Input: Besides food intake, smoking was also an important source for daily THg intake in the smoke group, contributing 11-18% to EDI of THg.


Input: Quantitative analysis of fungicide azoxystrobin in agricultural samples with rapid, simple and reliable monoclonal immunoassay.

azoxystrobin


Input: This work presents analytical performance of a kit-based direct competitive enzyme-linked immunosorbent assay (dc-ELISA) for azoxystrobin detection in agricultural products.

azoxystrobin


Input: The dc-ELISA was sufficiently sensitive for analysis of residue levels close to the maximum residue limits.


Input: The dc-ELISA did not show cross-reactivity to other strobilurin analogues.

strobilurin


Input: Absorbance decreased with the increase of methanol concentration in sample solution from 2% to 40%, while the standard curve became most linear when the sample solution contained 10% methanol.

methanol

methanol


Input: Agricultural samples were extracted with methanol, and the extracts were diluted with water to 10% methanol adequate.

methanol

methanol


Input: No significant matrix interference was observed.


Input: Satisfying recovery was found for all of spiked samples and the results were well agreed with the analysis with liquid chromatography.


Input: These results clearly indicate that the kit-based dc-ELISA is suitable for the rapid, simple, quantitative and reliable determination of the fungicide.


Input: CODEX-compliant eleven organophosphorus pesticides screening in multiple commodities using headspace-solid phase microextraction-gas chromatography-mass spectrometry.

organophosphorus


Input: A headspace-solid phase microextraction-gas chromatography-mass spectrometric (HS-SPME-GC-MS, hereafter abbreviated as " SPME ") method was developed for dedicated organophosphorus (OP) pesticides assessment in multiple vegetable and fruit commodities.

organophosphorus


Input: Specific extraction variables were optimised to achieve harmonised extraction performance of eleven OPs in a great span of seven characteristic commodities cataloged in Codex Alimentarius Commission.


Input: Comprehensive validation study confirmed analytical robustness of the SPME treatment in turnip, green cabbage, French beans, eggplant, apple, nectarine and grapes.


Input: Based on range-specific evaluation, extraction of individual OPs was characterised by sub-ppb level sensitivity and a wide 0. 01-2. 5 mg L (-1) dynamic range.


Input: Effective sample clean-up afforded precise quantification (0. 5-10. 9% R. S. D.) within a 70-120% recovery range at the MRL levels specified for individual commodities.


Input: Compared to conventional methods currently used, the SPME treatment developed here is quick, accurate, and relatively environmental friendly; it represents an attractive, practical way to deliver international standards in OP screening routines.


Input: Differential sensitivity of D-galactose-binding lectins from fruits of dwarf elder (Sambucus ebulus L.) to a simulated gastric fluid.

D-galactose


Input: Some lectins from Sambucus spp. share amino acid sequences with the pollen Sam n1 allergen.

amino acid


Input: The lectins ebulin f and SELfd from the early stages of growth were isolated and subjected to analysis by MALDI-TOF mass spectrometry, tryptic peptide fingerprinting, molecular characterization and pepsin digestibility.


Input: The molecular mass (33. 214) and other structural features of the Sam n1 allergen fit best with a monomeric lectin like SELlm (Mr 34. 2 kDa) found in shoots of dwarf elder.


Input: Ebulin f toxicity to mice was higher intraperitoneally than orally at the same dose (5mg/kg body weight).


Input: In contrast SELfd at the same dose lacks of apparent toxicity.


Input: Ebulin f, but not SELfd, undergoes extensive pepsin proteolysis, which could explain the differences in toxicity.


Input: The present study supports our hypothesis that the Sam n1 allergen could be a sequence-related monomeric lectin like SELlm present in shoots of Sambucus ebulus rather than ebulin.


Input: Identification, characterisation, and quantification of phenolic compounds in the antioxidant activity-containing fraction from the seeds of Korean perilla (Perilla frutescens) cultivars.


Input: The present research was the first to investigate phenolic compound profiles and antioxidant properties in the seeds of various perilla (Perilla frutescens) cultivars.


Input: The 80% methanol extract (50 mu g/ml) of this species showed potent antioxidant activities against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals.

methanol

2, 2-diphenyl-1-picrylhydrazyl

DPPH

2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid)

ABTS


Input: Phenolic compounds were characterised by nuclear magnetic resonance (NMR) spectroscopy, and ultra performance liquid chromatography with photodiode array detector and electrospray ionisation/mass (UPLC-PDA-ESI/MS) analysis.


Input: Nine compounds were elucidated as caffeic acid-3-O-glucoside (1), caffeic acid (2), luteolin-7-O-glucoside (3), apigenin-7-O-glucoside (4), rosmarinic acid-3-O-glucoside (5), rosmarinic acid (6), luteolin (7), apigenin (8), and chrysoeriol (9).

caffeic acid-3-O-glucoside

caffeic acid

rosmarinic acid-3-O-glucoside

rosmarinic acid

luteolin

apigenin

chrysoeriol


Input: The individual and total phenolic contents were remarkably different, especially rosmarinic acid-3-O-glucoside (5) and rosmarinic acid (6) which were the predominant compounds (> 95%) in all perilla cultivars.

rosmarinic acid-3-O-glucoside

rosmarinic acid


Input: Additionally, Yeupsil cultivar exhibited the highest phenolic content (5029. 0 mu g/g) and antioxidant activity, whereas the lowest was shown by Dasil (2138. 7 mu g/g).


Input: Therefore, these results suggest that antioxidant effects of perilla seeds are correlated with phenolic contents.


Input: Degradation kinetics of anthocyanins in acerola pulp: comparison between ohmic and conventional heat treatment.

anthocyanins


Input: Degradation kinetics of monomeric anthocyanins in acerola pulp during thermal treatment by ohmic and conventional heating was evaluated at different temperatures (75-90 degrees C).

anthocyanins


Input: Anthocyanin degradation fitted a first-order reaction model and the rate constants ranged from 5. 9 to 19. 7 x 10 (-3) min (-1).


Input: There were no significant differences between the rate constants of the ohmic and the conventional heating processes at all evaluated temperatures.


Input: D-Values ranged from 116. 7 to 374. 5 for ohmic heating and from 134. 9 to 390. 4 for conventional heating.


Input: Values of the free energy of inactivation were within the range of 100. 19 and 101. 35 kJ mol (-1).


Input: The enthalpy of activation presented values between 71. 79 and 71. 94 kJ mol (-1) and the entropy of activation ranged from-80. 15 to-82. 63 J mol (-1) K (-1).


Input: Both heating technologies showed activation energy of 74. 8 kJ mol (-1) and close values for all thermodynamic parameters, indicating similar mechanisms of degradation.


Input: Hypotriglyceridemic and hypoglycemic effects of vescalagin from Pink wax apple [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] in high-fructose diet-induced diabetic rats.

vescalagin

fructose


Input: Vescalagin, an active component from Pink wax apple [Syzygium samarangense (Blume) Merrill and Perry cv. Pink] fruit, with glucose uptake enhancing ability in insulin-resistant FL83B mouse hepatocytes, as shown in our previous study, was further evaluated for its hypotriglyceridemic and hypoglycemic effects in high-fructose diet (HFD)-induced diabetic rats.

Vescalagin

glucose

fructose


Input: Wistar rats were fed HFD for 16 weeks and orally administered with vescalagin from Pink wax apple daily during the last 4 weeks.

vescalagin


Input: The results of biochemical parameters showed that fasting blood glucose, C-peptide, fructosamine, triglyceride and free fatty acid contents decreased by 44. 7%, 46. 2%, 4. 0%, 42. 5%, and 10. 8%, respectively, in the HFD-induced diabetic rats administered with vescalagin at 30 mg/kg body weight in comparison with those of control HFD-induced diabetic rats.

glucose

fructosamine

triglyceride

fatty acid

vescalagin


Input: However, high-density-lipoprotein-cholesterol content increased by 14. 4% in the HFD rats treated with vescalagin.

cholesterol

vescalagin


Input: The present study reveals that vescalagin could have therapeutic value against diabetic progression via its anti-hypertriglyceridemic and anti-hyperglycemic effects.

vescalagin


Input: Carotenoid compositions of coloured tomato cultivars and contribution to antioxidant activities and protection against H (2) O (2)-induced cell death in H9c2.

H (2) O (2)


Input: The carotenoid compositions, antioxidant activities and the potential cardio-protective role of 13 tomato cultivars with distinct colour were studied.


Input: Colour coordinates were evaluated by colorimeter and the carotenoid compositions were analysed by UPLC.


Input: Red tomatoes had the highest total carotenoid contents (TCC) and antioxidant activities, followed by purple, orange, pink and yellow ones.


Input: The TCC were 120. 5-278. 0 mu g/gDW, and the antioxidant activities were 21. 32-40. 07 mu molTE/gDW (PCL), 64. 42-89. 98% (DPPH) and 10. 47-13. 76 mu molTE/g DW (ORAC), respectively.

DPPH


Input: The lipophilic extracts were also found to prevent cell death in a cell-based model system using cardiac H9c2 cells and H (2) O (2), via attenuation of the caspase-3 and matrix metalloproteinase-2 activities.

H (2) O (2)


Input: The extracts of different tomatoes showed strong but different antioxidant activities.


Input: Roles of total and individual carotenoids in the antioxidant activities were studied and lycopene showed the highest correlation.


Input: Results of this study can be used to guide the development of new tomato cultivars and functional foods, and benefit the consumers.


Input: Medium chain and behenic acid incorporated structured lipids from sal, mango and kokum fats by lipase acidolysis.

behenic acid


Input: Medium chain (MC) and behenic fatty acids were incorporated into kokum, sal and mango fats using 1, 3-specific lipase catalysed acidolysis.

fatty acids


Input: The incorporation of fatty acids increased with increase in concentration of fatty acids and duration of reaction.

fatty acids

fatty acids


Input: The order of incorporation of fatty acids was C22: 0 > C10: 0 > C8: 0, to the extent of 53%, 42. 5%, 35. 8%, respectively, after 16 h, using kokum as substrate.

fatty acids


Input: The same trend was observed with sal or mango fats as substrates though the percentages incorporated were different.


Input: The modified products with higher contents of MC were liquids with no solid fats, even at 0 degrees C, and which showed low cloud point due to an increase in triacylglycerols containing lower chain fatty acids.

triacylglycerols

fatty acids


Input: The modified products after incorporating both MC and C22: 0 showed long melting ranges and were suitable for use in bakery, confectionery, etc. as vanaspati substitutes.


Input: Comparison of the affinity and selectivity of insoluble fibres and commercial proteins for wine proanthocyanidins.

proanthocyanidins


Input: The fining action of commercial proteins and insoluble fibres for wine proanthocyanidin (PA) were compared.

proanthocyanidin


Input: Fibres were prepared from fresh apple and grape sources, and their corresponding pomaces.


Input: PA removal by fibre was via adsorption, and required a higher dose to achieve a fining effect comparable with proteins.


Input: A principal component analysis data model revealed that PA molecular mass was significant in defining the fining response, and reflected changes in the proportion of the dominant terminal PA subunits catechin and epicatechin, but not epicatechin-3-O-gallate.

catechin

epicatechin


Input: For PA extension subunits, changes in epigallocatechin were inversely correlated with epicatechin and epicatechin-3-O-gallate.

epigallocatechin

epicatechin


Input: Generally, the application of proteins and fibres reduced PA molecular mass.


Input: Selectivity for PAs by subunit composition was variable between treatments, but differences were minor.


Input: This work demonstrates the potential use of fibres as an alternative to proteins in winemaking.


Input: Benefits, and possible limitations of such an approach are discussed.


Input: The influence of the malaxation temperature on the activity of polyphenoloxidase and peroxidase and on the phenolic composition of virgin olive oil.


Input: The effect of the malaxation temperature under sealed conditions on the qualitative and quantitative composition of the phenolic compounds in virgin olive oils produced from four Italian cultivars was assessed for two atmospheric conditions.


Input: In both cases, the results show a positive relationship between temperature and the concentration of the derivatives of the secoiridoid aglycones; the effect of the temperature on the oxidoreductases that promote oxidation (polyphenoloxidase and peroxidase) was investigated to determine their optimal temperatures and thermal stability.

secoiridoid aglycones


Input: While olive peroxidase (POD) showed the highest activity at 37 degrees C and high stability in the temperature range tested, polyphenoloxidase (PPO) exhibited the optimum activity at approximately 50 degrees C, but showed low stability at 40 degrees C, with a large variation in stability according to the olive cultivar.


Input: These results may contribute to an understanding of the increase in the phenol concentration found in virgin olive oils obtained following higher temperatures of malaxation.

phenol


Input: Characterisation of kiwifruit and asparagus enzyme extracts, and their activities toward meat proteins.


Input: Two plant enzyme extracts from kiwifruit and asparagus were evaluated for their ability to hydrolyse commercially available substrates and proteins present in both beef connective tissue and topside myofibrillar extracts.


Input: The results show significant differences in protease activity depending on the assay used.


Input: Protease assays with connective tissue and meat myofibrillar extracts provide a more realistic evaluation of the potential of the enzymes for application in meat tenderization.


Input: Overall, the kiwifruit protease extract was found to be more effective at hydrolysing myofibrillar and collagen proteins than the asparagus protease extract.


Input: The two protease extracts appeared to target meat myofibrillar and collagen proteins differently, suggesting the potential of a synergistic effect of these proteases in improving the tenderness of specific cuts of meat, based on their intrinsic protein composition.


Input: Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L.

carnosol

betulinic acid


Input: The aim of this study was to investigate the antidepressant-like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2), hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity.

ethyl acetate

hexane

HEX

carnosol

betulinic acid


Input: Swiss mice were acutely administered by oral route (p. o.) with fractions, essential oil or isolated compounds, 60 min before the tail suspension test or open-field test.


Input: All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF fractions and essential oil (0. 1-100mg/kg, p. o); HEX (0. 1-10mg/kg, p. o) and AcOEt2 fraction (0. 1-1mg/kg, p. o), carnosol (0. 01-0. 1mg/kg, p. o.) isolated from the HEX fraction and betulinic acid (10mg/kg, p. o.), isolated from the AcOEt1 and AcOEt2 fractions.

HEX

carnosol

HEX

betulinic acid


Input: No psychostimulant effect was shown in the open-field test, indicating that the effects in the tail suspension test are specific.


Input: This study suggests that carnosol and betulinic acid could be responsible for the anti-immobility effect of extracts from R. officinalis.

carnosol

betulinic acid


Input: Feasibility and application of an HPLC/UVD to determine dinotefuran and its shorter wavelength metabolites residues in melon with tandem mass confirmation.

dinotefuran


Input: A new analytical method was developed for dinotefuran and its metabolites, MNG, UF, and DN, in melon using high-performance liquid chromatography (HPLC) coupled with an ultraviolet detector (UVD).

dinotefuran

MNG


Input: Due to shorter wavelength, lower sensitivity to UV detection, and high water miscibility of some metabolites, QuEChERs acetate-buffered version was modified for extraction and purification.


Input: Mobile phases with different ion pairing or ionisation agents were tested in different reverse phase columns, and ammonium bicarbonate buffer was found as the best choice to increase the sensitivity of target analytes to the UV detector.

ammonium bicarbonate


Input: After failure of dispersive SPE clean-up with primary secondary amine, different solid phase extraction cartridges (SPE) were used to check the protecting capability of analytes against matrix interference.

primary secondary amine


Input: Finally, samples were extracted with a simple and rapid method using acetonitrile and salts, and purified through C (18) SPE.

acetonitrile and salts


Input: The method was validated at two spiking levels (three replicates for each) in the matrix.


Input: Good recoveries were observed for all of the analytes and ranged between 70. 6% and 93. 5%, with relative standard deviations of less than 10%.


Input: Calibration curves were linear over the calibration ranges for all the analytes with r (2) >= 0. 998.


Input: Limits of detection ranged from 0. 02 to 0. 05 mg kg (-1), whereas limits of quantitation ranged from 0. 06 to 0. 16 mg kg (-1) for dinotefuran and its metabolites.

dinotefuran


Input: The method was successfully applied to real samples, where dinotefuran and UF residues were found in the field-incurred melon samples.

dinotefuran


Input: Residues were confirmed via LC-tandem mass spectrometry (LC-MS/MS) in positive-ion electrospray ionisation (ESI (+)) mode.


Input: Occurrence and sensory perception of Z-2-(beta-d-glucopyranosyloxy)-3-phenylpropenoic acid in rooibos (Aspalathus linearis).

Z-2-(beta-d-glucopyranosyloxy)-3-phenylpropenoic acid


Input: Z-2-(beta-d-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG), a compound postulated to contribute to the taste and mouthfeel of fermented rooibos tea (Aspalathus linearis), was isolated from unfermented rooibos plant material.

Z-2-(beta-d-glucopyranosyloxy)-3-phenylpropenoic acid

PPAG


Input: Its structure was unequivocally confirmed by LC-MS,-MS (2), FT-IR and NMR of the underivatised natural product, and optical rotation measurements of the hydrolysed sugar moiety.

sugar


Input: A similar compound, postulated to be E-2-(beta-d-glucopyranosyloxy)-3-phenylpropenoic acid, was also detected.

E-2-(beta-d-glucopyranosyloxy)-3-phenylpropenoic acid


Input: Analysis of the leaves of a large number of rooibos plants (n = 54), sampled at commercial plantations, showed that PPAG is not ubiquitously present in detectable quantities in the leaves of different plants.

PPAG


Input: This leads to large variation in the fermented plant material, infusions and food-grade extracts.


Input: PPAG was shown to have a slightly bitter to astringent taste and a detection threshold of 0. 4 mg/l in water.

PPAG


Input: Schisarisanlactones A and B: a new class of nortriterpenoids from the fruits of Schisandra arisanensis.

Schisarisanlactones A and B

nortriterpenoids


Input: Two novel highly oxygenated nortriterpenoids, schisarisanlactones A (1) and B (2), have been isolated from the fruits of Schisandra arisanensis, an endemic plant of Taiwan.

nortriterpenoids

schisarisanlactones A (1) and B


Input: Compounds 1 and 2 possess an unprecedented 5/5/7/5/5-fused pentacyclic ring system.


Input: The structures of both compounds were determined on the basis of spectroscopic analyses, especially 2D NMR and MS.


Input: A plausible biogenetic pathway of 1 was proposed.


Input: Schisarisanlactone A (1) showed significant anti-HIV activity.

Schisarisanlactone A


Input: Optimisation of resistant starch II and III levels in durum wheat pasta to reduce in vitro digestibility while maintaining processing and sensory characteristics.


Input: Foods with elevated levels of resistant starch (RS) may have beneficial effects on human health.


Input: Pasta was enriched with commercial resistant starches (RSII, Hi Maize (TM) 1043; RSIII, Novelose 330 (TM)) at 10%, 20% and 50% substitution of semolina for RSII and 10% and 20% for RSIII and compared with pasta made from 100% durum wheat semolina to investigate technological, sensory, in vitro starch digestibility and structural properties.


Input: The resultant RS content of pasta increased from 1. 9% to ~ 21% and was not reduced on cooking.


Input: Significantly, the results indicate that 10% and 20% RSII and RSIII substitution of semolina had no significant effects on pasta cooking loss, texture and sensory properties, with only a minimal reduction in pasta yellowness.


Input: Both RS types lowered the extent of in vitro starch hydrolysis compared to that of control pasta.


Input: X-ray diffraction and small-angle scattering verified the incorporation of RS and, compared to the control sample, identified enhanced crystallinity and a changed molecular arrangement following digestion.


Input: These results can be contrasted with the negative impact on pasta resulting from substitution with equivalent amounts of more traditional dietary fibre such as bran.


Input: The study suggests that these RS-containing formulations may be ideal sources for the preparation of pasta with reduced starch digestibility.


Input: Abietane diterpenoids from Isodon lophanthoides var. graciliflorus and their cytotoxicity.

Abietane diterpenoids


Input: Seven new (1-7) and three known (8-10) abietane diterpenoids were isolated from the methanolic extract of the aerial parts of Isodon lophanthoides var. graciliflorus (Lamiaceae), a folk Chinese medicine and an herb for functional beverages.

abietane diterpenoids


Input: They were identified as 16-acetoxylsugiol (1), graciliflorin E (2), graciliflorin F (3), 15-O-methylgraciliflorin F (4), 15-hydroxy-20-deoxocarnosol (5), 3 beta-hydroxysempervirol (6), 15-hydroxy-1-oxosalvibretol (7), abieta-8, 11, 13-triene-14, 19-diol (8), 6, 12, 15-trihydroxy-5, 8, 11, 13-abietatetraen-7-one (9), and 3 alpha-hinokiol (10) based on the spectroscopic data including COSY (correlated spectroscopy), HMBC (heteronuclear multiple bond correlation), and HR-ESI-MS (high-resolution electrospray ionization mass spectrometry).

graciliflorin E

graciliflorin F

15-O-methylgraciliflorin F

3 beta-hydroxysempervirol

abieta-8, 11, 13-triene-14, 19-diol

6, 12, 15-trihydroxy-5, 8, 11, 13-abietatetraen-7-one

3 alpha-hinokiol


Input: All the compounds except 10 were obtained from I. lophanthoides for the first time.


Input: Compounds 1, 2, 5, 6, 8, and 9 exhibited in vitro cytotoxicity against A549 (human lung adenocarcinoma), MCF-7 (human breast adenocarcinoma), and HeLa (human cervical carcinoma) cell lines with the IC (50) values of 1. 79-52. 67 mu M.


Input: Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone-hydrogel contact lenses.

timolol


Input: Glaucoma is the second major cause of blindness in the world after cataract.


Input: Glaucoma management through eye drops that reduce the intraocular pressure (IOP) has major deficiencies including low patient compliance and low bioavailability.


Input: Extended wear contact lenses that deliver glaucoma drugs for extended periods could increase patient compliance, while also increasing the bioavailability.


Input: To develop extended wear contact lenses that can also provide extended glaucoma therapy, we disperse nanoparticles of PGT (propoxylated glyceryl triacylate) that contain a glaucoma drug timolol.

PGT

propoxylated glyceryl triacylate

timolol


Input: The particles can also be loaded into prefabricated lenses by soaking the lenses in a solution of particles in ethanol.

ethanol


Input: The particle loaded gels can release timolol in phosphate buffered saline (PBS) for about a month at room temperature.

timolol

phosphate


Input: The most likely rate controlling mechanism is hydrolysis of the ester bond that links timolol to the PGT matrix, but other mechanisms such as water and drug diffusion, drug dissolution, drug-polymer chain cleavage, time-dependent drug permeability within the polymeric matrix, etc. may also be important.

timolol

PGT


Input: Nanoparticle incorporation in the silicone hydrogels results in reduction in ion and oxygen permeabilities, and an increase in modulus, and the impact on each of these properties is proportional to the particle loading.

oxygen


Input: A gel with 5% particle loading can deliver timolol at therapeutic doses for about a month at room temperature, with a minimal impact on critical lens properties.

timolol


Input: Preliminary animal studies in Beagle dogs conducted with lenses in which particles are loaded by soaking the lenses in ethanol show a reduction in IOP.


Input: Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors.


Input: Carboxylesterases (CEs) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics.


Input: They tend to be expressed in tissues likely to be exposed to such agents (e. g., lung and gut epithelia, liver) and can hydrolyze numerous agents, including many clinically used drugs.


Input: Due to the considerable structural similarity between cholinesterases (ChE) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver (hCE1) and the human intestinal CE (hiCE) isoforms.


Input: We observed inhibition of hCE1 and hiCE by carbamate-containing small molecules, including those used for the treatment of Alzheimer' s disease.

carbamate


Input: For example, rivastigmine resulted in greater than 95% inhibition of hiCE that was irreversible under the conditions used.

rivastigmine


Input: Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy.

carbamates


Input: Therefore drug: drug interactions should be carefully evaluated in individuals receiving ChE inhibitors.


Input: Assessing protection against OP pesticides and nerve agents provided by wild-type HuPON1 purified from Trichoplusia ni larvae or induced via adenoviral infection.


Input: Human paraoxonase-1 (HuPON1) has been proposed as a catalytic bioscavenger of organophosphorus (OP) pesticides and nerve agents.

organophosphorus


Input: We assessed the potential of this enzyme to protect against OP poisoning using two different paradigms.


Input: First, recombinant HuPON1 purified from cabbage loopers (iPON1; Trichoplusia ni) was administered to guinea pigs, followed by exposure to at least 2times the median lethal dose (LD50) of the OP nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF), or chlorpyrifos oxon, the toxic metabolite of the OP pesticide chlorpyrifos.

tabun

sarin

soman

cyclosarin

chlorpyrifos oxon

chlorpyrifos


Input: In the second model, mice were infected with an adenovirus that induced expression of HuPON1 and then exposed to sequential doses of GD, VX, or (as reported previously) diazoxon, the toxic metabolite of the OP pesticide diazinon.

diazoxon

diazinon


Input: In both animal models, the exogenously added HuPON1 protected animals against otherwise lethal doses of the OP pesticides but not against the nerve agents.


Input: Together, the results support prior modeling and in vitro activity data which suggest that wild-type HuPON1 does not have sufficient catalytic activity to provide in vivo protection against nerve agents.


Input: Seventy-two-hour release formulation of the poorly soluble drug silybin based on porous silica nanoparticles: in vitro release kinetics and in vitro/in vivo correlations in beagle dogs.

silybin

silica


Input: The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs).

silybin

SLB

silica


Input: The results of scanning electron microscopy and N (2) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385. 89 +/- 1. 12 m (2)/g) and a small pore size (2. 74 nm on average).


Input: The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0. 01, 0. 06 and 0. 08M) of Na (2) CO (3) solutions revealed that 0. 06 M Na (2) CO (3) solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics.

SLB

silybin

Na (2) CO (3)

Na (2) CO (3)

silybin

SLB


Input: Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established.

SLB

silybin


Input: Using 0. 06 M Na (2) CO (3) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs.

Na (2) CO (3)

SLB

silybin


Input: The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na (2) CO (3) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.

SLB

Na (2) CO (3)


Input: Zymomonas mobilis culture protects against sepsis by modulating the inflammatory response, alleviating bacterial burden and suppressing splenocyte apoptosis.


Input: Microorganisms with immunomodulating effects beneficially affect the host organism by improving the microbial equilibrium and balancing the immune system.


Input: Zymomonas mobilis is reported to have antagonistic properties against yeast and other pathogenic microorganisms in humans and animals.


Input: This study assessed the effects of Z. mobilis UFPEDA 202 (10 (9) CFU/mL) cultures on polymicrobial sepsis induced by cecal ligation and puncture (CLP).


Input: The survival of animals subjected to lethal sepsis was evaluated after pre-treatment, post-treatment or a combination of both.


Input: 6h after the induction of sepsis, neutrophil migration, the number of bacteria, myeloperoxidase, TNF-alpha, MCP-1, and IL-10 were performed in the peritoneal lavage of animals.


Input: Histopathological changes in the spleen of animals were evaluated by light microscopy, and apoptosis of splenocytes was analyzed by transmission electron microscopy.


Input: The results showed that the combination of prophylactic and therapeutic treatment with Z. mobilis increased the survival of animals by 50% at 96 h after the induction of sepsis.


Input: There was a reduction in the levels of TNF-alpha and myeloperoxidase (MPO) in lung tissue.


Input: There was also a reduction in the number of viable bacteria in peritoneal fluid.


Input: However, increases in neutrophil migration and IL-10 levels were observed.


Input: The observed levels of MCP-1 remained similar to the control.


Input: Histopathology analysis showed a decrease in acute lung injury.


Input: The group pre-treated with the Z. mobilis culture demonstrated a marked decrease in the number of apoptotic cells in the spleen (24%).


Input: This study demonstrates that Z. mobilis cultures increased the survival of animals with severe sepsis.


Input: This survival was mediated by improvement of neutrophil migration, enhanced activity against pathogenic enteric bacteria and reduced lung injury.


Input: Involvement of the ANGPTs/Tie-2 system in ovarian hyperstimulation syndrome (OHSS).


Input: Ovarian hyperstimulation syndrome (OHSS) is a disorder associated with ovarian stimulation.


Input: OHSS features are ovarian enlargement with fluid shifting to the third space.


Input: Disturbances in the vasculature are considered the main changes that lead to OHSS.


Input: Our aim was to analyze the levels of angiopoietins 1 and 2 (ANGPT1 and 2) and their soluble and membrane receptors (s/mTie-2) in follicular fluid (FF) and in granulosa-lutein cells culture (GLCs) from women at risk of developing OHSS.

lutein


Input: We also evaluated the effect of ANGPT1 on endothelial cell migration.


Input: In ovaries from an OHSS rat model, we analyzed the protein concentration of ANGPTs, their mTie-2 receptor, and platelet-derived growth factor PDGF-B,-D and PDGFR-beta.


Input: ANGPT1 levels were increased in both FF and GLCs from women at risk of OHSS.


Input: Incubation of these FF with an ANGPT1 neutralizing antibody decreased endothelial cell migration.


Input: In the ovaries of OHSS rat model, mTie-2 protein levels increased and PDGF-B and-D decreased.


Input: In summary, these results suggest that ANGPT1 could be another mediator in the development of OHSS.


Input: Estrogen receptor ESR1 regulates the phospholipase C-inositol phosphate signaling in the hippocampus from rats in proestrous and estrous phases.

Estrogen

inositol phosphate


Input: The aim of the present study was to investigate the involvement of estrogen receptors in the activation of phospholipase C (PLC)-phosphoinositide hydrolysis in the hippocampus from rats in estrous and proestrous phases.

estrogen


Input: 17 beta-Estradiol (E2) and ESR1-selective agonist PPT, but not ESR2-selective agonist DPN, induced a rapid increase on total [(3) H]-inositol phosphate accumulation in the hippocampus from both rats.

17 beta-Estradiol

PPT

DPN

[(3) H]-inositol phosphate


Input: These effects are mediated by PLC activation, since the inhibition of this protein decreased the total [(3) H]-inositol phosphate accumulation.

[(3) H]-inositol phosphate


Input: The pretreatment with ESR1 and ESR2 antagonist ICI 182, 780, but not with GPER antagonist G-15, blocked the total [(3) H]-inositol phosphate accumulation induced by E2 and PPT, confirming that ESR1 is upstream component regulating this rapid effect.

ICI 182, 780

[(3) H]-inositol phosphate

PPT


Input: SRC family of protein tyrosine kinases inhibitor PP2 blocked the total [(3) H]-inositol phosphate accumulation induced by E2 and PPT in hippocampus, suggesting that ESR1 undergoes translocation from the nuclei to the plasma membrane region via SRC to activate rapid signaling pathways.

tyrosine

[(3) H]-inositol phosphate

PPT


Input: Furthermore, the magnitude of the response to E2 and PPT was higher in hippocampus from rats in proestrous than in estrous.

PPT


Input: On the other hand, the expression of the ESR1 is higher in hippocampus from rats in estrous than in proestrous, indicating that the regulation of this receptor by estrous cycle does not play a role in the magnitude of the response to E2 and PPT in hippocampus.

PPT


Input: In conclusion, our results indicate that E2 activates SRC-mediated translocation of ESR1 to the plasma membrane, which results in the activation of PLC-inositol phosphate signaling pathway in rat hippocampus.

inositol phosphate


Input: Thus, these rapid estrogen actions in hippocampus might be a key step mediating cellular events important for learning and memory.

estrogen


Input: Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat.

atrazine


Input: Atrazine (ATR) is used as a pre-and post-emergent herbicide; although banned in several countries of the European Community, it is still used extensively around the world.

Atrazine

ATR


Input: A recent study in rats has shown that chronic, daily exposure to 10 mg ATR/kg BW causes hyperactivity, disrupts motor coordination and learning of behavioral tasks, and decreases dopamine levels in the brain.

ATR

dopamine


Input: In order to evaluate the short-term effect of ATR exposure on locomotor activity, monoamine markers, and antioxidants, adult male Sprague-Dawley rats received six IP injections of 100 mg ATR/kg BW or vehicle over two weeks.

ATR

monoamine

ATR


Input: After every ATR injection we found hypoactivity that lasted up to five days, and it was accompanied by reductions in levels of striatal DA, DOPAC, and HVA without any alteration in the striatal expression of the mRNAs for Mn-SOD, Trx-1, DAR-D (1), or DAR-D (2).

ATR

DOPAC

HVA

Mn


Input: In contrast, in the nucleus accumbens no changes in monoamine markers were observed, and a down-regulation of Trx-1 expression was detected shortly after the ATR treatment.

monoamine

ATR


Input: Moreover, in the ventral midbrain, we found that ATR induced a down-regulation of mRNA for Th and DAT, but it increased VMAT2 mRNA expression.

ATR


Input: Decreases of monoamine levels and of locomotor activity disappeared three months after ATR treatment; however, an amphetamine challenge (1 mg/kg) given two months after the ATR treatment resulted in a significant stimulation in the exposed group, revealing hidden effects of ATR on dopaminergic systems.

monoamine

ATR

amphetamine

ATR

ATR


Input: These results indicate that ATR exposure differentially modifies the dopaminergic systems, and these modifications may underlie the behavioral changes observed.

ATR


Input: Cadmium chelation by frustulins: a novel metal tolerance mechanism in Nitzschia palea (K u tzing) W.

Cadmium


Input: Smith.


Input: The ubiquity of diatom distribution, species richness, short generation time, and specific sensitivity to several environmental stressors such as metals, make diatoms particularly useful for scientific studies.


Input: Anthropogenic activities have increased the concentration of metals in air, soil and water.


Input: Due to their toxicity and persistent character, the effects of metals on organisms have been extensively studied.


Input: In this work, the association of cadmium to different extracellular molecules of Nitzschia palea cells was investigated.

cadmium


Input: Cells were grown in the absence and presence (0. 2 mg l (-1)) of cadmium in Chu no. 10 medium.

cadmium


Input: Extracellular polysaccharides were extracted, and subsamples were used for polysaccharide and Cd determination.

Cd


Input: The frustules were broken mechanically under liquid nitrogen and the intracellular and frustule fractions separated.

nitrogen


Input: Frustulins, a protein family found on the outmost frustule layer, constituting a protection coating to environmental stress, were extracted.


Input: In each fraction proteins were quantified by the BCA method and separated by gel electrophoresis (SDS-PAGE).


Input: Cadmium associated to each fraction was quantified by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis.

Cadmium


Input: Exposure of Nitzschia palea to cadmium decreased extracellular polysaccharides by 52. 8% and increased 6 times the amount of frustulins.

cadmium


Input: Cadmium was mostly retained extracellularly: 85. 4% was bound to the frustulin fraction, and 11. 1% to polysaccharides.

Cadmium


Input: The ability of Nitzschia palea to increase the production of frustulins due to the presence of Cd, the extracellular location of this frustulin coating and the ability of these proteins to bind Cd, suggests a new cellular defense mechanism to metals unknown until now.

Cd

Cd


Input: Kinetic properties of a novel Fusarium solani (phospho) lipase: a monolayer study.


Input: Using the monomolecular film technique, we studied interfacial properties of Fusarium solani lipase (FSL).


Input: This lipolytic enzyme was found to be unique among the fungal lipases possessing not only a lipase activity but also a high phospholipase one. The FSL was able to hydrolyze dicaprin films at various surface pressures.

dicaprin


Input: The surface pressure dependency, the stereospecificity, and the regioselectivity of FSL were performed using optically pure stereoisomers of diglyceride (1, 2-sn-dicaprin and 2, 3-sn-dicaprin) and a prochiral isomer (1, 3-sn-dicaprin) spread as monomolecular films at the air-water interface.

diglyceride

1, 2-sn-dicaprin

2, 3-sn-dicaprin

1, 3-sn-dicaprin


Input: The FSL prefers adjacent ester groups of the diglyceride isomers (1, 2-sn-dicaprin and 2, 3-sn-dicaprin) at low and high surface pressures.

ester

diglyceride

1, 2-sn-dicaprin

2, 3-sn-dicaprin


Input: Furthermore, FSL was found to be markedly stereospecific for the sn-1 position of the 1, 2-sn-enantiomer of dicaprin at both low and high surface pressures. Moreover, FSL shows high activities on phospholipids monolayers.

dicaprin


Input: However, this enzyme displays high preference to zwitterionic phospholipids compared to the negatively charged ones.


Input: Transparent nanowire network electrode for textured semiconductors.


Input: This work presents an inexpensive and easily manufacturable, highly conductive and transparent nanowire network electrode for textured semiconductors.


Input: It is based on lines of silver nanoparticles transformed into a nanowire network by microwave or furnace sintering.

silver


Input: The nanonetwork electrode on crystalline silicon is demonstrated experimentally, with the nanoparticles self-assembling in the valleys between the pyramids of the textured surface.

silicon


Input: Optical experiments show that this conductive nanowire network electrode can be essentially' invisible' when covered with the conventional anti-reflection coating (ARC), and thus could be employed in photovoltaic applications.


Input: Free energy simulation of helical transitions.


Input: An umbrella sampling method for the calculation of free energies for helical transitions is presented.


Input: The method biases structures toward helices of a desired radius and pitch.


Input: Although computationally complex, the method has negligible overhead in actual applications.


Input: To illustrate the method, calculations of the helical free energy landscape of several peptides are presented for both the CHARMM and the AMBER force fields.


Input: Contribution of Leydig and Sertoli cells to testosterone production in mouse fetal testes.

testosterone


Input: Testosterone is a final product of androgenic hormone biosynthesis, and Leydig cells are known to be the primary source of androgens.

Testosterone


Input: In the mammalian testis, two distinct populations of Leydig cells, the fetal and the adult Leydig cells, develop sequentially, and these two cell types differ both morphologically and functionally.


Input: It is well known that the adult Leydig cells maintain male reproductive function by producing testosterone.

testosterone


Input: However, it has been controversial whether fetal Leydig cells can produce testosterone, and the synthetic pathway of testosterone in the fetal testis is not fully understood.

testosterone

testosterone


Input: In the present study, we generated transgenic mice in which enhanced green fluorescence protein was expressed under the control of a fetal Leydig cell-specific enhancer of the Ad4BP/SF-1 (Nr5a1) gene.


Input: The transgene construct was prepared by mutating the LIM homeodomain transcription factor (LHX9)-binding sequence in the promoter, which abolished promoter activity in the undifferentiated testicular cells.


Input: These transgenic mice were used to collect highly pure fetal Leydig cells.


Input: Gene expression and steroidogenic enzyme activities in the fetal Leydig cells as well as in the fetal Sertoli cells and adult Leydig cells were analyzed.


Input: Our results revealed that the fetal Leydig cells synthesize only androstenedione because they lack expression of Hsd17b3, and fetal Sertoli cells convert androstenedione to testosterone, whereas adult Leydig cells synthesize testosterone by themselves.

androstenedione

androstenedione

testosterone

testosterone


Input: The current study demonstrated that both Leydig and Sertoli cells are required for testosterone synthesis in the mouse fetal testis.

testosterone


Input: Absorption of triphenylmethane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life products.

triphenylmethane

Brilliant Blue

Patent Blue


Input: Currently, there is evidence of health risks of triphenylmethane dyes after systemic absorption.

triphenylmethane


Input: This paper investigates the fate of Brilliant Blue (BB) and Patent Blue (PB) after 24-h in vitro diffusion, firstly through intact and secondly through shaven pig-ear skin (stored by freezing) from four leave-on cosmetics under in-use conditions.

Brilliant Blue

Patent Blue


Input: Both dyes showed no measurable permeation through intact skin but significant permeation was found through shaven skin.


Input: From 250 ng/cm (2) of dye in one applied dose there were found 52 ng/cm (2) of BB and 91 ng/cm (2) of PB from ethanol-based after-shave, 39 ng/cm (2) of BB and 86 ng/cm (2) of PB from ethanol-free facial-cleanser, 35 ng/cm (2) of BB and 43 ng/cm (2) of PB from O/W emulsion, and no amount from W/O emulsion, as available to become systemically absorbed.

ethanol

ethanol


Input: Thirdly, the paper focuses on lingual mucosa after licking lollipops.


Input: Ex vivo porcine tongue dorsum was exposed to human saliva with 15, 000 ng/cm (2) of dye for 20 min.


Input: 24-h diffusion resulted in 34 ng/cm (2) of BB and 86 ng/cm (2) of PB which can be directly absorbed into the blood system.


Input: Findings are troubling, particularly with regard to the frequent use of after-shave products by the male population and repeated lollipops licking by children.


Input: Alleviative effects of resveratrol on nonalcoholic fatty liver disease are associated with up regulation of hepatic low density lipoprotein receptor and scavenger receptor class B type I gene expressions in rats.

resveratrol


Input: Lipid metabolic disorders are widely considered to be one of the most critical and basic link in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).


Input: The aim of this study was to illustrate the alleviation function of resveratrol (Res) on NAFLD and the roles of hepatic fatty acid synthase (FAS), low density lipoprotein receptor (LDLr), scavenger receptor class B type I (SR-BI), and thyroid hormone receptor beta 1 (TR beta 1), which are the key molecules involved in lipid metabolism.

resveratrol

Res

fatty acid


Input: Adult male Wistar rats were fed a normal diet or high fat/sucrose diet (HFS) with or without resveratrol for 13 weeks.

sucrose

resveratrol


Input: HFS induced NAFLD formation and increased the lipids concentrations in serum and livers of rats, while noticeable improvement has been reached by Res intervention.

Res


Input: Moreover, Res protected against HFS-induced decrease in hepatic LDLr and SR-BI mRNA and protein expressions, whereas TR beta 1 expressions were impervious with/without Res.

Res

Res


Input: Unexpectedly, hepatic FAS gene expressions were markedly diminished in NAFLD rats and were gradually increased by treatment with Res.

Res


Input: These data indicate that the alleviative effects of Res on NAFLD are associated with up regulation of hepatic LDLr and SR-BI gene expressions, which provide new insights into the pharmacological targets of Res in the prevention of NAFLD.

Res

Res


Input: Consumption of tomato products is associated with lower blood mercury levels in Inuit preschool children.

mercury


Input: Some evidence suggests that various diet components and nutrients, including vegetables, fruit and food-derived antioxidants, could mitigate contaminant exposure and/or adverse health effects of contaminants.


Input: To examine the effect of the consumption of tomato products on blood mercury levels in Inuit preschool children, 155 Inuit children (25. 0 +/- 9. 1months) were recruited from 2006-2008 in Nunavik childcare centers (northern Qu e bec, Canada).

mercury


Input: Food frequency questionnaires were completed at home and at the childcare center, and total blood mercury concentration was measured by inductively coupled plasma-mass spectrometry.

mercury


Input: Multivariate regression analysis was performed after multiple imputation.


Input: The median blood concentration of mercury was 9. 5nmol/L.

mercury


Input: Age, duration of breastfeeding, annual consumption frequency of seal meat, and monthly consumption frequency of tomato products were significant predictors of blood mercury levels, whereas annual consumption frequencies of beluga muktuk, walrus, Arctic char, and caribou meat were not.

mercury


Input: Each time a participant consumed tomato products during the month before the interview was associated with a 4. 6% lower blood mercury level (p = 0. 0005).

mercury


Input: All other significant predictors in the model were positively associated with blood mercury levels.

mercury


Input: Further studies should explore interactions between consumption of healthy store-bought foods available in Arctic regions and contaminant exposure.


Input: Conjunctival modifications induced by medical and surgical therapies in patients with glaucoma.


Input: Lowering intra-ocular pressure, either medically or surgically, is the proven strategy to control glaucoma, though profound changes to the ocular surface and conjunctiva are caused.


Input: Toxicity and allergy initiated by medical therapy induce modifications, which progressively worsen with the length of treatment and number of drugs.


Input: Conjunctival changes lead to symptoms of ocular surface disease, reduced quality of life, reduced therapeutic compliance and increased risk of surgical failure.


Input: Surgery modifies conjunctiva by inducing bleb formation in fistulizing techniques, and by activating secondary aqueous humour outflow pathways, such as trans-scleral routes, in both filtration and bleb-less approaches.


Input: The use of unpreserved medications, limitation of intra-operative conjunctival damage and development of bleb-less surgery are advisable.


Input: Structure-based design of flavone derivatives as c-myc oncogene down-regulators.

flavone


Input: Based on molecular docking analysis of complexes between flavone and the c-myc G-quadruplex, we designed and screened 30 flavone derivatives containing various side chains that could potentially form interactions with the G-quadruplex grooves.

flavone

flavone


Input: As a proof-of-concept, the highest-scoring flavone derivatives containing cationic pyridinium side chains were synthesized and their interactions with the c-myc G-quadruplex were examined using a PCR-stop assay.

flavone

pyridinium


Input: The stabilizing effects of the flavone derivatives were found to be selective towards the c-myc G-quadruplex over other biologically relevant G-quadruplex structures, such as the human telomeric sequence (HTS).

flavone


Input: The interaction between the most potent compound of the series and the c-myc G-quadruplex was examined in depth using UV-Vis titration, molecular modeling and CD spectroscopy.


Input: Our results suggest that in addition to stabilizing the c-myc G-quadruplex, the flavone derivatives were capable of inducing the formation of the G-quadruplex structure even in the absence of monovalent cations.

flavone


Input: The flavone derivatives were found to be potent inhibitors of c-myc promoters within the cellular environment and displayed promising cytotoxic behavior against human cancer cell lines.

flavone


Input: Epidemiology and clinical effects of hump-nosed pit viper (Genus: Hypnale) envenoming in Sri Lanka.


Input: Hump-nosed pit vipers of Genus Hypnale are the commonest cause of snake bite in Sri Lanka.


Input: Although there are many reports of local effects, coagulopathy and acute kidney injury, it remains unclear how frequent these clinical effects are and therefore the medical importance of this snake genus.


Input: The genus has been recently revised to include Hypnale hypnale from Sri Lanka and Western Ghats of Southern India, and the two endemic species to Sri Lanka, Hypnale zara and Hypnale nepa.


Input: This was a prospective hospital-based clinical study of definite Hypnale spp. bites from July 2008 to July 2010 in six Sri Lankan hospitals.


Input: There were 114 patients included and all snakes were correctly identified by hospital staff as Hypnale spp.


Input: Of these, 93 snakes were identified as H. hypnale by an expert, 16 as H. zara and five as H. nepa.


Input: Most bites occurred on the lower limbs in the daytime.


Input: There was no difference in the clinical effects between the three species.


Input: Pain and fang marks were present in all patients, 101 had local swelling and only 16 (14%) developed extensive local swelling that spread proximally and involved more than half of the bitten limb.


Input: Systemic symptoms occurred in 18 patients; four patients had an abnormal 20 min whole blood clotting test and one patient developed an acute kidney injury that required haemodialysis.


Input: All patients were discharged alive with a median length of stay of 2 days.


Input: This study confirms that hump-nosed viper bites cause only minor effects in most cases.


Input: Future studies need to undertake formal coagulation studies and identify important early indicators of renal impairment.


Input: Induction of nuclear anomalies in exfoliated buccal cells of coca chewers: results of a field study.


Input: The leaves of coca (Erythroxylum coca var. coca), a South American shrub which contains cocaine, other alkaloids and phenolics are widely used by indigenous populations of the Andes.

cocaine


Input: It is currently not known if coca consumption causes genotoxic effects in humans.


Input: This information is important to predict potential long-term toxic effects such as cancer induction.


Input: Therefore, the buccal cytome assay was used to analyze oral cells from 45 uni-and bilateral chewers and 23 controls living in the Altiplano of the Peruvian Andes.


Input: In total, 123, 471 cells were evaluated from chewers and 57, 916 from controls.


Input: Information concerning the consumption levels and habits and also use of lime were collected with questionnaires.


Input: Chewing of the leaves did not induce nuclear anomalies reflecting genetic damage such as micronuclei (MNi) and nuclear buds; in the highest exposure group (but not in the overall group) even a significant decrease in the frequencies of cells with MNi (by 64%) was observed.


Input: However, we found significantly elevated levels of other nuclear anomalies (karyorrhexis and karyolysis) which reflect cytotoxic effects in the coca users.


Input: The frequencies of these anomalies increased with the daily consumption and when lime was used to improve the release of the alkaloids.


Input: In contrast to other chewing habits (betel, tobacco and khat), consumption of coca leaves does not induce genetic instability in cells from the oral cavity and our findings indicate that no adverse health effects take place in chewers which are associated with DNA damage.


Input: However, the significant increase in certain anomalies shows that acute toxic effects are caused by coca consumption.


Input: Characterization of substituted phenylpropylamides as highly selective agonists at the melatonin MT2 receptor.

phenylpropylamides

melatonin


Input: Melatonin is a widely distributed hormone that regulates several major physiological processes, including the circadian rhythm and seasonal adaptation.

Melatonin


Input: The two subtypes of mammalian G protein-coupled melatonin receptors are primarily responsible for mediating the actions of melatonin.

melatonin


Input: Because synthetic melatonin agonists have considerable therapeutic potentials in modulating insomnia and circadian-related sleep disorders, it is highly desirable to develop subtype-selective melatoninergic compounds.

melatonin


Input: The pharmacological potencies of a series of substituted N-[3-(3-methoxyphenyl) propyl] amides towards human melatonin MT (1) and MT (2) receptors were evaluated by the FLIPR high-throughput screening assay, whilst their subtype-selectivity was subsequently verified with ERK phosphorylation and cAMP assays.

N-[3-(3-methoxyphenyl) propyl] amides

melatonin

cAMP


Input: Structure-activity relationship analysis of highly potent subtype-selective ligands (MT (2) EC (50) 10-90 pM) revealed that a benzyloxyl substituent incorporated at C6 position of the 3-methoxyphenyl ring dramatically enhanced the MT (2) potency and at the same time decreased MT (1) potency.

benzyloxyl


Input: Incorporation of structural moieties conferring the subtype selectivity produced several extremely potent MT (2)-selective ligands.


Input: The most potent subtype-selective ligand, 2q had a substantially higher potency for MT (2) receptor than melatonin for elevation of [Ca (2 +)] i and inhibition of forskolin-elevated cAMP.

melatonin

Ca (2 +)


Input: Representative MT (2)-selective ligands also induced ERK phosphorylation in both recombinant and native cell lines, and no cross-reactivity to 17 other GPCRs could be detected.


Input: These ligands represent invaluable tools for delineating the functional roles of distinct melatonin receptor subtypes and are viable candidates for drug development.

melatonin


Input: Is poor research the cause of the declining productivity of the pharmaceutical industry?


Input: An industry in need of a paradigm shift.


Input: For the past 20 years target-based drug discovery has been the main research paradigm used by the pharmaceutical industry and billions of dollars have been invested into this approach.


Input: However, recent industry data strongly indicate that the target-based approach is not an effective drug discovery paradigm and is likely to be the cause of the productivity crisis the industry is experiencing.


Input: However, from a theoretical and scientific perspective the target-based approach appears sound, so why is it not more successful?


Input: The purpose of this paper is first to analyse the real-life implementation of the target-based approach to identify possible reasons for the high failure rate and second to suggest changes to the drug discovery approach, which can improve productivity.


Input: Large, chemically diverse dataset of logP measurements for benchmarking studies.


Input: Lipophilicity is a crucial parameter in drug development since it impacts both ADME properties and target affinity of drug candidates.


Input: In early drug discovery stage, accurate tools for logP prediction are highly desired.


Input: Many calculation methods were developed to aid pharmaceutical scientists in drug research; however almost all suffer from insufficient accuracy and variation of performance in several regions of the chemical space associated with new chemical entities.


Input: The low predictive power of existing software packages can be explained by limited availability and/or variable quality of experimental logP values associated with training set used, which stem from various protocols and poorly cover chemical space.


Input: In this study, a dataset of 1000 diverse test compounds out of 4. 5 million was generated; logP values of 759 purchasable compounds (46% non-ionizable, 30% basic, 17% acidic, 0. 5% zwitterionic and 6. 5% ampholytes) from this selected set were experimentally determined by UHPLC followed by UV detection or MS detection when necessary.


Input: Finally, a data collection of 707 validated logP values ranging from 0. 30 to 7. 50 is now available for benchmarking of existing and development of new approaches to predict octanol/water partition coefficients of chemical compounds.

octanol


Input: Discovery of novel cannabinoid receptor ligands by a virtual screening approach: further development of 2, 4, 6-trisubstituted 1, 3, 5-triazines as CB2 agonists.

2, 4, 6-trisubstituted 1, 3, 5-triazines


Input: 3D ligand-based virtual screening was employed to identify novel scaffolds for cannabinoid receptor ligand development.


Input: A total of 112 compounds with diverse structures were purchased from commercial vendors.


Input: 12 CB1 receptor antagonists/inverse agonists and 10 CB2 receptor agonists were identified in vitro.


Input: One of the CB2 agonists, N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1, 3, 5-triazin-2-amine (19,-logEC (50) = 7. 5, E (max) = 255%) was selected for further development.

N-cyclopentyl-4-ethoxy-6-(4-methylpiperidin-1-yl)-1, 3, 5-triazin-2-amine


Input: As far as we are aware, the compound' s 1, 3, 5-triazine scaffold represents a new core structure for CB2 agonists.

1, 3, 5-triazine


Input: A library of fifty-seven 2, 4, 6-trisubstituted-1, 3, 5-triazines was created to clarify the structure-activity relationship study of the analogs.

2, 4, 6-trisubstituted-1, 3, 5-triazines


Input: In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor.

dolutegravir


Input: Dolutegravir (DTG; S/GSK1349572) is a potent HIV-1 integrase inhibitor with a distinct resistance profile and a once-daily dose regimen that does not require pharmacokinetic boosting.

Dolutegravir

DTG


Input: This work investigated the in vitro drug transport and metabolism of DTG and assessed the potential for clinical drug-drug interactions.

DTG


Input: DTG is a substrate for the efflux transporters P-glycoprotein (Pgp) and human breast cancer resistance protein (BCRP).

DTG


Input: Its high intrinsic membrane permeability limits the impact these transporters have on DTG' s intestinal absorption.

DTG


Input: UDP-glucuronosyltransferase (UGT) 1A1 is the main enzyme responsible for the metabolism of DTG in vivo, with cytochrome P450 (P450) 3A4 being a notable pathway and UGT1A3 and UGT1A9 being only minor pathways.

UDP

DTG


Input: DTG demonstrated little or no inhibition (IC (50) values > 30 mu M) in vitro of the transporters Pgp, BCRP, multidrug resistance protein 2, organic anion transporting polypeptide 1B1/3, organic cation transporter (OCT) 1, or the drug metabolizing enzymes CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, UGT1A1, or 2B7.

DTG


Input: Further, DTG did not induce CYP1A2, 2B6, or 3A4 mRNA in vitro using human hepatocytes.

DTG


Input: DTG does inhibit the renal OCT2 (IC (50) = 1. 9 mu M) transporter, which provides a mechanistic basis for the mild increases in serum creatinine observed in clinical studies.

DTG

creatinine


Input: These in vitro studies demonstrate a low propensity for DTG to be a perpetrator of clinical drug interactions and provide a basis for predicting when other drugs could result in a drug interaction with DTG.

DTG

DTG


Input: Ligand-dependent actions of the vitamin D receptor are required for activation of TGF-beta signaling during the inflammatory response to cutaneous injury.

vitamin D


Input: The vitamin D receptor (VDR) has both 1, 25-dihydroxyvitamin D-dependent and-independent actions in the epidermis.

vitamin D

1, 25-dihydroxyvitamin D


Input: Ligand-dependent actions of the VDR have been shown to promote keratinocyte differentiation and to regulate formation of the epidermal barrier.


Input: In contrast, the actions of the VDR that regulate postmorphogenic hair cycling do not require 1, 25-dihydroxyvitamin D.

1, 25-dihydroxyvitamin D


Input: The VDR also has immunomodulatory actions that are dependent on its ligand, 1, 25-dihydroxyvitamin D.

1, 25-dihydroxyvitamin D


Input: To determine whether the ligand-dependent or-independent actions of the VDR regulate the inflammatory response to cutaneous injury, studies were performed in control, VDR knockout, and vitamin D-deficient mice.

vitamin D


Input: These investigations demonstrate that absence of receptor or ligand impairs the dermal response to cutaneous injury.


Input: Although neutrophil recruitment is not affected, the absence of VDR signaling leads to defects in macrophage recruitment and granulation tissue formation.


Input: Studies performed to identify the molecular basis for this phenotype demonstrate that absence of the VDR, or its ligand, impairs TGF-beta signaling in the dermis, characterized by decreased expression of monocyte chemotactic protein-1 and reduced phosphorylation of phosphorylated Smad-3 as well as attenuated phosphorylated Smad-3 phosphorylation in response to TGF-beta in primary dermal fibroblasts lacking the VDR.


Input: Thus, these data demonstrate that the liganded VDR interacts with the TGF-beta signaling pathway to promote the normal inflammatory response to cutaneous injury.


Input: Mechanical activation of CaO-based adsorbents for CO (2) capture.

CaO

CO (2)


Input: The reversible cycling of CaO adsorbents to CaCO (3) for high-temperature CO (2) capture is substantially improved by mechanical treatment.

CaO

CaCO (3)

CO (2)


Input: The mechanical milling intensity and conditions of grinding (e. g., wet vs. dry, planetary vs. vibratory milling) were determined to be the main factors that control the effectiveness of the mechanochemical synthesis to enhance the recycling stability of the sorbents prepared.


Input: In addition, MgO was used as an example of an inert binder to help mitigate CaCO (3) sintering.

MgO

CaCO (3)


Input: Wet planetary milling of MgO into CaCO (3) allowed efficient particle size reduction and the effective dispersion of MgO throughout the particles.

MgO

CaCO (3)

MgO


Input: Wet planetary milling yielded the most stable sorbents during 50 cycles of carbonation-calcination.


Input: Synthesis and evaluation of 3, 4-dihydropyrimidin-2 (1H)-ones as sodium iodide symporter inhibitors.

3, 4-dihydropyrimidin-2 (1H)-ones

sodium iodide


Input: The sodium iodide symporter (NIS) is responsible for the accumulation of iodide in the thyroid gland.

sodium iodide

iodide


Input: This transport process is involved in numerous thyroid dysfunctions and is the basis for human contamination in the case of exposure to radioactive iodine species.

iodine


Input: 4-Aryl-3, 4-dihydropyrimidin-2 (1H)-ones were recently discovered by high-throughput screening as the first NIS inhibitors.

4-Aryl-3, 4-dihydropyrimidin-2 (1H)-ones


Input: Described herein are the synthesis and evaluation of 115 derivatives with structural modifications at five key positions on the pyrimidone core.

pyrimidone


Input: This study provides extensive structure-activity relationships for this new class of inhibitors that will serve as a basis for further development of compounds with in vivo efficacy and adequate pharmacokinetic properties.


Input: In addition, the SAR investigation provided a more potent compound, which exhibits an IC (50) value of 3. 2 nM in a rat thyroid cell line (FRTL5).


Input: Silk fibroin/hyaluronic acid 3D matrices for cartilage tissue engineering.


Input: In spite of commercially available products, the complete and sustained repair of damaged articular cartilage still presents various challenges.


Input: Among biomaterials proposed for cartilage repair, silk fibroin (SF) has been recently proposed as a material template for porous scaffolds cultured with chondrocytes and investigated in static and dynamic conditions.


Input: In addition to fibroin-based constructs, literature has reported that the combination of hyaluronic acid (HA) with other scaffold materials can protect the chondral phenotype and the cells in vitro response to the scaffold.


Input: In this study, the effect of the addition of HA on the physical properties of SF sponges, with and without cross-linking with genipin, was investigated.


Input: Salt-leached scaffolds were characterized in terms of morphology and structural and physical properties, as well as mechanical performance.


Input: Un-cross-linked sponges resulted in the physical separation of highly hydrophilic HA from the SF, while cross-linking prevented this phenomenon, resulting in a homogeneous blend.


Input: The presence of HA also influenced fibroin crystallinity and tended to decrease the cross-linking degree of the scaffolds when compared to the pure SF material.


Input: Mechanisms of hepatocellular toxicity associated with dronedarone--a comparison to amiodarone.

dronedarone

amiodarone


Input: Dronedarone is a new antiarrhythmic drug with an amiodarone-like benzofuran structure.

Dronedarone

amiodarone

benzofuran


Input: Shortly after its introduction, dronedarone became implicated in causing severe liver injury.

dronedarone


Input: Amiodarone is a well-known mitochondrial toxicant.

Amiodarone


Input: The aim of our study was to investigate mechanisms of hepatotoxicity of dronedarone in vitro and to compare them with amiodarone.

dronedarone

amiodarone


Input: We used isolated rat liver mitochondria, primary human hepatocytes, and the human hepatoma cell line HepG2, which were exposed acutely or up to 24h.


Input: After exposure of primary hepatocytes or HepG2 cells for 24h, dronedarone and amiodarone caused cytotoxicity and apoptosis starting at 20 and 50 micro M, respectively.

dronedarone

amiodarone


Input: The cellular ATP content started to decrease at 20 micro M for both drugs, suggesting mitochondrial toxicity.

ATP


Input: Inhibition of the respiratory chain required concentrations of ~ 10 micro M and was caused by an impairment of complexes I and II for both drugs.


Input: In parallel, mitochondrial accumulation of reactive oxygen species (ROS) was observed.

oxygen


Input: In isolated rat liver mitochondria, acute treatment with dronedarone decreased the mitochondrial membrane potential, inhibited complex I, and uncoupled the respiratory chain.

dronedarone


Input: Furthermore, in acutely treated rat liver mitochondria and in HepG2 cells exposed for 24h, dronedarone started to inhibit mitochondrial beta-oxidation at 10 micro M and amiodarone at 20 micro M.

dronedarone

amiodarone


Input: Similar to amiodarone, dronedarone is an uncoupler and an inhibitor of the mitochondrial respiratory chain and of beta-oxidation both acutely and after exposure for 24h.

amiodarone

dronedarone


Input: Inhibition of mitochondrial function leads to accumulation of ROS and fatty acids, eventually leading to apoptosis and/or necrosis of hepatocytes.

fatty acids


Input: Mitochondrial toxicity may be an explanation for hepatotoxicity of dronedarone in vivo.


Input: Dioxin inhibits zebrafish epicardium and proepicardium development.

Dioxin


Input: Embryonic exposure to the environmental contaminant and aryl hydrocarbon receptor agonist, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), disrupts cardiac development and function in fish, birds, and mammals.

aryl hydrocarbon

2, 3, 7, 8-tetrachlorodibenzo-p-dioxin

TCDD

dioxin


Input: In zebrafish, the temporal window of sensitivity to the cardiotoxic effects of TCDD coincides with epicardium formation.

TCDD


Input: We hypothesized that this TCDD-induced heart failure results from disruption of epicardial development.

TCDD


Input: To determine whether embryonic TCDD exposure inhibits epicardium and proepicardium (PE) development in zebrafish, we used histology and fluorescence immunocytochemistry to examine the epicardium formation in fish exposed to TCDD.

TCDD

TCDD


Input: TCDD exposure prevented epicardium formation.

TCDD


Input: Using live imaging and in situ hybridization, we found that TCDD exposure blocked the formation of the PE cluster.

TCDD


Input: In situ hybridization experiments showed that TCDD exposure also prevented the expression of the PE marker tcf21 at the site where the PE normally forms.

TCDD


Input: TCDD also inhibited expansion of the epicardial layer across the developing heart: Exposure after PE formation was completed prevented further expansion of the epicardium.

TCDD


Input: However, TCDD exposure did not affect epicardial cells already present.

TCDD


Input: Because TCDD blocks epicardium formation, but is not directly toxic to the epicardium once complete, we propose that inhibition of epicardium formation can account for the window of sensitivity to TCDD cardiotoxicity in developing zebrafish.

TCDD

TCDD


Input: Epicardium development is crucial to heart development.


Input: Loss of this layer during development may account for most if not all of the TCDD-induced cardiotoxicity in zebrafish.

TCDD


Input: Protein-size molecularly imprinted polymer nanogels as synthetic antibodies, by localized polymerization with multi-initiators.


Input: A new approach is proposed for the synthesis of molecularly imprinted polymers (MIPs) (synthetic antibodies) as soluble nanogels with sizes close to the size of real antibodies.


Input: To imprint a molecular memory in particles consisting of only a few polymer chains, an initiator carrying multiple iniferter moieties is used.


Input: This allows for the simultaneous initiation of several polymer chains, and yields molecularly imprinted nanogels (17 nm, molecular weight (MW) = 97 kDa) with good affinity and selectivity for the target.


Input: A novel matrix for the short-term storage of cells: utility in drug metabolism and drug transporter studies with rat, dog and human hepatocytes.


Input: 1. The SureTran (TM) matrix is a novel method facilitating short-term maintenance of fresh primary hepatocyte cellular function and offers the potential use of primary cells " as fresh " for several days post isolation.


Input: In the study presented, the maintenance of several key phase I and II drug metabolizing enzyme and drug transporter activities is demonstrated with rat and dog hepatocytes preserved for up to 7 days after cell isolation.


Input: 2. Intrinsic clearance values were determined for 60 new chemical entities using rat hepatocytes freshly isolated at AstraZeneca and rat hepatocytes prepared at the facilities of Abcellute Ltd (SureTran (TM) purveyors), stored and incubated 24 hours after isolation.


Input: A very good correspondence in the intrinsic clearance values underlines the utility of the cell maintenance matrix.


Input: 3. For human hepatocytes many of the enzyme activities assayed were well maintained for 7 days of storage but some declined to below 50% of initial values between day 4 and 7 of storage.


Input: Human OATP1B1 activity was only determined with one batch and declined to 51% of the initial test value by day 4 and further down to 35% by day 7.


Input: Influence of resveratrol on rheumatoid fibroblast-like synoviocytes analysed with gene chip transcription.

resveratrol


Input: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily attacks joints and is therefore a common cause of chronic disability and articular destruction.


Input: The hyperplastic growth of RA-fibroblast-like synoviocytes (FLSs) and their resistance against apoptosis are considered pathological hallmarks of RA.


Input: The natural antioxidant resveratrol is known for its antiproliferative and pro-apoptotic properties.

resveratrol


Input: This study investigated the effect of resveratrol on RA-FLS.

resveratrol


Input: RA-FLS were isolated from the synovium of 10 RA patients undergoing synovectomy or joint replacement surgery.


Input: RA-FLS were first stressed by pre-incubation with interleukin 1beta (IL-1 beta) and then treated with 100 mu M resveratrol for 24h.

resveratrol


Input: In order to evaluate the influence of resveratrol on the transcription of genes, a Gene Chip Human Gene 1. 0 ST Array was applied.

resveratrol


Input: In addition, the effect of dexamethasone on proliferation and apoptosis of RA-FLS was compared with that of resveratrol.

dexamethasone

resveratrol


Input: Gene array analysis showed highly significant effects of resveratrol on the expression of genes involved in mitosis, cell cycle, chromosome segregation and apoptosis.

resveratrol


Input: qRT-PCR, caspase-3/7 and proliferation assays confirmed the results of gene array analysis.


Input: In comparison, dexamethasone showed little to no effect on reducing cell proliferation and apoptosis.

dexamethasone


Input: Our in vitro findings point towards resveratrol as a promising new therapeutic approach for local intra-articular application against RA, and further clinical studies will be necessary.

resveratrol


Input: Dietary exposure to mycotoxins and health risk assessment in the second French total diet study.


Input: Mycotoxins are produced in plants by micro-fungi species, and naturally contaminated the food chain.


Input: In the second French total diet study (TDS), mycotoxins were analyzed in 577 food samples collected in mainland France to be representative of the population diet and prepared ((as consumed)).


Input: Highest mean concentrations were found in wheat and cereal-based products (bread, breakfast cereals, pasta, pastries, pizzas and savoury pastries ...).


Input: Exposure of adult and child populations was assessed by combining national consumption data with analytical results, using lowerbound (LB) and upperbound (UB) assumptions for left-censorship management.


Input: Individual exposures were compared with available health-based guidance values (HBGV).


Input: Only the exposure to deoxynivalenol (DON) and its acetylated derivatives was found to significantly exceed the HBGV in LB in adults (0. 5% [0. 1; 0. 8]) and children (5% [4; 6]).

deoxynivalenol

DON


Input: HBGV was exceeded in UB only for T-2 and HT-2 toxins by, respectively, 0. 2% [0. 02; 0. 05] and 4% [3; 5] of adults, and 11% [9; 12] and 35% [32; 37] of children.


Input: Although the exposures assessed were generally lower than the previous French TDS, the results indicated a health concern for trichothecenes and a need to reduce dietary exposure as well as analytical limits.

trichothecenes


Input: The effect of copper on different phototrophic microorganisms determined in vivo and at cellular level by confocal laser microscopy.

copper


Input: Microbial mats are coastal ecosystems that consist mainly of cyanobacteria, primary producers in these habitats that play an important role in stabilising delta sediments.


Input: However, these ecosystems are subject to various kinds of pollution, including metal contamination, placing their survival at risk.


Input: Among heavy metals, copper is an essential metal at low doses and toxic at high doses.

copper


Input: This metal is present in different pesticides used in rice production, a thriving agro-industry in the Ebro Delta (Spain).


Input: For several years, our group has been studying the Ebro Delta microbial mats and has developed a method for determining the effect that metals cause on cyanobacteria populations.


Input: This method is based on confocal laser microscopy coupled to a spectrofluorometer, which rapidly provides simultaneous three-dimensional information on photosynthetic microorganisms and their fluorescence spectra profiles.


Input: The current study determines the copper effect on different photosynthetic microorganisms from culture collection (Chroococcus sp. PCC 9106 and Spirulina sp. PCC 6313) and isolated from the environment (Microcoleus-like and the microalga DE2009).

copper


Input: Comparing all results obtained it can be observed that the minimum dose of Cu that is capable of significantly altering chlorophyll a (chl a) fluorescence intensity were 1 x 10 (-7) M in Chroococcus sp.

Cu

chlorophyll a

chl a


Input: PCC 9106; 1 x 10 (-7) M in Spirulina sp.


Input: PCC 6313; 3 x 10 (-7) M in Microcoleus and 5 x 10 (-6) M in the microalga DE2009.


Input: Moreover, the sensitivity of the technique used was 1 x 10 (-7) M.


Input: New results on formaldehyde: the 2nd International Formaldehyde Science Conference (Madrid, 19-20 April 2012).

formaldehyde

Formaldehyde


Input: The toxicology and epidemiology of formaldehyde were discussed on the 2nd International Formaldehyde Science Conference in Madrid, 19-20 April 2012.

formaldehyde

Formaldehyde


Input: It was noted that a substantial amount of new scientific data has appeared within the last years since the 1st conference in 2007.


Input: Progress has been made in characterisation of genotoxicity, toxicokinetics, formation of exogenous and endogenous DNA adducts, controlled human studies and epidemiology.


Input: Thus, new research results are now at hand to be incorporated into existing evaluations on formaldehyde by official bodies.

formaldehyde


Input: Homogeneous palladium-catalyzed asymmetric hydrogenation.

palladium


Input: The transition metal catalyzed asymmetric hydrogenation of unsaturated compounds arguably presents one of the most attractive methods for the synthesis of chiral compounds.


Input: Over the last few decades, Pd has gradually grown up as a new and popular metal catalyst in homogeneous asymmetric hydrogenation the same as traditional Ru, Rh and Ir catalysts.

Pd

Ru

Rh

Ir


Input: Much progress has been successfully achieved in the asymmetric reduction of imines, enamines, olefins, ketones and heteroarenes.

imines

enamines

olefins

ketones

heteroarenes


Input: It was also found that palladium catalyzed asymmetric hydrogenation could be used as a key step in tandem reactions to quickly synthesize chiral compounds.

palladium


Input: This tutorial review intends to offer an overview of recent progress in homogeneous palladium catalyzed asymmetric hydrogenation and should serve as an inspiration for further advances in this area.

palladium


Input: The utility of modeling and simulation approaches to evaluate immunogenicity effect on the therapeutic protein pharmacokinetics.


Input: While therapeutic proteins (TP), particularly recombinant human proteins and fully human monoclonal antibodies, are designed to have a low immunogenic potential in humans, a clinical immune response does sometimes occur and cannot be predicted from preclinical studies.


Input: Changes in TP pharmacokinetics may be perceived as an early indication of antibody formation and serve as a surrogate for later changes in efficacy and safety in individual subjects.


Input: Given the substantial increase in number of biological products, including biosimilars, there is an urgent need to quantitatively predict and quantify the immune response and any consequential changes in TP pharmacokinetics.


Input: The purpose of this communication is to review the utility of population-based modeling and simulation approaches developed to date for investigating the development of an immune response and assessing its impact on TP pharmacokinetics.


Input: Two examples of empirical modeling approaches for pharmacokinetic assessment are presented.


Input: The first example presents methods to analyze pharmacokinetic data in the presence of anti-drug antibody (ADA) and confirm the effect of immunogenicity on TP pharmacokinetics in early phases of drug development.


Input: The second example provides a framework to analyze pharmacokinetic data in the absence or with very low incidence of ADA and confirm with enough power the lack of an immunogenicity effect on TP pharmacokinetics in late phases of drug development.


Input: Finally, a theoretical mechanism-based modeling framework is presented to mathematically relate the complex interaction among TP, their targets, and ADA.


Input: Determination of the dominant arachidonic acid cytochrome p450 monooxygenases in rat heart, lung, kidney, and liver: protein expression and metabolite kinetics.

arachidonic acid


Input: Cytochrome P450 (P450)-derived arachidonic acid (AA) metabolites serve pivotal physiological roles.

arachidonic acid


Input: Therefore, it is important to determine the dominant P450 AA monooxygenases in different organs.


Input: We investigated the P450 AA monooxygenases protein expression as well as regioselectivity, immunoinhibition, and kinetic profile of AA epoxygenation and hydroxylation in rat heart, lung, kidney, and liver.


Input: Thereafter, the predominant P450 epoxygenases and P450 hydroxylases in these organs were characterized.


Input: Microsomes from heart, lung, kidney, and liver were incubated with AA.


Input: The protein expression of CYP2B1/2, CYP2C11, CYP2C23, CYP2J3, CYP4A1/2/3, and CYP4Fs in the heart, lung, kidney, and liver were determined by Western blot analysis.


Input: The levels of AA metabolites were determined by liquid chromatography-electrospray ionization mass spectroscopy.


Input: This was followed by determination of regioselectivity, immunoinhibition effect, and the kinetic profile of AA metabolism.


Input: AA was metabolized to epoxyeicosatrienoic acids and 19-and 20-hydroxyeicosatetraenoic acid in the heart, lung, kidney, and liver but with varying metabolic activities and regioselectivity.

epoxyeicosatrienoic acids

19-and 20-hydroxyeicosatetraenoic acid


Input: Anti-P450 antibodies were found to differentially inhibit AA epoxygenation and hydroxylation in these organs.


Input: Our data suggest that the predominant epoxygenases are CYP2C11, CYP2B1, CYP2C23, and CYP2C11/CYP2C23 for the heart, lung, kidney, and liver, respectively.


Input: On the other hand, CYP4A1 is the major omega-hydroxylase in the heart and kidney; whereas CYP4A2 and/or CYP4F1/4 are probably the major hydroxlases in the lung and liver.


Input: These results provide important insights into the activities of P450 epoxygenases and P450 hydroxylases-mediated AA metabolism in different organs and their associated P450 protein levels.


Input: The neuropathic diabetic foot ulcer microbiome is associated with clinical factors.


Input: Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes.


Input: Microbial burden, or " bioburden, " is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity.


Input: We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene.


Input: Comparatively, wound cultures, the standard diagnostic in the clinic, vastly underrepresent microbial load, microbial diversity, and the presence of potential pathogens.


Input: DFU microbiomes were heterogeneous, even in our tightly restricted study population, but partitioned into three clusters distinguished primarily by dominant bacteria and diversity.


Input: Ulcer depth was associated with ulcer cluster, positively correlated with abundance of anaerobic bacteria, and negatively correlated with abundance of Staphylococcus.


Input: Ulcer duration was positively correlated with bacterial diversity, species richness, and relative abundance of Proteobacteria, but was negatively correlated with relative abundance of Staphylococcus.


Input: Finally, poor glycemic control was associated with ulcer cluster, with poorest median glycemic control concentrating to Staphylococcus-rich and Streptococcus-rich ulcer clusters.


Input: Analyses of microbial community membership and structure may provide the most useful metrics in prospective studies to delineate problematic bioburden from benign colonization that can then be used to drive clinical treatment.


Input: Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes.

gemfibrozil

itraconazole


Input: The plasma concentration of repaglinide is reported to increase greatly when given after repeated oral administration of itraconazole and gemfibrozil.

repaglinide

itraconazole

gemfibrozil


Input: The present study analyzed this interaction based on a physiologically based pharmacokinetic (PBPK) model incorporating inhibition of the hepatic uptake transporter and metabolic enzymes involved in repaglinide disposition.


Input: Firstly, the plasma concentration profiles of inhibitors (itraconazole, gemfibrozil, and gemfibrozil glucuronide) were reproduced by a PBPK model to obtain their pharmacokinetic parameters.

itraconazole

gemfibrozil

gemfibrozil glucuronide


Input: The plasma concentration profiles of repaglinide were then analyzed by a PBPK model, together with those of the inhibitors, assuming a competitive inhibition of CYP3A4 by itraconazole, mechanism-based inhibition of CYP2C8 by gemfibrozil glucuronide, and inhibition of organic anion transporting polypeptide (OATP) 1B1 by gemfibrozil and its glucuronide.

repaglinide

itraconazole

gemfibrozil glucuronide

gemfibrozil and its glucuronide


Input: The plasma concentration profiles of repaglinide were well reproduced by the PBPK model based on the above assumptions, and the optimized values for the inhibition constants (0. 0676 nM for itraconazole against CYP3A4; 14. 2 mu M for gemfibrozil against OATP1B1; and 5. 48 mu M for gemfibrozil glucuronide against OATP1B1) and the fraction of repaglinide metabolized by CYP2C8 (0. 801) were consistent with the reported values.

repaglinide

itraconazole

gemfibrozil

gemfibrozil glucuronide

repaglinide


Input: The validity of the obtained parameters was further confirmed by sensitivity analyses and by reproducing the repaglinide concentration increase produced by concomitant gemfibrozil administration at various timings/doses.

repaglinide

gemfibrozil


Input: The present findings suggested that the reported concentration increase of repaglinide, suggestive of synergistic effects of the coadministered inhibitors, can be quantitatively explained by the simultaneous inhibition of the multiple clearance pathways of repaglinide.

repaglinide

repaglinide


Input: Long range effect of mutations on specific conformational changes in the extracellular loop 2 of angiotensin II type 1 receptor.


Input: The topology of the second extracellular loop (ECL2) and its interaction with ligands is unique in each G protein-coupled receptor.


Input: When the orthosteric ligand pocket located in the transmembrane (TM) domain is occupied, ligand-specific conformational changes occur in the ECL2.


Input: In more than 90% of G protein-coupled receptors, ECL2 is tethered to the third TM helix via a disulfide bond.


Input: Therefore, understanding the extent to which the TM domain and ECL2 conformations are coupled is useful.


Input: To investigate this, we examined conformational changes in ECL2 of the angiotensin II type 1 receptor (AT1R) by introducing mutations in distant sites that alter the activation state equilibrium of the AT1R.


Input: Differential accessibility of reporter cysteines introduced at four conformation-sensitive sites in ECL2 of these mutants was measured.

cysteines


Input: Binding of the agonist angiotensin II (AngII) and inverse agonist losartan in wild-type AT1R changed the accessibility of reporter cysteines, and the pattern was consistent with ligand-specific " lid " conformations of ECL2.

losartan

cysteines


Input: Without agonist stimulation, the ECL2 in the gain of function mutant N111G assumed a lid conformation similar to AngII-bound wild-type AT1R.


Input: In the presence of inverse agonists, the conformation of ECL2 in the N111G mutant was similar to the inactive state of wild-type AT1R.


Input: In contrast, AngII did not induce a lid conformation in ECL2 in the loss of function D281A mutant, which is consistent with the reduced AngII binding affinity in this mutant.


Input: However, a lid conformation was induced by [Sar (1), Gln (2), Ile (8)] AngII, a specific analog that binds to the D281A mutant with better affinity than AngII.

Sar

Gln

Ile


Input: These results provide evidence for the emerging paradigm of domain coupling facilitated by long range interactions at distant sites on the same receptor.


Input: The effects of green tea consumption and resistance training on body composition and resting metabolic rate in overweight or obese women.


Input: Green tea has been shown to have thermogenic and antiobesity properties.


Input: Therefore, it is important to investigate its effect on weight loss in humans, especially in women.


Input: We investigated the effects of green tea consumption combined with resistance training on the body composition and the resting metabolic rate (RMR) in women who were overweight or obese (grade I).


Input: After 4 weeks on an adaptive diet, 36 women were divided into four groups (group 1 green tea; group 2 placebo; group 3 green tea plus resistance training; group 4 placebo plus resistance training).


Input: The study was double-blinded and placebo-controlled.


Input: The RMR and body composition were ascertained for each volunteer, blood tests were performed, and subjects in groups 3 and 4 were tested for their one repetition maximum.


Input: Each subject followed the protocol and continued the diet for eight additional weeks, and periodic evaluations were administered.


Input: The mean RMR of group 1 decreased significantly and was accompanied by weight loss, maintenance of lean body mass, and decreases in both waist circumference and body mass index.


Input: Group 2 showed no variations in anthropometric or blood variables and significantly decreased their mean RMR.


Input: Group 3 showed significant increases in RMR, lean body mass, and muscle strength, and significant decreases in body fat, triglycerides, and waist circumference as compared to group 4.

triglycerides


Input: Green tea combined with resistance training its potential is increased with decreasing body fat, waist circumference, and triacylglyceride levels and by increasing lean body mass and muscle strength.

triacylglyceride


Input: EGCG inhibits CTGF expression via blocking NF-kappa B activation in cardiac fibroblast.

EGCG


Input: Connective tissue growth factor (CTGF) has been reported to play an important role in tissue fibrosis and presents a promising therapeutic target for fibrotic diseases.


Input: In heart, inappropriate increase in level of CTGF promotes fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby exacerbating cardiac hypertrophy and subsequent failure.


Input: Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac fibrosis.

EGCG

polyphenol


Input: However, the molecular mechanism by which EGCG exerts its anti-fibrotic effects has not been well investigated.

EGCG


Input: In this study, we found that EGCG could significantly reduce collagen synthesis, fibronectin (FN) expression and cell proliferation in rat cardiac fibroblasts stimulated with angiotensinII (AngII).

EGCG


Input: It also ameliorated cardiac fibrosis in rats submitted to abdominal aortic constriction (AAC).


Input: Moreover, EGCG attenuated the excessive expression of CTGF induced by AAC or AngII, and reduced the nuclear translocation of NF-kappa B p65 subunit and degradation of I kappa B-alpha.

EGCG


Input: Subsequently, we demonstrated that in cardiac fibroblasts NF-kappa B inhibition could suppress AngII-induced CTGF expression.


Input: Taken together, these findings provide the first evidence that the effect of EGCG against cardiac fibrosis may be attributed to its inhibition on NF-kappa B activation and subsequent CTGF overexpression, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.

EGCG

EGCG


Input: A soluble guanylate cyclase stimulator, BAY 41-8543, preserves right ventricular function in experimental pulmonary embolism.

BAY 41-8543


Input: Pulmonary embolism (PE) increases pulmonary vascular resistance, causing right ventricular (RV) dysfunction, and poor clinical outcome.


Input: Present studies test if the soluble guanylate cyclase stimulator BAY 41-8543 reduces pulmonary vascular resistance and protects RV function.

BAY 41-8543


Input: Experimental PE was induced in anesthetized, male Sprague-Dawley rats by infusing 25 mu m polystyrene microspheres (1. 95 million/100 g body wt, right jugular vein) producing moderate PE.

polystyrene


Input: Pulmonary artery vascular resistance, estimated as RVPSP/CO, increased 3-fold after 5 h of PE.


Input: Treatment with BAY 41-8543 (50 mu g/kg, I. V.; given at the time of PE induction) normalized this index by reducing RVPSP and markedly increasing CO, via preservation of heart rate and stroke volume.

BAY 41-8543


Input: Ex vivo RV heart function showed minimal changes at 5 h of PE, but decreased significantly after 18 h of PE, including peak systolic pressure (PSP, Control 39 +/- 1 mmHg vs. 19 +/- 3 PE), + dP/dt (1192 +/- 93 mmHg/s vs. 444 +/- 64) and-dP/dt (-576 +/- 60 mmHg/s vs.-278 +/- 40).


Input: BAY 41-8543 significantly improved all three indices of RV heart function (PSP 35 +/- 3. 5, + dP/dt 1129 +/- 100,-dP/dt-568 +/- 87).

BAY 41-8543


Input: Experimental PE produced increased PVR and RV dysfunction, which were ameliorated by treatment with BAY 41-8543.

BAY 41-8543


Input: Thus, there is vasodilator reserve in this model of experimental PE that can be exploited to reduce the stress upon the heart and preserve RV contractile function.


Input: Microbiota of male genital tract: impact on the health of man and his partner.


Input: This manuscript describes the male genital tract microbiota and the significance of it on the host' s and his partner' s health.


Input: Microbiota exists in male lower genital tract, mostly in urethra and coronal sulcus while high inter-subject variability exists.


Input: Differences appear between sexually transmitted disease positive and negative men as well as circumcised and uncircumcised men.


Input: Upper genital tract is generally germ-free, except in case of infections.


Input: Prostatitis patients have frequently abundant polymicrobial communities in their semen, expressed prostatic secretion and/or post-massage urine.


Input: Coryneform bacteria have ambivalent role in male urogenital tract being frequently commensals but sometimes associated with prostatitis and urethritis.


Input: Interactions between male and female genital tract microbiota are highly likely yet there are very scarce studies on the couples' genital tract microbiota.


Input: Increase of bacterial vaginosis-type microbiota and coliforms are the most typical findings in men while the adverse effect of male genital tract bacteria on in vitro fertilization and pregnancy outcome has also been indicated.


Input: Effect of developmental dioxin exposure on methylation and expression of specific imprinted genes in mice.

dioxin


Input: 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disruptor affecting the reproductive system in humans.

2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin

TCDD