Input: The same fUS protocol was applied to 6 groups of mice with different times, increment t, between fUS application and BSA injection (increment t =-10, 2. 5, 10, 30, 60, 90min) followed by SPECT imaging.


Input: For increment t <= 30min we observed an exponential accumulation of activity in an area of the treated muscle which extended to a volume larger than the fUS pattern with highest accumulation for short waiting times increment t.


Input: The extent of extravasation decreased exponentially with increasing increment t, with a calculated half-life of ca.


Input: 21min, defining the time window of extravasation.


Input: The same treatment without MBs did not induce extravasation of BSA thus supporting MBs and drug co-injection strategies.


Input: These results provide essential information for the development of fUS based strategies for localized drug delivery.


Input: Comparative study on transcriptional activity of 17 parabens mediated by estrogen receptor alpha and beta and androgen receptor.

parabens

estrogen

androgen


Input: The structure-activity relationships of parabens which are widely used as preservatives for transcriptional activities mediated by human estrogen receptor alpha (hER alpha), hER beta and androgen receptor (hAR) were investigated.

parabens

estrogen

androgen


Input: Fourteen of 17 parabens exhibited hER alpha and/or hER beta agonistic activity at concentrations of >= 1 x 10 (-5) M, whereas none of the 17 parabens showed AR agonistic or antagonistic activity.

parabens

parabens


Input: Among 12 parabens with linear alkyl chains ranging in length from C1 to C12, heptylparaben (C7) and pentylparaben (C5) showed the most potent ER alpha and ER beta agonistic activity in the order of 10 (-7) M and 10 (-8) M, respectively, and the activities decreased in a stepwise manner as the alkyl chain was shortened to C1 or lengthened to C12.

parabens

alkyl

heptylparaben

pentylparaben


Input: Most parabens showing estrogenic activity exhibited ER beta-agonistic activity at lower concentrations than those inducing ER alpha-agonistic activity.

parabens


Input: The estrogenic activity of butylparaben was markedly decreased by incubation with rat liver microsomes, and the decrease of activity was blocked by a carboxylesterase inhibitor.

butylparaben


Input: These results indicate that parabens are selective agonists for ER beta over ER alpha; their interactions with ER alpha/beta are dependent on the size and bulkiness of the alkyl groups; and they are metabolized by carboxylesterases, leading to attenuation of their estrogenic activity.

parabens

alkyl


Input: DICO, a novel nonaromatic B-ring flavonoid, induces G2/M cell cycle arrest and apoptosis in human hepatoma cells.

DICO

flavonoid


Input: DICO was a novel nonaromatic B-ring flavonoid obtained from Macrothelypteris torresiana.

DICO

flavonoid


Input: In the present work, we investigated the antitumor activity and the antineoplastic mechanism of DICO.

DICO


Input: Our study showed that DICO inhibited the growth of HepG2 cells in dose and time-dependent manners.

DICO


Input: As well as DICO induced G2/M cell cycle arrest and apoptosis via a ROS-mediated mitochondrial pathway.

DICO


Input: Western blot assay demonstrated that DICO decreased Bcl-2 level and induced Bax translocation to cause cytochrome c release.

DICO


Input: Subsequently, caspase-9 and caspase-3 were activated.


Input: Meanwhile, the alterations of cyclin A and B1, p-CDK1 and p-cdc25c levels were also observed in response to DICO treatment.

DICO


Input: Taken together, DICO displayed a significant antitumor effect through G2/M cell cycle arrest and apoptosis induction, which suggested DICO might have therapeutic potential against tumors.

DICO

DICO


Input: Chloroquine causes similar electroretinogram modifications, neuronal phospholipidosis and marked impairment of synaptic vesicle transport in Albino and Pigmented Rats.

Chloroquine


Input: Retinal toxicity of chloroquine has been known for several years, but the mechanism (s) of toxicity remain controversial; some author support the idea that the binding of chloroquine to melanin pigments in the retinal pigmented epithelium (RPE) play a major toxic role by concentrating the drug in the eye.

chloroquine

chloroquine


Input: In our study, 12 albinos Sprague-Dawley (SD) and 12 pigmented Brown Norway (BN) rats were treated orally for 3 months with chloroquine to compare functional and pathological findings.

chloroquine


Input: On Flash electroretinograms (ERG) performed in scotopic conditions, similar and progressive (time-dependent) delayed onset and decreased amplitudes of oscillatory potentials (from Day 71) and b-waves (on Day 92) were identified in both BN and SD rats.


Input: In both strains, identical morphological changes consisted of neuronal phospholipidosis associated with UV auto-fluorescence without evidence of retinal degeneration and gliosis; the RPE did not show any morphological lesions or autofluorescence.


Input: IHC analyses demonstrated a decrease in GABA expression in the inner nuclear layer.

GABA


Input: In addition, a marked accumulation of synaptic vesicles coupled with a marked disruption of neurofilaments in the optic nerve fibers was identified.


Input: In conclusion, ERG observations were very similar to those described in humans.


Input: Comparable ERG modifications, histopathology and immunohistochemistry findings were observed in the retina of both rat strains suggesting that melanin pigment is unlikely involved. chloroquine-induced impairment of synaptic vesicle transport, likely related to disruption of neurofilaments was identified and non-previously reported.

chloroquine


Input: This new mechanism of toxicity may also be responsible for the burry vision described in humans chronically treated with chloroquine.

chloroquine


Input: Thiazolidin-4-one and thiazinan-4-one derivatives analogous to rosiglitazone as potential antihyperglycemic and antidyslipidemic agents.

rosiglitazone


Input: A number of thiazolidin-4-one and thiazinan-4-one derivatives were prepared by three component condensation in one pot reaction method.


Input: These compounds were evaluated for anti-hyperglycemic activity by in vitro and in vivo assay systems.


Input: The compounds with thiazolidin-4-one and thiazinan-4-one moieties exhibited significant anti-hyperglycemic activity.


Input: A few compounds (3a, 3b, 4a and 4b) have exhibited both anti-hyperglycemic and anti-dyslipidemic activities.


Input: Among them the thiazinan-4-one derivative 4a showed maximal (45%) improvement in oral glucose tolerance test in db/db mice at 30 mg/kg oral dose.

glucose


Input: Synthesis and biological evaluation of novel aliphatic amido-quaternary ammonium salts for anticancer chemotherapy: Part II.

aliphatic amido-quaternary ammonium salts


Input: A series of novel aliphatic amido-quaternary ammonium salts were synthesized and evaluated for their anticancer effects involving induction of RhoB.

aliphatic amido-quaternary ammonium salts


Input: Most of these compounds, featuring open-ring forms of aliphatic amido-quaternary ammonium salts, exhibited potent anti-proliferative activities in human cancer cell lines, including PC-3, NUGC-3, MDA-MB-231, ACHN, HCT-15, and NCI-H23.

aliphatic amido-quaternary ammonium salts


Input: In further evaluation, the representative compound N, N-diethyl-N-(2-(N-methyltetradecanamido) ethyl) prop-2-en-1-aminium bromide (3b) exhibited potent pro-apoptotic activity, through RhoB activation, in HeLa cells.

N, N-diethyl-N-(2-(N-methyltetradecanamido) ethyl) prop-2-en-1-aminium bromide


Input: Identification of novel FLT3 kinase inhibitors.


Input: FLT3 and PDGFR tyrosine kinases are important targets for therapy of different types of leukemia.

tyrosine


Input: Several FLT3/PDGFR inhibitors are currently under clinical investigation for combination with standard therapy for treatment of acute myeloid leukemia (AML), however these agents only induce partial remission and development of resistance has been reported.


Input: In this work we describe the identification of potent and novel dual FLT3/PDGFR inhibitors that resulted from our efforts to screen a library of 25, 607 small molecules against the FLT3 dependent cell line MOLM-13 and the PDGFR dependent cell line EOL-1.


Input: This effort led to the identification of five compounds that were confirmed to be active on additional FLT3 dependent cell lines (cellular EC50 values between 35 and 700 nM), while having no significant effect on 24 other tyrosine kinases.

tyrosine


Input: Preparation and antimalarial activity of semisynthetic lycorenine derivatives.

lycorenine


Input: A set of twenty one lycorenine derivatives has been prepared from the alkaloid hippeastrine (1).

lycorenine

hippeastrine


Input: The modifications performed on hippeastrine included some functional group transformations, structural simplification and preparation of dimers.

hippeastrine


Input: All alkaloids were tested as potential antimalarial agents, being the hippeastrine dimers the most active compounds.

hippeastrine


Input: Transport of gabapentin by LAT1 (SLC7A5).

gabapentin


Input: Gabapentin is used in the treatment of epilepsy and neuropathic pain.

Gabapentin


Input: Gabapentin has high and saturable permeability across the BBB, but no mechanistic studies underpinning this process have been reported.

Gabapentin


Input: The aim of the current study was to investigate the transport of gabapentin in a model of the BBB, identify the important drug transporter (s) and to use mathematical modelling to quantify the processes involved.

gabapentin


Input: A human brain endothelial cell line (hCMEC/D3) was utilised as an in-vitro model of the BBB.


Input: Uptake of radiolabeled gabapentin into cells in the presence of chemical inhibitors, siRNA or overexpressed drug transporters of interest was investigated.

radiolabeled gabapentin


Input: Gabapentin was demonstrated to be a LAT1 substrate in brain endothelial cells (LAT1-process; Km = 530 mu M and Vmax = 7039pmoles/million cells/min versus other-processes; Km = 923 mu M and Vmax = 3656pmoles/million cells/min) and in transfected HEK 293 LAT1 cells (LAT1-process; Km = 217 mu M and Vmax = 5192pmoles/million cells/min versus otherprocesses; Km = 1546 mu M and Vmax = 3375pmoles/million cells/min).

Gabapentin


Input: At physiological concentrations of gabapentin, LAT1 mediated transport was 3 or ~ 10-fold higher than the other transport processes in the two systems, respectively, demonstrating clear selectivity for gabapentin.

gabapentin

gabapentin


Input: In-silico structural homology modelling confirmed that LAT1 could have the LeuT conserved fold and functions by the alternative access mechanism.


Input: Mathematical modelling of this mechanism revealed revised significance of Vmax and Km so that a low Km may not necessarily imply a high affinity transport process.


Input: Gabapentin was negative for OCT like transport and LAT2 activity in the hCMEC/D3 and OCT1 transfected cells.

Gabapentin


Input: Our data shows that gabapentin is a substrate for the influx transporter LAT1 at therapeutic concentrations.

gabapentin


Input: Single-photon sources: non-blinking single-photon generation with anisotropic colloidal nanocrystals: towards room-temperature, efficient, colloidal quantum sources (adv. Mater. 14/2013).


Input: High-quality core/shell CdSe/CdS colloidal nanocrystals are demonstrated to be efficient sources of non-classical light.

CdSe

CdS


Input: As shown by Ferruccio Pisanello and co-workers on page 1974, the intrinsic anisotropy of these nanoparticles allows an independent tuning of shell length and thickness, resulting in a full control of photon statistics.


Input: This can be exploited to obtain non-blinking, room-temperature single-photon generation, thus bringing colloidal nanocrystals one step closer to non-classical light sources for quantum applications.


Input: Light-Emitting Field-Effect Transistors Having Combined Organic Semiconductor and Metal Oxide Layers.

Metal Oxide


Input: A new organic light-emitting field-effect transistor characterized by a metal oxide layer inserted between the organic layer and the gate insulator is proposed.

metal oxide


Input: The metal oxide is indirectly connected with source and drain electrodes through the organic layer.

metal oxide


Input: Upon increasing the potential difference between the source and drain electrodes, the emission becomes exceedingly strong and the emission region encompasses the whole channel zone.


Input: Patterned Growth of Crystalline Organic Heterostructures.


Input: Organic droplet epitaxy is presented as a method for growing nanopatterned crystalline heterostructures, thanks to the transport of molecules of an amorphous first-layer on top of a crystalline second-layer, where they form an epitaxial interface.


Input: Such heterostructures may be transferred to any substrates, raising particular interest for applications (e. g., for organic photovoltaics), where crystallinity and nanopatterning constitute well recognized advantages.


Input: Decreased consumption of sweet fluids in mu opioid receptor knockout mice: a microstructural analysis of licking behavior.


Input: RATIONALE: Evidence suggests that the palatability of food (i. e., the hedonic impact produced by its sensory features) can promote feeding and may underlie compulsive eating, leading to obesity.


Input: Pharmacological studies implicate opioid transmission in the hedonic control of feeding, though these studies often rely on agents lacking specificity for particular opioid receptors.


Input: OBJECTIVES: Here, we investigated the role of mu opioid receptors (MORs) specifically in determining hedonic responses to palatable sweet stimuli.


Input: METHODS: In Experiment 1, licking microstructure when consuming sucrose solution (2 to 20%) was compared in MOR knockout and wildtype mice as a function of sucrose concentration and level of food deprivation.

sucrose

sucrose


Input: In Experiment 2, a similar examination was conducted using the palatable but calorie-free stimulus sucralose (0. 001 to 1%), allowing study of licking behavior independent of homeostatic variables.

sucralose


Input: RESULTS: In Experiment 1, MOR knockout mice exhibited several alterations in sucrose licking.

sucrose


Input: Although wildtype mice exhibited a twofold increase in the burst length when food deprived, relative to the nondeprived test, this aspect of sucrose licking was generally insensitive to manipulations of food deprivation for MOR knockout mice.

sucrose


Input: Furthermore, during concentration testing, their rate of sucrose licking was less than half that of wildtype mice.

sucrose


Input: During sucralose testing (Experiment 2), MOR knockout mice licked at approximately half the wildtype rate, providing more direct evidence that MOR knockout mice were impaired in processing stimulus palatability.

sucralose


Input: CONCLUSIONS: These results suggest that transmission through MORs mediates hedonic responses to palatable stimuli, and therefore likely contributes to normal and pathological eating.


Input: Non-classical Pharmacology of the Dopamine Transporter: Atypical Inhibitors, Allosteric Modulators and Partial Substrates.

Dopamine


Input: The dopamine transporter (DAT) is a sodium-coupled symporter protein responsible for modulating the concentration of extraneuronal dopamine in the brain.

dopamine

sodium

dopamine


Input: The DAT is a principle target of various psychostimulant, nootropic and antidepressant drugs, as well as certain drugs used recreationally, including the notoriously addictive stimulant cocaine.

cocaine


Input: DAT ligands have traditionally been divided into two categories: cocaine-like inhibitors and amphetamine-like substrates.

cocaine

amphetamine


Input: Whereas inhibitors block monoamine uptake by the DAT, but are not translocated across the membrane, substrates are actively translocated and trigger DAT-mediated release of dopamine by reversal of the translocation cycle.

monoamine

dopamine


Input: As both inhibitors and substrates increase extraneuronal dopamine levels, it is often assumed that all DAT ligands posses an addictive liability equivalent to cocaine.

dopamine

cocaine


Input: However, the recent development of novel' atypical' inhibitors and' partial substrate' ligands with reduced or even a complete lack of cocaine-like rewarding effects suggests that addictiveness is not a constant property of DAT-affecting compounds.

cocaine


Input: These atypical ligands do not conform to the classical preconception that all DAT inhibitors (or substrates) are functionally and mechanistically alike.


Input: Instead, they suggest the possibility that the DAT exhibits some of the ligand-specific' pleiotropic' functional qualities inherent to G-protein-coupled receptors.


Input: That is, ligands with different chemical structures induce specific conformational changes in the transporter protein, which can be differentially transduced by the cell, ultimately eliciting unique behavioral and psychical effects.


Input: The present overview discusses compounds with conformation-specific activity, useful not only as tools for studying the mechanics of dopamine transport, but also as leads for medication development in addictive disorders.

dopamine


Input: Molecular Identification and Characterization of an Essential Pyruvate Transporter from Trypanosoma brucei.

Pyruvate


Input: Pyruvate export is an essential physiological process for the bloodstream form of T. brucei as the parasite would otherwise accumulate this end product of glucose metabolism to toxic levels.

Pyruvate

glucose


Input: In the studies reported here genetic complementation in Saccharomyces cerevisiae has been employed to identify a gene (TbPT0) that encodes this vital pyruvate transporter from T. brucei.

pyruvate


Input: Expression of TbPT0 in S. cerevisiae reveals that TbPT0 is a high affinity pyruvate transporter.

pyruvate


Input: TbPT0 belongs to a clustered multigene family consisting of five members, whose expression is up-regulated in the bloodstream form.


Input: Interestingly, TbPT family permeases are related to polytopic proteins from plants but not to characterized monocarboxylate transporters from mammals.

monocarboxylate


Input: Remarkably, inhibition of the TbPT gene family expression in bloodstream parasites by RNAi is lethal, confirming the physiological relevance of these transporters.


Input: The discovery of TbPT0 reveals for the first time the identity of the essential pyruvate transporter and provides a potential drug target against the mammalian life cycle stage of T. brucei.

pyruvate


Input: DNA repair and cytotoxic drugs: the potential role of RAD51 in clinical outcome of non-small-cell lung cancer patients.


Input: Many of the cytotoxic drugs used in the treatment of non-small-cell lung carcinoma patients can interfere with DNA activity and the definition of an individual DNA repair profile could be a key strategy to achieve better response to chemotherapeutic treatment.


Input: Although DNA repair mechanisms are important factors in the prevention of carcinogenesis, these molecular pathways are also involved in therapy response.


Input: RAD51 is a crucial element in DNA repair by homologous recombination and has been shown to interfere with the prognosis of patients treated with chemoradiotherapy.


Input: There is increasing evidence that genetic polymorphisms in repair enzymes can influence DNA repair capacity and, consequently, affect chemotherapy efficacy.


Input: We conducted this review to show the possible influence of the RAD51 genetic variants in damage repair capacity and treatment response in non-small-cell lung carcinoma patients.


Input: Extracellular Signal-Regulated Kinases (ERK) Inhibitors from Aristolochia yunnanensis.


Input: Six new sesquiterpenoids, aristoyunnolins A-F (1-6), an artifact of isolation [7-O-ethyl madolin W (7)], and 12 known analogues were isolated from stems of Aristolochia yunnanensis.

sesquiterpenoids

aristoyunnolins A-F

7-O-ethyl madolin W


Input: The structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds 2, 3, 5-7, 9, 14, and 17 were determined by the modified Mosher' s method and CD analysis.


Input: Compounds 1-19 were screened using a bioassay system designed to evaluate the effect on mitogen-activated protein kinases (MAPKs) signaling pathways.


Input: Among three MAPKs (ERK1/2, JNK, and p38), compounds 1, 4, 10-13, 16, 18, and 19 exhibited selective inhibition of the phosphorylation of ERK1/2.


Input: Compounds 16 and 19 were more active than the positive control PD98059, a known inhibitor of the ERK1/2 signaling pathway.


Input: Different levels of prenatal zinc and selenium had different effects on neonatal neurobehavioral development.

zinc

selenium


Input: Either deficient or excessive of essential nutrients had adverse effects.


Input: Effects of different levels of prenatal zinc (Zn) and selenium (Se) on fetal neurobehavioral development remain unclear.

zinc

Zn

selenium

Se


Input: To determine the effects of different cord serum levels of Zn and Se on neurobehavioral development in neonates and to explore possible threshold level of Zn and Se based on fetal neurodevelopment, we conducted this epidemiological research.

Zn

Se

Zn

Se


Input: In the multi-center study, we investigated these questions in 927 mother-newborn pairs in Shanghai, China, from 2008 through 2009.


Input: Umbilical cord serum concentrations of Zn and Se were measured and Neonatal Behavioral Neurological Assessment (NBNA) tests were conducted.

Zn

Se


Input: The median cord serum Zn and Se concentrations were 794. 3 mu g/L and 63. 1 mu g/L, respectively.

Zn

Se


Input: A nonlinear relationship was observed between cord serum Zn and NBNA after adjusting for potential confounders.

Zn


Input: NBNA score decreased with increasing Zn levels after 794. 3 mu g/L (adjusted beta =-3. 0, 95% CI:-3. 6 to-2. 4, p < 0. 001).

Zn


Input: Additionally, an invert U-shape with a threshold Se of 100 mu g/L was observed between cord serum Se and NBNA.

Se

Se


Input: The adjusted regression coefficient was 4. 4 (95% CI: 3. 6-5. 2, p < 0. 001) for Se < 100 mu g/L while-3. 6 (95% CI:-6. 1 to-1. 1, p < 0. 01) for Se >= 100 mu g/L.

Se

Se


Input: Of the 927 infants, 50% had a high level Zn (>= 794. 3 mu g/L) and 8. 6% had a high level Se (>= 100 mu g/L).

Zn

Se


Input: High levels of both Zn and Se mainly had adverse effects on behavior and passive tone (p < 0. 001).

Zn

Se


Input: Taken together, our study suggested that a threshold of cord blood Zn and Se was existed for fetal neurodevelopment and the prevalence of excessive Zn was high.

Zn

Se

Zn


Input: Thus, the supplementation of Zn during pregnancy should be considered with caution in Shanghai, China.

Zn


Input: Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1).

imidazopyridazines

calcium


Input: A series of imidazopyridazines which are potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was identified from a high-throughput screen against the isolated enzyme.

imidazopyridazines

calcium


Input: Subsequent exploration of the SAR and optimisation has yielded leading members which show promising in vitro anti-parasite activity along with good in vitro ADME and selectivity against human kinases.


Input: Initial in vivo testing has revealed good oral bioavailability in a mouse PK study and modest in vivo efficacy in a Plasmodium berghei mouse model of malaria.


Input: Development and evaluation of novel solid nanodispersion system for oral delivery of poorly water-soluble drugs.


Input: The aim of the present study was to develop and evaluate a novel drug solubilization platform (so-called solid nanodispersion) prepared by a simple co-grinding and solvent-free process.


Input: Using structurally diverse model compounds from the Pfizer drug library, including ingliforib, furosemide and celecoxib, we successfully prepared stable solid nanodispersions (SNDs) without the use of solvent or heat.

ingliforib

furosemide

celecoxib


Input: Stable colloidal particles (< 350nm) containing drug, polyvinylpyrrolidone (PVP) K12 and sodium dodecyl sulfate (SDS) in 1: 2. 75: 0. 25 ratio were produced after 2h of co-grinding.

polyvinylpyrrolidone (PVP) K12

sodium dodecyl sulfate

SDS


Input: The composition and particle size of SNDs were optimized by varying the grinding media size, powder-to-grinding media ratio, milling speed and milling time.


Input: The resulting formulations contained crystalline drug and were stable at room temperature for over one month.


Input: Greater than 80% of the drug was released from the SND in less than 30min, with sustained supersaturation over 4h.


Input: Using furosemide (BCS class IV compound) as a model compound, we conducted transport studies with Madin-Darby canine kidney cells transfected with human MDR1 gene (MDCK/MDR1), followed by pharmacokinetics studies in rats.

furosemide


Input: Results showed that the SND formulation enhanced the absorptive flux of furosemide by more than 3-fold.

furosemide


Input: In the pharmacokinetics studies, the SND formulation increased Cmax and AUC of furosemide by 36. 6 and 43. 2 fold respectively, relative to Methocel formulation.

furosemide


Input: Interestingly, physical mixture containing furosemide, PVP K12 and SDS produced a similar level of oral exposure as the SNDs, albeit with a longer Tmax than the SND formulation.

furosemide

PVP K12

SDS


Input: The results suggest that PVP K12 and SDS were able to increase the furosemide free fraction available for oral absorption.

PVP K12

SDS

furosemide


Input: Low solubility, poor permeability, and high first-pass effect of furosemide may also have produced the effect that small improvements in solubilization resulted in significant potentiation of the oral exposure of the physical mixture.

furosemide


Input: However the use of a physical mixture of drug, polymer and surfactant, to increase drug bioavailability cannot be generalized to all drugs.


Input: There are only a few reported cases of such phenomenon.


Input: While SNDs may not be the only option to solubilize compounds in every case, SNDs are expected to be applicable to a broader chemical space of pharmaceutical compounds compared to a physical mixture.


Input: Ultimately, formulation scientists have to exercise judgment in choosing the appropriate formulation strategy for the compound of interest.


Input: SNDs represent a significant improvement over current enabling technologies such as nanocrystal and spray-dried dispersion technologies, in that SNDs are simple, do not require solvent or heat, are applicable to a structurally diverse chemical space, and are amenable to the development of solid dosage forms.


Input: In vivo and in vitro anti-inflammatory potential of pentahydroxy-pregn-14-ol, 20-one-beta-d-thevetopyranoside in rats.

pentahydroxy-pregn-14-ol, 20-one-beta-d-thevetopyranoside


Input: Polyhydroxy pregnane glycoside (PPG), a steroidal glycoside was isolated from Wattakaka volubilis Linn.

Polyhydroxy pregnane glycoside

PPG

steroidal glycoside


Input: (Stap. f.).


Input: PPG was evaluated for in vivo and in vitro anti-inflammatory activity using acute inflammation and chronic model of inflammation in rats and LPS-induced RAW 264. 7 macrophage cells.

PPG


Input: PPG seemed to be responsible for the anti-inflammatory activity in the studied models.

PPG


Input: PPG at dose level of both 5 and 10mg/kg significantly reduced the edema induced by the carrageenan in acute model of inflammation.

PPG


Input: It also showed significant anti-proliferative effect (dry pellet weight basis) in chronic model of inflammation.


Input: Cellular content of granuloma was measured by assaying activity of N-acetyl glucosaminidase (NAG) and total nucleic acid content.

N-acetyl


Input: PPG at 5 and 10mg/kg significantly suppressed the cellular infiltration measured by total nucleic acid content.

PPG


Input: In contrast, NAG activity decreased over a period of 10 days resulting in inhibition of granuloma weight gain.


Input: PPG had a more effective response than the reference drug diclofenac sodium in both the models of inflammation.

PPG

diclofenac sodium


Input: Wattakaka volubilis steroidal glycoside mixture (WVSM) and PPG (1-50 mu M) significantly inhibited the COX-2 and iNOS enzymes resulting in low levels of PGE2 and NO in LPS-induced RAW 264. 7 macrophage cells.

steroidal glycoside

PPG


Input: Hence the study supports the traditional use of Wattakaka volubilis and its constituent PPG in treatment of inflammatory disorders.

PPG


Input: DNA repair activity in fish and interest in ecotoxicology: A review.


Input: The knowledge of DNA repair in a target species is of first importance as it is the primary line of defense against genotoxicants, and a better knowledge of DNA repair capacity in fish could help to interpret genotoxicity data and/or assist in the choice of target species, developmental stage and tissues to focus on, both for environmental biomonitoring studies and DNA repair testing.


Input: This review focuses in a first part on what is presently known on a mechanistic basis, about the various DNA repair systems in fish, in vivo and in established cell lines.


Input: Data on base excision repair (BER), direct reversal with O (6)-alkylguanine transferase and double strand breaks repair, although rather scarce, are being reviewed, as well as nucleotide excision repair (NER) and photoreactivation repair (PER), which are by far the most studied repair mechanisms in fish.

O (6)-alkylguanine

nucleotide


Input: Most of these repair mechanisms seem to be strongly species and tissue dependent; they also depend on the developmental stage of the organisms.


Input: BER is efficient in vivo, although no data has been found on in vitro models.


Input: NER activity is quite low or even inexistent depending on the studies; however this lack is partly compensated by a strong PER activity, especially in early developmental stage.


Input: In a second part, a survey of the ecotoxicological studies integrating DNA repair as a parameter responding to single or mixture of contaminant is realized.


Input: Three main approaches are being used: the measurement of DNA repair gene expression after exposure, although it has not yet been clearly established whether gene expression is indicative of repair capacity; the monitoring of DNA damage removal by following DNA repair kinetics; and the modulation of DNA repair activity following exposure in situ, in order to assess the impact of exposure history on DNA repair capacity.


Input: Since all DNA repair processes are possible targets for environmental pollutants, we can also wonder at which extent such a modulation of repair capacities in fish could be the base for the development of new biomarkers of genotoxicity.


Input: Knowing the importance of the germ cell DNA integrity in the reproductive success of aquatic organisms, the DNA repair capacity of such cells deserve to be more studied, as well as DNA repair capacities of established fish cell lines.


Input: The limited amount of available data, which shows low/slow DNA repair capacities of fish cell lines compared with mammalian cell lines, concerned mainly the NER system; thus this point merits to be explored more deeply.


Input: Additionally, since some of the DNA repair systems appear more efficient in embryo larval stages, it would be of interest to consider embryonic cell lineages more closely.


Input: The Ras-GTPase activity of neurofibromin restrains ERK-dependent FGFR signaling during endochondral bone formation.


Input: The severe defects in growth plate development caused by chondrocyte extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) gain or loss-of-function suggest that tight spatial and temporal regulation of mitogen-activated protein kinase signaling is necessary to achieve harmonious growth plate elongation and structure.


Input: We provide here evidence that neurofibromin, via its Ras guanosine triphosphatase-activating activity, controls ERK1/2-dependent fibroblast growth factor receptor (FGFR) signaling in chondrocytes.

guanosine


Input: We show first that neurofibromin is expressed in FGFR-positive prehypertrophic and hypertrophic chondrocytes during growth plate endochondral ossification.


Input: Using mice lacking neurofibromin 1 (Nf1) in type II collagen-expressing cells, (Nf1col2 (-/-) mutant mice), we then show that lack of neurofibromin in post-mitotic chondrocytes triggers a number of phenotypes reminiscent of the ones observed in mice characterized by FGFR gain-of-function mutations.


Input: Those include dwarfism, constitutive ERK1/2 activation, strongly reduced Ihh expression and decreased chondrocyte proliferation and maturation, increased chondrocytic expression of Rankl, matrix metalloproteinase 9 (Mmp9) and Mmp13 and enhanced growth plate osteoclastogenesis, as well as increased sensitivity to caspase-9 mediated apoptosis.


Input: Using wildtype (WT) and Nf1 (-/-) chondrocyte cultures in vitro, we show that FGF2 pulse-stimulation triggers rapid ERK1/2 phosphorylation in both genotypes, but that return to the basal level is delayed in Nf1 (-/-) chondrocytes.


Input: Importantly, in vivo ERK1/2 inhibition by daily injection of a recombinant form of C-type natriuretic peptide to post-natal pups for 18 days was able to correct the short stature of Nf1col2 (-/-) mice.


Input: Together, these results underscore the requirement of neurofibromin and ERK1/2 for normal endochondral bone formation and support the notion that neurofibromin, by restraining RAS-ERK1/2 signaling, is a negative regulator of FGFR signaling in differentiating chondrocytes.


Input: Stereoselective Glucuronidation of Ornidazole in Humans: Predominant Contribution of UDP-Glucuronosyltransferases 1A9 and 2B7.

Ornidazole

UDP


Input: Ornidazole [R, S-1-chloro-3-(2-methyl-5-nitro-1H-imidazol-1-yl) propan-2-ol] is a chiral 5-nitroimidazole class antimicrobial agent.

Ornidazole

R, S-1-chloro-3-(2-methyl-5-nitro-1H-imidazol-1-yl) propan-2-ol


Input: This study aimed to investigate the principal metabolic pathway of ornidazole in humans and identify the major enzymes involved.

ornidazole


Input: A total of 19 metabolites were identified in human urine collected from patients with hepatobiliary diseases after an intravenous drip infusion of 500 mg of racemic ornidazole.

racemic ornidazole


Input: Stereoselective glucuronidation, followed by renal excretion, was the principal metabolic pathway of ornidazole in humans, accounting for 37. 3% of the administered dose.

ornidazole


Input: Screening assays with 12 available human recombinant UDP-glucuronosyltransferases (UGTs) demonstrated that UGT1A9 was the predominant UGT isoform involved in R-ornidazole glucuronidation, whereas S-ornidazole glucuronidation was almost exclusively catalyzed by UGT2B7.

UDP

R-ornidazole

S-ornidazole


Input: Chemical inhibition study with niflumic acid and flurbiprofen supported these findings.

niflumic acid

flurbiprofen


Input: Enzyme kinetic parameters were then determined in human liver microsomes (HLMs), human kidney microsomes (HKMs), UGT1A9 and 2B7.


Input: The Km values for UGT1A9 (15. 6 +/- 1. 6 mM for R-ornidazole) and 2B7 (3. 8 +/- 0. 9 mM for S-ornidazole) were quite similar to those determined in HLMs and HKMs (20. 1 +/- 1. 4 and 17. 7 +/- 4. 0 mM for R-ornidazole; 6. 6 +/- 1. 3 and 3. 2 +/- 0. 4 mM for S-ornidazole).

R-ornidazole

S-ornidazole

R-ornidazole

S-ornidazole


Input: The in vitro intrinsic clearance (CLint) ratios of S-and R-ornidazole were approximately 4. 3 in HLMs and 6. 5 in HKMs, respectively.

S-and R-ornidazole


Input: The hepatic and renal clearances were estimated based on the well-stirred model.


Input: Overall, stereoselective glucuronidation was the principal metabolic pathway of ornidazole in humans.

ornidazole


Input: Furthermore, UGT1A9 and 2B7 were the predominant UGT isoforms responsible for R-and S-ornidazole glucuronidation in humans, respectively.

R-and S-ornidazole


Input: Ion Mobility Spectrometry-Mass Spectrometry Analysis for the Site of Aromatic Hydroxylation.


Input: Hydroxylated metabolites often retain the pharmacological activity of parent compound, and the position of hydroxylation determines the formation of chemically reactive intermediates such as quinones and analogues from para-and/or ortho-hydroxylation of phenols or arylamines.

quinones

phenols

arylamines


Input: Therefore, the identification of exact position of hydroxylation is often required at the early development stage of new drug candidates.


Input: In many cases, liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides identical MS/MS spectra among isomeric hydroxylated metabolites, and therefore, it alone cannot unequivocally identify the exact position (s) of hydroxylation.


Input: Ion mobility spectrometry (IMS), integrated with LC-MS/MS, recently demonstrates the capability of separating isomeric species based on differences in their drift times from IMS, which are linearly proportional to the collision cross-section (CCS) reflecting physical size and shape.


Input: In the present study, a chemical derivatization of isomeric hydroxylated metabolites with 2-fluoro-N-methyl pyridinium p-toluenesulfonate was found to confer distinct theoretical CCS value on each isomer by forming corresponding N-methyl pyridine (NMP) derivative.

2-fluoro-N-methyl pyridinium p-toluenesulfonate

N-methyl pyridine

NMP


Input: The regression lines established by the comparison between theoretical CCS values and observed drift times from IMS for each set of parent compound (labetalol, ezetimibe, atorvastatin and warfarin) and its MS/MS product ions accurately and selectively projected the actual drift times of NMP derivatives of corresponding aromatic or isomeric hydroxylated metabolites.

labetalol

ezetimibe

atorvastatin

warfarin

NMP


Input: The established method was used for the accurate assignment of predominant formation of 2-hydroxylated metabolite from imipramine in NADPH-fortified human liver microsomes.

imipramine

NADPH


Input: The present application expands the versatility of LC-IMS-MS technique to the structure identification of isomeric hydroxylated metabolites at the early stage for drug development.


Input: Pharmacovigilance Using Clinical Notes.


Input: With increasing adoption of electronic health records (EHRs), there is an opportunity to use the free-text portion of EHRs for pharmacovigilance.


Input: We present novel methods that annotate the unstructured clinical notes and transform them into a deidentified patient-feature matrix encoded using medical terminologies.


Input: We demonstrate the use of the resulting high-throughput data for detecting drug-adverse event associations and adverse events associated with drug-drug interactions.


Input: We show that these methods flag adverse events early (in most cases before an official alert), allow filtering of spurious signals by adjusting for potential confounding, and compile prevalence information.


Input: We argue that analyzing large volumes of free-text clinical notes enables drug safety surveillance using a yet untapped data source.


Input: Such data mining can be used for hypothesis generation and for rapid analysis of suspected adverse event risk. Clinical Pharmacology & Therapeutics (2013); advance online publication 10 April 2013. doi: 10. 1038/clpt. 2013. 47.


Input: Attenuation of erythrocytic actylcholinesterase by antidepressants: Evidence in an in vitro experiment.


Input: The current study was aimed to scrutinize acetylcholinesterase (AchE) inhibitory profile of two antidepressants, diazepam and phenobarbitone.

diazepam

phenobarbitone


Input: The experimental designed was based on Michaelis-Menten parameters (apparent Michaelis constant (aKm) and apparent maximum velocity (aVm)) that estimate inhibition (%) as well as the type of inhibition (mechanism).


Input: The results showed marked inhibition of AchE by diazepam and the values of aKm and aVm were 65. 5% and 52. 63%, respectively.

diazepam


Input: These values suggested a competitive type of antagonism for diazepam.

diazepam


Input: Similar trend of antagonism was shown by phenobarbitone when it was subjected to the challenge of AchE with aKm and aVm values of 51. 99% and 71. 80%, respectively.

phenobarbitone


Input: It is concluded that diazepam and phenobarbitone exhibited prominent AchE attenuation apart from their well-established antidepressant activity, which could be more useful in related diseased conditions.

diazepam

phenobarbitone


Input: A Role for Cargo in the Activation of ADP-Ribosylation Factors (Arf) and Adaptor Recruitment.

ADP


Input: Membrane traffic requires the specific concentration of protein cargos and exclusion of other proteins into nascent carriers.


Input: Critical components of this selectivity are the protein adaptors that bind to short, linear motifs in the cytoplasmic tails of transmembrane protein cargos and sequester them into nascent carriers.


Input: The recruitment of the adaptors is mediated by activated Arf GTPases and the Arf-adaptor complexes mark sites of carrier formation.


Input: However, the nature of the signal (s) that initiate carrier biogenesis remains unknown.


Input: We examined the specificity and initial sites of recruitment of Arf-dependent adaptors (AP-1 and GGAs) in response to the Golgi or endosomal localization of specific cargo proteins (furin, mannose-6-phosphate receptor (M6PR) and M6PR lacking a C-terminal domain M6PR Delta C).

C


Input: We find that cargo promotes the recruitment of specific adaptors, suggesting that it is part of an upstream signaling event.


Input: Cargos do not promote adaptor recruitment to all compartments in which they reside and thus additional factors regulate the cargo' s ability to promote Arf activation and adaptor recruitment.


Input: We document that within a given compartment different cargos recruit different adaptors suggesting that there is little or no free, activated Arf at the membrane and that Arf activation is spatially and temporally coupled to the cargo and the adaptor.


Input: Using temperature block, Brefeldin A, and recovery from each, we found that the cytoplasmic tail of M6PR causes the recruitment of AP-1 and GGAs to recycling endosomes and not at the Golgi, as predicted by steady state staining profiles.

Brefeldin A


Input: These results are discussed with respect to the generation of novel models for cargo-dependent regulation of membrane traffic.


Input: Gelation-induced visible supramolecular chiral recognition by fluorescent metal complexes of quinolinol-glutamide.

quinolinol

glutamide


Input: Three metal complexes consisting of Li (+), Zn (2 +), and Al (3 +) and quinolinol-functionalized l-glutamides (HQLG), (abbreviated as LiHQLG, Zn (HQLG) 2, and Al (HQLG) 3) were found to form fluorescent metallogels in several organic solvents.

Li (+)

Zn (2 +)

Al (3 +)

quinolinol-functionalized l-glutamides

HQLG

LiHQLG

Zn (HQLG) 2

Al (HQLG) 3


Input: In solution, these chiral complexes showed neither any CD signal in the chromophore region nor chiral recognition of the chiral species.


Input: However, upon gel formation, the supramolecular chirality emerged because of the self-assembled nanostructures, which provided an opportunity for the chiral recognition of enantiomeric ligands.


Input: The metallogels showed different fluorescence changes when they met with enantiomeric (R, R)-or (S, S)-1, 2-diaminocyclohexane.

(R, R)-or (S, S)-1, 2-diaminocyclohexane


Input: Among them, the Al (HQLG) 3 metallogels did not show any change whereas the LiHQLG gels exhibited the same decrease in fluorescence.

Al (HQLG) 3

LiHQLG


Input: Interestingly, the Zn (HQLG) 2 gels showed obviously different fluorescent color with respect to (R, R)-and (S, S)-1, 2-diaminocyclohexane, thus providing visible chiral recognition via the naked eye.

Zn (HQLG) 2

(R, R)-and (S, S)-1, 2-diaminocyclohexane


Input: Such different recognition ability was discussed on the basis of the assembled chiral nanostructures and the primary molecular structures of the metal complexes.


Input: It was shown that both of them played important roles in chiral recognition.


Input: JNK inhibitors as anti-inflammatory and neuroprotective agents.


Input: JNK is involved in a broad range of physiological processes.


Input: Several inflammatory and neurodegenerative diseases, such as multiple sclerosis, Alzheimer' s and Parkinson' s disease have been linked with the dysregulated JNK pathway.


Input: Research on disease models using the relevant knockout mice has highlighted the importance of specific JNK isoformsin-particular disorders and has stimulated further efforts in the drug-discovery area.


Input: However, most of the experimental evidence for the efficacy of JNK inhibition in animal models is from studies using JNK inhibitors, which are not isoform selective.


Input: Some of the more recent compounds exhibit good oral bioavailability, CNS penetration and selectivity against the rest of the kinome.


Input: Efforts to design isoform-selective inhibitors have produced a number of examples with various selectivity profiles.


Input: This article presents recent progress in this area and comment on the role of isoform selectivity for efficacy.


Input: Effects of 17 alpha-ethynylestradiol-induced cholestasis on the pharmacokinetics of doxorubicin in rats: reduced biliary excretion and hepatic metabolism of doxorubicin.

17 alpha-ethynylestradiol

doxorubicin

doxorubicin


Input: Abstract 1.


Input: Since the prevalent hormonal combination therapy with estrogen analogues in cancer patients has frequency and possibility to induce the cholestasis, the frequent combination therapy with 17 alpha-ethynylestradiol (EE, an oral contraceptive) and doxorubicin (an anticancer drug) might be monitored in aspect of efficacy and safety.

estrogen

17 alpha-ethynylestradiol

doxorubicin


Input: Doxorubicin is mainly excreted into the bile via P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily.

Doxorubicin


Input: Also the hepatic Mrp2 (not P-gp) and CYP3A subfamily levels were reduced in EE-induced cholestatic (EEC) rats.


Input: Thus, we herein report the pharmacokinetic changes of doxorubicin with respect to the changes in its biliary excretion and hepatic metabolism in EEC rats.

doxorubicin


Input: The pharmacokinetic study of doxorubicin after intravenous administration of its hydrochloride was conducted along with the investigation of bile flow rate and hepatobiliary excretion of doxorubicin in control and EEC rats.

doxorubicin

hydrochloride

doxorubicin


Input: The significantly greater AUC (58. 7% increase) of doxorubicin in EEC rats was due to the slower CL (32. 9% decrease).

doxorubicin


Input: The slower CL was due to the reduction of hepatic biliary excretion (67. 0% decrease) and hepatic CYP3A subfamily-mediated metabolism (21. 9% decrease) of doxorubicin.

doxorubicin


Input: These results might have broader implications to understand the altered pharmacokinetics and/or pharmacologic effects of doxorubicin via biliary excretion and hepatic metabolism in experimental and clinical estrogen-induced cholestasis.

doxorubicin

estrogen


Input: Oxidation of CO by Nickel Oxide Clusters Revealed by Post Heating.

CO

Nickel Oxide


Input: Reactions of nickel oxide cluster ions, NinOn + x (+) (n = 4-10, x =-1 ~ + 3), with CO in a He buffer gas were investigated using mass spectrometry.

nickel oxide

NinOn + x (+)

CO

He


Input: When the cluster ions react at room temperature, a CO molecule tends to attach readily to NinOn + x (+) for all of the cluster ions with different stoichiometry, although rate constants of the CO attachment reaction are more or less stoichiometry-dependent.

CO

NinOn + x (+)

CO


Input: However, CO was found to be released from the cluster ions when the cluster ions were heated up to 523 K after the reaction.

CO


Input: This finding is interpreted such that the CO molecule that physisorbs weakly to NinOn + x (+) at room temperature desorbs into the gas phase by the post heating.

CO

NinOn + x (+)


Input: In addition, we found that an oxygen extraction reaction by a CO molecule actually occurs for oxygen-rich clusters such as Ni6O7 (+) and Ni8O9 (+).

oxygen

CO

oxygen

Ni6O7 (+)

Ni8O9 (+)


Input: As the oxygen extraction reaction is one order of magnitude slower than physisorption, it lies hidden underneath of the faster physisorption processes in the mass spectrum but is revealed by the elimination of physisorption through the post heating.

oxygen


Input: Antigen presentation by dendritic cells in rheumatoid arthritis.


Input: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease that affects largely synovial joints.


Input: It has been postulated that activated autoreactive CD4 T cells play a key role in triggering and/or maintaining the chronic inflammatory process in RA.


Input: Dendritic cells (DCs) are antigen-presenting cells that activate cognate clonal CD4 T cells in the lymph nodes.


Input: The activation process involves the formation of a molecular structure at the DC-CD4 T cell contact zone called immunological synapse (IS).


Input: In RA, the synovium, a thin layer of tissue below the capsule in the joints, shows a massive infiltration of DCs and CD4 T cells.


Input: Subjects bearing HLA-DRB1 alleles of the Major Histocompatibility Complex II gene displaying a motif called RA " shared epitope (SE) ", have an enhanced susceptibility to suffer RA.


Input: Interestingly, the SE-containing HLA-DRB1 molecules display a pocket with a high affinity for citrullinated antigens, which are found at higher levels in subjects prone to develop RA.


Input: Thus, it is possible that the DCs of susceptible individuals may form IS with particular features that may present citrullinated peptides to autorreactive na i ve CD4 T clones that, after being activated, contribute to the initiation or development of the disease.


Input: Herein I put forward a model of RA initiation based on current information on the immune response and RA.


Input: Citrullinated peptides in the diagnosis of rheumatoid arthritis.


Input: Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing rheumatoid arthritis (RA).


Input: ACPAs may be detected several years before symptoms of RA appear, and their presence at disease onset is a good predictor of the development of erosive joint lesions.


Input: RA patients can be classified into two major groups: those who have ACPAs and those who do not.


Input: The presence of ACPAs at early stages of RA predicts the development of earlier and more widespread joint erosions, and low remission rates. Synthetic peptides can replace cognate proteins in solid-phase assays for specific autoantibody recognition in RA patients.


Input: The use of synthetic peptides instead of proteins represents an advantage in terms of the reproducibility of such immunoassays.


Input: Proteins also contain non-citrullinated epitopes that are recognized by non-RA sera and this could reduce the specificity of the test.


Input: The use of synthetic citrullinated peptides gives absolute control over the exact epitopes presented.


Input: Furthermore, it is difficult to prepare sufficient amounts of high-quality antigenic proteins with a well-defined degree of citrullination.


Input: Synthetic citrullinated peptides, in contrast, are easily obtained in a pure form with a well-defined chemical structure and the epitopes can be precisely oriented in the plate by covalent binding of the peptides. Chimeric peptides bearing different citrullinated protein domains have recently been used in the design of RA diagnosis systems.


Input: The results of the application of those systems indicate that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs.


Input: Each of the target molecules reported (fibrin, vimentin and filaggrin) helps to identify a particular subset of RA patients.


Input: Benchmark quantum-chemical calculations on a complete set of rotameric families of the DNA sugar-phosphate backbone and their comparison with modern density functional theory.

sugar

phosphate


Input: The DNA sugar-phosphate backbone has a substantial influence on the DNA structural dynamics.

sugar

phosphate


Input: Structural biology and bioinformatics studies revealed that the DNA backbone in experimental structures samples a wide range of distinct conformational substates, known as rotameric DNA backbone conformational families.


Input: Their correct description is essential for methods used to model nucleic acids and is known to be the Achilles heel of force field computations.


Input: In this study we report the benchmark database of MP2 calculations extrapolated to the complete basis set of atomic orbitals with aug-cc-pVTZ and aug-cc-pVQZ basis sets, MP2 (T, Q), augmented by Delta CCSD (T)/aug-cc-pVDZ corrections.


Input: The calculations are performed in the gas phase as well as using a COSMO solvent model.


Input: This study includes a complete set of 18 established and biochemically most important families of DNA backbone conformations and several other salient conformations that we identified in experimental structures.


Input: We utilize an electronically sufficiently complete DNA sugar-phosphate-sugar () backbone model system truncated to prevent undesired intramolecular interactions.

sugar

phosphate

sugar


Input: The calculations are then compared with other QM methods.


Input: The BLYP and TPSS functionals supplemented with Grimme' s D3 (BJ) dispersion term provide the best tradeoff between computational demands and accuracy and can be recommended for preliminary conformational searches as well as calculations on large model systems.


Input: Among the tested methods, the best agreement with the benchmark database has been obtained for the double-hybrid DSD-BLYP functional in combination with a quadruple-zeta basis set, which is, however, computationally very demanding.


Input: The new hybrid density functionals PW6B95-D3 and MPW1B95-D3 yield outstanding results and even slightly outperform the computationally more demanding PWPB95 double-hybrid functional.


Input: B3LYP-D3 is somewhat less accurate compared to the other hybrids.


Input: Extrapolated MP2 (D, T) calculations are not as accurate as the less demanding DFT-D3 methods.


Input: Preliminary force field tests using several charge sets reveal an almost order of magnitude larger deviations from the reference QM data compared to modern DFT-D3, underlining the challenges facing force field simulations of nucleic acids.


Input: As expected, inclusion of the solvent environment approximated by a continuum approach has a large impact on the relative stabilities of different backbone substates and is important when comparing the QM data with structural bioinformatics and other experimental data.


Input: Golimumab for the Treatment of Rheumatoid Arthritis After the Failure of Previous Disease-Modifying Antirheumatic Drugs: A NICE Single Technology Appraisal.


Input: As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of golimumab (Simponi ((R)); Merck Sharp & Dohme, USA) was invited to submit evidence for its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) after the failure of previous disease-modifying antirheumatic drugs (DMARDs).


Input: The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at The University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG).


Input: This article provides details of the manufacturer' s initial submission, the ERG' s clarification questions and the ERG report submitted to NICE.


Input: The decision made by NICE is provided alongside a brief comment on additional results produced from an additional analysis requested by NICE on behalf of the Committee.


Input: The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on upon the manufacturer' s submission to NICE.


Input: The clinical evidence was derived from three randomized controlled trials of golimumab in the treatment of moderate to severe RA: GO-FORWARD and Kay et al.


Input: (DMARD-experienced population) and GO-AFTER (tumour necrosis factor [TNF]-alpha inhibitor-experienced population).


Input: The ERG considered that the trials were of reasonable methodological quality and measured a clinically relevant range of outcomes.


Input: The trials for golimumab, as well as comparator treatments, were synthesized using mixed-treatment comparison methods for the DMARD-experienced population and an indirect comparison using the Bucher method for the TNF-alpha inhibitor-experienced population.


Input: The trials used were appropriate, although no definitive judgement regarding the comparative efficacy of golimumab with other biologics was possible.


Input: The manufacturer provided a DMARD-experienced population model and a TNF-alpha inhibitor-experienced population model.


Input: The models allowed sequences of treatments to be evaluated for each population, although a fully incremental analysis between the use of golimumab following DMARD failure and the use of golimumab following TNF-alpha inhibitor failure was not possible.


Input: Several limitations with the model were identified, and after a request from NICE and suspension of the appraisal, the manufacturer submitted sensitivity analyses with an additional American College of Rheumatology 70% improvement criteria (ACR70) health state included, using SF-36 data directly from the GO-FORWARD study.


Input: The annual rate of the Health Assessment Questionnaire (HAQ) score increase for patients receiving palliative treatment was also changed from 0. 09 to 0. 06.


Input: The further analyses provided highlighted the particular sensitivity of the results to HAQ progression rates and the re-administration frequency for rituximab in the TNF-alpha inhibitor-experienced population.


Input: The Appraisal Committee concluded that golimumab should be recommended in combination with methotrexate as an option for patients with severe active RA who have failed on conventional DMARDs, or who have failed on a TNF-alpha inhibitor and are contraindicated to or withdrawn from rituximab.

methotrexate


Input: Evolutionary concepts in ecotoxicology: tracing the genetic background of differential cadmium sensitivities in invertebrate lineages.

cadmium


Input: In many toxicological and ecotoxicological studies and experimental setups, the investigator is mainly interested in traditional parameters such as toxicity data and effects of toxicants on molecular, cellular or physiological functions of individuals, species or statistical populations.


Input: It is clear, however, that such approaches focus on the phenotype level of animal species, whilst the genetic and evolutionary background of reactions to environmental toxicants may remain untold.


Input: In ecotoxicological risk assessment, moreover, species sensitivities towards pollutants are often regarded as random variables in a statistical approach.


Input: Beyond statistics, however, toxicant sensitivity of every species assumes a biological significance, especially if we consider that sensitivity traits have developed in lineages of species with common evolutionary roots.


Input: In this article, the genetic and evolutionary background of differential Cd sensitivities among invertebrate populations and species and their potential of adaptation to environmental Cd exposure will be highlighted.

Cd

Cd


Input: Important evolutionary and population genetic concepts such as genome structure and their importance for evolutionary adaptation, population structure of affected individuals, as well as micro and macroevolutionary mechanisms of Cd resistance in invertebrate lineages will be stressed by discussing examples of work from our own laboratory along with a review of relevant literature data and a brief discussion of open questions along with some perspectives for further research.

Cd


Input: Both, differences and similarities in Cd sensitivity traits of related invertebrate species can only be understood if we consider the underlying evolutionary processes and genetic (or epigenetic) mechanisms.

Cd


Input: Keeping in mind this perception can help us to better understand and interpret more precisely why the sensitivity of some species or species groups towards a certain toxicant (or metal) may be ranked in the lower or higher range of species sensitivity distributions.


Input: Hence, such a perspective will transcend a purely statistical view of the sensitivity distributions concept, and will enhance ecotoxicology in many respects.


Input: A Platform for Large-Scale Graphene Electronics-CVD Growth of Single-Layer Graphene on CVD-Grown Hexagonal Boron Nitride.

Graphene

Graphene

Boron Nitride


Input: Direct chemical vapor deposition (CVD) growth of single-layer graphene on CVD-grown hexagonal boron nitride (h-BN) film can suggest a large-scale and high-quality graphene/h-BN film hybrid structure with a defect-free interface.

graphene

boron nitride

BN

graphene

BN


Input: This sequentially grown graphene/h-BN film shows better electronic properties than that of graphene/SiO2 or graphene transferred on h-BN film, and suggests a new promising template for graphene device fabrication.

graphene

BN

graphene

graphene

BN

graphene


Input: The cation-pi box is a specific phosphatidylcholine membrane targeting motif.

phosphatidylcholine


Input: PPeripheral membrane proteins can be targeted to specific organelles or the plasma membrane by differential recognition of phospholipid headgroups.


Input: While molecular determinants of specificity for several headgroups, including phosphatidylserine and phosphoinositides are well defined, specific recognition of the headgroup of the zwitterionic phosphatidylcholine (PC) is less well understood.

phosphatidylserine

phosphoinositides

phosphatidylcholine


Input: In cytosolic proteins the cation-pi box provides a suitable receptor for choline recognition and binding through the trimethylammonium moiety.

choline

trimethylammonium


Input: In PC, this moiety might provide a sufficient handle to bind to peripheral proteins via a cation-pi cage, where the pi systems of two or more aromatic residues are within 4-5 A of the quaternary amine.

quaternary amine


Input: We prove this hypothesis by engineering the cation-pi box into secreted phosphatidylinositol-specific phospholipase C from Staphylococcus aureus, which lacks specific PC recognition.

phosphatidylinositol


Input: The N254Y/H258Y variant selectively binds PC-enriched vesicles, and X-ray crystallography reveals N254Y/H258Y binds choline and dibutyroylphosphatidylcholine within the cation-pi motif.

choline

dibutyroylphosphatidylcholine


Input: Such simple PC recognition motifs could be engineered into a wide variety of secondary structures providing a generally applicable method for specific recognition of PC.


Input: Theoretical Investigation of Generator-Collector Microwell Arrays for Improving Electroanalytical Selectivity: Application to Selective Dopamine Detection in the Presence of Ascorbic Acid.

Dopamine

Ascorbic Acid


Input: Recessed generator-collector assemblies consisting of an array of recessed disks (generator electrodes) with a gold layer (collector electrode) deposited over the top-plane insulator reportedly allow increased selectivity and sensitivity during electrochemical detection of dopamine (DA) in the presence of ascorbic acid (AA), a situation which is frequently encountered.

dopamine

ascorbic acid


Input: In sensor design, the potential of the disk electrodes is set to the wave plateau of DA, whereas the plane electrode is biased at the irreversible wave plateau of AA before the onset of the DA oxidation wave.


Input: Thus, AA is scavenged but DA is allowed to enter the nanocavities to be oxidized at the disk electrodes, and its signal is further amplified by redox cycling between disk and plane electrodes.


Input: Several different theoretical approaches are elaborated herein to analyze the behavior of the system, and their conclusions are successfully tested by experiments.


Input: This reveals the crucial role of the plane-electrode area which screens access to the recessed disks (i. e. acts as a diffusional Faraday cage) and simultaneously contributes to amplification of the analyte signal through positive feedback, as occurs in interdigitated arrays and scanning electrochemical microscopy.


Input: Simulations also allow for the evaluation of the benefits of different geometries inspired by the above design and different operating modes for increasing the sensor performance.


Input: Tuning the Electrical and Optical Properties of Graphene by Ozone Treatment for Patterning Monolithic Transparent Electrodes.

Graphene

Ozone


Input: Tunable electrical and optical properties of graphene are vital to promote its use as film electrodes in a variety of devices.

graphene


Input: We developed an etching-free ozone treatment method to continuously tune the electrical resistance and optical transmittance of graphene films by simply varying the time and temperature of graphene exposure to ozone.

ozone

graphene

graphene

ozone


Input: Initially, ozone exposure dramatically decreases the electrical resistance of graphene films by p-doping, but this is followed by increases in the resistance and optical transmittance as a result of surface oxidation.

ozone

graphene


Input: The rate of resistance increase can be significantly increased by raising the treatment temperature.


Input: The ozone-oxidized graphene is not removed but is gradually transformed to graphene oxide (GO).

ozone

oxidized graphene

graphene oxide


Input: On the basis of such effects of ozone treatment, we demonstrate a well-defined graphene pattern by using ozone photolithography, in which the ozone-treated graphene electrodes are monolithic but separated by insulating GO regions.

ozone

graphene

ozone

ozone

graphene


Input: Such a monolithic graphene pattern shows low optical contrast, a clean and more hydrophilic surface, indicating the promising use of ozone treatment to achieve high-performance graphene-based optoelectronic devices.

graphene

ozone

graphene


Input: Asymmetric dimethylarginine predicts decline of glucose tolerance in men with stable coronary artery disease: a 4. 5-year follow-up study.

Asymmetric dimethylarginine

glucose


Input: BACKGROUND: Endothelial dysfunction, largely dependent on impaired nitric oxide bioavailability, has been reportedly associated with incident type 2 diabetes.

nitric oxide


Input: Our aim was to test the hypothesis that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide formation, might be linked to future deterioration in glucose tolerance in stable coronary artery disease (CAD).

asymmetric dimethylarginine

ADMA

nitric oxide

glucose


Input: METHODS: We studied 80 non-diabetic men (mean age 55 +/-11 years) with stable angina who underwent successful elective complex coronary angioplasty and were receiving a standard medical according to practice guidelines.


Input: Plasma ADMA and its structural isomer symmetric dimethylarginine (SDMA) were measured prior to coronary angiography.

ADMA

symmetric dimethylarginine

SDMA


Input: An estimate of insulin resistance by homeostasis model assessment (HOMA-IR index) was calculated from fasting insulin and glucose.

glucose


Input: Deterioration in glucose tolerance was defined as development of type 2 diabetes or progression from a normal glucose tolerance to impaired fasting glucose.

glucose

glucose

glucose


Input: RESULTS: Over a median follow-up of 55 months 11 subjects developed type 2 diabetes and 13 progressed to impaired fasting glucose.

glucose


Input: Incident deterioration of glucose tolerance was associated with ADMA (hazard ratio [HR] per 1-SD increment 1. 64 [95% CI: 1. 14--2. 35]; P = 0. 007), log (HOMA-IR index) (HR = 1. 60 [1. 16--2. 20]; P = 0. 004) and body-mass index (HR = 1. 44 [0. 95--2. 17]; P = 0. 08) by univariate Cox regression.

glucose

ADMA


Input: ADMA (HR = 1. 65 [1. 14--2. 38]; p = 0. 008) and log (HOMA-IR index) (HR = 1. 55 [1. 10--2. 17]; P = 0. 01) were multivariate predictors of a decline in glucose tolerance.

ADMA

glucose


Input: ADMA and SDMA were unrelated to body-mass index, HOMA-IR index, insulin or glucose.

ADMA

SDMA

glucose


Input: CONCLUSIONS: ADMA predicts future deterioration of glucose tolerance independently of baseline insulin resistance in men with stable CAD.

ADMA

glucose


Input: Whether this association reflects a contribution of endothelial dysfunction to accelerated decline of insulin sensitivity, or represents only an epiphenomenon accompanying pre-diabetes, remains to be elucidated.


Input: The observed relationship might contribute to the well-recognized ability of ADMA to predict cardiovascular outcome.

ADMA


Input: Sodium fluoride induces apoptosis in odontoblasts via a JNK-dependent mechanism.

Sodium fluoride


Input: Sodium fluoride (NaF) is widely used for the treatment of dental caries and dentin hypersensitivity.

Sodium fluoride

NaF


Input: However, its pro-apoptotic effect on odontoblasts may lead to harmful side-effects.


Input: The purpose of this study was to evaluate the pro-apoptotic effects of NaF in odontoblasts and elucidate the possible underlying molecular mechanisms.

NaF


Input: NaF generated cytotoxic effects in odontoblast-lineage cell (OLC) in a dose-and time-dependent manner.

NaF


Input: Exposure of cells to 4mM NaF for 24h induced caspase-3 activation, ultrastructural alterations, and resulted in the translocation of Bax to the mitochondria and the release of cytochrome c from the mitochondrial inter-membrane space into the cytosol, indicating that fluoride-mediated apoptosis is mitochondria-dependent.

NaF

fluoride


Input: Fluoride treatment also increased phosphorylation of JNK and ERK, but not p38, and apoptosis induced by fluoride was notably or partly suppressed by treatment with JNK or ERK inhibitors, respectively.

Fluoride

fluoride


Input: Taken together, these findings suggest that NaF induces apoptosis in OLC odontoblasts through a JNK-dependent mitochondrial pathway.

NaF


Input: Perinatal exposure to BDE-99 causes learning disorders and decreases serum thyroid hormone levels and BDNF gene expression in hippocampus in rat offspring.

thyroid hormone


Input: Exposure of pregnant women to polybrominated diphenyl ethers (PBDEs) may mean serious health risks.

polybrominated diphenyl ethers

PBDEs


Input: The main goal of the present study was to examine the neurobehavioral changes in rat offspring that were perinatally exposed to one of the most prevalent PBDEs congeners found in humans, 2, 2', 4, 4', 5-pentaBDE (BDE-99).

PBDEs

2, 2', 4, 4', 5-pentaBDE


Input: Rat dams were exposed to 0, 1 and 2mg/kg/day of BDE-99 from gestation day 6 to post-natal day 21.


Input: When pups were weaning, cortex and hippocampal gene expressions of brain-derived neurotrophic factor (BDNF) of the different isoforms of the thyroid hormone (TH) receptors (TRs) were evaluated.

thyroid hormone


Input: Serum TH levels were also determined.


Input: The remaining pups were assessed by neurobehavioral testing for learning and memory function.


Input: The results showed that maternal transference of BDE-99 produced a delay in the spatial learning task in the water maze test.


Input: Moreover, the open-field test revealed a significant dose-response anxiolytic effect.


Input: It was also found that the serum levels of triiodothyronine (T3), tetraiiodothyronine (T4) and free-T4 (FT4) decreased.

triiodothyronine

tetraiiodothyronine


Input: Although no effect on the gene expression of the different isoforms of TRs was observed, the expression of the TH-mediated gene BDNF was down-regulated in the hippocampus.


Input: These results indicate a clear signal disruption of TH and reinforce previous studies in which neurotoxic effects of PBDEs in animal research were observed at levels comparable to those found in humans.

PBDEs


Input: Reward and aversion in a heterogeneous midbrain dopamine system.

dopamine


Input: The ventral tegmental area (VTA) is a heterogeneous brain structure that serves a central role in motivation and reward processing.


Input: Abnormalities in the function of VTA dopamine (DA) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression.

dopamine


Input: Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections.


Input: These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events.


Input: Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse, in particular cocaine, alter circuit function within a heterogeneous midbrain DA system.

cocaine


Input: This article is part of a Special Issue entitled' NIDA 40th Anniversary Issue'.


Input: Phytotoxic effects of the cyanobacterial neurotoxin anatoxin-a: Morphological, physiological and biochemical responses in aquatic macrophyte, Ceratophyllum demersum.

anatoxin-a


Input: Anatoxin-a is one of the common and major cyanobacterial neurotoxins acting as a powerful agonist at nicotinic acetylcholine receptors (nAChR).

Anatoxin-a

acetylcholine


Input: In recent years, the toxin has become the focus of public attention, due to the mass development of cyanobacteria (cyanobacterial blooms) in freshwater bodies triggered by eutrophication and climate change.


Input: Anatoxin-a is suspected to have a distinct toxic mechanism depending on physiological and nervous systems in exposed organisms.

Anatoxin-a


Input: The numerous researches have been actively conducted with respect to the toxic effects of anatoxin-a on mammals; however, little research has aimed at its possible effects on aquatic plants, wherein well-structured nervous system is absent with the lack of various components of the acetylcholine mechanism.

anatoxin-a

acetylcholine


Input: In this study, submerged macrophyte Ceratophyllum demersum (C. demersum) was adopted to examine the effects of anatoxin-a on morphological (growth), physiological (photosynthetic pigment contents) and biochemical (hydrogen peroxide level, biotransformation and antioxidative enzymes) responses in the aquatic plant at environmentally relevant concentrations (0. 005, 0. 05, 0. 5, 5 and 50 mu g/L).

anatoxin-a

hydrogen peroxide


Input: The significant elevation of antioxidative enzymes in parallel with increased formation of hydrogen peroxide appeared from 0. 5 mu g/L of anatoxin-a.

hydrogen peroxide

anatoxin-a


Input: In the measurement of photosynthetic pigments, the decrease in chlorophyll a content was detected at 5 and 50 mu g/L, whereas the increase in carotenoids/total chlorophyll was observed from 0. 05 mu g/L.

chlorophyll a

chlorophyll


Input: Accordingly, the alteration in growth was manifested in the presence of 5 and 50 mu g/L of anatoxin-a.

anatoxin-a


Input: The results clearly indicate that anatoxin-a can disrupt homeostasis of C. demersum through induction of oxidative stress; furthermore this aquatic plant possesses effective defense mechanisms to cope with low concentrations of anatoxin-a.

anatoxin-a

anatoxin-a


Input: The next generation of novel low-density lipoprotein cholesterol-lowering agents: Proprotein convertase subtilisin/kexin 9 inhibitors.

cholesterol


Input: Proprotein convertase subtilisin/kexin 9 (PCSK9) has been shown to degrade hepatic low-density lipoprotein receptors (LDLR).


Input: Gain-of-function mutations promote the development of familial hypercholesterolemia, whereas loss-of-function mutations are associated with lower levels of circulating low-density lipoprotein cholesterol (LDL-C) and significant protection against coronary heart disease.


Input: The major classes of commonly prescribed lipid-lowering medications, such as statins, increase serum PCSK9 levels, thus PCSK9 inhibition would increase the efficacy of statins on LDL-C lowering.


Input: Therefore, PCSK9 is an attractive therapeutic target for the new generation of cholesterol-lowering drugs.

cholesterol


Input: Here, we present a brief overview of the development of PCSK9 inhibitors and highlight the effect of currently prescribed LDL-C-lowering drugs on PCSK9, and the strategies that are being explored for its therapeutic inhibition.


Input: Current research and clinical trial results indicate that a PCSK9 inhibitor may be an exciting new therapeutic drug for the treatment of dyslipidemia and relevant cardiovascular diseases.


Input: Role of plant stanol derivatives in the modulation of cholesterol metabolism and liver gene expression in mice.

stanol

cholesterol


Input: The present study was to evaluate the cholesterol-lowering effect of two novel plant stanol derivatives and its potential molecular mechanism in hyper-cholesterol mice induced by a high-cholesterol diet.

cholesterol

stanol

cholesterol

cholesterol


Input: Results showed that oral administration of plant stanyl hemisuccinate (2 x, 5 x) and plant stanyl sorbitol succinate (2 x, 5 x) effectively attenuated the serum total cholesterol and low density lipoprotein cholesterol levels, while had no effect on the serum triacylglycerol and high density lipoprotein cholesterol.

stanyl hemisuccinate

stanyl sorbitol succinate

cholesterol

cholesterol

triacylglycerol

cholesterol


Input: And plant stanol derivatives decreased liver cholesterol concentration and increased faecal cholesterol output.

stanol

cholesterol

cholesterol


Input: Meanwhile, both plant stanyl hemisuccinate and plant stanyl sorbitol succinate could remarkably promote liver X receptor alpha (LXR alpha) expression, and increased cholesterol 7 alpha-hydroxylase (CYP7A1) expression and faecal total bile acid output to varying degrees.

stanyl hemisuccinate

stanyl sorbitol succinate

cholesterol

bile acid


Input: These results suggested two novel plant stanol derivatives possessed hypocholesterolemic effect, and the cholesterol-lowering action of plant stanol derivatives may be through activating the potential LXR alpha-CYP7A1-bile acid excretion pathway.

stanol

stanol

bile acid


Input: An optimised method for the accurate determination of zeranol and diethylstilbestrol in animal tissues using isotope dilution-liquid chromatography/mass spectrometry.

zeranol

diethylstilbestrol


Input: Isotope dilution-liquid chromatography/mass spectrometry (ID-LC/MS) has been established as a candidate reference method for the accurate determination of growth promoters (zeranol, taleranol, and diethylstilbesterol) in raw meat samples.

zeranol

taleranol

diethylstilbesterol


Input: Sample preparation processes including an enzymatic hydrolysis, extraction, and SPE clean-up were optimised.


Input: The sensitivity difference of trans-and cis-diethylstilbestrol (isomerizing in sample preparation processes) by the LC/MS was measured by running a trans/cis mixture (ratio measured by a quantitative NMR) with and without sample matrices, and applied for the determination of total diethylstilbestrol.

trans-and cis-diethylstilbestrol

diethylstilbestrol


Input: Validity, repeatability, and reproducibility of the analytical method were tested by measuring gravimetrically fortified samples (chicken breast, bovine muscles, and porcine muscle) in a number of different time periods.


Input: Measurement results agreed with the fortified values within their uncertainties.


Input: The method provided accurate results of the target analytes in the range of 0. 05-15 mu g/kg with the relative expanded uncertainty of 2-15%.


Input: Characterization of Muscat wines aroma evolution using comprehensive gas chromatography followed by a post-analytic approach to 2D contour plots comparison.


Input: This study presents the application of a headspace solid-phase microextraction (HS-SPME) method on the analysis of Muscat-based wines volatiles by comprehensive two-dimensional gas chromatography (GC x GC) and Time-Of-Flight mass spectrometry (TOF-MS).


Input: The aroma patterns were established for different samples of Asti Spumante and Moscato d' Asti wines, stored in bottles for 6months at different temperatures.


Input: Wines stored at 5 degrees C for 6months did not show significant changes in flavor; otherwise, the samples stored at 15 and 25 degrees C, showed a significant decrease in linalool, beta-damascenone, ethyl hexanoate, and ethyl octanoate levels.

linalool

beta-damascenone

ethyl hexanoate

ethyl octanoate


Input: In these last samples, alpha-terpineol, hotrienol, nerol oxide, furanic linalool oxides A/B and rose oxide concentrations significantly increased.

alpha-terpineol

hotrienol

nerol oxide

furanic linalool oxides A/B

rose oxide


Input: A mathematical approach was developed and applied to raw data exported after the chromatographic course, in order (i) to normalise different 2D chromatograms, permitting their direct comparison and (ii) to automatically identify and calculate from pixel-to-pixel re-designed 2D chromatograms any differences among key volatile compounds.


Input: Evolution of quality parameters during red wine dealcoholization by osmotic distillation.


Input: Osmotic distillation technique was used for the total dealcoholization of a red wine (Aglianico grape variety) up to 0. 19vol.%.


Input: The dealcoholization process was performed in subsequent cycles which gave rise wine samples at different alcoholic degrees.


Input: The effect of processing on the main chemical and physical properties of Aglianico wine was evaluated.


Input: Among wine samples, no significant differences (p < 0. 05) of oenological parameters such as pH, total acidity were found.


Input: Similarly, the total phenolic, flavonoids and tartaric esters content and the composition of organic acids did not show significant differences (p < 0. 05) during the process.

phenolic

flavonoids

tartaric esters


Input: On the contrary, colour intensity and tonality of wine samples changed significantly when the alcohol reduction was over the 6. 5vol.%.

alcohol


Input: Finally, the total dealcoholized wine showed properties similar to Aglianico wine except for the volatile compounds, which decreased over 98%.


Input: Hence, flavour enrichment may be required to produce a pleasurable and delicious non alcoholic beverage from wine.


Input: The impact of catechin and epicatechin, total phenols and PPO activity on the Mal d 1 content in apple fruit.

catechin

epicatechin

phenols


Input: The most important apple allergen in Central Europe and North America is Mal d 1.


Input: Apples are a very important source of secondary plant metabolites like polyphenols in human nutrition.

polyphenols


Input: It is known that oxidised phenols can bind proteins.

oxidised phenols


Input: These irreversible bindings can lead to a reduced allergenicity.


Input: The most important phenols in apple are epicatechin, catechin and their polymeric structures, which have been identified as substrates of the polyphenoloxidase (PPO).

phenols

epicatechin

catechin


Input: The aim of this study was to analyse the influence of naturally occurring catechin and epicatechin contents in apple on the allergenicity of apple fruits.

catechin

epicatechin


Input: Fruits of the cultivars' Elstar',' Diwa' and' Boskoop' were harvested and stored for 8 and 12weeks in a cold-chamber at 2 degrees C.


Input: Mal d 1-, catechin-, epicatechin-and total phenol content as well as the activity of PPO were determined.

catechin

epicatechin

phenol


Input: Correlation analysis showed that naturally occurring catechin as well as epicatechin has no impact on the Mal d 1 content of the tested cultivars: correlation coefficient ranged from-0. 203 to 0. 501 for the correlation between Mal d 1 and catechin.

catechin

epicatechin

catechin


Input: The results further indicated that the activity of PPO is more important than the content of total phenols to reduce the Mal d 1 level.

phenols


Input: If there is a high PPO activity, Mal d 1 could be reduced even if the total phenol concentration is low.

phenol


Input: Modeling and prediction of extraction profile for microwave-assisted extraction based on absorbed microwave energy.


Input: A modeling technique based on absorbed microwave energy was proposed to model microwave-assisted extraction (MAE) of antioxidant compounds from cocoa (Theobroma cacao L.) leaves.


Input: By adapting suitable extraction model at the basis of microwave energy absorbed during extraction, the model can be developed to predict extraction profile of MAE at various microwave irradiation power (100-600W) and solvent loading (100-300ml).


Input: Verification with experimental data confirmed that the prediction was accurate in capturing the extraction profile of MAE (R-square value greater than 0. 87).


Input: Besides, the predicted yields from the model showed good agreement with the experimental results with less than 10% deviation observed.


Input: Furthermore, suitable extraction times to ensure high extraction yield at various MAE conditions can be estimated based on absorbed microwave energy.


Input: The estimation is feasible as more than 85% of active compounds can be extracted when compared with the conventional extraction technique.


Input: A new method for detection of five alternaria toxins in food matrices based on LC-APCI-MS.


Input: A new method for the detection of alternariol (AOH), alternariol monomethyl ether (AME), altenuene (ALT), tentoxin (TEN), and tenuazonic acid (TeA), five alternaria toxins (ATs) was developed by liquid chromatography-triple quadrupole mass spectrometry equipped with atmospheric pressure chemical ionisation (APCI).

alternariol

AOH

alternariol monomethyl ether

AME

altenuene

ALT

tentoxin

TEN

tenuazonic acid

TeA


Input: A single extraction was used to recover the five ATs by apple juices, beers, tomato sauces, olives and dried basil.


Input: Different Solid Phase Extractions (SPE) and clean-up were selected to optimise the purification step for each food matrix.


Input: Limits of detection and quantification were, respectively, in the range 0. 16-12. 31 and 0. 54-41. 04ngg (-1).


Input: Recovery rates were generally above 70%, except for dried basil and olives.


Input: Thirty out of 70 samples analysed (7 apple juices, 14 beers and 9 tomato sauces) resulted positive to at least one alternaria toxin investigated.


Input: AOH was the most common AT (14 samples), followed by ALT (10 samples).

AOH

ALT


Input: The highest concentration of ATs was found in commercial apple juices (35. 33ngg (-1)).


Input: Extraction of oak volatiles and ellagitannins compounds and sensory profile of wine aged with French winewoods subjected to different toasting methods: Behaviour during storage.


Input: In Merlot wines the evolution of volatile and non-volatile (ellagitannins) compounds extracted from winewoods while being macerated for 12months was studied.


Input: Seven types of winewoods subjected to different toasting methods were used.


Input: Different rates of extraction, depending mainly on wood compounds origin (toasting or naturally present in wood) and on the watering process during toasting, were observed, which were reflected in sensory differences.


Input: Globally, volatile phenols together with aldehydes, phenols and lactones showed an increase with increasing maceration time.

phenols

aldehydes

phenols

lactones


Input: Ellagitannins were extracted faster during the first 3months; after 6months an important decrease was observed.


Input: Wines with winewoods subjected to watering during toasting were lower in ellagitannins concentrations and demonstrated the greatest decrease of these compounds during maceration.


Input: Astringency and bitterness intensified with increasing ellagitannins.


Input: Lactones induced positive sweetness sensations, whereas furanic and guaiacol compounds influenced bitterness and astringency.

Lactones

furanic

guaiacol


Input: Spicy and vanilla descriptors were related to eugenol, vanillin and other odorous chemicals.

eugenol

vanillin


Input: Selenium bioaccessibility and speciation in biofortified Pleurotus mushrooms grown on selenium-rich agricultural residues.

Selenium

selenium


Input: Cultivation of saprophytic fungi on selenium-rich substrates can be an effective means to produce selenium-fortified food.

selenium

selenium


Input: Pleurotus florida, an edible species of oyster mushrooms, was grown on wheat straw from the seleniferous belt of Punjab (India) and its potential to mobilize and accumulate selenium from the growth substrate was studied.

selenium


Input: Selenium concentration in biofortified mushrooms was 800 times higher compared with control samples grown on wheat straw from non selenium-rich areas (141 vs 0. 17 mu gSeg (-1) dry weight).

Selenium

selenium

gSeg


Input: Seventy-five percent of the selenium was extracted after in vitro simulated gastrointestinal digestion and investigation of the selenium molecular fractions by size exclusion HPLC-ICP-MS revealed that proteins and any other high molecular weight selenium-containing molecule were hydrolyzed to peptides and low molecular weight selenocompounds.

selenium

selenium

selenium


Input: Analysis of the gastrointestinal hydrolysates by anion exchange HPLC-ICP-MS showed that the bioaccessible selenium was mainly present as selenomethionine, a good bioavailable source of selenium, which accounted for 73% of the sum of the detected species.

selenium

selenomethionine

selenium


Input: This study demonstrates the feasibility of producing selenium-biofortified edible mushrooms using selenium-rich agricultural by-products as growth substrates.

selenium

selenium


Input: The proposed approach can be used to evaluate whether selenium-contaminated plant waste materials harvested from high-selenium areas may be used to produce selenium-biofortified edible mushrooms based on the concentration, bioaccessibility and speciation of selenium in the mushrooms.

selenium

selenium

selenium

selenium


Input: Characterization of Hatay honeys according to their multi-element analysis using ICP-OES combined with chemometrics.


Input: Chemical characterisation has been carried out on 45 honey samples collected from Hatay region of Turkey.


Input: The concentrations of 17 elements were determined by inductively coupled plasma optical emission spectrometry (ICP-OES).


Input: Ca, K, Mg and Na were the most abundant elements, with mean contents of 219. 38, 446. 93, 49. 06 and 95. 91mgkg (-1) respectively.

Ca

K

Mg


Input: The trace element mean contents ranged between 0. 03 and 15. 07mgkg (-1).


Input: Chemometric methods such as principal component analysis (PCA) and cluster analysis (CA) techniques were applied to classify honey according to mineral content.


Input: The first most important principal component (PC) was strongly associated with the value of Al, B, Cd and Co.

Al

B

Cd

Co


Input: CA showed eight clusters corresponding to the eight botanical origins of honey.


Input: PCA explained 75. 69% of the variance with the first six PC variables.


Input: Chemometric analysis of the analytical data allowed the accurate classification of the honey samples according to origin.


Input: Proteolytic activities in fillets of selected underutilized Australian fish species.


Input: The hydrolytic activity of major endogenous proteases, responsible for proteolysis of myofibrillar proteins during post-mortem storage, may be an indicator of the textural quality of fish which influences consumer purchasing behaviour and thus market value of the final product.


Input: Furthermore, it may also influence the type and bioactive properties of the peptides released during post-mortem proteolysis of myofibrillar proteins.


Input: This study compared the activities of cathepsins B, B + L, D, H and calpain-like enzymes in crude muscle extracted from 16 Australian underutilized fish species.


Input: Fish species had a significant effect on the activity of these enzymes with barracouta showing the highest cathepsins B, B + L, D and H activities.


Input: Activities of cathepsins B and B + L were higher than cathepsin H for all studied species.


Input: The more commercially important rock ling and tiger flathead demonstrated higher cathepsin B + L activity, whereas gemfish and eastern school whiting showed higher activity towards cathepsin B.


Input: Underutilized fish species showing higher endogenous protease activities may be suitable for fish sauce production, whereas those with lower protease activities for surimi processing.


Input: Flavonol glycosides with lipid accumulation inhibitory activity and simultaneous quantitative analysis of 15 polyphenols and caffeine in the flower buds of Camellia sinensis from different regions by LCMS.

Flavonol glycosides

polyphenols

caffeine


Input: A simultaneous quantitative analytical method for 15 major polyphenols, e. g. five catechins (1-5) and 10 flavonols (6-15), as functional constituents in the extracts of " tea flowers ", the flower buds of Camellia sinensis (Theaceae), has been developed.

polyphenols

catechins

flavonols


Input: The content of caffeine (16), which showed similar chromatographic behaviour under the analytical conditions, was also determined.

caffeine


Input: To approve the validity of the newly developed protocol, thirteen extracts of the plant' s flower buds collected from different regions, i. e. China, Taiwan, Japan and India, were evaluated.


Input: The results indicated that the assay was reproducible and precise, and could be readily underutilised for the quality evaluation of tea flowers on the basis of polyphenols' contents.

polyphenols


Input: It was noteworthy that the contents of two major constituents, kaempferol 3-O-beta-d-glucopyranosyl-(1 --> 3)-alpha-l-rhamnopyranosyl-(1 --> 6)-beta-d-glucopyranoside (10) and kaempferol 3-O-beta-d-glucopyranosyl-(1 --> 3)-alpha-l-rhamnopyranosyl-(1 --> 6)-beta-d-galactopyranoside (11), varied by region where the flower buds were produced.

kaempferol 3-O-beta-d-glucopyranosyl-(1 --> 3)-alpha-l-rhamnopyranosyl-(1 --> 6)-beta-d-glucopyranoside

kaempferol 3-O-beta-d-glucopyranosyl-(1 --> 3)-alpha-l-rhamnopyranosyl-(1 --> 6)-beta-d-galactopyranoside


Input: A new flavonol glycoside, chakaflavonoside B (17), which was isolated in the course of this analytical study, was found to show oleic acid-albumin-induced lipid accumulation inhibitory activity.

flavonol glycoside

chakaflavonoside B

oleic acid


Input: Hemocyanin-derived phenoloxidase activity: A contributing factor to hyperpigmentation in Nephrops norvegicus.


Input: The phenomenon of hyperpigmentation (melanosis) in shellfish has long been attributed to phenoloxidase enzymes.


Input: Over the last number of years, the oxygen carrier hemocyanin, has demonstrated several immune-and physiological functionalities, most notably, inducible phenoloxidase activity.

oxygen


Input: In this study, hemocyanin purified from the hemolymph of Nephrops norvegicus displays diphenoloxidase activity in the presence of a number of elicitors and retains structural and functional integrity throughout the process of freeze-thawing (at-25 degrees C).


Input: Conversely, cellular phenoloxidase activity (present in cell-lysates), demonstrates > 98% reduction in activity after freeze-thawing.


Input: We present evidence that hemocyanin may act as a causative agent of hyperpigmentation in N. norvegicus.


Input: The inhibition of hemocyanin-derived phenoloxidase activity is discussed, and for the first time, the biophysical interactions of shellfish hemocyanin with known phenoloxidase inhibitors are presented.


Input: Residues and dissipation of kresoxim methyl in apple under field condition.

kresoxim methyl


Input: The dissipation and residual levels of kresoxim methyl in apple under field condition were determined by using HPLC-DAD with QuEChERS method.

kresoxim methyl


Input: At fortification levels of 0. 05, 0. 1, 0. 5 and 1. 0mgkg (-1) in apple, it was shown that recoveries were ranged from 91. 1% to 96. 9% with coefficient variation of the method (CV%) for repeatability ranged from 1. 27% to 4. 77%.


Input: The limit of quantification (LOQ) of the method was 0. 05mgkg (-1).


Input: The dissipation rates of kresoxim methyl were described by using first-order kinetics and its half-life, as they are ranged from 4. 58 to 4. 77days in apple.

kresoxim methyl


Input: The terminal residues of kresoxim methyl were below the FAO/WHO maximum residue limit (MRL, 0. 2mgkg (-1)) in apple when measured 14days after the final application, which suggested that the use of this fungicide was safe for humans.

kresoxim methyl


Input: This study would help in providing the basic information for developing regulation to guard a safe use of kresoxim methyl in apple orchard and to prevent health problem from consumers.

kresoxim methyl


Input: Impact of the Mediterranean fruit fly (Medfly) Ceratitis capitata on different peach cultivars: The possible role of peach volatile compounds.


Input: The relationship between susceptibility of different peach cultivars (cvs) to the Mediterranean fruit fly (medfly), Ceratitis capitata, and the volatile composition of ripe fruit of each cv has been investigated, since understanding the fruit-insect interaction mechanism is crucial for developing control strategies for such a pest.


Input: Volatile compounds were analyzed by SPME-GC-MS in three cvs highly susceptible to medfly attack (Fair Time, Flaminia, Sicilia Piatta), and in two less susceptible cvs (Percoca Romagnola 7 and Doctor Davis).


Input: Among the volatile compounds detected, 88 could be identified.


Input: The main differences found in the volatile composition of the cvs, concerned the relative abundance of esters.

esters