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1.
Artigo em Inglês | MEDLINE | ID: mdl-34888681

RESUMO

OBJECTIVES: Myocardial recovery allows for left ventricular assist device (LVAD) explantations after long-term support. Several surgical approaches, including interventional decommissioning, off-pump explantation using a custom-made plug and complete LVAD removal through redo sternotomy, have been described. We present the results from an evaluation of the long-term follow-up of patients who received a titanium sintered plug after LVAD explantation. METHODS: We performed a retrospective, European, multicentre analysis of patients who received a titanium sintered plug to seal the apical fixation ring after LVAD explantation. Data were collected from a questionnaire that included demographics, procedural details and follow-up information. RESULTS: Out of 54 contacted centres in 12 countries (n = 179 patients), a total of 68 patients were successfully included in the study. The median follow-up was 34 months (interquartile range: 17-58.5 months); 57 (84%) patients had >1-year follow-up. At the time of the last follow-up, 55 (81%) patients were alive, with a Kaplan-Meier 1-year survival of 90.1% (95% confidence interval: 84.0-98.1%) and a 5-year survival of 80.0% (95% confidence interval: 68.4-92.9%). One patient (1.5%) developed a plug infection originating from an infected part of the incorporated driveline and, after complete removal, is currently in good condition. No postoperative stroke has been reported after plug implantation. CONCLUSIONS: In this European multicentre study, the use of a custom-made titanium plug to close the apical fixation ring after LVAD explantation resulted in a low incidence of plug-related complications. With the volume of patients undergoing LVAD explantations after myocardial recovery increasing, the plug has evolved as a simple alternative to more invasive device explantation procedures or decommissioning with a high risk for infection of the remaining system or stroke.

2.
Heliyon ; 7(11): e08440, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34901497

RESUMO

Numerous studies in the last decades have provided evidence for the existence of a local renin-angiotensin system (RAS) in the central nervous system (CNS). Widespread distribution of the different RAS components in the brain demonstrates the pleiotropic role of this system in the structure and function of CNS. With the advent of new molecular techniques, a novel receptor has been identified within the beneficial arm of the RAS, the Mas-related G-protein coupled receptor D (MrgD), which can be stimulated by two heptapeptides, Ala1-(Ang-(1-7), also named alamandine, and Ang-(1-7). However, the biological and physiological relevance of this interaction remains obscure. Since several recent studies hinted at a role of MrgD in the CNS, we determined the distribution pattern of MrgD receptors in the adult mouse brain by using a genetic mouse model with tracers of MrgD expression. MrgD-positive cells could be identified in some forebrain areas, including cortex, hippocampus, amygdala, hypothalamus, habenular nuclei, striatum and pallidum, as well as in some mid-brain nuclei in a region-specific manner. The specific localization of MrgD in the reward- and limbic-related areas can hint at a role of MrgD in processes such as pain perception/modulation, synaptic plasticity, learning, memory and cognition.

3.
Medicina (Kaunas) ; 57(11)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34833397

RESUMO

Background: Minimally invasive mitral valve (MV) surgery has emerged as an alternative to conventional sternotomy aiming to decrease surgical trauma. The aim of the study was to describe our experience with minimally invasive MV surgery through partial upper sternotomy (PUS) regarding short- and long-term outcomes. Methods: From January 2004 through March 2014, 419 patients with a median age of 58.9 years (interquartile range 18.7; 31.7% females) underwent isolated primary MV surgery using PUS. Myxomatous degenerative MV disease was the predominant pathology (77%). The patients' mean EuroSCORE II risk profile was 3.9 ± 3.6%. Results: Mitral valve repair was performed in 384 patients (91.6%) and replacement in 35 patients (8.4%). Thirty-day mortality was 3.1%. In total, 29 (6.9%) deaths occurred during the follow-up. The overall estimated survival at 1, 5, and 10 years was 93.1 ± 1.3%, 87.1 ± 1.9%, and 81.1 ± 3.4%. Reoperation was necessary in 14 (3.3%) patients. The overall freedom from MV reoperation at 1, 5, and 10 years was 98.2 ± 0.7%, 96.1 ± 1.2%, and 86.7 ± 6.7% and the overall freedom from recurrent MV regurgitation > grade 2 in repaired valves at 1, 5, and 10 years was 98.8 ± 0.6%, 98.8 ± 0.6%, and 94.6 ± 3.3%. Conclusions: Minimally invasive MV surgery via PUS can be performed with particularly good early and late results. Thus, the PUS approach with the use of standard surgical instruments and cannulation techniques can be a valuable option for the MV surgery either in patients contraindicated or not suitable to minithoracotomy.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência da Valva Mitral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Reoperação , Estudos Retrospectivos , Esternotomia , Resultado do Tratamento
4.
Am J Cardiol ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34844737

RESUMO

Patients presenting with severe aortic stenosis and large aortic annuli are challenging to treat because of the size limitations of available transcatheter heart valves. In this study, we aimed to determine clinical and hemodynamic outcomes in patients presenting with large aortic annuli who underwent transcatheter aortic valve implantation (TAVI). Patients from the German Aortic Valve Registry who underwent TAVI either with the Edwards Sapien (ES) or Medtronic CoreValve (MCV) systems from 2011 to 2017 were included. They were further stratified into a large (aortic annulus diameter 26 to 29 mm for ES; 26 to 30 mm for MCV) and extra-large (aortic annulus diameter >29 mm for ES; >30 mm for MCV) group and analyzed using propensity score adjustment. Extra-large was set beyond the sizing limitations according to the manufacturer's instructions for use. Patients in the large (n = 5,628) and extra-large (n = 509) groups were predominantly male (large: 92.6% vs extra-large: 91.9%). The 30-day mortality was comparable (large: 3.9% vs extra-large: 5.0%, p = 0.458). Procedure duration (large: 78.9 minutes ± 0.82 vs extra-large: 86.4 minutes ± 1.9, p <0.001) was longer in the extra-large group. Likewise, vascular complications (large: 6.2% vs extra-large: 12%, p = 0.002) and the need for a permanent pacemaker implantation (large: 18.8% vs extra-large: 26.0%, p = 0.027) were more often present in the extra-large group. Aortic regurgitation ≥II after valve implantation was numerically higher (large: 3.0% vs extra-large: 5.3%, p = 0.082) in patients with extra-large anatomy. In conclusion, patients with large and extra-large aortic annulus diameters who underwent TAVI have comparable 30-day mortality. Beyond the recommended annulus range, there is a higher risk for vascular complications and permanent pacemaker implantation.

5.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34676824

RESUMO

Pestiviruses like bovine viral diarrhoea virus (BVDV) and classical swine fever virus (CSFV) belong to the family Flaviviridae. A special feature of the Flaviviridae is the importance of nonstructural (NS) proteins for both genome replication and virion morphogenesis. The NS2-3-4A region and its regulated processing by the NS2 autoprotease and the NS3/4A protease plays a central role in the pestiviral life cycle. We report the identification and characterization of a novel internal cleavage in BVDV NS2, which is mediated by the NS3/4A protease. Further mapping using the NS2 of BVDV-1 strain NCP7 showed that cleavage occurs between L188 and G189. This cleavage site represents a novel sequence motif recognized by the NS3/4A protease and is conserved between the pestivirus species A, B and D. Inhibition of this internal NS2 cleavage by mutating the cleavage site did not cause obvious effects on RNA replication or virion morphogenesis in cultured cell lines. Accordingly, this novel internal NS2 cleavage adds an additional layer to the already complex polyprotein processing of Pestiviruses and might further extend the repertoires of the multifunctional NS2. However, unravelling of the functional relevance of this novel processing event in NS2, therefore, awaits future in vivo studies.


Assuntos
Vírus da Diarreia Viral Bovina Tipo 1/metabolismo , Peptídeo Hidrolases/metabolismo , Pestivirus/metabolismo , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Motivos de Aminoácidos , Animais , Linhagem Celular , Vírus da Diarreia Viral Bovina Tipo 1/enzimologia , Pestivirus/química , Pestivirus/enzimologia , Proteínas não Estruturais Virais/genética , Replicação Viral
6.
Mol Cell Oncol ; 8(4): 1918529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616864

RESUMO

Resistance to tyrosine kinase inhibitors of the vascular endothelial growth factor receptor inevitably develops in most patients with metastatic kidney cancer. Our recent findings demonstrate that addition of angiotensin-(1-7) peptide can be a potential therapy that delays such resistance.

8.
J Card Surg ; 36(12): 4645-4651, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34547142

RESUMO

BACKGROUND: The aim of this study was to evaluate the longer-term results of bicuspid aortic valve (BAV) repair with or without aortic root replacement. METHODS: From 1999 to 2017, 142 patients with or without aortic root dilatation who underwent repair of a regurgitant BAV were included in the study. Ninety-four patients underwent isolated BAV repair (Group 1; median age 43 years) and 48 patients underwent valve-sparing aortic root replacement plus BAV repair (aortic valve reimplantation-Group 2; median age 48 years). Median clinical follow-up time was 5.9 years (range 0.5-15) in Group 1 and 3 years (range 0.5-16) in Group 2, respectively. RESULTS: In-hospital mortality was 1% in Group 1, and 2% in Group 2 (p = .6). The 5- and 10-year survival was 93 ± 2.9% and 81 ± 5.8% in Group 1 and 96 ± 3.1% and 96 ± 3.1% in Group 2, respectively (p = .31). Eleven patients of Group 1 (1.7%/patient-year) and five patients of Group 2 (2.2%/patient-year) underwent reoperation of the aortic valve (p = .5). The 5- and 10-year freedom from reoperation were 93.0 ± 2.1% and 77.1 ± 7.1% in Group 1 and 93.0 ± 5.0% and 76.7 ± 9.6% in Group 2 (p = .83), respectively. At the latest follow-up, only two patients of Group 1 and 1 patient of Group 2 had AV regurgitation = 2° (p = .7). The cumulative linearized incidence of all valve-related complications (bleeding, stroke, endocarditis, and reoperation) was 2.9%/patient-year in Group 1% and 4%/patient-year in Group 2, respectively (p = .6). CONCLUSIONS: Isolated BAV repair and combined aortic valve reimplantation plus BAV repair provide good clinical longer-term outcomes with relatively low reoperation rate and durable valve function.


Assuntos
Insuficiência da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Doenças das Valvas Cardíacas , Adulto , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
9.
Nanomaterials (Basel) ; 11(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34443947

RESUMO

A procedure based on energy-dispersive X-ray spectroscopy in a scanning electron microscope (SEM-EDXS) is proposed to measure ultra-thin oxide layer thicknesses to atomic scale precision in top-down instead of cross-sectional geometry. The approach is based on modelling the variation of the electron beam penetration depth and hence the depth of X-ray generation in the sample as a function of the acceleration voltage. This has been tested for the simple case of silica on silicon (SiO2/Si) which can serve as a model system to study gate oxides in metal-on-semiconductor field-effect transistors (MOS-FETs). Two possible implementations exist both of which rely on pairs of measurements to be made: in method A, the wafer piece of interest and a reference sample (here: ultra-clean fused quartz glass for calibration of the effective k-factors of X-ray lines from elements O and Si) are analysed at the same acceleration voltage. In method B, two measurements of the apparent O/Si ratio of the same wafer sample need to be made at different acceleration voltages and from their comparison to simulations the SiO2 layer thickness of the sample can be inferred. The precision attainable is ultimately shown to be limited by surface contamination during the experiments, as very thin carbonaceous surface layers can alter the results at very low acceleration voltages, while the sensitivity to ultra-thin surface oxides is much reduced at higher acceleration voltages. The optimal operation voltage is estimated to lie in the range of 3-15 kV. Method A has been experimentally verified to work well for test structures of thin oxides on Si-Ge/Si.

10.
SLAS Technol ; 26(5): 532-544, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34282663

RESUMO

Ambitions to improve the connectivity of devices to enable automation and digital representation of processes have been around for some time. Nevertheless, some companies, especially in life science and analytical science, tend to adopt these developments rather slowly. In the field of microbial analysis of drinking and process water, for example, a large part of the work is still carried out manually, although the high number of samples per day and the low fluctuation in work processes would predestine water analysis for a higher degree of automation. Obstacles such as the risk of bottlenecks and possible downtimes after machine failure, the spatial conditions together with the low flexibility of the automated system, a lack of trained personnel, and the high acquisition costs hinder this development, however.To lower these barriers, we have developed a system for the generation of flexibly expandable automated process lines, which handles sample handling and sample transport as a decisive step in the networking of several devices. The system allows the connection of devices that are distributed over the entire laboratory or close to each other, as well as those with a combination of both spatial situations. A functional or throughput expansion of the process can be realized by adding additional devices or storage areas to the network.With this concept, we have established a system for the automatic processing of defined steps of a routine Legionella pneumophila screening in drinking water testing. From this starting point, the process can be extended to cover further steps, such as concentrating or plating, up to the full analytical workflow.

11.
Phys Chem Chem Phys ; 23(31): 16537-16541, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34312639

RESUMO

Glass-forming liquids are well known to have significant dynamic heterogeneities, leading to spatially grossly varying elastic properties throughout the system. In this paper, we compare the local elastic response of supercooled 1-propanol monitored by triplet state solvation dynamics to the macroscopic dynamic shear modulus measured by a piezo-electric gauge. The time-dependent responses are found to be identical, which means that the dynamic macroscopic shear modulus provides a good measure of the average local elastic properties. Since the macroscopic shear modulus of a dynamically inhomogeneous system in general is not just the average of the local moduli, there was no reason to expect such a result. This surprising finding not only provides constraints for models of dynamical heterogeneities in glass-forming liquids, but also allows for a fairly straightforward check on elastic models for glassy dynamics.

12.
Eur J Cardiothorac Surg ; 60(5): 1139-1146, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33942061

RESUMO

OBJECTIVES: To determine the 5-year outcome in patients treated by isolated transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (sAVR)-a prospective observational cohort study. METHODS: A total of 18 010 patients were included (n = 8942 TAVI and n = 9068 sAVR) in the German Aortic Valve Registry (GARY) who were treated in 2011 and 2012 at 92 sites in central Germany. Eligible patients with TAVI and sAVR were matched using propensity scores in a nearest-neighbour approach. Patients with repeat procedures or unequivocal indication for one treatment option (e.g. frailty) were excluded (n = 4785 for TAVI and n = 2 for sAVR). This led to 13 223 patients (4157 TAVI and 9066 sAVR) as an unmatched subcohort. The main outcome measure was the 5-year all-cause mortality. RESULTS: TAVI patients were significantly older (80.9 ± 6.1 vs 68.5 ± 11.1 years, P < 0.001), had a higher Society of Thoracic Surgeons (STS) score (6.3 ± 4.9 vs 2.6 ± 3.0, P < 0.001) and a higher 5-year all-cause mortality (49.8% vs 16.5%, P < 0.0001). There was no major difference in in-hospital stroke, in-hospital myocardial infarction, or temporary and chronic dialysis. In the propensity score-matched group (n = 3640), there were 763 deaths (41.9%) among 1820 TAVI patients compared with 552 (30.3%) among 1820 treated with sAVR during the 5-year follow-up (hazard ratio 1.51, 95% confidence interval 1.35-1.68; P < 0.0001). New pacemaker implantation was performed in 448 patients (24.6%) after TAVI and in 201 (11.0%) after sAVR (P < 0.0001). CONCLUSIONS: The 5-year follow-up data show that TAVI patients were significantly older and had a higher STS score than sAVR patients. After propensity score matching, TAVI with early-generation prosthesis was associated with significantly higher 5-year all-cause mortality than sAVR.

13.
Anim Cogn ; 24(6): 1279-1297, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33978856

RESUMO

Extinction learning, the process of ceasing an acquired behavior in response to altered reinforcement contingencies, is not only essential for survival in a changing environment, but also plays a fundamental role in the treatment of pathological behaviors. During therapy and other forms of training involving extinction, subjects are typically exposed to several sessions with a similar structure. The effects of this repeated exposure are not well understood. Here, we studied the behavior of pigeons across several sessions of a discrimination-learning task in context A, extinction in context B, and a return to context A to test the context-dependent return of the learned responses (ABA renewal). By focusing on individual learning curves across animals, we uncovered a session-dependent variability of behavior: (1) during extinction, pigeons preferred the unrewarded alternative choice in one-third of the sessions, predominantly during the first one. (2) In later sessions, abrupt transitions of behavior at the onset of context B emerged, and (3) the renewal effect decayed as sessions progressed. We show that the observed results can be parsimoniously accounted for by a computational model based only on associative learning between stimuli and actions. Our work thus demonstrates the critical importance of studying the trial-by-trial dynamics of learning in individual sessions, and the power of "simple" associative learning processes.


Assuntos
Condicionamento Operante , Extinção Psicológica , Animais , Condicionamento Clássico , Aprendizagem , Reforço Psicológico
14.
J Clin Med ; 10(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805760

RESUMO

Membrane-bound angiotensin converting enzyme (ACE) 2 serves as a receptor for the Sars-CoV-2 spike protein, permitting viral attachment to target host cells. The COVID-19 pandemic brought into light ACE2, its principal product angiotensin (Ang) 1-7, and the G protein-coupled receptor for the heptapeptide (MasR), which together form a still under-recognized arm of the renin-angiotensin system (RAS). This axis counteracts vasoconstriction, inflammation and fibrosis, generated by the more familiar deleterious arm of RAS, including ACE, Ang II and the ang II type 1 receptor (AT1R). The COVID-19 disease is characterized by the depletion of ACE2 and Ang-(1-7), conceivably playing a central role in the devastating cytokine storm that characterizes this disorder. ACE2 repletion and the administration of Ang-(1-7) constitute the therapeutic options currently tested in the management of severe COVID-19 disease cases. Based on their beneficial effects, both ACE2 and Ang-(1-7) have also been suggested to slow the progression of experimental diabetic and hypertensive chronic kidney disease (CKD). Herein, we report a further step undertaken recently, utilizing this type of intervention in the management of evolving acute kidney injury (AKI), with the expectation of renal vasodilation and the attenuation of oxidative stress, inflammation, renal parenchymal damage and subsequent fibrosis. Most outcomes indicate that triggering the ACE2/Ang-(1-7)/MasR axis may be renoprotective in the setup of AKI. Yet, there is contradicting evidence that under certain conditions it may accelerate renal damage in CKD and AKI. The nature of these conflicting outcomes requires further elucidation.

15.
J Phys Chem Lett ; 12(14): 3685-3690, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33829796

RESUMO

One of the unsolved problems of dynamics in supercooled liquids are the differences in spectral shape of the structural relaxation observed among different methods and substances, and a possible generic line shape has long been debated. We show that the light scattering spectra of very different systems, e.g., hydrogen bonding, van der Waals liquids, and ionic systems, almost perfectly superimpose and show a generic line shape of the structural relaxation, following ∝ ω-1/2 at high frequencies. In dielectric spectra the generic behavior is recovered only for systems with low dipole moment, while in strongly dipolar liquids additional cross-correlation contributions mask the generic structural relaxation.

16.
Ann Thorac Surg ; 112(5): e321-e323, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33662303

RESUMO

Implantation of hybrid prostheses using the frozen elephant trunk technique has become a standard procedure for aortic arch and proximal descending aorta pathologies. New devices have been introduced to reduce surgical complexity by enabling the frozen elephant trunk technique to be performed in proximal segments of the aorta. This facilitates a minimally invasive approach and provides a safe and durable aortic arch repair. We herein report on the first human experience with the new trifurcated frozen elephant trunk aortic prosthesis, E-vita OPEN NEO (CryoLife/JOTEC GmbH, Hechingen, Germany), using a minimally invasive technique.


Assuntos
Falso Aneurisma/cirurgia , Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Implante de Prótese Vascular/métodos , Prótese Vascular , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Desenho de Prótese
17.
PLoS Negl Trop Dis ; 15(3): e0008906, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33755669

RESUMO

Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.


Assuntos
Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/mortalidade , Doença de Chagas/diagnóstico , Doença de Chagas/mortalidade , Citocinas/sangue , Biomarcadores/sangue , Doença de Chagas/sangue , Doença de Chagas/patologia , Quimiocina CXCL9/sangue , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/parasitologia , Fatores de Crescimento de Células Hematopoéticas/sangue , Fator de Crescimento de Hepatócito/sangue , Humanos , Oxirredutases Intramoleculares/sangue , Lectinas Tipo C/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Trypanosoma cruzi/fisiologia
19.
Eng Life Sci ; 21(3-4): 137-153, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33716613

RESUMO

Ethyl acetate is an organic solvent with many industrial applications, currently produced by energy-intensive chemical processes based on fossil carbon resources. Ethyl acetate can be synthesized from renewable sugars by yeasts like Kluyveromyces marxianus in aerobic processes. However, ethyl acetate is highly volatile and thus stripped from aerated cultivation systems which complicate the quantification of the produced ester. Synthesis of volatile metabolites is commonly monitored by repeated analysis of metabolite concentrations in both the gas and liquid phase. In this study, a model-based method for quantifying the synthesis and degradation of volatile metabolites was developed. This quantification of volatiles is solely based on repeatedly measured gas-phase concentrations and allows calculation of reaction rates and yields in high temporal resolution. Parameters required for these calculations were determined in abiotic stripping tests. The developed method was validated for ethyl acetate, ethanol and acetaldehyde which were synthesized by K. marxianus DSM 5422 during an iron-limited batch cultivation; it was shown that the presented method is more precise and less time-consuming than the conventional method. The biomass-specific synthesis rate and the yield of ethyl acetate varied over time and exhibited distinct momentary maxima of 0.50 g g‒1h‒1 and 0.38 g g‒1 at moderate iron limitation.

20.
Eng Life Sci ; 21(3-4): 154-168, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33716614

RESUMO

Ethyl acetate is currently produced from fossil carbon resources. This ester could also be microbially synthesized from sugar-rich wastes of the food industry. Wild-type strains with GRAS status are preferred for such applications. Production of ethyl acetate by wild-type yeasts has been repeatedly reported, but comparative studies with several strains at various induction modes are largely missing. Here, synthesis of ethyl acetate by three yeasts with GRAS status, Kluyveromyces marxianus DSM 5422, Cyberlindnera jadinii DSM 2361 and Wickerhamomyces anomalus DSM 6766, was studied under identical and well-defined conditions in an aerated bioreactor, by inducing the ester synthesis via iron or oxygen limitation. Balancing the ester synthesis was based on measured concentrations of ethyl acetate in the exhaust gas, delivering masses of synthesized ester and synthesis rates in a high temporal resolution. All tested yeasts synthesized ethyl acetate under these conditions, but the intensity varied with the strain and induction mode. The highest yields were achieved under iron limitation with K. marxianus (0.182 g g-1) and under oxygen limitation with W. anomalus (0.053 g g-1). Iron limitation proved to be the better inducer for ester synthesis while oxygen limitation favored ethanol formation. K. marxianus DSM 5422 was the most potent producer of ethyl acetate exhibiting the highest biomass-specific synthesis rate of 0.5 g g-1h-1 under moderate iron limitation.

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