PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with << vigabatrin >> (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase ([[ GABA-T ]]), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).


PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (<< VIG >>), an anticonvulsant which elevates brain GABA by inhibition of [[ GABA transaminase ]] (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).


PURPOSE: To compare phenelzine (PLZ), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (<< VIG >>), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase ([[ GABA-T ]]), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).


PURPOSE: To compare phenelzine (<< PLZ >>), an antidepressant drug with anxiolytic properties which inhibits [[ monoamine oxidase ]] (MAO) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).


PURPOSE: To compare phenelzine (<< PLZ >>), an antidepressant drug with anxiolytic properties which inhibits monoamine oxidase ([[ MAO ]]) but also elevates rat brain levels of the amino acids ?-aminobutyric acid (GABA) and alanine (ALA), with vigabatrin (VIG), an anticonvulsant which elevates brain GABA by inhibition of GABA transaminase (GABA-T), with regard to their actions on brain levels of GABA and ALA and on activities of MAO, GABA-T and ALA transaminase (ALA-T).


RESULTS: Both << PLZ >> and VIG inhibited [[ GABA-T ]] and elevated GABA levels.


RESULTS: Both PLZ and << VIG >> inhibited [[ GABA-T ]] and elevated GABA levels.


Only << PLZ >> inhibited [[ MAO ]] and ALA-T and elevated ALA levels.


Only << PLZ >> inhibited MAO and [[ ALA-T ]] and elevated ALA levels.


The effects of PLZ on both amino acids and their transaminases were blocked by pre-treatment with the << MAO >> inhibitor [[ tranylcypromine ]].


The effects of PLZ on both amino acids and their << transaminases >> were blocked by pre-treatment with the MAO inhibitor [[ tranylcypromine ]].


This pretreament had no effect on the inhibition of << GABA-T >> or the elevation of brain GABA levels produced by [[ VIG ]].


CONCLUSIONS: At the doses studied, PLZ was as effective as VIG at elevating brain GABA levels, but, unlike << VIG >>, also inhibited [[ MAO ]] and ALA-T (and increased brain ALA levels).


CONCLUSIONS: At the doses studied, PLZ was as effective as VIG at elevating brain GABA levels, but, unlike << VIG >>, also inhibited MAO and [[ ALA-T ]] (and increased brain ALA levels).


Pretreatment of rats with the << MAO >> inhibitor [[ tranylcypromine ]] prevented the increase in brain GABA and ALA levels with PLZ, but did not block the effect of VIG on GABA.


Clinical pharmacology of << enalkiren >>, a novel, dipeptide [[ renin ]] inhibitor.


Clinical pharmacology of enalkiren, a novel, << dipeptide >> [[ renin ]] inhibitor.


<< Enalkiren >> (A-64662), a potent, dipeptide [[ renin ]] inhibitor, mimics the transition state of the human renin substrate, angiotensinogen.


<< Enalkiren >> (A-64662), a potent, dipeptide renin inhibitor, mimics the transition state of the [[ human renin ]] substrate, angiotensinogen.


Enalkiren (<< A-64662 >>), a potent, dipeptide [[ renin ]] inhibitor, mimics the transition state of the human renin substrate, angiotensinogen.


Enalkiren (<< A-64662 >>), a potent, dipeptide renin inhibitor, mimics the transition state of the [[ human renin ]] substrate, angiotensinogen.


Enalkiren (A-64662), a potent, << dipeptide >> [[ renin ]] inhibitor, mimics the transition state of the human renin substrate, angiotensinogen.


Enalkiren (A-64662), a potent, << dipeptide >> renin inhibitor, mimics the transition state of the [[ human renin ]] substrate, angiotensinogen.


<< Enalkiren >> has been shown to produce dose-related suppression of plasma [[ renin ]] activity (PRA) and angiotensin II when administered intravenously.


<< Enalkiren >> has been shown to produce dose-related suppression of plasma renin activity (PRA) and [[ angiotensin II ]] when administered intravenously.


The results of clinical trials with << enalkiren >> are encouraging, and suggest that [[ renin ]] inhibitors may be safe, useful therapeutic agents in the management of hypertension.


Also in contrast to effects of multiple << METH >> injections, 1) MDMA caused little or no decrease in binding of the [[ DAT ]] ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal DA transport.


Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the [[ MDMA ]]-induced reduction in plasmalemmal DA transport.


Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal [[ DA ]] transport.


Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the << DAT >> ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of [[ DA ]] prevented the MDMA-induced reduction in plasmalemmal DA transport.


In addition to affecting << DAT >> function, MDMA rapidly decreased vesicular [[ DA ]] transport as assessed in striatal vesicles prepared from treated rats.


Concentration-dependent inhibitory effects of << baicalin >> on the metabolism of dextromethorphan, a dual probe of [[ CYP2D ]] and CYP3A, in rats.


Concentration-dependent inhibitory effects of << baicalin >> on the metabolism of dextromethorphan, a dual probe of CYP2D and [[ CYP3A ]], in rats.


Concentration-dependent inhibitory effects of baicalin on the metabolism of << dextromethorphan >>, a dual probe of [[ CYP2D ]] and CYP3A, in rats.


Concentration-dependent inhibitory effects of baicalin on the metabolism of << dextromethorphan >>, a dual probe of CYP2D and [[ CYP3A ]], in rats.


In the current study, we reveal the inhibitory effects of << baicalin >> on the metabolism of dextromethorphan (DXM), a dual probe substrate of [[ CYP2D ]] and CYP3A, in rats.


In the current study, we reveal the inhibitory effects of << baicalin >> on the metabolism of dextromethorphan (DXM), a dual probe substrate of CYP2D and [[ CYP3A ]], in rats.


In the current study, we reveal the inhibitory effects of baicalin on the metabolism of << dextromethorphan >> (DXM), a dual probe substrate of [[ CYP2D ]] and CYP3A, in rats.


In the current study, we reveal the inhibitory effects of baicalin on the metabolism of << dextromethorphan >> (DXM), a dual probe substrate of CYP2D and [[ CYP3A ]], in rats.


In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (<< DXM >>), a dual probe substrate of [[ CYP2D ]] and CYP3A, in rats.


In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (<< DXM >>), a dual probe substrate of CYP2D and [[ CYP3A ]], in rats.


Lineweaver-Burk plots demonstrated that << baicalin >> inhibited the activities of [[ CYP2D ]] and CYP3A in a non-competitive manner in rat liver microsomes (RLMs).


Lineweaver-Burk plots demonstrated that << baicalin >> inhibited the activities of CYP2D and [[ CYP3A ]] in a non-competitive manner in rat liver microsomes (RLMs).


The activity of << CYP3A >> in excised liver samples from rats following multiple [[ baicalin ]] treatment was significantly decreased compared to that of the control group (P<0.05), whereas multiple doses of baicalin had no obvious effect on the activity of CYP2D.


Taken together, these data demonstrate that << baicalin >> inhibits the metabolism of DXM in a concentration-dependent manner in rats, possibly through inhibiting hepatic [[ CYP2D ]] and CYP3A activities.


Taken together, these data demonstrate that << baicalin >> inhibits the metabolism of DXM in a concentration-dependent manner in rats, possibly through inhibiting hepatic CYP2D and [[ CYP3A ]] activities.


Taken together, these data demonstrate that baicalin inhibits the metabolism of << DXM >> in a concentration-dependent manner in rats, possibly through inhibiting hepatic [[ CYP2D ]] and CYP3A activities.


Taken together, these data demonstrate that baicalin inhibits the metabolism of << DXM >> in a concentration-dependent manner in rats, possibly through inhibiting hepatic CYP2D and [[ CYP3A ]] activities.


Identification of a novel << benzimidazole >> derivative as a highly potent [[ NPY Y5 receptor ]] antagonist with an anti-obesity profile.


We evaluated the clinical effectiveness of << esmolol >>, an ultra-short-acting [[ beta 1-adrenergic receptor ]] blocking drug, to control the sinus tachycardia and increase in arterial blood pressures induced by electroconvulsive therapy (ECT).


The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure.


The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists [[ clenbuterol ]] and fenoterol have similar beneficial effects in animal models of heart failure.


The beta(2)-adrenoceptor (<< beta(2)-AR >>) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure.


The << beta(2)-adrenoceptor >> (beta(2)-AR) agonists clenbuterol and [[ fenoterol ]] have similar beneficial effects in animal models of heart failure.


<< beta(1)-Adrenoceptor >> antagonism (10 mg kg(-1) [[ bisoprolol ]]) prevented 92% (P < 0.05) of apoptosis induced by all three agonists, but clenbuterol-induced apoptosis could also be prevented by 96% (P < 0.05) by beta(2)-AR antagonism (10 mg kg(-1) ICI 118 551).


The mouse << CYP2J >> subfamily includes members that have wide tissue distribution and are active in the metabolism of [[ arachidonic acid ]] (AA), linoleic acid (LA), and other lipids and xenobiotics.


The mouse << CYP2J >> subfamily includes members that have wide tissue distribution and are active in the metabolism of arachidonic acid (AA), [[ linoleic acid ]] (LA), and other lipids and xenobiotics.


<< CPT I >> (carnitine palmitoyltransferase I) catalyses the conversion of palmitoyl-CoA into [[ palmitoylcarnitine ]] in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.


CPT I (<< carnitine palmitoyltransferase I >>) catalyses the conversion of palmitoyl-CoA into [[ palmitoylcarnitine ]] in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.


<< CPT I >> (carnitine palmitoyltransferase I) catalyses the conversion of [[ palmitoyl-CoA ]] into palmitoylcarnitine in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.


CPT I (<< carnitine palmitoyltransferase I >>) catalyses the conversion of [[ palmitoyl-CoA ]] into palmitoylcarnitine in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria.


<< Cholesterol >> uptake from [[ lipoproteins ]], intracellular vesicle transport and lipid transfer are also modified by oxysterols.


In addition, the new compound << perviridicin B >> (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant [[ NF-κB ]] (p65) inhibitory activity in an ELISA assay.


In addition, the new compound << perviridicin B >> (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant NF-κB ([[ p65 ]]) inhibitory activity in an ELISA assay.


In addition, the new compound perviridicin B (2), three known << rocaglate >> derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant [[ NF-κB ]] (p65) inhibitory activity in an ELISA assay.


In addition, the new compound perviridicin B (2), three known << rocaglate >> derivatives (9, 11, 12), and a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant NF-κB ([[ p65 ]]) inhibitory activity in an ELISA assay.


In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known << sesquiterpene >>, 2-oxaisodauc-5-en-12-al (17), showed significant [[ NF-κB ]] (p65) inhibitory activity in an ELISA assay.


In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known << sesquiterpene >>, 2-oxaisodauc-5-en-12-al (17), showed significant NF-κB ([[ p65 ]]) inhibitory activity in an ELISA assay.


In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, << 2-oxaisodauc-5-en-12-al >> (17), showed significant [[ NF-κB ]] (p65) inhibitory activity in an ELISA assay.


In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), and a known sesquiterpene, << 2-oxaisodauc-5-en-12-al >> (17), showed significant NF-κB ([[ p65 ]]) inhibitory activity in an ELISA assay.


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


Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.


Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of [[ epinastine ]] on the noncholinergic contraction.


Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.


Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, [[ methysergide ]] (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.


Pretreatment of the tissues with combined << 5-HT1 >>/5-HT2 antagonists, methysergide (1 microM) or [[ methiothepin ]] (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.


Pretreatment of the tissues with combined 5-HT1/<< 5-HT2 >> antagonists, methysergide (1 microM) or [[ methiothepin ]] (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction.


Pretreatment with << tropisetron >> (1 microM), a [[ 5-HT3 ]] antagonist, ketanserin (10 microM), a 5-HT2 antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect.


Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, << ketanserin >> (10 microM), a [[ 5-HT2 ]] antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect.


Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, ketanserin (10 microM), a 5-HT2 antagonist, << thioperamide >> (10 microM), a [[ histamine H3 ]] antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect.


<< Chlorpheniramine >> (10 microM), another [[ histamine H1 receptor ]] antagonist without significant 5-HT receptor binding affinity, did not produce any inhibition of the eNANC contraction.


These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional [[ 5-HT1-like receptor ]], located to sensory nerves.


These results suggest that << epinastine >>, although identified as a 5-HT antagonist, acts as a [[ 5-HT1 ]] agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves.


<< Vitamin C >> forestalls cigarette smoke induced [[ NF-κB ]] activation in alveolar epithelial cells.


It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced NF-κB activation that involves degradation of [[ I-κBε ]] and nuclear translocation of c-Rel/p50 in alveolar epithelial cells.


It is possible that << vitamin C >>, an antioxidant, may prevent cigarette smoke (CS)-induced [[ NF-κB ]] activation that involves degradation of I-κBε and nuclear translocation of c-Rel/p50 in alveolar epithelial cells.


We observed a significant reduction in CSE induced luciferase expression, NF-κB DNA binding, << I-κBε >> degradation and c-Rel nuclear translocation in cells pretreated with [[ vitamin C ]].


Result showed that << vitamin C >> treatment resulted in markedly reduced [[ c-Rel ]] nuclear translocation.


All these results demonstrate that << vitamin C >> prevents CS(E)-induced [[ NF-κB ]] activation and thus it could be used for the prevention of CS-induced inflammatory diseases.


<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as [[ monocyte chemotactic protein-1 ]] (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE).


<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 ([[ MCP-1 ]]), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE).


<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), [[ tumor necrosis factor-α ]] (TNF-α), inducible NO synthase (iNOS), and receptor for AGE (RAGE).


<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α ([[ TNF-α ]]), inducible NO synthase (iNOS), and receptor for AGE (RAGE).


<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), [[ inducible NO synthase ]] (iNOS), and receptor for AGE (RAGE).


<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase ([[ iNOS ]]), and receptor for AGE (RAGE).


<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and [[ receptor for AGE ]] (RAGE).


<< Catalpol >> reduced the expression of pro-inflammatory mediates, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), inducible NO synthase (iNOS), and receptor for AGE ([[ RAGE ]]).


Promoter and electromobility shift assays showed that transcriptional activation of << NF-κB >> was significantly reduced by [[ catalpol ]] treatment, while AP-1 was not.


<< Catalpol >> also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of IκBα and the nuclear localization of [[ NF-κB ]].


<< Catalpol >> also suppressed AGE-induced phosphorylation of mitogen activated protein (MAP) kinases, degradation of [[ IκBα ]] and the nuclear localization of NF-κB.


<< Catalpol >> also suppressed AGE-induced phosphorylation of [[ mitogen activated protein (MAP) kinases ]], degradation of IκBα and the nuclear localization of NF-κB.


Moreover, the production of intracellular reactive oxygen species (ROS) elicited by AGE was also suppressed by << catalpol >> treatment, through dual action of reducing ROS itself and inhibiting [[ NADPH oxidase ]] activity.


Our findings indicate that << catalpol >> suppresses AGE-mediated inflammation by inhibiting ROS production and [[ NF-κB ]] activity.


<< Etoposide >> (VP-16) is a [[ topoisomerase-II ]] (topo II) inhibitor chemotherapeutic agent.


<< Etoposide >> (VP-16) is a topoisomerase-II ([[ topo II ]]) inhibitor chemotherapeutic agent.


Etoposide (<< VP-16 >>) is a [[ topoisomerase-II ]] (topo II) inhibitor chemotherapeutic agent.


Etoposide (<< VP-16 >>) is a topoisomerase-II ([[ topo II ]]) inhibitor chemotherapeutic agent.


<< MXF >> or VP-16 slightly affected cellular topo II activity in nuclear extracts derived from drug-treated cells while the combination enhanced inhibitory activity and the reduction in band depletion of [[ topo II ]].


MXF or << VP-16 >> slightly affected cellular topo II activity in nuclear extracts derived from drug-treated cells while the combination enhanced inhibitory activity and the reduction in band depletion of [[ topo II ]].


Apoptosis studies (DAPI staining and << caspase 3 >> activity) showed a marked increase in the presence of [[ MXF ]] and VP-16 compared to VP-16 alone.


Apoptosis studies (DAPI staining and << caspase 3 >> activity) showed a marked increase in the presence of MXF and [[ VP-16 ]] compared to VP-16 alone.


Apoptosis studies (DAPI staining and << caspase 3 >> activity) showed a marked increase in the presence of MXF and VP-16 compared to [[ VP-16 ]] alone.


In conclusion, the results suggest that the enhancement in the reduction of << topo II >> activity by the combined [[ MXF ]]/VP-16 treatments was probably due to the increase in the level of the DNA-enzyme cleavable complexes formed by both drugs.


In conclusion, the results suggest that the enhancement in the reduction of << topo II >> activity by the combined MXF/[[ VP-16 ]] treatments was probably due to the increase in the level of the DNA-enzyme cleavable complexes formed by both drugs.


<< TAS-102 >> currently undergoing clinical trials, has been demonstrated to have at least two mechanisms, inhibition of [[ TS ]] and incorporation into DNA.


In the present study, we measured the enzyme activity of thymidine kinase (TK), thymidine phosphorylase (TP) and << thymidilate synthase >> (TS) in human cancer xenografts to investigate the contribution of these enzymes to the sensitivity of [[ TAS-102 ]].


In the present study, we measured the enzyme activity of thymidine kinase (TK), thymidine phosphorylase (TP) and thymidilate synthase (<< TS >>) in human cancer xenografts to investigate the contribution of these enzymes to the sensitivity of [[ TAS-102 ]].


Because clinical studies investigating interactions between garlic and << human immunodeficiency virus protease >> inhibitors [[ saquinavir ]] and ritonavir have already been performed, we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first-pass intestinal metabolism changes.


Because clinical studies investigating interactions between garlic and << human immunodeficiency virus protease >> inhibitors saquinavir and [[ ritonavir ]] have already been performed, we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first-pass intestinal metabolism changes.


Labetalol (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the << isoprenaline >> responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors.


<< Labetalol >> (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused surmountable antagonism of the isoprenaline responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors.


Labetalol (> or = 3 x 10(-8) M) and << dilevalol >> (> or = 10(-8) M) caused surmountable antagonism of the isoprenaline responses of the atria and the pA2 values were 8.60 and 8.98 at the [[ beta 1-adrenoceptors ]] of the rat left atria and 7.90 and 8.31, respectively, on the guinea-pig left atria which has functional beta 1- and beta 2-adrenoceptors.


The isoprenaline attenuation responses of the portal vein were inhibited by labetalol and dilevalol (both at > or = 10(-7) M) and the pA2 value for the << labetalol >> at [[ beta 2-adrenoceptors ]] was 7.59.


It is concluded that << labetalol >> and dilevalol are [[ beta 1-adrenoceptor ]] selective antagonists.


It is concluded that labetalol and << dilevalol >> are [[ beta 1-adrenoceptor ]] selective antagonists.


<< PR mRNA >> abundance in both myometruim and leiomyomata (center and marginal area) was significantly decreased in 4 patients continuing [[ mifepristone ]] treatment before the operation but not in the other 2 patients stopping RU486 1 month before operation.


One of the mechanism of << mifepristone >> action on decreasing leiomyomata volume may be related to suppression on expression of [[ PR gene ]].


Experimental cystathioninuria was induced in rats by administration of the << cystathionine gamma-lyase >> inhibitor, [[ D,L-propargylglycine ]].


The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) with low dose of << flumazenil >> (5.0 mg/kg) - a [[ BDZ receptor ]] antagonist, immediately induced BDZ withdrawal signs in these animals.


The non-selective << adenosine receptor >> antagonist ([[ caffeine ]]), and the selective adenosine A1 receptor antagonist (DPCPX), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice.


The non-selective adenosine receptor antagonist (caffeine), and the selective << adenosine A1 receptor >> antagonist ([[ DPCPX ]]), injected 15 min before the application of pentetrazole and flumazenil, were able to intensify BDZ withdrawal signs in mice.


Cross-inhibition of << SR-BI >>- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and [[ glyburide ]].


Cross-inhibition of SR-BI- and << ABCA1 >>-mediated cholesterol transport by the small molecules BLT-4 and [[ glyburide ]].


Cross-inhibition of << SR-BI >>- and ABCA1-mediated [[ cholesterol ]] transport by the small molecules BLT-4 and glyburide.


Cross-inhibition of SR-BI- and << ABCA1 >>-mediated [[ cholesterol ]] transport by the small molecules BLT-4 and glyburide.


<< SR-BI >> is a receptor that binds HDL with high affinity and mediates both the selective lipid uptake of [[ cholesteryl esters ]] from lipid-rich HDL to cells and the efflux of unesterified cholesterol from cells to HDL.


<< SR-BI >> is a receptor that binds HDL with high affinity and mediates both the selective lipid uptake of cholesteryl esters from lipid-rich HDL to cells and the efflux of unesterified [[ cholesterol ]] from cells to HDL.


<< ABCA1 >> mediates the efflux of unesterified [[ cholesterol ]] and phospholipids from cells to lipid-poor apolipoprotein A-I (apoA-I).


The activities of << ABCA1 >> and other ATP binding cassette superfamily members are inhibited by the drug [[ glyburide ]], and SR-BI-mediated lipid transport is blocked by small molecule inhibitors called BLTs.


The activities of ABCA1 and other << ATP binding cassette superfamily >> members are inhibited by the drug [[ glyburide ]], and SR-BI-mediated lipid transport is blocked by small molecule inhibitors called BLTs.


Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (<< BLT-4 >>), blocked [[ ABCA1 ]]-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).


Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (<< BLT-4 >>), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of [[ SR-BI ]] (IC(50) approximately 55-60 microM).


Here, we show that one << BLT >>, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked [[ ABCA1 ]]-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).


Here, we show that one << BLT >>, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of [[ SR-BI ]] (IC(50) approximately 55-60 microM).


Here, we show that one BLT, [<< 1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea >>] (BLT-4), blocked [[ ABCA1 ]]-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).


Here, we show that one BLT, [<< 1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea >>] (BLT-4), blocked ABCA1-mediated cholesterol efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of [[ SR-BI ]] (IC(50) approximately 55-60 microM).


Here, we show that one BLT, [1-(2-methoxy-phenyl)-3-naphthalen-2-yl-urea] (BLT-4), blocked << ABCA1 >>-mediated [[ cholesterol ]] efflux to lipid-poor apoA-I at a potency similar to that for its inhibition of SR-BI (IC(50) approximately 55-60 microM).


Reciprocally, << glyburide >> blocked SR-BI-mediated selective lipid uptake and efflux at a potency similar to that for its inhibition of [[ ABCA1 ]] (IC(50) approximately 275-300 microM).


Reciprocally, << glyburide >> blocked [[ SR-BI ]]-mediated selective lipid uptake and efflux at a potency similar to that for its inhibition of ABCA1 (IC(50) approximately 275-300 microM).


The reciprocal inhibition of << SR-BI >> and ABCA1 by BLT-4 and [[ glyburide ]] raises the possibility that these proteins may share similar or common steps in their mechanisms of lipid transport.


The reciprocal inhibition of SR-BI and << ABCA1 >> by BLT-4 and [[ glyburide ]] raises the possibility that these proteins may share similar or common steps in their mechanisms of lipid transport.


The treatment of mice with << Fe-NTA >> alone enhances [[ ornithine decarboxylase ]] activity to 4.6 folds, protein carbonyl formation increased up to 2.9 folds and DNA synthesis expressed in terms of [(3)H] thymidine incorporation increased to 3.2 folds, and antioxidants and antioxidant enzymes decreased to 1.8-2.5 folds, compared with the corresponding saline-treated controls.


<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive [[ oxygen ]] species (ROS), which are capable of initiating and promoting carcinogenesis.


Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive [[ oxygen ]] species (ROS), which are capable of initiating and promoting carcinogenesis.


<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including [[ polycyclic aromatic hydrocarbons ]] (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.


Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including [[ polycyclic aromatic hydrocarbons ]] (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.


<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons ([[ PAHs ]]), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.


Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons ([[ PAHs ]]), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.


<< Aldo-keto reductases >> (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites ([[ o-quinones ]]) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.


Aldo-keto reductases (<< AKRs >>) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites ([[ o-quinones ]]) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis.


Exposure to << PAHs >>, their metabolites, and ROS further increase [[ AKRs ]] isoform expression that may amplify oxidative damage.


Despite the importance of << AKRs >> in [[ PAHs ]] metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs).


The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of [[ nitrate reductase ]], glutamine synthetase, glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings.


The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, [[ glutamine synthetase ]], glutamate synthase, and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings.


The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, [[ glutamate synthase ]], and glutamate dehydrogenase, promoting amino acid conversion and protein synthesis in soybean seedlings.


The pretreatment with 20 mg L(-1) << La(III) >> could alleviate the effects of UV-B radiation on the activities of nitrate reductase, glutamine synthetase, glutamate synthase, and [[ glutamate dehydrogenase ]], promoting amino acid conversion and protein synthesis in soybean seedlings.


Inhibition of << monoamine oxidase >> by [[ phthalide ]] analogues.


Based on recent reports that the small molecules, << isatin >> and phthalimide, are suitable scaffolds for the design of high potency [[ monoamine oxidase ]] (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues.


Based on recent reports that the small molecules, << isatin >> and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase ([[ MAO ]]) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues.


Based on recent reports that the small molecules, isatin and << phthalimide >>, are suitable scaffolds for the design of high potency [[ monoamine oxidase ]] (MAO) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues.


Based on recent reports that the small molecules, isatin and << phthalimide >>, are suitable scaffolds for the design of high potency monoamine oxidase ([[ MAO ]]) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [2-benzofuran-1(3H)-one] analogues.


Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase (MAO) inhibitors, the present study examines the << MAO >> inhibitory properties of a series of [[ phthalide ]] [2-benzofuran-1(3H)-one] analogues.


Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase (MAO) inhibitors, the present study examines the << MAO >> inhibitory properties of a series of phthalide [[[ 2-benzofuran-1(3H)-one ]]] analogues.


In most instances, C6-substituted << phthalides >> exhibit [[ MAO-B ]] specific inhibition.


The results also show that the binding modes of representative << phthalides >> are reversible and competitive at both [[ MAO ]] isoforms.


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


Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, [[ thymidine kinase-1 ]] and thymidylate synthase, in various types of cancer.


Immunohistochemical characterization of << pyrimidine >> synthetic enzymes, thymidine kinase-1 and [[ thymidylate synthase ]], in various types of cancer.


<< Thymidine kinase-1 >> (TK-1) and thymidylate synthase (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively.


Thymidine kinase-1 (<< TK-1) >> and thymidylate synthase (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively.


Thymidine kinase-1 (TK-1) and << thymidylate synthase >> (TS) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively.


Thymidine kinase-1 (TK-1) and thymidylate synthase (<< TS >>) are key enzymes for salvage and de novo [[ pyrimidine ]] synthesis, respectively.


<< TAS-102 >> is a novel drug containing trifluorothymidine, which is phosphorylated by TK-1 to its active monophosphated form, that in turn can inhibit [[ TS ]].


<< TAS-102 >> is a novel drug containing trifluorothymidine, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS.


TAS-102 is a novel drug containing << trifluorothymidine >>, which is phosphorylated by [[ TK-1 ]] to its active monophosphated form, that in turn can inhibit TS.


Gastrointestinal adenocarcinomas and squamous cell uterine carcinomas were often accompanied by high << TS >> expression, indicating activation of [[ pyrimidine ]] synthesis through both the salvage and de novo pathways.


The contractions to 5-HT were inhibited by << ketanserin >> and alosetron indicating involvement of [[ 5-HT(2A) ]] and 5-HT(3) receptors, respectively.


The contractions to 5-HT were inhibited by ketanserin and << alosetron >> indicating involvement of 5-HT(2A) and [[ 5-HT(3) ]] receptors, respectively.


Regarding << urease >> inhibition, [[ n-butanol ]] was the most potent fraction (IC50: 97 µg/mL).


The current U.S. military and civilian oxime countermeasure, 2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium chloride (2-PAM), is under consideration for replacement with a more effective << acetylcholinesterase >> reactivator, [[ 1,1'-methylenebis{4-hydroxyiminomethyl}pyridinium dimethanesulfonate ]] (MMB-4).


The current U.S. military and civilian oxime countermeasure, 2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium chloride (2-PAM), is under consideration for replacement with a more effective << acetylcholinesterase >> reactivator, 1,1'-methylenebis{4-hydroxyiminomethyl}pyridinium dimethanesulfonate ([[ MMB-4 ]]).


Methylation-specific PCR and bisulfite sequencing identified methylation of this << CpG >> ((m)CpG) island of the glut3 gene, frequency of methylation increasing 2.5-fold with a 1.6-fold increase in [[ DNA methyl transferase 3a ]] concentrations noted with advancing postnatal age (PN14 vs PN3).


Methylation-specific PCR and bisulfite sequencing identified methylation of this CpG (<< (m)CpG >>) island of the glut3 gene, frequency of methylation increasing 2.5-fold with a 1.6-fold increase in [[ DNA methyl transferase 3a ]] concentrations noted with advancing postnatal age (PN14 vs PN3).


5'-flanking region of glut3-luciferase reporter transient transfection in HT22 hippocampal neurons demonstrated that << (m)CpGs >> inhibit [[ glut3 ]] transcription.


Separate << 5-aza-2'-deoxycytidine >> pretreatment or in combination with trichostatin A reduced (m)CpG and specific small interference RNAs targeting [[ Mecp2 ]] and Creb1 separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.


Separate << 5-aza-2'-deoxycytidine >> pretreatment or in combination with trichostatin A reduced (m)CpG and specific small interference RNAs targeting Mecp2 and [[ Creb1 ]] separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.


Separate 5-aza-2'-deoxycytidine pretreatment or in combination with << trichostatin A >> reduced (m)CpG and specific small interference RNAs targeting [[ Mecp2 ]] and Creb1 separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.


Separate 5-aza-2'-deoxycytidine pretreatment or in combination with << trichostatin A >> reduced (m)CpG and specific small interference RNAs targeting Mecp2 and [[ Creb1 ]] separately or together depleting Mecp2 and/or Creb1 binding of glut3-(m)CpGs reduced glut3 expression in HT22 cells.


A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by << NET >>-inhibiting ADs such as [[ reboxetine ]], desipramine, and imipramine.


A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by << NET >>-inhibiting ADs such as reboxetine, [[ desipramine ]], and imipramine.


A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by << NET >>-inhibiting ADs such as reboxetine, desipramine, and [[ imipramine ]].


In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant << human UDP-glucuronosyltransferase 1A9 >>--potent inhibition by [[ niflumic acid ]].


In conclusion, of the seven NSAIDs investigated, << niflumic acid >> was the most potent inhibitor of recombinant [[ UGT1A9 ]] via 4-MUG in a competitive manner.


Neither the superoxide radical scavenger, tiron, nor the inhibitor of the << dopamine (DA) transporter >>, [[ GBR 12909 ]], prevented the metabolites' toxicity.


Importantly, pre-treatment with buthionine sulfoximine (<< BSO >>), an inhibitor of [[ γ-GCS ]], prevented α-MeDA induced increase in GSH levels, but did not augment this metabolite cytotoxicity.


Importantly, pre-treatment with << buthionine sulfoximine >> (BSO), an inhibitor of [[ γ-GCS ]], prevented α-MeDA induced increase in GSH levels, but did not augment this metabolite cytotoxicity.


<< MNU >>-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high [[ MGMT ]] staining.


<< MNU >>-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of [[ E-cadherin ]], and high MGMT staining.


The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters ([[ alanine aminotransferase ]], aspartate aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).


The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, [[ aspartate aminotransferase ]], alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine).


The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, [[ alkaline phosphatase ]], total protein, albumin, bilirubin, cholesterol, urea and creatinine).


The treatment with << arsenic >> exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, [[ albumin ]], bilirubin, cholesterol, urea and creatinine).


However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an [[ N-methyl d-aspartate receptor ]] (NMDAR) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting.


However, recent clinical studies have shown that a single low-dose injection of << ketamine >>, an N-methyl d-aspartate receptor ([[ NMDAR ]]) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting.


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


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


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


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


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


The slower CL was due to the reduction of hepatic biliary excretion (67.0% decrease) and hepatic << CYP3A >> subfamily-mediated metabolism (21.9% decrease) of [[ doxorubicin ]].


Activation of << AMP-activated Protein Kinase >> and Phosphorylation of Glycogen Synthase Kinase3 β Mediate [[ Ursolic Acid ]] Induced Apoptosis in HepG2 Liver Cancer Cells.


Activation of AMP-activated Protein Kinase and Phosphorylation of << Glycogen Synthase Kinase3 β >> Mediate [[ Ursolic Acid ]] Induced Apoptosis in HepG2 Liver Cancer Cells.


Interestingly, << ursolic acid >> increased the phosphorylation of [[ AMPK ]] and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.


Interestingly, << ursolic acid >> increased the phosphorylation of AMPK and [[ coenzyme A carboxylase ]] and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.


Interestingly, << ursolic acid >> increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of [[ GSK3β ]] at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.


Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas << ursolic acid >> attenuated the phosphorylation of [[ AKT ]] and mTOR in HepG2 cells.


Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3β at inactive form serine 9, whereas << ursolic acid >> attenuated the phosphorylation of AKT and [[ mTOR ]] in HepG2 cells.


Conversely, AMPK inhibitor compound C or GSK3β inhibitor SB216763 blocked the cleavages of << PARP >> and caspase 3 induced by [[ ursolic acid ]] in HepG2 cells.


Conversely, AMPK inhibitor compound C or GSK3β inhibitor SB216763 blocked the cleavages of PARP and << caspase 3 >> induced by [[ ursolic acid ]] in HepG2 cells.


Conversely, AMPK inhibitor << compound C >> or GSK3β inhibitor SB216763 blocked the cleavages of PARP and [[ caspase 3 ]] induced by ursolic acid in HepG2 cells.


Conversely, AMPK inhibitor compound C or GSK3β inhibitor << SB216763 >> blocked the cleavages of PARP and [[ caspase 3 ]] induced by ursolic acid in HepG2 cells.


Conversely, << AMPK >> inhibitor [[ compound C ]] or GSK3β inhibitor SB216763 blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells.


Conversely, AMPK inhibitor compound C or << GSK3β >> inhibitor [[ SB216763 ]] blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells.


Furthermore, proteosomal inhibitor MG132 suppressed << AMPK >> activation, GSK3β phosphorylation, cleaved PARP and deceased AEG-1 induced by [[ ursolic acid ]] in HepG2 cells.


Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, << GSK3β >> phosphorylation, cleaved PARP and deceased AEG-1 induced by [[ ursolic acid ]] in HepG2 cells.


Furthermore, proteosomal inhibitor << MG132 >> suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased [[ AEG-1 ]] induced by ursolic acid in HepG2 cells.


Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3β phosphorylation, cleaved PARP and deceased << AEG-1 >> induced by [[ ursolic acid ]] in HepG2 cells.


Furthermore, proteosomal inhibitor << MG132 >> suppressed [[ AMPK ]] activation, GSK3β phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells.


Furthermore, proteosomal inhibitor << MG132 >> suppressed AMPK activation, [[ GSK3β ]] phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells.


Overall, our findings suggest that << ursolic acid >> induced apoptosis in HepG2 cells via [[ AMPK ]] activation and GSK3β phosphorylation as a potent chemopreventive agent.


Overall, our findings suggest that << ursolic acid >> induced apoptosis in HepG2 cells via AMPK activation and [[ GSK3β ]] phosphorylation as a potent chemopreventive agent.


Using << paraoxon >> as a reference [[ acetylcholinesterase ]] (AChE) inhibitor, the objective of this study was to develop an adverse outcome pathway (AOP) that provided quantitative linkages across levels of biological organization during zebrafish embryogenesis.


Using << paraoxon >> as a reference acetylcholinesterase ([[ AChE ]]) inhibitor, the objective of this study was to develop an adverse outcome pathway (AOP) that provided quantitative linkages across levels of biological organization during zebrafish embryogenesis.


We then showed that static exposure of embryos to << paraoxon >> (31.2-500 nM) from 5 to 96 hpf resulted in significant stage- and concentration-dependent [[ AChE ]] inhibition, albeit these effects were fully reversible within 48 h following transfer to clean water.


Based on these studies, the frequency of spontaneous tail contractions at 26 hpf - a developmental stage with minimal << AChE >> expression and activity - was significantly higher following exposure to [[ paraoxon ]] concentrations as low as 31.2 nM.


There is, however, much information on the direct (acute and chronic) effects of << alcohol >> on the binding properties of opioid receptors, as well as modulation of opioid peptide synthesis and secretion (e.g. a suggested increase in [[ beta-endorphin ]] release).


Conversely, opioid antagonists such as naloxone and << naltrexone >> (which bind to non-selectively [[ opioid receptors ]]) have been shown to decrease alcohol consumption under various experimental conditions.


Conversely, opioid antagonists such as << naloxone >> and naltrexone (which bind to non-selectively [[ opioid receptors ]]) have been shown to decrease alcohol consumption under various experimental conditions.


<< Esmolol >>, a unique cardioselective [[ beta 1-adrenergic receptor ]] blocker with a half-life of 9 minutes, can enable some patients with relative contraindications to beta blockers to nevertheless benefit from early beta-blocking therapy.


In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by << acetazolamide >>, ethoxzolamide, and cyanate, [[ CA V ]] is very similar to CA II.


In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by << acetazolamide >>, ethoxzolamide, and cyanate, CA V is very similar to [[ CA II ]].


In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, << ethoxzolamide >>, and cyanate, [[ CA V ]] is very similar to CA II.


In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, << ethoxzolamide >>, and cyanate, CA V is very similar to [[ CA II ]].


In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, ethoxzolamide, and << cyanate >>, [[ CA V ]] is very similar to CA II.


In catalytic properties, mouse CA V is closest to CA I; however, in inhibition by acetazolamide, ethoxzolamide, and << cyanate >>, CA V is very similar to [[ CA II ]].


<< Adenylosuccinate synthetase >> (AdSS) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP.


Adenylosuccinate synthetase (<< AdSS >>) catalyzes the Mg2+ dependent condensation of a molecule of IMP with aspartate to form [[ adenylosuccinate ]], in a reaction driven by the hydrolysis of GTP to GDP.


Adenylosuccinate synthetase (<< AdSS >>) catalyzes the [[ Mg2+ ]] dependent condensation of a molecule of IMP with aspartate to form adenylosuccinate, in a reaction driven by the hydrolysis of GTP to GDP.


<< Phosphate >>, a product of the reaction, was found to be a potent inhibitor of [[ MjAdSS ]] showing biphasic inhibition of enzyme activity.


The anti-inflammatory drugs << sodium salicylate >> and aspirin inhibited the activation of [[ NF-kappa B ]], which further explains the mechanism of action of these drugs.


The anti-inflammatory drugs sodium salicylate and << aspirin >> inhibited the activation of [[ NF-kappa B ]], which further explains the mechanism of action of these drugs.


<< Sodium salicylate >> and aspirin also inhibited [[ NF-kappa B ]]-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.


<< Sodium salicylate >> and aspirin also inhibited NF-kappa B-dependent transcription from the [[ Ig kappa ]] enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.


Sodium salicylate and << aspirin >> also inhibited [[ NF-kappa B ]]-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.


Sodium salicylate and << aspirin >> also inhibited NF-kappa B-dependent transcription from the [[ Ig kappa ]] enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.


Galanin attenuates << cyclic AMP regulatory element-binding protein >> (CREB) phosphorylation induced by chronic [[ morphine ]] and naloxone challenge in Cath.a cells and primary striatal cultures.


Galanin attenuates cyclic AMP regulatory element-binding protein (<< CREB >>) phosphorylation induced by chronic [[ morphine ]] and naloxone challenge in Cath.a cells and primary striatal cultures.


Galanin attenuates << cyclic AMP regulatory element-binding protein >> (CREB) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures.


Galanin attenuates cyclic AMP regulatory element-binding protein (<< CREB >>) phosphorylation induced by chronic morphine and [[ naloxone ]] challenge in Cath.a cells and primary striatal cultures.


The << Na(+)/Ca(2+) exchanger >> (NCX) is a bidirectional transporter that normally extrudes Ca(2+) from the cell (forward mode), but also brings [[ Ca(2+) ]] into the cell (reverse mode) under special conditions such as intracellular Na(+) (Na(+)(i)) accumulation or membrane depolarization.


The << Na(+)/Ca(2+) exchanger >> (NCX) is a bidirectional transporter that normally extrudes [[ Ca(2+) ]] from the cell (forward mode), but also brings Ca(2+) into the cell (reverse mode) under special conditions such as intracellular Na(+) (Na(+)(i)) accumulation or membrane depolarization.


The pharmacology of NCX inhibitors has been studied extensively since the development of << KB-R7943 >>, a prototype benzyloxyphenyl [[ NCX ]] inhibitor, in 1996.


The pharmacology of NCX inhibitors has been studied extensively since the development of KB-R7943, a prototype << benzyloxyphenyl >> [[ NCX ]] inhibitor, in 1996.


Intriguingly, the inhibitory potency of << benzyloxyphenyl >> [[ NCX ]] inhibitors is directly coupled to the rate of Na(+)(i)-dependent inactivation.


Existing << ion channel >> blockers, such as amiodarone, dronedarone, bepridil, aprindine, and [[ cibenzoline ]], have been found to have an NCX inhibitory action.


Existing ion channel blockers, such as amiodarone, dronedarone, bepridil, aprindine, and << cibenzoline >>, have been found to have an [[ NCX ]] inhibitory action.


Existing << ion channel >> blockers, such as [[ amiodarone ]], dronedarone, bepridil, aprindine, and cibenzoline, have been found to have an NCX inhibitory action.


Existing ion channel blockers, such as << amiodarone >>, dronedarone, bepridil, aprindine, and cibenzoline, have been found to have an [[ NCX ]] inhibitory action.


Existing << ion channel >> blockers, such as amiodarone, [[ dronedarone ]], bepridil, aprindine, and cibenzoline, have been found to have an NCX inhibitory action.


Existing ion channel blockers, such as amiodarone, << dronedarone >>, bepridil, aprindine, and cibenzoline, have been found to have an [[ NCX ]] inhibitory action.


Existing << ion channel >> blockers, such as amiodarone, dronedarone, [[ bepridil ]], aprindine, and cibenzoline, have been found to have an NCX inhibitory action.


Existing ion channel blockers, such as amiodarone, dronedarone, << bepridil >>, aprindine, and cibenzoline, have been found to have an [[ NCX ]] inhibitory action.


Existing << ion channel >> blockers, such as amiodarone, dronedarone, bepridil, [[ aprindine ]], and cibenzoline, have been found to have an NCX inhibitory action.


Existing ion channel blockers, such as amiodarone, dronedarone, bepridil, << aprindine >>, and cibenzoline, have been found to have an [[ NCX ]] inhibitory action.


Efficacy and safety of the << dipeptidyl peptidase-4 >> inhibitor, [[ sitagliptin ]], in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin.


AIM: To assess the efficacy and safety of a 24-week treatment with << sitagliptin >>, a highly selective once-daily oral [[ dipeptidyl peptidase-4 ]] (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and <or=10.5%] while on glimepiride alone or in combination with metformin.


AIM: To assess the efficacy and safety of a 24-week treatment with << sitagliptin >>, a highly selective once-daily oral dipeptidyl peptidase-4 ([[ DPP-4 ]]) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and <or=10.5%] while on glimepiride alone or in combination with metformin.


<< HSYA >> suppressed the expression of TLR-4, [[ Myd88 ]], ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.


<< HSYA >> suppressed the expression of TLR-4, Myd88, [[ ICAM-1 ]], TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.


<< HSYA >> suppressed the expression of TLR-4, Myd88, ICAM-1, [[ TNFα ]], IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.


<< HSYA >> suppressed the expression of TLR-4, Myd88, ICAM-1, TNFα, [[ IL-1β ]] and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.


<< HSYA >> suppressed the expression of TLR-4, Myd88, ICAM-1, TNFα, IL-1β and [[ IL-6 ]] at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.


<< HSYA >> suppressed the expression of [[ TLR-4 ]], Myd88, ICAM-1, TNFα, IL-1β and IL-6 at the mRNA and protein level, and inhibited the adhesion of leukocytes to A549 cells.


<< HSYA >> treatment also decreased [[ NF-κB ]] p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK).


<< HSYA >> treatment also decreased NF-κB [[ p65 ]] nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK).


<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of [[ p38 ]] mitogen-activated protein kinase (p38 MAPK).


<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of p38 [[ mitogen-activated protein kinase ]] (p38 MAPK).


<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase ([[ p38 ]] MAPK).


<< HSYA >> treatment also decreased NF-κB p65 nuclear translocation and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 [[ MAPK ]]).


Synthesis and biological evaluation of << phosphorylated flavonoids >> as potent and selective inhibitors of [[ cholesterol esterase ]].


A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic [[ cholesterol esterase ]] (CEase) and acetylcholinesterase (AChE).


A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase ([[ CEase ]]) and acetylcholinesterase (AChE).


A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and [[ acetylcholinesterase ]] (AChE).


A series of << phosphorylated flavonoids >> were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and acetylcholinesterase ([[ AChE ]]).


The results showed that most of the synthesized compounds exhibited nanomolar potency against << CEase >>, much better than the parent [[ flavonoids ]].


Furthermore, these << phosphorylated flavonoids >> demonstrated good to high selectivity for [[ CEase ]] over AChE, which only showed micromolar potency inhibition of AChE.


Furthermore, these << phosphorylated flavonoids >> demonstrated good to high selectivity for CEase over [[ AChE ]], which only showed micromolar potency inhibition of AChE.


Furthermore, these << phosphorylated flavonoids >> demonstrated good to high selectivity for CEase over AChE, which only showed micromolar potency inhibition of [[ AChE ]].


The structure-activity relationships revealed that the free << hydroxyl >> group at position 5 and phosphate group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of [[ CEase ]].


The structure-activity relationships revealed that the free hydroxyl group at position 5 and << phosphate >> group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of [[ CEase ]].


The structure-activity relationships revealed that the free hydroxyl group at position 5 and phosphate group at position 7 of the << phosphorylated flavonoids >> are favorable to the inhibition of [[ CEase ]].


In healthy rats, << ATB-429 >> dose dependently (25, 50, or 100 mg/kg) attenuated CRD-induced hypersensitivity and significantly inhibited CRD-induced overexpression of spinal [[ c-FOS ]] mRNA, whereas mesalamine had no effect.


ATB-429-induced antinociception was reversed by << glibenclamide >>, a [[ ATP-sensitive K(+) (K(ATP)) channel ]] inhibitor.


Colonic << cyclooxygenase-2 >> and interkeukin-1beta mRNA and spinal c-FOS mRNA expression were significantly down-regulated by [[ ATB-429 ]], but not by mesalamine.


Colonic cyclooxygenase-2 and << interkeukin-1beta >> mRNA and spinal c-FOS mRNA expression were significantly down-regulated by [[ ATB-429 ]], but not by mesalamine.


Colonic cyclooxygenase-2 and interkeukin-1beta mRNA and spinal << c-FOS >> mRNA expression were significantly down-regulated by [[ ATB-429 ]], but not by mesalamine.


Block of human NaV1.5 << sodium channels >> by novel [[ alpha-hydroxyphenylamide ]] analogues of phenytoin.


Block of << human NaV1.5 >> sodium channels by novel [[ alpha-hydroxyphenylamide ]] analogues of phenytoin.


Block of human NaV1.5 << sodium channels >> by novel alpha-hydroxyphenylamide analogues of [[ phenytoin ]].


Block of << human NaV1.5 >> sodium channels by novel alpha-hydroxyphenylamide analogues of [[ phenytoin ]].


Block of human NaV1.5 << sodium channels >>[[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin.


Block of << human NaV1.5 >> [[ sodium ]] channels by novel alpha-hydroxyphenylamide analogues of phenytoin.


<< Voltage-gated sodium (Na) channels >>[[ Na ]]) channels are a critical component of electrically excitable cells.


<< Voltage-gated sodium (Na) channels >>[[ sodium ]] (Na) channels are a critical component of electrically excitable cells.


<< Phenytoin >> (diphenylhydantoin, DPH) is an established [[ sodium channel ]] blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.


Phenytoin (<< diphenylhydantoin >>, DPH) is an established [[ sodium channel ]] blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.


Phenytoin (diphenylhydantoin, << DPH >>) is an established [[ sodium channel ]] blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.


Phenytoin (diphenylhydantoin, DPH) is an established << sodium channel >>[[ sodium ]] channel blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain.


In this study, we have synthesized novel << alpha-hydroxyphenylamide >> analogues of diphenylhydantoin and examined their ability to inhibit [[ human Na(V)1.5 ]] sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells.


In this study, we have synthesized novel << alpha-hydroxyphenylamide >> analogues of diphenylhydantoin and examined their ability to inhibit human Na(V)1.5 [[ sodium channels ]] expressed in Chinese Hamster Ovary (CHO-K1) cells.


In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of << diphenylhydantoin >> and examined their ability to inhibit [[ human Na(V)1.5 ]] sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells.


In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of << diphenylhydantoin >> and examined their ability to inhibit human Na(V)1.5 [[ sodium channels ]] expressed in Chinese Hamster Ovary (CHO-K1) cells.


In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit << human Na(V)1.5 >> [[ sodium ]] channels expressed in Chinese Hamster Ovary (CHO-K1) cells.


In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(V)1.5 << sodium channels >>[[ sodium ]] channels expressed in Chinese Hamster Ovary (CHO-K1) cells.


In comparison to << diphenylhydantoin >>, the novel chloro-substituted alpha-hydroxyphenylamide compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of [[ Na(V)1.5 ]] channels with an IC(50) value of 14.5 microM.


In comparison to diphenylhydantoin, the novel << chloro >>-substituted alpha-hydroxyphenylamide compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of [[ Na(V)1.5 ]] channels with an IC(50) value of 14.5 microM.


In comparison to diphenylhydantoin, the novel chloro-substituted << alpha-hydroxyphenylamide >> compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of [[ Na(V)1.5 ]] channels with an IC(50) value of 14.5 microM.


This information may be useful in the development of more potent << sodium channel >>[[ sodium ]] channel blockers.


Effects of a << serotonin 5-HT(4) receptor >> antagonist [[ SB-207266 ]] on gastrointestinal motor and sensory function in humans.


METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist (SB-207266) on the [[ cisapride ]] mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects.


METHODS: Part A compared the effects of placebo to four doses of a << 5-HT(4) >> receptor antagonist ([[ SB-207266 ]]) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects.


METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (<< SB-207266 >>) on the cisapride mediated increase in plasma aldosterone (a [[ 5-HT(4) ]] mediated response) and orocaecal transit in 18 subjects.


<< Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of [[ polyamine ]] levels in human cells, as acetylation of spermidine and spermine triggers export or degradation.


<< Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of [[ spermidine ]] and spermine triggers export or degradation.


<< Spermidine/spermine N1-acetyltransferase >> (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of spermidine and [[ spermine ]] triggers export or degradation.


These unexpected and intriguing complexities seem likely to have some as yet undefined role in regulating << SSAT >> activity or stability as a part of [[ polyamine ]] homeostasis.


Treatment of C57 BL/6 mice with << bleomycin >> increased fibroblast viability and collagen production and significantly downregulated [[ Nrf2 ]].


In a cell-based model, << bleomycin >> suppressed Nrf2 activation via [[ extracellular signal-related kinase ]] phosphorylation, enhancing intracellular reactive oxygen species in lung fibroblasts and stimulating abnormal cell proliferation and collagen secretion.


In a cell-based model, << bleomycin >> suppressed [[ Nrf2 ]] activation via extracellular signal-related kinase phosphorylation, enhancing intracellular reactive oxygen species in lung fibroblasts and stimulating abnormal cell proliferation and collagen secretion.


To confirm this novel mechanism of bleomycin-induced fibrogenesis, we attempted to upregulate Nrf2 and related antioxidant proteins in bleomycin-treated fibroblasts using a putative << Nrf2 >> activator, [[ caffeic acid phenethyl ester ]], and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance.


To confirm this novel mechanism of << bleomycin >>-induced fibrogenesis, we attempted to upregulate [[ Nrf2 ]] and related antioxidant proteins in bleomycin-treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin-induced fibroblast proliferation and collagen content were attenuated through improved redox balance.


Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor << TAK-441 >> for the inhibition of [[ Gli1 ]] messenger RNA expression and antitumor efficacy in xenografted tumor model mice.


Pharmacokinetic and pharmacodynamic modeling of << hedgehog >> inhibitor [[ TAK-441 ]] for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice.


6-Ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide (<< TAK-441 >>) is a potent, selective [[ hedgehog ]] signaling pathway inhibitor that binds to Smo and is being developed for the treatment of cancer.


The IC50 values for << Gli1 >> mRNA inhibition in the tumor and skin by [[ TAK-441 ]] were estimated to be 0.0457 and 0.113 μg/ml, respectively.


In this report, we evaluated the growth-inhibitory effects of << sulindac sulfide >>, a [[ COX-1 ]] and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines.


In this report, we evaluated the growth-inhibitory effects of << sulindac sulfide >>, a COX-1 and [[ COX-2 ]] inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines.


In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and << nordihydroguaiaretic acid >> (NDGA), a [[ lipoxygenase ]] inhibitor on human lung cancer cell lines.


In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (<< NDGA >>), a [[ lipoxygenase ]] inhibitor on human lung cancer cell lines.


<< Phenothiazines >> inhibit [[ S100A4 ]] function by inducing protein oligomerization.


Using a unique biosensor-based assay, << trifluoperazine >> (TFP) was identified as an inhibitor that disrupts the [[ S100A4 ]]/myosin-IIA interaction.


Using a unique biosensor-based assay, << trifluoperazine >> (TFP) was identified as an inhibitor that disrupts the S100A4/[[ myosin-IIA ]] interaction.


Using a unique biosensor-based assay, trifluoperazine (<< TFP >>) was identified as an inhibitor that disrupts the [[ S100A4 ]]/myosin-IIA interaction.


Using a unique biosensor-based assay, trifluoperazine (<< TFP >>) was identified as an inhibitor that disrupts the S100A4/[[ myosin-IIA ]] interaction.


Assays examining the ability of TFP to block S100A4-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of S100A4 function occurs only at << TFP >> concentrations that promote [[ S100A4 ]] oligomerization.


Assays examining the ability of << TFP >> to block [[ S100A4 ]]-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of S100A4 function occurs only at TFP concentrations that promote S100A4 oligomerization.


Assays examining the ability of << TFP >> to block S100A4-mediated disassembly of [[ myosin-IIA ]] filaments demonstrate that significant inhibition of S100A4 function occurs only at TFP concentrations that promote S100A4 oligomerization.


Assays examining the ability of TFP to block S100A4-mediated disassembly of myosin-IIA filaments demonstrate that significant inhibition of << S100A4 >> function occurs only at [[ TFP ]] concentrations that promote S100A4 oligomerization.


Together these studies support a unique mode of inhibition in which << phenothiazines >> disrupt the [[ S100A4 ]]/myosin-IIA interaction by sequestering S100A4 via small molecule-induced oligomerization.


Together these studies support a unique mode of inhibition in which << phenothiazines >> disrupt the S100A4/[[ myosin-IIA ]] interaction by sequestering S100A4 via small molecule-induced oligomerization.


Cardiac effects of the << beta 3-adrenoceptor >> agonist [[ BRL35135 ]] in man.


The aim of the present study was to evaluate the cardiac effects of the << beta 3-adrenoceptor >> agonist [[ BRL35135 ]], and determine whether beta 3-receptors are involved in mediating chronotropic or inotropic responses in man.


Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist [[ salbutamol ]] 8 mg (SAL), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.


Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective << beta 2-adrenoceptor >> agonist salbutamol 8 mg ([[ SAL ]]), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.


Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), << bisoprolol >> 5 mg (B5) as a selective [[ beta 1-adrenoceptor ]] antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors.


Both << BRL >> and SAL produced a significant increase in postural finger tremor in keeping with [[ beta 2-adrenoceptor ]] stimulation, and this response was totally abolished by pretreatment with N20.


Both BRL and << SAL >> produced a significant increase in postural finger tremor in keeping with [[ beta 2-adrenoceptor ]] stimulation, and this response was totally abolished by pretreatment with N20.


Disruption of contact inhibition, which was induced by toxic AhR ligands << 2,3,7,8-tetrachlorodibenzo-p-dioxin >> (TCDD) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced [[ Cx43 ]] protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner.


Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (<< TCDD >>) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced [[ Cx43 ]] protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner.


Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or << polycyclic aromatic hydrocarbons >> in epithelial WB-F344 cells, reduced [[ Cx43 ]] protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner.


Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by << TCDD >>, siRNA-mediated [[ Cx43 ]] knock-down was not sufficient to stimulate proliferation in contact-inhibited cells.


Although both intracellular and membrane << Cx43 >> pools were markedly reduced in cells released from contact inhibition by [[ TCDD ]], siRNA-mediated Cx43 knock-down was not sufficient to stimulate proliferation in contact-inhibited cells.


<< Dexamethasone >> suppresses histamine synthesis by repressing both transcription and activity of [[ HDC ]] in allergic rats.


BACKGROUND: << Histamine >> synthesized by [[ histidine decarboxylase ]] (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.


BACKGROUND: << Histamine >> synthesized by histidine decarboxylase ([[ HDC ]]) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.


BACKGROUND: Histamine synthesized by << histidine decarboxylase >> (HDC) from [[ L-histidine ]] is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.


BACKGROUND: Histamine synthesized by histidine decarboxylase (<< HDC >>) from [[ L-histidine ]] is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity.


However the regulatory mechanism of << histamine >> synthesis by [[ HDC ]] remains to be elucidated.


Histamine content, << HDC >> activity and HDC mRNA expression in nasal mucosa were also significantly increased after [[ TDI ]] provocation.


Histamine content, HDC activity and << HDC >> mRNA expression in nasal mucosa were also significantly increased after [[ TDI ]] provocation.


Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, << HDC >> activity and HDC mRNA induced by [[ TDI ]] in TDI-sensitized rats.


Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by [[ TDI ]] in TDI-sensitized rats.


Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and << HDC >> mRNA induced by TDI in [[ TDI ]]-sensitized rats.


Pretreatment with << dexamethasone >> significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and [[ HDC ]] mRNA induced by TDI in TDI-sensitized rats.


Pretreatment with << dexamethasone >> significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, [[ HDC ]] activity and HDC mRNA induced by TDI in TDI-sensitized rats.


CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of [[ HDC ]] gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity.


CONCLUSIONS: These findings indicate that increased synthesis of << histamine >> through up-regulation of HDC gene expression and [[ HDC ]] activity in nasal mucosa plays an important role in the development of nasal hypersensitivity.


Repression of << HDC >> gene expression and HDC activity by [[ dexamethasone ]] may underlie its therapeutic effect in the treatment of allergy.


Repression of HDC gene expression and << HDC >> activity by [[ dexamethasone ]] may underlie its therapeutic effect in the treatment of allergy.


CONCLUSIONS A diet that partially replaces << carbohydrate >> with unsaturated fat may improve [[ insulin ]] sensitivity in a population at risk for cardiovascular disease.


In this study, we assessed the effects of << clopidogrel >> and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with [[ CYP2B6 ]] polymorphisms in humans.


In this study, we assessed the effects of << clopidogrel >> and clarithromycin, known [[ CYP2B6 ]] and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.


In this study, we assessed the effects of << clopidogrel >> and clarithromycin, known CYP2B6 and [[ CYP3A ]] inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.


In this study, we assessed the effects of clopidogrel and << clarithromycin >>, known [[ CYP2B6 ]] and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.


In this study, we assessed the effects of clopidogrel and << clarithromycin >>, known CYP2B6 and [[ CYP3A ]] inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans.


Increased << IL-5 >> activity in the serum was inhibited by both [[ pranlukast ]] and MCI-826 by over 90%.


Increased << IL-5 >> activity in the serum was inhibited by both pranlukast and [[ MCI-826 ]] by over 90%.


CONCLUSIONS: << CysLTs >> produced after antigen provocation sequentially induced IL-5 production from some immune component cells via [[ CysLT1 ]] receptor activation.


Extracellular application of meclofenamate (EC(50) = 25 microM) and << diclofenac >> (EC(50) = 2.6 microM) resulted in the activation of [[ KCNQ2/Q3 ]] K(+) currents, heterologously expressed in Chinese hamster ovary cells.


Extracellular application of << meclofenamate >> (EC(50) = 25 microM) and diclofenac (EC(50) = 2.6 microM) resulted in the activation of [[ KCNQ2/Q3 ]] K(+) currents, heterologously expressed in Chinese hamster ovary cells.


The selective << norepinephrine (NE) transporter >> inhibitor [[ atomoxetine ]] (formerly called tomoxetine or LY139603) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD).


The selective << norepinephrine (NE) transporter >> inhibitor atomoxetine (formerly called [[ tomoxetine ]] or LY139603) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD).


The selective << norepinephrine (NE) transporter >> inhibitor atomoxetine (formerly called tomoxetine or [[ LY139603 ]]) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD).


Lung inflammation, << IL-4 >> production, and airway mast cell activity were also prevented under this early short-term treatment with [[ PGE2 ]].


Local << PGE2 >> administration prevented the increase of airway [[ IL-13 ]] and osteopontin and kept lung plasmacytoid dendritic cell counts close to baseline.


Local << PGE2 >> administration prevented the increase of airway IL-13 and [[ osteopontin ]] and kept lung plasmacytoid dendritic cell counts close to baseline.


Reactivators showed different activity in the reactivation of << rat brain AChE >> after [[ dichlorvos ]], paraoxon and tabun inhibition.


Reactivators showed different activity in the reactivation of << rat brain AChE >> after dichlorvos, [[ paraoxon ]] and tabun inhibition.


Reactivators showed different activity in the reactivation of << rat brain AChE >> after dichlorvos, paraoxon and [[ tabun ]] inhibition.


<< AChE >> was easier reactivated after [[ paraoxon ]] treatment.


The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound [[ BT-07-4M ]], TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure.


The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, [[ TMB-4 ]] and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure.


The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and [[ obidoxime ]] from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure.


The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric [[ oximes ]], and BT-05 and BT-03 possessing asymmetric structure.


The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and [[ BT-05 ]] and BT-03 possessing asymmetric structure.


The reactivation of brain << AChE >> inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and [[ BT-03 ]] possessing asymmetric structure.


All compounds showed low activity toward inhibition of << AChE >> caused by [[ dichlorvos ]].


State-dependent << mibefradil >> block of [[ Na+ channels ]].


<< Mibefradil >> is a [[ T-type Ca2+ channel ]] antagonist with reported cross-reactivity with other classes of ion channels, including K+, Cl-, and Na+ channels.


Using whole-cell voltage clamp, we examined << mibefradil >> block of four [[ Na+ channel ]] isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), Nav1.4 (skeletal muscle), Nav1.2 (brain), and Nav1.7 (peripheral nerve).


Using whole-cell voltage clamp, we examined << mibefradil >> block of four Na+ channel isoforms expressed in human embryonic kidney cells: [[ Nav1.5 ]] (cardiac), Nav1.4 (skeletal muscle), Nav1.2 (brain), and Nav1.7 (peripheral nerve).


Using whole-cell voltage clamp, we examined << mibefradil >> block of four Na+ channel isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), [[ Nav1.4 ]] (skeletal muscle), Nav1.2 (brain), and Nav1.7 (peripheral nerve).


Using whole-cell voltage clamp, we examined << mibefradil >> block of four Na+ channel isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), Nav1.4 (skeletal muscle), [[ Nav1.2 ]] (brain), and Nav1.7 (peripheral nerve).


Using whole-cell voltage clamp, we examined << mibefradil >> block of four Na+ channel isoforms expressed in human embryonic kidney cells: Nav1.5 (cardiac), Nav1.4 (skeletal muscle), Nav1.2 (brain), and [[ Nav1.7 ]] (peripheral nerve).


<< Mibefradil >> blocked [[ Nav1.5 ]] in a use/frequency-dependent manner, indicating preferential binding to states visited during depolarization.


<< Mibefradil >> blocked currents of all [[ Na+ channel ]] isoforms with similar affinity and a dependence on holding potential, and drug off-rate was slowed at depolarized potentials (k(off) was 0.024/s at -130 mV and 0.007/s at -100 mV for Nav1.5).


<< Mibefradil >> blocked currents of all Na+ channel isoforms with similar affinity and a dependence on holding potential, and drug off-rate was slowed at depolarized potentials (k(off) was 0.024/s at -130 mV and 0.007/s at -100 mV for [[ Nav1.5 ]]).


In addition, inhibiting the binding of the fast inactivation lid (<< Nav1.5 >> ICM + MTSET) did not alter [[ mibefradil ]] block, confirming that the drug does not preferentially interact with the fast-inactivated state.


When selectively applied to channels after inducing slow inactivation with a 60-s pulse to -10 mV, << mibefradil >> (1 microM) produced 45% fractional block in [[ Nav1.5 ]] and greater block (88%) in an isoform (Nav1.4) that slow-inactivates more completely.


When selectively applied to channels after inducing slow inactivation with a 60-s pulse to -10 mV, << mibefradil >> (1 microM) produced 45% fractional block in Nav1.5 and greater block (88%) in an isoform ([[ Nav1.4 ]]) that slow-inactivates more completely.


Our results suggest that << mibefradil >> blocks [[ Na+ channels ]] in a state-dependent manner that does not depend on fast inactivation but probably involves interaction with one or more slow-inactivated state(s).


<< Docetaxel >> is a semisynthetic taxane that inhibit tumor growth by induction of microtubule stabilization and promotion of [[ bcl-2 ]] inactivation, which induce apoptosis.


Docetaxel is a semisynthetic << taxane >> that inhibit tumor growth by induction of microtubule stabilization and promotion of [[ bcl-2 ]] inactivation, which induce apoptosis.


Risperidone is metabolized to its active metabolite, << 9-hydroxyrisperidone >>, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4.


<< Risperidone >> is metabolized to its active metabolite, 9-hydroxyrisperidone, mainly by the [[ cytochrome P450 ]] enzymes CYP2D6 and 3A4.


Both << risperidone >> and 9-hydroxyrisperidone are substrates of [[ P-glycoprotein ]] (P-gp), a transport protein involved in drug absorption, distribution, and elimination.


Both << risperidone >> and 9-hydroxyrisperidone are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination.


Both risperidone and << 9-hydroxyrisperidone >> are substrates of [[ P-glycoprotein ]] (P-gp), a transport protein involved in drug absorption, distribution, and elimination.


Both risperidone and << 9-hydroxyrisperidone >> are substrates of P-glycoprotein ([[ P-gp ]]), a transport protein involved in drug absorption, distribution, and elimination.


bis(Ethyl) oligoamine analogues of polyamines, such as SL-11144 and SL-11158, as well as arylamine analogues [BW-1, a bis(phenylbenzyl) 3-7-3 analogue] blocked uptake and interconversion of spermine at micromolar levels and, in the case of << BW-1 >>, acted as substrate for [[ PAO ]].


<< SL-11158 >> inhibited [[ SSAT ]] activity with a mixed type of inhibition in which the analogue had a 70-fold higher affinity for the enzyme than the natural substrate, spermine.


Synthesis and in vitro evaluation of << N-Aryl pyrido-quinazolines >> derivatives as potent [[ EGFR ]] inhibitors.


A series of << pyrido-quinazolines >> have been synthesised, characterised and tested for their in vitro [[ EGFR ]] tyrosine kinase inhibitory activity.


A series of << pyrido-quinazolines >> have been synthesised, characterised and tested for their in vitro EGFR [[ tyrosine kinase ]] inhibitory activity.


Exposure to << Cu >> NPs decreased cell viability to 73% (p<0.01) and significantly (p<0.05) elevated levels of lactate dehydrogenase, intracellular reactive oxygen species and [[ interleukin-8 ]] that mirrored our findings from subacute in vivo inhalation studies in mice.


Exposure to << Cu >> NPs decreased cell viability to 73% (p<0.01) and significantly (p<0.05) elevated levels of [[ lactate dehydrogenase ]], intracellular reactive oxygen species and interleukin-8 that mirrored our findings from subacute in vivo inhalation studies in mice.


The Trx mimetics peptides (TXM) protected insulinoma INS 832/13 cells from oxidative stress induced by selectively inhibiting << TrxR >> with [[ auranofin ]] (AuF).


The Trx mimetics peptides (TXM) protected insulinoma INS 832/13 cells from oxidative stress induced by selectively inhibiting << TrxR >> with auranofin ([[ AuF ]]).


The TXM peptides were effective in inhibiting << AuF >>-induced [[ MAPK ]], JNK and p38(MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.


The TXM peptides were effective in inhibiting << AuF >>-induced MAPK, [[ JNK ]] and p38(MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.


The TXM peptides were effective in inhibiting << AuF >>-induced MAPK, JNK and [[ p38 ]](MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.


The TXM peptides were effective in inhibiting << AuF >>-induced MAPK, JNK and p38([[ MAPK ]]) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation.


Preferential block of late sodium current in the << LQT3 DeltaKPQ mutant >> by the class I(C) antiarrhythmic [[ flecainide ]].


<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the long QT syndrome 3 (LQT3) sodium channel alpha subunit mutation with three amino acids deleted ([[ DeltaKPQ ]]) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings.


<< Flecainide >> block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the [[ long QT syndrome 3 (LQT3) sodium channel alpha ]] subunit mutation with three amino acids deleted (DeltaKPQ) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings.


Flecainide block of Na(+) current (I(Na)) was investigated in wild-type (WT) or the << long QT syndrome 3 (LQT3) sodium channel alpha >>[[ sodium ]] channel alpha subunit mutation with three amino acids deleted (DeltaKPQ) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings.


Compared with WT, << DeltaKPQ >> I(Na) was more sensitive to [[ flecainide ]], and flecainide preferentially inhibited late I(Na) (mean current between 20 and 23.5 ms after depolarization) compared with peak I(Na).


Compared with WT, << DeltaKPQ >> I(Na) was more sensitive to flecainide, and [[ flecainide ]] preferentially inhibited late I(Na) (mean current between 20 and 23.5 ms after depolarization) compared with peak I(Na).


We conclude that << DeltaKPQ >> interacts differently with [[ flecainide ]] than with WT, leading to increased block and slowed recovery, especially for late I(Na).


Both << 5'-AMN >> and 5'-MABN had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and [[ μ-receptor ]] antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum.


Both 5'-AMN and << 5'-MABN >> had high affinity for κ-receptors (K (i) 1.36 ± 0.98 and 0.27 ± 0.08, respectively) and were revealed as potent κ-antagonists (pA(2) 7.43 and 8.18, respectively) and [[ μ-receptor ]] antagonists (pA(2) 7.62 and 7.85, respectively) in the ileum.


Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson's disease and this Letter describes the SAR of a series of << dihydropteridinone >> based [[ Plk-2 ]] inhibitors.


<< Sphingosine-1-phosphate >> promotes the nuclear translocation of β-catenin and thereby induces [[ osteoprotegerin ]] gene expression in osteoblast-like cell lines.


<< S1P >> activated [[ phosphatidylinositol 3-kinase ]] (PI3K)/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.


<< S1P >> activated phosphatidylinositol 3-kinase ([[ PI3K ]])/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.


<< S1P >> activated phosphatidylinositol 3-kinase (PI3K)/[[ Akt ]] signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.


<< S1P >> activated phosphatidylinositol 3-kinase (PI3K)/Akt signaling, leading to the inhibition of [[ glycogen synthase kinase-3β ]] and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells.


<< S1P >> increased the amount of [[ osteoprotegerin ]] at both mRNA and protein levels, and increased the activity of alkaline phosphatase, leading to the mineralization.