RESUMO
One of the advanced oxidative processes is gamma irradiation, an efficient technique for removing pesticides and pharmaceutical products. Radiolytic degradation leads to free radical's formation, which facilitates molecular lesion and breaks the chemical bonds. The use of pharmaceutical compounds, such as hydroxychloroquine (HCQ), is increasing nowadays due to the Covid 19 pandemic situation. This study focused on gamma radiation-induced degradation of HCQ in aqueous solution. The degradation was monitored by High-Performance Liquid Chromatography (HPLC) using an Eclipse XDB-C18 column (150 × 3.0 mm, 3.5 µm) and a mobile phase composed of 94% water (phosphate buffer at pH = 3.6) and 6% acetonitrile, with a DAD detection at λ = 343 nm. The effect of different gamma radiation doses (from 0.05 to 3 kGy) was investigated. Chromatographic analysis shows that 1 kGy dose is effective to degrade completely HCQ at 20 ppm and following a first-pseudo-kinetic order with a dose constant corresponding to 4.2 kGy-1. A comparison was done between gamma degradation and other methods. LC-QToF-MS/MS identified the intermediate products, and their kinetic constants were determined. A mechanism pathway was proposed for HCQ degradation under gamma irradiation.
RESUMO
The geometric structure, electronic, optical and photocatalytic properties of MSSe-g-GaN (M = Mo, W) van der Waals (vdW) heterostructures are investigated by performing first-principles calculations. We find that the MoSSe-g-GaN heterostructure exhibits type-II band alignment for all stacking patterns. While the WSSe-g-GaN heterostructure forms the type-II or type-I band alignment for the stacking model-I or model II, respectively. The average electrostatic potential shows that the potential of g-GaN is deeper than the MSSe monolayer, leading to the formation of an electrostatic field across the interface, causing the transfer of photogenerated electrons and holes. Efficient interfacial formation of interface and charge transfer reduce the work function of MSSe-g-GaN vdW heterostructures as compared to the constituent monolayer. The difference in the carrier mobility for electrons and holes suggests that these heterostructures could be utilized for hole/electron separation. Absorption spectra demonstrate that strong absorption from infrared to visible light in these vdW heterostructures can be achieved. Appropriate valence and conduction band edge positions with standard redox potentials provide enough force to drive the photogenerated electrons and holes to dissociate water into H+/H2 and O2/H2O at pH = 0.
RESUMO
Vertical stacking of two-dimensional materials into layered van der Waals heterostructures has recently been considered as a promising candidate for photocatalytic and optoelectronic devices because it can combine the advantages of the individual 2D materials. Janus transition metal dichalcogenides (JTMDCs) have emerged as an appealing photocatalytic material due to the desirable electronic properties. Hence, in this work, we systematically investigate the geometric features, electronic properties, charge density difference, work function, band alignment and photocatalytic properties of ZnO-JTMDC heterostructures using first-principles calculations. Due to the different kinds of chalcogen atoms on both sides of JTMDC monolayers, two different possible stacking patterns of ZnO-JTMDC heterostructures have been constructed and considered. We find that all these stacking patterns of ZnO-JTMDC heterostructures are dynamically and energetically feasible. Moreover, both ZnO-MoSSe and ZnO-WSSe heterostructures are indirect band gap semiconductors and present type-I and type-II band alignments for model-I and model-II, respectively. The Rashba spin polarization of the ZnO-WSSe heterostructure for model-I is greater than that in the others. Furthermore, valence (conduction) band edge potentials are calculated to understand the photocatalytic behavior of these systems. Energetically favorable band edge positions in ZnO-Janus heterostructures make them suitable for water splitting at zero pH. We found that the ZnO-Janus heterostructures are promising candidates for water splitting with conduction and valence band edges positioned just outside of the redox interval.
RESUMO
van der Waals heterostructures (vdWHs), obtained by vertically stacking different two-dimensional (2D) layered materials are being considered intensively as potential materials for nanoelectronic and optoelectronic devices because they can show the most potential advantages of individual 2D materials. Here, we construct the SnSe2/MoS2 vdWH and investigate its electronic and optical properties using first-principles calculations. We find that the band structures of both MoS2 and SnSe2 monolayers are well kept in the SnSe2/MoS2 vdWH because of their weakly interacting features via vdW interaction. The SnSe2/MoS2 vdWH forms a type-I band alignment and exhibits an indirect semiconductor band gap of 0.45 eV. The type-I band alignment makes the SnSe2/MoS2 vdWH a promising material for optoelectronic nanodevices, such as light emitting diodes because of ultra-fast recombination of electrons and holes. Moreover, the band gap and band alignment of the SnSe2/MoS2 vdWH can be tailored by the electric field and the insertion of a graphene sheet. After applying an electric field, type-I to type-II and semiconductor to metal transitions can be achieved in the SnSe2/MoS2 vdWH. Besides, when a graphene sheet is inserted into the SnSe2/MoS2 vdWH to form three stacking types of G/SnSe2/MoS2, SnSe2/G/MoS2 and SnSe2/MoS2/G, the p-type semiconductor of the SnSe2/MoS2 vdWH is converted to an n-type Ohmic contact. These findings provide theoretical guidance for designing future nanoelectronic and optoelectronic devices based on the SnSe2/MoS2 vdWH.
RESUMO
OBJECTIVE: Autotaxin is a secreted lysophospholipase that mediates the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator. Autotaxin levels in plasma and synovial fluid correlate with disease severity in patients with knee osteoarthritis (OA). The goal of this study was to develop and characterize a novel small molecule inhibitor of autotaxin to inhibit LPA production in vivo and determine its efficacy in animal models of musculoskeletal pain. DESIGN: Compound libraries were screened using an LPC coupled enzyme assay that measures the amount of choline released from LPC by the action of autotaxin. Hits from this assay were tested in a plasma assay to assess inhibition of endogenous plasma autotaxin and subsequently tested for their ability to lower plasma LPA levels upon oral dosing of rats. The best compounds were then tested in animal models of musculoskeletal pain. RESULTS: Compound screening led to the identification of compounds with nanomolar potency for inhibition of autotaxin activity. Studies in rats demonstrated a good correlation between compound exposure levels and a decrease in LPA levels in plasma. The leading molecule (compound-1) resulted in a dose dependent decrease in joint pain in the mono-sodium iodoacetate (MIA) and meniscal tear models and a decrease in bone fracture pain in the osteotomy model in rats. CONCLUSION: We have identified and characterized a novel small molecule inhibitor of autotaxin and demonstrated its efficacy in animal models of musculoskeletal pain. The inhibitor has the potential to serve as an analgesic for human OA and bone fracture.
Assuntos
Artralgia/metabolismo , Artrite Experimental/metabolismo , Osteoartrite do Joelho/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/efeitos dos fármacos , Animais , Artralgia/etiologia , Artralgia/fisiopatologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/complicações , Artrite Experimental/fisiopatologia , Cães , Humanos , Ácido Iodoacético/toxicidade , Lisofosfatidilcolinas/metabolismo , Lisofosfolipídeos/metabolismo , Masculino , Meniscos Tibiais/cirurgia , Osteoartrite do Joelho/induzido quimicamente , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/fisiopatologia , Osteotomia , Diester Fosfórico Hidrolases/metabolismo , Ratos , Ratos Endogâmicos Lew , Lesões do Menisco TibialRESUMO
OBJECTIVE: Emerging evidence suggests that osteoarthritis (OA) has a neuropathic component; however, the identity of the molecules responsible for this peripheral neuropathy is unknown. The aim of this study was to determine the contribution of the bioactive lipid lysophosphatidic acid (LPA) to joint neuropathy and pain. DESIGN: Male Lewis rats received an intra-articular injection of 50 µg of LPA into the knee and allowed to recover for up to 21 days. Saphenous nerve myelination was assessed by g-ratio calculation from electron micrographs and afferent nerve damage visualised by activation transcription factor-3 (ATF-3) expression. Nerve conduction velocity was measured electrophysiologically and joint pain was determined by hindlimb incapacitance. The effect of the LPA antagonist Ki-16425 was also evaluated. Experiments were repeated in the sodium monoiodoacetate (MIA) model of OA. RESULTS: LPA caused joint nerve demyelination which resulted in a drop in nerve conduction velocity. Sensory neurones were ATF-3 positive and animals exhibited joint pain and knee joint damage. MIA-treated rats also showed signs of demyelination and joint neuropathy with concomitant pain. Nerve damage and pain could be ameliorated by Ki-16425 pre-treatment. CONCLUSION: Intra-articular injection of LPA caused knee joint neuropathy, joint damage and pain. Pharmacological blockade of LPA receptors inhibited joint nerve damage and hindlimb incapacitance. Thus, LPA is a candidate molecule for the development of OA nerve damage and the origin of joint neuropathic pain.
Assuntos
Fator 3 Ativador da Transcrição/efeitos dos fármacos , Artrite Experimental/fisiopatologia , Lisofosfolipídeos/farmacologia , Condução Nervosa/efeitos dos fármacos , Osteoartrite/fisiopatologia , Nervos Periféricos/efeitos dos fármacos , Fator 3 Ativador da Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Artralgia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Comportamento Animal , Estudos de Casos e Controles , Cromatografia Líquida , Inibidores Enzimáticos/toxicidade , Feminino , Humanos , Injeções Intra-Articulares , Ácido Iodoacético/toxicidade , Isoxazóis/farmacologia , Lisofosfolipídeos/antagonistas & inibidores , Lisofosfolipídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Neuralgia , Osteoartrite/induzido quimicamente , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite do Joelho/metabolismo , Nervos Periféricos/metabolismo , Nervos Periféricos/ultraestrutura , Propionatos/farmacologia , Ratos Endogâmicos Lew , Líquido Sinovial/químicaRESUMO
Foot-and-mouth disease virus (FMDV) is endemic in Vietnam, a country that plays an important role in livestock trade within Southeast Asia. The large populations of FMDV-susceptible species in Vietnam are important components of food production and of the national livelihood. In this study, we investigated the phylogeny of FMDV O/PanAsia in Vietnam, reconstructing the virus' ancestral host species (pig, cattle or buffalo), clinical stage (subclinical carrier or clinically affected) and geographical location. Phylogenetic divergence time estimation and character state reconstruction analyses suggest that movement of viruses between species differ. While inferred transmissions from cattle to buffalo and pigs and from pigs to cattle are well supported, transmission from buffalo to other species, and from pigs to buffalo may be less frequent. Geographical movements of FMDV O/PanAsia virus appears to occur in all directions within the country, with the South Central Coast and the Northeast regions playing a more important role in FMDV O/PanAsia spread. Genetic selection of variants with changes at specific sites within FMDV VP1 coding region was different depending on host groups analyzed. The overall ratio of non-synonymous to synonymous nucleotide changes was greater in pigs compared to cattle and buffalo, whereas a higher number of individual amino acid sites under positive selection were detected in persistently infected, subclinical animals compared to viruses collected from clinically diseased animals. These results provide novel insights to understand FMDV evolution and its association with viral spread within endemic countries. These findings may support animal health organizations in their endeavor to design animal disease control strategies in response to outbreaks.
Assuntos
Vírus da Febre Aftosa/genética , Febre Aftosa/virologia , Animais , Teorema de Bayes , Búfalos/virologia , Bovinos/virologia , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/virologia , Febre Aftosa/epidemiologia , Filogenia , Filogeografia , Vietnã/epidemiologiaRESUMO
We present a method for the formation of an epitaxialâ surface layer involving B, N, and Si atoms on a ZrB2(0001) thin film on Si(111). It has the potential to be an insulating growth template for 2D semiconductors. The chemical reaction of NH3 molecules with the silicene-terminated ZrB2 âsurface was characterized by synchrotron-based, high-resolution core-level photoelectron spectroscopy and low-energy electron diffraction. In particular, the dissociative chemisorption of NH3 at 400 °C leads to surfaceâ nitridation, and subsequent annealing up to 830 °C results in a solid phase reaction with the ZrB2 subsurface layers. In this way, a new nitride-based epitaxialâ surface layer is formed with hexagonal symmetry and a single in-plane crystal orientation.
RESUMO
Since epitaxial silicene is not chemically inert under ambient conditions, its application in devices and the ex-situ characterization outside of ultrahigh vacuum environments require the use of an insulating capping layer. Here, we report on a study of the feasibility of encapsulating epitaxial silicene on ZrB2(0001) thin films grown on Si(111) substrates by aluminum nitride (AlN) deposited using trimethylaluminum (TMA) and ammonia (NH3) precursors. By in-situ high-resolution core-level photoelectron spectroscopy, the chemical modifications of the surface due to subsequent exposure to TMA and NH3 molecules, at temperatures of 300 °C and 400 °C, respectively, have been investigated. While an AlN-related layer can indeed be grown, silicene reacts strongly with both precursor molecules resulting in the formation of Si-C and Si-N bonds such that the use of these precursors does not allow for the protective AlN encapsulation that leaves the electronic properties of silicene intact.
RESUMO
4-{(R)-(3-Aminophenyl)[4-(4-fluorobenzyl)-piperazin-1-yl]methyl}-N,N-diethylbenzamide (AZD2327) is a highly potent and selective agonist of the δ-opioid receptor. AZD2327 and N-deethylated AZD2327 (M1) are substrates of cytochrome P450 3A (CYP3A4) and comprise a complex multiple inhibitory system that causes competitive and time-dependent inhibition of CYP3A4. The aim of the current work was to develop a physiologically based pharmacokinetic (PBPK) model to predict quantitatively the magnitude of CYP3A4 mediated drug-drug interaction with midazolam as the substrate. Integrating in silico, in vitro and in vivo PK data, a PBPK model was successfully developed to simulate the clinical accumulation of AZD2327 and its primary metabolite. The inhibition of CYP3A4 by AZD2327, using midazolam as a probe drug, was reasonably predicted. The predicted maximum concentration (Cmax) and area under the concentration-time curve (AUC) for midazolam were increased by 1.75 and 2.45-fold, respectively, after multiple dosing of AZD2327, indicating no or low risk for clinically relevant drug-drug interactions (DDI). These results are in agreement with those obtained in a clinical trial with a 1.4 and 1.5-fold increase in Cmax and AUC of midazolam, respectively. In conclusion, this model simulated DDI with less than a two-fold error, indicating that complex clinical DDI associated with multiple mechanisms, pathways and inhibitors (parent and metabolite) can be predicted using a well-developed PBPK model.
Assuntos
Benzamidas/farmacocinética , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Midazolam/farmacocinética , Modelos Biológicos , Piperazinas/farmacocinética , Receptores Opioides delta/agonistas , Benzamidas/sangue , Benzamidas/metabolismo , Benzamidas/farmacologia , Ligação Competitiva , Células CACO-2 , Citocromo P-450 CYP3A/genética , Inibidores do Citocromo P-450 CYP3A/sangue , Inibidores do Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/farmacologia , Interações Medicamentosas , Humanos , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Piperazinas/sangue , Piperazinas/metabolismo , Piperazinas/farmacologia , Ligação Proteica , Proteínas Recombinantes , Especificidade por Substrato , Fatores de TempoRESUMO
To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Aminoglicosídeos/efeitos adversos , Antibacterianos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Injúria Renal Aguda/microbiologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/patologia , Adulto , Idoso , Aminoglicosídeos/administração & dosagem , Antibacterianos/administração & dosagem , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/patologia , Esquema de Medicação , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Choque Séptico/microbiologia , Choque Séptico/mortalidade , Choque Séptico/patologia , Análise de SobrevidaRESUMO
As silicene is not chemically inert, the study and exploitation of its electronic properties outside of ultrahigh vacuum environments require the use of insulating capping layers. In order to understand if aluminum oxide might be a suitable encapsulation material, we used high-resolution synchrotron photoelectron spectroscopy to study the interactions of Al atoms and O2 molecules, as well as the combination of both, with epitaxial silicene on thin ZrB2(0001) films grown on Si(111). The deposition of Al atoms onto silicene, up to the coverage of about 0.4 Al per Si atoms, has little effect on the chemical state of the Si atoms. The silicene-terminated surface is also hardly affected by exposure to O2 gas, up to a dose of 4500 L. In contrast, when Al-covered silicene is exposed to the same dose, a large fraction of the Si atoms becomes oxidized. This is attributed to dissociative chemisorption of O2 molecules by Al atoms at the surface, producing reactive atomic oxygen species that cause the oxidation. It is concluded that aluminum oxide overlayers prepared in this fashion are not suitable for encapsulation since they do not prevent but actually enhance the degradation of silicene.
RESUMO
From the analysis of high-resolution Si 2p photoelectron and near-edge x-ray absorption fine structure (NEXAFS) spectra, we show that core level excitations of epitaxial silicene on ZrB2(0001) thin films are characteristically different from those of sp(3)-hybridized silicon. In particular, it is revealed that the lower Si 2p binding energies and the low onset in the NEXAFS spectra as well as the occurrence of satellite features in the core level spectra are attributed to the screening by low-energy valence electrons and interband transitions between π bands, respectively. The analysis of observed Si 2p intensities related to chemically distinct Si atoms indicates the presence of at least one previously unidentified component. The presence of this component suggests that the observation of stress-related stripe domains in scanning tunnelling microscopy images is intrinsically linked to the relaxation of Si atoms away from energetically unfavourable positions.
RESUMO
BACKGROUND: The intake of a Western diet enriched in animal fat has been shown to be a major risk factor for Type 2 diabetes and obesity. Previous rodent studies have indicated that these conditions may be triggered by the accumulation of the sphingolipid ceramide in insulin-sensitive tissues. However, data are lacking in this regard from both humans and non-human primates. OBJECTIVE: Here we have investigated the relationship between plasma ceramides and metabolic syndrome in Rhesus macaques fed a high-fat and high-fructose (HFFD) 'western' diet. METHODS: We investigated this relationship in cohorts of monkeys fed a HFFD for a period of 8 months to 5 years. Animals were classified as control, pre-diabetic or diabetic based on fasting plasma parameters and insulin sensitivity. RESULTS: HFFD treatment produced significant increases in body weight and body fat and also resulted in a decline in insulin sensitivity. In parallel to the reduction in insulin sensitivity, significant increases in both plasma ceramide and dihydroceramide levels were observed, which further increased as animals progressed to the diabetic state. Plasma levels of the rare sphingolipid C18:0 deoxysphinganine, a marker of increased metabolic flux through serine palmitoyl transferase (SPT), were also elevated in both pre- and diabetic animals. Furthermore, plasma serine levels were significantly elevated in diabetic monkeys, which may indicate a shift in SPT substrate selectivity from serine to alanine or glycine. In contrast, branch chain amino acids were unchanged in pre-diabetic non-human primates, and only plasma valine levels were elevated in diabetic animals. CONCLUSION: Together, these data indicate that HFFD induces de novo synthesis of ceramides in non-human primates, and that increased production of plasma ceramides is significantly correlated with the decline in insulin sensitivity.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Dieta Hiperlipídica/efeitos adversos , Síndrome Metabólica/sangue , Obesidade/sangue , Serina C-Palmitoiltransferase/sangue , Esfingolipídeos/sangue , Animais , Biomarcadores/sangue , Ceramidas/sangue , Diabetes Mellitus Tipo 2/etiologia , Modelos Animais de Doenças , Progressão da Doença , Frutose/efeitos adversos , Resistência à Insulina , Macaca mulatta , Masculino , Síndrome Metabólica/etiologia , Obesidade/complicações , Fatores de Risco , Valina/sangueRESUMO
A new approach for the isolation of chromosome-specific subsets from a human genomic yeast artificial chromosome (YAC) library is described. It is based on the hybridization with an Alu polymerase chain reaction (PCR) probe. We screened a 1.5 genome equivalent YAC library of megabase insert size with Alu PCR products amplified from hybrid cell lines containing human chromosome 21, and identified a subset of 63 clones representative of this chromosome. The majority of clones were assigned to chromosome 21 by the presence of specific STSs and in situ hybridization. Twenty-nine of 36 STSs that we tested were detected in the subset, and a contig spanning 20 centimorgans in the genetic map and containing 8 STSs in 4 YACs was identified. The proposed approach can greatly speed efforts to construct physical maps of the human genome.
Assuntos
Cromossomos Fúngicos , Cromossomos Humanos Par 21 , Biblioteca Gênica , Genoma Humano , Sequência de Bases , Clonagem Molecular , DNA/genética , Técnicas Genéticas , Humanos , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Over the past decade the use of LC-MS/MS has increased significantly in the hospital laboratories. Clinical laboratories have switched from immunoassays to LC-MS/MS methods due to the promise of improvements in sensitivity and specificity, better standardization with often non-commutable international standards, and better between-laboratory comparison. However, it remains unclear whether routine performance of the LC-MS/MS methods have met these expectations. METHOD: This study examined the EQAS results, from the Dutch SKML, of serum cortisol, testosterone, 25OH-vitaminD and cortisol in urine and saliva over 9 surveys (2020 to first half of 2021). RESULTS: The study found a significant increase in the number of compounds and in the number of results measured in the different matrices, with LC-MS/MS over a period of eleven years. In 2021, approximately 4000 LC-MS/MS results were submitted (serum: urine: saliva = 58:31:11%) compared to only 34 in 2010. When compared to the individual immunoassays, the LC-MS/MS based methods for serum cortisol, testosterone and 25OH-vitaminD showed comparable but also higher between-laboratory CVs in different samples of the surveys. For cortisol, testosterone and 25OH-vitaminD the median CV was 6.8%, 6.1% and 4.7% respectively for the LC-MS/MS compared to 3.9-8.0%,4.5-6.7%, and 7.5-18.3% for immunoassays. However, the bias and imprecision of the LC-MS/MS was better than that of the immunoassays. CONCLUSION: Despite the expectation that LC-MS/MS methods would result in smaller between-laboratory differences, as they are relatively matrix independent and better to standardize, the results of the SKML round robins do not reflect this for some analytes and may be in part explained by the fact that in most cases laboratory developed tests were used.
Assuntos
Hidrocortisona , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Química Clínica , TestosteronaRESUMO
Five new compounds, 16,23,29-trihydroxy-3-oxo-olean-12-en-28-oic acid (1), 4,23,29-trihydroxy-3,4-seco-olean-12-en-3-oate-28-oic acid (2), 3ß,6ß,23-trihydroxyolean-12-en-28-oic acid 28-O-ß-D-glucopyranoside (3), 3-O-[2,3-di-O-acetyl-α-L-arabinopyranosyl]hederagenin 28-O-α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranoside (4), and 3-O-[3,4-di-O-acetyl-α-L-arabinopyranosyl]hederagenin 28-O-α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranoside (5), as well as 10 known compounds (6-15), were isolated from the stem bark of Kalopanax pictus. Compounds 1-5 and 7-14 inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50 values ranging from 0.6 to 16.4 µM. Furthermore, the transcriptional inhibitory function of these compounds was confirmed on the basis of decreases in COX-2 and iNOS gene expression in HepG2 cells. The structure-activity relationship of the compounds with respect to anti-inflammatory activity is also discussed.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Kalopanax/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Anti-Inflamatórios/química , Sequência de Bases , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Células Hep G2 , Humanos , Coreia (Geográfico) , Estrutura Molecular , NF-kappa B/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Casca de Planta/química , Saponinas/química , Relação Estrutura-Atividade , Triterpenos/químicaRESUMO
We report the electrical resistivity of atomic layer deposited TiN thin films in the thickness range 2.5-20 nm. The measurements were carried out using the circular transfer length method structures. For the films with thickness in the range of 10-20 nm, the measurements exhibited linear current-voltage (I-V) curves. The sheet resistance R(sh) was determined, and the resistivity was calculated. A value of 120 microohms-cm was obtained for a 20 nm TiN layer. With decreasing film thickness, the resistivity slightly increased and reached 135 microohms-cm for a 10 nm film. However, the measurements on 2.5-5.0 nm thick films revealed non-linear I-V characteristics, implying the dependence of the measured resistance, and therefore the resistivity, of the layers on applied voltage. The influence of the native oxidation due to the exposure of the films to air was taken into account. To fully eliminate this oxidation, a highly-resistive amorphous silicon layer was deposited directly after the ALD of TiN. The electrical measurements on the passivated 2.5- and 3.5 nm TiN layers then exhibited linear I-V characteristics. A resistivity of 400 and 310 microohms-cm was obtained for a 2.5- and 3.5 nm TiN film, respectively.