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1.
Mol Med ; 30(1): 39, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493090

RESUMO

OBJECTIVE: Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration. METHODS: Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2's effect on tau phosphorylation. RESULTS: Sevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats. CONCLUSION: Sevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.


Assuntos
Anestésicos Inalatórios , Disfunção Cognitiva , Éteres Metílicos , Idoso , Animais , Humanos , Lactente , Ratos , Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/metabolismo , Cognição , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Éteres Metílicos/farmacologia , Éteres Metílicos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sevoflurano/metabolismo , Sevoflurano/farmacologia , Proteínas tau/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo
2.
Neuropathology ; 43(6): 431-440, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37037475

RESUMO

Sevoflurane (SEV) is a commonly used anesthetic in pediatric surgery. Recent studies reported that repeated use of SEV contributes to cognitive impairment. Engeletin has been discovered to exert anti-inflammatory effects in various diseases. However, the detailed roles and mechanisms of engeletin in SEV-induced cognitive dysfunction of neonatal mice remain unclear. In this study, C57BL/6 neonatal mice were randomly divided into Ctrl, SEV, SEV + Engeletin (10 mg /kg), SEV + Engeletin (20 mg/kg), and SEV + Engeletin (40 mg/kg) groups. The Morris water maze (MWM) test suggested that engeletin treatment significantly improved SEV-induced cognitive impairment in neonatal mice. Employing ELISA and Nissl staining analysis, engeletin reduced neuroinflammation and loss of nerve cells caused by SEV, respectively. The treatment of engeletin dramatically suppressed the activation of microglia and apoptosis induced by SEV in the hippocampus of neonatal mice. Furthermore, the inhibition of PPAR-γ obviously reversed the abovementioned effects of engeletin in the hippocampus of newborn mice. In conclusion, this study verified that engeletin notably ameliorated SEV-induced cognitive deficiencies in neonatal mice at least partially by mediating the expression of PPAR-γ.


Assuntos
Disfunção Cognitiva , Éteres Metílicos , Animais , Camundongos , Animais Recém-Nascidos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Hipocampo , Éteres Metílicos/efeitos adversos , Éteres Metílicos/metabolismo , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo , PPAR gama/farmacologia , Sevoflurano/efeitos adversos , Sevoflurano/metabolismo
3.
Ecotoxicol Environ Saf ; 255: 114763, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37032576

RESUMO

Methyl tertiary-butyl ether (MTBE) is a new unleaded gasoline additive, which is considered to be associated with abnormal lipid metabolism in many studies, but the metabolic characteristics and mechanism are still unclear. To observe the characteristics of lipid metabolism induced by MTBE and possible pathways, 21 male Wistar rats got intragastric administration for 24 weeks. The serum lipid metabolism indexes and metabolites were analyzed separately by a biochemical analyzer and untargeted metabolomics. And found that serum high-density lipoprotein cholesterol (HDL-C) levels in the exposure group were significantly reduced, and serum very low-density lipoprotein (VLDL) levels were significantly increased. In untargeted metabolomics, 190 differential metabolites were obtained. Among them, 23 metabolites were found to show the same trend in MTBE exposure groups, which might play a key role in systemic energy metabolism. Further metabolic pathways analysis showed that D-Glutamine, D-glutamate metabolism, and the other three pathways were affected by MTBE significantly. Therefore, we evaluated serum glutamine and glutamate levels and found that MTBE exposure significantly reduced glutamine levels and increased glutamate levels in rat serum and L-02 cells. Further, the key regulatory gene of glutamine metabolism, glutaminase 1 isoform (GLS1), was significantly up-regulated in rat liver and L-02 cells exposed to MTBE. While the effect of glutamine and glutamate metabolism induced by MTBE could be weakened by BPTES, an antagonist of GLS1. In conclusion, our results indicated that MTBE exposure could change the level of glutamine metabolism by promoting GLS1 expression and ultimately lead to abnormal lipid metabolism.


Assuntos
Poluentes Atmosféricos , Transtornos do Metabolismo dos Lipídeos , Éteres Metílicos , Ratos , Masculino , Animais , Poluentes Atmosféricos/metabolismo , Glutaminase/metabolismo , Metabolismo dos Lipídeos , Glutamina , Regulação para Cima , Ratos Wistar , Éteres Metílicos/metabolismo , Isoformas de Proteínas/metabolismo
4.
Protein J ; 42(2): 112-124, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36905495

RESUMO

BACKGROUND: The health benefits of natural products have a long history. Chaga (Inonotus obliques) is used in traditional medicine and is an essential antioxidant for protecting the body from oxidants. Reactive oxygen species (ROS) are produced routinely due to metabolic processes. However, environmental pollution factors such as methyl tert-butyl ether (MTBE) can increase oxidative stress in the human body. MTBE is widely used as a fuel oxygenator that can harm health. The widespread use of MTBE has posed significant threats to the environment by polluting environmental resources, including groundwater. This compound can accumulate in the bloodstream by inhaling polluted air, with a strong affinity for blood proteins. The primary mechanism of MTBE's harmful effects is ROS production. The use of antioxidants may help reduce MTBE oxidation conditions. The present study proposes that biochaga, as an antioxidant, can reduce MTBE damage in the bovine serum albumin (BSA) structure. METHODS AND RESULTS: This study investigated the role of different concentrations of biochaga in the structural change of BSA in the presence of MTBE by biophysical methods such as UV-Vis, fluorescence, FTIR spectroscopy, DPPH radical inhibition method, aggregation test, and molecular docking. Research at the molecular level is critical to investigate the structural change of proteins by MTBE and the protective effect of the ideal dose (2.5 µg/ml) of biochaga. CONCLUSION: the results of spectroscopic examinations showed that the concentration of 2.5 µg/ml of biochaga has the least destructive effect on the structure of BSA in the presence and absence of MTBE, and it can play as an antioxidant.


Assuntos
Éteres Metílicos , Soroalbumina Bovina , Humanos , Espécies Reativas de Oxigênio/metabolismo , Simulação de Acoplamento Molecular , Antioxidantes/farmacologia , Éteres Metílicos/farmacologia , Éteres Metílicos/química , Éteres Metílicos/metabolismo
5.
Neurotoxicology ; 93: 348-354, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36404432

RESUMO

Studies have shown that sevoflurane, a halogenated inhalational anesthetic, interferes with neurogenesis in the developing rodent brain. However, the mechanisms by which sevoflurane affects neural stem cells (NSCs) differentiation require further elucidation. Pregnant rats (gestational day 14) were anesthetized with 3.5% sevoflurane for 2 h, with or without ML385 pretreatment. ML385 is a specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor. NRF2 expression and the downstream Sonic Hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) signaling cascade were determined by western blotting in the fetal brain at 24 h and 72 h after maternal sevoflurane exposure. Immunofluorescence and western blotting were performed to evaluate NSC neuronal and astrocytic differentiation in fetal brain tissues at 24 h and 72 h post-anesthesia as well as in the hippocampus on postnatal day (P) 28. Nissl staining was performed to measure the neuronal density on P28. Morris Water Maze tests were used to evaluate learning and memory function on P28-33. Neuronal and astrocytic differentiation of NSCs was markedly promoted in the fetal brain at 24 h and 72 h after maternal sevoflurane exposure, accompanied by upregulated NRF2. However, neuronal reduction and astrocyte proliferation were observed in the rat hippocampus at P28. Pretreatment with ML385 reversed sevoflurane-induced premature differentiation of NSCs, accompanied by suppression of SHH/GLI1 signaling. Furthermore, ML385 rescued sevoflurane-induced decreased neuronal density and impaired learning and memory function in the offspring. Prenatal sevoflurane exposure promotes neuronal and astrocytic differentiation of NSCs in the fetal rat brain, leading to long-term neuron reduction but astrocyte proliferation in the postnatal rat hippocampus. Prenatal sevoflurane exposure modulates NSC differentiation through NRF2/SHH/GLI1.


Assuntos
Éteres Metílicos , Células-Tronco Neurais , Gravidez , Feminino , Ratos , Animais , Sevoflurano , Fator 2 Relacionado a NF-E2/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Éteres Metílicos/metabolismo , Éteres Metílicos/farmacologia , Proteínas Hedgehog/metabolismo , Diferenciação Celular
6.
Acta Biomater ; 153: 585-595, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36167235

RESUMO

As an alternative strategy to achieve the desired bone augmentation, tenting screw technology (TST) has considerably broadened the indications for implant treatment. Titanium tenting screws are typically used in TST to maintain the space for bone regeneration. However, a high degree of osteogenic integration complicate titanium tenting screw removal and impact the bone healing micro-environment. Previous efforts have been focused on modifying titanium surfaces to enhance osseointegration while ignoring the opposite process. Due to the vital role of bone marrow mesenchymal stem cells (BMSCs) in bone regeneration, it might be feasible to reduce osseointegration around titanium tenting screws by resisting the adhesion of BMSCs. Herein, poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was incorporated with a Ti surface in terms of surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The cell apoptosis analysis showed that the new surface would not induce the apoptosis of BMSCs. Then, the adhesive and proliferative behaviors of BMSCs on the surface were analyzed which indicated that the poly(PEGMA) surface could inhibit the proliferation of BMSCs through resisting the adhesion process. Furthermore, in vivo experiments revealed the presence of the poly(PEGMA) on the surface resulted in a lower bone formation and osseointegration compared with the Ti group. Collectively, this dense poly(PEGMA) surface of Ti may serve as a promising material for clinical applications in the future. STATEMENT OF SIGNIFICANCE: The poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was grafted onto a Ti surface by surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The PEGMA surface could reduce the osteogenic integration by preventing the adhesion of cells, resulting in a lower pullout force of the modified implant and thereby desirable and feasible applications in dental surgery.


Assuntos
Incrustação Biológica , Células-Tronco Mesenquimais , Éteres Metílicos , Osseointegração , Titânio/farmacologia , Incrustação Biológica/prevenção & controle , Metacrilatos/farmacologia , Metacrilatos/metabolismo , Polietilenoglicóis/farmacologia , Polietilenoglicóis/metabolismo , Éteres Metílicos/metabolismo , Propriedades de Superfície , Células da Medula Óssea/metabolismo
7.
J Neuroendocrinol ; 34(2): e13033, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34495563

RESUMO

Pregnenolone methyl-ether (PME) is a synthetic derivative of the endogenous neuroactive steroid pregnenolone (PREG), which is an important modulator of several brain functions. In addition to being the precursor of steroids, PREG acts directly on various targets including microtubules (MTs), the functioning of which is fundamental for the development and homeostasis of nervous system. The coordination of MT dynamics is supported by a plethora of MT-associated proteins (MAPs) and by a specific MT code that is defined by the post-translational modifications of tubulin. Defects associated with MAPs or tubulin post-translational modifications are linked to different neurological pathologies including mood and neurodevelopmental disorders. In this review, we describe the beneficial effect of PME in major depressive disorders (MDDs) and in CDKL5 deficiency disorder (CDD), two pathologies that are joint by defective MT dynamics. Growing evidence indeed suggests that PME, as well as PREG, is able to positively affect the MT-binding of MAP2 and the plus-end tracking protein CLIP170 that are both found to be deregulated in the above mentioned pathologies. Furthermore, PME influences the state of MT acetylation, the deregulation of which is often associated with neurological abnormalities including MDDs. By contrast to PREG, PME is not metabolised into other downstream molecules with specific biological properties, an aspect that makes this compound more suitable for therapeutic strategies. Thus, through the analysis of MDDs and CDD, this work focuses attention on the possible use of PME for neuronal pathologies associated with MT defects.


Assuntos
Transtorno Depressivo Maior , Éteres Metílicos , Síndromes Epilépticas , Humanos , Éteres Metílicos/metabolismo , Éteres Metílicos/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/farmacologia , Microtúbulos/metabolismo , Pregnenolona/metabolismo , Pregnenolona/uso terapêutico , Proteínas Serina-Treonina Quinases , Espasmos Infantis , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/farmacologia
8.
Chemosphere ; 239: 124724, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31505447

RESUMO

Combination of sulfuric acid modified bagasse activated carbon-bone biochar beads and Acinetobacter indicus screened from petroleum contaminated soil was the best condition for gaseous methyl tert-butyl ether (MTBE) removal. It was found that H2SO4 modified bagasse AC in powder form had higher adsorption capacity (989.33 mg g-1) than that in bead form (1.94 mg g-1). In addition, bone biochar in powder form (3.51 mg g-1) also had higher adsorption capacity than that in bead form (1.63 mg g-1). This was the fact that material beads contained high moisture content that inhibited the penetration of gaseous MTBE into the material. And a mixed material of H2SO4 modified bagasse AC-bone biochar beads had the highest adsorption capacity (2.22 mg g-1) compared to individual H2SO4 modified bagasse AC beads (1.94 mg g-1) and bone biochar beads (1.63 mg g-1) due to a mixed material had more rough surface and high surface area on its material. So, gaseous MTBE can penetrate through this material more easily. Although the maximum adsorption capacity of H2SO4 modified bagasse AC in powder form was the highest but microorganism cannot sustain and survive in this form for a long time. Therefore, the material beads were more suitable for microorganism to grow and degrade gaseous MTBE. Microorganism can degrade MTBE and caused no secondary wastes. Moreover, A. indicus was a novel strain for MTBE removal that has not been previously reported. Therefore, a combination of A. indicus-mixed material beads was a good choice for MTBE removal in a biofilter system.


Assuntos
Acinetobacter/metabolismo , Celulose/química , Carvão Vegetal/química , Éteres Metílicos/química , Acinetobacter/isolamento & purificação , Adsorção , Biodegradação Ambiental , Células Imobilizadas , Poluição Ambiental , Gases , Éteres Metílicos/isolamento & purificação , Éteres Metílicos/metabolismo , Petróleo , Microbiologia do Solo , Ácidos Sulfúricos/química , Gerenciamento de Resíduos/métodos
9.
Biosci Rep ; 38(6)2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30287506

RESUMO

Monocyclic monoterpenes have been recognized as useful pharmacological ingredients due to their ability to treat numerous diseases. Limonene and perillyl alcohol as well as their metabolites (especially perillic acid and its methyl ester) possess bioactivities such as antitumor, antiviral, anti-inflammatory, and antibacterial agents. These therapeutic properties have been well documented. Based on the aforementioned biological properties of limonene and its metabolites, their structural modification and development into effective drugs could be rewarding. However, utilization of these monocyclic monoterpenes as scaffolds for the design and developments of more effective chemoprotective agents has not received the needed attention by medicinal scientists. Recently, some derivatives of limonene metabolites have been synthesized. Nonetheless, there have been no thorough studies on their pharmacokinetic and pharmacodynamic properties as well as their inhibition against isoprenylation enzymes. In this review, recent research progress in the biochemical significance of limonene and its metabolites was summarized with emphasis on their antitumor effects. Future prospects of these bioactive monoterpenes for drug design and development are also highlighted.


Assuntos
Desenho de Fármacos , Limoneno/uso terapêutico , Neoplasias/tratamento farmacológico , Cicloexenos/química , Cicloexenos/metabolismo , Cicloexenos/uso terapêutico , Humanos , Limoneno/química , Limoneno/metabolismo , Éteres Metílicos/química , Éteres Metílicos/metabolismo , Éteres Metílicos/uso terapêutico , Monoterpenos/química , Monoterpenos/metabolismo , Monoterpenos/uso terapêutico , Neoplasias/patologia
10.
Appl Microbiol Biotechnol ; 102(7): 3387-3397, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29478141

RESUMO

The increasing use of biobased fuels and fuel additives can potentially change the typical fuel-related contamination in soil and groundwater. Anaerobic biotransformation of the biofuel additive ethyl tert-butyl ether (EtBE), as well as of methyl tert-butyl ether (MtBE), benzene, and tert-butyl alcohol (TBA, a possible oxygenate metabolite), was studied at an industrially contaminated site and in the laboratory. Analysis of groundwater samples indicated that in the field MtBE was degraded, yielding TBA as major product. In batch microcosms, MtBE was degraded under different conditions: unamended control, with medium without added electron acceptors, or with ferrihydrite or sulfate (with or without medium) as electron acceptor, respectively. Degradation of EtBE was not observed under any of these conditions tested. TBA was partially depleted in parallel with MtBE. Results of microcosm experiments with MtBE substrate analogues, i.e., syringate, vanillate, or ferulate, were in line with the hypothesis that the observed TBA degradation is a cometabolic process. Microcosms with ferulate, syringate, isopropanol, or diethyl ether showed EtBE depletion up to 86.5% of the initial concentration after 83 days. Benzene was degraded in the unamended controls, with medium without added electron acceptors and with ferrihydrite, sulfate, or chlorate as electron acceptor, respectively. In the presence of nitrate, benzene was only degraded after addition of an anaerobic benzene-degrading community. Nitrate and chlorate hindered MtBE, EtBE, and TBA degradation.


Assuntos
Biodegradação Ambiental , Microbiologia Industrial/métodos , Poluentes Químicos da Água/metabolismo , Anaerobiose , Etil-Éteres/metabolismo , Éteres Metílicos/metabolismo , Oxirredução , terc-Butil Álcool/metabolismo
11.
Neurochem Int ; 112: 124-133, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29174382

RESUMO

Epilepsy is a neurological disease that affects more than 70 million people worldwide and is characterized by the presence of spontaneous unprovoked recurrent seizures. Existing anti-seizure drugs (ASDs) have side effects and fail to control seizures in 30% of patients due to drug resistance. Hence, safer and more efficacious drugs are sorely needed. Flavonoids are polyphenolic structures naturally present in most plants and consumed daily with no adverse effects reported. These structures have shown activity in several seizure and epilepsy animal models through allosteric modulation of GABAA receptors, but also via potent anti-inflammatory action in the brain. As such, dietary flavonoids offer an interesting source for ASD and anti-epileptogenic drug (AED) discovery, but their pharmaceutical potential is often hampered by metabolic instability and low oral bioavailability. It has been argued that their drug-likeness can be improved via methylation of the free hydroxyl groups, thereby dramatically enhancing metabolic stability and membrane transport, facilitating absorption and highly increasing bioavailability. Since no scientific data is available regarding the use of methylated flavonoids in the fight against epilepsy, we studied naringenin (NRG), kaempferol (KFL), and three methylated derivatives, i.e., naringenin 7-O-methyl ether (NRG-M), naringenin 4',7-dimethyl ether (NRG-DM), and kaempferide (4'-O-methyl kaempferol) (KFD) in the zebrafish pentylenetetrazole (PTZ) seizure model. We demonstrate that the methylated flavanones NRG-DM and NRG-M are highly effective against PTZ-induced seizures in larval zebrafish, whereas NRG and the flavonols KFL and KFD possess only a limited activity. Moreover, we show that NRG-DM is active in two standard acute mouse seizure models, i.e., the timed i.v. PTZ seizure model and the 6-Hz psychomotor seizure model. Based on these results, NRG-DM is proposed as a lead compound that is worth further investigation for the treatment of generalized seizures and drug-resistant focal seizures. Our data therefore highlights the potential of methylated flavonoids in the search for new and improved ASDs.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/prevenção & controle , Flavanonas/uso terapêutico , Flavonoides/uso terapêutico , Éteres Metílicos/uso terapêutico , Convulsões/prevenção & controle , Animais , Anticonvulsivantes/metabolismo , Relação Dose-Resposta a Droga , Epilepsia/induzido quimicamente , Epilepsia/metabolismo , Flavanonas/metabolismo , Flavonoides/metabolismo , Masculino , Éteres Metílicos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Convulsões/induzido quimicamente , Convulsões/metabolismo , Peixe-Zebra
12.
Anesth Analg ; 125(3): 783-789, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28678075

RESUMO

BACKGROUND: Sevoflurane is a volatile anesthetic commonly used to maintain anesthesia in patients with end-stage liver disease (ESLD) undergoing orthotopic liver transplantation (OLT). Growing evidence suggests that patients with ESLD have decreased anesthetic requirements compared to patients with preserved liver function. The potency of volatile anesthetics is expressed as the minimum alveolar concentration (MAC). In this prospective, blinded study, we compared the MAC of sevoflurane among patients with ESLD undergoing OLT and patients with normal liver function undergoing major abdominal surgery. METHODS: After propofol-induced anesthesia, the MAC of sevoflurane was assessed by evaluating motor response to initial skin incision in patients undergoing OLT and in patients with normal liver function undergoing major abdominal surgery. The MAC was determined using Dixon "up-and-down" method and compared between groups. In addition, the bispectral index was documented immediately before and after skin incision. RESULTS: Twenty patients undergoing OLT and 20 control patients were included in the study. The MAC of sevoflurane in patients undergoing OLT was 1.3% (95% confidence interval [CI], 1.1-1.4). In comparison, the MAC of sevoflurane in patients with normal liver function was 1.7% (95% CI, 1.6-1.9), equal to a relative reduction of the MAC in patients with ESLD of 26% (95% CI, 14-39). The bispectral index was higher in patients with ESLD than in control patients at 3 minutes before (47 [95% CI, 40-53] vs 35 [95% CI, 31-40], P = .011), 1 minute before (48 [95% CI, 42-54] vs 37 [95% CI, 33-43], P = .03), and 1 minute after skin incision (57 [95% CI, 50-64] vs 41 [95% CI, 36-47], P < .001). CONCLUSIONS: Our results suggest that the MAC of sevoflurane is lower in patients with ESLD than in patients with normal liver function after propofol-induced anesthesia. However, as we did not measure propofol concentrations at the time of skin incision, the difference in MAC should be interpreted with caution given that residual propofol may have been present at the time of skin incision.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Doença Hepática Terminal/tratamento farmacológico , Doença Hepática Terminal/cirurgia , Transplante de Fígado , Éteres Metílicos/administração & dosagem , Adulto , Idoso , Anestésicos Inalatórios/metabolismo , Doença Hepática Terminal/metabolismo , Feminino , Humanos , Transplante de Fígado/tendências , Masculino , Éteres Metílicos/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/metabolismo , Sevoflurano , Método Simples-Cego
13.
Sci Total Environ ; 583: 88-96, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28109662

RESUMO

BTEX (benzene, toluene, ethylbenzene, ortho-, meta-, and para-xylenes), methyl tert-butyl ether (MTBE), cis-1,2-dichloroethylene (cis-DCE), and trichloroethylene (TCE) are among the major soil and groundwater contaminants frequently co-existing, as a result of their widespread uses. Pseudomonas plecoglossicida was immobilized on waste scrap tyre to remove these contaminants mixture from synthetic contaminated water. The microbial activity was enhanced in the immobilized system, shown by the higher colony forming units (CFUs) (40%), while BTEX were used as growth substrates. The adsorption capacity of tyres toward contaminants reached a maximum within one day, with BTEX (76.3%) and TCE (64.3%) showing the highest sorption removal capacities, followed by cis-DCE (30.0%) and MTBE (11.0%). The adsorption data fitted the Freundlich isotherm with a good linear correlation (0.989-0.999) for the initial contaminants concentration range applied (25-125mg/L). The monoaromatic hydrocarbons were almost completely removed in the immobilized system and the favourable removal efficiencies of 78% and 90% were obtained for cis-DCE and TCE, respectively. The hybrid (biological, immobilization/physical, sorption) system was further evaluated with the contaminants spiked intermittently for the stable performance. The addition of mineral salt medium further enhanced the bioremoval of contaminants by stimulating the microbial growth to some extent.


Assuntos
Hidrocarbonetos/química , Pseudomonas/metabolismo , Reciclagem , Poluentes Químicos da Água/metabolismo , Benzeno/metabolismo , Derivados de Benzeno/metabolismo , Biodegradação Ambiental , Dicloroetilenos/metabolismo , Recuperação e Remediação Ambiental/métodos , Dicloretos de Etileno/metabolismo , Éteres Metílicos/metabolismo , Tolueno/metabolismo , Tricloroetileno/metabolismo , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Xilenos/metabolismo
14.
J Am Chem Soc ; 139(5): 1742-1745, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28040895

RESUMO

The biosynthesis of branched alkoxy groups, such as the unique t-butyl group found in a variety of natural products, is still poorly understood. Recently, cystobactamids were isolated and identified from Cystobacter sp as novel antibacterials. These metabolites contain an isopropyl group proposed to be formed using CysS, a cobalamin-dependent radical S-adenosylmethionine (SAM) methyltransferase. Here, we reconstitute the CysS-catalyzed reaction, on p-aminobenzoate thioester substrates, and demonstrate that it not only catalyzes sequential methylations of a methyl group to form ethyl and isopropyl groups but remarkably also sec-butyl and t-butyl groups. To our knowledge, this is the first in vitro reconstitution of a cobalamin-dependent radical SAM enzyme catalyzing the conversion of a methyl group to a t-butyl group.


Assuntos
Antibacterianos/biossíntese , Asparagina/análogos & derivados , Éteres Metílicos/metabolismo , Metiltransferases/metabolismo , S-Adenosilmetionina/metabolismo , Vitamina B 12/metabolismo , Alquilação , Antibacterianos/química , Asparagina/biossíntese , Asparagina/química , Biocatálise , Radicais Livres/química , Radicais Livres/metabolismo , Éteres Metílicos/química , Metiltransferases/química , Estrutura Molecular , Nitrocompostos/química , S-Adenosilmetionina/química , Vitamina B 12/química
15.
Water Sci Technol ; 74(12): 2889-2897, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27997398

RESUMO

Extractive membrane biofilm reactor (EMBFR) technology offers productive solutions for volatile and semi-volatile compound removal from water bodies. In this study, the bacterial strains Paenibacillus etheri SH7T (CECT 8558), Agrobacterium sp. MS2 (CECT 8557) and Rhodococcus ruber strains A5 (CECT 8556), EE6 (CECT 8612) and EE1 (CECT 8555), previously isolated from fuel-contaminated sites, were tested for adherence on tubular semipermeable membranes in laboratory-scale systems designed for methyl tert-butyl ether (MTBE) bioremediation. Biofilm formation on the membrane surface was evaluated through observation by field-emission scanning electron microscope (FESEM) as well as the acute toxicity (as EC50) of the bacterial growth media. Moreover, extracellular polymeric substance (EPS) production for each strain under different MTBE concentrations was measured. Strains A5 and MS2 were biofilm producers and their adherence increased when the MTBE flowed through the inner tubular semipermeable membrane. No biofilm was formed by Paenibacillus etheri SH7T, nevertheless, the latter and strain MS2 exhibited the lowest toxicity after growth on the EMBFR. The results obtained from FESEM and toxicity analysis demonstrate that bacterial strains R. ruber EE6, A5, P. etheri SH7T and Agrobacterium sp. MS2 could be excellent candidates to be used as selective inocula in EMBFR technology for MTBE bioremediation.


Assuntos
Agrobacterium/fisiologia , Biofilmes , Éteres Metílicos/metabolismo , Paenibacillus/fisiologia , Rhodococcus/fisiologia , Biodegradação Ambiental , Meios de Cultura , Éteres Metílicos/toxicidade
16.
PLoS One ; 11(12): e0167494, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27907122

RESUMO

This study investigated the aerobic biodegradation of methyl tertiary-butyl ether (MTBE) by a microbial consortium in a continuous up-flow packed-bed biofilm reactor using tezontle stone particles as a supporting material for the biofilm. Although MTBE is toxic for microbial communities, the microbial consortium used here was able to resist MTBE loading rates up to 128.3 mg L-1 h-1, with removal efficiencies of MTBE and chemical oxygen demand (COD) higher than 90%. A linear relationship was observed between the MTBE loading rate and the MTBE removal rate, as well as between the COD loading rate and the COD removal rate, within the interval of MTBE loading rates from 11.98 to 183.71 mg L-1 h-1. The metabolic intermediate tertiary butyl alcohol (TBA) was not detected in the effluent during all reactor runs, and the intermediate 2-hydroxy butyric acid (2-HIBA) was only detected at MTBE loading rates higher than 128.3 mg L-1 h-1. The results of toxicity bioassays with organisms from two different trophic levels revealed that the toxicity of the influent was significantly reduced after treatment in the packed-bed reactor. The packed-bed reactor system used in this study was highly effective for the continuous biodegradation of MTBE and is therefore a promising alternative for detoxifying MTBE-laden wastewater and groundwater.


Assuntos
Biodegradação Ambiental , Biofilmes , Reatores Biológicos , Éteres Metílicos/metabolismo , Consórcios Microbianos , Bioensaio , Biomassa , Éteres Metílicos/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-27608032

RESUMO

Co-metabolic bioremediation is supposed to be an impressive and promising approach in the elimination technology of methyl tert-butyl ether (MTBE), which was found to be a common pollutant worldwide in the ground or underground water in recent years. In this paper, bacterial strain DZ13 (which can co-metabolically degrade MTBE) was isolated and named as Pseudomonas sp. DZ13 based on the result of 16S rRNA gene sequencing analysis. Strain DZ13 could grow on n-alkanes (C5-C8), accompanied with the co-metabolic degradation of MTBE. Diverse n-alkanes with different carbon number showed a significant influence on the degradation rate of MTBE and accumulation of tert-butyl alcohol (TBA). When Pseudomonas sp. DZ13 co-metabolically degraded MTBE with n-pentane as the growth substrate, a higher MTBE-degrading rate (Vmax = 38.1 nmol/min/mgprotein, Ks = 6.8 mmol/L) and lower TBA-accumulation was observed. In the continuous degradation experiment, the removal efficiency of MTBE by Pseudomonas sp. Strain DZ13 did not show an obvious decrease after five times of continuous addition.


Assuntos
Poluentes Ambientais/metabolismo , Éteres Metílicos/metabolismo , Pseudomonas/metabolismo , Biodegradação Ambiental , Pentanos/metabolismo , Pseudomonas/genética , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , terc-Butil Álcool/metabolismo
18.
Electron. j. biotechnol ; 19(5): 12-20, Sept. 2016. ilus
Artigo em Inglês | LILACS | ID: lil-797332

RESUMO

Background: Methyl tert-butyl ether (MTBE) is a pollutant that causes deleterious effects on human and environmental health. Certain microbial cultures have shown the ability to degrade MTBE, suggesting that a novel bacterial species capable of degrading MTBE could be recovered. The goal of this study was to isolate, identify and characterize the members of a bacterial consortium capable of degrading MTBE. Results: The IPN-120526 bacterial consortium was obtained through batch enrichment using MTBE as the sole carbon and energy source. The cultivable fraction of the consortium was identified; of the isolates, only Stenotrophomonas maltophilia IPN-TD and Sphingopyxis sp. IPN-TE were capable of degrading MTBE. To the best of our knowledge, this report is the first demonstrating that S. maltophilia and Sphingopyxis sp. are capable of degrading MTBE. The degradation kinetics of MTBE demonstrated that S. maltophilia IPN-TD had a significantly higher overall MTBE degradation efficiency and rate (48.39 ± 3.18% and 1.56 ± 0.12 mg L-1 h-1, respectively) than the IPN-120526 consortium (38.59 ± 2.17% and 1.25 ± 0.087 mg L-1 respectively). The kinetics of MTBE removal by both cultures fit first-order and pseudo-first-order reaction models. Conclusions: These findings suggest that S. maltophilia IPN-TD in axenic culture has considerable potential for the detoxification of MTBE-contaminated water.


Assuntos
Microbiologia do Solo , Stenotrophomonas maltophilia/isolamento & purificação , Stenotrophomonas maltophilia/metabolismo , Éteres Metílicos/metabolismo , Biodegradação Ambiental , Gasolina , Cinética , Reação em Cadeia da Polimerase , Poluição Ambiental , Consórcios Microbianos , Éteres Metílicos/análise
19.
Microbiology (Reading) ; 162(9): 1563-1571, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27450417

RESUMO

Methyl-tert-butyl ether (MTBE) and its degradation by-product, tert-butyl alcohol (TBA), are widespread contaminants detected frequently in groundwater in California. Since MTBE was used as a fuel oxygenate for almost two decades, leaking underground fuel storage tanks are an important source of contamination. Gasoline components such as BTEX (benzene, toluene, ethylbenzene and xylenes) are often present in mixtures with MTBE and TBA. Investigations of interactions between BTEX and MTBE degradation have not yielded consistent trends, and the molecular mechanisms of BTEX compounds' impact on MTBE degradation are not well understood. We investigated trends in transcription of biodegradation genes in the MTBE-degrading bacterium, Methylibium petroleiphilum PM1 upon exposure to MTBE, TBA, ethylbenzene and benzene as individual compounds or in mixtures. We designed real-time quantitative PCR assays to target functional genes of strain PM1 and provide evidence for induction of genes mdpA (MTBE monooxygenase), mdpJ (TBA hydroxylase) and bmoA (benzene monooxygenase) in response to MTBE, TBA and benzene, respectively. Delayed induction of mdpA and mdpJ transcription occurred with mixtures of benzene and MTBE or TBA, respectively. bmoA transcription was similar in the presence of MTBE or TBA with benzene as in their absence. Our results also indicate that ethylbenzene, previously proposed as an inhibitor of MTBE degradation in some bacteria, inhibits transcription of mdpA, mdpJ and bmoAgenes in strain PM1.


Assuntos
Proteínas de Bactérias/genética , Derivados de Benzeno/metabolismo , Benzeno/metabolismo , Betaproteobacteria/genética , Betaproteobacteria/metabolismo , Éteres Metílicos/metabolismo , Proteínas de Bactérias/metabolismo , Betaproteobacteria/isolamento & purificação , Biodegradação Ambiental , Transcrição Gênica
20.
Environ Sci Technol ; 50(3): 1455-64, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26727046

RESUMO

The widespread use of methyl tert-butyl ether (MTBE) has caused major contamination of groundwater sources and is a concern due to its taste and odor problems, as well as its toxicity. MTBE can be degraded anaerobically which makes bioremediation of contaminated aquifers a potential solution. Nevertheless, the organisms and mechanisms that are responsible for anaerobic MTBE degradation are still unknown. The aim of our research was to identify the organisms actively degrading MTBE. For this purpose we characterized an anaerobic methanogenic culture enriched with MTBE as the sole carbon source from the New Jersey Arthur Kill intertidal strait sediment. The cultures were analyzed using stable isotope probing (SIP) combined with terminal restriction fragment length polymorphism (T-RFLP), high-throughput sequencing and clone library analysis of bacterial 16S rRNA genes. The sequence data indicated that phylotypes belonging to the Ruminococcaceae in the Firmicutes were predominant in the methanogenic cultures. SIP experiments also showed sequential incorporation of the (13)C labeled MTBE by the bacterial community with a bacterium most closely related to Saccharofermentans acetigenes identified as the bacterium active in O-demethylation of MTBE. Identification of the microorganisms responsible for the activity will help us better understand anaerobic MTBE degradation processes in the field and determine biomarkers for monitoring natural attenuation.


Assuntos
Clostridiales/metabolismo , Éteres Metílicos/metabolismo , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Clostridiales/genética , Metano/metabolismo , RNA Bacteriano/genética , RNA Ribossômico 16S/genética
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