The Effect of Copper Addition on the Activity and Stability of Iron-Based CO₂ Hydrogenation Catalysts.

PubMed

Bradley, Matthew J; Ananth, Ramagopal; Willauer, Heather D; Baldwin, Jeffrey W; Hardy, Dennis R; Williams, Frederick W

2017-09-20

Iron-based CO₂ catalysts have shown promise as a viable route to the production of olefins from CO₂ and H₂ gas. However, these catalysts can suffer from low conversion and high methane selectivity, as well as being particularly vulnerable to water produced during the reaction. In an effort to improve both the activity and durability of iron-based catalysts on an alumina support, copper (10-30%) has been added to the catalyst matrix. In this paper, the effects of copper addition on the catalyst activity and morphology are examined. The addition of 10% copper significantly increases the CO₂ conversion, and decreases methane and carbon monoxide selectivity, without significantly altering the crystallinity and structure of the catalyst itself. The FeCu/K catalysts form an inverse spinel crystal phase that is independent of copper content and a metallic phase that increases in abundance with copper loading (>10% Cu). At higher loadings, copper separates from the iron oxide phase and produces metallic copper as shown by SEM-EDS. An addition of copper appears to increase the rate of the Fischer-Tropsch reaction step, as shown by modeling of the chemical kinetics and the inter- and intra-particle transport of mass and energy.

How do somatosensory deficits in the arm and hand relate to upper limb impairment, activity, and participation problems after stroke? A systematic review.

PubMed

Meyer, Sarah; Karttunen, Auli H; Thijs, Vincent; Feys, Hilde; Verheyden, Geert

2014-09-01

The association between somatosensory impairments and outcome after stroke remains unclear. The aim of this study was to systematically review the available literature on the relationship between somatosensory impairments in the upper limb and outcome after stroke. The electronic databases PubMed, CINAHL, EMBASE, Cochrane Library, PsycINFO, and Web of Science were systematically searched from inception until July 2013. Studies were included if adult patients with stroke (minimum n=10) were examined with reliable and valid measures of somatosensation in the upper limb to investigate the relationship with upper limb impairment, activity, and participation measures. Exclusion criteria included measures of somatosensation involving an overall score for upper and lower limb outcome and articles including only lower limb outcomes. Eligibility assessment, data extraction, and quality evaluation were completed by 2 independent reviewers. A cutoff score of ≥65% of the maximal quality score was used for further inclusion in this review. Six articles met all inclusion criteria. Two-point discrimination was shown to be predictive for upper limb dexterity, and somatosensory evoked potentials were shown to have predictive value in upper limb motor recovery. Proprioception was significantly correlated with perceived level of physical activity and social isolation and had some predictive value in functional movements of the upper limb. Finally, the combination of light touch and proprioception impairment was shown to be significantly related to upper limb motor recovery as well as handicap situations during activities of daily living. Heterogeneity of the included studies warrants caution when interpreting results. Large variation in results was found due to heterogeneity of the studies. However, somatosensory deficits were shown to have an important role in upper limb motor and functional performance after stroke. © 2014 American Physical Therapy Association.

Self-regulation of the anterior insula: Reinforcement learning using real-time fMRI neurofeedback.

PubMed

Lawrence, Emma J; Su, Li; Barker, Gareth J; Medford, Nick; Dalton, Jeffrey; Williams, Steve C R; Birbaumer, Niels; Veit, Ralf; Ranganatha, Sitaram; Bodurka, Jerzy; Brammer, Michael; Giampietro, Vincent; David, Anthony S

2014-03-01

The anterior insula (AI) plays a key role in affective processing, and insular dysfunction has been noted in several clinical conditions. Real-time functional MRI neurofeedback (rtfMRI-NF) provides a means of helping people learn to self-regulate activation in this brain region. Using the Blood Oxygenated Level Dependant (BOLD) signal from the right AI (RAI) as neurofeedback, we trained participants to increase RAI activation. In contrast, another group of participants was shown 'control' feedback from another brain area. Pre- and post-training affective probes were shown, with subjective ratings and skin conductance response (SCR) measured. We also investigated a reward-related reinforcement learning model of rtfMRI-NF. In contrast to the controls, we hypothesised a positive linear increase in RAI activation in participants shown feedback from this region, alongside increases in valence ratings and SCR to affective probes. Hypothesis-driven analyses showed a significant interaction between the RAI/control neurofeedback groups and the effect of self-regulation. Whole-brain analyses revealed a significant linear increase in RAI activation across four training runs in the group who received feedback from RAI. Increased activation was also observed in the caudate body and thalamus, likely representing feedback-related learning. No positive linear trend was observed in the RAI in the group receiving control feedback, suggesting that these data are not a general effect of cognitive strategy or control feedback. The control group did, however, show diffuse activation across the putamen, caudate and posterior insula which may indicate the representation of false feedback. No significant training-related behavioural differences were observed for valence ratings, or SCR. In addition, correlational analyses based on a reinforcement learning model showed that the dorsal anterior cingulate cortex underpinned learning in both groups. In summary, these data demonstrate that it is possible to regulate the RAI using rtfMRI-NF within one scanning session, and that such reward-related learning is mediated by the dorsal anterior cingulate. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Antimalarial Tafenoquine on Blood Platelet Activity and Survival.

PubMed

Cao, Hang; Bissinger, Rosi; Umbach, Anja T; Al Mamun Bhuyan, A; Lang, Florian; Gawaz, Meinrad

2017-01-01

The 8-aminoquinoline tafenoquine has been shown to be effective against Plasmodia, Leishmania and Trypanosoma. The substance is at least in part effective by triggering apoptosis of the parasites. Moreover, tafenoquine has been shown to trigger eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. The effect of tafenoquine on eryptosis is in part due to stimulation of Ca2+ entry and oxidative stress. Ca2+ entry is a critical event in the activation of blood platelets by thrombin and collagen related peptide (CRP). The present study explored, whether tafenoquine influences Ca2+ entry, activation and apoptosis of blood platelets. Platelets isolated from wild-type mice were exposed for 30 minutes to tafenoquine (2.5 µg/ml) without or with an additional treatment with thrombin (0.01 U/ml) or CRP (2 µg/ml or 5 µg/ml). Flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+] i ) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from α IIb β 3 integrin abundance, phosphatidylserine abundance from annexin-V-binding, relative platelet volume from forward scatter, reactive oxygen species (ROS) from DCF fluorescence, caspase 3 activity with an active caspase-3 Staining kit, and aggregation utilizing staining with CD9-APC and CD9-PE. Both, thrombin (0.01 U/ml) and CRP (2 µg/ml or 5 µg/ml), significantly increased [Ca2+] i , P-selectin abundance, active α IIb β 3 integrin, and annexin-V-binding, and both significantly decreased platelet volume, activated caspase 3 and stimulated aggregation. Administration of tafenoquine (2.5 µg/ml, 30 min) significantly decreased [Ca2+] i both, in the absence and presence of thrombin and CRP. Tafenoquine significantly blunted the effect of thrombin and CRP on [Ca2+] i , P-selectin abundance, and active α IIb β 3 integrin, but significantly increased ROS and annexin-V-binding, significantly augmented the effect of thrombin on caspase 3 activity and platelet volume and significantly enhanced platelet aggregation. Tafenoquine counteracts thrombin and CRP induced increase of cytosolic Ca2+ activity and platelet activation, but enhances platelet apoptosis and platelet aggregation. © 2017 The Author(s) Published by S. Karger AG, Basel.

The effect of activated dimethicone and a proprietary antacid preparation containing this agent on the absorption of phenytoin.

PubMed Central

McElnay, J C; Uprichard, G; Collier, P S

1982-01-01

1 The bioavailabilty of phenytoin sodium (Epanutin both alone and in combination with activated dimethicone and Asilone (a proprietary antacid preparation containing activated dimethicone) was examined in six healthy male volunteers. 2 The bioavailability of phenytoin when given concomitantly with Asilone was decreased in five of six volunteer subjects (by greater than 30% in three subjects) although this decrease was not shown to be statistically significant. 3 Dimethicone, which has been shown to decrease phenytoin absorption in vitro did not affect phenytoin bioavailability in vivo. 4 It is recommended that when treating patients stabilised on phenytoin one should exercise caution with concomitant phenytoin and antacid therapy to guard against possible changed drug absorption. PMID:7066165

Buckwheat (Fagopyrum esculentum M.) Sprout Treated with Methyl Jasmonate (MeJA) Improved Anti-Adipogenic Activity Associated with the Oxidative Stress System in 3T3-L1 Adipocytes

PubMed Central

Lee, Young-Jun; Kim, Kui-Jin; Park, Kee-Jai; Yoon, Bo-Ra; Lim, Jeong-Ho; Lee, Ok-Hwan

2013-01-01

Buckwheat sprouts contain various bioactive compounds including rutin which have a number of biological activities. We have previously shown that buckwheat sprouts (TBWE) treated with methyl jasmonate (MeJA) significantly increased the amount of phenolics and the antioxidant activity. The aim of this study was to demonstrate the effect of TBWE on anti-adipogenesis and pro-oxidant enzyme in 3T3-L1 adipocytes. We also evaluated the anti-oxidative activity of TBWE in adipocytes by using the nitroblue tetrazolium assay. Our data showed that TBWE markedly inhibited adipocyte differentiation and ROS production in 3T3-L1 cells compared with control groups. Moreover, TBWE has strongly shown the inhibition of adipogenic transcription factor as well as pro-oxidant enzymes. Together, we demonstrate that the MeJA treatment significantly increased the amount of phenolic compound, resulting in the suppression of adipogenesis and ROS production in the 3T3-L1 cells. These findings indicate that TBWE has the potential for anti-adipogenesis activity with anti-oxidative properties. PMID:23344050

Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities

PubMed Central

Rahmani, Arshad H; shabrmi, Fahad M Al; Aly, Salah M

2014-01-01

The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities. PMID:25057339

Activated mineral powders for asphalt concrete mixture

NASA Astrophysics Data System (ADS)

Kuznetsov, D. A.; Lukash, E. A.

2018-03-01

Possibilities of activation of disperse mineral powders from the technogenic raw materials of KMA by ultraviolet irradiation are considered in this article. The optimum time of ultraviolet exposure for each material is determined during which the concentration of exchange centers is increased, the rate of rehydration is slowed down and the moisture absorption is significantly reduced. It is shown that both physical and mechanical characteristics, as well as durability of asphalt concrete prepared on the basis of modified mineral powders are significantly increased.

Wheelchair-specific fitness of persons with a long-term spinal cord injury: cross-sectional study on effects of time since injury and physical activity level.

PubMed

de Groot, Sonja; van der Scheer, Jan W; Bakkum, Arjan J T; Adriaansen, Jacinthe J E; Smit, Christof A; Dijkstra, Catja; Post, Marcel W M; van der Woude, Lucas H V

2016-01-01

To study the impact of time since injury (TSI) and physical activity (PA) on fitness of persons with spinal cord injury (SCI). Cross-sectional study. Persons with SCI (N = 158) in three TSI strata: 10-19, 20-29 and ≥30 years after SCI and divided in an active and inactive group. Fitness [peak power output (POpeak) and peak oxygen uptake (VO2peak)] was assessed. In persons with tetraplegia, no significant relationship was found between TSI and fitness after controlling for confounders, while a higher activity level was related to a higher POpeak in this group. Active people with tetraplegia also showed less decline in POpeak with an increase in TSI compared to inactive people. In persons with paraplegia, after controlling for confounders, it was shown that TSI had a negative effect on POpeak, while PA was not significantly associated with fitness in people with paraplegia. In people with paraplegia, fitness was significantly lower in those with a longer TSI. Persons with a long TSI might need more attention to remain fit and PA might be an important element in that respect as shown by the results of the group with a tetraplegia. Wheelchair-specific fitness seems to diminish over time after paraplegia. An active lifestyle is related to wheelchair-specific fitness in persons with tetraplegia. Prevention of long-term deconditioning is very important.

Mean platelet volume, an indicator of platelet reactivity, is increased in patients with patent foramen ovale.

PubMed

Varol, Ercan; Uysal, Bayram A; Ersoy, Ibrahim; Ozaydin, Mehmet; Erdogan, Dogan; Dogan, Abdullah

2013-09-01

Numerous studies have shown an association between patent foramen ovale (PFO) and cryptogenic stroke suggesting that paradoxical emboli may be an important cause of stroke. In addition, some authors have proposed that platelet activation is present in PFO patients and this might be the cause of the stroke. The aim of this study was to assess the mean platelet volume (MPV), an indicator of platelet activation and/or reactivity in patients with PFO. The study group consisted of 77 patients with PFO. An age, sex, BMI-matched control group was composed of 43 healthy volunteers. We measured serum MPV values in patients and controls. MPV was significantly higher among PFO patients when compared with control group (9.0±0.8 vs. 8.3±0.9 fl, respectively; P<0.001). We have shown that MPV was significantly elevated in patients with PFO compared with controls.

Neural mechanisms of attentional control differentiate trait and state negative affect.

PubMed

Crocker, Laura D; Heller, Wendy; Spielberg, Jeffrey M; Warren, Stacie L; Bredemeier, Keith; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2012-01-01

The present research examined the hypothesis that cognitive processes are modulated differentially by trait and state negative affect (NA). Brain activation associated with trait and state NA was measured by fMRI during an attentional control task, the emotion-word Stroop. Performance on the task was disrupted only by state NA. Trait NA was associated with reduced activity in several regions, including a prefrontal area that has been shown to be involved in top-down, goal-directed attentional control. In contrast, state NA was associated with increased activity in several regions, including a prefrontal region that has been shown to be involved in stimulus-driven aspects of attentional control. Results suggest that NA has a significant impact on cognition, and that state and trait NA disrupt attentional control in distinct ways.

Ethnopharmacological investigation of the diuretic and hemodynamic properties of native species of the Brazilian biodiversity.

PubMed

Lima Prando, Thiago Buno; Barboza, Lorena Neris; Gasparotto, Francielly Mourão; Araújo, Valdinei de Oliveira; Slgnor Tirloni, Cleide Adriane; de Souza, Lauro Mera; Lourenço, Emerson Luiz Botelho; Gasparotto Junior, Arquimedes

2015-11-04

Although Echinodorus grandiflorus, Cuphea carthagenensis, and Phyllanthus tenellus infusions are used in Brazilian folk medicine due to their possible diuretic effect, none of these species was critically investigated as a diuretic drug. So, the aim of this study was to evaluate the possible acute diuretic activity of ethanol soluble fractions (ES) obtained from these species and assess the relationship between renal cortical blood flow and their antioxidant and hypotensive activity using normotensive Wistar rats. The preparation obtained from E. grandiflorus (ES-EG), C. carthagenensis (ES-CC), and P. tenellus (ES-PT) infusions was orally administered in a single dose to rats. Urine excretion rate, pH, density, conductivity and Na(+), K(+), Cl(-) and HCO3(-) contents were measured in the urine of saline-loaded animals. Concentration of electrolytes, total protein, urea, creatinine, and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The involvement of the renal cortical blood flow and antioxidative activity in the hypotensive and diuretic effects was also determined. Water and Na(+), Cl(-) and Na(+) excretion rates were significantly increased by ES-EG, while urinary bicarbonate excretion was reduced. Moreover, ES obtained from E. grandiflorus was able to significantly increase renal blood flow and reduce mean arterial pressure and oxidative stress in "in vitro" and "in vivo" models. All other parameters evaluated were not affected by any treatment. The results presented here shown that the ES-EG obtained from E. grandiflorus leaves shown a significant diuretic and hypotensive activity and suggest that these effects could be related with an important renal and systemic vasodilator effect. In addition, it was shown for the first time that the pharmacological effects of ES obtained from P. tenellus and C. carthagenensis do not support its popular use as a diuretic agent. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Variations in solar Lyman alpha irradiance on short time scales

NASA Astrophysics Data System (ADS)

Pap, J. M.

1992-10-01

Variations in solar UV irradiance at Lyman alpha are studied on short time scales (from days to months) after removing the long-term changes over the solar cycle. The SME/Lyman alpha irradiance is estimated from various solar indices using linear regression analysis. In order to study the nonlinear effects, Lyman alpha irradiance is modeled with a 5th-degree polynomial as well. It is shown that the full-disk equivalent width of the He line at 1083 nm, which is used as a proxy for the plages and active network, can best reproduce the changes observed in Lyman alpha. Approximately 72 percent of the solar-activity-related changes in Lyman alpha irradiance arise from plages and the network. The network contribution is estimated by the correlation analysis to be about 19 percent. It is shown that significant variability remains in Lyman alpha irradiance, with periods around 300, 27, and 13.5d, which is not explained by the solar activity indices. It is shown that the nonlinear effects cannot account for a significant part of the unexplained variation in Lyman alpha irradiance. Therefore, additional events (e.g., large-scale motions and/or a systematic difference in the area and intensity of the plages and network observed in the lines of Ca-K, He 1083, and Lyman alpha) may explain the discrepancies found between the observed and estimated irradiance values.

Variations in solar Lyman alpha irradiance on short time scales

NASA Technical Reports Server (NTRS)

Pap, J. M.

1992-01-01

Variations in solar UV irradiance at Lyman alpha are studied on short time scales (from days to months) after removing the long-term changes over the solar cycle. The SME/Lyman alpha irradiance is estimated from various solar indices using linear regression analysis. In order to study the nonlinear effects, Lyman alpha irradiance is modeled with a 5th-degree polynomial as well. It is shown that the full-disk equivalent width of the He line at 1083 nm, which is used as a proxy for the plages and active network, can best reproduce the changes observed in Lyman alpha. Approximately 72 percent of the solar-activity-related changes in Lyman alpha irradiance arise from plages and the network. The network contribution is estimated by the correlation analysis to be about 19 percent. It is shown that significant variability remains in Lyman alpha irradiance, with periods around 300, 27, and 13.5d, which is not explained by the solar activity indices. It is shown that the nonlinear effects cannot account for a significant part of the unexplained variation in Lyman alpha irradiance. Therefore, additional events (e.g., large-scale motions and/or a systematic difference in the area and intensity of the plages and network observed in the lines of Ca-K, He 1083, and Lyman alpha) may explain the discrepancies found between the observed and estimated irradiance values.

Synthetic bioactive novel ether based Schiff bases and their copper(II) complexes

NASA Astrophysics Data System (ADS)

Shabbir, Muhammad; Akhter, Zareen; Ismail, Hammad; Mirza, Bushra

2017-10-01

Novel ether based Schiff bases (HL1- HL4) were synthesized from 5-chloro-2-hydroxy benzaldehyde and primary amines (1-amino-4-phenoxybenzene, 4-(4-aminophenyloxy) biphenyl, 1-(4-aminophenoxy) naphthalene and 2-(4-aminophenoxy) naphthalene). From these Schiff bases copper(II) complexes (Cu(L1)2-Cu(L4)2)) were synthesized and characterized by elemental analysis and spectroscopic (FTIR, NMR) techniques. The synthesized Schiff bases and copper(II) complexes were further assessed for various biological studies. In brine shrimp assay the copper(II) complexes revealed 4-fold higher activity (LD50 3.8 μg/ml) as compared with simple ligands (LD50 12.4 μg/ml). Similar findings were observed in potato disc antitumor assay with higher activities for copper(II) complexes (IC50 range 20.4-24.1 μg/ml) than ligands (IC50 range 40.5-48.3 μg/ml). DPPH assay was performed to determine the antioxidant potential of the compounds. Significant antioxidant activity was shown by the copper(II) complexes whereas simple ligands have shown no activity. In DNA protection assay significant protection behavior was exhibited by simple ligand molecules while copper(II) complexes showed neutral behavior (neither protective nor damaging).

Stiffness and Damping in Postural Control Increase with Age

PubMed Central

Cenciarini, Massimo; Loughlin, Patrick J.; Sparto, Patrick J.; Redfern, Mark S.

2011-01-01

Upright balance is believed to be maintained through active and passive mechanisms, both of which have been shown to be impacted by aging. A compensatory balance response often observed in older adults is increased co-contraction, which is generally assumed to enhance stability by increasing joint stiffness. We investigated the effect of aging on standing balance by fitting body sway data to a previously-developed postural control model that includes active and passive stiffness and damping parameters. Ten young (24 ± 3 y) and seven older (75 ± 5 y) adults were exposed during eyes-closed stance to perturbations consisting of lateral pseudorandom floor tilts. A least-squares fit of the measured body sway data to the postural control model found significantly larger active stiffness and damping model parameters in the older adults. These differences remained significant even after normalizing to account for different body sizes between the young and older adult groups. An age effect was also found for the normalized passive stiffness, but not for the normalized passive damping parameter. This concurrent increase in active stiffness and damping was shown to be more stabilizing than an increase in stiffness alone, as assessed by oscillations in the postural control model impulse response. PMID:19770083

Improvement of thermostability and activity of firefly luciferase through [TMG][Ac] ionic liquid mediator.

PubMed

Ebrahimi, Mehdi; Hosseinkhani, Saman; Heydari, Akbar; Khavari-Nejad, Ramazan Ali; Akbari, Jafar

2012-10-01

Firefly luciferase catalyzes production of light from luciferin in the presence of Mg(2+)-ATP and oxygen. This enzyme has wide range of applications in biotechnology and development of biosensors. The low thermal stability of wild-type firefly luciferase is a limiting factor in most applications. Improvements in activity and stability of few enzymes in the presence of ionic liquids were shown in many reports. In this study, kinetic and thermal stability of firefly luciferase from Photinus pyralis in the presence of three tetramethylguanidine-based ionic liquids was investigated. The enzyme has shown improved activity in the presence of [1, 1, 3, 3-tetramethylguanidine][acetate], but in the presence of [TMG][trichloroacetate] and [TMG][triflouroacetate] activity, it decreased or unchanged significantly. Among these ionic liquids, only [TMG][Ac] has increased the thermal stability of luciferase. Incubation of [TMG][Ac] with firefly luciferase brought about with decrease of K(m) for ATP.

Flavocoxid, a Nutraceutical Approach to Blunt Inflammatory Conditions

PubMed Central

Squadrito, Francesco; Mecchio, Anna

2014-01-01

Flavonoids, from Scutellaria baicalensis (Chinese skullcap) and Acacia catechu (black catechu), have been shown to exert a variety of therapeutic effects, including anti-inflammatory, antiviral, antibacterial, and anticancer activities. Flavocoxid is a mixed extract containing baicalin and catechin and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Controlled clinical trials and a postmarketing study have clearly shown that flavocoxid is as effective as naproxen in managing the signs and symptoms of osteoarthritis of the knee and it has better upper gastrointestinal, renal, and respiratory safety profile than naproxen. Flavocoxid may therefore provide a potential therapeutic approach to the treatment of chronic inflammatory conditions. PMID:25242871

Flavocoxid, a nutraceutical approach to blunt inflammatory conditions.

PubMed

Bitto, Alessandra; Squadrito, Francesco; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Mecchio, Anna; Galfo, Federica; Altavilla, Domenica

2014-01-01

Flavonoids, from Scutellaria baicalensis (Chinese skullcap) and Acacia catechu (black catechu), have been shown to exert a variety of therapeutic effects, including anti-inflammatory, antiviral, antibacterial, and anticancer activities. Flavocoxid is a mixed extract containing baicalin and catechin and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Controlled clinical trials and a postmarketing study have clearly shown that flavocoxid is as effective as naproxen in managing the signs and symptoms of osteoarthritis of the knee and it has better upper gastrointestinal, renal, and respiratory safety profile than naproxen. Flavocoxid may therefore provide a potential therapeutic approach to the treatment of chronic inflammatory conditions.

Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1DeltaE9 mouse model of Alzheimer's disease.

PubMed

Toledo, E M; Inestrosa, N C

2010-03-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, accumulation of the amyloid-beta-peptide (Abeta) and synaptic alterations. Treatment with lithium has been shown to provide neuroprotection against several insults, including protection against Abeta neurotoxicity in vitro. Rosiglitazone, a peroxisome proliferator activated receptor-gamma agonist, has been shown to attenuate Abeta-peptide neurotoxic effects, including the inflammatory response of microglia and astrocytes. Both types of drugs activate Wnt signaling, a pathway that has been shown to be related to AD. In this study, a double transgenic mouse model, which coexpresses APPswe and the exon 9 deletion of the presenilin 1 (PSEN1) gene, was used to examine, in vivo, the effect of lithium and rosiglitazone on Abeta neurotoxicity. Mice were tested for spatial memory, and their brain samples were used for histochemical and biochemical analysis. In this study, we report that both drugs significantly reduced (1) spatial memory impairment induced by amyloid burden; (2) Abeta aggregates and Abeta oligomers; and (3) astrocytic and microglia activation. They also prevented changes in presynaptic and postsynaptic marker proteins. Finally, both drugs activate Wnt signaling shown by the increase in beta-catenin and by the inhibition of the glycogen synthase kinase-3beta. We conclude that lithium and rosiglitazone, possibly by the activation of the Wnt signaling pathway, reduce various AD neuropathological markers and may be considered as potential therapeutic agents against the disease.

The role of turmerones on curcumin transportation and P-glycoprotein activities in intestinal Caco-2 cells.

PubMed

Yue, Grace G L; Cheng, Sau-Wan; Yu, Hua; Xu, Zi-Sheng; Lee, Julia K M; Hon, Po-Ming; Lee, Mavis Y H; Kennelly, Edward J; Deng, Gary; Yeung, Simon K; Cassileth, Barrie R; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B S

2012-03-01

The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most well-studied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of α- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. α-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e., inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and P-gp (MDR1 gene) mRNA expression levels. The effects of α- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases.

The Role of Turmerones on Curcumin Transportation and P-Glycoprotein Activities in Intestinal Caco-2 Cells

PubMed Central

Yue, Grace G.L.; Cheng, Sau-Wan; Yu, Hua; Xu, Zi-Sheng; Lee, Julia K.M.; Hon, Po-Ming; Lee, Mavis Y.H.; Kennelly, Edward J.; Deng, Gary; Yeung, Simon K.; Cassileth, Barrie R.; Fung, Kwok-Pui; Leung, Ping-Chung

2012-01-01

Abstract The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most well-studied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of α- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. α-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e., inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and P-gp (MDR1 gene) mRNA expression levels. The effects of α- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases. PMID:22181075

Phillips CO-oxidation catalyts for long-lived CO2 lasers: Activity and initial characterization studies

NASA Technical Reports Server (NTRS)

Kolts, J. H.; Elliott, D. J.; Pennella, F.

1990-01-01

Four different catalysts have been developed specifically for use in sealed carbon dioxide lasers. The catalysts have been designed to be low dusting, stable to shock and vibration, have high activity at low temperatures and have long active lifetimes. Measured global CO oxidation rates range from 1.4 to 2.2 cc CO converted per minute per gram of catalyst at ambient temperature. The catalysts also retain substantial activity at temperatures as low as -35 C. The Phillips laser catalysts are prepared in a variety of different shapes to meet the different pressure drop and gas flow profiles present in the many different styles of lasers. Each catalyst has been tested in sealed TEA lasers and has been shown to substantially increase the sealed life of the laser. Activity measurements made on the precious metal catalysts which were prepared with and without activity promoters showed that the promoter materials increase catalyst CO oxidation activity at least an order of magnitude at ambient temperature. Initial studies using H2 and CO chemisorption, X ray diffraction (XRD) and X ray photoelectron spectroscopy (XPS) have shown that the activity promoters do not significantly affect the precious metal crystallite size or the electronic structure around the precious metal. In addition, the formation or lack of formation of solid solutions between the precious metal and promoters has also been shown not to affect the activity of the promoted catalyst.

Antinociceptive and anti-inflammatory activity of the ethanolic extract of Cymbidium aloifolium (L.).

PubMed

Howlader, Md Amran; Alam, Mahmudul; Ahmed, Kh Tanvir; Khatun, Farjana; Apu, Apurba Sarker

2011-10-01

The ethanol leaf extract of Cymbidium aloifolium (L.) was evaluated for its analgesic and antiinflammatory activities. The extract, at the dose of 200 and 400 mg kg(-1) body weight, exerted the analgesic activity by observing the number of abdominal contractions and anti-inflammatory activity against Carrageenin induced paw edema in mice by measuring the paw volume. The ethanolic extract of Cymbidium aloifolium (L.) showed statistically significant (p < 0.05) reduction of percentage of writhing of 33.57 and 61.31% at 200 and 400 mg kg(-1) oral dose, respectively, when compared to negative control. The Ethanolic plant extract also showed significant (p < 0.05) dose dependent reduction of mean increase of formation of paw edema. The results of the experiment and its statistical analysis showed that the ethanolic plant extract had shown significant (p < 0.05) dose dependent analgesic and anti-inflammatory activities when compared to the control.

New insights into the impact of neuro-inflammation in rheumatoid arthritis

PubMed Central

Fuggle, Nicholas R.; Howe, Franklyn A.; Allen, Rachel L.; Sofat, Nidhi

2014-01-01

Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA. PMID:25414636

Exposure to waterpipe smoke induces renal functional and oxidative biomarkers variations in mice.

PubMed

Rababa'h, Abeer M; Sultan, Bilal B; Alzoubi, Karem H; Khabour, Omar F; Ababneh, Mera A

2016-09-01

Waterpipe smoking (WPS) has been known for over 400 years. It has been spread widely especially between youth because of the addition of pleasant flavor and because it was misconsidered to be less harmful than cigarette. In this study, we investigated the effect of waterpipe smoking on renal oxidative and functional parameters and compared that at acute and chronic exposure time in mice. Mice were divided into three groups, namely acute, chronic and fresh air control. Acute group was exposed to waterpipe smoke for one hour daily for six days using whole-body exposure system, while chronic group was exposed to waterpipe smoke for one hour daily for 30 days using whole-body exposure system. Exposure to waterpipe smoke has shown significant changes on the mice kidney functional parameters such as creatinine and blood urea nitrogen. Both exposures (acute and chronic) has shown a significant reduction in superoxide dismutase (SOD) activity (p < 0.05), whereas the activity of other antioxidant enzymes (catalase and GPx) reduced only with chronic exposure to waterpipe smoke (p < 0.05). Additionally, the level of thiobarbituric acid reactive substances (TBARS) in mice kidney homogenates has shown a significant elevation following chronic exposure to waterpipe smoke (p < 0.05). In conclusion, chronic waterpipe smoke affects the kidney parameter and antioxidant markers, therefore affecting its functionality of detoxifying and removal of poisonous material from the body.

Antioxidant and antiproliferative activities in different maturation stages of broccoli (Brassica oleracea Italica) biofortified with selenium.

PubMed

Bachiega, Patricia; Salgado, Jocelem Mastrodi; de Carvalho, João Ernesto; Ruiz, Ana Lúcia T G; Schwarz, Kélin; Tezotto, Tiago; Morzelle, Maressa Caldeira

2016-01-01

In this work, three different broccoli maturity stages subjected to biofortification with selenium were evaluated for antioxidant and antiproliferative activities. Antioxidant trials have shown that the maturation stages biofortified with selenium had significantly higher amounts of phenolic compounds and antioxidant activity, especially seedlings. Although non-polar extracts of all samples show antiproliferative activity, the extract of broccoli seedlings biofortified with selenium stood out, presenting cytocidal activity for a glioma line (U251, GI50 28.5 mg L(-1)). Copyright © 2015 Elsevier Ltd. All rights reserved.

Orally available stilbene derivatives as potent HDAC inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts.

PubMed

Kachhadia, Virendra; Rajagopal, Sridharan; Ponpandian, Thanasekaran; Vignesh, Radhakrishnan; Anandhan, Karnambaram; Prabhu, Daivasigamani; Rajendran, Praveen; Nidhyanandan, Saranya; Roy, Anshu Mittal; Ahamed, Fakrudeen Ali; Surendran, Narayanan; Rajagopal, Sriram; Narayanan, Shridhar; Gopalan, Balasubramanian

2016-01-27

Herein we report the synthesis and activity of a novel class of HDAC inhibitors based on 2, 3-diphenyl acrylic acid derivatives. The compounds in this series have shown to be potent HDAC inhibitors possessing significant antiproliferative activity. Further compounds in this series were subjected to metabolic stability in human liver microsomes (HLM), mouse liver microsomes (MLM), and exhibits promising stability in both. These efforts culminated with the identification of a developmental candidate (5a), which displayed desirable PK/PD relationships, significant efficacy in the xenograft models and attractive ADME profiles. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Physangulidines A, B, and C: three new antiproliferative withanolides from Physalis angulata L.

PubMed

Jin, Zhuang; Mashuta, Mark S; Stolowich, Neal J; Vaisberg, Abraham J; Stivers, Nicole S; Bates, Paula J; Lewis, Walter H; Hammond, Gerald B

2012-03-02

Bioassay-directed fractionation of the whole plant of Physalis angulata L. afforded three new antiproliferative withanolides with an unusual carbon framework: physangulidines A (1), B (2), and C (3). Structures of the three isomeric withanolides were determined by a combination of HRMS, NMR spectroscopic, and X-ray crystallographic methods. Each has shown significant antiproliferative activity against DU145 prostate cancer cells. Physangulidine A (1) was further tested against a wide range of additional cancer cell lines and found to exhibit significant antiproliferative activity. © 2012 American Chemical Society

Synthesis of (-)-callicarpenal a natural arthropod-repellent terpenoid

USDA-ARS?s Scientific Manuscript database

Callicarpenal, a natural terpenoid extracted from American beautyberry (Callicarpa americana), has shown significant repellent activity against mosquitoes, ticks and imported fire ants. Here we report an efficient synthetic approach to this natural product. We also present results of the mosquito ...

Toward an objective indexing system for ADHD-screening using children's activity monitoring.

PubMed

Kam, Hye Jin; Choi, Jong Pil; Park, Rae Woong

2008-11-06

Signs of ADHD are discernible in specific situations, and usually assessed according to subjective impressions. We performed a preliminary comparative study from children's activity at a natural classroom environment with 3-axis accelerator for a feasible objective index. From a total of 157 children (7-9 yrs) and clinically diagnosed 24 children out of them, variances in 1-min epoch mean activity had shown significant differences among the subgroups: (1) ADHD=.0194, Other Diseases=.0080, Normal=.0009; (2) ADHD=.0194, non-ADHD=.0057(p<.01, respectively). There were also significant differences in high-level activity (>1.6G) features among subgroups with the same order (p<.01, respectively). ADHD patients exhibited more dispersed activities and higher high-level activity ratio than normal. Activity features can be useful to build an objective indexing system for screening ADHD patients.

THE EFFECTS OF ULTRAVIOLET LIGHT AND GAMMA RAYS ON CELL LIPIDS AND THE PHYSIOLOGICAL ACTION OF IRRADIATED LIPIDS. Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernheim, F.; Wilbur, K.M.

1962-03-26

Results are summarized from a series of studies on the effects of ultraviolet and ionizing radiation on the oxidation of cell lipids. It was shown that both in vitro and in vivo radiation produced oxidation products of lipids that inhibited the activity of certain oxidative enzymes, depolymerized desoxyribonucleoprotein, inhibited the division of marine eggs, and retarded bacterial growth. The presence of antioxidant activity was also demonstrated in tissues. The significant feature of antioxidant compounds with respect to the biological effects of radiation was shown to be the inhibition of the oxidation of lipids. In irradiated animals the antioxidant activity ofmore » the intestinal mucosa and the activity of phospholipase decreased. Experiments showed that radiation had not destroyed the enzyme but had inactivated the activator. Results are also summarized from a study on the effects of ionizing radiation on cell growth and protein synthesis in yeast. (C.H.)« less

The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine.

PubMed

Gomez-Ramirez, Manuel; Higgins, Beth A; Rycroft, Jane A; Owen, Gail N; Mahoney, Jeannette; Shpaner, Marina; Foxe, John J

2007-01-01

: Ingestion of the nonproteinic amino acid theanine (5-N-ethylglutamine) has been shown to increase oscillatory brain activity in the so-called alpha band (8-14 Hz) during resting electroencephalographic recordings in humans. Independently, alpha band activity has been shown to be a key component in selective attentional processes. Here, we set out to assess whether theanine would cause modulation of anticipatory alpha activity during selective attentional deployments to stimuli in different sensory modalities, a paradigm in which robust alpha attention effects have previously been established. : Electrophysiological data from 168 scalp electrode channels were recorded while participants performed a standard intersensory attentional cuing task. : As in previous studies, significantly greater alpha band activity was measured over parieto-occipital scalp for attentional deployments to the auditory modality than to the visual modality. Theanine ingestion resulted in a substantial overall decrease in background alpha levels relative to placebo while subjects were actively performing this demanding attention task. Despite this decrease in background alpha activity, attention-related alpha effects were significantly greater for the theanine condition. : This increase of attention-related anticipatory alpha over the right parieto-occipital scalp suggests that theanine may have a specific effect on the brain's attention circuitry. We conclude that theanine has clear psychoactive properties, and that it represents a potentially interesting, naturally occurring compound for further study, as it relates to the brain's attentional system.

Neural Mechanisms of Attentional Control Differentiate Trait and State Negative Affect

PubMed Central

Crocker, Laura D.; Heller, Wendy; Spielberg, Jeffrey M.; Warren, Stacie L.; Bredemeier, Keith; Sutton, Bradley P.; Banich, Marie T.; Miller, Gregory A.

2012-01-01

The present research examined the hypothesis that cognitive processes are modulated differentially by trait and state negative affect (NA). Brain activation associated with trait and state NA was measured by fMRI during an attentional control task, the emotion-word Stroop. Performance on the task was disrupted only by state NA. Trait NA was associated with reduced activity in several regions, including a prefrontal area that has been shown to be involved in top-down, goal-directed attentional control. In contrast, state NA was associated with increased activity in several regions, including a prefrontal region that has been shown to be involved in stimulus-driven aspects of attentional control. Results suggest that NA has a significant impact on cognition, and that state and trait NA disrupt attentional control in distinct ways. PMID:22934089

Synaptic Activation of Ribosomal Protein S6 Phosphorylation Occurs Locally in Activated Dendritic Domains

ERIC Educational Resources Information Center

Pirbhoy, Patricia Salgado; Farris, Shannon; Steward, Oswald

2016-01-01

Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6)…

Increased erythrocyte Na+ pump and NaK-ATPase activity during lithium therapy.

PubMed

Hokin-Neaverson, M; Burckhardt, W A; Jefferson, J W

1976-05-01

A significant mean increase of 18% in erythrocyte sodium pump activity (p less than 0.01, t test) was observed during lithium treatment, as compared with the activity before lithium treatment was started, in a group of 20 patients who were treated with lithium therapy for a variety of psychiatric conditions. The mean level of erythrocyte membrane ouabain-sensitive ATPase activity in a group of 35 subjects who were receiving lithium therapy was significantly higher than that of a different group of 38 subjects who were not receiving lithium therapy (p less than 0.005, t test). These observations may offer a biochemical mode of action for lithium in the treatment of bipolar affective disorder, since a deficiency of sodium pump activity has been shown to be associated with that disorder.

Impacts of human activity modes and climate on heavy metal "spread" in groundwater are biased.

PubMed

Chen, Ming; Qin, Xiaosheng; Zeng, Guangming; Li, Jian

2016-06-01

Groundwater quality deterioration has attracted world-wide concerns due to its importance for human water supply. Although more and more studies have shown that human activities and climate are changing the groundwater status, an investigation on how different groundwater heavy metals respond to human activity modes (e.g. mining, waste disposal, agriculture, sewage effluent and complex activity) in a varying climate has been lacking. Here, for each of six heavy metals (i.e. Fe, Zn, Mn, Pb, Cd and Cu) in groundwater, we use >330 data points together with mixed-effect models to indicate that (i) human activity modes significantly influence the Cu and Mn but not Zn, Fe, Pb and Cd levels, and (ii) annual mean temperature (AMT) only significantly influences Cu and Pb levels, while annual precipitation (AP) only significantly affects Fe, Cu and Mn levels. Given these differences, we suggest that the impacts of human activity modes and climate on heavy metal "spread" in groundwater are biased. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased serum butyrylcholinesterase activity in type IIb hyperlipidaemic patients.

PubMed

Kálmán, János; Juhász, Anna; Rakonczay, Zoltán; Abrahám, György; Zana, Marianna; Boda, Krisztina; Farkas, Tibor; Penke, Botond; Janka, Zoltán

2004-07-23

The inheritance of the apolipoprotein E4 (APOE4) allele has been shown to increase the plasma cholesterol level, but little information is as concerns the association of the APOE genotype and hyperlipidaemia and the activities of two serum enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Blood samples from 55 type IIb hyperlipidaemic, non-demented patients and 55 age- and sex-matched controls were therefore examined in this pilot study. A significantly increased BChE activity was found in the serum of type IIb hyperlipidaemic patients, but the AChE activity did not differ significantly as compared with that in the control group. The APOE4 allele was significantly overrepresented among the hyperlipidaemic probands, but neither serum cholinesterase activity was affected by the dosage of the APOE4 gene. Our results point to a possible association between an abnormal lipid metabolism and the BChE activity and might have implications as regards the pathomechanism of both Alzheimer's and vascular dementias and the cholinesterase inhibitor therapy of dementing disorders.

Cross-modal pattern of brain activations associated with the processing of self- and significant other's name.

PubMed

Tacikowski, Pawel; Brechmann, André; Nowicka, Anna

2013-09-01

Previous neuroimaging studies have shown that the patterns of brain activity during the processing of personally relevant names (e.g., own name, friend's name, partner's name, etc.) and the names of famous people (e.g., celebrities) are different. However, it is not known how the activity in this network is influenced by the modality of the presented stimuli. In this fMRI study, we investigated the pattern of brain activations during the recognition of aurally and visually presented full names of the subject, a significant other, a famous person and unknown individuals. In both modalities, we found that the processing of self-name and the significant other's name was associated with increased activation in the medial prefrontal cortex (MPFC). Acoustic presentations of these names also activated bilateral inferior frontal gyri (IFG). This pattern of results supports the role of MPFC in the processing of personally relevant information, irrespective of their modality. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Driver fatigue: electroencephalography and psychological assessment.

PubMed

Lal, Saroj K L; Craig, Ashley

2002-05-01

Fatigue has major implications for transportation system safety; therefore, investigating the psychophysiological links to fatigue could enhance our understanding and management of fatigue in the transport industry. This study examined the psychophysiological changes that occurred during a driver simulator task in 35 randomly selected subjects. Results showed that significant electroencephalographic changes occur during fatigue. Delta and theta activity were found to increase significantly during fatigue. Heart rate was significantly lower after the driving task. Blink rate also changed during the fatigue task. Increased trait anxiety, tension-anxiety, fatigue-inertia and reduced vigor-activity were shown to be associated with neurophysiological indicators of fatigue such as increased delta and theta activity. The results are discussed in light of directions for future studies and for the development of a fatigue countermeasure device.

[Itraconazole action on Toxoplasma gondii].

PubMed

Jamra, L M; Amato Neto, V; Braz, L M; Camargo, M E

1992-01-01

With the purpose to increase our knowledge about the spectrum of therapeutic action of itraconazole, the activity of a new triazolic derivative against Toxoplasma gondii was studied in vivo and in vitro with the aid of an experimental infection model in mice. The trial also aimed at a possible improvement of the therapy of toxoplasmosis in regard to safety and dosing easiness. The present study has not shown significant activity of itraconazole against Toxoplasma gondii, differing from a previous observation that showed it's activity against Trypanosoma cruzi.

The energy expenditure of an activity-promoting video game compared to sedentary video games and TV watching.

PubMed

Mitre, Naim; Foster, Randal C; Lanningham-Foster, Lorraine; Levine, James A

2011-01-01

In the present study we investigated the effect of television watching and the use of activity-promoting video games on energy expenditure in obese and lean children. Energy expenditure and physical activity were measured while participants were watching television, playing a video game on a traditional sedentary video game console, and while playing the same video game on an activity-promoting video game console. Energy expenditure was significantly greater than television watching and playing video games on a sedentary video game console when children played the video game on the activity-promoting console. When examining movement with accelerometry, children moved significantly more when playing the video game on the Nintendo Wii console. Activity-promoting video games have shown to increase movement, and be an important tool to raise energy expenditure by 50% when compared to sedentary activities of daily living.

In Vitro Screening for Cytotoxic Activity of Herbal Extracts

PubMed Central

Lombardi, Valter R. M.; Cacabelos, Ramón

2017-01-01

Experimental studies have shown that a variety of chemopreventive plant components affect tumor initiation, promotion, and progression and the main difference, between botanical medicines and synthetic drugs, resides in the presence of complex metabolite mixtures shown by botanical medicine which in turn exert their action on different levels and via different mechanisms. In the present study, we performed an in vitro screening of ethanol extracts from commercial plants in order to investigate potential antitumor activity against human tumor cell lines. Experimental results obtained through a variety of methods and techniques indicated that extracts of I. verum, G. glabra, R. Frangula, and L. usitatissimum present significant reduction in in vitro tumor cell proliferation, suggesting these extracts as possible chemotherapeutical adjuvants for different cancer treatments. PMID:28386288

The Effect of Chronic Renal Failure on Drug Metabolism and Transport

PubMed Central

Dreisbach, Albert W; Lertora, Juan JL

2009-01-01

Background Chronic renal failure (CRF) has been shown to significantly reduce the nonrenal clearance and alter bioavailability of drugs predominantly metabolized by the liver and intestine. Objectives The purpose of this article is to review all significant animal and clinical studies dealing with the effect of CRF on drug metabolism and transport. Methods The National Library of Medicine PubMed was utilized with the search terms ‘chronic renal failure, cytochrome P450, liver metabolism, efflux drug transport and uptake transport’ including relevant articles back to 1969. Results Animal studies in CRF have shown a major downregulation (40-85%) of hepatic and intestinal cytochrome P450 (CYP) metabolism. High levels of parathyroid hormone, cytokines, and uremic toxins have been shown to reduce CYP activity. Phase II reactions and drug transporters such as P-glycoprotein (Pgp) and organic anion transporting polypeptide (OATP) are also affected. Conclusion CRF alters intestinal, renal, and hepatic drug metabolism and transport producing a clinically significant impact on drug disposition and increasing the risk for adverse drug reactions. PMID:18680441

Immobilization of fungal beta-glucosidase on silica gel and kaolin carriers.

PubMed

Karagulyan, Hakob K; Gasparyan, Vardan K; Decker, Stephen R

2008-03-01

Beta-glucosidase is a key enzyme in the hydrolysis of cellulose for producing feedstock glucose for various industrial processes. Reuse of enzyme through immobilization can significantly improve the economic characteristics of the process. Immobilization of the fungal beta-glucosidase by covalent binding and physical adsorption on silica gel and kaolin was conducted for consequent application of these procedures in large-scale industrial processes. Different immobilization parameters (incubation time, ionic strength, pH, enzyme/support ratio, glutaric aldehyde concentration, etc.) were evaluated for their effect on the thermal stability of the immobilized enzyme. It was shown that the immobilized enzyme activity is stable at 50 degrees C over 8 days. It has also been shown that in the case of immobilization on kaolin, approximately 95% of the initial enzyme was immobilized onto support, and loss of activity was not observed. However, covalent binding of the enzyme to silica gel brings significant loss of enzyme activity, and only 35% of activity was preserved. In the case of physical adsorption on kaolin, gradual desorption of enzyme takes place. To prevent this process, we have carried out chemical modification of the protein. As a result, after repeated washings, enzyme desorption from kaolin has been reduced from 75 to 20-25% loss.

Induction of sister chromatid exchanges and cell division delays in human lymphocytes by the anti-tumour agent homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenoxy acetic acid.

PubMed

Tselepi, M R; Demopoulos, N A; Catsoulacos, P

1989-09-01

3 beta-Hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl) aminophenoxyacetate (NSC 294859) is a new modified steroidal alkylating agent. This compound was given by i.p. administration to mice bearing different types of tumour. It was found to exhibit good activity in L1210 and P388 leukaemias with maintenance of activity against advanced tumours. The treatment of colon 26 tumour and B16 melanoma resulted in positive antineoplastic activity. The drug was not shown to be active in a melphalan-resistant P388 line. In this study, NSC 294859 was found to be effective in causing statistically significant increases in sister-chromatid exchange (SCE) rates and cell division delays. The alkylating agent component, p-bis-(2-chloroethyl)aminophenoxy acetic acid, was shown to be less effective than the parent compound, while the modified steroid component, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, showed no effect. There were no statistically significant differences among donors regarding the induction of SCEs and replication indices (RIs) for the compounds tested.

Immobilization of Fungal β-Glucosidase on Silica Gel and Kaolin Carriers

NASA Astrophysics Data System (ADS)

Karagulyan, Hakob K.; Gasparyan, Vardan K.; Decker, Stephen R.

β-Glucosidase is a key enzyme in the hydrolysis of cellulose for producing feedstock glucose for various industrial processes. Reuse of enzyme through immobilization can significantly improve the economic characteristics of the process. Immobilization of the fungal β-glucosidase by covalent binding and physical adsorption on silica gel and kaolin was conducted for consequent application of these procedures in large-scale industrial processes. Different immobilization parameters (incubation time, ionic strength, pH, enzyme/support ratio, glutaric aldehyde concentration, etc.) were evaluated for their effect on the thermal stability of the immobilized enzyme. It was shown that the immobilized enzyme activity is stable at 50 °C over 8 days. It has also been shown that in the case of immobilization on kaolin, approximately 95% of the initial enzyme was immobilized onto support, and loss of activity was not observed. However, covalent binding of the enzyme to silica gel brings significant loss of enzyme activity, and only 35% of activity was preserved. In the case of physical adsorption on kaolin, gradual desorption of enzyme takes place. To prevent this process, we have carried out chemical modification of the protein. As a result, after repeated washings, enzyme desorption from kaolin has been reduced from 75 to 20-25% loss.

Geomagnetically Induced Currents Around the World During the 17 March 2015 Storm

NASA Technical Reports Server (NTRS)

Carter, B. A.; Yizengaw, E.; Pradipta, R.; Weygand, J. M.; Piersanti, M.; Pulkkinen, Antti Aleksi; Moldwin, M. B.; Norman, R.; Zhang, K.

2016-01-01

Geomagnetically induced currents (GICs) represent a significant space weather issue for power grid and pipeline infrastructure, particularly during severe geomagnetic storms. In this study, magnetometer data collected from around the world are analyzed to investigate the GICs caused by the 2015 St. Patricks Day storm. While significant GIC activity in the high-latitude regions due to storm time substorm activity is shown for this event, enhanced GIC activity was also measured at two equatorial stations in the American and Southeast Asian sectors. This equatorial GIC activity is closely examined, and it is shown that it is present both during the arrival of the interplanetary shock at the storm sudden commencement (SSC) in Southeast Asia and during the main phase of the storm approximately 10 h later in South America. The SSC caused magnetic field variations at the equator in Southeast Asia that were twice the magnitude of those observed only a few degrees to the north, strongly indicating that the equatorial electrojet (EEJ) played a significant role. The large equatorial magnetic field variations measured in South America are also examined, and the coincident solar wind data are used to investigate the causes of the sudden changes in the EEJ approximately 10 h into the storm. From this analysis it is concluded that sudden magnetopause current increases due to increases in the solarwind dynamic pressure, and the sudden changes in the resultant magnetospheric and ionospheric current systems, are the primary drivers of equatorial GICs.

RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells.

PubMed

Ning, R B; Zhu, J; Chai, D J; Xu, C S; Xie, H; Lin, X Y; Zeng, J Z; Lin, J X

2013-12-13

An inflammatory response induced by high glucose is a cause of endothelial dysfunction in diabetes and is an important contributing link to atherosclerosis. Diabetes is an independent risk factor of atherosclerosis and activation of retinoid X receptor (RXR) has been shown to exert anti-atherogenic effects. In the present study, we examined the effects of the RXR ligands 9-cis-retinoic acid (9-cis-RA) and SR11237 on high glucose-induced inflammation in human umbilical endothelial vein endothelial cells (HUVECs) and explored the potential mechanism. Our results showed that the inflammation induced by high-glucose in HUVECs was mainly mediated by the activation of nuclear factor-B (NF- κB). High glucose-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were in comparison, significantly decreased by treatment with RXR. The effect of RXR agonists was mainly due to the inhibition of NF-κB activation. Using pharmacological inhibitors and siRNA, we confirmed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was an upstream activator of NF-κB. Furthermore, RXR agonists significantly inhibited high glucose-induced activation of NADPH oxidase and significantly decreased the production of reactive oxygen species (ROS). To explore whether the rapid inhibitory effects of RXR agonists were in fact mediated by RXR, we examined the effect of RXR downregulation by RXR siRNA. Our results showed that RXR siRNA largely abrogated the effects of RXR agonists, suggesting the requirement of RXR expression. Therefore, we have shown that RXR is involved in the regulation of NADPH oxidase- NF-κB signal pathway, as the RXR ligands antagonized the inflammatory response in HUVECs induced by high glucose.

Fructans from aged garlic extract produce a delayed immunoadjuvant response to ovalbumin antigen in BALB/c mice.

PubMed

Chandrashekar, Puthanapura M; Venkatesh, Yeldur P

2012-02-01

Garlic (Allium sativum) is known for its innumerable biological activities including immunomodulation. Aged garlic extract (AGE), an odorless garlic preparation, has been shown to have superior immunomodulatory properties over raw garlic extract. Although garlic is a very rich source of fructans (17%, fresh weight basis), AGE contains only 0.22% of raw garlic fructans. Aged garlic fructans (AGF) have recently been shown to possess immunomodulatory activities in vitro. Natural adjuvants capable of eliciting better immune response of a model antigen are important in developing newer vaccines. In the present study, the adjuvant activity of AGF has been investigated in BALB/c mice using ovalbumin (OVA, 30 µg) as an experimental antigen. The body weights of animals did not change significantly indicating that the administration of garlic fructans is well-tolerated. AGF produce a significant humoral (serum IgG) response to OVA in BALB/c mice administered mucosally by either intranasal or oral route--a delayed response appearing on 50th day at a dose of 30 µg AGF by intranasal route. However, the serum IgG response was seen earlier on 35th day at a dose of 100 µg AGF by oral route. Higher concentrations of AGF (>50 µg) were inhibitory for adjuvant activity by intranasal administration. These observations indicate that AGF display immunoadjuvant activity for a test antigen though the humoral immune response is delayed.

Postprandial anti-hyperglycemic activity of marine Streptomyces coelicoflavus SRBVIT13 mediated gold nanoparticles in streptozotocin induced diabetic male albino Wister rats.

PubMed

Sathish Kumar, Sathyanarayanan Ravi; Bhaskara Rao, Kokati Venkata

2016-10-01

The present study focuses on the biosynthesis of gold nanoparticles (AuNPs) using Streptomyces coelicoflavus ( S. coelicoflavus ) SRBVIT13 isolated from marine salt pan soils collected from Ongole, Andhra Pradesh, India. The biosynthesised AuNPs are characterised by UV-visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, high-resolution transmission electron microscopy and energy-dispersive X-ray analysis. Transmission electron microscopy study suggests that the biosynthesised AuNPs are spherical in shape within a size range of 12-20 nm (mean diameter as 14 nm). The anti-type II diabetes activity of AuNPs is carried out by testing it in vitro α -glucosidase and α -amylase enzyme inhibition activity and in vivo postprandial anti-hyperglycemic activity in sucrose and glucose-loaded streptozotocin induced diabetic albino Wister rats. AuNPs has shown a significant inhibitory activity of 84.70 and 87.82% with IC 50 values of 67.65 and 65.59 μg/mL to α -glucosidase and α -amylase enzymes, while the diabetic rats have shown significant reduction in the post postprandial blood glucose level by 57.80 and 88.09%, respectively compared with control group after AuNPs treatment at the concentration of 300 and 600 mg/kg body weight. Hence, this biosynthesised AuNPs might be useful in combating type II diabetes mellitus for the betterment of human life.

Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

PubMed Central

Yue, Grace G. L.; Chan, Ben C. L.; Hon, Po-Ming; Lee, Mavis Y. H.; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B. S.

2010-01-01

The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. PMID:20438793

Preparation and characterization of nanocomposite polyvinyl chloride films with NO-generating activity

NASA Astrophysics Data System (ADS)

Kozakevych, Roman B.; Korobeinyk, Alina V.; Bolbukh, Yulia M.; Tertykh, Valentin A.; Mikhalovska, Lyuba I.; Zienkiewicz-Strzałka, Malgorzlata; Deryło-Marczewska, Anna

2018-03-01

The silica and copper oxide nanoparticles were embedded into the polyvinyl chloride film and obtained filled composites were tested as a catalyst in the reaction of the NO release from appropriate biomolecules. Obtained materials were characterized using scanning electron, atomic-force microscopies and thermomechanical analysis. It has been shown that the introduced particles are distributed uniformly in the polymeric matrix of hybrid composite and such film produces a significant amount of NO when reacts with S-nitrosothiols. At the same time, the unfilled polyvinyl chloride film had no statistically significant catalytic activity.

[The efficacy of the combined use of 5-fluorouracil electrophoresis and magnetotherapy in experimental pancreatitis].

PubMed

Kents, V V; Tsympilova, T A; Mavrodiĭ, V M; Godlevskiĭ, L S

1994-01-01

As shown on the experimental model of rat acute pancreatitis, an intensive 5-fluorouracil electrophoresis course in combination with magnetotherapy significantly reduces the activity of blood trypsin, amylase, lipase and corticosterone. The treatment is thought effective in experimental pancreatitis.

Preparation and Anti-Tumour Activity of Some Arylbismuth(III) Oxine Complexes

PubMed Central

Smith, Katharine A.; Deacon, Glen B.; Jackson, W. Roy; Tiekink, Edward R. T.; Rainone, Silvina; Webster, Lorraine K.

1998-01-01

New arylbismuth(lll) oxinates, PhBi(MeOx)2, (p-MeC6H4)Bi(Ox)2, (p-MeC6H4)Bi(MeOx)2, (p-ClC6H4)Bi(Ox)2, and (p-ClC6H4)Bi(MeOx)2 (Ox− = quinolin-8-olate and MeOx−=2-methylquinolin-8-olate) have been prepared by reaction of the appropriate diarylbismuth chlorides with Na(Ox) or Na(MeOx) in the presence of 15-crown-5. An X-ray crystallographic study has shown PhBi(MeOx)2 to be a five coordinate monomer with distorted square pyramidal stereochemistry. Chelating MeOx ligands have a cisoid arrangement in the square plane and the phenyl group is apical. The lattice is stabilised by significant π-π interactions between centrosymmetric molecules. A range of these complexes has been shown to have high in vitro biological activity (comparable with or better than cisplatin) against L1210 leukaemia, the corresponding cisplatin resistant line, and a human ovarian cell line, SKOV-3. However, initial in vivo testing against a solid mouse plasmacytoma (PC6) and P388 leukaemia has not revealed significant activity. PMID:18475861

Antibacterial activity of essential oil components and their potential use in seed disinfection.

PubMed

Lo Cantore, Pietro; Shanmugaiah, Vellasamy; Iacobellis, Nicola Sante

2009-10-28

Among the main (> or = 0.7%) components of some essential oils, considerable antibacterial activity was shown by terpenoid and phenylpropanoid derivatives containing phenol and alcohol functionalities. A reduced or no activity was shown by those derivatives containing ketones, aldehydes, ethers, and ester functionalities as well as the remaining terpenoids. Eugenol emulsion treatments (1-8 mg/mL) of bean seeds bearing about 2.6 x 10(6) cfu/seed of strain ICMP239 of Xanthomonas campestris pv. phaseoli var. fuscans determined a highly significant reduction of the bacteria on seeds. In particular, eugenol at 4 mg/mL disinfect seeds bearing about 7.0 x 10(2) cfu/seed and lower densities. However, after 72 h, incubation treatments with 2, 4, and 8 mg/mL of eugenol caused germination reduction of 3%, 7%, and 16%, respectively, which was significantly different from the controls. No effect on germination was observed with 1 mg/mL eugenol emulsion treatment. These data indicate eugenol as potentially useful for bean seed disinfection from X. campestris pv. phaseoli var. fuscans. Further studies on the effects on seed vitality and on formulation of essential oils are needed.

Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains.

PubMed

Naumenko, V S; Kondaurova, E M; Bazovkina, D V; Tsybko, A S; Tikhonova, M A; Kulikov, A V; Popova, N K

2012-07-12

The effect of brain-derived neurotrophic factor (BDNF) on depressive-like behavior and serotonin (5-HT) system in the brain of antidepressant sensitive cataleptics (ASC)/Icg mouse strain, characterized by depressive-like behavior, in comparison with the parental nondepressive CBA/Lac mouse strain was examined. Significant decrease of catalepsy and tail suspension test (TST) immobility was shown 17days after acute central BDNF administration (300ng i.c.v.) in ASC mice. In CBA mouse strain, BDNF moderately decreased catalepsy without any effect on TST immobility time. Significant difference between ASC and CBA mice in the effect of BDNF on 5-HT system was revealed. It was shown that central administration of BDNF led to increase of 5-HT(1A) receptor gene expression but not 5-HT(1A) functional activity in ASC mice. Increased tryptophan hydroxylase-2 (Tph-2) and 5-HT(2A) receptor genes expression accompanied by 5-HT(2A) receptor sensitization was shown in BDNF-treated ASC but not in CBA mouse strain, suggesting BDNF-induced increase of the brain 5-HT system functional activity and activation of neurogenesis in "depressive" ASC mice. There were no changes found in the 5-HT transporter mRNA level in BDNF-treated ASC and CBA mice. In conclusion, central administration of BDNF produced prolonged ameliorative effect on depressive-like behavior accompanied by increase of the Tph-2, 5-HT(1A) and 5-HT(2A) genes expression and 5-HT(2A) receptor functional activity in animal model of hereditary behavior disorders. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Immunomodulatory effects of hydroxyethylated Hericium erinaceus polysaccharide on macrophages RAW264.7.

PubMed

Ren, Zhe; Qin, Tao; Qiu, Fuan; Song, Yulong; Lin, Dandan; Ma, Yufang; Li, Jian; Huang, Yifan

2017-12-01

Hericium erinaceus polysaccharide (HEP) has been shown to possess a variety of biological activities. In present study, HEP was successfully modified to obtain its hydroxyethylated derivative hHEP. Its potential immunomodulatory activities on RAW264.7 macrophages were investigated. Results showed that the hHEP were significantly stronger than that of the corresponding unmodified polysaccharide, HEP. Meanwhile, the NO, IL-6 and TNF-α production activities of macrophages were enhanced in the RAW264.7 macrophages by stimulation of hHEP. In addition, the hHEP increase significantly higher iNOS expression than HEP. These results indicated that the hydroxyethylated derivative hHEP could enhance the activation of peritoneal macrophages, and hydroxyethylation modification can enhance the immunomodulation function of HEP. Copyright © 2017 Elsevier B.V. All rights reserved.

Does neighbourhood walkability moderate the effects of mass media communication strategies to promote regular physical activity?

PubMed

Barnes, R; Giles-Corti, B; Bauman, A; Rosenberg, M; Bull, F C; Leavy, J E

2013-02-01

Mass media campaigns are widely used in Australia and elsewhere to promote physical activity among adults. Neighbourhood walkability is consistently shown to be associated with walking and total activity. Campaigns may have different effects on individuals living in high and low walkable neighbourhoods. The purpose of this study is to compare pre- and post-campaign cognitive and behavioural impacts of the Heart Foundation's Find Thirty every day® campaign, in respondents living in high and lower walkable neighbourhoods. Pre- and post-campaign cross-sectional survey data were linked with objectively measured neighbourhood walkability. Cognitive and behavioural impacts were assessed using logistic regression stratified by walkability. Cognitive impacts were significantly higher post-campaign and consistently higher in respondents in high compared with lower walkable neighbourhoods. Post campaign sufficient activity was significantly higher and transport walking significantly lower, but only in residents of lower walkable areas. Cognitive impacts of mass media physical activity campaigns may be enhanced by living in a more walkable neighbourhood.

Immunomodulatory effects of an acetylated Cyclocarya paliurus polysaccharide on murine macrophages RAW264.7.

PubMed

Liu, Xin; Xie, Jianhua; Jia, Shuo; Huang, Lixin; Wang, Zhijun; Li, Chang; Xie, Mingyong

2017-05-01

Polysaccharides (CP) extracted from the leaves of Cyclocarya paliurus (C. paliurus) have been shown to possess a variety of biological activities. In present study, CP was successfully modified to obtain its acetylated derivative Ac-CP. Its potential immunomodulatory activities on RAW264.7 macrophages were investigated. Results showed that the acetylated polysaccharide Ac-CP could significantly stimulate macrophage proliferation, its actions were significantly stronger than that of the corresponding unmodified polysaccharide, CP. Meanwhile, the NO production activities of macrophages were not significantly enhanced by Ac-CP compared to CP group. In addition, both the phagocytic activity and levels of cytokines TNF-a, IL-1β and IL-6 were enhanced in the RAW264.7 macrophages by stimulation of Ac-CP. These results indicated that the acetylated derivative Ac-CP could enhance the activation of peritoneal macrophages, and acetylation modification can enhance the immunomodulation function of CP, indicating the potential application of acetylated polysaccharide as an immunotherapeutic adjuvant. Copyright © 2017 Elsevier B.V. All rights reserved.

Antiurease and anti-oxidant activity of Vaccinium macrocarpon fruit.

PubMed

Noreen, Shabana; Shaheen, Ghazala; Akram, Muhammad; Rashid, Abid; Shah, Syed Muhammad Ali

2016-07-01

The objective of present study was to evaluate the antiurease and anti-oxidant activity of Vaccinium macrocarpon fruit. The parent extract was ethanolic extract while its sub fractions were prepared in n-hexane, chloroform and n-butanol. The method based on scavenging activity and reduction capability of 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH). N-butanol fraction was the most effective antioxidant with 87.0±1.15 activity but the activity was less than ascorbic acid i.e. 93.74±0.12. Highly significant urease inhibition was shown by crude ethanolic extract (71.00±0.2a) with IC50 (392.66±2.1) followed by aqueous fraction (68.00±0.5e) with IC50 (159.83±2.8). The results of crude ethanolic extract and aqueous extracts were highly significant (p<0.05) than standard Thiourea. Present study showed that Vaccinium macrocarpon exhibits potent antiurease and antioxidant activities.

[Tobacco consumption and its relationship to the level of regular physical activity and physical fitness in adolescents from the region of Murcia (Spain)].

PubMed

García-Cantó, Eliseo; Rodríguez García, Pedro Luis; Pérez-Soto, Juan José; López Villalba, Francisco José; Rosa-Guillamón, Andrés

2015-12-01

This study looks at the relationship between tobacco consumption and the physical activity and fitness levels of adolescents. In a sample of 533 adolescents, both a questionnaire to obtain information regarding tobacco consumption and the International Physical Activity Questionnaire for information on physical activity were implemented; a battery of tests to assess physical fitness were also applied. Tobacco consumption was significantly higher in females (32.5%) than in males (25.7%). Levels of physical activity in both males and females were significantly associated with tobacco consumption (p<0.0005). Moreover, subjects who consumed tobacco showed lower overall averages in physical fitness tests than those who did not (4.26 vs. 5.77 in males and 4.54 vs. 6.71 in females). Tobacco consumption is therefore shown to be related to lower levels of physical activity and physical fitness in adolescents.

Fish hepatic glutathione-S-transferase activity is affected by the cestode parasites Schistocephalus solidus and Ligula intestinalis: evidence from field and laboratory studies.

PubMed

Frank, Sabrina Nadine; Faust, Steffen; Kalbe, Martin; Trubiroha, Achim; Kloas, Werner; Sures, Bernd

2011-06-01

The activity of hepatic glutathione-S-transferase (GST) was analysed in 3 different fish species with respect to fish sex and infection with parasites. In both sexes of laboratory bred three-spined sticklebacks (Gasterosteus aculeatus) experimentally infected with Schistocephalus solidus (Cestoda), a significantly lower GST-activity was found for infected fish compared to control. After field sampling of roach (Rutilus rutilus) from Lake Müggelsee (MS) and the Reservoir Listertalsperre (LTS), the GST-activity showed significantly lower values for males infected with Ligula intestinalis from MS (25%) and for infected females from LTS (55%). L. intestinalis-infected female chub (Leuciscus cephalus) from LTS also appeared to have a lower GST-activity. Thus, it could be shown that the presence of parasites significantly affects GST-activity in different fish species resulting in a decreased GST-activity due to infection. Our results therefore emphasize the need for more integrative approaches in environmental pollution research to clearly identify the possible effects of parasites in an effort to develop biomarkers for evaluating environmental health.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder.

PubMed

Hassel, Stefanie; Almeida, Jorge R; Frank, Ellen; Versace, Amelia; Nau, Sharon A; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2009-11-01

The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. BD individuals scored significantly higher on these spectrum measures than healthy individuals (p<0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p<0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p<0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p<0.02) and neutral faces (p<0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Small sample size of predominantly medicated BD individuals. This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

Effect of kumquat (Fortunella crassifolia) pericarp on natural killer cell activity in vitro and in vivo.

PubMed

Nagahama, Kiyoko; Eto, Nozomu; Shimojo, Tomofumi; Kondoh, Tomomi; Nakahara, Keiko; Sakakibara, Yoichi; Fukui, Keiichi; Suiko, Masahito

2015-01-01

Natural killer (NK) cells play a key role in innate immune defense against infectious disease and cancer. A reduction of NK activity is likely to be associated with increased risk of these types of disease. In this study, we investigate the activation potential of kumquat pericarp acetone fraction (KP-AF) on NK cells. It is shown to significantly increase IFN-γ production and NK cytotoxic activity in human KHYG-1 NK cells. Moreover, oral administration of KP-AF significantly improves both suppressed plasma IFN-γ levels and NK cytotoxic activity per splenocyte in restraint-stressed mice. These results indicate that raw kumquat pericarp activates NK cells in vitro and in vivo. To identify the active constituents, we also examined IFN-γ production on KHYG-1 cells by the predicted active components. Only β-cryptoxanthin increased IFN-γ production, suggesting that NK cell activation effects of KP-AF may be caused by carotenoids such as β-cryptoxanthin.

Dopamine modulates reward system activity during subconscious processing of sexual stimuli.

PubMed

Oei, Nicole Y L; Rombouts, Serge Arb; Soeter, Roelof P; van Gerven, Joop M; Both, Stephanie

2012-06-01

Dopaminergic medication influences conscious processing of rewarding stimuli, and is associated with impulsive-compulsive behaviors, such as hypersexuality. Previous studies have shown that subconscious subliminal presentation of sexual stimuli activates brain areas known to be part of the 'reward system'. In this study, it was hypothesized that dopamine modulates activation in key areas of the reward system, such as the nucleus accumbens, during subconscious processing of sexual stimuli. Young healthy males (n=53) were randomly assigned to two experimental groups or a control group, and were administered a dopamine antagonist (haloperidol), a dopamine agonist (levodopa), or placebo. Brain activation was assessed during a backward-masking task with subliminally presented sexual stimuli. Results showed that levodopa significantly enhanced the activation in the nucleus accumbens and dorsal anterior cingulate when subliminal sexual stimuli were shown, whereas haloperidol decreased activations in those areas. Dopamine thus enhances activations in regions thought to regulate 'wanting' in response to potentially rewarding sexual stimuli that are not consciously perceived. This running start of the reward system might explain the pull of rewards in individuals with compulsive reward-seeking behaviors such as hypersexuality and patients who receive dopaminergic medication.

Iron Supplementation During Pregnancy- A Necessary or Toxic Supplement?

PubMed Central

Wilmet, Stephanie; Legssyer, Rachida; Crichton, Robert R.

2003-01-01

The effects of a single intramuscular iron dose, 10mg, to pregnant rats on Day of pregnancy, on the outcome of pregnancy, with respect to foetal weight and mother’s immune function has been investigated. Despite significantly elevated hepatic iron stores after iron supplementation in pregnant rats this had no significant effect upon blood haemoglobin or transferrin saturation levels. However the mean weight of the foetuses at Day 20-21 was significantly lower than that of the non-supplemented pregnant rats. Iron supplements significantly increased the activity of NADPH oxidase in the maternal alveolar macrophages, the primary event in the formation of the phagolysosome to combat invading organisms. However inducible nitric oxide synthase activity was significantly reduced in these macrophages as shown by decreases in LPSinduced and LPS+IFNγ-induced NOS activation. Iron supplementation to rats of normal iron status at the commencement of pregnancy did not show any beneficial effects to either the foetus or the mother. PMID:18365051

21 CFR 310.543 - Drug products containing active ingredients offered over-the-counter (OTC) for human use in...

Code of Federal Regulations, 2012 CFR

2012-04-01

... (protease), and lipase. Significant differences have been shown in the bioavailability of marketed exocrine pancreatic insufficiency drug products produced by different manufacturers. These differences raise a potential for serious risk to patients using these drug products. The bioavailability of pancreatic enzymes...

21 CFR 310.543 - Drug products containing active ingredients offered over-the-counter (OTC) for human use in...

Code of Federal Regulations, 2011 CFR

2011-04-01

... (protease), and lipase. Significant differences have been shown in the bioavailability of marketed exocrine pancreatic insufficiency drug products produced by different manufacturers. These differences raise a potential for serious risk to patients using these drug products. The bioavailability of pancreatic enzymes...

The Effect of Explanations on Mathematical Reasoning Tasks

ERIC Educational Resources Information Center

Norqvist, Mathias

2018-01-01

Studies in mathematics education often point to the necessity for students to engage in more cognitively demanding activities than just solving tasks by applying given solution methods. Previous studies have shown that students that engage in creative mathematically founded reasoning to construct a solution method, perform significantly better in…

Selenium is a Chemotherapeutic Agent for the Treatment of Prostate Cancer

DTIC Science & Technology

2006-02-01

receptor activity by a hammerhead ribozyme . Mol Endrocrinol 1998;12:1558-1566. 10. Ko YJ, Devi GR, London CA, et al. Androgen receptor down-regulation...Strategic targeting of the AR with ribozymes , antisense oligomers, and small interfering RNAs has been shown to significantly inhibit prostate cancer

Science as a Moving Experience for All Learners

ERIC Educational Resources Information Center

Rye, James; Richards, Ann; Mauk, Diane; Waterworth, Brenda; Poling, James R.; Cool, Tina

2007-01-01

Students with disabilities (SWDs), students at risk, and even honors students can have a hard time relating to traditional science instruction and often disengage. However, research has shown that when science teachers use inquiry or activities-based approaches to teaching science, students' achievement is significantly higher, compared to those…

Land-Grant University-Industry Relationships in Biotechnology: A Comparison with the Non-Land-Grant Research Universities.

ERIC Educational Resources Information Center

Curry, James; Kenney, Martin

1990-01-01

Presents study of industrial involvement in biotechnology research, comparing faculty surveys from land-grant colleges of agriculture and nonagricultural research universities. Agricultural biotechnologists report higher industrial involvement and more optimism about it. Industrial funding levels shown as significant factor in activities and…

Synthesis Of Reactive Nano-Fe/Pd Bimetallic System-Impregnated Activated Carbon For The Simultaneous Adsorption And Dechlorination Of PCBs

EPA Science Inventory

Synthesis and use of reactive metal particles have shown significant environmental implications for the remediation of groundwater and sediment contaminated with chlorinated compounds. Herein, we have developed an effective strategy, employing a series of innovative granular act...

Technologies for physical activity self-monitoring: a study of differences between users and non-users

PubMed Central

Åkerberg, Anna; Söderlund, Anne; Lindén, Maria

2017-01-01

Background Different kinds of physical activity (PA) self-monitoring technologies are used today to monitor and motivate PA behavior change. The user focus is essential in the development process of this technology, including potential future users such as representatives from the group of non-users. There is also a need to study whether there are differences between the groups of users and non-users. The aims of this study were to investigate possible differences between users and non-users regarding their opinions about PA self-monitoring technologies and to investigate differences in demographic variables between the groups. Materials and methods Participants were randomly selected from seven municipalities in central Sweden. In total, 107 adults responded to the Physical Activity Products Questionnaire, which consisted of 22 questions. Results Significant differences between the users and non-users were shown for six of the 20 measurement-related items: measures accurately (p=0.007), measures with high precision (p=0.024), measures distance (p=0.020), measures speed (p=0.003), shows minutes of activity (p=0.004), and shows geographical position (p=0.000). Significant differences between the users and non-users were also found for two of the 29 encouragement items: measures accurately (p=0.001) and has long-term memory (p=0.019). Significant differences between the groups were also shown for level of education (p=0.030) and level of physical exercise (p=0.037). Conclusion With a few exceptions, the users and the non-users in this study had similar opinions about PA self-monitoring technologies. Because this study showed significant differences regarding level of education and level of physical exercise, these demographic variables seemed more relevant to investigate than differences in opinions about the PA self-monitoring technologies. PMID:28280399

Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28.

PubMed

Hulshof, Janneke W; Casarosa, Paola; Menge, Wiro M P B; Kuusisto, Leena M S; van der Goot, Henk; Smit, Martine J; de Esch, Iwan J P; Leurs, Rob

2005-10-06

US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 [5-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylpentanenitrile] as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

Mining pathway associations for disease-related pathway activity analysis based on gene expression and methylation data.

PubMed

Lee, Hyeonjeong; Shin, Miyoung

2017-01-01

The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into distinctive associations between pathway activities in case and control samples.

[Different responses of DD/He and CC57BR/Mv mice to fasting].

PubMed

Baginskaia, N V; Vasil'eva, E D; Il'nitskaia, S I; Kaledin, V I

2004-03-01

Reaction to fasting of 2 mice strains differing in their sensitivity to spontaneous and induced hepatocarcinogenesis, has been investigated. It was shown that mice of both strains displayed similar stress reaction after 3-day fasting manifested in increase in blood corticosterone level; and decrease in testosterone level. At the same time, both strains demonstrated opposite changes at tissue- and enzyme levels in the liver. It was shown that DD/He mice, highly sensitive to induction of liver tumors, were characterized by significant increase in tyrosine aminotransferase (TAT) activity and reduction of lipid droplets in hepatocytes. CC57BR/Mv mice, demonstrating high frequency of spontaneous hepatomas and insensitive to induction of such tumors, were characterized by a decrease in the TAT activity and fatty infiltration of the liver.

Application of fMRI to obesity research: differences in reward pathway activation measured with fMRI BOLD during visual presentation of high and low calorie foods

NASA Astrophysics Data System (ADS)

Tsao, Sinchai; Adam, Tanja C.; Goran, Michael I.; Singh, Manbir

2012-03-01

The factors behind the neural mechanisms that motivate food choice and obesity are not well known. Furthermore, it is not known when these neural mechanisms develop and how they are influenced by both genetic and environmental factors. This study uses fMRI together with clinical data to shed light on the aforementioned questions by investigating how appetite-related activation in the brain changes with low versus high caloric foods in pre-pubescent girls. Previous studies have shown that obese adults have less striatal D2 receptors and thus reduced Dopamine (DA) signaling leading to the reward-deficit theory of obesity. However, overeating in itself reduces D2 receptor density, D2 sensitivity and thus reward sensitivity. The results of this study will show how early these neural mechanisms develop and what effect the drastic endocrinological changes during puberty has on these mechanisms. Our preliminary results showed increased activations in the Putamen, Insula, Thalamus and Hippocampus when looking at activations where High Calorie > Low Calorie. When comparing High Calorie > Control and Low Calorie > Control, the High > Control test showed increased significant activation in the frontal lobe. The Low > Control also yielded significant activation in the Left and Right Fusiform Gyrus, which did not appear in the High > Control test. These results indicate that the reward pathway activations previously shown in post-puberty and adults are present in pre-pubescent teens. These results may suggest that some of the preferential neural mechanisms of reward are already present pre-puberty.

Cytochrome P450-mediated activation of the fragrance compound geraniol forms potent contact allergens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hagvall, Lina; Baron, Jens Malte; Boerje, Anna

2008-12-01

Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered to be a weak allergen, although its chemical structure does not indicate it to be a contact sensitizer. We have shown that geraniol autoxidizes and forms allergenic oxidation products. In the literature, it is suggested but not shown that geraniol could be metabolically activated to geranial. Previously, a skin-like CYP cocktailmore » consisting of cutaneous CYP isoenzymes, was developed as a model system to study cutaneous metabolism. In the present study, we used this system to investigate CYP-mediated activation of geraniol. In incubations with the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed followed by 6,7-epoxygeraniol. The allergenic activities of the identified metabolites were determined in the murine local lymph node assay (LLNA). Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and 6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1 and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly responsible for the metabolic activation of geraniol in the skin, as they are expressed constitutively at significantly higher levels than CYP2B6. Thus, geraniol is activated through both autoxidation and metabolism. The allergens geranial and neral are formed via both oxidation mechanisms, thereby playing a large role in the sensitization to geraniol.« less

Travelling waves in a model of quasi-active dendrites with active spines

NASA Astrophysics Data System (ADS)

Timofeeva, Y.

2010-05-01

Dendrites, the major components of neurons, have many different types of branching structures and are involved in receiving and integrating thousands of synaptic inputs from other neurons. Dendritic spines with excitable channels can be present in large densities on the dendrites of many cells. The recently proposed Spike-Diffuse-Spike (SDS) model that is described by a system of point hot-spots (with an integrate-and-fire process) embedded throughout a passive tree has been shown to provide a reasonable caricature of a dendritic tree with supra-threshold dynamics. Interestingly, real dendrites equipped with voltage-gated ion channels can exhibit not only supra-threshold responses, but also sub-threshold dynamics. This sub-threshold resonant-like oscillatory behaviour has already been shown to be adequately described by a quasi-active membrane. In this paper we introduce a mathematical model of a branched dendritic tree based upon a generalisation of the SDS model where the active spines are assumed to be distributed along a quasi-active dendritic structure. We demonstrate how solitary and periodic travelling wave solutions can be constructed for both continuous and discrete spine distributions. In both cases the speed of such waves is calculated as a function of system parameters. We also illustrate that the model can be naturally generalised to an arbitrary branched dendritic geometry whilst remaining computationally simple. The spatio-temporal patterns of neuronal activity are shown to be significantly influenced by the properties of the quasi-active membrane. Active (sub- and supra-threshold) properties of dendrites are known to vary considerably among cell types and animal species, and this theoretical framework can be used in studying the combined role of complex dendritic morphologies and active conductances in rich neuronal dynamics.

Cytochrome P450-mediated activation of the fragrance compound geraniol forms potent contact allergens.

PubMed

Hagvall, Lina; Baron, Jens Malte; Börje, Anna; Weidolf, Lars; Merk, Hans; Karlberg, Ann-Therese

2008-12-01

Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered to be a weak allergen, although its chemical structure does not indicate it to be a contact sensitizer. We have shown that geraniol autoxidizes and forms allergenic oxidation products. In the literature, it is suggested but not shown that geraniol could be metabolically activated to geranial. Previously, a skin-like CYP cocktail consisting of cutaneous CYP isoenzymes, was developed as a model system to study cutaneous metabolism. In the present study, we used this system to investigate CYP-mediated activation of geraniol. In incubations with the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed followed by 6,7-epoxygeraniol. The allergenic activities of the identified metabolites were determined in the murine local lymph node assay (LLNA). Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and 6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1 and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly responsible for the metabolic activation of geraniol in the skin, as they are expressed constitutively at significantly higher levels than CYP2B6. Thus, geraniol is activated through both autoxidation and metabolism. The allergens geranial and neral are formed via both oxidation mechanisms, thereby playing a large role in the sensitization to geraniol.

Anticancer activity of the new photosensitizers: dose and cell type dependence

NASA Astrophysics Data System (ADS)

Gyulkhandanyan, Grigor V.; Ghambaryan, Sona S.; Amelyan, Gayane V.; Ghazaryan, Robert K.; Haroutiunian, Samvel G.; Gyulkhandanyan, Aram G.; Gasparyan, Gennadi H.

2005-04-01

The necessity of researches of antitumor efficiency of new photosensitizers (PS) is explained by the opportunity of their application in photodynamic therapy of tumors. PS, selectively accumulated in cancer cells and activated by the light, generate the active oxygen species that cause apoptosis. Earlier, it was shown that PS chlorin e6 (0.3-0.5 μg/ml) induces rat embryo fibroblast-like cell apoptosis. In present work antitumor activity of the new photosensitizers, water-soluble cationic porphyrins and their metal complexes, is investigated. The dose-dependent destruction of cancer cells was shown on PC-12 (pheochromocytoma, rat adrenal gland) and Jurkat (human lymphoma) cell lines. Meso-tetra-[4-N-(2 `- oxyethyl) pyridyl] porphyrin (TOEPyP) and chlorin e6 possessed the same toxicity at LD50 dose on PC-12 cell line, whereas phototoxicity of TOEPyP was 3 times less compared to chlorin e6(LD50=0.2 and 0.075 μg/ml accordingly). The results have shown weak photosensitizing effect of Zn-and Ag-derivatives of TOEPyP on PC-12 cell line. TOEPyP and Zn-TOEPyP (0.1 - 50 μg/ml) were non-toxic for Jurkat cell line, whereas Ag-TOEPyP was toxic at 10 μg/ml (LD90). TOEPyP and chlorin e6 have shown phototoxic effect in the same dose range (LD50=0.5 and 0.3 μg/ml accordingly). The investigation of toxic and phototoxic effects of the new porphyrins revealed significantly different sensitivity of various cell lines to PSs.

Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

PubMed Central

Qi, Jian; Chen, Chen; Meng, Qing-Xi; Wu, Yan; Wu, Haitao; Zhao, Ting-Bao

2016-01-01

Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund’s Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression. And, microglia were also significantly activated with the presence of increased Iba-1 expression. Intrathecal administration of c-fos antisense oligodeoxynucleotides (ASO) or minocycline (a specific microglia inhibitor) attenuated mechanical allodynia. Moreover, intrathecal administration of c-fos ASO significantly suppressed the activation of neurons and microglia. Interestingly, inhibition of microglia activation by minocycline significantly suppressed the activation of both neurons and microglia in spinal dorsal horn. P38 inhibitor SB203580 suppressed IL-6 production, and inhibition of IL-6 receptor (IL-6R) activation by tocilizumab suppressed Fos expression. Together, our data suggest that the presence of a “crosstalk” between activated microglia and neurons in the spinal dorsal horn, which might contribute to the stress-induced hyperactivated state, leading to an increased pain sensitivity. PMID:27995982

The pharmacological activity of medical herbs after microbiological decontamination by irradiation

NASA Astrophysics Data System (ADS)

Owczarczyk, H. B.; Migdał, W.; K ȩdzia, B.

2000-03-01

In the Institute of Nuclear Chemistry and Technology research on microbiological decontamination of medicinal herbs by irradiation has been carried out since 1996. It was shown that using ionizing radiation (a dose of 10 kGy) can obtain satisfactory results of microbiological decontamination of these products. The content of essential biologically active substances such as essential oils, flavonoids, glycosides, anthocyans, antra-compounds, poliphenoloacids, triterpene saponins, oleanosides and plants mucus did not change significantly after irradiation. Pharmacological activity of medicinal herbs has been found satisfactory after microbiological decontamination by irradiation.

Importance of questionnaire context for a physical activity question.

PubMed

Jørgensen, M E; Sørensen, M R; Ekholm, O; Rasmussen, N K

2013-10-01

Adequate information about physical activity habits is essential for surveillance, implementing, and evaluating public health initiatives in this area. Previous studies have shown that question order and differences in wording result in systematic differences in people's responses to questionnaires; however, this has never been shown for physical activity questions. The aim was to study the influence of different formulations and question order on self-report physical activity in a population-based health interview survey. Four samples of each 1000 adults were drawn at random from the National Person Register. A new question about physical activity was included with minor differences in formulations in samples 1-3. Furthermore, the question in sample 2 was included in sample 4 but was placed in the end of the questionnaire. The mean time spent on moderate physical activity varied between the four samples from 57 to 100 min/day. Question order was associated with the reported number of minutes spent on moderate-intensity physical activity and with prevalence of meeting the recommendation, whereas physical inactivity was associated with the differences in formulation of the question. Questionnaire context influences the way people respond to questions about physical activity significantly and should be tested systematically in validation studies of physical activity questionnaires. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability

PubMed Central

Cheng, Xiaohui; Liu, Yan; Zhang, Hui; Zhao, Shiqing; Yang, Zhenbo; Li, Mingyuan; Li, Zhiping; Mei, Xingguo

2016-01-01

Oxaliplatin (OXP) was reported to show low anti-tumor activity when used alone and to display side effects; this low activity was attributed to high partitioning to erythrocytes and low accumulation in tumors. Thermosensitive liposomes (TSL) were considered able to specifically deliver drugs to heated tumors and to resolve the OXP distribution problem. Regretfully, TSL encapsulating doxorubicin did not demonstrate significant improvement in progression-free survival. Drug release below 41°C and significant leakage were considered major reasons for the failure. The purpose of this study was to acquire OXP TSL with rapid release at the triggered temperature and high stability at body temperature and at storage temperatures. A small quantity of poloxamer 188 was introduced into the TSL formulation to stabilize the encapsulated drug. It was shown that the addition of poloxamer 188 had no influence on the TSL characteristics. More than 90% of OXP was released within 10 min at 42°C, and less than 15% was released within 60 min at temperatures below 39°C. TSL were stable at 37°C for 96 h and at 4°C for 6 months. The anti-tumor activity of TSL at the dose of 2.5 mg/kg was certified to be equal to those of OXP injection and non-thermosensitive liposomes (NTSL) at the dose of 5 mg/kg, and significant improvement of tumor inhibition was observed in TSL compared with injection and NTSL at the same dose. It was also shown from the histological transmutation of tumors that TSL had stronger anti-tumor activity. Therefore, it could be concluded that TSL composed of a proper amount of poloxamer had rapid release and high stability, and OXP TSL would be anticipated to exert prominent anti-tumor activity in the clinic. PMID:27415823

Structure and biological activity of a fucosylated chondroitin sulfate from the sea cucumber Cucumaria japonica.

PubMed

Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Shashkov, Alexander S; Kusaykin, Mikhail I; Stonik, Valentin A; Nifantiev, Nikolay E; Usov, Anatolii I

2016-05-01

A fucosylated chondroitin sulfate (FCS) was isolated from the body wall of Pacific sea cucumber Cucumaria japonicaby extraction in the presence of papain followed by Cetavlon precipitation and anion-exchange chromatography. FCS was shown to contain D-GalNAc, D-GlcA, L-Fuc and sulfate in molar proportions of about 1:1:1:4.5. Structure of FCS was elucidated using NMR spectroscopy and methylation analysis of the native polysaccharide and products of its desulfation and carboxyl reduction. The polysaccharide was shown to contain a typical chondroitin core → 3)-β-D-GalNAc-(1 → 4)-β-D-GlcA-(1 →. Sulfate groups in this core occupy O-4 and the majority of O-6 of GalNAc. Fucosyl branches are represented by 3,4- and 2,4-disulfated units in a ratio of 4:1 and are linked to O-3 of GlcA. In addition, ∼ 33% of GlcA are 3-O-sulfated, and hence, the presence of short fucooligosaccharide chains side by side with monofucosyl branches cannot be excluded. FCS was shown to inhibit platelets aggregation in vitro mediated by collagen and ristocetin, but not adenosine diphosphate, and demonstrated significant anticoagulant activity, which is connected with its ability to enhance inhibition of thrombin and factor Xa by antithrombin III, as well as to influence von Willebrand factor activity. The latest property significantly distinguished FCS from low-molecular-weight heparin. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Bactericidal activity of colloidal silver against grampositive and gramnegative bacteria].

PubMed

Afonina, I A; Kraeva, L A; Tseneva, G Ia

2010-01-01

It was shown that colloidal silver solution prepared in cooperation with the A. F. Ioffe Physical Technical Institute of the Russian Academy of Sciences, had significant bactericidal activity. Stable bactericidal effect on gramnegative microorganisms was observed after their 2-hour exposition in the solution of colloidal silver at a concentration of 10 ppm. Grampositive capsule-forming microorganisms were less susceptible to the colloidal silver solution: their death was observed after the 4-hour exposition in the solution.

A 4'-phosphopantetheinyl transferase mediates non-ribosomal peptide synthetase activation in Aspergillus fumigatus.

PubMed

Neville, Claire; Murphy, Alan; Kavanagh, Kevin; Doyle, Sean

2005-04-01

Aspergillus fumigatus is a significant human pathogen. Non-ribosomal peptide (NRP) synthesis is thought to be responsible for a significant proportion of toxin and siderophore production in the organism. Furthermore, it has been shown that 4'-phosphopantetheinylation is required for the activation of key enzymes involved in non-ribosomal peptide synthesis in other species. Here we report the cloning, recombinant expression and functional characterisation of a 4'-phosphopantetheinyl transferase from A. fumigatus and the identification of an atypical NRP synthetase (Afpes1), spanning 14.3 kb. Phylogenetic analysis has shown that the NRP synthetase exhibits greatest identity to NRP synthetases from Metarhizium anisolpiae (PesA) and Alternaria brassicae (AbrePsy1). Northern hybridisation and RT-PCR analysis have confirmed that both genes are expressed in A. fumigatus. A 120 kDa fragment of the A. fumigatus NRP synthetase, containing a putative thiolation domain, was cloned and expressed in the baculovirus expression system. Detection of a 4'-phosphopantetheinylated peptide (SFSAMK) from this protein, by MALDI-TOF mass spectrometric analysis after coincubation of the 4'-phosphopantetheinyl transferase with the recombinant NRP synthetase fragment and acetyl CoA, confirms that it is competent to play a role in NRP synthetase activation in A. fumigatus. The 4'-phosphopantetheinyl transferase also activates, by 4'-phosphopantetheinylation, recombinant alpha-aminoadipate reductase (Lys2p) from Candida albicans, a key enzyme involved in lysine biosynthesis.

Antibacterial and antiviral roles of a fish β-defensin expressed both in pituitary and testis.

PubMed

Jin, Jun-Yan; Zhou, Li; Wang, Yang; Li, Zhi; Zhao, Jiu-Gang; Zhang, Qi-Ya; Gui, Jian-Fang

2010-12-20

Defensins are a group of cationic peptides that exhibit broad-spectrum antimicrobial activity. In this study, we cloned and characterized a β-defensin from pituitary cDNA library of a protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides). Interestingly, the β-defensin was shown to be dominantly expressed in pituitary and testis by RT-PCR and Western blot analysis, and its transcript level is significantly upregulated in reproduction organs from intersexual gonad to testis during the natural and artificial sex reversal. Promoter sequence and the responsible activity region analyses revealed the pituitary-specific POU1F1a transcription binding site and testis-specific SRY responsible site, and demonstrated that the pituitary-specific POU1F1a transcription binding site that locates between -180 and -208 bp is the major responsible region of grouper β-defensin promoter activity. Immunofluorescence localization observed its pituicyte expression in pituitary and spermatogonic cell expression in testis. Moreover, both in vitro antibacterial activity assay of the recombinant β-defensin and in vivo embryo microinjection of the β-defensin mRNA were shown to be effective in killing gram-negative bacteria. And, its antiviral role was also demonstrated in EPC cells transfected with the β-defensin construct. Additionally, the antibacterial activity was sensitive to concentrations of Na(+), K(+), Ca(2+) and Mg(2+). The above intriguing findings strongly suggest that the fish β-defensin might play significant roles in both innate immunity defense and reproduction endocrine regulation.

Comparative analysis of topoisomerase IB inhibition and DNA intercalation by flavonoids and similar compounds: structural determinates of activity

PubMed Central

2004-01-01

Flavonoids and other polyphenolic compounds have been shown to inhibit human topoisomerase IB (topo I) through both inhibition of relaxation activity and through stabilization of the cleavable complex (poisoning). Some flavonoids have also been shown to intercalate DNA, and an association of topoisomerase inhibition with intercalation has been noted. We surveyed 34 polyphenolic compounds, primarily flavonoid glycones and aglycones, for their ability to inhibit topo I and to intercalate DNA using an in vitro gel electrophoresis method. We show that the most potent topo I poisons are the flavones and flavonols, and that these generally, but not always, are found to be DNA intercalators. There was no clear correlation, however, of topo-I-poisoning activity with the degree of DNA unwinding. Surprisingly, both DNA intercalation and topo I poisoning were shown to occur with some flavone glycones, including the C-glycosylflavone orientin. Inhibition of relaxation activity by flavonoids was found to be difficult to quantify and was most likely to be due to non-specific inhibition through flavonoid aggregation. As part of a structure–activity analysis, we also investigated the acid–base chemistry of flavonoids and determined that many flavonoids show acid–base activity with a pKa in the physiological pH region. For this reason, subtle pH changes can have significant effects on solution activity of flavonoids and their concomitant biological activity. In addition, these effects may be complicated by pH-dependent aggregation and oxidative degradation. Finally, we develop a simple model for the intercalation of flavonoids into DNA and discuss possible consequences of intercalation and topoisomerase inhibition on a number of cellular processes. PMID:15312049

In vivo procedures for assessment of hair greasiness.

PubMed

Knott, C A; Daykin, K; Ryan, J

1983-06-01

Synopsis Greasy hair is a common problem in Europe. The first step in developing anti-grease hair products must be to establish a sensitive protocol for measuring any changes in perceived hair greasiness. Sensitive clinical trials and in vivo evaluation methods of determining hair greasiness have been developed that show significant differences in the perceived hair greasiness following the use of different shampoos. Products tested in two clinical trials for efficacy as anti-grease shampoos were an anti-grease shampoo containing 2% 3,4-thiolanediol as the active ingredient, and a baby shampoo based on mild surfactants. The same placebo shampoo based on ether sulphates used in typical European shampoo formulations was used in both tests. A shampoo containing 2% zinc pyrithione was included in the trials as a control, since there were indications that this would increase the amount of hair greasiness. Neither of the test products were shown to be effective anti-grease shampoos. The shampoo containing 2% zinc pyrithione was shown to produce significantly more greasiness than both the placebo and the test shampoos. Since significant differences could be shown between the different shampoos, the protocol and in vivo evaluation techniques used in these clinical trials are considered to be validated.

Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: their anti-inflammatory and anti-nociceptive activities.

PubMed

Shafi, Syed; Alam, Mohammad Mahboob; Mulakayala, Naveen; Mulakayala, Chaitanya; Vanaja, G; Kalle, Arunasree M; Pallu, Reddanna; Alam, M S

2012-03-01

A focused library of novel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles were synthesized using click chemistry approach. The synthesized compounds have been tested for their anti-inflammatory activity by using biochemical cyclooxygenase (COX) activity assays and carrageenan-induced hind paw edema. Among the tested compounds, compound 4d demonstrated a potent selective COX-2 inhibition with COX-2/COX-1 ratio of 0.44. Results from carrageenan-induced hind paw edema showed that compounds 4a, 4d, 4e and 4f posses significant anti-inflammatory activity as compared to the standard drug Ibuprofen. The compounds showing significant activity were further subjected to anti-nociceptive activity by writhing test. These four compounds have shown comparable activity with the standard Ibuprofen. Further ulcerogenic studies shows that none of these compounds causing gastric ulceration. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Paraoxonase and Arylesterase Activities in Dipper and Non-Dipper Prehypertensive Subjects

PubMed Central

Yuksel, Murat; Yildiz, Abdulkadir; Tekbas, Ebru; Gunduz, Ercan; Ekinci, Aysun; Bilik, Mehmet Zihni; Ozaydogdu, Necdet; Atilgan, Zuhal

2015-01-01

Abstract Paraoxonase-1, a high-density lipoprotein linked enzyme complex, was shown to be decreased in several cardiovascular diseases. We aimed to explore whether serum paraoxonase and arylesterase activities differ in dipper and non-dipper prehypertensive subjects compared to healthy controls. Sixty prehypertensive subjects and 30 controls were enrolled. All subjects underwent echocardiographic assessment and 24-hour ambulatory blood pressure monitoring (ABPM). According to the blood pressure (BP) course on ABPM, prehypertensive subjects were categorized into two: non-dipper prehypertensive (NDPH) and dipper prehypertensive (DPH) groups. Serum paraoxonase and arylesterase activities were detected spectrophotometrically. Paraoxonase and arylesterase activities were significantly lower in patients with NDPH compared to both DPH and control groups. Both paraoxonase and arylesterase activities showed significant negative correlations with BP and left ventricular mass index. We have demonstrated that NDPH subjects have lower paraoxonase and arylesterase activities compared to DPH subjects and normotensives. Further prospective studies are needed to clarify the role of paraoxonase and arylesterase activities in the development of overt hypertension in prehypertensive subjects. PMID:25929926

Paraoxonase and arylesterase activities in dipper and non-dipper prehypertensive subjects.

PubMed

Yuksel, Murat; Yildiz, Abdulkadir; Tekbas, Ebru; Gunduz, Ercan; Ekinci, Aysun; Bilik, Mehmet Zihni; Ozaydogdu, Necdet; Atilgan, Zuhal

2015-05-01

Paraoxonase-1, a high-density lipoprotein linked enzyme complex, was shown to be decreased in several cardiovascular diseases. We aimed to explore whether serum paraoxonase and arylesterase activities differ in dipper and non-dipper prehypertensive subjects compared to healthy controls.Sixty prehypertensive subjects and 30 controls were enrolled. All subjects underwent echocardiographic assessment and 24-hour ambulatory blood pressure monitoring (ABPM). According to the blood pressure (BP) course on ABPM, prehypertensive subjects were categorized into two: non-dipper prehypertensive (NDPH) and dipper prehypertensive (DPH) groups. Serum paraoxonase and arylesterase activities were detected spectrophotometrically.Paraoxonase and arylesterase activities were significantly lower in patients with NDPH compared to both DPH and control groups. Both paraoxonase and arylesterase activities showed significant negative correlations with BP and left ventricular mass index.We have demonstrated that NDPH subjects have lower paraoxonase and arylesterase activities compared to DPH subjects and normotensives. Further prospective studies are needed to clarify the role of paraoxonase and arylesterase activities in the development of overt hypertension in prehypertensive subjects.

Evaluation of Radical Scavenging Activity of Sempervivum tectorum and Corylus avellana Extracts with Different Phenolic Composition.

PubMed

Alberti, Ágnes; Riethmüller, Eszter; Béni, Szabolcs; Kéry, Ágnes

2016-04-01

Semnpervivum tectorum L. and Corylus avellana L. are traditional herbal remedies exhibiting antioxidant activity and representing diverse phenolic composition. The aim of this study was to reveal the contribution of certain compounds to total radical scavenging activity by studying S. tectorum and C. avellana extracts prepared with solvents of different selectivity for diverse classes of phenolics. Antioxidant activity of S. tectorum and C. avellana samples was determined in the ABTS and DPPH radical scavenging assays, and phenolic composition was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Correlations between antioxidant activity and phenolic content of houseleek extracts have been revealed. Significant differences regarding antioxidant activity have been shown between S. tectorum 80% (v/v) methanol extract and its fractions. Additionally, synergism among the constituents present together in the whole extract was assumed. Significantly higher radical scavenging activity of hazel extracts has been attributed to the differences in phenolic composition compared with houseleek extracts.

Apollo 8 crew shown during intravehicular activity during mission

NASA Technical Reports Server (NTRS)

1968-01-01

Astronaut Frank Borman, commander, is shown during intravehicular activity on the Apollo 8 lunar orbit mission. This still print was made from movie film taken by an on-board 16mm motion picture camera (56531); Astronaut William A. Anders, lunar module pilot, is shown during intravehicular activity on the Apollo 8 lunar orbit mission (56532); Astronaut James A. Lovell Jr., command module milot, is shown during intravehicular activity on the Apollo 8 lunar orbit mission (56533).

Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP) knockout mice

PubMed Central

Hattori, Satoko; Takao, Keizo; Tanda, Koichi; Toyama, Keiko; Shintani, Norihito; Baba, Akemichi; Hashimoto, Hitoshi; Miyakawa, Tsuyoshi

2012-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide acting as a neurotransmitter, neuromodulator, or neurotrophic factor. PACAP is widely expressed throughout the brain and exerts its functions through the PACAP-specific receptor (PAC1). Recent studies reveal that genetic variants of the PACAP and PAC1 genes are associated with mental disorders, and several behavioral abnormalities of PACAP knockout (KO) mice are reported. However, an insufficient number of backcrosses was made using PACAP KO mice on the C57BL/6J background due to their postnatal mortality. To elucidate the effects of PACAP on neuropsychiatric function, the PACAP gene was knocked out in F1 hybrid mice (C57BL/6J × 129SvEv) for appropriate control of the genetic background. The PACAP KO mice were then subjected to a behavioral test battery. PACAP deficiency had no significant effects on neurological screen. As shown previously, the mice exhibited significantly increased locomotor activity in a novel environment and abnormal anxiety-like behavior, while no obvious differences between genotypes were shown in home cage (HC) activity. In contrast to previous reports, the PACAP KO mice showed normal prepulse inhibition (PPI) and slightly decreased depression-like behavior. Previous study demonstrates that the social interaction (SI) in a resident-intruder test was decreased in PACAP KO mice. On the other hand, we showed that PACAP KO mice exhibited increased SI in Crawley's three-chamber social approach test, although PACAP KO had no significant impact on SI in a HC. PACAP KO mice also exhibited mild performance deficit in working memory in an eight-arm radial maze (RM) and the T-maze (TM), while they did not show any significant abnormalities in the left-right discrimination task in the TM. These results suggest that PACAP has an important role in the regulation of locomotor activity, social behavior, anxiety-like behavior and, potentially, working memory. PMID:23060763

Influence of WFIKKN1 on BMP1-mediated activation of latent myostatin.

PubMed

Szláma, György; Vásárhelyi, Viktor; Trexler, Mária; Patthy, László

2016-12-01

The NTR domain of WFIKKN1 protein has been shown to have significant affinity for the prodomain regions of promyostatin and latent myostatin but the biological significance of these interactions remained unclear. In view of its role as a myostatin antagonist, we tested the assumption that WFIKKN1 inhibits the release of myostatin from promyostatin and/or latent myostatin. WFIKKN1 was found to have no effect on processing of promyostatin by furin, the rate of cleavage of latent myostatin by BMP1, however, was significantly enhanced in the presence of WFIKKN1 and this enhancer activity was superstimulated by heparin. Unexpectedly, WFIKKN1 was also cleaved by BMP1 and our studies have shown that the KKN1 fragment generated by BMP1-cleavage of WFIKKN1 contributes most significantly to the observed enhancer activity. Analysis of a pro-TGF-β -based homology model of homodimeric latent myostatin revealed that the BMP1-cleavage sites are buried and not readily accessible to BMP1. In view of this observation, the most plausible explanation for the BMP1-enhancer activity of the KKN1 fragment is that it shifts a conformational equilibrium of latent myostatin from the closed circular structure of the homodimer to a more open form, making the cleavage sites more accessible to BMP1. On the other hand, the observation that the enhancer activity of KKN1 is superstimulated in the presence of heparin is explained by the fact KKN1, latent myostatin, and BMP1 have affinity for heparin and these interactions with heparin increase the local concentrations of the reactants thereby facilitating the action of BMP1. Furin: EC 3.4.21.75; BMP1, bone morphogentic protein 1 or procollagen C-endopeptidase: EC 3.4.24.19. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Neuroprotective effects of the antiparkinson drug Mucuna pruriens.

PubMed

Manyam, Bala V; Dhanasekaran, Muralikrishnan; Hare, Theodore A

2004-09-01

Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. The present study evaluated the neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson's disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the presence of NADH and coenzyme Q-10. Copyright (c) 2004 John Wiley & Sons, Ltd.

Project SEARCH: Work-Based Transition Program for Young Adults with Disabilities

ERIC Educational Resources Information Center

Green, Teresa D.

2013-01-01

Historically people with significant disabilities were restricted to places such as adult activity centers, sheltered workshops, nursing homes, and institutions. Studies have shown the high school drop-out rate for this population is higher than those who are non-disabled. Policy makers concluded that these individuals needed to be better prepared…

77 FR 23484 - Agency Information Collection Activities; Proposed Collection; Comment Request; Medical Device...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

... appropriate, and other forms of information technology. I. Background A recent study of obesity indicates that... estimates, as much as $140 billion were spent in 2008 to treat obesity-related diseases (Ref. 2). Studies have shown that weight loss can significantly reduce the burden of obesity-related comorbidities (Refs...

Improving Learners' Oral Fuency through Computer-Mediated Emotional Intelligence Activities

ERIC Educational Resources Information Center

Abdolrezapour, Parisa

2017-01-01

Previous studies have shown that emotional intelligence (henceforth, EI) has a significant impact on important life outcomes (e.g., mental and physical health, academic achievement, work performance, and social relationships). This study aimed to see whether there is any relationship between EI and English as a foreign language (EFL) learners'…

Teaching, Learning, and Communicating in the Digital Age.

ERIC Educational Resources Information Center

Kenny, Robert

Younger students live in a media-centric world. Researchers have shown that youth today spend more time watching television and movies than most any other leisure-time activity (Pearl, 1982). In addition, the presentation speed of passages on commercial television has increased significantly in the past 50 years (Stephens, 1996). Researchers have…

Astro 101 Students' Perceptions of Science: Results from the "Thinking about Science Survey Instrument"

ERIC Educational Resources Information Center

Wallace, Colin S.; Prather, Edward E.; Mendelsohn, Benjamin M.

2013-01-01

What are the underlying worldviews and beliefs about the role of science in society held by students enrolled in a college-level, general education, introductory astronomy course (Astro 101)--and are those beliefs affected by active engagement instruction shown to significantly increase students' conceptual knowledge and reasoning abilities…

Adolescent Perceptions of the National Lottery and Scratchcards: A Qualitative Study Using Group Interviews.

ERIC Educational Resources Information Center

Wood, Richard T. A.; Griffiths, Mark D.

2002-01-01

Recent research has shown that a small but significant minority of youth engage in illegal lottery and scratchcard gambling. This study examines the perceptions of such adolescents. Results revealed many salient themes including winning money, socialization, different forms of excitement associated with these activities, control, and awareness of…

Applying the Socratic Method to Physics Education

NASA Astrophysics Data System (ADS)

Corcoran, Ed

2005-04-01

We have restructured University Physics I and II in accordance with methods that PER has shown to be effective, including a more interactive discussion- and activity-based curriculum based on the premise that developing understanding requires an interactive process in which students have the opportunity to talk through and think through ideas with both other students and the teacher. Studies have shown that in classes implementing this approach to teaching as compared to classes using a traditional approach, students have significantly higher gains on the Force Concept Inventory (FCI). This has been true in UPI. However, UPI FCI results seem to suggest that there is a significant conceptual hole in students' understanding of Newton's Second Law. Two labs in UPI which teach Newton's Second Law will be redesigned replacing more activity with students as a group talking through, thinking through, and answering conceptual questions asked by the TA. The results will be measured by comparing FCI results to those from previous semesters, coupled with interviews. The results will be analyzed, and we will attempt to understand why gains were or were not made.

Gemfibrozil modulates cytochrome P450 and peroxisome proliferation-inducible enzymes in the liver of the yellow European eel (Anguilla anguilla).

PubMed

Lyssimachou, Angeliki; Thibaut, Rémi; Gisbert, Enric; Porte, Cinta

2014-01-01

The human lipid regulator gemfibrozil (GEM) has been shown to induce peroxisome proliferation in rodents leading to hepatocarcinogenesis. Since GEM is found at biological active concentrations in the aquatic environment, the present study investigates the effects of this drug on the yellow European eel (Anguilla anguilla). Eels were injected with different concentrations of GEM (0.1 to 200 μg/g) and sampled 24- and 96-h post-injection. GEM was shown to inhibit CYP1A, CYP3A and CYP2K-like catalytic activities 24-h post-injection, but at 96-h post-injection, only CYP1A was significantly altered in fish injected with the highest GEM dose. On the contrary, GEM had little effect on the phase II enzymes examined (UDP-glucuronyltransferase and glutathione-S-transferase). Peroxisome proliferation inducible enzymes (liver peroxisomal acyl-CoA oxidase and catalase) were very weakly induced. No evidence of a significant effect on the endocrine system of eels was observed in terms of plasmatic steroid levels or testosterone esterification in the liver.

Bioactive Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

PubMed Central

Tai, Chi-Jen; Su, Jui-Hsin; Huang, Ming-Shyan; Wen, Zhi-Hong; Dai, Chang-Feng; Sheu, Jyh-Horng

2011-01-01

Four new eunicellin-based diterpenoids, krempfielins A–D (1–4), along with two known compounds (5 and 6) have been isolated from a soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compounds 5 and 6 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 2, 3, 5 and 6 were shown to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. PMID:22073008

Loss of calreticulin function decreases NFκB activity by stabilizing IκB protein.

PubMed

Massaeli, Hamid; Jalali, Shahrzad; Viswanathan, Divya; Mesaeli, Nasrin

2014-11-01

Transcription factor NFκB is activated by several processes including inflammation, endoplasmic-reticulum (ER) stress, increase in Akt signaling and enhanced proteasomal degradation. Calreticulin (CRT) is an ER Ca(2+)-binding chaperone that regulates many cellular processes. Gene-targeted deletion of CRT has been shown to induce ER stress that is accompanied with a significant increase in the proteasome activity. Loss of CRT function increases the resistance of CRT-deficient (crt-/-) cells to UV- and drug-induced apoptosis. Based on these reports we hypothesized that loss of CRT will activate NFκB signaling thus contributing to enhanced resistance to apoptosis. In contrast to our hypothesis, we observed a significant decrease in the basal transcriptional activity of NFκB in CRT-deficient cells. Treatment with lipopolysaccharide failed to increase the transcriptional activity of NFκB in the crt-/- cells to the same level as in the wt cells. Our data illustrate that the mechanism of decreased NFκB activity in CRT-deficient cells is mediated by a significant increase in IκB protein expression. Furthermore, we showed a significant increase in protein phosphatase 2A activity inhibition which resulted in decreased IκBα protein level in CRT-deficient cells. Based on our data we concluded that loss of CRT increases the stability of IκB protein thus reducing NFκB activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Acupuncture inhibits cue-induced heroin craving and brain activation.

PubMed

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-11-25

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation.

PubMed

Okano, Takaichi; Saegusa, Jun; Nishimura, Keisuke; Takahashi, Soshi; Sendo, Sho; Ueda, Yo; Morinobu, Akio

2017-02-10

Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis. Here we demonstrated that 3-bromopyruvate (BrPA), a specific HK2 inhibitor, significantly decreased the arthritis scores and the histological scores in SKG mice, with a significant increase in Treg cells, decrease in Th17 cells, and decrease in activated DCs in the spleen. In vitro, BrPA facilitated the differentiation of Treg cells, suppressed Th17 cells, and inhibited the activation of DCs. These results suggested that BrPA may be a therapeutic target of murine arthritis. Although the role of IL-17 is not clarified in the treatment of RA, targeting cell metabolism to alter the immune cell functions might lead to a new therapeutic strategy for RA.

Inhibiting social support from massage-like stroking increases morphine dependence.

PubMed

Bates, M L Shawn; Emery, Michael A; Wellman, Paul J; Eitan, Shoshana

2017-12-01

Our previous studies showed that altering solely the drug experience of the cage mates with which rodents are housed affects the development of morphine dependence. In this study, we used designer receptors exclusively activated by designer drugs to artificially increase or decrease the activity of peripheral dorsal root ganglia sensory neurons expressing the G-protein-coupled receptor MRGPRB4. This is because sensory MRGPRB4-expressing neurons were shown to specifically detect the sensation of massage-like stroking resulting from social grooming, which is an important affiliative social behavior in the rodent. Blocking the sensation of social grooming in morphine-treated mice housed with drug-naive mice (i.e. morphine cage mates) significantly increased the display of jumping behavior in morphine-withdrawn animals. Activating the sensation of social grooming in morphine-treated animals housed solely with other morphine-treated animals (i.e. morphine only) did not significantly alter the display of jumping behavior in morphine-withdrawn animals. Repetitive jumping behaviors have been shown to correlate with morphine dependence. Thus, this study showed a role of social grooming in the protective effect of being housed with drug-naive mice on the development of morphine dependence. It further confirms a role of social support in the development of substance use problems.

Anti-inflammatory and anti-pyretic properties of Spirulina platensis and Spirulina lonar: a comparative study.

PubMed

Somchit, Muhammad Nazrul; Mohamed, Nor Azura; Ahmad, Zuraini; Zakaria, Zainul Amiruddin; Shamsuddin, Lokman; Omar-Fauzee, Mohd Sofian; Kadir, Arifah Abdul

2014-09-01

Spirulina spp. is a blue-green algae belongs to the family of Oscillatoriaceae, which having diverse biological activity. The aim of this current study was to evaluate and compare the anti-pyretic and anti-inflammatory activity of Spirulina platensis/SP and Spirulina lonar/SL extracts. In the anti-pyretic study, the ability to reduce the rectal temperature of rats induced pyrexia with 2g/kg Brewer's Yeast (BY) was performed. Rats were dosed either 2 or 4 mg/kg SP or SL. Rectal temperature was taken every hour for 8 hours. Results shown that there were significant dose-dependent (p<0.05) reduction of both treatments. However, SP treatment revealed faster reduction in rectal temperature. For anti-inflammatory activity, the reduction in the volume of paw edema induced by Prostaglandin E2 (100 IU/rat intraplantar) was measured. Rats were dosed orally with 2 or 4 mg/kg SP or SL. The paw edema was measured every 30 minutes for 4 hours using plethysmometer. Results had shown a significant dose dependent reduction in diameter of paw edema (p<0.05). The finding suggests that SP and SL extracts have anti-pyretic and anti-inflammatory properties. However, SP was found to be more effective than SL as anti-pyretic and anti-inflammatory agent.

The oncolytic peptide LTX-315 induces cell death and DAMP release by mitochondria distortion in human melanoma cells

PubMed Central

Eike, Liv-Marie; Yang, Nannan; Rekdal, Øystein; Sveinbjørnsson, Baldur

2015-01-01

Host defense peptides (HDPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line defense against intruding pathogens, and several HDPs have been shown to possess anticancer activity. Structure-activity relationship studies on the HDP bovine lactoferricin revealed a de novo design of a nonamer peptide LTX-315, with oncolytic properties. In the present study, we investigated the oncolytic activity of LTX-315 in human melanoma cells (A375). LTX-315 induced a rapid plasma membrane disruption and cell death within 2 hours. At a low concentration, fluorescence-labeled LTX-315 was internalized and accumulated in cytoplasmic vacuoles in close proximity to the mitochondria. The mitochondrial membrane potential was shown to depolarize as a consequence of LTX-315 treatment and at ultrastructural level, the mitochondria morphology was significantly altered. Release of danger signals (DAMPs) such as ATP, Cytochrome C and HMGB1 into the cell supernatant of cultured cells was evident minutes after peptide treatment. The oncolytic effect of LTX-315 involving perturbation of both the cell membrane and the mitochondria with subsequent release of DAMPs may highlight the ability of LTX-315 to induce complete regression and long-term protective immune responses as previously reported in experimental animal models. PMID:26472184

Methanolic extract of Momordica cymbalaria enhances glucose uptake in L6 myotubes in vitro by up-regulating PPAR-γ and GLUT-4.

PubMed

Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V; Manjunath, Kirangadur; Viswanatha, Gollapalle L; Ashok, Godavarthi

2014-12-01

The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria (MFMC) on PPARγ (Peroxisome Proliferator Activated Receptor gamma) and GLUT-4 (Glucose transporter-4) with respect to glucose transport. Various concentrations of MFMC ranging from 62.5 to 500 μg·mL(-1) were evaluated for glucose uptake activity in vitro using L6 myotubes, rosiglitazone was used as a reference standard. The MFMC showed significant and dose-dependent increase in glucose uptake at the tested concentrations, further, the glucose uptake activity of MFMC (500 μg·mL(-1)) was comparable with rosigilitazone. Furthermore, MFMC has shown up-regulation of GLUT-4 and PPARγ gene expressions in L6 myotubes. In addition, the MFMC when incubated along with cycloheximide (CHX), which is a protein synthesis inhibitor, has shown complete blockade of glucose uptake. This indicates that new protein synthesis is required for increased GLUT-4 translocation. In conclusion, these findings suggest that MFMC is enhancing the glucose uptake significantly and dose dependently through the enhanced expression of PPARγ and GLUT-4 in vitro. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

2012 Workplace and Gender Relations Survey of Active Duty Members: Nonresponse Bias Analysis Report

DTIC Science & Technology

2014-01-01

Control and Prevention ), or command climate surveys (e.g., DEOCS). 6 Table 1. Comparison of Trends in WGRA and SOFS-A Response Rates (Shown in...DMDC draws optimized samples to reduce survey burden on members as well as produce high levels of precision for important domain estimates by using...statistical significance at α= .05 Because paygrade is a significant predictor of survey response, we next examined the odds ratio of each paygrade levels

Overcoming failure to repair demyelination in EAE: gamma-secretase inhibition of Notch signaling.

PubMed

Jurynczyk, Maciej; Jurewicz, Anna; Bielecki, Bartosz; Raine, Cedric S; Selmaj, Krzysztof

2008-02-15

In multiple sclerosis (MS), myelin destroyed by the immune attack is not effectively repaired by oligodendrocytes (OLs) and MS foci eventually undergo glial scarring. Although oligodendrocyte precursor cells (OPCs) are normally recruited to the lesion areas, they fail to mature and remyelinate the damaged fibers. Activation of the Notch pathway has been shown to inhibit OPC differentiation and to hamper their ability to produce myelin during CNS development. We have recently shown that inhibition of gamma-secretase within the CNS of SJL/J mice with experimental autoimmune encephalomyelitis (EAE) blocks Notch pathway activation in OLs, promotes remyelination, reduces axonal damage and significantly enhances clinical recovery from the disease. Our results suggest that inhibiting the non-myelin permissive environment maintained by Notch pathways within the mature CNS offers a new strategy for treating autoimmune demyelination, including MS.

Pore diffusion limits removal of monochloramine in treatment of swimming pool water using granular activated carbon.

PubMed

Skibinski, Bertram; Götze, Christoph; Worch, Eckhard; Uhl, Wolfgang

2018-04-01

Overall apparent reaction rates for the removal of monochloramine (MCA) in granular activated carbon (GAC) beds were determined using a fixed-bed reactor system and under conditions typical for swimming pool water treatment. Reaction rates dropped and quasi-stationary conditions were reached quickly. Diffusional mass transport in the pores was shown to be limiting the overall reaction rate. This was reflected consistently in the Thiele modulus, in the effect of temperature, pore size distribution and of grain size on the reaction rates. Pores <2.5 times the diameter of the monochloramine molecule were shown to be barely accessible for the monochloramine conversion reaction. GACs with a significant proportion of large mesopores were found to have the highest overall reactivity for monochloramine removal. Copyright © 2017 Elsevier Ltd. All rights reserved.

WNK4 inhibits NCC protein expression through MAPK ERK1/2 signaling pathway.

PubMed

Zhou, Bo; Wang, Dexuan; Feng, Xiuyan; Zhang, Yiqian; Wang, Yanhui; Zhuang, Jieqiu; Zhang, Xuemei; Chen, Guangping; Delpire, Eric; Gu, Dingying; Cai, Hui

2012-03-01

WNK [with no lysine (K)] kinase is a subfamily of serine/threonine kinases. Mutations in two members of this family (WNK1 and WNK4) cause pseudohypoaldosteronism type II featuring hypertension, hyperkalemia, and metabolic acidosis. WNK1 and WNK4 were shown to regulate sodium chloride cotransporter (NCC) activity through phosphorylating SPAK and OSR1. Previous studies including ours have also shown that WNK4 inhibits NCC function and its protein expression. A recent study reported that a phorbol ester inhibits NCC function via activation of extracellular signal-regulated kinase (ERK) 1/2 kinase. In the current study, we investigated whether WNK4 affects NCC via the MAPK ERK1/2 signaling pathway. We found that WNK4 increased ERK1/2 phosphorylation in a dose-dependent manner in mouse distal convoluted tubule (mDCT) cells, whereas WNK4 mutants with the PHA II mutations (E562K and R1185C) lost the ability to increase the ERK1/2 phosphorylation. Hypertonicity significantly increased ERK1/2 phosphorylation in mDCT cells. Knock-down of WNK4 expression by siRNA resulted in a decrease of ERK1/2 phosphorylation. We further showed that WNK4 knock-down significantly increases the cell surface and total NCC protein expressions and ERK1/2 knock-down also significantly increases cell surface and total NCC expression. These data suggest that WNK4 inhibits NCC through activating the MAPK ERK1/2 signaling pathway.

[Strategies for obesity prevention in children and adolescents].

PubMed

Sichieri, Rosely; Souza, Rita Adriana de

2008-01-01

Few studies on treatment or prevention of obesity have shown significant results. Theoretically, in children and adolescents as compared to adults, prevention of excessive weight gain should be easy due to the energy expended during growth, associated with more time spent in leisure-time activities. However, numerous factors that stimulate overeating and sedentary behaviors are difficult to overcome. Additionally, most intervention studies have focused on a minor portion of the many factors associated with obesity. Important aspects of the obesity epidemic such as the role of the food industry, fast food chains, advertising, and a lifestyle that limits children to sedentary activities and overeating cannot be explored by a traditional clinical trial design. At any rate, among the published interventions, those including the family in weight-reduction strategies have shown the best results, as compared to children-centered approaches. Meanwhile, studies on specific nutrient or dietary composition (such as calcium, protein, or glycemic index) related to prevention or treatment of obesity have failed to yield good results. Reducing the intake of high-sugar carbonated drinks and juices has shown promising but still inconclusive results.

Spontaneous locomotor activity and life span. A test of the rate of living theory in Drosophila melanogaster.

PubMed

Lints, F A; Le Bourg, E; Lints, C V

1984-01-01

The spontaneous locomotor activity and life span of approximately 600 individuals of both sexes and of three widely different genotypes of Drosophila melanogaster have been measured. Neither at the individual nor at the populational level could a significant correlation between spontaneous locomotor activity and life span be found. The results are discussed in relation with Pearl's [The rate of living, London University Press, London 1928] rate of living theory. That theory has been tested in relation with environmental temperature, oxygen consumption and activity. It is shown that the theory has received no definite confirmation until now.

Multimodality therapy of local regional esophageal cancer.

PubMed

Kelsen, David P

2005-12-01

Recent trials regarding the use of multimodality therapy for patients with cancers of the esophagus and gastroesophageal junction have not conclusively shown benefit. Regimens containing cisplatin and fluorouracil administered preoperatively appear to be tolerable and do not increase operative morbidity or mortality when compared with surgery alone. Yet clinical trials have not clearly shown that such regimens improve outcome as measured by survival. Likewise, trials of postoperative chemoradiation have not reported a significant improvement in median or overall survival. The reasons for the lack of clinical benefit from multimodality therapy are not completely understood, but improvements in systemic therapy will probably be necessary before disease-free or overall survival improves substantially. Some new single agents such as the taxanes (docetaxel or paclitaxel) and the camptothecan analog irinotecan have shown modest activity for palliative therapy.

Temporal expression of the human alcohol dehydrogenase gene family during liver development correlates with differential promoter activation by hepatocyte nuclear factor 1, CCAAT/enhancer-binding protein alpha, liver activator protein, and D-element-binding protein.

PubMed Central

van Ooij, C; Snyder, R C; Paeper, B W; Duester, G

1992-01-01

The human class I alcohol dehydrogenase (ADH) gene family consists of ADH1, ADH2, and ADH3, which are sequentially activated in early fetal, late fetal, and postnatal liver, respectively. Analysis of ADH promoters revealed differential activation by several factors previously shown to control liver transcription. In cotransfection assays, the ADH1 promoter, but not the ADH2 or ADH3 promoter, was shown to respond to hepatocyte nuclear factor 1 (HNF-1), which has previously been shown to regulate transcription in early liver development. The ADH2 promoter, but not the ADH1 or ADH3 promoter, was shown to respond to CCAAT/enhancer-binding protein alpha (C/EBP alpha), a transcription factor particularly active during late fetal liver and early postnatal liver development. The ADH1, ADH2, and ADH3 promoters all responded to the liver transcription factors liver activator protein (LAP) and D-element-binding protein (DBP), which are most active in postnatal liver. For all three promoters, the activation by LAP or DBP was higher than that seen by HNF-1 or C/EBP alpha, and a significant synergism between C/EBP alpha and LAP was noticed for the ADH2 and ADH3 promoters when both factors were simultaneously cotransfected. A hierarchy of ADH promoter responsiveness to C/EBP alpha and LAP homo- and heterodimers is suggested. In all three ADH genes, LAP bound to the same four sites previously reported for C/EBP alpha (i.e., -160, -120, -40, and -20 bp), but DBP bound strongly only to the site located at -40 bp relative to the transcriptional start. Mutational analysis of ADH2 indicated that the -40 bp element accounts for most of the promoter regulation by the bZIP factors analyzed. These studies suggest that HNF-1 and C/EBP alpha help establish ADH gene family transcription in fetal liver and that LAP and DBP help maintain high-level ADH gene family transcription in postnatal liver. Images PMID:1620113

Tectonics and Volcanism of East Africa as Seen Using Remote Sensing Imagery

NASA Technical Reports Server (NTRS)

Hutt, Duncan John

1996-01-01

The East African Rift is the largest area of active continental geology. The tectonics of this area has been studied with remote sensing data, including AVHRR, Landsat MSS and TM, SPOT, and electronic still camera from Shuttle. Lineation trends have been compared to centers of volcanic and earthquake activity as well as the trends shown on existing geologic maps. Remote sensing data can be used effectively to reveal and analyze significant tectonic features in this area.

Sedative effect of galphimine B, a nor-seco-triterpenoid from Galphimia glauca.

PubMed

Tortoriello, J; Ortega, A

1993-10-01

Galphimia glauca Cav. (Malpighiaceae) is used in Mexican traditional medicine as a sedative in the treatment of mental disorders. Sedative properties of a methanolic extract of the aerial parts of this plant have been established in animal trials and an active compound, named galphimine B, has already been isolated. This compound was submitted to neuropharmacological testing, where it was shown that galphimine B had no significant effect as an anticonvulsant, while it exhibited a strong depressant activity on the nervous system.

Porcine circovirus type 2 replication is impaired by inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei Li; Liu Jue

Postweaning multisystemic wasting syndrome, which is primarily caused by porcine circovirus type 2 (PCV2), is an emerging and important swine disease. We have recently shown that PCV2 induces nuclear factor kappa B activation and its activation is required for active replication, but the other cellular factors involved in PCV2 replication are not well defined. The extracellular signal-regulated kinase (ERK) which served as an important component of cellular signal transduction pathways has been shown to regulate many viral infections. In this report, we show that PCV2 activates ERK1/2 in PCV2-infected PK15 cells dependent on viral replication. The PCV2-induced ERK1/2 leads tomore » phosphorylation of the ternary complex factor Elk-1, which kinetically paralleled ERK1/2 activation. Inhibition of ERK activation with U0126, a specific MEK1/2 inhibitor, significantly reduced viral progeny release. Investigations into the mechanism of ERK1/2 regulation revealed that inhibition of ERK activation leads to decreased viral transcription and lower virus protein expression. These data indicate that the ERK signaling pathway is involved in PCV2 infection and beneficial to PCV2 replication in the cultured cells.« less

Digestive stimulant action of spices: a myth or reality?

PubMed

Platel, Kalpana; Srinivasan, K

2004-05-01

Spices have long been recognized for their digestive stimulant action. Several spices are also employed in medicinal preparations against digestive disorders in traditional and Indian systems of medicine. Earlier reports on the digestive stimulant action of spices are largely empirical; only in recent years, this beneficial attribute of spices has been authenticated in exhaustive animal studies. Animal studies have shown that many spices induce higher secretion of bile acids which play a vital role in fat digestion and absorption. When consumed through the diet also spices produce significant stimulation of the activities of pancreatic lipase, amylase and proteases. A few of them also have been shown to have beneficial effect on the terminal digestive enzymes of small intestinal mucosa. Concomitant with such a stimulation of either bile secretion or activity of digestive enzymes by these spices, leading to an accelerated digestion, a reduction in the food transit time in the gastrointestinal tract has also been shown. Thus, the digestive stimulant action of spices seems to be mediated through two possible modes: (i) by stimulating the liver to secrete bile rich in bile acids, components that are vital for fat digestion and absorption, and (ii) by a stimulation of enzyme activities that are responsible for digestion. This review highlights the available information on the influence of spices on the digestive secretions and enzymes.

The relationship of PON1 QR 192 and LM 55 polymorphisms with serum paraoxonase activities of Turkish diabetic patients.

PubMed

Altuner, Durdu; Ates, Ilker; Suzen, Sinan H; Koc, Gonul Varan; Aral, Yalcin; Karakaya, Asuman

2011-11-01

Paraoxonase (PON1) is a serum esterase responsible for the protection against xenobiotics toxicity such as paraoxon. Alterations in PON1 concentrations have been reported in a variety of diseases including diabetes mellitus (DM). It has been shown that the serum PON1 concentration and activity are decreased in patients with both type 1 and type 2 DM. This study aimed to investigate the lipid profiles and the relationship between PON1 activity and PON1, QR192 and LM55 polymorphisms in Turkish type 2 diabetic patients and non-diabetic control subjects. According to our results, RR variant had significantly higher PON activity than QQ and QR variants (p < 0.01) and LL variant had significantly higher PON activity than MM variant in both control and patient groups (p < 0.05). In conclusion, we found that PON1 192RR and 55LL genotypes are associated with higher PON activity than QQ and MM genotypes. This may be more protective to lipid peroxidation.

Does α-Amino-β-methylaminopropionic Acid (BMAA) Play a Role in Neurodegeneration?

PubMed Central

Chiu, Alexander S.; Gehringer, Michelle M.; Welch, Jeffrey H.; Neilan, Brett A.

2011-01-01

The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks and monkeys have shown that it can cause neurodegenerative symptoms such as ataxia and convulsions. Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential. PMID:22016712

Hemocompatibility Assessment of Carbonic Anhydrase Modified Hollow Fiber Membranes for Artificial Lungs

PubMed Central

Oh, Heung-Il; Ye, Sang-Ho; Johnson, Carl A.; Woolley, Joshua R.; Federspiel, William J.; Wagner, William R.

2011-01-01

Hollow fiber membrane (HFM)-based artificial lungs can require a large blood-contacting membrane surface area to provide adequate gas exchange. However, such a large surface area presents significant challenges to hemocompatibility. One method to improve carbon dioxide (CO2) transfer efficiency might be to immobilize carbonic anhydrase (CA) onto the surface of conventional HFMs. By catalyzing the dehydration of bicarbonate in blood, CA has been shown to facilitate diffusion of CO2 toward the fiber membranes. This study evaluated the impact of surface modifying a commercially available microporous HFM-based artificial lung on fiber blood biocompatibility. A commercial poly(propylene) Celgard HFM surface was coated with a siloxane, grafted with amine groups, and then attached with CA which has been shown to facilitate diffusion of CO2 toward the fiber membranes. Results following acute ovine blood contact indicated no significant reduction in platelet deposition or activation with the siloxane coating or the siloxane coating with grafted amines relative to base HFMs. However,HFMs with attached CA showed a significant reduction in both platelet deposition and activation compared with all other fiber types. These findings, along with the improved CO2 transfer observed in CA modified fibers, suggest that its incorporation into HFM design may potentiate the design of a smaller, more biocompatible HFM-based artificial lung. PMID:20633159

Acupuncture inhibits cue-induced heroin craving and brain activation★

PubMed Central

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-01-01

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving. PMID:25368637

Anticancer activity of bacteriophage T4 and its mutant HAP1 in mouse experimental tumour models.

PubMed

Dabrowska, Krystyna; Opolski, Adam; Wietrzyk, Joanna; Switala-Jelen, Kinga; Godlewska, Joanna; Boratynski, Janusz; Syper, Danuta; Weber-Dabrowska, Beata; Gorski, Andrzej

2004-01-01

Previously, we have shown the ability of the bacteriophage T4 and its substrain HAP1 (selected for a higher affinity to melanoma cells) to reveal antimetastatic activity in a mouse melanoma model. Here, we investigated the potential phage anticancer activity in primary tumour models. Mice were inoculated subcutaneously with B16 or LLC cells (collected from in vitro culture). Bacteriophages T4 and HAP1 were injected intraperitoneally daily (8 x 10(8)pfu/mouse, except the experiment concerning the dose-dependence). Treatment with purified preparations of bacteriophage T4 resulted in significant reduction of tumour size, the effect being dose-dependent. HAP1 was more effective than T4 and its activity was also dose-dependent. Parallel experiments with non-purified bacteriophage lysates resulted in significant stimulation of tumour growth. These data suggest that purified bacteriophages may inhibit tumour growth, a phenomenon with potentially important clinical implications in oncology.

Dopaminergic modulation of the voltage-gated sodium current in the cochlear afferent neurons of the rat.

PubMed

Valdés-Baizabal, Catalina; Soto, Enrique; Vega, Rosario

2015-01-01

The cochlear inner hair cells synapse onto type I afferent terminal dendrites, constituting the main afferent pathway for auditory information flow. This pathway receives central control input from the lateral olivocochlear efferent neurons that release various neurotransmitters, among which dopamine (DA) plays a salient role. DA receptors activation exert a protective role in the over activation of the afferent glutamatergic synapses, which occurs when an animal is exposed to intense sound stimuli or during hypoxic events. However, the mechanism of action of DA at the cellular level is still not completely understood. In this work, we studied the actions of DA and its receptor agonists and antagonists on the voltage-gated sodium current (INa) in isolated cochlear afferent neurons of the rat to define the mechanisms of dopaminergic control of the afferent input in the cochlear pathway. Experiments were performed using the voltage and current clamp techniques in the whole-cell configuration in primary cultures of cochlear spiral ganglion neurons (SGNs). Recordings of the INa showed that DA receptor activation induced a significant inhibition of the peak current amplitude, leading to a significant decrease in cell excitability. Inhibition of the INa was produced by a phosphorylation of the sodium channels as shown by the use of phosphatase inhibitor that produced an inhibition analogous to that caused by DA receptor activation. Use of specific agonists and antagonists showed that inhibitory action of DA was mediated both by activation of D1- and D2-like DA receptors. The action of the D1- and D2-like receptors was shown to be mediated by a Gαs/AC/cAMP/PKA and Gαq/PLC/PKC pathways respectively. These results showed that DA receptor activation constitutes a significant modulatory input to SGNs, effectively modulating their excitability and information flow in the auditory pathway.

In view of an optimal gut antifungal therapeutic strategy: an in vitro susceptibility and toxicity study testing a novel phyto-compound.

PubMed

Metugriachuk, Yussef; Kuroi, Olivia; Pavasuthipaisit, Kanok; Tsuchiya, Junji; Minelli, Emilio; Okura, Ruichi; Fesce, Edoardo; Marotta, F

2005-01-01

In view of the raising concern for gut fungal infection, the aim of the present research was to carry out a systematic in vitro study testing the antifungal activity and possible toxicity of a polygodyal-anethole compound (Kolorex) in several strains of Candida albicans and in other fungal pathogens. The in vitro susceptibility tests were carried out on 4 strains of C. albicans (C. krusei, C. lipolytica, C. tropicalis, C. utilis), Aspergillus flavus and A. fumigatus. Cultures were also analyzed by varying medium, pH and inoculum size, and a time-course killing test was carried out. In the present study the polygodyal-anethole compound showed remarkable in vitro activity against the most common fungi, which was significantly better than polygodyal alone. Moreover, such mixture compound was shown to exert its activity against a wide spectrum of fungi, including C. lipolytica and C. tropicalis, which required significantly higher MIC of polygodyal to be unfeasible in clinical application. The activity of the polygodyal-anethole compound was significantly better than polygodyal alone with high inoculum size and low pH. Moreover, it proved to exert a significantly faster biological activity against low inoculum. This study suggests that the mixture compound Kolorex has a very good profile of antifungal activity in terms of effectiveness and spectrum of action while being devoid of any significant toxicity.

Pedagogies of Protest: African American Teachers and the History of the Civil Rights Movement, 1940-1963

ERIC Educational Resources Information Center

Baker, Scott

2011-01-01

Background/Context: Although the dominant narrative of the civil rights movement marginalizes the role of black educators, revisionist scholars have shown that a significant number of black teachers encouraged student protest and activism. There has, however, been little analysis of the work of black teachers inside segregated schools in the…

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2014-10-01

has also been shown to produce human-beta-3-defensin. These antimicrobial peptides are implicated in the resistance of epithelial surfaces to...gonadotrophin receptors that regulate prostaglandin production and activity. Epithelial cells manufacture multiple vasoactive peptides , growth factors...200734 P-RCT (n Z 102) PT burns Processed Amnion vs topical antimicrobials . Significantly less dressing changes with amnion. Time to healing, length

[Concentrated adsorbed, cultured antirabies vaccine].

PubMed

Dulina, A V; Shafeeva, R S; Morogova, V M; Krutilina, D V; Nigamov, F N

1980-11-01

In animal experiments the antigenic activity of adsorbed concentrated tissue-culture rabies vaccine was shown to be significantly higher in comparison with the nonadsorbed concentrated preparation when introduced in 2 intramuscular injections at an interval of 21 and 30 days, as well as in comparison with commercial tissue-culture vaccine when introduced subcutaneously in a 14-day course of daily injections.

Effect of different brewing times on antioxidant activity and polyphenol content of loosely packed and bagged black teas (Camellia sinensis L.).

PubMed

Nikniaz, Zeinab; Mahdavi, Reza; Ghaemmaghami, Seyed Jamal; Lotfi Yagin, Neda; Nikniaz, Leila

2016-01-01

Determination and comparison of the effect of infusion time on the antioxidant activity and total polyphenol contents of bagged and loosely packed black teas. For twenty loosely packed and eleven bagged tea samples, the antioxidant activity and total polyphenol content were analyzed using FRAP and Folin-Ciocalteau methods, respectively. The ANOVA with Tukey post-hoc test and independent t-test were used for statistical analysis. The antioxidant activity and polyphenol content of various brands of tea samples were significantly different. There were significant differences in the antioxidant activity of loosely packed teas between 5, 15(p=0.03), 30(p=0.02) and 60(p=0.007) minutes of brewing times. Besides, there was a significant difference in antioxidant activity of bagged samples infused for 1 minute with four other infusion time points (p<0.001). In the case of polyphenol content, in loosely-packed tea samples, there were not significant differences between different brewing times (p=0.15). However, in bagged samples, the polyphenol contents of samples that were brewed for 1 minute were significantly lower than samples brewed for 3, 4, and 5 minutes (p<0.05). The antioxidant activity and polyphenol content of tea bags were significantly higher than those ofloosely-packed forms of the same brands at 5-min of brewing time (p<0.001). The infusion time and the form of tea (loosely packed or bagged) were shown to be important determinants of the antioxidant activity and polyphenol content of black tea infusions in addition to the variety, growing environment and manufacturing conditions.

King cobra (Ophiophagus hannah) venom L-amino acid oxidase induces apoptosis in PC-3 cells and suppresses PC-3 solid tumor growth in a tumor xenograft mouse model.

PubMed

Lee, Mui Li; Fung, Shin Yee; Chung, Ivy; Pailoor, Jayalakshmi; Cheah, Swee Hung; Tan, Nget Hong

2014-01-01

King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors.

Analysis of the activation status of Akt, NFkappaB, and Stat3 in human diffuse gliomas.

PubMed

Wang, Huamin; Wang, Hua; Zhang, Wei; Huang, Helen J; Liao, Warren S L; Fuller, Gregory N

2004-08-01

Loss of phosphatase and tensin homolog (PTEN) and amplification of the epidermal growth factor receptor (EGFR) gene contribute to the progression of gliomas. As downstream targets of the PTEN and EGFR signaling pathways, Akt, NFkappaB, and signal transducer and activator of transcription-3 (Stat3) have been shown to play important roles in the control of cell proliferation, apoptosis, and oncogenesis. We examined the activation status of Akt, NFkappaB, and Stat3 in 259 diffuse gliomas using tissue microarrays and immunohistochemistry, and evaluated their association with glioma grade. We observed significant positive correlations between the activation status of Akt and NFkappaB and glioma grade. In contrast, only focal immunoreactivity for phospho-Stat3 was observed in < 9% of high-grade gliomas. In addition, we observed a significant correlation between the activation of Akt and NFkappaB. Functional correlation between Akt activation and the activation of NFkappaB was confirmed in U251MG GBM cells in which inhibition of Akt activation either by stable expression of PTEN or by the PI3-kinase inhibitors, wortmannin and LY294002, led to a concomitant decrease in NFkappaB-binding activity. Thus, our results demonstrate that constitutive activation of Akt and NFkappaB, but not Stat3, contributes significantly to the progression of diffuse gliomas, and activation of Akt may lead to NFkappaB activation in high-grade gliomas.

Physical activity, energy intake, and obesity prevalence among urban and rural schoolchildren aged 11-12 years in Japan.

PubMed

Itoi, Aya; Yamada, Yosuke; Watanabe, Yoshiyuki; Kimura, Misaka

2012-12-01

The prevalence of childhood overweight and obesity has been shown to differ among regions, including rural-urban regional differences within nations. This study obtained simultaneous accelerometry-derived physical activity, 24 h activity, and food records to clarify the potential contributing factors to rural-urban differences in childhood overweight and obesity in Japan. Sixth-grade children (n = 227, 11-12 years old) from two urban elementary schools in Kyoto and four rural elementary schools in Tohoku participated in the study. The children were instructed to wear a pedometer that included a uniaxial accelerometer and, assisted by their parents, keep minute-by-minute 24 h activity and food records. For 12 children, the total energy expenditure was measured by the doubly labeled water method that was used to correct the Lifecorder-predicted activity energy expenditure and physical activity level. The overweight and obesity prevalence was significantly higher in rural than in urban children. The number of steps per day, activity energy expenditure, physical activity level, and duration of walking to school were significantly lower in rural than in urban children. In contrast, the reported energy intake did not differ significantly between the regions. The physical activity and duration of the walk to school were significantly correlated with body mass index. Rural children had a higher prevalence of overweight and obesity, and this may be at least partly caused by lower physical activity, especially less time spent walking to school, than urban children.

Racial variation in lipoprotein-associated phospholipase A2 in older adults

PubMed Central

2011-01-01

Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor of cardiovascular events that has been shown to vary with race. The objective of this study was to examine factors associated with this racial variation. Methods We measured Lp-PLA2 mass and activity in 714 healthy older adults with no clinical coronary heart disease and not taking dyslipidemia medication. We evaluated the association between race and Lp-PLA2 mass and activity levels after adjustment for various covariates using multivariable linear regression. These covariates included age, sex, diabetes, hypertension, body mass index, lipid measurements, C-reactive protein, smoking status, physical activity, diet, income, and education level. We further examined genetic covariates that included three single nucleotide polymorphisms shown to be associated with Lp-PLA2 activity levels. Results The mean age was 66 years. Whites had the highest Lp-PLA2 mass and activity levels, followed by Hispanics and Asians, and then African-Americans; in age and sex adjusted analyses, these differences were significant for each non-White race as compared to Whites (p < 0.0001). For example, African-Americans were predicted to have a 55.0 ng/ml lower Lp-PLA2 mass and 24.7 nmol/ml-min lower activity, compared with Whites, independent of age and sex (p < 0.0001). After adjustment for all covariates, race remained significantly correlated with Lp-PLA2 mass and activity levels (p < 0.001) with African-Americans having 44.8 ng/ml lower Lp-PLA2 mass and 17.3 nmol/ml-min lower activity compared with Whites (p < 0.0001). Conclusion Biological, lifestyle, demographic, and select genetic factors do not appear to explain variations in Lp-PLA2 mass and activity levels between Whites and non-Whites, suggesting that Lp-PLA2 mass and activity levels may need to be interpreted differently for various races. PMID:21714927

Memantine ameliorates autistic behavior, biochemistry & blood brain barrier impairments in rats.

PubMed

Kumar, Hariom; Sharma, Bhupesh

2016-06-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, commonly characterized by altered social behavior, communication, biochemistry and pathological conditions. One percent of the worldwide population suffers from autism and males suffer more than females. NMDA receptors have the important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. This study has been designed to investigate the role of memantine, a NMDA receptor modulator, in prenatal valproic acid-induced autism in rats. Animals with prenatal valproic acid have shown the reduction in social interaction (three-chamber social behavior apparatus), spontaneous alternation (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, prenatal valproic acid-treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood-brain barrier permeability. Treatment with memantine has significantly attenuated prenatal valproic acid-induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, memantine has also attenuated the prenatal valproic acid-induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood-brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behavior, biochemistry and blood-brain barrier impairment in animals, which were significantly attenuated by memantine. NMDA receptor modulators like memantine should be explored further for the therapeutic benefits in autism. Copyright © 2016 Elsevier Inc. All rights reserved.

Intensive rehabilitation for dementia improved cognitive function and reduced behavioral disturbance in geriatric health service facilities in Japan.

PubMed

Toba, Kenji; Nakamura, Yu; Endo, Hidetoshi; Okochi, Jiro; Tanaka, Yukiko; Inaniwa, Chiyako; Takahashi, Akira; Tsunoda, Naoko; Higashi, Kentaro; Hirai, Motoharu; Hirakawa, Hiroyuki; Yamada, Shizuru; Maki, Yohko; Yamaguchi, Tomoharu; Yamaguchi, Haruyasu

2014-01-01

To examine the efficacy of rehabilitation for elderly individuals with dementia at intermediate facilities between hospitals and home, based on the policies for elderly individuals to promote community-based care at home and dehospitalization. Participants were older adults with dementia newly admitted to intermediate facilities. A total of 158 in the intervention group who claimed Long-Term Care Insurance for three consecutive months, and 54 in the control group were included in the analysis. The interventions were carried out in a tailor-made manner to meet individual needs. The personal sessions were carried out three times a week for 3 months after admission by physical, occupational or speech therapists. Outcome measures were cognitive tests (Hasegawa Dementia Scale revised [HDS-R] and Mini-Mental State Examination), and observational assessments of dementia severity, activities of daily living (ADL), social activities, behavioral and psychological symptoms of dementia (BPSD) using a short version of the Dementia Disturbance Scale (DBD13), depressive mood, and vitality. Significant improvement in the intervention group was shown in cognitive function measured by HDS-R (interaction F[1, 196] = 5.190, P = 0.024), observational evaluation of dementia severity (F[1,198] = 9.550, P = 0.002) and BPSD (DBD13; F[1,197] = 4.506, P = 0.035). Vitality, social activities, depressive mood and ADL were significantly improved only in the intervention group, although interaction was not significant. Significant improvement by intervention was shown in multiple domains including cognitive function and BPSD. Cognitive decline and worsening of BPSD are predictors of care burden and hospitalization, thus intensive rehabilitation for dementia was beneficial for both individuals with dementia and their caregivers. © 2013 Japan Geriatrics Society.

The Stroop Effect in Kana and Kanji Scripts in Native Japanese Speakers: An fMRI Study

PubMed Central

Coderre, Emily L.; Filippi, Christopher G.; Newhouse, Paul A.; Dumas, Julie A.

2008-01-01

Prior research has shown that the two writing systems of the Japanese orthography are processed differently: kana (syllabic symbols) are processed like other phonetic languages such as English, while kanji (a logographic writing system) are processed like other logographic languages like Chinese. Previous work done with the Stroop task in Japanese has shown that these differences in processing strategies create differences in Stroop effects. This study investigated the Stroop effect in kanji and kana using functional magnetic resonance imaging (fMRI) to examine the similarities and differences in brain processing between logographic and phonetic languages. Nine native Japanese speakers performed the Stroop task both in kana and kanji scripts during fMRI. Both scripts individually produced significant Stroop effects as measured by the behavioral reaction time data. The imaging data for both scripts showed brain activation in the anterior cingulate gyrus, an area involved in inhibiting automatic processing. Though behavioral data showed no significant differences between the Stroop effects in kana and kanji, there were differential areas of activation in fMRI found for each writing system. In fMRI, the Stroop task activated an area in the left inferior parietal lobule during the kana task and the left inferior frontal gyrus during the kanji task. The results of the present study suggest that the Stroop task in Japanese kana and kanji elicits differential activation in brain regions involved in conflict detection and resolution for syllabic and logographic writing systems. PMID:18325582

Fast and slow active control of combustion instabilities in liquid-fueled combustors

NASA Astrophysics Data System (ADS)

Lee, Jae-Yeon

This thesis describes an experimental investigation of two different novel active control approaches that are employed to suppress combustion instabilities in liquid-fueled combustors. A "fast" active controller requires continuous modulation of the fuel injection rate at the frequency of the instability with proper phase and gain. Use of developed optical tools reveals that the "fast" active control system suppresses the instability by changing the nearly flat distribution of the phase between pressure and heat release oscillations to a gradually varying phase distribution, thus dividing the combustion zone into regions that alternately damp and drive combustor oscillations. The effects of these driving/damping regions tend to counter one another, which result in significant damping of the unstable oscillations. In contrast, a "slow" active controller operates at a rate commensurate with that at which operating conditions change during combustor operation. Consequently, "slow" controllers need infrequent activation in response to changes in engine operating conditions to assure stable operation at all times. Using two types of fuel injectors that can produce large controllable variation of fuel spray properties, it is shown that by changing the spray characteristics it is possible to significantly damp combustion instabilities. Similar to the aforementioned result of the "fast" active control study, "slow" change of the fuel spray properties also modifies the nearly flat phase distribution during unstable operation to a gradually varying phase distribution, resulting in combustor "stabilization". Furthermore, deconvolutions of CH*-chemiluminescence images reveal the presence of vortex-flame interaction during unstable operation. Strong driving of instabilities occurs where the mean axial velocity of the flow is approximately zero, a short distance downstream of the flame holder where a significant fraction of the fuel burns in phase with the pressure oscillations. It is shown that the "fast" and "slow" active control approaches suppress combustion instabilities in a different manner. Nevertheless, the both control approaches successfully suppress combustion instabilities by modifying the temporal and spatial behavior of the combustion process heat release that is responsible for driving the instability.

Activation of the serotonergic system by pedaling exercise changes anterior cingulate cortex activity and improves negative emotion.

PubMed

Ohmatsu, Satoko; Nakano, Hideki; Tominaga, Takanori; Terakawa, Yuzo; Murata, Takaho; Morioka, Shu

2014-08-15

Pedaling exercise (PE) of moderate intensity has been shown to ease anxiety and discomfort; however, little is known of the changes that occur in brain activities and in the serotonergic (5-HT) system after PE. Therefore, this study was conducted for the following reasons: (1) to localize the changes in the brain activities induced by PE using a distributed source localization algorithm, (2) to examine the changes in frontal asymmetry, as used in the Davidson model, with electroencephalography (EEG) activity, and (3) to examine the effect of PE on the 5-HT system. A 32-channel EEG was used to record before and after PE. Profile of Mood States tests indicated that there was a significant decrease in tension-anxiety and a significant increase in vigor after PE. A standardized low-resolution brain electromagnetic tomography analysis showed a significant decrease in brain activities after PE in the alpha-2 band (10-12.5 Hz) in the anterior cingulate cortex (ACC). Moreover, a significant increase in frontal EEG asymmetry was observed after PE in the alpha-1 band (7.5-10 Hz). Urine 5-HT levels significantly increased after PE. Urine 5-HT levels positively correlated with the degree of frontal EEG asymmetry in the alpha-1 band and negatively correlated with brain activity in ACC. Our results suggested that PE activates the 5-HT system and consequently induces increases in frontal EEG asymmetry in the alpha-1 band and reductions of brain activity in the alpha-2 band in the ACC region. Copyright © 2014 Elsevier B.V. All rights reserved.

Nitrones as Therapeutics

PubMed Central

Floyd, Robert A.; Kopke, Richard D.; Choi, Chul-Hee; Foster, Steven B.; Doblas, Sabrina; Towner, Rheal A.

2008-01-01

Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones including PBN (α-phenyl-tert-butylnitrone) have been shown to have potent biological activity in many experimental animal models. Many diseases of aging including stroke, cancer development, Parkinson’s disease and Alzheimer’s disease are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development in stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several experimental cancer models and have potential as therapeutics in some cancers. Also in recent observations nitrones have been shown to act synergistically in combination with antioxidants in the prevention of acute acoustic noise induced hearing loss. The mechanistic basis of the potent biological activity of PBN-related nitrones is not known. Even though PBN-related nitrones do decrease oxidative stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular signaling processes can not readily be explained by conventional notions of free radical trapping biochemistry. This review is focused on our observations and others where the use of selected nitrones as novel therapeutics have been evaluated in experimental models in the context of free radical biochemical and cellular processes considered important in pathologic conditions and age-related diseases. PMID:18793715

The impact of Rhodiola rosea on the gut microbial community of Drosophila melanogaster.

PubMed

Labachyan, Khachik E; Kiani, Dara; Sevrioukov, Evgueni A; Schriner, Samuel E; Jafari, Mahtab

2018-01-01

The root extract of Rhodiola rosea has historically been used in Europe and Asia as an adaptogen, and similar to ginseng and Shisandra , shown to display numerous health benefits in humans, such as decreasing fatigue and anxiety while improving mood, memory, and stamina. A similar extract in the Rhodiola family, Rhodiola crenulata , has previously been shown to confer positive effects on the gut homeostasis of the fruit fly, Drosophila melanogaster. Although, R. rosea has been shown to extend lifespan of many organisms such as fruit flies, worms and yeast, its anti-aging mechanism remains uncertain. Using D. melanogaster as our model system, the purpose of this work was to examine whether the anti-aging properties of R. rosea are due to its impact on the microbial composition of the fly gut. Rhodiola rosea treatment significantly increased the abundance of Acetobacter , while subsequently decreasing the abundance of Lactobacillales of the fly gut at 10 and 40 days of age. Additionally, supplementation of the extract decreased the total culturable bacterial load of the fly gut, while increasing the overall quantifiable bacterial load. The extract did not display any antimicrobial activity when disk diffusion tests were performed on bacteria belonging to Microbacterium , Bacillus , and Lactococcus . Under standard and conventional rearing conditions, supplementation of R. rosea significantly alters the microbial community of the fly gut, but without any general antibacterial activity. Further studies should investigate whether R. rosea impacts the gut immunity across multiple animal models and ages.

Using cranial electrotherapy stimulation to treat pain associated with spinal cord injury.

PubMed

Tan, Gabriel; Rintala, Diana H; Thornby, John I; Yang, June; Wade, Walter; Vasilev, Christine

2006-01-01

Treatments for chronic pain in persons with spinal cord injury (SCI) have been less than effective. Cranial electrotherapy stimulation (CES), a noninvasive technique that delivers a microcurrent to the brain via ear clip electrodes, has been shown to effectively treat several neurological and psychiatric disorders. The present study examined the effects of daily 1-hour active CES or sham CES treatment (randomly assigned) for 21 days on pain intensity and interference with activities in 38 males with SCI. The active CES group (n = 18) reported significantly decreased daily pain intensity compared with the sham CES group (n = 20) (mean change: active CES = -0.73, sham CES = -0.08; p = 0.03). Additionally, the active CES group reported significantly decreased pain interference (-14.6 pre- vs postintervention, p = 0.004) in contrast to the nonsignificant decrease in the sham CES group (-4.7 pre- vs postintervention, p = 0.24). These results suggest that CES can effectively treat chronic pain in persons with SCI.

Statistical modeling of Earth's plasmasphere

NASA Astrophysics Data System (ADS)

Veibell, Victoir

The behavior of plasma near Earth's geosynchronous orbit is of vital importance to both satellite operators and magnetosphere modelers because it also has a significant influence on energy transport, ion composition, and induced currents. The system is highly complex in both time and space, making the forecasting of extreme space weather events difficult. This dissertation examines the behavior and statistical properties of plasma mass density near geosynchronous orbit by using both linear and nonlinear models, as well as epoch analyses, in an attempt to better understand the physical processes that precipitates and drives its variations. It is shown that while equatorial mass density does vary significantly on an hourly timescale when a drop in the disturbance time scale index ( Dst) was observed, it does not vary significantly between the day of a Dst event onset and the day immediately following. It is also shown that increases in equatorial mass density were not, on average, preceded or followed by any significant change in the examined solar wind or geomagnetic variables, including Dst, despite prior results that considered a few selected events and found a notable influence. It is verified that equatorial mass density and and solar activity via the F10.7 index have a strong correlation, which is stronger over longer timescales such as 27 days than it is over an hourly timescale. It is then shown that this connection seems to affect the behavior of equatorial mass density most during periods of strong solar activity leading to large mass density reactions to Dst drops for high values of F10.7. It is also shown that equatorial mass density behaves differently before and after events based on the value of F10.7 at the onset of an equatorial mass density event or a Dst event, and that a southward interplanetary magnetic field at onset leads to slowed mass density growth after event onset. These behavioral differences provide insight into how solar and geomagnetic conditions impact mass density at geosynchronous orbit, enabling operators to better anticipate the response to space weather events and magnetosphere models to include mass density effects in magnetosphere simulations. It is shown that it is possible to classify an equatorial mass density event onset as being distinct from the three hours preceding it, indicating that there are distinguishing characteristics of solar wind and geomagnetic conditions surrounding an event. It is also been shown that given four days of solar and geomagnetic conditions, an event can be forecasted a day in advance with reasonable accuracy, but also with a number of false positives. These false positives have similarly distributed values as the true positives, though, indicating more data are needed to distinguish impending events.

The effects of an instant haw beverage on lipid levels, antioxidant enzyme and immune function in hyperlipidemia patients.

PubMed

Chen, Jidi; Xue, Bin; Li, Keji; Shi, Jingda; Krempin, D; Zhu, M; Garland, C

2002-05-01

To determine the effectiveness of an instant haw beverage in regulating lipid disturbance, enhancing antioxidant enzyme activity and immune function. Data was collected from 60 hyperlipidemic subjects. In this crossover design, each subject randomly received either the instant haw beverage (100 ml corresponding to 3 g of haw powder or 30 g of fresh haw fruit plus the carrier-guar gum plus some starch) or placebo (guar gum 1.5 g plus some starch as the carrier of the beverage) twice daily. Each supplementation lasted 31 days with a 28-day washout period between treatments. The instant haw beverage significantly reduced total serum cholesterol (9.6%), triglyceride (12.1%), LDLC (18%) while significantly increased SOD activities (7.5%). The placebo was shown to have positive results in some of the lipid profiles, though the effects of the instant haw beverage demonstrated greater significance. Serum triglyceride levels were significantly decreased and SOD activity significantly increased only as subjects were supplemented with the instant haw beverage while no significant changes were seen with placebo. Supplementation with the instant haw beverage positively affects blood lipid profile, antioxidant status and immune function in individuals with hyperlipidemia.

Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression.

PubMed

Kim, Yesl; Lee, Seung Min; Kim, Jung-Hyun

2014-01-01

Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown to have anti-oxidant and anti-carcinogenic activities. However, the effects and mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145 cells were treated with ethanol or water extract of unripe or ripe RCM and examined for cell invasion, migration, and matrix metalloproteinases (MMPs) activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were examined. Unripe RCM extracts exerted significant inhibitory effects on cell migration, invasion, and MMPs activities. A significant reduction in MMPs activities by unripe RCM ethanol extract treatment (UE) was associated with reduction of MMPs expression and induction of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was diminished by UE treatment. In this study, we demonstrated that UE decreased metastatic potential of prostate cancer cells by reducing MMPs expression through the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and enhancing TIMPs expression.

Antioxidant status in oral subchronic toxicity of fipronil and fluoride co-exposure in buffalo calves.

PubMed

Gill, Kamalpreet Kaur; Dumka, Vinod Kumar

2016-02-01

The effects of fipronil and fluoride co-exposure were investigated on antioxidant status of buffalo calves. A total of 24 healthy male buffalo calves divided into 4 groups were treated for 98 consecutive days. Group I, receiving no treatment, served as the control. Animals of groups II and III were orally administered with fipronil at the dosage of 0.5 mg/kg/day and sodium fluoride (NaF) at the dosage of 6.67 mg/kg/day, respectively, for 98 days. Group IV was coadministered with fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced significant elevation in lipid peroxidation (LPO) and decrease in the levels of nonenzymatic antioxidant glutathione (GSH). However, it did not produce any significant effect on the activities of enzymatic antioxidants including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). NaF exposure led to enhanced oxidative stress as shown by significant increase in the LPO and SOD activities while GPx and CAT activities and GSH levels were significantly decreased. Co-exposure to fipronil and NaF showed additive effects on LPO, GPx activity, and GSH levels. © The Author(s) 2013.

Influence of phosphorylation of THR-3, SER-11, and SER-15 on deoxycytidine kinase activity and stability.

PubMed

Smal, C; Ntamashimikiro, S; Arts, A; Van Den Neste, E; Bontemps, F

2010-06-01

Deoxycytidine kinase (dCK) is a key enzyme in the salvage of deoxyribonucleosides and in the activation of several anticancer and antiviral nucleoside analogues. We have recently shown that dCK is a phosphoprotein. Four in vivo phosphorylation sites were identified: Thr-3, Ser-11, Ser-15, and Ser-74. Site-directed mutagenesis demonstrated that phosphorylation of Ser-74, the major phosphorylated residue, strongly influences dCK activity in eucaryotic cells. Here, we show that phosphorylation of the three other sites, located in the N-terminal extremity of the protein, does not significantly modify dCK activity, but phosphorylation of Thr-3 could promote dCK stability.

Relationship between cancer-related fatigue and physical activity in inpatient cancer rehabilitation.

PubMed

Kummer, Franziska; Catuogno, Silvio; Perseus, Josef M; Bloch, Wilhelm; Baumann, Freerk T

2013-08-01

Fatigue is a serious problem for the majority of patients with cancer. In this context, several studies have shown benefits of physical activity during and following treatment. However, uncertainties remain regarding the optimal type and duration of physical activity. Therefore, this study examined the relationship between cancer-related fatigue and physical activity in the course of inpatient rehabilitation. Fatigue (Multidimensional Fatigue Inventory) and physical activity (Freiburg Questionnaire of Physical Activity) were assessed in a consecutive series of 35 patients with cancer attending oncological inpatient rehabilitation during a six-month study period. The three-week rehabilitation program included daily exercise therapy consisting of aerobic endurance training, moderate resistance training, coordination exercises, relaxation training and individual physiotherapy. At discharge, a significant improvement in each dimension of cancer-related fatigue (p=0.001-0.003) and a significant increase of physical activity levels (p=0.001) were observed. A small, but significant negative correlation was found between cancer-related fatigue and the level of physical activity (R=-0.438, p=0.004). The largest effects were associated with a weekly energy expenditure of 3000 kcal through physical activity. The results support a non-linear dose-response relationship between cancer-related fatigue and physical activity. Since this is the first study providing specific exercise recommendations for an effective treatment of cancer-related fatigue in the context of inpatient rehabilitation, further research is required to validate the observed trends.

Near infrared radiation protects against oxygen-glucose deprivation-induced neurotoxicity by down-regulating neuronal nitric oxide synthase (nNOS) activity in vitro.

PubMed

Yu, Zhanyang; Li, Zhaoyu; Liu, Ning; Jizhang, Yunneng; McCarthy, Thomas J; Tedford, Clark E; Lo, Eng H; Wang, Xiaoying

2015-06-01

Near infrared radiation (NIR) has been shown to be neuroprotective against neurological diseases including stroke and brain trauma, but the underlying mechanisms remain poorly understood. In the current study we aimed to investigate the hypothesis that NIR may protect neurons by attenuating oxygen-glucose deprivation (OGD)-induced nitric oxide (NO) production and modulating cell survival/death signaling. Primary mouse cortical neurons were subjected to 4 h OGD and NIR was applied at 2 h reoxygenation. OGD significantly increased NO level in primary neurons compared to normal control, which was significantly ameliorated by NIR at 5 and 30 min post-NIR. Neither OGD nor NIR significantly changed neuronal nitric oxide synthase (nNOS) mRNA or total protein levels compared to control groups. However, OGD significantly increased nNOS activity compared to normal control, and this effect was significantly diminished by NIR. Moreover, NIR significantly ameliorated the neuronal death induced by S-Nitroso-N-acetyl-DL-penicillamine (SNAP), a NO donor. Finally, NIR significantly rescued OGD-induced suppression of p-Akt and Bcl-2 expression, and attenuated OGD-induced upregulation of Bax, BAD and caspase-3 activation. These results suggest NIR may protect against OGD at least partially through reducing NO production by down-regulating nNOS activity, and modulating cell survival/death signaling.

Synthesis of new bioactive aminophosphonates and study of their antioxidant, anti-inflammatory and antibacterial activities as well the assessment of their toxicological activity

NASA Astrophysics Data System (ADS)

Damiche, Rebiha; Chafaa, Salah

2017-02-01

Two new categories of α-aminophosphonates molecules were synthesized and characterized by UV-Vis, IR, and NMR. Their spectral properties show a perfect convergence. Their biological activities were evaluated. Molecules 1a, 2a, and 1d present a greater antioxidant potential than BHT and vitamin C. The best anti-inflammatory activity is shown by the 2b molecule and that of 1a, 2a, and 2c molecules are closely comparable to that of diclofenac. The antibacterial activity of the synthesized compounds is significantly higher than the antibiotic amoxicillin. The hemolysis rate HR of compounds 1b, 1c, 2b, and 2c was lower than 5%.

Childhood Obesity, Physical Activity, and Exercise.

PubMed

Nemet, Dan

2017-02-01

As the incidence of childhood obesity increases, there is a need to promote leisure time physical activity. Traditional approaches to promote the population physical activity levels have shown at best moderate improvements. High percentage of children today carry a cell phone, thus the use of this portable device seems promising for enhancing physical activity. Pokémon Go, is a smartphone game that uses augmented reality, where players are incentivized to get out and walk significant distances to catch the Pokémon. Initial reports suggested increases in the number of steps that players performed, yet this effect of the game was not sustained. Incorporating physical activity into modern technology seems promising, clearly there is need to explore creative ways to achieve a longer term effect.

Randomized Trial of a Lifestyle Physical Activity Intervention for Breast Cancer Survivors: Effects on Transtheoretical Model Variables.

PubMed

Scruggs, Stacie; Mama, Scherezade K; Carmack, Cindy L; Douglas, Tommy; Diamond, Pamela; Basen-Engquist, Karen

2018-01-01

This study examined whether a physical activity intervention affects transtheoretical model (TTM) variables that facilitate exercise adoption in breast cancer survivors. Sixty sedentary breast cancer survivors were randomized to a 6-month lifestyle physical activity intervention or standard care. TTM variables that have been shown to facilitate exercise adoption and progress through the stages of change, including self-efficacy, decisional balance, and processes of change, were measured at baseline, 3 months, and 6 months. Differences in TTM variables between groups were tested using repeated measures analysis of variance. The intervention group had significantly higher self-efficacy ( F = 9.55, p = .003) and perceived significantly fewer cons of exercise ( F = 5.416, p = .025) at 3 and 6 months compared with the standard care group. Self-liberation, counterconditioning, and reinforcement management processes of change increased significantly from baseline to 6 months in the intervention group, and self-efficacy and reinforcement management were significantly associated with improvement in stage of change. The stage-based physical activity intervention increased use of select processes of change, improved self-efficacy, decreased perceptions of the cons of exercise, and helped participants advance in stage of change. These results point to the importance of using a theory-based approach in interventions to increase physical activity in cancer survivors.

Oral Contraceptives and Bone Health in Female Runners

DTIC Science & Technology

2006-10-01

activity. Previous cross-sectional research has shown that women with exercise - induced menstrual irregularities have a significantly higher...6. Cumming D.C. Exercise -associated amenorrhea , low BMD, and estrogen replacement therapy. Arch Intern Med. 156:2193-2195, 1996. 34 7. De...Science in Sports & Exercise . (i) Abstract from manuscript, “Randomized trial of the effect of oral contraceptives on bone mass and stress

77 FR 38299 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... 0910-New) I. Background A recent study of obesity indicates that 35.5 percent of men and 35.8 percent... were spent in 2008 to treat obesity-related diseases (Ref. 2). Studies have shown that weight loss can significantly reduce the burden of obesity-related comorbidities (Refs. 3 and 4), and that weight lost as a...

The phase of prestimulus alpha oscillations affects tactile perception.

PubMed

Ai, Lei; Ro, Tony

2014-03-01

Previous studies have shown that neural oscillations in the 8- to 12-Hz range influence sensory perception. In the current study, we examined whether both the power and phase of these mu/alpha oscillations predict successful conscious tactile perception. Near-threshold tactile stimuli were applied to the left hand while electroencephalographic (EEG) activity was recorded over the contralateral right somatosensory cortex. We found a significant inverted U-shaped relationship between prestimulus mu/alpha power and detection rate, suggesting that there is an intermediate level of alpha power that is optimal for tactile perception. We also found a significant difference in phase angle concentration at stimulus onset that predicted whether the upcoming tactile stimulus was perceived or missed. As has been shown in the visual system, these findings suggest that these mu/alpha oscillations measured over somatosensory areas exert a strong inhibitory control on tactile perception and that pulsed inhibition by these oscillations shapes the state of brain activity necessary for conscious perception. They further suggest that these common phasic processing mechanisms across different sensory modalities and brain regions may reflect a common underlying encoding principle in perceptual processing that leads to momentary windows of perceptual awareness.

Mosquito larvae can detect water vibration patterns from a nearby predator.

PubMed

Roberts, D

2017-08-01

Mosquito larvae have been shown to respond to water-borne kairomones from nearby predators by reducing their activity, and thus visibility. If they can identify the predator, they can then alter their response depending upon the associated predation risk. No studies have shown that mosquito larva may also detect water-borne vibrations from the predator. Final instar larvae of three mosquitoes: Culiseta longiareolata, Culex perexiguus and C. quinquefasciatus, were exposed to recorded vibrations from feeding dragonfly nymphs, to dragonfly kairomones and the combined effect of both. Predator vibrations caused C. longiareolata to significantly reduce bottom feeding and instead increased the more passive surface filter feeding. The larvae also significantly increased escape swimming activity. These behavioural changes were not significantly different from the effect of dragonfly kairomones, and there was no synergistic or additional effect of the two. C. perexiguus gave a smaller (but still significant) response to both dragonfly vibrations and to kairomones, probably due to a different feeding behaviour: when lying on the bottom, it was an inactive filter feeder. C. quinquefasciatus did not respond to either vibrations or kairomones and during these experiments was entirely an inactive surface filter feeder. Both C. longiareolata and C. perexiguus were thus able to detect and identify vibrations from feeding dragonfly nymphs as an anti-predator strategy. The lack of response in C. quinquefasciatus is probably a result of living in water that is highly polluted with organic material, where few predators can survive.

(+)-(S)-alapyridaine--a general taste enhancer?

PubMed

Soldo, Tomislav; Blank, Imre; Hofmann, Thomas

2003-06-01

N-(1-Carboxyethyl)-6-hydroxymethyl-pyridinium-3-ol inner salt (alapyridaine), recently identified in heated sugar/amino acid mixtures as well as in beef bouillon, has been shown to exhibit general taste-enhancing activities, although tasteless on its own. Differing from other taste enhancers reported so far, racemic (R/S)-alapyridaine and, to an even greater extent (+)-(S)-alapyridaine, the physiologically active enantiomer, are able to enhance more than one basic taste quality. The threshold concentrations for the sweet taste of glucose and sucrose, for the umami taste of monosodium L-glutamate (MSG) and guanosine-5'-monophosphate (GMP), as well as the salty taste of NaCl, were significantly decreased when alapyridaine was present. In contrast, perception of the bitter tastes of caffeine and L-phenylalanine, as well as of sour-tasting citric acid, was unaffected. Furthermore, alapyridaine was shown to intensify known taste synergies such as, for example, the enhancing effect of L-arginine on the salty taste of NaCl, as well as that of GMP on the umami taste of MSG. The activity of (+)-(S)-alapyridaine could be observed not only in solutions of single taste compounds, but also in more complex tastant mixtures; for example, the umami, sweet and salty taste of a solution containing MSG, sucrose, NaCl and caffeine was significantly modulated, thus indicating that alapyridaine is a general taste enhancer.

Hepatoprotective effects of aqueous extract from Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (higher basidiomycetes) on α-amanitin-induced liver injury in mice.

PubMed

Wu, Xin; Zeng, Jun; Hu, Jinsong; Liao, Qiong; Zhou, Rong; Zhang, Ping; Chen, Zuohong

2013-01-01

The Lingzhi or Reishi mushroom Ganoderma lucidum is a well-known traditional medicinal mushroom that has been shown to have obvious hepatoprotective effects. The aim of this study was to evaluate the hepatoprotective effects of G. lucidum aqueous extracts (GLEs) on liver injury induced by α-amanitin (α-AMA) in mice and to analyze the possible hepatoprotective mechanisms related to radical scavenging activity. Mice were treated with α-AMA prepared from Amanita exitialis and then administrated with GLE after the α-AMA injection. The hepatoprotective activity of the GLE was compared with the reference drug silibinin (SIL). α-AMA induced a significant elevation in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and provoked a significant reduction of superoxide dismutase (SOD) and catalase (CAT) activities and a significant increment of malondialdehyde (MDA) content in liver homogenate. Treatment with GLE or SIL significantly decreased serum ALT and AST levels, significantly increased SOD and CAT activities, and decreased MDA content in liver compared with the α-AMA control group. The histopathological examination of liver sections was consistent with that of biochemical parameters. The results demonstrated that GLE induces hepatoprotective effects on acute liver injury induced by α-AMA; these protective effects may be related in part to the antioxidant properties of GLE.

Physicochemical and functional properties of peeled and unpeeled pumpkin flour.

PubMed

Noor Aziah, A A; Komathi, C A

2009-09-01

This study was intended to investigate the potential of peeled and unpeeled pumpkin pulp as a raw material for the production of flour that could be used in composite blend with wheat flour or as a functional ingredient in food products. The peeled and unpeeled pumpkin pulp were soaked in sodium metabisulphite solution, sliced and dried overnight in a hot air oven, followed by milling into peeled pumpkin pulp flour (PPPF) and unpeeled pumpkin pulp flour (UPPF), respectively. The flours were then evaluated for physicochemical attributes (color, proximate compositions, and water activity) and functional properties (water holding capacity and oil holding capacity), in comparison to the commercial wheat flour. PPPF and UPPF were observed to be more attractive in terms of color than wheat flour, as indicated by the significantly higher results (P or= 0.05) was shown in water holding capacity of PPPF and wheat flour. However, the oil holding capacity of PPPF and UPPF was shown to be significantly higher (P

Regulation of the immune response by dehydroepiandrosterone and its metabolites.

PubMed

Loria, R M; Padgett, D A; Huynh, P N

1996-09-01

Dehydroepiandrosterone (5-androsten-3 beta-ol-17-one, DHEA) has been shown to protect mice from a variety of lethal infections. This includes, but is not limited to, infection with viruses (herpes virus type 2, coxsackie virus B4 (CB4)), bacteria (Enterococcus faecalis, Pseudomonas aeruginosa), and a parasite (Cryptosporidium parvum). We have previously reported that androstenediol (5-androstene-3 beta, 17 beta-diol, AED), derived from DHEA, is at least 100 x more effective in up-regulating systemic resistance against CB4 infection than its precursor. Furthermore, androstenetriol (5-androstene-3 beta,7 beta, 17 beta-triol, AET) which is formed by 7 beta hydroxylation of AED, was more effective against CB4 infection than its precursor, AED. Neither steroid, however, has shown any significant direct antiviral effects. The in vitro influences of DHEA, AED and AET on a mitogen-induced mixed splenocyte proliferation assay were determined. The results showed that DHEA suppressed the proliferation of concanavalin A (ConA)- or lipopolysaccharide-activated cultures in a dose-dependent manner. AED had little influence on the activation response. However, AET potentiated the response to both mitogens significantly above the control level. The regulation of interleukin (IL)-2 and IL-3 secretion from ConA-activated lymphocytes was analogous to these observations. These functions were depressed by DHEA, unaffected by AED, and potently increased by AET. Moreover, the classic immunosuppressive effects of hydrocortisone on ConA-induced lymphocyte proliferation, as well as IL-2 and IL-3 production, were unaffected by co-culture with DHEA and only minimally counteracted by AED. In contrast. AET significantly counteracted the effect of hydrocortisone when co-cultured together. These data show that while DHEA, AED and AET each function in a similar manner in vivo, in vitro their effects are dramatically different from one another with only AET potentiating the cellular response by increasing lymphocyte activation and counteracting the immunosuppressive activity of hydrocortisone.

Antimicrobial activity of the essential oils of Thymus vulgaris L. measured using a bioimpedometric method.

PubMed

Marino, M; Bersani, C; Comi, G

1999-09-01

The essential oils obtained from Thymus vulgaris L. harvested at four ontogenetic stages were evaluated for their biological activity and chemical composition. The thyme essential oils were tested for their inhibitory effects against nine strains of gram-negative bacteria and six strains of gram-positive bacteria. The bioimpedance method was chosen for studying the antibacterial activity of the essential oils and the parameter chosen for defining and quantifying the antibacterial activity of the essential oils was the detection time. The plate counting technique was used to study the inhibitory effect by direct contact. All the thyme essential oils examined had a significant bacteriostatic activity against the microorganisms tested. This activity was more marked against the gram-positive bacteria. The oil from thyme in full flower was the most effective at stopping the growth of the microbial species examined. The oils tested were also shown to have good antibacterial activity by direct contact, which appeared to be more marked against the gram-negative bacteria. Only a few of the species were capable of recovering at least 50% of their metabolic function after contact with the inhibitor, while most of the strains were shown to have been inactivated almost completely. Escherichia coli O157:H7 was the most sensitive species, given that after contact with even the lowest concentration of oil cells could not be recovered.

Nickel(II) and palladium(II) triphenylphosphine complexes incorporating tridentate Schiff base ligands: Synthesis, characterization and biocidal activities

NASA Astrophysics Data System (ADS)

Shabbir, Muhammad; Akhter, Zareen; Ashraf, Ahmad Raza; Ismail, Hammad; Habib, Anum; Mirza, Bushra

2017-12-01

Nickel(II) and palladium(II) triphenylphosphine complexes incorporating tridentate Schiff bases have been prepared and characterized by elemental analysis as well as by spectroscopic techniques (FTIR & NMR). The synthesized compounds were assessed to check their potential biocidal activity by using different biological assays (brine shrimp cytotoxicity, antimicrobial, antioxidant, antitumor and drug-DNA interaction). Results of brine shrimp cytotoxicity assay showed that ligand molecules are more bioactive than metal complexes with LD50 as low as 12.4 μg/mL. The prominent antitumor activity was shown by nickel complexes while the palladium complexes exhibited moderate activity. The synthesized compounds have shown high propensity for DNA binding either through intercalation or groove binding which represents the mechanism of antitumor effect of these compounds. Additionally, ligand molecules and nickel metal complexes showed significant antioxidant activity with IC50 values as low as 3.1 μg/mL and 18.9 μg/mL respectively while palladium complexes exhibited moderate activity. Moreover, in antimicrobial assays H2L1, Ni(L1)PPh3 and H2L3 showed dual inhibition against bacterial and fungal strains while for the rest of the compounds varying degree of activity was recorded against different strains. Overall comparison of results suggests that the synthesized compounds can be promising candidate for drug formulation and development.

Promyelocytic leukemia protein enhances apoptosis of gastric cancer cells through Yes-associated protein.

PubMed

Xu, Zhipeng; Chen, Jiamin; Shao, Liming; Ma, Wangqian; Xu, Dingting

2015-09-01

It has been shown that Yes-associated protein (YAP) acts as a transcriptional co-activator to regulate p73-dependent apoptosis in response to DNA damage in some cell types, and promyelocytic leukemia (PML) protein is involved in the regulation loop through stabilization of YAP through sumoylation. Although YAP has been shown to be significantly upregulated in gastric cancer, whether the YAP/PML/p73 regulation loop also functions in gastric cancer is unknown. Here, we show significantly higher levels of YAP and significantly lower levels of PML in the gastric cancer specimen. Overexpression of YAP in gastric cancer cells significantly increased cell growth, but did not affect apoptosis. However, overexpression of PML in gastric cancer cells significantly increased cell apoptosis, resulting in decreases in cell growth, which seemed to require the presence of YAP. The effect of PML on apoptosis appeared to be conducted through p73-mediated modulation of apoptosis-associated genes, Bcl-2, Bak, and caspase9. Thus, our study suggests the presence of a YAP/PML/p73 regulatory loop in gastric cancer, and highlights PML as a promising tumor suppressor in gastric cancer through YAP-coordinated cancer cell apoptosis.

July 1973 ground survey of active Central American volcanoes

NASA Technical Reports Server (NTRS)

Stoiber, R. E. (Principal Investigator); Rose, W. I., Jr.

1973-01-01

The author has identified the following significant results. Ground survey has shown that thermal anomalies of various sizes associated with volcanic activity at several Central American volcanoes should be detectable from Skylab. Anomalously hot areas of especially large size (greater than 500 m in diameter) are now found at Santiaguito and Pacaya volcanoes in Guatemala and San Cristobal in Nicaragua. Smaller anomalous areas are to be found at least seven other volcanoes. This report is completed after ground survey of eleven volcanoes and ground-based radiation thermometry mapping at these same points.

Influence of wildfires in the boreal forests of Eastern Siberia on atmospheric aerosol parameters

NASA Astrophysics Data System (ADS)

Tomshin, Oleg A.; Solovyev, Vladimir S.

2017-11-01

The results of studies of the dynamics of forest fires in the boreal forests of Yakutia (Eastern Siberia) for 2001-2016 are presented. Variations of aerosol optical thickness (AOT), aerosol index (AI) and total carbon monoxide content during May-September were studied depending on the different forest fire activity level. It is shown that the seasonal variations of AOT, AI and CO in the most fire-dangerous years differ significantly from the fire seasons when forest fire activity was medium or low.

Vector optical activity in the Weyl semimetal TaAs

DOE PAGES

Norman, M. R.

2015-12-15

Here, it is shown that the Weyl semimetal TaAs can have a significant polar vector contribution to its optical activity. This is quantified by ab initio calculations of the resonant x-ray diffraction at the Ta L1 edge. For the Bragg vector (400), this polar vector contribution to the circular intensity differential between left and right polarized x-rays is predicted to be comparable to that arising from linear dichroism. Implications this result has in regards to optical effects predicted for topological Weyl semimetals are discussed.

The role of ACTH and glucocorticoids in nonenzymatic fibrinolysis during immobilization stress in animals

NASA Technical Reports Server (NTRS)

Kudryashov, B. A.; Shapiro, F. B.; Lomovskaya, E. G.; Lyapina, L. A.

1980-01-01

The role of the altered hormonal status of an organism in the activation of the anticoagulative system during stress is investigated. The 30 minute immobilization stress was shown to raise significantly the nonenzymatic fibrinolytic activity of blood in rats. Combined with adrenocorticotropin (ACTH) the effect is still greater. Intravenous administration of 0.2 m1 0.01 percent solution of protamine sulphate prevented the nonenzymatic fibrinolysis induced by the stress. Administration of ACTH after protomine sulphate again raised the fibrinolysis. This suggests that ACTH stimulates the release of heparin.

Chiral Thioxanthones as Modulators of P-glycoprotein: Synthesis and Enantioselectivity Studies.

PubMed

Lopes, Ana; Martins, Eva; Silva, Renata; Pinto, Madalena M M; Remião, Fernando; Sousa, Emília; Fernandes, Carla

2018-03-10

Recently, thioxanthone derivatives were found to protect cells against toxic P-glycoprotein (P-gp) substrates, acting as potent inducers/activators of this efflux pump. The study of new P-gp chiral modulators produced from thioxanthone derivatives could clarify the enantioselectivity of this ABC transporter towards this new class of modulators. The aim of this study was to evaluate the P-gp modulatory ability of four enantiomeric pairs of new synthesized chiral aminated thioxanthones (ATxs) 1 - 8 , studying the influence of the stereochemistry on P-gp induction/ activation in cultured Caco-2 cells. The data displayed that all the tested compounds (at 20 μM) significantly decreased the intracellular accumulation of a P-gp fluorescent substrate (rhodamine 123) when incubated simultaneously for 60 min, demonstrating an increased activity of the efflux, when compared to control cells. Additionally, all of them except ATx 3 (+), caused similar results when the accumulation of the P-gp fluorescent substrate was evaluated after pre-incubating cells with the test compounds for 24 h, significantly reducing the rhodamine 123 intracellular accumulation as a result of a significant increase in P-gp activity. However, ATx 2 (-) was the only derivative that, after 24 h of incubation, significantly increased P-gp expression. These results demonstrated a significantly increased P-gp activity, even without an increase in P-gp expression. Therefore, ATxs 1 - 8 were shown to behave as P-gp activators. Furthermore, no significant differences were detected in the activity of the protein when comparing the enantiomeric pairs. Nevertheless, ATx 2 (-) modulates P-gp expression differently from its enantiomer, ATx 1 (+). These results disclosed new activators and inducers of P-gp and highlight the existence of enantioselectivity in the induction mechanism.

In vitro antioxidant and antihyperlipidemic activities of Bauhinia variegata Linn

PubMed Central

Rajani, G.P.; Ashok, Purnima

2009-01-01

Objectives: To evaluate the ethanolic and aqueous extracts of Bauhinia variegata Linn. for in vitro antioxidant and antihyperlipidemic activity. Materials and Methods: Ethanolic and aqueous extracts of the stem bark and root of B. variegata Linn. were prepared and assessed for in vitro antioxidant activity by various methods namely total reducing power, scavenging of various free radicals such as 1,2-diphenyl-2-picrylhydrazyl (DPPH), super oxide, nitric oxide, and hydrogen peroxide. The percentage scavenging of various free radicals were compared with standard antioxidants such as ascorbic acid and butylated hydroxyl anisole (BHA). The extracts were also evaluated for antihyperlipidemic activity in Triton WR-1339 (iso-octyl polyoxyethylene phenol)-induced hyperlipidemic albino rats by estimating serum triglyceride, very low density lipids (VLDL), cholesterol, low-density lipids (LDL), and high-density lipid (HDL) levels. Result: Significant antioxidant activity was observed in all the methods, (P < 0.01) for reducing power and (P < 0.001) for scavenging DPPH, super oxide, nitric oxide, and hydrogen peroxide radicals. The extracts showed significant reduction (P < 0.01) in cholesterol at 6 and 24 h and (P < 0.05) at 48 h. There was significant reduction (P < 0.01) in triglyceride level at 6, 24, and 48 h. The VLDL level was also significantly (P < 0.05) reduced from 24 h and maximum reduction (P < 0.01) was seen at 48 h. There was significant increase (P < 0.01) in HDL at 6, 24, and 48 h. Conclusion: From the results, it is evident that alcoholic and aqueous extracts of B. variegata Linn. can effectively decrease plasma cholesterol, triglyceride, LDL, and VLDL and increase plasma HDL levels. In addition, the alcoholic and aqueous extracts have shown significant antioxidant activity. By the virtue of its antioxidant activity, B. variegata Linn. may show antihyperlipidemic activity. PMID:20177495

Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity.

PubMed

Ueda, Akihiro; Shima, Sayuri; Murate, Kenitiroh; Kikuchi, Kouichi; Nagao, Ryunosuke; Maeda, Toshiki; Muto, Eri; Niimi, Yoshiki; Mizutani, Yasuaki; Mutoh, Tatsuro

2018-06-01

Previous studies have shown that patients with Guillain-Barré syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated. nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in neuronal cells. Activation of this enzyme leads to ceramide production, which is a known second messenger of the cell-death program in neuronal cells. We have explored the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells stably transfected with human trk cDNA (PCtrk cells) by determining their effects on nSMase2 activity. The data we present here strongly suggest that anti-GM1 caused a significant change in sphingomyelin content of the membrane fraction in PCtrk cells. Both nSMase2 activity and the level of nSMase2 protein were significantly decreased by anti-GM1 treatment of PCtrk cells, while acidic SMase activities remained unchanged. Our results indicate, for the first time, that anti-GM1 may produce profound impacts on lipid metabolism in neuronal cell membranes. Copyright © 2018 Elsevier Inc. All rights reserved.

Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscle

NASA Technical Reports Server (NTRS)

Hilder, Thomas L.; Tou, Janet C L.; Grindeland, Richard E.; Wade, Charles E.; Graves, Lee M.

2003-01-01

c-Jun NH(2)-terminal kinase (JNK) has been shown to negatively regulate insulin signaling through serine phosphorylation of residue 307 within the insulin receptor substrate-1 (IRS-1) in adipose and liver tissue. Using a rat hindlimb suspension model for muscle disuse atrophy, we found that JNK activity was significantly elevated in atrophic soleus muscle and that IRS-1 was phosphorylated on Ser(307) prior to the degradation of the IRS-1 protein. Moreover, we observed a corresponding reduction in Akt activity, providing biochemical evidence for the development of insulin resistance in atrophic skeletal muscle.

Synthesis of gadolinium doped titanium(IV) oxide and their photocatalytic activity to decrease chemical oxygen demand (COD) value of water pollutants

NASA Astrophysics Data System (ADS)

Eddy, Diana Rakhmawaty; Dwiyanti, Dina; Rahayu, Iman; Hastiawan, Iwan; Bahti, Husein H.

2017-05-01

Pesticides are widely used for the control of plant disease. Unfortunately they are highly toxic to terraneous and aquatic life; this is a particular problem in agricultural areas. TiO2 is widely used for pesticide control because of its photocatalytic activity, but it still has inadequacy in its wide band gap. Alternatively, the wide band gap of TiO2 could be narrowed by modification with rare earth element such as gadolinium, so the photocatalytic activity of TiO2could be significantly enhanced. The purpose of this experiment is to synthesize Gd/TiO2 and its application to reduce COD of water pollutants such as carbosulfan pesticide. This experiment is done by doping gadolinium oxide into titanium tetra isopropoxide by sol-gel method. The crystal structure is characterized by using XRD, shown anatase successfully obtained with the smallest crystallite size is 37.655 nm, indicated optimum calcination time is 4 hours. SEM-EDX result shown morphology of crystal is big aggregates. Photocatalytic activity is tested to carbosulfan pesticide, obtained the COD percent decreases up to 87.88%.

Effect of TNF-alpha blockade on coagulopathy and endothelial cell activation in xenoperfused porcine kidneys.

PubMed

Ramackers, Wolf; Klose, Johannes; Tiede, Andreas; Werwitzke, Sonja; Rataj, Dennis; Friedrich, Lars; Johanning, Kai; Vondran, Florian W R; Bergmann, Sabine; Schuettler, Wolfgang; Bockmeyer, Clemens Luitpold; Becker, Jan Ulrich; Klempnauer, Jürgen; Winkler, Michael

2015-01-01

Following pig-to-primate kidney transplantation, endothelial cell activation and xenogenic activation of the recipient's coagulation eventually leading to organ dysfunction and microthrombosis can be observed. In this study, we examined the effect of a TNF-receptor fusion protein (TNF-RFP) on endothelial cell activation and coagulopathy utilizing an appropriate ex vivo perfusion system. Using an ex vivo perfusion circuit based on C1-Inhibitor (C1-Inh) and low-dose heparin administration, we have analyzed consumptive coagulopathy following contact of human blood with porcine endothelium. Porcine kidneys were recovered following in situ cold perfusion with Histidine-tryptophan-ketoglutarate (HTK) organ preservation solution and were immediately connected to a perfusion circuit utilizing freshly drawn pooled porcine or human AB blood. The experiments were performed in three individual groups: autologous perfusion (n = 5), xenogenic perfusion without any further pharmacological intervention (n = 10), or with addition of TNF-RFP (n = 5). After perfusion, tissue samples were obtained for real-time PCR and immunohistological analyses. Endothelial cell activation was assessed by measuring the expression levels of E-selectin, ICAM-1, and VCAM-1. Kidney survival during organ perfusion with human blood, C1-Inh, and heparin, but without any further pharmacological intervention was 126 ± 78 min. Coagulopathy was observed with significantly elevated concentrations of D-dimer and thrombin-antithrombin complex (TAT), resulting in the formation of multiple microthrombi. Endothelial cell activation was pronounced, as shown by increased expression of E-selectin and VCAM-1. In contrast, pharmacological intervention with TNF-RFP prolonged organ survival to 240 ± 0 min (max. perfusion time; no difference to autologous control). Formation of microthrombi was slightly reduced, although not significantly, if compared to the xenogenic control. D-dimer and TAT were elevated at similar levels to the xenogenic control experiments. In contrast, endothelial cell activation, as shown by real-time PCR, was significantly reduced in the TNF-RFP group. We conclude that although coagulopathy was not affected, TNF-RFP is able to suppress inflammation occurring after xenoperfusion in this ex vivo perfusion model. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Extracellular pH monitoring for use in closed-loop vagus nerve stimulation

NASA Astrophysics Data System (ADS)

Cork, Simon C.; Eftekhar, Amir; Mirza, Khalid B.; Zuliani, Claudio; Nikolic, Konstantin; Gardiner, James V.; Bloom, Stephen R.; Toumazou, Christofer

2018-02-01

Objective. Vagal nerve stimulation (VNS) has shown potential benefits for obesity treatment; however, current devices lack physiological feedback, which limit their efficacy. Changes in extracellular pH (pHe) have shown to be correlated with neural activity, but have traditionally been measured with glass microelectrodes, which limit their in vivo applicability. Approach. Iridium oxide has previously been shown to be sensitive to fluctuations in pH and is biocompatible. Iridium oxide microelectrodes were inserted into the subdiaphragmatic vagus nerve of anaesthetised rats. Introduction of the gut hormone cholecystokinin (CCK) or distension of the stomach was used to elicit vagal nerve activity. Main results. Iridium oxide microelectrodes have sufficient pH sensitivity to readily detect changes in pHe associated with both CCK and gastric distension. Furthermore, a custom-made Matlab script was able to use these changes in pHe to automatically trigger an implanted VNS device. Significance. This is the first study to show pHe changes in peripheral nerves in vivo. In addition, the demonstration that iridium oxide microelectrodes are sufficiently pH sensitive as to measure changes in pHe associated with physiological stimuli means they have the potential to be integrated into closed-loop neurostimulating devices.

Infinite non-causality in active cancellation of random noise

NASA Astrophysics Data System (ADS)

Friot, Emmanuel

2006-03-01

Active cancellation of broadband random noise requires the detection of the incoming noise with some time advance. In an duct for example this advance must be larger than the delays in the secondary path from the control source to the error sensor. In this paper it is shown that, in some cases, the advance required for perfect noise cancellation is theoretically infinite because the inverse of the secondary path, which is required for control, can include an infinite non-causal response. This is shown to be the result of two mechanisms: in the single-channel case (one control source and one error sensor), this can arise because of strong echoes in the control path. In the multi-channel case this can arise even in free field simply because of an unfortunate placing of sensors and actuators. In the present paper optimal feedforward control is derived through analytical and numerical computations, in the time and frequency domains. It is shown that, in practice, the advance required for significant noise attenuation can be much larger than the secondary path delays. Practical rules are also suggested in order to prevent infinite non-causality from appearing.

Attenuation of dichlorvos-induced microglial activation and neuronal apoptosis by 4-hydroxy TEMPO.

PubMed

Sunkaria, Aditya; Sharma, Deep Raj; Wani, Willayat Yousuf; Gill, Kiran Dip

2014-02-01

The neurotoxic consequences of acute high-level as well as chronic low-level organophosphates exposure are associated with a range of abnormalities in nerve functions. Previously, we have shown that after 24 h of dichlorvos exposure, microglia become activated and secrete pro-inflammatory molecules like nitric oxide, tumour necrosis factor-α and interleukin-1β. Here, we extended our findings and focused on the neuronal damage caused by dichlorvos via microglial activation. For this, neurons and microglia were isolated separately from 1-day-old Wistar rat pups. Microglia were treated with dichlorvos for 24 h and supernatant was collected (dichlorvos-induced conditioned medium, DCM). However, when 4-hydroxy TEMPO (4-HT) pretreatment was given, we observed significant attenuation of dichlorvos-induced microglial activation; we also collected the supernatant of this culture (4-HT + DCM, TDCM). Next, we checked the effects of DCM on neurons and found heavy loss in viability as evident from NF-H immunostaining and MTT results, whereas dichlorvos alone-treated neurons showed comparatively less damage. However, we observed significant increase in neuronal viability when cells were treated with TDCM. Semi-quantitative PCR and western blot results revealed significant increase in p53, Bax and cytochrome c levels along with caspase 3 activation after 24 h of DCM treatment. However, TDCM-treated neurons showed significant decrease in the expression of these pro-apoptotic molecules. Taken together, these findings suggest that 4-HT can significantly attenuate dichlorvos-induced microglial activation and prevent apoptotic neuronal cell death.

Heart rate at the onset of muscle contraction and during passive muscle stretch in humans: a role for mechanoreceptors

PubMed Central

Gladwell, V F; Coote, J H

2002-01-01

Previous evidence suggests that the heart rate (HR) increase observed with isometric exercise is dependent on different afferent mechanisms to those eliciting the increase in blood pressure (BP). Central command and muscle metaboreceptors have been shown to contribute to this differential effect. However, in experimental animals passive stretch of the hindlimb increases HR suggesting that small fibre mechanoreceptors could also have a role. This has not been previously shown in humans and was investigated in this study. Healthy human volunteers were instrumented to record BP, ECG, respiration, EMG of rectus femoris and gastrocnemius and contraction force of triceps surae. Voluntary isometric contraction of triceps surae elicited a significant HR change in the first three respiratory cycles at 40 % of maximum voluntary contraction whereas BP did not change significantly until after 30 s. This suggests that different mechanisms are involved in the initiation of the cardiovascular changes. Sustained passive stretch of triceps surae for 1 min, by dorsiflexion of the foot, caused a significant (P < 0.05) increase in HR (5 ± 2.6 beats min−1) with no significant change in BP. A time domain measure of cardiac vagal activity was reduced significantly during passive stretch from 69.7 ± 12.9 to 49.6 ± 8.9 ms. Rapid rhythmic passive stretch (0.5 Hz for 1 min) was without significant effect suggesting that large muscle proprioreceptors are not involved. We conclude that in man small fibre muscle mechanoreceptors responding to stretch, inhibit cardiac vagal activity and thus increase HR. These afferents could contribute to the initial cardiac acceleration in response to muscle contraction. PMID:11986394

Anti-diabetic effects of Ganoderma lucidum.

PubMed

Ma, Haou-Tzong; Hsieh, Jung-Feng; Chen, Shui-Tein

2015-06-01

Ganoderma lucidum is a white rot fungus widely used as a tonic for the promotion of longevity and health. Extracts of G. lucidum have been recognized as an alternative adjuvant treatment for diabetes. Among the many biologically active constituents of G. lucidum, polysaccharides, proteoglycans, proteins and triterpenoids have been shown to have hypoglycemic effects. G. lucidum polysaccharides have been reported to have hypoglycemic activity by increasing plasma insulin levels and decreasing plasma sugar levels in mice. Protein tyrosine phosphatase 1B is a promising therapeutic target in diabetes, and G. lucidum proteoglycan can inhibit this enzyme in vitro. Moreover, G. lucidum triterpenoids were shown to have inhibitory activity on aldose reductase and α-glucosidase that can suppress postprandial hyperglycemia. In addition, a protein Ling Zhi-8 extracted from G. lucidum significantly decreased lymphocyte infiltration and increased the antibody detection of insulin in diabetic mice. This review summarizes most of the research about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins and tritrerpenoids from G. lucidum as a guide for future research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Processive Endoglucanases Mediate Degradation of Cellulose by Saccharophagus degradans▿ †

PubMed Central

Watson, Brian J.; Zhang, Haitao; Longmire, Atkinson G.; Moon, Young Hwan; Hutcheson, Steven W.

2009-01-01

Bacteria and fungi are thought to degrade cellulose through the activity of either a complexed or a noncomplexed cellulolytic system composed of endoglucanases and cellobiohydrolases. The marine bacterium Saccharophagus degradans 2-40 produces a multicomponent cellulolytic system that is unusual in its abundance of GH5-containing endoglucanases. Secreted enzymes of this bacterium release high levels of cellobiose from cellulosic materials. Through cloning and purification, the predicted biochemical activities of the one annotated cellobiohydrolase Cel6A and the GH5-containing endoglucanases were evaluated. Cel6A was shown to be a classic endoglucanase, but Cel5H showed significantly higher activity on several types of cellulose, was the highest expressed, and processively released cellobiose from cellulosic substrates. Cel5G, Cel5H, and Cel5J were found to be members of a separate phylogenetic clade and were all shown to be processive. The processive endoglucanases are functionally equivalent to the endoglucanases and cellobiohydrolases required for other cellulolytic systems, thus providing a cellobiohydrolase-independent mechanism for this bacterium to convert cellulose to glucose. PMID:19617364

NF-kappaB mediates FGF signal regulation of msx-1 expression.

PubMed

Bushdid, P B; Chen, C L; Brantley, D M; Yull, F; Raghow, R; Kerr, L D; Barnett, J V

2001-09-01

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic Press.

The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study.

PubMed

Kempton, Matthew J; Haldane, Morgan; Jogia, Jigar; Christodoulou, Tessa; Powell, John; Collier, David; Williams, Steven C R; Frangou, Sophia

2009-04-01

The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypexgender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest.

Subetta increases phosphorylation of insulin receptor β-subunit alone and in the presence of insulin

PubMed Central

Gorbunov, E A; Nicoll, J; Kachaeva, E V; Tarasov, S A; Epstein, O I

2015-01-01

It has been previously shown that Subetta (a drug containing released-active forms of antibodies to the insulin receptor β-subunit and antibodies to endothelial nitric oxide synthase) stimulated insulin-induced adiponectin production by mature human adipocytes in the absence of insulin. Therefore, it was assumed that Subetta could activate the insulin receptor. To confirm this hypothesis, the capacity of Subetta to activate the insulin receptor in mature human adipocytes in the absence or presence of the insulin was investigated. Cells were incubated either with Subetta or with vehicle, or with basal medium for 3 days. Then, adipocytes were treated with water or insulin (100 nm) for 15 min. Following treatment, lysates were prepared and phosphorylation of insulin receptor β-subunits was analyzed by western blot analysis. It was shown that Subetta significantly increased (P<0.001) the ‘phosphorylated-insulin receptor β-subunit/total insulin receptor β-subunit' ratios in both the presence and the absence of insulin. These results support previously published data and indicate that Subetta could activate the insulin receptor through the effect on its β-subunits, whose conformational state is essential for insulin receptor activation. This action might serve as one of the primary mechanisms of the drug's antidiabetic effect. PMID:26148148

A Lunchtime Walk in Nature Enhances Restoration of Autonomic Control during Night-Time Sleep: Results from a Preliminary Study.

PubMed

Gladwell, Valerie F; Kuoppa, Pekka; Tarvainen, Mika P; Rogerson, Mike

2016-03-03

Walking within nature (Green Exercise) has been shown to immediately enhance mental well-being but less is known about the impact on physiology and longer lasting effects. Heart rate variability (HRV) gives an indication of autonomic control of the heart, in particular vagal activity, with reduced HRV identified as a risk factor for cardiovascular disease. Night-time HRV allows vagal activity to be assessed whilst minimizing confounding influences of physical and mental activity. The aim of this study was to investigate whether a lunchtime walk in nature increases night-time HRV. Participants (n = 13) attended on two occasions to walk a 1.8 km route through a built or a natural environment. Pace was similar between the two walks. HRV was measured during sleep using a RR interval sensor (eMotion sensor) and was assessed at 1-2 h after participants noted that they had fallen asleep. Markers for vagal activity were significantly greater after the walk in nature compared to the built walk. Lunchtime walks in nature-based environments may provide a greater restorative effect as shown by vagal activity than equivalent built walks. Nature walks may improve essential recovery during night-time sleep, potentially enhancing physiological health.

Association between Sleep Disturbances and Leisure Activities in the Elderly: A Comparison between Men and Women

PubMed Central

Hellström, Amanda; Hellström, Patrik; Fagerström, Cecilia

2014-01-01

It has been suggested that physical or social activity is associated with fewer sleep disturbances among elderly people. Women report more sleep disturbances than men, which could indicate a variation in activity patterns between the genders. The aim of this study was to investigate associations between sleep disturbances and leisure activities in men and women (n = 945) aged ≥60 years in a Swedish population. Sleep disturbances were measured using eight dichotomous questions and seventeen variables, covering a wide range of leisure activities. Few leisure activities were found to be associated with sleep disturbances and their importance decreased when the models were adjusted for confounders and gender interactions. After clustering the leisure activities and investigating individual activities, sociointellectual activities were shown to be significant for sleep. However, following adjustment for confounders and gender interactions, home maintenance was the only activity significant for sleep. Being a female increased the effect of home maintenance. Besides those leisure activities, poor/fair self-rated health (OR 7.50, CI: 4.27–11.81) and being female (OR 4.86, CI: 2.75–8.61) were found to have the highest association with poor sleep. Leisure activities pursued by elderly people should focus on activities of a sociointellectual nature, especially among women, to promote sleep. PMID:24575303

Association between Sleep Disturbances and Leisure Activities in the Elderly: A Comparison between Men and Women.

PubMed

Hellström, Amanda; Hellström, Patrik; Willman, Ania; Fagerström, Cecilia

2014-01-01

It has been suggested that physical or social activity is associated with fewer sleep disturbances among elderly people. Women report more sleep disturbances than men, which could indicate a variation in activity patterns between the genders. The aim of this study was to investigate associations between sleep disturbances and leisure activities in men and women (n = 945) aged ≥60 years in a Swedish population. Sleep disturbances were measured using eight dichotomous questions and seventeen variables, covering a wide range of leisure activities. Few leisure activities were found to be associated with sleep disturbances and their importance decreased when the models were adjusted for confounders and gender interactions. After clustering the leisure activities and investigating individual activities, sociointellectual activities were shown to be significant for sleep. However, following adjustment for confounders and gender interactions, home maintenance was the only activity significant for sleep. Being a female increased the effect of home maintenance. Besides those leisure activities, poor/fair self-rated health (OR 7.50, CI: 4.27-11.81) and being female (OR 4.86, CI: 2.75-8.61) were found to have the highest association with poor sleep. Leisure activities pursued by elderly people should focus on activities of a sociointellectual nature, especially among women, to promote sleep.

Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines.

PubMed

Gulec, Cagri; Coban, Neslihan; Ozsait-Selcuk, Bilge; Sirma-Ekmekci, Sema; Yildirim, Ozlem; Erginel-Unaltuna, Nihan

2017-04-01

ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analyses of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gulec, Cagri, E-mail: cagri.gulec@gmail.com; Coban, Neslihan, E-mail: neslic@istanbul.edu.tr; Ozsait-Selcuk, Bilge, E-mail: ozsaitb@istanbul.edu.tr

ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analysesmore » of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses.« less

Oxidative stress enzyme and histopathological lesions in Colossoma macropomum (pisces, ariidae) for environmental impact assessment

NASA Astrophysics Data System (ADS)

Andrade, Ticianne de Sousa de Oliveira Mota; Sousa, Debora Batista Pinheiro; Dantas, Janaina Gomes; Castro, Jonatas da Silva; Neta, Raimunda Nonata Fortes Carvalho

2015-12-01

This study used oxidative stress enzyme (Glutathione S-Transferase and Catalase), histopathological lesions (Branchial lesions) and biometric data in the freshwater fish tambaqui, Colossoma macropomum, to assess environmental impacts in an Environmental Protection Area at São Luis, Brazil. Fish were sampled from two locations (A1 = contaminated area and A2 = reference site) within the protected area on four occasions. The activity of catalase (CAT) and glutathione S-transferase (GST) in C. macropomum was compared with biometric data and histopathological lesions. Results have shown that biometric data decreased significantly in fish (p<0.05) at the contaminated site. The activity of CAT was higher in fish specifically caught in A1. A significant difference was observed in the GST activity in the liver of C. macropomum when comparing fish from the contaminated site and those from the reference site (p<0.05).

Groundwater storage inferred from earthquake activities around East Asia and West Pacific Ocean

NASA Astrophysics Data System (ADS)

Shih, David Ching-Fang

2017-01-01

Groundwater is a necessary and indispensable resource in the gradual depletion of the amount in the world. Groundwater storage is an important indicator to evaluate the capability of volume of water can be released from the aquifer. This research highlights a new assessment to infer the storage of aquifer using earthquakes activated around East Asia and the ring of fire at West Pacific Ocean. Ten significant seismic events are used to evaluate the groundwater storage at an observation station. By analyzing the spectra of groundwater level and seismogram, it is evident that the period varied in 7-25 s of Rayleigh waves significantly dominate propagation from the epicenter of earthquakes to the observation station. The storage coefficient is then shown in the order of 10-4-10-3. The major innovation of this study suggests that to concretely deduce the groundwater storage by earthquake activity has become feasible.

Low levels of physical activity in Sudanese individuals with some features of metabolic syndrome: Population based study.

PubMed

Khalil, Samah; Almobarak, Ahmed O; Awadalla, Heitham; Elmadhoun, Wadie M; Noor, Sufian K; Sulaiman, Amel A; Ahmed, Mohamed H

2017-12-01

The aim of this study was to evaluate the level of physical activity among Sudanese population. A descriptive cross sectional study composed of 323 participants from Khartoum state, Sudan. Data collected using pretested designed questionnaire based on previously validated Global Physical Activity Questionnaire. The demographic and physical measurement including blood glucose, anthropometric and blood pressure. The Mean age of participants was 35.5. Males were 59.9% and females 47.1% and the prevalence of inactivity was 53.8%. Despite the fact that males are more active than females (P<0.000) physical activity tends to decrease with age but this not statistically significant. Physical activity is significantly decreased with obesity, higher education and doing sedentary jobs (P<0.018, P<0.000 and P<0.000 respectively). While majority of individuals with hypertension and pre-hypertension tend to do less physical activity (P<0.045 and P<0.008 respectively). Logistic regression analysis shown that gender is absolute risk factor for physical activity. Males have more than three times probability of being physically active than women OR3.82 (1.91-7.30). In this study, physical activity was not affected by central obesity (P<0.497), diabetes (P<0.378) and being married or not (P<0.135). Physical activity in Sudanese women was significantly decreased in comparison with men. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Effects of active recovery during interval training on plasma catecholamines and insulin.

PubMed

Nalbandian, Harutiun M; Radak, Zsolt; Takeda, Masaki

2018-06-01

BACKGROUNDː Active recovery has been used as a method to accelerate the recovery during intense exercise. It also has been shown to improve performance in subsequent exercises, but little is known about its acute effects on the hormonal and metabolic profile. The aim of this research was to study the effects of active recovery on plasma catecholamines and plasma insulin during a high-intensity interval exercise. METHODSː Seven subjects performed two high-intensity interval training protocols which consisted of three 30-second high-intensity bouts (constant intensity), separated by a recovery of 4 minutes. The recovery was either active recovery or passive recovery. During the main test blood samples were collected and plasma insulin, plasma catecholamines and blood lactate were determined. Furthermore, respiratory gasses were also measured. RESULTSː Plasma insulin and blood lactate were significantly higher in the passive recovery trial, while plasma adrenaline was higher in the active recovery. Additionally, VO2 and VCO2 were significantly more increased during the active recovery trials. CONCLUSIONSː These results suggest that active recovery affects the hormonal and metabolic responses to high-intensity interval exercise. Active recovery produces a hormonal environment which may favor lipolysis and oxidative metabolism, while passive recovery may be favoring glycolysis.

Oleamide: a member of the endocannabinoid family?

PubMed Central

Fowler, Christopher J

2003-01-01

The fatty acid amide class of compounds, which include the endocannabinoid anandamide and the sleep-inducing compound oleamide, have been shown in vitro to have a multiplicity of actions upon different neurochemical systems. In the present issue of this journal, Leggett et al present data indicating that oleamide functionally activates CB1 cannabinoid receptors in vitro. The significance of their finding is discussed in this commentary. PMID:14691053

Self-Disinfection and Decontaminating Interior Surfaces Based on Photocatalytic Titania/Easy-Release Coatings

DTIC Science & Technology

2002-01-01

DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release, distribution unlimited 13. SUPPLEMENTARY NOTES This article is from ADA409494 Proceedings of...been shown to be independently capable, respectively, of diminishing viability and minimizing bioburdens on interior surfaces. Unique combinations of...active bacterial bioburdens and total retained biomass can be significantly reduced by these surface modifications. Interior surface coatings of TiO2

[Interaction of immobilization stress and food-getting learning].

PubMed

Levshina, I P; Stashkevich, I S; Shuĭkin, N N

2009-01-01

The behavioral effects of emotional negative stress (immobilization) were studied in Wistar rats intact and those that had previous positive emotion experience. The food-getting learning has been chosen as positive emotion experience. Animals were trained in food pellet-reaching task by their preferred paw. It was shown that immobilization of intact rats leads to suppression of motor activity and increasing the duration of grooming. These effects indicate enhancement of passive-avoidance reactions. It was also shown that motor learning in group of rats with food reinforcement before immobilisation significantly reduces appearance of passive-avoidance reactions. It was found that immobilization stress does not inverse the initial direction of limb preference in majority of rats.

Enzyme activity in the aestivating green-striped burrowing frog (Cyclorana alboguttata).

PubMed

Mantle, Beth L; Guderley, Helga; Hudson, Nicholas J; Franklin, Craig E

2010-10-01

Green-striped burrowing frogs (Cyclorana alboguttata) can depress their resting metabolism by more than 80% during aestivation. Previous studies have shown that this species is able to withstand long periods of immobilisation during aestivation while apparently maintaining whole muscle mass and contractile performance. The aim of this study was to determine the effect of prolonged aestivation on the levels of metabolic enzymes (CCO, LDH and CS) in functionally distinct skeletal muscles (cruralis, gastrocnemius, sartorius, iliofibularis and rectus abdominus) and liver of C. alboguttata. CS activity was significantly reduced in all tissues except for the cruralis, gastrocnemius and the liver. LDH activity was significantly reduced in the sartorius and rectus abdominus, but remained at control (active) levels in the other tissues. CCO activity was significantly reduced in the gastrocnemius and rectus abdominus, and unchanged in the remaining tissues. Muscle protein was significantly reduced in the sartorius and iliofibularis during aestivation, and unchanged in the remaining muscles. The results suggest that the energy pathways involved in the production and consumption of ATP are remodelled during prolonged aestivation but selective. Remodelling and subsequent down-regulation of metabolic activity seem to target the smaller non-jumping muscles, while the jumping muscles retain enzyme activities at control levels during aestivation. These results suggest a mechanism by which aestivating C. alboguttata are able to maintain metabolic depression while ensuring that the functional capacity of critical muscles is not compromised upon emergence from aestivation.

Increase in the free radical scavenging capability of bitter gourd by a heat-drying process.

PubMed

Wei, Lu; Shaoyun, Wang; Shutao, Liu; Jianwu, Zhou; Lijing, Ke; Pingfan, Rao

2013-12-01

Bitter gourd (Momordica charantia Linn.) is widely regarded as one of the best remedy foods for diabetes. The positive effect of bitter gourd on diabetes has been attributed in part to the remarkable free radical scavenging activity of its boiled water extract from sun-dried fruits. It is well known that a heat process significantly influences the antioxidant activity of fresh fruits. However, the heat drying processes of bitter gourd have not been studied so far. Here, we show that the free radical scavenging capability of bitter gourd extract significantly increases after the heat drying process, while the content of flavonoids and phenols, which are generally regarded as the main antioxidant components in bitter gourd, remain unaffected. Furthermore, the content of free amino acids and the total reducing sugar were found to decrease with increasing browning index, indicating the progression of the Maillard reaction, products of which are known to possess significant antioxidant activity. Therefore, it suggests that Maillard reaction products may be the main contributors to the increase in antioxidant capability. Finally, the bitter gourd extract with the higher antioxidant activity, was shown to manifest a corresponding higher proliferation activity on NIT-1 beta-cells. These results suggest that controllable conditions in the heat-drying processing of fresh bitter gourd fruit is of significance for enhancing the total free radical scavenging capacity, beta-cell proliferation activity and possibly the anti-diabetic activity of this fruit.

The evolution of selective estrogen receptor modulators in osteoporosis therapy

PubMed Central

2012-01-01

Selective estrogen receptor modulators (SERMs), which exhibit estrogen receptor agonist or antagonist activity based on the target tissue, have evolved through multiple generations for the prevention and/or treatment of postmenopausal osteoporosis. An ideal SERM would protect bone without stimulating the breast or endometrium. Raloxifene, lasofoxifene, and bazedoxifene have demonstrated unique preclinical profiles. Raloxifene, lasofoxifene, and bazedoxifene have shown significant reduction in the risk of vertebral fracture and improvement in bone mineral density versus placebo in postmenopausal women with osteoporosis. Raloxifene has been shown to reduce the risk of non-vertebral fractures in women with severe prevalent fractures at baseline. Lasofoxifene 0.5 mg, but not lasofoxifene 0.25 mg, has shown reduction in the incidence of non-vertebral fractures. Bazedoxifene 20 mg has been associated with a significant reduction in the risk of non-vertebral fracture versus placebo and raloxifene 60 mg in women at higher baseline fracture risk. Neither raloxifene, lasofoxifene, nor bazedoxifene has shown an increase in the incidence of endometrial hyperplasia or carcinoma. All SERMs have been associated with increased venous thromboembolic events and hot flushes. SERMs are effective alternatives for women who cannot tolerate or are unwilling to take bisphosphonates and may be appropriate for women at higher risk of fracture, particularly younger women who expect to remain on therapy for many years and are concerned about the long-term safety of bisphosphonates. PMID:22853318

Racial and genetic determinants of plasma factor XIII activity.

PubMed

Saha, N; Aston, C E; Low, P S; Kamboh, M I

2000-12-01

Factor XIII (F XIII), a plasma transglutaminase, is essential for normal hemostasis and fibrinolysis. Plasma F XIII consists of two catalytic A (F XIIIA) and two non-catalytic B (F XIIIB) subunits. Activated F XIII is involved in the formation of fibrin gel by covalently crosslinking fibrin monomers. As the characteristics of the fibrin gel structure have been shown to be associated with the risk of coronary heart disease (CHD), F XIII activity may play a seminal role in its etiology. In this investigation, we determined plasma F XIII activity in two racial groups, including Asian Indians (n = 258) and Chinese (n = 385). Adjusted plasma F XIII activity was significantly higher in Indian men (142 vs. 110%; P<0.0001) and women (158 vs. 111%; P<0.0001) than their Chinese counterparts. As compared to Indians where the distribution of F XIII activity was almost normal, in Chinese it was skewed towards low activity. In both racial groups, bivariate and multivariate analyses showed strong correlation of F XIII activity with plasma fibrinogen and plasminogen levels. Race explained about 25% of the variation in F XIII activity even after the adjustment of significant correlates. We also determined the contribution of common genetic polymorphisms in the F XIIIA and F XIIIB genes in affecting plasma F XIII activity. Both loci showed significant and independent effects on plasma F XIII activity in Indians (F XIIIA, P< 0.01; F XIIIB, P<0.05) and Chinese (F XIIIA, P<0.0001; F XIIIB, P<0.13) in a gene dosage fashion. This study shows that both racial and genetic components play a significant role in determining plasma F XIII activity, and consequently it may affect the quantitative risk of CHD. Copyright 2000 Wiley-Liss, Inc.

Nanoscale structure-activity relationships, mode of action, and biocompatibility of gold nanoparticle antibiotics.

PubMed

Bresee, Jamee; Bond, Constance M; Worthington, Roberta J; Smith, Candice A; Gifford, Jennifer C; Simpson, Carrie A; Carter, Carly J; Wang, Guankui; Hartman, Jesse; Osbaugh, Niki A; Shoemaker, Richard K; Melander, Christian; Feldheim, Daniel L

2014-04-09

The emergence of resistance to multiple antimicrobial agents by pathogenic bacteria has become a significant global public health threat. Multi-drug-resistant (MDR) Gram-negative bacteria have become particularly problematic, as no new classes of small-molecule antibiotics for Gram-negative bacteria have emerged in over two decades. We have developed a combinatorial screening process for identifying mixed ligand monolayer/gold nanoparticle conjugates (2.4 nm diameter) with antibiotic activity. The method previously led to the discovery of several conjugates with potent activity against the Gram-negative bacterium Escherichia coli. Here we show that these conjugates are also active against MDR E. coli and MDR Klebsiella pneumoniae. Moreover, we have shown that resistance to these nanoparticles develops significantly more slowly than to a commercial small-molecule drug. These results, combined with their relatively low toxicity to mammalian cells and biocompatibility in vivo, suggest that gold nanoparticles may be viable new candidates for the treatment of MDR Gram-negative bacterial infections.

Influences of Histidine-1 and Azaphenylalanine-4 on the Affinity, Anti-inflammatory, and Antiangiogenic Activities of Azapeptide Cluster of Differentiation 36 Receptor Modulators.

PubMed

Chignen Possi, Kelvine; Mulumba, Mukandila; Omri, Samy; Garcia-Ramos, Yesica; Tahiri, Houda; Chemtob, Sylvain; Ong, Huy; Lubell, William D

2017-11-22

Azapeptide analogues of growth hormone releasing peptide-6 (GHRP-6) exhibit promising affinity, selectivity, and modulator activity on the cluster of differentiation 36 receptor (CD36). For example, [A 1 , azaF 4 ]- and [azaY 4 ]-GHRP-6 (1a and 2b) were previously shown to bind selectively to CD36 and exhibited respectively significant antiangiogenic and slight angiogenic activities in a microvascular sprouting assay using choroid explants. The influences of the 1- and 4-position residues on the affinity, anti-inflammatory, and antiangiogenic activity of these azapeptides have now been studied in detail by the synthesis and analysis of a set of 25 analogues featuring Ala 1 or His 1 and a variety of aromatic side chains at the aza-amino acid residue in the 4-position. Although their binding affinities differed only by a factor of 17, the analogues exhibited significant differences in ability to modulate production of nitric oxide (NO) in macrophages and choroidal neovascularization.

Design, synthesis, and characterization of 2,2-bis(2,4-dinitrophenyl)-2-(phosphonatomethylamino)acetate as a herbicidal and biological active agent.

PubMed

Kumar, Vijay; Singh, Simranjeet; Singh, Rohit; Upadhyay, Niraj; Singh, Joginder

2017-10-01

The present study was designed to synthesize the bioactive molecule 2,2-bis(2,4-dinitrophenyl)-2-(phosphonatomethylamino)acetate ( 1 ), having excellent applications in the field of plant protection as a herbicide. Structure of newly synthesized molecule 1 was confirmed by using the elemental analysis, mass spectrometric, NMR, UV-visible, and FTIR spectroscopic techniques. To obtain better structural insights of molecule 1 , 3D molecular modeling was performed using the GAMESS programme. Microbial activities of 1 were checked against the pathogenic strains Aspergillus fumigatus (NCIM 902) and Salmonella typhimurium (NCIM 2501). Molecule 1 has shown excellent activities against fungal strain A. fumigates (35 μg/l) and bacterial strain S. typhimurium (25 μg/l). To check the medicinal significance of molecule 1 , interactions with bovine serum albumin (BSA) protein were checked. The calculated value of binding constant of molecule 1 -BSA complex was 1.4 × 10 6  M -1 , which were similar to most effective drugs like salicylic acid. More significantly, as compared to herbicide glyphosate, molecule 1 has exhibited excellent herbicidal activities, in pre- and post-experiments on three weeds; barnyard grass ( Echinochloa Crus ), red spranglitop ( Leptochloa filiformis ), and yellow nuts ( Cyperus Esculenfus ). Further, effects of molecule 1 on plant growth-promoting rhizobacterial (PGPR) strains were checked. More interestingly, as compared to glyphosate, molecule 1 has shown least adverse effects on soil PGPR strains including the Rhizobium leguminosarum (NCIM 2749), Pseudomonas fluorescens (NCIM 5096), and Pseudomonas putida (NCIM 2847).

Green Synthesis of AgNPs Stabilized with biowaste and their antimicrobial activities

PubMed Central

Jasuja, Nakuleshwar Dut; Gupta, Deepak Kumar; Reza, Mohtashim; Joshi, Suresh C.

2014-01-01

In the present study, rapid reduction and stabilization of Ag+ ions with different NaOH molar concentration (0.5 mM, 1.0 mM and 1.5 mM) has been carried out in the aqueous solution of silver nitrate by the bio waste peel extract of P.granatum. Generally, chemical methods used for the synthesis of AgNPs are quite toxic, flammable and have adverse effect in medical application but green synthesis is a better option due to eco-friendliness, non-toxicity and safe for human. Stable AgNPs were synthesized by treating 90 mL aqueous solution of 2 mM AgNO3 with the 5 mL plant peels extract (0.4% w/v) at different NaOH concentration (5 mL). The synthesized AgNPs were characterized by UV-Vis spectroscopy, TEM and SEM. Further, antimicrobial activities of AgNPs were performed on Gram positive i.e. Staphylococcus aureus, Bacillus subtilius and Gram negative i.e. E. coli, Pseudomonas aeruginosa bacteria. The AgNPs synthesized at 1.5 mM NaOH concentration had shown maximum zone of inhibition (ZOI) i.e. 49 ± 0.64 in E. coli, whereas Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilius had shown 40 ± 0.29 mm, 28 ± 0.13 and 42 ± 0.49 mm ZOI respectively. The MIC value of 30 μg/mL observed for E. coli Whereas, Staphylococcus aureus, Bacillus subtilius and Pseudomonas aeruginosa had shown 45 μg/mL, 38 μg/mL, 35 μg/mL respectively. The study revealed that AgNPs had shown significant antimicrobial activity as compared to Streptomycin. PMID:25763037

Green Synthesis of AgNPs Stabilized with biowaste and their antimicrobial activities.

PubMed

Jasuja, Nakuleshwar Dut; Gupta, Deepak Kumar; Reza, Mohtashim; Joshi, Suresh C

2014-01-01

In the present study, rapid reduction and stabilization of Ag+ ions with different NaOH molar concentration (0.5 mM, 1.0 mM and 1.5 mM) has been carried out in the aqueous solution of silver nitrate by the bio waste peel extract of P.granatum. Generally, chemical methods used for the synthesis of AgNPs are quite toxic, flammable and have adverse effect in medical application but green synthesis is a better option due to eco-friendliness, non-toxicity and safe for human. Stable AgNPs were synthesized by treating 90 mL aqueous solution of 2 mM AgNO₃ with the 5 mL plant peels extract (0.4% w/v) at different NaOH concentration (5 mL). The synthesized AgNPs were characterized by UV-Vis spectroscopy, TEM and SEM. Further, antimicrobial activities of AgNPs were performed on Gram positive i.e. Staphylococcus aureus, Bacillus subtilius and Gram negative i.e. E. coli, Pseudomonas aeruginosa bacteria. The AgNPs synthesized at 1.5 mM NaOH concentration had shown maximum zone of inhibition (ZOI) i.e. 49 ± 0.64 in E. coli, whereas Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilius had shown 40 ± 0.29 mm, 28 ± 0.13 and 42 ± 0.49 mm ZOI respectively. The MIC value of 30 μg/mL observed for E. coli Whereas, Staphylococcus aureus, Bacillus subtilius and Pseudomonas aeruginosa had shown 45 μg/mL, 38 μg/mL, 35 μg/mL respectively. The study revealed that AgNPs had shown significant antimicrobial activity as compared to Streptomycin.

Analysis of the essential oil of Origanum dubium growing wild in Cyprus. Investigation of its antioxidant capacity and antimicrobial activity.

PubMed

Karioti, A; Vrahimi-Hadjilouca, T; Droushiotis, D; Rancic, A; Hadjipavlou-Litina, D; Skaltsa, H

2006-11-01

The volatile composition of Origanum dubium in two different maturation stages has been studied. The essential oils were obtained by hydrodistillation in a modified Clevenger-type apparatus, and their analyses were performed by GC and GC-MS. Identification of the components was made by comparison of mass spectra and retention indices with literature records and by co-chromatography with authentic compounds. Carvacrol was shown to be the main constituent. The essential oils were evaluated for antimicrobial activity and proved to be active against all tested microorganisms. Furthermore, their potential antioxidant activity was investigated and found to be significant in scavenging O2-. The samples were further evaluated for inhibition of soybean lipoxygenase LOX and showed high inhibitory activity.

Oceanographic applications of laser technology

NASA Technical Reports Server (NTRS)

Hoge, F. E.

1988-01-01

Oceanographic activities with the Airborne Oceanographic Lidar (AOL) for the past several years have primarily been focussed on using active (laser induced pigment fluorescence) and concurrent passive ocean color spectra to improve existing ocean color algorithms for estimating primary production in the world's oceans. The most significant results were the development of a technique for selecting optimal passive wavelengths for recovering phytoplankton photopigment concentration and the application of this technique, termed active-passive correlation spectroscopy (APCS), to various forms of passive ocean color algorithms. Included in this activity is use of airborne laser and passive ocean color for development of advanced satellite ocean color sensors. Promising on-wavelength subsurface scattering layer measurements were recently obtained. A partial summary of these results are shown.

Study of behavioral parameters during learning of rats in an operant feeding task and evaluation of biochemical indexes after dietary consumption of the phytoecdysteroid extract.

PubMed

Murtazina, E P; Sidorova, Yu S; Zhuravlev, B V; Mazo, V K; Zorin, S N; Volodin, V V

2014-11-01

Experiments on rats were performed to study the process of operant feeding learning, locomotor activity, oxygen consumption, and concentrations of corticosterone, β-endorphin, and prostaglandin E in blood serum after dietary treatment with the phytoecdysteroid extract. Administration of phytoecdysteroids was followed by the improvement of learning and increase in oxygen consumption and locomotor activity. Locomotor activity and oxygen consumption in the majority of control rats and phytoecdysteroid-treated animals were shown to be interrelated with the total locomotor activity and goal-directed operant behavior, respectively. No significant differences were found in the concentration of hormones in blood serum from animals of the control and treatment groups.

Reducing the health burden of HPV infection through vaccination.

PubMed

Soper, David

2006-01-01

Human papillomavirus (HPV), a sexually transmitted infection and the etiologic cause of genital warts and cervical cancer, is highly prevalent in sexually active men and women. Although cervical screening procedures have significantly reduced the disease burden associated with HPV infection, they are expensive and abnormal results cause significant emotional distress. Therefore, prevention may be an effective strategy for reducing the economic, psychosocial, and disease burden of HPV infection. Multivalent vaccines are now in clinical development. A bivalent vaccine that protects against HPV 16 and 18, and a quadrivalent vaccine which protects against HPV types 6, 11, 16, and 18, have been shown to significantly reduce the occurrence of incident and persistent HPV infections in phase 2 clinical trials; phase 3 trials are currently underway. HPV vaccines will be most effective when administered prior to initiation of sexual activity, and vaccination campaigns should aggressively target preadolescent and adolescent populations.

Reducing the Health Burden of HPV Infection Through Vaccination

PubMed Central

Soper, David

2006-01-01

Human papillomavirus (HPV), a sexually transmitted infection and the etiologic cause of genital warts and cervical cancer, is highly prevalent in sexually active men and women. Although cervical screening procedures have significantly reduced the disease burden associated with HPV infection, they are expensive and abnormal results cause significant emotional distress. Therefore, prevention may be an effective strategy for reducing the economic, psychosocial, and disease burden of HPV infection. Multivalent vaccines are now in clinical development. A bivalent vaccine that protects against HPV 16 and 18, and a quadrivalent vaccine which protects against HPV types 6, 11, 16, and 18, have been shown to significantly reduce the occurrence of incident and persistent HPV infections in phase 2 clinical trials; phase 3 trials are currently underway. HPV vaccines will be most effective when administered prior to initiation of sexual activity, and vaccination campaigns should aggressively target preadolescent and adolescent populations. PMID:16967913

The effect of levocabastine and furosemide pretreatment on hyperreactive response after nasal provocation with hypotonic aerosol in subjects with allergic rhinitis.

PubMed

Anzic, Srdjan Ante; Dzepina, Davor; Kalogjera, Livije

2007-11-01

Patients with allergic rhinitis demonstrate hyperreactive response in distilled water nasal provocation, shown by significant increase in nasal airway resistance (NAR). Antihistamines, including topical antihistamine, levocabastine, reduce response in non-specific nasal provocation tests. Furosemide is a diuretic which reduces hyperreactivity in lower airways, but the mode of its action is not yet fully understood. In this study, we hypothesized that either levocabastine or furosemide pre-treatment in allergic rhinitis patients reduced response to nasal challenge with non-isotonic aerosol. To test the hypothesis, we measured the effect of pre-treatment with levocabastine and furosemide in topical application on suppression of hyperreactive response to distilled water nasal inhalation. Nasal resistance was measured, prior to and after the provocation, by active anterior rhinomanometry in two randomized groups of patients, according to pre-treatment, either by levocabastine or furosemide, 20 patients in each group, respectively. Nasal airflow resistance and level of hyperreactive response considering nasal eosinophilia were tested. Significant increase in nasal resistance following provocation was found at baseline conditions (without pre-medication); pre-treatment with levocabastine and furosemide has suppressed such response. Patients with positive nasal eosinophilia showed a significantly higher increase in nasal resistance compared to those with negative smears. Furosemide has shown significantly better protective effect on nasal resistance increase in patients with positive eosinophils nasal smears. Levocabastine and furosemide pre-treatment suppress hyperreactive response to distilled water nasal provocation. Comparison of resistances (pre-treatment vs. without) showed more protective effect of furosemide, measured on both better and worse patent side of nose, in contrast to levocabastine group for which it was shown only on better patent side prior to provocation. Protection of furosemide was significantly more pronounced in patients with significant nasal eosinophilia.

Activity coefficients from molecular simulations using the OPAS method

NASA Astrophysics Data System (ADS)

Kohns, Maximilian; Horsch, Martin; Hasse, Hans

2017-10-01

A method for determining activity coefficients by molecular dynamics simulations is presented. It is an extension of the OPAS (osmotic pressure for the activity of the solvent) method in previous work for studying the solvent activity in electrolyte solutions. That method is extended here to study activities of all components in mixtures of molecular species. As an example, activity coefficients in liquid mixtures of water and methanol are calculated for 298.15 K and 323.15 K at 1 bar using molecular models from the literature. These dense and strongly interacting mixtures pose a significant challenge to existing methods for determining activity coefficients by molecular simulation. It is shown that the new method yields accurate results for the activity coefficients which are in agreement with results obtained with a thermodynamic integration technique. As the partial molar volumes are needed in the proposed method, the molar excess volume of the system water + methanol is also investigated.

The Role of Strigolactone in the Cross-Talk Between Arabidopsis thaliana and the Endophytic Fungus Mucor sp.

PubMed Central

Rozpądek, Piotr; Domka, Agnieszka M.; Nosek, Michał; Ważny, Rafał; Jędrzejczyk, Roman J.; Wiciarz, Monika; Turnau, Katarzyna

2018-01-01

Over the last years the role of fungal endophytes in plant biology has been extensively studied. A number of species were shown to positively affect plant growth and fitness, thus attempts have been made to utilize these microorganisms in agriculture and phytoremediation. Plant-fungi symbiosis requires multiple metabolic adjustments of both of the interacting organisms. The mechanisms of these adaptations are mostly unknown, however, plant hormones seem to play a central role in this process. The plant hormone strigolactone (SL) was previously shown to activate hyphae branching of mycorrhizal fungi and to negatively affect pathogenic fungi growth. Its role in the plant–endophytic fungi interaction is unknown. The effect of the synthetic SL analog GR24 on the endophytic fungi Mucor sp. growth, respiration, H2O2 production and the activity of antioxidant enzymes was evaluated. We found fungi colony growth rate was decreased in a GR24 concentration dependent manner. Additionally, the fungi accumulated more H2O2 what was accompanied by an altered activity of antioxidant enzymes. Symbiosis with Mucor sp. positively affected Arabidopsis thaliana growth, but SL was necessary for the establishment of the beneficial interaction. A. thaliana biosynthesis mutants max1 and max4, but not the SL signaling mutant max2 did not develop the beneficial phenotype. The negative growth response was correlated with alterations in SA homeostasis and a significant upregulation of genes encoding selected plant defensins. The fungi were also shown to be able to decompose SL in planta and to downregulate the expression of SL biosynthesis genes. Additionally, we have shown that GR24 treatment with a dose of 1 μM activates the production of SA in A. thaliana. The results presented here provide evidence for a role of SL in the plant–endophyte cross-talk during the mutualistic interaction between Arabidopsis thaliana and Mucor sp. PMID:29615990

Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients.

PubMed

Kim, Young-Woo; Eom, Bang Wool; Kook, Myeong-Cherl; Kim, Han-Seong; Kim, Mi-Kyung; Hwang, Hai-Li; Chandra, Vishal; Poojan, Shiv; Song, Yura; Koh, Jae-Soo; Bae, Chang-Dae; Ro, Jungsil; Hong, Kyeong-Man

2015-11-06

Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.

The effect of insoles on foot pain and daily activities.

PubMed

Amer, Ahmed O; Jarl, Gustav M; Hermansson, Liselotte N

2014-12-01

Foot pain decreases individuals' ability to perform daily activities. Insoles are often prescribed to reduce the pain which, in turn, may promote return to normal activities. To evaluate the effects of insoles on foot pain and daily activities, and to investigate the relationship between individuals' satisfaction with insoles and actual use of them. A 4-week pre-post intervention follow-up. Brief Pain Inventory, International Physical Activity Questionnaire and Lower Extremities Functional Status were used as outcome measures. Client Satisfaction with Device was used in the follow-up. A total of 67 participants answered the questionnaires (81% women). Overall, a reduction in Pain Severity (p = 0.002) and Pain Interference (p = 0.008) was shown. Secondary analyses revealed a significant effect only in women. No changes in daily activities (Walking, p = 0.867; Total Physical Activity, p = 0.842; Lower Extremities Functional Status, p = 0.939) could be seen. There was no relation between Client Satisfaction with Device measures and duration of insole use. A difference in sex was shown; women scored higher than men on Pain Severity. Insoles reduce pain and pain interference with daily activities for women with foot pain. Satisfaction with the insoles is not a predictor of actual insole use. The effect of insoles on activity performance needs further study. This study provides evidence for prescribing insoles to people with foot pain. Nonetheless, insoles are not enough to increase their physical activity level in the short term. Satisfaction with insoles and duration of use are not correlated and cannot be inferred from each other. © The International Society for Prosthetics and Orthotics 2013.

Anti-oxidative and anti-genotoxic effects of methanolic extract of Mentha pulegium on human lymphocyte culture.

PubMed

Alpsoy, Lokman; Sahin, Hilal; Karaman, Seyda

2011-08-01

In the present work, methanolic extract of Mentha pulegium from Erzurum, Turkey, was used in order to report the results of anti-oxidant capacity, anti-oxidant activity and anti-genotoxic effects. The total antioxidant capacity and total phenolic content were measured by using CUPRAC, ABTS and Folin-Ciocalteu colorimetric methods. The total phenolic content was higher than the total antioxidant capacity (for the results of both the CUPRAC and ABTS methods) of methanolic extract of M pulegium (ME). Also, we evaluated the anti-oxidant enzyme activity such as superoxide dismutase (SOD) and glutation peroxidase, total glutation (GSH) and malondialdehyde (MDA) in human lymphocyte culture. In CCl₄-treated group, the activity of SOD, glutathione peroxidase (GPx) and GSH decreased significantly and the level of MDA increased significantly. A significant increase in the activity of SOD, GPx and the level of GSH were seen when supplemented with ME to CCl₄-treated group. Furthermore, a significant decrease in the level of MDA was observed when compared with CCl₄ alone treated group. In addition, anti-genotoxic effect of ME was studied by using sister chromatid exchange (SCE) method. As a result, ME has shown anti-genotoxic effect depend on anti-oxidative effect on human lymphocyte culture.

Screening of Bunium bulbocastanum for antibacterial, antifungal, phytotoxic and haemagglutination activities.

PubMed

Khan, Ibrar; Ahmad, Haroon; Ali, Nasir; Ahmad, Bashir; Tanoli, Hamid

2013-07-01

The current study was aimed at screening the Bunium bulbocastanum for its antibacterial, antifungal, phytotoxic and haemagglutination activities.The crude methanolic extract and n-hexane fraction showed significant (89%) and good activity (61%) against Staphylococcus aureus while the CHCl3fraction was moderately active against S.aureus (53%). Moderate activitywas shown by the EtOAc fraction against B. subtilis (44%). This fraction was inactive against P.aerogenosa and S.aureus. The aqueous fraction showed significant activity against B. subtilis (85%), moderate against S.aureus(34 %) and E. coli (33%)and low activity against P.aerogenosa(29%). Our results for antifungal assay indicated that all the test samples were inactive against all the test fungi. The phytotoxic activity of the plant at 1000 and 100 μg/ml was: crude methanolic extract (53.33 and 46.66%), n-hexane (46.66 and 26.66%), CHCl3 (20 and 6.66%), EtOAc (46.66 and 26.66%) and aqueous (40 and 33.33%). All the test samples (crude methanolic extract and fractions) of B. bulbocastanum were unable to agglutinate RBCs of the human blood indicating that this species lack phytolectins.

Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.

PubMed

Rezvani, Amir H; Cauley, Marty; Xiao, Yingxian; Kellar, Kenneth J; Levin, Edward D

2013-03-01

Nicotine and nicotinic agonists have been shown to improve attentional function. Nicotinic receptors are easily desensitized, and all nicotinic agonists are also desensitizing agents. Although both receptor activation and desensitization are components of the mechanism that mediates the overall effects of nicotinic agonists, it is not clear how each of the two opposed actions contributes to attentional improvements. Sazetidine-A has high binding affinity at α4β2 nicotinic receptors and causes a relatively brief activation followed by a long-lasting desensitization of the receptors. Acute administration of sazetidine-A has been shown to significantly improve attention by reversing impairments caused by the muscarinic cholinergic antagonist scopolamine and the NMDA glutamate antagonist dizocilpine. In the current study, we tested the effects of chronic subcutaneous infusion of sazetidine-A (0, 2, or 6 mg/kg/day) on attention in Sprague-Dawley rats. Furthermore, we investigated the effects of chronic sazetidine-A treatment on attentional impairment induced by an acute administration of 0.02 mg/kg scopolamine. During the first week period, the 6-mg/kg/day sazetidine-A dose significantly reversed the attentional impairment induced by scopolamine. During weeks 3 and 4, the scopolamine-induced impairment was no longer seen, but sazetidine-A (6 mg/kg/day) significantly improved attentional performance on its own. Chronic sazetidine-A also reduced response latency and response omissions. This study demonstrated that similar to its acute effects, chronic infusions of sazetidine-A improve attentional performance. The results indicate that the desensitization of α4β2 nicotinic receptors with some activation of these receptors may play an important role in improving effects of sazetidine-A on attention.

Gender differences in bone turnover in 2-year-old Thoroughbreds.

PubMed

Jackson, B F; Lonnell, C; Verheyen, K; Wood, J L N; Pfeiffert, D U; Price, J S

2003-11-01

Injuries to the skeleton are a major cause of morbidity and mortality in racehorses and age, gender and season have all been shown to influence risk of injury. To use biochemical markers of bone cell activity to establish to whether cellular processes in bone underlie these described effects. Blood samples were collected monthly from 2-year-old horses in race training between November 1998 and September 1999. Mean age at the start of the study was 20 months (range 18-23 months), with no significant difference in average age between colts (n = 84) and fillies (n = 63). Three markers were measured; osteocalcin (OC, bone formation), the carboxyterminal cross-linked telopeptide of type I collagen (ICTP, bone resorption) and the carboxyterminal propeptide of type I collagen (PICP), which is less 'bone-specific' than the other 2 markers. Colts had, on average, 3.62 ng/ml higher OC concentrations (P = 0.044) and 0.68 mg/l higher ICTP concentrations (P = 0.01) than fillies. The effect of gender was not statistically significant for PICP. However, in May, PICP concentrations were on average 157 mg/l higher in fillies than colts. There was no effect of age or season on marker concentrations. This study has shown that there are gender differences in bone turnover markers in 2-year-old Thoroughbreds; however, age, within the limited range studied, did not have a significant effect on bone cell activity. Lower bone marker concentrations may reflect smaller bone size and/or earlier skeletal maturation in fillies. An increase in concentrations of PICP in fillies in spring and early summer may relect an influence of sex hormones on collagen turnover. Gender differences in bone cell activity in 2-year-old colts and fillies may influence bone's adaptive responses to training and risk of injury.

Modulatory role of Pterocarpus santalinus against alcohol-induced liver oxidative/nitrosative damage in rats.

PubMed

Bulle, Saradamma; Reddy, Vaddi Damodara; Padmavathi, Pannuru; Maturu, Paramahamsa; N Ch, Varadacharyulu

2016-10-01

Pterocarpus santalinus, a traditional medicinal plant has shown protective mechanisms against various complications. The aim of the present study is to evaluate therapeutic efficacy of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced oxidative/nitrosative stress leading to hepatotoxicity. In-vitro studies revealed that PSE possess strong DPPH (1,1-diphenyl-2-picryl hydrazyl) and nitric oxide radical scavenging activity. For in vivo studies male albino Wistar rats were treated with 20% alcohol (5g/kg b.wt/day) and PSE (250mg/kg b.wt/day) for 60days. Results showed that alcohol administration significantly altered plasma lipid profile with marked increase in the levels of plasma transaminases (ALT and AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (γGT). Moreover, lipid peroxides, nitric oxide (NOx) levels in plasma and liver were increased with increased iNOS protein expression in liver was noticed in alcohol administered rats and these levels were significantly brought back close to normal level by PSE administration except iNOS protein expression. Alcohol administration also decreased the content of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-s transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) in liver, which were significantly enhanced by administration of PSE. The active compounds pterostilbene, lignan and lupeols present in PSE might have shown protection against alcohol-induced hepatic damage by possibly reducing the rate of lipid peroxidation, NOx levels and increasing the antioxidant defence mechanism in alcohol administered rats. Both biochemical and histopathological results in the alcohol-induced liver damage model emphasize beneficial action of PSE as a hepatoprotective agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Aniracetam improves contextual fear conditioning and increases hippocampal gamma-PKC activation in DBA/2J mice.

PubMed

Smith, Amy M; Wehner, Jeanne M

2002-01-01

DBA/2J (D2) mice display poor contextual learning and have less membrane-bound hippocampal protein kinase C (PKC) compared with C57BL/6 (B6) mice. Aniracetam and oxiracetam were previously shown to improve contextual learning in D2 mice and increase PKC activity. This study investigated a possible mechanism for learning enhancement by examining the effects of aniracetam on contextual fear conditioning and activation of the y isoform of PKC (gamma-PKC) in male D2 mice. In comparison to animals treated with vehicle only (10% 2-hydroxypropyl-beta-cyclodextrin), mice treated with aniracetam (100 mg/kg) 30 min prior to fear conditioning training demonstrated significantly improved contextual learning when tested 30 min and 24 h after training. This corresponded with a significant increase in activated, membrane-bound hippocampal gamma-PKC 30 min after training. No increase in learning or gamma-PKC was found 5 min after training. These results suggest an altered time course of activation of gamma-PKC in response to treatment with aniracetam, which improves learning in D2 mice.

Ask-the-expert: Active Learning Based Knowledge Discovery Using the Expert

NASA Technical Reports Server (NTRS)

Das, Kamalika; Avrekh, Ilya; Matthews, Bryan; Sharma, Manali; Oza, Nikunj

2017-01-01

Often the manual review of large data sets, either for purposes of labeling unlabeled instances or for classifying meaningful results from uninteresting (but statistically significant) ones is extremely resource intensive, especially in terms of subject matter expert (SME) time. Use of active learning has been shown to diminish this review time significantly. However, since active learning is an iterative process of learning a classifier based on a small number of SME-provided labels at each iteration, the lack of an enabling tool can hinder the process of adoption of these technologies in real-life, in spite of their labor-saving potential. In this demo we present ASK-the-Expert, an interactive tool that allows SMEs to review instances from a data set and provide labels within a single framework. ASK-the-Expert is powered by an active learning algorithm for training a classifier in the backend. We demonstrate this system in the context of an aviation safety application, but the tool can be adopted to work as a simple review and labeling tool as well, without the use of active learning.

Ask-the-Expert: Active Learning Based Knowledge Discovery Using the Expert

NASA Technical Reports Server (NTRS)

Das, Kamalika

2017-01-01

Often the manual review of large data sets, either for purposes of labeling unlabeled instances or for classifying meaningful results from uninteresting (but statistically significant) ones is extremely resource intensive, especially in terms of subject matter expert (SME) time. Use of active learning has been shown to diminish this review time significantly. However, since active learning is an iterative process of learning a classifier based on a small number of SME-provided labels at each iteration, the lack of an enabling tool can hinder the process of adoption of these technologies in real-life, in spite of their labor-saving potential. In this demo we present ASK-the-Expert, an interactive tool that allows SMEs to review instances from a data set and provide labels within a single framework. ASK-the-Expert is powered by an active learning algorithm for training a classifier in the back end. We demonstrate this system in the context of an aviation safety application, but the tool can be adopted to work as a simple review and labeling tool as well, without the use of active learning.

In vivo activity assessment of a "honey-bee pollen mix" formulation.

PubMed

Küpeli Akkol, Esra; Orhan, Didem Deliorman; Gürbüz, Ilhan; Yesilada, Erdem

2010-03-01

Honey-bee pollen mix (HBM) formulation is claimed to be effective for the treatment of asthma, bronchitis, cancers, peptic ulcers, colitis, various types of infections including hepatitis B, and rheumatism by the herb dealers in northeast Turkey. In the present study, in vivo antinociceptive, anti-inflammatory, gastroprotective and antioxidant effects of pure honey and HBM formulation were evaluated comparatively. HBM did not show any significant gastroprotective activity in a single administration at 250 mg/kg dose, whereas a weak activity was observed after three days of successive administration at 500 mg/kg dose. On the other hand, HBM displayed significant antinociceptive (p <0.01) and anti-inflammatory (p <0.01) activities at 500 mg/kg dose orally without inducing any apparent acute toxicity or gastric damage. HBM was also shown to possess potent antilipidperoxidant activity (p <0.01) at 500 mg/kg dose against acetaminophen-induced liver necrosis model in mice. On the other hand, pure honey did not exert any remarkable antinociceptive, anti-inflammatory and gastroprotective activity, but a potent antilipidperoxidant activity (p <0.01) was determined. Results have clearly proved that mixing pure honey with bee pollen significantly increased the healing potential of honey and provided additional support for its traditional use. Total phenolic and flavonoid contents of HBM were found to be 145 and 59.3 mg/100 g of honey, which were estimated as gallic acid and quercetin equivalents, respectively.

Evaluation of Light-Activated Provisional Resin Materials for Periodontal Soft Tissue Management

PubMed Central

Jun, Soo-Kyung; Lee, Hae-Hyoung

2016-01-01

The purpose of this study was to determine mechanical properties using a compressive test with cylinder specimen (h = 6 mm and ϕ = 4 mm) as well as cytotoxicity using elutes from disk specimen (ϕ = 10 mm and h = 2 mm) against human gingival fibroblasts and oral keratinocytes with light-activated provisional resin materials (Revotek LC and Luxatemp Solar) compared to chemically activated counterpart (Snap, Trim II, and Jet). Significantly increased compressive strength (210~280 MPa) was detected in light-activated products compared to chemically activated ones (20~65 MPa, P < 0.05) and similar compressive modulus was detected in both types (0.8~1.5 and 0.5~1.3 GPa). Simultaneously, the light-activated products showed less adverse effects on the periodontal soft tissue cells in any polymerization stage compared to the chemically activated products. Particularly, chemically activated products had significantly greater adverse effects during the “polymerizing” phase compared to those that were “already set” (P < 0.05), as shown in confocal microscopic images of live and dead cells. In conclusion, light-activated provisional resin materials have better mechanical properties as well as biocompatibility against two tested types of oral cells compared to the chemically activated counterpart, which are considered as more beneficial choice for periodontal soft tissue management. PMID:27672651

Evaluation of Light-Activated Provisional Resin Materials for Periodontal Soft Tissue Management.

PubMed

Jun, Soo-Kyung; Lee, Hae-Hyoung; Lee, Jung-Hwan

The purpose of this study was to determine mechanical properties using a compressive test with cylinder specimen ( h = 6 mm and ϕ = 4 mm) as well as cytotoxicity using elutes from disk specimen ( ϕ = 10 mm and h = 2 mm) against human gingival fibroblasts and oral keratinocytes with light-activated provisional resin materials (Revotek LC and Luxatemp Solar) compared to chemically activated counterpart (Snap, Trim II, and Jet). Significantly increased compressive strength (210~280 MPa) was detected in light-activated products compared to chemically activated ones (20~65 MPa, P < 0.05) and similar compressive modulus was detected in both types (0.8~1.5 and 0.5~1.3 GPa). Simultaneously, the light-activated products showed less adverse effects on the periodontal soft tissue cells in any polymerization stage compared to the chemically activated products. Particularly, chemically activated products had significantly greater adverse effects during the "polymerizing" phase compared to those that were "already set" ( P < 0.05), as shown in confocal microscopic images of live and dead cells. In conclusion, light-activated provisional resin materials have better mechanical properties as well as biocompatibility against two tested types of oral cells compared to the chemically activated counterpart, which are considered as more beneficial choice for periodontal soft tissue management.

Stimulus-induced dissociation of neuronal firing rates and local field potential gamma power and its relationship to the blood oxygen level-dependent signal in macaque primary visual cortex

PubMed Central

Bartolo, M J; Gieselmann, M A; Vuksanovic, V; Hunter, D; Sun, L; Chen, X; Delicato, L S; Thiele, A

2011-01-01

The functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) signal is regularly used to assign neuronal activity to cognitive function. Recent analyses have shown that the local field potential (LFP) gamma power is a better predictor of the fMRI BOLD signal than spiking activity. However, LFP gamma power and spiking activity are usually correlated, clouding the analysis of the neural basis of the BOLD signal. We show that changes in LFP gamma power and spiking activity in the primary visual cortex (V1) of the awake primate can be dissociated by using grating and plaid pattern stimuli, which differentially engage surround suppression and cross-orientation inhibition/facilitation within and between cortical columns. Grating presentation yielded substantial V1 LFP gamma frequency oscillations and significant multi-unit activity. Plaid pattern presentation significantly reduced the LFP gamma power while increasing population multi-unit activity. The fMRI BOLD activity followed the LFP gamma power changes, not the multi-unit activity. Inference of neuronal activity from the fMRI BOLD signal thus requires detailed a priori knowledge of how different stimuli or tasks activate the cortical network. PMID:22081989

Distribution of Phenolic Compounds and Antioxidative Activities of Rice Kernel and Their Relationships with Agronomic Practice

PubMed Central

Kesarwani, Amit; Chiang, Po-Yuan; Chen, Shih-Shiung

2014-01-01

The phenolic and antioxidant activity of ethanolic extract of two Japonica rice cultivars, Taikeng no. 16 (medium and slender grain) and Kaohsiung no. 139 (short and round grain), grown under organic and conventional farming were examined. Analyses shows that Kaohsiung no. 139 contains the highest amount of secondary metabolites and continuous farming can increase its production. Results also suggest that phenolic content under different agronomic practices, has not shown significant differences but organically grown rice has proven to be better in higher accumulation of other secondary metabolites (2,2-diphenyl-1-picrylhydrazyl (DPPH), flavonoid content, and ferrous chelating capacity). In nutshell, genetic traits and environment have significant effect on phenolic compounds and the least variation reported under agronomic practices. PMID:25506072

Atomic layer deposition synthesized TiO{sub x} thin films and their application as microbolometer active materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanrikulu, Mahmud Yusuf, E-mail: mytanrikulu@adanabtu.edu.tr; Rasouli, Hamid Reza; Ghaffari, Mohammad

2016-05-15

This paper demonstrates the possible usage of TiO{sub x} thin films synthesized by atomic layer deposition as a microbolometer active material. Thin film electrical resistance is investigated as a function of thermal annealing. It is found that the temperature coefficient of resistance values can be controlled by coating/annealing processes, and the value as high as −9%/K near room temperature is obtained. The noise properties of TiO{sub x} films are characterized. It is shown that TiO{sub x} films grown by atomic layer deposition technique could have a significant potential to be used as a new active material for microbolometer-based applications.

Microbiological Activities of Lysostaphin and Penicillins Against Bacteriophage 80/81 Strains of Staphylococcus aureus

PubMed Central

Zygmunt, Walter A.; Harrison, Edward F.; Browder, Henry P.

1965-01-01

Using 20 clinical isolates of S. aureus (all bacteriophage 80/81 type), we found that lysostaphin inhibits the growth of all cultures at concentrations significantly lower than those observed with any of eight penicillins, a penicillin-like compound (cephalothin), or fusidic acid (a steroid antibiotic). All test cultures were shown to be resistant to penicillin G, ampicillin, and propicillin. Of the remaining penicillins (all penicillinase-insensitive), oxacillin, nafcillin, cloxacillin, and cephalothin were approximately equal in antimicrobial activity. Ancillin was slightly less active, and methicillin was even lower in potency. Cultures varied more widely in susceptibility to fusidic acid. None of the clinical isolates tested was found to be resistant to lysostaphin. PMID:14325294

Emerging Therapies for Diabetic Nephropathy Patients: Beyond Blockade of the Renin-Angiotensin System

PubMed Central

Tanios, Bassem Y.; Ziyadeh, Fuad N.

2012-01-01

Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The mainstay of treatment has been glycemic control and blood pressure lowering using agents blocking the renin-angiotensin system. Clinical trials are currently under way using novel agents for the treatment of patients with diabetic nephropathy. Promising agents emerging from some of the completed trials include pirfenidone and bardoxolone methyl, which have been shown in two recent randomized controlled trials in patients with diabetic nephropathy to result in an improved estimated glomerular filtration rate compared to placebo. Also, paricalcitol has been shown to decrease the urinary albumin-to-creatinine ratio, whereas sulodexide failed to do so in a large randomized double-blind placebo-controlled trial. Of note, pyridoxamine has also shown promise in the treatment of diabetic nephropathy if started early in the disease course. These preliminary trials have shown significant promise for managing patients with diabetic nephropathy, sparking active research in this field and providing the rationale for further clinical testing in long-term, hard-outcomes trials. PMID:23599705

Redistribution of boron in leaves reduces boron toxicity.

PubMed

Reid, Robert J; Fitzpatrick, Kate L

2009-11-01

High soil boron (B) concentrations lead to the accumulation of B in leaves, causing the development of necrotic regions in leaf tips and margins, gradually extending back along the leaf. Plants vary considerably in their tolerance to B toxicity, and it was recently discovered that one of the tolerance mechanisms involved extrusion of B from the root. Expression of a gene encoding a root B efflux transporter was shown to be much higher in tolerant cultivars. In our current research we have shown that the same gene is also upregulated in leaves. However, unlike in the root, the increased activity of the B efflux transporter in the leaves cannot reduce the tissue B concentration. Instead, we have shown that in tolerant cultivars, these transporters redistribute B from the intracellular phase where it is toxic, into the apoplast which is much less sensitive to B. These results provide an explanation of why different cultivars with the same leaf B concentrations can show markedly different toxicity symptoms. We have also shown that rain can remove a large proportion of leaf B, leading to significant improvements of growth of both leaves and roots.

Role of coupled dynamics in the catalytic activity of prokaryotic-like prolyl-tRNA synthetases.

PubMed

Sanford, Brianne; Cao, Bach; Johnson, James M; Zimmerman, Kurt; Strom, Alexander M; Mueller, Robyn M; Bhattacharyya, Sudeep; Musier-Forsyth, Karin; Hati, Sanchita

2012-03-13

Prolyl-tRNA synthetases (ProRSs) have been shown to activate both cognate and some noncognate amino acids and attach them to specific tRNA(Pro) substrates. For example, alanine, which is smaller than cognate proline, is misactivated by Escherichia coli ProRS. Mischarged Ala-tRNA(Pro) is hydrolyzed by an editing domain (INS) that is distinct from the activation domain. It was previously shown that deletion of the INS greatly reduced cognate proline activation efficiency. In this study, experimental and computational approaches were used to test the hypothesis that deletion of the INS alters the internal protein dynamics leading to reduced catalytic function. Kinetic studies with two ProRS variants, G217A and E218A, revealed decreased amino acid activation efficiency. Molecular dynamics studies showed motional coupling between the INS and protein segments containing the catalytically important proline-binding loop (PBL, residues 199-206). In particular, the complete deletion of INS, as well as mutation of G217 or E218 to alanine, exhibited significant effects on the motion of the PBL. The presence of coupled dynamics between neighboring protein segments was also observed through in silico mutations and essential dynamics analysis. Altogether, this study demonstrates that structural elements at the editing domain-activation domain interface participate in coupled motions that facilitate amino acid binding and catalysis by bacterial ProRSs, which may explain why truncated or defunct editing domains have been maintained in some systems, despite the lack of catalytic activity.

Role of Coupled-Dynamics in the Catalytic Activity of Prokaryotic-like Prolyl-tRNA Synthetases

PubMed Central

Sanford, Brianne; Cao, Bach; Johnson, James M.; Zimmerman, Kurt; Strom, Alexander M.; Mueller, Robyn M.; Bhattacharyya, Sudeep; Musier-Forsyth, Karin; Hati, Sanchita

2012-01-01

Prolyl-tRNA synthetases (ProRSs) have been shown to activate both cognate and some noncognate amino acids and attach them to specific tRNAPro substrates. For example, alanine, which is smaller than cognate proline, is misactivated by Escherichia coli ProRS. Mischarged Ala-tRNAPro is hydrolyzed by an editing domain (INS) that is distinct from the activation domain. It was previously shown that deletion of the INS greatly reduced cognate proline activation efficiency. In the present study, experimental and computational approaches were used to test the hypothesis that INS deletion alters the internal protein dynamics leading to reduce catalytic function. Kinetic studies with two ProRS variants, G217A and E218A, revealed decreased amino acid activation efficiency. Molecular dynamics studies showed motional coupling between the INS and protein segments containing the catalytically important proline-binding loop (PBL, residues 199–206). In particular, the complete deletion of INS, as well as mutation of G217 or E218 to alanine, exhibited significant effects on the motion of the PBL. The presence of coupled-dynamics between neighboring protein segments was also observed through in silico mutations and essential dynamics analysis. Taken together, the present study demonstrates that structural elements at the editing domain-activation domain interface participate in coupled motions that facilitate amino acid binding and catalysis by bacterial ProRSs, which may explain why truncated or defunct editing domains have been maintained in some systems, despite the lack of catalytic activity. PMID:22356126

Investigating Commercial Cellulase Performances Toward Specific Biomass Recalcitrance Factors Using Reference Substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, Xiaohui; Bowden, Mark E.; Engelhard, Mark H.

Three commercial cellulase preparations, Novozymes Cellic® Ctec2, Dupont Accellerase® 1500, and DSM Cytolase CL, were evaluated for their hydrolytic activity using a set of reference biomass substrates with controlled substrate characteristics. It was found that lignin remains a significant recalcitrance factor to all the preparations, although different enzyme preparations respond to the inhibitory effect of lignin differently. Also, different types of biomass lignin can inhibit cellulose enzymes in different manners. Enhancing enzyme activity toward biomass fiber swelling is an area significantly contributing to potential improvement in cellulose performance. While the degree of polymerization of cellulose in the reference substrates didmore » not present a major recalcitrance factor to Novozymes Cellic® Ctec2, cellulose crystallite has been shown to have a significant lower reactivity toward all enzyme mixtures. The presence of polysaccharide monooxygenases (PMOs) in Novozymes Ctec2 appears to enhance enzyme activity toward decrystallization of cellulose. This study demonstrated that reference substrates with controlled chemical and physical characteristics of structural features can be applied as an effective and practical strategy to identify cellulosic enzyme activities toward specific biomass recalcitrance factor(s) and provide specific targets for enzyme improvement.« less

Investigating commercial cellulase performances toward specific biomass recalcitrance factors using reference substrates.

PubMed

Ju, Xiaohui; Bowden, Mark; Engelhard, Mark; Zhang, Xiao

2014-05-01

Three commercial cellulase preparations, Novozymes Cellic(®) Ctec2, Dupont Accellerase(®) 1500, and DSM Cytolase CL, were evaluated for their hydrolytic activity using a set of reference biomass substrates with controlled substrate characteristics. It was found that lignin remains a significant recalcitrance factor to all the preparations, although different enzyme preparations respond to the inhibitory effect of lignin differently. Also, different types of biomass lignin can inhibit cellulase enzymes in different manners. Enhancing enzyme activity toward biomass fiber swelling is an area significantly contributing to potential improvement in cellulase performance. While the degree of polymerization of cellulose in the reference substrates did not present a major recalcitrance factor to Novozymes Cellic(®) Ctec2, cellulose crystallite has been shown to have a significant lower reactivity toward all enzyme mixtures. The presence of polysaccharide monooxygenases (PMOs) in Novozymes Ctec2 appears to enhance enzyme activity toward decrystallization of cellulose. This study demonstrated that reference substrates with controlled chemical and physical characteristics of structural features can be applied as an effective and practical strategy to identify cellulosic enzyme activities toward specific biomass recalcitrance factor(s) and provide specific targets for enzyme improvement.

Effects of radix polygoni multiflori components on tyrosinase activity and melanogenesis.

PubMed

Guan, Shuyu; Su, Weiwei; Wang, Ning; Li, Peibo; Wang, Yonggang

2008-04-01

Radix Polygoni multiflori is a herb used effectively to prevent graying and treat skin depigmentation diseases in traditional Chinese medicine but its active ingredients have not been discovered yet. In this investigation, we tested six compounds isolated from Radix Polygoni multiflori, to discover the active component on melanogenesis. Three experiments were performed in the present investigation: mushroom tyrosinase activity, melanin content B16 cell proliferation assay. Among all the six components tested, THSG showed the most potent effects on tyrosinase activation and melanogenesis; it was shown to be a potent tyrosinase activator and a melanogenesis stimulator in this study. On the other hand, we found that gallic acid significantly inhibited tyrosinase and, in addition, anthraquinones were cytotoxic to melanoma cells. They were both harmful to melanogenesis. Therefore, we propose that THSG acts as the active ingredient of Radix Polygoni multiflori on melanogenesis.

Antidepressant Activity of Brahmi in Albino Mice

PubMed Central

Kadali, SLDV Ramana Murty; M.C., Das; Rao A.S.R., Srinivasa; Sri G, Karuna

2014-01-01

Context: In traditional system of medicine brahmi has been used to enhance memory. Recently it has been reported to have action in psychiatric disorders. With these backgrounds the work has been undertaken to study antidepressant activity of brahmi in albino mice. Aim: To evaluate antidepressant activity of brahmi in experimental models. Materials and Methods: The antidepressant activity was studied in albino mice using forced swimming test (FST), tail suspension test (TST) and shock induced depression (SID). Imipramine (10mg/kg), fluoxetine (30mg/kg) were used as standard drugs and brahmi (10, 20, 30mg/kg) was used as test drug. Results: Brahmi exhibited significant decrease in duration of immobility in FST and reduced the shock induced decrease in activity in SID models. It didn’t show any activity in the TST model. Conclusion: Brahmi has shown antidepressant activity in FST and SID. PMID:24783074

Synthesis of novel ferrocenyl Mannich bases and their antibacterial activities

NASA Astrophysics Data System (ADS)

Liu, Yuting; Xin, Hong; Yin, Jingyi; Yin, Dawei; Yang, Zijiang; Li, Jie

2018-04-01

In this work, a series of Mannich bases bearing ferrocenyl groups were synthesized via Mannich reactions. The effects of different conditions on the reaction were explored, and the newly synthesized compounds were well characterized by NMR and FT-IR. All compounds have been screened for in vitro antibacterial and antifungal, and the compounds 1-ferrocenyl-3-phenyl-3-(m-nitrophenylamino)-1-acetone (2f) and 1-ferrocenyl-3-phenyl-3-(p-nitrophenylamino)-1-acetone (2g) were shown to be significant activity against all the tested bacterial strains, such as Staphylococcus aureus, Streptococcus, Actinomycete, Escherichia coli, Saccharomyces cerevisiae.

[OPEN FIELD BEHAVIOR AS A PREDICTIVE CRITERIA REFLECTING RATS CORTICOSTERONELEVEL BEFORE AND AFTER STRESS].

PubMed

Umriukhin, P E; Grigorchuk, O S

2015-12-01

In the presented study we investigated the possibility to use the open field behavior data for prediction of corticosterone level in rat blood plasma before and after stress. It is shown that the most reliable open field behavior parameters, reflecting high probability of significant upregulation of corticosterone after 3 hours of immobilization, are the short latency of first movement and low locomotor activity during the test. Rats with high corticosterone at normal non-stress conditions are characterized by low locomotor activity and on the contrary long latency period for the entrance of open field center.

Test and theory for piezoelectric actuator-active vibration control of rotating machinery

NASA Technical Reports Server (NTRS)

Palazzolo, A. B.; Lin, R. R.; Alexander, R. M.; Kascak, A. F.; Montague, J.

1989-01-01

The application of piezoelectric actuators for active vibration control (AVC) of rotating machinery is examined. Theory is derived and the resulting predictions are shown to agree closely with results of tests performed on an air turbine driven-overhung rotor. The test results show significant reduction in unbalance, transient and sub-synchronous responses. Results from a 30-hour endurance test support the AVD system reliability. Various aspects of the electro-mechanical stability of the control system are also discussed and illustrated. Finally, application of the AVC system to an actual jet engine is discussed.

Active chainmail fabrics for soft robotic applications

NASA Astrophysics Data System (ADS)

Ransley, Mark; Smitham, Peter; Miodownik, Mark

2017-08-01

This paper introduces a novel type of smart textile with electronically responsive flexibility. The chainmail inspired fabric is modelled parametrically and simulated via a rigid body physics framework with an embedded model of temperature controlled actuation. Our model assumes that individual fabric linkages are rigid and deform only through their own actuation, thereby decoupling flexibility from stiffness. A physical prototype of the active fabric is constructed and it is shown that flexibility can be significantly controlled through actuator strains of ≤10%. Applications of these materials to soft-robotics such as dynamically reconfigurable orthoses and splints are discussed.

[Mechanism of changes in the rate of glycolysis and levels of ATP and 2,3-diphosphoglycerate in human erythrocytes during aging].

PubMed

Bogatskaia, L N; Pisaruk, A V

1987-01-01

Reasons which have induced changes in the glycolysis rate, ATP and 2,3-diphosphoglycerate content in human erythrocytes with ageing are studied. A fall of the hexokinase activity is shown to be one of the reasons of a significant decrease in the glycolysis rate. The total ATPase activity in erythrocytes does not change with the age. At the same time the decay rate of 2,3-diphosphoglycerate increases, that, evidently, is one of the reasons of the 2,3-diphosphoglycerate content decrease in erythrocytes with ageing.

Low temperature deactivation of Ge heavily n-type doped by ion implantation and laser thermal annealing

NASA Astrophysics Data System (ADS)

Milazzo, R.; Impellizzeri, G.; Piccinotti, D.; De Salvador, D.; Portavoce, A.; La Magna, A.; Fortunato, G.; Mangelinck, D.; Privitera, V.; Carnera, A.; Napolitani, E.

2017-01-01

Heavy doping of Ge is crucial for several advanced micro- and optoelectronic applications, but, at the same time, it still remains extremely challenging. Ge heavily n-type doped at a concentration of 1 × 1020 cm-3 by As ion implantation and melting laser thermal annealing (LTA) is shown here to be highly metastable. Upon post-LTA conventional thermal annealing As electrically deactivates already at 350 °C reaching an active concentration of ˜4 × 1019 cm-3. No significant As diffusion is detected up to 450 °C, where the As activation decreases further to ˜3 × 1019 cm-3. The reason for the observed detrimental deactivation was investigated by Atom Probe Tomography and in situ High Resolution X-Ray Diffraction measurements. In general, the thermal stability of heavily doped Ge layers needs to be carefully evaluated because, as shown here, deactivation might occur at very low temperatures, close to those required for low resistivity Ohmic contacting of n-type Ge.

Cinnamic acid and its derivatives inhibit fructose-mediated protein glycation.

PubMed

Adisakwattana, Sirichai; Sompong, Weerachat; Meeprom, Aramsri; Ngamukote, Sathaporn; Yibchok-Anun, Sirintorn

2012-01-01

Cinnamic acid and its derivatives have shown a variety of pharmacologic properties. However, little is known about the antiglycation properties of cinnamic acid and its derivatives. The present study sought to characterize the protein glycation inhibitory activity of cinnamic acid and its derivatives in a bovine serum albumin (BSA)/fructose system. The results demonstrated that cinnamic acid and its derivatives significantly inhibited the formation of advanced glycation end products (AGEs) by approximately 11.96-63.36% at a concentration of 1 mM. The strongest inhibitory activity against the formation of AGEs was shown by cinnamic acid. Furthermore, cinnamic acid and its derivatives reduced the level of fructosamine, the formation of N(ɛ)-(carboxymethyl) lysine (CML), and the level of amyloid cross β-structure. Cinnamic acid and its derivatives also prevented oxidative protein damages, including effects on protein carbonyl formation and thiol oxidation of BSA. Our findings may lead to the possibility of using cinnamic acid and its derivatives for preventing AGE-mediated diabetic complications.

Cinnamic Acid and Its Derivatives Inhibit Fructose-Mediated Protein Glycation

PubMed Central

Adisakwattana, Sirichai; Sompong, Weerachat; Meeprom, Aramsri; Ngamukote, Sathaporn; Yibchok-anun, Sirintorn

2012-01-01

Cinnamic acid and its derivatives have shown a variety of pharmacologic properties. However, little is known about the antiglycation properties of cinnamic acid and its derivatives. The present study sought to characterize the protein glycation inhibitory activity of cinnamic acid and its derivatives in a bovine serum albumin (BSA)/fructose system. The results demonstrated that cinnamic acid and its derivatives significantly inhibited the formation of advanced glycation end products (AGEs) by approximately 11.96–63.36% at a concentration of 1 mM. The strongest inhibitory activity against the formation of AGEs was shown by cinnamic acid. Furthermore, cinnamic acid and its derivatives reduced the level of fructosamine, the formation of Nɛ-(carboxymethyl) lysine (CML), and the level of amyloid cross β-structure. Cinnamic acid and its derivatives also prevented oxidative protein damages, including effects on protein carbonyl formation and thiol oxidation of BSA. Our findings may lead to the possibility of using cinnamic acid and its derivatives for preventing AGE-mediated diabetic complications. PMID:22408423

Potential Energy Surface of the Chromium Dimer Re-re-revisited with Multiconfigurational Perturbation Theory.

PubMed

Vancoillie, Steven; Malmqvist, Per Åke; Veryazov, Valera

2016-04-12

The chromium dimer has long been a benchmark molecule to evaluate the performance of different computational methods ranging from density functional theory to wave function methods. Among the latter, multiconfigurational perturbation theory was shown to be able to reproduce the potential energy surface of the chromium dimer accurately. However, for modest active space sizes, it was later shown that different definitions of the zeroth-order Hamiltonian have a large impact on the results. In this work, we revisit the system for the third time with multiconfigurational perturbation theory, now in order to increase the active space of the reference wave function. This reduces the impact of the choice of zeroth-order Hamiltonian and improves the shape of the potential energy surface significantly. We conclude by comparing our results of the dissocation energy and vibrational spectrum to those obtained from several highly accurate multiconfigurational methods and experiment. For a meaningful comparison, we used the extrapolation to the complete basis set for all methods involved.

The effect of a healthy lifestyle programme on 8-9 year olds from social disadvantage.

PubMed

Breslin, Gavin; Brennan, Deirdre; Rafferty, Ruth; Gallagher, Alison M; Hanna, Donncha

2012-07-01

This study assessed the efficacy of a school-based healthy lifestyle intervention (Sport for LIFE) for increasing physical activity, decreasing sedentary behaviour, reducing screen time behaviour, encouraging healthy attitudes and behaviour to nutrition, and reducing body mass index (BMI) in 8-9-year-old primary school children from lower socioeconomic backgrounds in Northern Ireland. A non-randomised controlled trial of 416 children from 24 schools took part. Schools were randomly assigned to one of two groups, an intervention or control group with 12 schools in each group. The intervention group received a 12-week school-based programme based on social cognitive theory. At baseline and follow-up, groups completed questionnaires assessing physical activity, screen time behaviour and dietary patterns. On each occasion anthropometric assessments of height and weight were taken. Physical activity and sedentary behaviour were measured by accelerometry. Significant effects were observed for vigorous, moderate and light activity for the intervention group at follow-up. Sedentary behaviour was significantly reduced for the intervention group but not for the control group. No significant effects of the intervention on BMI, screen time behaviour or attitudes to nutrition, with the exception of non-core foods, were shown. The programme was effective in increasing physical activity and reducing sedentary behaviour, however no significant changes in screen time behaviour and attitude to nutrition, with the exception of non-core foods, were observed. Future research ideas are offered for tackling low levels of physical activity in children.

Youth Attitude Tracking Study. Volume 1. Spring 1976.

DTIC Science & Technology

1976-07-01

Service In the Spring wave the question as to when the positive youth would plan to enlist was split into active duty and National Guard/Reserve parts...In Table 5.6 it is shown that positive propensity respondents usually do not know more about the educational benefits than negative propensity respond...GI BILL EDUCATIONAL BENEFITS RELATED TO PROPENSITY Propensity Toward Each Service Significant Positive Negative Difference Difference Air Force 5.03

Standardization and Digital Enclosure: The Privatization of Standards, Knowledge, and Policy in the Age of Global Information Technology. Part of the Advances in IT Standards and Standardization Research (AISSR) Book Series

ERIC Educational Resources Information Center

Schoechle, Timothy, Ed.

2009-01-01

Recent trends have shown increasing privatization of standardization activities under various corporations, trade associations, and consortia, raising significant public policy issues about how the public interest may be represented. This book establishes a framework of analysis for public policy discussion and debate. Discussing topics such as…

A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

DTIC Science & Technology

2013-10-01

changes in brain function have indicated significant increases in brain activity supporting theory of mind and emotion regulation abilities in...depicted in the scenarios; adults with ASD have previously shown hypoactivation in the temporo- parietal-junction theory of mind (ToM) network when...treatment MRI data have been collected with processing speed, perspective-taking, theory of mind , and emotion regulation fMRI measures on participants

Antimicrobial peptides at work: interaction of myxinidin and its mutant WMR with lipid bilayers mimicking the P. aeruginosa and E. coli membranes

NASA Astrophysics Data System (ADS)

Lombardi, Lucia; Stellato, Marco Ignazio; Oliva, Rosario; Falanga, Annarita; Galdiero, Massimiliano; Petraccone, Luigi; D'Errico, Geradino; de Santis, Augusta; Galdiero, Stefania; Del Vecchio, Pompea

2017-03-01

Antimicrobial peptides are promising candidates as future therapeutics in order to face the problem of antibiotic resistance caused by pathogenic bacteria. Myxinidin is a peptide derived from the hagfish mucus displaying activity against a broad range of bacteria. We have focused our studies on the physico-chemical characterization of the interaction of myxinidin and its mutant WMR, which contains a tryptophan residue at the N-terminus and four additional positive charges, with two model biological membranes (DOPE/DOPG 80/20 and DOPE/DOPG/CL 65/23/12), mimicking respectively Escherichia coli and Pseudomonas aeruginosa membrane bilayers. All our results have coherently shown that, although both myxinidin and WMR interact with the two membranes, their effect on membrane microstructure and stability are different. We further have shown that the presence of cardiolipin plays a key role in the WMR-membrane interaction. Particularly, WMR drastically perturbs the DOPE/DOPG/CL membrane stability inducing a segregation of anionic lipids. On the contrary, myxinidin is not able to significantly perturb the DOPE/DOPG/CL bilayer whereas interacts better with the DOPE/DOPG bilayer causing a significant perturbing effect of the lipid acyl chains. These findings are fully consistent with the reported greater antimicrobial activity of WMR against P. aeruginosa compared with myxinidin.

The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size.

PubMed

Zwicker, Jeffrey I; Peyvandi, Flora; Palla, Roberta; Lombardi, Rossana; Canciani, Maria Teresa; Cairo, Andrea; Ardissino, Diego; Bernardinelli, Luisa; Bauer, Kenneth A; Lawler, Jack; Mannucci, Pier

2006-08-15

The N700S polymorphism of thrombospondin-1 (TSP-1) has been identified as a potential genetic risk factor for myocardial infarction (MI). In a large case-control study of 1425 individuals who survived a myocardial infarction prior to age 45, the N700S polymorphism was a significant risk factor for myocardial infarction in both homozygous (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.3, P = .01) and heterozygous carriers of the S700 allele (OR 1.4, 95% CI 1.1-3.3, P = .01). TSP-1 has been shown to reduce von Willebrand factor (VWF) multimer size, and the domain responsible for VWF-reducing activity has been localized to the calcium-binding C-terminal sequence. As the N700S polymorphism was previously shown to alter the function of this domain, we investigated whether the altered VWF-reducing activity of TSP-1 underlies the observed prothrombotic phenotype. The TSP1 N700S polymorphism did not influence VWF multimer size in patients homozygous for either allele nor was there a significant reduction of VWF multimer size following incubation with recombinant N700S fragments or platelet-derived TSP-1.

The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size

PubMed Central

Zwicker, Jeffrey I.; Peyvandi, Flora; Palla, Roberta; Lombardi, Rossana; Canciani, Maria Teresa; Cairo, Andrea; Ardissino, Diego; Bernardinelli, Luisa; Bauer, Kenneth A.; Lawler, Jack; Mannucci, Pier

2006-01-01

The N700S polymorphism of thrombospondin-1 (TSP-1) has been identified as a potential genetic risk factor for myocardial infarction (MI). In a large case-control study of 1425 individuals who survived a myocardial infarction prior to age 45, the N700S polymorphism was a significant risk factor for myocardial infarction in both homozygous (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.3, P = .01) and heterozygous carriers of the S700 allele (OR 1.4, 95% CI 1.1-3.3, P = .01). TSP-1 has been shown to reduce von Willebrand factor (VWF) multimer size, and the domain responsible for VWF-reducing activity has been localized to the calcium-binding C-terminal sequence. As the N700S polymorphism was previously shown to alter the function of this domain, we investigated whether the altered VWF-reducing activity of TSP-1 underlies the observed prothrombotic phenotype. The TSP1 N700S polymorphism did not influence VWF multimer size in patients homozygous for either allele nor was there a significant reduction of VWF multimer size following incubation with recombinant N700S fragments or platelet-derived TSP-1. PMID:16684956

Changes in expression of genes involved in apoptosis in activated human T-cells in response to modeled microgravity

NASA Astrophysics Data System (ADS)

Ward, Nancy E.; Pellis, Neal R.; Risin, Diana; Risin, Semyon A.; Liu, Wenbin

2006-09-01

Space flights result in remarkable effects on various physiological systems, including a decline in cellular immune functions. Previous studies have shown that exposure to microgravity, both true and modeled, can cause significant changes in numerous lymphocyte functions. The purpose of this study was to search for microgravity-sensitive genes, and specifically for apoptotic genes influenced by the microgravity environment and other genes related to immune response. The experiments were performed on anti-CD3 and IL-2 activated human T cells. To model microgravity conditions we have utilized the NASA rotating wall vessel bioreactor. Control lymphocytes were cultured in static 1g conditions. To assess gene expression we used DNA microarray chip technology. We had shown that multiple genes (approximately 3-8% of tested genes) respond to microgravity conditions by 1.5 and more fold change in expression. There is a significant variability in the response. However, a certain reproducible pattern in gene response could be identified. Among the genes showing reproducible changes in expression in modeled microgravity, several genes involved in apoptosis as well as in immune response were identified. These are IL-7 receptor, Granzyme B, Beta-3-endonexin, Apo2 ligand and STAT1. Possible functional consequences of these changes are discussed.

Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation.

PubMed

Ma, Kun; Kwon, Sun Hyung; Padmanabhan, Jagannath; Duscher, Dominik; Trotsyuk, Artem A; Dong, Yixiao; Inayathullah, Mohammed; Rajadas, Jayakumar; Gurtner, Geoffrey C

2018-05-15

Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries. To address this issue, we have developed a pullulan collagen-based hydrogel to deliver FAKI to excisional and burn wounds in mice. Specifically, two distinct drug-laden hydrogels were developed for rapid or sustained release of FAKI for treatment of burn wounds and excisional wounds, respectively. Controlled delivery of FAKI via pullulan collagen hydrogels accelerated wound healing, reduced collagen deposition and activation of scar forming myofibroblasts in both wound healing models. Our study highlights a biomaterial-based drug delivery approach for wound and scar management that has significant translational implications. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Targeting Alertness to Improve Cognition in Older Adults: A Preliminary Report of Benefits in Executive Function and Skill Acquisition

PubMed Central

Van Vleet, Thomas M.; DeGutis, Joseph M.; Merzenich, Michael M.; Simpson, Gregory V.; Zomet, Ativ; Dabit, Sawsan

2016-01-01

Efficient self-regulation of alertness declines with age exacerbating normal declines in performance across multiple cognitive domains, including learning and skill acquisition. Previous cognitive intervention studies have shown that it is possible to enhance alertness in patients with acquired brain injury and marked attention impairments, and that this benefit generalizes to improvements in more global cognitive functions. In the current preliminary studies, we sought to test whether this approach, that targets both tonic (over a period of minutes) and phasic (moment-to-moment) alertness, can improve key executive functioning declines in older adults, and enhance the rate of skill acquisition. The results of both experiments 1 and 2 demonstrate that, compared to active control training, alertness training significantly enhanced performance in several validated executive function measures. In experiment 2, alertness training significantly improved skill acquisition compared to active control training in a well-characterized speed of processing task, with the largest benefits shown in the most challenging speed of processing blocks. The results of the current study suggest that targeting intrinsic alertness in cognitive training provides a novel approach to improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. PMID:27372902

DNA Methylation Pyrosequencing Assay Is Applicable for the Assessment of Epigenetic Active Environmental or Clinical Relevant Chemicals

PubMed Central

Florea, Ana-Maria

2013-01-01

Exposure of cells and organisms to stressors might result in epigenetic changes. Here it is shown that investigation of DNA methylation using pyrosequencing is an alternative for in vitro and in vivo toxicological testing of epigenetic effects induced by chemicals and drugs. An in vitro evaluation of global and CpG site specific DNA methylation upon treatment of cells with chemicals/drugs is shown. Bisulfite genomic sequencing of methylation controls showed high methylation of LINE1 in methylation positive control and low methylation in the negative controls. The CpG sites within the LINE1 element are methylated at different levels. In vitro cell cultures show a methylation level ranging from 56% to 49%. Cultures of drug resistant tumor cells show significant hypomethylation as compared with the originating nonresistant tumor cells. The in vitro testing of epigenetically active chemicals (5-methyl-2'-deoxycytidine and trichostatin A) revealed a significant change of LINE1 methylation status upon treatment, while specific CpG sites were more prone to demethylation than others (focal methylation). In conclusion, DNA methylation using pyrosequencing might be used not only for testing epigenetic toxins/drugs but also in risk assessment of drugs, food, and environmental relevant pollutants. PMID:24093099

Carlina acaulis Exhibits Antioxidant Activity and Counteracts Aβ Toxicity in Caenorhabditis elegans.

PubMed

Link, Pille; Roth, Kevin; Sporer, Frank; Wink, Michael

2016-07-02

Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Aβ toxicity were studied in the Caenorhabditis elegans model. A dichloromethane extract of the roots of C. acaulis was prepared and characterised via gas-liquid-chromatography/mass-spectrometry (GLC-MS). The in vitro antioxidant activity was confirmed via 2,2-diphenyl-1-picrylhydracyl assay. The extract was further separated by thin layer chromatography into two fractions, one of which was a fraction of the dichloromethane extract of C. acaulis containing mostly Carlina oxide (CarOx). Different strains of C. elegans were employed to study the expression of hsp-16.2p::GFP as a marker for oxidative stress, delocalisation of the transcription factor DAF-16 as a possible mechanism of antioxidant activity, the effect of the drug under lethal oxidative stress, and the effect against beta-amyloid (Aβ) toxicity in a paralysis assay. The C. acaulis extract and CarOx showed high antioxidant activity (stress reduction by 47% and 64%, respectively) in C. elegans and could activate the transcription factor DAF-16 which directs the expression of anti-stress genes. In paralysis assay, only the total extract was significantly active, delaying paralysis by 1.6 h. In conclusion, in vivo antioxidant activity was shown for C. acaulis for the first time in the C. elegans model. The active antioxidant compound is Carlina oxide. This activity, however, is not sufficient to counteract Aβ toxicity. Other mechanisms and possibly other active compounds are involved in this effect.

Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract of Polyalthia suberosa Leaves

PubMed Central

Yasmen, Nelufar; Tajmim, Afsana; Akter, Mst. Irin; Hazra, Amit Kumar; Rahman, S. M. Mushiur

2018-01-01

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti-inflammatory activities of diethyl ether and n-hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin-induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene-induced ear edema test was used to evaluate anti-inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti-inflammatory activities in mice. In formalin-induced paw licking test, acetic acid induced writhing test, and xylene-induced ear edema test, the extracts exhibited significant inhibition (⁎P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant (⁎P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents which support its use in traditional medicine. PMID:29599807

Adherence to Diet and Physical Activity Cancer Prevention Guidelines and Cancer Outcomes: A Systematic Review.

PubMed

Kohler, Lindsay N; Garcia, David O; Harris, Robin B; Oren, Eyal; Roe, Denise J; Jacobs, Elizabeth T

2016-07-01

Many studies have reported that adherence to health promotion guidelines for diet, physical activity, and maintenance of healthy body weight may decrease cancer incidence and mortality. A systematic review was performed to examine associations between adherence to established cancer prevention guidelines for diet and physical activity and overall cancer incidence and mortality. PubMed, Google Scholar, and Cochrane Reviews databases were searched following the current recommendations of Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA). Twelve studies met inclusion criteria for this review. High versus low adherence to established nutrition and physical activity cancer prevention guidelines was consistently and significantly associated with decreases of 10% to 61% in overall cancer incidence and mortality. Consistent significant reductions were also shown for breast cancer incidence (19%-60%), endometrial cancer incidence (23%-60%), and colorectal cancer incidence in both men and women (27%-52%). Findings for lung cancer incidence were equivocal, and no significant relationships were found between adherence and ovarian or prostate cancers. Adhering to cancer prevention guidelines for diet and physical activity is consistently associated with lower risks of overall cancer incidence and mortality, including for some site-specific cancers. Cancer Epidemiol Biomarkers Prev; 25(7); 1018-28. ©2016 AACR. ©2016 American Association for Cancer Research.

Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract of Polyalthia suberosa Leaves.

PubMed

Yasmen, Nelufar; Aziz, Md Abdullah; Tajmim, Afsana; Akter, Mst Irin; Hazra, Amit Kumar; Rahman, S M Mushiur

2018-01-01

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti-inflammatory activities of diethyl ether and n-hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin-induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene-induced ear edema test was used to evaluate anti-inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti-inflammatory activities in mice. In formalin-induced paw licking test, acetic acid induced writhing test, and xylene-induced ear edema test, the extracts exhibited significant inhibition ( ⁎ P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant ( ⁎ P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents which support its use in traditional medicine.

Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4.

PubMed

Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2015-10-13

Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.

Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4

PubMed Central

Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2015-01-01

Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent. PMID:26473845

Magnetoencephalography with temporal spread imaging to visualize propagation of epileptic activity.

PubMed

Shibata, Sumiya; Matsuhashi, Masao; Kunieda, Takeharu; Yamao, Yukihiro; Inano, Rika; Kikuchi, Takayuki; Imamura, Hisaji; Takaya, Shigetoshi; Matsumoto, Riki; Ikeda, Akio; Takahashi, Ryosuke; Mima, Tatsuya; Fukuyama, Hidenao; Mikuni, Nobuhiro; Miyamoto, Susumu

2017-05-01

We describe temporal spread imaging (TSI) that can identify the spatiotemporal pattern of epileptic activity using Magnetoencephalography (MEG). A three-dimensional grid of voxels covering the brain is created. The array-gain minimum-variance spatial filter is applied to an interictal spike to estimate the magnitude of the source and the time (Ta) when the magnitude exceeds a predefined threshold at each voxel. This calculation is performed through all spikes. Each voxel has the mean Ta () and spike number (N sp ), which is the number of spikes whose source exceeds the threshold. Then, a random resampling method is used to determine the cutoff value of N sp for the statistically reproducible pattern of the activity. Finally, all the voxels where the source exceeds the threshold reproducibly shown on the MRI with a color scale representing . Four patients with intractable mesial temporal lobe epilepsy (MTLE) were analyzed. In three patients, the common pattern of the overlap between the propagation and the hypometabolism shown by fluorodeoxyglucose-positron emission tomography (FDG-PET) was identified. TSI can visualize statistically reproducible patterns of the temporal and spatial spread of epileptic activity. TSI can assess the statistical significance of the spatiotemporal pattern based on its reproducibility. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Citrus bergamia Juice Extract Attenuates β-Amyloid-Induced Pro-Inflammatory Activation of THP-1 Cells Through MAPK and AP-1 Pathways.

PubMed

Currò, Monica; Risitano, Roberto; Ferlazzo, Nadia; Cirmi, Santa; Gangemi, Chiara; Caccamo, Daniela; Ientile, Riccardo; Navarra, Michele

2016-02-08

Flavonoids have been shown to be effective in protecting against age-related cognitive and motor decline in both in vitro and in vivo models. Recently, a flavonoid-rich extract of Citrus bergamia juice (BJe) has been shown to display anti-oxidant and anti-inflammatory properties against LPS-induced activation of human THP-1 monocytes. In the light of these observations, we wondered whether BJe may be beneficial against neuroinflammatory processes, such as those observed in Alzheimer's disease. To this aim we used THP-1 monocytes to investigate the mechanisms underlying the beneficial potential of BJe against amyloid-beta1-42 (Aβ1-42) -mediated inflammation. Exposure of THP-1 cells to Aβ1-42 significantly induced the expression and secretion of IL-6 and IL-1β in THP-1 cells and increased the phosphorylation of ERK 1/2 as well as p46 and p54 members of JNK family. Moreover, Aβ1-42 raises AP-1 DNA binding activity in THP-1-treated cells. Interestingly, all these effects were reduced in the presence of BJe. Our data indicate that BJe may effectively counteract the pro-inflammatory activation of monocytes/microglial cells exposed to amyloid fibrils, suggesting a promising role as a natural drug against neuroinflammatory processes.

Transfer of in vitro expanded T lymphocytes after activation with dendritomas prolonged survival of mice challenged with EL4 tumor cells.

PubMed

Li, Jinhua; Theofanous, Leigh; Stickel, Sara; Bouton-Verville, Hilary; Burgin, Kelly E; Jakubchak, Susan; Wagner, Thomas E; Wei, Yanzhang

2007-07-01

Adoptive T cell transfer after in vitro expansion represents an attractive cancer immunotherapy. The majority of studies so far have been focusing on the expansion of tumor infiltrated lymphocytes (TIL) and some have shown very encouraging results. Recently, we have developed a unique tumor immune response activator, dendritomas, by fusion of dendritic cells and tumor cells. Animal studies and early clinical trials have shown that dendritomas are able to activate tumor specific immune responses. In this study, we hypothesized that naïve T cells can be primed with dendritomas and expanded in vitro to develop an adoptive transfer therapy for patients who do not have solid tumors, such as leukemia. T cells were isolated and purified from lymph nodes of mice. The cells were then incubated with dendritomas made from syngeneic DCs and tumor cells and expanded in vitro using Dynabeads mouse CD3/CD28 T cell expander for approximately three weeks. The in vitro primed and expanded T cells showed tumor cell specific CTL activity and increased secretion of IFN-gamma. Tumor bearing mice receiving the in vitro expanded T cells survived significantly longer than control mice. Furthermore, the depletion of regulator T cells enhanced the survival of the mice that received the adoptive transfer therapy.

Sexual Revictimization: A Routine Activity Theory Explanation.

PubMed

Culatta, Elizabeth; Clay-Warner, Jody; Boyle, Kaitlin M; Oshri, Assaf

2017-04-01

Research has shown that victims of sexual assault are at a significant risk of revictimization. We use routine activity theory to predict how sexual victimization in adolescence relates to depression, substance use, and ultimately revictimization as a young adult. We frame our research within routine activity theory and predict that sexual victimization increases substance use and depressive symptoms, both of which increase the likelihood of revictimization. We test the hypotheses with three waves of data from the Longitudinal Study of Violence Against Women. Using structural equation modeling, we examine the direct and indirect effects of previous sexual victimization, depressive symptoms, and substance use on the odds of victimization during the sophomore year of college. Results suggest that sexual victimization during the sophomore year of college is predicted directly by previous sexual victimization and also indirectly through depressive symptomology, though not substance use. Although understudied in the literature, depression is shown to mediate the relationship between victimization and revictimization, and this finding is consistent with routine activity theory, as well as the state dependence perspective on revictimization. Our findings suggest that depressive symptoms, a long acknowledged consequence of sexual victimization, should also be understood as a source of revictimization risk, indicating the importance of depression screening and intervention for decreasing sexual victimization.

Focused library design and synthesis of 2-mercapto benzothiazole linked 1,2,4-oxadiazoles as COX-2/5-LOX inhibitors

NASA Astrophysics Data System (ADS)

Yatam, Satayanarayana; Gundla, Rambabu; Jadav, Surender Singh; Pedavenkatagari, Narayana reddy; Chimakurthy, Jithendra; Rani B, Namratha; Kedam, Thyagaraju

2018-05-01

Mercapto benzothiazole linked 1,2,4-oxadiazole derivatives were designed (4a-u) as new anti-inflammatory agents using bioisosteric approach and docking studies. The docking results clearly indicated that the compounds 4a-u shown good docking interaction towards COX-2 enzyme. In silico drug-like properties were also calculated for compounds (4a-u) and exhibited significant H-bond acceptor ratio. All compounds were synthesized and biologically evaluated using in vitro COX-1, COX-2 and 5-LOX assays. Compound 4k and 4q (IC50 = 6.8 μM and IC50 = 5.0 μM) found to be potent, selective COX-2 inhibitors and display better anti-inflammatory activity than standard Ibuprofen. Compound 4l and 4e found to be potent inhibitors against 5-LOX (IC50 = 5.1 μM and IC50 = 5.5 μM). The in vivo anti-inflammatory activity studies shown that the compounds 4q and 4k effectively reducing the paw edema volume at 3h and 5h than standard drug Ibuprofen. The DPPH radical scavenging activity provided anti-oxidant activity of compound 4e (IC50 = 25.6 μM) than reference standard Ascorbic acid.

Antimicrobial activity of tempeh gembus hydrolyzate

NASA Astrophysics Data System (ADS)

Noviana, A.; Dieny, F. F.; Rustanti, N.; Anjani, G.; Afifah, D. N.

2018-02-01

Tropical disease can be prevented by consumming fermented foods that have antimicrobial activity. One of them is tempeh gembus that has short shelf life. It can be overcome by processing it into hydrolyzate. This study aimed to determine antimicrobial activity of tempeh gembus hydrolyzate. Tempeh gembus was made of local soybean from Grobogan. They were added 5,000 ppm, 8,000 ppm, and 10,000 ppm of bromelain enzyme (TGH BE). Antimicrobial effects of TGH BE were tested against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Steptococcus mutans. Antimicrobial test was carried out using Kirby-Bauer Disc Diffussion method. Soluble protein test used Bradford method. The largest inhibition zone against S. aureus and S. mutans were shown by TGH BE 8,000 ppm, 0.89±0.53 mm and 2.40±0.72 mm. The largest inhibition zone of B. subtilis, 7.33±2,25 mm, was shown by TGH BE 5,000 ppm. There wasn’t antimicrobial effect of TGH BE against E. coli. There weren’t significant differences of soluble protein (P=0.293) and the inhibition zones againt S. aureus (P = 0.967), E. coli (P = 1.000), B. subtilis (P = 0.645), S. mutans (P=0.817) of all treatments. There were antimicrobial activities of TGH BE against S. aureus, B. subtilis, and S. mutans.

Comparative evaluation of antibacterial property and substantivity of chlorhexidine containing dentifrices with sodium lauryl sulfate and Tween as surfactants: an in vivo study.

PubMed

Venu, V; Prabhakar, A R; Basappa, N

2013-01-01

The aim of the study was to determine the antibacterial property and substantivity of chlorhexidine containing dentifrices with sodium lauryl sulfate (SLS) and Tween as surfactants. It is a double-blind cross over the study, a total of 20 children within their mixed dentition period (7-13 year) having Streptococci mutans count more than 10(6) were selected for the main study. Three types of chlorhexidine containing dentifrices were used with a washout period of 1 week. Out of the three toothpastes, one was without surfactant and other two toothpastes contained SLS and Tween as surfactants respectively. 20 volunteers brushed for 1 min during the study day with their assigned toothpaste. Saliva samples were collected before brushing, immediately after brushing and 1, 3, 5, and 7 hand sent for microbial analysis. The culture carried out by inoculating saliva sample onto Mitis salivarius agar for selective isolation of S. mutans followed by counting of colony forming unit. Group I and III (Chlorhexidine and CHX + Tween) had shown statistically significant reduction in bacterial count until 7 h when compared to their baseline values ( P < 0.001). Group II toothpaste (CHX + SLS) had shown significant reduction in bacterial count until 3 h only. On inter group comparison, Group III had shown good amount of percentage reduction in bacterial count when compared to other groups. CHX + Tween toothpaste had shown statistically significant reduction in antibacterial activity and substantivity than other groups. These findings show chlorhexidine containing toothpaste with non-ionic surfactant will be able to maintain the antibacterial property and substantivity of chlorhexidine.

Topical stabilized retinol treatment induces the expression of HAS genes and HA production in human skin in vitro and in vivo.

PubMed

Li, Wen-Hwa; Wong, Heng-Kuan; Serrano, José; Randhawa, Manpreet; Kaur, Simarna; Southall, Michael D; Parsa, Ramine

2017-05-01

Skin Aging manifests primarily with wrinkles, dyspigmentations, texture changes, and loss of elasticity. During the skin aging process, there is a loss of moisture and elasticity in skin resulting in loss of firmness finally leading to skin sagging. The key molecule involved in skin moisture is hyaluronic acid (HA), which has a significant water-binding capacity. HA levels in skin decline with age resulting in decrease in skin moisture, which may contribute to loss of firmness. Clinical trials have shown that topically applied ROL effectively reduces wrinkles and helps retain youthful appearance. In the current study, ROL was shown to induce HA production and stimulates the gene expression of all three forms of hyaluronic acid synthases (HAS) in normal human epidermal keratinocytes monolayer cultures. Moreover, in human skin equivalent tissues and in human skin explants, topical treatment of tissues with a stabilized-ROL formulation significantly induced the gene expression of HAS mRNA concomitant with an increased HA production. Finally, in a vehicle-controlled human clinical study, histochemical analysis confirmed increased HA accumulation in the epidermis in ROL-treated human skin as compared to vehicle. These results show that ROL increases skin expression of HA, a significant contributing factor responsible for wrinkle formation and skin moisture, which decrease during aging. Taken together with the activity to increase collagen, elastin, and cell proliferation, these studies establish that retinol provides multi-functional activity for photodamaged skin.

The Role of GH/IGF-I Axis in Muscle Homeostasis During Weightlessness

NASA Technical Reports Server (NTRS)

Schwartz, Robert J.

1997-01-01

Exposure to reduced gravity during space travel profoundly alters the loads placed on bone and muscle. Astronauts suffer significant losses of muscle and bone strength during weightlessness. Exercise as a countermeasure is only partially effective in remedying severe muscle atrophy and bone demineralization. Similar wasting of muscles and bones affects people on Earth during prolonged bed rest or immobilization due to injury. In the absence of weight bearing activity, atrophy occurs primarily in the muscles that act in low power, routine movements and in maintaining posture. Hormonal disfunction could contribute in part to the loss of muscle and bone during spaceflight. Reduced levels of human Growth Hormone (hGH) were found in astronauts during space flight, as well as reduced GH secretory activity was observed from the anterior pituitary in 7-day space flight rats. Growth hormone has been shown to be required for maintenance of muscle mass and bone mineralization, in part by mediating the biosynthesis IGF-I, a small polypeptide growth factor. IGF biosynthesis and secretion plays an important role in potentiating muscle cell differentiation and has been shown to drive the expression of myogenin, a myogenic specific basic helix-loop-helix factor. IGF-I has also been shown to have an important role in potentiating muscle regeneration, repair and adult muscle hypertrophy.

Purification and Characterization of Bacteriocin Produced by Weissella confusa A3 of Dairy Origin

PubMed Central

Goh, Hweh Fen; Philip, Koshy

2015-01-01

A dramatic increase in bacterial resistance towards currently available antibiotics has raised worldwide concerns for public health. Therefore, antimicrobial peptides (AMPs) have emerged as a promisingly new group of therapeutic agents for managing infectious diseases. The present investigation focusses on the isolation and purification of a novel bacteriocin from an indigenous sample of cow milk and it’s mode of action. The bacteriocin was isolated from Weissella confusa A3 that was isolated from the sample and was shown to have inhibitory activity towards pathogenic bacteria namely Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Micrococcus luteus. The bacteriocin was shown to be heat stable and functioned well at low pH (2 to 6). Reduction of activity was shown after treatment with proteinase K, trypsin and peptidase that confirmed the proteinaceous nature of the compound. MALDI-TOF analysis of the sample gave a mass approximating 2.7 kDa. The membrane of the bacteria was disrupted by the bacteriocin causing SYTOX® green dye to enter the cell and bind to the bacterial DNA giving fluorescence signal. Bacterial cell treated with the bacteriocin also showed significant morphological changes under transmission electron microscope. No virulence and disease related genes can be detected from the genome of the strain. PMID:26474074

Purification and Characterization of Bacteriocin Produced by Weissella confusa A3 of Dairy Origin.

PubMed

Goh, Hweh Fen; Philip, Koshy

2015-01-01

A dramatic increase in bacterial resistance towards currently available antibiotics has raised worldwide concerns for public health. Therefore, antimicrobial peptides (AMPs) have emerged as a promisingly new group of therapeutic agents for managing infectious diseases. The present investigation focusses on the isolation and purification of a novel bacteriocin from an indigenous sample of cow milk and it's mode of action. The bacteriocin was isolated from Weissella confusa A3 that was isolated from the sample and was shown to have inhibitory activity towards pathogenic bacteria namely Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Micrococcus luteus. The bacteriocin was shown to be heat stable and functioned well at low pH (2 to 6). Reduction of activity was shown after treatment with proteinase K, trypsin and peptidase that confirmed the proteinaceous nature of the compound. MALDI-TOF analysis of the sample gave a mass approximating 2.7 kDa. The membrane of the bacteria was disrupted by the bacteriocin causing SYTOX® green dye to enter the cell and bind to the bacterial DNA giving fluorescence signal. Bacterial cell treated with the bacteriocin also showed significant morphological changes under transmission electron microscope. No virulence and disease related genes can be detected from the genome of the strain.

Action mechanism and signal pathways of Psidium guajava L. aqueous extract in killing prostate cancer LNCaP cells.

PubMed

Chen, Kuan-Chou; Peng, Chiung-Chi; Chiu, Wen-Ta; Cheng, Yu-Ting; Huang, Guan-Ta; Hsieh, Chiu-Lan; Peng, Robert Y

2010-01-01

Aqueous extract of Psidium guajava L. budding leaves (PE) has been shown to possess anti-prostate cancer activity in a cell line model. We examined whether its bioactivity could be conserved either in the presence or the absence of synthetic androgen R1881. In both cases, PE was shown to inhibit LNCaP cell proliferation and down-regulate expressions of androgen receptor (AR) and prostate specific antigen (PSA). The cytotoxicity of PE was shown by enhanced LDH release in LNCaP cells. The flow cytometry analysis revealed cell cycle arrests at G(0)/G(1) phase with huge amount of apoptotic LNCaP cells after treatment with PE for 48 h in a dose-responsive manner, which was also confirmed by TUNEL assay. From the results of decreased Bcl-2/Bax ratio, inactivation of phosphor-Akt, activation of phosphor-p38, phospho-Erk1/phospho-Erk2, the molecular action mechanism of PE to induce apoptosis in LNCaP cells was elucidated. Compatible with the in vitro study findings, treatment with PE (1.5 mg/mouse/day) significantly diminished both the PSA serum levels and tumor size in a xenograft mouse tumor model. Conclusively, PE is a promising anti-androgen-sensative prostate cancer agent.

Assessment of Olea europaea L. fruit extracts: Phytochemical characterization and anticancer pathway investigation.

PubMed

Maalej, Amina; Bouallagui, Zouhaier; Hadrich, Fatma; Isoda, Hiroko; Sayadi, Sami

2017-06-01

Olea europaea L. has been widely used as an advantageous rich source of bioactive compounds of high economic value leading to its use in pharmaceutical, cosmetic, and agriculture industries. Ethanolic extracts of olive fruits from three different cultivars (OFE) were studied for their phytochemical contents and were investigated for antioxidant activities and anticancer potential. Major polyphenols detected in these extracts were tyrosol, hydroxytyrosol, oleuropein, rutin, quercetin and glucoside forms of luteolin and apigenin. All these compounds have shown to significantly contribute to the antioxidant activity of OFE, which was evaluated by DPPH and ABTS assays. Proliferation of hepatic and colon cancer cells, HepG2 and Caco-2, were shown to be sensitive to OFE with IC 50 less than 1.6mg/ml for all tested extracts. Moreover, flow cytometry analysis showed that OFE induced cell cycle arrest in the S-phase within both HepG2 and Caco-2 cells. This has triggered a cell death mechanism as shown by DNA fragmentation, expression of p53 and phosphorylation level of Akt and Erk proteins. Interestingly, these extracts could be further used as a potential source of natural compounds with both antioxidant and anticancer effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Astaxanthin attenuates glutamate-induced apoptosis via inhibition of calcium influx and endoplasmic reticulum stress.

PubMed

Lin, Xiaotong; Zhao, Yan; Li, Shanhe

2017-07-05

Astaxanthin (AST) is a carotenoid that has been shown to have neuroprotective effects. In this study, it was found that AST significantly inhibited glutamate-induced loss of cell viability and apoptosis. AST pretreatment attenuated glutamate-induced activation of caspase-3, reduction of anti-apoptotic protein Bcl-2, and increase of pro-apoptotic protein Bak. In addition, AST pretreatment suppressed the production of intracellular reactive oxygen species. AST treatment also prevented glutamate-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK), which has been shown to promote apoptotic events. Furthermore, AST treatment greatly reduced the elevation of intracellular calcium level induced by glutamate and inhibited the activity of calpain, a calcium-dependent protease that plays an important role in mediating apoptosis stimulated by calcium overload in cytoplasm. Both oxidative stress and calcium overload can lead to endoplasmic reticulum (ER) stress. C/EBP-homologous protein (CHOP) is a bZIP transcription factor that can be activated by ER stress and promotes apoptosis. Here we found that AST attenuated glutamate-induced elevation of CHOP and ER chaperone glucose-regulated protein (GRP78). Overall, these results suggested that AST might protect cells against glutamate-induced apoptosis through maintaining redox balance and inhibiting glutamate-induced calcium influx and ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

A structural–functional basis for dyslexia in the cortex of Chinese readers

PubMed Central

Siok, Wai Ting; Niu, Zhendong; Jin, Zhen; Perfetti, Charles A.; Tan, Li Hai

2008-01-01

Developmental dyslexia is a neurobiologically based disorder that affects ≈5–17% of school children and is characterized by a severe impairment in reading skill acquisition. For readers of alphabetic (e.g., English) languages, recent neuroimaging studies have demonstrated that dyslexia is associated with weak reading-related activity in left temporoparietal and occipitotemporal regions, and this activity difference may reflect reductions in gray matter volume in these areas. Here, we find different structural and functional abnormalities in dyslexic readers of Chinese, a nonalphabetic language. Compared with normally developing controls, children with impaired reading in logographic Chinese exhibited reduced gray matter volume in a left middle frontal gyrus region previously shown to be important for Chinese reading and writing. Using functional MRI to study language-related activation of cortical regions in dyslexics, we found reduced activation in this same left middle frontal gyrus region in Chinese dyslexics versus controls, and there was a significant correlation between gray matter volume and activation in the language task in this same area. By contrast, Chinese dyslexics did not show functional or structural (i.e., volumetric gray matter) differences from normal subjects in the more posterior brain systems that have been shown to be abnormal in alphabetic-language dyslexics. The results suggest that the structural and functional basis for dyslexia varies between alphabetic and nonalphabetic languages. PMID:18391194

Virucidal activities of medium- and long-chain fatty alcohols and lipids against respiratory syncytial virus and parainfluenza virus type 2: comparison at different pH levels.

PubMed

Hilmarsson, H; Traustason, B S; Kristmundsdóttir, T; Thormar, H

2007-01-01

Recent studies have shown that some lipids and fatty alcohols have microbicidal activities against a broad variety of pathogens. In this study, virucidal activities of fatty acids, monoglycerides and fatty alcohols were tested against respiratory syncytial virus (RSV) and human parainfluenza virus type 2 (HPIV2) at different concentrations, times and pH levels. The most active compounds were mixed with milk products and fruit juices and the mixtures tested for virucidal effects. The aim was to determine which compounds are the most active against these respiratory viruses and could possibly be used in pharmaceutical formulations or as additives to milk products or juice. Several compounds caused a significant inactivation of virus, and there was generally a good agreement between the activities against RSV and parainfluenza virus. By changing the pH from 7 to 4.2, the virucidal activities of some of the compounds were greatly increased, i.e., they inactivated virus in a shorter time and at lower concentrations. The most active compound tested was 1-monoglyceride of capric acid, monocaprin, which also showed activity against influenza A virus and significant virucidal activities after addition to milk products and fruit juices, even at a concentration as low as 0.06-0.12%. The significant virucidal activities of fatty alcohols and lipids on RSV and parainfluenza virus demonstrated in this in vitro study raise the question of the feasibility of using such compounds as ingredients in pharmaceutical dosage forms against respiratory infections caused by these viruses, and possibly other paramyxo- and myxoviruses.

A Novel Antifungal Is Active against Candida albicans Biofilms and Inhibits Mutagenic Acetaldehyde Production In Vitro

PubMed Central

Nieminen, Mikko T.; Novak-Frazer, Lily; Rautemaa, Vilma; Rajendran, Ranjith; Sorsa, Timo; Ramage, Gordon; Bowyer, Paul; Rautemaa, Riina

2014-01-01

The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 µM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm infections. PMID:24867320

NF-κB DNA-binding activity in embryos responding to a teratogen, cyclophosphamide

PubMed Central

Torchinsky, Arkady; Lishanski, Lucy; Wolstein, Orit; Shepshelovich, Jeanne; Orenstein, Hasida; Savion, Shoshana; Zaslavsky, Zeev; Carp, Howard; Brill, Alexander; Dikstein, Rivka; Toder, Vladimir; Fein, Amos

2002-01-01

Background The Rel/NF-κB transcription factors have been shown to regulate apoptosis in different cell types, acting as inducers or blockers in a stimuli- and cell type-dependent fashion. One of the Rel/NF-κB subunits, RelA, has been shown to be crucial for normal embryonic development, in which it functions in the embryonic liver as a protector against TNFα-induced physiological apoptosis. This study assesses whether NF-κB may be involved in the embryo's response to teratogens. Fot this, we evaluated how NF-KappaB DNA binding activity in embryonic organs demonstraiting differential sensitivity to a reference teratogen, cyclophosphamide, correlates with dysmorphic events induced by the teratogen at the cellular level (excessive apoptosis) and at the organ level (structural anomalies). Results The embryonic brain and liver were used as target organs. We observed that the Cyclophosphamide-induced excessive apoptosis in the brain, followed by the formation of severe craniofacial structural anomalies, was accompanied by suppression of NF-κB DNA-binding activity as well as by a significant and lasting increase in the activity of caspases 3 and 8. However, in the liver, in which cyclophosphamide induced transient apoptosis was not followed by dysmorphogenesis, no suppression of NF-κB DNA-binding activity was registered and the level of active caspases 3 and 8 was significantly lower than in the brain. It has also been observed that both the brain and liver became much more sensitive to the CP-induced teratogenic insult if the embryos were exposed to a combined treatment with the teratogen and sodium salicylate that suppressed NF-κB DNA-binding activity in these organs. Conclusion The results of this study demonstrate that suppression of NF-κB DNA-binding activity in embryos responding to the teratogenic insult may be associated with their decreased resistance to this insult. They also suggest that teratogens may suppress NF-κB DNA-binding activity in the embryonic tissues in an organ type- and dose-dependent fashion. PMID:11893254

The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and serves as a positive regulator of transcriptional activation by STAT6.

PubMed

Arimura, Akinori; vn Peer, Maartje; Schröder, Andreas J; Rothman, Paul B

2004-07-23

Transcriptional activation by signal transducer and activator of transcription 6 (STAT6) has been shown to require the direct interaction not only with co-activators such as p300 and cAMP-responsive element-binding protein-binding protein (CBP) but also with nuclear co-activator 1, a member of the p160/steroid receptor co-activator family. Among the p160/steroid receptor co-activators, only p/CIP (nuclear co-activator 3) has been shown to be up-regulated by interleukin (IL)-4 in B cells through a STAT-6-dependent mechanism using Gene-Chip analysis. In this study, we have investigated the function of p/CIP in the transcriptional activation by STAT6. We found that p/CIP indirectly interacted with STAT6 via p300, and overexpression of the CBP-interacting domain of p/CIP (p/CIP(947-1084)) prevented the interaction of p/CIP with STAT6 by blocking the binding of p/CIP to p300. Whereas expression of p/CIP(947-1084) resulted in a marked reduction of STAT6-mediated transactivation, overexpression of wild type p/CIP resulted in significant enhancement of it. In addition, p/CIP(947-1084) markedly reduced CD23 expression on B cells stimulated with IL-4, whereas overexpression of wild type p/CIP enhanced it. Chromatin immunoprecipitations demonstrate that IL-4 increases the interaction of p/CIP with the murine immunoglobulin heavy chain germ line epsilon promoter in B cells. These results suggest that p/CIP positively regulates STAT6 transcriptional activation through formation of a STAT6, p300/CBP, and p/CIP complex.

Internal optical losses in very thin CW heterojunction laser diodes

NASA Technical Reports Server (NTRS)

Butler, J. K.; Kressel, H.; Ladany, I.

1975-01-01

Theoretical calculations are presented showing the relationship between the internal laser absorption and structural parameters appropriate for CW room-temperature lasers. These diodes have submicron-thick recombination regions, and very small spacings between the heat sink and the recombination region to minimize the thermal resistance. The optical loss is shown to be strongly dependent on the degree of radiation confinement to the active region. In particular, absorption in the surface GaAs layer providing the ohmic contact becomes very significant when the intermediate (AlGa)As layer is reduced below about 1 micron. It is further shown that excessive penetration into the GaAs regions gives rise to anomalies in the far-field radiation profiles in the direction perpendicular to the junction plane.

The influence of the distance between the donor-acceptor groups of polymethine dyes on their photovoltaic properties

NASA Astrophysics Data System (ADS)

Seliverstova, E.; Ibrayev, N.

2018-01-01

Spectral-luminescent and photovoltaic properties of polymethine dyes of various structures are studied. It is shown that an increase in the length of the methylene chain between the active chromophores leads to a red-wave shift of the absorption and fluorescence spectra. Significant changes in the absorptivity and lifetime of fluorescence do not occur in this case. The best photovoltaic parameters have cells sensitized with shorter dye molecules. It is shown, that for a longer dye the resistance associated with electron recombination on the TiO2/electrolyte surface is much higher than the electron transfer resistance in the semiconductor, which reduces the efficiency of electron transfer in the solar cell, sensitized with longer dye molecules.

Inhibitory effects of Physalis angulata on tumor metastasis and angiogenesis.

PubMed

Hseu, You-Cheng; Wu, Chi-Rei; Chang, Hsueh-Wei; Kumar, K J Senthil; Lin, Ming-Kuem; Chen, Chih-Sheng; Cho, Hsin-Ju; Huang, Chun-Yin; Huang, Chih-Yang; Lee, Hong-Zin; Hsieh, Wen-Tsong; Chung, Jing-Gung; Wang, Hui-Min; Yang, Hsin-Ling

2011-06-01

ETHNOPHARMACOLOGICAL RELAVENCE: Physalis angulata is well-known in traditional Chinese medicine as a ingredient for various herbal formulation; also, it has been shown to exhibit anti-cancer and anti-inflammatory effects. In this study, the ability of P. angulata to inhibit tumor metastasis and angiogenesis was investigated. Anti-proliferative activity of ethyl acetate extracts of P. angulata (PA extracts), was determined against human oral squamous carcinoma (HSC-3) and human umbilical vein endothelial cells (HUVECs) by trypan blue exclusion method. Wound-healing migration, trans-well invasion, Western blotting and chick chorioallantoic membrane assay were carried out to determine the anti-metastatic and anti-angiogenic effects of PA extracts in vitro and in vivo. We demonstrated that at sub-cytotoxic concentrations of PA extracts (5-15 μg/mL) markedly inhibited the migration and invasion of highly metastatic HSC-3 cells as shown by wound-healing repair assay and trans-well assay. Gelatin zymography assay showed that PA extracts suppressed the activity of matrix metalloproteinase (MMP)-9 and -2, and urokinase plasminogen activator (u-PA) in HSC-3 cells. In addition, Western blot analysis confirmed that PA extracts significantly decreased MMP-2 and u-PA protein expression in HSC-3 cells. Notably, PA extracts significantly augmented the expression of their endogenous inhibitors, including tissue inhibitors of MMP (TIMP-1 and -2), and plasminogen activator inhibitors (PAI-1 and -2). Further investigations revealed that non-cytotoxic concentration of PA extracts (5-15 μg/mL) inhibited vascular endothelial growth factor (VEGF)-induced proliferation, and migration/invasion of HUVECs in vitro. PA extracts also suppressed the activity of MMP-9, but not MMP-2, in HUVECs. Further, we observed, PA extracts strongly suppressed neovessel formation in the chorioallantoic membrane of chick embryos in vivo. These results strongly support an anti-metastatic and anti-angiogenic activity of P. angulata that may contribute to the development of better chemopreventive agent for cancer and inflammation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Haemostatic agent etamsylate in vitro and in vivo antagonizes anti-coagulant activity of heparin.

PubMed

Cobo-Nuñez, M Yolanda; El Assar, Mariam; Cuevas, Pedro; Sánchez-Ferrer, Alberto; Martínez-González, Jennifer; Rodríguez-Mañas, Leocadio; Angulo, Javier

2018-05-15

Etamsylate is indicated for several anti-hemorrhagic indications in human and veterinary medicine. However, etamsylate has been shown to be effective only in specific hemorrhagic situations. Furthermore, mechanism of action of etamsylate is not known but recent research has shown its ability to inhibit heparin binding to several growth factors. We have evaluated the ability of etamsylate to interfere with the activities of heparin. Effects of etamsylate on vasodilatory activity of heparin were evaluated in rat aortic segments. Influence of etamsylate on anticoagulant activity of heparin was evaluated in vitro by determining prothrombin (PT) time and activated partial thromboplastin time (aPTT) in dog blood and in vivo by determining the interference of systemic and topical etamsylate on heparin-induced extension in bleeding time (BT) in rats. Despite failing to inhibit heparin-induced vasodilation of rat aorta, etamsylate significantly reduced the increase in aPTT caused by heparin (+30.4 ± 6.7% vs. +15.0 ± 2.8% for etamsylate at 100 µM, P < 0.05). Etamsylate also antagonized the anticoagulant effects driven by heparin in vivo since prevented the heparin-induced increase in BT when systemically (i.p.) administered (+94.6 ± 7.5% vs. +57.9 ± 9.2% at 10 mg/kg, P < 0.05, vs. +22.2 ± 16.8% at 30 mg/kg, P < 0.01). Additionally, topically applied etamsylate (125 mg/ml) significantly reduced heparin-induced BT increase (+102.5 ± 3.2% vs. +54.0 ± 5.8%, P < 0.01). These evidences show a pharmacological interference by etamsylate on heparin activities antagonizing pro-hemorrhagic effects of heparin in vitro and in vivo without inhibiting its vasodilatory properties. This ability could help to explain pharmacological effects of etamsylate and proposes its role for reversing pro-hemorrhagic states. Copyright © 2018 Elsevier B.V. All rights reserved.

Testing for tumor promoters in Euphorbia lathyris: Analysis of possible health hazards

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bissell, M.J.; Nemethy, E.K.; Riddle, L.

1981-12-01

A sensitive test system for the detection of unknown tumor promoters is reported. A description is given of the use of the system in detecting promoter activity in Euphorbia lathyris extracts before and after treatment with organic solvents in the preparation of synthetic fuels. Using both normal and ts-virus infected cells, tumor promoter-like activities were detected and identified as ingenol esters in the active fraction of the latex of E. lathyris. These activities were shown to be inactive after extraction of potential sources of fuel. Results indicate that there should be no toxicological dangers after mechanical harvesting and drying. Thismore » finding has much potential significance, both for the further processing of E. lathyris and for other possible sources of energy. (JMT)« less

Synthesis and biological evaluation of some novel substituted 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxamides

NASA Astrophysics Data System (ADS)

Jaismy Jacob, P.; Thomas, Anoop; Venkataraman, S.; Hareeshbabu, E.; Manju, S. L.

2017-11-01

A novel class of substituted 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxamide has been synthesized by simple, modified Hantzsch condensation reaction using N-arylacetoacetamides, aryl aldehydes and ammonia. Characterisation of the newly synthesized compounds was carried out by spectral analysis (IR, 1H NMR and Mass Spectroscopy). Antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans and antiulcer activity by aspirin induced and pyloric ligation ulcer model was studied. Results revealed that most of the compounds exhibit significant antimicrobial activity along with antiulcer activity. The compound 6i 4-dimethylamino phenyl group at 4th position of 1,4-dihydropyridine had shown 65% ulcer protection at 10 mg/kg administration in male albino rats.

Forecasting the zeolite-containing catalyst activity in catalytic cracking technology taking into account the feedstock composition

NASA Astrophysics Data System (ADS)

Ivashkina, Elena; Nazarova, Galina; Shafran, Tatyana; Stebeneva, Valeriya

2017-08-01

The effect of the feedstock composition and the process conditions on the current catalyst activity in catalytic cracking technology using a mathematical model is performed in this research. The mathematical model takes into account the catalyst deactivation by coke for primary and secondary cracking reactions. The investigation results have shown that the feedstock has significant effect on the yield and the content of coke on the catalyst. Thus, the relative catalyst activity is significantly reduced by 7.5-10.7 %. With increasing the catalytic cracking temperature due to the catalyst flow temperature rising, the coke content and the yield per feedstock increase and the catalyst activity decreases by 5.3-7.7%. Rising the process temperature together with the catalyst circulation ratio contributes to increase of the coke yield per feedstock in the catalytic cracking and decrease of the coke content on the catalyst. It is connected with the catalyst flow rising to the riser and the contact time decreasing in the reaction zone. Also, the catalyst activity decreases in the range of 3.8-5.5% relatively to the regenerated catalyst activity (83 %).

Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo

NASA Astrophysics Data System (ADS)

Deng, Yan; Wang, Wei; Yu, Pingfeng; Xi, Zhijiang; Xu, Lijian; Li, Xiaolong; He, Nongyue

2013-04-01

The purpose of this study is to determine if amino acid neurotransmitters such as gamma-aminobutyric acid (GABA), taurine, glutamate (Glu), and aspartate (Asp) can scavenge activated carbonyl toxicants. In vitro, direct reaction between malondialdehyde (MDA) and amino acids was researched using different analytical methods. The results indicated that scavenging activated carbonyl function of taurine and GABA is very strong and that of Glu and Asp is very weak in pathophysiological situations. The results provided perspective into the reaction mechanism of taurine and GABA as targets of activated carbonyl such as MDA in protecting nerve terminals. In vivo, we studied the effect of taurine and GABA as antioxidants by detecting MDA concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. It was shown that MDA concentration was decreased significantly, and the activities of SOD and GSH-Px were increased significantly in the cerebral cortex and hippocampus of acute epileptic state rats, after the administration of taurine and GABA. The results indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against activated carbonyl in vivo and in vitro.

Characterization of putative class II bacteriocins identified from a non-bacteriocin-producing strain Lactobacillus casei ATCC 334.

PubMed

Kuo, Yang-Cheng; Liu, Cheng-Feng; Lin, Jhao-Fen; Li, An-Chieh; Lo, Ta-Chun; Lin, Thy-Hou

2013-01-01

Several putative class II bacteriocin-like genes were identified in Lactobacillus casei ATCC 334, all of which might encode peptides with a double-glycine leader. Six peptides encoded by these genes were heterologously expressed in Escherichia coli and then partially purified in order to test their bacteriocin activity. The results revealed that the mature LSEI_2163 peptide was a class IId bacteriocin that exhibited antimicrobial activity against some lactobacilli and several Listeria species. Similarly, mature LSEI_2386 was a putative pheromone peptide that also had significant bacteriocin activity against several Listeria species. The activities of both peptides tolerated 121°C for 30 min but not treatment with proteinase K or trypsin. The two Cys residues located at positions 4 and 24 in the mature LSEI_2163 peptide were shown by mass spectrometry to form a disulfide bridge, which was required for optimal antibacterial activity. However, replacement of one or both Cys with Ser would cause significant reduction of the antibacterial activity, the reduction being greater when only one of the Cys residues (C4S) was replaced than when both (C4S/C24S) were replaced.

Activation of silenced cytokine gene promoters by the synergistic effect of TBP-TALE and VP64-TALE activators.

PubMed

Anthony, Kim; More, Abhijit; Zhang, Xiaoliu

2014-01-01

Recent work has shown that the combinatorial use of multiple TALE activators can selectively activate certain cellular genes in inaccessible chromatin regions. In this study, we aimed to interrogate the activation potential of TALEs upon transcriptionally silenced immune genes in the context of non-immune cells. We designed a unique strategy, in which a single TALE fused to the TATA-box binding protein (TBP-TALE) is coupled with multiple VP64-TALE activators. We found that our strategy is significantly more potent than multiple TALE activators alone in activating expression of IL-2 and GM-CSF in diverse cell origins in which both genes are otherwise completely silenced. Chromatin analysis revealed that the gene activation was due in part to displacement of a distinctly positioned nucleosome. These studies provide a novel epigenetic mechanism for artificial gene induction and have important implications for targeted cancer immunotherapy, DNA vaccine development, as well as rational design of TALE activators.

Activation of Silenced Cytokine Gene Promoters by the Synergistic Effect of TBP-TALE and VP64-TALE Activators

PubMed Central

Anthony, Kim; More, Abhijit; Zhang, Xiaoliu

2014-01-01

Recent work has shown that the combinatorial use of multiple TALE activators can selectively activate certain cellular genes in inaccessible chromatin regions. In this study, we aimed to interrogate the activation potential of TALEs upon transcriptionally silenced immune genes in the context of non-immune cells. We designed a unique strategy, in which a single TALE fused to the TATA-box binding protein (TBP-TALE) is coupled with multiple VP64-TALE activators. We found that our strategy is significantly more potent than multiple TALE activators alone in activating expression of IL-2 and GM-CSF in diverse cell origins in which both genes are otherwise completely silenced. Chromatin analysis revealed that the gene activation was due in part to displacement of a distinctly positioned nucleosome. These studies provide a novel epigenetic mechanism for artificial gene induction and have important implications for targeted cancer immunotherapy, DNA vaccine development, as well as rational design of TALE activators. PMID:24755922

Research and Teaching: Instructor Use of Group Active Learning in an Introductory Biology Sequence

ERIC Educational Resources Information Center

Auerbach, Anna Jo; Schussler, Elisabeth E.

2016-01-01

Active learning (or learner-centered) pedagogies have been shown to enhance student learning in introductory biology courses. Student collaboration has also been shown to enhance student learning and may be a critical part of effective active learning practices. This study focused on documenting the use of individual active learning and group…

MMP-mediated collagen breakdown induced by activated protein C in equine cartilage is reduced by corticosteroids.

PubMed

Garvican, Elaine R; Vaughan-Thomas, Anne; Redmond, Colette; Gabriel, Natalie; Clegg, Peter D

2010-03-01

The plasma serine protease activated protein C (APC) is synthesized by human chondrocytes at sites of pathological cartilage fibrillation. APC levels are increased in osteoarthritis (OA) synovial fluid, and in vitro APC has been shown to synergize with interleukin-1beta (IL-1) to promote degradation from ovine cartilage. A model of equine cartilage degradation was established and used to explore corticosteroid activities. Intraarticular corticosteroids are a commonly prescribed treatment for joint disease, however their role in disease modification remains unclear. APC synergized with IL-1 or tumor necrosis factor-alpha (TNFalpha), promoting significant collagen degradation from equine cartilage explants within 4 days, but did not augment glycoaminoglycan (GAG) release. APC activated pro-matrix metalloproteinases (MMP)-2 but not pro-MMP-9, as assessed by gelatin zymography. APC did not directly activate pro-MMP-13. Dexamethasone, triamcinolone, and methylprednisolone acetate (MPA) were evaluated at concentrations between 10(- 5)M and 10(-10)M. High concentrations significantly increased GAG release from IL-1+APC-treated explants. With the exception of MPA at 10(-10)M, all concentrations of corticosteroids caused significant decreases in IL-1+APC-driven hydroxyproline loss. Treatment with corticosteroids suppressed expression of MMP-1, -3, and -13 mRNA. The collagenolysis associated with IL-1+APC synergy, and the inhibition of this effect by corticosteroids may involve gelatinase activation and downregulation of MMP expression, respectively.

Task Dependence, Tissue Specificity, and Spatial Distribution of Widespread Activations in Large Single-Subject Functional MRI Datasets at 7T

PubMed Central

Gonzalez-Castillo, Javier; Hoy, Colin W.; Handwerker, Daniel A.; Roopchansingh, Vinai; Inati, Souheil J.; Saad, Ziad S.; Cox, Robert W.; Bandettini, Peter A.

2015-01-01

It was recently shown that when large amounts of task-based blood oxygen level–dependent (BOLD) data are combined to increase contrast- and temporal signal-to-noise ratios, the majority of the brain shows significant hemodynamic responses time-locked with the experimental paradigm. Here, we investigate the biological significance of such widespread activations. First, the relationship between activation extent and task demands was investigated by varying cognitive load across participants. Second, the tissue specificity of responses was probed using the better BOLD signal localization capabilities of a 7T scanner. Finally, the spatial distribution of 3 primary response types—namely positively sustained (pSUS), negatively sustained (nSUS), and transient—was evaluated using a newly defined voxel-wise waveshape index that permits separation of responses based on their temporal signature. About 86% of gray matter (GM) became significantly active when all data entered the analysis for the most complex task. Activation extent scaled with task load and largely followed the GM contour. The most common response type was nSUS BOLD, irrespective of the task. Our results suggest that widespread activations associated with extremely large single-subject functional magnetic resonance imaging datasets can provide valuable information about the functional organization of the brain that goes undetected in smaller sample sizes. PMID:25405938

Alkaline phosphatase activity in human colostrum as a valuable predictive biomarker for lactational mastitis in nursing mothers.

PubMed

Bjelakovic, Ljiljana; Kocic, Gordana; Bjelakovic, Bojko; Zivkovic, Nikola; Stojanović, Dusica; Sokolovic, Danka; Mladenovic-Ciric, Ivana; Sokolovic, Dusan

2012-08-01

Biochemical investigations have shown that an indigenous milk enzyme - alkaline phosphatase (ALP) - which is detectable in the lactocytes, plays a very important diagnostic role in clinical medicine, since its activity varies in different tissues and serves as a specific indicator of disease states. The purpose of this study was to evaluate ALP activity in human colostrum as a possible early predictive biomarker for lactational mastitis in nursing mothers. During a period from May to July 2010, a total of 60 healthy nursing mothers were recruited for this study. The mean level of colostrum ALP activity from the affected breasts was significantly higher when compared with ALP activity from the contralateral asymptomatic as well as 'healthy' breasts (p < 0.01). Determining ALP activity in colostrum could be a valuable biochemical marker for an early prediction of mastitis in nursing mothers.

Immunomodulatory activity of purified arabinoxylans from finger millet (Eleusine coracana, v. Indaf 15) bran.

PubMed

Savitha Prashanth, M R; Shruthi, R R; Muralikrishna, G

2015-09-01

Biological activities of alkali extracted (Barium hydroxide: BE-480 kDa, Potassium hydroxide: KE1-1080 and KE2-40 kDa), purified arabinoxylans (AX) from the finger millet bran varying in their molecular weight, phenolic acid content, arabinose to xylose ratios were evaluated for their immune-stimulatory activities using murine lymphocytes and peritoneal exudate macrophages. All three purified AX displayed significant (p < 0.001) mitogenic activity and activation of macrophages including phagocytosis. Among these BE has shown higher enhancing lymphocyte proliferation (>2 fold) and macrophage phagocytosis than KE1 and KE2. The above results clearly documented that the immunostimulatory activity of arabinoxylans is directly proportional to the amount of ferulic acid content (0.11 mg/100 g), whereas molecular weight as well as arabinose/xylose ratio, did not have any bearing. Purified AX from the finger millet bran can be explored as a potent natural immunomodulator.

Emerging pharmaceutical therapies for COPD.

PubMed

Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

2017-01-01

COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ) agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising.

Characterization of taurine as inhibitor of sodium glucose transporter.

PubMed

Kim, Ha Won; Lee, Alexander John; You, Seungkwon; Park, Taesun; Lee, Dong Hee

2006-01-01

The most characterized roles of taurine include osmoregulator and membrane-stabilizing activities. However, much remains to be understood about its role in human physiology concerning its anti-hyperglycemic effect. Studies indicate that taurine-supplemented diet helps alleviate hyperglycemia or insulin resistance. This hypoglycemic effect has been postulated as taurine helping to increase the excretion of cholesterol. Alternatively, this study investigated the effect of taurine on glucose transporter using heterologous expression of sodium-glucose transporter-1 (SGLT-1). SGLT-1 was expressed in Xenopus oocytes and the effect of taurine on the expressed SGLT-1 was analyzed utilizing 2-deoxy-D-glucose (2-DOG) uptake and voltage clamp studies. In the oocytes expressing SGLT-1, taurine was shown to inhibit SGLT-1 activity compared to the non-treated controls in a dose-dependent manner. In the presence of taurine, the glucose uptake was greatly inhibited and the glucose-generated current was significantly inhibited. Synthetic taurine analogs were also shown to be effective in inhibiting SGLT-1 activity in a manner comparable to taurine. These effects might offer a promising opportunity in designing functional foods with anti-hyperglycemic potential by supplementing taurine and its analogs to the diet.

Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling

PubMed Central

Yuen, Hiu-Fung; Chan, Ka-Kui; Platt-Higgins, Angela; Dakir, El-Habib; Matchett, Kyle B.; Haggag, Yusuf Ahmed; Jithesh, Puthen V.; Habib, Tanwir; Faheem, Ahmed; Dean, Fennell A.; Morgan, Richard; Rudland, Philip S.; El-Tanani, Mohamed

2016-01-01

It has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival. Here, we show that knockdown of Ran leads to a reduction of Met receptor expression in several breast and lung cancer cell lines. This, in turn suppressed HGF expression and the Met-mediated activation of the Akt pathway, as well as cell adhesion, migration, and invasion. In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. We further demonstrate that Met reduction-mediated by knockdown of Ran, occurs at the post-transcriptional level, probably via a matrix metalloproteinase. Moreover, the level of immunoreactive Ran and Met are positively associated in human breast cancer specimens, suggesting that a high level of Ran may be a pre-requisite for Met overexpression. Interestingly, a high level of immunoreactive Ran dictates the prognostic significance of Met, indicating that the co-overexpression of Met and Ran may be associated with cancer progression and could be used in combination as a prognostic indicator. PMID:27716616

Research Thinking Development by Teaching Archaeoastronomy

NASA Astrophysics Data System (ADS)

Muglova, P. V.; Stoev, A. D.

2006-08-01

A model of research thinking development by teaching archaeoastronomy in specialized three-year extra-curriculum Astronomy programme and creation of favourable socio-educational surroundings is suggested. It is shown as a didactic system of conditions, influences and possibilities of answering specific hierarchic complex of personal needs in the 14 - 18 year age interval. Transformation of these needs in worldly values secures an active position of the students in the educational process and determines their personality development. It is also shown that the Archaeoastronomy School, as an educational environment, executes specific work of students' teaching, upbringing and progress as well as their inclusion in the real process of scientific research. Thus, they have the possibility of generating scientific ideas and obtaining results in the science archaeoastronomy. In consequence of this, their activity acquires social significance. Usages of this model of scientific school in the extra-curriculum Astronomy education reproduces norms and traditions of the real scientific research and directly relay subject content, cultural norms and values of archaeoastronomy in the educative process. Students' participation in archaeoastronomical expeditions, their competent work during the research of concrete archaeoastronomical objects create an investigation style of thinking and steady habits of scientific activity.

Emerging pharmaceutical therapies for COPD

PubMed Central

Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

2017-01-01

COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ) agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising. PMID:28790817

Maximization of beta-galactosidase production: a simultaneous investigation of agitation and aeration effects.

PubMed

Alves, Fernanda Germano; Filho, Francisco Maugeri; de Medeiros Burkert, Janaína Fernandes; Kalil, Susana Juliano

2010-03-01

In this work, the agitation and aeration effects in the maximization of the beta-galactosidase production from Kluyveromyces marxianus CCT 7082 were investigated simultaneously, in relation to the volumetric enzyme activity and the productivity, as well as the analysis of the lactose consumption and production of glucose, and galactose of this process. Agitation and aeration effects were studied in a 2 L batch stirred reactor. A central composite design (2(2) trials plus three central points) was carried out. Agitation speed varied from 200 to 500 rpm and aeration rate from 0.5 to 1.5 vvm. It has been shown in this study that the volumetric enzyme production was strongly influenced by mixing conditions, while aeration was shown to be less significant. Linear models for activity and productivity due to agitation and aeration were obtained. The favorable condition was 500 rpm and 1.5 vvm, which lead to the best production of 17 U mL(-1) for enzymatic activity, 1.2 U mL(-1) h(-1) for productivity in 14 h of process, a cellular concentration of 11 mg mL(-1), and a 167.2 h(-1) volumetric oxygen transfer coefficient.

Influence of Deformation Mechanisms on the Mechanical Behavior of Metals and Alloys: Experiments, Constitutive Modeling, and Validation

NASA Astrophysics Data System (ADS)

Gray, G. T.; Cerreta, E.; Chen, Shuh Rong; Maudlin, P. J.

2004-06-01

Jim Williams has made seminal contributions to the field of structure / property relations and its controlling effects on the mechanical behavior of metals and alloys. This talk will discuss experimental results illustrating the role of interstitial content, grain size, texture, temperature, and strain rate on the operative deformation mechanisms, mechanical behavior, and substructure evolution in titanium, zirconium, hafnium, and rhenium. Increasing grain size is shown to significantly decrease the dynamic flow strength of Ti and Zr while increasing work-hardening rates due to an increased incidence of deformation twinning. Increasing oxygen interstitial content is shown to significantly alter both the constitutive response and α-ω shock-induced phase transition in Zr. The influence of crystallographic texture on the mechanical behavior in Ti, Zr, and Hf is discussed in terms of slip system and deformation twinning activity. An example of the utility of incorporation of operative deformation mechanisms into a polycrystalline plasticity constitutive model and validation using Taylor cylinder impact testing is presented.

Creating a Critical Thinker

ERIC Educational Resources Information Center

Piergiovanni, Polly R.

2014-01-01

A college education is expected to improve students' critical thinking skills. Keeping students active in class--through writing activities and class discussion--has been shown to help students think critically. In this article, creative hands-on activities, which are common in engineering courses, are shown to improve students' critical thinking…

Orexin-A increases the firing activity of hippocampal CA1 neurons through orexin-1 receptors.

PubMed

Chen, Xin-Yi; Chen, Lei; Du, Yi-Feng

2017-07-01

Orexins including two peptides, orexin-A and orexin-B, are produced in the posterior lateral hypothalamus. Much evidence has indicated that central orexinergic systems play numerous functions including energy metabolism, feeding behavior, sleep/wakefulness, and neuroendocrine and sympathetic activation. Morphological studies have shown that the hippocampal CA1 regions receive orexinergic innervation originating from the hypothalamus. Positive orexin-1 (OX 1 ) receptors are detected in the CA1 regions. Previous behavioral studies have shown that microinjection of OX 1 receptor antagonist into the hippocampus impairs acquisition and consolidation of spatial memory. However, up to now, little has been known about the direct electrophysiological effects of orexin-A on hippocampal CA1 neurons. Employing multibarrel single-unit extracellular recordings, the present study showed that micropressure administration of orexin-A significantly increased the spontaneous firing rate from 2.96 ± 0.85 to 8.45 ± 1.86 Hz (P < 0.001) in 15 out of the 23 hippocampal CA1 neurons in male rats. Furthermore, application of the specific OX 1 receptor antagonist SB-334867 alone significantly decreased the firing rate from 4.02 ± 1.08 to 2.11 ± 0.58 Hz in 7 out of the 17 neurons (P < 0.05), suggesting that endogenous orexinergic systems modulate the firing activity of CA1 neurons. Coapplication of SB-334867 completely blocked orexin-A-induced excitation of hippocampal CA1 neurons. The PLC pathway may be involved in activation of OX 1 receptor-induced excitation of CA1 neurons. Taken together, the present study's results suggest that orexin-A produces excitatory effects on hippocampal neurons via OX 1 receptors. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Interactive effects of sex hormones and gender stereotypes on cognitive sex differences--a psychobiosocial approach.

PubMed

Hausmann, Markus; Schoofs, Daniela; Rosenthal, Harriet E S; Jordan, Kirsten

2009-04-01

Biological and social factors have been shown to affect cognitive sex differences. For example, several studies have found that sex hormones have activating effects on sex-sensitive tasks. On the other hand, it has been shown that gender stereotypes can influence the cognitive performance of (gender-) stereotyped individuals. However, few studies have investigated the combined effects of both factors. The present study investigated the interaction between sex hormones and gender stereotypes within a psychobiosocial approach. One hundred and fourteen participants (59 women) performed a battery of sex-sensitive cognitive tasks, including mental rotation, verbal fluency, and perceptual speed. Saliva samples were taken immediately after cognitive testing. Levels of testosterone (T) were analysed using chemiluminescence immunoassay (LIA). To activate gender stereotypes, a questionnaire was applied to the experimental group that referred to the cognitive tasks used. The control group received an identical questionnaire but with a gender-neutral content. As expected, significant sex differences favouring males and females appeared for mental rotation and verbal fluency tasks, respectively. The results revealed no sex difference in perceptual speed. The male superiority in the Revised Vandenberg and Kuse Mental Rotations Tests (MRT-3D) was mainly driven by the stereotype-active group. No significant sex difference in MRT-3D appeared in the control group. The MRT-3D was also the task in which a strong gender-stereotype favouring males was present for both males and females. Interestingly, T levels of the stereotype-activated group were 60% higher than that of male controls. The results suggest that sex hormones mediate the effects of gender stereotypes on specific cognitive abilities.

Estrogen Receptor-β Agonist Diarylpropionitrile: Biological Activities of R- and S-Enantiomers on Behavior and Hormonal Response to Stress

PubMed Central

Weiser, Michael J.; Wu, T. John; Handa, Robert J.

2009-01-01

Estrogens have been shown to have positive and negative effects on anxiety and depressive-like behaviors, perhaps explained by the existence of two distinct estrogen receptor (ER) systems, ERα and ERβ. The ERβ agonist, diarylpropionitrile (DPN) has been shown to have anxiolytic properties in rats. DPN exists as a racemic mixture of two enantiomers, R-DPN and S-DPN. In this study, we compared R-DPN and S-DPN for their in vitro binding affinity, ability to activate transcription in vitro at an estrogen response element, and in vivo endocrine and behavioral responses. In vitro binding studies using recombinant rat ERβ revealed that S-DPN has a severalfold greater relative binding affinity for ERβ than does R-DPN. Furthermore, cotransfection of N-38 immortalized hypothalamic cells with an estrogen response element-luc reporter and ERβ revealed that S-DPN is a potent activator of transcription in vitro, whereas R-DPN is not. Subsequently, we examined anxiety-like behaviors using the open-field test and elevated plus maze or depressive-like behaviors, using the forced swim test. Ovariectomized young adult female Sprague Dawley rats treated with racemic DPN, S-DPN, and the ERβ agonist, WAY-200070, showed significantly decreased anxiety-like behaviors in both the open-field and elevated plus maze and significantly less depressive-like behaviors in the forced swim test compared with vehicle-, R-DPN-, or propylpyrazoletriol (ERα agonist)-treated animals. In concordance with the relative binding affinity and transcriptional potency, these results demonstrate that the S-enantiomer is the biologically active form of DPN. These studies also indicate that estrogen's positive effects on mood, including its anxiolytic and antidepressive actions, are due to its actions at ERβ. PMID:19074580

A Novel Gene, OZONE-RESPONSIVE APOPLASTIC PROTEIN1, Enhances Cell Death in Ozone Stress in Rice1

PubMed Central

Ueda, Yoshiaki; Siddique, Shahid; Frei, Michael

2015-01-01

A novel protein, OZONE-RESPONSIVE APOPLASTIC PROTEIN1 (OsORAP1), was characterized, which was previously suggested as a candidate gene underlying OzT9, a quantitative trait locus for ozone stress tolerance in rice (Oryza sativa). The sequence of OsORAP1 was similar to that of ASCORBATE OXIDASE (AO) proteins. It was localized in the apoplast, as shown by transient expression of an OsORAP1/green fluorescent protein fusion construct in Nicotiana benthamiana leaf epidermal and mesophyll cells, but did not possess AO activity, as shown by heterologous expression of OsORAP1 in Arabidopsis (Arabidopsis thaliana) mutants with reduced background AO activity. A knockout rice line of OsORAP1 showed enhanced tolerance to ozone stress (120 nL L−1 average daytime concentration, 20 d), as demonstrated by less formation of leaf visible symptoms (i.e. cell death), less lipid peroxidation, and lower NADPH oxidase activity, indicating reduced active production of reactive oxygen species. In contrast, the effect of ozone on chlorophyll content was not significantly different among the lines. These observations suggested that OsORAP1 specifically induced cell death in ozone stress. Significantly enhanced expression of jasmonic acid-responsive genes in the knockout line implied the involvement of the jasmonic acid pathway in symptom mitigation. Sequence analysis revealed extensive polymorphisms in the promoter region of OsORAP1 between the ozone-susceptible cv Nipponbare and the ozone-tolerant cv Kasalath, the OzT9 donor variety, which could be responsible for the differential regulation of OsORAP1 reported earlier. These pieces of evidence suggested that OsORAP1 enhanced cell death in ozone stress, and its expression levels could explain the effect of a previously reported quantitative trait locus. PMID:26220952

In vitro and ex vivo distribution of [3H]harmane, an endogenous beta-carboline, in rat brain.

PubMed

Anderson, Neil J; Tyacke, Robin J; Husbands, Stephen M; Nutt, David J; Hudson, Alan L; Robinson, Emma S J

2006-03-01

The endogenous beta-carboline, harmane, has been shown to bind to monoamine oxidase A (MAO-A) and a separate, high affinity, non-MAO site. Research in our laboratory has shown that harmane is an active component of clonidine-displacing substance (CDS), the proposed endogenous ligand for imidazoline binding sites (IBS). In the present study we have investigated the distribution of [3H]harmane in rat brain, and related the binding profile to the distribution of the MAO-A selective ligand [3H]Ro41-1049 and the I2BS ligand [3H]2-BFI. The in vivo distribution of [3H]harmane following intravenous administration was also investigated. Receptor autoradiography revealed a highly significant correlation for the distribution of [3H]harmane and [3H]Ro41-1049, and a significant correlation for [3H]harmane and the I2BS ligand [3H]2-BFI. The in vivo distribution of [3H]harmane suggests that the ligand accumulates in the adrenal gland and throughout the brain with the primary route of excretion occurring via the duodenum. In conclusion, these studies have shown that [3H]harmane labels a population of binding sites that reflect the distribution of MAO-A. Further evidence for a non-MAO, IBS [3H]harmane population has not been shown but the high level of expression of the MAO-A site is likely to have masked the much smaller population of I2BS.

Fatty acid synthase inhibition activates AMP-activated protein kinase in SKOV3 human ovarian cancer cells.

PubMed

Zhou, Weibo; Han, Wan Fang; Landree, Leslie E; Thupari, Jagan N; Pinn, Michael L; Bililign, Tsion; Kim, Eun Kyoung; Vadlamudi, Aravinda; Medghalchi, Susan M; El Meskini, Rajaa; Ronnett, Gabriele V; Townsend, Craig A; Kuhajda, Francis P

2007-04-01

Fatty acid synthase (FAS), the enzyme responsible for the de novo synthesis of fatty acids, is highly expressed in ovarian cancers and most common human carcinomas. Inhibition of FAS and activation of AMP-activated protein kinase (AMPK) have been shown to be cytotoxic to human cancer cells in vitro and in vivo. In this report, we explore the cytotoxic mechanism of action of FAS inhibition and show that C93, a synthetic FAS inhibitor, increases the AMP/ATP ratio, activating AMPK in SKOV3 human ovarian cancer cells, which leads to cytotoxicity. As a physiologic consequence of AMPK activation, acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis, was phosphorylated and inhibited whereas glucose oxidation was increased. Despite these attempts to conserve energy, the AMP/ATP ratio increased with worsening cellular redox status. Pretreatment of SKOV3 cells with compound C, an AMPK inhibitor, substantially rescued the cells from C93 cytotoxicity, indicating its dependence on AMPK activation. 5-(Tetradecyloxy)-2-furoic acid, an ACC inhibitor, did not activate AMPK despite inhibiting fatty acid synthesis pathway activity and was not significantly cytotoxic to SKOV3 cells. This indicates that substrate accumulation from FAS inhibition triggering AMPK activation, not end-product depletion of fatty acids, is likely responsible for AMPK activation. C93 also exhibited significant antitumor activity and apoptosis against SKOV3 xenografts in athymic mice without significant weight loss or cytotoxicity to proliferating cellular compartments such as bone marrow, gastrointestinal tract, or skin. Thus, pharmacologic FAS inhibition selectively activates AMPK in ovarian cancer cells, inducing cytotoxicity while sparing most normal human tissues from the pleiotropic effects of AMPK activation.

Screening of Bauhinia purpurea Linn. for analgesic and anti-inflammatory activities

PubMed Central

Shreedhara, C.S.; Vaidya, V.P.; Vagdevi, H.M.; Latha, K.P.; Muralikrishna, K.S.; Krupanidhi, A.M.

2009-01-01

Objectives: Ethanol extract of the stem of Bauhinia purpurea Linn. was subjected to analgesic and anti-inflammatory activities in animal models. Materials and Methods: Albino Wistar rats and mice were the experimental animals respectively. Different CNS depressant paradigms like analgesic activity (determined by Eddy's hot plate method and acetic acid writhing method) and anti-inflammatory activity determined by carrageenan induced paw edema using plethysmometer in albino rats) were carried out, following the intra-peritoneal administration of ethanol extract of Bauhinia purpurea Linn. (BP) at the dose level of 50 mg/kg and 100 mg/kg. Results: The analgesic and anti-inflammatory activities of ethanol extracts of BP were significant (P < 0.001). The maximum analgesic effect was observed at 120 min at the dose of 100 mg/kg (i.p.) and was comparable to that of standard analgin (150 mg/kg) and the percentage of edema inhibition effect was 46.4% and 77% for 50 mg/kg and 100 mg/kg (i.p) respectively. Anti-inflammatory activity was compared with standard Diclofenac sodium (5 mg/kg). Conclusion: Ethanol extract of Bauhinia purpurea has shown significant analgesic and anti-inflammatory activities at the dose of 100 mg/kg and was comparable with corresponding standard drugs. The activity was attributed to the presence of phytoconstituents in the tested extract. PMID:20336222

Caloric vestibular stimulation and postural control in patients with spatial neglect following stroke.

PubMed

Sturt, Ruth; Punt, T David

2013-01-01

The impact of spatial neglect remains a substantial challenge to patients undergoing rehabilitation following stroke. Beyond the relatively well-described implications for visuospatial function, neglect is increasingly shown to have a negative impact on the wider aspects of sensori-motor performance with corresponding implications for activities including gait and balance. Caloric vestibular stimulation (CVS) administered to the contralesional ear has previously been shown to improve performance in patients with spatial neglect. Here, in Experiment One, we investigated the effect of CVS on clinical measures of spatial neglect and postural control in three groups of patients following stroke; left brain damaged patients (LBD, n = 6), right brain damaged patients without neglect (RBD-, n = 6), and right brain damaged patients with neglect (RBD+ , n = 6). While post-stimulation scores demonstrated an improvement for participants with spatial neglect, further analysis of postural scores indicated that improvement was selective for asymmetrical activities, with symmetrical activities remaining unchanged. We interpret these results with reference to the related problem of extinction which predicts that activities demanding synchronous bilateral activity (symmetrical activities) would cause greater difficulties for patients with neglect. In Experiment Two, we tested a further six RBD+ patients on the same measures following CVS to the ipsilesional (right) ear. There was no significant improvement in perceptual or postural scores. Our findings are supportive of previous studies that demonstrate improvement in perception and movement for patients with spatial neglect following contralesional CVS and suggest that these improvements may have clinical benefits.

PEMFC catalyst layers: the role of micropores and mesopores on water sorption and fuel cell activity.

PubMed

Soboleva, Tatyana; Malek, Kourosh; Xie, Zhong; Navessin, Titichai; Holdcroft, Steven

2011-06-01

The effects of carbon microstructure and ionomer loading on water vapor sorption and retention in catalyst layers (CLs) of PEM fuel cells are investigated using dynamic vapor sorption. Catalyst layers based on Ketjen Black and Vulcan XC-72 carbon blacks, which possess distinctly different surface areas, pore volumes, and microporosities, are studied. It is found that pores <20 nm diameter facilitate water uptake by capillary condensation in the intermediate range of relative humidities. A broad pore size distribution (PSD) is found to enhance water retention in Ketjen Black-based CLs whereas the narrower mesoporous PSD of Vulcan CLs is shown to have an enhanced water repelling action. Water vapor sorption and retention properties of CLs are correlated to electrochemical properties and fuel cell performance. Water sorption enhances electrochemical properties such as the electrochemically active surface area (ESA), double layer capacitance and proton conductivity, particularly when the ionomer content is very low. The hydrophilic properties of a CL on the anode and the cathode are adjusted by choosing the PSD of carbon and the ionomer content. It is shown that a reduction of ionomer content on either cathode or anode of an MEA does not necessarily have a significant detrimental effect on the MEA performance compared to the standard 30 wt % ionomer MEA. Under operation in air and high relative humidity, a cathode with a narrow pore size distribution and low ionomer content is shown to be beneficial due to its low water retention properties. In dry operating conditions, adequate ionomer content on the cathode is crucial, whereas it can be reduced on the anode without a significant impact on fuel cell performance. © 2011 American Chemical Society

Salivary cortisol and alpha-amylase levels during an assessment procedure correlate differently with risk-taking measures in male and female police recruits

PubMed Central

van den Bos, Ruud; Taris, Ruben; Scheppink, Bianca; de Haan, Lydia; Verster, Joris C.

2013-01-01

Recent laboratory studies have shown that men display more risk-taking behavior in decision-making tasks following stress, whilst women are more risk-aversive or become more task-focused. In addition, these studies have shown that sex differences are related to levels of the stress hormone cortisol (indicative of activation of the hypothalamus-pituitary-adrenocortical-axis): the higher the levels of cortisol the more risk-taking behavior is shown by men, whereas women generally display more risk-aversive or task-focused behavior following higher levels of cortisol. Here, we assessed whether such relationships hold outside the laboratory, correlating levels of cortisol obtained during a job-related assessment procedure with decision-making parameters in the Cambridge Gambling Task (CGT) in male and female police recruits. The CGT allows for discriminating different aspects of reward-based decision-making. In addition, we correlated levels of alpha-amylase [indicative of activation of the sympatho-adrenomedullary-axis (SAM)] and decision-making parameters. In line with earlier studies men and women only differed in risk-adjustment in the CGT. Salivary cortisol levels correlated positively and strongly with risk-taking measures in men, which was significantly different from the weak negative correlation in women. In contrast, and less strongly so, salivary alpha-amylase levels correlated positively with risk-taking in women, which was significantly different from the weak negative correlation with risk-taking in men. Collectively, these data support and extend data of earlier studies indicating that risky decision-making in men and women is differently affected by stress hormones. The data are briefly discussed in relation to the effects of stress on gambling. PMID:24474909

On the comparability of knowledge transfer activities - a case study at the German Baltic Sea Coast focusing regional climate services

NASA Astrophysics Data System (ADS)

Meinke, Insa

2017-06-01

In this article the comparability of knowledge transfer activities is discussed by accounting for external impacts. It is shown that factors which are neither part of the knowledge transfer activity nor part of the participating institution may have significant impact on the potential usefulness of knowledge transfer activities. Differences in the potential usefulness are leading to different initial conditions of the knowledge transfer activities. This needs to be taken into account when comparing different knowledge transfer activities, e.g., in program evaluations. This study is focusing on regional climate services at the German Baltic Sea coast. It is based on two surveys and experiences with two identical web tools applied on two regions with different spatial coverage. The results show that comparability among science based knowledge transfer activities is strongly limited through several external impacts. The potential usefulness and thus the initial condition of a particular knowledge transfer activity strongly depends on (1) the perceived priority of the focused topic, (2) the used information channels, (3) the conformity between the research agenda of service providing institutions and information demands in the public, as well as (4) on the spatial coverage of a service. It is suggested to account for the described external impacts for evaluations of knowledge transfer activities. The results show that the comparability of knowledge transfer activities is limited and challenge the adequacy of quantitative measures in this context. Moreover, as shown in this case study, in particular regional climate services should be individually evaluated on a long term perspective, by potential user groups and/or by its real users. It is further suggested that evaluation criteria should be co-developed with these stakeholder groups.

Control of the immune response by DHEA and its metabolites.

PubMed

Loria, R M; Padgett, D A

1998-06-01

The 17 keto steroid, Dehydroepiandrosterone (5-androsten-3 beta-17-one, DHEA) has been shown to protect mice from a variety of lethal infections. This includes, but is not limited to, infection with viruses (herpesvirus type 2, coxsackievirus B4-CVB4),bacteria (Enterococcus faecalis, Pseudomonas aeruginosa), and a parasite (Cryptosporidium parvum). We have reported that androstenediol (5-androsten-3 beta-17 beta-diol, beta AED), which is derived from DHEA, is at least 100x more effective in up-regulating systemic resistance against CVB4-infection than its precursor. Furthermore, androstenetriol (5-androstene-3 beta-7 beta-17 beta-triol beta AET) which is formed by 7 beta hydroxylation of beta AED, was more effective against CVB4-infection than its precursor beta AED. Neither steroid however has shown any significant direct antiviral effects. The in-vitro influences of DHEA, beta AED, and beta AET on a mitogen-induced mixed splenocyte proliferation assay were determined. The results showed that DHEA suppressed the proliferation of concanavalin A (Con A) or lipopolysaccharide (LPS) activated cultures in a dose dependent manner. beta AED had little influence on the activation response. However, beta AET potentiated the response to both mitogens significantly above control. The regulation of interleukin-2 and interleukin-3 secretion from Con A-activated lymphocytes was analogous to these observations. These functions were suppressed by DHEA, unaffected by beta AED, and potently increased by beta AET. Moreover, the classic immuno-suppressive effects of hydro-cortisone on Con A-induced lymphocyte proliferation, as well as IL-2 and IL-3 production were unaffected by co-cultured with DHEA and only minimally counteracted by beta AED. In contrast, beta AET significantly counteracted the effect of hydrocortisone when co-cultured together. These results show that while in-vivo, DHEA, beta AED, and beta AET each function in a similar manner. In-vitro, their effects are dramatically different from one another with only beta AET potentiating the cellular response by increasing lymphocyte activation and counteracting the immuno-suppressive activity of hydrocortisone.

Comparison of the release of microRNAs and extracellular vesicles from platelets in response to different agonists.

PubMed

Ambrose, Ashley R; Alsahli, Mohammed A; Kurmani, Sameer A; Goodall, Alison H

2018-07-01

On activation platelets release microRNAs and extracellular vesicles (EV) into circulation. The release of EV from platelets has been shown to be dependent on the agonist; in this study, we investigated whether the microRNA profile or EV released from platelets was also agonist specific. Washed platelets from healthy subjects were maximally stimulated with agonists specific for the receptors for collagen (Glycoprotein VI (GPVI)), thrombin (PAR1/PAR4), or ADP (P2Y1/P2Y12) with/without inhibiting secondary mediators, using aspirin to block cyclooxygenase-1 and apyrase to remove ADP. The released microRNAs were profiled using TaqMan microRNA microarray cards. Platelet-derived EV (pdEV) were characterized by size (Nanoparticle Tracking Analysis, NTA), for procoagulant activity (Annexin-V binding and support of thrombin generation), and for the EV markers CD63 and HSP70. Platelet activation triggered the release of 57-79 different microRNAs, dependent upon agonist, with a core of 46 microRNAs observed with all agonists. There was a high level of correlation between agonists (r 2  > 0.98; p < 0.0001 for all), and with the microRNA content of the parent platelets (r 2  > 0.98; p < 0.0001). The 46 microRNAs seen in all samples are predicted to have significant effects on the translation of proteins involved in endocytosis, cell cycle control, and differentiation. MiR-223-3p was the most abundant in all samples and has previously been implicated in myeloid lineage development and demonstrated to have anti-inflammatory effects. Stimulation through GPVI produced a pdEV population with significantly more procoagulant activity than the other agonists. Apyrase significantly reduced microRNA and pdEV release, while aspirin had little effect. These data suggest that all tested agonists trigger the release of a similar microRNA profile while the procoagulant activity of the pdEV was agonist dependent. ADP was shown to play an important role in the release of both microRNAs and pdEV.

The Role of Stromally Produced Cathepsin D in Promoting Prostate Tumorigenesis

DTIC Science & Technology

2014-11-01

was related to TGF-β activity. It has been previously shown in in vitro experiments that CathD can liberate TGF-β from the latency inhibitor complex...was performed fol- lowing a protocol that was described previously [31]. CathepsinDandProstateCancer 3 The Prostate Tissue slides were then incubated... low grade and high grade malignant prostate tissue. P-values less than 0.05 were consid- ered statistically significant. RESULTS

Engineering the formation of secondary building blocks within hollow interiors.

PubMed

Li, Xiaobo; Liu, Xiao; Ma, Yi; Li, Mingrun; Zhao, Jiao; Xin, Hongchuan; Zhang, Lei; Yang, Yan; Li, Can; Yang, Qihua

2012-03-15

Secondary building blocks within the cavities of primary silica-architecture building blocks are successfully engineered. The immobilized surfactant directs the selective dissolution and reassembly of dissolved silicate species for the formation of secondary building blocks (hollow nanospheres/nanorods; see figure). Supported TiO(2) on nanostructures with multilevel interiors is shown to exhibit significantly enhanced activity in photocatalytic H(2) production. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microbial exchange experiment AR-002

NASA Technical Reports Server (NTRS)

Taylor, G. R.; Kropp, K. D.; Henney, M. R.; Ekblad, S. S.; Groves, T. O.; Molina, T. C.; Decelle, J. G.; Carmichael, C. F.; Gehring, N. J.; Young, E. L.

1976-01-01

Operational aspects associated with the experiment and the activities of medically important microorganisms recovered from the Apollo crewmen are evaluated. A variety of potential pathogens was recovered from each of the prime and backup crew members before and after flight. However, no disease events were reported. Candida albicans and Staphylococcus aureus were shown to be transferred from one crewmember to another during the flight. No other medically significant changes in the microbial population were observed.

Effects of Increased Physical Activity on Motor Skills and Marks in Physical Education: An Intervention Study in School Years 1 through 9 in Sweden

ERIC Educational Resources Information Center

Ericsson, Ingegerd

2011-01-01

Background: Studies have shown that some children do not participate in sport or exercise because they did not establish early coordination and basic motor skills while at school. Basic motor skills form significant parts of the goals for students to achieve in the Swedish school subject Physical Education and Health (PEH). Aims: The aim was to…

Research review. Interactions between environmental chemicals and drug biotransformation in man.

PubMed

Alvares, A P

1978-01-01

Many factors influence the metabolism of drugs in man. Besides genetic factors, environmental factors may play a significant role in explaining the variation observed in the rates of drug metabolism between different individuals. Intentional or unintentional exposure to environmental chemicals could enhance or inhibit the activity of hepatic mixed function oxidases that metabolise drugs and other foreign chemicals, as well as endogenous substrates such as steroid hormones. A major source of such exposure may be occupational. Exposure to the heavy metal, lead, has been shown to inhibit drug metabolism; whereas intensive exposure to chlorinated insecticides, and other halogenated hydrocarbons such as polychlorinated biphenyls, has been shown to enhance the metabolism of test drugs such as antipyrine and phenylbutazone. An intentional source of exposure to foreign chemicals is cigarette smoke. Cigarette smoke contains polycyclic hydrocarbons, which are known inducers of hepatic mixed function oxidases. A number of studies have shown that cigarette smoking can alter the pharmacological action and/or the metabolism of some drugs. Pharmacokinetic studies have shown that cigarette smoking decreases the bioavailability of phenacetin and increases dosage requirements of theophylline by enhancing their rate of metabolism. Data, which are not very conclusive, indicate that heavy marijuana use may have an inhibitory effect on metabolism of some drugs and an inducing effect on others such as theophylline. Dietary factors may also play a significant role in the regulation of drug metabolism. Charcoal broiling which introduces polycyclic hydrocarbons into foods has been shown to enhance the metabolism of the test drug, antipyrine, and of such commonly used drugs as phenacetin and theophylline. Such intentional or unintentional exposure to environmental chemicals which may alter the rates of drug metabolism in man indicates the importance of individualisation of drug therapy.

AGN jets under the microscope: A divide? Doctoral Thesis Award Lecture 2011

NASA Astrophysics Data System (ADS)

Karouzos, M.; Britzen, S.; Witzel, A.; Zensus, A. J.; Eckart, A.

2012-06-01

A new paradigm for active galactic jet kinematics has emerged through detailed investigations of BL Lac objects using very long baseline radio interferometry. In this new scheme, most, if not all, jet components appear to remain stationary with respect to the core but show significant non-radial motions. This paper presents results from our kinematic investigation of the jets of a statistically complete sample of radio-loud flat-spectrum active galaxies, focusing on the comparison between the jet kinematic properties of BL Lacs and flat-spectrum radio-quasars. It is shown that there is a statistically significant difference between the kinematics of the two AGN classes, with BL Lacs showing more bent jets, that are wider and show slower movement along the jet axis, compared to flat-spectrum radio-quasars. This is interpreted as evidence for helically structured jets.

Inhibitors of signal peptide peptidase (SPP) affect HSV-1 infectivity in vitro and in vivo

PubMed Central

Allen, Sariah J.; Mott, Kevin R.; Ghiasi, Homayon

2014-01-01

Recently we have shown that the highly conserved herpes simplex virus glycoprotein K (gK) binds to signal peptide peptidase (SPP), also known as minor histocompatibility antigen H13. In this study we have demonstrated for the first time that inhibitors of SPP, such as L685,458, (Z-LL)2 ketone, aspirin, ibuprofen and DAPT, significantly reduced HSV-1 replication in tissue culture. Inhibition of SPP activity via (Z-LL)2 ketone significantly reduced viral transcripts in the nucleus of infected cells. Finally, when administered during primary infection, (Z-LL)2 ketone inhibitor reduced HSV-1 replication in the eyes of ocularly infected mice. Thus, blocking SPP activity may represent a clinically effective and expedient approach to the reduction of viral replication and the resulting pathology. PMID:24768597

Empirically derived pain-patient MMPI subgroups: prediction of treatment outcome.

PubMed

Moore, J E; Armentrout, D P; Parker, J C; Kivlahan, D R

1986-02-01

Fifty-seven male chronic pain patients admitted to an inpatient multimodal pain treatment program at a Midwestern Veterans Administration hospital completed the MMPI, Profile of Mood States (POMS), Tennessee Self-Concept Scale (TSCS), Rathus Assertiveness Schedule (RAS), activity diaries, and an extensive pain questionnaire. All patients were assessed both before and after treatment, and most also were assessed 2-5 months prior to treatment. No significant changes occurred during the baseline period, but significant improvements were evident at posttreatment on most variables: MMPI, POMS, TSCS, RAS, pain severity, sexual functioning, and activity diaries. MMPI subgroup membership, based on a hierarchical cluster analysis in a larger sample, was not predictive of differential treatment outcome. Possible reasons for comparable treatment gains among these subgroups, which previously have been shown to differ on many psychological and behavioral factors, are discussed.

Acute morphine effects on respiratory activity in mice with target deletion of the tachykinin 1 gene (Tac1-/-).

PubMed

Shvarev, Yuri; Berner, Jonas; Bilkei-Gorzo, Andras; Lagercrantz, Hugo; Wickström, Ronny

2010-01-01

Search for physiological mechanisms which could antagonize the opioid-induced respiratory depression is of important clinical value. In this study, we investigated the acute effects of morphine on respiratory activity in genetically modified newborn (P2) mice with target deletion of the (Tac1 -/-) gene lacking substance P (SP) and neurokinin A (NKA). In vivo, as shown with whole-body flow barometric plethysmography technique, morphine induced significantly attenuated minute ventilation during intermittent hypoxia in control animals. In contrast, knockout mice revealed significant increase in minute ventilation. In vitro, in brainstem preparation, knockout mice demonstrated greater changes in burst frequency during intermittent anoxia challenge. The data suggest that hereditary deficiency in tachykinins, SP and NKA results in more robust hypoxic response in newborn Tac1-/- mice during respiratory depression induced by morphine.

Stimulation of erythrocyte death by phloretin.

PubMed

Bissinger, Rosi; Fischer, Salome; Jilani, Kashif; Lang, Florian

2014-01-01

Phloretin, a natural component of apples, pears and strawberries, has previously been shown to stimulate apoptosis of nucleated cells. Erythrocytes may similarly enter suicidal death or eryptosis, which is characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)]i), ceramide, ATP depletion, and activation of protein kinase C (PKC) as well as p38 mitogen activated protein kinase (p38 kinase). Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca(2+)]i from Fluo3-fluorescence, and ceramide abundance from binding of specific antibodies. A 48 h exposure of human erythrocytes to phloretin significantly increased the percentage of annexin-V-binding cells (≥100 µM) without significantly influencing forward scatter. Phloretin did not significantly modify [Ca(2+)]i and the stimulation of annexin-V-binding by phloretin (300 µM) did not require presence of extracellular Ca(2+). Phloretin did not significantly modify erythrocyte ATP levels, and the effect of phloretin on annexin-V-binding was not significantly altered by PKC inhibitor staurosporine (1 µM) or p38 kinase inhibitor SB2203580 (2 µM). However, phloretin significantly increased the ceramide abundance at the cell surface. Phloretin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect at least partially due to up-regulation of ceramide abundance.

Analysis of the dimensional dependence of semiconductor optical amplifier recovery speeds

NASA Astrophysics Data System (ADS)

Giller, Robin; Manning, Robert J.; Talli, Giuseppe; Webb, Roderick P.; Adams, Michael J.

2007-02-01

We investigate the dependence of the speed of recovery of optically excited semiconductor optical amplifiers (SOAs) on the active region dimensions. We use a picosecond pump-probe arrangement to experimentally measure and compare the gain and phase dynamics of four SOAs with varying active region dimensions. A sophisticated time domain SOA model incorporating amplified spontaneous emission (ASE) agrees well with the measurements and shows that, in the absence of a continuous wave (CW) beam, the ASE plays a similar role to such a holding beam. The experimental results are shown to be consistent with a recovery rate which is inversely proportional to the optical area. A significant speed increase is predicted for an appropriate choice of active region dimensions.

Recent Developments of Electrochemical Promotion of Catalysis in the Techniques of DeNOx

PubMed Central

Tang, Xiaolong; Yi, Honghong; Chen, Chen; Wang, Chuan

2013-01-01

Electrochemical promotion of catalysis reactions (EPOC) is one of the most significant discoveries in the field of catalytic and environmental protection. The work presented in this paper focuses on the aspects of reaction mechanism, influencing factors, and recent positive results. It has been shown with more than 80 different catalytic systems that the catalytic activity and selectivity of conductive catalysts deposited on solid electrolytes can be altered in the last 30 years. The active ingredient of catalyst can be activated by applying constant voltage or constant current to the catalysts/electrolyte interface. The effect of EPOC can improve greatly the conversion rate of NOx. And it can also improve the lifetime of catalyst by inhibiting its poisoning. PMID:23970835

Antibiotics as immunomodulant agents in COPD.

PubMed

Blasi, Francesco; Mantero, Marco; Aliberti, Stefano

2012-06-01

It is widely accepted that some antibiotics have activities beyond their direct antibacterial effects. Macrolide is the antibiotic class with more convincing studies and evidence on its immunomodulatory and anti-inflammatory activities. Different clinical studies have shown that macrolide prophylaxis in patients with moderate-severe chronic obstructive pulmonary disease (COPD) can have a significant impact on the exacerbation rate reducing morbidity and, potentially, mortality of the disease. Other antibiotics, such as fluoroquinolones, demonstrate a variety of immunomodulatory effects but only few clinical data are available in COPD. New macrolide derivatives devoid of antibacterial activity have been synthetized. This review analyses the relevance of immunomodulatory and anti-inflammatory effects of antibiotics in the management of COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Enhanced resistance to emotional stress through the use of D-phenylalanine].

PubMed

Iumatov, E A; Sarychev, E I; Kozlovskiĭ, I I; Mineeva, M F; Demidov, V M; Morozov, I S; Kozlovskaia, M M

1991-01-01

Stress-protective action was studied of D-phenylalanine, having an ability to decrease destruction of endogenic enkefalins. In the experiments stability of the experimental (receiving D-phenylalanine) and control groups of male rats of August line to emotional stress was compared in conditions of immobilization stress by parameters of animals survival rate, adrenal glands hypertrophy development, involution of thymus, pathologic changes in lungs (abscesses development), ulcero-dystrophic disturbances in stomach, and also the activity and kinetic properties of enzyme tyrosin-hydroxylase in the hypothalamus were determined. It was shown that by several of the mentioned physiological parameters the D-phenylalanine significantly increased the animals stability to the emotional stress and decreased tyrosinhydroxylase activity which participates in activation of katecholaminergic processes.

Biflorin: an o-naphthoquinone of clinical significance.

PubMed

Wisintainer, Gabrielle G N S; Simões, Evelyne R B; Lemos, Telma L G; Moura, Sidnei; Souza, Luciana G S; Fonseca, Aluisio M; Moraes, Manoel Odorico; Pessoa, Claudia; Roesch-Ely, Mariana; Henriques, João A P

2014-12-01

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

Biflorin: an o-naphthoquinone of clinical significance.

PubMed

Wisintainer, Gabrielle G N S; Simões, Evelyne R B; Lemos, Telma L G; Moura, Sidnei; Souza, Luciana G S; Fonseca, Aluisio M; Moraes, Manoel Odorico; Pessoa, Claudia; Roesch-Ely, Mariana; Henriques, João A P

2014-10-14

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis.

PubMed

Sugano, M; Tsuchida, K; Makino, N

2000-06-16

High-density lipoproteins (HDL) levels have been shown to be inversely correlated with coronary heart disease, but the mechanisms of the direct protective effect of HDL on endothelial cells are not fully understood. The apoptosis of endothelial cells induced by cytokines and/or oxidized low-density lipoproteins, etc. may provide a mechanistic clue to the "response-to-injury" hypothesis of atherogenesis. Here we report that HDL prevent the apoptosis of human umbilical venous endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha) via an inhibition of CPP32-like protease activity. The incubation of HUVECs with TNF-alpha significantly increased the CPP32-like protease activity, and induced apoptosis. Preincubation of HUVECs with HDL before incubation with TNF-alpha significantly suppressed the increase in the CPP32-like protease activity, preventing apoptosis in a concentration-dependent manner. These results suggest that HDL prevent the suicide pathway leading to apoptosis of endothelial cells by decreasing the CPP32-like protease activity and that HDL thus play a protective role against the "response-to-injury" hypothesis of atherogenesis. Copyright 2000 Academic Press.

In vitro and in vivo activity of LS 4477 and LS 4559, novel analogues of the tubulin binder estramustine.

PubMed

Nicholson, K M; Phillips, R M; Shnyder, S D; Bibby, M C

2002-01-01

LS 4477 and LS 4559, two of a series of N-acyl-aminoalkyl phenyl ethers, are rationally designed compounds based on the tubulin binder estramustine. This study investigated their mechanism of action and compared their effectiveness in relation to estramustine in vitro against a panel of human and murine cell lines and in vivo against two murine colon tumour models (MAC). At biologically relevant concentrations, LS 4477 and LS 4559 caused a 59.9 and 56% reduction in tubulin assembly, respectively, compared with a 28.4% reduction in tubulin assembly by estramustine. The analogues were approximately 100 times more potent in chemosensitivity tests in vitro than the parent compound. Both analogues were orally active against the MAC 15A murine tumour model, to a greater extent than estramustine, producing significant growth delays (P<0.01). Significant activity was also shown against the slower growing MAC 26 tumour for LS 4577 (the soluble pro-drug of LS 4559). The results presented in this study suggest these compounds warrant further development with a view to assessing their clinical activity.

Effects of traditional medical herbs "minor bupleurum decoction" on the non-specific immune responses of white shrimp (Litopenaeus vannamei).

PubMed

Wu, Yu-Sheng; Lee, Meng-Chou; Huang, Cheng-Ting; Kung, Tzu-Chi; Huang, Chih-Yang; Nan, Fan-Hua

2017-05-01

This study is investigating the effect of minor bupleurum decoction (Xiao-Chai-Hu decoction) on the non-specific immune response of white shrimp (Litopenaeus vannamei). To determine prophenoloxidase activity (proPO), reactive oxygen species production (ROS), superoxide anion production (O 2 - ), nitric oxide production (NO), phagocytic rate (PR), phagocytic index (PI), superoxide dismutase activity (SOD), total haemocyte count (THC) and differential haemocyte count (DHC). In this experiment, treating with different dosages (0, 0.25, 0.5 and, 1%) of minor bupleurum decoction to detect immune parameters on day 0, 1, 2, 4, 7, 14, 21 and 28. Result is shown that 0.25% treatment significantly enhanced the superoxide dismutase (SOD) activity and, 0.25 and 1% treatment significantly increased the ROS production, nitric oxide (NO) production and phagocytic rate (PR) moreover, 0.5 and 1% treatment induced the proPO activity and superoxide anion (O 2 - ) production. Evidence exactly indicated that minor bupleurum decoction is able to enhance the non-specific immunity responses of white shrimp via in vivo examination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute and subacute toxicities effect of oxytetracycline pharmaceutical wastewater on Zebrafish

NASA Astrophysics Data System (ADS)

Wu, Pengpeng; Shen, Hong-Yan

2018-02-01

Oxytetracycline wastewater is a major category of pharmaceutical wastewater, and its toxic effects on aquatic organisms have aroused people’s attention. In this study, Zebrafish were separately exposed to four Oxytetracycline wastewater treatments (20%, 40%, 60%, 80%) and a control group were sampled on days 3, 6, 9, 12, and 15. Superoxide dismutase (SOD) activities showed significant inhibition, but the highest SOD activity was found in 20% and 40% the treatment groups (195.12U/mgprot, 187.43U/mgprot, respectively) on the 12th day. MDA contents increased significantly compared with control group. MDA contents showed that the higher the volume concentration, the higher the contents of MDA with the increase of exposure time. The highest MDA content shown in 60% exposure group (5.49nmol/mgprot) on the 12th day. And SOD activities and MDA contents showed a trend of “Λ” type. In conclusion, Oxytetracycline wastewater induced oxidative stress and toxicity in Zebrafish muscle tissue.

Can activity within the external abdominal oblique be measured using real-time ultrasound imaging?

PubMed

John, E K; Beith, I D

2007-11-01

Differences in the function of the anterolateral abdominal muscles have been the subject of much investigation, but primarily using electromyography. Recently changes in thickness of transversus abdominis and internal oblique measured from real-time ultrasound images have been shown to represent activity within these muscles. However it is still unclear if such a change in thickness in external oblique similarly represents activity within that muscle. The purpose of this study was to investigate the relationship between change in thickness and muscle activity in the external oblique using real-time ultrasound and surface electromyography. Simultaneous measurements of electromyography and real-time ultrasound images of external oblique were studied in up to 24 subjects during two tasks compared to the muscle at rest (1) isometric trunk rotation and (2) drawing in the lower abdomen. Changes in muscle thickness correlated significantly with electromyography during isometric trunk rotation in the majority of subjects but with a significant difference between subjects. In contrast, the relationship between change in thickness and electrical activity in the muscle when drawing in the lower abdomen was significant in less than 50% of subjects and the muscle often got thinner. Thickness changes of external oblique can be used as a valid indicator of electromyography activity during isometric trunk rotation, though the relationship is not as good as previously published data for transversus abdominis. Thickness changes of external oblique measured during lower abdominal drawing in cannot be used to detect activity within this muscle.

Malaysian brown seaweeds Sargassum siliquosum and Sargassum polycystum: Low density lipoprotein (LDL) oxidation, angiotensin converting enzyme (ACE), α-amylase, and α-glucosidase inhibition activities.

PubMed

Nagappan, Hemlatha; Pee, Poh Ping; Kee, Sandra Hui Yin; Ow, Ji Tsong; Yan, See Wan; Chew, Lye Yee; Kong, Kin Weng

2017-09-01

Two Malaysian brown seaweeds, Sargassum siliquosum and Sargassum polycystum were first extracted using methanol to get the crude extract (CE) and further fractionated to obtain fucoxanthin-rich fraction (FRF). Samples were evaluated for their phenolic, flavonoid, and fucoxanthin contents, as well as their inhibitory activities towards low density lipoprotein (LDL) oxidation, angiotensin converting enzyme (ACE), α-amylase, and α-glucosidase. In LDL oxidation assay, an increasing trend in antioxidant activity was observed as the concentration of FRF (0.04-0.2mg/mL) and CE (0.2-1.0mg/mL) increased, though not statistically significant. As for serum oxidation assay, significant decrease in antioxidant activity was observed as concentration of FRF increased, while CE showed no significant difference in inhibitory activity across the concentrations used. The IC 50 values for ACE inhibitory activity of CE (0.03-0.42mg/mL) were lower than that of FRF (0.94-1.53mg/mL). When compared to reference drug Voglibose (IC 50 value of 0.61mg/mL) in the effectiveness in inhibiting α-amylase, CE (0.58mg/mL) gave significantly lower IC 50 values while FRF (0.68-0.71mg/mL) had significantly higher IC 50 values. The α-glucosidase inhibitory activity of CE (IC 50 value of 0.57-0.69mg/mL) and FRF (IC 50 value of 0.50-0.53mg/mL) were comparable to that of reference drug (IC 50 value of 0.54mg/mL). Results had shown the potential of S. siliquosum and S. polycystum in reducing cardiovascular diseases related risk factors following their inhibitory activities on ACE, α-amylase and α-glucosidase. In addition, it is likelihood that FRF possessed antioxidant activity at low concentration level. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antioxidant potential of fungal metabolite nigerloxin during eye lens abnormalities in galactose-fed rats.

PubMed

Suresha, Bharathinagar S; Srinivasan, Krishnapura

2013-10-01

The role of osmotic and oxidative stress has been strongly implicated in the pathogenesis of cataract. Nigerloxin, a fungal metabolite, has been shown to possess aldose reductase inhibition and improved antioxidant defense system in lens of diabetic rats. In the present study, the beneficial influence of nigerloxin was investigated in galactose-induced cataract in experimental animals. Cataract was induced in Wistar rats by feeding 30% galactose in diet. Groups of galactose-fed rats were orally administered with nigerloxin (25 and 100 mg/kg body weight/day) for 24 days. Lens aldose reductase activity was increased significantly in galactose-fed animals. Lens lipid peroxides and advanced glycation end products were also significantly increased. Antioxidant molecule - reduced glutathione, total thiols and activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were decreased in the lens of galactose-fed animals. Oral administration of nigerloxin once a day for 24 days at a dose of 100 mg/kg body weight, significantly decreased lens lipid peroxides and advanced glycation end products in galactose-fed rats. Lens aldose reductase activity was reduced and lens antioxidant molecules and antioxidant enzyme activities were elevated significantly by nigerloxin administration. The results suggest that alteration in polyol pathway and antioxidant defense system were countered by nigerloxin in the lens of galactose-fed animals, suggesting the potential of nigerloxin in ameliorating the development of galactose-induced cataract in experimental animals.

Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users.

PubMed

Nestor, Liam; Roberts, Gloria; Garavan, Hugh; Hester, Robert

2008-04-15

The consumption of cannabis has been linked to impairments in human learning and memory, as well as aspects of executive functioning. Cannabis-related impairments in learning and memory in chronic cannabis users, it has been argued, are caused by the effects of cannabis on hippocampal functioning. The current study involved two experiments. Experiment 1 compared 35 current users of cannabis and 38 well-matched controls on a face-name task, previously shown to activate the hippocampal region. Based on the results of experiment 1, experiment 2 used fMRI and a modified version of the face-name task, to examine cortical and (para)hippocampal activity during learning and recall in 14 current users of cannabis and 14 controls. Results of experiment 1 showed that cannabis users were significantly worse with respect to learning, short and long-term memory performance. Experiment 2 showed that despite non-significant differences in learning and memory performance, cannabis users had significantly lower levels of BOLD activity in the right superior temporal gyrus, right superior frontal gyrus, right middle frontal gyrus and left superior frontal gyrus compared to controls during learning. Results also showed that cannabis users had significantly higher BOLD activity in the right parahippocampal gyrus during learning. Hypoactivity in frontal and temporal cortices, and relative hyperactivity in the parahippocampus identify functional deficits and compensatory processes in cannabis users.

Activity of 10 antimicrobial agents against intracellular Rhodococcus equi.

PubMed

Giguère, Steeve; Berghaus, Londa J; Lee, Elise A

2015-08-05

Studies with facultative intracellular bacterial pathogens have shown that evaluation of the bactericidal activity of antimicrobial agents against intracellular bacteria is more closely associated with in vivo efficacy than traditional in vitro susceptibility testing. The objective of this study was to determine the relative activity of 10 antimicrobial agents against intracellular Rhodococcus equi. Equine monocyte-derived macrophages were infected with virulent R. equi and exposed to erythromycin, clarithromycin, azithromycin, rifampin, ceftiofur, gentamicin, enrofloxacin, vancomycin, imipenem, or doxycycline at concentrations achievable in plasma at clinically recommended dosages in foals. The number of intracellular R. equi was determined 48h after infection by counting colony forming units (CFUs). The number of R. equi CFUs in untreated control wells were significantly higher than those of monolayers treated with antimicrobial agents. Numbers of R. equi were significantly lower in monolayers treated with enrofloxacin followed by those treated with gentamicin, and vancomycin, when compared to monolayers treated with other antimicrobial agents. Numbers of R. equi in monolayers treated with doxycycline were significantly higher than those of monolayers treated with other antimicrobial agents. Differences in R. equi CFUs between monolayers treated with other antimicrobial agents were not statistically significant. Enrofloxacin, gentamicin, and vancomycin are the most active drugs in equine monocyte-derived macrophages infected with R. equi. Additional studies will be needed to determine if these findings correlate with in vivo efficacy. Copyright © 2015 Elsevier B.V. All rights reserved.

The associations between increasing degrees of homeostatic model assessment for insulin resistance and muscular strengthening activities among euglycaemic US adults.

PubMed

Boyer, William R; Johnson, Tammie M; Fitzhugh, Eugene C; Richardson, Michael R; Churilla, James R

2015-11-01

To examine the associations between the homeostatic model assessment for insulin resistance and self-reported muscular strengthening activity in a nationally representative sample of euglycaemic US adults. Sample included euglycaemic adults (⩾20 years of age (n = 2009)) from the 1999 to 2004 National Health and Nutrition Examination Survey. Homeostatic model assessment for insulin resistance was categorized into quartiles and was the primary independent variable of interest. No reported muscular strengthening activity was the dependent variable. Following adjustment for covariates, those with homeostatic model assessment for insulin resistance values in fourth (odds ratio: 2.04, 95% confidence interval: 1.35-3.06, p < 0.001) quartile were found to have significantly greater odds of reporting no muscular strengthening activity. Following further adjustment for non-muscular strengthening activity specific aerobic leisure-time physical activity, results remained significant for the fourth (odds ratio: 2.30, 95% confidence interval: 1.50-3.52, p < 0.001) quartile. A significant trend was seen across quartiles of homeostatic model assessment for insulin resistance for increasing prevalence of no muscular strengthening activity (p < 0.001). Having a higher homeostatic model assessment for insulin resistance value is associated with greater odds of reporting no muscular strengthening activity among euglycaemic US adults. This implies that subjects with an increasing degree of insulin resistance are more likely to not engage in muscular strengthening activity, an exercise modality that has been shown to reduce the risk of several cardiometabolic diseases and improve glycaemic status. © The Author(s) 2015.

Downregulation of spinal glutamate transporter EAAC1 following nerve injury is regulated by central glucocorticoid receptors in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Yang, Liling; Sung, Backil; Mao, Jianren

2006-01-01

Previous studies have shown that glucocorticoid receptors (GR) were upregulated, whereas glutamate transporters were downregulated, within the spinal cord dorsal horn after peripheral nerve injury. However, the relationship between the expression of spinal GR and glutamate transporter after nerve injury remains unknown. In the present study, we examined the hypothesis that central GR would regulate the expression of spinal glutamate transporter EAAC1 following chronic constriction nerve injury (CCI) in rats. CCI induced a significant downregulation of EAAC1 expression primarily within the ipsilateral spinal cord dorsal horn when examined on postoperative day 7 using both Western blot and immunohistochemistry. The downregulation of EAAC1 was significantly diminished after either the GR antagonist RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide was administered intrathecally twice daily for postoperative day 1-6. Moreover, CCI induced a significant downregulation of nuclear factor kappaB (NF-kappaB) within the ipsilateral spinal cord dorsal horn, which also was attenuated by either RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide. The immunohistochemical data indicated a pattern of colocalization between GR and EAAC1 as well as GR and NF-kappaB within the spinal cord dorsal horn. Since, NF-kappaB has been shown to regulate the expression of those cellular elements linked to inflammation and tissue injury and its activity can be negatively regulated by GR activation, these results suggest that spinal GR through NF-kappaB may play a significant role in the regulation of EAAC1 expression after peripheral nerve injury, a cellular pathway that may contribute to the development of neuropathic pain behaviors in rats.

Molecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept.

PubMed

Vakhitova, Y V; Sadovnikov, S V; Borisevich, S S; Ostrovskaya, R U; A Gudasheva, T; Seredenin, S B

2016-01-01

This study was performed in order to reveal the effect of Noopept (ethyl ester of N-phenylacetyl-Lprolylglycine, GVS-111) on the DNA-binding activity of transcriptional factors (TF) in HEK293 cells transiently transfected with luciferase reporter constructs containing sequences for CREB, NFAT, NF-κB, p53, STAT1, GAS, VDR, HSF1, and HIF-1. Noopept (10 μM) was shown to increase the DNA-binding activity of HIF-1 only, while lacking the ability to affect that of CREB, NFAT, NF-κB, p53, STAT1, GAS, VDR, and HSF1. Noopept provoked an additional increase in the DNA-binding activity of HIF-1 when applied in conditions of CoCl2-induced HIF- 1 stabilization. The degree of this HIF-positive effect of Noopept was shown to be concentration-dependent. Piracetam (1 mM) failed to affect significantly any of the TF under study. The results of molecular docking showed that Noopept (L-isomer), as well as its metabolite, L-isomer of N-phenyl-acetylprolyl, unlike its pharmacologically ineffective D-isomer, is able to bind to the active site of prolyl hydroxylase 2. Taking into account the important role of the genes activated by HIF-1 in the formation of an adaptive response to hypoxia, data on the ability of Noopept to provoke a selective increase in the DNA-binding activity of HIF-1 explain the wide spectrum of neurochemical and pharmacological effects of Noopept revealed before. The obtained data allow one to propose the HIF-positive effect as the primary mechanism of the activity of this Pro-Gly-containing dipeptide.

Focal adhesion kinase (FAK) regulates polymerase activity of multiple influenza A virus subtypes.

PubMed

Elbahesh, Husni; Bergmann, Silke; Russell, Charles J

2016-12-01

Influenza A viruses (IAVs) cause numerous pandemics and yearly epidemics resulting in ~500,000 annual deaths globally. IAV modulates cellular signaling pathways at every step of the infection cycle. Focal adhesion kinase (FAK) has been shown to play a critical role in endosomal trafficking of influenza A viruses, yet it is unclear how FAK kinase activity regulates IAV replication. Using mini-genomes derived from H1N1, H5N1 and H7N9 viruses, we dissected RNA replication by IAVs independent of viral entry or release. Our results show FAK activity promotes efficient IAV polymerase activity and inhibiting FAK activity with a chemical inhibitor or a kinase-dead mutant significantly reduces IAV polymerase activity. Using co-immunoprecipitations and proximity ligation assays, we observed interactions between FAK and the viral nucleoprotein, supporting a direct role of FAK in IAV replication. Altogether, the data indicates that FAK kinase activity is important in promoting IAV replication by regulating its polymerase activity. Copyright © 2016 Elsevier Inc. All rights reserved.

PPAR{gamma} agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Seong-Ryong; Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, Taegu; Kim, Hahn-Young

2009-02-27

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation withmore » pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.« less

The use of antioxidants to prevent glutamate-induced derangement of calcium ion metabolism in rat cerebral cortex synaptosomes.

PubMed

Avrova, N F; Shestak, K I; Zakharova, I O; Sokolova, T V; Tyurina, Y Y; Tyurin, V A

2000-01-01

Glutamate is shown to induce increases in intracellular Ca2+ concentrations ([Ca2+]i), increases in 45Ca2+ influx, decreases in the activity of Na+,K+-ATPase activity, and activation of the Na+/Ca2+ exchanger in rat cerebral cortex synaptosomes. NMDA receptor antagonists virtually prevented these effects. Preincubation of synaptosomes with alpha-tocopherol, superoxide dismutase, and ganglioside GM1 normalized [Ca2+]i, 45Ca2+ influx, and Na+,K+-ATPase activity in rat cerebral cortex synaptosomes exposed to glutamate. Glutamate and GM1 activated the Na+/K+ exchanger, and their effects were additive. Calcium ions entering cerebral cortex nerve cells via NMDA receptors during exposure to high glutamate concentrations appeared to be only the trigger for the processes activating free-radical reactions. Activation of these reactions led to increases in Ca2+ influx into cells, decreases in Na+,K+-ATPase activity, and significant increases in [Ca2+]i, though this could be prevented by antioxidants and gangliosides.

Antidiabetes and Anti-obesity Activity of Lagerstroemia speciosa

PubMed Central

Klein, Guy; Kim, Jaekyung; Himmeldirk, Klaus; Cao, Yanyan

2007-01-01

The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases. In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide. Since then, researchers have conducted numerous in vitro and in vivo studies that consistently confirmed the antidiabetic activity of banaba. Scientists have identified different components of banaba to be responsible for its activity. Using tumor cells as a cell model, corosolic acid was isolated from the methanol extract of banaba and shown to be an active compound. More recently, a different cell model and the focus on the water soluble fraction of the extract led to the discovery of other compounds. The ellagitannin Lagerstroemin was identified as an effective component of the banaba extract responsible for the activity. In a different approach, using 3T3-L1 adipocytes as a cell model and a glucose uptake assay as the functional screening method, Chen et al. showed that the banaba water extract exhibited an insulin-like glucose transport inducing activity. Coupling HPLC fractionation with a glucose uptake assay, gallotannins were identified in the banaba extract as components responsible for the activity, not corosolic acid. Penta-O-galloyl-glucopyranose (PGG) was identified as the most potent gallotannin. A comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin. Chen et al. have also shown that PGG exhibits anti-adipogenic properties in addition to stimulating the glucose uptake in adipocytes. The combination of glucose uptake and anti-adipogenesis activity is not found in the current insulin mimetic drugs and may indicate a great therapeutic potential of PGG. PMID:18227906

Decreased activation along the dorsal visual pathway after a 3-month treatment with galantamine in mild Alzheimer disease: a functional magnetic resonance imaging study.

PubMed

Bokde, Arun L W; Karmann, Michaela; Teipel, Stefan J; Born, Christine; Lieb, Martin; Reiser, Maximilian F; Möller, Hans-Jürgen; Hampel, Harald

2009-04-01

Visual perception has been shown to be altered in Alzheimer disease (AD) patients, and it is associated with decreased cognitive function. Galantamine is an active cholinergic agent, which has been shown to lead to improved cognition in mild to moderate AD patients. This study examined brain activation in a group of mild AD patients after a 3-month open-label treatment with galantamine. The objective was to examine the changes in brain activation due to treatment. There were 2 tasks to visual perception. The first task was a face-matching task to test the activation along the ventral visual pathway, and the second task was a location-matching task to test neuronal function along the dorsal pathway. Brain activation was measured using functional magnetic resonance imaging. There were 5 mild AD patients in the study. There were no differences in the task performance and in the cognitive scores of the Consortium to Establish a Registry for Alzheimer's Disease battery before and after treatment. In the location-matching task, we found a statistically significant decrease in activation along the dorsal visual pathway after galantamine treatment. A previous study found that AD patients had higher activation in the location-matching task compared with healthy controls. There were no differences in activation for the face-matching task after treatment. Our data indicate that treatment with galantamine leads to more efficient visual processing of stimuli or changes the compensatory mechanism in the AD patients. A visual perception task recruiting the dorsal visual system may be useful as a biomarker of treatment effects.

An in vitro examination of the antioxidant and anti-inflammatory properties of buckwheat honey.

PubMed

van den Berg, A J J; van den Worm, E; van Ufford, H C Quarles; Halkes, S B A; Hoekstra, M J; Beukelman, C J

2008-04-01

Hydroxyl radical and hypochlorite anion formed at the wound site from superoxide anion produced by activated polymorphonuclear neutrophils (PMNs) are considered important factors in impaired wound healing. Superoxide anion may also react with nitric oxide produced by macrophages to form peroxynitrite, a third strong oxidant that damages surrounding tissue. In order to select honey for use in wound-healing products, different samples were compared for their capacity to reduce levels of reactive oxygen species (ROS) in vitro. Honey samples were tested in assays for inhibition of ROS production by activated human PMNs, antioxidant activity (scavenging of superoxide anion in a cell-free system) and inhibition of human complement (reducing levels of ROS by limiting formation of complement factors that attract and stimulate PMNs). For buckwheat honey (NewYork, US), moisture and free acid content were determined by refractive index measurement and potentiometric titration respectively. Honey constituents other than sugars were investigated by thin layer chromatography, using natural product reagent to detect phenolic compounds. Constituents with antioxidant properties were detected by spraying the chromatogram with DPPH. Although most honey samples were shown to be active, significant differences were observed, with the highly active honey exceeding the activities of samples with minor effects by factors of 4 to 30. Most pronounced activities were found for American buckwheat honey from the state of NewYork. Phenolic constituents of buckwheat honey were shown to have antioxidant activity. As buckwheat honey was most effective in reducing ROS levels, it was selected for use in wound-healing products. The major antioxidant properties in buckwheat honey derive from its phenolic constituents, which are present in relatively large amounts. Its phenolic compounds may also exert antibacterial activity, whereas its low pH and high free acid content may assist wound healing.

The association between aerobic fitness and cognitive function in older men mediated by frontal lateralization.

PubMed

Hyodo, Kazuki; Dan, Ippeita; Kyutoku, Yasushi; Suwabe, Kazuya; Byun, Kyeongho; Ochi, Genta; Kato, Morimasa; Soya, Hideaki

2016-01-15

Previous studies have shown that higher aerobic fitness is related to higher cognitive function and higher task-related prefrontal activation in older adults. However, a holistic picture of these factors has yet to be presented. As a typical age-related change of brain activation, less lateralized activity in the prefrontal cortex during cognitive tasks has been observed in various neuroimaging studies. Thus, this study aimed to reveal the relationship between aerobic fitness, cognitive function, and frontal lateralization. Sixty male older adults each performed a submaximal incremental exercise test to determine their oxygen intake (V·O2) at ventilatory threshold (VT) in order to index their aerobic fitness. They performed a color-word Stroop task while prefrontal activation was monitored using functional near infrared spectroscopy. As an index of cognitive function, Stroop interference time was analyzed. Partial correlation analyses revealed significant correlations among higher VT, shorter Stroop interference time and greater left-lateralized dorsolateral prefrontal cortex (DLPFC) activation when adjusting for education. Moreover, mediation analyses showed that left-lateralized DLPFC activation significantly mediated the association between VT and Stroop interference time. These results suggest that higher aerobic fitness is associated with cognitive function via lateralized frontal activation in older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

Disk Susceptibility Studies with Cefazolin and Cephalothin

PubMed Central

Actor, Paul; Guarini, Joseph; Uri, Joseph; Dickson, Judith; Pauls, John F.; Weisbach, Jerry A.

1974-01-01

Cefazolin and cephalothin disk susceptibility and minimal inhibitory concentration determinations were conducted on 591 clinical isolates. Cefazolin demonstrated superior activity, as shown by lower minimal inhibitory concentrations, and a greater percentage of isolates inhibited in the disk susceptibility test. The cephalothin antibiotic class disk by the standard Bauer-Kirby method failed to detect susceptibility to cefazolin in a significant percentage of Escherchia coli, Enterobacter species, and Enterococcus isolates. A separate cefazolin disk with a susceptibility cut-off point of 18 mm is recommended. An alternative to a separate cefazolin disk would be a reinterpretation of the cephalothin susceptibility disk zone diameters so that it would more adequately predict cefazolin activity. PMID:4840450

A Case Report of Supplement-Induced Hepatitis in an Active Duty Service Member.

PubMed

Brazeau, Michael J; Castaneda, Joni L; Huitron, Sonny S; Wang, James

2015-07-01

The incidence of drug-induced hepatic injury has been increasing as a result of more widespread use of workout supplements containing anabolic steroids to increase muscle mass. Synthetic androgenic steroids are shown to cause cholestatic liver injury, but the exact mechanism of injury is not completely understood. We present a case of a healthy, young, active duty Army male soldier who developed pruritis and jaundice shortly after starting to take a body-building supplement containing anabolic steroids, and was subsequently found to have significant biopsy proven drug-induced liver injury. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Effect of filtration of signals of brain activity on quality of recognition of brain activity patterns using artificial intelligence methods

NASA Astrophysics Data System (ADS)

Hramov, Alexander E.; Frolov, Nikita S.; Musatov, Vyachaslav Yu.

2018-02-01

In present work we studied features of the human brain states classification, corresponding to the real movements of hands and legs. For this purpose we used supervised learning algorithm based on feed-forward artificial neural networks (ANNs) with error back-propagation along with the support vector machine (SVM) method. We compared the quality of operator movements classification by means of EEG signals obtained experimentally in the absence of preliminary processing and after filtration in different ranges up to 25 Hz. It was shown that low-frequency filtering of multichannel EEG data significantly improved accuracy of operator movements classification.

Influence of socio-economic status on habitual physical activity and sedentary behavior in 8- to 11-year old children.

PubMed

Drenowatz, Clemens; Eisenmann, Joey C; Pfeiffer, Karin A; Welk, Greg; Heelan, Kate; Gentile, Douglas; Walsh, David

2010-04-27

While socio-economic status has been shown to be an important determinant of health and physical activity in adults, results for children and adolescents are less consistent. The purpose of this study, therefore, is to examine whether physical activity and sedentary behavior differs in children by socio-economic status (SES) independent of body mass index. Data were from two cohorts including 271 children (117 males; 154 females) in study 1 and 131 children in study 2 (63 males; 68 females). The average age was 9.6 and 8.8 years respectively. Height and body mass were assessed according to standard procedures and body mass index (BMI, kg/m2) was calculated. Parent-reported household income was used to determine SES. Habitual, free-living physical activity (PA) was assessed by a pedometer (steps/day) in study 1 and accelerometer (time spent in moderate-to-vigorous PA) in study 2. Self-reported time spent watching TV and on the computer was used as measure of sedentary behavior. Differences in PA and sedentary behavior by SES were initially tested using ANOVA. Further analyses used ANCOVA controlling for BMI, as well as leg length in the pedometer cohort. In study 1, mean daily steps differed significantly among SES groups with lower SES groups approximating 10,500 steps/day compared to about 12,000 steps/day in the higher SES groups. These differences remained significant (p < 0.05) when controlling for leg length. Lower SES children, however, had higher body mass and BMI compared to higher SES groups (p < 0.05) and PA no longer remained significant when further controlling for BMI. In study 2 results depended on the methodology used to determine time spent in moderate-to-vigorous physical activity (MVPA). Only one equation resulted in significant group differences (p = 0.015), and these differences remained after controlling for BMI. Significant differences between SES groups were shown for sedentary behavior in both cohorts (P < 0.05) with higher SES groups spending less time watching TV than low SES groups. Children from a low SES show a trend of lower PA levels and spend more time in sedentary behavior than high SES children; however, differences in PA were influenced by BMI. The higher BMI in these children might be another factor contributing to increased health risks among low SES children compared to children from with a higher SES.

Cannabidiol lowers incidence of diabetes in non-obese diabetic mice.

PubMed

Weiss, L; Zeira, M; Reich, S; Har-Noy, M; Mechoulam, R; Slavin, S; Gallily, R

2006-03-01

Cannabidinoids are components of the Cannabis sativa (marijuana) plant that have been shown capable of suppressing inflammation and various aspects of cell-mediated immunity. Cannabidiol (CBD), a non-psychoactive cannabidinoid has been previously shown by us to suppress cell-mediated autoimmune joint destruction in an animal model of rheumatoid arthritis. We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice. CBD treatment also resulted in the significant reduction of plasma levels of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha. Th1-associated cytokine production of in vitro activated T-cells and peritoneal macrophages was also significantly reduced in CBD-treated mice, whereas production of the Th2-associated cytokines, IL-4 and IL-10, was increased when compared to untreated control mice. Histological examination of the pancreatic islets of CBD-treated mice revealed significantly reduced insulitis. Our results indicate that CBD can inhibit and delay destructive insulitis and inflammatory Th1-associated cytokine production in NOD mice resulting in a decreased incidence of diabetes possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.

Diverse amide analogs of sulindac for cancer treatment and prevention.

PubMed

Mathew, Bini; Hobrath, Judith V; Connelly, Michele C; Kiplin Guy, R; Reynolds, Robert C

2017-10-15

Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivo antitumor activity that was comparable to sulindac in a human colon tumor xenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good activity relative to the parent (1), including five analogs that also possess nanomolar inhibitory potencies against acute lymphoblastic leukemia cells. Several new analogs identified may serve as anticancer lead candidates for further development. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning.

PubMed

Sun, Li; Liang, Peipeng; Jia, Xiuqin; Qi, Zhigang; Li, Kuncheng

2014-01-01

Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning.

The Effect of Reflective Activities on Reflective Thinking Ability in an Undergraduate Pharmacy Curriculum.

PubMed

Tsingos-Lucas, Cherie; Bosnic-Anticevich, Sinthia; Schneider, Carl R; Smith, Lorraine

2016-05-25

Objective. To determine the effectiveness of integrating reflective practice activities into a second-year undergraduate pharmacy curriculum and their impact on reflective thinking ability. Design. A cross-over design with repeated measures was employed. Newly developed reflective modules based on real hospital and community pharmacy cases were integrated into the second-year pharmacy practice curriculum. A novel strategy, the Reflective Ability Clinical Assessment (RACA), was introduced to enhance self- and peer reflection. Assessment. Student responses (n=214) to the adapted Kember et al(1) Reflective Thinking Questionnaire (RTQ) were compared before and after reflective activities were undertaken. Significant improvement in three indicators of reflective thinking was shown after students engaged in reflective activities. Conclusion. Integration of reflective activities into a pharmacy curriculum increased the reflective thinking capacity of students. Enhancing reflective thinking ability may help students make better informed decisions and clinical judgments, thus improving future practice.

The Effect of Reflective Activities on Reflective Thinking Ability in an Undergraduate Pharmacy Curriculum

PubMed Central

Bosnic-Anticevich, Sinthia; Schneider, Carl R.; Smith, Lorraine

2016-01-01

Objective. To determine the effectiveness of integrating reflective practice activities into a second-year undergraduate pharmacy curriculum and their impact on reflective thinking ability. Design. A cross-over design with repeated measures was employed. Newly developed reflective modules based on real hospital and community pharmacy cases were integrated into the second-year pharmacy practice curriculum. A novel strategy, the Reflective Ability Clinical Assessment (RACA), was introduced to enhance self- and peer reflection. Assessment. Student responses (n=214) to the adapted Kember et al1 Reflective Thinking Questionnaire (RTQ) were compared before and after reflective activities were undertaken. Significant improvement in three indicators of reflective thinking was shown after students engaged in reflective activities. Conclusion. Integration of reflective activities into a pharmacy curriculum increased the reflective thinking capacity of students. Enhancing reflective thinking ability may help students make better informed decisions and clinical judgments, thus improving future practice. PMID:27293232

Activity affects intraspecific body-size scaling of metabolic rate in ectothermic animals.

PubMed

Glazier, Douglas Stewart

2009-10-01

Metabolic rate is commonly thought to scale with body mass (M) to the 3/4 power. However, the metabolic scaling exponent (b) may vary with activity state, as has been shown chiefly for interspecific relationships. Here I use a meta-analysis of literature data to test whether b changes with activity level within species of ectothermic animals. Data for 19 species show that b is usually higher during active exercise (mean +/- 95% confidence limits = 0.918 +/- 0.038) than during rest (0.768 +/- 0.069). This significant upward shift in b to near 1 is consistent with the metabolic level boundaries hypothesis, which predicts that maximal metabolic rate during exercise should be chiefly influenced by volume-related muscular power production (scaling as M (1)). This dependence of b on activity level does not appear to be a simple temperature effect because body temperature in ectotherms changes very little during exercise.

PPAR{alpha} agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Xiaoyang; Division of Cardiothoracic Surgery, The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, BCM 390, One Baylor Plaza, Houston, TX 77030; Shen, Ying H.

2010-04-09

Oxidative stress has been shown to play an important role in the development of hypertensive renal injury. Peroxisome proliferator-activated receptors {alpha} (PPAR{alpha}) has antioxidant effect. In this study, we demonstrated that fenofibrate significantly reduced proteinuria, inflammatory cell recruitment and extracellular matrix (ECM) proteins deposition in the kidney of SHRs without apparent effect on blood pressure. To investigate the mechanisms involved, we found that fenofibrate treatment markedly reduced oxidative stress accompanied by reduced activity of renal NAD(P)H oxidase, increased activity of Cu/Zn SOD, and decreased phosphorylation of p38MAPK and JNK in the kidney of SHRs. Taken together, fenofibrate treatment can protectmore » against hypertensive renal injury without affecting blood pressure by inhibiting inflammation and fibrosis via suppression of oxidative stress and MAPK activity.« less

Honey Antibacterial Effect Boosting Using Origanum vulgare L. Essential Oil

PubMed Central

Imtara, Hamada; Elamine, Youssef

2018-01-01

The appearance of new bacterial strains which cause pathogenic diseases and which are resistant to the most used antibiotics requires probing new antibacterial agents sources. Therefore, the main aim of the present work was to follow the antibacterial activity of honey samples from Palestine and Morocco, after the combination with Origanum vulgare L. essential oil, and figure out whether the honey physicochemical parameters and geographic origin influence the final activity. The results of this study showed good geographical discrimination between the Palestinians and Moroccan honey samples. The antioxidant and antimicrobial activities showed a significant correlation with honey color, melanoidins, and phenolic and flavonoids contents. Furthermore, the possible effect of honey physicochemical parameters on the gained antimicrobial activities was assessed using the principal component analysis (PCA). Some parameters showed a promising effect and seem to be important in the process of honey samples selection. Namely, melanoidins content, phenolic content, electrical conductivity, and mineral content were shown to be positively influencing the gained antibacterial activity after the combination with essential oil against the tested strains, although a significant negative correlation was seen with the FIC only in the case of Escherichia coli (ATB: 57). PMID:29736180

The infant mirror neuron system studied with high density EEG.

PubMed

Nyström, Pär

2008-01-01

The mirror neuron system has been suggested to play a role in many social capabilities such as action understanding, imitation, language and empathy. These are all capabilities that develop during infancy and childhood, but the human mirror neuron system has been poorly studied using neurophysiological measures. This study measured the brain activity of 6-month-old infants and adults using a high-density EEG net with the aim of identifying mirror neuron activity. The subjects viewed both goal-directed movements and non-goal-directed movements. An independent component analysis was used to extract the sources of cognitive processes. The desynchronization of the mu rhythm in adults has been shown to be a marker for activation of the mirror neuron system and was used as a criterion to categorize independent components between subjects. The results showed significant mu desynchronization in the adult group and significantly higher ERP activation in both adults and 6-month-olds for the goal-directed action observation condition. This study demonstrate that infants as young as 6 months display mirror neuron activity and is the first to present a direct ERP measure of the mirror neuron system in infants.

Effect of the French Oak Wood Extract Robuvit on Markers of Oxidative Stress and Activity of Antioxidant Enzymes in Healthy Volunteers: A Pilot Study

PubMed Central

Orszaghova, Zuzana; Laubertova, Lucia; Sabaka, Peter; Rohdewald, Peter; Durackova, Zdenka; Muchova, Jana

2014-01-01

We examined in vitro antioxidant capacity of polyphenolic extract obtained from the wood of oak Quercus robur (QR), Robuvit, using TEAC (Trolox equivalent antioxidant capacity) method and the effect of its intake on markers of oxidative stress, activity of antioxidant enzymes, and total antioxidant capacity in plasma of 20 healthy volunteers. Markers of oxidative damage to proteins, DNA, and lipids and activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the erythrocytes. We have found an in vitro antioxidant capacity of Robuvit of 6.37 micromole Trolox equivalent/mg of Robuvit. One month intake of Robuvit in daily dose of 300 mg has significantly decreased the serum level of advanced oxidation protein products (AOPP) and lipid peroxides (LP). Significantly increased activities of SOD and CAT as well as total antioxidant capacity of plasma after one month intake of Robuvit have been shown. In conclusion, we have demonstrated for the first time that the intake of Robuvit is associated with decrease of markers of oxidative stress and increase of activity of antioxidant enzymes and total antioxidant capacity of plasma in vivo. PMID:25254080

Honey Antibacterial Effect Boosting Using Origanum vulgare L. Essential Oil.

PubMed

Imtara, Hamada; Elamine, Youssef; Lyoussi, Badiâa

2018-01-01

The appearance of new bacterial strains which cause pathogenic diseases and which are resistant to the most used antibiotics requires probing new antibacterial agents sources. Therefore, the main aim of the present work was to follow the antibacterial activity of honey samples from Palestine and Morocco, after the combination with Origanum vulgare L. essential oil, and figure out whether the honey physicochemical parameters and geographic origin influence the final activity. The results of this study showed good geographical discrimination between the Palestinians and Moroccan honey samples. The antioxidant and antimicrobial activities showed a significant correlation with honey color, melanoidins, and phenolic and flavonoids contents. Furthermore, the possible effect of honey physicochemical parameters on the gained antimicrobial activities was assessed using the principal component analysis (PCA). Some parameters showed a promising effect and seem to be important in the process of honey samples selection. Namely, melanoidins content, phenolic content, electrical conductivity, and mineral content were shown to be positively influencing the gained antibacterial activity after the combination with essential oil against the tested strains, although a significant negative correlation was seen with the FIC only in the case of Escherichia coli (ATB: 57).

Physiological changes, sleep, and morning mood in an isolated environment

NASA Technical Reports Server (NTRS)

Kraft, Norbert O.; Inoue, Natsuhiko; Mizuno, Koh; Ohshima, Hiroshi; Murai, Tadashi; Sekiguchi, Chiharu; Orasanu, J. M. (Principal Investigator)

2002-01-01

BACKGROUND: Previous isolation studies have shown increased 24-h urine volumes and body weight gains in subjects. This project examined those and other physiological variables in relationship to sleep motor activity, subjective sleep quality, mood, and complaints during confinement. METHODS: Six male and two female subjects lived for 7 d in the National Space Development Agency of Japan's isolation chamber, which simulates the interior of the Japanese Experiment Module. Each 24-h period included 6 h of sleep, 3 meals, and 20 min of exercise. Each morning, subjects completed Sleep Sensation and Complaint Index questionnaires. Catecholamine and creatinine excretion, urine volume, and body weight were measured on the 2 d before and 2 d after confinement, and sleep motor activity was measured during confinement. RESULTS: Confinement produced no significant change in body weight, urine volume, or questionnaire results. In contrast, epinephrine, norepinephrine, and sleep motor activity exhibited significant differences during confinement (p < 0.05). Higher nocturnal norepinephrine excretion correlated with higher sleep motor activity. CONCLUSION: The 24-h epinephrine values were slightly higher than normal throughout the experiment, but lower than for subjects working under time-stress. High sympathetic activity (as indicated by norepinephrine) may have interfered with sleep.

Genetics of regular exercise and sedentary behaviors.

PubMed

de Geus, Eco J C; Bartels, Meike; Kaprio, Jaakko; Lightfoot, J Timothy; Thomis, Martine

2014-08-01

Studies on the determinants of physical activity have traditionally focused on social factors and environmental barriers, but recent research has shown the additional importance of biological factors, including genetic variation. Here we review the major tenets of this research to arrive at three major conclusions: First, individual differences in physical activity traits are significantly influenced by genetic factors, but genetic contribution varies strongly over age, with heritability of leisure time exercise behavior ranging from 27% to 84% and heritability of sedentary behaviors ranging from 9% to 48%. Second, candidate gene approaches based on animal or human QTLs or on biological relevance (e.g., dopaminergic or cannabinoid activity in the brain, or exercise performance influencing muscle physiology) have not yet yielded the necessary evidence to specify the genetic mechanisms underlying the heritability of physical activity traits. Third, there is significant genetic modulation of the beneficial effects of daily physical activity patterns on strength and endurance improvements and on health-related parameters like body mass index. Further increases in our understanding of the genetic determinants of sedentary and exercise behaviors as well as the genetic modulation of their effects on fitness and health will be key to meaningful future intervention on these behaviors.

Higher-order cognitive training effects on processing speed-related neural activity: a randomized trial.

PubMed

Motes, Michael A; Yezhuvath, Uma S; Aslan, Sina; Spence, Jeffrey S; Rypma, Bart; Chapman, Sandra B

2018-02-01

Higher-order cognitive training has shown to enhance performance in older adults, but the neural mechanisms underlying performance enhancement have yet to be fully disambiguated. This randomized trial examined changes in processing speed and processing speed-related neural activity in older participants (57-71 years of age) who underwent cognitive training (CT, N = 12) compared with wait-listed (WLC, N = 15) or exercise-training active (AC, N = 14) controls. The cognitive training taught cognitive control functions of strategic attention, integrative reasoning, and innovation over 12 weeks. All 3 groups worked through a functional magnetic resonance imaging processing speed task during 3 sessions (baseline, mid-training, and post-training). Although all groups showed faster reaction times (RTs) across sessions, the CT group showed a significant increase, and the WLC and AC groups showed significant decreases across sessions in the association between RT and BOLD signal change within the left prefrontal cortex (PFC). Thus, cognitive training led to a change in processing speed-related neural activity where faster processing speed was associated with reduced PFC activation, fitting previously identified neural efficiency profiles. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The biological function of antibodies induced by the RTS,S/AS01 malaria vaccine candidate is determined by their fine specificity.

PubMed

Chaudhury, Sidhartha; Ockenhouse, Christian F; Regules, Jason A; Dutta, Sheetij; Wallqvist, Anders; Jongert, Erik; Waters, Norman C; Lemiale, Franck; Bergmann-Leitner, Elke

2016-05-31

Recent vaccine studies have shown that the magnitude of an antibody response is often insufficient to explain efficacy, suggesting that characteristics regarding the quality of the antibody response, such as its fine specificity and functional activity, may play a major role in protection. Previous studies of the lead malaria vaccine candidate, RTS,S, have shown that circumsporozoite protein (CSP)-specific antibodies and CD4(+) T cell responses are associated with protection, however the role of fine specificity and biological function of CSP-specific antibodies remains to be elucidated. Here, the relationship between fine specificity, opsonization-dependent phagocytic activity and protection in RTS,S-induced antibodies is explored. A new method for measuring the phagocytic activity mediated by CSP-specific antibodies in THP-1 cells is presented and applied to samples from a recently completed phase 2 RTS,S/AS01 clinical trial. The fine specificity of the antibody response was assessed using ELISA against three antigen constructs of CSP: the central repeat region, the C-terminal domain and the full-length protein. A multi-parameter analysis of phagocytic activity and fine-specificity data was carried out to identify potential correlates of protection in RTS,S. Results from the newly developed assay revealed that serum samples from RTS,S recipients displayed a wide range of robust and repeatable phagocytic activity. Phagocytic activity was correlated with full-length CSP and C-terminal specific antibody titres, but not to repeat region antibody titres, suggesting that phagocytic activity is primarily driven by C-terminal antibodies. Although no significant difference in overall phagocytic activity was observed with respect to protection, phagocytic activity expressed as 'opsonization index', a relative measure that normalizes phagocytic activity with CS antibody titres, was found to be significantly lower in protected subjects than non-protected subjects. Opsonization index was identified as a surrogate marker of protection induced by the RTS,S/AS01 vaccine and determined how antibody fine specificity is linked to opsonization activity. These findings suggest that the role of opsonization in protection in the RTS,S vaccine may be more complex than previously thought, and demonstrate how integrating multiple immune measures can provide insight into underlying mechanisms of immunity and protection.

Pathogenesis of vascular leak in dengue virus infection.

PubMed

Malavige, Gathsaurie Neelika; Ogg, Graham S

2017-07-01

Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease. © 2017 John Wiley & Sons Ltd.

Reactive oxygen species (ROS) activity of ambient fine particles (PM2.5) measured in Seoul, Korea.

PubMed

Park, Jieun; Park, Eun Ha; Schauer, James J; Yi, Seung-Muk; Heo, Jongbae

2018-05-16

Substantial increase in level of particulate matter has raised concerns in South Korea recently. Ambient particulate matter is classified as Group I carcinogen (IARC, 2013) and multiple epidemiological studies has demonstrated adverse health effects due to exposure of particulate matter. Fine particulate matter (PM 2.5 ) which has a diameter <2.5 μm is likely to penetrate deeply into lung and is known to be eliciting adverse health effects. A number of epidemiological studies have been conducted on adverse health effects of PM-related diseases and mortality rate, yet particulate matter (PM)-induced reactive oxygen species (ROS) activity at the cellular level has not been actively studied in Korea. This study assessed PM-induced oxidative potential by exposure of collected ambient PM 2.5 samples to the rat alveolar macrophage cell line. The characteristics of PM 2.5 in Korea were further characterized by linking chemical constituents and contributing sources to ROS. PM 2.5 mass concentration during the cold season was relatively higher than mass concentration during the warm season and chemical constituents except for Secondary Organic Carbon (SOC) and SO 4 2- which both showed similar trends in both the cold and cold seasons. The concentration of crustal elements was especially high during the cold season which can be an indication of long range transport of Asian dust. Water soluble organic carbon and water soluble transition metals (Cr and Zn) were also shown to be correlated to oxidative potential and metals such as As and V were shown to have a high contribution to ROS activity according to stepwise multiple linear regression. Principal Component Analysis (PCA) results identified six factors that can be interpreted as soil, mobile, industry, secondary inorganic aerosol, secondary organic aerosol and oil combustion. Moreover, through Principal Component Regression (PCR), industry, soil, mobile and SIA were shown to be statistically significant sources in a relation to ROS activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

[CHANGING OF ISCHEMIC M. SOLEUS TETANIC CONTRACTION PARAMETERS IN RATS WITH CHRONIC ALCOHOL INTOXICATION].

PubMed

Melnychuk, O A; Motuziuk, O P; Shvayko, S Ye

2015-01-01

This article deals with the changes of isolated ischemic m. soleus tetanus parameters in rats with chronic alcohol intoxication. The experiments were carried out on 15 male Wistar rats that were divided into three groups for 5 animals in each: group I (control) and two groups in which was induced hind limbs acute muscles ischemia: group II - rats without alcoholic intoxication, group III - rats with chronic alcoholic intoxication. Strain measurement muscle mechanical activity were conducted in isometric mode under conditions of direct electrical muscular preparation stimulation. It is proved that ischemic m. soleus tetanic force in rats with chronic alcoholic intoxication in comparison with rats without alcoholic intoxication does not significant changes. But signifycantly increases the reaching tetanus peak time. It is shown that in rats without alcoholic intoxication and with chronic alcoholic intoxication in comparison with intact animals, significantly decreases the duration of ischemic m. soleus stabile force level. It is shoved significant changes of individual muscles contraction time course of ischemic m. soleus tetanus in this rats group in comparison to intact animal. It is shown that these changes influence on successive muscular contraction efficiency of frequency summation in ischemic m. soleus tetanus and their speed-power characteristics.

Indomethacin Enhances Brown Fat Activity.

PubMed

Hao, Lei; Kearns, Jamie; Scott, Sheyenne; Wu, Dayong; Kodani, Sean D; Morisseau, Christophe; Hammock, Bruce D; Sun, Xiaocun; Zhao, Ling; Wang, Shu

2018-06-01

Indomethacin, a nonsteroidal anti-inflammatory drug, has been shown to induce white adipocyte differentiation; however, its roles in brown adipocyte differentiation and activation in brown adipose tissue (BAT) and obesity are unknown. To address this issue, we treated mouse brown preadipocytes with different doses of indomethacin, and delivered indomethacin to interscapular BAT (iBAT) of obese mice using implanted osmotic pumps. Indomethacin dose dependently increased brown preadipocyte differentiation and upregulated both mRNA and protein expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor (PPAR) γ coactivator 1-alpha. The mechanistic study showed that indomethacin significantly activated the reporter driven by the PPAR response element, indicating that indomethacin may work as a PPAR γ agonist in this cell line. Consistently, indomethacin significantly decreased iBAT mass and fasting blood glucose levels in high-fat diet-induced obesity (DIO) mice. Histologic analysis showed that brown adipocytes of indomethacin-treated mice contained smaller lipid droplets compared with control mice, suggesting that indomethacin alleviated the whitening of BAT induced by the high-fat diet. Moreover, indomethacin significantly increased UCP1 mRNA expression in iBAT. Taken together, this study indicates that indomethacin can promote mouse brown adipocyte differentiation, and might increase brown fat and glucose oxidation capacity in DIO mice. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Energy Deposition in the Body from External Sources to Chemically Trigger Cellular Responses in Desired Localized Regions

NASA Astrophysics Data System (ADS)

Ibsen, Stuart Duncan

One of the major challenges of modern chemotherapy is to deliver a therapeutic dose of active drug to the tumor tissue without causing systemic exposure. The realization of this goal could considerably reduce the negative side effects experienced by patients. The work conducted in this thesis looks at two different approaches to trigger drug activation with the use of external energy sources. This avoids the challenges of relying solely on biochemical and environmental differences as triggers. The two triggers used were low intensity focused ultrasound and 365 nm light delivered with a custom designed needle UV LED fiber optic system. Both can be localized within the body to spatially highlight just the tumor tissue creating a stark differentiation between it and the healthy tissue. The 365nm light based delivery scheme developed here was the first demonstration of a photoactivatable doxorubicin (DOX) prodrug called DOX-PCB. DOX-PCB was shown to be 200 times less toxic than DOX and could be activated to a fully therapeutic form upon exposure to 365nm light. The pharmacokinetics showed a circulation half life comparable to that of DOX and stability against in vivo metabolic degradation. The 365 nm light was shown to adequately irradiate a centimeter of tumor tissue and cause localized activation. In vivo tumors exposed to the light had significantly higher doses of DOX than unexposed control tumors in the same individual. The second delivery scheme made use of focused ultrasound to activate echogenic drug delivery vehicles. These vehicles were the first demonstration of encapsulating microbubbles within liposomes. Specially designed optical equipment documented that the microbubble was ultrasound responsive. The microbubble was shown to violently cavitate and rupture the outer liposome membrane releasing the payload contents. The three dimensional localization of activation was demonstrated in tissue phantoms. The strengths of these two delivery schemes could complement each other when used together. The delivery vehicle could achieve high doses of DOX-PCB within the tumor while the low toxicity prevents harm to the liver and spleen. The 365 nm light could then activate just the DOX-PCB found within the tumor itself causing localized cell death.

Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

PubMed Central

Son, Dong Ju; Akiba, Satoshi; Hong, Jin Tae; Yun, Yeo Pyo; Hwang, Seock Yeon; Park, Young Hyun; Lee, Sung Eun

2014-01-01

PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum) and long pepper (Piper longum), was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX)-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA) metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2), COX-1, COX-2, and thromboxane A2 (TXA2) synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PG)E2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms. PMID:25153972

Dietary selenium increases the antioxidant levels and ATPase activity in the arteries and veins of poultry.

PubMed

Cao, Changyu; Zhao, Xia; Fan, Ruifeng; Zhao, Jinxin; Luan, Yilin; Zhang, Ziwei; Xu, Shiwen

2016-07-01

Selenium (Se) deficiency is associated with the pathogenesis of vascular diseases. It has been shown that oxidative levels and ATPase activity were involved in Se deficiency diseases in humans and mammals; however, the mechanism by how Se influences the oxidative levels and ATPase activity in the poultry vasculature is unclear. We assessed the effects of dietary Se deficiency on the oxidative stress parameters (superoxide dismutase, catalase, and hydroxyl radical) and ATPase (Na(+)K(+)-ATPase, Ca(++)-ATPase, Mg(++)-ATPase, and Ca(++)Mg(++)-ATPase) activity in broiler poultry. A total of 40 broilers (1-day old) were randomly divided into a Se-deficient group (L group, fed a Se-deficient diet containing 0.08 mg/kg Se) and a control group (C group, fed a diet containing sodium selenite at 0.20 mg/kg Se). Then, arteries and veins were collected following euthanasia when typical symptoms of Se deficiency appeared. Antioxidant indexes and ATPase activity were evaluated using standard assays in arteries and veins. The results indicated that superoxide dismutase activity in the artery according to dietary Se deficiency was significantly lower (p < 0.05) compared with the C group. The catalase activity in the veins and hydroxyl radical inhibition in the arteries and veins by dietary Se deficiency were significantly higher (p < 0.05) compared with the C group. The Se-deficient group showed a significantly lower (p < 0.05) tendency in Na(+)K(+)-ATPase activity, Ca(++)-ATPase activity, and Ca(++)Mg(++)-ATPase activity. There were strong correlations between antioxidant indexes and Ca(++)-ATPase activity. Thus, these results indicate that antioxidant indexes and ATPases may have special roles in broiler artery and vein injuries under Se deficiency.

Turmeric and black pepper spices decrease lipid peroxidation in meat patties during cooking.

PubMed

Zhang, Yanjun; Henning, Susanne M; Lee, Ru-Po; Huang, Jianjun; Zerlin, Alona; Li, Zhaoping; Heber, David

2015-05-01

Spices are rich in natural antioxidants and have been shown to be potent inhibitors of lipid peroxidation during cooking of meat. Turmeric contains unique conjugated curcuminoids with strong antioxidant activity. Piperine, one of the main constituents of black pepper, is known to increase the bioavailability of curcuminoids in mouse and human studies when consumed with turmeric. We investigated whether adding black pepper to turmeric powder may further inhibit lipid peroxidation when added to meat patties prior to cooking. The addition of black pepper to turmeric significantly decreased the lipid peroxidation in hamburger meat. When investigating the antioxidant activity of the main chemical markers, we determined that piperine did not exhibit any antioxidant activity. Therefore, we conclude that other black pepper ingredients are responsible for the increased antioxidant activity of combining black pepper with turmeric powder.

Turmeric and black pepper spices decrease lipid peroxidation in meat patties during cooking

PubMed Central

Zhang, Yanjun; Henning, Susanne M.; Lee, Ru-Po; Huang, Jianjun; Zerlin, Alona; Li, Zhaoping; Heber, David

2015-01-01

Abstract Spices are rich in natural antioxidants and have been shown to be potent inhibitors of lipid peroxidation during cooking of meat. Turmeric contains unique conjugated curcuminoids with strong antioxidant activity. Piperine, one of the main constituents of black pepper, is known to increase the bioavailability of curcuminoids in mouse and human studies when consumed with turmeric. We investigated whether adding black pepper to turmeric powder may further inhibit lipid peroxidation when added to meat patties prior to cooking. The addition of black pepper to turmeric significantly decreased the lipid peroxidation in hamburger meat. When investigating the antioxidant activity of the main chemical markers, we determined that piperine did not exhibit any antioxidant activity. Therefore, we conclude that other black pepper ingredients are responsible for the increased antioxidant activity of combining black pepper with turmeric powder. PMID:25582173

Bruton's tyrosine kinase regulates B cell antigen receptor-mediated JNK1 response through Rac1 and phospholipase C-gamma2 activation.

PubMed

Inabe, Kazunori; Miyawaki, Toshio; Longnecker, Richard; Matsukura, Hiroyoshi; Tsukada, Satoshi; Kurosaki, Tomohiro

2002-03-13

Bruton's tyrosine kinase (Btk) is essential for B cell development and B cell antigen receptor (BCR) function. Recent studies have shown that Btk plays an important role in BCR-mediated c-Jun NH(2)-terminal kinase (JNK) 1 activation; however, the mechanism by which Btk participates in the JNK1 response remains elusive. Here we show that the BCR-mediated Rac1 activation is significantly inhibited by loss of Btk, while this Rac1 activation is not affected by loss of phospholipase C-gamma2 (PLC-gamma2). Since PLC-gamma2 is also required for BCR-mediated JNK1 response, our results suggest that Btk regulates Rac1 pathway as well as PLC-gamma2 pathway, both of which contribute to the BCR-mediated JNK1 response.

Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents.

PubMed

Mangasuli, Sumitra N; Hosamani, Kallappa M; Devarajegowda, Hirihalli C; Kurjogi, Mahantesh M; Joshi, Shrinivas D

2018-02-25

A series of novel coumarin-theophylline hybrids were synthesized and examined for their anti-tubercular activity in vitro against Mycobacterium tuberculosis H 37 Rv, anti-microbial activity in vitro against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacterias (Escherichia coli, Salmonella typhi) as well as fungi (Candida albicans). The compound (3a) has shown excellent anti-tubercular activity with MIC of 0.12 μg/mL. Electron donating compounds (3a, 3f) have displayed significant anti-microbial activity. The compounds have also been precisely elucidated using single crystal X-ray diffraction techniques. Molecular docking study has been performed against 4DQU enzyme of Mycobacterium tuberculosis showed good binding interactions and is in agreement with the in vitro results. Copyright © 2018. Published by Elsevier Masson SAS.

Influence of Microtexture on Early Plastic Slip Activity in Ti-6Al-4V Polycrystals

NASA Astrophysics Data System (ADS)

Hémery, Samuel; Dang, Van Truong; Signor, Loïc; Villechaise, Patrick

2018-06-01

Microtextured regions are known to influence the fatigue performance of titanium alloys. Previous studies revealed that crack initiation, accounting for most of the fatigue life, is triggered by slip activity. The influence of microtextured regions on the early plastic slip activity was presently investigated by means of an in situ tensile test performed inside a scanning electron microscope on a bimodal Ti-6Al-4V polycrystalline specimen. A slip trace analysis was carried out in several regions with different crystallographic textures to highlight potentially different deformation behaviors. Significant stress heterogeneities were revealed through an early slip activation in microtextured regions with a predominant [0001] orientation. This point was shown to be related to a locally increased resolved shear stress. Consequences on behavior under cyclic loadings are finally discussed.

Effect of a dietary supplement containing blueberry and sea buckthorn concentrate on antioxidant capacity in type 1 diabetic children.

PubMed

Nemes-Nagy, E; Szocs-Molnár, T; Dunca, I; Balogh-Sămărghiţan, V; Hobai, S; Morar, R; Pusta, D L; Crăciun, E C

2008-12-01

Many studies have shown that oxidative stress plays an important role in the etiology of diabetes and its complications. New methods of treatment for prevention and control of this disease is a priority for the international scientific community. We investigated the relationship between the glycated hemoglobin, C peptide and two antioxidant enzymes. Thirty type 1 diabetic children were treated with a blueberry and sea buckthorn concentrate for two months. After two months of administering the product to diabetic children, the erythrocyte superoxide dismutase activity was significantly higher (p < 0.05). Levels of glycated hemoglobin were significantly lower (p < 0.05). The activity of whole blood glutathione peroxidase was moderately increased but the difference was not statistically significant. C peptide concentration was significantly higher after treatment with this dietary supplement (p < 0.05). These results suggest that treatment with this dietary supplement has a beneficial effect in the treatment of type 1 diabetic children and it should be considered as a phytotherapeutic product in the fight against diabetes mellitus.

Metabolic consequences of limited substrate anion permeability in brown fat mitochondria from a hibernator, the golden hamster.

PubMed

Cannon, B; Bernson, V S; Nedergaard, J

1984-08-31

Brown fat mitochondria obtained from a hibernator, the golden hamster, were investigated in order to elucidate the significance of membrane permeability for metabolic functioning at different temperatures. The mitochondria were shown to have active permeases for phosphate and pyruvate, but very poorly developed permeases for di- and tricarboxylate substrate anions. This was shown with both osmotic swelling techniques and respiration-driven uptake studies. It was shown that the very limited malate permeation observed was compatible with it being a non-carrier-mediated diffusion process. The role of malate transport in supporting fatty-acid oxidation in vitro as a function of temperature was studied in detail. The results support our earlier suggestion that physiologically pyruvate carboxylase probably functions to generate oxaloacetate when high concentrations of condensing partner are needed during thermogenesis. They may also explain earlier observations that acetate was produced from palmitoyl-carnitine at low temperatures even when malate was present; this is here shown to be due to the limited malate permeability at these low temperatures. Thus, even at the body temperature of the hibernating hamster (4-5 degrees C), brown fat is probably able to combust fatty acids totally.

Redistribution of boron in leaves reduces boron toxicity

PubMed Central

Fitzpatrick, Kate L

2009-01-01

High soil boron (B) concentrations lead to the accumulation of B in leaves, causing the development of necrotic regions in leaf tips and margins, gradually extending back along the leaf. Plants vary considerably in their tolerance to B toxicity, and it was recently discovered that one of the tolerance mechanisms involved extrusion of B from the root. Expression of a gene encoding a root B efflux transporter was shown to be much higher in tolerant cultivars. In our current research we have shown that the same gene is also upregulated in leaves. However, unlike in the root, the increased activity of the B efflux transporter in the leaves cannot reduce the tissue B concentration. Instead, we have shown that in tolerant cultivars, these transporters redistribute B from the intracellular phase where it is toxic, into the apoplast which is much less sensitive to B. These results provide an explanation of why different cultivars with the same leaf B concentrations can show markedly different toxicity symptoms. We have also shown that rain can remove a large proportion of leaf B, leading to significant improvements of growth of both leaves and roots. PMID:20009556

Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial.

PubMed

Johannesson, Elisabet; Simrén, Magnus; Strid, Hans; Bajor, Antal; Sadik, Riadh

2011-05-01

Physical activity has been shown to be effective in the treatment of conditions, such as fibromyalgia and depression. Although these conditions are associated with irritable bowel syndrome (IBS), no study has assessed the effect of physical activity on gastrointestinal (GI) symptoms in IBS. The aim was to study the effect of physical activity on symptoms in IBS. We randomized 102 patients to a physical activity group and a control group. Patients of the physical activity group were instructed by a physiotherapist to increase their physical activity, and those of the control group were instructed to maintain their lifestyle. The primary end point was to assess the change in the IBS Severity Scoring System (IBS-SSS). A total of 38 (73.7% women, median age 38.5 (19-65) years) patients in the control group and 37 (75.7% women, median age 36 (18-65) years) patients in the physical activity group completed the study. There was a significant difference in the improvement in the IBS-SSS score between the physical activity group and the control group (-51 (-130 and 49) vs. -5 (-101 and 118), P=0.003). The proportion of patients with increased IBS symptom severity during the study was significantly larger in the control group than in the physical activity group. Increased physical activity improves GI symptoms in IBS. Physically active patients with IBS will face less symptom deterioration compared with physically inactive patients. Physical activity should be used as a primary treatment modality in IBS.

SMA Hybrid Composites for Dynamic Response Abatement Applications

NASA Technical Reports Server (NTRS)

Turner, Travis L.

2000-01-01

A recently developed constitutive model and a finite element formulation for predicting the thermomechanical response of Shape Memory Alloy (SMA) hybrid composite (SMAHC) structures is briefly described. Attention is focused on constrained recovery behavior in this study, but the constitutive formulation is also capable of modeling restrained or free recovery. Numerical results are shown for glass/epoxy panel specimens with embedded Nitinol actuators subjected to thermal and acoustic loads. Control of thermal buckling, random response, sonic fatigue, and transmission loss are demonstrated and compared to conventional approaches including addition of conventional composite layers and a constrained layer damping treatment. Embedded SMA actuators are shown to be significantly more effective in dynamic response abatement applications than the conventional approaches and are attractive for combination with other passive and/or active approaches.

Oestrogen receptor-alpha activation augments post-exercise myoblast proliferation.

PubMed

Thomas, A; Bunyan, K; Tiidus, P M

2010-01-01

Our laboratory has shown that oestrogen acts to augment myoblast (satellite cell) activation, proliferation and total number and that this may occur through an oestrogen receptor (OR)-mediated mechanism. The purpose of this study was to further investigate the mechanism of oestrogen influence on augmentation of post-exercise myoblast numbers through use of a specific OR-alpha agonist, propyl pyrazole triol (PPT). Ovariectomized rats were used (n = 64) and separated into four groups: sham, oestrogen supplemented, agonist supplemented, and a combined oestrogen and agonist supplemented group. These groups were further subdivided into control (unexercised) and exercise groups. Surgical removal of white vastus and soleus muscles was performed 72 h post-exercise. Muscle samples were immunostained for the myoblast markers Pax7 and MyoD. A significant increase in total (Pax7-positive) and activated (MyoD-positive) myoblasts was found in all groups post-exercise. A further significant augmentation of total and activated myoblasts occurred in oestrogen supplemented, agonist supplemented and the combined oestrogen and agonist supplemented groups post-exercise in white vastus and soleus muscles relative to unsupplemented animals. These results demonstrate that both oestrogen and the specific OR-alpha receptor agonist, PPT, can significantly and to similar degrees augment myoblast number and activation following exercise-induced muscle damage. This suggests that oestrogen acts through an OR-mediated mechanism to stimulate myoblast proliferation following exercise, with OR-alpha playing a primary role.

Malassezia yeasts produce a collection of exceptionally potent activators of the Ah (dioxin) receptor detected in diseased human skin

PubMed Central

Magiatis, Prokopios; Pappas, Periklis; Gaitanis, George; Mexia, Nikitia; Melliou, Eleni; Galanou, Maria; Vlachos, Christophoros; Stathopoulou, Konstantina; Skaltsounis, Alexios Leandros; Marselos, Marios; Velegraki, Aristea; Denison, Michael S.; Bassukas, Ioannis D.

2013-01-01

Malassezia yeasts are commensal microorganisms which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia associated diseases demonstrated 10–1000 fold higher AhR activating capacity than control skin extracts. LC/MS/MS analysis of the patients’ extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9/12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture-extracts and pure metabolites in HaCaT cells by Reverse Transcriptase Real-Time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1 and AhRR. Indirubin and FICZ activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared to the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development. PMID:23448877

Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS.

PubMed

Brown, Audrey E; Dibnah, Beth; Fisher, Emily; Newton, Julia L; Walker, Mark

2018-06-29

Skeletal muscle fatigue and post-exertional malaise are key symptoms of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (ME/CFS). We have previously shown that AMP-activated protein kinase (AMPK) activation and glucose uptake are impaired in primary human skeletal muscle cell cultures derived from patients with ME/CFS in response to electrical pulse stimulation (EPS), a method which induces contraction of muscle cells in vitro The aim of the present study was to assess if AMPK could be activated pharmacologically in ME/CFS. Primary skeletal muscle cell cultures from patients with ME/CFS and healthy controls were treated with either metformin or compound 991. AMPK activation was assessed by Western blot and glucose uptake measured. Both metformin and 991 treatment significantly increased AMPK activation and glucose uptake in muscle cell cultures from both controls and ME/CFS. Cellular ATP content was unaffected by treatment although ATP content was significantly decreased in ME/CFS compared with controls. Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS. This suggests that the failure of EPS to activate AMPK in these muscle cultures is due to a defect proximal to AMPK. Further work is required to delineate the defect and determine whether pharmacological activation of AMPK improves muscle function in patients with ME/CFS. © 2018 The Author(s).

A novel hydroxyapatite film coated with ionic silver via inositol hexaphosphate chelation prevents implant-associated infection

NASA Astrophysics Data System (ADS)

Funao, Haruki; Nagai, Shigenori; Sasaki, Aya; Hoshikawa, Tomoyuki; Tsuji, Takashi; Okada, Yasunori; Koyasu, Shigeo; Toyama, Yoshiaki; Nakamura, Masaya; Aizawa, Mamoru; Matsumoto, Morio; Ishii, Ken

2016-03-01

Various silver-coated implants have been developed to prevent implant-associated infections, and have shown dramatic effects in vitro. However, the in vivo results have been inconsistent. Recent in vitro studies showed that silver exerts antibacterial activity by mediating the generation of reactive oxygen species in the presence of oxygen. To maintain its antibacterial activity in vivo, the silver should remain in an ionic state and be stably bound to the implant surface. Here, we developed a novel bacteria-resistant hydroxyapatite film in which ionic silver is immobilized via inositol hexaphosphate chelation using a low-heat immersion process. This bacteria-resistant coating demonstrated significant antibacterial activity both in vitro and in vivo. In a murine bioluminescent osteomyelitis model, no bacteria were detectable 21 days after inoculation with S. aureus and placement of this implant. Serum interleukin-6 was elevated in the acute phase in this model, but it was significantly lower in the ionic-silver group than the control group on day 2. Serum C-reactive protein remained significantly higher in the control group than the ionic-silver group on day 14. Because this coating is produced by a low-heat immersion process, it can be applied to complex structures of various materials, to provide significant protection against implant-associated infections.

The difference in the effect of glutamate and NO synthase inhibitor on free calcium concentration and Na+, K+-ATPase activity in synaptosomes from various brain regions.

PubMed

Avrova, N F; Shestak, K I; Zakharova, I O; Sokolova, T V; Leont'ev, V G

1999-09-01

The significant increase of free calcium concentration ([Ca2+]i) was found in rat cerebral cortex synaptosomes and hippocampal crude synaptosomal fraction after their exposure to glutamate. But no change of [Ca2+]i was revealed in cerebellar synaptosomes, the slight increase of [Ca2+]i in striatal synaptosomes was not significant. The presence of Ng-nitro-L-arginine methyl ester (L-NAME) in the incubation medium practically prevented the increase of [Ca2+]i initiated by glutamate in cerebral cortex synaptosomes, but not in hippocampal ones. The significant diminution of [Ca2+]i in the presence of this inhibitor was shown in striatal synaptosomes exposed to glutamate. Na+,K+-ATPase activity is significantly lower in cerebral cortex, striatal and hippocampal synaptosomes exposed to glutamate. L-NAME prevented the inactivation of this enzyme by glutamate. In cerebellar synaptosomes the tendency to the decrease of enzymatic activity in the presence of L-NAME was on the contrary noticed. Thus, the data obtained provide evidence of the protective effect of NO synthase inhibitor in brain cortex and striatal synaptosomes, but not in cerebellar synaptosomes. Synaptosomes appear to be an adequate model to study the regional differences in the mechanism of toxic effect of excitatory amino acids.

Effects of nitrogen fertilization on the phenolic composition and antioxidant properties of basil (Ocimum basilicum L.).

PubMed

Nguyen, Phuong M; Niemeyer, Emily D

2008-09-24

Many herbs and spices have been shown to contain high levels of polyphenolic compounds with potent antioxidant properties. In the present study, we explore how nutrient availability, specifically nitrogen fertilization, affects the production of polyphenolic compounds in three cultivars (Dark Opal, Genovese, and Sweet Thai) of the culinary herb, basil ( Ocimum basilicum L.). Nitrogen fertilization was found to have a significant effect on total phenolic levels in Dark Opal ( p < 0.001) and Genovese ( p < 0.001) basil with statistically higher phenolic contents observed when nutrient availability was limited at the lowest (0.1 mM) applied nitrogen treatment. Similarly, basil treated at the lowest nitrogen fertilization level generally contained significantly higher rosmarinic ( p = 0.001) and caffeic ( p = 0.001) acid concentrations than basil treated at other nitrogen levels. Nitrogen fertilization also affected antioxidant activity ( p = 0.002) with basil treated at the highest applied nitrogen level, 5.0 mM, exhibiting lower antioxidant activity than all other nitrogen treatments. The anthocyanin content of Dark Opal basil was not affected by applied nitrogen level, but anthocyanin concentrations were significantly impacted by growing season ( p = 0.001). Basil cultivar was also determined to have a statistically significant effect on total phenolic levels, rosmarinic and caffeic acid concentrations, and antioxidant activities.

Interaction of vitamin E and exercise training on oxidative stress and antioxidant enzyme activities in rat skeletal muscles.

PubMed

Chang, Chen-Kang; Huang, Hui-Yu; Tseng, Hung-Fu; Hsuuw, Yan-Der; Tso, Tim K

2007-01-01

It has been shown that free radicals are increased during intensive exercise. We hypothesized that vitamin E (vit E) deficiency, which will increase oxidative stress, would augment the training-induced adaptation of antioxidant enzymes. This study investigated the interaction effect of vit E and exercise training on oxidative stress markers and activities of antioxidant enzymes in red quadriceps and white gastrocnemius of rats in a 2x2 design. Thirty-two male rats were divided into trained vit E-adequate, trained vit E-deficient, untrained vit E-adequate, and untrained vit E-deficient groups. The two trained groups swam 6 h/day, 6 days/week for 8 weeks. The two vit E-deficient groups consumed vit E-free diet for 8 weeks. Vitamin E-training interaction effect was significant on thiobarbituric acid reactive substances (TBARSs), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in both muscles. The trained vit E-deficient group showed the highest TBARS and GPX activity and the lowest SOD activity in both muscles. A significant vit E effect on glutathione reductase and catalase was present in both muscles. Glutathione reductase and catalase activities were significantly lower in the two vit E-adequate groups combined than in the two vit E-deficient groups combined in both muscles. This study shows that vit E status and exercise training have interactive effect on oxidative stress and GPX and SOD activities in rat skeletal muscles. Vitamin E deprivation augmented the exercise-induced elevation in GPX activity while inhibiting exercise-induced SOD activity, possibly through elevated oxidative stress.

Response of Gut Microbiota to Metabolite Changes Induced by Endurance Exercise.

PubMed

Zhao, Xia; Zhang, Zhujun; Hu, Bin; Huang, Wei; Yuan, Chao; Zou, Lingyun

2018-01-01

A few animal studies have shown that wheel running could reverse an unhealthy status by shifting the gut microbial composition, but no investigations have studied the effect of endurance running, such as marathon running, on human gut microbial communities. Since many findings have shown that marathon running immediately causes metabolic changes in blood, urine, muscles and lymph that potentially impact the gut microbiota (GM) within several hours. Here, we investigated whether the GM immediately responds to the enteric changes in amateur half-marathon runners. Alterations in the metabolic profile and microbiota were investigated in fecal samples based on an untargeted metabolomics methodology and 16S rDNA sequencing analysis. A total of 40 fecal metabolites were found significantly changed after finishing a half-marathon race. The most significantly different metabolites were organic acids (the major increased metabolites) and nucleic acid components (the major decreased metabolites). The enteric changes induced by running did not affect the α-diversity of the GM, but the abundances of certain microbiota members were shown to be significantly different before and after running. The family Coriobacteriaceae was identified as a potential biomarker that links exercise with health improvement. Functional prediction showed a significantly activated "Cell motility" function of GM within participants after running. Correlation analysis indicated that the observed differential GM in our study might have been the shared outcome of running and diet. This study provided knowledge regarding the health impacts of marathon running from the perspective of GM for the first time. Our data indicated that long-distance endurance running can immediately cause striking metabolic changes in the gut environment. Gut microbes can rapidly respond to the altered fecal metabolites by adjusting certain bacterial taxa. These findings highlighted the health-promoting benefits of exercise from the perspective of GM.

Citrus bergamia Juice Extract Attenuates β-Amyloid-Induced Pro-Inflammatory Activation of THP-1 Cells Through MAPK and AP-1 Pathways

PubMed Central

Currò, Monica; Risitano, Roberto; Ferlazzo, Nadia; Cirmi, Santa; Gangemi, Chiara; Caccamo, Daniela; Ientile, Riccardo; Navarra, Michele

2016-01-01

Flavonoids have been shown to be effective in protecting against age-related cognitive and motor decline in both in vitro and in vivo models. Recently, a flavonoid-rich extract of Citrus bergamia juice (BJe) has been shown to display anti-oxidant and anti-inflammatory properties against LPS-induced activation of human THP-1 monocytes. In the light of these observations, we wondered whether BJe may be beneficial against neuroinflammatory processes, such as those observed in Alzheimer’s disease. To this aim we used THP-1 monocytes to investigate the mechanisms underlying the beneficial potential of BJe against amyloid-beta1–42 (Aβ1−42) -mediated inflammation. Exposure of THP-1 cells to Aβ1−42 significantly induced the expression and secretion of IL-6 and IL-1β in THP-1 cells and increased the phosphorylation of ERK 1/2 as well as p46 and p54 members of JNK family. Moreover, Aβ1−42 raises AP-1 DNA binding activity in THP-1-treated cells. Interestingly, all these effects were reduced in the presence of BJe. Our data indicate that BJe may effectively counteract the pro-inflammatory activation of monocytes/microglial cells exposed to amyloid fibrils, suggesting a promising role as a natural drug against neuroinflammatory processes. PMID:26853104

Biochemical and Pharmacological Characterizations of ESI-09 Based EPAC Inhibitors: Defining the ESI-09 “Therapeutic Window”

PubMed Central

Zhu, Yingmin; Chen, Haijun; Boulton, Stephen; Mei, Fang; Ye, Na; Melacini, Giuseppe; Zhou, Jia; Cheng, Xiaodong

2015-01-01

The cAMP signaling cascade is one of the most frequently targeted pathways for the development of pharmaceutics. A plethora of recent genetic and pharmacological studies suggest that exchange proteins directly activated by cAMP (EPACs) are implicated in multiple pathologies. Selective EPAC inhibitors have been recently developed. One specific inhibitor, ESI-09, has been shown to block EPAC activity and functions, as well as to recapitulate genetic phenotypes of EPAC knockout mice when applied in vivo. However, a recent study raised concern that ESI-09 might act as a non-specific protein denaturant. Herein, we present a detailed biochemical and pharmacological characterization, as well as a structure-activity relationship (SAR) analysis of ESI-09. Our studies show that ESI-09 dose-dependently inhibits activity of both EPAC1 and EPAC2 with apparent IC50 values well below the concentrations shown to induce “protein denaturation”. Moreover, the ESI-09's action towards EPAC proteins is highly sensitive to minor modifications of the 3-chlorophenyl moiety. Taken together, these results demonstrate that ESI-09 indeed acts as an EPAC specific antagonist and does not significantly destabilize/denature proteins at pharmacological effective concentrations. This conclusion is further supported by NMR data showing that ESI-09 induces residue-dependent chemical shift changes at low concentrations, while preserving well dispersed peaks. PMID:25791905

Nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice.

PubMed

Ragelle, Héloïse; Crauste-Manciet, Sylvie; Seguin, Johanne; Brossard, Denis; Scherman, Daniel; Arnaud, Philippe; Chabot, Guy G

2012-05-10

The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has shown antitumour activity but its administration is complicated by its low water solubility. Our aim was to incorporate fisetin into a nanoemulsion to improve its pharmacokinetics and therapeutic efficacy. Solubility and emulsification tests allowed to develop an optimal nanoemulsion composed of Miglyol 812N/Labrasol/Tween 80/Lipoid E80/water (10%/10%/2.5%/1.2%/76.3%). The nanoemulsion had an oil droplet diameter of 153 ± 2 nm, a negative zeta potential (-28.4 ± 0.6 mV) and a polydispersity index of 0.129. The nanoemulsion was stable at 4 °C for 30 days, but phase separation occurred at 20 °C. Pharmacokinetic studies in mice revealed that the fisetin nanoemulsion injected intravenously (13 mg/kg) showed no significant difference in systemic exposure compared to free fisetin. However, when the fisetin nanoemulsion was administered intraperitoneally, a 24-fold increase in fisetin relative bioavailability was noted, compared to free fisetin. Additionally, the antitumour activity of the fisetin nanoemulsion in Lewis lung carcinoma bearing mice occurred at lower doses (36.6 mg/kg) compared to free fisetin (223 mg/kg). In conclusion, we have developed a stable nanoemulsion of fisetin and have shown that it could improve its relative bioavailability and antitumour activity. Copyright © 2012 Elsevier B.V. All rights reserved.

Biochemical and pharmacological characterizations of ESI-09 based EPAC inhibitors: defining the ESI-09 "therapeutic window".

PubMed

Zhu, Yingmin; Chen, Haijun; Boulton, Stephen; Mei, Fang; Ye, Na; Melacini, Giuseppe; Zhou, Jia; Cheng, Xiaodong

2015-03-20

The cAMP signaling cascade is one of the most frequently targeted pathways for the development of pharmaceutics. A plethora of recent genetic and pharmacological studies suggest that exchange proteins directly activated by cAMP (EPACs) are implicated in multiple pathologies. Selective EPAC inhibitors have been recently developed. One specific inhibitor, ESI-09, has been shown to block EPAC activity and functions, as well as to recapitulate genetic phenotypes of EPAC knockout mice when applied in vivo. However, a recent study raised concern that ESI-09 might act as a non-specific protein denaturant. Herein, we present a detailed biochemical and pharmacological characterization, as well as a structure-activity relationship (SAR) analysis of ESI-09. Our studies show that ESI-09 dose-dependently inhibits activity of both EPAC1 and EPAC2 with apparent IC50 values well below the concentrations shown to induce "protein denaturation". Moreover, the ESI-09's action towards EPAC proteins is highly sensitive to minor modifications of the 3-chlorophenyl moiety. Taken together, these results demonstrate that ESI-09 indeed acts as an EPAC specific antagonist and does not significantly destabilize/denature proteins at pharmacological effective concentrations. This conclusion is further supported by NMR data showing that ESI-09 induces residue-dependent chemical shift changes at low concentrations, while preserving well dispersed peaks.

Activated protein C (APC) can increase bone anabolism via a protease-activated receptor (PAR)1/2 dependent mechanism.

PubMed

Shen, Kaitlin; Murphy, Ciara M; Chan, Ben; Kolind, Mille; Cheng, Tegan L; Mikulec, Kathy; Peacock, Lauren; Xue, Meilang; Park, Sang-Youel; Little, David G; Jackson, Chris J; Schindeler, Aaron

2014-12-01

Activated Protein C (APC) is an anticoagulant with strong cytoprotective properties that has been shown to promote wound healing. In this study APC was investigated for its potential orthopedic application using a Bone Morphogenetic Protein 2 (rhBMP-2) induced ectopic bone formation model. Local co-administration of 10 µg rhBMP-2 with 10 µg or 25 µg APC increased bone volume at 3 weeks by 32% (N.S.) and 74% (p<0.01) compared to rhBMP-2 alone. This was associated with a significant increase in CD31+ and TRAP+ cells in tissue sections of ectopic bone, consistent with enhanced vascularity and bone turnover. The actions of APC are largely mediated by its receptors endothelial protein C receptor (EPCR) and protease-activated receptors (PARs). Cultured pre-osteoblasts and bone nodule tissue sections were shown to express PAR1/2 and EPCR. When pre-osteoblasts were treated with APC, cell viability and phosphorylation of ERK1/2, Akt, and p38 were increased. Inhibition with PAR1 and sometimes PAR2 antagonists, but not with EPCR blocking antibodies, ameliorated the effects of APC on cell viability and kinase phosphorylation. These data indicate that APC can affect osteoblast viability and signaling, and may have in vivo applications with rhBMP-2 for bone repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Design of 2.4Ghz CMOS Floating Active Inductor LNA using 130nm Technology

NASA Astrophysics Data System (ADS)

Muhamad, M.; Soin, N.; Ramiah, H.

2018-03-01

This paper presents about design and optimization of CMOS active inductor integrated circuit. This active inductor implements using Silterra 0.13μm technology and simulated using Cadence Virtuoso and Spectre RF. The center frequency for this active inductor is at 2.4 GHz which follow IEEE 802.11 b/g/n standard. To reduce the chip size of silicon, active inductor is used instead of passive inductor at low noise amplifier LNA circuit. This inductor test and analyse by low noise amplifier circuit. Comparison between active with passive inductor based on LNA circuit has been performed. Result shown that the active inductor has significantly reduce the chip size with 73 % area without sacrificing the noise figure and gain of LNA which is the most important criteria in LNA. The best low noise amplifier provides a power gain (S21) of 20.7 dB with noise figure (NF) of 2.1dB.

Antithrombotic Potential of Tormentil Extract in Animal Models

PubMed Central

Marcinczyk, Natalia; Jarmoc, Dominika; Leszczynska, Agnieszka; Zakrzeska, Agnieszka; Kramkowski, Karol; Strawa, Jakub; Gromotowicz-Poplawska, Anna; Chabielska, Ewa; Tomczyk, Michal

2017-01-01

Potentilla species that have been investigated so far display pharmacological activity mainly due to the presence of polyphenols. Recently, it was shown that polyphenol-rich extract from rhizome of Potentilla erecta (tormentil extract) affects the metabolism of arachidonic acid and exerts both anti-inflammatory and anti-oxidant activities, suggesting a possible effect on thrombosis. Accordingly, the aim of the study was to evaluate the effect of tormentil extract on haemostasis in a rat model of thrombosis. Lyophilized water-methanol extract from P. erecta rhizome was administrated per os for 14 days in doses of 100, 200, and 400 mg/kg in a volume of 2 mL/kg in a 5% water solution of gummi arabici (VEH). In the in vivo experiment an electrically induced carotid artery thrombosis model with blood flow monitoring was used in Wistar rats. Collected blood samples were analyzed ex vivo functionally and biochemically for changes in haemostasis. Tormentil extract (400 mg/kg) significantly decreased thrombus weight and prolonged the time to carotid artery occlusion and bleeding time without changes in the blood pressure. In the ex vivo experiment tormentil extract (400 mg/kg) reduced thromboxane production and decreased t-PA activity, while total t-PA concentration, as well as total PAI-1 concentration and PAI-1 activity remained unchanged. Furthermore, tormentil extract (400 mg/kg) decreased bradykinin concentration and shortened the time to reach maximal optical density during fibrin generation. Prothrombin time, activated partial thromboplastin time, QUICK index, fibrinogen level, and collagen-induced aggregation remained unchanged. To investigate the involvement of platelets in the antithrombotic effect of tormentil, the extract was administrated per os for 2 days to mice and irreversible platelets activation after ferric chloride induced thrombosis was evaluated under intravital conditions using confocal microscopy system. In this model tormentil extract (400 mg/kg) significantly reduced platelet activation at the same extent as acetylsalicylic acid. Taken together, we have shown for the first time that tormentil extract inhibits arterial thrombosis in platelet- and endothelial-dependent mechanisms without hemodynamic changes. Further studies on the detailed mechanism of action of tormentil extract toward fibrinolysis and the kinin system should be carried out. PMID:28860991

Evidence of Jovian active longitude: 3. Observational constraints

NASA Astrophysics Data System (ADS)

Galopeau, P. H. M.; Boudjada, M. Y.

2010-12-01

The occurrence probability of the Io-controlled Jovian decameter radio emissions depends on the central meridian longitude and the orbital phase of the satellite Io. Investigations by Galopeau et al. (2004, 2007) have shown that some specific Jovian "active" longitudes favor the radiation. The authors proposed a model which involves the cyclotron maser instability (CMI) as the mechanism at the origin of the Jovian radio emissions produced near the local gyrofrequency, along an active magnetic field line carried away by Io through its revolution around Jupiter. Those studies brought out the existence of an active longitude anchored in Jupiter's magnetic field and directly related to the efficiency of the CMI. In the present analysis, we model the four occurrence regions associated to Io-controlled sources. This approach is in a reverse way of the parametric method developed by Galopeau et al. (2007). The properties of the propagation and polarization of the radio wave, derived from the CMI, are the key ingredients for the study of the beaming cone. It is shown that the lead angle of the active magnetic field line relative to Io has a significant effect on both the selection of the propagation conditions and the limit between the right- and left-hand polarization states. The modeled and observed occurrence regions are found to be similar for a lead angle of about 20°. However, it seems that the behaviors of the southern and northern sources are not alike despite a common generation mechanism.

Decadal variability in the Northern Hemisphere winter circulation: Role of internal and external drivers

NASA Astrophysics Data System (ADS)

Maliniemi, V.; Asikainen, T.; Mursula, K.

2017-12-01

Northern Hemisphere winter circulation is known to be affected by both internal and external (solar-related) forcings. Earlier studies have shown ENSO and volcanic activity to produce negative and positive North Atlantic Oscillation (NAO) type responses, respectively. In addition, recent studies have shown a positive NAO response related to both geomagnetic activity (proxy for solar wind driven particle precipitation) and sunspot activity (proxy for solar irradiance). These solar-related signals have been suggested to be due to the changes in the polar vortex. Here the relative role of these four internal and external drivers on wintertime circulation in the Northern Hemisphere is studied. The phase of the quasi-biennial oscillation (QBO) is used to study the driver responses for different stratospheric conditions. Moreover, the effects are separated for early (Dec/Jan) and late (Feb/Mar) winter. The global pattern of ENSO is very similar (negative NAO) otherwise, but in early winter and westerly QBO the pattern is changed in the Atlantic sector to a weakly positive NAO. The positive NAO pattern due to volcanic activity is more pronounced for westerly QBO in both early and late winter. The positive NAO pattern produced by geomagnetic activity is obtained during easterly QBO phase in both early and late winter. Sunspot related NAO response in late winter is also strongly modulated by the QBO phase. These results imply that the stratospheric conditions expressed by QBO significantly modulate the way the internal and external drivers affect the Northern Hemisphere winter climate.

Aluminum-activated citrate and malate transporters from the MATE and ALMT families function independently to confer Arabidopsis aluminum tolerance.

PubMed

Liu, Jiping; Magalhaes, Jurandir V; Shaff, Jon; Kochian, Leon V

2009-02-01

Aluminum-activated root malate and citrate exudation play an important role in plant Al tolerance. This paper characterizes AtMATE, a homolog of the recently discovered sorghum and barley Al-tolerance genes, shown here to encode an Al-activated citrate transporter in Arabidopsis. Together with the previously characterized Al-activated malate transporter, AtALMT1, this discovery allowed us to examine the relationship in the same species between members of the two gene families for which Al-tolerance genes have been identified. AtMATE is expressed primarily in roots and is induced by Al. An AtMATE T-DNA knockdown line exhibited very low AtMATE expression and Al-activated root citrate exudation was abolished. The AtALMT1 AtMATE double mutant lacked both Al-activated root malate and citrate exudation and showed greater Al sensitivity than the AtALMT1 mutant. Therefore, although AtALMT1 is a major contributor to Arabidopsis Al tolerance, AtMATE also makes a significant but smaller contribution. The expression patterns of AtALMT1 and AtMATE and the profiles of Al-activated root citrate and malate exudation are not affected by the presence or absence of the other gene. These results suggest that AtALMT1-mediated malate exudation and AtMATE-mediated citrate exudation evolved independently to confer Al tolerance in Arabidopsis. However, a link between regulation of expression of the two transporters in response to Al was identified through work on STOP1, a transcription factor that was previously shown to be necessary for AtALMT1 expression. Here we show that STOP1 is also required for AtMATE expression and Al-activated citrate exudation.

Efficient activation of transcription in yeast by the BPV1 E2 protein.

PubMed Central

Stanway, C A; Sowden, M P; Wilson, L E; Kingsman, A J; Kingsman, S M

1989-01-01

The full-length gene product encoded by the E2 open reading frame (ORF) of bovine papillomavirus type 1 (BPV1) is a transcriptional transactivator. It is believed to mediate its effect on the BPV1 long control region (LCR) by binding to motifs with the consensus sequence ACCN6GGT. The minimal functional cis active site, called the E2 response element (E2RE), in mammalian cells comprises two copies of this motif. Here we have shown that E2 can function in Saccharomyces cerevisiae by placing an E2RE upstream of a synthetic yeast assay promoter which consists of a TATA motif and an mRNA initiation site, spaced correctly. This E2RE-minimal promoter is only transcriptionally active in the presence of E2 protein and the resulting mRNA is initiated at the authentic start site. This is the first report of a mammalian viral transactivator functioning in yeast. The level of activation by E2 via the E2RE was the same as observed with the highly efficient authentic PGK promoter where the upstream activation sequence is composed of three distinct elements. Furthermore a single E2 motif which is insufficient in mammalian cells as an activation site was as efficiently utilized in yeast as the E2RE (2 motifs). Previous studies have shown that mammalian cellular activators can function in yeast and our data now extend this to viral-specific activators. Our data indicate however that while the mechanism of transactivation is broadly conserved there may be significant differences at the detailed level. Images PMID:2539584

Chronic inhibition of Ca(2+)/calmodulin kinase II activity in the pilocarpine model of epilepsy.

PubMed

Churn, S B; Kochan, L D; DeLorenzo, R J

2000-09-01

The development of symptomatic epilepsy is a model of long-term plasticity changes in the central nervous system. The rat pilocarpine model of epilepsy was utilized to study persistent alterations in calcium/calmodulin-dependent kinase II (CaM kinase II) activity associated with epileptogenesis. CaM kinase II-dependent substrate phosphorylation and autophosphorylation were significantly inhibited for up to 6 weeks following epileptogenesis in both the cortex and hippocampus, but not in the cerebellum. The net decrease in CaM kinase II autophosphorylation and substrate phosphorylation was shown to be due to decreased kinase activity and not due to increased phosphatase activity. The inhibition in CaM kinase II activity and the development of epilepsy were blocked by pretreating seizure rats with MK-801 indicating that the long-lasting decrease in CaM kinase II activity was dependent on N-methyl-D-aspartate receptor activation. In addition, the inhibition of CaM kinase II activity was associated in time and regional localization with the development of spontaneous recurrent seizure activity. The decrease in enzyme activity was not attributed to a decrease in the alpha or beta kinase subunit protein expression level. Thus, the significant inhibition of the enzyme occurred without changes in kinase protein expression, suggesting a long-lasting, post-translational modification of the enzyme. This is the first published report of a persistent, post-translational alteration of CaM kinase II activity in a model of epilepsy characterized by spontaneous recurrent seizure activity.

Polysaccharide enhances Radix Saposhnikoviae efficacy through inhibiting chromones decomposition in intestinal tract.

PubMed

Yang, Jing-Ming; Jiang, Hua; Dai, Hong-Liang; Wang, Zi-Wei; Jia, Gui-Zhi; Meng, Xiang-Cai

2016-09-06

Vegetative but not reproductive stage of Saposhnikovia divaricate (Turxz.) schischk possesses pharmacological activities. However, our recent study showed that reproductive S. divaricate supplemented with polysaccharide showed evidently elevated pharmacological activities and increased cimifugin content in rat serum. The aims of present study were to assess the influence of polysaccharides on the chromones pharmacological activities in Radix Saposhnikoviae (RS), the dried root of vegetative stage of S. divaricate, and to explore the underlying mechanisms. Only cimifugin was detected in the plasma of chromone treated animals and RS polysaccharide significantly increased the plasma content of cimifugin. It was shown that neither cimifugin absorption nor glycoside components transformation in simulated digestive fluid was affected by RS polysaccharide. However, a significant promotion of transformation of cimifugin to more stable prime-O-glucosylcimifugin (PGCN) by RS polysaccharide, and a protective effect of polysaccharide on chromone components were observed in small intestine solutions. Meanwhile, RS polysaccharide produced a significant elevation of cimifugin and PGCN concentration in vivo. Based on these findings, we concluded that RS polysaccharide could greatly increase the content of cimifugin, which might be related to its degradation-proof effect on cimifugin, via transforming cimifugin to comparatively more stable PGCN and spatial structure protection.

A concise review of testosterone and bone health

PubMed Central

Mohamad, Nur-Vaizura; Soelaiman, Ima-Nirwana; Chin, Kok-Yong

2016-01-01

Osteoporosis is a condition causing significant morbidity and mortality in the elderly population worldwide. Age-related testosterone deficiency is the most important factor of bone loss in elderly men. Androgen can influence bone health by binding to androgen receptors directly or to estrogen receptors (ERs) indirectly via aromatization to estrogen. This review summarized the direct and indirect effects of androgens on bone derived from in vitro, in vivo, and human studies. Cellular studies showed that androgen stimulated the proliferation of preosteoblasts and differentiation of osteoblasts. The converted estrogen suppressed osteoclast formation and resorption activity by blocking the receptor activator of nuclear factor k-B ligand pathway. In animal studies, activation of androgen and ERα, but not ERβ, was shown to be important in acquisition and maintenance of bone mass. Human epidemiological studies demonstrated a significant relationship between estrogen and testosterone in bone mineral density and fracture risk, but the relative significance between the two remained debatable. Human experimental studies showed that estrogen was needed in suppressing bone resorption, but both androgen and estrogen were indispensable for bone formation. As a conclusion, maintaining optimal level of androgen is essential in preventing osteoporosis and its complications in elderly men. PMID:27703340

Nesting behavior of house mice (Mus domesticus) selected for increased wheel-running activity.

PubMed

Carter, P A; Swallow, J G; Davis, S J; Garland, T

2000-03-01

Nest building was measured in "active" (housed with access to running wheels) and "sedentary" (without wheel access) mice (Mus domesticus) from four replicate lines selected for 10 generations for high voluntary wheel-running behavior, and from four randombred control lines. Based on previous studies of mice bidirectionally selected for thermoregulatory nest building, it was hypothesized that nest building would show a negative correlated response to selection on wheel-running. Such a response could constrain the evolution of high voluntary activity because nesting has also been shown to be positively genetically correlated with successful production of weaned pups. With wheel access, selected mice of both sexes built significantly smaller nests than did control mice. Without wheel access, selected females also built significantly smaller nests than did control females, but only when body mass was excluded from the statistical model, suggesting that body mass mediated this correlated response to selection. Total distance run and mean running speed on wheels was significantly higher in selected mice than in controls, but no differences in amount of time spent running were measured, indicating a complex cause of the response of nesting to selection for voluntary wheel running.

Pembrolizumab and its role in relapsed/refractory classical Hodgkin's lymphoma: evidence to date and clinical utility.

PubMed

Shindiapina, Polina; Alinari, Lapo

2018-04-01

Immune evasion is a critical mechanism of malignant cell survival, and relies in part on molecular signaling through the programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) axis that contributes to T cell exhaustion. Immune modulatory therapy with monoclonal antibodies against PD-1 designed to enhance antitumor immune response have shown promise in the treatment of advanced solid tumors and hematologic malignancies. Classical Hodgkin's lymphoma (cHL), a unique B cell malignancy characterized by an extensive but ineffective immune cell infiltrate surrounding a small number of tumor cells, has shown significant response to anti-PD-1 directed therapy. The anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab have shown similarly remarkable activity in relapsed/refractory cHL and have been approved by the Food and Drug Administration for treatment of this disease. In this article we review the rationale of targeting the PD-1/PD-L1 axis in cHL and the pharmacology of pembrolizumab, and summarize the data on activity and safety profile of this agent in the treatment of relapsed/refractory cHL. We also discuss the potential benefits and pitfalls of using PD-1 blockade in the setting of allogeneic stem-cell transplantation, and summarize ongoing prospective trials of single-agent pembrolizumab and combination strategies as well as future directions.

Pembrolizumab and its role in relapsed/refractory classical Hodgkin’s lymphoma: evidence to date and clinical utility

PubMed Central

Shindiapina, Polina; Alinari, Lapo

2018-01-01

Immune evasion is a critical mechanism of malignant cell survival, and relies in part on molecular signaling through the programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) axis that contributes to T cell exhaustion. Immune modulatory therapy with monoclonal antibodies against PD-1 designed to enhance antitumor immune response have shown promise in the treatment of advanced solid tumors and hematologic malignancies. Classical Hodgkin’s lymphoma (cHL), a unique B cell malignancy characterized by an extensive but ineffective immune cell infiltrate surrounding a small number of tumor cells, has shown significant response to anti-PD-1 directed therapy. The anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab have shown similarly remarkable activity in relapsed/refractory cHL and have been approved by the Food and Drug Administration for treatment of this disease. In this article we review the rationale of targeting the PD-1/PD-L1 axis in cHL and the pharmacology of pembrolizumab, and summarize the data on activity and safety profile of this agent in the treatment of relapsed/refractory cHL. We also discuss the potential benefits and pitfalls of using PD-1 blockade in the setting of allogeneic stem-cell transplantation, and summarize ongoing prospective trials of single-agent pembrolizumab and combination strategies as well as future directions. PMID:29623180

The effect of ISM absorption on stellar activity measurements and its relevance for exoplanet studies

NASA Astrophysics Data System (ADS)

Fossati, L.; Marcelja, S. E.; Staab, D.; Cubillos, P. E.; France, K.; Haswell, C. A.; Ingrassia, S.; Jenkins, J. S.; Koskinen, T.; Lanza, A. F.; Redfield, S.; Youngblood, A.; Pelzmann, G.

2017-05-01

Past ultraviolet and optical observations of stars hosting close-in Jupiter-mass planets have shown that some of these stars present an anomalously low chromospheric activity, significantly below the basal level. For the hot Jupiter planet host WASP-13, observations have shown that the apparent lack of activity is possibly caused by absorption from the intervening interstellar medium (ISM). Inspired by this result, we study the effect of ISM absorption on activity measurements (S and log R 'HK indices) for main-sequence late-type stars. To this end, we employ synthetic stellar photospheric spectra combined with varying amounts of chromospheric emission and ISM absorption. We present the effect of ISM absorption on activity measurements by varying several instrumental (spectral resolution), stellar (projected rotational velocity, effective temperature, and chromospheric emission flux), and ISM parameters (relative velocity between stellar and ISM Ca II lines, broadening b-parameter, and Ca II column density). We find that for relative velocities between the stellar and ISM lines smaller than 30-40 km s-1 and for ISM Ca II column densities log NCaII ⪆ 12, the ISM absorption has a significant influence on activity measurements. Direct measurements and three dimensional maps of the Galactic ISM absorption indicate that an ISM Ca II column density of log NCaII = 12 is typically reached by a distance of about 100 pc along most sight lines. In particular, for a Sun-like star lying at a distance greater than 100 pc, we expect a depression (bias) in the log R'HK value larger than 0.05-0.1 dex, about the same size as the typical measurement and calibration uncertainties on this parameter. This work shows that the bias introduced by ISM absorption must always be considered when measuring activity for stars lying beyond 100 pc. We also consider the effect of multiple ISM absorption components. We discuss the relevance of this result for exoplanet studies and revise the latest results on stellar activity versus planet surface gravity correlation. We finally describe methods with which it would be possible to account for ISM absorption in activity measurements and provide a code to roughly estimate the magnitude of the bias. Correcting for the ISM absorption bias may allow one to identify the origin of the anomaly in the activity measured for some planet-hosting stars.

SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging.

PubMed

Zarzuelo, María José; López-Sepúlveda, Rocío; Sánchez, Manuel; Romero, Miguel; Gómez-Guzmán, Manuel; Ungvary, Zoltan; Pérez-Vizcaíno, Francisco; Jiménez, Rosario; Duarte, Juan

2013-05-01

Vascular aging is characterized by up-regulation of NADPH oxidase, oxidative stress and endothelial dysfunction. Previous studies demonstrate that the activity of the evolutionarily conserved NAD(+)-dependent deacetylase SIRT1 declines with age and that pharmacological activators of SIRT1 confer significant anti-aging cardiovascular effects. To determine whether dysregulation of SIRT1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of SIRT1 (nicotinamide, sirtinol, EX527) in aorta segments isolated from young Wistar rats. Inhibition of SIRT1 induced endothelial dysfunction, as shown by the significantly reduced relaxation to the endothelium-dependent vasodilators acetylcholine and the calcium ionophore A23187. Endothelial dysfunction induced by SIRT1 inhibition was prevented by treatment of the vessels with the NADPH oxidase inhibitor apocynin or superoxide dismutase. Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by resveratrol. Peroxisome proliferator-activated receptor-α (PPARα) activation mimicked the effects of resveratrol while PPARα inhibition prevented the effects of this SIRT1 activator. SIRT1 co-precipitated with PPARα and nicotinamide increased the acetylation of the PPARα coactivator PGC-1α, which was suppressed by resveratrol. In conclusion, impaired activity of SIRT1 induces endothelial dysfunction and up-regulates NADPH oxidase-derived ROS production in the vascular wall, mimicking the vascular aging phenotype. Moreover, a new mechanism for controlling endothelial function after SIRT1 activation involves a decreased PGC-1α acetylation and the subsequent PPARα activation, resulting in both decreased NADPH oxidase-driven ROS production and NO inactivation. Copyright © 2013 Elsevier Inc. All rights reserved.

Ozone Depletion at Mid-Latitudes: Coupling of Volcanic Aerosols and Temperature Variability to Anthropogenic Chlorine

NASA Technical Reports Server (NTRS)

Solomon, S.; Portmann, R. W.; Garcia, R. R.; Randel, W.; Wu, F.; Nagatani, R.; Gleason, J.; Thomason, L.; Poole, L. R.; McCormick, M. P.

1998-01-01

Satellite observations of total ozone at 40-60 deg N are presented from a variety of instruments over the time period 1979-1997. These reveal record low values in 1992-3 (after Pinatubo) followed by partial but incomplete recovery. The largest post-Pinatubo reductions and longer-term trends occur in spring, providing a critical test for chemical theories of ozone depletion. The observations are shown to be consistent with current understanding of the chemistry of ozone depletion when changes in reactive chlorine and stratospheric aerosol abundances are considered along with estimates of wave-driven fluctuations in stratospheric temperatures derived from global temperature analyses. Temperature fluctuations are shown to make significant contributions to model calculated northern mid-latitude ozone depletion due to heterogeneous chlorine activation on liquid sulfate aerosols at temperatures near 200-210 K (depending upon water vapor pressure), particularly after major volcanic eruptions. Future mid-latitude ozone recovery will hence depend not only on chlorine recovery but also on temperature trends and/or variability, volcanic activity, and any trends in stratospheric sulfate aerosol.

Polarimetric passive remote sensing of periodic surfaces

NASA Technical Reports Server (NTRS)

Veysoglu, Murat E.; Yueh, H. A.; Shin, R. T.; Kong, J. A.

1991-01-01

The concept of polarimetry in active remote sensing is extended to passive remote sensing. The potential use of the third and fourth Stokes parameters U and V, which play an important role in polarimetric active remote sensing, is demonstrated for passive remote sensing. It is shown that, by the use of the reciprocity principle, the polarimetric parameters of passive remote sensing can be obtained through the solution of the associated direct scattering problem. These ideas are applied to study polarimetric passive remote sensing of periodic surfaces. The solution of the direct scattering problem is obtained by an integral equation formulation which involves evaluation of periodic Green's functions and normal derivative of those on the surface. Rapid evaluation of the slowly convergent series associated with these functions is observed to be critical for the feasibility of the method. New formulas, which are rapidly convergent, are derived for the calculation of these series. The study has shown that the brightness temperature of the Stokes parameter U can be significant in passive remote sensing. Values as high as 50 K are observed for certain configurations.

Limiting Speed of the Bacterial Flagellar Motor

NASA Astrophysics Data System (ADS)

Nirody, Jasmine; Berry, Richard; Oster, George

The bacterial flagellar motor (BFM) drives swimming in a wide variety of bacterial species, making it crucial for several fundamental biological processes including chemotaxis and community formation. Recent experiments have shown that the structure of this nanomachine is more dynamic than previously believed. Specifically, the number of active torque-generating units (stators) was shown to vary across applied loads. This finding invalidates the experimental evidence reporting that limiting (zero-torque) speed is independent of the number of active stators. Here, we put forward a model for the torque generation mechanism of this motor and propose that the maximum speed of the motor increases as additional torque-generators are recruited. This is contrary to the current widely-held belief that there is a universal upper limit to the speed of the BFM. Our result arises from the assumption that stators disengage from the motor for a significant portion of their mechanochemical cycles at low loads. We show that this assumption is consistent with current experimental evidence and consolidate our predictions with arguments that a processive motor must have a high duty ratio at high loads.

Mitomycin C and endoscopic sinus surgery: where are we?

PubMed

Tabaee, Abtin; Brown, Seth M; Anand, Vijay K

2007-02-01

Mitomycin C has been used successfully in various ophthalmologic and, more recently, otolaryngologic procedures. Its modulation of fibroblast activity allows for decreased scarring and fibrosis. Several recent trials have examined the efficacy of mitomycin C in reducing synechia and stenosis following endoscopic sinus surgery. Basic science studies using fibroblast cell lines have demonstrated a dose-dependent suppression of activity with the use of mitomycin C. This is further supported by animal studies that have shown lower rates of maxillary ostial restenosis following application of mitomycin C. No human trial, however, has demonstrated a statistically significant impact of mitomycin C on the incidence of postoperative synechia or stenosis following sinus surgery. The limitations of the literature are discussed. The antiproliferative properties of mitomycin C may theoretically decrease the incidence of synechia and stenosis following endoscopic sinus surgery. Although this is supported by basic science studies and its successful use in other fields, the clinical evidence to date has not shown the application of mitomycin C to be effective in preventing stenosis after endoscopic sinus surgery. Future prospective studies are required before definitive conclusions can be made.

Determination of the coronal magnetic field from vector magnetograph data

NASA Technical Reports Server (NTRS)

Mikic, Zoran

1991-01-01

A new algorithm was developed, tested, and applied to determine coronal magnetic fields above solar active regions. The coronal field above NOAA active region AR5747 was successfully estimated on 20 Oct. 1989 from data taken at the Mees Solar Observatory of the Univ. of Hawaii. It was shown that observational data can be used to obtain realistic estimates of coronal magnetic fields. The model has significantly extended the realism with which the coronal magnetic field can be inferred from observations. The understanding of coronal phenomena will be greatly advanced by a reliable technique, such as the one presented, for deducing the detailed spatial structure of the coronal field. The payoff from major current and proposed NASA observational efforts is heavily dependent on the success with which the coronal field can be inferred from vector magnetograms. In particular, the present inability to reliably obtain the coronal field has been a major obstacle to the theoretical advancement of solar flare theory and prediction. The results have shown that the evolutional algorithm can be used to estimate coronal magnetic fields.

The impact of the lacto-ovo vegetarian diet on the erythrocyte superoxide dismutase activity: a study in the Romanian population.

PubMed

Boancă, M M; Colosi, H A; Crăciun, E C

2014-02-01

Recent studies have shown that vitamin B12 scavenges superoxide anion as effectively as superoxide dismutase (SOD), and has a key role in the defense against oxidative stress. The status of vitamin B12 is suboptimal in a substantial number of vegans and even vegetarians. We therefore evaluated in lacto-ovo vegetarians (LOVs) who did not take vitamin B12 supplements the impact of the duration of this diet on the vitamin B12 status, the erythrocyte SOD activity and the serum malondialdehyde (MDA) concentration. The study group included 38 non-vegetarians and 48 LOVs divided, according to the duration of this diet, into two subgroups: LOV1 (2-10 years) and LOV2 (11-29 years). The erythrocyte SOD activity and the serum concentrations of vitamin B12 and MDA were assayed. In LOVs, the mean serum vitamin B12 concentration, the erythrocyte SOD activity and the mean serum MDA concentration were statistically significantly lower that in non-vegetarians. No significant association between the serum vitamin B12 and MDA concentrations and the duration of the LOV diet were observed. A significant inverse linear correlation between SOD activity and the duration of adherence to LOV diet was observed in LOVs. The duration of LOV diet has impact only on SOD activity. Further researches, both in vitro and in vivo, are necessary to understand the underlying molecular mechanism.

Carvedilol, a third-generation β-blocker prevents oxidative stress-induced neuronal death and activates Nrf2/ARE pathway in HT22 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouyang, Ying; Chen, Ziwei; Tan, Min

Highlights: •Carvedilol significantly prevented oxidative stress-induced cell death. •Carvedilol significantly decreased the production of ROS. •Carvedilol activated Nrf2/ARE pathway. •Carvedilol increased the protein levels of HO-1 and NQO-1. -- Abstract: Carvedilol, a nonselective β-adrenoreceptor blocker with pleiotropic activities has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. Here we investigated the effect of carvedilol on oxidative stress-induced cell death (glutamate 2 mM and H{sub 2}O{sub 2}more » 600 μM) and the activity of Nrf2/ARE pathway in HT22 hippocampal cells. Carvedilol significantly increased cell viability and decreased ROS in HT22 cells exposed to glutamate or H{sub 2}O{sub 2}. Furthermore, carvedilol activated the Nrf2/ARE pathway in a concentration-dependent manner, and increased the protein levels of heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1(NQO-1), two downstream factors of the Nrf2/ARE pathway. Collectively, our results indicate that carvedilol protects neuronal cell against glutamate- and H{sub 2}O{sub 2}-induced neurotoxicity possibly through activating the Nrf2/ARE signaling pathway.« less

Optimum DMOS cell doping profiles for high-voltage discrete and integrated device technologies

NASA Astrophysics Data System (ADS)

Shenai, Krishna

1992-05-01

It is shown that the implantation and activation sequences of B and As result in significant variations in the contact resistance and p-base sheet resistance beneath the n+-source diffusion of a DMOSFET cell. For identical process parameters, the contact resistance of As-doped n+ silicon was significantly improved when high-dose B was implanted due to higher As surface concentration. The SUPREM III process modeling results were found to be in qualitative agreement with the measured spreading resistance profiles and the discrepancies could be attributed to larger high-temperature diffusion constants used in SUPREM III and the coupled As-B diffusion/activation effects that are not accounted for in process modeling. The experimental results are discussed within the framework of fabricating high-performance DMOSFET cells and CMOS high-voltage devices on the same chip for discrete and smart-power applications.

Anti-colorectal cancer effects of tripolinolate A from Tripolium vulgare.

PubMed

Chen, Lu; Wang, Wen-Ling; Song, Teng-Fei; Xie, Xin; Ye, Xue-Wei; Liang, Ying; Huang, Hao-Cai; Yan, Shi-Lun; Lian, Xiao-Yuan; Zhang, Zhi-Zhen

2017-08-01

Tripolinolate A (TLA) is recently identified as a new compound from a halophyte plant Tripolium vulgare and has been shown to have significant in vitro activity against the proliferation of colorectal cancer and glioma cells. This study was designed to further investigate the effects of TLA on the proliferation of human normal cells, and the apoptosis and cell cycle in colorectal cancer cells, and the growth of tumors in the colorectal cancer-bearing animals. The data obtained from this study demonstrated that: 1) TLA had much less cytotoxicity in the human normal cells than the colorectal cancer cells; 2) TLA remarkably induced apoptosis in the human colorectal cancer cells and blocked cell cycle at G 2 /M phase, and 3) TLA had significant anti-colorectal cancer activity in the tumor-bearing animals. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Evaluating the features of the brain waves to quantify ADHD improvement by neurofeedback.

PubMed

Dehghanpour, Peyman; Einalou, Zahra

2017-10-23

Attention-deficit/hyperactivity disorder (ADHD), as one of the most common neurological disorders in children and adolescents, is characterized by decentralization, slow learning, distraction and hyperactivity. Studies have shown that in addition to medication, neurofeedback training can also be used to partially control the brain activity of these patients. In this study, using the brain signals processing before and after the treatment in 10 children treated by neurofeedback, the changes were evaluated by non-parametric statistical analysis and impact of neurofeedback on brain frequency bands was investigated. Finally, the results were compared with the protocols introduced in this paper and before researches. The results of Kruskal-Wallis test showed an approximately significant increase in the relative power of gamma and an approximately significant reduction in the ratio of relative power of alpha/beta. It represents the emotional response, elicited by the successful learning and diminished ratio of slow learning to active learning respectively.

Superabsorbent polymer-containing wound dressings have a beneficial effect on wound healing by reducing PMN elastase concentration and inhibiting microbial growth.

PubMed

Wiegand, C; Abel, M; Ruth, P; Hipler, U C

2011-11-01

A comprehensive in vitro approach was used to assess the effects of superabsorbent polymer (SAP) containing wound dressings in treatment of non-healing wounds. A slight negative effect on HaCaT cells was noted in vitro which is most likely due to the Ca(2+) deprivation of the medium by binding to the SAP. It could be shown that SAP wound dressings are able to bind considerable amounts of elastase reducing enzyme activity significantly. Furthermore, SAP's inhibit the formation of free radicals. The SAP-containing wound dressings tested also exhibited a significant to strong antimicrobial activity effectively impeding the growth of gram-negative and gram-positive bacteria as well as yeasts. In conclusion, in vitro data confirm the positive effect of SAP wound dressings observed in vivo and suggest that they should be specifically useful for wound cleansing.

Cytoprotective effects of essential oil of Pinus halepensis L. against aspirin-induced toxicity in IEC-6 cells.

PubMed

Bouzenna, Hafsia; Hfaiedh, Najla; Bouaziz, Mouhamed; Giroux-Metges, Marie-Agnès; Elfeki, Abdelfattah; Talarmin, Hélène

2017-12-01

Essential oils from Pinus species have been reported to have various therapeutic properties. This study was undertaken to identify the chemical composition and cytoprotective effects of the essential oil of Pinus halepensis L. against aspirin-induced damage in cells in vitro. The cytoprotection of the oil against toxicity of aspirin on the small intestine epithelial cells IEC-6 was tested. The obtained results have shown that 35 different compounds were identified. Aspirin induced a decrease in cell viability, and exhibited significant damage to their morphology and an increase in superoxide dismutase (SOD) and catalase (CAT) activities. However, the co-treatment of aspirin with the essential oil of Pinus induced a significant increase in cell viability and a decrease in SOD and CAT activities. Overall, these finding suggest that the essential oil of Pinus halepensis L. has potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

Oxidation of platinum nickel nanowires to improve durability of oxygen-reducing electrocatalysts

DOE PAGES

Alia, Shaun M.; Pylypenko, Svitlana; Dameron, Arrelaine; ...

2016-01-12

In this study, the impact of heat treating platinum-coated nickel (Pt-Ni) nanowires in oxygen is examined to determine the effect on oxygen reduction (ORR) activity and durability. Pt-Ni nanowires exhibit promising ORR mass activities (3 times greater than Pt nanoparticles, 1.5 times greater than U.S. Department of Energy target) both before and after potential cycling for all but the highest annealing temperatures explored. The annealing of Pt-Ni nanowires in oxygen with increasing temperature is found to reduce surface area and ORR activity in comparison to the untreated material, but also reduces activity losses following durability testing. Following potential cycling, unannealedmore » Pt-Ni nanowires show significant losses in surface area (23%) and specific activity (18%) while Pt-Ni nanowires annealed at 200°C show modest increases in surface area (2%) and specific activity (6%) after potential cycling. Increasing annealing temperatures also show a clear trend of decreasing Ni dissolution rates. While oxygen annealing has shown the ability to improve durability of Pt-Ni nanowires, significant Ni dissolution was observed in all samples and suggests oxide passivation while showing promise for improved durability, when employed by itself is insufficient to prevent all contamination concerns involving Ni dissolution.« less

Effect of probiotic strain Lactobacillus acidophilus (LBKV-3) on fecal residual lactase activity in undernourished children below 10 years.

PubMed

Hajare, Sunil Tulshiram; Bekele, Genene

2017-01-01

Clinically proven Lactobacillus acidophilus strain LBKV-3 intended as probiotic for humans was used to test its effect on fecal residual lactase activity in undernourished children below 10 years of age. The children were selected from malnutrition-declared area of Maharashtra (India). One of the major causes of malnutrition is lactose intolerance which leads to diarrhea. The basic consideration in selecting the probiotic strain of L. acidophilus (LBKV-3) in this investigation was the fact that the organism is isolated from human vaginal surface swab and it was found extensively studied for probiotic characteristic. LBKB 3 is tested by several workers as probiotic for hypocholesterolemic activity, implantation ability, therapeutic effects on gastrointestinal (GI) and related ailments. The results of present investigation have shown that the fecal residual lactase activity significantly increased than its initial value (which was almost zero). It appeared that the fecal residual β-galactosidase activity is an indication of positive implementation abilities of the cultures under investigation. These trends were compared with the control and blank group of children receiving Dahi and buffalo milk (BM). It was observed that both these products failed to exert any significant impact on increase in residual lactase activity.

[Role of oxotremorine in arginine vasopressin-induced hypothermia and its effects on behavioral thermoregulatory response in rats].

PubMed

Shen, Zi-Ling; Yang, Yong-Lu; Sun, Bing; Tang, Yu; Wang, Nian

2012-03-01

To investigate the role of oxotremorine in arginine vasopressin (AVP)-induced hypothermia and its effects on the behavioral thermoregulatory response. Core temperature (Tc), brown adipose tissue (BAT) temperature and motor activities were monitored in undisturbed female SD rats using radiotelemetry. The behavioral thermoregulatory response was monitored in rats using radiotelemetric temperature gradient apparatus. Effect of AVP (10 microg/kg) and oxotremorine (0.25 mg/kg) on Tc, motor activities, BAT temperature (T(BAT)), grooming activities and the behavioral thermoregulatory response were observed in rats. Administration of AVP and oxotremorine caused a significant drop in Tc, T(BAT), and an increases in grooming activities, respectively. The hypothermic responses were accompanied with a preference for cooler ambient temperature. Oxotremorine augmented the reduction of Tc, T(BAT), and the elevation of grooming activities resulting from AVP, and lasting a longer time. Administration of oxotremorine followed immediately by AVP injection in rats was also shown to induce a preference for cooler ambient temperature, but there was no significant difference compared with AVP. AVP-induced hypothermia was related with the set point temperature reduction, inhibiton of BAT thermogenesis and an increases in grooming activities. Oxotremorine could participate in peripheral AVP-induced hypothermia by affecting BAT thermogenesis and behavioral thermoregulation.

Bacillus subtilis glutamine synthetase regulates its own synthesis by acting as a chaperone to stabilize GlnR-DNA complexes.

PubMed

Fisher, Susan H; Wray, Lewis V

2008-01-22

The Bacillus subtilis GlnR repressor controls gene expression in response to nitrogen availability. Because all GlnR-regulated genes are expressed constitutively in mutants lacking glutamine synthetase (GS), GS is required for repression by GlnR. Feedback-inhibited GS (FBI-GS) was shown to activate GlnR DNA binding with an in vitro electophoretic mobility shift assay (EMSA). The activation of GlnR DNA binding by GS in these experiments depended on the feedback inhibitor glutamine and did not occur with mutant GS proteins defective in regulating GlnR activity in vivo. Although stable GS-GlnR-DNA ternary complexes were not observed in the EMSA experiments, cross-linking experiments showed that a protein-protein interaction occurs between GlnR and FBI-GS. This interaction was reduced in the absence of the feedback inhibitor glutamine and with mutant GS proteins. Because FBI-GS significantly reduced the dissociation rate of the GlnR-DNA complexes, the stability of these complexes is enhanced by FBI-GS. These results argue that FBI-GS acts as a chaperone that activates GlnR DNA binding through a transient protein-protein interaction that stabilizes GlnR-DNA complexes. GS was shown to control the activity of the B. subtilis nitrogen transcription factor TnrA by forming a stable complex between FBI-GS and TnrA that inhibits TnrA DNA binding. Thus, B. subtilis GS is an enzyme with dual catalytic and regulatory functions that uses distinct mechanisms to control the activity of two different transcription factors.

Aldosterone does not require angiotensin II to activate NCC through a WNK4-SPAK-dependent pathway.

PubMed

van der Lubbe, Nils; Lim, Christina H; Meima, Marcel E; van Veghel, Richard; Rosenbaek, Lena Lindtoft; Mutig, Kerim; Danser, Alexander H J; Fenton, Robert A; Zietse, Robert; Hoorn, Ewout J

2012-06-01

We and others have recently shown that angiotensin II can activate the sodium chloride cotransporter (NCC) through a WNK4-SPAK-dependent pathway. Because WNK4 was previously shown to be a negative regulator of NCC, it has been postulated that angiotensin II converts WNK4 to a positive regulator. Here, we ask whether aldosterone requires angiotensin II to activate NCC and if their effects are additive. To do so, we infused vehicle or aldosterone in adrenalectomized rats that also received the angiotensin receptor blocker losartan. In the presence of losartan, aldosterone was still capable of increasing total and phosphorylated NCC twofold to threefold. The kinases WNK4 and SPAK also increased with aldosterone and losartan. A dose-dependent relationship between aldosterone and NCC, SPAK, and WNK4 was identified, suggesting that these are aldosterone-sensitive proteins. As more functional evidence of increased NCC activity, we showed that rats receiving aldosterone and losartan had a significantly greater natriuretic response to hydrochlorothiazide than rats receiving losartan only. To study whether angiotensin II could have an additive effect, rats receiving aldosterone with losartan were compared with rats receiving aldosterone only. Rats receiving aldosterone only retained more sodium and had twofold to fourfold increase in phosphorylated NCC. Together, our results demonstrate that aldosterone does not require angiotensin II to activate NCC and that WNK4 appears to act as a positive regulator in this pathway. The additive effect of angiotensin II may favor electroneutral sodium reabsorption during hypovolemia and may contribute to hypertension in diseases with an activated renin-angiotensin-aldosterone system.

Effect of potential probiotic Rhodotorula benthica D30 on the growth performance, digestive enzyme activity and immunity in juvenile sea cucumber Apostichopus japonicus.

PubMed

Wang, Ji-hui; Zhao, Liu-qun; Liu, Jin-feng; Wang, Han; Xiao, Shan

2015-04-01

The effects of dietary addition of yeast Rhodotorula benthica (R. benthica) D30 which isolated from local sea mud at levels of 0 (control), 10(5), 10(6) and 10(7) CFU/g feed on the growth performance, digestive enzyme activity, immunity and disease resistance of juvenile sea cucumber Apostichopus japonicus were investigated. It was shown that dietary addition of R. benthica D30 significantly increased the growth rates of sea cucumbers (p < 0.05). The amylase activity, cellulase activity and alginase activity were increased for the animals from three probiotics treated groups. And with the supplemented concentration increased, the values of those digestive enzyme activities increased as well. Dietary addition of R. benthica D30 at the level of 10(7) CFU significantly increased the lysozyme, phagocytic and total nitric oxide synthase activity of A. japonicus (p < 0.05). While, the highest values of the phenoloxidase and alkaline phosphatase activity were found in sea cucumbers fed with R. benthica D30 at the level of 10(6) CFU. Whereas adding R. benthica D30 to diet had no significant effects on the total coelomocyte counts and acid phosphatase activity of A. japonicus (p > 0.05). It was observed that adding R. benthica D30 could significantly decrease the cumulative mortality of sea cucumbers. The present study demonstrated that dietary addition of R. benthica D30 could increase growth performance and some digestive enzyme activities, improve immunity and disease resistance of A. japonicus. And the medium (10(6) CFU) and high (10(7) CFU) additional levels showed better effects. It suggests that yeast R. benthica D30 could be a good probiotic for aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hydrothermally Driven Transformation of Oxygen Functional Groups at Multiwall Carbon Nanotubes for Improved Electrocatalytic Applications.

PubMed

Suryanto, Bryan H R; Chen, Sheng; Duan, Jingjing; Zhao, Chuan

2016-12-28

The role of carbon nanotubes in the advancement of energy conversion and storage technologies is undeniable. In particular, carbon nanotubes have attracted significant applications for electrocatalysis. However, one central issue related to the use of carbon nanotubes is the required oxidative pretreatment that often leads to significant damage of graphitic structures which deteriorates their electrochemical properties. Traditionally, the oxidized carbon nanomaterials are treated at high temperature under an inert atmosphere to repair the oxidation-induced defect sites, which simultaneously removes a significant number of oxygen functional groups. Nevertheless, recent studies have shown that oxygen functional groups on the surface of MWCNT are the essential active centers for a number of important electrocatalytic reactions such as hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR). Herein we first show that hydrothermal treatment as a mild method to improve the electrochemical properties and activities of surface-oxidized MWCNT for OER, HER, and ORR without significantly altering the oxygen content. The results indicate that hydrothermal treatment could potentially repair the defects without significantly reducing the pre-existing oxygen content, which has never been achieved before with conventional high-temperature annealing treatment.

In vitro antimicrobial activity and chemical composition of the essential oil of Foeniculum vulgare Mill.

PubMed

Aprotosoaie, Ana Clara; Hăncianu, Monica; Poiată, Antonia; Tuchiluş, Cristina; Spac, A; Cioană, Oana; Gille, Elvira; Stănescu, Ursula

2008-01-01

In our study, four samples of volatile oil from Foeniculum vulgare, cultivated in different pedoclimatic conditions, were investigated for their antimicrobial activity and chemical composition. Organisms. Staphylococcus aureus ATCC 25923, Bacillus cereus, Pseudomonas aeruginosa, Escherichia coli ATCC 25922, Candida albicans were included in the report. Antimicrobial susceptibility tests. The comparative inhibitory activity of volatile oil samples with other antimicrobial agents was quantitative determined by minimum inhibitory concentration (MIC). Oil samples are the volatile oils extracted by steam distillation, from two ecological vegetative populations of Foeniculum vulgare. Gas chromatography coupled to mass spectrometry (GC-MS) was used to determine the chemical composition of the essential oils. All oil samples have a good activity against E. coli and S. aureus at low concentrations. Against B. cereus and P. aeruginosa these oil samples are less active. The oil samples were generally bactericidal at a concentration up to twofold or fourfold higher than the MIC value. Significantly synergic activity with amoxicillin or tetracycline showed all fennel samples against E. coli, Sarcina lutea and B. subtilis strains. Fennel oil samples have shown high activity against Candida albicans. No significant antimicrobial activity variations were observed for Foeniculum vulgare volatile oil samples obtained after two or three years cultivation period. The most important identified compounds in all samples of fennel volatile oils were trans-anethole, estragole, fenchone, limonene, alpha-pinene and gamma-terpinene.

Antiatherogenic effect of quercetin is mediated by proteasome inhibition in the aorta and circulating leukocytes.

PubMed

Pashevin, Denis A; Tumanovska, Lesya V; Dosenko, Victor E; Nagibin, Vasyl S; Gurianova, Veronika L; Moibenko, Alexey A

2011-01-01

Quercetin, a plant-derived flavonoid, has attracted considerable attention as promising compound for heart disease prevention and therapy. It has been linked to decreased mortality from heart disease and decreased incidence of stroke. Here, we report new data showing the angioprotective properties of quercetin mediated by its effect on proteasomal proteolysis. This study was designed to investigate the ability of quercetin to modulate proteasomal activity in a rabbit model of cholesterol-induced atherosclerosis. First, we show proteasomal trypsin-like (TL) activity increased up to 2.4-fold, chymotrypsin-like (CTL) activity increased by up to 43% and peptidyl-glutamyl peptide-hydrolyzing (PGPH) activity increased by up to 10% after 8 weeks of a cholesterol-rich diet. A single intravenous injection of the water-soluble form of quercetin (Corvitin) significantly decreased proteasomal TL activity 1.85-fold in monocytes, and decreased the CTL and PGPH activities more than 2-fold in polymorphonuclear leukocytes (PMNL) after 2 h. Prolonged administration (1 month) of Corvitin to animals following a cholesterol-rich diet significantly decreased all types of proteolytic proteasome activities both in tissues and in circulating leukocytes and was associated with the reduction of atherosclerotic lesion areas in the aorta. Additionally, the pharmacological form of quercetin (Quertin) was shown to have an antiatherogenic effect and an ability to inhibit proteasome activities.

Cedrus deodara: In vitro antileishmanial efficacy & immumomodulatory activity.

PubMed

Narayan, Shyam; Thakur, Chandreshwar Prasad; Bahadur, Shiv; Thakur, Meenakshi; Pandey, Shashi Nath; Thakur, Ajit Kumar; Mitra, Dipendra K; Mukherjee, Pulok K

2017-12-01

The existing antileishmanial drugs for complete cure of visceral leishmaniasis (kala-azar) are limited. The available drugs are either toxic or less effective leading to disease relapse or conversion to post-kala-azar dermal leishmaniasis. Several herbal extracts have been shown to have antileishmanial activity, but a herbal drug may not always be safe. In the present study, the extract of Cedrus deodara leaves has been standardized and tested for immunomodulatory antileishmanial activities. The extracts of C. deodara leaves with different solvents such as benzene, chloroform, ethyl acetate and methanol were made by soxhlation process. Solvents were removed under reduced pressure and temperature using rotary evaporator. The antileishmanial bioassay test was performed with in vitro maintained parasites. Immunomodulatory activity of different extracts was tested by flow cytometry. Standardization of the effective fraction was performed with Linalool as a marker compound through reverse-phase high-performance liquid chromatography. The extract with the use of benzene solvent showed strong antileishmanial activities within a dose 25-200 μg/ml culture with non-significant haemolytic activities and significant immunomodulant activities against the host cells. Linalool was found to be 1.29 per cent in the effective extract of C. deodara. The antileishmanial activity of C. deodara, as assessed by bioassay testing on. parasites and immunomodulatory effect of benzene extract of leaves on host cells indicated that it might be a potential new safe therapeutic target to cure the visceral leishmaniasis.

Daily activity level improvement with antidepressant medications predicts long-term clinical outcomes in outpatients with major depressive disorder.

PubMed

Jha, Manish K; Teer, Raymond B; Minhajuddin, Abu; Greer, Tracy L; Rush, A John; Trivedi, Madhukar H

2017-01-01

Major depressive disorder (MDD) significantly impacts performance of both work- and nonwork-related routine daily activities. We have shown that work productivity is significantly impaired in employed MDD patients, but the extent of impairments in nonwork-related routine activities and its association with antidepressant treatment outcomes has not been established. Activity impairment was measured using the sixth item of Work Productivity and Activity Impairment Scale in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (n=665). Published norms were used to define activity impairment levels. The relationship between activity impairment and baseline sociodemographic and clinical characteristics was evaluated along with changes in activity impairment and its relationship with other clinical outcomes such as symptom severity, function, and side effect burden. Remission status at 3 and 7 months was predicted based on week 6 activity impairment level. Higher psychosocial and cognitive impairments and greater number of comorbid medical conditions were associated with greater activity impairment at baseline. Proportion of participants with severe activity impairment declined from 47.6% at baseline to 18.7% at 3 months, while mean activity impairment decreased from 57.1 at baseline to 32.8 at 3 months. During course of treatment, levels of activity impairment correlated most strongly with psychosocial function among measures of symptom severity, function, quality of life, and side effect burden. No or minimal activity impairment at week 6 was associated with two to three times higher rates of remission at 3 and 7 months as compared to moderate or severe activity impairment levels even after controlling for remission status at week 6 and select baseline variables. Depressed patients have high levels of nonwork-related activity impairment at baseline that improves significantly with treatment and independently predicts long-term clinical outcomes. Brief systematic assessment of activity impairment during the course of antidepressant treatment can help inform clinical decision-making.

Protective Effects of LSGYGP from Fish Skin Gelatin Hydrolysates on UVB-Induced MEFs by Regulation of Oxidative Stress and Matrix Metalloproteinase Activity.

PubMed

Ma, Qingyu; Liu, Qiuming; Yuan, Ling; Zhuang, Yongliang

2018-03-28

A previous study has shown that tilapia fish skin gelatin hydrolysates inhibited photoaging in vivo, and that, Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) identified in the hydrolysate had a high hydroxyl radical scavenging activity. In this study, activities of LSGYGP were further evaluated using ultraviolet B (UVB)-induced mouse embryonic fibroblasts (MEFs). UVB irradiation significantly increased the intercellular reactive oxygen species (ROS) production and matrix metalloproteinases (MMPs) activities and decreased the content of collagen in MEFs. LSGYGP reduced the intercellular ROS generation in UVB-induced MEFs. Meanwhile, the decrease of superoxide dismutase (SOD) activity and the increase of malondiaidehyde (MDA) content were inhibited by LSGYGP. LSGYGP reduced MMP-1 and MMP-9 activities in a dose-dependent manner. Molecular docking simulation indicated that LSGYGP inhibited MMPs activities by docking the active sites of MMP-1 and MMP-9. Furthermore, LSGYGP also affected the intercellular phosphorylation of UVB-induced the mitogen-activated protein kinase pathway. LSGYGP could protect collagen synthesis in MEFs under UVB irradiation by inhibiting oxidative stress and regulating MMPs activities.

Protective Effects of LSGYGP from Fish Skin Gelatin Hydrolysates on UVB-Induced MEFs by Regulation of Oxidative Stress and Matrix Metalloproteinase Activity

PubMed Central

Ma, Qingyu; Liu, Qiuming; Yuan, Ling; Zhuang, Yongliang

2018-01-01

A previous study has shown that tilapia fish skin gelatin hydrolysates inhibited photoaging in vivo, and that, Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) identified in the hydrolysate had a high hydroxyl radical scavenging activity. In this study, activities of LSGYGP were further evaluated using ultraviolet B (UVB)-induced mouse embryonic fibroblasts (MEFs). UVB irradiation significantly increased the intercellular reactive oxygen species (ROS) production and matrix metalloproteinases (MMPs) activities and decreased the content of collagen in MEFs. LSGYGP reduced the intercellular ROS generation in UVB-induced MEFs. Meanwhile, the decrease of superoxide dismutase (SOD) activity and the increase of malondiaidehyde (MDA) content were inhibited by LSGYGP. LSGYGP reduced MMP-1 and MMP-9 activities in a dose-dependent manner. Molecular docking simulation indicated that LSGYGP inhibited MMPs activities by docking the active sites of MMP-1 and MMP-9. Furthermore, LSGYGP also affected the intercellular phosphorylation of UVB-induced the mitogen-activated protein kinase pathway. LSGYGP could protect collagen synthesis in MEFs under UVB irradiation by inhibiting oxidative stress and regulating MMPs activities. PMID:29597313

Antimicrobial activity of some medicinal barks used in Peruvian Amazon.

PubMed

Kloucek, P; Svobodova, B; Polesny, Z; Langrova, I; Smrcek, S; Kokoska, L

2007-05-04

The aim of this study was to evaluate the antimicrobial activity of six barks traditionally used in Callería District (Ucayali Department, Peru) for treating conditions likely to be associated with microorganisms. Ethanol extracts of stem barks of Abuta grandifolia (Menispermaceae), Dipteryx micrantha (Leguminosae), Cordia alliodora (Boraginaceae), Naucleopsis glabra (Moraceae), Pterocarpus rohrii (Leguminosae), and root bark of Maytenus macrocarpa (Celastraceae) were tested against nine bacteria and one yeast using the broth microdilution method. All plants possessed significant antimicrobial effect, however, the extract of Naucleopsis glabra exhibited the strongest activity against Gram-positive bacteria (MICs ranging from 62.5 to 125 microg/ml), while the broadest spectrum of action was shown by the extract of Maytenus macrocarpa, which inhibited all the strains tested with MICs ranging from 125 to 250 microg/ml.

Pt/SnO2-based CO-oxidation catalysts for long-life closed-cycle CO2 lasers

NASA Technical Reports Server (NTRS)

Schryer, David R.; Upchurch, Billy T.; Hess, Robert V.; Wood, George M.; Sidney, Barry D.; Miller, Irvin M.; Brown, Kenneth G.; Vannorman, John D.; Schryer, Jacqueline; Brown, David R.

1990-01-01

Noble-metal/tin-oxide based catalysts such as Pt/SnO2 have been shown to be good catalysts for the efficient oxidation of CO at or near room temperature. These catalysts require a reductive pretreatment and traces of hydrogen or water to exhibit their full activity. Addition of Palladium enhances the activity of these catalysts with about 15 to 20 percent Pt, 4 percent Pd, and the balance SnO2 being an optimum composition. Unfortunately, these catalysts presently exhibit significant decay due in part to CO2 retention, probably as a bicarbonate. Research on minimizing the decay in activity of these catalysts is currently in progress. A proposed mechanism of CO oxidation on Pt/SnO2-based catalysts has been developed and is discussed.

Recruitment of Anterior and Posterior Structures in Lexical-Semantic Processing: An fMRI Study Comparing Implicit and Explicit Tasks

ERIC Educational Resources Information Center

Ruff, Ilana; Blumstein, Sheila E.; Myers, Emily B.; Hutchison, Emmette

2008-01-01

Previous studies examining explicit semantic processing have consistently shown activation of the left inferior frontal gyrus (IFG). In contrast, implicit semantic processing tasks have shown activation in posterior areas including the superior temporal gyrus (STG) and the middle temporal gyrus (MTG) with less consistent activation in the IFG.…

CDDO and Its Role in Chronic Diseases.

PubMed

Mathis, Bryan J; Cui, Taixing

2016-01-01

There has been a continued interest in translational research focused on both natural products and manipulation of functional groups on these compounds to create novel derivatives with higher desired activities. Oleanolic acid, a component of traditional Chinese medicine used in hepatitis therapy, was modified by chemical processes to form 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO). This modification increased anti-inflammatory activity significantly and additional functional groups on the CDDO backbone have shown promise in treating conditions ranging from kidney disease to obesity to diabetes. CDDO's therapeutic effect is due to its upregulation of the master antioxidant transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) through conformational change of Nrf2-repressing, Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) and multiple animal and human studies have verified subsequent activation of Nrf2-controlled antioxidant genes via upstream Antioxidant Response Element (ARE) regions. At the present time, positive results have been obtained in the laboratory and clinical trials with CDDO derivatives treating conditions such as lung injury, inflammation and chronic kidney disease. However, clinical trials for cancer and cardiovascular disease have not shown equally positive results and further exploration of CDDO and its derivatives is needed to put these shortcomings into context for the purpose of future therapeutic modalities.

[Impact of Delivery Method on Antiviral Activity of Phosphodiester, Phosphorothioate, and Phosphoryl Guanidine Oligonucleotides in MDCK Cells Infected with H5N1 Bird Flu Virus].

PubMed

Levina, A S; Repkova, M N; Chelobanov, B P; Bessudnova, E V; Mazurkova, N A; Stetsenko, D A; Zarytova, V F

2017-01-01

We have previously described nanocomposites containing conjugates or complexes of native oligodeoxyribonucleotides with poly-L-lysine and TiO2 nanoparticles. We have shown that these nanocomposites efficiently suppressed influenza A virus reproduction in MDCK cells. Here, we have synthesized previously undescribed nanocomposites that consist of TiO2 nanoparticles and polylysine conjugates with oligonucleotides that contain phosphoryl guanidine or phosphorothioate internucleotide groups. These nanocomposites have been shown to exhibit antiviral activity in MDCK cells infected with H5N1 influenza A virus. The nanocomposites containing phosphorothioate oligonucleotides inhibited virus replication ~130-fold. More potent inhibition, i.e., ~5000-fold or ~4600-fold, has been demonstrated by nanocomposites that contain phosphoryl guanidine or phosphodiester oligonucleotides, respectively. Free oligonucleotides have been nearly inactive. The antiviral activity of oligonucleotides of all three types, when delivered by Lipofectamine, has been significantly lower compared to the oligonucleotides delivered in the nanocomposites. In the former case, the phosphoryl guanidine oligonucleotide has appeared to be the most efficient; it has inhibited the virus replication by a factor of 400. The results make it possible to consider phosphoryl guanidine oligonucleotides, along with other oligonucleotide derivatives, as potential antiviral agents against H5N1 avian flu virus.

Anthelmintic activity of trans-cinnamaldehyde and A- and B-type proanthocyanidins derived from cinnamon (Cinnamomum verum)

PubMed Central

Williams, Andrew R.; Ramsay, Aina; Hansen, Tina V. A.; Ropiak, Honorata M.; Mejer, Helena; Nejsum, Peter; Mueller-Harvey, Irene; Thamsborg, Stig M.

2015-01-01

Cinnamon (Cinnamomum verum) has been shown to have anti-inflammatory and antimicrobial properties, but effects on parasitic worms of the intestine have not been investigated. Here, extracts of cinnamon bark were shown to have potent in vitro anthelmintic properties against the swine nematode Ascaris suum. Analysis of the extract revealed high concentrations of proanthocyanidins (PAC) and trans-cinnamaldehyde (CA). The PAC were subjected to thiolysis and HPLC-MS analysis which demonstrated that they were exclusively procyanidins, had a mean degree of polymerization of 5.2 and 21% of their inter-flavan-3-ol links were A-type linkages. Purification of the PAC revealed that whilst they had activity against A. suum, most of the potency of the extract derived from CA. Trichuris suis and Oesophagostomum dentatum larvae were similarly susceptible to CA. To test whether CA could reduce A. suum infection in pigs in vivo, CA was administered daily in the diet or as a targeted, encapsulated dose. However, infection was not significantly reduced. It is proposed that the rapid absorption or metabolism of CA in vivo may prevent it from being present in sufficient concentrations in situ to exert efficacy. Therefore, further work should focus on whether formulation of CA can enhance its activity against internal parasites. PMID:26420588

The effects of participation in leisure activities on neuropsychiatric symptoms of persons with cognitive impairment: a cross-sectional study.

PubMed

Chiu, Yi-Chen; Huang, Chien-Ying; Kolanowski, Ann M; Huang, Hsiu-Li; Shyu, Yeaing Lotus; Lee, Shu-Hwa; Lin, Ching-Rong; Hsu, Wen-Chuin

2013-10-01

People with cognitive impairment have been shown to engage in few structured activities. During periods of unoccupied time or boredom, these patients most likely manifest neuropsychiatric symptoms. The purposes of this study were to (1) describe the leisure-activity indicators (variety in leisure activities, appraisal of each activity's restorative function, and leisure dysfunction, i.e. failure to appreciate the importance of restorative aspects of leisure activity), of community-dwelling older Taiwanese adults with cognitive impairment, and (2) explore the relationships between these indicators and neuropsychiatric symptoms in this population. Cross-sectional. Memory disorder and geriatric psychiatric clinics of two hospitals in northern Taiwan. Patient-family caregiver dyads (N=60). Patients' dementia severity, based on Clinical Dementia Rating scores, was 0.5-2.0. Family caregivers completed the Chinese Neuropsychiatric Inventory to assess patients' behavioral problems and the Restorative Activity Questionnaire to assess patients' participation in leisure activities, restorative experience, and leisure dysfunction. On average, patients participated in approximately five individual leisure activities, but very few group leisure activities. The top three leisure activities were watching TV, taking a walk, and talking to relatives and friends. The leisure activities in which participants least commonly engaged were fishing, attending cultural exhibitions, and chess/card playing. All leisure-activity indicators were significantly correlated with disease stage, global cognitive function, and neuropsychiatric symptoms. Two leisure-activity indicators (leisure dysfunction and restorative experiences) were significantly correlated with depressive symptoms. Only leisure dysfunction significantly and consistently predicted neuropsychiatric symptoms. These results can be used by home health or community health nurses to design tailored leisure-activity plans for improving the care quality of patients with cognitive impairment. Health professionals can develop leisure-education programmes to emphasize the value of leisure pursuit and to modify attitudes toward participating in leisure activities. Finally, parks and recreational agencies may re-examine their services and facilities to meet the increasing needs of this population. Copyright © 2013 Elsevier Ltd. All rights reserved.

Unraveling the Transcriptional Basis of Temperature-Dependent Pinoxaden Resistance in Brachypodium hybridum

PubMed Central

Matzrafi, Maor; Shaar-Moshe, Lidor; Rubin, Baruch; Peleg, Zvi

2017-01-01

Climate change endangers food security and our ability to feed the ever-increasing human population. Weeds are the most important biotic stress, reducing crop-plant productivity worldwide. Chemical control, the main approach for weed management, can be strongly affected by temperature. Previously, we have shown that temperature-dependent non-target site (NTS) resistance of Brachypodium hybridum is due to enhanced detoxification of acetyl-CoA carboxylase inhibitors. Here, we explored the transcriptional basis of this phenomenon. Plants were characterized for the transcriptional response to herbicide application, high-temperature and their combination, in an attempt to uncover the genetic basis of temperature-dependent pinoxaden resistance. Even though most of the variance among treatments was due to pinoxaden application (61%), plants were able to survive pinoxaden application only when grown under high-temperatures. Biological pathways and expression patterns of members of specific gene families, previously shown to be involved in NTS metabolic resistance to different herbicides, were examined. Cytochrome P450, glucosyl transferase and glutathione-S-transferase genes were found to be up-regulated in response to pinoxaden application under both control and high-temperature conditions. However, biological pathways related to oxidation and glucose conjugation were found to be significantly enriched only under the combination of pinoxaden application and high-temperature. Analysis of reactive oxygen species (ROS) was conducted at several time points after treatment using a probe detecting H2O2/peroxides. Comparison of ROS accumulation among treatments revealed a significant reduction in ROS quantities 24 h after pinoxaden application only under high-temperature conditions. These results may indicate significant activity of enzymatic ROS scavengers that can be correlated with the activation of herbicide-resistance mechanisms. This study shows that up-regulation of genes related to metabolic resistance is not sufficient to explain temperature-dependent pinoxaden resistance. We suggest that elevated activity of enzymatic processes at high-temperature may induce rapid and efficient pinoxaden metabolism leading to temperature-dependent herbicide resistance. PMID:28680434

Effect of extraction solvents on the biomolecules and antioxidant properties of Scorzonera undulata (Asteraceae): Application of factorial design optimization phenolic extraction.

PubMed

Athmouni, Khaled; Belghith, Taheni; Bellassouad, Khaled; Feki, Abdelfattah El; Ayadi, Habib

2015-01-01

Phenolic compounds were extracted and isolated from S. undulata roots. Sample of roots from E. hirta was tested for phenolic compounds, and in vitro antioxidant activity by diphenyl-1-picrylhydrazyl (DPPH) assay, ABTS, FRAP and reducing power was measured using cyano- ferrate method. The methanolic fraction exhibited the highest total phenol content (6.12 ±0.11 mg AGE/g DW). On the other hand, the highest flavonoids concentration was observed in ethyl acetate fraction (2.90 ±0.05 mg CE/g DW) in addition to anthocyanins (28.56 ±3.96 mg/l). Besides, the highest level of tannins content was measured in the polar aprotic solvent ethyl acetate extract (3.25 ±0.06 mg CE/g DW). The different extracts of S. undulata were evaluated for their radical scavenging activities by means of the DPPH assay. The strongest scavenging activity was observed in methanolic fraction scavenged radicals effectively with IC   values of 0.14 ±0.02 mg/ml. Similarly, the potassium ferricyanide reduction (FRAP) and ABTS•+ of methanol extract. On the other hand, the total reducing power of ethyl acetate extract was found higher than of other extracts. This paper presents the application of the design-of experiment method for optimizing the extraction of phenolic content using methanol solvent. The resulting regression model has shown that the effect of temperature is not statistically significant (with >95% certainty), while that of agitation speed is. The two main effects are contributed by the solvent concentration and the maceration period. Our results clearly showed that the extraction of phenolic compounds and their antioxidant capacity is significantly affected by solvent combinations. S. undulata presented the highest total phenolic content, total flavonoids content and antioxidant capacity values. The resulting regression model has shown that the effect of temperature is not statistically significant (with >95% certainty), while that of agitation speed is.

Uncovering the Molecular Mechanism of Anti-Allergic Activity of Silkworm Pupa-Grown Cordyceps militaris Fruit Body.

PubMed

Wu, Ting-Feng; Chan, Yu-Yi; Shi, Wan-Yin; Jhong, Meng-Ting

2017-01-01

Cordyceps militaris has been widely used as an herbal drug and tonic food in East Asia and has also been recently studied in the West because of its various pharmacological activities such as antitumoral, anti-inflammatory and immunomodulatory effects. In this study, we examined the molecular mechanism underlying the anti-allergic activity of ethanol extract prepared from silkworm pupa-cultivated Cordyceps militaris fruit bodies in activated mast cells. Our results showed that ethanol extract treatment significantly inhibited the release of [Formula: see text]-hexosaminidase (a degranulation marker) and mRNA levels of tumor necrosis factor-[Formula: see text] as well as interleukin-4 in RBL-2H3 cells. The cells were sensitized with 2,4-dinitrophenol specific IgE and then stimulated with human serum albumin conjugated with 2,4-dinitrophenol. Oral administration of 300[Formula: see text]mg/kg ethanol extract significantly ameliorated IgE-induced allergic reaction in mice with passive cutaneous anaphylaxis. Western immunoblotting results demonstrated that ethanol extract incubation significantly inhibited Syk/PI3K/MEKK4/JNK/c-jun biochemical cascade in activated RBL-2H3 cells, which activated the expression of various allergic cytokines. In addition, it suppressed Erk activation and PLC[Formula: see text] evocation, which would respectively evoke the synthesis of lipid mediators and Ca[Formula: see text] mobilization to induce degranulation in stimulated RBL-2H3 cells. A compound, identified as [Formula: see text]-sitostenone, was shown to inhibit [Formula: see text]-hexosaminidase secretion from activated mast cells. Our study demonstrated that ethanol extract contained the ingredients, which could inhibit immediate degranulation and de novo synthesis of allergic lipid mediators and cytokines in activated mast cells.

Activation of the Nrf2-ARE Pathway in Hepatocytes Protects Against Steatosis in Nutritionally Induced Non-alcoholic Steatohepatitis in Mice

PubMed Central

Lee, Lung-Yi; Köhler, Ulrike A.; Zhang, Li; Roenneburg, Drew; Werner, Sabine; Johnson, Jeffrey A.; Foley, David P.

2014-01-01

Oxidative stress is implicated in the development of non-alcoholic steatohepatitis (NASH). The Nrf2-antioxidant response element pathway protects cells from oxidative stress. Studies have shown that global Nrf2 deficiency hastens the progression of NASH. The purpose of this study was to determine whether long-term hepatocyte-specific activation of Nrf2 mitigates NASH progression. Transgenic mice expressing a constitutively active Nrf2 construct in hepatocytes (AlbCre+/caNrf2+) and littermate controls were generated. These mice were fed standard or methionine-choline-deficient (MCD) diet, a diet used to induce NASH development in rodents. After 28 days of MCD dietary feeding, mice developed significant increases in steatosis, inflammation, oxidative stress, and HSC activation compared with those mice on standard diet. AlbCre+/caNrf2+ animals had significantly decreased serum transaminases and reduced steatosis when compared with the AlbCre+/caNrf2− animals. This significant reduction in steatosis was associated with increased expression of genes involved in triglyceride export (MTTP) and β-oxidation (CPT2). However, there were no differences in the increased oxidative stress, inflammation, and HSC activation from MCD diet administration between the AlbCre+/caNrf2− and AlbCre+/caNrf2+ animals. We conclude that hepatocyte-specific activation of Nrf2-mediated gene expression decreased hepatocellular damage and steatosis in a dietary model of NASH. However, hepatocyte-specific induction of Nrf2-mediated gene expression alone is insufficient to mitigate inflammation, oxidative stress, and HSC activation in this nutritional NASH model. PMID:25294219

Evaluation of lectin pathway activity and mannan-binding lectin levels in the course of pregnancy complicated by diabetes type 1, based on the genetic background.

PubMed

Pertyńska Marczewska, Magdalena; Cedzyński, Maciej; Swierzko, Anna; Szala, Agnieszka; Sobczak, Małgorzata; Cypryk, Katarzyna; Wilczyński, Jan

2009-01-01

There are numerous indications that either mannan-binding lectin (MBL) deficiency or its excessive activity are associated with adverse pregnancy outcomes. High MBL concentrations and corresponding MBL2 genotypes were shown to be associated with microvascular complications in type 1 diabetes. The aim of this study was to evaluate levels of MBL and MBL-dependent activity of the lectin pathway (LP) of complement in the course of pregnancy in diabetic mothers, based on genetic background. These parameters were determined in samples from healthy non-pregnant (control), diabetic non-pregnant, healthy pregnant, and pregnant diabetic women. No significant differences in median MBL levels or LP activities were found in any study group compared to the control. However, statistically significant differences in MBL levels were noted during pregnancy between the 1st and 3rd trimesters in both healthy controls and pregnant diabetics. With regard to LP values, similar trends were evident, but statistically significant results were obtained only in the healthy pregnant group. When data analysis was confined to patients carrying the A/A (wild-type) MBL2 genotype, an increase in MBL level during pregnancy (in both healthy and diabetic pregnant women) was still observed. Similarly, LP activity increased during both healthy and diabetic pregnancies, significantly so for the former. Diabetes, an autoimmune disease, is a serious complication of pregnancy. Therefore, determination of MBL status might be beneficial in identifying type 1 diabetic patients who are at increased risk of developing both vascular complications and poor pregnancy outcomes.

Serum and tissue angiotensin-converting enzyme in patients with alopecia areata.

PubMed

Fahim, Shabnam; Montazer, Fatemeh; Tohidinik, Hamid Reza; Naraghi, Zahra Safaei; Abedini, Robabeh; Nasimi, Maryam; Ghandi, Narges

2018-03-27

Alopecia areata is an immune-dependent disorder characterized by the interaction of T-lymphocytes with follicular antigens. Recent studies have shown the existence of a local renin-angiotensin system in the skin, where angiotensin-converting enzyme (ACE) plays a role in autoimmunity and inflammation. The objective of this study was to evaluate serum and tissue ACE activity in patients with alopecia areata. This case-control study was conducted on patients with alopecia areata and healthy controls. Serum and tissue ACE activity were assessed and compared between the two groups. Twenty-five alopecia areata patients (60% male, mean age 32.1 ± 9.9 years) and 24 controls (50% male, mean age 37.4 ± 8.8 years) were included. Mean serum ACE activity was 52.1 ± 9 U/L in cases and 55.3 ± 14.7 U/L in controls (P = 0.37). Tissue ACE activity was significantly lower in cases in all parts of the skin i.e. epidermis (P = 0.016), follicular epithelium (P = 0.004), and endothelium (P = 0.037). Among cases, serum ACE activity was significantly higher in patients with more severe disease (P = 0.030), nonpatchy alopecia areata (alopecia universalis; ophiasis, patchy and ophiasis, diffuse) (P = 0.029), and with nail involvement (P = 0.027). The sample size was too small to draw definite conclusions. Further, most of the patients had only mild or moderate alopecia areata. Unlike in some other inflammatory diseases, the tissue level of ACE seems to be significantly lower in alopecia areata compared to normal controls. Serum ACE was significantly higher in patients with more severe disease.

Antioxidant Activity of γ-Oryzanol: A Complex Network of Interactions

PubMed Central

Minatel, Igor Otavio; Francisqueti, Fabiane Valentini; Corrêa, Camila Renata; Lima, Giuseppina Pace Pereira

2016-01-01

γ-oryzanol (Orz), a steryl ferulate extracted from rice bran layer, exerts a wide spectrum of biological activities. In addition to its antioxidant activity, Orz is often associated with cholesterol-lowering, anti-inflammatory, anti-cancer and anti-diabetic effects. In recent years, the usefulness of Orz has been studied for the treatment of metabolic diseases, as it acts to ameliorate insulin activity, cholesterol metabolism, and associated chronic inflammation. Previous studies have shown the direct action of Orz when downregulating the expression of genes that encode proteins related to adiposity (CCAAT/enhancer binding proteins (C/EBPs)), inflammatory responses (nuclear factor kappa-B (NF-κB)), and metabolic syndrome (peroxisome proliferator-activated receptors (PPARs)). It is likely that this wide range of beneficial activities results from a complex network of interactions and signals triggered, and/or inhibited by its antioxidant properties. This review focuses on the significance of Orz in metabolic disorders, which feature remarkable oxidative imbalance, such as impaired glucose metabolism, obesity, and inflammation. PMID:27517904

Cytophotometric study of ATPase activity in brain neurons and gliocytes of paradoxical sleep-deprived rats.

PubMed

Klenikova, V A; Taranova, N P

1989-01-01

Conditions were chosen for optimal demonstration of ATPases in brain slices by a modified method of Wachstein and Meisel, and the reaction was shown to obey the Bouguer-Beer laws, confirming that ATPase activity can be determined quantitatively in single cells by cytophotometry. In rats in a state of relative physiological rest specific activity of both Na+, K+-ATPase and Mg++-ATPase in gliocytes of the hippocampus and dorsal raphe was found to be considerably higher than in neurons. Deprivation of the paradoxical phase of sleep of the rats for 24 h led to a significant increase in Na+, K+-ATPase activity in hippocampal neurons and to a decrease in its activity in gliocytes of the hippocampus and dorsal nucleus raphe. It is suggested that these changes in Na+, K+-ATPase activity may be due to some extent to a change in excitability of neurons and depolarization of the glia when sleep is disturbed.

Antioxidant Activity of γ-Oryzanol: A Complex Network of Interactions.

PubMed

Minatel, Igor Otavio; Francisqueti, Fabiane Valentini; Corrêa, Camila Renata; Lima, Giuseppina Pace Pereira

2016-08-09

γ-oryzanol (Orz), a steryl ferulate extracted from rice bran layer, exerts a wide spectrum of biological activities. In addition to its antioxidant activity, Orz is often associated with cholesterol-lowering, anti-inflammatory, anti-cancer and anti-diabetic effects. In recent years, the usefulness of Orz has been studied for the treatment of metabolic diseases, as it acts to ameliorate insulin activity, cholesterol metabolism, and associated chronic inflammation. Previous studies have shown the direct action of Orz when downregulating the expression of genes that encode proteins related to adiposity (CCAAT/enhancer binding proteins (C/EBPs)), inflammatory responses (nuclear factor kappa-B (NF-κB)), and metabolic syndrome (peroxisome proliferator-activated receptors (PPARs)). It is likely that this wide range of beneficial activities results from a complex network of interactions and signals triggered, and/or inhibited by its antioxidant properties. This review focuses on the significance of Orz in metabolic disorders, which feature remarkable oxidative imbalance, such as impaired glucose metabolism, obesity, and inflammation.

Psychometric Properties of Physical Activity and Leisure Motivation Scale in Farsi: an International Collaborative Project on Motivation for Physical Activity and Leisure.

PubMed

Zarei, Sahar; Memari, Amir-Hossein; Moshayedi, Pouria; Mosayebi, Fatolla; Mansournia, Mohammad Ali; Khoo, Selina; Morris, Tony

2016-10-01

Given the importance of regular physical activity, it is crucial to evaluate the factors favoring participation in physical activity. We aimed to report the psychometric analysis of the Farsi version of the Physical Activity and Leisure Motivation Scale (PALMS). The Farsi version of PALMS was completed by 406 healthy adult individuals to test its factor structure and concurrent validity and reliability. Conducting the exploratory factor analysis revealed nine factors that accounted for 64.6% of the variances. The PALMS reliability was supported with a high internal consistency of 0.91 and a high test-retest reliability of 0.97 (95% CI: 0.97-0.98). The association between the PALMS and its previous version Recreational Exercise Motivation Measure scores was strongly significant (r= 0.86, P < 0.001). We have shown that the Farsi version of the PALMS appears to be a valuable instrument to measure motivation for physical activity and leisure.

Self-Reflection and the Inner Voice: Activation of the Left Inferior Frontal Gyrus During Perceptual and Conceptual Self-Referential Thinking

PubMed Central

Morin, Alain; Hamper, Breanne

2012-01-01

Inner speech involvement in self-reflection was examined by reviewing 130 studies assessing brain activation during self-referential processing in key self-domains: agency, self-recognition, emotions, personality traits, autobiographical memory, and miscellaneous (e.g., prospection, judgments). The left inferior frontal gyrus (LIFG) has been shown to be reliably recruited during inner speech production. The percentage of studies reporting LIFG activity for each self-dimension was calculated. Fifty five percent of all studies reviewed indicated LIFG (and presumably inner speech) activity during self-reflection tasks; on average LIFG activation is observed 16% of the time during completion of non-self tasks (e.g., attention, perception). The highest LIFG activation rate was observed during retrieval of autobiographical information. The LIFG was significantly more recruited during conceptual tasks (e.g., prospection, traits) than during perceptual tasks (agency and self-recognition). This constitutes additional evidence supporting the idea of a participation of inner speech in self-related thinking. PMID:23049653

Self-reflection and the inner voice: activation of the left inferior frontal gyrus during perceptual and conceptual self-referential thinking.

PubMed

Morin, Alain; Hamper, Breanne

2012-01-01

Inner speech involvement in self-reflection was examined by reviewing 130 studies assessing brain activation during self-referential processing in key self-domains: agency, self-recognition, emotions, personality traits, autobiographical memory, and miscellaneous (e.g., prospection, judgments). The left inferior frontal gyrus (LIFG) has been shown to be reliably recruited during inner speech production. The percentage of studies reporting LIFG activity for each self-dimension was calculated. Fifty five percent of all studies reviewed indicated LIFG (and presumably inner speech) activity during self-reflection tasks; on average LIFG activation is observed 16% of the time during completion of non-self tasks (e.g., attention, perception). The highest LIFG activation rate was observed during retrieval of autobiographical information. The LIFG was significantly more recruited during conceptual tasks (e.g., prospection, traits) than during perceptual tasks (agency and self-recognition). This constitutes additional evidence supporting the idea of a participation of inner speech in self-related thinking.

Single cell active force generation under dynamic loading - Part I: AFM experiments.

PubMed

Weafer, P P; Reynolds, N H; Jarvis, S P; McGarry, J P

2015-11-01

A novel series of experiments are performed on single cells using a bespoke AFM system where the response of cells to dynamic loading at physiologically relevant frequencies is uncovered. Measured forces for the untreated cells are dramatically different to cytochalasin-D (cyto-D) treated cells, indicating that the contractile actin cytoskeleton plays a critical role in the response of cells to dynamic loading. Following a change in applied strain magnitude, while maintaining a constant applied strain rate, the compression force for contractile cells recovers to 88.9±7.8% of the steady state force. In contrast, cyto-D cell compression forces recover to only 38.0±6.7% of the steady state force. Additionally, untreated cells exhibit strongly negative (pulling) forces during unloading half-cycles when the probe is retracted. In comparison, negligible pulling forces are measured for cyto-D cells during probe retraction. The current study demonstrates that active contractile forces, generated by actin-myosin cross-bridge cycling, dominate the response of single cells to dynamic loading. Such active force generation is shown to be independent of applied strain magnitude. Passive forces generated by the applied deformation are shown to be of secondary importance, exhibiting a high dependence on applied strain magnitude, in contrast to the active forces in untreated cells. A novel series of experiments are performed on single cells using a bespoke AFM system where the response of cells to dynamic loading at physiologically relevant frequencies is uncovered. Contractile cells, which contain the active force generation machinery of the actin cytoskeleton, are shown to be insensitive to applied strain magnitude, exhibiting high resistance to dynamic compression and stretching. Such trends are not observed for cells in which the actin cytoskeleton has been chemically disrupted. These biomechanical insights have not been previously reported. This detailed characterisation of single cell active and passive stress during dynamic loading has important implications for tissue engineering strategies, where applied deformation has been reported to significantly affect cell mechanotransduction and matrix synthesis. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Data on changes in red wine phenolic compounds, headspace aroma compounds and sensory profile after treatment of red wines with activated carbons with different physicochemical characteristics.

PubMed

Filipe-Ribeiro, Luís; Milheiro, Juliana; Matos, Carlos C; Cosme, Fernanda; Nunes, Fernando M

2017-06-01

Data in this article presents the changes on phenolic compounds, headspace aroma composition and sensory profile of a red wine spiked with 4-ethylphenol and 4-ethylguaiacol and treated with seven activated carbons with different physicochemical characteristics, namely surface area, micropore volume and mesopore volume ("Reduction of 4-ethylphenol and 4-ethylguaiacol in red wine by activated carbons with different physicochemical characteristics: impact on wine quality" Filipe-Ribeiro et al. (2017) [1]). Data on the physicochemical characteristics of the activated carbons are shown. Statistical data on the sensory expert panel consistency by General Procrustes Analysis is shown. Statistical data is also shown, which correlates the changes in chemical composition of red wines with the physicochemical characteristics of activated carbons used.

Progress in aeronautical research and technology applicable to civil air transports

NASA Technical Reports Server (NTRS)

Bower, R. E.

1981-01-01

Recent progress in the aeronautical research and technology program being conducted by the United States National Aeronautics and Space Administration is discussed. Emphasis is on computational capability, new testing facilities, drag reduction, turbofan and turboprop propulsion, noise, composite materials, active controls, integrated avionics, cockpit displays, flight management, and operating problems. It is shown that this technology is significantly impacting the efficiency of the new civil air transports. The excitement of emerging research promises even greater benefits to future aircraft developments.

Synthesis of 6-Substituted-2,4-Diamino-5,6,7,8-Tetrahydropyrimido (4-5-d) Pyrimidines. Revised.

DTIC Science & Technology

1981-07-01

SUPPLEMENTARY NOTES IS. KEY WOROSIUXau on avere aide Inocoeay end Identity by block acemb.,) Tetrahydropyrimido (4,!:-d) pyrimidines Phenylethylamines ...not see continuation of further members of the original target compounds as cost effective . Because of extreme dif- ficulties and time-consuming...have shown significant activity are the 4-Cl (3), 3,4-C1 2 (3,4) and CF3 (5). Spacers such as the Y = -CH2- (6) were also reported to be effective

Einstein observations of active galaxies and quasars

NASA Technical Reports Server (NTRS)

Schreier, E. J.

1979-01-01

The radio galaxies Centaurus A and Signus B are discussed. In both these sources, a comparison of the radio and imaged X-ray flux is allowed for the measurement of the magnetic fields. Einstein observations of quasars are discussed. The number of known X-ray emitting QSO's was increased from 3 to 22 and the distances where these QSO's were seen to correspond to an age of 15 billion years. It was shown that these quasars contributed significantly to the X-ray background.

Molecular-Orbital Models for the Catayltic Activity and Selectivity of Coordinatively Unsaturated Platinum Surfaces and Complexes.

DTIC Science & Technology

1980-12-31

surfaces. Reactions involving the Pt(O)- triphenylphosphine complexes Pt(PPh 3)n, where n = 2, 3, 4, have been shown to have precise analogues on Pt...12], the triphenylphosphine (PPh 3 ) group is modeled by the simpler but chemically similar phosphine (PH3) group. The appropriate Pt-P bond distances...typically refractory oxides ) are of sufficient magnitude as to suggest significant chemical and electronic modifications of the metal at the metal-support

Characterization of Pulsed Vortex Generator Jets for Active Flow Control

DTIC Science & Technology

2001-06-01

approaches to calculating these quantities shown to not to play a significant role in the developing vortex, were assessed; most of which used Amtec ...obtained very close to Since this method was developed. Amtec Engineering’s CFD the wall, but not completely through the laminar sub-layer. The...Francisco, California, July 18-23 1999. 31 "’Khan, Z.U. & Jolmston, J.P., "On Vortex Generating Jets," " Amtec Engineering Inc., ©1988-2000 [http

Kinetics and thermodynamics of DNA polymerases with exonuclease proofreading

NASA Astrophysics Data System (ADS)

Gaspard, Pierre

2016-04-01

Kinetic theory and thermodynamics are applied to DNA polymerases with exonuclease activity, taking into account the dependence of the rates on the previously incorporated nucleotide. The replication fidelity is shown to increase significantly thanks to this dependence at the basis of the mechanism of exonuclease proofreading. In particular, this dependence can provide up to a 100-fold lowering of the error probability under physiological conditions. Theory is compared with numerical simulations for the DNA polymerases of T7 viruses and human mitochondria.

Molecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept

PubMed Central

Vakhitova, Y. V.; Sadovnikov, S. V.; Borisevich, S. S.; Ostrovskaya, R. U.; A.Gudasheva, T.; Seredenin, S. B.

2016-01-01

This study was performed in order to reveal the effect of Noopept (ethyl ester of N-phenylacetyl-Lprolylglycine, GVS-111) on the DNA-binding activity of transcriptional factors (TF) in HEK293 cells transiently transfected with luciferase reporter constructs containing sequences for CREB, NFAT, NF-κB, p53, STAT1, GAS, VDR, HSF1, and HIF-1. Noopept (10 μM) was shown to increase the DNA-binding activity of HIF-1 only, while lacking the ability to affect that of CREB, NFAT, NF-κB, p53, STAT1, GAS, VDR, and HSF1. Noopept provoked an additional increase in the DNA-binding activity of HIF-1 when applied in conditions of CoCl2-induced HIF- 1 stabilization. The degree of this HIF-positive effect of Noopept was shown to be concentration-dependent. Piracetam (1 mM) failed to affect significantly any of the TF under study. The results of molecular docking showed that Noopept (L-isomer), as well as its metabolite, L-isomer of N-phenyl-acetylprolyl, unlike its pharmacologically ineffective D-isomer, is able to bind to the active site of prolyl hydroxylase 2. Taking into account the important role of the genes activated by HIF-1 in the formation of an adaptive response to hypoxia, data on the ability of Noopept to provoke a selective increase in the DNA-binding activity of HIF-1 explain the wide spectrum of neurochemical and pharmacological effects of Noopept revealed before. The obtained data allow one to propose the HIF-positive effect as the primary mechanism of the activity of this Pro-Gly-containing dipeptide. PMID:27099787

Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure.

PubMed

Collino, Massimo; Pini, Alessandro; Mugelli, Niccolò; Mastroianni, Rosanna; Bani, Daniele; Fantozzi, Roberto; Papucci, Laura; Fazi, Marilena; Masini, Emanuela

2013-07-01

We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.