Input: Chemical probes of a trisubstituted pyrrole to identify its protein target (s) in Plasmodium sporozoites.

pyrrole


Input: Malaria is a disease that has a major impact in many developing nations, especially on the African continent.


Input: There is a need to develop new therapeutics and prophylactic treatments against it.


Input: A trisubstituted pyrrole was recently found to inhibit infection of mammalian hepatocytes by Plasmodium sporozoites, but the target of this agent is not known.

pyrrole


Input: In this study trisubstituted pyrrole derivatives with different substituents on a piperidinyl nitrogen were prepared.

pyrrole

piperidinyl nitrogen


Input: We determined if modifications of the piperidinyl nitrogen would accommodate a drug-biotin linking strategy for affinity purification of the trisubstituted pyrrole' s target protein (s).

piperidinyl nitrogen

biotin

pyrrole


Input: Growth factor delivery from hydrogel particle aggregates to promote tubular regeneration after acute kidney injury.


Input: Local delivery of growth factors (GFs) can accelerate regeneration of injured tissue, but for many medical applications, injectable GF delivery systems are required for clinical success.


Input: Viscoelastic, injectable aggregates of micrometer-sized hydrogel particles made of multiarmed polyethylene glycol (starPEG) and heparin were prepared and tested for site-specific paracrine stimulation of tissue regeneration.

polyethylene glycol


Input: Heparin was used as it binds, protects and releases numerous GFs.


Input: Hydrogel based delivery of basic fibroblast growth factor (bFGF) and murine epidermal growth factor (EGF) was monitored utilizing enzyme-linked immunosorbent assay (ELISA).


Input: bFGF was released slowly because of its high affinity to the heparin while the significantly higher release of the non-specific binding EGF was controlled by diffusion only.


Input: To investigate GF delivery in vivo, a hydrogel loaded with murine EGF or bFGF was injected subcapsularly into the left kidney of mice with experimental acute kidney injury caused by glycerol induced rhabdomyolysis.

glycerol


Input: Visual examination confirmed sustained stability of the injected gel aggregates during the timescale of the experiment.


Input: The number of proliferating kidney tubular epithelial cells was quantified both in the injected kidney and the non-injected contralateral kidney.


Input: bFGF delivery from hydrogels induced a significant increase in cell proliferation in the injected kidney, although small effects were also seen in the non-injected kidney due to a systemic effect.


Input: EGF delivery strongly increased cell proliferation for both kidneys, but also showed a local effect on the injected kidney.


Input: The hydrogel without loaded GFs was used as a control and showed no increase in cell proliferation.


Input: Our results suggest that this novel starPEG-heparin hydrogel system can be an effective approach to deliver GFs locally.


Input: Ozonolysis efficiency and safety evaluation of aflatoxin B1 in peanuts.

aflatoxin B1


Input: Ozonolysis efficiency of aflatoxin-contaminated peanuts (ACPs) was investigated, and the safety of ACPs untreated/treated by ozone was evaluated after 28-day intragastrically administration in male and female Wistar rats.

aflatoxin

ozone


Input: 89. 40% of aflatoxin B1 (AFB1) in peanuts was decomposed by ozone with a concentration of 50mg/L, flow rate of 5L/min for 60h.

aflatoxin B1

ozone


Input: After 60h, the ozonolysis efficiency of AFB1 was not further improved.


Input: In the subchronic toxicity experiment, all rats did not have unusual changes in behavior, and no signs of intoxication were observed except for several dead rats due to inappropriate gavage or anesthesia.


Input: The results of subchronic toxicity indicated that rats fed on ACPs alone had significantly decreased in body weight gain and feed conversion efficiency.


Input: Most serum biochemical indexes of rats had apparently changed compared with those in the negative control, and gender difference significantly affected most indexes of subchronic toxicity except for the ratios of organ to body weight and histopathological observation.


Input: Rats fed on ACPs treated by ozone showed significant beneficial health effects.

ozone


Input: All the results suggested that the deleterious effects of AFB1 could be highly reduced by ozone, and ozone itself did not show any toxic effects on animals in this processing.

ozone

ozone


Input: Elevation of 4-hydroxynonenal and malondialdehyde modified protein levels in cerebral cortex with cognitive dysfunction in rats exposed to 1-bromopropane.

malondialdehyde


Input: 1-Bromopropane (1-BP), an alternative to ozone-depleting solvents (ODS), exhibits central nervous system (CNS) toxicity in animals and humans.

ozone


Input: This study was designed to relate CNS damage by Morris water maze (MWM) test and oxidative stress to 1-BP exposure in the rat.


Input: Male Wistar rats were randomly divided into 4 groups (n = 10), and treated with 0, 200, 400 and 800mg/kgbw 1-BP for consecutive 12 days, respectively.


Input: From day 8 to day 12 of the experiment, MWM test was employed to assess the cognitive function of rats.


Input: The cerebral cortex of rats was obtained immediately following the 24h after MWM test conclusion.


Input: Glutathione (GSH), oxidized glutathione (GSSG) and total thiol (total-SH) content, GSH reductase (GR) and GSH peroxidase (GSH-Px) activities, malondialdehyde (MDA) level, as well as 4-hydroxynonenal (4-HNE) and MDA modified proteins in homogenates of cerebral cortex were measured.

Glutathione

GSH

oxidized glutathione

GSSG

thiol

SH

GSH

GSH

GSH

malondialdehyde

MDA

MDA


Input: The obtained results showed that 1-BP led to cognitive dysfunction of rats, which was evidenced by delayed escape latency time and swimming distances in MWM performance.


Input: GSH and total-SH content, GSH/GSSG ratio, GR activity significantly decreased in cerebral cortex of rats, coupling with the increase of MDA level.

GSH

SH

GSH

GSSG

MDA


Input: 4-HNE and MDA modified protein levels obviously elevated after 1-BP exposure.

MDA


Input: GSH-Px activities in cerebral cortex of rats also increased.

GSH


Input: These data suggested that 1-BP resulted in enhanced lipid peroxidation of brain, which might play an important role in CNS damage induced by 1-BP.


Input: RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA.


Input: RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity.


Input: Natural cellular RNA substrates of mammalian Pol II, however, have not been identified and the cellular function of the Pol II RdRP activity is unknown.


Input: We found that Pol II can use a non-coding RNA, B2 RNA, as both a substrate and a template for its RdRP activity.


Input: Pol II extends B2 RNA by 18 nt on its 3'-end in an internally templated reaction.


Input: The RNA product resulting from extension of B2 RNA by the Pol II RdRP can be removed from Pol II by a factor present in nuclear extracts.


Input: Treatment of cells with alpha-amanitin or actinomycin D revealed that extension of B2 RNA by Pol II destabilizes the RNA.

alpha-amanitin

actinomycin D


Input: Our studies provide compelling evidence that mammalian Pol II acts as an RdRP to control the stability of a cellular RNA by extending its 3'-end.


Input: Effect of repeated dosing on rifampin exposure in BALB/c mice.

rifampin


Input: The discovery of novel therapeutics for the treatment of tuberculosis involves routine testing in a mouse model over four weeks of daily dosing with test compounds.


Input: In this model, daily oral administration of rifampin (10mg/kg) showed significantly lower plasma exposure on day 5 compared to day 1.

rifampin


Input: The absence of PXR-mediated induction of mouse Cyp3a isoforms was confirmed in the present study by incubating liver microsomes prepared from control and rifampin treated mice with probe substrates of CYP3A.

rifampin


Input: To test whether the reduction in exposure was due to Pgp-mediated efflux, verapamil, a known Pgp inhibitor, was dosed to the rifampin pre-treated mice which led to an increase in exposure to that obtained after a single dose of rifampin, suggesting the role of Pgp induction in reducing exposure to rifampin.

verapamil

rifampin

rifampin

rifampin


Input: To further confirm Pgp induction in rifampin treated mice, digoxin, a known substrate of Pgp, was administered to the rifampin pre-treated mice, and a significant drop in the digoxin exposure was observed compared to the control group.

rifampin

digoxin

rifampin

digoxin


Input: Collectively, our results show that repeated administration of rifampin in mice leads to a reduction in oral exposure due to induction of Pgp-mediated efflux of rifampin, and not via induction of CYP3A isoforms.

rifampin

rifampin


Input: Mini-review: Foldosome regulation of androgen receptor action in prostate cancer.

androgen


Input: Steroid hormone receptors play diverse roles in many aspects of human physiology including cell division, apoptosis and homeostasis, tissue differentiation, sexual development and response to stress.

Steroid hormone


Input: These ligand-activated transcription factors require the functional activity of numerous chaperone and chaperone-associated proteins, collectively termed the foldosome, at the crucial step of ligand recognition and binding.


Input: Since the initial isolation of foldosome components and pioneering research by Pratt, Toft and colleagues we understand much regarding cytosolic receptor function.


Input: The classical view, that the role of foldosome components is restricted to the cytosol, has been modified over recent years by research highlighting additional roles of chaperone proteins in nuclear translocation and target gene expression.


Input: Further, dysregulation of chaperone activity and expression has been implicated in various cancers, including breast and prostate cancer.


Input: Consequently, the foldosome provides an attractive therapeutic target in steroid hormone receptor-driven malignancies.

steroid hormone


Input: This review summarises current knowledge of how the foldosome impacts upon androgen receptor signalling, which is the key therapeutic target on prostate cancer, and how foldosome components may be used as biomarkers or therapeutic targets in this disease.

androgen


Input: Interspecies extrapolation based on the RepDose database--a probabilistic approach.


Input: Repeated dose toxicity studies from the RepDose database (DB) were used to determine interspecies differences for rats and mice.


Input: NOEL (no observed effect level) ratios based on systemic effects were investigated for three different types of exposure: inhalation, oral food/drinking water and oral gavage.


Input: Furthermore, NOEL ratios for local effects in inhalation studies were evaluated.


Input: On the basis of the NOEL ratio distributions, interspecies assessment factors (AF) are evaluated.


Input: All data sets were best described by a lognormal distribution.


Input: No difference was seen between inhalation and oral exposure for systemic effects.


Input: Rats and mice were on average equally sensitive at equipotent doses with geometric mean (GM) values of 1 and geometric standard deviation (GSD) values ranging from 2. 30 to 3. 08.


Input: The local AF based on inhalation exposure resulted in a similar distribution with GM values of 1 and GSD values between 2. 53 and 2. 70.


Input: Our analysis confirms former analyses on interspecies differences, including also dog and human data.


Input: Furthermore it supports the principle of allometric scaling according to caloric demand in the case that body doses are applied.


Input: In conclusion, an interspecies distribution animal/human with a GM equal to allometric scaling and a GSD of 2. 5 was derived.


Input: Molecular dissection of botulinum neurotoxin reveals interdomain chaperone function.


Input: Clostridium botulinum neurotoxin (BoNT) is a multi-domain protein made up of the approximately 100 kDa heavy chain (HC) and the approximately 50 kDa light chain (LC).


Input: The HC can be further subdivided into two halves: the N-terminal translocation domain (TD) and the C-terminal Receptor Binding Domain (RBD).

N

C


Input: We have investigated the minimal requirements for channel activity and LC translocation.


Input: We utilize a cellular protection assay and a single channel/single molecule LC translocation assay to characterize in real time the channel and chaperone activities of BoNT/A truncation constructs in Neuro 2A cells.


Input: The unstructured, elongated belt region of the TD is demonstrated to be dispensable for channel activity, although may be required for productive LC translocation.


Input: We show that the RBD is not necessary for channel activity or LC translocation, however it dictates the pH threshold of channel insertion into the membrane.


Input: These findings indicate that each domain functions as a chaperone for the others in addition to their individual functions, working in concert to achieve productive intoxication.


Input: Photochemical activation of TRPA1 channels in neurons and animals.


Input: Optogenetics is a powerful research tool because it enables high-resolution optical control of neuronal activity.


Input: However, current optogenetic approaches are limited to transgenic systems expressing microbial opsins and other exogenous photoreceptors.


Input: Here, we identify optovin, a small molecule that enables repeated photoactivation of motor behaviors in wild-type zebrafish and mice.

optovin


Input: To our surprise, optovin' s behavioral effects are not visually mediated.

optovin


Input: Rather, photodetection is performed by sensory neurons expressing the cation channel TRPA1.


Input: TRPA1 is both necessary and sufficient for the optovin response.

optovin


Input: Optovin activates human TRPA1 via structure-dependent photochemical reactions with redox-sensitive cysteine residues.

Optovin

cysteine


Input: In animals with severed spinal cords, optovin treatment enables control of motor activity in the paralyzed extremities by localized illumination.

optovin


Input: These studies identify a light-based strategy for controlling endogenous TRPA1 receptors in vivo, with potential clinical and research applications in nontransgenic animals, including humans.


Input: Overcoming chemotherapy resistance of ovarian cancer cells by liposomal cisplatin: molecular mechanisms unveiled by gene expression profiling.

cisplatin


Input: Previously we reported that liposomal cisplatin (CDDP) overcomes CDDP resistance of ovarian A2780cis cancer cells (Krieger et al., Int. J. Pharm. 389, 2010, 10-17).

cisplatin

CDDP

CDDP


Input: Here we find that the cytotoxic activity of liposomal CDDP is not associated with detectable DNA platination in resistant ovarian cancer cells.

CDDP


Input: This suggests that the mode of action of liposomal CDDP is different from the free drug.

CDDP


Input: To gain insight into mechanisms of liposomal CDDP activity, we performed a transcriptome analysis of untreated A2780cis cells, and A2780cis cells in response to exposure with IC50 values of free or liposomal CDDP.

CDDP

CDDP


Input: A process network analysis of upregulated genes showed that liposomal CDDP induced a highly different gene expression profile in comparison to the free drug.

CDDP


Input: p53 was identified as a key player directing transcriptional responses to free or liposomal CDDP.

CDDP


Input: The free drug induced expression of essential genes of the intrinsic (mitochondrial) apoptosis pathway (BAX, BID, CASP9) most likely through p38MAPK activation.


Input: In contrast, liposomal CDDP induced expression of genes from DNA damage pathways and several genes of the extrinsic pathway of apoptosis (TNFRSF10B-DR5, CD70-TNFSF7).

CDDP


Input: It thus appears that liposomal CDDP overcomes CDDP resistance by inducing DNA damage and in consequence programmed cell death by the extrinsic pathway.

CDDP

CDDP


Input: Predictions from gene expression data with respect to apoptosis activation were confirmed at the protein level by an apoptosis antibody array.


Input: This sheds new light on liposomal drug carrier approaches in cancer and suggests liposomal CDDP as promising strategy for the treatment of CDDP resistant ovarian carcinomas.

CDDP

CDDP


Input: Protective effect of Codium fragile against UVB-induced pro-inflammatory and oxidative damages in HaCaT cells and BALB/c mice.


Input: Acute exposure to ultraviolet (UV) radiation causes pro-inflammatory responses via diverse mechanisms including oxidative stress.


Input: Codium fragile is a green alga of Codiales family and has been reported to exhibit anti-edema, anti-allergic, anti-protozoal and anti-mycobacterial activities.


Input: In this study, we have investigated a novel anti-inflammatory potential of C. fragile using in vitro cell culture as well as in vivo animal models.


Input: In HaCaT cells, buthanol and ethylacetate fractions of 80% methanol C. fragile extract (CFB or CFE) and a single compound, clerosterol (CLS) isolated from CFE attenuated UVB (60mJ/cm (2))-induced cytotoxicity and reduced expression of pro-inflammatory proteins including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-alpha).

buthanol

ethylacetate

methanol

clerosterol

CLS

nitric oxide


Input: Moreover, CFB, CFE and CLS effectively suppressed UVB-induced production of pro-inflammatory mediators such as prostaglandin E2 (PGE2) and nitric oxide (NO).

CLS

prostaglandin E2

nitric oxide

NO


Input: In another experiment, topical application of CFB, CFE or CLS prior to UVB irradiation (200mJ/cm (2)) on BALB/c mice, inhibited the UVB-elevated protein levels of COX-2, iNOS, and TNF-alpha.

CLS


Input: Furthermore, CFB, CFE and CLS suppressed oxidative damages caused by UVB irradiation for example lipid peroxidation and/or protein carbonylation, which seemed to be mediated by up-regulation of antioxidant defense enzymes.

CLS


Input: These results suggest that C. fragile could be an effective therapeutic agent providing protection against UVB-induced inflammatory and oxidative skin damages.


Input: Involvement of organic anion-transporting polypeptides in the hepatic uptake of dioscin in rats and humans.

dioscin


Input: The objective of this study was to clarify the mechanism underlying hepatic uptake of dioscin (diosgenyl 2, 4-di-O-a-L-rhamnopyranosyl-p-D-glucopyranoside), an herbal ingredient with antihepatitis activity, in rats and humans.

dioscin

diosgenyl 2, 4-di-O-a-L-rhamnopyranosyl-p-D-glucopyranoside


Input: The liver uptake index (LUI) in vivo, perfused rat liver in situ, rat liver slices, isolated rat hepatocytes, and human organic anion-transporting polypeptide (OATP)-transfected cells in vitro were used to evaluate hepatic uptake of dioscin.

dioscin


Input: Values of 11. 9% +/- 1. 6% and 15. 0% +/- 0. 9% of dose for uptake of dioscin were observed by LUI in vivo and perfused rat livers in situ, respectively.

dioscin


Input: The time course of dioscin uptake by rat liver slices was temperature-dependent.

dioscin


Input: Uptake of dioscin by rat liver slices and isolated rat hepatocytes was inhibited significantly by Oatp modulators, such as ibuprofen (Oatp1a1 inhibitor), digoxin (Oatp1a4 substrate), and glycyrrhizic acid (Oatp1b2 inhibitor), but not by TEA or p-aminohippurate.

dioscin

ibuprofen

digoxin

glycyrrhizic acid

TEA

p-aminohippurate


Input: Uptake of dioscin in rat hepatocytes and OATP1B3-human embryonic kidney (HEK) 293 cells indicated a saturable process with a Km of 3. 75 +/- 0. 51 mu M and 2. 08 +/- 0. 27 mu M, respectively.

dioscin


Input: (-)-Epigallocatechin gallate, cyclosporin A, rifampicin, and telmisartan inhibited transport of dioscin in OATP1B3-HEK293 cells.

(-)-Epigallocatechin gallate

cyclosporin A

rifampicin

telmisartan

dioscin


Input: However, transcellular transport of dioscin in OATP1B1-or OATP1B1/multidrug resistance-associated protein 2-Madin-Darby canine kidney strain II cells was not observed.

dioscin


Input: These results indicate that hepatic uptake of dioscin is involved in OATP1B3 in humans, and multiple Oatps might participate in this process in rats.

dioscin


Input: Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors.


Input: MarR family proteins constitute a group of > 12 000 transcriptional regulators encoded in bacterial and archaeal genomes that control gene expression in metabolism, stress responses, virulence and multi-drug resistance.


Input: There is much interest in defining the molecular mechanism by which ligand binding attenuates the DNA-binding activities of these proteins.


Input: Here, we describe how PcaV, a MarR family regulator in Streptomyces coelicolor, controls transcription of genes encoding beta-ketoadipate pathway enzymes through its interaction with the pathway substrate, protocatechuate.

protocatechuate


Input: This transcriptional repressor is the only MarR protein known to regulate this essential pathway for aromatic catabolism.


Input: In in vitro assays, protocatechuate and other phenolic compounds disrupt the PcaV-DNA complex.

protocatechuate

phenolic


Input: We show that PcaV binds protocatechuate in a 1: 1 stoichiometry with the highest affinity of any MarR family member.

protocatechuate


Input: Moreover, we report structures of PcaV in its apo form and in complex with protocatechuate.

protocatechuate


Input: We identify an arginine residue that is critical for ligand coordination and demonstrate that it is also required for binding DNA.

arginine


Input: We propose that interaction of ligand with this arginine residue dictates conformational changes that modulate DNA binding.

arginine


Input: Our results provide new insights into the molecular mechanism by which ligands attenuate DNA binding in this large family of transcription factors.


Input: Arylamine organic dyes for dye-sensitized solar cells.

Arylamine


Input: Arylamine organic dyes with donor (D), pi-bridge (pi) and acceptor (A) moieties for dye-sensitized solar cells (DSCs) have received great attention in the last decade because of their high molar absorption coefficient, low cost and structural variety.

Arylamine


Input: In the early stages, the efficiency of DSCs with arylamine organic dyes with D-pi-A character was far behind that of DSCs with ruthenium (II) complexes partly due to the lack of information about the relationship between the chemical structures and the photovoltaic performance.

arylamine

ruthenium (II)


Input: However, exciting progress has been recently made, and power conversion efficiencies over 10% were obtained for DSCs with arylamine organic dyes.

arylamine


Input: It is thus that the recent research and development in the field of arylamine organic dyes employing an iodide/triiodide redox couple or polypyridyl cobalt redox shuttles as the electrolytes for either DSCs or solid-state DSCs has been summarized.

arylamine

iodide

triiodide

polypyridyl cobalt


Input: The cell performance of the arylamine organic dyes are compared, providing a comprehensive overview of arylamine organic dyes, demonstrating the advantages/disadvantages of each class, and pointing out the field that needs to reinforce the research direction in the further application of DSCs.

arylamine

arylamine


Input: Impaired cliff avoidance reaction in dopamine transporter knockout mice.

dopamine


Input: RATIONALE: Impulsivity is a key feature of disorders that include attention-deficit/hyperactivity disorder (ADHD).


Input: The cliff avoidance reaction (CAR) assesses maladaptive impulsive rodent behavior.


Input: Dopamine transporter knockout (DAT-KO) mice display features of ADHD and are candidates in which to test other impulsive phenotypes.

Dopamine


Input: OBJECTIVES: Impulsivity of DAT-KO mice was assessed in the CAR paradigm.


Input: For comparison, attentional deficits were also assessed in prepulse inhibition (PPI) in which DAT-KO mice have been shown to exhibit impaired sensorimotor gating.


Input: RESULTS: DAT-KO mice exhibited a profound CAR impairment compared to wild-type (WT) mice.


Input: As expected, DAT-KO mice showed PPI deficits compared to WT mice.


Input: Furthermore, the DAT-KO mice with the most impaired CAR exhibited the most severe PPI deficits.


Input: Treatment with methylphenidate or nisoxetine ameliorated CAR impairments in DAT-KO mice.

methylphenidate

nisoxetine


Input: CONCLUSION: These results suggest that DAT-KO mice exhibit impulsive CAR behavior that correlates with their PPI deficits.


Input: Blockade of monoamine transporters, especially the norepinephrine transporter (NET) in the prefrontal cortex (PFC), may contribute to pharmacological improvement of impulsivity in these mice.

monoamine

norepinephrine


Input: The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social isolation in rats.

risperidone


Input: RATIONALE: Rearing rats in isolation from weaning is an established preclinical neurodevelopmental model which induces behavioural deficits with apparent translational relevance to some core symptoms of schizophrenia.


Input: OBJECTIVE: This study evaluated the ability of the atypical antipsychotic risperidone to reverse behavioural deficits induced by post-weaning social isolation of rat pups and to further characterise the predictive validity of this model.

risperidone


Input: METHOD: Forty-five male Lister hooded rats were housed in groups of 3-4 (n = 16) or singly (n = 29) for 4 weeks immediately after weaning on postnatal day (PND) 22-24.


Input: On PND 51, novel cage-induced locomotor activity (LMA) was assessed to subdivide rats into groups balanced for behavioural response.


Input: On PNDs 58, 59, 65 and 72, rats received either vehicle (1 ml/kg; i. p.) or risperidone (0. 2 or 0. 5 mg/kg; i. p.) 30 min prior to testing in LMA, novel object discrimination (NOD), prepulse inhibition (PPI) of acoustic startle and conditioned emotional response (CER) learning paradigms, respectively.

risperidone


Input: RESULTS: Isolation rearing had no effect on PPI, but produced LMA hyperactivity and impaired NOD and CER compared to group-housed controls.


Input: Risperidone caused a dose-dependent reduction in LMA, irrespective of rearing condition, but selectively reversed the NOD deficit in isolation-reared rats.

Risperidone


Input: Risperidone did not reverse the isolation rearing-induced CER deficit.

Risperidone


Input: CONCLUSIONS: Similar to its clinical profile, risperidone only partially reverses the schizophrenic symptomology; since it reversed some, but not all, of the learning and memory deficits induced by post-weaning isolation, the isolation rearing model may be useful to predict antipsychotic activity of novel therapeutic agents.

risperidone


Input: Impaired function of prejunctional adenosine A1 receptors expressed by perivascular sympathetic nerves in DOCA-salt hypertensive rats.

adenosine

DOCA


Input: Increased sympathetic nervous system activity contributes to deoxycorticosterone acetate (DOCA)-salt hypertension in rats.

deoxycorticosterone acetate

DOCA


Input: ATP and norepinephrine (NE) are coreleased from perivascular sympathetic nerves.

ATP

norepinephrine


Input: NE acts at prejunctional alpha 2-adrenergic receptors (alpha 2ARs) to inhibit NE release, and alpha 2AR function is impaired in DOCA-salt rats.

DOCA


Input: Adenosine, an enzymatic ATP degradation product, acts at prejunctional A1 adenosine receptors (A1Rs) to inhibit NE release.

Adenosine

ATP

adenosine


Input: We tested the hypothesis that prejunctional A1R function is impaired in sympathetic nerves supplying mesenteric arteries (MAs) and veins (MVs) of DOCA-salt rats.

DOCA


Input: Electrically evoked NE release and constrictions of blood vessels were studied in vitro with use of amperometry to measure NE oxidation currents and video microscopy, respectively.


Input: Immunohistochemical methods were used to localize tyrosine hydroxylase (TH) and A1Rs in perivascular sympathetic nerves.

tyrosine


Input: TH and A1Rs colocalized to perivascular sympathetic nerves.


Input: Adenosine and N (6)-cyclopentyl-adenosine (CPA, A1R agonist) constricted MVs but not MAs.

Adenosine

N (6)-cyclopentyl-adenosine

CPA


Input: Adenosine and CPA (0. 001-10 micro M) inhibited neurogenic constrictions and NE release in MAs and MVs.

Adenosine

CPA


Input: DOCA-salt arteries were resistant to adenosine and CPA-mediated inhibition of NE release and constriction.

DOCA

adenosine

CPA


Input: The A2A adenosine receptor agonist CGS21680 (C23H29N7O6. HCl. xH2O) (0. 001-0. 1 mu M) did not alter NE oxidation currents.

adenosine

C23H29N7O6. HCl. xH2O


Input: We conclude that there are prejunctional A1Rs in arteries and both pre-and postjunctional A1Rs in veins; thus, adenosine selectively constricts the veins.

adenosine


Input: Prejunctional A1R function is impaired in arteries, but not veins, from DOCA-salt rats.

DOCA


Input: Sympathetic autoreceptor dysfunction is not specific to alpha 2ARs, but there is a more general disruption of prejunctional mechanisms controlling sympathetic neurotransmitter release in DOCA-salt hypertension.

DOCA


Input: Temperature Effects of Sputtering of Langmuir-Blodgett Multilayers.


Input: Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and atomic force microscopy (AFM) are employed to characterize a wedge-shaped crater eroded by a 40 keV C (60) (+) cluster ion beam on an organic thin film of 402 nm of barium arachidate (AA) multilayers prepared by the Langmuir-Blodgett (LB) technique.

C (60) (+)

barium arachidate


Input: Sample cooling to 90 K was used to help reduce chemical damage, improve depth resolution and maintain constant erosion rate during depth profiling.


Input: The film was characterized at 90 K, 135 K, 165 K, 205 K, 265 K and 300 K.


Input: It is shown that sample cooling to 205 K or lower helps to inhibit erosion rate decay, whereas at 300 K and 265 K the erosion rate continues to drop after 250 nm of erosion, reaching about half of the initial value after removal of the entire film.


Input: Depth profiles are acquired from the SIMS images of the eroded wedge crater.


Input: The results suggest that sample cooling only slightly improves the altered layer thickness, but eliminates the decrease in erosion rate observed above 265 K.


Input: Lipid Efflux Mediated by Alkylphospholipids in HepG2 Cells.


Input: Antitumoural alkylphospholipid (APL) analogues alter cholesterol homoeostasis in HepG2 cells by interfering with cholesterol transport from the plasma membrane to the endoplasmic reticulum (ER) and at the same time stimulating the release of considerable quantities of membrane cholesterol.

cholesterol

cholesterol

cholesterol


Input: The capacity of APLs to stimulate cholesterol efflux is suppressed when cells are incubated simultaneously with APLs and serum whilst the inhibition of cholesterol transport to the ER (measured in terms of the synthesis of esterified cholesterol) persists, indicating that both effects are independent of each other.

cholesterol

cholesterol

esterified cholesterol


Input: Interestingly, our results suggest that both raft and non-raft membrane domains contribute to the cholesterol released to APLs.

cholesterol


Input: In addition, a marked efflux of choline-bearing phospholipids (phosphatidylcholine (PC) and sphingomyelins (SM)) was found to be related to this release of cholesterol.

choline

phosphatidylcholine

sphingomyelins

cholesterol


Input: Finally, we observed that APL micelles composed of cholesterol might act as donor/acceptor cholesterol systems.

cholesterol

cholesterol


Input: Thus, the findings of this study clearly demonstrate that antitumoural APLs act as extracellular acceptors, stimulating cholesterol and phospholipid efflux, although they may also play a role as cholesterol donors.

cholesterol

cholesterol


Input: Prolactin and sex steroids levels in congenital lifetime isolated GH deficiency.

steroids


Input: Growth hormone (GH) and prolactin share similarities in structure and function.


Input: We have previously shown that women with congenital isolated GH deficiency (IGHD) caused by a homozygous mutation in the GHRH receptor gene (GHRHR) (MUT/MUT) have a short reproductive life, with anticipated climacteric.


Input: At climacteric, they have lower prolactin levels than normal controls (N/N).


Input: Because they are able to breast feed, we hypothesized that this prolactin reduction is limited to climacteric, as result of lower estradiol exposure of the lactotrophs.

estradiol


Input: The purposes of this work were to assess prolactin levels in broader age adults homozygous and heterozygous (MUT/N) for the mutation and in normal controls (N/N), and to correlate them to sex steroids levels.

steroids


Input: We enrolled 24 GH-na i ve MUT/MUT (12 female), 25 MUT/N (14 female), and 25 N/N (11 female) subjects, aged 25-65 years.


Input: Anthropometric data and serum prolactin, estradiol, total testosterone, and sex hormone binding globulin (SHBG) were measured.

estradiol

testosterone


Input: Free testosterone was calculated.

testosterone


Input: Prolactin levels were similar in the three groups.


Input: In males, testosterone and SHBG levels were higher in MUT/MUT in comparison to N/N.

testosterone


Input: There was no difference in free testosterone among groups.

testosterone


Input: In all 74 individuals, prolactin correlated inversely with age (p < 0. 0001) and directly with serum estradiol (p = 0. 018).

estradiol


Input: Prolactin levels in subjects with IGHD due to a homozygous GHRHR mutation are similar to heterozygous and normal homozygous, but total testosterone and SHBG are higher in male MUT/MUT, with no difference in free testosterone.

testosterone

testosterone


Input: The reduced prolactin level is limited to climacteric period, possibly due to reduced estrogen exposure.

estrogen


Input: Lithium/sulfur batteries with high specific energy: old challenges and new opportunities.

Lithium

sulfur


Input: In this review, we begin with a brief discussion of the operating principles and scientific/technical challenges faced by the development of lithium/sulfur cells.

lithium

sulfur


Input: We then introduce some recent progress in exploring cathodes, anodes, and electrolytes for lithium/sulfur cells.

lithium

sulfur


Input: In particular, several effective strategies used to enhance energy/power density, obtain good efficiencies, and prolong cycle life will be highlighted.


Input: We also discuss recent advancements in techniques for investigating electrode reactions in real time and monitoring structural/morphological changes of electrode materials under cell operating conditions to gain a better understanding of the mechanistic details of electrode processes.


Input: Finally, the opportunities and perspective for future research directions will be discussed.


Input: Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells.


Input: Iodothyronine deiodinase types I, II, and III (D1, D2, and D3, respectively), which constitute a family of selenoenzymes, activate and inactivate thyroid hormones through the removal of specific iodine moieties from thyroxine and its derivatives.

Iodothyronine

iodine

thyroxine


Input: These enzymes are important in the biological effects mediated by thyroid hormones.


Input: The expression of activating and inactivating deiodinases plays a critical role in a number of cell systems, including the neuronal system, during development as well as in adult vertebrates.


Input: To investigate deiodinase-disrupting chemicals based on transcriptomic responses, we examined differences in gene expression profiles between T3-treated and deiodinase-knockdown SH-SY5Y cells using microarray analysis and quantitative real-time RT-PCR.


Input: A total of 1, 558 genes, consisting of 755 upregulated and 803 downregulated genes, were differentially expressed between the T3-treated and deiodinase-knockdown cells.


Input: The expression levels of 10 of these genes (ID2, ID3, CCL2, TBX3, TGOLN2, C1orf71, ZNF676, GULP1, KLF9, and ITGB5) were altered by deiodinase-disrupting chemicals (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, polychlorinated biphenyls, propylthiouracil, iodoacetic acid, methylmercury, beta-estradiol, methimazole, 3-methylcholanthrene, aminotriazole, amiodarone, cadmium chloride, dimethoate, fenvalerate, octylmethoxycinnamate, iopanoic acid, methoxychlor, and 4-methylbenzylidene-camphor).

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

polychlorinated biphenyls

propylthiouracil

iodoacetic acid

methylmercury

beta-estradiol

methimazole

aminotriazole

amiodarone

cadmium chloride

dimethoate

fenvalerate

octylmethoxycinnamate

iopanoic acid

methoxychlor


Input: These genes are potential biomarkers for detecting deiodinase deficiency and predicting their effects on thyroid hormone production.


Input: Treatment of pretibial myxedema with dexamethazone injected subcutaneously by mesotherapy needles.

dexamethazone


Input: Pretibial myxedema (PTM) is a rare extrathyroidal manifestation of Graves' disease that requires treatment when the clinical picture is markedly evident.


Input: In addition to topical treatment with steroid ointments, there have been previous reports of subcutaneous injections of steroids.

steroid

steroids


Input: This procedure may cause nodular degeneration of the skin due to fat atrophy when standard needles are used.


Input: In the present study, we have tried a novel modality of treatment of PTM by injecting a solution of dexamethasone in the subcutaneous tissue using needles employed for mesotherapy.

dexamethasone


Input: These needles are <= 4 mm long and deliver the medication within the dermis or the first layer of the subcutaneous fat.


Input: We have treated five patients, four with diffuse and one with elephanthiasic PTM.


Input: We utilized multiple injections of a solution of dexamethasone, lidocaine, and saline in the PTM plaque and in the pretibial area, both in the PTM plaque and in the area surrounding the lesions, once a week for three consecutive weeks.

dexamethasone

lidocaine


Input: Two patients with a more severe form of PTM underwent another two cycles four to six weeks after initial treatment.


Input: Patients were studied before and after treatment by clinical assessment and ultrasound of the pretibial skin.


Input: The treatment was well-tolerated, with only moderate pain upon injection of the solution.


Input: One month after treatment, all patients showed improvement of PTM at clinical assessment and a reduction of the thickness of the lesions at ultrasound of ~ 15%, involving mostly the dermis.


Input: Moreover, all patients reported amelioration of the leg appearance.


Input: The present study, although preliminary, shows that intralesion steroid injection with mesotherapy needles in PTM is effective and well tolerated, and does not cause undesired long-term modifications of the skin.

steroid


Input: More studies are warranted to standardize such treatment in larger groups of patients.


Input: Predicting temperature-dependent solid vapor pressures of explosives and related compounds using a quantum mechanical continuum solvation model.


Input: Temperature-dependent vapor pressures of solid explosives and their byproducts are calculated to an accuracy of 0. 32 log units using a modified form of the conductor-like screening model for real solvents (COSMO-RS).


Input: Accurate predictions for solids within COSMO-RS require correction for the free energy of fusion as well as other effects such as van der Waals interactions.


Input: Limited experimental data on explosives is available to determine these corrections, and thus we have extended the COSMO-RS model by introducing a quantitative structure-property relationship to estimate a lumped correction factor using only information from standard quantum chemistry calculations.


Input: This modification improves the COSMO-RS estimate of ambient vapor pressure by more than 1 order of magnitude for a range of nitrogen-rich explosives and their derivatives, bringing the theoretical predictions to within typical experimental error bars for vapor pressure measurements.

nitrogen


Input: The estimated temperature dependence of these vapor pressures also agrees well with available experimental data, which is particularly important for estimating environmental transport and gas evolution for buried explosives or environmentally contaminated locations.


Input: This technique is then used to predict vapor pressures for a number of explosives and degradation products for which experimental data is not readily available.


Input: Inductive tuning of Fano-resonant metasurfaces using plasmonic response of graphene in the mid-infrared.

graphene


Input: Graphene is widely known for its anomalously strong broadband optical absorptivity of 2. 3% that enables seeing its single-atom layer with the naked eye.

Graphene


Input: However, in the mid-infrared part of the spectrum graphene represents a quintessential lossless zero-volume plasmonic material.

graphene


Input: We experimentally demonstrate that, when integrated with Fano-resonant plasmonic metasurfaces, single-layer graphene (SLG) can be used to tune their mid-infrared optical response.

graphene


Input: SLG' s plasmonic response is shown to induce large blue shifts of the metasurface' s resonance without reducing its spectral sharpness.


Input: This effect is explained by a generalized perturbation theory of SLG-metamaterial interaction that accounts for two unique properties of the SLG that set it apart from all other plasmonic materials: its anisotropic response and zero volume.


Input: These results pave the way to using gated SLG as a platform for dynamical spectral tuning of infrared metamaterials and metasurfaces.


Input: SiO2 @Au core-shell nanospheres self-assemble to form colloidal crystals that can be sintered and surface modified to produce pH-controlled membranes.

Au


Input: We prepared colloidal crystals by self-assembly of gold-coated silica nanospheres, and free-standing nanoporous membranes by sintering these colloidal crystals.

silica


Input: We modified the nanopore surface with ionizable functional groups, by forming a monolayer of L-cysteine or by surface-initiated polymerization of methacrylic acid.

L-cysteine

methacrylic acid


Input: Diffusion experiments for the cationic dye Rhodamine B through L-cysteine-modified membranes showed a decrease in flux upon addition of an acid due to the nanopore surface becoming positively charged.

Rhodamine B

L-cysteine


Input: Diffusion experiments for the neutral dye, ferrocenecarboxaldehyde, through the PMAA-modified membranes showed a 13-fold increase in flux upon addition of an acid resulting from the protonated polymer collapsing onto the nanopore surface leading to larger pore size.

ferrocenecarboxaldehyde

PMAA


Input: Our results demonstrate that SiO2 @Au core-shell nanospheres can self-assemble into colloidal crystals and that transport through the corresponding surface-modified Au-coated colloidal membranes can be controlled by pH.

Au

Au


Input: Mexican antidiabetic herbs: valuable sources of inhibitors of alpha-glucosidases.


Input: Type II-diabetes mellitus (TII-DM) has been regarded as one of the most important public health problems in all nations in the 21st century.


Input: Although allopathic therapies remain the most important for the initial management of TII-DM, herbal remedies have gained wide acceptance for treating this condition.


Input: These alternative therapies are particularly valued in countries such as Mexico, rich in medicinal plants strongly attached to the cultural values of the population.


Input: Medicinal plants are prized sources of alpha-glucosidase inhibitors, which delay the liberation of glucose from complex carbohydrates, retarding glucose absorption, and thus controlling the characteristic hyperglycemia of TII-DM.

glucose

carbohydrates

glucose


Input: Among the plant species used for treating diabetes in Mexico only 38 have been analyzed for their inhibitory activity of alpha-glucosidases.


Input: Most of these studies, reviewed in the present work, have focused on the evaluation of different types of extracts on the activity of alpha-glucosidases from diverse sources.


Input: Four species have been thoroughly analyzed in order to discover novel alpha-glucosidase inhibitors, namely, Hintonia latiflora and Hintonia standleyana (Rubiaceae), Ligusticum porteri (Apiaceae), and Brickellia cavanillesii (Asteraceae).


Input: Their ethnomedical uses, pharmacological and toxicological studies, chemical composition, and antihyperglycemic principles with alpha-glucosidase inhibitory activity are summarized.


Input: Lessons in microcapsule assembly from imaging delivery of a bioluminescent enzyme.


Input: Layer-by-layer assembled microcapsules have potential applications as delivery and biosensing systems, which make them attractive tools for use in various aspects of nanomedicine.


Input: We examined the effect of microcapsule location on activity of the bioluminescent enzyme luciferase in both intact capsules and following cell uptake.


Input: In intact capsules, the rate of reaction of luciferase was greatest for luciferase in the outer layer and least in the core.


Input: Following cell uptake, luciferase in the outer layer was rapidly reactive, and a similar rate of reaction and activity was observed for luciferase placed in capsule interior (core).


Input: By contrast, there was minimal activity detected when microcapsules with luciferase sandwiched between polyelectrolytes in a middle layer were delivered to cells.


Input: This study informs us of the availability of bioactive molecules located in different positions within microcapsules and will enable better microcapsule construction in line with the intended application, particularly delivery of functional proteins to cells.


Input: Magnetoelectric control of superparamagnetism.


Input: Here we demonstrate electric-field induced magnetic anisotropy in a multiferroic composite containing nickel nanocrystals strain coupled to a piezoelectric substrate.

nickel


Input: This system can be switched between a superparamagnetic state and a single-domain ferromagnetic state at room temperature.


Input: The nanocrystals show a shift in the blocking temperature of 40 K upon electric poling.


Input: We believe this is the first example of a system where an electric field can be used to switch on and off a permanent magnetic moment.


Input: Daily physical activity assessment with accelerometers: new insights and validation studies.


Input: The field of application of accelerometry is diverse and ever expanding.


Input: Because by definition all physical activities lead to energy expenditure, the doubly labelled water (DLW) method as gold standard to assess total energy expenditure over longer periods of time is the method of choice to validate accelerometers in their ability to assess daily physical activities.


Input: The aim of this paper was to provide a systematic overview of all recent (2007-2011) accelerometer validation studies using DLW as the reference.


Input: The PubMed Central database was searched using the following keywords: doubly or double labelled or labeled water in combination with accelerometer, accelerometry, motion sensor, or activity monitor.


Input: Limits were set to include articles from 2007 to 2011, as earlier publications were covered in a previous review.


Input: In total, 38 articles were identified, of which 25 were selected to contain sufficient new data.


Input: Eighteen different accelerometers were validated.


Input: There was a large variability in accelerometer output and their validity to assess daily physical activity.


Input: Activity type recognition has great potential to improve the assessment of physical activity-related health outcomes.


Input: So far, there is little evidence that adding other physiological measures such as heart rate significantly improves the estimation of energy expenditure.


Input: Increased PD-1 on CD4 (+) CD28 (-) T cell and soluble PD-1 ligand-1 in patients with T2DM: Association with atherosclerotic macrovascular diseases.


Input: OBJECTIVE: To study the role of the programmed death-1 (PD-1)/programmed death-1 ligand 1 (PD-L1) coinhibitory pathway in regulating CD4 (+) CD28 (-) T cells, and to explore the association of soluble PD-L1 (sPD-L1) in the development of T2DM with atherosclerotic macrovascular diseases.


Input: METHODS: The percentage of CD4 (+) CD28 (-) T lymphocyte subsets from peripheral blood mononuclear cells (PBMCs) and the expression of PD-1/PD-L1 on lymphocytes were analyzed by immunostaining and flow cytometry, respectively.


Input: The serum levels of sPD-L1 and IFN-gamma were determined by ELISA system.


Input: T cell proliferation was determined by cocultivation and WST-8 incorporation.


Input: RESULTS: In 125 T2DM patients and 48 healthy donors, CD4 (+) CD28 (-) T cells from patients with T2DM expressed higher PD-1 than that of the cells from healthy individuals, and the proliferation response of CD4 (+) CD28 (-) T cells could be enhanced by advanced glycation end products (AGEs).


Input: The levels of sPD-L1 in patients were also much higher than those of healthy donors, and the increase was displayed in an exacerbation-dependent manner in the T2DM with atherosclerotic macrovascular patients especially with acute coronary syndrome (ACS).


Input: The production of sPD-L1 was significantly positively correlated with the level of IFN-gamma and could enhance T cell proliferation.


Input: CONCLUSION: Both the upregulation of PD-1 and the increase of sPD-L1 were closely associated with the severity of diabetic atherosclerotic macrovascular diseases.


Input: sPD-L1 may contribute to the continuous T cell activation and development of diabetic macrovascular diseases.


Input: Synthesis and biological evaluation of guanidino analogues of roscovitine.

guanidino

roscovitine


Input: A series of 2, 9-substituted 6-guanidinopurines, structurally related to the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine, has been synthesized and characterized.

2, 9-substituted 6-guanidinopurines

olomoucine

roscovitine


Input: A new copper-catalyzed method for the synthesis of 2-substituted 6-guanidino-9-isopropylpurines under mild reaction conditions has been developed.

copper

2-substituted 6-guanidino-9-isopropylpurines


Input: All prepared compounds were screened for their CDK1 and CDK2 inhibitory activities, cytotoxicity and antiproliferative effects in the breast cancer-derived cell line MCF7.


Input: The most active derivative 16g possessed an identical side chain in the C2 position to roscovitine; this compound displayed approximately five fold higher inhibitory activity towards CDK2/cyclin E and more than ten fold increase in cytotoxicity in MCF7 cells.

roscovitine


Input: Interestingly and in contrast to previously described findings, (S)-6-guanidinopurine derivatives were generally more active than their (R)-counterparts.


Input: Kinase selectivity profiling of (R)-and (S)-enantiomers 16e and 16g, respectively, revealed that introduction of a guanidino group at the C6 position of the purine moiety decreased selectivity towards protein kinases compared to roscovitine.

guanidino

purine

roscovitine


Input: Nevertheless, increased inhibitory activity and decreased selectivity offer a good starting point for further development of new protein kinase inhibitors.


Input: Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

Agmatine

ethanol

imidazoline


Input: The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents.

agmatine

ethanol

imidazoline


Input: Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1. 25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively.

agmatine

ethanol


Input: Agmatine inhibited the acquisition but not the expression of ethanol CPP.

Agmatine

ethanol


Input: Furthermore, both the I (1) receptor antagonist, efaroxan (9 mg/kg) and the I (2) receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition.

efaroxan

agmatine

ethanol


Input: In contrast, the I (2) receptor agonist, 2-BFI (5 mg/kg) and I (1) receptor agonist, moxonidine (0. 4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP.

moxonidine

agmatine

ethanol


Input: Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity.

Agmatine

imidazoline


Input: Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I (1) or I (2)) receptors.

agmatine

ethanol

imidazoline


Input: In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

agmatine

imidazoline

ethanol


Input: The critical effect of polarization on the dynamical structure of guanine quadruplex DNA.

guanine


Input: Guanine quadruplex DNA (G-DNA), found in eukaryotic telomeres and recently in non-telomeric genomic DNA, plays important biological roles and their structures are being explored as potential targets for therapeutic intervention.

Guanine


Input: Since the quadruplex structure of G-DNA is stabilized by cations, electrostatic interaction is expected to play important roles in the dynamical structure of G-DNA.


Input: In current work, MD simulation was carried out to study the dynamical structure of a special G-DNA (with sequence d (G (4) T (4) G (4))) complexed with five K (+) ions.

K (+)


Input: In order to properly include polarization in MD simulation, a new set of polarized nucleic acid specific charge based on fragment quantum chemistry calculation was developed for G-DNA.


Input: Our study showed that polarization of the nucleobases by K (+) enhanced electrostatic attraction between the base and ions.

nucleobases

K (+)


Input: This increased attractive interaction is critical to stabilizing the stem-loop junction ions in G-DNA.


Input: Without this polarization effect, as in MD simulation using a standard (nonpolarizable) force field, the top and bottom cations escaped into the solvent within just a few nanoseconds.


Input: Furthermore, an incorrect bifurcated bonding geometry of G-DNA, found in previous MD simulation study under a standard force field but not observed in experiments, disappeared in the present stimulation using the new polarized force field.


Input: The current study bridged an important gap between the simulation study and experimental observation on the dynamical structure of G-DNA.


Input: Chemically-synthesised, atomically-precise gold clusters deposited and activated on titania.

titania


Input: Synchrotron XPS was used to investigate a series of chemically-synthesised, atomically-precise gold clusters Au (n) (PPh (3)) (y) (n = 8, 9, 11 and 101, with y depending on cluster size) immobilized on titania nanoparticles.

Au (n) (PPh (3)) (y)

titania


Input: The gold clusters were washed with toluene at 100 degrees C or calcined at 200 degrees C to remove the organic ligand.

toluene


Input: From the position of the Au 4f (7/2) peak it is concluded that cluster size is not altered through the deposition.

Au


Input: From the analysis of the phosphorous spectra, it can be concluded that the applied heat treatment removes the organic ligands.

phosphorous


Input: Washing and calcination leads to partial oxidation and partial agglomeration of the clusters.


Input: Oxidation of the clusters is most likely due to the interaction of the cluster core with the oxygen of the titania surface after removal of ligands.

oxygen

titania


Input: The position of the Au 4f (7/2) peak indicates that the size of the agglomerated clusters is still smaller than that of Au (101).

Au

Au (101)


Input: Population pharmacokinetic/pharmacodynamic modeling to assist dosing schedule selection for dovitinib.

dovitinib


Input: Dovitinib is an oral multitargeted kinase inhibitor with potent activity against receptors for vascular endothelial growth factor, platelet-derived growth factor, and basic fibroblast growth factor.

Dovitinib


Input: Initial phase 1 to 2 studies of dovitinib using a continuous daily dosing schedule has shown that dovitinib exhibits a prolonged and overproportional increase in dose and exposure relationship above 400 mg/d.

dovitinib

dovitinib


Input: To address this, intermittent dosing schedules were explored using a model-based approach.


Input: A semi-mechanistic population pharmcokinetic/pharmacodynamic (PD) model was developed from 4 dovitinib phase 1 studies with daily dosing schedules.

dovitinib


Input: Autoinduction of cytochrome P450 1A (CYP1A) responsible for dovitinib metabolism was described using an indirect response model.

dovitinib


Input: Simulation of dovitinib plasma concentration profiles following 4 intermittent dosing schedules suggested that intermittent dosing could prevent prolonged drug accumulation.

dovitinib


Input: Based on the simulated plasma profiles, PD response, and patient compliance, a 5-days-on/2-days-off intermittent dosing schedule was selected for a phase 1 to 2 clinical study.


Input: The observed dovitinib plasma concentrations in this study confirmed the model predictions.

dovitinib


Input: Furthermore, dovitinib was well tolerated, and antitumor activity was observed as well in this new study.

dovitinib


Input: The 5-days-on/2-days-off dosing schedule is currently used in a dovitinib registration trial and other clinical trials.

dovitinib


Input: Effects of amlodipine on the oral bioavailability of cephalexin and cefuroxime axetil in healthy volunteers.

amlodipine

cephalexin

cefuroxime axetil


Input: In this study, the authors compared the effects of amlodipine (AML) on the bioavailability of cephalexin (LEX) and cefuroxime axetil (CXM).

amlodipine

AML

cephalexin

LEX

cefuroxime axetil

CXM


Input: Twenty-four healthy men were randomized to 4 treatments according to a crossover design with a 14-day washout.


Input: After an overnight fast, they were administered orally LEX 500 mg alone, LEX 500 mg 2 hours after oral administration of AML 5 mg, CXM 500 mg alone, and CXM 500 mg 2 hours after oral administration of AML 5 mg.

LEX

LEX

AML

CXM

CXM

AML


Input: All participants completed the whole study without side effects being observed.


Input: Pharmacokinetic data were analyzed by noncompartmental modeling with WinNonlin software.


Input: The geometric mean (GM) ratios were 1. 38 (90% confidence interval [CI], 1. 32-1. 45) for the area under the concentration-time curve (AUC) for LEX and 1. 27 (1. 18-1. 36) for the maximum concentration of drug in serum (C (max)) for LEX followed by AML versus alone.

LEX

LEX

AML


Input: In contrast, no significant differences were found in the pharmacokinetic parameters of CXM between treatments (P <. 05).

CXM


Input: They authors conclude that AML possesses an enhancement effect in beta-lactam antibiotic bioavailability (in this case, LEX), and this interaction may be specific to the peptidomimetic beta-lactam antibiotics.

AML

beta-lactam

LEX

beta-lactam


Input: Correlation between carbapenem consumption and antimicrobial resistance rates of Acinetobacter baumannii in a university-affiliated hospital in China.

carbapenem


Input: To investigate the correlation between carbapenem consumption and rates of antimicrobial resistance in Acinetobacter baumannii, carbapenem consumption was expressed as defined daily dose based on the World Health Organization (WHO) anatomical therapeutic chemical classification index.

carbapenem

carbapenem


Input: Clinical isolates from 2001-2009 were collected and analyzed using WHONET 5. 4 software.


Input: Results show that the consumption of imipenem/cilastatin, meropenem, and total carbapenem is significantly correlated with imipenem resistance in A baumannii (r = 0. 818, P =. 007; r = 0. 817, P =. 007; r = 0. 827, P =. 006).

imipenem

cilastatin

meropenem

carbapenem

imipenem


Input: Furthermore, total carbapenem consumption is significantly correlated with meropenem resistance in A baumannii (r = 0. 900, P =. 037).

carbapenem

meropenem


Input: In addition, consumption of imipenem/cilastatin, meropenem, and total carbapenem is associated with A baumannii resistance to piperacillin-tazobactam, ceftazidime, cefepime, amikacin, and levofloxacin.

imipenem

cilastatin

meropenem

carbapenem

piperacillin

tazobactam

ceftazidime

cefepime

amikacin

levofloxacin


Input: These drugs are mainly beta-lactams, aminoglycosides, and fluoroquinolones.

beta-lactams

aminoglycosides

fluoroquinolones


Input: The imipenem and meropenem resistance rates are significantly correlated with resistance rates to numerous antimicrobial drugs (eg, beta-lactams, aminoglycosides, and fluoroquinolones) in A baumannii.

imipenem

meropenem

beta-lactams

aminoglycosides

fluoroquinolones


Input: Therefore, increased consumption of carbapenem may contribute to the development of resistance in A baumannii to imipenem, meropenem, and other antimicrobial drugs.

carbapenem

imipenem

meropenem


Input: Cross-resistance possibly occurs among imipenem/cilastatin and meropenem, as well as with beta-lactams, aminoglycosides, and fluoroquinolones.

imipenem

cilastatin

meropenem

beta-lactams

aminoglycosides

fluoroquinolones


Input: Environmental fate of three novel brominated flame retardants in aquatic mesocosms.


Input: Currently, little is known about the environmental fate and persistence of novel brominated flame retardants (NBFRs).


Input: The recent detection of NBFRs in sediment cores and air samples provides insight into their persistence and potential for transport.


Input: Limited numbers of laboratory studies have examined the fate and behavior of these compounds, but field-based fate studies have been especially lacking.


Input: The authors conducted an aquatic mesocosm experiment to assess the behavior of three NBFRs: bis (tribromophenoxy) ethane (BTBPE), tetrabromobisphenol A bis (2, 3-dibromopropyl ether; TBBPA-DBPE), and Firemaster BZ-54, a commercial mixture containing bis (2-ethylhexyl) tetrabromophthalate (BEHTBP) and 2-ethylhexyl-2, 3, 4, 5-tetrabromobenzoate (EHTeBB) in a ratio of 1: 4.

bis (tribromophenoxy) ethane

BTBPE

tetrabromobisphenol A bis (2, 3-dibromopropyl ether

TBBPA

DBPE

Firemaster BZ-54

bis (2-ethylhexyl) tetrabromophthalate

BEHTBP

2-ethylhexyl-2, 3, 4, 5-tetrabromobenzoate

EHTeBB


Input: Analysis by gas chromatography-mass spectrometry, operated in the electron capture negative ionization mode, revealed partitioning between the particulate and sediment phases, with BTBPE, TBBPA-DBPE, and BEHTBP identified as being environmentally persistent in both the particulate and the sediment compartments.

BTBPE

TBBPA

DBPE

BEHTBP


Input: The median dissipation times (DT50) differed in each compartment, with more rapid disappearance in the particulate (9-30 d) compared with the sediment compartment (> 100 d) for each compound.


Input: The degradation products were more concentrated in the particulate compartment and corresponded to known photodegradation products.


Input: The ratio of EHTeBB to BEHTBP differed in the mesocosm compartments compared with the technical product used for treatment, indicating increased degradation of EHTeBB relative to BETHBP.

EHTeBB

BEHTBP

EHTeBB

BETHBP


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1060-1068.


Input: (c) 2013 SETAC.


Input: Acute exposure to DE-71 causes alterations in visual behavior in zebrafish larvae.


Input: Polybrominated diphenyl ethers (PBDEs) cause neurobehavioral toxicity, but their effects on visual behavior remain unknown.

Polybrominated diphenyl ethers

PBDEs


Input: In the present study, the impact of PBDEs on visual behavior was examined using optokinetic responses and phototaxis in zebrafish larvae.

PBDEs


Input: Zebrafish embryos were exposed to pentabrominated diphenyl ethers mixture (DE-71) at concentrations of 0, 0. 32, 3. 58, and 31. 0 micro g/L until 15 d postfertilization.

pentabrominated diphenyl ethers


Input: The authors then assessed photoreceptor opsin expression, retinal histology, and visual behavior of the larvae.


Input: The results showed that the transcriptions of the opsin genes, zfrho and zfgr1, were significantly upregulated.


Input: Western blotting further demonstrated a significant increase in rhodopsin protein expression after exposure of the larvae to DE-71.


Input: Histological examination revealed the following morphological alterations in the retina: increased area of inner nuclear layer, decreased area of inner plexiform layer, and decreased density of ganglion cells.


Input: Tests of optokinetic and phototactic behavior showed hyperactive responses on exposure to DE-71, including increased saccadic eye movements and phototactic response.


Input: The present study is the first to demonstrate that the acute exposure of zebrafish larvae to DE-71 causes biochemical and structural changes in the eye that lead to behavioral alterations.


Input: Analysis of these visual behavioral paradigms may be useful in predicting the adverse effects of toxicants on visual function in fish.


Input: Environ Toxicol Chem 2013; 32: 1370-1375.


Input: (c) 2013 SETAC.


Input: Rash associated with dabigatran etexilate.

dabigatran etexilate


Input: Patients experiencing atrial fibrillation are at an increased risk for thromboembolic events.


Input: Therefore, anticoagulation therapy is imperative to prevent thrombus formation and stroke.


Input: Dabigatran etexilate was approved by the Food and Drug Administration in 2010 as anticoagulant prophylaxis for patients with nonvalvular atrial fibrillation.

Dabigatran etexilate


Input: The frequency of dermatologic reactions to dabigatran etexilate is estimated in the product labeling to be less than 0. 1%.

dabigatran etexilate


Input: To date, five cases of dabigatran etexilate-associated rash have reported, including three published cases.

dabigatran etexilate


Input: We describe the sixth reported case of dabigatran etexilate-associated rash, in a 59-year-old man with a history of atrial fibrillation who received dabigatran etexilate 150 mg twice/day for atrial flutter before cardioversion.

dabigatran etexilate

dabigatran etexilate


Input: The patient had taken dabigatran etexilate for 5 days before the rash was noted on hospital admission.

dabigatran etexilate


Input: He had no known previous drug allergies, and his platelet count, serum creatinine concentration, and hepatic function were normal.

creatinine


Input: The rash resolved 7 days after the discontinuation of dabigatran etexilate, and the patient was stabilized on warfarin therapy.

dabigatran etexilate

warfarin


Input: Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 5) between the patient' s development of the rash and dabigatran etexilate therapy.

dabigatran etexilate


Input: Clinicians should be aware of this adverse effect of dabigatran etexilate and monitor for dermatologic reactions during follow-up visits.

dabigatran etexilate


Input: Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein.


Input: Human relaxin-2 (hereafter simply defined as " relaxin ") is a 6-kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes.


Input: This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling.


Input: It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4).


Input: Research looks toward the in-depth examination and complete understanding of relaxin in its various pleiotropic actions.


Input: The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect.


Input: Relaxin is already being considered as a promising drug, especially in acute heart failure.


Input: A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.


Input: Quantum Dot-Based Thermal Spectroscopy and Imaging of Optically Trapped Microspheres and Single Cells.


Input: Laser-induced thermal effects in optically trapped microspheres and single cells are investigated by quantum dot luminescence thermometry.


Input: Thermal spectroscopy has revealed a non-localized temperature distribution around the trap that extends over tens of micrometers, in agreement with previous theoretical models besides identifying water absorption as the most important heating source.


Input: The experimental results of thermal loading at a variety of wavelengths reveal that an optimum trapping wavelength exists for biological applications close to 820 nm.


Input: This is corroborated by a simultaneous analysis of the spectral dependence of cellular heating and damage in human lymphocytes during optical trapping.


Input: This quantum dot luminescence thermometry demonstrates that optical trapping with 820 nm laser radiation produces minimum intracellular heating, well below the cytotoxic level (43 degrees C), thus, avoiding cell damage.


Input: A self-organized anisotropic liquid-crystal plasmonic metamaterial.


Input: A composite material that leads to self organization of mesogen-coated gold nanospheres is synthesized and shows enhanced anisotropic optical properties due to synergistic effects of the mesogens intrinsic birefringence and its ability to drive the self-assembly process into highly anisotropic architectures with densely packed nanospheres.


Input: Such nanoengineered matter sustains a response beyond that achievable by its individual constituents, i. e., a metamaterial.


Input: Nonribosomal assembly of natural lipocyclocarbamate lipoprotein-associated phospholipase inhibitors.


Input: EXPANDING OUR KNOWLEDGE: Natural lipocyclocarbamate natural products have provided the inspiration for the first-in-class synthetic phospholipase inhibitor darapladib, currently in phase III clinical trials for the treatment of atherosclerosis.

darapladib


Input: Here, we discuss their biosynthesis by a nonribosomal peptide synthetase.


Input: Engineering new protein-protein interactions on the beta-propeller fold by yeast cell surface display.


Input: REINVENTING THE WHEEL: The beta-propeller domain folds like a wheel to provide key protein-protein interactions in the cell.


Input: Here we used high-throughput yeast sorting to " invent " beta-propellers of new binding specificities with cellular targets.


Input: Joining Copper Oxide Nanotube Arrays Driven by the Nanoscale Kirkendall effect.

Copper Oxide


Input: Various annealing conditions (environment, temperature, and duration) are applied to study the nanoscale Kirkendall effect of copper (Cu) nanowire (NW) arrays on a Si substrate.

copper

Cu

Si


Input: The results show that an appropriate amount of oxygen supply is crucial for uniform transformation from Cu NWs (average diameter ~ 50 nm) into Cu oxide nanotube arrays.

oxygen

Cu

Cu oxide


Input: An annealing duration of 30 min at 200 degrees C in a low vacuum environment reveals that the voids are not uniformly distributed at the Cu/Cu oxide interface.

Cu

Cu oxide


Input: This suggests that void growth is due to surface diffusion of Cu along void surfaces.

Cu


Input: Annealing above 200 degrees C for 60 min resulted in complete transformation from Cu NWs into Cu oxide nanotubes.

Cu

Cu oxide


Input: X-ray photoelectron spectroscopy characterization indicates that the Cu oxides formed at 200 degrees C and 300 degrees C are Cu (2) O and CuO, respectively.

Cu oxides

Cu (2) O

CuO


Input: It is demonstrated that the transformation from Cu NW arrays into Cu oxide nanotube arrays can be combined with the joining of stacked Si chips in a single-process step with reasonable joint shear strength.

Cu

Cu oxide

Si


Input: Transmission electron microscopy-electron energy loss spectroscopy elemental mapping analysis reveals that the joint interface is Cu oxide.

Cu oxide


Input: The outward diffusion of Cu driven by the nanoscale Kirkendall effect is believed to enhance the joining process.

Cu


Input: By controlling the environment, temperature, and duration, joined Cu (2) O or CuO nanotube stacked chips can be achieved, which serve as a platform for the further development of nanostructured, stacked devices.

Cu (2) O

CuO


Input: Protein-Carbohydrate Complex Reveals Circulating Metastatic Cells in a Microfluidic Assay.

Carbohydrate


Input: Advances in carbohydrate sequencing technologies reveal the tremendous complexity of the glycome and the role that glycomics might have to bring insight into the biological functions.

carbohydrate


Input: Carbohydrate-protein interactions, in particular, are known to be crucial to most mammalian physiological processes as mediators of cell adhesion and metastasis, signal transducers, and organizers of protein interactions.

Carbohydrate


Input: An assay is developed here to mimic the multivalency of biological complexes that selectively and sensitively detect carbohydrate-protein interactions.

carbohydrate


Input: The binding of beta-galactosides and galectin-3-a protein that is correlated to the progress of tumor and metastasis-is examined.

beta-galactosides


Input: The efficiency of the assay is related to the expression of the receptor while anchoring to the interaction' s strength.


Input: Comparative binding experiments reveal molecular binding preferences.


Input: This study establishes that the assay is robust to isolate metastatic cells from colon affected patients and paves the way to personalized medicine.


Input: Modulation of photophysics and pKa shift of the anti-cancer drug camptothecin in the nanocavities of supramolecular hosts.

camptothecin


Input: This article reports the pK (a) shift of an anti-cancer drug, 20 (S)-camptothecin (CPT), upon encapsulation into the nanocavity of a cucurbit [7] uril (CB7) macrocycle.

20 (S)-camptothecin

CPT

cucurbit [7] uril


Input: Steady-state, time-resolved fluorescence and electrospray ionisation mass spectrometry (ESI-MS) studies provide evidence for the formation of both 1: 1 and 2: 1 (CB7. CPT) stoichiometries.

CPT


Input: Astonishingly, we have found that protonation of CPT takes place at a higher concentration of macrocycle (>= 50 mu M) when the 2: 1 stoichiometric complex develops.

CPT


Input: However, we did not find any proof for protonation of CPT when it is encased by a beta-cyclodextrin cavity, which has a cavity size almost the same as that of CB7.

CPT

beta-cyclodextrin


Input: Hence, we conclude that electron-rich carbonyl portals of CB7 have an important role in protonation of the drug in the 2: 1 inclusion complex.

carbonyl


Input: Docking and semi-empirical quantum chemical calculations have been employed to gain an insight into the molecular picture of orientation of CPT in the inclusion complexes.

CPT


Input: It is clearly seen from the optimised structure of the 2: 1 (CB7. CPT) inclusion complex that the quinoline nitrogen of CPT does not reside within either of the CB7 cavities, rather it is almost sandwiched between two CB7 rings, and therefore, it experiences huge electron density exerted by both carbonyl portals of the macrocycles.

CPT

quinoline nitrogen

CPT

carbonyl


Input: As a result, the pK (a) of CPT shifts from 1. 2 to 6. 2.

CPT


Input: Finally, controlled release of the drug has been achieved through the introduction of NaCl, which is rich in cells, as an external stimulus.

NaCl


Input: We hope this recognition-mediated binding and release mechanism can be useful for activation of the drug and controlled release of the drug in therapeutic uses.


Input: Species difference in the mechanism of nonlinear pharmacokinetics of e2074, a novel sodium channel inhibitor, in rats, dogs, and monkeys.

sodium


Input: New chemical entities often exhibit nonlinear pharmacokinetics (PK) profiles in experimental animals.


Input: However, the number of studies that have focused on species differences in nonlinear PK is very limited; thus, the aim of this study was to clarify the mechanism of the nonlinear PK of E2074 (2-[(2R)-2-fluoro-3-{(3r)-[(3-fluorobenzyl) oxy]-8-azabicyclo [3. 2. 1] oct-8-yl} propyl]-4, 5-dimethyl-2, 4-dihydro-3H-1, 2, 4-triazol-3-one), a novel sodium channel inhibitor, in rats, dogs, and monkeys.

2-[(2R)-2-fluoro-3-{(3r)-[(3-fluorobenzyl) oxy]-8-azabicyclo [3. 2. 1] oct-8-yl} propyl]-4, 5-dimethyl-2, 4-dihydro-3H-1, 2, 4-triazol-3-one

sodium


Input: Nonlinear PK profiles with more than dose-proportional increases of Cmax and area under the plasma concentration curve were observed in all species after oral administration.


Input: The Michaelis-Menten constant (Km) values of hepatic microsomal metabolism were 7. 23 and 0. 41 mu M in rats and dogs in vitro, respectively, which were lower than the unbound maximum plasma concentrations after oral administration in vivo, indicating that the nonlinear PK in rats and dogs was attributable to the saturation of hepatic metabolism.


Input: However, we do not believe that the saturation of hepatic metabolism was the mechanism of nonlinearity in monkeys because of the high Km value (42. 44 mu M) observed in liver microsomes.


Input: Intestinal metabolism was observed in monkey intestinal microsomes but not in rats and dogs, and the nonlinear PK in monkeys was diminished by inhibition of intestinal metabolism with a concomitant oral dose of ketoconazole.

ketoconazole


Input: These results suggest that saturation of the intestinal metabolism is the potential mechanism of nonlinearity in monkeys.


Input: P-glycoprotein was not involved in the nonlinear PK profiles in any species.


Input: In conclusion, the mechanism of the nonlinear PK of E2074 is species dependent, with the saturation of hepatic metabolism in rats and dogs and that of intestinal metabolism in monkeys being the primary cause.


Input: Interaction of silymarin flavonolignans with organic anion-transporting polypeptides.

flavonolignans


Input: Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug absorption and elimination, including the intestine and liver.


Input: Silymarin is a popular herbal supplement often used by patients with chronic liver disease; higher oral doses than those customarily used (140 mg three times/day) are being evaluated clinically.


Input: The present study examined the effect of silymarin flavonolignans on OATP1B1-, OATP1B3-, and OATP2B1-mediated transport in cell lines stably expressing these transporters and in human hepatocytes.

flavonolignans


Input: In overexpressing cell lines, OATP1B1-and OATP1B3-mediated estradiol-17 beta-glucuronide uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin flavonolignans investigated.

estradiol-17 beta-glucuronide

flavonolignans


Input: OATP1B1-, OATP1B3-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1. 3, 2. 2 and 0. 3 micro M, respectively), silybin A (IC50 values of 9. 7, 2. 7 and 4. 5 micro M, respectively), silybin B (IC50 values of 8. 5, 5. 0 and 0. 8 micro M, respectively), and silychristin (IC50 values of 9. 0, 36. 4, and 3. 6 micro M, respectively).

silybin A

silybin B

silychristin


Input: Furthermore, silymarin, silybin A, and silybin B (100 micro M) significantly inhibited OATP-mediated estradiol-17 beta-glucuronide and rosuvastatin uptake into human hepatocytes.

silybin A

silybin B

estradiol-17 beta-glucuronide

rosuvastatin


Input: Calculation of the maximal unbound portal vein concentrations/IC50 values indicated a low risk for silymarin-drug interactions in hepatic uptake with a customary silymarin dose.


Input: The extent of silymarin-drug interactions depends on OATP isoform specificity and concentrations of flavonolignans at the site of drug transport.

flavonolignans


Input: Higher than customary doses of silymarin, or formulations with improved bioavailability, may increase the risk of flavonolignan interactions with OATP substrates in patients.

flavonolignan


Input: Thiolates chemically induce redox activation of BTZ043 and related potent nitroaromatic anti-tuberculosis agents.

Thiolates

nitroaromatic


Input: The development of multidrug resistant (MDR) and extensively drug resistant (XDR) forms of tuberculosis (TB) has stimulated research efforts globally to expand the new drug pipeline.


Input: Nitroaromatic compounds, including 1, 3-benzothiazin-4-ones (BTZs) and related agents, are a promising new class for the treatment of TB.

Nitroaromatic

1, 3-benzothiazin-4-ones

BTZs


Input: Research has shown that the nitroso intermediates of BTZs that are generated in vivo cause suicide inhibition of decaprenylphosphoryl-beta-D-ribose 2' oxidase (DprE1), which is responsible for cell wall arabinogalactan biosynthesis.

nitroso

BTZs

decaprenylphosphoryl-beta-D-ribose


Input: We have designed and synthesized novel anti-TB agents inspired from BTZs and other nitroaromatic compounds.

BTZs

nitroaromatic


Input: Computational studies indicated that the unsubstituted aromatic carbons of BTZ043 and related nitroaromatic compounds are the most electron-deficient and might be prone to nucleophilic attack.

carbons

nitroaromatic


Input: Our chemical studies on BTZ043 and the additional nitroaromatic compounds synthesized by us and others confirmed the postulated reactivity.

nitroaromatic


Input: The results indicate that nucleophiles such as thiolates, cyanide, and hydride induce nonenzymatic reduction of the nitro groups present in these compounds to the corresponding nitroso intermediates by addition at the unsubstituted electron-deficient aromatic carbon present in these compounds.

thiolates

cyanide

hydride

nitro

nitroso

carbon


Input: Furthermore, we demonstrate here that these compounds are good candidates for the classical von Richter reaction.


Input: These chemical studies offer an alternate hypothesis for the mechanism of action of nitroaromatic anti-TB agents, in that the cysteine thiol (ate) or a hydride source at the active site of DprE1 may trigger the reduction of the nitro groups in a manner similar to the von Richter reaction to the nitroso intermediates, to initiate the inhibition of DprE1.

nitroaromatic

cysteine thiol (ate)

hydride

nitro

nitroso


Input: A low-overpotential potassium-oxygen battery based on potassium superoxide.

potassium

oxygen

potassium superoxide


Input: Li-O (2) battery is regarded as one of the most promising energy storage systems for future applications.

Li-O (2)


Input: However, its energy efficiency is greatly undermined by the large overpotentials of the discharge (formation of Li (2) O (2)) and charge (oxidation of Li (2) O (2)) reactions.

Li (2) O (2)

Li (2) O (2)


Input: The parasitic reactions of electrolyte and carbon electrode induced by the high charging potential cause the decay of capacity and limit the battery life.

carbon


Input: Here, a K-O (2) battery is report that uses K (+) ions to capture O (2) (-) to form the thermodynamically stable KO (2) product.

K-O (2)

K (+)

O (2) (-)

KO (2)


Input: This allows for the battery to operate through the one-electron redox process of O (2)/O (2) (-).

O (2)

O (2) (-)


Input: Our studies confirm the formation and removal of KO (2) in the battery cycle test.

KO (2)


Input: Furthermore, without the use of catalysts, the battery shows a low discharge/charge potential gap of less than 50 mV at a modest current density, which is the lowest one that has ever been reported in metal-oxygen batteries.

metal-oxygen


Input: A membrane vesicle-based assay to enable prediction of human biliary excretion.


Input: Abstract 1.


Input: Prediction of biliary excretion is a challenge due to the lack of in vitro assays.


Input: Our laboratory previously demonstrated a highly significant correlation between in vitro IC (50) values against mrp2 using rat canalicular liver plasma membrane vesicles and in vivo biliary excretion (Colombo et al., 2012).


Input: This study explores the possibility of predicting in vivo biliary excretion in human using membrane vesicles prepared from MDCKII cells transfected with human ABCC2.


Input: In vitro MRP2 activity was determined by measuring the ATP-dependent uptake of 5 (6)-carboxy-2', 7'-dichlorofluorescein (CDCF) in inside-out membrane vesicles isolated from MDCK-ABCC2 cells.

ATP

5 (6)-carboxy-2', 7'-dichlorofluorescein

CDCF


Input: CDCF uptake was time-and concentration-dependent (K (m) of 4. 0 +/- 1. 2 micro M and a V (max) of 7. 8 +/- 0. 9 pmol/mg/min) and inhibited by benzbromarone and MK-571 with IC (50) values of 1. 2 and 7. 6 micro M, respectively.

CDCF

benzbromarone


Input: A significant linear correlation (r (2) = 0. 790) between the in vitro IC (50) values from the described MRP2 assay and in vivo biliary excretion in humans was observed using 11 well-documented drugs covering low to high biliary excretions.


Input: This study demonstrates, for the first time, that inhibition of CDCF uptake in MDCKII-ABCC2 vesicles not only provides a screening assay to assess MRP2 drug-drug interaction potential, but is also predictive of human MRP2-mediated biliary excretion.

CDCF


Input: Effects of hydrogen bonding on internal conversion of GFP-like chromophores.

hydrogen


Input: II.


Input: The meta-amino systems.

meta-amino


Input: To rationalize the efficient quenching of the fluorescence and the Z --> E photoisomerization of m-ABDI, the meta-amino analogue of the green fluorescent protein (GFP) chromophore, in protic solvents, the femtosecond time-resolved fluorescence and transient infrared (TRIR) spectra of m-ABDI in CD3CN, CH3OH, and CD3OD are determined.

m-ABDI

meta-amino

m-ABDI


Input: For solutions in CD3CN, the fluorescence decay lifetime is ~ 7. 9 ns and IR absorption lines near 1513, 1531, 1557, and 1613 cm (-1) of m-ABDI in its electronically excited state were observed with a decay time > 5 ns.

m-ABDI


Input: For solutions in CH3OH, the fluorescence decay is double exponential with time constants of ~ 16 and 62 ps.


Input: In addition to IR absorption lines of m-ABDI in its electronically excited state with a decay time of ~ 16 ps, new features near 1513, 1532, 1554, and 1592 cm (-1) were observed to have a rise time of ~ 19 ps and a decay constant of ~ 58 ps, indicating formation of an intermediate.

m-ABDI


Input: The assignments for the IR spectra of the ground and excited states were assisted with DFT and TDDFT calculations, respectively.


Input: We conclude that the torsion of the exocyclic C = C bond (the tau torsion) is responsible for the nonradiative decay of electronically excited m-ABDI in CD3CN.

C = C

m-ABDI


Input: However, in CH3OH and CD3OD, the solute-solvent hydrogen bonding (SSHB) interactions diminish significantly the barrier of the tau torsion and induce a new pathway that competes successfully with the tau torsion, consistent with the efficient fluorescence quenching and the diminished yield for Z --> E photoisomerization.

hydrogen


Input: The new pathway is likely associated with excited-state proton transfer (ESPT) from the solvent to m-ABDI, particularly the carbonyl group, and generates an intermediate (ESPT *) that is weakly fluorescent.

m-ABDI

carbonyl


Input: Oxidation of tertiary amine-derivatized surfaces to control protein adhesion.

tertiary amine


Input: Selective oxidation of omega-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them.

omega-tertiary amine

thiol

tertiary amine N-oxides


Input: Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1H-7-azabenzotriazol-1-yl)-1, 1, 3, 3-tetramethyl hexafluorophosphate methanaminium uronium (HATU).

secondary and tertiary linker amides

amide

quartz

2-(1H-7-azabenzotriazol-1-yl)-1, 1, 3, 3-tetramethyl hexafluorophosphate methanaminium uronium

HATU


Input: Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM.

hydrogen peroxide

phosphate


Input: Tertiary amine-functionalized sensors adsorbed multilayers of aggregated lysozyme, whereas tertiary amine N-oxides and triethylene glycol-terminated monolayers are consistent with small protein aggregates.

Tertiary amine

tertiary amine N-oxides

triethylene glycol


Input: The surface containing a dimethylamine N-oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins.

dimethylamine N-oxide

ethyl secondary amide


Input: Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques.

tertiary amine


Input: Innate immune response and programmed cell death following carrier-mediated delivery of unmodified mRNA to respiratory cells.


Input: In this report we show that carrier-mediated delivery of mRNA may activate TLR3 signaling in respiratory cells.


Input: This activation of the innate immune system was accompanied with a massive production of type 1 interferons and other immunostimulating cytokines.


Input: The recognition of mRNA by the innate immune system was also associated with cell death, which proceeded in human respiratory cells via pyroptosis, a form of programmed cell death mediated by substantial overexpression of caspase-1.


Input: This indicated that the delivered mRNA is most likely also recognized by NOD-like receptors which regulate caspase-1 production.


Input: The viability of murine respiratory cells was less affected by mRNA transfection, which is in line with the lower transfection efficiency, lower innate immune response and the absence of a massive caspase-1 upregulation in these cells.


Input: Finally, we also demonstrated that the recognition of the delivered mRNA by the innate immune system had a negative effect on mRNA translation.


Input: Sexually dimorphic behavior after developmental exposure to characterize endocrine-mediated effects of different non-dioxin-like PCBs in rats.

dioxin

PCBs


Input: Many chemicals are known to exhibit endocrine activity and affect reproductive functions in vertebrates and invertebrates.


Input: Endocrine effects include influences on sexual differentiation of the brain during development and reproductive and non-reproductive behavior in adult offspring.


Input: We previously demonstrated that developmental exposure to a mixture of polychlorinated biphenyls (PCBs) which was reconstituted according to the congener pattern found in human breast milk caused feminization of sweet preference as a sexually dimorphic behavior in adult male rats, following decreases in aromatase activity in the brain of newborn male pups.

polychlorinated biphenyls

PCBs


Input: This result may be due to dioxin-like or non-dioxin-like (NDL) PCBs and their respective effects on steroid hormones.

dioxin

dioxin

PCBs

steroid


Input: The aim of the present experiments was to determine if exposure to highly purified NDL-PCBs (to remove Ah receptor active contaminants) also results in alteration of sweet preference.

PCBs


Input: Pregnant rats were orally exposed to PCB52 (6 dose groups, total dose of 0-3000mg/kg body weight) or PCB180 (6 dose groups, total dose of 0-1000mg/kg body weight).


Input: In a further experiment rat dams were treated with equimolar doses of PCB74 or PCB95 (total dose, 760 mu mol/kg body weight, corresponding to 229mg/kg or 248mg/kg body weight of PCB74 and PCB95, respectively).


Input: Adult male and female offspring were given a choice between a bottle of saccharin solution (0. 25%) and a bottle of tap water on five consecutive days.

saccharin


Input: Control females consumed approximately twice as much sweetened solution compared with control males, thus, demonstrating sexual dimorphism of this behavior.


Input: Only non-significant reduction of sweet preference was found at the top dose level in female offspring after exposure to PCB52.


Input: Female offspring exposed to PCB180 exhibited signs of supernormal behavior as illustrated by increased saccharin consumption at intermediate dose levels.

saccharin


Input: Decreased sweet preference was observed in females after developmental PCB74, whereas males were unaffected.


Input: Only PCB95 increased saccharin consumption in exposed males, leading to decreased sexual dimorphism of this behavior and behavioral feminization.

saccharin


Input: The results demonstrate that different NDL-PCBs exhibit differential effects on sexually dimorphic behavior and that feminization occurs after removal of Ah receptor active contaminants.

PCBs


Input: Comparison with data from the literature reveals little evidence for a relation to anti-androgenic activity of the studied NDL-PCBs.

PCBs


Input: Characterization of anti-crotalic antibodies.


Input: Crotalus durissus terrificus, C.


Input: d. collilineatus, C.


Input: d. cascavella and C.


Input: d. marajoensis are responsible minor but severe snake bites in Brazil.


Input: The venoms of these snakes share the presence of crotoxin, a neurotoxin comprising of two associated components, crotapotin and phospholipase A2 (PLA2).


Input: Treatment of the victims with specific antiserum is the unique effective therapeutic measure.


Input: The ability of anti-Crotalus antisera produced by the routine using crude venom to immunize horses or purified crotoxin and PLA2 as individual immunogens was compared.


Input: Antisera obtained from horses immunized with C. durissus terrificus crude venom were able to recognize and neutralize not only the toxins presents in C. durissus terrificus, but also the ones present in the venoms from C.


Input: d. collilineatus, C.


Input: d. cascavella and C.


Input: d. marajoensis.


Input: Antisera from horses immunized with individual crotoxin or PLA2, although in lesser titers, were also able of recognizing the toxins in all four Crotalus species and neutralize the lethality of the C.


Input: d. terrificus venom.


Input: Combined effects of organochlorine pesticides heptachlor and hexachlorobenzene on the promotion stage of hepatocarcinogenesis in rats.

organochlorine

heptachlor

hexachlorobenzene


Input: We aimed to investigate the combined effect of organochlorine pesticides heptachlor (HEP) and hexachlorobenzene (HCB) by using a medium-term rat liver bioassay.

organochlorine

heptachlor

HEP

hexachlorobenzene

HCB


Input: Male F344 rats were initially administered diethylnitrosamine (DEN, 200mg/kgi. p.); after a 2-week non-dosing period, they were given diets containing HEP (5 or 25ppm), HCB (70 or 350ppm), or their mixtures (5 and 70ppm or 25 and 350ppm) for 6weeks.

diethylnitrosamine

DEN

HEP

HCB


Input: All rats were subjected to partial hepatectomy at week 3 and killed at week 8.


Input: We observed additive or synergistic effects of HEP and HCB in groups treated with mixtures of these pesticides.

HEP

HCB


Input: Number and area of preneoplastic foci positive for glutathione S-transferase placental form (GST-P) were consistently higher in these groups than the sum of individual values in the groups treated with HEP or HCB alone.

glutathione S

HEP

HCB


Input: Consistent with these findings, HEP and HCB had additive or synergistic effects on cell proliferation induction within the preneoplastic foci and cytochrome P450 (CYP) 2B1 and 3A1 induction, which may lead to more efficient metabolic activation of HEP and HCB.

HEP

HCB

HEP

HCB


Input: On the basis of these findings, we conclude that HEP and HCB have additive and synergistic effects on the development of GST-P-positive foci and that higher risks are associated with a combination of residual organochlorine pesticides in foods than with individual residual organochlorine pesticides.

HEP

HCB

organochlorine

organochlorine


Input: Monitoring of arsenic levels in some ready-to-use anti-malaria herbal products from drug sales outlets in the Madina area of Accra, Ghana.

arsenic


Input: In Ghana anti-malaria herbal medicines or products are used to compliment commercial drugs in treatment and prevention of Plasmodium falciparum infections.


Input: In this study, four common aqueous based anti-malaria herbal products (coded HEB, KFE, MDM and NIB) which are used by Ghanaian population from pharmacy/herbal stores in the Madina area, Accra were blindly and randomly sampled for cadmium (Cd), arsenic (As) and Lead (Pb) analysis using Atomic Absorption Spectrophotometry technique.

cadmium

Cd

arsenic

As

Pb


Input: Arsenic concentrations were 1. 087 mu g/mL (108. 7%), 1. 027 mu g/mL (102. 7%), 0. 330 mu g/mL (33. 0%) and 0. 274 mu g/mL (27. 4%) in MDM, KFE, NIB and HEB respectively.

Arsenic


Input: Arsenic concentration determined in MDM and KFE were above the maximum permissible limit of 1. 0ppm determined by WHO/FAO.

Arsenic


Input: Cadmium concentration in each of the four products as well as lead concentration in KFE, NIB and HEB were below the detection limit of < 0. 002mg/mL (Cd) and < 0. 005mg/mL (Pb) respectively.

Cadmium

Cd

Pb