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1.
PLoS One ; 15(2): e0228908, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32107483

RESUMO

The aim of the current study was to develop membrane-based transdermal patches of lornoxicam gel using oleic acid (OA)and propylene glycol (PG) as penetration enhancers to improve drug delivery across the skin and to evaluate in vivo analgesic and anti-inflammatory activity. For this purpose, nine formulations were developed in accordance with 32 factorial design using Design Expert® 11. The concentration of propylene glycol (X1) and oleic acid (X2) were selected as independent variable whereas Q10 (Y1), flux (Y2) and lag time (Y3) were considered as the response variables. The impact of drug loading, surface area, gel concentration, membrane variation and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction, analgesic activity and anti-inflammatory action of the optimized patch were also determined in Albino Wistar rats. Stability studies were performed for three months at three different temperature conditions. The result suggests that a membrane-based system with controlled zero-order drug release of 95.8 ± 1.121% for 10 h exhibiting flux of 126.51±1.19 µg/cm2/h and lag time of 0.908 ±0.57h was optimized with the desired analgesic and anti-inflammatory effect can be obtained by using propylene glycol and oleic acid co-solvents as a penetration enhancer. The patch was also found stable at 4˚C for a period of 6.44 months. Formulation F9 comprising of 10% PG and 3% OA was selected as an optimized formulation. The study demonstrates that the fabricated transdermal system of lornoxicam can deliver the drug through the skin in a controlled manner with desired analgesic and anti-inflammatory activity and can be considered as a suitable alternative of the oral route.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Piroxicam/análogos & derivados , Administração Cutânea , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Química Farmacêutica , Preparações de Ação Retardada/farmacologia , Géis/metabolismo , Masculino , Ácido Oleico/farmacologia , Piroxicam/farmacologia , Propilenoglicol/farmacologia , Ratos , Ratos Wistar , Pele/metabolismo , Absorção Cutânea/fisiologia , Solventes/farmacologia , Adesivo Transdérmico
2.
PLoS One ; 15(2): e0228543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32045426

RESUMO

Two molecules, 7-(diethylamino)coumarin-3-carbohydrazide (DCCH) and fluorescein-5-thiosemicarbazide (FTSC) were investigated in different solvents, under varying pH conditions regarding their spectroscopic properties for the usage as a Förster Resonance Energy Transfer (FRET) pair to study the molecular interaction between cellulosic surfaces. All the relevant spectroscopic properties to determine the Förster distance were measured and the performance as a FRET system was checked. From the results, it is clear that the environmental conditions need to be accurately controlled as both, but especially the FTSC dyes are sensitive to changes. For high enough concentrations positive FRET systems were observed in DMF, DMSO, H2O, THF and alkaline DMF. However due to the low quantum yield of the unmodified DCCH throughout the investigated parameter range and the strong environmental dependency of FTSC, both dyes are not preferable for being used in a FRET system for studying interaction between cellulosic surfaces.


Assuntos
Cumarínicos/química , Fluoresceínas/química , Transferência Ressonante de Energia de Fluorescência/métodos , Hidrazinas/química , Solventes/química , Análise Espectral/métodos , Transferência de Energia/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Solventes/farmacologia , Espectrometria de Fluorescência/métodos , Espectrofotometria Ultravioleta/métodos
3.
Sheng Wu Gong Cheng Xue Bao ; 35(10): 1857-1869, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31668034

RESUMO

Enzymes have a wide range of applications and great industrial potential. However, large-scale applications of enzymes are restricted by the harsh industrial environment, such as high temperature, strong acid/alkali, high salt, organic solvents, and high substrate concentration. Adaptive modification (such as rational or semi-rational design, directed evolution and immobilization) is the most common strategy to improve the catalysis of enzymes under industrial conditions. Here, we review the catalysis of enzymes in the industrial environment and various methods adopted for the adaptive modifications in recent years, to provide reference for the adaptive modifications of enzymes.


Assuntos
Biocatálise , Biotecnologia , Enzimas/química , Enzimas/metabolismo , Engenharia de Proteínas , Biocatálise/efeitos dos fármacos , Temperatura Alta , Concentração de Íons de Hidrogênio , Solventes/química , Solventes/farmacologia
4.
Arch Oral Biol ; 108: 104538, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476521

RESUMO

AIM: To investigate the effect of different alcohol concentrations on the development of apical periodontitis (AP) in rats. METHODS: Forty Wistar rats were arranged into five groups: (C) - control rats receiving sterile water as the only liquid; (G5) - animals receiving an alcohol solution at 5%, (G10) - alcohol solution at 10%, (G15) - alcohol solution at 15%, and (G20) - alcohol solution at 20%. The alcoholic solution or water was given to the groups as the sole source of hydration throughout the 30 days of the experiment. AP was induced in the mandibular molars on the first day. In the end, the animals were euthanized for histopathological and IL-1b, RANKL, OPG, and TRAP analyses. The Kruskal-Wallis test was used for nonparametric data, and ANOVA followed by the Tukey test were performed for parametric data, p < 0.05. RESULTS: G15 and G20 had a greater chronic inflammatory infiltrate (Score 3) and AP size bigger (1.59 ±â€¯0.41 and 1.83 ±â€¯0.38, respectively) than the C, G5 and G10 (p < 0.05). No significant difference was found in the IL-1b analyses. The G15 and G20 showed the highest immunolabeling pattern for RANKL and the lowest for OPG. The G20 had greater TRAP cells per mm (4.70 ±â€¯0.99) compared to the C, G5, and G10 (p < 0.05). Furthermore, G15 presented 3.92 ±â€¯0.64 TRAP cells/mm, higher than C (p < 0.05). CONCLUSIONS: G5 and G10 did not exert a protective or aggravating effect on the AP development. However, G15 and G20 had a significant effect on the AP severity, exacerbating the inflammation and osteoclast markers.


Assuntos
Etanol , Periodontite Periapical , Solventes , Animais , Etanol/farmacologia , Inflamação , Osteoclastos/efeitos dos fármacos , Ratos , Ratos Wistar , Solventes/farmacologia
5.
Int J Biol Macromol ; 140: 1037-1046, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31449862

RESUMO

Azo dyes are the most widely applied chemical dyes that have also raised great concerns for environmental contamination and human health issues. There has been a growing interest in discovering bioremediation methods to degrade azo dyes for environmental and economic purposes. Azoreductases are key enzymes evolved in nature capable of degrading azo dyes. The current work reports the identification, expression, and properties of a novel azoreductase (AzoRed2) from Streptomyces sp. S27 which shows an excellent stability against pH change and organic solvents. To overcome the requirements of coenzyme while degrading azo dyes, we introduced a coenzyme regeneration enzyme, Bacillus subtilis glucose 1-dehydrogenase (BsGDH), to construct a recycling system in living cells. The whole-cell biocatalyst containing AzoRed2 and BsGDH was used to degrade a representative azo dye methyl red. The degradation rate of methyl red was up to 99% in 120 min with high substrate concentration (250 µM) and no external coenzyme added. The degradation rate was still 98% in the third batch trial. To sum up, a novel azoreductase with good properties was found, which was applied to construct whole-cell biocatalyst. Both the enzymes and whole-cell biocatalysts are good candidates for the industrial wastewater treatment and environmental restoration.


Assuntos
Compostos Azo/isolamento & purificação , NADH NADPH Oxirredutases/metabolismo , Streptomyces/enzimologia , Águas Residuárias/química , Sequência de Aminoácidos , Compostos Azo/química , Biocatálise , Biodegradação Ambiental , Detergentes/farmacologia , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Íons , Metais/farmacologia , NADH NADPH Oxirredutases/química , Filogenia , Solventes/farmacologia , Espectrofotometria Ultravioleta , Especificidade por Substrato , Temperatura
6.
Mol Microbiol ; 112(5): 1564-1575, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31468587

RESUMO

Hopanoids are a class of membrane lipids found in diverse bacterial lineages, but their physiological roles are not well understood. The ethanol fermenter Zymomonas mobilis features the highest measured concentration of hopanoids, leading to the hypothesis that these lipids can protect against the solvent toxicity. However, the lack of genetic tools for manipulating hopanoid composition in this bacterium has limited their further functional analysis. Due to the polyploidy (>50 genome copies per cell) of Z. mobilis, we found that disruptions of essential hopanoid biosynthesis (hpn) genes act as genetic knockdowns, reliably modulating the abundance of different hopanoid species. Using a set of hpn transposon mutants, we demonstrate that both reduced hopanoid content and modified hopanoid polar head group composition mediate growth and survival in ethanol. In contrast, the amount of hopanoids, but not their head group composition, contributes to fitness at low pH. Spectroscopic analysis of bacterial-derived liposomes showed that hopanoids protect against several ethanol-driven phase transitions in membrane structure, including lipid interdigitation and bilayer dissolution. We propose that hopanoids act through a combination of hydrophobic and inter-lipid hydrogen bonding interactions to stabilize bacterial membranes during solvent stress.


Assuntos
Anti-Infecciosos Locais/farmacologia , Tolerância a Medicamentos/genética , Etanol/farmacologia , Triterpenos/metabolismo , Zymomonas/genética , Membrana Celular/metabolismo , Lipídeos de Membrana/classificação , Lipídeos de Membrana/metabolismo , Solventes/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Zymomonas/efeitos dos fármacos
7.
Int J Biol Macromol ; 138: 1-12, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302127

RESUMO

In this study, a CotA laccase from Bacillus subtilis cjp3 was successfully immobilized onto magnetic graphene oxide (MGO) nanomaterials via covalent bonding with hydrochloride/N-hydroxysuccinimide (EDC/NHS). The morphology, structure, and properties of the MGO-laccase were then characterized by scanning-electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray-photoelectron spectroscopy (XPS), and a magnetic-property-measurement system (MPMS). The magnetic composite exhibited an extremely high binding capacity of ~145.04mg/g and maintained maximal relative enzyme activities at 25°C, pH7, and a reaction time of 2h. The pH, thermal, operational, and storage stabilities of MGO-laccase were significantly improved over those of free laccase. Moreover, MGO-laccase exhibited a higher tolerance than that of free laccase in the presence of organic solvents, inhibitors, metal ions, and salts. Furthermore, MGO-laccase showed good decolorization performance of malachite green (MG), with decolorization rates reaching 99% after 5h of reaction at 30°C and pH6. In addition, the maximum saturation magnetization of MGO-laccase was 27.7emu/g, allowing for rapid magnetic separation. Accordingly, magnetic separation allowed MGO-laccase to maintain 75% of its activity after ten consecutive decolorization cycles.


Assuntos
Bacillus subtilis/enzimologia , Grafite/química , Lacase/química , Lacase/metabolismo , Imãs/química , Corantes de Rosanilina/metabolismo , Inibidores Enzimáticos/farmacologia , Estabilidade Enzimática , Enzimas Imobilizadas/antagonistas & inibidores , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Cinética , Lacase/antagonistas & inibidores , Metais/farmacologia , Corantes de Rosanilina/isolamento & purificação , Sais/farmacologia , Solventes/farmacologia , Succinimidas/química
8.
Int J Biol Macromol ; 137: 442-454, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31254575

RESUMO

LipMF3 is a new lipase isolated from a metagenomic library derived from a fat-contaminated soil. It belongs to the lipase subfamily I.1 and has identities of 68% and 67% with lipases of Chromobacterium violaceum and C. amazonense, respectively. Genes encoding LipMF3 and its cognate foldase, LifMF3, were cloned and co-expressed in Escherichia coli. The highest hydrolytic activity of purified Lip-LifMF3 was at 40 °C and pH 6.5. Under these conditions, the highest activity was against tributyrin (1650 U mg-1), but it also had high activity against olive oil (862 U mg-1). It was stable in hydrophilic organic solvents (25%, v/v in water) with residual activity around 100% after 24 h. It also showed stability over a wide pH range (5.5 to 11) with residual activity above 80% after 24 h. Lip-LifMF3 was immobilized by covalent bonding onto Immobead 150P and by adsorption onto Sepabeads FP-BU. The latter preparation gave the best results, producing 94% conversion after 5 h for the synthesis of ethyl oleate and a 90% enantiomeric excess of the product (R)­1­phenylethyl acetate for the kinetic resolution of (R,S)­1­phenyl­1­ethanol. The results obtained in this work provide a basis for the development of applications of Lip-LifMF3 in biocatalysis.


Assuntos
Ácidos Graxos/análise , Biblioteca Gênica , Lipase/química , Lipase/metabolismo , Metagenoma , Microbiologia do Solo , Solo/química , Sequência de Aminoácidos , Chromobacterium/enzimologia , Estabilidade Enzimática , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Modelos Moleculares , Conformação Proteica , Solventes/farmacologia , Temperatura , Triglicerídeos/metabolismo
9.
Int J Biol Macromol ; 136: 1086-1095, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31233790

RESUMO

As a new generation of green solvent, the utilization of natural deep eutectic solvents (NADESs) in enzymatic reactions has attracted widespread academic and industrial interests. Especially, choline chloride-glycerol (C-Gly) has been extensively used in many green chemistry processes. In this study, a series of C-Gly-water binary systems with extremely low viscosity were successfully constructed, and the enzyme performance in these binary systems was measured. The results showed that Candida antarctica lipase B (CALB) can be activated up to 156.64 ±â€¯8.12% (7832.00 ±â€¯162.47 U/mL) (when the mole fraction (x(D2O)) of water was 0.3), and a relatively high recycle stability (90.12 ±â€¯1.77%) can be maintained when the mole fraction of water was from 0.0 to 0.6. Moreover, the enzyme performance was also explored in enzymatic synthesis of lauroyl glycine, and the results were highly agreement with pNPP assay. Molecular interaction between CALB and NADESs was studied by molecular dynamics methods. When x(D2O) was 0.3, a balance between the structural rigidity and flexibility can be maintained, while the balance was destroyed when x(D2O) was increased up to 0.7. Moreover, we also found that both clusters and monomers of NADESs can maintain high activity and stability of Candida antarctica lipase B (CALB). Therefore, this approach could provide a platform for the further utilization of NADESs in enzymatic reactions.


Assuntos
Colina/química , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Glicerol/química , Lipase/química , Lipase/metabolismo , Solventes/química , Solventes/farmacologia , Água/química , Ativação Enzimática/efeitos dos fármacos , Estabilidade Enzimática/efeitos dos fármacos , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Conformação Proteica , Solventes/metabolismo , Viscosidade
10.
Int J Biol Macromol ; 136: 296-304, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31176858

RESUMO

In presented study analysis of physicochemical properties of deep eutectic solvents (DESs) and their usefulness as an element of reaction medium for ß-galactosidase from Kluyveromyces lactis was conducted. Analyzed DESs were based on choline salt derivatives: choline chloride, choline acetate and hydrogen bond-donors (HBD) such as: glycerol, ethylene glycol, urea, thiourea and levulinic acid. Results showed that reaction medium with appropriate amount of DES based on choline acetate had beneficial effect on activity of ß-galactosidase. The 5% (v/v) addition of developed choline acetate:glycerol DES mixture enhanced enzyme activity almost three fold. The results of performed experiments have also revealed that ß-galactosidase activity is less affected by the organic anion as choline acetate in ionic liquid, than inorganic anion as choline chloride. The developed green solvents as DES based on choline acetate exhibit a wide application potential that can be used to increase efficiency of enzyme-based industrial process.


Assuntos
Fenômenos Químicos , Colina/química , Solventes/química , Solventes/farmacologia , beta-Galactosidase/metabolismo , Condutividade Elétrica , Viscosidade
11.
Nucleic Acids Res ; 47(13): 6569-6577, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31170298

RESUMO

The RNA World hypothesis posits that RNA was once responsible for genetic information storage and catalysis. However, a prebiotic mechanism has yet to be reported for the replication of duplex RNA that could have operated before the emergence of polymerase ribozymes. Previously, we showed that a viscous solvent enables information transfer from one strand of long RNA duplex templates, overcoming 'the strand inhibition problem'. Here, we demonstrate that the same approach allows simultaneous information transfer from both strands of long duplex templates. An additional challenge for the RNA World is that structured RNAs (like those with catalytic activity) function poorly as templates in model prebiotic RNA synthesis reactions, raising the question of how a single sequence could serve as both a catalyst and as a replication template. Here, we show that a viscous solvent also facilitates the transition of a newly synthesized hammerhead ribozyme sequence from its inactive, duplex state to its active, folded state. These results demonstrate how fluctuating environmental conditions can allow a ribozyme sequence to alternate between acting as a template for replication and functioning as a catalyst, and illustrate the potential for temporally changing environments to enable molecular processes necessary for the origin of life.


Assuntos
Modelos Genéticos , Origem da Vida , RNA Catalítico/efeitos dos fármacos , RNA de Cadeia Dupla/genética , Solventes/farmacologia , Moldes Genéticos , Catálise , Eletroforese em Gel de Ágar , Técnicas In Vitro , Conformação de Ácido Nucleico , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , RNA Catalítico/metabolismo , RNA de Cadeia Dupla/biossíntese , Viscosidade
12.
Biochem Soc Trans ; 47(3): 919-932, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31085615

RESUMO

Biological membranes form the boundaries to cells. They are integral to cellular function, retaining the valuable components inside and preventing access of unwanted molecules. Many different classes of molecules demonstrate disruptive properties to the plasma membrane. These include alcohols, detergents and antimicrobial agents. Understanding this disruption and the mechanisms by which it can be mitigated is vital for improved therapeutics as well as enhanced industrial processes where the compounds produced can be toxic to the membrane. This mini-review describes the most common molecules that disrupt cell membranes along with a range of in vitro liposome-based techniques that can be used to monitor and delineate these disruptive processes.


Assuntos
Lipossomos , Modelos Biológicos , Anestésicos Locais/farmacologia , Anti-Infecciosos/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Detergentes/farmacologia , Solventes/farmacologia
13.
Viruses ; 11(3)2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30866548

RESUMO

BACKGROUND: Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related members of the Semliki Forest complex within the genus alphavirus and are transmitted by arthropods, causing acute febrile illness in humans. CHIKV has spread to almost all continents, whereas autochthonous MAYV infections have been reported in South America and in the Caribbean. Nevertheless, there was concern about potential spread of MAYV to other regions similar to CHIKV in the past. The risk for transmission of emerging viruses by blood transfusion and the safety of plasma-derived medicinal products (PDMPs) are constant concerns. The manufacturing processes of PDMPs include procedures to inactivate/remove viruses. METHODS: In this study, we investigated the reduction of MAYV and CHIKV by heat inactivation in various matrices, solvent/detergent treatment and nanofiltration. RESULTS: Unexpectedly, MAYV was significantly more resistant to heat and solvent/detergent treatment compared to CHIKV. However, being similar in size, both MAYV and CHIKV were removed below the detection limit by 35 nm virus filters. CONCLUSIONS: The inactivation profiles of different alphavirus members vary considerably, even within the Semliki Forest Complex. However, robust dedicated viral inactivation/removal procedures commonly used in the plasma product industry are effective in inactivating or removing MAYV and CHIKV.


Assuntos
Alphavirus/isolamento & purificação , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/isolamento & purificação , Temperatura Alta , Plasma/virologia , Inativação de Vírus , Animais , Febre de Chikungunya/transmissão , Chlorocebus aethiops , Detergentes/farmacologia , Filtração/métodos , Nanotecnologia/métodos , Solventes/farmacologia , Células Vero
14.
Mil Med ; 184(Suppl 1): 615-620, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901442

RESUMO

OBJECTIVE: Information is summarized from the overall body of published literature regarding ototoxic chemicals encountered outside of clinical exposures, largely in occupational settings. While summarizing the most common non-pharmaceutical ototoxins, this review provides clinically relevant information and recommendations such that hearing health professionals may adopt a more comprehensive and appropriate diagnostic case history, test battery, documentation scheme, and education delivery. METHODS: Solvents, metals, and asphyxiants literature was reviewed using PubMed, national and international agency websites, and communications with known ototoxicity experts. RESULTS: Initial intentions to summarize the existing programs for occupational ototoxicity monitoring fell short when it was discovered that such programs have not yet formalized across the major oversight agencies in the United States. Instead, recommended guidance documents and fact sheets, which highlight existing occupational exposure limits and suggest monitoring and education are discussed. CONCLUSIONS: While evidence in humans is limited, potentially ototoxic substances are worthy of improved surveillance and further research to understand their ototoxic mechanisms, effects, and possible mitigation strategies. A triad approach of monitoring, protecting, and educating is recommended for effective prevention of hearing loss: the Department of Defense Hearing Center of Excellence's Comprehensive Hearing Health Program model employs such an approach.


Assuntos
Dispositivos de Proteção das Orelhas/normas , Perda Auditiva/etiologia , Exposição Ocupacional/efeitos adversos , Perda Auditiva/prevenção & controle , Humanos , Metais/efeitos adversos , Metais/farmacologia , Militares/estatística & dados numéricos , Exposição Ocupacional/análise , Fatores de Risco , Solventes/efeitos adversos , Solventes/farmacologia , Estados Unidos
15.
Metab Eng ; 54: 83-95, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30885767

RESUMO

Green organic solvents such as ionic liquids (ILs) have versatile use but are inhibitory to microbes even at low concentrations of 0.5-1.0% (v/v) ILs. We discovered the oleaginous yeast Yarrowia lipolytica can grow in 10% (v/v) of 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), which makes it more tolerant than most engineered microorganisms and naturally screened isolates. However, the underlying mechanism of IL tolerance in Y. lipolytica is not understood. Through adaptive laboratory evolution, in combination with physiological characterization and omics analysis, we shed light on the underlying mechanism of how Y. lipolytica restructures its membrane to tolerate different types of ILs at high levels up to 18% ILs. Specifically, we discovered that sterols play a key role for exceptional IL tolerance in Y. lipolytica.


Assuntos
Membrana Celular , Evolução Molecular Direcionada , Imidazóis/farmacologia , Líquidos Iônicos/farmacologia , Solventes/farmacologia , Yarrowia , Membrana Celular/genética , Membrana Celular/metabolismo , Yarrowia/genética , Yarrowia/metabolismo
16.
Medicina (Kaunas) ; 55(3)2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30862060

RESUMO

Background and objectives: Zingerone is an ingredient of ginger (Zingiber officinale) with different pharmacological activities. Several studies have investigated the effect of zingerone on various gastrointestinal diseases, including irritable bowel syndrome and diarrhea. This study is aimed to evaluate the effect of zingerone on ethanol-induced gastric ulcers in rats. Materials and Methods: Gastric ulcers were induced by ethanol (96%, 5 mL/kg, po) in male wistar rats and zingerone (50, 100, and 200 mg/kg) was administrated orally. Normal saline and ranitidine were used as negative and positive control, respectively. In this study, the number and length of ulcers, and malondialdehyde (MDA) and nitric oxide (NO) levels in stomach tissues were determined. Results: The findings showed that the mean number and length of gastric ulcers were significantly lower in zingerone-received groups than ethanol group (P < 0.05). The level of malondialdehyde was decreased in the stomach of zingerone groups (P < 0.05) compared to the ethanol group. In addition, zingerone treatment prevented the decrease of nitric oxide level by ethanol in the stomach tissue. Conclusions: The present study showed that zingerone has a protective effect on the ethanol-induced gastric ulcer, which may be due to its free radical scavenging activity.


Assuntos
Antiulcerosos/uso terapêutico , Gengibre/química , Guaiacol/análogos & derivados , Fitoterapia , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Modelos Animais de Doenças , Etanol/administração & dosagem , Etanol/efeitos adversos , Etanol/farmacologia , Mucosa Gástrica/metabolismo , Guaiacol/administração & dosagem , Guaiacol/farmacologia , Guaiacol/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Necrose , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Solventes/administração & dosagem , Solventes/efeitos adversos , Solventes/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle
17.
J Biotechnol ; 296: 1-6, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30853640

RESUMO

In this study, a commercial lipase derived from Candida cylindracea was chemically modified with dextran by conjugating ε-amine in the lysine residue with the carbonyl residue in oxidized dextran using the borane-pyridine complex as a reducing agent to increase the hydrophilicity of the microenvironment around the lipase in the presence of organic solvents. The degree of modification (53.2%), amount of dextran (0.66 g/g-lipase), specific activity (similar to that of the unmodified lipase), and stability in the presence of ethanol and 2-propanol (the half-lives were 2.24 and 1.86 times longer than those of the unmodified lipase) were higher for the lipase modified at pH 8.0 than for the lipases modified at other pH levels. Following modification with dextran at pH 8.0, the stability of the modified lipase was higher than that of the unmodified lipase in the presence of 25% (v/v) DMSO, ethanol, 2-propanol, toluene, n-hexane, and isooctane (the half-lives were 1.45, 2.24, 1.86, 1.76, 2.67 and 2.95 times longer than those of the unmodified lipase). Therefore, chemical modification with polysaccharides such as dextran using the borane-pyridine complex as a reducing agent could be a promising approach for improving the organic solvent stability of enzymes.


Assuntos
Candida/enzimologia , Estabilidade Enzimática/efeitos dos fármacos , Lipase/química , Solventes/química , Boranos/química , Dextranos/química , Compostos Orgânicos/química , Compostos Orgânicos/farmacologia , Piridinas/química , Solventes/farmacologia
18.
Int J Biol Macromol ; 130: 253-265, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30797006

RESUMO

Biocatalysts exerting activity against ester bonds have a broad range of applications in modern biotechnology. Some of the most industrially relevant enzymes of this type are lipolytic and their market is predicted to uphold leadership up till 2024. In this study, a novel bacterial hormone-sensitive lipase-like (bHSL) family homologue, designated EstAG1, was discovered by mining gDNA of bacteria isolated from fat contaminated soil in Lithuania. Putative lipolytic enzyme was cloned, overexpressed in E. coli, purified and characterized determining its biochemical properties. While the true physiological role of the discovered leaderless, ~36 kDa enzyme is unknown, metal-activated EstAG1 possessed optima at 45-47.5 °C, pH 7.5-8, with a generally intermediate activity profile between esterases and lipases. Furthermore, EstAG1 was hyperactivated by ethanol, dioxane and DMSO, implicating that it could be industrially applicable enzyme for the synthesis of valuable products such as biodiesel, flavor esters, etc. Sequence analysis and structure modeling revealed that the highest sequence homology of EstAG1 with the closest structurally and functionally described protein makes up only 26%. It was also revealed that EstAG1 has some differences in the bHSL family-characteristic conserved sequence motives. Therefore, EstAG1 presents interest both in terms of biotechnological applications and basic research.


Assuntos
Lipase/metabolismo , Compostos Orgânicos/farmacologia , Solventes/farmacologia , Staphylococcus saprophyticus/enzimologia , Sequência de Aminoácidos , Biocatálise , Técnicas de Química Sintética , Detergentes/farmacologia , Estabilidade Enzimática , Regulação Bacteriana da Expressão Gênica , Concentração de Íons de Hidrogênio , Lipase/química , Lipase/genética , Metais/farmacologia , Modelos Moleculares , Filogenia , Conformação Proteica , Análise de Sequência , Staphylococcus saprophyticus/genética , Estereoisomerismo , Especificidade por Substrato , Temperatura
19.
Eur J Pharm Sci ; 132: 55-62, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30797027

RESUMO

The effect of heat on the follicular absorption of drugs into the skin has not previously been investigated. In comparison to drug delivery across the continuous stratum corneum (SC), follicular absorption is known to be relatively rapid and therefore the use of short durations of heat may be particularly useful for enhancing drug delivery to the hair follicles, as well as being practical for patients to use. In this study erythromycin has been used as a model drug and the combined use of heat and chemical penetration enhancers was found to be able to synergistically increase the penetration of erythromycin into human skin via the follicular route. Moreover durations of heat application as short as 10 min in combination with particular enhancer systems were found to be sufficient to significantly increase erythromycin delivery to the skin. Overall the data indicate that the use of heat with chemical penetration enhancers offers a potentially valuable strategy for delivering drugs via the follicular route.


Assuntos
Eritromicina/farmacocinética , Folículo Piloso/metabolismo , Temperatura Alta , Absorção Cutânea/efeitos dos fármacos , Pele/metabolismo , Solventes/farmacologia , Administração Cutânea , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Eritromicina/administração & dosagem , Humanos , Técnicas In Vitro , Solubilidade , Solventes/química
20.
Biophys J ; 116(5): 755-759, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30777306

RESUMO

Methanol is a common solubilizing agent used to study transmembrane proteins/peptides in biological and synthetic membranes. Using small angle neutron scattering and a strategic contrast-matching scheme, we show that methanol has a major impact on lipid dynamics. Under increasing methanol concentrations, isotopically distinct 1,2-dimyristoyl-sn-glycero-3-phosphocholine large unilamellar vesicle populations exhibit increased mixing. Specifically, 1,2-dimyristoyl-sn-glycero-3-phosphocholine transfer and flip-flop kinetics display linear and exponential rate enhancements, respectively. Ultimately, methanol is capable of influencing the structure-function relationship associated with bilayer composition (e.g., lipid asymmetry). The use of methanol as a carrier solvent, despite better simulating some biological conditions (e.g., antimicrobial attack), can help misconstrue lipid scrambling as the action of proteins or peptides, when in actuality it is a combination of solvent and biological agent. As bilayer compositional stability is crucial to cell survival and protein reconstitution, these results highlight the importance of methanol, and solvents in general, in biomembrane and proteolipid studies.


Assuntos
Dimiristoilfosfatidilcolina/química , Dimiristoilfosfatidilcolina/metabolismo , Metanol/farmacologia , Difração de Nêutrons , Espalhamento a Baixo Ângulo , Cinética , Solventes/farmacologia , Lipossomas Unilamelares/química , Lipossomas Unilamelares/metabolismo
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