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1.
Rev Esp Anestesiol Reanim (Engl Ed) ; 69(2): 71-78, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35183469

RESUMO

BACKGROUND: Celiac plexus neurolysis (CPN) has been used to control pancreatic cancer (PC) pain, up to our knowledge, there is no study compared intraoperative CPN and computed tomography (CT)-guided techniques. OBJECTIVES: To compare the effects of intraoperative and CT-guided CPN in unresectable PC on pain intensity and analgesic requirements. METHODS: A total of 90 patients were enrolled in this prospective, randomized, open label, controlled, non-inferiority study, 20 patients were excluded or lost to follow up. The patients were randomly allocated to either intraoperative or CT-guided CPN group. A mixture of 20 mL ethanol 90%, 100 mg lignocaine and 5 mg dexamethasone was infused on each side of the aorta in both groups. Visual analogue score (VAS) and oral daily tramadol consumption were recorded at day 7, 14, 30, 60, 120 and 180 days after intervention. Occurrence of any intervention related complications were reported. RESULTS: Median VAS was similar in both intraoperative and CT-guided CPN groups from day 7 up to 180 days after intervention. The median daily analgesic consumption of oral tramadol (mg) was comparable in both intraoperative and CT-guided CPN groups after intervention at day 7 (50 versus 50), day14 (50 versus 50), day 30 (50 versus 50), day 60 (50 versus 50), day 120 (100 versus 75) and day 180 (100 versus 100). The incidence of diarrhea, vomiting, hypotension and back pain was similar in both groups. CONCLUSION: Intraoperative CPN is non-inferior to CT-guided CPN as both techniques were similarly associated with reduced pain severity and analgesics requirements.


Assuntos
Dor do Câncer , Plexo Celíaco , Neoplasias Pancreáticas , Tramadol , Dor Abdominal/etiologia , Analgésicos , Plexo Celíaco/cirurgia , Humanos , Neoplasias Pancreáticas/cirurgia , Estudos Prospectivos , Tramadol/uso terapêutico , Neoplasias Pancreáticas
2.
Biotechnol Bioeng ; 119(2): 493-503, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34796477

RESUMO

Lignin valorization may offer a sustainable approach to achieve a chemical industry that is not completely dependent on fossil resources for the production of aromatics. However, lignin is a recalcitrant, heterogeneous, and complex polymeric compound for which only very few catalysts can act in a predictable and reproducible manner. Laccase is one of those catalysts and has often been referred to as an ideal "green" catalyst, as it is able to oxidize various linkages within lignin to release aromatic products, with the use of molecular oxygen and formation of water as the only side product. The extent and rate of laccase-catalyzed lignin conversion were measured using the label-free analytical technique isothermal titration calorimetry (ITC). IITC provides the molar enthalpy of the reaction, which reflects the extent of conversion and the time-dependent power trace, which reflects the rate of the reaction. Calorimetric assessment of the lignin conversion brought about by various fungal and bacterial laccases in the absence of mediators showed marked differences in the extent and rate of conversion for the different enzymes. Kraft lignin conversion by Trametes versicolor laccase followed Michaelis-Menten kinetics and was characterized by the following thermodynamic and kinetic parameters ΔHITC = -(2.06 ± 0.06)·103 kJ mol-1 , KM = 6.6 ± 1.2 µM and Vmax = 0.30 ± 0.02 U/mg at 25°C and pH 6.5. We envision calorimetric techniques as important tools for the development of enzymatic lignin valorization strategies.


Assuntos
Calorimetria/métodos , Lacase , Lignina , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Cinética , Lacase/química , Lacase/metabolismo , Lignina/análise , Lignina/química , Lignina/metabolismo , Polyporaceae/enzimologia , Polyporaceae/genética
3.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34565567

RESUMO

BACKGROUND: Celiac plexus neurolysis (CPN) has been used to control pancreatic cancer (PC) pain, up to our knowledge, there is no study compared intraoperative CPN and computed tomography (CT)-guided techniques. OBJECTIVES: To compare the effects of intraoperative and CT-guided CPN in unresectable PC on pain intensity and analgesic requirements. METHODS: A total of 90 patients were enrolled in this prospective, randomized, open label, controlled, non-inferiority study, 20 patients were excluded or lost to follow up. The patients were randomly allocated to either intraoperative or CT-guided CPN group. A mixture of 20ml ethanol 90%, 100mg lignocaine and 5mg dexamethasone was infused on each side of the aorta in both groups. Visual analogue score (VAS) and oral daily tramadol consumption were recorded at day 7, 14, 30, 60, 120 and 180 days after intervention. Occurrence of any intervention related complications were reported. RESULTS: Median VAS was similar in both intraoperative and CT-guided CPN groups from day 7 up to 180 days after intervention. The median daily analgesic consumption of oral tramadol (mg) was comparable in both intraoperative and CT-guided CPN groups after intervention at day 7 (50 versus 50), day14 (50 versus 50), day 30 (50 versus 50), day 60 (50 versus 50), day 120 (100 versus 75) and day 180 (100 versus 100). The incidence of diarrhea, vomiting, hypotension and back pain was similar in both groups. CONCLUSION: Intraoperative CPN is non-inferior to CT-guided CPN as both techniques were similarly associated with reduced pain severity and analgesics requirements.

4.
Molecules ; 26(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374759

RESUMO

Humans have witnessed three deadly pandemics so far in the twenty-first century which are associated with novel coronaviruses: SARS, Middle East respiratory syndrome (MERS), and COVID-19. All of these viruses, which are responsible for causing acute respiratory tract infections (ARTIs), are highly contagious in nature and/or have caused high mortalities. The recently emerged COVID-19 disease is a highly transmittable viral infection caused by another zoonotic novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to the other two coronaviruses such as SARS-CoV-1 and MERS-CoV, SARS-CoV-2 is also likely to have originated from bats, which have been serving as established reservoirs for various pathogenic coronaviruses. Although, it is still unknown how SARS-CoV-2 is transmitted from bats to humans, the rapid human-to-human transmission has been confirmed widely. The disease first appeared in Wuhan, China, in December 2019 and quickly spread across the globe, infected 48,539,872 people, and caused 1,232,791 deaths in 215 countries, and the infection is still spreading at the time of manuscript preparation. So far, there is no definite line of treatment which has been approved or vaccine which is available. However, different types of potential vaccines and therapeutics have been evaluated and/or are under clinical trials against COVID-19. In this review, we summarize different types of acute respiratory diseases and briefly discuss earlier outbreaks of coronaviruses and compare their occurrence and pathogenicity with the current COVID-19 pandemic. Various epidemiological aspects of COVID-19 such as mode of spread, death rate, doubling time, etc., have been discussed in detail. Apart from this, different technical issues related to the COVID-19 pandemic including use of masks and other socio-economic problems associated with the pandemic have also been summarized. Additionally, we have reviewed various aspects of patient management strategies including mechanism of action, available diagnostic tools, etc., and also discussed different strategies for the development of effective vaccines and therapeutic combinations to deal with this viral outbreak. Overall, by the inclusion of various references, this review covers, in detail, the most important aspects of the COVID-19 pandemic.


Assuntos
COVID-19/epidemiologia , Pandemias , Antivirais/uso terapêutico , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Humanos , SARS-CoV-2/isolamento & purificação , Tratamento Farmacológico da COVID-19
5.
AMB Express ; 9(1): 176, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673872

RESUMO

Essential oils (EOs) from the stems and leaves of Origanum vulgare L. grown in Saudi Arabia and Jordan were analyzed by gas chromatography-mass spectrometry (GC-MS) and GC-flame ionization detector (FID) techniques on two different columns (polar and nonpolar). A detailed phytochemical analysis led to the identification of 153 constituents of these essential oils. Both Saudi and Jordanian plants are classified by chemotypes rich in cymyl-compounds. However, the Saudi Origanum contains carvacrol as the major component and is, thus, characterized as a carvacrol chemotype, while the Jordanian Origanum contains thymol as the major component, and, thus, it is classified as a thymol chemotype. In addition, the antimicrobial activities of the studied EOs and their major components, including carvacrol and thymol, were evaluated against various Gram-positive and Gram-negative microorganisms. All the tested compounds exhibited significant antimicrobial activity against all the tested bacteria. Among them, thymol demonstrated superior activity against all the tested organisms, followed by carvacrol. Moreover, results on oil composition and oil yield of O. vulgare L. from different parts of the world is compared in detail with the present outcomes.

6.
J R Soc Interface ; 16(155): 20190237, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31238838

RESUMO

Co-axial electrohydrodynamic atomization was used to prepare core/shell polymethylsilsesquioxane particles for co-delivery of metformin and glibenclamide in a sustained release manner. The drug-loaded microparticles were mostly spherical and uniformly distributed in size, with average diameters between 3 and 5 µm across various batches. FTIR was used to confirm the presence of drugs within the particles while X-ray diffraction studies revealed drugs encapsulated existed predominantly in the amorphous state. Intended as systems that potentially can act as depot formulations for long-term release of antidiabetics, a detailed analysis of drug release from these particles was necessary. Drugs of different solubilities were selected in order to study the effects of drug solubility from a core/shell particle system. Further analyses to determine how conditions such as release into a limited volume of media, sampling rate and partitioning of drug between the core and shell layers influenced drug release were conducted by comparing experimental and mathematically modelled outcomes. It was found that while the solubility of drug may affect release from such systems, rate of removal of drug (sampling frequency) which upsets local equilibrium at the particle/solution interface prompting a rapid release to redress the equilibrium influenced release more.


Assuntos
Portadores de Fármacos , Glibureto , Metformina , Compostos de Organossilício/química , Polímeros/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Glibureto/química , Glibureto/farmacocinética , Metformina/química , Metformina/farmacocinética , Solubilidade
7.
J R Soc Interface ; 15(145)2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30158187

RESUMO

Single and coaxial electrospraying was used to prepare Eudragit L100-55 polymer microparticles containing prednisolone as the active pharmaceutical ingredient. Different compositions of prednisolone and Eudragit L100-55 were used to develop five different formulations with different polymer : drug ratios. The resultant microparticles had a toroidal shape with a narrow size distribution. Prednisolone was present in an amorphous physical state, as confirmed by X-ray diffraction analysis. Dissolution studies were carried out in order to investigate the feasibility of the proposed system for site-specific release of prednisolone. The release rates were interpreted in terms of diffusion-controlled release. It was shown that utilization of pH-responsive Eudragit L100-55 could minimize the release of prednisolone in the acidic conditions of the stomach, which was followed by rapid release as the pH of the release medium was adjusted to 6.8 after the first 2 h. This is especially desirable for the treatment of conditions including inflammatory bowel disease and colon cancer.


Assuntos
Portadores de Fármacos , Intestinos , Prednisolona , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Resinas Acrílicas/farmacologia , Animais , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Prednisolona/química , Prednisolona/farmacocinética , Prednisolona/farmacologia , Fatores de Tempo
8.
Open Microbiol J ; 12: 123-134, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29785219

RESUMO

INTRODUCTION: Anaerobic digestion for methane production comprises of an exceptionally diverse microbial consortium, a profound understanding about which is still constrained. In this study, the methanogenic archaeal communities in three full-scale anaerobic digesters of a Municipal Wastewater Treatment Plant were analyzed by Fluorescence in situ hybridization and quantitative real-time Polymerase Chain Reaction (qPCR) technique. METHODS & MATERIALS: Fluorescence in situ hybridization (FISH) was performed to detect and quantify the methanogenic Archaea in the sludge samples whereas qPCR was carried out to support the FISH analysis. Multiple probes targeting domain archaea, different orders and families of Archaea were used for the studies. RESULTS AND DISCUSSION: In general, the aceticlastic organisms (Methanosarcinaceae & Methanosaetaceae) were more abundant than the hydrogenotrophic organisms (Methanobacteriales, Methanomicrobiales, Methanobacteriaceae & Methanococcales). Both FISH and qPCR indicated that family Methanosaetaceae was the most abundant suggesting that aceticlastic methanogenesis is probably the dominant methane production pathway in these digesters. CONCLUSION: Future work involving high-throughput sequencing methods and correlating archaeal communities with the main operational parameters of anaerobic digesters will help to obtain a better understanding of the dynamics of the methanogenic archaeal community in wastewater treatment plants in United Arab Emirates (UAE) which in turn would lead to improved performance of anaerobic sludge digesters.

9.
APMIS ; 126(3): 215-226, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29484747

RESUMO

Customary consumption of unpasteurized milk by the population in the central Najed region of Saudi Arabia may pose a health risk. Therefore, 80 camel milk samples were collected aseptically from seven different stations of Riyadh region. The biochemical and microbiological properties of these milk samples were determined. Nutrient agar and brain heart infusion agar were used to determine mesophilic aerobic counts (MACs). The MAC in each mL of milk varied from 60 to 16 × 104  CFU/mL on nutrient agar. Based on the colony morphology, 176 colonies were collected from different samples, and these isolates were de-replicated into 80 unique isolates using rep-PCR analysis. Surprisingly, the 16S rRNA sequence analysis of these strains revealed that more than one-third of the collected milk samples contained strains that share maximum sequence similarities with well-known pathogens, such as Brucella, Bacillus anthracis, Listeria monocytogenes, and MRSA. Furthermore, many strains exhibit 16S rRNA gene similarity with opportunistic pathogens such as Citrobacter freundii and Kytococcus schroeteri. Many strains exhibit ß-hemolytic activity and resistant to six different antibiotics. Our study suggested that consumption of raw camel milk from this region constitutes a great health risk.


Assuntos
Bactérias/isolamento & purificação , Leite/química , Leite/microbiologia , Animais , Bacillus anthracis/genética , Bacillus anthracis/isolamento & purificação , Bactérias/genética , Carga Bacteriana , Brucella/genética , Brucella/isolamento & purificação , Camelus , Citrobacter freundii/genética , Citrobacter freundii/isolamento & purificação , Microbiologia de Alimentos , Humanos , Listeria monocytogenes/genética , Listeria monocytogenes/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Micrococcaceae/genética , Micrococcaceae/isolamento & purificação , Pasteurização , RNA Ribossômico 16S/genética , Arábia Saudita
10.
Proc Natl Acad Sci U S A ; 114(15): 3843-3848, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28348243

RESUMO

The kinetics of hydrogen oxidation and evolution by [FeFe]-hydrogenases have been investigated by electrochemical impedance spectroscopy-resolving factors that determine the exceptional activity of these enzymes, and introducing an unusual and powerful way of analyzing their catalytic electron transport properties. Attached to an electrode, hydrogenases display reversible electrocatalytic behavior close to the 2H+/H2 potential, making them paradigms for efficiency: the electrocatalytic "exchange" rate (measured around zero driving force) is therefore an unusual parameter with theoretical and practical significance. Experiments were carried out on two [FeFe]-hydrogenases, CrHydA1 from the green alga Chlamydomonas reinhardtii, which contains only the active-site "H cluster," and CpI from the fermentative anaerobe Clostridium pasteurianum, which contains four low-potential FeS clusters that serve as an electron relay in addition to the H cluster. Data analysis yields catalytic exchange rates (at the formal 2H+/H2 potential, at 0 °C) of 157 electrons (78 molecules H2) per second for CpI and 25 electrons (12 molecules H2) per second for CrHydA1. The experiments show how the potential dependence of catalytic electron flow comprises frequency-dependent and frequency-independent terms that reflect the proficiencies of the catalytic site and the electron transfer pathway in each enzyme. The results highlight the "wire-like" behavior of the Fe-S electron relay in CpI and a low reorganization energy for electron transfer on/off the H cluster.


Assuntos
Hidrogênio/química , Hidrogenase/metabolismo , Catálise , Domínio Catalítico , Chlamydomonas reinhardtii/enzimologia , Clostridium/enzimologia , Espectroscopia de Ressonância de Spin Eletrônica , Transporte de Elétrons , Cinética , Modelos Moleculares , Conformação Proteica
11.
Acta Microbiol Immunol Hung ; 64(2): 203-216, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28218004

RESUMO

Although the antimicrobial activity of the engineered nanoparticles (NPs) is well known, the biochemical mechanisms underlying this activity are not clearly understood. Therefore, four NPs with the highest global production, namely SiO2, TiO2, ZnO, and Ag, were synthesized and characterized. The synthesized SiO2, TiO2, ZnO, and Ag NPs exhibit an average size of 11.12, 13.4, 35, and 50 nm, respectively. The antimicrobial activity of the synthesized NPs against bacteria and fungi were also determined. NPs-mediated inhibition of two very important enzymes, namely urease and DNA polymerase, is also reported. The synthesized NPs especially Ag and ZnO show significant antimicrobial activity against bacteria and fungi including methicillin-resistant Staphylococcus aureus even at low concentration. The DNA polymerase activity was inhibited at a very low concentration range of 2-4 µg/ml, whereas the urease activity was inhibited at a high concentration range of 50-100 µg/ml. Based on their ability to inhibit the urease and DNA polymerase, NPs can be arranged in the following order: Ag > ZnO > SiO2 > TiO2 and Ag > SiO2 > ZnO > TiO2, respectively. As the synthesized NPs inhibit bacterial growth and suppress the activity of urease and DNA polymerase, the use of these NPs to control pathogens is proposed.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Nanopartículas/química , Inibidores da Síntese de Ácido Nucleico/síntese química , Inibidores da Síntese de Ácido Nucleico/farmacologia , Anti-Infecciosos/química , Bactérias/enzimologia , Bactérias/genética , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fungos/enzimologia , Fungos/genética , Testes de Sensibilidade Microbiana , Inibidores da Síntese de Ácido Nucleico/química
12.
Biochemistry ; 56(1): 132-142, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28001048

RESUMO

The active site of Hyd-1, an oxygen-tolerant membrane-bound [NiFe]-hydrogenase from Escherichia coli, contains four highly conserved residues that form a "canopy" above the bimetallic center, closest to the site at which exogenous agents CO and O2 interact, substrate H2 binds, and a hydrido intermediate is stabilized. Genetic modification of the Hyd-1 canopy has allowed the first systematic and detailed kinetic and structural investigation of the influence of the immediate outer coordination shell on H2 activation. The central canopy residue, arginine 509, suspends a guanidine/guanidinium side chain at close range above the open coordination site lying between the Ni and Fe atoms (N-metal distance of 4.4 Å): its replacement with lysine lowers the H2 oxidation rate by nearly 2 orders of magnitude and markedly decreases the H2/D2 kinetic isotope effect. Importantly, this collapse in rate constant can now be ascribed to a very unfavorable activation entropy (easily overriding the more favorable activation enthalpy of the R509K variant). The second most important canopy residue for H2 oxidation is aspartate 118, which forms a salt bridge to the arginine 509 headgroup: its mutation to alanine greatly decreases the H2 oxidation efficiency, observed as a 10-fold increase in the potential-dependent Michaelis constant. Mutations of aspartate 574 (also salt-bridged to R509) to asparagine and proline 508 to alanine have much smaller effects on kinetic properties. None of the mutations significantly increase sensitivity to CO, but neutralizing the expected negative charges from D118 and D574 decreases O2 tolerance by stabilizing the oxidized resting NiIII-OH state ("Ni-B"). An extensive model of the catalytic importance of residues close to the active site now emerges, whereby a conserved gas channel culminates in the arginine headgroup suspended above the Ni and Fe.


Assuntos
Domínio Catalítico , Proteínas de Escherichia coli/química , Hidrogenase/química , Oxirredutases/química , Oxigênio/química , Sequência de Aminoácidos , Arginina/química , Arginina/genética , Arginina/metabolismo , Ácido Aspártico/química , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Sítios de Ligação/genética , Dióxido de Carbono/farmacologia , Cristalografia por Raios X , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Hidrogênio/química , Hidrogênio/metabolismo , Hidrogenase/genética , Hidrogenase/metabolismo , Cinética , Lisina/química , Lisina/genética , Lisina/metabolismo , Modelos Moleculares , Mutação de Sentido Incorreto , Oxirredução/efeitos dos fármacos , Oxirredutases/genética , Oxirredutases/metabolismo , Oxigênio/metabolismo , Prolina/química , Prolina/genética , Prolina/metabolismo , Domínios Proteicos , Homologia de Sequência de Aminoácidos , Termodinâmica
13.
J Environ Sci (China) ; 47: 49-62, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27593272

RESUMO

We have studied the genotoxic and apoptotic potential of ferric oxide nanoparticles (Fe2O3-NPs) in Raphanus sativus (radish). Fe2O3-NPs retarded the root length and seed germination in radish. Ultrathin sections of treated roots showed subcellular localization of Fe2O3-NPs, along with the appearance of damaged mitochondria and excessive vacuolization. Flow cytometric analysis of Fe2O3-NPs (1.0mg/mL) treated groups exhibited 219.5%, 161%, 120.4% and 161.4% increase in intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), nitric oxide (NO) and Ca(2+) influx in radish protoplasts. A concentration dependent increase in the antioxidative enzymes glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (LPO) has been recorded. Comet assay showed a concentration dependent increase in deoxyribonucleic acid (DNA) strand breaks in Fe2O3-NPs treated groups. Cell cycle analysis revealed 88.4% of cells in sub-G1 apoptotic phase, suggesting cell death in Fe2O3-NPs (2.0mg/mL) treated group. Taking together, the genotoxicity induced by Fe2O3-NPs highlights the importance of environmental risk associated with improper disposal of nanoparticles (NPs) and radish can serve as a good indicator for measuring the phytotoxicity of NPs grown in NP-polluted environment.


Assuntos
Poluentes Ambientais/toxicidade , Compostos Férricos/toxicidade , Nanopartículas Metálicas/toxicidade , Mutagênicos/toxicidade , Catalase/metabolismo , Morte Celular , Dano ao DNA , Monitoramento Ambiental/métodos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Mutagenicidade , Estresse Oxidativo , Raphanus , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
14.
J Appl Toxicol ; 36(10): 1284-93, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26918645

RESUMO

Copper ferrite nanoparticles (NPs) have the potential to be applied in biomedical fields such as cell labeling and hyperthermia. However, there is a lack of information concerning the toxicity of copper ferrite NPs. We explored the cytotoxic potential of copper ferrite NPs in human lung (A549) and liver (HepG2) cells. Copper ferrite NPs were crystalline and almost spherically shaped with an average diameter of 35 nm. Copper ferrite NPs induced dose-dependent cytotoxicity in both types of cells, evident by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and neutral red uptake assays. However, we observed a quite different susceptibility in the two kinds of cells regarding toxicity of copper ferrite NPs. Particularly, A549 cells showed higher susceptibility against copper ferrite NP exposure than those of HepG2 cells. Loss of mitochondrial membrane potential due to copper ferrite NP exposure was observed. The mRNA level as well as activity of caspase-3 enzyme was higher in cells exposed to copper ferrite NPs. Cellular redox status was disturbed as indicated by induction of reactive oxygen species (oxidant) generation and depletion of the glutathione (antioxidant) level. Moreover, cytotoxicity induced by copper ferrite NPs was efficiently prevented by N-acetylcysteine treatment, which suggests that reactive oxygen species generation might be one of the possible mechanisms of cytotoxicity caused by copper ferrite NPs. To the best of our knowledge, this is the first report showing the cytotoxic potential of copper ferrite NPs in human cells. This study warrants further investigation to explore the mechanisms of differential toxicity of copper ferrite NPs in different types of cells. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Cobre/toxicidade , Compostos Ferrosos/toxicidade , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Células A549 , Acetilcisteína/farmacologia , Técnicas de Cultura de Células , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Relação Dose-Resposta a Droga , Compostos Ferrosos/química , Citometria de Fluxo , Sequestradores de Radicais Livres/farmacologia , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanopartículas/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
15.
J Phys Chem B ; 119(43): 13690-7, 2015 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-26176986

RESUMO

Protein film electrochemistry has been used to investigate reactions of highly active nickel-containing carbon monoxide dehydrogenases (CODHs). When attached to a pyrolytic graphite electrode, these enzymes behave as reversible electrocatalysts, displaying CO2 reduction or CO oxidation at minimal overpotential. The O2 sensitivity of CODH is suppressed by adding cyanide, a reversible inhibitor of CO oxidation, or by raising the electrode potential. Reduction of N2O, isoelectronic with CO2, is catalyzed by CODH, but the reaction is sluggish, despite a large overpotential, and results in inactivation. Production of H2 and formate under highly reducing conditions is consistent with calculations predicting that a nickel-hydrido species might be formed, but the very low rates suggest that such a species is not on the main catalytic pathway.


Assuntos
Aldeído Oxirredutases/química , Técnicas Eletroquímicas , Complexos Multienzimáticos/química , Níquel/química , Aldeído Oxirredutases/metabolismo , Biocatálise , Eletrodos , Grafite/química , Grafite/metabolismo , Modelos Moleculares , Conformação Molecular , Complexos Multienzimáticos/metabolismo , Níquel/metabolismo , Oxigênio/química , Oxigênio/metabolismo , Thermoanaerobacterium/enzimologia
16.
J Appl Toxicol ; 35(6): 640-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25663373

RESUMO

Dolomite is a natural mineral of great industrial and commercial importance. With the advent of nanotechnology, natural minerals including dolomite in the form of nanoparticles (NPs) are being utilized in various applications to improve the quality of products. However, safety or toxicity information of dolomite NPs is largely lacking. This study evaluated the cytotoxicity of dolomite NPs in two widely used in vitro cell culture models: human airway epithelial (HEp2) and human liver (HepG2) cells. Concentration-dependent decreased cell viability and damaged cell membrane integrity revealed the cytotoxicity of dolomite NPs. We further observed that dolomite NPs induce oxidative stress in a concentration-dependent manner, as indicated by depletion of glutathione and induction of reactive oxygen species (ROS) and lipid peroxidation. Quantitative real-time PCR data demonstrated that the mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were up-regulated whereas the anti-apoptotic gene bcl-2 was down-regulated in HEp2 and HepG2 cells exposed to dolomite NPs. Moreover, the activity of apoptotic enzymes (caspase-3 and caspase-9) was also higher in both kinds of cells treated with dolomite NPs. It is also worth mentioning that HEp2 cells seem to be marginally more susceptible to dolomite NPs exposure than HepG2 cells. Cytotoxicity induced by dolomite NPs was efficiently prevented by N-acetyl cysteine treatment, which suggests that oxidative stress is primarily responsible for the cytotoxicity of dolomite NPs in both HEp2 and HepG2 cells. Toxicity mechanisms of dolomite NPs warrant further investigations at the in vivo level.


Assuntos
Carbonato de Cálcio/toxicidade , Células Hep G2/efeitos dos fármacos , Mucosa Laríngea/efeitos dos fármacos , Magnésio/toxicidade , Nanopartículas Metálicas/toxicidade , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Sobrevivência Celular , Relação Dose-Resposta a Droga , Glutationa/análise , Células Hep G2/química , Humanos , Mucosa Laríngea/química , Mucosa Laríngea/citologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/análise , Reação em Cadeia da Polimerase em Tempo Real , Proteína Supressora de Tumor p53/análise
17.
Colloids Surf B Biointerfaces ; 125: 73-81, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25437066

RESUMO

The present investigation was aimed to study the cytotoxicity, oxidative stress, and genotoxicity induced by molybdenum nanoparticles (Mo-NPs) in mouse skin fibroblast cells (L929). Cells were exposed to different concentrations (1-100 µg/ml) of Mo-NPs (size 40 nm) for 24 and 48 h. After the exposure, different cytotoxicity assays (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide, MTT; neutral red uptake, NRU; and cellular morphology) and oxidative stress markers (lipid peroxidation, LPO; glutathione, GSH; and catalase) were studied. Further, Mo-NPs-induced intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), cell cycle arrest, and DNA damage were also studied. L929 cells treated with Mo-NPs showed a concentration- and time-dependent decrease in cell viability and a loss of the normal cell morphology. The percentage cell viability was recorded as 25%, 42%, and 58% by MTT assay and 24%, 46%, and 56% by NRU assay at 25, 50, and 100 µg/ml of Mo-NPs, respectively after 48 h exposure. Furthermore, the cells showed a significant induction of oxidative stress. This was confirmed by the increase in LPO and ROS generation, as well as the decrease in the GSH and catalase levels. The decrease in MMP also confirms the impaired mitochondrial membrane. The cell cycle analysis and comet assay data revealed that Mo-NPs induced G2/M arrest and DNA damage in a concentration-dependent manner. Our results demonstrated, for the first time, Mo-NPs induced cytotoxicity, oxidative stress and genotoxicity in L929 cells. Thus, data suggest the potential hazardous nature of Mo-NPs.


Assuntos
Fragmentação do DNA/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Molibdênio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Catalase/antagonistas & inibidores , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Relação Dose-Resposta a Droga , Fibroblastos/citologia , Fibroblastos/metabolismo , Glutationa/antagonistas & inibidores , Glutationa/metabolismo , Peroxidação de Lipídeos , Potencial da Membrana Mitocondrial , Nanopartículas Metálicas/química , Camundongos , Molibdênio/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo
18.
Eur J Oral Sci ; 122(6): 397-403, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25311638

RESUMO

Species of the genus Rothia that inhabit the oral cavity have recently been implicated in a number of diseases. To minimize their role in oral infections, it is imperative to reduce and/or control the growth and biofilm formation activity of Rothia spp. In this study, two bacterial isolates, Ora-7 and Ora-16, were obtained from the oral cavity of a healthy male subject and identified as Rothia dentocariosa and Rothia mucilaginosa, respectively, using a polyphasic taxonomic approach. Antimicrobial and anti-biofilm formation activities of zinc oxide nanoparticles (ZnO-NPs), of average size 35 nm, were assessed in in vitro assays using Crystal Violet and live and dead staining techniques. The ZnO-NPs exhibited an IC50 value of 53 and 76 µg ml(-1) against R. dentocariosa and R. mucilaginosa, respectively. Biofilm-formation assays, performed on the surfaces of polystyrene plates, artificial teeth, and dental prostheses, revealed the efficacy of ZnO-NPs as a potential antibacterial agent for controlling the growth of Rothia isolates in both planktonic form and biofilm.


Assuntos
Actinomycetaceae/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Nanopartículas Metálicas/uso terapêutico , Boca/microbiologia , Óxido de Zinco/farmacologia , Actinomycetaceae/classificação , Adulto , Carga Bacteriana/efeitos dos fármacos , Técnicas Bacteriológicas , Corantes , Prótese Dentária/microbiologia , Corantes Fluorescentes , Violeta Genciana , Humanos , Indóis , Masculino , Teste de Materiais , Filogenia , Poliestirenos , Propídio , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Dente Artificial/microbiologia
19.
Toxicol Appl Pharmacol ; 273(2): 289-97, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24035972

RESUMO

The present study has demonstrated the translocation of zinc ferrite nanoparticles (ZnFe2O4-NPs) into the cytoplasm of human amnion epithelial (WISH) cells, and the ensuing cytotoxicity and genetic damage. The results suggested that in situ NPs induced oxidative stress, alterations in cellular membrane and DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48 ± 1.6% and 50.73 ± 2.1% reduction in cell viability with 100 µg/ml of ZnFe2O4-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (ΔΨm) and 7.4-fold higher DNA damage after 48h of ZnFe2O4-NPs treatment. Real-time PCR (qPCR) analysis of p53, CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation, and 0.18-fold down regulation of bcl 2 gene vis-à-vis untreated control. RT(2) Profiler™ PCR array data elucidated differential up-regulation of mRNA transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7-folds. The flow cytometry based cell cycle analysis suggested the transfer of 15.2 ± 2.1% (p<0.01) population of ZnFe2O4-NPs (100 µg/ml) treated cells into apoptotic phase through intrinsic pathway. Over all, the data revealed the potential of ZnFe2O4-NPs to induce cellular and genetic toxicity in cells of placental origin. Thus, the significant ROS production, reduction in ΔΨm, DNA damage, and activation of genes linked to inflammation, oxidative stress, proliferation, DNA damage and repair could serve as the predictive toxicity and stress markers for ecotoxicological assessment of ZnFe2O4-NPs induced cellular and genetic damage.


Assuntos
Quimiocina CCL21/metabolismo , Células Epiteliais/metabolismo , Interleucina-1beta/metabolismo , Nanopartículas Metálicas/toxicidade , Subunidade p50 de NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Âmnio/efeitos dos fármacos , Âmnio/metabolismo , Âmnio/patologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Compostos Férricos/toxicidade , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Zinco/toxicidade
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