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Water scarcity affects already a large part of the world's population. To overcome this situation, water management is needed, and wastewater reuse must be implemented and included as a new approach. To achieve that objective water quality must comply with the parameters established in the Regulation (EU) 2020/741 of the European Parliament and the Council of the European Union and new treatment solutions have to be developed. The main goal of this pilot study was to evaluate the peracetic acid (PAA) disinfection efficiency in a real wastewater treatment plant (WWTP) in order to accomplish the wastewater reuse objective. To this end, six disinfection conditions were studied, three PAA doses (5, 10, and 15) and three contact times (5, 10, and 15) based on the commonly used disinfection operational conditions in real WWTP. Comparing the Total Suspended Solids (TSS), turbidity, Biological Oxygen Demand (BOD5) and Escherichia coli content, after and before the disinfection step, was possible to conclude that PAA ensures the Regulation (EU) 2020/741 requirements and that the disinfected effluent can be reused for several uses. All the conditions in which the PAA dose was 15 mg/L and the condition with 10 mg/L of PAA with a contact time of 15 min were the most promising, presenting the second highest water quality class achieved. The results of this study illustrate the potential of PAA as an alternative disinfectant for wastewater treatment and, bring it closer to the water reuse objective by presenting several possibilities for water uses.
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Desinfetantes , Purificação da Água , Ácido Peracético , Águas Residuárias , Projetos Piloto , Monitoramento Ambiental , Desinfecção/métodos , Escherichia coli , Purificação da Água/métodos , Eliminação de Resíduos Líquidos/métodosRESUMO
In this work we study the coupling between ionization and conformational properties of two IDPs, histatin-5 and ß-amyloid 42, in the presence of neutral and charged crowders. The latter is modeled to resemble bovine serum albumin (BSA). With this aim, semi-grand canonical Monte Carlo simulations are performed, so that the IDP charge is a dynamic property, undergoing protonation/deprotonation processes. Both ionization properties (global and specific amino acid charge and binding capacitance) and radius of gyration are analyzed in a large range of pH values and salt concentrations. Without crowder agents, the titration curve of histatin-5, a polycation, is salt-dependent while that of ß-amyloid 42, a polyampholyte, is almost unaffected. The salt concentration is found to be particularly relevant at pH values where the protein binding capacitance (directly linked with charge fluctuation) is larger. Upon addition of neutral crowders, charge regulation is observed in histatin-5, while for ß-amyloid 42 this effect is very small. The main mechanism for charge regulation is found to be the effective increase in the ionic strength due to the excluded volume. In the presence of charged crowders, a significant increase in the charge of both IDPs is observed in almost all the pH range. In this case, the IDP charge is altered not only by the increase in the effective ionic strength but also by its direct electrostatic interaction with the charged crowders.
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Proteínas Intrinsicamente Desordenadas , Substâncias Macromoleculares , Método de Monte Carlo , Conformação Proteica , Eletricidade EstáticaRESUMO
Presently, water quantity and quality problems persist both in developed and developing countries, and concerns have been raised about the presence of emerging pollutants (EPs) in water. The circular economy provides ways of achieving sustainable resource management that can be implemented in the water sector, such as the reuse of drinking water treatment sludges (WTSs). This study evaluated the potential of WTS containing a high concentration of activated carbon for the removal of two EPs: the steroid hormones 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2). To this end, WTSs from two Portuguese water treatment plants (WTPs) were characterised and tested for their hormone adsorbance potential. Both WTSs showed a promising adsorption potential for the two hormones studied due to their textural and chemical properties. For WTS1, the final concentration for both hormones was lower than the limit of quantification (LOQ). As for WTS2, the results for E2 removal were similar to WTS1, although for EE2, the removal efficiency was lower (around 50%). The overall results indicate that this method may lead to new ways of using this erstwhile residue as a possible adsorbent material for the removal of several EPs present in wastewaters or other matrixes, and as such contributing to the achievement of Sustainable Development Goals (SDG) targets.
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Esgotos/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água , Elementos Químicos , Concentração de Íons de Hidrogênio , Minerais/análise , TermogravimetriaRESUMO
17ß-Estradiol (E2) is a natural estrogen produced by the feminine endocrine system. It is excreted mainly through urine and feces. Exposure to E2 may affect the reproductive system of both animals and humans, especially since the removal of E2 in conventional processes and technologies present in the wastewater treatment plants is not sufficient. Chlorine is one of the most studied and used oxidant worldwide. Although there are studies that demonstrate the endocrine disrupting compounds removal like E2, its reaction with organic matter can originate by-products, namely, trihalomethanes, which are known to have high toxic potential. The main aim of the present study was to evaluate the removal of E2 (50 µg E2 L-1-maximum concentration) using peracetic acid (PAA), a seeming cleaner and innocuous alternative to chlorine. To this end, a series of jar tests were performed, using different peracetic acid concentrations (1, 5, 10, and 15 mg L-1) and contact times (10, 15, and 20 min). The results obtained showed that a peracetic acid concentration of 15 mg L-1 with a contact time of 20 min had a removal efficacy of approximately 100%. The second main goal of this study was to evaluate the ecotoxicological potential of the tested treatments on the zebrafish Danio rerio. Several oxidative stress biomarkers were evaluated, namely glutathione S-transferase, lipid peroxidation, and catalase, besides vitellogenin. Both peracetic acid and E2 caused significant increases in the oxidative stress biomarkers, although this did not lead to increased lipid peroxidation levels. In addition, peracetic acid significantly decreased the estrogenic activity of E2, as indicated by decreased vitellogenin levels. Peracetic acid demonstrated to have great potential as an alternative disinfectant for chlorine treatments, and indications for future research are discussed.
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Monitoramento Ambiental , Estrogênios/análise , Ácido Peracético/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Animais , Cloro , Desinfetantes , Disruptores Endócrinos/análise , Estradiol/análise , Estrona , Humanos , Trialometanos , Vitelogeninas , Águas ResiduáriasRESUMO
Increasing concerns have been raised on endocrine disrupting chemicals like the sex hormone 17α-ethinylestradiol (EE2), the more since traditional wastewater (WW) treatments appear to be ineffective for their removal. The efficacy of the relatively novel disinfectant peracetic acid (PAA) in EE2 removal was evaluated, as well as its potential effects on WW quality parameters. The treatments tested for EE2 removal were also evaluated in terms of toxicity, through the determination of biochemical responses (antioxidant enzymes, lipid peroxidation and vitellogenin induction) using zebrafish (Danio rerio) as a biological model. PAA contact times less than 20 min appeared insufficient regardless of the PAA dose tested, but a 100% EE2 removal was attained at a PAA concentration of 15 mg/L with a contact time of 20 min. Total suspended solids, chemical oxygen demand and pH in PAA treatments remained well within levels set in European legislation for WW discharge. EE2 induced significant increased vitellogenin (VTG) levels in both female and male fish, indicating increased estrogenic activity, especially in males suggesting an endocrine disruption effect. With the addition of PAA (15 mg/L), however, VTG levels in both sexes returned to control values. Although this PAA treatment showed increased levels of the antioxidant enzyme catalase, the lipid peroxidation levels were similar or even lower than in controls. Overall the results suggest that the use of PAA appears a promising way forward as a less toxic alternative to chlorine disinfection with high efficiency in the removal of EDC like EE2.
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Etinilestradiol/química , Ácido Peracético/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Poluentes Químicos da Água/química , Anticoncepcionais , Estradiol , Etinilestradiol/análise , Ácido Peracético/análise , Vitelogeninas , Poluentes Químicos da Água/análiseRESUMO
Macrophagic myofasciitis (MMF) is a rare immune-mediated myopathy that seems to be triggered by aluminium hydroxide adjuvant used in vaccines. Its presentation is relatively heterogeneous and treatment with steroids leads to improvement, although there is little evidence regarding the role of other immunosuppressants. The histological findings in MMF seem to be the result of an abnormal presence in the inoculation site of aluminium, which can induce an immune-mediated muscular disease in susceptible persons. The authors describe the case of a patient with an atypical presentation of macrophagic myofasciitis, with histological confirmation in a muscle biopsy distant from the inoculation site, and a good therapeutic response to tacrolimus and mycophenolate mofetil, as well as a discussion on the pathologic basis, controversies and emerging treatments for this condition.
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Adsorption of polyions onto charged surfaces has long been recognized as a crucial phenomenon in biological and technological applications. An intuitive model relating polyelectrolyte adsorption with the imposed features of polarizable surfaces of different compositions and charges is proposed based on Monte Carlo simulations using a coarse-grained approach. The excellent performance of the equation allows simultaneously describing a wide range of adsorption regimes and accounting for specific non-monotonic trends. For a constant surface charge density, the surface composition governs adsorption, promoting variations exceeding 100%. Adsorption increases with the number of attractive charges in the surface until reaching a maximum, decreasing thereafter due to the presence of polyanion-like charged particles. The presence of crowders hampers adsorption. These results can be used to efficiently predict and modulate the interaction between charged macromolecules and different substrates with direct implications in de novo designs of vehicles and biomedical devices.
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BACKGROUND: The potential use of Fe(III) ions in biomedical applications may predict the interest of its combination with pDNA-PEI polyplexes. The present work aims at assessing the impact of this metal on pDNA complex properties. METHODS: Variations in the formation of complexes were imposed by using two types of biological buffers at different salt conditions. The incorporation of pDNA in complexes was characterised by gel electrophoresis and dynamic light scattering. Transfection efficiency and cytotoxicity were evaluated in HeLa and HUH-7 cell lines, supported by flow cytometry assays. RESULTS: Fe(III) enhances pDNA incorporation in the complex, irrespective of the buffer used. Transfection studies reveal that the addition of Fe(III) to complexes at low ionic strength reduces gene transfection, while those prepared under high salt content do not affect or, in a specific case, increase gene transfection up to 5 times. This increase may be a consequence of a favoured interaction of polyplexes with cell membrane and uptake. At low salt conditions, results attained with chloroquine indicate that the metal may inhibit polyplex endosomal escape. A reduction on the amount of PEI (N/P 5) formed at intermediary ionic strength, complemented by Fe(III), reduces the size of complexes while maintaining a transfection efficiency similar to that obtained to N/P 6. CONCLUSIONS: Fe(III) emerges as a good supporting condensing agent to modulate pDNA-PEI properties, including condensation, size and cytotoxicity, without a large penalty on gene transfection. GENERAL SIGNIFICANCE: This study highlights important aspects that govern pDNA transfection and elucidates the benefits of incorporating the versatile Fe(III) in a gene delivery system.
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Cloretos/metabolismo , Compostos Férricos/metabolismo , Plasmídeos/metabolismo , Polietilenoimina/metabolismo , Transfecção/métodos , Trifosfato de Adenosina/metabolismo , Soluções Tampão , Cloretos/química , Cloretos/toxicidade , Ensaio de Desvio de Mobilidade Eletroforética , Metabolismo Energético/efeitos dos fármacos , Compostos Férricos/química , Compostos Férricos/toxicidade , Regulação da Expressão Gênica , Genes Reporter , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Luz , Luciferases/genética , Luciferases/metabolismo , Conformação de Ácido Nucleico , Concentração Osmolar , Plasmídeos/química , Polietilenoimina/química , Polietilenoimina/toxicidade , Espalhamento de RadiaçãoRESUMO
This work evaluated the effect of lysozyme on lactobacilli isolated from Port wine. Bacterial growth experiments were conducted in MRS/TJ medium and inactivation studies were performed in phosphate buffer (KH2PO4), distilled water and wine supplemented with different concentrations of lysozyme. The response of bacteria to lysozyme was found to be highly strain dependent. Some strains of Lactobacillus hilgardii together with Lactobacillus collinoides and Lactobacillus fructivorans were found to be resistant to concentrations of lysozyme as high as 2000 mg/L. It was observed that among the L. hilgardii taxon the resistant strains possess an S-layer coat. Apparently, the strains of L. collinoides and L. fructivorans studied are also S-layer producers as suggested by the total protein profile obtained by SDS-PAGE. Thus, the hypothetical protective role of the S-layer against the action of lysozyme was investigated. From the various treatments used to remove the protein from the surface of the cells, the one employing LiCl (5 M) was the most effective. LiCl pre-treated cells exposed to lysozyme (2000 mg/L) in KH2PO4 buffer maintained its resistance. However, when cells were suspended in distilled water an increased sensitivity to lysozyme was observed. Moreover, it was found that the addition of ethanol (20% v/v) to the suspension medium (distilled water) triggered a strong inactivation effect especially on cells previously treated with LiCl (reduction of >6 CFU log cycles). The results suggest that the S-layer exerts a protective effect against lysozyme and that the cell suspension medium influences the bacteriolysis efficiency. It was also noted that ethanol enhances the inactivation effect of lysozyme.
Assuntos
Aditivos Alimentares/farmacologia , Lactobacillus/efeitos dos fármacos , Muramidase/farmacologia , Vinho/microbiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Eletroforese em Gel de Poliacrilamida , Lactobacillus/classificação , Lactobacillus/genética , Lactobacillus/metabolismo , Viabilidade Microbiana/efeitos dos fármacos , Especificidade da EspécieRESUMO
This work aims to shed light on the mechanism of interaction between components of ternary DNA-PEI-Fe(III) complexes, using experimental and theoretical approaches. In the experimental part, the chelation between PEI-Fe(III) was inspected by potentiometry and electrical conductance measurements and the respective importance for the condensation of DNA analyzed. To this end, three different mixing protocols for the components were imposed using different PEIs, branched (bPEI1.2 and bPEI10) and linear (lPEI2.5 and lPEI25). A delay in DNA condensation was observed when PEI and Fe(III) were premixed and then added to DNA. The set of observations was complemented by determination of the amount of Fe(III) included in the polyplexes, which was found to be dependent on the order of mixture and on the type of PEI used, decreasing with intrinsic PEI condensation efficiency. Overall, a coherent picture in which Fe(III) compensates PEI, probably modulating the respective charge, emerges. Some points arisen from the experimental part were rationalized using Monte Carlo simulations. Different architectured polycation (PC) chains were modeled and an interaction between PC and multivalent ions, mimicking the chelation of Fe(III) by the PEI, was imposed. It was found that chelation enhances polyanion (PA) compaction, irrespective of the PC architecture and charge density. The amount of multivalent ions in each polyplex compensates the negative charge unbalanced by the PC. The charge density and the ability of chelation of each PC dictate the disposition of each condensing agent along the PA backbone, and their coexistence strengthens PA compaction. The deep understanding of these ternary mixtures is a step forward in the optimization of such systems for application in gene delivery.
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DNA/química , Compostos Férricos/química , Polietilenoimina/química , Método de Monte CarloRESUMO
This study deals with the build-up of biomaterials consisting of biopolymers, namely DNA, and soft particles, poly(amido amine) (PAMAM) dendrimers, and how to model their interactions. We adopted and applied an analytical model to provide further insight into the complexation between DNA (4331 bp) and positively charged PAMAM dendrimers of generations 1, 2, 4, 6 and 8, previously studied experimentally. The theoretical models applied describe the DNA as a semiflexible polyelectrolyte that interacts with dendrimers considered as either hard (impenetrable) spheres or as penetrable and soft spheres. We found that the number of DNA turns around one dendrimer, thus forming a complex, increases with the dendrimer size or generation. The DNA penetration required for the complex to become charge neutral depends on dendrimer generation, where lower generation dendrimers require little penetration to give charge neutral complexes. High generation dendrimers display charge inversion for all considered dendrimer sizes and degrees of penetration. Consistent with the morphologies observed experimentally for dendrimer/DNA aggregates, where highly ordered rods and toroids are found for low generation dendrimers, the DNA wraps less than one turn around the dendrimer. Disordered globular structures appear for high generation dendrimers, where the DNA wraps several turns around the dendrimer. Particularly noteworthy is that the dendrimer generation 4 complexes, where the DNA wraps about one turn around the dendrimers, are borderline cases and can form all types of morphologies. The net-charges of the aggregate have been estimated using zeta potential measurements and are discussed within the theoretical framework.
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DNA/química , DNA/ultraestrutura , Dendrímeros/química , Modelos Químicos , Modelos Moleculares , Sítios de Ligação , Simulação por Computador , Substâncias Macromoleculares/química , Conformação de Ácido Nucleico , Eletricidade EstáticaRESUMO
BACKGROUND: Reduced plasma nitrate (NO(x)) levels and increased urinary norepinephrine (U-NE) levels have been described in severe obstructive sleep apnea (OSA), and are reverted by continuous positive airway pressure (CPAP). The effect of CPAP on these biomarkers in mild-moderate OSA is not well understood. The aim of this study was to compare NO(x) and U-NE levels and blood pressure (BP) between male patients with mild-moderate and severe OSA and determine the impact of 1 month of CPAP therapy on these parameters. METHODS: We undertook a prospective study of 67 consecutive OSA patients (36 mild-moderate, 31 severe). Measurements of plasma NO(x) at 11 pm, 4 am and 7 am, 24-h U-NE and ambulatory BP were obtained at baseline and after 1 month of CPAP. RESULTS: At baseline, NO(x) levels showed a significant decrease during the night in both groups (p < 0.001). U-NE level and BP were significantly higher in the severe OSA group. After 1 month of CPAP, there was a significant increase in NO(x) levels and a reduction in U-NE level and BP only in patients with severe OSA. CONCLUSIONS: One month of CPAP results in significant improvements in NO(x) levels, 24-h U-NE level and BP in patients with severe OSA, but not in patients with mild-moderate OSA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01769807.
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Pressão Positiva Contínua nas Vias Aéreas/métodos , Nitratos/sangue , Norepinefrina/urina , Síndromes da Apneia do Sono/metabolismo , Síndromes da Apneia do Sono/terapia , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Monitorização Ambulatorial da Pressão Arterial , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Polissonografia , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Nucleic acid delivery to cells is an important therapeutic strategy that requires the transport of nucleic acids to intracellular compartments and their protection from enzymatic degradation. This can be achieved through the complexation of the nucleic acids with polycations. Poly(amidoamine) (PAMAM) dendrimers and peptide-conjugated dendrimers have been investigated as delivery vectors. Inspired by these studies and the role of flexible peptide domains in protein-DNA interactions, we studied the impact of conjugating two peptides (tails) to generation 2 (G2) PAMAM dendrimers on DNA condensation and polyplex formation. Using gel electrophoresis, dye exclusion assays, atomic force microscopy, and Monte Carlo simulations, it is shown that the steric impact of neutral peptide tails is to hinder the formation of DNA-G2 polyplexes composed of multiple DNA chains. If the tails are negatively charged, which results in overall neutral G2 conjugates, then the interaction of G2 with DNA is hindered. Increasing the net positive charge of the tails resulted in the complexation capacity of G2 with the DNA being restored. While DNA complexation is obtained for a similar net charge balance for G2 and G2 conjugates with positive tails, fewer of the latter are required to achieve a comparable condensation degree. Furthermore, it is shown that about 40% of the DNA remains accessible to binding by small molecules. Overall, this shows that tuning the net charge of peptide tails conjugated to PAMAM dendrimers offers a handle to control the complexation capacity of DNA, which can be explored as a novel route for optimization as gene delivery vehicles.
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Thymomas and thymic carcinomas are rare mediastinal neoplasms arising from thymic epithelial cells, and the presence of synchronous or metachronous primary thymic neoplasms in a single patient is an extremely rare event. Thymoma patients appear to have an inherent predisposition toward developing additional neoplasms. This additionally presents a diagnostic challenge, revealing the importance of multidisciplinary expertise to the management of these patients. This is a case report of a patient with a thymoma and thymic carcinoma, submitted to surgical resection and postoperative radiotherapy.
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The macroscopic phase behavior and other physicochemical properties of dilute aqueous mixtures of DNA and the cationic surfactant hexadecyltrimethylammounium bromide (CTAB), DNA and the polyamine spermine, or DNA, CTAB, and (2-hydroxypropyl)-ß-cyclodextrin (2HPßCD) were investigated. When DNA is mixed with CTAB we found, with increasing surfactant concentration, (1) free DNA coexisting with surfactant unimers, (2) free DNA coexisting with aggregates of condensed DNA and CTAB, (3) a miscibility gap where macroscopic phase separation is observed, and (4) positively overcharged aggregates of condensed DNA and CTAB. The presence of a clear solution beyond the miscibility gap cannot be ascribed to self-screening by the charges from the DNA and/or the surfactant; instead, hydrophobic interactions among the surfactants are instrumental for the observed behavior. It is difficult to judge whether the overcharged mixed aggregates represent an equilibrium situation or not. If the excess surfactant was not initially present, but added to a preformed precipitate, redissolution was, in consistency with previous reports, not observed; thus, kinetic effects have major influence on the behavior. Mixtures of DNA and spermine also displayed a miscibility gap; however, positively overcharged aggregates were not identified, and redissolution with excess spermine can be explained by electrostatics. When 2HPßCD was added to a DNA-CTAB precipitate, redissolution was observed, and when it was added to the overcharged aggregates, the behavior was essentially a reversal of that of the DNA-CTAB system. This is attributed to an effectively quantitative formation of 1:1 2HPßCD-surfactant inclusion complexes, which results in a gradual decrease in the concentration of effectively available surfactant with increasing 2HPßCD concentration.
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Compostos de Cetrimônio/química , Ciclodextrinas/química , DNA/química , Espermina/química , Tensoativos/química , Cátions/química , Cetrimônio , Dicroísmo Circular , Luz , Espalhamento de Radiação , Espectrofotometria UltravioletaRESUMO
Efficient DNA condensation and decondensation, as well as low toxicity, are required for an efficient gene delivery vehicle. We report on the condensation of DNA by a mixture of cationic agents, low-molecular-weight polyethylenimine (PEI, 1.2 KDa) and Fe(III) ions, and respective decondensation, using experimental and theoretical methods. It was found that a significant reduction in the amount of PEI necessary to induce DNA condensation is achieved by the addition of the trivalent ions, which are very inefficient on their own. In addition, the mixture makes DNA decompaction by heparin easier, starting from similar degrees of condensation. The results obtained using simulations of coarse-grain models are coherent with those obtained experimentally. It was also found that the improved effect of the multivalent ions is related to the preferred positioning of the trivalent ions in the DNA areas less populated by the polycation chains, in between the polycation chains and at the ends of the DNA, which facilitates the overall condensation.
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DNA/química , Compostos Férricos/química , Método de Monte Carlo , Animais , Bacteriófago T4 , Cátions/química , Masculino , Modelos Moleculares , Simulação de Dinâmica Molecular , Polietilenoimina/química , Salmão , Testículo/químicaRESUMO
Four cationic chiral amino acid-based surfactants, cis- and trans-1 and cis- and trans-2, have been studied as DNA-condensing agents with enhanced properties and the absence of cell toxicity. The polar head of the surfactant is made of a cyclobutane ß-amino acid in which the amino group is a hydrochloride salt and the carboxyl group is involved in an amide bond, allowing the link with hydrophobic C12 (surfactant 1) or C16 (surfactant 2) chains. The ability of these surfactants to condense DNA was investigated using a dye exclusion assay, gel electrophoresis, and circular dichroism and compared with the well-studied dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB). The surfactant with the longest chain length and the trans stereochemistry (trans-2) was found to be the most efficient in condensing the DNA, including CTAB. Surfactant cis-2 was found to be less efficient, probably due to its poorer solubility. The ß-amino acid surfactants with the shorter chain length behaved similarly, such that the cis/trans stereochemistry does not seem to play a role in this case. Interestingly, these were also found to induce DNA condensation for the same concentration as trans-2 and CTAB but showed a lower binding cooperativity. Therefore, a longer alkyl chain only slightly improved the effectiveness of these surfactants. Further, atomic force microscopy revealed that they compact DNA into small complexes of about 55-110 nm in diameter.
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Aminoácidos , Tensoativos , Cetrimônio , Dicroísmo Circular , DNA/química , Tensoativos/químicaRESUMO
INTRODUCTION: Septic arthritis of a native joint represents a medical emergency. Drainage and effective antibiotic treatment are critical to avoid joint destruction and long-term impairment. The aim of this study was to evaluate epidemiological and clinical characteristics of patients with the diagnosis of septic arthritis to help establish local guidelines for empirical antibiotic treatment. MATERIAL AND METHODS: Retrospective analysis of adult patients admitted at Centro Hospitalar Universitário do Porto from 2009 to 2017 with suspected native joint septic arthritis. Relevant demographics, microbiology findings and respective antibiotic susceptibilities were analysed. RESULTS: Ninety-seven patients, predominantly males (59.8%) with a median age of 61 years old were included. The most commonly reported comorbidity associated with septic arthritis was diabetes mellitus (20.6%). The knee was the most commonly affected joint (71.1%). Arthrocentesis was performed in all patients, but only 50.5% had positive microbial growth in the synovial fluid. Staphylococcus aureus was the most frequently identified microorganism, 86% of which were methicillin susceptible. Gram-negative bacteria were the causative agent in 15% of cases. A wide range of empirical antibiotic regimens were prescribed with a combination of vancomycin/carbapenem being the most common (30.9%). Analysis of antibiotic susceptibility profiles revealed that amoxicillin/clavulanate would have been appropriate as the initial regimen in 89% of cases. DISCUSSION: The main causative pathogen was Staphylococcus aureus, with methicillin resistant Staphylococcus aureus remaining rare. The proportion of Gram-negative bacteria implies that these agents should be covered by empirical treatment, although no case of Pseudomonas infection has been identified. Therefore, antipseudomonal coverage is not necessary in empirical regimens. CONCLUSION: Routine coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is not warranted but must be considered when specific risk factors are found. Amoxicillin/clavulanate can provide adequate antibiotic coverage as an empirical treatment for adult native joint septic arthritis. Its use may allow a reduction in use of broader spectrum antibiotics.
Introdução: A artrite séptica representa uma patologia grave que pode levar à destruição articular e diminuição funcional a longo prazo. Adicionalmente à drenagem articular, uma antibioterapia efetiva é crucial. O objetivo deste estudo consistiu em avaliar as características epidemiológicas e clínicas dos doentes admitidos com diagnóstico de artrite séptica e analisar a terapêutica antimicrobiana, estabelecendo orientações locais de tratamento antibiótico empírico. Material e Métodos: Análise retrospetiva de doentes adultos admitidos no Centro Hospitalar Universitário do Porto com artrite séptica de articulação nativa de 2009 a 2017. Foram revistos os resultados microbiológicos, os perfis de suscetibilidade aos antimicrobianos e os registos médicos. Resultados: Dos 97 doentes incluídos, 59,8% eram do género masculino, com uma idade média de 61 anos. A comorbilidade mais comum foi a diabetes mellitus (20,6%). O joelho foi a articulação mais afetada (71,1%). Realizou-se artrocentese em todos os doentes, com isolamento microbiano em 50,5% dos produtos. O Staphylococcus aureus foi o microrganismo mais frequente, sendo sensível à meticilina, em 86% dos casos. As bactérias Gram-negativo foram o agente causal em 15% das infeções. A associação do carbapenemo e vancomicina foi a antibioterapia empírica mais comummente iniciada (30,9%), embora em 89% dos casos a amoxicilina/clavulanato teria sido apropriada como regime inicial. Discussão: O principal agente etiológico foi o Staphylococcus aureus, continuando o Staphylococcus aureus resistente à meticilina a ser um agente raro. A percentagem de bactérias Gram-negativo implica a sua cobertura como terapêutica empírica, embora não tenha havido casos de infeção por Pseudomonas. Por isso, a utilização empírica de um antibiótico com atividade antipseudomónica não é necessária. Conclusão: A cobertura antibiótica de Staphylococcus aureus resistente à meticilina e Pseudomonas não é obrigatória, mas pode ser considerada na presença de alguns fatores de risco específicos. A amoxicilina/ clavulanato é uma antibioterapia empírica adequada para a artrite séptica de articulação nativa, permitindo reduzir a utilização inadequada de antibióticos de espectro mais alargado.
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Artrite Infecciosa , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Adulto , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/epidemiologia , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologiaRESUMO
This work addresses the impact of pH variation on DNA-polyethylenimine (PEI) complex formation, in aqueous solution and at constant ionic strength. An initial potentiometric characterization of the acid-base behavior of PEI is carried out to measure the concentration of ionized species in the relevant systems. The characterization of the DNA-PEI complexes is performed by precipitation assays, agarose gel electrophoresis, photon correlation spectroscopy, and zeta potential analysis. It is observed that the variations on the electrophoretic mobility, size, and electrical properties of complexes display nonmonotonic, nontrivial trends with pH, if the same polycation/polyanion charge ratios are used for different values of pH. It is seen that both linear charge density and the relative number of chains of the condensing agent are important factors governing the condensation behavior. Complexes prepared at pH 4, for example, indicate strong binding and a large mean size, while those prepared at pH 8 are smaller, in a more uniform population. Finally, charge inversion was observed for all studied pH values (even below charge neutralization).
Assuntos
DNA/química , DNA/metabolismo , Polietilenoimina/química , Testículo/química , Animais , Dicroísmo Circular , DNA/genética , Eletroforese em Gel de Ágar , Concentração de Íons de Hidrogênio , Masculino , Concentração Osmolar , Tamanho da Partícula , Salmão/genéticaRESUMO
We present a case of a 56-year-old man with a history of episcleritis (left) and cluster headache (left) who had a penetrating trauma of the left eye leading to amaurosis 1 month previously. Since then, he developed multiple cranial neuropathy of the right side (V, VII, VIII, IX, X, XI and XII cranial pairs). Magnetic resonance imaging (MRI) revealed an infiltrative lesion of the base of the skull which extended to the retropharyngeal and jugular space, which progressed to multiple leptomeningeal masses extending to the clivus, despite aggressive immunosuppression. Rebiopsy of 1 meningeal mass supported the diagnosis of neurosarcoidosis. The patient finally responded to high-dose prolonged infliximab therapy, with complete remission. LEARNING POINTS: Neurosarcoidosis can present as multiple cranial neuropathy, with extensive nerve involvement depending on the brain and meningeal lesions.Large leptomeningeal pseudotumoural granulomatous masses should be promptly biopsied and lead to aggressive immunosuppressive treatment.Immunosuppressant weaning should be carried out cautiously to avoid rebound worsening.