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1.
Eur J Crim Pol Res ; : 1-23, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37361417

RESUMEN

The growing dissension towards the political handling of COVID-19, widespread job losses, backlash to extended lockdowns, and hesitancy surrounding the vaccine are propagating toxic far-right discourses in the UK. Moreover, the public is increasingly reliant on different social media platforms, including a growing number of participants on the far-right's fringe online networks, for all pandemic-related news and interactions. Therefore, with the proliferation of harmful far-right narratives and the public's reliance on these platforms for socialising, the pandemic environment is a breeding ground for radical ideologically-based mobilisation and social fragmentation. However, there remains a gap in understanding how these far-right online communities, during the pandemic, utilise societal insecurities to attract candidates, maintain viewership, and form a collective on social media platforms. The article aims to better understand online far-right mobilisation by examining, via a mixed-methodology qualitative content analysis and netnography, UK-centric content, narratives, and key political figures on the fringe platform, Gab. Through the dual-qualitative coding and analyses of 925 trending posts, the research outlines the platform's hate-filled media and the toxic nature of its communications. Moreover, the findings illustrate the far-right's online discursive dynamics, showcasing the dependence on Michael Hogg's uncertainty-identity mechanisms in the community's exploitation of societal insecurity. From these results, I propose a far-right mobilisation model termed Collective Anxiety, which illustrates that toxic communication is the foundation for the community's maintenance and recruitment. These observations set a precedent for hate-filled discourse on the platform and consequently have widespread policy implications that need addressing.

2.
J Ind Microbiol Biotechnol ; 49(3)2022 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-35259264

RESUMEN

The cis-dihydroxylation of arenes by Rieske dearomatizing dioxygenases (RDDs) represents a powerful tool for the production of chiral precursors in organic synthesis. Here, the substrate specificity of the RDD benzoate dioxygenase (BZDO) in Ralstonia eutropha B9 whole cells was explored using quantitative 1H nuclear magnetic resonance spectroscopy (q1H-NMR). The specific activity, specific carbon uptake, and regioselectivity of the dihydroxylation reaction were evaluated in resting cell cultures for a panel of 17 monosubstituted benzoates. Two new substrates of this dioxygenase system were identified (2-methyl- and 3-methoxybenzoic acid) and the corresponding cis-diol metabolites were characterized. Higher activities were observed for benzoates with smaller substituents, predominantly at the 3-position. Elevated activities were also observed in substrates bearing greater partial charge at the C-2 position of the benzoate ring. The regioselectivity of the reaction was directly measured using q1H-NMR and found to have positive correlation with increasing substituent size. These results widen the pool of cis-diol metabolites available for synthetic applications and offer a window into the substrate traits that govern specificity for BZDO.


Asunto(s)
Cupriavidus necator , Dioxigenasas , Benzoatos/metabolismo , Cupriavidus necator/metabolismo , Dioxigenasas/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Especificidad por Sustrato
3.
Biotechnol Bioeng ; 112(11): 2316-23, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26012371

RESUMEN

The formation of stable emulsions in biphasic biotransformations catalyzed by microbial cells turned out to be a major hurdle for industrial implementation. Recently, a cost-effective and efficient downstream processing approach, using supercritical carbon dioxide (scCO2 ) for both irreversible emulsion destabilization (enabling complete phase separation within minutes of emulsion treatment) and product purification via extraction has been proposed by Brandenbusch et al. (2010). One of the key factors for a further development and scale-up of the approach is the understanding of the mechanism underlying scCO2 -assisted phase separation. A systematic approach was applied within this work to investigate the various factors influencing phase separation during scCO2 treatment (that is pressure, exposure of the cells to CO2 , and changes of cell surface properties). It was shown that cell toxification and cell disrupture are not responsible for emulsion destabilization. Proteins from the aqueous phase partially adsorb to cells present at the aqueous-organic interface, causing hydrophobic cell surface characteristics, and thus contribute to emulsion stabilization. By investigating the change in cell-surface hydrophobicity of these cells during CO2 treatment, it was found that a combination of catastrophic phase inversion and desorption of proteins from the cell surface is responsible for irreversible scCO2 mediated phase separation. These findings are essential for the definition of process windows for scCO2 -assisted phase separation in biphasic whole-cell biocatalysis.


Asunto(s)
Biocatálisis , Biotecnología/métodos , Dióxido de Carbono , Cromatografía con Fluido Supercrítico/métodos , Emulsiones/química , Proteínas de la Membrana/química , Adsorción
4.
J Ind Microbiol Biotechnol ; 42(7): 1011-26, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25916765

RESUMEN

Emulsion stability plays a crucial role for mass transfer and downstream processing in organic-aqueous bioprocesses based on whole microbial cells. In this study, emulsion stability dynamics and the factors determining them during two-liquid phase biotransformation were investigated for stereoselective styrene epoxidation catalyzed by recombinant Escherichia coli. Upon organic phase addition, emulsion stability rapidly increased correlating with a loss of solubilized protein from the aqueous cultivation broth and the emergence of a hydrophobic cell fraction associated with the organic-aqueous interface. A novel phase inversion-based method was developed to isolate and analyze cellular material from the interface. In cell-free experiments, a similar loss of aqueous protein did not correlate with high emulsion stability, indicating that the observed particle-based emulsions arise from a convergence of factors related to cell density, protein adsorption, and bioreactor conditions. During styrene epoxidation, emulsion destabilization occurred correlating with product-induced cell toxification. For biphasic whole-cell biotransformations, this study indicates that control of aqueous protein concentrations and selective toxification of cells enables emulsion destabilization and emphasizes that biological factors and related dynamics must be considered in the design and modeling of respective upstream and especially downstream processes.


Asunto(s)
Escherichia coli/metabolismo , Biocatálisis , Reactores Biológicos , Biotransformación , Emulsiones , Proteínas de Escherichia coli/química , Interacciones Hidrofóbicas e Hidrofílicas , Oxidación-Reducción , Soluciones , Estireno/metabolismo
5.
Protein Eng Des Sel ; 372024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38484121

RESUMEN

Proline-rich antimicrobial peptides (PrAMPs) are attractive antibiotic candidates that target gram-negative bacteria ribosomes. We elucidated the sequence-function landscape of 43 000 variants of a recently discovered family member, Tur1a, using the validated SAMP-Dep platform that measures intracellular AMP potency in a high-throughput manner via self-depletion of the cellular host. The platform exhibited high replicate reproducibility (ρ = 0.81) and correlation between synonymous genetic variants (R2 = 0.93). Only two segments within Tur1a exhibited stringent mutational requirements to sustain potency: residues 9YLP11 and 19FP20. This includes the aromatic residue in the hypothesized binding domain but not the PRP domain. Along with unexpected mutational tolerance of PRP, the data contrast hypothesized importance of the 1RRIR4 motif and arginines in general. In addition to mutational tolerance of residue segments with presumed significance, 77% of mutations are functionally neutral. Multimutant performance mainly shows compounding effects from removed combinations of prolines and arginines in addition to the two segments of residues showing individual importance. Several variants identified as active from SAMP-Dep were externally produced and maintained activity when applied to susceptible species exogenously.


Asunto(s)
Antibacterianos , Péptidos Antimicrobianos , Compuestos de Fenilmercurio , Reproducibilidad de los Resultados , Antibacterianos/farmacología , Antibacterianos/química , Mutación
6.
bioRxiv ; 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38352424

RESUMEN

Antimicrobial peptides (AMPs) are essential elements of natural cellular combat and candidates as antibiotic therapy. Elevated function may be needed for robust physiological performance. Yet, both pure protein design and combinatorial library discovery are hindered by the complexity of antimicrobial activity. We applied a recently developed high-throughput technique, sequence-activity mapping of AMPs via depletion (SAMP-Dep), to proline-rich AMPs. Robust self-inhibition was achieved for metalnikowin 1 (Met) and apidaecin 1b (Api). SAMP-Dep exhibited high reproducibility with correlation coefficients 0.90 and 0.92, for Met and Api, respectively, between replicates and 0.99 and 0.96 for synonymous genetic variants. Sequence-activity maps were obtained via characterization of 26,000 and 34,000 mutants of Met and Api, respectively. Both AMPs exhibit similar mutational profiles including beneficial mutations at one terminus, the C-terminus for Met and N-terminus for Api, which is consistent with their opposite binding orientations in the ribosome. While Met and Api reside with the family of proline-rich AMPs, different proline sites exhibit substantially different mutational tolerance. Within the PRP motif, proline mutation eliminates activity, whereas non-PRP prolines readily tolerate mutation. Homologous mutations are more tolerated, particularly at alternating sites on one 'face' of the peptide. Important and consistent epistasis was observed following the PRP domain within the segment that extends into the ribosomal exit tunnel for both peptides. Variants identified from the SAMP-Dep platform were produced and exposed toward Gram-negative species exogenously, showing either increased potency or specificity for strains tested. In addition to mapping sequence-activity space for fundamental insight and therapeutic engineering, the results advance the robustness of the SAMP-Dep platform for activity characterization.

7.
Int J Cardiol ; 395: 131594, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-37979795

RESUMEN

BACKGROUND: Since the COVID-19 pandemic, post-COVID syndrome (persistent symptoms/complications lasting >12 weeks) continues to pose medical and economic challenges. In military personnel, where optimal fitness is crucial, prolonged limitations affecting their ability to perform duties has occupational and psychological implications, impacting deployability and retention. Research investigating post-COVID syndrome exercise capacity and cardiopulmonary effects in military personnel is limited. METHODS: UK military personnel were recruited from the Defence Medical Services COVID-19 Recovery Service. Participants were separated into healthy controls without prior SARS-CoV-2 infection (group one), and participants with prolonged symptoms (>12 weeks) after mild-moderate (community-treated) and severe (hospitalised) COVID-19 illness (group 2 and 3, respectively). Participants underwent cardiac magnetic resonance imaging (CMR) and spectroscopy, echocardiography, pulmonary function testing and cardiopulmonary exercise testing (CPET). RESULTS: 113 participants were recruited. When compared in ordered groups (one to three), CPET showed stepwise decreases in peak work, work at VT1 and VO2 max (all p < 0.01). There were stepwise decreases in FVC (p = 0.002), FEV1 (p = 0.005), TLC (p = 0.002), VA (p < 0.001), and DLCO (p < 0.002), and a stepwise increase in A-a gradient (p < 0.001). CMR showed stepwise decreases in LV/RV volumes, stroke volumes and LV mass (LVEDVi/RVEDVi p < 0.001; LVSV p = 0.003; RVSV p = 0.001; LV mass index p = 0.049). CONCLUSION: In an active military population, post-COVID syndrome is linked to subclinical changes in maximal exercise capacity. Alongside disease specific changes, many of these findings share the phenotype of deconditioning following prolonged illness or bedrest. Partitioning of the relative contribution of pathological changes from COVID-19 and deconditioning is challenging in post-COVID syndrome recovery.


Asunto(s)
COVID-19 , Personal Militar , Humanos , Tolerancia al Ejercicio , Pandemias , SARS-CoV-2 , Pulmón , Prueba de Esfuerzo
8.
Am Polit Res ; 51(2): 223-234, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38603294

RESUMEN

Due to the COVID-19 Pandemic, the decision to reopen schools for in-person instruction has become a pressing policy issue. This study examines what overall factors drive public support for schools re-opening in person and whether members of the public are willing to comply with school re-opening decisions based on their own preferences and/or the level of government from which the order comes. Through two rounds of national surveys with an embedded experiment, I find consistent evidence that 1) trust in information from elites - not contact with COVID - best explain preferences for reopening, 2) political ideology and racial and class identification help explain preferences as well, and 3) the President of the United States is best positioned to generate compliance with a school reopening mandate. This study suggests that politics - not public health - drives public support for schools reopening and compliance with government orders to reopen.

9.
Nat Commun ; 14(1): 8168, 2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38071224

RESUMEN

We present a process for solid phase peptide synthesis (SPPS) that completely eliminates all solvent intensive washing steps during each amino acid addition cycle. A key breakthrough is the removal of a volatile Fmoc deprotection base through bulk evaporation at elevated temperature while preventing condensation on the vessel surfaces with a directed headspace gas flushing. This process was demonstrated at both research and production scales without any impact on product quality and when applied to a variety of challenging sequences (up to 89 amino acids in length). The overall result is an extremely fast, high purity, scalable process with a massive waste reduction (up to 95%) while only requiring 10-15% of the standard amount of base used. This transformation of SPPS represents a step-change in peptide manufacturing process efficiency, and should encourage expanded access to peptide-based therapeutics.


Asunto(s)
Péptidos , Técnicas de Síntesis en Fase Sólida , Péptidos/química , Aminoácidos/química
10.
Invest New Drugs ; 30(3): 1012-27, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21494837

RESUMEN

The natural compound pancratistatin (PST), isolated from the Hymenocallis littoralis plant, specifically induces apoptosis in many cancer cell lines. Unlike many other chemotherapeutics, PST is not genotoxic and has minimal adverse effects on non-cancerous cells. However, its availability for preclinical and clinical work is limited due to its low availability in its natural source and difficulties in its chemical synthesis. Several synthetic analogues of 7-deoxypancratistatin with different modifications at C-1 were synthesized and screened for apoptosis inducing activity in human colorectal cancer (CRC) cells. We found that a C-1 acetoxymethyl derivative of 7-deoxypancratistatin, JC-TH-acetate-4 (JCTH-4), was effective in inducing apoptosis in both p53 positive (HCT 116) and p53 negative (HT-29) human CRC cell lines, demonstrating similar efficacy to that of natural PST. JCTH-4 was able to decrease mitochondrial membrane potential (MMP), increase levels of reactive oxygen species in isolated mitochondria, cause release of the apoptogenic factor cytochrome c (Cyto c) from isolated mitochondria, and induce autophagy in HCT 116 and HT-29 cells. Interestingly, when JCTH-4 was administered with tamoxifen (TAM), there was an enhanced effect in apoptosis induction, reactive oxygen species (ROS) production and Cyto c release by isolated mitochondria, and autophagic induction by CRC cells. Minimal toxicity was exhibited by a normal human fetal fibroblast (NFF) and a normal colon fibroblast (CCD-18Co) cell line. Hence, JCTH-4 is a novel compound capable of selectively inducing apoptosis and autophagy in CRC cells alone and in combination with TAM and may serve as a safer and more effective alternative to current cancer therapies.


Asunto(s)
Alcaloides de Amaryllidaceae/farmacología , Antineoplásicos/farmacología , Neoplasias Colorrectales/patología , Isoquinolinas/farmacología , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Tamoxifeno/farmacología , Clorometilcetonas de Aminoácidos/farmacología , Apoptosis/efectos de los fármacos , Inhibidores de Caspasas , Caspasas/metabolismo , Línea Celular , Neoplasias Colorrectales/metabolismo , Inhibidores de Cisteína Proteinasa/farmacología , Células HCT116 , Células HT29 , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo
11.
J Ind Microbiol Biotechnol ; 39(7): 1049-59, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22383177

RESUMEN

In an earlier study, biocatalytic carbon oxyfunctionalization with water serving as oxygen donor, e.g., the bioconversion of quinaldine to 4-hydroxyquinaldine, was successfully achieved using resting cells of recombinant Pseudomonas putida, containing the molybdenum-enzyme quinaldine 4-oxidase, in a two-liquid phase (2LP) system (Ütkür et al. J Ind Microbiol Biotechnol 38:1067-1077, 2011). In the study reported here, key parameters determining process performance were investigated and an efficient and easy method for product recovery was established. The performance of the whole-cell biocatalyst was shown not to be limited by the availability of the inducer benzoate (also serving as growth substrate) during the growth of recombinant P. putida cells. Furthermore, catalyst performance during 2LP biotransformations was not limited by the availability of glucose, the energy source to maintain metabolic activity in resting cells, and molecular oxygen, a possible final electron acceptor during quinaldine oxidation. The product and the organic solvent (1-dodecanol) were identified as the most critical factors affecting biocatalyst performance, to a large extent on the enzyme level (inhibition), whereas substrate effects were negligible. However, none of the 13 alternative solvents tested surpassed 1-dodecanol in terms of toxicity, substrate/product solubility, and partitioning. The use of supercritical carbon dioxide for phase separation and an easy and efficient liquid-liquid extraction step enabled 4-hydroxyquinaldine to be isolated at a purity of >99.9% with recoveries of 57 and 84%, respectively. This study constitutes the first proof of concept on an integrated process for the oxyfunctionalization of toxic substrates with a water-incorporating hydroxylase.


Asunto(s)
Biocatálisis , Microbiología Industrial , Metaloproteínas/metabolismo , Oxidorreductasas/metabolismo , Pseudomonas putida/enzimología , Quinaldinas/metabolismo , Benzoatos/metabolismo , Biotransformación , Dodecanol/química , Glucosa/metabolismo , Metaloproteínas/química , Molibdeno/metabolismo , Oxidación-Reducción , Oxidorreductasas/química , Oxígeno/metabolismo , Pseudomonas putida/crecimiento & desarrollo , Pseudomonas putida/metabolismo
12.
J Appl Physiol (1985) ; 133(5): 1175-1191, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36173325

RESUMEN

The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O2. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po2 gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease.NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.


Asunto(s)
COVID-19 , Humanos , Pruebas de Función Respiratoria , Respiración Artificial , Pulmón , Respiración
13.
J Org Chem ; 75(9): 3069-84, 2010 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-20373760

RESUMEN

An efficient synthesis of C-1 derivatives of 7-deoxypancratistatin is reported. The key steps include the following: selective opening of an epoxide with aluminum acetylide in the presence of an aziridine; solid-state silica-gel-catalyzed opening of an aziridine; and oxidative cleavage of a phenanthrene core and its recyclization to phenanthridone to provide the key C-1 aldehyde 22. The conversion of this aldehyde to C-1 acetoxymethyl and C-1 hydroxymethyl derivatives is described along with the evaluation of their biological activity against several cancer cell lines and in an apoptosis study. The C-1 acetoxymethyl derivative has shown promising activity comparable to that of the natural product. In addition, a total synthesis of trans-dihydrolycoricidine and a formal total synthesis of 7-deoxypancratistatin are reported from aldehyde 22. Detailed experimental and spectral data are provided for all new compounds.


Asunto(s)
Alcaloides de Amaryllidaceae/síntesis química , Antineoplásicos Fitogénicos/síntesis química , Isoquinolinas/síntesis química , Aldehídos/química , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Aziridinas/química , Catálisis , Línea Celular Tumoral , Ciclización , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Epoxi/química , Humanos , Isoquinolinas/química , Isoquinolinas/farmacología , Estructura Molecular , Oxidación-Reducción , Fenantrenos/química , Estereoisomerismo , Relación Estructura-Actividad
14.
Methods Mol Biol ; 2103: 95-109, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31879920

RESUMEN

The unique combination of microwave heating with optimized carbodiimide activation has proven to be an indispensable technique for high-throughput peptide production. Here, we describe new methods in microwave-assisted solid phase peptide synthesis and optimized post-synthesis modifications that have been recently developed. These methods have drastically reduced synthesis time and solvent requirement while delivering peptides in high crude purities.


Asunto(s)
Microondas , Péptidos/síntesis química , Técnicas de Síntesis en Fase Sólida/métodos , Secuencia de Aminoácidos , Proteínas Anticongelantes/química , Automatización , Técnicas de Química Sintética , Cromatografía Líquida de Alta Presión , Disulfuros , Ensayos Analíticos de Alto Rendimiento , Espectrometría de Masas , Péptidos/análisis , Péptidos/aislamiento & purificación , Fosfopéptidos/síntesis química , Fosfopéptidos/química , Técnicas de Síntesis en Fase Sólida/instrumentación , Solventes
15.
Org Biomol Chem ; 7(12): 2619-27, 2009 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-19503938

RESUMEN

A series of benzoate esters (methyl, ethyl, n-Pr, i-Pr, n-Bu, t-Bu, allyl, and propargyl) were subjected to enzymatic dihydroxylation by E. coli JM 109(pDTG 601) strain in a whole-cell fermentation. The cis-cyclohexadienediols were obtained in yields of approximately 1g/L except for n-propyl- and i-propyl benzoate which were found to be poor substrates. n-Butyl and t-butyl benzoates were not oxidized at all. The absolute stereochemistry for all metabolites was determined by comparison with a standard prepared from (1S-cis)-3-bromo-3,5-cyclohexadiene-1,2-diol, whose absolute configuration is well established. The free diols were found to be quite stable compared to other cis-dihydrodiols of this type, however, their acetonides underwent a dimerization via a regio- and stereoselective Diels-Alder cycloaddition. The diol derived from ethyl benzoate was subjected to a stereo- and regioselective inverse electron demand Diels-Alder cycloadditions with several dienophiles. The new adducts were completely characterized. The hetero-Diels-Alder reaction of this diol with an acyl nitroso dienophile yielded regio- and stereoselectively a bicyclic oxazine, which upon reduction provided a useful derivative of amino shikimate that can be exploited in an approach to oseltamivir (Tamiflu) and other amino cyclitols. The diol was also converted to carba-alpha-L-galactopyranose to demonstrate its potential utility as a source of pseudo sugars. Experimental and spectral data are provided for all new compounds.


Asunto(s)
Benzoatos/química , Compuestos Bicíclicos con Puentes/síntesis química , Carbohidratos/química , Ciclitoles/síntesis química , Dioxigenasas/metabolismo , Ésteres/química , Ésteres/metabolismo , Escherichia coli/metabolismo , Galactosa/síntesis química , Hidroxilación , Oseltamivir/síntesis química , Oxidación-Reducción , Pseudomonas putida/enzimología , Estereoisomerismo
16.
J Intensive Care Soc ; 20(1): 40-45, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30792761

RESUMEN

BACKGROUND: Tidal hyperinflation can still occur with mechanical ventilation using low tidal volume (LVT) (6 mL/kg predicted body weight (PBW)) in acute respiratory distress syndrome (ARDS), despite a well-demonstrated reduction in mortality. METHODS: Retrospective chart review from August 2012 to October 2014. Inclusion: Age >18years, PaO2/FiO2<200 with bilateral pulmonary infiltrates, absent heart failure, and ultra-protective mechanical ventilation (UPMV) defined as tidal volume (VT) <6 mL/kg PBW. Exclusion: UPMV use for <24 h. Demographics, admission Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, arterial blood gas, serum bicarbonate, ventilator parameters for pre-, during, and post-UPMV periods including modes, VT, peak inspiratory pressure (PIP), plateau pressure (Pplat), driving pressure, etc. were gathered. We compared lab and ventilator data for pre-, during, and post-UPMV periods. RESULTS: Fifteen patients (male:female = 7:8, age 42.13 ± 11.29 years) satisfied criteria, APACHEII 20.6 ± 7.1, mean days in intensive care unit and hospitalization were 18.5 ± 8.85 and 20.81 ± 9.78 days, 9 (60%) received paralysis and 7 (46.67%) required inotropes. Eleven patients had echocardiogram, 7 (63.64%) demonstrated right ventricular volume or pressure overload. Eleven patients (73.33%) survived. During-UPMV, VT ranged 2-5 mL/kg PBW(3.99 ± 0.73), the arterial partial pressure of carbon dioxide (PaCO2) was higher than pre-UPMV values (84.81 ± 18.95 cmH2O vs. 69.16 ± 33.09 cmH2O), but pH was comparable and none received extracorporeal carbon dioxide removal (ECCO2-R). The positive end-expiratory pressure (14.18 ± 7.56 vs. 12.31 ± 6.84 cmH2O), PIP (38.21 ± 12.89 vs. 32.59 ± 9.88), and mean airway pressures (19.98 ± 7.61 vs. 17.48 ± 6.7 cm H2O) were higher during UPMV, but Pplat and PaO2/FiO2 were comparable during- and pre-UPMV. Driving pressure was observed to be higher in those who died than who survived (24.18 ± 12.36 vs. 13.42 ± 3.25). CONCLUSION: UPMV alone may be a safe alternative option for ARDS patients in centers without ECCO2-R.

17.
J Antimicrob Chemother ; 61(4): 901-7, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18272512

RESUMEN

OBJECTIVES: To report an outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit (ITU). METHODS: An outbreak of colonization with linezolid-resistant S. epidermidis affecting 16 patients in an ITU was investigated using PFGE. Environmental and staff screening was carried out as part of the investigation. Usage of linezolid in the hospital and in the ITU was reviewed. Resistant strains were screened for the presence of the G2576T mutation using PCR-RFLP genotyping. The interventions made to control the outbreak were restriction of linezolid prescription and specific infection control measures, including isolation of colonized patients and increased environmental cleaning. RESULTS: Linezolid-resistant S. epidermidis strains from the 16 colonized patients were genetically related. The same strain was also cultured from environmental samples in the ITU. An increase in linezolid usage in the hospital and in the ITU occurred in the 6 months prior to the emergence of the resistant strain. Infection control measures and restriction of linezolid prescription controlled the outbreak. All resistant isolates contained the G2576T mutation. CONCLUSIONS: An outbreak of colonization with linezolid-resistant S. epidermidis occurred in the ITU in our institution. The resistant strain colonized the environment and probably spread from patient to patient. The outbreak was associated with an increase in the linezolid usage in the ITU and in the institution as a whole. Restriction of linezolid usage and infection control measures were introduced to control the outbreak. The emergence of linezolid resistance in S. epidermidis has implications for the use of linezolid as a therapeutic agent.


Asunto(s)
Acetamidas/farmacología , Antibacterianos/farmacología , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Farmacorresistencia Bacteriana/genética , Oxazolidinonas/farmacología , Infecciones Estafilocócicas/epidemiología , Staphylococcus epidermidis/efectos de los fármacos , Acetamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Infección Hospitalaria/microbiología , Dermatoglifia del ADN , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Microbiología Ambiental , Femenino , Genotipo , Humanos , Control de Infecciones/métodos , Unidades de Cuidados Intensivos , Linezolid , Masculino , Persona de Mediana Edad , Oxazolidinonas/uso terapéutico , Mutación Puntual , Reacción en Cadena de la Polimerasa , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/clasificación , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/aislamiento & purificación
18.
Org Lett ; 10(3): 361-4, 2008 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-18163635

RESUMEN

Solid-state silica-gel-catalyzed opening of aziridine 6 provided phenanthrene 7, whose oxidative cleavage, recyclization, and further elaboration furnished the C-1 aldehyde and carboxylic acid derivatives of 7-deoxypancratistatin for potential analogue synthesis.


Asunto(s)
Alcaloides de Amaryllidaceae/síntesis química , Aziridinas/química , Isoquinolinas/síntesis química , Fenantrenos/química , Alcaloides de Amaryllidaceae/química , Ácidos Carboxílicos , Catálisis , Ciclización , Isoquinolinas/química , Estructura Molecular
19.
J Med Microbiol ; 57(Pt 1): 15-20, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18065662

RESUMEN

Pandoraea species are emerging opportunistic pathogens capable of causing chronic lung infections in cystic fibrosis patients. This study examined the interactions of 17 Pandoraea isolates from the five identified species (Pandoraea apista, Pandoraea norimbergensis, Pandoraea pulmonicula, Pandoraea sputorum and Pandoraea pnomenusa) plus two Pandoraea genomospecies isolates with lung epithelial cells and their ability to form biofilms in vitro. Only three isolates showed an ability to invade A549 lung epithelial cells, and only one isolate was able to form biofilms. In contrast, all isolates triggered a pronounced pro-inflammatory response, with elevation of both interleukin (IL)-6 (two- to 19-fold) and IL-8 (10- to 50-fold) above that observed for a control strain of Escherichia coli. This property is likely to be a major factor in the pathogenesis of the genus.


Asunto(s)
Betaproteobacteria/patogenicidad , Biopelículas/crecimiento & desarrollo , Células Epiteliales/microbiología , Pulmón/patología , Virulencia/genética , Betaproteobacteria/efectos de los fármacos , Betaproteobacteria/inmunología , Betaproteobacteria/fisiología , Línea Celular
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