcinoma (ACC) and their CK profiles of the primary and metastatic masses. Both patients-one male and one female-were diagnosed with an ACC cribriform and tubular, respectively, with lung metastases. In case 1, the metastatic mass presented the same histotype and CK profile of the primary tumor. For case 2, the metastatic lung mass was distinct from the primary mass (a solid ACC) and presented a different CK profile. Although salivary gland metastatic disease presents a poor prognosis, both patients reported herein are alive despite the presence of the disease in long-term follow-up. Therefore, the modifications seen in the CK profiles do not appear to be predictive of tumor behavior and outcome. The use of a CK profile seems to be useful to identify the nature of a distant mass and its possible correlations with a primary salivary gland tumor.
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http://dx.doi.org/10.4322/acr.2016.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304563PMC
December 2016

Constructed wetlands for the removal of metals from livestock wastewater - Can the presence of veterinary antibiotics affect removals?

Ecotoxicol Environ Saf 2017 Mar 19;137:143-148. Epub 2016 Dec 19.

Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR / CIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal.

The presence of emergent antibiotics, in livestock wastewater may affect constructed wetlands (CWs) performance in the removal of other pollutants. The main objective of this study was to evaluate the influence of two antibiotics commonly used in livestock industry, enrofloxacin and ceftiofur, on metal removal by CWs. Microcosms (0.4m×0.3m×0.3m), simulating CWs, were constructed with Phragmites australis to treat livestock wastewater spiked or not with 100µg/L of enrofloxacin or ceftiofur (individually or in mixture). Wastewater was treated during 20 one-week cycles. After one-week cycle wastewater was removed and replaced by new wastewater (with or without spiking). At weeks 1, 2, 4, 8, 14, 18 and 20, treated wastewater was analysed to determine the removal rates of metals (Zn, Cu, Fe and Mn) and of each antibiotic. At weeks 1, 8 and 20 portions of the plant root substrate were collected and metals determined. At the end of the experiment metal levels were also determined in plant tissues. Removal rate of Fe from wastewater was 99%. Removal rates of Cu and Zn were higher than 85% and 89%, respectively, whereas for Mn removal rates up to 75% were obtained. In general, no significant differences were observed through time in the removals of the different metals, indicating that the systems maintained their functionality during the experimental period. Antibiotics did not interfere with the system depuration capacity, in terms of metals removals from wastewater, and ceftiofur even promoted metal uptake by P. australis. Therefore, CWs seem to be a valuable alternative to remove pollutants, including antibiotics and metals, from livestock wastewaters, reducing the risk the release of these wastewaters might pose into the environment, although more research should be conducted with other antibiotics in CWs.
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http://dx.doi.org/10.1016/j.ecoenv.2016.11.021DOI Listing
March 2017