De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function.

PubMed

Gebert, Dorothea; Auer, Matthias K; Stieg, Mareike R; Freitag, Martin T; Lahne, Madlén; Fuss, Johannes; Schilbach, Katharina; Schopohl, Jochen; Stalla, Günter K; Kopczak, Anna

2018-02-01

Despite the high prevalence of panhypopituitarism and diabetes insipidus in patients with craniopharyngioma (CP), little is known about the functioning of the neuropeptide oxytocin in these patients. This is of special interest as tumor-associated lesions often impair sites critical for oxytocin production and release, and affective dysfunction in CP links with elsewhere reported prosocial, antidepressant and anxiolytic oxytocin effects. Using a prospective study-design, we tested whether oxytocin is reduced in CP-patients, and whether altered oxytocin levels account for affective and emotional dysfunction. 26 adult CP-patients and 26 healthy controls matched in sex and age underwent physical exercise, a stimulus previously shown to induce oxytocin release. Baseline and stimulated salivary oxytocin levels, as well as empathy, depression and anxiety scores were measured. Results showed that patients overall did not present with lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but baseline oxytocin levels were indeed reduced in patients with hypothalamic damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response to exercise-induced stimulation, all CP-patients showed a blunted oxytocin-release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with oxytocin levels. Regarding affective function, unexpectedly, higher baseline oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020, CI[.478; 5.292]); the positive link with higher depression failed to reach statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=-2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin measures. In conclusion, we observed reduced baseline oxytocin levels only in CP-patients with hypothalamic damage. Exercise-induced stimulation de-masked an oxytocin-deficiency in all CP-patients. Baseline oxytocin levels and stimulated OT-responses might have different effects on affective function, which should be considered in future substitution paradigms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume

PubMed Central

Ivannikov, Maxim V.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

2012-01-01

Synaptic plasticity in many regions of the central nervous system leads to the continuous adjustment of synaptic strength, which is essential for learning and memory. In this study, we show by visualizing synaptic vesicle release in mouse hippocampal synaptosomes that presynaptic mitochondria and specifically, their capacities for ATP production are essential determinants of synaptic vesicle exocytosis and its magnitude. Total internal reflection microscopy of FM1-43 loaded hippocampal synaptosomes showed that inhibition of mitochondrial oxidative phosphorylation reduces evoked synaptic release. This reduction was accompanied by a substantial drop in synaptosomal ATP levels. However, cytosolic calcium influx was not affected. Structural characterization of stimulated hippocampal synaptosomes revealed that higher total presynaptic mitochondrial volumes were consistently associated with higher levels of exocytosis. Thus, synaptic vesicle release is linked to the presynaptic ability to regenerate ATP, which itself is a utility of mitochondrial density and activity. PMID:22772899

Radioactive release during nuclear accidents in Chernobyl and Fukushima

NASA Astrophysics Data System (ADS)

Nur Ain Sulaiman, Siti; Mohamed, Faizal; Rahim, Ahmad Nabil Ab

2018-01-01

Nuclear accidents that occurred in Chernobyl and Fukushima have initiated many research interests to understand the cause and mechanism of radioactive release within reactor compound and to the environment. Common types of radionuclide release are the fission products from the irradiated fuel rod itself. In case of nuclear accident, the focus of monitoring will be mostly on the release of noble gases, I-131 and Cs-137. As these are the only accidents have been rated within International Nuclear Events Scale (INES) Level 7, the radioactive release to the environment was one of the critical insights to be monitored. It was estimated that the release of radioactive material to the atmosphere due to Fukushima accident was approximately 10% of the Chernobyl accident. By referring to the previous reports using computational code systems to model the release rate, the release activity of I-131 and Cs-137 in Chernobyl was significantly higher compare to Fukushima. The simulation code also showed that Chernobyl had higher release rate of both radionuclides on the day of accident. Other factors affecting the radioactive release for Fukushima and Chernobyl accidents such as the current reactor technology and safety measures are also compared for discussion.

Responsiveness of blood and sputum inflammatory cells in Japanese COPD patients, non-COPD smoking controls, and non-COPD nonsmoking controls

PubMed Central

Kawayama, Tomotaka; Kinoshita, Takashi; Matsunaga, Kazuko; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm; Hoshino, Tomoaki

2016-01-01

Purpose To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC). Patients and methods This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation. Results In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α). Conclusion This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation. PMID:26929615

Responsiveness of blood and sputum inflammatory cells in Japanese COPD patients, non-COPD smoking controls, and non-COPD nonsmoking controls.

PubMed

Kawayama, Tomotaka; Kinoshita, Takashi; Matsunaga, Kazuko; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm; Hoshino, Tomoaki

2016-01-01

To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC). This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation. In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α). This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation.

Rechargeable anticandidal denture material with sustained release in saliva.

PubMed

Malakhov, A; Wen, J; Zhang, B-X; Wang, H; Geng, H; Chen, X-D; Sun, Y; Yeh, C-K

2016-07-01

Candida-induced denture stomatitis is a common debilitating problem among denture wearers. Previously, we described the fabrication of a new denture material that released antifungal drugs when immersed in phosphate buffered saline. Here, we use more clinically relevant immersion conditions (human saliva; 37°C) and measure miconazole release and bioactivity. Disks were prepared by grafting PNVP [poly(N-vinyl-2-pyrrolidinone)] onto PMMA [poly(methylmethacrylate)] using plasma initiation (PMMA-g-PNVP) and then loaded with miconazole. Drug-loaded disks were immersed in 10-100% human saliva (1-30 days). Miconazole release was measured and then tested for bioactivity vs miconazole-sensitive and miconazole-resistant Candida isolates. HPLC was used to quantify miconazole levels in saliva. Miconazole-loaded disks released antifungal drug for up to 30 days. Higher drug release was found with higher concentrations of saliva, and, interestingly, miconazole solubility was increased with higher saliva concentrations. The released miconazole retained its anticandidal activity. After immersion, the residual miconazole could be quenched and the disks recharged. Freshly recharged disks displayed the same release kinetics and bioactivity as the original disks. Quenched disks could also be charged with chlorhexidine that displayed anticandidal activity. These results suggest that PMMA-g-PNVP is a promising new denture material for long-term management of denture stomatitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

"They Call Me Wonder Woman": The Job Jurisdictions and Work-Related Learning of Higher Level Teaching Assistants

ERIC Educational Resources Information Center

Hancock, Roger; Hall, Thelma; Cable, Carrie; Eyres, Ian

2010-01-01

This paper reports on an in-depth interview study of the roles, job jurisdictions and associated learning of higher level teaching assistants (HLTAs). This role has the core purpose of covering classes to enable teacher release for planning, preparation and assessment. HLTAs' individual job jurisdictions are described and discussed as are…

The syntheses and characterization of molecularly imprinted polymers for the controlled release of bromhexine.

PubMed

Azodi-Deilami, Saman; Abdouss, Majid; Javanbakht, Mehran

2011-05-01

Imprinted polymers are now being increasingly considered for active biomedical uses such as drug delivery. In this work, the use of molecularly imprinted polymers (MIPs) in designing new drug delivery devices was studied. Imprinted polymers were prepared from methacrylic acid (functional monomer), ethylene glycol dimethacrylate (cross-linker), and bromhexine (as a drug template) using bulk polymerization method. The influence of the template/functional monomer proportion and pH on the achievement of MIPs with pore cavities with a high enough affinity for the drug was investigated. The polymeric devices were further characterized by FT-IR, thermogravimetric analysis, scanning electron microscopy, and binding experiments. The imprinted polymers showed a higher affinity for bromhexine and a slower release rate than the non-imprinted polymers. The controlled release of bromhexine from the prepared imprinted polymers was investigated through in vitro dissolution tests by measuring absorbance at λ (max) of 310 nm by HPLC-UV. The dissolution media employed were hydrochloric acid at the pH level of 3.0 and phosphate buffers, at pH levels of 6.0 and 8.0, maintained at 37.0 and 25.0 ± 0.5 °C. Results from the analyses showed the ability of MIP polymers to control the release of bromhexine In all cases The imprinted polymers showed a higher affinity for bromhexine and a slower release rate than the non-imprinted polymers. At the pH level of 3.0 and at the temperature of 25 °C, slower release of bromhexine imprinted polymer occurred.

Ipamorelin, the first selective growth hormone secretagogue.

PubMed

Raun, K; Hansen, B S; Johansen, N L; Thøgersen, H; Madsen, K; Ankersen, M; Andersen, P H

1998-11-01

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.

Rechargeable calcium phosphate orthodontic cement with sustained ion release and re-release

NASA Astrophysics Data System (ADS)

Zhang, Ling; Weir, Michael D.; Chow, Laurence C.; Reynolds, Mark A.; Xu, Hockin H. K.

2016-11-01

White spot lesions (WSL) due to enamel demineralization are major complications for orthodontic treatments. Calcium phosphate (CaP) dental resins with Ca and P ion releases are promising for remineralization. However, previous Ca and P releases lasted for only weeks. Experimental orthodontic cements were developed using pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA) at mass ratio of 1:1 (PE); and PE plus 10% of 2-hydroxyethyl methacrylate (HEMA) and 5% of bisphenol A glycidyl dimethacrylate (BisGMA) (PEHB). Particles of amorphous calcium phosphate (ACP) were incorporated into PE and PEHB at 40% filler level. Specimens were tested for bracket-enamel shear bond strength, water sorption, CaP release, and ion recharge and re-release. PEHB+40ACP had higher bracket-enamel bond strength and ion release and rechargeability than PE+40ACP. ACP incorporation into the novel orthodontic cement did not adversely affect the bracket-enamel bond strength. Ion release and re-release from the novel ACP orthodontic cement indicated favorable release and re-release patterns. The recharged orthodontic cement could release CaP ions continuously for four weeks without further recharge. Novel rechargeable orthodontic cement containing ACP was developed with a high bracket-enamel bond strength and the ability to be repeatedly recharged to maintain long-term high levels of CaP ion releases.

Masking release by combined spatial and masker-fluctuation effects in the open sound field.

PubMed

Middlebrooks, John C

2017-12-01

In a complex auditory scene, signals of interest can be distinguished from masking sounds by differences in source location [spatial release from masking (SRM)] and by differences between masker-alone and masker-plus-signal envelopes. This study investigated interactions between those factors in release of masking of 700-Hz tones in an open sound field. Signal and masker sources were colocated in front of the listener, or the signal source was shifted 90° to the side. In Experiment 1, the masker contained a 25-Hz-wide on-signal band plus flanking bands having envelopes that were either mutually uncorrelated or were comodulated. Comodulation masking release (CMR) was largely independent of signal location at a higher masker sound level, but at a lower level CMR was reduced for the lateral signal location. In Experiment 2, a brief signal was positioned at the envelope maximum (peak) or minimum (dip) of a 50-Hz-wide on-signal masker. Masking was released in dip more than in peak conditions only for the 90° signal. Overall, open-field SRM was greater in magnitude than binaural masking release reported in comparable closed-field studies, and envelope-related release was somewhat weaker. Mutual enhancement of masking release by spatial and envelope-related effects tended to increase with increasing masker level.

Double loaded self-decomposable SiO2 nanoparticles for sustained drug release

NASA Astrophysics Data System (ADS)

Zhao, Saisai; Zhang, Silu; Ma, Jiang; Fan, Li; Yin, Chun; Lin, Ge; Li, Quan

2015-10-01

Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases.Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03029c

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

PubMed

Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

2001-09-01

To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

Kinematic Description of Elite Vs. Low Level Players in Team-Handball Jump Throw

PubMed Central

Wagner, Herbert; Buchecker, Michael; von Duvillard, Serge P.; Müller, Erich

2010-01-01

The jump throw is the most applied throwing technique in team- handball (Wagner et al., 2008); however, a comprehensive analysis of 3D-kinematics of the team-handball jump throw is lacking. Therefore, the purpose of our study was: 1) to measure differences in ball release speed in team- handball jump throw and anthropometric parameters between groups of different levels of performance and (2) to analyze upper body 3D-kinematics (flexion/extension and rotation) to determine significant differences between these groups. Three-dimensional kinematic data was analyzed via the Vicon MX 13 motion capturing system (Vicon Peak, Oxford, UK) from 26 male team-handball players of different performance levels (mean age: 21.2 ± 5.0 years). The participants were instructed to throw the ball (IHF Size 3) onto a target at 8 m distance, and to hit the center of a square of 1 × 1 m at about eye level (1.75 m), with maximum ball release speed. Significant differences between elite vs. low level players were found in the ball release speed (p < 0.001), body height (p < 0.05), body weight (p < 0.05), maximal trunk internal rotation (p < 0.05), trunk flexion (p < 0.01) and forearm pronation (p < 0.05) as well as trunk flexion (p < 0.05) and shoulder internal rotation (p < 0.001) angular velocity at ball release. Results of our study suggest that team-handball players who were taller and of greater body weight have the ability to achieve a higher ball release speed in the jump throw, and that an increase in trunk flexion and rotation angular velocity improve the performance in team-handball jump throw that should result in an increase of ball release speed. Key points Team-handball players who were taller and of greater body weight have the ability to achieve a higher ball release speed. An increase in trunk flexion, trunk rotation and shoulder internal rotation angular velocity should result in an increase of ball release speed. Trunk movements are normally well observable for experienced coaches, easy correctable and therefore practical to improve the performance in team-handball jump throw of low level players during training without using complex measurement devices. PMID:24149381

Kinematic description of elite vs. Low level players in team-handball jump throw.

PubMed

Wagner, Herbert; Buchecker, Michael; von Duvillard, Serge P; Müller, Erich

2010-01-01

The jump throw is the most applied throwing technique in team- handball (Wagner et al., 2008); however, a comprehensive analysis of 3D-kinematics of the team-handball jump throw is lacking. Therefore, the purpose of our study was: 1) to measure differences in ball release speed in team- handball jump throw and anthropometric parameters between groups of different levels of performance and (2) to analyze upper body 3D-kinematics (flexion/extension and rotation) to determine significant differences between these groups. Three-dimensional kinematic data was analyzed via the Vicon MX 13 motion capturing system (Vicon Peak, Oxford, UK) from 26 male team-handball players of different performance levels (mean age: 21.2 ± 5.0 years). The participants were instructed to throw the ball (IHF Size 3) onto a target at 8 m distance, and to hit the center of a square of 1 × 1 m at about eye level (1.75 m), with maximum ball release speed. Significant differences between elite vs. low level players were found in the ball release speed (p < 0.001), body height (p < 0.05), body weight (p < 0.05), maximal trunk internal rotation (p < 0.05), trunk flexion (p < 0.01) and forearm pronation (p < 0.05) as well as trunk flexion (p < 0.05) and shoulder internal rotation (p < 0.001) angular velocity at ball release. Results of our study suggest that team-handball players who were taller and of greater body weight have the ability to achieve a higher ball release speed in the jump throw, and that an increase in trunk flexion and rotation angular velocity improve the performance in team-handball jump throw that should result in an increase of ball release speed. Key pointsTeam-handball players who were taller and of greater body weight have the ability to achieve a higher ball release speed.An increase in trunk flexion, trunk rotation and shoulder internal rotation angular velocity should result in an increase of ball release speed.Trunk movements are normally well observable for experienced coaches, easy correctable and therefore practical to improve the performance in team-handball jump throw of low level players during training without using complex measurement devices.

Human peripheral blood mononuclear cells (PBMCs) from smokers release higher levels of IL-1-like cytokines after exposure to combustion-generated ultrafine particles.

PubMed

De Falco, Gianluigi; Terlizzi, Michela; Sirignano, Mariano; Commodo, Mario; D'Anna, Andrea; Aquino, Rita P; Pinto, Aldo; Sorrentino, Rosalinda

2017-02-22

Ultrafine particles (UFP) generated by combustion processes are often associated with adverse health effects. However, little is known about the inflammatory processes generated by UFP that may underlie their toxicological activity. Murine macrophages (J774.1 cells) and human peripheral blood mononuclear cells (PBMCs) were used to evaluate the molecular mechanism underlying the pro-inflammatory activity of UFP. The addition of soot particles to J774.1 cells induced a concentration-dependent release of IL-1α, IL-1β and IL-33 This effect was not associated with cell death and, in contrast to literature, was pronounced at very low concentrations (5-100 pg/ml). Similarly, UFP induced the release of IL-1α, IL-18 and IL-33 by PBMCs. However, this effect was solely observed in PBMCs obtained from smokers, as the PBMCs from non-smokers instead released higher levels of IL-10. The release of these cytokines after UFP exposure was caspase-1- and NLRP3 inflammasome-dependent in PBMCs from healthy smokers, whereas IL-1α release was calpain-dependent. These results show that UFP at very low concentrations are able to give rise to an inflammatory process that is responsible for IL-1α, IL-18 and IL-33 release, which is pronounced in PBMCs from smokers, confirming that these individuals are especially susceptible to inflammatory-based airway diseases once exposed to air pollution.

Relation of gastric acid and pepsin secretion to serum gastrin levels in dogs given bombesin and gastrin-17.

PubMed

Hirschowitz, B I; Molina, E

1983-05-01

To quantitate bombesin stimulation of gastric acid and pepsin via release of gastrin, five gastric fistula dogs were given graded doses (60-1,250 pmol X kg-1 X h-1) of bombesin tetradecapeptide and 40-2,000 pmol X kg-1 X h-1 of synthetic gastrin-17 (G-17). Acid and pepsin output and serum gastrin were proportional to the dose of stimulant. The half-maximal dose of bombesin for gastrin release was 200 pmol X kg-1 X h-1. Bombesin-stimulated acid secretion related to serum gastrin concentrations was congruent with the G-17 curve, but with a maximum of only 62% of the G-17 maximum before declining by 27% despite higher serum gastrin levels. This suggested that bombesin stimulates acid secretion only via gastrin release and inhibits at higher doses by releasing another inhibitory peptide, most likely somatostatin, which is also released by bombesin. The same mechanism could apply to supramaximal inhibition of acid and pepsin seen with high doses of G-17. Because the pepsin curve related to serum gastrin was to the left of the G-17 curve, we concluded that another secretagogue released by bombesin acts synergistically with gastrin on pepsin secretion. Therefore, bombesin stimulates gastric secretion through gastrin release, but its effects are modified by peptides coreleased to a) increase pepsin output at low doses and b) limit the output of acid and pepsin to 50-60% of the G-17 maximum.

Human peripheral blood mononuclear cells (PBMCs) from smokers release higher levels of IL-1-like cytokines after exposure to combustion-generated ultrafine particles

PubMed Central

De Falco, Gianluigi; Terlizzi, Michela; Sirignano, Mariano; Commodo, Mario; D’Anna, Andrea; Aquino, Rita P.; Pinto, Aldo; Sorrentino, Rosalinda

2017-01-01

Ultrafine particles (UFP) generated by combustion processes are often associated with adverse health effects. However, little is known about the inflammatory processes generated by UFP that may underlie their toxicological activity. Murine macrophages (J774.1 cells) and human peripheral blood mononuclear cells (PBMCs) were used to evaluate the molecular mechanism underlying the pro-inflammatory activity of UFP. The addition of soot particles to J774.1 cells induced a concentration-dependent release of IL-1α, IL-1β and IL-33 This effect was not associated with cell death and, in contrast to literature, was pronounced at very low concentrations (5–100 pg/ml). Similarly, UFP induced the release of IL-1α, IL-18 and IL-33 by PBMCs. However, this effect was solely observed in PBMCs obtained from smokers, as the PBMCs from non-smokers instead released higher levels of IL-10. The release of these cytokines after UFP exposure was caspase-1- and NLRP3 inflammasome-dependent in PBMCs from healthy smokers, whereas IL-1α release was calpain-dependent. These results show that UFP at very low concentrations are able to give rise to an inflammatory process that is responsible for IL-1α, IL-18 and IL-33 release, which is pronounced in PBMCs from smokers, confirming that these individuals are especially susceptible to inflammatory-based airway diseases once exposed to air pollution. PMID:28223692

Delivering enhanced testosterone replacement therapy through nanochannels.

PubMed

Ferrati, Silvia; Nicolov, Eugenia; Bansal, Shyam; Zabre, Erika; Geninatti, Thomas; Ziemys, Arturas; Hudson, Lee; Ferrari, Mauro; Goodall, Randal; Khera, Mohit; Palapattu, Ganesh; Grattoni, Alessandro

2015-02-18

Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease.

PubMed

Hara, Katsuko; Hirowatari, Yuji; Shimura, Yuko; Takahashi, Hakuo

2011-11-01

Patients with diabetes mellitus (DM) are prone to atherosclerosis. Atherosclerosis activates platelets; activated platelets release serotonin, and therefore, evaluation of serotonin levels in blood could be a valuable biomarker for future risk of cardiovascular events. Plasma serotonin levels obtained from patients with DM complicated with chronic kidney disease were measured using HPLC and were compared to serotonin levels of healthy control subjects. Patients with DM were classified into 2 subgroups of mildly (group 1) and moderately/severely (group 2) impaired renal function. Serotonin concentration in platelet-poor plasma for group 1 was significantly higher than that of healthy control subjects (p < 0.01), and was significantly higher than that of patients from group 2 (p < 0.05). The concentration of serotonin in whole blood for group 2 patients was significantly lower than that measured from healthy control subjects (p < 0.01). The ratio of the plasma to whole blood level was significantly elevated in both groups 1 and 2 compared with healthy controls (p < 0.01). Our results indicate that platelets are activated to release serotonin into plasma in diabetic patients with mildly impaired renal function. When renal damage is advanced, platelets are over-activated to release serotonin. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Bioavailability of ambroxol sustained release preparations. Part II: Single and multiple oral dose studies in man.

PubMed

Janssen, T J; Guelen, P J; Vree, T B; Botterblom, M H; Valducci, R

1988-01-01

The bioavailability of a new ambroxol sustained release preparation (75 mg) based on a dialyzing membrane for controlled release was studied in healthy volunteers after single and multiple oral dose in comparison with a standard sustained release formulation in a cross-over study under carefully controlled conditions. Plasma concentrations of ambroxol were measured by means of a HPLC method. Based on AUC data both preparations are found to be bioequivalent, but show different plasma concentration profiles. The test preparation showed a more pronounced sustained release profile than the reference preparation (single dose) resulting in significantly higher steady state plasma levels.

Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design

PubMed Central

Enayatifard, Reza; Mahjoob, Aiding; Ebrahimi, Pouneh; Ebrahimnejad, Pedram

2015-01-01

Objective(s): A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design. Materials and Methods: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates. Results: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 °C and 24 hr, respectively. Conclusion: This study showed that by controllinig the physical variables optimum drug release were obtained. PMID:26351563

Immediate versus modified release hydrocortisone in mitotane-treated patients with adrenocortical cancer.

PubMed

Weigel, Marianne; Hahner, Stefanie; Sherlock, Mark; Agha, Amar; Behan, Lucy Ann; Stewart, Paul M; Arlt, Wiebke; Beier, Daniela; Frey, Kathrin; Zopf, Kathrin; Quinkler, Marcus

2017-04-01

Mitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane-treated ACC patients yet. Case series to compare serum cortisol, calculated free serum cortisol and ACTH levels in ACC patients on mitotane treatment with immediate and modified release hydrocortisone. Pharmacokinetics of immediate and modified release hydrocortisone, each administered at a dose of 40-20-0 mg, in nine patients with ACC and adjuvant mitotane treatment. For comparison, ten patients with secondary adrenal insufficiency (SAI) on three different hydrocortisone regimens and ten healthy males were included. Serum cortisol and plasma ACTH were measured by chemiluminescent enzyme immunoassay, and CBG by RIA, followed by calculation of free cortisol. Calculated free serum cortisol levels after 40 mg immediate release hydrocortisone in ACC patients (46 ± 14 nmol/l) were similar to those after 10 mg immediate release hydrocortisone intake in men with SAI (64 ± 16 nmol/l) or to the physiological morning free cortisol levels in healthy subjects (31 ± 5 nmol/l). Compared to immediate release hydrocortisone, free cortisol levels after 40 mg modified release hydrocortisone in ACC patients were significantly lower (12 ± 3 nmol/l; P = 0·03) resulting in a generally lower AUC (98 ± 21 vs 149 ± 37 nmol h/l; P = 0·02). 40-20-0 mg immediate release, but not modified release hydrocortisone, resulted in sufficient glucocorticoid coverage in patients with ACC receiving mitotane treatment. The use of equivalent doses of modified release hydrocortisone preparation should be avoided in patients on mitotane treatment. © 2017 John Wiley & Sons Ltd.

Extra virgin olive oil aroma release after interaction with human saliva from individuals with different body mass index.

PubMed

Genovese, Alessandro; Rispoli, Tiziana; Sacchi, Raffaele

2018-07-01

The interindividual variability observed in saliva characteristics raises the question of its relationship with variability in fat sensory perception, particularly in aroma compounds. In the present study, which aimed to measure aroma release from different individuals, eleven key aroma compounds of extra virgin olive oil (EVOO) were monitored and quantified in dynamic headspace after an in vitro interaction between EVOO and human saliva. Therefore, 60 individuals were studied from those who were normal weight (NW), overweight (OW) and obese (O). OW and O demonstrate a higher release of C 6 compounds compared to NW. By contrast, NW have a higher release of C 5 compounds. Pentanal and hexanal also increased after saliva interaction in a refined olive oil that is free from volatiles. Among the saliva samples with a higher release in NW individuals, only pentanal was different. However, the low levels of these lipid oxidation end-products do not appear to be very important with respect to increasing odorous fat sensitivity. The results obtained in the present study demonstrate the important role of saliva in the aroma release of EVOO, indicating that humans can perceive it differently in relation to their body mass index. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Conditional Release Placements of Insanity Acquittees in Oregon: 2012-2014.

PubMed

Novosad, David; Banfe, Shelley; Britton, Juliet; Bloom, Joseph D

2016-03-01

Between January 1, 2012 and December 31, 2014, there was a large population (N = 200) of insanity acquittees placed on conditional release (CR) in the state of Oregon. This article looks at the demographic and system characteristics of this large group of individuals. The authors then focus on the initial housing placement and what happens to individuals after their release in relation to their housing placement. In Oregon, insanity acquittees are either conditionally released directly by the court or placed in the hospital prior to potential CR by a supervising board. In general, once CR occurs, individuals tend to stay in their initial placement without moving to less structured levels of care, raising concerns about transinstitutionalization. This is especially true for individuals released to the most structured living arrangement (secure residential treatment facility). Those individuals who are conditionally released to less structured settings have a higher rate of revocation back to the hospital. Those individuals who do move to less structured levels of care usually have longer hospital stays and start off in more structured levels of care to start their CR. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The effects of extreme nutritional conditions on the neurochemistry of reward and addiction

NASA Astrophysics Data System (ADS)

Pothos, Emmanuel N.

2001-08-01

Weight loss is a frequent problem in space flights. We now claim that it may affect performance and drug-seeking behavior by altering midbrain neurochemistry. In food-deprived rats (20-30% underweight) basal extracellular dopamine levels in the nucleus accumbens decrease to 40-50% of normal and locomotion is depressed. However, amphetamine-induced dopamine release and locomotion are higher than in controls (1825% vs. 595% after a 25 μM d-amphetamine intraaccumbens infusion). The lower basal and the higher stimulated dopamine levels suggest that the neurotransmitter accumulates presynaptically in the accumbens of the underweight rats due to subnormal basal release. Psychostimulants are more rewarding for underweight subjects possibly because they release significantly more dopamine from elevated presynaptic stores into the accumbens. Consequently, weight loss can lead both to depression of performance and propensity to substance abuse. These effects should be considered when providing nutritional resources for space flights so that weight loss is limited.

Antioxidant treatment prevents the development of fructose-induced abdominal adipose tissue dysfunction.

PubMed

Fariña, Juan Pablo; García, María Elisa; Alzamendi, Ana; Giovambattista, Andrés; Marra, Carlos Alberto; Spinedi, Eduardo; Gagliardino, Juan José

2013-07-01

In the present study, we tested the effect of OS (oxidative stress) inhibition in rats fed on an FRD [fructose-rich diet; 10% (w/v) in drinking water] for 3 weeks. Normal adult male rats received a standard CD (commercial diet) or an FRD without or with an inhibitor of NADPH oxidase, APO (apocynin; 5 mM in drinking water; CD-APO and FRD-APO). We thereafter measured plasma OS and metabolic-endocrine markers, AAT (abdominal adipose tissue) mass and cell size, FA (fatty acid) composition (content and release), OS status, LEP (leptin) and IRS (insulin receptor substrate)-1/IRS-2 mRNAs, ROS (reactive oxygen species) production, NADPH oxidase activity and LEP release by isolated AAT adipocytes. FRD-fed rats had larger AAT mass without changes in body weight, and higher plasma levels of TAG (triacylglycerol), FAs, TBARS (thiobarbituric acid-reactive substance) and LEP. Although no significant changes in glucose and insulin plasma levels were observed in these animals, their HOMA-IR (homoeostasis model assessment of insulin resistance) values were significantly higher than those of CD. The AAT from FRD-fed rats had larger adipocytes, higher saturated FA content, higher NADPH oxidase activity, greater ROS production, a distorted FA content/release pattern, lower insulin sensitivity together with higher and lower mRNA content of LEP and IRS-1-/2 respectively, and released a larger amount of LEP. The development of all the clinical, OS, metabolic, endocrine and molecular changes induced by the FRD were significantly prevented by APO co-administration. The fact that APO treatment prevented both changes in NADPH oxidase activity and the development of all the FRD-induced AAT dysfunctions in normal rats strongly suggests that OS plays an important role in the FRD-induced MS (metabolic syndrome) phenotype.

Phosphorus and greenhouse gas dynamics in a drained calcareous wetland soil in Minnesota.

PubMed

Berryman, Erin M; Venterea, Rodney T; Baker, John M; Bloom, Paul R; Elf, Brandy

2009-01-01

Restoration of wetland hydrology can produce ecological benefits but may have unintended consequences. We examined effects of altered water level on release of dissolved reactive phosphorus (DRP) and greenhouse gases (GHG) in soil cores from a marsh being evaluated for restoration. We also measured field concentrations of DRP and other constituents in wetland porewater. Intact cores from a sampling location with higher Fe and lower calcium carbonate (CaCO(3)) contents released more DRP than another location, and displayed higher DRP under completely saturated compared to partly drained conditions. Porewater samples collected from the high-Fe location also contained higher DRP levels. Chemical data suggest that redox-driven reactions largely controlled DRP levels at the high-Fe site, while CaCO(3) adsorption was more important at the low-Fe site. Over the long term, water table elevation may attenuate P draining from the wetland due to decreased mineralization. However, such measures may increase P release in the short term. Raising the water level in soil cores resulted in decreased nitrous oxide (N(2)O) emissions, increased methane (CH(4)) emissions, and an overall increase in total global warming potential (GWP). The proportion of total GWP contributed by N(2)O decreased from 14% to < or = 1% as water level was raised, while the proportion contributed by CH(4) increased from 10 to 20% to 60 to 80%. Restoration of hydrology in the Rice Lake wetland has the potential to affect both local water quality and global air quality. These combined effects complicate the cost-to-benefit analysis of such wetland restoration efforts.

Rechargeable calcium phosphate orthodontic cement with sustained ion release and re-release

PubMed Central

Zhang, Ling; Weir, Michael D.; Chow, Laurence C.; Reynolds, Mark A.; Xu, Hockin H. K.

2016-01-01

White spot lesions (WSL) due to enamel demineralization are major complications for orthodontic treatments. Calcium phosphate (CaP) dental resins with Ca and P ion releases are promising for remineralization. However, previous Ca and P releases lasted for only weeks. Experimental orthodontic cements were developed using pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA) at mass ratio of 1:1 (PE); and PE plus 10% of 2-hydroxyethyl methacrylate (HEMA) and 5% of bisphenol A glycidyl dimethacrylate (BisGMA) (PEHB). Particles of amorphous calcium phosphate (ACP) were incorporated into PE and PEHB at 40% filler level. Specimens were tested for bracket-enamel shear bond strength, water sorption, CaP release, and ion recharge and re-release. PEHB+40ACP had higher bracket-enamel bond strength and ion release and rechargeability than PE+40ACP. ACP incorporation into the novel orthodontic cement did not adversely affect the bracket-enamel bond strength. Ion release and re-release from the novel ACP orthodontic cement indicated favorable release and re-release patterns. The recharged orthodontic cement could release CaP ions continuously for four weeks without further recharge. Novel rechargeable orthodontic cement containing ACP was developed with a high bracket-enamel bond strength and the ability to be repeatedly recharged to maintain long-term high levels of CaP ion releases. PMID:27808251

Beta-endorphin and arginine vasopressin following stressful sensory stimuli in man

NASA Technical Reports Server (NTRS)

Kohl, Randall L.

1992-01-01

This experimentation partially defines, for the first time, the response of beta-endorphin (ENDO) in man during tests designed to elicit nausea and motion sickness. These responses are similar to those associated with arginine vasopressin (AVP) and adreno-corticotropin (ACTH) to the extent that all hormones rise in response to motion sickness (p less than 0.003). Repeated exposure diminished motion-induced release of ENDO (p less than 0.005) and AVP (p less than 0.004) despite a three-fold increase in resistance to motion stimuli. Higher post-stress levels of AVP (p less than 0.04) and ACTH (p less than 0.02) were correlated with greater resistance to motion sickness. These data support the hypothesis that release of AVP is a significant link between stressful motion and motion-induced nausea and other autonomic system changes. Further, resistant individual apparently can tolerate higher peripheral levels of AVP before nausea results. Peripheral release of ENDO and ACTH may follow release of AVP; however, given the extensive and complex functional interactions that exist between AVP and the opiate systems, it is not yet possible to define a clear role for ENDO in the etiology of motion sickness.

The portal-drained viscera release fibroblast growth factor 19 in humans.

PubMed

Koelfat, Kiran V K; Bloemen, Johanne G; Jansen, Peter L M; Dejong, Cornelis H C; Schaap, Frank G; Olde Damink, Steven W M

2016-12-01

Fibroblast growth factor 19 (FGF19) is an ileum-derived endrocrine factor that is produced in response to transepithelial bile salt flux. FGF19 represses bile salt synthesis in the liver. Despite the general assumption that FGF19 signals to the liver via portal blood, no human data are available to support this notion. The aim was to study portal FGF19 levels, and determined bile salt and FGF19 fluxes across visceral organs in humans. Bile salt and FGF19 levels were assessed in arterial, portal, and hepatic venous blood collected from fasted patients who underwent partial liver resection for colorectal liver metastases (n = 30). Fluxes across the portal-drained viscera (PDV), liver, and splanchnic area were calculated. Portal bile salt levels (7.8 [5.0-12.4] μmol/L) were higher than levels in arterial (2.7 [1.7-5.5] μmol/L, P < 0.0001) and hepatic venous blood (3.4 [2.5-6.5] μmol/L, P < 0.0001). Bile salts released by the PDV (+1.2 [+0.7-+2.0] mmol kg -1  h -1 , P < 0.0001) were largely taken up by the liver (-1.0 [-1.8 to -0.4] mmol kg -1  h -1 , P < 0.0001). Portal levels of FGF19 (161 ± 78 pg/mL) were higher than arterial levels (135 ± 65 pg/mL, P = 0.046). A net release of FGF19 by the PDV (+4.0 [+2.1 to +9.9] ng kg -1  h -1 , P < 0.0001) was calculated. There was no significant flux of FGF19 across the liver (-0.2 [-3.7 to +7.4] ng kg -1  h -1 , P = 0.93). In conclusion, FGF19 levels in human portal blood are higher than in arterial blood. FGF19 is released by the portal-drained viscera under fasted steady state conditions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Consonant identification in noise using Hilbert-transform temporal fine-structure speech and recovered-envelope speech for listeners with normal and impaired hearinga)

PubMed Central

Léger, Agnès C.; Reed, Charlotte M.; Desloge, Joseph G.; Swaminathan, Jayaganesh; Braida, Louis D.

2015-01-01

Consonant-identification ability was examined in normal-hearing (NH) and hearing-impaired (HI) listeners in the presence of steady-state and 10-Hz square-wave interrupted speech-shaped noise. The Hilbert transform was used to process speech stimuli (16 consonants in a-C-a syllables) to present envelope cues, temporal fine-structure (TFS) cues, or envelope cues recovered from TFS speech. The performance of the HI listeners was inferior to that of the NH listeners both in terms of lower levels of performance in the baseline condition and in the need for higher signal-to-noise ratio to yield a given level of performance. For NH listeners, scores were higher in interrupted noise than in steady-state noise for all speech types (indicating substantial masking release). For HI listeners, masking release was typically observed for TFS and recovered-envelope speech but not for unprocessed and envelope speech. For both groups of listeners, TFS and recovered-envelope speech yielded similar levels of performance and consonant confusion patterns. The masking release observed for TFS and recovered-envelope speech may be related to level effects associated with the manner in which the TFS processing interacts with the interrupted noise signal, rather than to the contributions of TFS cues per se. PMID:26233038

Effects of sulfate on heavy metal release from iron corrosion scales in drinking water distribution system.

PubMed

Sun, Huifang; Shi, Baoyou; Yang, Fan; Wang, Dongsheng

2017-05-01

Trace heavy metals accumulated in iron corrosion scales within a drinking water distribution system (DWDS) could potentially be released to bulk water and consequently deteriorate the tap water quality. The objective of this study was to identify and evaluate the release of trace heavy metals in DWDS under changing source water conditions. Experimental pipe loops with different iron corrosion scales were set up to simulate the actual DWDS. The effects of sulfate levels on heavy metal release were systemically investigated. Heavy metal releases of Mn, Ni, Cu, Pb, Cr and As could be rapidly triggered by sulfate addition but the releases slowly decreased over time. Heavy metal release was more severe in pipes transporting groundwater (GW) than in pipes transporting surface water (SW). There were strong positive correlations (R 2  > 0.8) between the releases of Fe and Mn, Fe and Ni, Fe and Cu, and Fe and Pb. When switching to higher sulfate water, iron corrosion scales in all pipe loops tended to be more stable (especially in pipes transporting GW), with a larger proportion of stable constituents (mainly Fe 3 O 4 ) and fewer unstable compounds (β-FeOOH, γ-FeOOH, FeCO 3 and amorphous iron oxides). The main functional iron reducing bacteria (IRB) communities were favorable for the formation of Fe 3 O 4 . The transformation of corrosion scales and the growth of sulfate reducing bacteria (SRB) accounted for the gradually reduced heavy metal release with time. The higher metal release in pipes transporting GW could be due to increased Fe 6 (OH) 12 CO 3 content under higher sulfate concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

10 CFR 850.31 - Release criteria.

Code of Federal Regulations, 2010 CFR

2010-01-01

... lowest contamination level practicable, but not to exceed the levels established in paragraphs (b) and (c... contamination level of equipment or item surfaces does not exceed the higher of 0.2 µg/100 cm 2 or the... the equipment or item and its future use and the nature of the beryllium contamination. (c) Before...

Impacts of the Fukushima nuclear power plants on marine radioactivity.

PubMed

Buesseler, Ken; Aoyama, Michio; Fukasawa, Masao

2011-12-01

The impacts on the ocean of releases of radionuclides from the Fukushima Dai-ichi nuclear power plants remain unclear. However, information has been made public regarding the concentrations of radioactive isotopes of iodine and cesium in ocean water near the discharge point. These data allow us to draw some basic conclusions about the relative levels of radionuclides released which can be compared to prior ocean studies and be used to address dose consequences as discussed by Garnier-Laplace et al. in this journal. The data show peak ocean discharges in early April, one month after the earthquake and a factor of 1000 decrease in the month following. Interestingly, the concentrations through the end of July remain higher than expected implying continued releases from the reactors or other contaminated sources, such as groundwater or coastal sediments. By July, levels of (137)Cs are still more than 10,000 times higher than levels measured in 2010 in the coastal waters off Japan. Although some radionuclides are significantly elevated, dose calculations suggest minimal impact on marine biota or humans due to direct exposure in surrounding ocean waters, though considerations for biological uptake and consumption of seafood are discussed and further study is warranted.

Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

PubMed

Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

2003-07-01

The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of swelling and erosion within this matrix at lower fat-wax level which is also supported by release exponent values and Fickian fraction release against time profile of this agent. The results generated in this study showed that proper selection of these hydrophobic materials based on their physico-chemical properties is important in designing wax matrix tablets with desired dissolution profile.

Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.

PubMed

Medina, M; Alberto, M R; Sierra, L; Van Nieuwenhove, C; Saad, S; Isla, M I; Jerez, S

2014-07-01

The present study evaluated the plasma fatty acid levels and the vascular prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was measured in plasma. The levels of PG and nitric oxide (NO) released from the aorta were also determined. Vascular morphology of the aorta was characterized by intima and media thickness measurements. The rabbits fed with HD had higher levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic acid level was unchanged. PGI(2) and NO were diminished and PGF(2α) levels, the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed with HD. In conclusion, feeding HD for a short period increased ARA plasma levels and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway to vasoconstrictor metabolite release. These lipid metabolism alterations in addition to the reduced NO levels and the moderate changes in the vascular morphology contributed to the endothelial dysfunction in this animal model. Therefore, the present findings support the importance of early correction or prevention of high cholesterol levels to disrupt the endothelial dysfunction process that leads to cardiovascular disease.

Stress response of wild bottlenose dolphins (Tursiops truncatus) during capture-release health assessment studies.

PubMed

Fair, Patricia A; Schaefer, Adam M; Romano, Tracy A; Bossart, Gregory D; Lamb, Stephen V; Reif, John S

2014-09-15

There is a growing concern about the impacts of stress in marine mammals as they face a greater array of threats. The stress response of free-ranging dolphins (Tursiops truncatus) was examined by measuring their physiologic response to capture and handling. Samples were collected from 168 dolphins during capture-release health assessments 2003-2007 at two study sites: Charleston, SC (CHS) and the Indian River Lagoon, FL (IRL). Adrenocorticotropic hormone (ACTH), cortisol, aldosterone (ALD) and catecholamines (epinephrine (EPI), norepinephrine (NOR), dopamine (DA)), were measured in blood and cortisol in urine. Mean time to collect pre-examination samples after netting the animals was 22min; post-examination samples were taken prior to release (mean 1h 37min). EPI and DA concentrations decreased significantly with increased time to blood sampling. ACTH and cortisol levels increased from the initial capture event to the post-examination sample. EPI concentrations increased significantly with increasing time to the pre-examination sample and decreased significantly with time between the pre- and post-examination sample. Cortisol concentrations increased between the pre- and post-examination in CHS dolphins. Age- and sex-adjusted mean pre-examination values of catecholamines were significantly higher in CHS dolphins; ALD was higher in IRL dolphins. Significant differences related to age or sex included higher NOR concentrations in males; higher ALD and urine cortisol levels in juveniles than adults. Wild dolphins exhibited a typical mammalian response to acute stress of capture and restraint. Further studies that relate hormone levels to biological and health endpoints are warranted. Published by Elsevier Inc.

HEPC-based liposomes trigger cytokine release from peripheral blood cells: effects of liposomal size, dose and lipid composition.

PubMed

Yamamoto, Sayaka; Ishida, Tatsuhiro; Inoue, Akiko; Mikami, Junko; Muraguchi, Masahiro; Ohmoto, Yasukazu; Kiwada, Hiroshi

2002-04-02

The immune response caused by liposome stimulation was studied by assessing the level of several cytokines released from human peripheral blood cells. Liposome stimulation resulted in the release of IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma. The size of the liposomes affected the degree of the cytokine releases with larger sized liposomes causing higher levels of cytokine induction. In addition, it appears that the lipid composition of liposomes had no effect on the degree of cytokine release. The release of cytokines occurred even in the absence of serum, suggesting that serum proteins did not contribute to liposome stimulation in peripheral blood cells. The release of cytokines induced by liposome stimulation was inhibited by the presence of either protein kinase-C (PKC) or protein tyrosine kinase (PTK) inhibitor, but not by the presence of an endocytosis inhibitor. This indicates that signal transduction via PKC or PTK is necessary, in order for human peripheral blood cells to release cytokines (IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma) as the result of liposome stimulation. These quantitative data on the release of cytokines by liposomal stimulation provide useful information for the development of rational drug delivery systems and the safety of cytokine induction via the use of liposomes.

Myocardial revascularization with miniaturized extracorporeal circulation versus off pump: Evaluation of systemic and myocardial inflammatory response in a prospective randomized study.

PubMed

Formica, Francesco; Broccolo, Francesco; Martino, Antonello; Sciucchetti, Jennifer; Giordano, Vincenzo; Avalli, Leonello; Radaelli, Gianluigi; Ferro, Orazio; Corti, Fabrizio; Cocuzza, Clementina; Paolini, Giovanni

2009-05-01

This prospective randomized study sought to verify the systemic inflammatory response, inflammatory myocardial damage, and early clinical outcome in coronary surgery with the miniaturized extracorporeal circulation system or on the beating heart. Sixty consecutive patients were randomized to miniaturized extracorporeal circulation (n = 30) or off-pump coronary revascularization (off-pump coronary artery bypass grafting, n = 30). Intraoperative and postoperative data were recorded. Plasma levels of interleukin-6 and tumor necrosis factor-alpha were measured from systemic blood intraoperatively, at the end of operation, and 24 and 48 hours thereafter. Levels of the same markers and blood lactate were measured from coronary sinus blood intraoperatively to evaluate myocardial inflammation. Markers of myocardial damage were also analyzed. One patient died in the off-pump coronary artery bypass grafting group. There was no statistical difference in early clinical outcome in both groups. Release of interleukin-6 was higher in the off-pump coronary artery bypass grafting group 24 hours after the operation (P = .03), whereas levels of tumor necrosis factor-alpha were not different in both groups. Cardiac release of interleukin-6, tumor necrosis factor-alpha, and blood lactate were not different in both groups. Release of troponin T was not significantly different in both groups. Levels of creatine kinase mass were statistically higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group, but only at the end of the operation (P < .0001). Hemoglobin levels were significantly higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group after 24 hours (P = .01). Miniaturized extracorporeal circulation can be considered similar to off-pump surgery in terms of systemic inflammatory response, myocardial inflammation and damage, and early outcome.

Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate.

PubMed

Allam, Ayat; Fetih, Gihan

2016-01-01

The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug's bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability) of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes), while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration) following sublingual administration was found to be significantly higher (91.06%±13.28%), as compared with that after oral tablet administration (39.37%±11.4%). These results indicate that the fast dissolving niosomal film could be a promising delivery system to enhance the bioavailability and prolong the therapeutic effect of metoprolol tartrate.

Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

PubMed Central

Allam, Ayat; Fetih, Gihan

2016-01-01

The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability) of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes), while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration) following sublingual administration was found to be significantly higher (91.06%±13.28%), as compared with that after oral tablet administration (39.37%±11.4%). These results indicate that the fast dissolving niosomal film could be a promising delivery system to enhance the bioavailability and prolong the therapeutic effect of metoprolol tartrate. PMID:27536063

Chronic Obstructive Pulmonary Disease-Derived Circulating Cells Release IL-18 and IL-33 under Ultrafine Particulate Matter Exposure in a Caspase-1/8-Independent Manner

PubMed Central

De Falco, Gianluigi; Colarusso, Chiara; Terlizzi, Michela; Popolo, Ada; Pecoraro, Michela; Commodo, Mario; Minutolo, Patrizia; Sirignano, Mariano; D’Anna, Andrea; Aquino, Rita P.; Pinto, Aldo; Molino, Antonio; Sorrentino, Rosalinda

2017-01-01

Chronic obstructive pulmonary disease (COPD) is considered the fourth-leading causes of death worldwide; COPD is caused by inhalation of noxious indoor and outdoor particles, especially cigarette smoke that represents the first risk factor for this respiratory disorder. To mimic the effects of particulate matter on COPD, we isolated peripheral blood mononuclear cells (PBMCs) and treated them with combustion-generated ultrafine particles (UFPs) obtained from two different fuel mixtures, namely, pure ethylene and a mixture of ethylene and dimethylfuran (the latter mimicking the combustion of biofuels). UFPs were separated in two fractions: (1) sub-10 nm particles, named nano organic carbon (NOC) particles and (2) primarily soot particles of 20–40 nm and their agglomerates (200 nm). We found that both NOC and soot UFPs induced the release of IL-18 and IL-33 from unstable/exacerbated COPD-derived PBMCs. This effect was associated with higher levels of mitochondrial dysfunction and derived reactive oxygen species, which were higher in PBMCs from unstable COPD patients after combustion-generated UFP exposure. Moreover, lower mRNA expression of the repairing enzyme OGG1 was associated with the higher levels of 8-OH-dG compared with non-smoker and smokers. It was interesting that IL-18 and IL-33 release from PBMCs of unstable COPD patients was not NOD-like receptor 3/caspase-1 or caspase-8-dependent, but rather correlated to caspase-4 release. This effect was not evident in stable COPD-derived PBMCs. Our data suggest that combustion-generated UFPs induce the release of caspase-4-dependent inflammasome from PBMCs of COPD patients compared with healthy subjects, shedding new light into the biology of this key complex in COPD. PMID:29123531

Effects of cryopreservation and hypothermic storage on cell viability and enzyme activity in recombinant encapsulated cells overexpressing alpha-L-iduronidase.

PubMed

Mayer, Fabiana Quoos; Baldo, Guilherme; de Carvalho, Talita Giacomet; Lagranha, Valeska Lizzi; Giugliani, Roberto; Matte, Ursula

2010-05-01

Here, we show the effects of cryopreservation and hypothermic storage upon cell viability and enzyme release in alginate beads containing baby hamster kidney cells overexpressing alpha-L-iduronidase (IDUA), the enzyme deficient in mucopolysaccharidosis type I. In addition, we compared two different concentrations of alginate gel (1% and 1.5%) in respect to enzyme release from the beads and their shape and integrity. Our results indicate that in both alginate concentrations, the enzyme is released in lower amounts compared with nonencapsulated cells. Alginate 1% beads presented increased levels of IDUA release, although this group presented more deformities when compared with alginate 1.5% beads. Importantly, both encapsulated groups presented higher cell viability after long cryopreservation period and hypothermic storage. In addition, alginate 1.5% beads presented higher enzyme release after freezing protocols. Taken together, our findings suggest a benefic effect of alginate upon cell viability and functionality. These results may have important application for treatment of both genetic and nongenetic diseases using microencapsulation-based artificial organs.

Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses.

PubMed

White, Charles James; DiPasquale, Stephen Anthony; Byrne, Mark Edward

2016-04-01

The majority of contact lens wearers experience a significant level of ocular discomfort associated with lens wear, often within hours of wear, related to dry lenses, inflammation, protein adhesion to the lens surface, etc. Application of controlled drug release techniques has focused on the incorporation and/or release of a single comfort molecule from a lens including high molecular weight comfort agents or pharmaceutical agents. Previous studies have sought to mitigate the occurrence of only single propagators of discomfort. Clinical studies with eye drop solutions have shown that a mixture of diverse comfort agents selected to address multiple propagators of discomfort provide the greatest and longest lasting sensations of comfort for the patient. In this paper, multiple propagators of discomfort are addressed through the simultaneous release of four molecules from a novel contact lens to ensure high level of lens wear comfort. Silicone hydrogel contact lenses were engineered via molecular imprinting strategies to simultaneously release up to four template molecules including hydropropyl methylcellulose (HPMC), trehalose, ibuprofen, and prednisolone. By adjusting the ratio of functional monomer to comfort molecule, a high level of control was demonstrated over the release rate. HPMC, trehalose, ibuprofen, and prednisolone were released at therapeutically relevant concentrations with varying rates from a single lens. The results indicate use as daily disposable lenses for single day release or extended-wear lenses with multiple day release. Imprinted lenses are expected to lead to higher efficacy for patients compared to topical eye drops by improving compliance and mitigating concentration peaks and valleys associated with multiple drops.

Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses

PubMed Central

White, Charles J.; DiPasquale, Stephen A.; Byrne, Mark E.

2016-01-01

Purpose The majority of contact lens wearers experience a significant level of ocular discomfort associated with lens wear, often within hours of wear, related to dry lenses, inflammation, protein adhesion to the lens surface, etc. Application of controlled drug release techniques has focused on the incorporation and/or release of a single comfort molecule from a lens including high molecular weight comfort agents or pharmaceutical agents. Previous studies have sought to mitigate the occurrence of only single propagators of discomfort. Clinical studies with eye drop solutions have shown that a mixture of diverse comfort agents selected to address multiple propagators of discomfort provide the greatest and longest lasting sensations of comfort for the patient. In this paper, multiple propagators of discomfort are addressed through the simultaneous release of four molecules from a novel contact lens to ensure high level of lens wear comfort. Methods Silicone hydrogel contact lenses were engineered via molecular imprinting strategies to simultaneously release up to four template molecules including hydropropyl methylcellulose (HPMC), trehalose, ibuprofen, and prednisolone. Results By adjusting the ratio of functional monomer to comfort molecule, a high level of control was demonstrated over the release rate. HPMC, trehalose, ibuprofen, and prednisolone were released at therapeutically relevant concentrations with varying rates from a single lens. Conclusions The results indicate use as daily disposable lenses for single day release or extended-wear lenses with multiple day release. Imprinted lenses are expected to lead to higher efficacy for patients compared to topical eye drops by improving compliance and mitigating concentration peaks and valleys associated with multiple drops. PMID:26945177

Long-term effects of trauma: post-traumatic stress among civilian internees of the Japanese during World War II.

PubMed

Potts, M K

1994-09-01

This study examined predictors and health-related effects of post-traumatic stress among 129 civilian internees of the Japanese during World War II. Post-traumatic stress disorder was noted in 36.7% within the 6 months after their release and in 15.0% within the most recent 6 months. Women were more likely than men to indicate post-traumatic stress disorder within the 6 months after their release. Higher incomes were associated with lower levels of post-traumatic stress within the most recent 6 months. After controlling for demographic and internment-related factors, higher levels of post-traumatic stress were associated with poorer physical health. This association was stronger among older internees than among their younger counterparts. Implications of the findings for clinical gerontology are discussed.

Presynaptic strontium dynamics and synaptic transmission.

PubMed Central

Xu-Friedman, M A; Regehr, W G

1999-01-01

Strontium can replace calcium in triggering neurotransmitter release, although peak release is reduced and the duration of release is prolonged. Strontium has therefore become useful in probing release, but its mechanism of action is not well understood. Here we study the action of strontium at the granule cell to Purkinje cell synapse in mouse cerebellar slices. Presynaptic residual strontium levels were monitored with fluorescent indicators, which all responded to strontium (fura-2, calcium orange, fura-2FF, magnesium green, and mag-fura-5). When calcium was replaced by equimolar concentrations of strontium in the external bath, strontium and calcium both entered presynaptic terminals. Contaminating calcium was eliminated by including EGTA in the extracellular bath, or by loading parallel fibers with EGTA, enabling the actions of strontium to be studied in isolation. After a single stimulus, strontium reached higher peak free levels than did calcium (approximately 1.7 times greater), and decayed more slowly (half-decay time 189 ms for strontium and 32 ms for calcium). These differences in calcium and strontium dynamics are likely a consequence of greater strontium permeability through calcium channels, lower affinity of the endogenous buffer for strontium, and less efficient extrusion of strontium. Measurements of presynaptic divalent levels help to explain properties of release evoked by strontium. Parallel fiber synaptic currents triggered by strontium are smaller in amplitude and longer in duration than those triggered by calcium. In both calcium and strontium, release consists of two components, one more steeply dependent on divalent levels than the other. Strontium drives both components less effectively than does calcium, suggesting that the affinities of the sensors involved in both phases of release are lower for strontium than for calcium. Thus, the larger and slower strontium transients account for the prominent slow component of release triggered by strontium. PMID:10096899

The slack test does not assess maximal shortening velocity of muscle fascicle in human.

PubMed

Hager, Robin; Dorel, Sylvain; Nordez, Antoine; Rabita, Giuseppe; Couturier, Antoine; Hauraix, Hugo; Duchateau, Jacques; Guilhem, Gaël

2018-06-14

The application of a series of extremely high accelerative motor-driven quick releases while muscles contract isometrically (i.e. slack test) has been proposed to assess unloaded velocity in human muscle. This study aimed to measure gastrocnemius medialis fascicle (V F ) and tendinous tissues shortening velocity during motor-driven quick releases performed at various activation levels to assess the applicability of the slack test method in human. Maximal fascicle shortening velocity and joint velocity recorded during quick releases and during fast contraction without external load (ballistic condition) were compared. Gastrocnemius medialis fascicle behaviour was investigated from 25 participants using high-frame rate ultrasound during quick releases performed at various activation levels (from 0% to 60% of maximal voluntary isometric torque) and ballistic contractions. Unloaded joint velocity calculated using the slack test method increased whereas V F decreased with muscle activation level (P≤0.03). Passive and low-level quick releases elicited higher V F values (≥ 41.4±9.7 cm.s -1 ) compared to ballistic condition (36.3±8.7 cm.s -1 ), while quick releases applied at 60% of maximal voluntary isometric torque produced the lowest V F These findings suggest that initial fascicle length, complex fascicle-tendon interactions, unloading reflex and motor-driven movement pattern strongly influence and limit the shortening velocity achieved during the slack test. Furthermore, V F elicited by quick releases is likely to reflect substantial contributions of passive processes. Therefore, the slack test is not appropriate to assess maximal muscle shortening velocity in vivo. © 2018. Published by The Company of Biologists Ltd.

Micronization increases vitamin E carrying and releasing abilities of insoluble fiber.

PubMed

Hsu, Pang-Kuei; Chien, Po-Jung; Chau, Chi-Fai

2008-03-26

This study was to investigate the effects of micronization on vitamin-carrying capacity and slow-release ability of carambola (starfruit) insoluble fiber (IF) and cellulose using in vitro and in vivomodels. Upon micronization, carambola IF (8.1 microm) underwent structural changes to expose more functional groups in the fiber matrix and to exhibit higher oil-holding capacity ( approximately 20.4-fold). Micronized fibers in forms of fiber-vitamin composites, particularly the micronized carambola IF-vitamin composite, were capable of carrying vitamin E (alpha-tocopherol) up to 9.6-fold over their unmicronized forms and releasing nutrient gradually. Animal studies demonstrated that the adminstration of micronized carambola IF-vitamin composite could maintain the plasma vitamin E of rats at relatively higher levels (2.1-3.6-fold of the initial values) for at least 5 h. The results suggested that micronized fibers, particularly the micronized carambola IF, could be exploited as potential nutrient carriers in food applications and also be used to produce slow-release formulations.

The higher exercise intensity and the presence of allele I of ACE gene elicit a higher post-exercise blood pressure reduction and nitric oxide release in elderly women: an experimental study.

PubMed

Santana, Hugo A P; Moreira, Sérgio R; Neto, Willson B; Silva, Carla B; Sales, Marcelo M; Oliveira, Vanessa N; Asano, Ricardo Y; Espíndola, Foued S; Nóbrega, Otávio T; Campbell, Carmen S G; Simões, Herbert G

2011-12-02

The absence of the I allele of the angiotensin converting enzyme (ACE) gene has been associated with higher levels of circulating ACE, lower nitric oxide (NO) release and hypertension. The purposes of this study were to analyze the post-exercise salivary nitrite (NO2-) and blood pressure (BP) responses to different exercise intensities in elderly women divided according to their ACE genotype. Participants (n = 30; II/ID = 20 and DD = 10) underwent three experimental sessions: incremental test - IT (15 watts workload increase/3 min) until exhaustion; 20 min exercise 90% anaerobic threshold (90% AT); and 20 min control session without exercise. Volunteers had their BP and NO2- measured before and after experimental sessions. Despite both intensities showed protective effect on preventing the increase of BP during post-exercise recovery compared to control, post-exercise hypotension and increased NO2- release was observed only for carriers of the I allele (p < 0.05). Genotypes of the ACE gene may exert a role in post-exercise NO release and BP response.

Effects of polyvinylpyrrolidone both as a binder and pore-former on the release of sparingly water-soluble topiramate from ethylcellulose coated pellets.

PubMed

Yang, Meiyan; Xie, Si; Li, Qiu; Wang, Yuli; Chang, Xinyi; Shan, Li; Sun, Lei; Huang, Xiaoli; Gao, Chunsheng

2014-04-25

Delivering sparingly water-soluble drugs from ethylcellulose (EC) coated pellets with a controlled-release pattern remains challenging. In the present study, hydrophilic polyvinylpyrrolidone (PVP) was used both as a binder and a pore-former in EC coated pellets to deliver sparingly water-soluble topiramate, and the key factors that influenced drug release were identified. When the binder PVP content in drug layers below 20% w/w was decreased, the physical state of topiramate changed from amorphous to crystalline, making much difference to drug solubility and dissolution rates while modifying the drug release profile from first-order to zero-order. In addition, without PVP in drug layering solution, drug layered particles were less sticky during layering process, thus leading to a shorter process and higher loading efficiency. Furthermore, PVP level as a pore-former in EC coating layers mainly governed drug release from the coated pellets with the sensitivity ranging from 23% to 29%. PVP leaching rate and water permeability from EC/PVP film increased with the PVP level, which was perfectly correlated with drug release rate. Additionally, drug release from this formulation was independent of pH of release media or of the paddle mixing speed, but inversely proportional to the osmolality of release media above the physiological range. Copyright © 2014. Published by Elsevier B.V.

Influence of the autonomic nervous system on calcium homeostasis in the rat.

PubMed

Stern, J E; Cardinali, D P

1994-01-01

The local surgical manipulation of sympathetic and parasympathetic nerves innervating the thyroid-parathyroid territory was employed to search for the existence of a peripheral neuroendocrine link controlling parathyroid hormone (PTH) and calcitonin (CT) release. From 8 to 24 h after superior cervical ganglionectomy (SCGx), at the time of wallerian degeneration of thyroid-parathyroid sympathetic nerve terminals, an alpha-adrenergic inhibition, together with a minor beta-adrenergic stimulation, of hypercalcemia-induced CT release, and an alpha-adrenoceptor inhibition of hypocalcemia-induced PTH release were found. In chronically SCGx rats PTH response to EDTA was slower, and after CaCl2 injection, serum calcium attained higher levels in face of normal CT levels. SCGx blocked the PTH increase found in sham-operated rats stressed by a subcutaneous injection of turpentine oil, but did not affect the greater response to EDTA. The higher hypocalcemia seen after turpentine oil was no longer observed in SCGx rats. The effects of turpentine oil stress on calcium and CT responses to a bolus injection of CaCl2 persisted in rats subjected to SCGx 14 days earlier. Interruption of thyroid-parathyroid parasympathetic input conveyed by the thyroid nerves (TN) and the inferior laryngeal nerves (ILN) caused a fall in total serum calcium, an increase of PTH levels and a decrease of CT levels, when measured 10 days after surgery. Greater responses of serum CT and PTH were detected in TN-sectioned, and in TN- or ILN-sectioned rats, respectively. Physiological concentrations of CT decreased, and those of PTH increased, in vitro cholinergic activity in rat SCG, measured as specific choline uptake, and acetylcholine synthesis and release. The results indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis.

Effect of decreasing temperature on the strobilation of Aurelia sp.1

NASA Astrophysics Data System (ADS)

Shi, Yan; Yu, Zhigang; Zhen, Yu; Wang, Guoshan; Wang, Xungong; Mi, Tiezhu

2018-03-01

The worldwide proliferation of marine jellyfish has become a crucial ecological and social issue, and as a cosmopolitan species, Aurelia spp. have received increasing scientific attentions. In the present study, the responses of strobilation in Aurelia sp.1 to decreasing temperature were illuminated through the expression levels of the retinoid x receptor (RxR) gene and the gene encoding a secreted protein, CL390. We observed that a higher final temperature decreased the strobilation prophase and strobilation interphase periods, and the growth rate of the strobilae ratio increased with increasing CL390 gene expression. The ratio of strobilae at 12°C was highest, and the strobilae showed the higher releasing ratios at both 12°C and 16°C compared with those at 4°C and 8°C. Furthermore, more ephyrae were released at the higher final temperature. Additionally, up-regulation and down-regulation of the CL390 gene were observed in response to the four decreasing temperatures. Although the four CL390 gene transcript levels increased more significantly than the transcript levels of the RxR gene, similar trends were observed in both genes.

Unexpectedly increased anorexigenic postprandial responses of PYY and GLP-1 to fast ice cream consumption in adult patients with Prader-Willi syndrome.

PubMed

Rigamonti, A E; Bini, S; Grugni, G; Agosti, F; De Col, A; Mallone, M; Cella, S G; Sartorio, A

2014-10-01

The effect of eating rate on the release of anorexigenic gut peptides in Prader-Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far. Postprandial PYY and GLP-1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age-matched patients with simple obesity and normal-weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety. Fast ice cream consumption stimulated GLP-1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP-1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP-1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding. Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age-matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions. © 2013 John Wiley & Sons Ltd.

[Traffic-related PM2.5 regulates IL-2 releasing in Jurkat T cells by calcium signaling pathway].

PubMed

Tong, Guoqiang; Zhang, Zhihong; Han, Jianbiao; Qiu, Yong; Xu, Jianjun

2013-09-01

To explore the effects of traffic-related PM2.5 on interleukin-2 (IL-2) in Jurkat T cells and the regulatory action of calcium signaling pathway. The cells were exposed to 100 microg/ml of PM2.5 for 3, 6 and 24 h. Normal saline group, blank filter group, calcium chelating agent EGTA group and the calcineurin antagonist cyclosporine A (CSA) group were as parallel control. The level of IL-2 was detected by ELISA kits, the mRNA expression of CaN, NFAT were determined by QRT-PCR. The nuclear distribution of NFAT was observed by immunofluorescence microscopy. The level of IL-2 in Jurkat T cells exposed to 100 microg/ml PM2.5 was significantly lower than parallel groups, but higher than PM2.5 + CSA group and PM2.5 + EGTA group (P < 0.05). With the increase of time, the releasing level of IL-2 appeared reducing trend in 100 microg/ml of PM2.5 group. The mRNA expression level of NFAT and CaN were higher than parallel groups, PM2.5 + CSA group and PM2.5 + EGTA group (P < 0.05). PM2.5 can induce NFAT protein with dephosphorylation and be activated, and NFAT protein can shift into nuclear. The level of IL-2 was negatively associated with the expression level of NFAT and CaN gene (P < 0.05). Traffic-related PM2.5 may inhibit the releasing of IL-2, Ca(2+)-CaN-NFAT signal pathway may involve in the regulation of IL-2.

Effects of hatchery rearing on Florida largemouth bass Micropterus floridanus resource allocation and performance under semi-natural conditions.

PubMed

Garlock, T M; Monk, C T; Lorenzen, K; Matthews, M D; St Mary, C M

2014-12-01

This study examined the growth, activity, metabolism and post-release survival of three groups of Florida largemouth bass Micropterus floridanus: wild-caught fish, hatchery fish reared according to standard practice (hatchery standard) and hatchery fish reared under reduced and unpredictable food provisioning (hatchery manipulated). Hatchery-standard fish differed from wild-caught fish in all measured variables, including survival in semi-natural ponds. Hatchery-standard and hatchery-manipulated fish showed higher activity levels, faster growth and lower standard metabolic rates than wild-caught fish in the hatchery. Fish reared under the manipulated feeding regime showed increased metabolic rates and increased post-release growth, similar to wild-caught fish. Their activity levels and post-release survival, however, remained similar to those of hatchery-standard fish. Activity was negatively correlated with post-release survival and failure of the feed manipulation to reduce activity may have contributed to its failure to improve post-release survival. Activity and post-release survival may be influenced by characteristics of the rearing environment other than the feeding regime, such as stock density or water flow rates. © 2014 The Fisheries Society of the British Isles.

Fission gas release during power bumping at high burnup

NASA Astrophysics Data System (ADS)

Cunningham, M. E.; Freshley, M. D.; Lanning, D. D.

1993-03-01

Research to define the behavior of Zircaloy-clad light-water reactor fuel irradiated to high burnup levels was conducted by the High Burnup Effects Program (HBEP). One activity conducted by the HBEP was to "bump" the power level of irradiated, commercial light-water reactor fuel rods to design limit linear heat generation rates at end-of-life. These bumping irradiations simulated end-of-life design limit linear heat generation rates and provided data on the effects of short-term, high power irradiations at high burnup applicable to the design and operating constraints imposed by maximum allowable fuel rod internal gas pressure limits. Based on net fission gas release during the bumping irradiations, it was observed that higher burnup rods had greater rod-average fractional fission gas release than lower burnup rods at equal bumping powers. It was also observed that a hold period of 48 hours at the peak power was insufficient to achieve equilibrium fission gas release. Finally, differences in the prebump location of fission gas, i.e., within the UO 2 matrix or at grain boundaries, affected the fission gas release during the bumping irradiations.

Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis.

PubMed

Ruderman, Michael A; Wilson, Deirdra F; Reid, Savanna

2015-01-01

This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05-4.17), drug violations (HR 2.44 95% CI: 2.00-2.98), non-violent violations (HR 2.14 95% CI: 1.73-2.64), violent and serious violations (HR 1.88 95% CI: 1.45-2.43), and technical violations (HR 1.86 95% CI: 1.37-2.53). Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted.

Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis

PubMed Central

Ruderman, Michael A.; Wilson, Deirdra F.; Reid, Savanna

2015-01-01

Objective This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Background Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Methods Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Results Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05–4.17), drug violations (HR 2.44 95% CI: 2.00–2.98), non-violent violations (HR 2.14 95% CI: 1.73–2.64), violent and serious violations (HR 1.88 95% CI: 1.45–2.43), and technical violations (HR 1.86 95% CI: 1.37–2.53). Conclusions Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted. PMID:26492490

Interaural level differences do not suffice for restoring spatial release from masking in simulated cochlear implant listening.

PubMed

Ihlefeld, Antje; Litovsky, Ruth Y

2012-01-01

Spatial release from masking refers to a benefit for speech understanding. It occurs when a target talker and a masker talker are spatially separated. In those cases, speech intelligibility for target speech is typically higher than when both talkers are at the same location. In cochlear implant listeners, spatial release from masking is much reduced or absent compared with normal hearing listeners. Perhaps this reduced spatial release occurs because cochlear implant listeners cannot effectively attend to spatial cues. Three experiments examined factors that may interfere with deploying spatial attention to a target talker masked by another talker. To simulate cochlear implant listening, stimuli were vocoded with two unique features. First, we used 50-Hz low-pass filtered speech envelopes and noise carriers, strongly reducing the possibility of temporal pitch cues; second, co-modulation was imposed on target and masker utterances to enhance perceptual fusion between the two sources. Stimuli were presented over headphones. Experiments 1 and 2 presented high-fidelity spatial cues with unprocessed and vocoded speech. Experiment 3 maintained faithful long-term average interaural level differences but presented scrambled interaural time differences with vocoded speech. Results show a robust spatial release from masking in Experiments 1 and 2, and a greatly reduced spatial release in Experiment 3. Faithful long-term average interaural level differences were insufficient for producing spatial release from masking. This suggests that appropriate interaural time differences are necessary for restoring spatial release from masking, at least for a situation where there are few viable alternative segregation cues.

Ion release and mechanical properties of calcium silicate and calcium hydroxide materials used for pulp capping.

PubMed

Natale, L C; Rodrigues, M C; Xavier, T A; Simões, A; de Souza, D N; Braga, R R

2015-01-01

To compare the ion release and mechanical properties of a calcium hydroxide (Dycal) and two calcium silicate (MTA Angelus and Biodentine) cements. Calcium and hydroxyl ion release in water from 24-h set cements were calculated from titration with HCl (n = 3). Calcium release after 7, 14, 21 and 28 days at pH 5.5 and 7.0 was measured using ICP-OES (n = 6). Flexural strength (FS) and modulus (E) were tested after 48-h storage, and compressive strength (CS) was tested after 48 h and 7 days (n = 10). Ion release and mechanical data were subjected to anova/Tukey and Kruskal-Wallis/Mann-Whitney tests, respectively (α = 0.05). Titration curves revealed that Dycal released significantly fewer ions in solution than calcium silicates (P < 0.001). Calcium release remained constant at pH 7.0, whilst at pH 5.5, it dropped significantly by 24% after 21 days (P < 0.05). At pH 5.5, MTA Angelus released significantly more calcium than Dycal (P < 0.01), whilst Biodentine had superior ion release than Dycal at pH 7.0 (P < 0.01). Biodentine had superior flexural strength, flexural modulus and compressive strength than the other cements, whilst MTA Angelus had higher modulus than Dycal (P < 0.001). Immediate calcium and hydroxyl ion release in solution was significantly lower for Dycal. In general, all materials released constant calcium levels over 28 days, but release from Dycal was significantly lower than Biodentine and MTA Angelus depending on pH conditions. Biodentine had substantially higher strength and modulus than MTA Angelus and Dycal, both of which demonstrated low stress-bearing capabilities. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Development of metoprolol tartrate extended-release matrix tablet formulations for regulatory policy consideration.

PubMed

Nellore, R V; Rekhi, G S; Hussain, A S; Tillman, L G; Augsburger, L L

1998-01-02

This research study was designed to develop model extended-release (ER) matrix tablet formulations for metoprolol tartrate (100 mg) sufficiently sensitive to manufacturing variable and to serve as the scientific basis for regulatory policy development on scale-up and post approval changes for modified-release dosage forms (SUPAC-MR). Several grades and levels of hydroxypropyl methylcellulose (Methocel K4M, K15M, K100M and K100LV), fillers and binders and studied. Three granulation processes were evaluated; direct compression, fluid-bed or high-shear granulation. Lubrication was performed in a V-blender and tablets were compressed on an instrumented rotary tablet press. Direct compression formulations exhibited poor flow, picking and sticking problems during tableting. High-shear granulation resulted in the formation of hard granules that were difficult to mill but yielded good tablets. Fluid-bed granulations were made using various binders and appeared to be satisfactory in terms of flow and tableting performance. In vitro drug release testing was performed in pH 6.8 phosphate buffer using USP apparatus 2 (paddle) at 50 rpm. At a fixed polymer level, drug release from the higher viscosity grades (K100M) was slower as compared to the lower viscosity grades (K100LV). In addition, release from K100LV was found to be more sensitive to polymer level changes. Increased in polymer level from 10 to 40% and/or filler change from lactose to dicalcium phosphate resulted in about 25-30% decrease in the amount of metoprolol release after 12 h. The results of this study led to the choice of Methocel K100LV as the hydrophilic matrix polymer and fluid-bed granulation as the process of choice for further evaluation of critical and non-critical formulation and processing variables.

Changes in lipid transport-involved proteins of epicardial adipose tissue associated with coronary artery disease.

PubMed

Salgado-Somoza, Antonio; Teijeira-Fernández, Elvis; Fernández, Ángel Luis; González-Juanatey, José Ramón; Eiras, Sonia

2012-10-01

Recent studies have focused on the potential role of epicardial adipose tissue (EAT) in the physiopathology of several metabolic and cardiovascular diseases, especially coronary artery disease (CAD). We aimed to study whether there are differences in the proteome and the secretome between epicardial and subcutaneous adipose tissue (SAT) from patients with and without CAD. EAT and SAT samples were collected from 64 patients undergoing elective cardiac surgery either for coronary artery bypass grafting or valve surgery. One or two-dimensional electrophoresis were performed on tissue samples and media collected at 3, 6, 24 or 48 of tissue culture. Protein identification was performed with mass spectrometry, and the results were then validated with Western blot or enzyme immunoassay. mRNA expression levels were analysed by real time polymerase chain reaction. The release of several proteins was found to be higher in EAT that in SAT. Remarkably, there were higher levels of apolipoprotein A-I and glutation S-transferase P release, whereas mRNA expression of fatty acid binding protein 4 was lower in EAT. Although apolipoprotein A-I protein quantity in EAT was similar between CAD and non CAD patients, its released levels from this fat pad were lower in CAD. EAT and SAT show different profiles of protein release and a different pattern was also found in samples from patients with CAD. These findings might support the hypothesis that EAT plays an interesting role in the physiopathology of atherosclerosis and CAD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Investigation of the effect of hydroxypropyl methylcellulose on the phase transformation and release profiles of carbamazepine-nicotinamide cocrystal.

PubMed

Li, Mingzhong; Qiu, Shi; Lu, Yan; Wang, Ke; Lai, Xiaojun; Rehan, Mohammad

2014-09-01

The aim of this work was to investigate the influence of hydroxypropyl methylcellulose (HPMC) on the phase transformation and release profile of carbamazepine-nicotinamide (CBZ-NIC) cocrystal in solution and in sustained release matrix tablets. The polymorphic transitions of the CBZ-NIC cocrystal and its crystalline properties were examined by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Raman spectroscopy, and scanning electron microscopy (SEM). The apparent CBZ solubility and dissolution rate of CBZ-NIC cocrystal were constant in different concentrations of HPMC solutions. In a lower percentage of HPMC in the matrix tablets, the CBZ release profile of the CBZ-NIC cocrystal was nonlinear and declined over time. With an increased HPMC content in the tablets, the CBZ-NIC cocrystal formulation showed a significantly higher CBZ release rate in comparison with the other two formulations of CBZ III and the physical mixture. Because of a significantly improved dissolution rate of the CBZ-NIC cocrystal, the rate of CBZ entering into solution is significantly faster than the rate of formation of the CBZ-HPMC soluble complex in solution, leading to a higher supersaturation level of CBZ and subsequently precipitation of CBZ dihydrate.

An Ecological and Human Biomonitoring Investigation of Mercury Contamination at the Aamjiwnaang First Nation

PubMed Central

Cryderman, Diana; Letourneau, Lisa; Miller, Fiona; Basu, Niladri

2016-01-01

The Aamjiwnaang First Nations community is located in Canada’s ‘Chemical Valley’ situated in southwest Ontario near Sarnia. Mercury pollution in the region has been known since the 1940s but little is known about levels in the environment and area residents. The current study, using ecological and human exposure assessment methods, was conducted at the community’s request to help fill these gaps. First, Canada’s National Pollutant Release Inventory (NPRI) and the U.S. Toxics Release Inventory (TRI) were queried to investigate mercury releases from area facilities. In 2010, 700 pounds of mercury were emitted into the air, 25 pounds were released into water bodies, and 93 thousand pounds were disposed of on-site via underground injections or into landfills, and together these show continued releases into the region. Second, mercury levels were measured in stream sediment and nearby soil from sites at Aamjiwnaang (n=4) and off Reserve (n=19) in Canada and the U.S. during three seasons that spanned 2010–2011. Total mercury in sediment across all sites and sampling seasons ranged from 5.0 to 398.7μg/kg, and in soils ranged from 1.2 to 696.2μg/kg. Sediment and soil mercury levels at Aamjiwnaang were higher than the reference community, and Aamjiwnaang’s Talfourd Creek site had the highest mercury levels. Third, a biomonitoring study was performed with 43 mother-child pairs. Hair (mean±SD of all participants: 0.18±0.16μg/g) and blood (1.6±2.0μg/L) mercury levels did not differ between participants studied on- and off-Reserve, likely because of limited seafood intake (<1 serving/week). Urine mercury levels (0.5±0.8μg/L) were significantly higher (1.5–2.5 times) in mother-child pairs living on-Reserve versus those living off-Reserve. In general, the study links evidence of mercury sources, environmental fate, and human exposures, and in doing so it shows that mercury levels in ecological and human samples are similar to values found in other areas, though there are some trends and evidence of contamination at Aamjiwnaang that warrant attention. PMID:27645755

The effect of poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity.

PubMed

Yan, Fei; Zhang, Chao; Zheng, Yi; Mei, Lin; Tang, Lina; Song, Cunxian; Sun, Hongfan; Huang, Laiqiang

2010-02-01

The aim of this work was to investigate the effect of triblock copolymer poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity. Docetaxel-loaded nanoparticles were prepared by oil-in-water emulsion/solvent evaporation technique using biodegradable poly(lactic-co-glycolic acid) (PLGA) with or without addition of poloxamer 188, respectively. The resulting nanoparticles were found to be spherical with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in the docetaxel-resistant MCF-7 TAX30 human breast cancer cell line could be found in comparison with that of PLGA nanoparticles. In addition, the docetaxel-loaded PLGA/poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than that of docetaxel-loaded PLGA nanoparticles and Taxotere (P < .05). In conclusion, the results showed advantages of docetaxel-loaded PLGA nanoparticles incorporated with poloxamer 188 compared with the nanoparticles without incorporation of poloxamer 188 in terms of sustainable release and efficacy in breast cancer chemotherapy. The effects of poloxamer 188, a triblock copolymer were studied on nanoparticle morphology, size, cancer cell uptake and cytotoxicity. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in resistant human breast cancer cell line was demonstrated, resulting in a significantly higher level of cytotoxicity. Copyright 2010 Elsevier Inc. All rights reserved.

Enhanced oral bioavailability and antiasthmatic efficacy of curcumin using redispersible dry emulsion.

PubMed

Jang, Dong-Jin; Kim, Sung Tae; Oh, Euichaul; Lee, Kooyeon

2014-01-01

Dry emulsion containing curcumin (DE-CUR) was prepared for oral delivery of poorly water-soluble curcumin, and its oral bioavailability and antiasthmatic efficacy was evaluated. After comparison of the solubility of curcumin in various oils, Plurol® Oleique CC497 was selected to be the oil phase due to its higher solubility of CUR than other oils. A dry emulsion prepared by spray-drying of a homogenized oil-in-water emulsion was well-reconstituted in water, fabricating similar particle distribution and in vitro release to that of a dispersed homogeneous emulsion before spraying. The release of DE-CUR was much higher than that of curcumin (85.3 vs. 1.7% release at 60 min). Consequently, DE-CUR resulted in 12.0- and 7.1-fold higher Cmax and AUC0-24h than curcumin. In a murine asthma model, DE-CUR effectively suppressed airway hyperresponsiveness and levels of T-helper cytokines such as interleukin-4, inteleukin-5, and interleukin-13. These findings demonstrate that the DE-CUR shows a potential for the development of functional foods or medicines including CUR.

Marine biodiversity–ecosystem functions under uncertain environmental futures

PubMed Central

Bulling, Mark T.; Hicks, Natalie; Murray, Leigh; Paterson, David M.; Raffaelli, Dave; White, Piran C. L.; Solan, Martin

2010-01-01

Anthropogenic activity is currently leading to dramatic transformations of ecosystems and losses of biodiversity. The recognition that these ecosystems provide services that are essential for human well-being has led to a major interest in the forms of the biodiversity–ecosystem functioning relationship. However, there is a lack of studies examining the impact of climate change on these relationships and it remains unclear how multiple climatic drivers may affect levels of ecosystem functioning. Here, we examine the roles of two important climate change variables, temperature and concentration of atmospheric carbon dioxide, on the relationship between invertebrate species richness and nutrient release in a model benthic estuarine system. We found a positive relationship between invertebrate species richness and the levels of release of NH4-N into the water column, but no effect of species richness on the release of PO4-P. Higher temperatures and greater concentrations of atmospheric carbon dioxide had a negative impact on nutrient release. Importantly, we found significant interactions between the climate variables, indicating that reliably predicting the effects of future climate change will not be straightforward as multiple drivers are unlikely to have purely additive effects, resulting in increased levels of uncertainty. PMID:20513718

Pheromonal communication in nereids and the likely intervention by petroleum derived pollutants.

PubMed

Müller, Carsten T; Priesnitz, Frank M; Beckmann, Manfred

2005-01-01

Nereis succinea and Platynereis dumerilii (Annelida, Polychaeta) are broadcast spawners and reproduce semelparously. The final events in reproduction, swarming and spawning are co-ordinated by sex pheromones.A water-soluble fraction of crude oil, the volatile fraction (C9-C16) of EKO FISK crude oil was found to induce release of gametes in male nereids at levels <0.3 ppm.Using vacuum distillation, column chromatography, preparative GC and GC-MS analysis we showed that C(5)-alkylated benzenes were most potent in inducing sperm release, of those n-butyl-4-methylbenzene and 1,4-diethyl-2-methylbenzene were found to induce release of gametes at concentrations ≥4 nM. This threshold is lower than those reported for natural pheromones (nereithione: 60 nM, uric acid: 600 nM) but higher than background levels of aromatic compounds of 0.05 nM and below.Other oil fractions showed additional effects, blocking pheromone reception or narcotising and intoxicating animals. Part of these effects could be assigned to naphthalenes at levels down to approx. 320 nM. In the original mixtures, their action was modified or compensated by the presence of gamete release inducing alkylated benzenes. Other highly paralysing substances remained elusive.

Marine biodiversity-ecosystem functions under uncertain environmental futures.

PubMed

Bulling, Mark T; Hicks, Natalie; Murray, Leigh; Paterson, David M; Raffaelli, Dave; White, Piran C L; Solan, Martin

2010-07-12

Anthropogenic activity is currently leading to dramatic transformations of ecosystems and losses of biodiversity. The recognition that these ecosystems provide services that are essential for human well-being has led to a major interest in the forms of the biodiversity-ecosystem functioning relationship. However, there is a lack of studies examining the impact of climate change on these relationships and it remains unclear how multiple climatic drivers may affect levels of ecosystem functioning. Here, we examine the roles of two important climate change variables, temperature and concentration of atmospheric carbon dioxide, on the relationship between invertebrate species richness and nutrient release in a model benthic estuarine system. We found a positive relationship between invertebrate species richness and the levels of release of NH(4)-N into the water column, but no effect of species richness on the release of PO(4)-P. Higher temperatures and greater concentrations of atmospheric carbon dioxide had a negative impact on nutrient release. Importantly, we found significant interactions between the climate variables, indicating that reliably predicting the effects of future climate change will not be straightforward as multiple drivers are unlikely to have purely additive effects, resulting in increased levels of uncertainty.

Bioaccumulation factors and the steady state assumption for cesium isotopes in aquatic foodwebs near nuclear facilities.

PubMed

Rowan, D J

2013-07-01

Steady state approaches, such as transfer coefficients or bioaccumulation factors, are commonly used to model the bioaccumulation of (137)Cs in aquatic foodwebs from routine operations and releases from nuclear generating stations and other nuclear facilities. Routine releases from nuclear generating stations and facilities, however, often consist of pulses as liquid waste is stored, analyzed to ensure regulatory compliance and then released. The effect of repeated pulse releases on the steady state assumption inherent in the bioaccumulation factor approach has not been evaluated. In this study, I examine the steady state assumption for aquatic biota by analyzing data for two cesium isotopes in the same biota, one isotope in steady state (stable (133)Cs) from geologic sources and the other released in pulses ((137)Cs) from reactor operations. I also compare (137)Cs bioaccumulation factors for similar upstream populations from the same system exposed solely to weapon test (137)Cs, and assumed to be in steady state. The steady state assumption appears to be valid for small organisms at lower trophic levels (zooplankton, rainbow smelt and 0+ yellow perch) but not for older and larger fish at higher trophic levels (walleye). Attempts to account for previous exposure and retention through a biokinetics approach had a similar effect on steady state, upstream and non-steady state, downstream populations of walleye, but were ineffective in explaining the more or less constant deviation between fish with steady state exposures and non-steady state exposures of about 2-fold for all age classes of walleye. These results suggest that for large, piscivorous fish, repeated exposure to short duration, pulse releases leads to much higher (137)Cs BAFs than expected from (133)Cs BAFs for the same fish or (137)Cs BAFs for similar populations in the same system not impacted by reactor releases. These results suggest that the steady state approach should be used with caution in any situation where reactor releases are episodic or pulse in nature, even if the magnitude of these releases is small. Copyright © 2012. Published by Elsevier Ltd.

Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

PubMed Central

Zorov, Dmitry B.; Juhaszova, Magdalena; Sollott, Steven J.

2014-01-01

Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo. PMID:24987008

The effect of platform switching on the levels of metal ion release from different implant–abutment couples

PubMed Central

Alrabeah, Ghada O; Knowles, Jonathan C; Petridis, Haralampos

2016-01-01

The improved peri-implant bone response demonstrated by platform switching may be the result of reduced amounts of metal ions released to the surrounding tissues. The aim of this study was to compare the levels of metal ions released from platform-matched and platform-switched implant–abutment couples as a result of accelerated corrosion. Thirty-six titanium alloy (Ti-6Al-4V) and cobalt–chrome alloy abutments were coupled with titanium cylinders forming either platform-switched or platform-matched groups (n=6). In addition, 18 unconnected samples served as controls. The specimens were subjected to accelerated corrosion by static immersion in 1% lactic acid for 1 week. The amount of metal ions ion of each test tube was measured using inductively coupled plasma mass spectrometry. Scanning electron microscope (SEM) images and energy dispersive spectroscopy X-ray analyses were performed pre- and post-immersion to assess corrosion at the interface. The platform-matched groups demonstrated higher ion release for vanadium, aluminium, cobalt, chrome, and molybdenum compared with the platform-switched groups (P<0.05). Titanium was the highest element to be released regardless of abutment size or connection (P<0.05). SEM images showed pitting corrosion prominent on the outer borders of the implant and abutment platform surfaces. In conclusion, implant–abutment couples underwent an active corrosion process resulting in metal ions release into the surrounding environment. The highest amount of metal ions released was recorded for the platform-matched groups, suggesting that platform-switching concept has a positive effect in reducing the levels of metal ion release from the implant–abutment couples. PMID:27357323

Influence of type and level of water-soluble additives on drug release and surface and mechanical properties of Surelease films.

PubMed

Rohera, Bhagwan D; Parikh, Nilesh H

2002-11-01

Ethylcellulose in combination with water-soluble additives has been used in the development of microporous membrane-coated dosage forms. In the present study, application of three types of water-soluble additives, namely polyethylene glycols (PEG 400, 3350, and 8000), maltodextrins (Maltrin M150, M100, and M040 in the order of lower to higher average polymer size and molecular weight; dextrose equivalence 16.9, 11.1, and 4.8, respectively), and xylitol, as porosity modifiers in the films of a commercially available aqueous ethylcellulose dispersion (Surelease/E-7-7060 plasticized with glyceryl tricaprylate/caprate) was investigated. The effect of type and level of these additives on drug release characteristics and surface and mechanical properties of the polymeric films was studied. Each additive was incorporated at 20 and 30% levels in the polymeric dispersion based on its solids content. Ibuprofen tablets were coated using the polymeric dispersion with and without additive at 3% w/w coat level in a fluid-bed equipment. The coated tablets were evaluated for their drug release rate, coat reflectivity (gloss), Brinell hardness, and elastic modulus. Differential scanning calorimetric analysis of the films was performed to determine the physico-chemical changes in the applied film-coats. The rate of drug release, hence film porosity, was observed to be dependent on the type and level of the additive added. The molecular weight of the additive and its concentration in the polymeric dispersion had significant influence on the rate of drug release, hardness, and elasticity of the film-coats.

Reduced ex vivo release of pro-inflammatory cytokines and elevated plasma interleukin-6 are inflammatory signatures of post-stroke delirium.

PubMed

Kowalska, Katarzyna; Klimiec, Elzbieta; Weglarczyk, Kazimierz; Pera, Joanna; Slowik, Agnieszka; Siedlar, Maciej; Dziedzic, Tomasz

2018-04-18

Experimental studies suggest that systemic inflammation contributes to the pathophysiology of delirium. The aim of our study was to determine blood-derived inflammatory signatures of post-stroke delirium. We included 144 ischemic stroke patients. We assessed delirium on a daily basis during the first 7 days of hospitalization. Venous blood was collected at day 3 after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). We measured LPS-induced cytokine concentration (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70) as well as plasma levels of IL-6 and TNFα. Delirium was diagnosed in 21.5% of patients. After correction for monocyte count, patients with delirium had reduced LPS-induced TNFα, IP-10, IL-1β, IL-6, and IL-12 release. The plasma IL-6 level was higher in delirious patients compared to patients without delirium. After adjusting for stroke severity and infections, higher ex vivo TNFα (OR 0.29, 95%CI 0.11-0.72, P = 0.01), IP-10 (OR 0.25, 95%CI 0.08-0.73, P = 0.01), IL-1β (OR 0.42, 95%CI 0.20-0.89, P = 0.02), and IL-12 (OR 0.07, 95%CI 0.01-0.70, P = 0.02) release was associated with the reduced risk of delirium. In multivariate analysis, the higher plasma IL-6 was associated with the increased risk of delirium (OR 1.61, 95%CI 1.00-2.58, P = 0.04). Reduced ex vivo release of pro-inflammatory cytokines after LPS stimulation and the elevated plasma IL-6 are signatures of post-stroke delirium.

Acetylcholine release from the rabbit isolated superior cervical ganglion preparation.

PubMed

Dawes, P M; Vizi, E S

1973-06-01

1. The rabbit isolated superior cervical ganglion preparation has been used to measure the release of acetylcholine from the tissue at rest and during preganglionic nerve stimulation.2. In the presence of physostigmine, the resting release of acetylcholine was 0.13 +/- 0.01 (nmol/g)/min (10 experiments) and that during stimulation with 300 shocks at 10 Hz was 3.1 +/- 0.4 (pmol/g)/volley in 4 experiments (means +/- S.E.M.). The volley output was independent of the frequency of stimulation over the range 1 to 10 Hz but was higher at 0.3 Hz.3. Tetrodotoxin, 0.8 muM, had no effect on the resting release of acetylcholine but reduced the stimulated release below detectable levels (2 pmol). Lowering the temperature of the bathing fluid to 5 degrees C reduced to below detectable levels both the resting release and that produced by nerve stimulation.4. The resting release of acetylcholine was increased by a potassium-rich (49.4 mM K(+)) bathing solution and by replacing the sodium chloride in the solution with lithium chloride (113 mM Li(+)).5. (-)-Noradrenaline bitartrate, 3 muM, and (+/-)-adrenaline bitartrate, 1.5 muM, reduced by 70% the output of acetylcholine induced by stimulation at 0.3 Hz, but failed to reduce the resting release or that evoked by stimulation at 10 Hz. The inhibition was reversed by phentolamine.6. It is concluded that the rabbit superior cervical ganglion in vitro is a suitable preparation for studying transmitter release and that the ganglion blocking effect of catecholamines is due to a reduction in transmitter release.

Effects of awakening and the use of topical dexamethasone and levofloxacin on the cytokine levels in tears following corneal transplantation.

PubMed

Fodor, Mariann; Petrovski, Goran; Pásztor, Dorottya; Gogolák, Péter; Rajnavölgyi, Éva; Berta, András

2014-01-01

To study the short-term effect of eye opening and use of topical dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in human tears. Prospective experimental design was used for tear collection from eyes of 10 healthy controls and 20 patients four days after penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or levofloxacin. The concentrations of different cytokines were measured by cytometric bead array. At eye opening, IL-6 levels were higher in the PKP group as compared to the controls. Thirty minutes later, the released levels of IL-10, IL-13, IL-17, IFNγ, and CCL5 increased in controls, while CXCL8 decreased in both control and PKP groups. The release of the cytokines remained stable after 30 mins except for IFNγ, which showed a decrease in the controls following levofloxacin instillation. No short-term effects of the topically used dexamethasone and levofloxacin could be detected on the cytokine levels in controls and after PKP. Evidence of changes in the levels and time course of tear cytokines after awakening or eye opening could be established and the short-term confounding effects of dexamethasone and levofloxacin on the levels of released cytokines in human tears could be excluded.

Ion release from orthodontic brackets in 3 mouthwashes: an in-vitro study.

PubMed

Danaei, Shahla Momeni; Safavi, Afsaneh; Roeinpeikar, S M Mehdi; Oshagh, Morteza; Iranpour, Shiva; Omidkhoda, Maryam; Omidekhoda, Maryam

2011-06-01

Stainless steel orthodontic brackets can release metal ions into the saliva. Fluoridated mouthwashes are often recommended to orthodontic patients to reduce the risk of white-spot lesions around their brackets. However, little information is available regarding the effect of different mouthwashes in ion release of orthodontic brackets. The purpose of this study was to measure the amount of metal ion release from orthodontic brackets when kept in different mouthwashes. One hundred sixty stainless steel brackets (0.022-in, 3M Unitek, Monrovia, Calif) were divided randomly into 4 equal groups and immersed in Oral B (Procter & Gamble, Weybridge, United Kingdom), chlorhexidine (Shahdaru Labratories, Tehran, Iran), and Persica (Poursina Pharmaceutical Laboratories, Tehran, Iran) mouthwashes and distilled deionized water and incubated at 37°C for 45 days. Nickel, chromium, iron, copper, and manganese released from the orthodontic brackets were measured with an inductively coupled plasma spectrometer. For statistical analysis, 1-way analysis of variance (ANOVA) and the Duncan multiple-range tests were used. The results showed that ion release in deionized water was significantly (P <0.05) higher than in the 3 mouthwashes. Higher ion release was found with chlorhexidine compared with the other 2 mouthwashes. There was no significant difference (P >0.05) in nickel, chromium, iron, and copper ion release in the Oral B and Persica mouthwashes. The level of manganese release was significantly different in all 4 groups. If ion release is a concern, Oral B and Persica mouthwashes might be better options than chlorhexidine for orthodontic patients with stainless steel brackets. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Central effects of corticotropin releasing factor (CRF): evidence for similar interactions with environmental novelty and with caffeine.

PubMed

Britton, D R; Indyk, E

1990-01-01

Centrally administered rat/human corticotropin-releasing factor (rCRF) increases low levels of locomotor activity by rats tested in a familiar environment but suppresses the higher levels of activity associated with exposure of the animals to a novel environment. These opposing responses do not appear to be manifestations of a simple rate-dependent effect, since ICV-administered rCRF did not lower the higher levels of locomotor activity associated with the dark (active) phase of the animal's activity cycle. Caffeine, which has anxiogenic effects in man, produces effects in rats which are similar to those of rCRF. That is, both compounds elevate activity in a familiar environment but lower activity in a novel environment. Furthermore, caffeine appears to substitute for novelty in determining the direction of the locomotor effect of rCRF. Animals made hyperactive by caffeine show decreased activity when co-administered rCRF. These findings are consistent with the view that CRF acts through pathways which also subserve the responsiveness to novelty and to the anxiogenic compound caffeine.

Sirt1 S-nitrosylation induces acetylation of HMGB1 in LPS-activated RAW264.7 cells and endotoxemic mice.

PubMed

Kim, Young Min; Park, Eun Jung; Kim, Hye Jung; Chang, Ki Churl

2018-06-18

Excessive inflammation plays a detrimental role in endotoxemia. A recent study indicated that alarmins such as high mobility group box 1 (HMGB1) have drawn attention as therapeutic targets of sepsis. Post-translational modification (i.e., acetylation of lysine residues) of HMGB1 leads to the release of HMGB1 into the cellular space, operating as a warning signal that induces inflammation. Sirtuin 1 (SIRT1) has been shown to negatively regulate HMGB1 hyperacetylation and its extracellular release in sepsis. Therefore, we hypothesized that the S-nitrosylation (SNO) of SIRT1 may disrupt the ability of SIRT1 to negatively regulate the hyperacetylation of HMGB1. As long as the S-nitrosylation of SIRT1 occurs during septic conditions, it may worsen the situation. We found that the activity of SIRT1 decreased as the SNO-SIRT1 levels increased, resulting in HMGB1 release by LPS in RAW264.7 cells. Both the iNOS inhibitor (1400 W) and silencing iNOS significantly inhibited SNO-SIRT1, allowing increases in SIRT1 activity that decreased the HMGB1 release by LPS. SNAP, a NO donor, significantly increased both SNO-SIRT1 levels and the HMGB1 release that was accompanied by decreased sirt1 activity. However, sirtinol, a Sirt1 inhibitor, by itself decreased Sirt1 activity compared to that of the control, so that it did not affect already increased SNO-SIRT levels by SNAP. Most importantly, in lung tissues of LPS-endotoxic mice, significantly increased levels of SNO-SIRT were found, which was inhibited by 1400 W treatment. Plasma nitrite and HMGB1 levels were significantly higher than those in the sham controls, and the elevated levels were significantly lowered in the presence of 1400 W. We concluded that the S-nitrosylation of Sirt1 under endotoxic conditions may uninhibit the acetylation of HMGB1 and its extracellular release. Copyright © 2018 Elsevier Inc. All rights reserved.

Polarized release of hepatic microRNAs into bile and serum in response to cellular injury and impaired liver function.

PubMed

Verhoeven, Cornelia J; Farid, Waqar R R; Roest, Henk P; Ramakrishnaiah, Vedashree; de Ruiter, Petra E; de Jonge, Jeroen; Kwekkeboom, Jaap; Metselaar, Herold J; Tilanus, Hugo W; Kazemier, Geert; Ijzermans, Jan N M; van der Laan, Luc J W

2016-06-01

Extracellular microRNAs (miRNAs) in serum and bile are currently under intense investigation for biomarker purposes in liver disease. However, the directions and pathways by which miRNAs are released from hepatic cells remains largely unknown. Here, we investigated the release of hepatocyte and cholangiocyte-derived miRNAs (HDmiRs and CDmiRs) into blood and bile during various (patho)physiological hepatic conditions. MiRNA release was analysed using longitudinally collected tissue and paired bile and serum samples (n = 124) that were obtained from liver transplant recipients during follow-up. Cell-type specificity of HDmiRs and CDmiRs was confirmed in liver and common bile duct biopsies (P < 0.001). Analysis of paired bile and serum samples showed up to 20-times higher miRNA-levels in bile compared to serum (P < 0.0001). Fractionation of bile showed the majority of miRNAs being present in the unpelletable supernatant, where protein conjunctions protect miRNAs against degradation (P < 0.0001). During episodes of liver injury and histologically proven rejection in liver transplant recipients, relative HDmiR-levels in bile decreased while its levels in serum increased (P ≤ 0.015). Simultaneously, relative CDmiR-levels in bile significantly increased, while their levels in serum decreased. Related to liver excretory function, a strong positive correlation was observed between HDmiR-122 levels and bilirubin excretion into bile (R = 0.694, P < 0.0001), whereas CDmiRs showed an inverse correlation (P < 0.05). During impaired excretory function and injury, the liver shows polarized release of extracellular HDmiRs and CDmiRs. This sheds new light on the biology of hepatic miRNA release which is relevant for the interpretation of hepatic miRNAs as biomarkers. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels

PubMed Central

Maltsev, Alexander V.; Maltsev, Victor A.; Stern, Michael D.

2017-01-01

Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s). Background Ca (in locations lacking LCRs) quickly decays to resting Ca levels (<100 nM) at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates. PMID:28792496

Physicochemical aspects involved in methotrexate release kinetics from biodegradable spray-dried chitosan microparticles

NASA Astrophysics Data System (ADS)

Mesquita, Philippe C.; Oliveira, Alice R.; Pedrosa, Matheus F. Fernandes; de Oliveira, Anselmo Gomes; da Silva-Júnior, Arnóbio Antônio

2015-06-01

Spray dried methotrexate (MTX) loaded chitosan microparticles were prepared using different drug/copolymer ratios (9%, 18%, 27% and 45% w/w). The physicochemical aspects were assessed in order to select particles that were able to induce a sustained drug release effect. Particles were successfully produced which exhibited desired physicochemical aspects such as spherical shape and high drug loading. XRD and FT-IR analysis demonstrated that drug is not bound to copolymer and is only homogeneously dispersed in an amorphous state into polymeric matrix. Even the particles with higher drug loading levels presented a sustained drug release profile, which were mathematically modeled using adjusted Higuchi model. The drug release occurred predominantly with drug dissolution and diffusion through swollen polymeric matrix, with the slowest release occurring with particles containing 9% of drug, demonstrating an interesting and promising drug delivery system for MTX.

Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic Polymeric Films.

PubMed

Ammar, Hussein O; Ghorab, Mamdouh M; Felton, Linda A; Gad, Shadeed; Fouly, Aya A

2016-06-01

Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL(TM) T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level.

In vitro retinoid binding and release from a collagen sponge material in a simulated intravaginal environment.

PubMed

Dorr, R T; Surwit, E A; Droegemueller, W; Alberts, D S; Meyskens, F L; Chvapil, M

1982-11-01

Four in vitro preparations were constructed to simulate the intravaginal release of two retinoids, all-trans-retinoic acid (t-RA) and 13-cis-retinoic acid (c-RA), from a 0.7% collagen sponge diaphragm insert. Four t-RA concentrations, 0.019, 0.05, 0.1, and 0.15% in methanol were added to the sponge. The release into an artificial vaginal fluid was monitored serially over 72 h by serial analysis for t-RA and c-RA using high-pressure liquid chromatography. In each preparation, retinoid release was immediate and noncontinuous. At 37 degrees C, the retinoids were stable for at least 48 h. Trans-retinoic acid was the predominant retinoid recovered. Only trace amounts of the cis-isomer were released. Peak t-RA levels were 20 microM after 0.01%, 60-80 microM after 0.05%, 100-200 microM after 0.1%, and 320 microM after 0.15%. When the vaginal fluid bath was changed after 5 h, no further significant retinoid release occurred. There was significant loss of up to 70% of the applied t-RA into the collagen sponge. The retinoid binding was concentration dependent (higher binding with higher concentrations) and was maximal only after 24 h of co-incubation. The discontinuous release of t-RA and the high degree of binding to collagen would seem to preclude use of the diaphragm insert as a vaginal drug delivery system, at least for retinoids.

Influence of Porous Spherical-Shaped Hydroxyapatite on Mechanical Strength and Bioactive Function of Conventional Glass Ionomer Cement.

PubMed

Chiu, Szu-Yu; Shinonaga, Yukari; Abe, Yoko; Harada, Kyoko; Arita, Kenji

2017-01-03

Glass-ionomer-cement (GIC) is helpful in Minimal Intervention Dentistry because it releases fluoride ions and is highly biocompatible. The aim of this study is to investigate the mechanisms by which hydroxyapatite (HAp) improves the mechanical strength and bioactive functioning of GIC when these materials are combined to make apatite ionomer cement (AIC). A conventional GIC powder was mixed with porous, spherical-HAp particles (HApS), crystalline HAp (HAp200) or one of two types of cellulose. The micro-compressive strengths of the additive particles were measured, and various specimens were evaluated with regard to their compressive strengths (CS), fluoride release concentrations (fluoride electrode) and multi-element release concentrations. The AIC was found to release higher concentrations of fluoride (1.2 times) and strontium ions (1.5 times) compared to the control GIC. It was detected the more release of calcium originated from HApS than HAp200 in AIC. The CS of the AIC incorporating an optimum level of HAp was also significantly higher than that of the GIC. These results suggest that adding HAp can increase the release concentration of ions required for remineralization while maintaining the CS of the GIC. This effect does not result from a physical phenomenon, but rather from chemical reactions between the HAp and polyacrylic acid of GIC.

Influence of Porous Spherical-Shaped Hydroxyapatite on Mechanical Strength and Bioactive Function of Conventional Glass Ionomer Cement

PubMed Central

Chiu, Szu-Yu; Shinonaga, Yukari; Abe, Yoko; Harada, Kyoko; Arita, Kenji

2017-01-01

Glass-ionomer-cement (GIC) is helpful in Minimal Intervention Dentistry because it releases fluoride ions and is highly biocompatible. The aim of this study is to investigate the mechanisms by which hydroxyapatite (HAp) improves the mechanical strength and bioactive functioning of GIC when these materials are combined to make apatite ionomer cement (AIC). A conventional GIC powder was mixed with porous, spherical-HAp particles (HApS), crystalline HAp (HAp200) or one of two types of cellulose. The micro-compressive strengths of the additive particles were measured, and various specimens were evaluated with regard to their compressive strengths (CS), fluoride release concentrations (fluoride electrode) and multi-element release concentrations. The AIC was found to release higher concentrations of fluoride (1.2 times) and strontium ions (1.5 times) compared to the control GIC. It was detected the more release of calcium originated from HApS than HAp200 in AIC. The CS of the AIC incorporating an optimum level of HAp was also significantly higher than that of the GIC. These results suggest that adding HAp can increase the release concentration of ions required for remineralization while maintaining the CS of the GIC. This effect does not result from a physical phenomenon, but rather from chemical reactions between the HAp and polyacrylic acid of GIC. PMID:28772386

Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

PubMed Central

Spengler, Julia; Lugonja, Božo; Jimmy Ytterberg, A.; Zubarev, Roman A.; Creese, Andrew J.; Pearson, Mark J.; Grant, Melissa M.; Milward, Michael; Lundberg, Karin; Buckley, Christopher D.; Filer, Andrew; Raza, Karim; Cooper, Paul R.; Chapple, Iain L.

2015-01-01

Objective In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. Methods Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. Results Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. Conclusion Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA. PMID:26245941

Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma

PubMed Central

Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E.; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

2016-01-01

Abstract We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (β = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05). We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

Enemy release and plant invasion: patterns of defensive traits and leaf damage in Hawaii.

PubMed

Funk, Jennifer L; Throop, Heather L

2010-04-01

Invasive species may be released from consumption by their native herbivores in novel habitats and thereby experience higher fitness relative to native species. However, few studies have examined release from herbivory as a mechanism of invasion in oceanic island systems, which have experienced particularly high loss of native species due to the invasion of non-native animal and plant species. We surveyed putative defensive traits and leaf damage rates in 19 pairs of taxonomically related invasive and native species in Hawaii, representing a broad taxonomic diversity. Leaf damage by insects and pathogens was monitored in both wet and dry seasons. We found that native species had higher leaf damage rates than invasive species, but only during the dry season. However, damage rates across native and invasive species averaged only 2% of leaf area. Native species generally displayed high levels of structural defense (leaf toughness and leaf thickness, but not leaf trichome density) while native and invasive species displayed similar levels of chemical defenses (total phenolics). A defense index, which integrated all putative defense traits, was significantly higher for native species, suggesting that native species may allocate fewer resources to growth and reproduction than do invasive species. Thus, our data support the idea that invasive species allocate fewer resources to defense traits, allowing them to outperform native species through increased growth and reproduction. While strong impacts of herbivores on invasion are not supported by the low damage rates we observed on mature plants, population-level studies that monitor how herbivores influence recruitment, mortality, and competitive outcomes are needed to accurately address how herbivores influence invasion in Hawaii.

Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.

PubMed

TruneČka, P; Klempnauer, J; Bechstein, W O; Pirenne, J; Friman, S; Zhao, A; Isoniemi, H; Rostaing, L; Settmacher, U; Mönch, C; Brown, M; Undre, N; Tisone, G

2015-07-01

DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals Inc.

Evidence for the dissolution of molybdenum during tribocorrosion of CoCrMo hip implants in the presence of serum protein.

PubMed

Simoes, Thiago A; Bryant, Michael G; Brown, Andy P; Milne, Steven J; Ryan, Mary; Neville, Anne; Brydson, Rik

2016-11-01

We have characterized CoCrMo, Metal-on-Metal (MoM) implant, wear debris particles and their dissolution following cycling in a hip simulator, and have related the results to the tribocorrosion of synthetic wear debris produced by milling CoCrMo powders in solutions representative of environments in the human body. Importantly, we have employed a modified ICP-MS sample preparation procedure to measure the release of ions from CoCrMo alloys during wear simulation in different media; this involved use of nano-porous ultrafilters which allowed complete separation of particles from free ions and complexes in solution. As a result, we present a new perspective on the release of metal ions and formation of metal complexes from CoCrMo implants. The new methodology enables the mass balance of ions relative to complexes and particles during tribocorrosion in hip simulators to be determined. A much higher release of molybdenum ions relative to cobalt and chromium has been measured. The molybdenum dissolution was enhanced by the presence of bovine serum albumin (BSA), possibly due to the formation of metal-protein complexes. Overall, we believe that the results could have significant implications for the analysis and interpretation of metal ion levels in fluids extracted from hip arthroplasty patients; we suggest that metal levels, including molybdenum, be analysed in these fluids using the protocol described here. We have developed an important new protocol for the analysis of metal ion levels in fluids extracted from hip implant patients and also hip simulators. Using this procedure, we present a new perspective on the release of metal ions from CoCrMo alloy implants, revealing significantly lower levels of metal ion release during tribocorrosion in hip simulators than previously thought, combined with the release of much higher percentages of molybdenum ions relative to cobalt and chromium. This work is of relevance, both from the perspective of the fundamental science and study of metal-protein interactions, enabling understanding of the ongoing problem associated with the biotribocorrosion and the link to inflammation associated with Metal-on-Metal (MoM) hip implants made from CoCrMo alloys. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms

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

Broström, Julia M.; Ye, Zhi-wei; Axmon, Anna

Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected frommore » workers exposed to < 5 ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10 min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose–response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting “sneezing”, the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity. - Highlights: • Human epithelial cells release autotaxin in response to 1 nM toluene diisocyanate (TDI). • The release involves P2X4 and P2X7 receptors and is modulated by ATP and MCP-1. • Lysophosphatidic acid (LPA) was measured in workers exposed to < 5 ppb TDI. • LPA in plasma correlated to TDI exposure biomarkers in workers. • Symptomatic workers had higher LPA levels than those without symptoms.« less

MDMA, cortisol, and heightened stress in recreational ecstasy users.

PubMed

Parrott, Andrew C; Montgomery, Cathy; Wetherell, Mark A; Downey, Luke A; Stough, Con; Scholey, Andrew B

2014-09-01

Stress develops when an organism requires additional metabolic resources to cope with demanding situations. This review will debate how recreational 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can increase some aspects of acute and chronic stress in humans. Laboratory studies on the acute effects of MDMA on cortisol release and neurohormone levels in drug-free regular ecstasy/MDMA users have been reviewed, and the role of the hypothalamic-pituitary-adrenal (HPA) axis in chronic changes in anxiety, stress, and cognitive coping is debated. In the laboratory, acute ecstasy/MDMA use can increase cortisol levels by 100-200%, whereas ecstasy/MDMA-using dance clubbers experience an 800% increase in cortisol levels, because of the combined effects of the stimulant drug and dancing. Three-month hair samples of abstinent users revealed cortisol levels 400% higher than those in controls. Chronic users show heightened cortisol release in stressful environments and deficits in complex neurocognitive tasks. Event-related evoked response potential studies show altered patterns of brain activation, suggestive of increased mental effort, during basic information processing. Chronic mood deficits include more daily stress and higher depression in susceptible individuals. We conclude that ecstasy/MDMA increases cortisol levels acutely and subchronically and that changes in the HPA axis may explain why recreational ecstasy/MDMA users show various aspects of neuropsychobiological stress.

Influence of plasticizer level on the drug release from sustained release film coated and hot-melt extruded dosage forms.

PubMed

Zhu, Yucun; Mehta, Ketan A; McGinity, James W

2006-01-01

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.

Enhancement of wound closure by modifying dual release patterns of stromal-derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels.

PubMed

Kim, Yang-Hee; Tabata, Yasuhiko

2017-11-01

The objective of the present study is to evaluate the effects of the release patterns of stromal derived factor (SDF)-1 and sphingosine-1 phosphate agonist (SEW2871), used as MSC and macrophage recruitment agents, on the wound closure of diabetic mouse skin defects. To achieve different release patterns, hydrogels were prepared using two types of gelatin with isoelectric points (IEP) of 5 and 9, into which SDF-1 and SEW2871 were then incorporated in various combinations. When the hydrogels incorporating SDF-1 and SEW2871 were applied into wound defects of diabetic mice, the number of MSCs and macrophages recruited to the defects and the levels of pro- and anti- inflammatory cytokines were found to be dependent on the release profiles of SDF-1 and SEW2871. Of particular interest was the case of a rapid release of SDF-1 combined with a controlled release of SEW2871. This resulted in a higher number of M2 macrophages and gene expression levels of anti-inflammatory cytokines 3 days after implantation and faster wound closure than when pairing the controlled release of SDF-1 with a rapid release of SEW2871. Therefore, the present study demonstrates that different release patterns of SDF-1 and SEW2871 can enhance the in vivo recruitment of MSCs and macrophages, and can promote skin wound closure through the modulation of inflammation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Evoked-potential recovery during double click stimulation in a beluga whale: implications for biosonar gain control.

PubMed

Supin, Alexander Ya; Popov, Vladimir V

2015-05-01

Auditory evoked potentials (AEPs) were recorded in a beluga whale Delphinapterus leucas using a double-pulse stimulation paradigm, specifically measuring the recovery (release from masking) of the second (test) response as a function of delay after the first (conditioning) pulse at various levels of the conditioning and test stimuli. The conditioning/test stimulus level ratio influenced the recovery time (the higher the ratio, the longer the recovery). This interrelation was used to evaluate the intensity/time trade in release from forward masking. Trade was evaluated as 32.2 dB per time decade. Data were considered as simulating interactions between the transmitted pulse and echo during echolocation, assuming that a transmitted sonar pulse produces forward masking of the echo response. With increased target distance, the attenuation of the echo may be compensated by the release from masking. According to the model, the compensation results in substantial stabilization of the echo response even if the intensity/time trade of release from masking is not precisely equal to the rate of echo attenuation with distance.

Effect of iodine on mercury concentrations in dental-unit wastewater.

PubMed

Stone, Mark E; Kuehne, John C; Cohen, Mark E; Talbott, Jonathan L; Scott, John W

2006-02-01

This study was undertaken to determine whether iodine used to control bacteria in dental unit waterlines could increase mercury concentrations in dental wastewater. The study was conducted in four parts. Part 1. Solutions containing iodine in concentrations ranging from zero (control) to 20 mg/L were mixed with ground and sieved dental amalgam and then allowed to equilibrate by settling. Cold vapor atomic absorption spectrometry was used to determine mercury levels in the settled supernatants at 24 h and at 7 days. Part 2. Deionized water was pumped through an iodine-releasing water-treatment cartridge, collected, and mixed with ground and sieved dental amalgam. Mercury levels in settled supernatants were measured at 24 h and at 7 days. Part 3. Iodine in water from two commercial iodine-releasing cartridges was measured using Inductively Couple Plasma Mass Spectrometry. Part 4. Baseline mercury levels in settled supernatants from wastewater collected from two dental chairs were compared to samples taken from chairs equipped with iodine-releasing cartridges. Part 1. A linear correlation between iodine and mercury concentration (r2=0.9167 and 0.9459, respectively, both P<0.001) was seen at both 24 h and 7 days. Part 2. Mean mercury levels in 24h samples were 3.0 times higher than the controls (0.2864 mg/L compared with 0.0939mg/L for the 24 h controls). Mean mercury levels in the 7-day samples were 5.9 times higher than the 7-day controls (0.2048 mg/L compared with 0.0348 mg/L for the 7-day controls). Part 3. The effluent from two iodine-releasing cartridges showed iodine concentrations averaging 3.2 mg/L (n=10, SD=0.8, range=2.5-4.6). Part 4. Data from the clinical study showed a statistically significant 2.5-fold increase in mercury levels with iodine-containing samples compared to baseline (0.0853 mg/L, n=18, SD=0.0441 and 0.0345 mg/L, n=18, SD=0.0145, respectively; P<0.001). Data suggest that iodine can increase concentrations of dissolved mercury in dental unit wastewater.

Sustained release of bactericidal concentrations of penicillin in the pleural space via an antibiotic-eluting pigtail catheter coated with electrospun nanofibers: results from in vivo and in vitro studies.

PubMed

Chao, Yin-Kai; Lee, Cheng-Hung; Liu, Kuo-Sheng; Wang, Yi-Chuan; Wang, Chih-Wei; Liu, Shih-Jung

2015-01-01

Inadequate intrapleural drug concentrations caused by poor penetration of systemic antibiotics into the pleural cavity is a major cause of treatment failure in empyema. Herein, we describe a novel antibiotic-eluting pigtail catheter coated with electrospun nanofibers used for the sustained release of bactericidal concentrations of penicillin in the pleural space. Electrospun nanofibers prepared using polylactide-polyglycolide copolymer and penicillin G sodium dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol were used to coat the surface of an Fr6 pigtail catheter. The in vitro patterns of drug release were tested by placing the catheter in phosphate-buffered saline. In vivo studies were performed using rabbits treated with penicillin either intrapleurally (Group 1, 20 mg delivered through the catheter) or systemically (Group 2, intramuscular injection, 10 mg/kg). Penicillin concentrations in the serum and pleural fluid were then measured and compared. In vitro studies revealed a burst release of penicillin (10% of the total dose) occurring in the first 24 hours, followed by a sustained release in the subsequent 30 days. Intrapleural drug levels were significantly higher in Group 1 than in Group 2 (P<0.001). In the former, penicillin concentrations remained above the minimum inhibitory concentration breakpoint throughout the entire study period. In contrast, serum penicillin levels were significantly higher in Group 2 than in Group 1 (P<0.001). Notably, all Group 2 rabbits showed signs of systemic toxicity (paralytic ileus and weight loss). We conclude that our antibiotic-eluting catheter may serve as a novel therapeutic option to treat empyema.

Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis.

PubMed

Matthews, J B; Wright, H J; Roberts, A; Cooper, P R; Chapple, I L C

2007-02-01

Some evidence exists that peripheral neutrophils from patients with chronic periodontitis generate higher levels of reactive oxygen species (ROS) after Fcgamma-receptor stimulation than those from healthy controls. We hypothesized that peripheral neutrophils in periodontitis also show both hyper-reactivity to plaque organisms and hyperactivity in terms of baseline, unstimulated generation and release of ROS. Peripheral neutrophils from chronic periodontitis patients and age/sex/smoking-matched healthy controls (18 pairs) were assayed for total ROS generation and extracellular ROS release, with and without stimulation (Fcgamma-receptor and Fusobacterium nucleatum), using luminol and isoluminol chemiluminescence. Assays were performed with and without priming with Escherichia coli lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Phox gene expression (p22, p47, p67, gp91) was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Neutrophils from patients produced higher mean levels of ROS in all assays. Total generation and extracellular release of ROS by patients' cells were significantly greater than those from controls after FcgammaR-stimulation, with (P = 0.023) and without (P < or = 0.023) priming with GM-CSF. Differences in unstimulated total ROS generation were not significant. By contrast, patients' cells demonstrated greater baseline, extracellular ROS release than those from controls (P = 0.004). This difference was maintained after priming with LPS (P = 0.028) but not GM-CSF (P = 0.217). Phox gene expression was similar in patient and control cells at baseline and stimulation with F. nucleatum (3 h) consistently reduced gp91(PHOX) transcripts. Our data demonstrate that peripheral neutrophils from periodontitis patients exhibit hyper-reactivity following stimulation (Fcgamma-receptor and F. nucleatum) and hyperactivity in terms of excess ROS release in the absence of exogenous stimulation. This hyperactive/-reactive neutrophil phenotype is not associated with elevated phox gene expression.

50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

PubMed

Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

2016-02-01

The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Acetylcholine release from the rabbit isolated superior cervical ganglion preparation

PubMed Central

Dawes, P. M.; Vizi, E. S.

1973-01-01

1. The rabbit isolated superior cervical ganglion preparation has been used to measure the release of acetylcholine from the tissue at rest and during preganglionic nerve stimulation. 2. In the presence of physostigmine, the resting release of acetylcholine was 0·13 ± 0·01 (nmol/g)/min (10 experiments) and that during stimulation with 300 shocks at 10 Hz was 3·1 ± 0·4 (pmol/g)/volley in 4 experiments (means ± S.E.M.). The volley output was independent of the frequency of stimulation over the range 1 to 10 Hz but was higher at 0·3 Hz. 3. Tetrodotoxin, 0·8 μM, had no effect on the resting release of acetylcholine but reduced the stimulated release below detectable levels (2 pmol). Lowering the temperature of the bathing fluid to 5° C reduced to below detectable levels both the resting release and that produced by nerve stimulation. 4. The resting release of acetylcholine was increased by a potassium-rich (49·4 mM K+) bathing solution and by replacing the sodium chloride in the solution with lithium chloride (113 mM Li+). 5. (-)-Noradrenaline bitartrate, 3 μM, and (±)-adrenaline bitartrate, 1·5 μM, reduced by 70% the output of acetylcholine induced by stimulation at 0·3 Hz, but failed to reduce the resting release or that evoked by stimulation at 10 Hz. The inhibition was reversed by phentolamine. 6. It is concluded that the rabbit superior cervical ganglion in vitro is a suitable preparation for studying transmitter release and that the ganglion blocking effect of catecholamines is due to a reduction in transmitter release. PMID:4733726

Pharmaceutical studies of levothyroxine sodium hydrate suppository provided as a hospital preparation.

PubMed

Hamada, Yuhei; Masuda, Kazushi; Okubo, Masato; Nakasa, Hiromitsu; Sekine, Yuko; Ishii, Itsuko

2015-01-01

The levothyroxine sodium hydrate suppository (L-T4-suppository) is provided as a hospital preparation for the treatment of hypothyroid patients with dysphagia in Japan because only oral preparations of levothyroxine sodium (L-T4) are approved for the treatment of hypothyroidism. However, it has been found that serum thyroxine and triiodothyronine levels do not increase as expected with the hospital preparation, requiring a higher dosage of L-T4 in the L-T4-suppository than in the oral preparations. In this study, to determine an effective thyroid gland hormone-replacement therapy for patients with dysphagia, the pharmaceutical properties of the L-T4-suppository were investigated. Suppositories containing 300 µg L-T4 in a base of Witepsol H-15 and Witepsol E-75 (ratio of 1 : 1) were prepared according to Chiba University Hospital's protocol. Content uniformity, stability, and suppository release were tested. The L-T4-suppository had uniform weight and content. The content and release property were stable over 90 d when the L-T4-suppository was stored at 4 °C and protected from light. The release rate of L-T4 increased as pH increased. However, no L-T4 was released below pH 7.2. The release rate of L-T4 decreased as temperature decreased. These findings suggest that the low level of release of L-T4 in the rectum under physiological conditions may be the cause of the low serum thyroxine and triiodothyronine levels following L-T4-suppository administration.

Strategic 3-hydroxy-2-butanone release in the dominant male lobster cockroach, Nauphoeta cinerea

NASA Astrophysics Data System (ADS)

Chen, Shu-Chun; Yang, Rou-Ling; Ho, Hsiao-Yung; Chou, Szu-Ying; Kou, Rong

2007-11-01

In the lobster cockroach Nauphoete cinerea, the dominant subordinate hierarchy formed via the agonistic interactions is unstable, and changes in rank order are common. Our previous results showed that in the first encounter fight during initial rank formation, microgram levels of 3H-2B are released by the aggressive posture (AP)-adopting dominant male. In the present study, the pattern of daily pheromone (3H-2B) release during the domination period and on the day of rank switch, rank duration, and rank switch frequency were investigated in three-male groups and six-male groups to examine the effect of higher frequency of agonistic encounters. The results showed that, in the three-male groups (50-day observation period), daily 3H-2B release rate was not constant, but fluctuated, the average duration of dominant rank was 16.6 ± 2.0 days, rank switch occurred in 58.8% of groups, and the frequency of rank switching (average number of rank switches/group/50 days) was 1.4 ± 0.2. For the six-male groups (30-day observation period), the daily 3H-2B release rate also fluctuated, but the duration of dominant rank was significantly shorter at 4.2 ± 0.6 days, rank switch occurred in 100% of groups, and the frequency of rank switching (average number of rank switches/group/30 days) was significantly higher at 6.9 ± 0.6. The results for both sets of male groups showed that as a new rank formed (either on the first encounter day or on the day of rank switching), the dominant status was significantly associated with a higher 3H-2B release rate. In the animal kingdom, fighting usually involves communication or the exchange of signals, and the results of this study indicated that the fluctuating daily 3H-2B release rate adopted by the dominants is a kind of strategic release and the 3H-2B release rate is a signal used to determine dominance.

Direct and indirect trophic effects of predator depletion on basal trophic levels.

PubMed

Chen, Huili; Hagerty, Steven; Crotty, Sinead M; Bertness, Mark D

2016-02-01

Human population growth and development have heavily degraded coastal ecosystems with cascading impacts across multiple trophic levels. Understanding both the direct and indirect trophic effects of human activities is important for coastal conservation. In New England, recreational overfishing has triggered a regional trophic cascade. Predator depletion releases the herbivorous purple marsh crab from consumer control and leads to overgrazing of marsh cordgrass and salt marsh die-off. The direct and indirect trophic effects of predator depletion on basal trophic levels, however, are not understood. Using observational and experimental data, we examined the hypotheses that (1) direct trophic effects of predator depletion decrease meiofaunal abundance by releasing deposit feeding fiddler crabs from consumer control, and/or (2) indirect trophic effects of predator depletion increase meiofaunal abundance by releasing blue carbon via the erosion of centuries of accreted marsh peat. Experimental deposit feeder removal led to 23% higher meiofaunal density at die-off than at healthy sites, while reciprocally transplanting sediment from die-off and healthy sites revealed that carbon-rich die-off sediment increased meiofauna density by over 164%: six times stronger than direct trophic effects. Recovering sites had both carbon-rich sediment and reduced deposit feeding leading to higher meiofauna densities than both die-off and healthy sites. This suggests that consequences of the trophic downgrading of coastal habitats can be driven by both direct and indirect trophic mechanisms that may vary in direction and magnitude, making their elucidation dependent on experimental manipulations.

Gentamicin release from commercially-available gentamicin-loaded PMMA bone cements in a prosthesis-related interfacial gap model and their antibacterial efficacy.

PubMed

Neut, Daniëlle; Kluin, Otto S; Thompson, Jonathan; van der Mei, Henny C; Busscher, Henk J

2010-11-10

Around about 1970, a gentamicin-loaded poly (methylmethacrylate) (PMMA) bone cement brand (Refobacin Palacos R) was introduced to control infection in joint arthroplasties. In 2005, this brand was replaced by two gentamicin-loaded follow-up brands, Refobacin Bone Cement R and Palacos R + G. In addition, another gentamicin-loaded cement brand, SmartSet GHV, was introduced in Europe in 2003. In the present study, we investigated differences in gentamicin release and the antibacterial efficacy of the eluent between these four cement brands. 200 μm-wide gaps were made in samples of each cement and filled with buffer in order to measure the gentamicin release. Release kinetics were related to bone cement powder particle characteristics and wettabilities of the cement surfaces. Gaps were also inoculated with bacteria isolated from infected prostheses for 24 h and their survival determined. Gentamicin release and bacterial survival were statistically analysed using the Student's t-test. All three Palacos variants showed equal burst releases but each of the successor Palacos cements showed significantly higher sustained releases. SmartSet GHV showed a significantly higher burst release, while its sustained release was comparable with original Palacos. A gentamicin-sensitive bacterium did not survive in the high gentamicin concentrations in the interfacial gaps, while a gentamicin-resistant strain did, regardless of the type of cement used. Survival was independent of the level of burst release by the bone cement. Although marketed as the original gentamicin-loaded Palacos cement, orthopaedic surgeons should be aware that the successor cements do not appear to have the same release characteristics as the original one. Overall, high gentamicin concentrations were reached inside our prosthesis-related interfacial gap model. These concentrations may be expected to effectively decontaminate the prosthesis-related interfacial gap directly after implantation, provided that these bacteria are sensitive for gentamicin.

Optimization of chlorphenesin emulgel formulation.

PubMed

Mohamed, Magdy I

2004-10-11

This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 2(3) factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activity, and stability. Commercially available CHL topical powder was used for comparison. All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. They also exhibited higher drug release and antifungal activity than the CHL powder. It was found that the emulsifying agent concentration had the most pronounced effect on the drug release from the emulgels followed by the oil phase concentration and finally the type of the gelling agent. The drug release from all the emulgels was found to follow diffusion-controlled mechanism. Rheological studies revealed that the CHL emulgels exhibited a shear-thinning behavior with thixotropy. Stability studies showed that the physical appearance, rheological properties, drug release, and antifungal activity in all the prepared emulgels remained unchanged upon storage for 3 months. As a general conclusion, it was suggested that the CHL emulgel formulation prepared with HPMC with the oil phase concentration in its low level and emulsifying agent concentration in its high level was the formula of choice since it showed the highest drug release and antifungal activity.

Seed release by invasive thistles: the impact of plant and environmental factors

PubMed Central

Jongejans, Eelke; Pedatella, Nicholas M; Shea, Katriona; Skarpaas, Olav; Auhl, Richard

2007-01-01

Dispersal is a key process in biological studies of spatial dynamics, but the initiation of dispersal has often been neglected, despite strong indications that differential timing of dispersal can significantly affect dispersal distances. To investigate which plant and environmental factors determine the release of plumed seeds by the invasive thistles Carduus acanthoides and Carduus nutans, we exposed 192 flower heads of each species to increasing wind speeds in a full-factorial wind tunnel experiment with four air flow turbulence, three flower head wetness and two flower head temperature levels. The number of seed releases was highest under dry and turbulent conditions and from heads that had already lost a considerable number of seeds, but was not affected by flower head size, head angle or temperature. Inspection of the trials on video showed that higher wind speeds were needed to meet the seed release threshold in laminar flows and for C. acanthoides heads that had been wet for a longer time. Species differences were minimal, although seed release was more sensitive to lower levels of turbulence in the larger-headed and more open C. nutans heads. Knowledge of seed release biases towards weather conditions favourable for long-distance dispersal improves our understanding of the spread of invaders and allows managers to increase the efficiency of their containment strategies by applying them at crucial times. PMID:17666379

Development of an Extended-Release Formulation for Apremilast and a Level A in Vitro-in Vivo Correlation Study in Beagle Dogs.

PubMed

Tang, Meiqiong; Hu, Ping; Huang, Shigui; Zheng, Qiang; Yu, Hao; He, Yun

2016-11-01

The primary objective of the present study was to develop extended-release matrix formulations of apremilast for the oral delivery and to study their in vitro and in vivo correlation. Five extended-release formulations containing hydroxypropylmethylcellulose (HPMC) as the retarding excipient with different release rate of apremilast were prepared. Dissolution tests of all the formulated tablets were performed in water, pH 4.0 and 6.8 buffer solutions. The in vitro release kinetics was studied and supported by Korsmeyer-Peppas's equation as it presented highest values of correlation coefficients (r 2 up to 0.966). Among all formulated tablets, F2 (HPMC 25%) and F4 (HPMC 35%) were selected to perform an in vivo study in beagle dogs to obtain various pharmacokinetic parameters, i.e., peak plasma concentration (C max ), time to peak plasma concentration (t max ), area under the plasma-concentration vs. time curve (AUC). Higher t max and t 1/2 , lower C max and elimination coefficient (K e ) were observed for both extended formulations compared to marketed immediate-release products (Otezla ® ). Level A in vitro-in vivo correlations were created with the help of Wagner-Nelson and numeric deconvolution methods. Both formulations showed good in vitro-in vivo correlations whose accuracies were further verified by an internal validation.

Testosterone and cortisol release among Spanish soccer fans watching the 2010 World Cup final.

PubMed

van der Meij, Leander; Almela, Mercedes; Hidalgo, Vanesa; Villada, Carolina; Ijzerman, Hans; van Lange, Paul A M; Salvador, Alicia

2012-01-01

This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50) watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem.

Testosterone and Cortisol Release among Spanish Soccer Fans Watching the 2010 World Cup Final

PubMed Central

van der Meij, Leander; Almela, Mercedes; Hidalgo, Vanesa; Villada, Carolina; IJzerman, Hans; van Lange, Paul A. M.; Salvador, Alicia

2012-01-01

This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50) watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem. PMID:22529940

Evaluation of calcium ion, hydroxyl ion release and pH levels in various calcium hydroxide based intracanal medicaments: An in vitro study

PubMed Central

Fulzele, Punit; Baliga, Sudhindra; Thosar, Nilima; Pradhan, Debaprya

2011-01-01

Aims: Evaluation of calcium ion and hydroxyl ion release and pH levels in various calcium hydroxide based intracanal medicaments. Objective: The purpose of this study was to evaluate calcium and hydroxyl ion release and pH levels of calcium hydroxide based products, namely, RC Cal, Metapex, calcium hydroxide with distilled water, along with the new gutta-percha points with calcium hydroxide. Materials and Methods: The materials were inserted in polyethylene tubes and immersed in deionized water. The pH variation, Ca++ and OH- release were monitored periodically for 1 week. Statistical Analysis Used: Statistical analysis was carried out using one-way analysis of variance and Tukey's post hoc tests with PASW Statistics version 18 software to compare the statistical difference. Results: After 1 week, calcium hydroxide with distilled water and RC Cal raised the pH to 12.7 and 11.8, respectively, while a small change was observed for Metapex, calcium hydroxide gutta-percha points. The calcium released after 1 week was 15.36 mg/dL from RC Cal, followed by 13.04, 1.296, 3.064 mg/dL from calcium hydroxide with sterile water, Metapex and calcium hydroxide gutta-percha points, respectively. Conclusions: Calcium hydroxide with sterile water and RC Cal pastes liberate significantly more calcium and hydroxyl ions and raise the pH higher than Metapex and calcium hydroxidegutta-percha points. PMID:22346155

Determination of sound types and source levels of airborne vocalizations by California sea lions, Zalophus californianus, in rehabilitation at the Marine Mammal Center in Sausalito, California

NASA Astrophysics Data System (ADS)

Schwalm, Afton Leigh

California sea lions (Zalophus californianus) are a highly popular and easily recognized marine mammal in zoos, aquariums, circuses, and often seen by ocean visitors. They are highly vocal and gregarious on land. Surprisingly, little research has been performed on the vocalization types, source levels, acoustic properties, and functions of airborne sounds used by California sea lions. This research on airborne vocalizations of California sea lions will advance the understanding of this aspect of California sea lions communication, as well as examine the relationship between health condition and acoustic behavior. Using a PhillipsRTM digital recorder with attached microphone and a calibrated RadioShackRTM sound pressure level meter, acoustical data were recorded opportunistically on California sea lions during rehabilitation at The Marine Mammal Center in Sausalito, CA. Vocalizations were analyzed using frequency, time, and amplitude variables with Raven Pro: Interactive Sound Analysis Software Version 1.4 (The Cornell Lab of Ornithology, Ithaca, NY). Five frequency, three time, and four amplitude variables were analyzed for each vocalization. Differences in frequency, time, and amplitude variables were not significant by sex. The older California sea lion group produced vocalizations that were significantly lower in four frequency variables, significantly longer in two time variables, significantly higher in calibrated maximum and minimum amplitude variables, and significantly lower in frequency at maximum and minimum amplitude compared with pups. Six call types were identified: bark, goat, growl/grumble, bark/grumble, bark/growl, and grumble/moan. The growl/grumble call was higher in dominant beginning, ending, and minimum frequency, as well as in the frequency at maximum amplitude compared with the bark, goat, bark/grumble calls in the first versus last vocalization sample. The goat call was significantly higher in first harmonic interval than any other call type in the all vocalizations sample. The "fate" of a sea lion was categorized as: released, placed at another facility, remained at TMMC, euthanized, or died. To determine if acoustic features could be used to assess the recovery of a pup, the acoustic features of a pup's first recorded vocalization were compared with the frequency, time, and amplitude of the last vocalization recorded (i.e., before it was released or placed at another facility). In addition, all first vocalizations were pooled and all last vocalizations were pooled for acoustic analysis, regardless of their fate. Released pups had shorter duration calls, a greater first harmonic interval, and a higher dominant maximum frequency than either pups that died or pups remaining at TMMC. Released pups had a higher frequency at maximum and minimum amplitude compared to dead and remaining pups. Pups that died had significantly lower dominant ending frequency and a lower dominant minimum frequency than released or remaining pups. These results were supported by other studies on different species of otariids, phocids, and cetaceans. The preliminary analyses presented in this thesis holds promise that with additional data acoustic features of California sea lion airborne vocalizations could indicate sex, age, and possibly health condition or the potential for release.

Cytotoxicity evaluation of ceramic particles of different sizes and shapes.

PubMed

Yamamoto, Akiko; Honma, Rieko; Sumita, Masae; Hanawa, Takao

2004-02-01

When artificial hip or knee joints are implanted in the human body, they release metallic, ceramic, and polymeric debris into the surrounding tissues. The toxicity of the released particles is of two types: chemical, caused by the released soluble ions and monomers, and mechanical, a result of mechanical stimulation produced by the insoluble particles. In this study, the cytotoxicity of particles of TiO2, Al2O3, ZrO2, Si3N4, and SiC for murine fibroblasts and macrophages were examined to evaluate just their mechanical toxicity because these particles are not expected to release soluble metal ions. Different sizes and shapes of TiO2 particles were used to evaluate the effect of size and shape on particle cytotoxicity. The results suggest that the cytotoxicity of ceramic particles does not depend on their chemical species. Cytotoxicity levels were lower than those of corresponding metal ions, indicating that the mechanical toxicity of particles is lower than the chemical toxicity of released soluble ions and monomers. The differences in size did not affect the mechanical toxicity of these particles. The dendritic particles had a higher cytotoxicity level for macrophages than did spindle and spheric particles. Copyright 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 244-256, 2004

Mitochondrial alkaline pH-responsive drug release mediated by Celastrol loaded glycolipid-like micelles for cancer therapy.

PubMed

Tan, Yanan; Zhu, Yun; Zhao, Yue; Wen, Lijuan; Meng, Tingting; Liu, Xuan; Yang, Xiqin; Dai, Suhuan; Yuan, Hong; Hu, Fuqiang

2018-02-01

Mitochondria, crucial regulators of inducing tumor cells apoptosis, can be treated as the prime target for tumor therapy. The selective and responsive release of proapoptotic therapeutics into mitochondria may notably improve antitumor efficiency. Herein, (4-Carboxybutyl) triphenylphosphonium bromide (CTPP), a lipophilic cation, was conjugated with glucolipid-like conjugates (CSOSA) to produce mitochondria-targeted conjugates (CTPP-CSOSA). Loading with weakly acidic drug Celastrol (Cela), CTPP-CSOSA/Cela micelles could selectively respond to mitochondrial alkaline pH (pH 8.0), controlled by the weaker interaction between hydrophobic core of micelles and Cela with higher solubility at pH 8.0. However, there was a slow drug release behavior at pH 7.4 and pH 5.0. It illustrated that CTPP-CSOSA/Cela could realize mitochondrial fast drug release, and decrease drug leakage in the cytoplasm and lysosome. CTPP-CSOSA/Cela highly enhanced ROS levels, which further induced mitochondria membrane potential decreasing and more Cytochrome C releasing into cytoplasm, then promoted tumor cells apoptosis notably. In vivo, CTPP-CSOSA had an enhanced accumulation in tumor tissue, compared with CSOSA. Moreover, the tumor-inhibition rate of CTPP-CSOSA/Cela was 80.17%, which was significantly higher than CSOSA/Cela (58.35%) and Cela (54.89%). Thus, CTPP-CSOSA/Cela micelles with mitochondrial targeting and alkaline pH-responsive release capability could provide a new strategy for tumor therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

5 CFR 351.608 - Permissive temporary exceptions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REDUCTION IN FORCE Release From Competitive Level § 351.608 Permissive temporary exceptions. (a) General. (1.... This does not preclude the employee from receiving or accepting a job offer in the same competitive... more than 30 days, it must: (1) Notify in writing each higher standing employee in the same competitive...

Coronary microvascular dysfunction and diastolic load correlate with cardiac troponin T release measured by a highly sensitive assay in patients with nonischemic heart failure.

PubMed

Takashio, Seiji; Yamamuro, Megumi; Izumiya, Yasuhiro; Sugiyama, Seigo; Kojima, Sunao; Yamamoto, Eiichiro; Tsujita, Kenichi; Tanaka, Tomoko; Tayama, Shinji; Kaikita, Koichi; Hokimoto, Seiji; Ogawa, Hisao

2013-08-13

This study investigated factors associated with cardiac troponin T (cTnT) release from failing myocardium. Persistent and modest elevation of serum cTnT is frequently observed in heart failure (HF) patients free of coronary artery disease, although the mechanisms underlying this finding remain unclear. We evaluated serum cTnT levels in the aortic root (Ao) and coronary sinus (CS) using a highly sensitive assay in 90 nonischemic HF patients and 47 non-HF patients. Transcardiac cTnT and plasma B-type natriuretic peptide (BNP) release were described as the differences between CS and Ao cTnT levels [ΔcTnT (CS-Ao)] and BNP levels [ΔBNP (CS-Ao)], respectively. Coronary flow reserve (CFR) was measured in 68 HF patients using an intracoronary Doppler guidewire. ΔcTnT (CS-Ao) levels were available in 76 HF patients and 28 non-HF patients (84% vs. 60%; p = 0.001), and higher in HF patients than non-HF patients (p < 0.001). Among HF patients, log[ΔcTnT (CS-Ao)] correlated with log[ΔBNP (CS-Ao)] (r = 0.368, p = 0.001), pulmonary capillary wedge pressure (r = 0.253, p = 0.03) and left ventricular end-diastolic pressure (LVEDP) (r = 0.321, p = 0.005). Multivariate regression analysis identified LVEDP as an independent parameter that correlated with ΔcTnT (CS-Ao). ΔcTnT (CS-Ao) levels were available in 58 HF patients who were evaluated for CFR. Coronary microvascular dysfunction, diagnosed by CFR <2.0, was observed in 18 HF patients. ΔcTnT (CS-Ao) was higher in patients with coronary microvascular dysfunction (4.8 [2.0 to 8.1] ng/l) than those without (2.0 [1.2 to 4.6] ng/l; p = 0.04). cTnT release from failing myocardium correlated with diastolic load and coronary microvascular dysfunction in nonischemic HF patients. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Silicate release from glass for pharmaceutical preparations.

PubMed

Bohrer, Denise; Bortoluzzi, Fabiana; Nascimento, Paulo Cícero; Carvalho, Leandro Machado; Ramirez, Adrian Gustavo

2008-05-01

Glass is made of polymeric silica and other minor components, which are necessary for turning the silica into a material more easily moldable and resistant to temperature changes. Glass containers for pharmaceutical usage are classified according to their resistance to a chemical attack, a test carried out in the presence of water and heat. The test is designed to show the released alkalinity, a variable dependent on the amount of sodium oxide, one of the minor components added to the glass mass. In this work, the release of silica from glass by action of constituents from pharmaceutical formulations was investigated. The study included products used in large volumes and usually stored in glass containers. Solutions of amino acids, electrolytes, glucose, oligoelements and others such as heparin and sodium bicarbonate were individually stored in glass containers and heated at 121 degrees C for 30min, as in the water attack test. The test was also carried out only with water, where the pH varied from 2 to 12. The released silicate was measured either by photometry or atomic absorption spectrometry, depending on the nature of the sample. The results showed that silicate is released during the heating cycle even if the contact is with pure water only. The pH exerts a considerable influence on the release, being that the higher the pH, the higher the silica dissolved. An elevated pH, however, is not the only factor responsible for silica dissolution. While in the solutions of NaCl, KCl, Mg Cl2 and ZnSO4 and in most of the amino acids, the concentration of silicate was as high as in pure water (0.1-1.0mg Si/L). In the solutions of sodium acetate, bicarbonate and gluconate, its concentration was much higher, over 30mg Si/L. These results were confirmed by the analysis of commercial products, where in solutions of amino acids the level of silicate ranged from 0.14 to 0.19mg Si/L. On the other hand, calcium gluconate, sodium bicarbonate and potassium phosphate presented silicate levels from 1 to 4mg/L. Although silica is not considered a toxic substance for humans, it is necessary to be aware of its presence in solutions for parenteral nutrition due to the direct introduction into the bloodstream and the large volume usually administrated, even to pre-term infants.

Vpu-Mediated Counteraction of Tetherin Is a Major Determinant of HIV-1 Interferon Resistance

PubMed Central

Kmiec, Dorota; Iyer, Shilpa S.; Stürzel, Christina M.; Sauter, Daniel; Hahn, Beatrice H.

2016-01-01

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) groups M, N, O, and P are the result of independent zoonotic transmissions of simian immunodeficiency viruses (SIVs) infecting great apes in Africa. Among these, only Vpu proteins of pandemic HIV-1 group M strains evolved potent activity against the restriction factor tetherin, which inhibits virus release from infected cells. Thus, effective Vpu-mediated tetherin antagonism may have been a prerequisite for the global spread of HIV-1. To determine whether this particular function enhances primary HIV-1 replication and interferon resistance, we introduced mutations into the vpu genes of HIV-1 group M and N strains to specifically disrupt their ability to antagonize tetherin, but not other Vpu functions, such as degradation of CD4, down-modulation of CD1d and NTB-A, and suppression of NF-κB activity. Lack of particular human-specific adaptations reduced the ability of HIV-1 group M Vpu proteins to enhance virus production and release from primary CD4+ T cells at high levels of type I interferon (IFN) from about 5-fold to 2-fold. Interestingly, transmitted founder HIV-1 strains exhibited higher virion release capacity than chronic control HIV-1 strains irrespective of Vpu function, and group M viruses produced higher levels of cell-free virions than an N group HIV-1 strain. Thus, efficient virus release from infected cells seems to play an important role in the spread of HIV-1 in the human population and requires a fully functional Vpu protein that counteracts human tetherin. PMID:27531907

Hyperinsulinemia is Associated with Increased Soluble Insulin Receptors Release from Hepatocytes

PubMed Central

Hiriart, Marcia; Sanchez-Soto, Carmen; Diaz-Garcia, Carlos Manlio; Castanares, Diana T.; Avitia, Morena; Velasco, Myrian; Mas-Oliva, Jaime; Macias-Silva, Marina; González-Villalpando, Clicerio; Delgado-Coello, Blanca; Sosa-Garrocho, Marcela; Vidaltamayo, Román; Fuentes-Silva, Deyanira

2014-01-01

It has been generally assumed that insulin circulates freely in blood. However it can also interact with plasma proteins. Insulin receptors are located in the membrane of target cells and consist of an alpha and beta subunits with a tyrosine kinase cytoplasmic domain. The ectodomain, called soluble insulin receptor (SIR) has been found elevated in patients with diabetes mellitus. We explored if insulin binds to SIRs in circulation under physiological conditions and hypothesize that this SIR may be released by hepatocytes in response to high insulin concentrations. The presence of SIR in rat and human plasmas and the culture medium of hepatocytes was explored using Western blot analysis. A purification protocol was performed to isolated SIR using affinity, gel filtration, and ion exchange chromatographies. A modified reverse hemolytic plaque assay was used to measure SIR release from cultured hepatocytes. Incubation with 1 nmol l−1 insulin induces the release of the insulin receptor ectodomains from normal rat hepatocytes. This effect can be partially prevented by blocking protease activity. Furthermore, plasma levels of SIR were higher in a model of metabolic syndrome, where rats are hyperinsulinemic. We also found increased SIR levels in hyperinsulinemic humans. SIR may be an important regulator of the amount of free insulin in circulation. In hyperinsulinemia, the amount of this soluble receptor increases and this could lead to higher amounts of insulin bound to this receptor, rather than free insulin, which is the biologically active form of the hormone. This observation could enlighten the mechanisms of insulin resistance. PMID:24995000

Hyperinsulinemia is Associated with Increased Soluble Insulin Receptors Release from Hepatocytes.

PubMed

Hiriart, Marcia; Sanchez-Soto, Carmen; Diaz-Garcia, Carlos Manlio; Castanares, Diana T; Avitia, Morena; Velasco, Myrian; Mas-Oliva, Jaime; Macias-Silva, Marina; González-Villalpando, Clicerio; Delgado-Coello, Blanca; Sosa-Garrocho, Marcela; Vidaltamayo, Román; Fuentes-Silva, Deyanira

2014-01-01

It has been generally assumed that insulin circulates freely in blood. However it can also interact with plasma proteins. Insulin receptors are located in the membrane of target cells and consist of an alpha and beta subunits with a tyrosine kinase cytoplasmic domain. The ectodomain, called soluble insulin receptor (SIR) has been found elevated in patients with diabetes mellitus. We explored if insulin binds to SIRs in circulation under physiological conditions and hypothesize that this SIR may be released by hepatocytes in response to high insulin concentrations. The presence of SIR in rat and human plasmas and the culture medium of hepatocytes was explored using Western blot analysis. A purification protocol was performed to isolated SIR using affinity, gel filtration, and ion exchange chromatographies. A modified reverse hemolytic plaque assay was used to measure SIR release from cultured hepatocytes. Incubation with 1 nmol l(-1) insulin induces the release of the insulin receptor ectodomains from normal rat hepatocytes. This effect can be partially prevented by blocking protease activity. Furthermore, plasma levels of SIR were higher in a model of metabolic syndrome, where rats are hyperinsulinemic. We also found increased SIR levels in hyperinsulinemic humans. SIR may be an important regulator of the amount of free insulin in circulation. In hyperinsulinemia, the amount of this soluble receptor increases and this could lead to higher amounts of insulin bound to this receptor, rather than free insulin, which is the biologically active form of the hormone. This observation could enlighten the mechanisms of insulin resistance.

Cell wall polysaccharides released during the alcoholic fermentation by Schizosaccharomyces pombe and S. japonicus: quantification and characterization.

PubMed

Domizio, P; Liu, Y; Bisson, L F; Barile, D

2017-02-01

The present work demonstrates that yeasts belonging to the Schizosaccharomyces genus release a high quantity of polysaccharides of cell wall origin starting from the onset of the alcoholic fermentation. By the end of the alcoholic fermentation, all of the Schizosaccharomyces yeast strains released a quantity of polysaccharides approximately 3-7 times higher than that released by a commercial Saccharomyces cerevisiae yeast strain under the same fermentative conditions of synthetic juice. A higher content of polysaccharide was found in media fermented by Schizosaccharomyces japonicus with respect to that of Schizosaccharomyces pombe. Some of the strains evaluated were also able to produce high levels of pyruvic acid, which has been shown to be an important compound for color stability of wine. The presence of strains with different malic acid consumption patterns along with high polysaccharide release would enable production of naturally modified wines with enhanced mouth feel and reduced acidity. The chemical analysis of the released polysaccharides demonstrated divergence between the two yeast species S. pombe and S. japonicus. A different mannose/galactose ratio and a different percentage of proteins was observed on the polysaccharides released by S. pombe as compared to S. japonicus. Analysis of the proteins released in the media revealed the presence of a glycoprotein with a molecular size around 32-33 kDa only for the species S. japonicus. Mass spectrometry analysis of carbohydrate moieties showed similar proportions among the N-glycan chains released in the media by both yeast species but differences between the two species were also observed. These observations suggest a possible role of rapid MALDI-TOF screening of N-glycans compositional fingerprint as a taxonomic tool for this genus. Polysaccharides release in the media, in particular galactomannoproteins in significant amounts, could make these yeasts particularly interesting also for the industrial production of exogenous polysaccharide preparations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cell wall polysaccharides released during the alcoholic fermentation by Schizosaccharomyces pombe and S. japonicus: quantification and characterization

PubMed Central

Domizio, P.; Liu, Y.; Bisson, L.F.; Barile, D.

2016-01-01

The present work demonstrates that yeasts belonging to the Schizosaccharomyces genus release a high quantity of polysaccharides of cell wall origin starting from the onset of the alcoholic fermentation. By the end of the alcoholic fermentation, all of the Schizosaccharomyces yeast strains released a quantity of polysaccharides approximately 3-7 times higher than that released by a commercial Saccharomyces cerevisiae yeast strain under the same fermentative conditions of synthetic juice. A higher content of polysaccharide was found in media fermented by Schizosaccharomyces japonicus with respect to that of Schizosaccharomyces pombe. Some of the strains evaluated were also able to produce high levels of pyruvic acid, which has been shown to be an important compound for color stability of wine. The presence of strains with different malic acid consumption patterns along with high polysaccharide release would enable production of naturally modified wines with enhanced mouth feel and reduced acidity. The chemical analysis of the released polysaccharides demonstrated divergence between the two yeast species S. pombe and S. japonicus. A different mannose/galactose ratio and a different percentage of proteins was observed on the polysaccharides released by S. pombe as compared to S. japonicus. Analysis of the proteins released in the media revealed the presence of a glycoprotein with a molecular size around 32-33 kDa only for the species S. japonicus. Mass spectrometry analysis of carbohydrate moieties showed similar proportions among the N-glycan chains released in the media by both yeast species but differences between the two species were also observed. These observations suggest a possible role of rapid MALDI-TOF screening of N-glycans compositional fingerprint as a taxonomic tool for this genus. Polysaccharides release in the media, in particular galactomannoproteins in significant amounts, could make these yeasts particularly interesting also for the industrial production of exogenous polysaccharide preparations. PMID:27697163

Evaluation of buprenorphine hydrochloride Pluronic® gel formulation in male C57BL/6NCrl mice

PubMed Central

Blankenship-Paris, Terry L.; Dutton, John W.; Goulding, David R.; McGee, Christopher A.; Kissling, Grace E.; Myers, Page H.

2016-01-01

Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic® F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use. PMID:27654688

Factors affecting the presence of dissolved glutathione in estuarine waters.

PubMed

Tang, Degui; Shafer, Martin M; Karner, Dawn A; Overdier, Joel; Armstrong, David E

2004-08-15

We investigated factors influencing the presence of the thiol glutathione (GSH) in estuarine waters. Our study addressed thiol phase-association, the biological release from algal cultures, and the role of copper in both thiol release and preservation. Our measurements in three diverse estuaries in the continental United States (San Diego Bay, Cape Fear Estuary, and Norfolk Estuary) show that dissolved GSH, present at sub-nanomolar levels, is preferentially partitioned into the ultra-filtrate fraction (<1 kDa) in comparison with dissolved organic carbon (DOC). Concentrations of GSH generally increased with increases in total copper (Cu)levels, although large variability was observed among estuaries. In 30-h exposure experiments, release of dissolved GSH from the diatom Thalassiosira weissflogii into organic ligand-free experimental media was a strong function of added Cu concentration. The released GSH increased from about 0.02 to 0.27 fmol/cell as Cu was increased from the background level (0.5 nM) to 310 nM in the modified Aquil media. However, excretion of GSH was lower (up to 0.13 fmol/cell) when cells were grown in surface waters of San Diego Bay, despite much higher total Cu concentrations. Experiments conducted in-situ in San Diego Bay water indicated that high concentrations of added Cu destabilized GSH, while both Mn(II) and natural colloids promoted GSH stability. In contrast, laboratory experiments in synthetic media indicated that moderate levels of added Cu enhanced GSH stability.

Platelet TGF-β1 contributions to plasma TGF-β1, cardiac fibrosis, and systolic dysfunction in a mouse model of pressure overload

PubMed Central

Meyer, Alexander; Wang, Wei; Qu, Jiaxiang; Croft, Lori; Degen, Jay L.; Coller, Barry S.

2012-01-01

Circulating platelets contain high concentrations of TGF-β1 in their α-granules and release it on platelet adhesion/activation. We hypothesized that uncontrolled in vitro release of platelet TGF-β1 may confound measurement of plasma TGF-β1 in mice and that in vivo release and activation may contribute to cardiac pathology in response to constriction of the transverse aorta, which produces both high shear and cardiac pressure overload. Plasma TGF-β1 levels in blood collected from C57Bl/6 mice by the standard retro-bulbar technique were much higher than those obtained when prostaglandin E1 was added to inhibit release or when blood was collected percutaneously from the left ventricle under ultrasound guidance. Even with optimal blood drawing, plasma TGF-β1 was lower in mice rendered profoundly thrombocytopenic or mice with selectively low levels of platelet TGF-β1 because of megakaryocytespecific disruption of their TGF-β1 gene (Tgfb1flox). Tgfb1flox mice were also partially protected from developing cardiac hypertrophy, fibrosis, and systolic dysfunction in response to transverse aortic constriction. These studies demonstrate that plasma TGF-β1 levels can be assessed accurately, but it requires special precautions; that platelet TGF-β1 contributes to plasma levels of TGF-β1; and that platelet TGF-β1 contributes to the pathologic cardiac changes that occur in response to aortic constriction. PMID:22134166

Circulating levels of cholecystokinin and gastrin-releasing peptide in rainbow trout fed different diets.

PubMed

Jönsson, Elisabeth; Forsman, Antti; Einarsdottir, Ingibjörg E; Egnér, Barbro; Ruohonen, Kari; Björnsson, Björn Thrandur

2006-09-01

Cholecystokinin (CCK) and gastrin-releasing peptide (GRP) are gastrointestinal peptides thought to be important regulators of intake and digestion of food in vertebrates. In this study, pre- and postprandial plasma levels of CCK and GRP were measured in rainbow trout (Oncorhynchus mykiss) by the establishment of homologous radioimmunoassays, and the hormonal levels assessed in relation to dietary lipid:protein ratio and food intake. Fish were acclimated to either a high protein/low lipid diet (HP/LL diet; 14.1% lipids) or a normal protein/high lipid diet (NP/HL diet; 31.4% lipids). On three consecutive sampling days, radio-dense lead-glass beads were included in the diets for assessment of feed intake. Fish were terminally sampled for blood and stomach contents prior to feeding at time 0, and at 0.3, 1, 2, 4, 6, and 24 h after feeding. There was a postprandial elevation of plasma CCK levels, which was most evident after 4 and 6 h. Fish fed the NP/HL diet had higher plasma CCK levels compared with those fed the HP/LL diet. Plasma CCK levels were not affected by the amount of food ingested. GRP levels in plasma were not influenced by sampling time, diet, or feed intake. The results indicate that the endocrine release of gastrointestinal CCK is increased during feeding and may be further influenced by the dietary lipid:protein ratio in rainbow trout. Plasma GRP levels, on the other hand, appear not to be influenced by feeding or diet composition.

A Microelectromechanical High-Density Energy Storage/Rapid Release System

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

Rodgers, M. Steven; Allen, Jim J.; Meeks, Kent D.

1999-07-21

One highly desirable characteristic of electrostatically driven microelectromechanical systems (MEMS) is that they consume very little power. The corresponding drawback is that the force they produce may be inadequate for many applications. It has previously been demonstrated that gear reduction units or microtransmissions can substantially increase the torque generated by microengines. Operating speed, however, is also reduced by the transmission gear ratio. Some applications require both high speed and high force. If this output is only required for a limited period of time, then energy could be stored in a mechanical system and rapidly released upon demand. We have designed,more » fabricated, and demonstrated a high-density energy storage/rapid release system that accomplishes this task. Built using a 5-level surface micromachining technology, the assembly closely resembles a medieval crossbow. Energy releases on the order of tens of nanojoules have already been demonstrated, and significantly higher energy systems are under development.« less

Microelectromechanical high-density energy storage/rapid release system

NASA Astrophysics Data System (ADS)

Rodgers, M. Steven; Allen, James J.; Meeks, Kent D.; Jensen, Brian D.; Miller, Samuel L.

1999-08-01

One highly desirable characteristic of electrostatically driven microelectromechanical systems (MEMS) is that they consume very little power. The corresponding drawback is that the force they produce may be inadequate for many applications. It has previously been demonstrated that gear reduction units or microtransmissions can substantially increase the torque generated by microengines. Operating speed, however, is also reduced by the transmission gear ratio. Some applications require both high speed and high force. If this output is only required for a limited period of time, then energy could be stored in a mechanical system and rapidly released upon demand. We have designed, fabricated, and demonstrated a high-density energy storage/rapid release system that accomplishes this task. Built using a 5-level surface micromachining technology, the assembly closely resembles a medieval crossbow. Energy releases on the order of tens of nanojoules have already been demonstrated, and significantly higher energy systems are under development.

In vitro atrazine-exposure inhibits human natural killer cell lytic granule release

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

Rowe, Alexander M.; Brundage, Kathleen M.; Center for Immunopathology and Microbial Pathogenesis, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506

2007-06-01

The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesizedmore » that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test this hypothesis, flow cytometry and fluorescent microscopy were employed to analyze NK cell-target cell co-cultures following atrazine exposure. These assays demonstrated no significant decrease in the level of target cell binding. However, the levels of NK intracellular lytic protein retained and the amount of lytic protein released were assessed following a 4-h incubation with K562 target cells. The relative level of intracellular lytic protein was 25-50% higher, and the amount of lytic protein released was 55-65% less in atrazine-treated cells than vehicle-treated cells following incubation with the target cells. These results indicate that ATR exposure inhibits the ability of NK cells to lyse target cells by blocking lytic granule release without affecting the ability of the NK cell to form stable conjugates with target cells.« less

5 CFR 351.601 - Order of release from competitive level.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Order of release from competitive level... REGULATIONS REDUCTION IN FORCE Release From Competitive Level § 351.601 Order of release from competitive level. (a) Each agency must select competing employees for release from a competitive level (including...

5 CFR 351.601 - Order of release from competitive level.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Order of release from competitive level... REGULATIONS REDUCTION IN FORCE Release From Competitive Level § 351.601 Order of release from competitive level. (a) Each agency must select competing employees for release from a competitive level (including...

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

PubMed

Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C

2003-10-01

The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Investigating effects of hydroxypropyl methylcellulose (HPMC) molecular weight grades on lag time of press-coated ethylcellulose tablets.

PubMed

Patadia, Riddhish; Vora, Chintan; Mittal, Karan; Mashru, Rajashree

2016-11-01

The research undertaken exemplifies the effects of hydroxypropyl methylcellulose (HPMC) molecular weight (MW) grades of on lag time of press-coated ethylcellulose (EC) tablets. The formulation comprised an immediate release core (containing prednisone as a model drug) surrounded by compression coating with variegated EC-HPMC blends. Five selected HPMC grades (E5, E15, E50, K100LV and K4M) were explored at three different concentrations (10% w/w, 20% w/w and 30% w/w in outer coat) to understand their effects on lag time and drug release. In vitro drug release testing demonstrated that, with increase in concentration of E5 and E15, up to 30% w/w, the mean lag time decreased progressively; whereas with remaining grades, the mean lag time initially decreased up to 20% w/w level and thereafter increased for 30% w/w level. Importantly, with increase in HPMC concentration in the outer coat, the variability in lag time (%RSD; n = 6) was decreased for each of E5, E15 and E50, whereas increased for K100LV and K4M. In general, the variability in lag time was increased with increase in HPMC MW at studied concentration levels. Markedly, tablets with 30% w/w K4M in outer coat exhibited slight premature release (before the rupture of outer coat) along with high variability in lag time. Overall, the study concluded that low MW HPMCs (E5, E15 and E50) were found rather efficient than higher MW HPMCs for developing robust EC-based press-coated pulsatile release formulations where precise lag time followed by sharp burst release is desired.

Reduced carbon sequestration potential of biochar in acidic soil.

PubMed

Sheng, Yaqi; Zhan, Yu; Zhu, Lizhong

2016-12-01

Biochar application in soil has been proposed as a promising method for carbon sequestration. While factors affecting its carbon sequestration potential have been widely investigated, the number of studies on the effect of soil pH is limited. To investigate the carbon sequestration potential of biochar across a series of soil pH levels, the total carbon emission, CO 2 release from inorganic carbon, and phospholipid fatty acids (PLFAs) of six soils with various pH levels were compared after the addition of straw biochar produced at different pyrolysis temperatures. The results show that the acidic soils released more CO 2 (1.5-3.5 times higher than the control) after the application of biochar compared with neutral and alkaline soils. The degradation of both native soil organic carbon (SOC) and biochar were accelerated. More inorganic CO 2 release in acidic soil contributed to the increased degradation of biochar. Higher proportion of gram-positive bacteria in acidic soil (25%-36%) was responsible for the enhanced biochar degradation and simultaneously co-metabolism of SOC. In addition, lower substrate limitation for bacteria, indicated by higher C-O stretching after the biochar application in the acidic soil, also caused more CO 2 release. In addition to the soil pH, other factors such as clay contents and experimental duration also affected the phsico-chemical and biotic processes of SOC dynamics. Gram-negative/gram-positive bacteria ratio was found to be negatively related to priming effects, and suggested to serve as an indicator for priming effect. In general, the carbon sequestration potential of rice-straw biochar in soil reduced along with the decrease of soil pH especially in a short-term. Given wide spread of acidic soils in China, carbon sequestration potential of biochar may be overestimated without taking into account the impact of soil pH. Copyright © 2016 Elsevier B.V. All rights reserved.

Photoinitiator-free 3D scaffolds fabricated by excimer laser photocuring.

PubMed

Farkas, Balázs; Dante, Silvia; Brandi, Fernando

2017-01-20

Photoinitiator-free fabrication of poly(ethylene glycol) diacrylate (PEGDA) scaffolds is achieved using a novel three-dimensional (3D) printing method called mask projected excimer laser stereolithography (MPExSL). The spatial resolution of photoinitiator-free curing is suitable for 3D layer-by-layer fabrication with a single layer thickness well controllable at tens to hundreds of microns using 248 nm wavelength for the irradiation. The photoinitiator-free scaffolds are superior compared to their counterparts fabricated by using photoinitiator molecules, showing a higher level of biocompatibility. A release of toxic chemicals from the photoinitiator containing scaffolds is proven by cell proliferation tests. In contrast, no toxic release is found from the photoinitiator-free scaffolds, resulting in the very same level of cell proliferation as the control sample. The demonstration of photoinitiator-free PEGDA scaffolds enables the fabrication of 3D scaffolds with the highest level of biocompatibility for both in vitro and in vivo applications.

Endocrine correlates of susceptibility to motion sickness

NASA Technical Reports Server (NTRS)

Kohl, R. L.

1985-01-01

Motion sickness releases ACTH, epinerphrine, and norepinephrine. The endocrine responses to motion sickness, adaptive responses leading to the resolution of the syndrome, and the way in which antimotion-sickness drugs influence the endocrine responses were studied. Susceptible or insusceptible subjects were administered antimotion-sickness drugs prior to stressful stimulation. Insusceptible subjects displayed more pronounced elevations of ACTH, epinephrine, and norepinephrine after stressful motion. Predrug levels of ACTH were higher in insusceptible subjects (p less than 0.01). Acute blockade of hormone responses to stressful motion or alteration of levels of ACTH by drugs were not correlated with individual susceptibility. No correlation was apparent between epinephrine and ACTH release. These endocrine differences may represent neurochemical markers for susceptibility to motion, stress, or general adaptability, and it may be that the chronic modulation of their levels might be more effective in preventing motion sickness than the acute blockage or stimulation of specific receptors.

Lack of endogenous adenosine tonus on sympathetic neurotransmission in spontaneously hypertensive rat mesenteric artery.

PubMed

Sousa, Joana Beatriz; Vieira-Rocha, Maria Sofia; Sá, Carlos; Ferreirinha, Fátima; Correia-de-Sá, Paulo; Fresco, Paula; Diniz, Carmen

2014-01-01

Increased sympathetic activity has been implicated in hypertension. Adenosine has been shown to play a role in blood flow regulation. In the present study, the endogenous adenosine neuromodulatory role, in mesenteric arteries from normotensive and spontaneously hypertensive rats, was investigated. The role of endogenous adenosine in sympathetic neurotransmission was studied using electrically-evoked [3H]-noradrenaline release experiments. Purine content was determined by HPLC with fluorescence detection. Localization of adenosine A1 or A2A receptors in adventitia of mesenteric arteries was investigated by Laser Scanning Confocal Microscopy. Results indicate a higher electrically-evoked noradrenaline release from hypertensive mesenteric arteries. The tonic inhibitory modulation of noradrenaline release is mediated by adenosine A1 receptors and is lacking in arteries from hypertensive animals, despite their purine levels being higher comparatively to those determined in normotensive ones. Tonic facilitatory adenosine A2A receptor-mediated effects were absent in arteries from both strains. Immunohistochemistry revealed an adenosine A1 receptors redistribution from sympathetic fibers to Schwann cells, in adventitia of hypertensive mesenteric arteries which can explain, at least in part, the absence of effects observed for these receptors. Data highlight the role of purines in hypertension revealing that an increase in sympathetic activity in hypertensive arteries is occurring due to a higher noradrenaline/ATP release from sympathetic nerves and the loss of endogenous adenosine inhibitory tonus. The observed nerve-to-glial redistribution of inhibitory adenosine A1 receptors in hypertensive arteries may explain the latter effect.

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

PubMed

Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

2000-03-01

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Leishmania amazonensis fails to induce the release of reactive oxygen intermediates by CBA macrophages.

PubMed

Almeida, T F; Palma, L C; Mendez, L C; Noronha-Dutra, A A; Veras, P S T

2012-10-01

CBA mouse macrophages effectively control Leishmania major infection, yet are permissive to Leishmania amazonensis. It has been established that some Leishmania species are destroyed by reactive oxygen species (ROS). However, other species of Leishmania exhibit resistance to ROS or even down-modulate ROS production. We hypothesized that L. amazonensis-infected macrophages reduce ROS production soon after parasite-cell interaction. Employing a highly sensitive analysis technique based on chemiluminescence, the production of superoxide (O(·-)(2)) and hydrogen peroxide (H(2)O(2)) by L. major- or L. amazonensis-infected CBA macrophages were measured. L. major induces macrophages to release levels of (O(·-)(2)) 3·5 times higher than in uninfected cells. This (O(·-)(2)) production is partially dependent on NADPH oxidase (NOX) type 2. The level of accumulated H(2)O(2) is 20 times higher in L. major-than in L. amazonensis-infected cells. Furthermore, macrophages stimulated with L. amazonensis release amounts of ROS similar to uninfected cells. These findings support previous studies showing that CBA macrophages are effective in controlling L. major infection by a mechanism dependent on both (O(·-)(2)) production and H(2)O(2) generation. Furthermore, these data reinforce the notion that L. amazonensis survive inside CBA macrophages by reducing ROS production during the phagocytic process. © 2012 Blackwell Publishing Ltd.

Preparation and release study of Triclosan in polyethylene/Triclosan anti-bacterial blend.

PubMed

Kamalipour, Jamshid; Masoomi, Mahmood; Khonakdar, Hossein Ali; Razavi, Seyed Mohammad Reza

2016-09-01

In this study, medium density polyethylene (MDPE) incorporated with Triclosan antibacterial substance has been prepared and Triclosan release rate was investigated. The crystallinity level and matrix polarity, as two significant parameters in antibacterial release control, were studied. Triclosan, a well-established widespread antibacterial agent, was incorporated into medium density polyethylene (MDPE) and Maleic anhydride grafted polyethylene (PE-g-MA) was used to change the polarity of the MDPE matrix. A masterbatch of 10wt% Triclosan incorporated with the MDPE and various PE-g-MA concentrations were prepared using an internal mixer. Then the masterbatch was diluted in the MDPE matrix to produce compounds with 0.1, 0.5, and1wt% Triclosan via twin screw extruder. The compounds were molded by compression molding method and then were cooled in three different cooling rate methods: isothermal cooling (I), quenching (Q),and moderate 5-10°C/min cooling rate (M). Cooling rate effects on crystallinity level were investigated applying sample density measurement. UV-vis absorption spectroscopy was used to probe the release of Triclosan. Antibacterial properties of the compounds against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were measured. The results showed that by addition of PE-g-MA, Triclosan release rate was increased. It was confirmed that the sample crystallinity was decreased by the cooling rate enhancement. The results also showed that quenched samples indicated higher release of Triclosan. Cooling rate reduction and raising the polarity increased the release of Triclosan and improved the antibacterial properties of the compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Receptor activated bladder and spinal ATP release in neurally intact and chronic spinal cord injured rats

PubMed Central

Salas, Nilson A.; Somogyi, George T.; Gangitano, David A.; Boone, Timothy B.; Smith, Christopher P.

2009-01-01

Neurally intact (NI) rats and chronic spinal cord injured (SCI) rats were studied to determine how activation of mechanosensory or cholinergic receptors in the bladder urothelium evokes ATP release from afferent terminals in the bladder as well as in the spinal cord. Spinal cord transection was performed at the T9-T10 level 2–3 weeks prior to the experiment and a microdialysis fiber was inserted in the L6-S1 lumbosacral spinal cord. Mechanically evoked (i.e. 10cm/w bladder pressure) ATP release into the bladder lumen was approximately 6.5 fold higher in SCI compared to NI rats (p<0.05). Intravesical carbachol (CCh) induced a significantly greater release of ATP in the bladder from SCI as compared to NI rats (3424.32 ± 1255.57 vs. 613.74 ± 470.44 pmol/ml, respectively, p<0.05). However, ATP release in NI or SCI rats to intravesical CCh was not affected by the muscarinic antagonist atropine (Atr). Spinal release of ATP to bladder stimulation with 10cm/w pressure was 5-fold higher in SCI compared to NI rats (p<0.05). CCh also induced a significantly greater release of spinal ATP in SCI rats compared to controls (4.3 ± 0.9 vs. 0.90 ± 0.15 pmol, p < 0.05). Surprisingly, the percent inhibitory effect of Atr on CCh-induced ATP release was significantly less in SCI as compared to NI rats (49% vs. 89%, respectively). SCI induces a dramatic increase in intravesical pressure and cholinergic receptor evoked bladder and spinal ATP release. Muscarinic receptors do not mediate intravesical CCh induced ATP release into the bladder lumen in NI or SCI rats. In NI rats sensory muscarinic receptors are the predominant mechanism by which CCh induces ATP release from primary afferents within the lumbosacral spinal cord. Following SCI, however, nicotinic or purinergic receptor mechanisms become active, as evidenced by the fact that Atr was only partially effective in inhibiting CCh-induced spinal ATP release. PMID:17067723

Influence of Carbopol 71G-NF on the release of dextromethorphan hydrobromide from extended-release matrix tablets.

PubMed

Fayed, Mohamed H; Mahrous, Gamal M; Ibrahim, Mohamed A; Sakr, Adel

2013-01-01

The objective of this study was to evaluate the potential of Carbopol(®) 71G-NF on the release of dextromethorphan hydrobromide (DM) from matrix tablets in comparison with hydroxypropyl methylcellulose (HPMC(®) K15M) and Eudragit(®) L100-55 polymers. Controlled release DM matrix tablets were prepared using Carbopol 71G-NF, HPMC K15M, and Eudragit L100-55 at different drug to polymer ratios by direct compression technique. The mechanical properties of the tablets as tested by crushing strength and friability tests were improved as the concentration of Carbopol, HPMC, and Eudragit increased. However, Carbopol-based tablets showed a significantly (P<0.05) higher crushing strength and a lower friability than HPMC and Eudragit tablets. No significant differences in weight uniformity and thickness values were observed between the different formulations. It was also found that Carbopol significantly (P<0.05) delayed the release of DM in comparison with HPMC K15M and Eudragit L100-55. A combination of HPMC K15M and Eudragit L100-55 in a 1:1 ratio at 20 and 30% significantly (P<0.05) delayed the release of DM than Eudragit L100-55 alone. Moreover, blends of Carbopol and HPMC at a 1:1 ratio at the 10, 20, and 30% total polymer concentration were investigated. The blend of Carbopol and HPMC at 10% level significantly (P<0.05) slowed the release of DM than Carbopol or HPMC alone, whereas blends at 20 and 30% level significantly (P<0.05) delayed the release of DM compared with HPMC or Carbopol alone. The results with these polymer blends showed that it was possible to reduce the total amount of polymers when used as a combination in formulation.

Beneficial reuse of empty DUF{sub 6} cylinders

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

Nieves, L.A.; Arnish, J.; Nabelssi, B.

1997-02-01

This paper discusses options for the disposal of depleted UF{sub 6} storage cylinders as they are freed over the next 20 years. Presently there are 46,000 mild steel cylinders in use, and projections show 600,000 tons of steel being freed over 20 years. The paper discusses the results of studies which have looked at various aspects of this issue: health risks; environmental impacts; costs and hassles; impact of DOE metal recycle policy. The general conclusions were that chemical and trauma risks dominate the risk evaluations, that risk levels are broadly speaking level for the studied disposition options, that environmental risksmore » are highest for burial, and lowest for free release, while costs are higher for burial and recycling, than for reuse or free release.« less

Equity Overlooked: Charter Schools and Civil Rights Policy

ERIC Educational Resources Information Center

Frankenberg, Erica; Siegel-Hawley, Genevieve

2009-01-01

The Civil Rights Project (CRP) is in the midst of an analysis of rapidly growing charter school enrollment, which the authors anticipate releasing next month. Similar to trends described in their 2003 report and in other research on racial isolation in charter schools, they find higher levels of segregation for black students in charter schools…

76 FR 68668 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0100 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... compressive stress during braking at higher deceleration levels outside the regular fatigue load spectrum. [T]he high compressive stress locally exceeds the elasticity limit of the material, leaving a residual tensile stress at release of the heavy braking load. Subsequently, this local residual tensile stress...

[Effects of water conditions and controlled release urea on yield and leaf senescence physiological characteristics in summer maize.

PubMed

Li, Guang Hao; Liu, Ping Ping; Zhao, Bin; Dong, Shu Ting; Liu, Peng; Zhang, Ji Wang; Tian, Cui Xia; He, Zai Ju

2017-02-01

In an soil column experiment with Zhengdan 958 (a summer maize cultivar planted widely in China), treatments of three water levels,severe water stress W 1 which the soil moisture kept (35±5)% of the field capacity, mild water stress W 2 which was (55±5)%,normal water W 3 which was (75±5)%, and four levels of controlled release urea fertilizer (N 0 , N 1 was 150 kg N·hm -2 ,N 2 was 225 kg N·hm -2 and N 3 was 300 kg N·hm -2 ) were included to study the interactive effects of water and controlled release urea on yield and leaf senescence characteristics of summer maize. The results showed that the coupling of water and controlled release urea had significant effects on increasing yield, delaying the senescence and keeping the high efficiency of the functional leaves. Under the same nitrogen condition, yield, LAI, chlorophyll content and the activities of SOD, POD, CAT and soluble protein content in summer maize ear leaf were significantly increased with more water supplying, and the content of MDA decreased significantly. Under the condition of the same moisture, these indicators were also significantly increased with the increasing nitrogen application and MDA content was reduced significantly. However, these indicators (except MDA) of W 3 N 3 , W 3 N 2 and W 2 N 3 treatments were maintained at a higher level and the MDA content was lo-wer compared with other treatments despite the fact that there were no significant difference among these three treatments, which indicated that the interactive effects of water and controlled release urea had an important role in maintaining the function of ear leaf, delaying the leaf senescence, and was beneficial to the photosynthates production and obtaining higher yield of summer maize. Integrating the yield, LAI, chlorophyll content, various protective enzymes activity, MDA and soluble protein content, controlled release urea application rate of 225 kg N·hm -2 was the best treatment as the soil moisture content was (75±5)% of field capacity. Continuous increase in the nitrogen application could not enhance the activities of protective enzymes, oppositely, it could cause the decline of protective enzymes activities and the increase of MDA content rapidly and speed up plants translation to senescence, which was not conductive to the efficient use of nitrogen. We suggested that coupling controlled release urea application rate of 300 kg N·hm -2 with soil moisture content of (55±5)% of field capacity was optimum.

Effects of gonadotropin-releasing hormone agonist/recombinant follicle-stimulating hormone versus gonadotropin-releasing hormone antagonist/recombinant follicle-stimulating hormone on follicular fluid levels of adhesion molecules during in vitro fertilization.

PubMed

Fornaro, Felice; Cobellis, Luigi; Mele, Daniela; Tassou, Argyrò; Badolati, Barbara; Sorrentino, Simona; De Lucia, Domenico; Colacurci, Nicola

2007-01-01

To compare the effects of GnRH-agonist/recombinant rFSH versus GnRH-antagonist/recombinant FSH stimulation on follicular fluid levels of soluble intercellular adhesion molecule (sICAM)-1 and vascular cell adhesion molecule-1 (sVCAM-1) during in vitro fertilization (IVF). Prospective, randomized study. University hospital. Seventy-three women underwent IVF. GnRH-agonist/rFSH or GnRH-antagonist/rFSH administration and collection of follicular fluid from 3 small (11-14 mm in diameter) and 3 large (18-21 mm in diameter) follicles on the day of oocyte retrieval. Follicular fluid levels of sICAM-1 and sVCAM-1 and intrafollicular estradiol and progesterone were also measured. Women who underwent GnRH-agonist/rFSH showed higher concentrations of sICAM-1 in both small and large follicles were compared with patients who received GnRH-antagonist/rFSH treatment; follicular fluid levels of sVCAM-1 were similar between the 2 stimulation protocols. Content of sICAM-1 in small and large follicles positively correlated with the number of follicles of > or =15 mm and the number of oocytes that were retrieved in both study groups. Concentrations of follicular fluid sVCAM-1 and progesterone were higher in large than in small follicles and were correlated positively to each other in both follicular classes. In IVF, GnRH-agonist/rFSH is associated with higher follicular fluid levels of sICAM-1 compared with GnRH-antagonist/rFSH regimen. Intrafollicular sICAM-1 content may predict ovarian response, and sVCAM-1 appears as an indicator of the degree of follicular luteinization.

The possible role of neuropeptide Y after spontaneous subarachnoid hemorrhage.

PubMed

Schebesch, Karl-Michael; Brawanski, Alexander; Kagerbauer, Simone Maria; Martin, Jan; Bele, Sylvia; Herbst, Andreas; Feigl, Günther; Stoerr, Eva-Maria; Lohmeier, Anette; Proescholdt, Martin

2011-08-01

Neuropeptide Y (NPY), a highly potent vasoconstrictive neuropeptide, is widely expressed in the human brain, regulating vessel diameter and cerebral blood flow. Earlier studies focusing on the possible role of NPY in the context of aneurismal subarachnoid hemorrhage (SAH) and vasospasm have produced conflicting results. However, despite extensive research efforts, the pathophysiological mechanisms underlying the SAH-related vasospasm and delayed cerebral ischemia (DCI) have not been clarified. We, therefore, attempted to investigate the role of NPY in SAH-induced vasospasm in a larger, well documented patient population utilizing modern analytical tools. We focused on the release of the potent vasoconstrictor NPY in cerebrospinal fluid (CSF) and blood, and its correlation to vasospasm and stroke in the early clinical stage. Thirty-seven patients with SAH and a control group consisting of 29 patients were included. Eighteen patients developed stroke, 21 patients met the Doppler sonographical criteria for vasospasm. Twenty-nine patients had aneurysms of the anterior circulation and four patients of the posterior circulation. All patients had ventricular drainage inserted and an arterial catheter. Blood and CSF were drawn daily for NPY analysis during a 10-day interval. The levels of NPY in CSF and plasma were significantly higher after SAH than in the control group (p = 0.001). The vasospasm group showed NPY levels in CSF which continuously ranged above the NPY levels of the non-vasospasm group (p = 0.001). Patients with stroke caused by vasospasm had significantly higher levels of NPY (p = 0.001). NPY is released excessively into blood and CSF following SAH. Patients with cerebral infarction caused by vasospasm had significantly higher levels of NPY. Our results indicate a certain role for NPY in the pathophysiology of vasospasm due to SAH and justify further studies in this area of research.

Time-resolved comparative metabolomes for Koji fermentation with brown-, white-, and giant embryo-rice.

PubMed

Lee, Da Eun; Lee, Sunmin; Singh, Digar; Jang, Eun Seok; Shin, Hye Won; Moon, Byoung Seok; Lee, Choong Hwan

2017-09-15

A time-resolved non-targeted metabolomic study towards evaluating the effects of three rice substrate types viz., white rice (WR), giant embryo rice (GER), and brown rice (BR), on Koji fermentation was performed. Notwithstanding the relatively higher proportions of metabolites in unfermented BR (BR 0>WR 0, GER 0), the relative levels of metabolic repertoire in BR Koji were marginally enhanced during 36h fermentation except those for phenolic acids, fatty acids, and vitamins. The WR Koji showed higher levels of lysophospholipids (LysoPC's) and protease-released amino acids (WR 36>GER 36>BR 36). The higher β-glucosidase activity in GER Koji effected the increased levels of sugars and flavonoid aglycons complementing its higher antioxidant activity (GER Koji>BR Koji∼WR Koji). The present study holistically underpins the dynamic metabolomes and enzymatic states during rice Koji fermentation with varying substrate types. The present study finds applications in optimization of commercial Koji production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of chloride, sulfate and natural organic matter (NOM) on the accumulation and release of trace-level inorganic contaminants from corroding iron.

PubMed

Peng, Ching-Yu; Ferguson, John F; Korshin, Gregory V

2013-09-15

This study examined effects of varying levels of anions (chloride and sulfate) and natural organic matter (NOM) on iron release from and accumulation of inorganic contaminants in corrosion scales formed on iron coupons exposed to drinking water. Changes of concentrations of sulfate and chloride were observed to affect iron release and, in lesser extent, the retention of representative inorganic contaminants (vanadium, chromium, nickel, copper, zinc, arsenic, cadmium, lead and uranium); but, effects of NOM were more pronounced. DOC concentration of 1 mg/L caused iron release to increase, with average soluble and total iron concentrations being four and two times, respectively, higher than those in the absence of NOM. In the presence of NOM, the retention of inorganic contaminants by corrosion scales was reduced. This was especially prominent for lead, vanadium, chromium and copper whose retention by the scales decreased from >80% in the absence of NOM to <30% in its presence. Some of the contaminants, notably copper, chromium, zinc and nickel retained on the surface of iron coupons in the presence of DOC largely retained their mobility and were released readily when ambient water chemistry changed. Vanadium, arsenic, cadmium, lead and uranium retained by the scales were largely unsusceptible to changes of NOM and chloride levels. Modeling indicated that the observed effects were associated with the formation of metal-NOM complexes and effects of NOM on the sorption of the inorganic contaminants on solid phases that are typical for iron corrosion in drinking water. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neutrophil contribution to the crescentic glomerulonephritis in SCG/Kj mice.

PubMed

Ishida-Okawara, Akiko; Ito-Ihara, Toshiko; Muso, Eri; Ono, Takahiko; Saiga, Kan; Nemoto, Kyuichi; Suzuki, Kazuo

2004-07-01

Myeloperoxidase-specific anti-neutrophil cytoplasmic auto-antibody (MPO-ANCA) has been a useful diagnostic marker in systemic vasculitis with crescentic glomerulonephritis (CrGN). It is highly suspected that the antigenic enzyme MPO released from activated neutrophils is involved in these lesions. We evaluated the relationship between neutrophil functions including peripheral neutrophil counts and renal lesions in SCG/Kj mice as a model of ANCA-associated CrGN and vasculitis. Peripheral neutrophil counts, the plasma levels of MPO-ANCA and tumour necrosis factor alpha (TNF-alpha) were measured. The capacity of MPO release and superoxide generation were evaluated as neutrophil activity. The renal lesions were estimated by grade of proteinuria, histopathological lesion, such as glomerular neutrophil infiltration and active or chronic renal injury scores with crescent formation. MPO-ANCA and TNF-alpha levels were higher than those of normal mice C57BL/6 even before overt proteinuria; subsequently, peripheral neutrophils increased. In the phase of nephritis with low grade proteinuria, the spontaneous release of MPO from peripheral neutrophils increased, while superoxide generation increased before spontaneous MPO release occurred. In addition, the renal lesion in histological observations was aggravated with ageing and the glomerular neutrophil infiltration was positively correlated with MPO-ANCA levels, as well as with histological indices of nephritis, active renal injury score; in particular, crescent formation was correlated with spontaneous MPO release. In contrast, superoxide generation was negatively correlated with the severity of this lesion during the progression. These findings indicate that neutrophils are activated and contribute to the development of the active crescentic lesion in SCG/Kj mice.

Antidepressants differentially affect striatal amphetamine-stimulated dopamine and serotonin release in rats with high and low novelty-oriented behaviour.

PubMed

O'Leary, Aet; Kõiv, Kadri; Raudkivi, Karita; Harro, Jaanus

2016-11-01

In the studies of depression pathogenesis and antidepressant action, the monoaminergic hypothesis of depression has mainly focused on the serotonergic and noradrenergic mechanisms. However, dopaminergic neurotransmission is also linked to both depressive symptomatology as well as antidepressant effects. We have previously shown that persistent inter-individual differences in the rat behavioural activity in novel environments is associated with differences in the striatal extracellular levels of dopamine and serotonin, depressive-like behaviour and the expression of several depression-related genes. The aim of the current study was to investigate the relative potency of the tricyclic antidepressant imipramine, the selective serotonin re-uptake inhibitor fluoxetine, and the selective noradrenaline re-uptake inhibitor reboxetine (all drugs administered in the dose of 10mg/kg, i.p.) to enhance amphetamine-stimulated dopamine and serotonin release in the striatum using in vivo microdialysis in awake, freely-moving rats, categorized into high explorers (HE) and low explorers (LE) based on their spontaneous novelty-oriented behaviour. The basal extracellular dopamine and serotonin concentration in the striatum did not differ between the LE- and HE-rats. None of the antidepressants alone were able to modify baseline striatal dopamine levels, but the amphetamine-stimulated dopamine release was significantly higher in the HE-rats after acute and chronic imipramine (but not fluoxetine or reboxetine). Acute imipramine and fluoxetine, but not reboxetine, increased both the basal and amphetamine-stimulated levels of serotonin in the striatum. Again, the HE-rats had higher amphetamine-stimulated serotonin release after fluoxetine administration. These findings suggest that rats with depressive-like phenotype are less sensitive to the neurochemical effects of antidepressants in the striatum. These results may have relevance in understanding the neurobiological bases for inter-individual differences in antidepressant treatment response in humans and development of novel medicines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reproductive hormones in menstrual blood.

PubMed

Zhou, J P; Fraser, I S; Caterson, I; Grivas, A; McCarron, G; Norman, T; Tan, K

1989-08-01

Menstrual and peripheral blood samples were collected from 19 regularly cycling women on days 1-3 of the menstrual cycle. Menstrual samples were collected with a soft silicone rubber menstrual cup. Hematocrit, PRL, LH, FSH, estradiol (E2), and progesterone (P4) were measured in all samples. Validation studies were carried out for RIAs of PRL, LH, and FSH in menstrual plasma. The menstrual plasma PRL level was significantly higher than its peripheral blood level on day 1 (63.3 +/- 14.7 and 12.1 +/- 2.9 micrograms/L, respectively; t = 3.331; P less than 0.01), and menstrual PRL was significantly higher on day 1 than on day 2 (t = 3.340; P less than 0.01). There was a strong negative correlation between log menstrual PRL concentration and time of onset of menstruation (r = -0.596; P less than 0.01). Menstrual plasma FSH levels were significantly lower than peripheral levels on each of days 1-3 (day 1:t = 4.787; P less than 0.001), and there was a significant positive correlation between menstrual and peripheral levels (r = 0.607; P less than 0.01). By contrast, menstrual plasma LH was significantly higher than the peripheral level on days 1 and 2 (day 1:t = 3.105; day 2:t = 3.180; P less than 0.01), with no correlation between menstrual and peripheral levels. Menstrual E2 was slightly lower than and significantly positively correlated with peripheral E2 (r = 0.646; P less than 0.01). Menstrual P4 was lower than but showed no correlation with peripheral levels. As expected, the menstrual blood hematocrit was less than 0.20 and highly significantly lower than that of peripheral venous blood. These results suggest that PRL is released in substantial amounts from secretory endometrium into the menstrual flow during the first day of menstrual breakdown. LH may also be released in small amounts from menstrual endometrium, while menstrual FSH, E2, and P4 probably arise entirely from the peripheral circulation.

Comparative pharmacokinetics of two prodrugs of zidovudine in rabbits: enhanced levels of zidovudine in brain tissue.

PubMed

Lupia, R H; Ferencz, N; Lertora, J J; Aggarwal, S K; George, W J; Agrawal, K C

1993-04-01

The pharmacokinetics of two prodrugs of zidovudine (AZT), 1,4-dihydro-1-methyl-3-[(pyridylcarbonyl)oxy] ester and isoleucinyl ester (DPAZT and IAZT, respectively), were investigated in a rabbit model to determine their potential utility as drugs against human immunodeficiency virus. Drugs were administered by intravenous infusion over 5 min at doses equal to 10 mg of AZT per kg of body weight. The levels of the prodrugs and of released AZT in plasma, cerebrospinal fluid (CSF), and brain were determined by high-performance liquid chromatography analysis. DPAZT disappeared rapidly from plasma, whereas IAZT maintained a sustained level in plasma for up to 4 h. The levels in plasma of AZT released from DPAZT were consistently lower than the levels of AZT released from IAZT or AZT itself. At 75 min after infusion of AZT, DPAZT, and IAZT, the CSF plasma AZT ratios were 0.23, 0.30, and 0.25, while the brain/CSF AZT ratios were 0.32, 0.63, and 0.64, respectively. These results indicate that the administration of each of the prodrugs produced a higher concentration of AZT in the brain than did the direct administration of AZT. Both prodrugs therefore may be superior to AZT itself with respect to achieving anti-human immunodeficiency virus concentrations within the central nervous system.

Comparative pharmacokinetics of two prodrugs of zidovudine in rabbits: enhanced levels of zidovudine in brain tissue.

PubMed Central

Lupia, R H; Ferencz, N; Lertora, J J; Aggarwal, S K; George, W J; Agrawal, K C

1993-01-01

The pharmacokinetics of two prodrugs of zidovudine (AZT), 1,4-dihydro-1-methyl-3-[(pyridylcarbonyl)oxy] ester and isoleucinyl ester (DPAZT and IAZT, respectively), were investigated in a rabbit model to determine their potential utility as drugs against human immunodeficiency virus. Drugs were administered by intravenous infusion over 5 min at doses equal to 10 mg of AZT per kg of body weight. The levels of the prodrugs and of released AZT in plasma, cerebrospinal fluid (CSF), and brain were determined by high-performance liquid chromatography analysis. DPAZT disappeared rapidly from plasma, whereas IAZT maintained a sustained level in plasma for up to 4 h. The levels in plasma of AZT released from DPAZT were consistently lower than the levels of AZT released from IAZT or AZT itself. At 75 min after infusion of AZT, DPAZT, and IAZT, the CSF plasma AZT ratios were 0.23, 0.30, and 0.25, while the brain/CSF AZT ratios were 0.32, 0.63, and 0.64, respectively. These results indicate that the administration of each of the prodrugs produced a higher concentration of AZT in the brain than did the direct administration of AZT. Both prodrugs therefore may be superior to AZT itself with respect to achieving anti-human immunodeficiency virus concentrations within the central nervous system. PMID:8494380

Leishmania infantum Induces the Release of sTREM-1 in Visceral Leishmaniasis

PubMed Central

Bomfim, Lays G. S.; Magalhães, Lucas S.; Santos-Filho, Marcello A. A.; Peres, Nalu T. A.; Corrêa, Cristiane B.; Tanajura, Diego M.; Silva, Angela M.; Lipscomb, Michael W.; Borges, Valéria M.; Jesus, Amélia R.; Almeida, Roque P.; de Moura, Tatiana R.

2017-01-01

Visceral leishmaniasis (VL) is a systemic transmissible disease that remains to be a major global health problem. The inflammatory response during VL is characterized by the release of several cytokines and other pro-inflammatory mediators. Triggering Receptor Expressed on Myeloid Cells (TREM) are a group of evolutionarily conserved membrane-bound surface receptors expressed on neutrophils and monocytes. Engagement of TREM-1 directs intracellular signaling events that drive cytokine production, degranulation, and phagocytosis. In certain inflammatory-associated diseases, TREM-1 can also be found as a soluble form (sTREM-1), which can negatively regulate TREM-1 receptor signaling. In these studies, we now find that high levels of circulating sTREM-1 correlate directly with VL disease severity. In particular, high levels of sTREM-1 were observed in non-survivor VL patients. Furthermore, these levels of sTREM-1 positively correlated with liver size and negatively correlated with leukocyte counts and hemoglobin concentration. Moreover, we found that neutrophils exposure in vitro to Leishmania infantum modulates TREM-1, DAP12, and IL-8 gene expression, while also increasing release of sTREM-1. Finally, results revealed that higher sTREM-1 levels are associated with increasing parasite ratio. Taken together, these studies suggest that L. infantum may modulate TREM-1 in neutrophils and high levels of this molecule is associated with severe VL. PMID:29201022

Magnesium substitution in the structure of orthopedic nanoparticles: A comparison between amorphous magnesium phosphates, calcium magnesium phosphates, and hydroxyapatites.

PubMed

Nabiyouni, Maryam; Ren, Yufu; Bhaduri, Sarit B

2015-01-01

As biocompatible materials, magnesium phosphates have received a lot of attention for orthopedic applications. During the last decade multiple studies have shown advantages for magnesium phosphate such as lack of cytotoxicity, biocompatibility, strong mechanical properties, and high biodegradability. The present study investigates the role of Mg(+2) and Ca(+2) ions in the structure of magnesium phosphate and calcium phosphate nanoparticles. To directly compare the effect of Mg(+2) and Ca(+2) ions on structure of nanoparticles and their biological behavior, three groups of nanoparticles including amorphous magnesium phosphates (AMPs) which release Mg(+2), calcium magnesium phosphates (CMPs) which release Mg(+2) and Ca(+2), and hydroxyapatites (HAs) which release Ca(+2) were studied. SEM, TEM, XRD, and FTIR were used to evaluate the morphology, crystallinity, and chemical properties of the particles. AMP particles were homogeneous nanospheres, whereas CMPs were combinations of heterogeneous nanorods and nanospheres, and HAs which contained heterogeneous nanosphere particles. Cell compatibility was monitored in all groups to determine the cytotoxicity effect of particles on studied MC3T3-E1 preosteoblasts. AMPs showed significantly higher attachment rate than the HAs after 1 day and both AMPs and CMPs showed significantly higher proliferation rate when compared to HAs after 7days. Gene expression level of osteoblastic markers ALP, COL I, OCN, OPN, RUNX2 were monitored and they were normalized to GAPDH housekeeping gene. Beta actin expression level was monitored as the second housekeeping gene to confirm the accuracy of results. In general, AMPs and CMPs showed higher expression level of osteoblastic genes after 7 days which can further confirm the stimulating role of Mg(+2) and Ca(+2) ions in increasing the proliferation rate, differentiation, and mineralization of MC3T3-E1 preosteoblasts. Copyright © 2015 Elsevier B.V. All rights reserved.

Drought stress release increased growth rate but did not affect levels of storage carbohydrates in Scots pine trees

NASA Astrophysics Data System (ADS)

Schönbeck, Leonie; Gessler, Arthur; Rigling, Andreas; Schaub, Marcus; Li, Mai-He

2017-04-01

For trees, energy storage in the form of non-structural carbohydrates (NSCs) plays an important role for survival and growth, especially during stress events such as drought. It is hypothesized, that tree individuals that experience long-term drought stress use up larger amounts of NSCs than trees that do not experience drought. Consequently, such drought-induced depletion might lead to a decrease in tree vigor and carbon starvation, a mechanism that is subject of intensive debates in recent literature. Hence, if carbon starvation is occurring during drought, drought stress release should again increase NSC concentrations. A long-term (13 years) irrigation experiment is being conducted in the Pfyn forest, the largest Pinus sylvestris dominated forest in Switzerland, located in the dry inner-Alpine Swiss Rhone valley (average precipitation 600 mm/year, with frequent dry spells). Water addition ( 600 mm/year) is executed every year during the growing season between April and October. Tree height, stem diameter and crown transparency are being measured since 2003. In February, July and October 2015, roots, stem sapwood and needles were harvested from 30 irrigated and 30 control trees and 5 different crown transparency classes. Shoot length, needle morphology, soluble sugars, starch concentrations, needle δ13C and δ15N were measured. Shoot and stem growth were higher in irrigated trees than in control trees. Growth decreased with increasing crown transparency in both treatments. Only in July, needle starch levels were higher in irrigated trees than in control trees but there was no treatment effect for wood and root starch concentrations. Tissue starch and sugar levels were negatively correlated with crown transparency, particularly in the roots (p<0.001), independent of the treatment. Needle δ13C values were higher in the control trees than in the irrigated trees, where needle δ13C values were positively correlated with increasing transparency (p<0.01). Annual shoot growth was positively correlated with starch levels in the roots. The results show that 13 years of irrigation did lead to increased growth but not to increased NSC levels hence not confirming our initial hypothesis. δ13C levels indicate that control trees experienced more drought stress than irrigated trees. However, we found irrigated trees from high crown transparency classes with similar δ13C levels as for non-irrigated control trees. The release of drought stress has benefited the initially vital trees, whereas the initially inferior trees still show signs of drought stress. The results point to a 'winner takes it all principle', where differences between individuals increase when environment conditions improve. This caused the irrigation treatment not being effective in generally releasing drought stress and NSC depletion in all trees. As increasing crown transparency over both treatments is correlated with decreasing growth and decreasing NSC levels, there are still indications that reduced NSC is related to reduced tree vigor under drought.

Comparison of the Levels of Pro-Inflammatory Cytokines Released in the Vastus Lateralis Muscle of Patients with Fibromyalgia and Healthy Controls during Contractions of the Quadriceps Muscle – A Microdialysis Study

PubMed Central

Christidis, Nikolaos; Ghafouri, Bijar; Larsson, Anette; Palstam, Annie; Mannerkorpi, Kaisa; Bileviciute-Ljungar, Indre; Löfgren, Monika; Bjersing, Jan; Kosek, Eva; Gerdle, Björn; Ernberg, Malin

2015-01-01

Objective Fibromyalgia is associated with central hyperexcitability, but it is suggested that peripheral input is important to maintain central hyperexcitability. The primary aim was to investigate the levels of pro-inflammatory cytokines released in the vastus lateralis muscle during repetitive dynamic contractions of the quadriceps muscle in patients with fibromyalgia and healthy controls. Secondarily, to investigate if the levels of pro-inflammatory cytokines were correlated with pain or fatigue during these repetitive dynamic contractions. Material and Methods 32 women with fibromyalgia and 32 healthy women (controls) participated in a 4 hour microdialysis session, to sample IL-1β, IL-6, IL-8, and TNF from the most painful point of the vastus lateralis muscle before, during and after 20 minutes of repeated dynamic contractions. Pain (visual analogue scale; 0–100) and fatigue Borg’s Rating of Perceived Exertion Scale; 6–20) were assessed before and during the entire microdialysis session. Results The repetitive dynamic contractions increased pain in the patients with fibromyalgia (P < .001) and induced fatigue in both groups (P < .001). Perceived fatigue was significantly higher among patients with fibromyalgia than controls (P < .001). The levels of IL-1β did not change during contractions in either group. The levels of TNF did not change during contractions in patients with fibromyalgia, but increased in controls (P < .001) and were significantly higher compared to patients with fibromyalgia (P = .033). The levels of IL-6 and IL-8 increased in both groups alike during and after contractions (P’s < .001). There were no correlations between pain or fatigue and cytokine levels after contractions. Conclusion There were no differences between patients with fibromyalgia and controls in release of pro-inflammatory cytokines, and no correlations between levels of pro-inflammatory cytokines and pain or fatigue. Thus, this study indicates that IL-1β, IL-6, IL-8, and TNF do not seem to play an important role in maintenance of muscle pain in fibromyalgia. PMID:26624891

Climate Change and Tritrophic Interactions: Will Modifications to Greenhouse Gas Emissions Increase the Vulnerability of Herbivorous Insects to Natural Enemies?

PubMed

Boullis, Antoine; Francis, Frederic; Verheggen, François J

2015-04-01

Insects are highly dependent on odor cues released into the environment to locate conspecifics or food sources. This mechanism is particularly important for insect predators that rely on kairomones released by their prey to detect them. In the context of climate change and, more specifically, modifications in the gas composition of the atmosphere, chemical communication-mediating interactions between phytophagous insect pests, their host plants, and their natural enemies is likely to be impacted. Several reports have indicated that modifications to plants caused by elevated carbon dioxide and ozone concentrations might indirectly affect insect herbivores, with community-level modifications to this group potentially having an indirect influence on higher trophic levels. The vulnerability of agricultural insect pests toward their natural enemies under elevated greenhouse gases concentrations has been frequently reported, but conflicting results have been obtained. This literature review shows that the higher levels of carbon dioxide, as predicted for the coming century, do not enhance the abundance or efficiency of natural enemies to locate hosts or prey in most published studies. Increased ozone levels lead to modifications in herbivore-induced volatile organic compounds (VOCs) released by damaged plants, which may impact the attractiveness of these herbivores to the third trophic level. Furthermore, other oxidative gases (such as SO2 and NO2) tend to reduce the abundance of natural enemies. The impact of changes in atmospheric gas emissions on plant-insect and insect-insect chemical communication has been under-documented, despite the significance of these mechanisms in tritrophic interactions. We conclude by suggesting some further prospects on this topic of research yet to be investigated. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hypoxia-inducible factor 1-alpha release after intracoronary versus intramyocardial stem cell therapy in myocardial infarction.

PubMed

Gyöngyösi, Mariann; Hemetsberger, Rayyan; Posa, Aniko; Charwat, Silvia; Pavo, Noemi; Petnehazy, Ors; Petrasi, Zsolt; Pavo, Imre J; Hemetsberger, Hani; Benedek, Imre; Benedek, Teodora; Benedek, Istvan; Kovacs, Istvan; Kaun, Christoph; Maurer, Gerald

2010-04-01

We have investigated the effect of stem cell delivery on the release of hypoxia-inducible factor 1 alpha (HIF-1alpha) in peripheral circulation and myocardium in experimental myocardial ischemia. Closed-chest, reperfused myocardial infarction (MI) was created in domestic pigs. Porcine mesenchymal stem cells (MSCs) were cultured and delivered (9.8 +/- 1.2 x 10(6)) either percutaneously NOGA-guided transendocardially (Group IM) or intracoronary (Group IC) 22 +/- 4 days post-MI. Pigs without MSC delivery served as sham control (Group S). Plasma HIF-1alpha was measured at baseline, immediately post- and at follow-up (FUP; 2 h or 24 h) post-MSC delivery by ELISA kit. Myocardial HIF-1alpha expression of infarcted, normal myocardium, or border zone was determined by Western blot. Plasma level of HIF-1alpha increased immediately post-MI (from 278 +/- 127 to 631 +/- 375 pg/ml, p < 0.05). Cardiac delivery of MSCs elevated the plasma levels of HIF-1alpha significantly (p < 0.05) in groups IC and IM immediately post-MSC delivery, and returned to baseline level at FUP, without difference between the groups IC and IM. The myocardial tissue HIF-1alpha expression in the infarcted area was higher in Group IM than in Group IC or S (1,963 +/- 586 vs. 1,307 +/- 392 vs. 271 +/- 110 activity per square millimeter, respectively, p < 0.05), while the border zone contained similarly lower level of HIF-1alpha, but still significantly higher as compared with Group S. Trend towards increase in myocardial expression of HIF-1alpha was measured in Group IM at 24 h, in contrast to Group IC. In conclusion, both stem cell delivery modes increase the systemic and myocardial level of HIF-1alpha. Intramyocardial delivery of MSC seems to trigger the release of angiogenic HIF-1alpha more effectively than does intracoronary delivery.

The NASA/GEWEX Surface Radiation Budget Release 4 Integrated Product: An Assessment of Improvements in Algorithms and Inputs

NASA Astrophysics Data System (ADS)

Stackhouse, P. W., Jr.; Cox, S. J.; Mikovitz, J. C.; Zhang, T.; Gupta, S. K.

2016-12-01

The NASA/GEWEX Surface Radiation Budget (SRB) project produces, validates and analyzes shortwave and longwave surface and top of atmosphere radiative fluxes for the 1983-near present time period. The current release 3.0/3.1 consists of 1x1 degree radiative fluxes (available at gewex-srb.larc.nasa.gov) and is produced using the International Satellite Cloud Climatology Project (ISCCP) DX product for pixel level radiance and cloud information. This ISCCP DX product is subsampled to 30 km. ISCCP is currently recalibrating and reprocessing their entire data series, to be released as the H product series, with its highest resolution at 10km pixel resolution. The nine-fold increase in number of pixels will allow SRB to produce a higher resolution gridded product (e.g. 0.5 degree or higher), as well as the production of pixel-level fluxes. Other key input improvements include a detailed aerosol history using the Max Planck Institute Aerosol Climatology (MAC), temperature and moisture profiles from HIRS, and new topography, surface type, and snow/ice maps. Here we present results for the improved GEWEX Shortwave and Longwave algorithm (GSW and GLW) with new ISCCP data (for at least 5 years, 2005-2009), various other improved input data sets and incorporation of many additional internal SRB model improvements. We assess the radiative fluxes from new SRB products and contrast these at various resolutions. All these fluxes are compared to both surface measurements and to CERES SYN1Deg and EBAF data products for assessment of the effect of improvements. The SRB data produced will be released as part of the Release 4.0 Integrated Product that shares key input and output quantities with other GEWEX global products providing estimates of the Earth's global water and energy cycle (i.e., ISCCP, SeaFlux, LandFlux, NVAP, etc.).

Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis

PubMed Central

Matthews, J B; Wright, H J; Roberts, A; Cooper, P R; Chapple, I L C

2007-01-01

Some evidence exists that peripheral neutrophils from patients with chronic periodontitis generate higher levels of reactive oxygen species (ROS) after Fcγ-receptor stimulation than those from healthy controls. We hypothesized that peripheral neutrophils in periodontitis also show both hyper-reactivity to plaque organisms and hyperactivity in terms of baseline, unstimulated generation and release of ROS. Peripheral neutrophils from chronic periodontitis patients and age/sex/smoking-matched healthy controls (18 pairs) were assayed for total ROS generation and extracellular ROS release, with and without stimulation (Fcγ-receptor and Fusobacterium nucleatum), using luminol and isoluminol chemiluminescence. Assays were performed with and without priming with Escherichia coli lipopolysaccharide (LPS) and granulocyte–macrophage colony-stimulating factor (GM-CSF). Phox gene expression (p22, p47, p67, gp91) was investigated using reverse transcription–polymerase chain reaction (RT–PCR). Neutrophils from patients produced higher mean levels of ROS in all assays. Total generation and extracellular release of ROS by patients' cells were significantly greater than those from controls after FcγR-stimulation, with (P = 0·023) and without (P ≤ 0·023) priming with GM-CSF. Differences in unstimulated total ROS generation were not significant. By contrast, patients' cells demonstrated greater baseline, extracellular ROS release than those from controls (P = 0·004). This difference was maintained after priming with LPS (P = 0·028) but not GM-CSF (P = 0·217). Phox gene expression was similar in patient and control cells at baseline and stimulation with F. nucleatum (3 h) consistently reduced gp91PHOX transcripts. Our data demonstrate that peripheral neutrophils from periodontitis patients exhibit hyper-reactivity following stimulation (Fcγ-receptor and F. nucleatum) and hyperactivity in terms of excess ROS release in the absence of exogenous stimulation. This hyperactive/-reactive neutrophil phenotype is not associated with elevated phox gene expression. PMID:17223966

A Discussion of SY-101 Crust Gas Retention and Release Mechanisms

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

SD Rassat; PA Gauglitz; SM Caley

1999-02-23

The flammable gas hazard in Hanford waste tanks was made an issue by the behavior of double-shell Tank (DST) 241-SY-101 (SY-101). Shortly after SY-101 was filled in 1980, the waste level began rising periodically, due to the generation and retention of gases within the slurry, and then suddenly dropping as the gases were released. An intensive study of the tank's behavior revealed that these episodic releases posed a safety hazard because the released gas was flammable, and, in some cases, the volume of gas released was sufficient to exceed the lower flammability limit (LFL) in the tank headspace (Allemann etmore » al. 1993). A mixer pump was installed in SY-101 in late 1993 to prevent gases from building up in the settled solids layer, and the large episodic gas releases have since ceased (Allemann et al. 1994; Stewart et al. 1994; Brewster et al. 1995). However, the surface level of SY-101 has been increasing since at least 1995, and in recent months the level growth has shown significant and unexpected acceleration. Based on a number of observations and measurements, including data from the void fraction instrument (VFI), we have concluded that the level growth is caused largely by increased gas retention in the floating crust. In September 1998, the crust contained between about 21 and 43% void based on VFI measurements (Stewart et al. 1998). Accordingly, it is important to understand the dominant mechanisms of gas retention, why the gas retention is increasing, and whether the accelerating level increase will continue, diminish or even reverse. It is expected that the retained gas in the crust is flammable, with hydrogen as a major constituent. This gas inventory would pose a flammable gas hazard if it were to release suddenly. In May 1997, the mechanisms of bubble retention and release from crust material were the subject of a workshop. The evaluation of the crust and potential hazards assumed a more typical void of roughly 15% gas. It could be similar to percolati on in single-shell tank (SST) waste forms. The much higher void being currently observed in SY-101 represents essentially a new crust configuration, and the mechanisms for sudden gas release need to be evaluated. The purpose of this study is to evaluate the situation of gas bubbles in crust based on the previous work on gas bubble retention, migration, and release in simulants and actual waste. We have also conducted some visual observations of bubble migration through simulated crusts to help understand the interaction of the various mechanisms.« less

Iodine-129 in snow and seawater in the Antarctic: level and source.

PubMed

Xing, Shan; Hou, Xiaolin; Aldahan, Ala; Possnert, Göran; Shi, Keliang; Yi, Peng; Zhou, Weijian

2015-06-02

Anthropogenic (129)I has been released to the environment in different ways and chemical species by human nuclear activities since the 1940s. These sources provide ideal tools to trace the dispersion of volatile pollutants in the atmosphere. Snow and seawater samples collected in Bellingshausen, Amundsen, and Ross Seas in Antarctica in 2011 were analyzed for (129)I and (127)I, including organic forms; it was observed that (129)I/(127)I atomic ratios in the Antarctic surface seawater ((6.1-13) × 10(-12)) are about 2 orders of magnitude lower than those in the Antarctic snow ((6.8-9.5) × 10(-10)), but 4-6 times higher than the prenuclear level (1.5 × 10(-12)), indicating a predominantly anthropogenic source of (129)I in the Antarctic environment. The (129)I level in snow in Antarctica is 2-4 orders of magnitude lower than that in the Northern Hemisphere, but is not significantly higher than that observed in other sites in the Southern Hemisphere. This feature indicates that (129)I in Antarctic snow mainly originates from atmospheric nuclear weapons testing from 1945 to 1980; resuspension and re-emission of the fallout (129)I in the Southern Hemisphere maintains the (129)I level in the Antarctic atmosphere. (129)I directly released to the atmosphere and re-emitted marine discharged (129)I from reprocessing plants in Europe might not significantly disperse to Antarctica.

Magnesium sulphate attenuates arterial pressure increase during laparoscopic cholecystectomy.

PubMed

Jee, D; Lee, D; Yun, S; Lee, C

2009-10-01

Magnesium is well known to inhibit catecholamine release and attenuate vasopressin-stimulated vasoconstriction. We investigated whether i.v. magnesium sulphate attenuates the haemodynamic stress responses to pneumoperitoneum by changing neurohumoral responses during laparoscopic cholecystectomy. Thirty-two patients undergoing laparoscopic cholecystectomy were randomly assigned to two groups; a control group was given saline, and a magnesium group received magnesium sulphate 50 mg kg(-1) immediately before pneumoperitoneum. Arterial pressure, heart rate, serum magnesium, plasma renin activity (PRA), and catecholamine, cortisol, and vasopressin levels were measured. Systolic and diastolic arterial pressures were greater in the control group (P<0.05) than in the magnesium group at 10, 20, and 30 min post-pneumoperitoneum. Norepinephrine or epinephrine levels [pg ml(-1), mean (SD)] were higher in the control group than in the magnesium group at 5 [211 (37) vs 138 (18)] or 10 min [59 (19) vs 39 (9)] post-pneumoperitoneum, respectively (P<0.05). In the control group, vasopressin levels [pg ml(-1), mean (SD)] were higher compared with the magnesium group at 5 [64 (18) vs 35 (9), P<0.01] and 10 min [65 (18) vs 47 (11), P<0.05] post-pneumoperitoneum. There were no significant differences between the groups in PRA and cortisol levels. I.V. magnesium sulphate before pneumoperitoneum attenuates arterial pressure increases during laparoscopic cholecystectomy. This attenuation is apparently related to reductions in the release of catecholamine, vasopressin, or both.

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

PubMed Central

Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai

2015-01-01

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. PMID:26416858

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model.

PubMed

Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai; Zhang, Chang-Qing; Rahaman, Mohamed N

2015-12-01

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Study on fluorouracil-chitosan nanoparticle preparation and its antitumor effect.

PubMed

Chen, Gaimin; Gong, Rudong

2016-05-01

To successfully prepare fluorouracil-chitosan nanoparticles, and further analyze its anti-tumor activity mechanism, this paper makes a comprehensive study of existing preparation prescription and makes a detailed analysis of fluorouracil-chitosan in vitro release and pharmacodynamic behavior of animals. Two-step synthesis method is adopted to prepare 5-FU-CS-mPEG prodrugs, and infrared, (1)H NMR and differential thermal analysis are adopted to analyze characterization synthetic products of prepared drugs. To ensure clinical efficacy of prepared drugs, UV spectrophotometry is adopted for determination of drug loading capacity of prepared drugs, transmission electron microscopy is adopted to observe the appearance, dynamic dialysis method is used to observe in vitro drug release of prepared drugs and fitting of various release models is done. Anti-tumor effect is studied via level of animal pharmacodynamics. After the end of the experiment, tumor inhibition rate, spleen index and thymus index of drugs are calculated. Experimental results show that the prepared drugs are qualified in terms of regular shape, dispersion, drug content, etc. Animal pharmacodynamics experiments have shown that concentration level of drug loading capacity of prepared drugs has a direct impact on anti-tumor rate. The higher the concentration, the higher the anti-tumor rate. Results of pathological tissue sections of mice show that the prepared drugs cause varying degrees of damage to receptor cells, resulting in cell necrosis or apoptosis problem. It can thus be concluded that ion gel method is an effective method to prepare drug-loading nanoparticles, with prepared nanoparticles evenly distributed in regular shape which demonstrate good slow-release characteristics in receptor vitro and vivo. At the same time, after completion of drug preparation, relatively strong anti-tumor activity can be generated for the receptor, so this mode of preparation enjoys broad prospects for development.

Impact of treatment on Pb release from full and partially replaced harvested Lead Service Lines (LSLs).

PubMed

Cartier, Clément; Doré, Evelyne; Laroche, Laurent; Nour, Shokoufeh; Edwards, Marc; Prévost, Michèle

2013-02-01

Release of lead from 80% partially replaced service lines was compared to full lead service lines using harvested-stabilized lead pipes and field brass connectors. After more than a year of stabilization, lead release was consistent with field samples. Over the relatively short duration partial replacement of lead pipe by copper pipe (3 months), generated high lead release, attributed to galvanic corrosion, resulting in a final outcome for lead release that was even worse than for a full lead pipe. Increased lead release was especially evident at higher flow rates. Orthophosphate reduced lead release from full lead pipes by 64%. For partially replaced samples with copper, lead concentrations were unchanged by phosphate dosing at moderate flow (103 ± 265 vs 169 ± 349 μg/L) and were increased to very high levels when sampled at high flow rates (1001 ± 1808 vs 257 ± 224 μg/L). The increase lead release was in the form of particulate lead (>90%). In comparison to the condition without treatment, increased sulfate treatment had little impact on lead release from 100%-Pb rigs but reduced lead release from partially replaced lead pipes with copper. Our results also raise questions concerning protocols based on short 30 min stagnation (as those used in Canada) due to their incapacity to consider particulate lead release generated mostly after longer stagnation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury

PubMed Central

Kuster, Diederik W. D.; Cardenas-Ospina, Adriana; Miller, Lawson; Liebetrau, Christoph; Troidl, Christian; Nef, Holger M.; Möllmann, Helge; Hamm, Christian W.; Pieper, Karen S.; Mahaffey, Kenneth W.; Kleiman, Neal S.; Stuyvers, Bruno D.; Marian, Ali J.

2013-01-01

Diagnosis of myocardial infarction (MI) is based on ST-segment elevation on electrocardiographic evaluation and/or elevated plasma cardiac troponin (cTn) levels. However, troponins lack the sensitivity required to detect the onset of MI at its earliest stages. Therefore, to confirm its viability as an ultra-early biomarker of MI, this study investigates the release kinetics of cardiac myosin binding protein-C (cMyBP-C) in a porcine model of MI and in two human cohorts. Release kinetics of cMyBP-C were determined in a porcine model of MI (n = 6, pigs, either sex) by measuring plasma cMyBP-C level serially from 30 min to 14 days after coronary occlusion, with use of a custom-made immunoassay. cMyBP-C plasma levels were increased from baseline (76 ± 68 ng/l) at 3 h (767 ± 211 ng/l) and peaked at 6 h (2,418 ± 780 ng/l) after coronary ligation. Plasma cTnI, cTnT, and myosin light chain-3 levels were all increased 6 h after ligation. In a cohort of patients (n = 12) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy, cMyBP-C was significantly increased from baseline (49 ± 23 ng/l) in a time-dependent manner, peaking at 4 h (560 ± 273 ng/l). In a cohort of patients with non-ST segment elevation MI (n = 176) from the SYNERGY trial, cMyBP-C serum levels were significantly higher (7,615 ± 4,514 ng/l) than those in a control cohort (416 ± 104 ng/l; n = 153). cMyBP-C is released in the blood rapidly after cardiac damage and therefore has the potential to positively mark the onset of MI. PMID:24337456

Platelet granule release is associated with reactive oxygen species generation during platelet storage: A direct link between platelet pro-inflammatory and oxidation states.

PubMed

Ghasemzadeh, Mehran; Hosseini, Ehteramolsadat

2017-08-01

Upon platelet stimulation with agonists, reactive oxygen species (ROS) generation enhances platelet activation and granule release. Whether ROS generation during platelet storage could be directly correlated with the expression of proinflammatory molecules and granule release has been investigated in this study. PRP-platelet concentrates were subjected to flowcytometry analysis to assess the expression of platelet activation marker, P-selectin and CD40L during storage. Intracellular ROS generation was also detected in platelet by flowcytometry using dihydrorhodamine (DHR) 123. Through the dual staining, ROS production was analyzed in either P-selectin positive or negative populations. ROS formation in platelet population was significantly increased by either TRAP (a potent agonist that induces granule release) or PMA (a classic inducer of ROS generation), while the effects of each agonists on P-selectin expression and ROS generation in platelets were comparable. Platelet storage was also associated with the increasing levels of ROS (day 0 vs. day 5; p<0.001) while this increasing pattern was directly correlated with the either expressed P-selectin or CD40L. In addition, in 5 day-stored platelets, samples with ROS levels above 40% showed significantly higher levels of P-selectin and CD40L expression. P-selectin negative population of platelet did not show significant amount of ROS. Our data demonstrated decreased levels of important platelet pro-inflammatory molecules in stored platelets with lower levels of intraplatelet ROS. However, whether quenching of ROS generation during platelet storage can attenuate adverse transfusion reactions raised by platelet pro-inflammatory status is required to be further studied. Copyright © 2017 Elsevier Ltd. All rights reserved.

Significance of the DNA-Histone Complex Level as a Predictor of Major Adverse Cardiovascular Events in Hemodialysis Patients: The Effect of Uremic Toxin on DNA-Histone Complex Formation.

PubMed

Jeong, Jong Cheol; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Ryu, Ji Won; Kim, Dong Ki; Joo, Kwon Wook; Kim, Hyun Kyung

2016-01-01

Neutrophils can release the DNA-histone complex into circulation following exposure to inflammatory stimuli. This prospective study investigated whether the DNA-histone complex and other biomarkers could predict major cardiovascular adverse events (MACEs) in hemodialysis (HD) patients. The levels of circulating DNA-histone complexes, cell-free DNA, interleukin (IL)-6, and neutrophil elastase were measured in 60 HD patients and 28 healthy controls. MACE was assessed at 24 months. Uremic toxin-induced neutrophil released contents were measured in vitro. Compared with controls, HD patients showed higher levels of DNA-histone complexes and IL-6. The DNA-histone complex level was inversely associated with the Kt/V. In a multivariable Cox analysis, the high level of DNA-histone complexes was a significant independent predictor of MACE. The uremic toxins induced DNA-histone complex formation in normal neutrophils in vitro. The DNA-histone complex is a potentially useful marker to predict MACE in HD patients. Uremic toxins induced DNA-histone complex formation in vitro. © 2015 S. Karger AG, Basel.

In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) copolymer

PubMed Central

Gong, Chang Yang; Shi, Shuai; Dong, Peng Wei; Zheng, Xiu Ling; Fu, Shao Zhi; Guo, Gang; Yang, Jing Liang; Wei, Yu Quan; Qian, Zhi Yong

2009-01-01

Background Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy. Results A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 μg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate. Conclusion The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields. PMID:19210779

5 CFR 351.603 - Actions subsequent to release from competitive level.

Code of Federal Regulations, 2010 CFR

2010-01-01

... competitive level. 351.603 Section 351.603 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Release From Competitive Level § 351.603 Actions subsequent to release from competitive level. An employee reached for release from a competitive level shall be offered...

5 CFR 351.603 - Actions subsequent to release from competitive level.

Code of Federal Regulations, 2011 CFR

2011-01-01

... competitive level. 351.603 Section 351.603 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Release From Competitive Level § 351.603 Actions subsequent to release from competitive level. An employee reached for release from a competitive level shall be offered...

Annual Coded Wire Tag Program; Oregon Stock Assessment, 2000 Annual Report.

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

Lewis, Mark; Mallette, Christine; Murray, William

2002-03-01

This annual report is in fulfillment of contract obligations with Bonneville Power Administration which is the funding source for the Oregon Department of Fish and Wildlife's Annual Stock Assessment - Coded Wire Tag Program (ODFW) Project. Tule stock fall chinook were caught primarily in British Columbia and Washington ocean, and Columbia Basin fisheries. Up-river bright stock fall chinook contributed primarily to Alaska and British Columbia ocean commercial, Columbia Basin gillnet and freshwater sport fisheries. Contribution of Rogue stock fall chinook released in the lower Columbia River occurred primarily in Oregon ocean commercial, Columbia Basin gillnet and freshwater sport fisheries. Willamettemore » stock spring chinook contributed primarily to Alaska and British Columbia ocean, and Columbia Basin sport fisheries. Willamette stock spring chinook released by CEDC contributed to similar ocean fisheries, but had much higher catch in Columbia Basin gillnet fisheries than the same stocks released in the Willamette Basin. Up-river stocks of spring chinook contributed almost exclusively to Columbia Basin fisheries. The up-river stocks of Columbia River summer steelhead contributed almost exclusively to the Columbia Basin gillnet and freshwater sport fisheries. Coho ocean fisheries from Washington to California were closed or very limited from 1994 through 1999 (1991 through 1996 broods). This has resulted in a lower percent of catch in Washington, Oregon and California ocean fisheries, and a higher percent of catch in Alaska and British Columbia ocean and Columbia Basin freshwater fisheries. Coho stocks released by ODFW below Bonneville Dam were caught mainly in Oregon, Washington, and British Columbia ocean, Columbia Gillnet and freshwater sport fisheries. Coho stocks released in the Klaskanine River and Youngs Bay area had similar ocean catch distributions, but a much higher percent catch in gillnet fisheries than the other coho releases. Ocean catch distribution of coho stocks released above Bonneville Dam was similar to the other coho groups. However, they had a higher percent catch in gillnet fisheries above Bonneville Dam than coho released below the dam. Survival rates of salmon and steelhead are influenced, not only by factors in the hatchery (disease, density, diet, size and time of release) but also by environmental factors in the river and ocean. These environmental factors are influenced by large scale oceanic and weather patterns such as El Nino. Changes in rearing conditions in the hatchery do impact survival, however, these can be offset by impacts caused by environmental factors. Coho salmon released in the Columbia River generally experience better survival rates when released later in the spring. However, for the 1990 brood year June releases of Columbia River coho had much lower survival than May releases, for all ODFW hatcheries. In general survival of ODFW Columbia River hatchery coho has declined to low levels in recent years. Preliminary results from the evaluation of Visual Implant Elastomer (VIE) tags showed tagging rate and pre-release tag retention improved from the first to second years of tagging. Tagging rate remained identical from 1999 to 2000 while pre-release tag retention dropped to 95%. Returning jack and adult salmon were sampled for CWT and VIE tags in the fall of 2000. Of 606 adults recovered at Sandy Fish Hatchery in 2000, only 1 or 0.2%, retained their VIE tag. Of 36 jacks recovered in 2000, 13 or 36.1% retained their VIE tag.« less

Controlled release of isoproturon, imidacloprid, and cyromazine from alginate-bentonite-activated carbon formulations.

PubMed

Garrido-Herrera, F J; Gonzalez-Pradas, E; Fernandez-Pérez, M

2006-12-27

Different alginate-based systems of isoproturon, imidacloprid, and cyromazine have been investigated in order to obtain controlled release (CR) properties. The basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was modified using different amounts of bentonite and activated carbon. The higher values of encapsulation efficiency corresponded to those formulations prepared with higher percentages of activated carbon, showing higher encapsulation efficiency values for isoproturon and imidacloprid than for cyromazine, which has a higher water solubility. The kinetic experiments of imidacloprid/isoproturon release in water have shown us that the release rate is higher in imidacloprid systems than in those prepared with isoproturon. Moreover, it can be deduced that the use of bentonite and/or activated carbon sorbents reduces the release rate of the isoproturon and imidacloprid in comparison with the technical product and with alginate formulation without modifying agents. The highest decrease in release rate corresponds to the formulations prepared with the highest percentage of activated carbon. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T50, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the pesticide release data, the release of isoproturon and imidacloprid from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents and the permeability of the formulations were the most important factors modulating pesticide release. Finally, a linear correlation of the T50 values and the content of activated carbon in formulations were obtained.

Proton transfer reaction mass spectrometry and time intensity perceptual measurement of flavor release from lipid emulsions using trained human subjects.

PubMed

Frank, Damian; Appelqvist, Ingrid; Piyasiri, Udayasika; Wooster, Tim J; Delahunty, Conor

2011-05-11

The effect of the fat component of liquid emulsions on dynamic "in-nose" flavor release was examined using a panel of trained human subjects (n = 6), proton transfer reaction mass spectrometry (PTR-MS), and time intensity (TI) sensory evaluation. A rigorous breathing and consumption protocol was developed, which synchronized subjects' breathing cycles and also the timing of sample introduction. Temporal changes in volatile release were measured in exhaled nostril breath by real-time PTR-MS. Corresponding changes in the perceived odor intensity could also be simultaneously measured using a push button TI device. The method facilitated accurate examination of both "preswallow" and "postswallow" phases of volatile release and perception. Volatile flavor compounds spanning a range of octanol/water partition coefficient (K(o/w)) values (1-1380) were spiked into water (0% fat) or lipid emulsions with various fat contents (2, 5, 10, and 20% fat). Replicate samples for each fat level were consumed according to the consumption protocol by six subjects. Statistical comparisons were made at the individual level and across the group for the effects of changes in the food matrix, such as fat content, on both pre- and postswallow volatile release. Significant group differences in volatile release parameters including area under the concentration curve (AUC) and maximum concentration (I(max)) were measured according to the lipid content of emulsions and volatile K(o/w). In a second experiment, using single compounds (2-heptanone, ethyl butanoate, and ethyl hexanoate), significant decreases in both in-nose volatile release and corresponding perceived odor intensities were measured with increasing fat addition. Overall, the effect of fat on in vivo release conformed to theory; fat had little effect on compounds with low K(o/w) values, but increased for volatiles with higher lipophilicity. In addition, significant pre- and postswallow differences were observed in AUC and I(max), as a result of changing fat levels. In the absence of fat, more than half of the total amount of volatile was released in the preswallow phase. As the content of fat was increased in the emulsion systems, the ratio of volatile released postswallow increased compared to preswallow. These data may provide new insights into why low-fat and high-fat foods are perceived differently.

Evaluation of sonication treatment and buffer composition on rumen bacteria protein extraction and carboxymethylcellulase activity.

PubMed

Prauchner, Carlos A; Kozloski, Gilberto V; Farenzena, Roberta

2013-05-01

The methodological procedures for studying the fibrolytic activity of rumen bacteria are not clearly established. In this study the efficiency of sonication treatment and buffer composition (i.e. buffer varying in tonicity or pH) on the level of protein extraction from the residue of forage samples incubated in the rumen of a grazing steer and the effect of buffer composition or CaCl₂ concentration on the carboxymethylcellulase (CMCase) activity of the released protein were evaluated. The amount of protein released from the residue of incubation was higher (P < 0.05) for the sonicated material and increased linearly with increasing buffer pH (P < 0.05). The CMCase activity of the released protein was not improved by sonication treatment, whereas it was higher (P < 0.05) for hypotonic than for hypertonic buffer. Both linear and quadratic effects (P < 0.05) of buffer pH on CMCase activity were significant, with CMCase activity being maximal at pH 5.4-6.1. CMCase activity was higher (P < 0.05) at a CaCl₂ concentration of 1 mmol L(-1) compared with lower values. Although sonication treatment increases the amount of protein extracted from rumen bacteria adhered to the residue of incubation, the CMCase activity of the released protein might be measured without sonication treatment and should be carried out with a hypotonic buffer solution that includes a calcium source. When pH is not a treatment factor, the buffer pH should be between 5.5 and 6. © 2012 Society of Chemical Industry.

Significance of air humidity and air velocity for fungal spore release into the air

NASA Astrophysics Data System (ADS)

Pasanen, A.-L.; Pasanen, P.; Jantunen, M. J.; Kalliokoski, P.

Our previous field studies have shown that the presence of molds in buildings does not necessarily mean elevated airborne spore counts. Therefore, we investigated the release of fungal spores from cultures of Aspergillus fumigatus, Penicillium sp. and Cladosporium sp. at different air velocities and air humidities. Spores of A. fumigatus and Penicillium sp. were released from conidiophores already at air velocity of 0.5 ms -1, whereas Cladosporium spores required at least a velocity of 1.0 ms -1. Airborne spore counts of A. fumigatus and Penicillium sp. were usually higher in dry than moist air, being minimal at relative humidities (r.h.) above 70%, while the effect of r.h. on the release of Cladosporium sp. was ambivalent. The geometric mean diameter of released spores increased when the r.h. exceeded a certain level which depends on fungal genus. Thus, spores of all three fungi were hygroscopic but the hygroscopicity of various spores appeared at different r.h.-ranges. This study indicates that spore release is controlled by external factors and depends on fungal genus which can be one reason for considerable variation of airborne spore counts in buildings with mold problems.

Functional hierarchy of two L domains in porcine endogenous retrovirus (PERV) that influence release and infectivity

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

Marcucci, Katherine T.; Kellogg School of Science and Technology, Scripps Research Institute, La Jolla, CA, 92037; Martina, Yuri

2008-06-05

The porcine endogenous retrovirus (PERV) Gag protein contains two late (L) domain motifs, PPPY and P(F/S)AP. Using viral release assays we demonstrate that PPPY is the dominant L domain involved in PERV release. PFAP represents a novel retroviral L domain variant and is defined by abnormal viral assembly phenotypes visualized by electron microscopy and attenuation of early PERV release as measured by viral genomes. PSAP is functionally dominant over PFAP in early PERV release. PSAP virions are 3.5-fold more infectious in vitro by TCID{sub 50} and in vivo results in more RNA positive tissues and higher levels of proviral DNAmore » using our human PERV-A receptor (HuPAR-2) transgenic mouse model [Martina, Y., Marcucci, K.T., Cherqui, S., Szabo, A., Drysdale, T., Srinivisan, U., Wilson, C.A., Patience, C., Salomon, D.R., 2006. Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection. J. Virol. 80 (7), 3135-3146]. The functional hierarchies displayed by PERV L domains, demonstrates that L domain selection in viral evolution exists to promote efficient viral assembly, release and infectivity in the virus-host context.« less

Serotonin release varies with brain tryptophan levels

NASA Technical Reports Server (NTRS)

Schaechter, Judith D.; Wurtman, Richard J.

1990-01-01

This study examines directly the effects on serotonin release of varying brain tryptophan levels within the physiologic range. It also addresses possible interactions between tryptophan availability and the frequency of membrane depolarization in controlling serotonin release. We demonstrate that reducing tryptophan levels in rat hypothalamic slices (by superfusing them with medium supplemented with 100 microM leucine) decreases tissue serotonin levels as well as both the spontaneous and the electrically-evoked serotonin release. Conversely, elevating tissue tryptophan levels (by superfusing slices with medium supplemented with 2 microM tryptophan) increases both the tissue serotonin levels and the serotonin release. Serotonin release was found to be affected independently by the tryptophan availability and the frequency of electrical field-stimulation (1-5 Hz), since increasing both variables produced nearly additive increases in release. These observations demonstrate for the first time that both precursor-dependent elevations and reductions in brain serotonin levels produce proportionate changes in serotonin release, and that the magnitude of the tryptophan effect is unrelated to neuronal firing frequency. The data support the hypothesis that serotonin release is proportionate to intracellular serotonin levels.

Elucidating the Role of Carbon Sources on Abiotic and Biotic Release of Arsenic into Cambodian Aquifers

NASA Astrophysics Data System (ADS)

Koeneke, M.

2017-12-01

Arsenic (As) is a naturally occurring contaminant in Cambodia that has been contaminating well-water sources of millions of people. Commonly, studies look into the biotic factors that cause the arsenic to be released from aquifer sediments to groundwater. However, abiotic release of As from sediments, though little studied, may also play key roles in As contamination of well water. The goal of this research is to quantitatively compare organic-carbon mediated abiotic and biotic release of arsenic from sediments to groundwater. Batch anaerobic incubation experiments under abiotic (sodium azide used to immobilize microbes) and biotic conditions were conducted using Cambodian aquifer sediments, four different organic carbon sources (sodium lactate, sodium citrate, sodium oxalate, and humic acid), and six different carbon concentrations (0, 1, 2.5, 5, 10, 25mg C/L). Dissolved arsenic, iron(Fe), and manganese(Mn) concentrations in the treatments were measured 112 days . In addition, sediment and solution carbon solution was measured . Collectively, these show how different carbon sources, different carbon concentrations, and how abiotic and biotic factors impact the release of arsenic from Cambodian sediments into aquifers. Overall, an introduction of organic carbon to the soil increases the amount of As released from the sediment. The biotic + abiotic and abiotic conditions seemed to play a minimal role in the amount of As released. Dissolved species analysis showed us that 100% of the As was As(V), Our ICP-MS results vary due to the heterogeneity of samples, but when high levels are Fe are seen in solution, we also see high levels of As. We also see higher As concentrations when there is a smaller amount of Mn in solution.

Do ion levels in metal-on-metal hip resurfacing differ from those in metal-on-metal THA at long-term followup?

PubMed

Savarino, Lucia; Cadossi, Matteo; Chiarello, Eugenio; Baldini, Nicola; Giannini, Sandro

2013-09-01

Metal-on-metal hip resurfacing arthroplasty (MOM HR) has become an established alternative to traditional metal-on-metal total hip arthroplasty (MOM THA) for younger, more active patients. Nevertheless, concerns remain regarding wear and corrosion of the bearing surfaces and the resulting systemic metal ion distribution. We therefore asked whether (1) serum ion concentrations in patients with MOM HR at the time of long-term followup were higher than concentrations in a control population with no hip implants; (2) the ion concentrations in patients with MOM HR were different from those in patients with MOM THA; and (3) sex would influence ion levels with regard to implant type. The MOM HR and MOM THA groups consisted of 25 patients (evaluated at a minimum of 96 months) and 16 patients (evaluated at a minimum of 106 months), respectively. Forty-eight healthy donors were recruited for reference values. Cobalt, chromium, nickel, and molybdenum were measured by furnace graphite atomic absorption spectrophotometry. Ion concentrations of cobalt, chromium, and molybdenum in MOM HR were higher than in controls. Chromium and cobalt release were higher in MOM HR than in MOM THA. The sex-based analysis showed the difference was because women had higher concentrations in the MOM HR group than in the MOM THA group, whereas there was no difference between the men in the two groups. In MOM HR, high metal ion release persists for the long term. Consequently, it is important to implement strict biomonitoring for patients who have received these implants. The sustained high levels of chromium in females within the MOM HR group are concerning and merits strong consideration when choosing implants in this patient group.

[Coronary disease extension determines mobilization of endothelial progenitor cells and cytokines after a first myocardial infarction with ST elevation].

PubMed

Jiménez-Navarro, Manuel F; González, Francisco Jesús; Caballero-Borrego, Juan; Marchal, Juan Antonio; Rodríguez-Losada, Noela; Carrillo, Esmeralda; García-Pinilla, José Manuel; Hernández-García, José M; Pérez-González, Rita; Ramírez, Gemma; Aránega, Antonia; de Teresa Galván, Eduardo

2011-12-01

Multivessel coronary disease is still a postinfarction prognostic marker despite new forms of reperfusion, such as primary angioplasty. The aim of this study was to determine the time sequence of various sets of endothelial progenitor cells and angiogenic cytokines (vascular endothelial growth factor, hepatocyte growth factor) according to the degree of extension of the postinfarction coronary disease. We studied the release kinetics in 32 patients admitted for a first myocardial infarction with ST elevation, grouped according to whether they had single or multivessel disease, and 26 controls. The patients had a higher number of endothelial progenitor cells and angiogenic cytokines than the controls at all 3 measurements (admission, day 3, and day 7) of the following subsets: CD34, CD34+CD133+, CD34+KDR+, and CD34+CD133+KDR+CD45+(weak); this latter was higher on day 7. The levels of these cell subsets were all higher in the patients with single-vessel disease and at all 3 measurements. The vascular endothelial growth factor levels were raised during the first week and the hepatocyte growth factor showed an early peak on admission for infarction. No significant differences were seen in the cytokines according to coronary disease extension. Although the release kinetics of different subsets of endothelial progenitor cells in patients with a first acute myocardial infarction with ST elevation was similar in those with single vessel disease to those with multivessel disease, the number of circulating endothelial progenitor cells was greater in the patients with single vessel disease. The vascular endothelial growth factor levels were raised during the first postinfarction week and the hepatocyte growth factor were higher on admission. Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Altering the level of calcium changes the physical properties and digestibility of casein-based emulsion gels.

PubMed

McIntyre, Irene; O Sullivan, Michael; O Riordan, Dolores

2017-04-19

Casein-based emulsion gels prepared with different types of lipid (i.e. milk fat or rapeseed oil) were formulated with high (774 mg Ca per 100 g) or low (357 mg Ca per 100 g) calcium levels by blending acid and rennet casein. Their physicochemical characteristics (i.e. composition, texture, microstructure & water mobility) and in vitro digestibility were compared to conventionally formulated high-calcium (723 mg Ca per 100 g) emulsion gels made from rennet casein with calcium chelating salts (CCS). CCS-free, high-calcium emulsion gels were significantly (p ≤ 0.05) softer than those with low calcium levels (possibly due to their shorter manufacture time and higher pH) and showed the highest rates of disintegration during simulated gastric digestion. Despite having a higher moisture to protein ratio, the high-calcium emulsion gels containing CCS had broadly similar hardness values to those of high-calcium concentration prepared without CCS, but had higher cohesiveness. The high-calcium matrices containing CCS had quite a different microstructure and increased water mobility compared to those made without CCS and showed the slowest rate (p ≤ 0.05) of disintegration in the gastric environment. Gastric resistance was not affected by the type of lipid phase. Conversely, fatty acid release was similar for all emulsion gels prepared from milk fat, however, high-calcium emulsion gels (CCS-free) prepared from rapeseed oil showed higher lipolysis. Results suggest that food matrix physical properties can be modified to alter resistance to gastric degradation which may have consequences for the kinetics of nutrient release and delivery of bioactives sensitive to the gastric environment.

Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China.

PubMed

Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng

2015-12-01

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β2-MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g(-1), p<0.0001), but the mean level of ΣPBDEs in the exposure group was not significantly higher than that in the controls (139.32 vs. 75.74 ng g(-1), p>0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (p<0.05). The mean level of ΣPCBs was negatively correlated with levels of FT3, FT4, monocytes and lymphocytes (p<0.05) and positively correlated with levels of neutrophils, hemoglobin, serum creatinine and β2-MG (p<0.05). Additionally, the mean level of ΣPBDEs was positively correlated with levels of white blood cells, hemoglobin and platelets (p<0.05). Our data suggest that exposure to an e-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released from e-waste may contribute to abnormal changes in body levels of thyroid hormone, hematology and kidney injury markers. Copyright © 2015. Published by Elsevier B.V.

Glucagon effects on 3H-histamine uptake by the isolated guinea-pig heart during anaphylaxis.

PubMed

Rosic, Mirko; Parodi, Oberdan; Jakovljevic, Vladimir; Colic, Maja; Zivkovic, Vladimir; Jokovic, Vuk; Pantovic, Suzana

2014-01-01

We estimated the influence of acute glucagon applications on (3)H-histamine uptake by the isolated guinea-pig heart, during a single (3)H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2 (-), and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change (3)H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, (3)H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of (3)H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9-7.38 × 10(-8) μM) is significantly lower than the histamine level in the absence of glucagon (10.35-10.45 × 10(-8) μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, O2 (-) level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.

In vitro biocorrosion of Co-Cr-Mo implant alloy by macrophage cells.

PubMed

Lin, Hsin-Yi; Bumgardner, Joel D

2004-11-01

We hypothesized that macrophage cells and their released reactive chemical species (RCS) affect Co-Cr-Mo alloy's corrosion properties and that alloy corrosion products change macrophage cell behavior. A custom cell culture corrosion cell was used to evaluate how culture medium, cells, and RCS altered alloy corrosion in 3-day tests. Corrosion was evaluated by measuring total charge transfer at a constant potential using a potentiostat and metal ion release by atomic emission spectroscopy. Viability, proliferation, and NO (nitric oxide) and IL-1beta (interlukin-1beta) release were used to assess cellular response to alloy corrosion products. In the presence of activated cells, total charge transfers and Co ion release were the lowest (p < 0.05). This was attributed to an enhancement of the surface oxide by RCS. Cr and Mo release were not different between cells and activated cells. Low levels of metal ions did not affect cell viability, proliferation, or NO release, though IL-1beta released from the activated cells was higher on the alloy compared to the controls. These data support the hypothesis that macrophage cells and their RCS affect alloy corrosion. Changes in alloy corrosion by cells may be important to the development of host responses to the alloy and its corrosion products.

Observations of the release of non-methane hydrocarbons from fractured shale.

PubMed

Sommariva, Roberto; Blake, Robert S; Cuss, Robert J; Cordell, Rebecca L; Harrington, Jon F; White, Iain R; Monks, Paul S

2014-01-01

The organic content of shale has become of commercial interest as a source of hydrocarbons, owing to the development of hydraulic fracturing ("fracking"). While the main focus is on the extraction of methane, shale also contains significant amounts of non-methane hydrocarbons (NMHCs). We describe the first real-time observations of the release of NMHCs from a fractured shale. Samples from the Bowland-Hodder formation (England) were analyzed under different conditions using mass spectrometry, with the objective of understanding the dynamic process of gas release upon fracturing of the shale. A wide range of NMHCs (alkanes, cycloalkanes, aromatics, and bicyclic hydrocarbons) are released at parts per million or parts per billion level with temperature- and humidity-dependent release rates, which can be rationalized in terms of the physicochemical characteristics of different hydrocarbon classes. Our results indicate that higher energy inputs (i.e., temperatures) significantly increase the amount of NMHCs released from shale, while humidity tends to suppress it; additionally, a large fraction of the gas is released within the first hour after the shale has been fractured. These findings suggest that other hydrocarbons of commercial interest may be extracted from shale and open the possibility to optimize the "fracking" process, improving gas yields and reducing environmental impacts.

The Role of Glutamate Release on Voltage-Dependent Anion Channels (VDAC)-Mediated Apoptosis in an Eleven Vessel Occlusion Model in Rats

PubMed Central

Park, Eunkuk; Lee, Gi-Ja; Choi, Samjin; Choi, Seok-Keun; Chae, Su-Jin; Kang, Sung-Wook; Pak, Youngmi Kim; Park, Hun-Kuk

2010-01-01

Voltage-dependent anion channel (VDAC) is the main protein in mitochondria-mediated apoptosis, and the modulation of VDAC may be induced by the excessive release of extracellular glutamate. This study examined the role of glutamate release on VDAC-mediated apoptosis in an eleven vessel occlusion model in rats. Male Sprague-Dawley rats (250–350 g) were used for the 11 vessel occlusion ischemic model, which were induced for a 10-min transient occlusion. During the ischemic and initial reperfusion episode, the real-time monitoring of the extracellular glutamate concentration was measured using an amperometric microdialysis biosensor and the cerebral blood flow (CBF) was monitored by laser-Doppler flowmetry. To confirm neuronal apoptosis, the brains were removed 72 h after ischemia to detect the neuron-specific nuclear protein and pro-apoptotic proteins (cleaved caspase-3, VDAC, p53 and BAX). The changes in the mitochondrial morphology were measured by atomic force microscopy. A decrease in the % of CBF was observed, and an increase in glutamate release was detected after the onset of ischemia, which continued to increase during the ischemic period. A significantly higher level of glutamate release was observed in the ischemia group. The increased glutamate levels in the ischemia group resulted in the activation of VDAC and pro-apoptotic proteins in the hippocampus with morphological alterations to the mitochondria. This study suggests that an increase in glutamate release promotes VDAC-mediated apoptosis in an 11 vessel occlusion ischemic model. PMID:21203570

Data Stewardship and Long-Term Archive of ICESat Data at the National Snow and Ice Data Center (NSIDC)

NASA Astrophysics Data System (ADS)

Fowler, D. K.; Moses, J. F.; Duerr, R. E.; Webster, D.; Korn, D.

2010-12-01

Data Stewardship is becoming a principal part of a data manager’s work at NSIDC. It is vitally important that our organization makes a commitment to both current and long-term goals of data management and the preservation of our scientific data. Data must be available to researchers not only during active missions, but long after missions end. This includes maintaining accurate documentation, data tools, and a knowledgeable user support staff. NSIDC is preparing for long-term support of the ICESat mission data. Though ICESat has seen its last operational day, the data is still being improved and NSIDC is scheduled to archive the final release, Release 33, starting late in 2010. This release will include the final adjustments to the processing algorithms and will produce the best possible products to date. Along with the higher-level data sets, all supporting documentation will be archived at NSIDC. For the long-term archive, it is imperative that there is sufficient information about how products were prepared in order to convince future researchers that the scientific results are reproducible. The processing algorithms along with the Level 0 and ancillary products used to create the higher-level products will be archived and made available to users. This can enable users to examine production history, to derive revised products and to create their own products. Also contained in the long-term archive will be pre-launch, calibration/validation, and test data. These data are an important part of the provenance which must be preserved. For longevity, we’ll need to archive the data and documentation in formats that will be supported in the years to come.

Evaluation of mixed valent iron oxides as reactive adsorbents for arsenic removal.

PubMed

Mishra, Dhananjay; Farrell, James

2005-12-15

The objective of this research was to determine if Fe(II)-bearing iron oxides generate ferric hydroxides at sufficient rates for removing low levels of arsenic in packed-bed reactors, while at the same time avoiding excessive oxide production that contributes to bed clogging in oxygenated waters. Column experiments were performed to determine the effectiveness of three media for arsenic removal over a range in empty bed contact times, influent arsenic concentrations, dissolved oxygen (DO) levels, and solution pH values. Corrosion rates of the media as a function of the water composition were determined using batch and electrochemical methods. Rates of arsenic removal were first order in the As(V) concentration and were greater for media with higher corrosion rates. As(V) removal increased with increasing DO levels primarily due to faster oxidation of the Fe2+ released by media corrosion. To obtain measurable amounts of arsenic removal in 15 mM NaCl electrolyte solutions containing 50 microg/L As(V), the rate of Fe2+ released by the media needed to be at least 15 times greater than the As(V) feed rate into the column. In waters containing 30 mg/L of silica and 50 microg/L of As(V), measurable amounts of arsenic removal were obtained only for Fe2+ release rates that were at least 200 times greater than the As(V) feed rate. Although all columns showed losses in hydraulic conductivity overthe course of 90 days of operation, the conductivity values remained high, and the losses could be reversed by backwashing the media. The reaction products produced by the media in domestic tap water had average As-to-Fe ratios that were approximately 25% higher than those for a commercially available adsorbent.

Changes in avidity and level of immunoglobulin G antibodies to Mycobacterium tuberculosis in sera of patients undergoing treatment for pulmonary tuberculosis.

PubMed

Arias-Bouda, Lenka M Pereira; Kuijper, Sjoukje; Van der Werf, Anouk; Nguyen, Lan N; Jansen, Henk M; Kolk, Arend H J

2003-07-01

Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens.

Changes in Avidity and Level of Immunoglobulin G Antibodies to Mycobacterium tuberculosis in Sera of Patients Undergoing Treatment for Pulmonary Tuberculosis

PubMed Central

Pereira Arias-Bouda, Lenka M.; Kuijper, Sjoukje; Van Der Werf, Anouk; Nguyen, Lan N.; Jansen, Henk M.; Kolk, Arend H. J.

2003-01-01

Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens. PMID:12853408

Differential BPA levels in sewage wastewater effluents from metro Detroit communities.

PubMed

Santos, Julia M; Putt, David A; Jurban, Michael; Joiakim, Aby; Friedrich, Klaus; Kim, Hyesook

2016-10-01

The endocrine disruptor Bisphenol A (BPA) is ubiquitous in both aquatic and surface sediment environments because it is continuously released into sewage wastewater effluent. The measurement of BPA at wastewater treatment plants is rarely performed even though the United States Environmental Protection Agency (EPA) states that current levels of environmental BPA could be a threat to aquatic organisms. Therefore, the aims of this study were to measure BPA levels in sewage wastewater at different collection points over a 1-year period and to compare the levels of BPA to 8-isoprostane, a human derived fatty acid, found in sewage wastewater. We analyzed pre-treated sewage samples collected from three source points located in different communities in the metropolitan Detroit area provided by the Detroit Water and Sewerage Department. Human urine samples were also used in the study. BPA and 8-isoprostane were measured using ELISA kits from Detroit R&D, Inc. BPA levels from the same collection point oscillated more than 10-fold over 1 year. Also, BPA levels fluctuated differentially at each collection point. Highly fluctuating BPA values were confirmed by LC/MS/MS. The concentration of BPA in sewage wastewater was ~100-fold higher than the concentration of 8-isoprostane, while urinary concentration was ~20-fold higher. Thus, BPA levels discharged into the sewage network vary among communities, and differences are also observed within communities over time. The difference in BPA and 8-isoprostane levels suggest that most of the BPA discharged to sewage wastewater might be derived from industries rather than from human urine. Therefore, the continuous monitoring of BPA could account for a better regulation of BPA release into a sewage network.

Synthesis, maturation and extracellular release of procathepsin D as influenced by cell proliferation or transformation.

PubMed

Isidoro, C; Demoz, M; De Stefanis, D; Baccino, F M; Bonelli, G

1995-12-11

The relationship between cell growth and intra- and extracellular accumulation of cathepsin D (CD), a lysosomal endopeptidase involved in cell protein breakdown, was examined in cultures of normal and transformed BALB/c mouse 3T3 fibroblasts grown at various cell densities. In crowded cultures of normal 3T3 cells (doubling time, Td, 53 hr) intracellular CD activity was 2-fold higher than in sparse, rapidly-growing (Td, 27 hr) cultures. In uncrowded (Td, 18 hr) and crowded (Td, 32 hr) cultures of benzo[a]pyrene-transformed cells intracellular CD levels were one third and two thirds, respectively, of those measured in hyperconfluent 3T3 cultures. Regardless of cell density, SV-40-virus-transformed cells (Td, 12 hr) contained one third of CD levels found in hyperconfluent 3T3 cells. Both transformed cell lines released into the medium a higher proportion of CD, compared with their untransformed counterpart, yet the amount secreted was not sufficient to account for the reduced intracellular level of the enzyme. Serum withdrawal induced a marked increase of both intra- and extracellular levels of CD activity. In both normal and virally or chemically transformed 3T3 cells CD comprised a precursor (52 kDa) and processed mature polypeptides; the latter were mostly represented by a 48-kDa peptide, but a minor part was in a double-chain form (31 and 16 kDa respectively). The proportion of mature enzyme vs. precursor was much higher in confluent, slowly-growing cells than in fast-growing cells, whether normal or transformed. In the latter, conversion of mature 48-kDa peptide into the double-chain form occurred more efficiently.

Targeting hepatic glutaminase activity to ameliorate hyperglycemia.

PubMed

Miller, Russell A; Shi, Yuji; Lu, Wenyun; Pirman, David A; Jatkar, Aditi; Blatnik, Matthew; Wu, Hong; Cárdenas, César; Wan, Min; Foskett, J Kevin; Park, Junyoung O; Zhang, Yiyi; Holland, William L; Rabinowitz, Joshua D; Birnbaum, Morris J

2018-05-01

Glucagon levels increase under homeostatic, fasting conditions, promoting the release of glucose from the liver by accelerating the breakdown of glycogen (also known as glycogenolysis). Glucagon also enhances gluconeogenic flux, including from an increase in the hepatic consumption of amino acids. In type 2 diabetes, dysregulated glucagon signaling contributes to the elevated hepatic glucose output and fasting hyperglycemia that occur in this condition. Yet, the mechanism by which glucagon stimulates gluconeogenesis remains incompletely understood. Contrary to the prevailing belief that glucagon acts primarily on cytoplasmic and nuclear targets, we find glucagon-dependent stimulation of mitochondrial anaplerotic flux from glutamine that increases the contribution of this amino acid to the carbons of glucose generated during gluconeogenesis. This enhanced glucose production is dependent on protein kinase A (PKA) and is associated with glucagon-stimulated calcium release from the endoplasmic reticulum, activation of mitochondrial α-ketoglutarate dehydrogenase, and increased glutaminolysis. Mice with reduced levels of hepatic glutaminase 2 (GLS2), the enzyme that catalyzes the first step in glutamine metabolism, show lower glucagon-stimulated glutamine-to-glucose flux in vivo, and GLS2 knockout results in higher fasting plasma glucagon and glutamine levels with lower fasting blood glucose levels in insulin-resistant conditions. As found in genome-wide association studies (GWAS), human genetic variation in the region of GLS2 is associated with higher fasting plasma glucose; here we show in human cryopreserved primary hepatocytes in vitro that these natural gain-of-function missense mutations in GLS2 result in higher glutaminolysis and glucose production. These data emphasize the importance of gluconeogenesis from glutamine, particularly in pathological states of increased glucagon signaling, while suggesting a possible new therapeutic avenue to treat hyperglycemia.

ER stress-mediated cell damage contributes to the release of EDA+ fibronectin from hepatocytes in nonalcoholic fatty liver disease.

PubMed

He, Lei; Yuan, Fa-Hu; Chen, Ting; Huang, Qiang; Wang, Yu; Liu, Zhi-Guo

2017-04-01

Fibronectin containing extra domain A (EDA + FN), a functional glycoprotein participating in several cellular processes, correlates with chronic liver disease. Herein, we aim to investigate the expression and secretion of EDA + FN from hepatocytes in nonalcoholic fatty liver disease (NAFLD) and the underlying mechanisms. Circulating levels of EDA + FN were determined by ELISA in clinical samples. Western blotting and flow cytometry were performed on L02 and HepG2 cell lines to analyze whether the levels of EDA + FN were associated with endoplasmic reticulum (ER) stress-related cell death. Circulating levels of EDA + FN in NAFLD patients were significantly higher than those in control subjects, and positively related with severity of ultrasonographic steatosis score. In cultured hepatocytes, palmitate up-regulated the expression of EDA + FN in a dose-dependent manner. Conversely, when the cells were pretreated with 4-phenylbutyrate, a specific inhibitor of ER stress, up-regulation of EDA + FN could be abrogated. Moreover, silencing CHOP by shRNA enhanced the release of EDA + FN from hepatocytes following palmitate treatment, which was involved in ER stress-related cell damage. These findings suggest that the up-regulated level of EDA + FN is associated with liver damage in NAFLD, and ER stress-mediated cell damage contributes to the release of EDA + FN from hepatocytes.

Radiocarbon age-offsets in an arctic lake reveal the long-term response of permafrost carbon to climate change

USGS Publications Warehouse

Gaglioti, Benjamin V.; Mann, Daniel H.; Jones, Benjamin M.; Pohlman, John W.; Kunz, Michael L.; Wooller, Matthew J.

2014-01-01

Continued warming of the Arctic may cause permafrost to thaw and speed the decomposition of large stores of soil organic carbon (OC), thereby accentuating global warming. However, it is unclear if recent warming has raised the current rates of permafrost OC release to anomalous levels or to what extent soil carbon release is sensitive to climate forcing. Here we use a time series of radiocarbon age-offsets (14C) between the bulk lake sediment and plant macrofossils deposited in an arctic lake as an archive for soil and permafrost OC release over the last 14,500 years. The lake traps and archives OC imported from the watershed and allows us to test whether prior warming events stimulated old carbon release and heightened age-offsets. Today, the age-offset (2 ka; thousand of calibrated years before A.D. 1950) and the depositional rate of ancient OC from the watershed into the lake are relatively low and similar to those during the Younger Dryas cold interval (occurring 12.9–11.7 ka). In contrast, age-offsets were higher (3.0–5.0 ka) when summer air temperatures were warmer than present during the Holocene Thermal Maximum (11.7–9.0 ka) and Bølling-Allerød periods (14.5–12.9 ka). During these warm times, permafrost thaw contributed to ancient OC depositional rates that were ~10 times greater than today. Although permafrost OC was vulnerable to climate warming in the past, we suggest surface soil organic horizons and peat are presently limiting summer thaw and carbon release. As a result, the temperature threshold to trigger widespread permafrost OC release is higher than during previous warming events.

Development of sustained release antipsychotic tablets using novel polysaccharide isolated from Delonix regia seeds and its pharmacokinetic studies

PubMed Central

Krishnaraj, Kaliaperumal; Chandrasekar, Mulla Joghi Nanjan; Nanjan, Mulla Joghi; Muralidharan, Selvadurai; Manikandan, Duraikannu

2011-01-01

A natural polysaccharide was isolated from the seeds of Delonix regia. The isolated polysaccharide could maintain aqueous equilibrium between the dosage form and the surrounding medium due to its massive competence of water absorption (80.72%) and swelling index (266.7%). The Scanning Electron Micrograph of a polysaccharide exhibits rough surface with pores and crevices, hence, the drug release will be retarded because of the drug particles entrapment in the pores and crevices. Further, the surface tension of polysaccharide is higher than that of water, which may facilitate sustained release of drugs from dosage forms. An antipsychotic drug, quetiapine fumarate has a short half-life of 6 h and administered multiple times per day. Hence the quetiapine fumarate oral sustained release tablets were formulated using this polysaccharide in the concentration of 5–30% to avoid the side effects and increase patient compliance. Dissolution of the developed tablets with 25% polysaccharide content showed a better release profile than the other batches (5–20%) at the end of 12 h. The strong matrix complex has low solubility in water, it does not dissolve rapidly and the drug continues to diffuse through the gel layer at a consistent rate. Drug release from the matrix tablets follows matrix type except F-4 and F-5 which follow first order and Hix.crow type. The bioavailability study was carried out using healthy male New Zealand white rabbits that show the AUC(0–inf) value for developed SR tablets is 1.44 times higher than the reference thus, indicating more efficient and sustained drug delivery capable of maintaining plasma drug levels better. PMID:24115903

Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

PubMed Central

Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

2015-01-01

Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours. Conclusion In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy. PMID:26035710

Do Dietary Habits Influence Trace Elements Release from Fixed Orthodontic Appliances?

PubMed

Wołowiec, Paulina; Chojnacka, Katarzyna; Loster, Bartłomiej W; Mikulewicz, Marcin

2017-12-01

The objective was to investigate the effect of dietary habits on the release of Cr and Ni ions from orthodontic appliances by hair mineral analysis. Patients (N = 47) underwent electronic questionnaire survey to investigate the effect of dietary habits on Cr and Ni levels in hair. The research was carried out on hair sampled at the beginning and in the 4th, 8th, and 12th months of the treatment. The content of Cr and Ni in the collected samples was determined by ICP-OES. The study showed that consumption of acidic dietary products may have the effect on increasing the release of Cr and Ni ions from orthodontic appliances. The release of Cr from orthodontic appliances in patients who consumed fruit juice, coffee, yoghurt, and vinegar was higher. The coefficients enabling comparison of metal ions release pattern at a given sampling points were defined. The comparison of the coefficients yielded the information on the possible magnification of metal ions released as the result of the additional factor consumption of acidic food or drink that intensifies metal ions release. The following magnification pattern was found for chromium: coffee (7.57 times) > yoghurt (2.53) > juice (1.86) > vinegar (1.08), and for nickel: vinegar (2.2) > coffee (1.22) > juice (1.05). Yoghurt did not intensify the release of nickel. Concluding, orthodontic patients should avoid drinking/eating coffee, yoghurt, fruit juices, and vinegar.

The Human Exposure Potential from Propylene Releases to the Environment

PubMed Central

Morgott, David A.

2018-01-01

A detailed literature search was performed to assess the sources, magnitudes and extent of human inhalation exposure to propylene. Exposure evaluations were performed at both the community and occupational levels for those living or working in different environments. The results revealed a multitude of pyrogenic, biogenic and anthropogenic emission sources. Pyrogenic sources, including biomass burning and fossil fuel combustion, appear to be the primary contributors to atmospheric propylene. Despite a very short atmospheric lifetime, measurable levels could be detected in highly remote locations as a result of biogenic release. The indoor/outdoor ratio for propylene has been shown to range from about 2 to 3 in non-smoking homes, which indicates that residential sources may be the largest contributor to the overall exposure for those not occupationally exposed. In homes where smoking takes place, the levels may be up to thirty times higher than non-smoking residences. Atmospheric levels in most rural regions are typically below 2 ppbv, whereas the values in urban levels are much more variable ranging as high as 10 ppbv. Somewhat elevated propylene exposures may also occur in the workplace; especially for firefighters or refinery plant operators who may encounter levels up to about 10 ppmv. PMID:29300328

Nanostructured glass–ceramic coatings for orthopaedic applications

PubMed Central

Wang, Guocheng; Lu, Zufu; Liu, Xuanyong; Zhou, Xiaming; Ding, Chuanxian; Zreiqat, Hala

2011-01-01

Glass–ceramics have attracted much attention in the biomedical field, as they provide great possibilities to manipulate their properties by post-treatments, including strength, degradation rate and coefficient of thermal expansion. In this work, hardystonite (HT; Ca2ZnSi2O7) and sphene (SP; CaTiSiO5) glass–ceramic coatings with nanostructures were prepared by a plasma spray technique using conventional powders. The bonding strength and Vickers hardness for HT and SP coatings are higher than the reported values for plasma-sprayed hydroxyapatite coatings. Both types of coatings release bioactive calcium (Ca) and silicon (Si) ions into the surrounding environment. Mineralization test in cell-free culture medium showed that many mushroom-like Ca and phosphorus compounds formed on the HT coatings after 5 h, suggesting its high acellular mineralization ability. Primary human osteoblasts attach, spread and proliferate well on both types of coatings. Higher proliferation rate was observed on the HT coatings compared with the SP coatings and uncoated Ti-6Al-4V alloy, probably due to the zinc ions released from the HT coatings. Higher expression levels of Runx2, osteopontin and type I collagen were observed on both types of coatings compared with Ti-6Al-4V alloy, possibly due to the Ca and Si released from the coatings. Results of this study point to the potential use of HT and SP coatings for orthopaedic applications. PMID:21292725

2-[(Hydroxymethyl)amino]ethanol in water as a preservative: Study of formaldehyde released by Taguchi's method

NASA Astrophysics Data System (ADS)

Wisessirikul, W.; Loykulnant, S.; Montha, S.; Fhulua, T.; Prapainainar, P.

2016-06-01

This research studied the quantity of free formaldehyde released from 2- [(hydroxymethyl)amino]ethanol (HAE) in DI water and natural rubber latex mixture using high-performance liquid chromatography (HPLC) technique. The quantity of formaldehyde retained in the solution was cross-checked by using titration technique. The investigated factors were the concentration of preservative (HAE), pH, and temperature. Taguchi's method was used to design the experiments. The number of experiments was reduced to 16 experiments from all possible experiments by orthogonal arrays (3 factors and 4 levels in each factor). Minitab program was used as a tool for statistical calculation and for finding the suitable condition for the preservative system. HPLC studies showed that higher temperature and higher concentration of the preservative influence the amount of formaldehyde released. It was found that conditions at which formaldehyde was released in the lowest amount were 1.6%w/v HAE, 4 to 40 °C, and the original pH. Nevertheless, the pH value of NR latex should be more than 10 (the suitable pH value was found to be 13). This preservative can be used to replace current preservative systems and can maintain the quality of latex for long-term storage. Use of the proposed preservative system was also shown to have reduced impact on the toxicity of the environment.

Cost-Minimization Analysis of Open and Endoscopic Carpal Tunnel Release.

PubMed

Zhang, Steven; Vora, Molly; Harris, Alex H S; Baker, Laurence; Curtin, Catherine; Kamal, Robin N

2016-12-07

Carpal tunnel release is the most common upper-limb surgical procedure performed annually in the U.S. There are 2 surgical methods of carpal tunnel release: open or endoscopic. Currently, there is no clear clinical or economic evidence supporting the use of one procedure over the other. We completed a cost-minimization analysis of open and endoscopic carpal tunnel release, testing the null hypothesis that there is no difference between the procedures in terms of cost. We conducted a retrospective review using a private-payer and Medicare Advantage database composed of 16 million patient records from 2007 to 2014. The cohort consisted of records with an ICD-9 (International Classification of Diseases, Ninth Revision) diagnosis of carpal tunnel syndrome and a CPT (Current Procedural Terminology) code for carpal tunnel release. Payer fees were used to define cost. We also assessed other associated costs of care, including those of electrodiagnostic studies and occupational therapy. Bivariate comparisons were performed using the chi-square test and the Student t test. Data showed that 86% of the patients underwent open carpal tunnel release. Reimbursement fees for endoscopic release were significantly higher than for open release. Facility fees were responsible for most of the difference between the procedures in reimbursement: facility fees averaged $1,884 for endoscopic release compared with $1,080 for open release (p < 0.0001). Endoscopic release also demonstrated significantly higher physician fees than open release (an average of $555 compared with $428; p < 0.0001). Occupational therapy fees associated with endoscopic release were less than those associated with open release (an average of $237 per session compared with $272; p = 0.07). The total average annual reimbursement per patient for endoscopic release (facility, surgeon, and occupational therapy fees) was significantly higher than for open release ($2,602 compared with $1,751; p < 0.0001). Our data showed that the total average fees per patient for endoscopic release were significantly higher than those for open release, although there currently is no strong evidence supporting better clinical outcomes of either technique. Value-based health-care models that favor delivering high-quality care and improving patient health, while also minimizing costs, may favor open carpal tunnel release.

Elevated CSF Corticotropin-Releasing Factor Concentrations in Posttraumatic Stress Disorder

PubMed Central

Bremner, J. Douglas; Licinio, Julio; Darnell, Adam; Krystal, John H.; Owens, Michael J.; Southwick, Steven M.; Nemeroff, Charles B.; Charney, Dennis S.

2011-01-01

Objective Corticotropin-releasing factor (CRF) and somatostatin both play important roles in mediating responses to acute and chronic stress. The purpose of this study was to measure CSF concentrations of CRF and somatostatin in patients with chronic combat-related post-traumatic stress disorder (PTSD) and comparison subjects. Method Lumbar punctures for collection of CSF were performed in Vietnam combat veterans with PTSD (N=11) and comparison subjects (N=17). CSF concentrations of CRF and somatostatin were compared between the two groups. Results CSF concentrations of CRF were higher in the PTSD patients than in the comparison subjects (mean=29.0 pg/ml, SD=7.8, versus mean=21.9 pg/ml, SD=6.0). This group difference remained significant after covariance for age. CSF somatostatin concentrations in PTSD patients were higher than those of the comparison subjects (mean=19.9 pg/ml, SD=5.4, versus mean=13.7 pg/ml, SD=8.0). However, covarying for age reduced the level of significance. Conclusions Higher CSF CRF concentrations in patients with PTSD may reflect alterations in stress-related neurotransmitter systems. The higher CSF CRF concentrations may play a role in disturbances of arousal in patients with PTSD. PMID:9137116

Statistics Report on TEQSA Registered Higher Education Providers, 2017

ERIC Educational Resources Information Center

Australian Government Tertiary Education Quality and Standards Agency, 2017

2017-01-01

The "Statistics Report on TEQSA Registered Higher Education Providers" ("the Statistics Report") is the fourth release of selected higher education sector data held by is the fourth release of selected higher education sector data held by the Australian Government Tertiary Education Quality and Standards Agency (TEQSA) for its…

Estimating the timing of quantal releases during end-plate currents at the frog neuromuscular junction.

PubMed Central

Van der Kloot, W

1988-01-01

1. Following motor nerve stimulation there is a period of greatly enhanced quantal release, called the early release period or ERP (Barrett & Stevens, 1972b). Until now, measurements of the probability of quantal releases at different points in the ERP have come from experiments in which quantal output was greatly reduced, so that the time of release of individual quanta could be detected or so that the latency to the release of the first quantum could be measured. 2. A method has been developed to estimate the timing of quantal release during the ERP that can be used at much higher levels of quantal output. The assumption is made that each quantal release generates an end-plate current (EPC) that rises instantaneously and then decays exponentially. The peak amplitude of the quantal currents and the time constant for their decay are measured from miniature end-plate currents (MEPCs). Then a number of EPCs are averaged, and the times of release of the individual quanta during the ERP estimated by a simple mathematical method for deconvolution derived by Cohen, Van der Kloot & Attwell (1981). 3. The deconvolution method was tested using data from preparations in high-Mg2+ low-Ca2+ solution. One test was to reconstitute the averaged EPCs from the estimated times of quantal release and the quantal currents, by using Fourier convolution. The reconstructions fit well to the originals. 4. Reconstructions were also made from averaged MEPCs which do not rise instantaneously and the estimated times of quantal release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2466987

In vitro fluoride release from a different kind of conventional and resin modified glass-ionomer cements.

PubMed

Selimović-Dragaš, Mediha; Hasić-Branković, Lajla; Korać, Fehim; Đapo, Nermin; Huseinbegović, Amina; Kobašlija, Sedin; Lekić, Meliha; Hatibović-Kofman, Šahza

2013-08-01

Fluoride release is important characteristic of glass-ionomer cements. Quantity of fluoride ions released from the glass-ionomer cements has major importance in definition of their biological activity. The objectives of this study were to define the quantity of fluoride ions released from the experimental glass-ionomer cements and to define the effect of fluoride ions released from the experimental glass-ionomer cements on their cytotoxicity. Concentrations of the fluoride ions released in the evaluated glass-ionomer cements were measured indirectly, by the fluoride-selective WTW, F500 electrode potential, combined with reference R503/D electrode. Statistical analyses of F-ion concentrations released by all glass-ionomers evaluated at two time points, after 8 and after 24 hours, show statistically higher fluoride releases from RMGICs: Vitrebond, Fuji II LC and Fuji Plus, when compared to conventional glass-ionomer cements: Fuji Triage, Fuji IX GP Fast and Ketac Silver, both after 8 and after 24 hours. Correlation coefficient between concentrations of fluoride ion released by evaluated glass-ionomer cements and cytotoxic response of UMR-106 osteoblast cell-line are relatively high, but do not reach levels of biological significance. Correlation between concentrations of fluoride ion released and cytotoxic response of NIH3T3 mouse fibroblast cell line after 8 hours is high, positive and statistically significant for conventional GICs, Fuji Triage and Fuji IX GP Fast, and RMGIC, Fuji II LC. Statistically significant Correlation coefficient between concentrations of fluoride ion released and cytotoxic response of NIH3T3 cell line after 24 hours is defined for RMGIC Fuji II LC only.

Coupling tree rings and eddy covariance to estimate long-term above and belowground carbon storage at the stand level

NASA Astrophysics Data System (ADS)

Dye, A.; Alexander, M. R.; Bishop, D.; Pederson, N.; Hessl, A. E.

2016-12-01

Storage of carbon in terrestrial plants and soils directly reduces atmospheric carbon concentration, and it is thereby imperative to improve our understanding of where carbon is being stored and released in an ecosystem and how storages and releases are changing over time. At data-rich sites, coupling alternative measurements of carbon flux can improve this understanding. Here, we present a methodology to inversely model stand-level net storage and release of above- and belowground carbon over a period of 1-2 decades using co-located tree-ring plots and eddy covariance towers at three eastern U.S. forests. We reconstructed annual aboveground wood production (aNPP) from tree rings collected near eddy covariance towers. We compared our aNPP reconstructions with annual tower NEE to address whether interannual variations are correlated. Despite modest correlation, we observed magnitude differences between both records that vary annually. We interpret these differences as indicative of changes in belowground carbon storage, i.e. an aNPP:NEE ratio > 1 indicates a net release of belowground carbon and a ratio < 1 a net storage of belowground carbon. For this interpretation, we assume the following: a) carbon not directed to above or belowground pools is insignificant, b) carbon not stored above ground is stored below ground, and c) mature trees do not add to a storage pool at a higher level every year. While the offset between biometric aNPP and tower NEE could partially be attributed to the diversion of assimilated carbon to nonstructural carbohydrates instead of growth, we argue that this becomes a less important factor over longer time scales in a mature tree. Our approach does not quantify belowground NPP or allocation, but we present a method for estimating belowground carbon storage and release at the stand level, an otherwise difficult task at this scale due to heterogeneity across the stand.

Interrupted breeding in a songbird migrant triggers development of nocturnal locomotor activity.

PubMed

Mukhin, Andrey; Kobylkov, Dmitry; Kishkinev, Dmitry; Grinkevich, Vitaly

2018-04-03

Long-distance avian migrants, e.g. Eurasian reed warblers (Acrocephalus scirpaceus), can precisely schedule events of their annual cycle. However, the proximate mechanisms controlling annual cycle and their interplay with environmental factors are poorly understood. We artificially interrupted breeding in reed warblers by bringing them into captivity and recording birds' locomotor activity for 5-7 days. Over this time, most of the captive birds gradually developed nocturnal locomotor activity not observed in breeding birds. When the birds were later released and radio-tracked, the individuals with highly developed caged activity performed nocturnal flights. We also found that reed warblers kept indoors without access to local cues developed a higher level of nocturnal activity compared to the birds kept outdoors with an access to the familiar environment. Also, birds translocated from a distant site (21 km) had a higher motivation to fly at night-time after release compared to the birds captured within 1 km of a study site. Our study suggests that an interrupted breeding triggers development of nocturnal locomotor activity in cages, and the level of activity is correlated with motivation to perform nocturnal flights in the wild, which can be restrained by familiar environment.

Physicochemical and mechanical properties of freeze cast hydroxyapatite-gelatin scaffolds with dexamethasone loaded PLGA microspheres for hard tissue engineering applications.

PubMed

Ghorbani, Farnaz; Nojehdehian, Hanieh; Zamanian, Ali

2016-12-01

Hydroxyapatite (HA)-gelatin scaffolds incorporated with dexamethasone-loaded polylactic-co-glycolic acid (PLGA) microspheres were synthesized by freeze casting technique. Scanning electron microscopy (SEM) micrographs demonstrated a unidirectional microstructure and a decrease in the pore size as a function of temperature gradient. Higher amounts of HA resulted in a decrease in the pore size. According to the results, at lower cooling rates, the formation of a lamellar structure decreased the mechanical strength, but at the same time, enhanced the swelling ratio, biodegradation rate and drug release level. On the other hand, higher weight ratios of HA increased the compressive strength, and reduced the swelling ratio, biodegradation rate and drug release level. The results obtained by furrier transform infrared spectroscopy (FTIR) and bioactivity analysis illustrated that the interactions of the materials support the apatite formation in the simulated body fluid (SBF) solution. Based on the obtained results, the synthesized composite scaffolds have the necessary mechanical and physicochemical features to support the regeneration of defects and to maintain their stability during the neo-tissue formation. Copyright © 2016 Elsevier B.V. All rights reserved.

In Vivo Release of Vancomycin from Calcium Phosphate Cement.

PubMed

Uchida, Kentaro; Sugo, Ken; Nakajima, Takehiko; Nakawaki, Mitsufumi; Takano, Shotaro; Nagura, Naoshige; Takaso, Masashi; Urabe, Ken

2018-01-01

Calcium phosphate cement (CPC) has good release efficiency and has therefore been used as a drug delivery system for postoperative infection. The release profile of CPC has mainly been evaluated by in vitro studies, which are carried out by immersing test specimens in a relatively large amount of solvent. However, it remains unclear whether antibiotic-impregnated CPC has sufficient clinical effects and release in vivo . We examined the in vivo release profile of CPC impregnated with vancomycin (VCM) and compared this with that of polymethylmethacrylate (PMMA) cement. To evaluate the release profile in vitro , the test specimens were immersed in 10 mL sterile phosphate-buffered saline per gram of test specimen and incubated at 37°C for 56 days in triplicate. For in vivo experiments, the test specimens were implanted between the fascia and muscle of the femur of rats. Residual VCM was extracted from the removed test specimens to determine the amount of VCM released into rat tissues. CPC released more VCM over a longer duration than PMMA in vitro . Released levels of VCM from CPC/VCM in vivo were 3.4-fold, 5.0-fold, and 8.6-fold greater on days 1, 7, and 28, respectively, than those released on the corresponding days from PMMA/VCM and were drastically greater on day 56 due to inefficient release from PMMA/VCM. The amount of VCM released from CPC and PMMA was much higher than the minimum inhibitory concentration (1.56  μ g) and lower than the detection limit, respectively. Our findings suggest that CPC is a suitable material for releasing antibiotics for local action against established postoperative infection.

High-purity capture and release of circulating exosomes using an exosome-specific dual-patterned immunofiltration (ExoDIF) device.

PubMed

Kang, Yoon-Tae; Kim, Young Jun; Bu, Jiyoon; Cho, Young-Ho; Han, Sae-Won; Moon, Byung-In

2017-09-21

We present a microfluidic device for the capture and release of circulating exosomes from human blood. The exosome-specific dual-patterned immunofiltration (ExoDIF) device is composed of two distinct immuno-patterned layers, and is capable of enhancing the chance of binding between the antibody and exosomes by generating mechanical whirling, thus achieving high-throughput exosome isolation with high specificity. Moreover, follow-up recovery after the immuno-affinity based isolation, via cleavage of a linker, enables further downstream analysis. We verified the performance of the present device using MCF-7 secreted exosomes and found that both the concentration and proportion of exosome-sized vesicles were higher than in the samples obtained from the conventional exosome isolation kit. We then isolated exosomes from the human blood samples with our device to compare the exosome level between cancer patients and healthy donors. Cancer patients show a significantly higher exosome level with higher selectivity when validating the exosome-sized vesicles using both electron microscopy and nanoparticle tracking analysis. The captured exosomes from cancer patients also express abundant cancer-associated antigens, the epithelial cell adhesion molecule (EpCAM) on their surface. Our simple and rapid exosome recovery technique has huge potential to elucidate the function of exosomes in cancer patients and can thus be applied for various exosome-based cancer research studies.

Anti-inflammatory and antioxidant activity of polyphenolic extracts from Lactuca sativa (var. Maravilla de Verano) under different farming methods.

PubMed

Adesso, Simona; Pepe, Giacomo; Sommella, Eduardo; Manfra, Michele; Scopa, Antonio; Sofo, Adriano; Tenore, Gian Carlo; Russo, Mariateresa; Di Gaudio, Francesca; Autore, Giuseppina; Campiglia, Pietro; Marzocco, Stefania

2016-09-01

Besides their nutritional value, vegetables are a source of health-promoting compounds, such as polyphenols, and their content can be influenced by the particular farming method. In this study polyphenolic extracts from Lactuca sativa (var. Maravilla de verano) plants cultivated with different farming methods were chemically characterised and tested in vitro and ex vivo inflammation models. The tested extacts (250-2.5 µg mL(-1) ) were able to reduce both the inflammatory and oxidative stress in LPS-stimulated J774A.1 murine monocyte macrophage cells, by lowering the release of nitric oxide (NO) and reactive oxygen species (ROS) and promoting nuclear translocation of nuclear factor (erythroid-derived 2)-like 2; (Nrf2) and nuclear factor-κB (NF-κB). In this regard, quantitative profiles revealed different amounts of polyphenols, in particular quercetin levels were higher in plants under mineral fertilised treatment. Those extract showed an enhanced anti-inflammatory and antioxidant activity. Our data showed the anti-inflammatory and antioxidant potential of Maravilla de Verano polyphenolic extracts. The effect of farming methods on polyphenolic levels was highlighted. The higher reduction of inflammatory mediators release in extracts from plants cultivated under mineral fertilisation treatment was correlated to the higher amount of quercetin. These results can be useful for both nutraceutical or agronomic purposes. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Assessment of tar pollution on the United Arab emirates beaches

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

Abu-Hilal, A.H.; Khordagui, H.K.

1993-01-01

In light of the inadequate information concerning stranded tar on the southwest beaches of the Arabian Gulf and the Gulf of Oman, particularly following the massive oil releases during the Gulf War, the present investigation was designed to provide reference-integrated information on the nature, location, and levels of stranded tar balls on the beaches of the United Arab Emirates (UAE). The recorded levels appeared to be higher than expected or previously reported. The tar distribution pattern, in addition to the degree of weathering, indicates that the massive oil release during the Gulf War did not reach the UAE shorelines. Themore » highest reported levels of stranded tar ever recorded in the Arabian Gulf at Jabal Dhannah apparently originated from oil spills and tankers' ballast water at the main oil terminal at the Al-Ruwaiss oil refinery some 10 km to the east. The surprising, relatively high levels of stranded tar on the beaches of the Gulf of Oman were solely attributed to the heavy navigation traffic close to the shorelines. 19 refs., 2 figs., 3 tabs.« less

Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L.

PubMed

Lee, You-Jeong; Kim, Chung-Hoon; Kwack, Jae-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

2014-11-01

To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 µg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH.

Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L

PubMed Central

Lee, You-Jeong; Kwack, Jae-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

2014-01-01

Objective To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. Methods This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 µg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). Results The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). Conclusion TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH. PMID:25469340

Pavlovian autoshaping procedures increase plasma corticosterone levels in rats.

PubMed

Tomie, Arthur; Silberman, Yuval; Williams, Kayon; Pohorecky, Larissa A

2002-06-01

Pavlovian autoshaping conditioned responses (CRs) are complex sequences of conditioned stimulus (CS)-directed skeletal-motor responses that are elicited by CS objects predictive of food unconditioned stimulus (US). Autoshaping CRs are observed under conditions known to be conducive to elevations in plasma corticosterone levels, as, for example, in response to the eating of food as well as in response to signals predictive of food. Two experiments investigated the relationships between Pavlovian autoshaping procedures, the performance of Pavlovian autoshaping CRs, and plasma corticosterone levels in male Long-Evans rats. In Experiment 1, rats in the CS-US paired group (n=30) were given 20 daily sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of the food US. Tail blood samples obtained after the 20th autoshaping session revealed higher plasma corticosterone levels in the CS-US paired group than in the CS-US random control group (n=10). In Experiment 2, rats (n=35) were assessed for basal plasma corticosterone levels 2 weeks prior to autoshaping training. Plasma samples obtained immediately following the first autoshaping session, and prior to the acquisition of lever-press autoshaping CR performance, revealed higher plasma corticosterone levels in the CS-US paired group (n=24) relative to basal levels. This effect was not observed in the CS-US random control group (n=11). Data suggest that corticosterone release is a physiological endocrine Pavlovian CR induced by lever CS-food US pairings during Pavlovian autoshaping procedures, rather than a by-product of autoshaping CR performance. Implications of the link between autoshaping procedures and corticosterone release are discussed.

β2-Adrenergic stimulation enhances Ca2+ release and contractile properties of skeletal muscles, and counteracts exercise-induced reductions in Na+–K+-ATPase Vmax in trained men

PubMed Central

Hostrup, M; Kalsen, A; Ørtenblad, N; Juel, C; Mørch, K; Rzeppa, S; Karlsson, S; Backer, V; Bangsbo, J

2014-01-01

The aim of the present study was to examine the effect of β2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca2+ release and uptake, and Na+–K+-ATPase activity before and after fatiguing exercise in trained men. The study consisted of two experiments (EXP1, n = 10 males, EXP2, n = 20 males), where β2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction (MVC) of m. quadriceps was measured, followed by exercise to fatigue at 120% of maximal oxygen uptake (). A muscle biopsy was taken after MVC (non-fatigue) and at time of fatigue. In EXP2, contractile properties of m. quadriceps were measured with electrical stimulations before (non-fatigue) and after two fatiguing 45 s sprints. Non-fatigued MVCs were 6 ± 3 and 6 ± 2% higher (P < 0.05) with terbutaline than placebo in EXP1 and EXP2, respectively. Furthermore, peak twitch force was 11 ± 7% higher (P < 0.01) with terbutaline than placebo at non-fatigue. After sprints, MVC declined (P < 0.05) to the same levels with terbutaline as placebo, whereas peak twitch force was lower (P < 0.05) and half-relaxation time was prolonged (P < 0.05) with terbutaline. Rates of SR Ca2+ release and uptake at 400 nm [Ca2+] were 15 ± 5 and 14 ± 5% (P < 0.05) higher, respectively, with terbutaline than placebo at non-fatigue, but declined (P < 0.05) to similar levels at time of fatigue. Na+–K+-ATPase activity was unaffected by terbutaline compared with placebo at non-fatigue, but terbutaline counteracted exercise-induced reductions in maximum rate of activity (Vmax) at time of fatigue. In conclusion, increased contractile force induced by β2-adrenergic stimulation is associated with enhanced rate of Ca2+ release in humans. While β2-adrenergic stimulation elicits positive inotropic and lusitropic effects on non-fatigued m. quadriceps, these effects are blunted when muscles fatigue. PMID:25344552

The Involvement of Danger-Associated Molecular Patterns in the Development of Immunoparalysis in Cardiac Arrest Patients.

PubMed

Timmermans, Kim; Kox, Matthijs; Gerretsen, Jelle; Peters, Esther; Scheffer, Gert Jan; van der Hoeven, Johannes G; Pickkers, Peter; Hoedemaekers, Cornelia W

2015-11-01

After cardiac arrest, patients are highly vulnerable toward infections, possibly due to a suppressed state of the immune system called "immunoparalysis." We investigated if immunoparalysis develops following cardiac arrest and whether the release of danger-associated molecular patterns could be involved. Observational study. ICU of a university medical center. Fourteen post-cardiac arrest patients treated with mild therapeutic hypothermia for 24 hours and 11 control subjects. Plasma cytokines showed highest levels within 24 hours after cardiac arrest and decreased during the next 2 days. By contrast, ex vivo production of cytokines interleukin-6, tumor necrosis factor-α, and interleukin-10 by lipopolysaccharide-stimulated leukocytes was severely impaired compared with control subjects, with most profound effects observed at day 0, and only partially recovering afterward. Compared with incubation at 37°C, incubation at 32°C resulted in higher interleukin-6 and lower interleukin-10 production by lipopolysaccharide-stimulated leukocytes of control subjects, but not of patients. Plasma nuclear DNA, used as a marker for general danger-associated molecular pattern release, and the specific danger-associated molecular patterns (EN-RAGE and heat shock protein 70) were substantially higher in patients at days 0 and 1 compared with control subjects. Furthermore, plasma heat shock protein 70 levels were negatively correlated with ex vivo production of inflammatory mediators interleukin-6, tumor necrosis factor-α, and interleukin-10. Extracellular newly identified receptor for advanced glycation end products-binding protein levels only showed a significant negative correlation with ex vivo production of interleukin-6 and tumor necrosis factor-α and a borderline significant inverse correlation with interleukin-10. No significant correlations were observed between plasma nuclear DNA levels and ex vivo cytokine production. None. Release of danger-associated molecular patterns during the first days after cardiac arrest is associated with the development of immunoparalysis. This could explain the increased susceptibility toward infections in cardiac arrest patients.

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

Stone, J.P.; Holtsman, S.; Shellabarger, C.J.

Pellets containing 5 mg (/sup 3/H) diethylstilbestrol (DES) and 15 mg cholesterol were implanted S.C. in 84-day-old female Sprague-Dawley (S-D) and ACl rats. DES was released from the implanted pellets exponentially, and the release was not significantly different in S-D rats than in ACl rats. No mammary tumors developed in any treated or untreated S-D rats. In contrast, 90% of the DES-treated ACl rats developed mammary adenocarcinomas. A significant increase in the weight of the pituitary was noted in DES-treated ACl rats. The pituitarities of the treated ACl rats were 2 to 7 times as heavy as were controls, andmore » plasma prolactin levels were 10 to 40 times higher than in controls. In contrast, the pituitaries of treated S-D rats did not significantly increase in weight, and plasma prolactin levels were only 3 to 5 times higher than controls. The uteri of treated S-D rats were significantly heavier than those of control rats and contained large amounts of fluid. This effect was not seen in ACl rats. Although the release of DES from the implanted pellet was essentially the same in ACl and S-D rats, three distinctive strain differences in response to DES were noted: mammary adenocarcinomas were found only in treated ACl rats; pituitary prolactin-cell adenomas and associated elevated plasma prolactins levels were seen only in treated ACl rats; and pyometritis was induced only in treated S-D rats. Mammary adenocarcinomas and prolactin-cell adenoma responses in the treated ACl rats appear to be correlated with the increasing levels of plasma prolactin. This study demonstrates that the prolonged estrogen treatment of ACl and S-D female rats produces distinctly different mammary and pituitary neoplastic responses. This disparity in neoplastic responses appears to be reflected in the difference of degree to which the hypophysical prolactin cells are stimulated to grow and secrete hormone.« less

Prenatal glucocorticoid programming of brain corticosteroid receptors and corticotrophin-releasing hormone: possible implications for behaviour.

PubMed

Welberg, L A; Seckl, J R; Holmes, M C

2001-01-01

Glucocorticoids may underlie the association between low birth weight and adult disorders such as hypertension, type 2 diabetes and affective dysfunction. We investigated the behavioural and molecular consequences of two paradigms of prenatal dexamethasone administration in rats. Rats received dexamethasone (100 microg/kg per day) throughout pregnancy (DEX1-3), in the last third of pregnancy only (DEX3) or vehicle. Both dexamethasone treatments reduced birth weight, only DEX1-3 offspring had reduced body weight in adulthood. In adult offspring, both prenatal dexamethasone paradigms reduced exploratory behaviour in an open field. In contrast, only DEX3 reduced exploration in an elevated plus-maze and impaired behavioural responses and learning in a forced-swim test. This behavioural inhibition may reflect increased baseline corticotrophin-releasing hormone mRNA levels (30% higher) in the central nucleus of the amygdala in both dexamethasone-exposed groups. Adult DEX3 offspring also showed increased corticotrophin-releasing hormone mRNA with unaltered glucocorticoid receptor mRNA in the hypothalamic paraventricular nucleus and reduced hippocampal glucocorticoid- and mineralocorticoid receptor mRNA expression, suggesting reduced hippocampal sensitivity to glucocorticoid suppression of the stress axis. In contrast, DEX1-3 rats had no changes in hippocampal corticosteroid receptors, but showed increased mRNA levels for both receptors in the basolateral nucleus of the amygdala. From this data we suggest that prenatal glucocorticoid exposure programs behavioural inhibition perhaps via increased amygdalar corticotrophin-releasing hormone levels, while DEX3 also impairs coping and learning in aversive situations, possibly via altered hippocampal corticosteroid receptor levels. Overexposure to glucocorticoids, especially late in gestation, may explain the link between reduced early growth and adult affective dysfunction.

Development of a slow non-viral DNA release system from PDLLA scaffolds fabricated using a supercritical CO2 technique.

PubMed

Heyde, Mieke; Partridge, Kris A; Howdle, Steven M; Oreffo, Richard O C; Garnett, Martin C; Shakesheff, Kevin M

2007-10-15

Polyamidoamine polymers (PAA) comprising methylene-bisacrylamide/dimethylethylene-diamine monomers were synthesized, complexed with DNA and incorporated into porous P(DL)LA scaffolds by using a supercritical CO(2) (scCO(2)) technique. Scaffolds were made in a dry state consequently there was a need to lyophilize the complexes. A statistically significant reduction of the transfection efficiency was observed in the absence of trehalose when compared to the original complex after freeze-drying. Increasing concentrations (0-10% w/v) of trehalose were added to the complex prior to freeze-drying. Structure dependent differences in DNA binding were evaluated by gel electrophoresis and thermal transition analysis. TEM and PCS showed aggregate formation after freeze-drying without trehalose. Scaffolds were characterized by pore sizes of 173 +/- 73 microm and a porosity of 71%. The transfection potential of the released DNA was investigated by seeding scaffolds with A549 cells and following firefly luciferase as a marker gene after 48 h exposure. Low but continuous levels of transfection were observed for PAA complexes during a 60-day study. Complexes made with Lipofectaminetrade mark gave initially higher levels of DNA release but no further expression was seen after 40 days. Uncomplexed DNA showed background levels of transfection. Culturing cells on 3D scaffolds showed a benefit in retention of transfection activity with time compared to 2D controls. Transfection levels could be increased when cells were grown in OptiMEM. This study demonstrated that PAA/DNA complexes incorporated into a P(DL)LA scaffold made by using scCO(2) processing exhibited a slow release and extended gene expression profile. Copyright 2007 Wiley Periodicals, Inc.

Ethanol exposure induces oxidative stress and impairs nitric oxide availability in the human placental villi: a possible mechanism of toxicity.

PubMed

Kay, H H; Grindle, K M; Magness, R R

2000-03-01

We undertook this investigation to explore the effects of ethanol exposure on nitric oxide synthase levels and nitric oxide release. Our hypothesis was that ethanol exposure modifies nitric oxide activity within the placenta as a result of oxidative stress. Four 10-g samples of term normal human placental villous tissue were perifused with nonrecirculating Dulbecco's modified Eagle's medium and 25-mmol/L N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] with 0-, 50-, 100-, or 200-mmol/L ethanol. After 2 hours of exposure, tissue was removed, fixed, and frozen for analysis. Immunohistochemical analysis was performed for subtype I or neuronal nitric oxide synthase (nNOS), subtype II or inducible nitric oxide synthase (iNOS), and subtype III or endothelial nitric oxide synthase (eNOS) localization. Western blot analysis was performed for eNOS quantitation. Cyclic guanosine monophosphate and copper-zinc superoxide dismutase levels were measured by electroimmunoassay and kinetic assay, respectively. Nitric oxide release was analyzed by a Sievers nitric oxide analyzer. Immunohistochemical examination confirmed that only eNOS was localized to the syncytiotrophoblasts. After ethanol exposure, eNOS protein expression increased 2.5- to 3.0-fold over that of the control. Tissue cyclic guanosine monophosphate content and nitric oxide release into the effluent were decreased, whereas superoxide dismutase levels were increased at higher ethanol levels (P <.05). Ethanol exposure appears to induce oxidative stress, which may account for the decreased nitric oxide release, because nitric oxide may be shunted toward scavenging free radicals. Increased eNOS protein expression may be a response to the increased demand for nitric oxide. Decreased nitric oxide availability could adversely affect placental blood flow regulation, which could, in turn, account for the growth restriction seen in ethanol-exposed fetuses.

Radioactive contamination of nest materials of the Eurasian Tree Sparrow Passer montanus due to the Fukushima nuclear accident: The significance in the first year.

PubMed

Matsui, Shin; Kasahara, Satoe; Morimoto, Gen; Mikami, Osamu K; Watanabe, Mamoru; Ueda, Keisuke

2015-11-01

The 2011 Fukushima nuclear accident contaminated large areas of eastern and northeastern Japan, releasing vast amounts of radiation. Here we investigated radioactive contamination of the nest materials of the Eurasian Tree Sparrow Passer montanus from the breeding season of 2011 directly after the accident to the next breeding season of 2012 at two sites. In Tokyo (222 km southwest of the plant), ambient dose rates in the nestboxes were lower than those in Ibaraki (175 km southwest of the plant), where the levels of 2011 were higher than those of 2012. Further, the amount of radioactive Cs in each nest increased with the increase in nest weight, with a higher increment at Ibaraki than at Tokyo. These data suggested higher nest contamination levels in the breeding season directly after a nuclear accident than in later seasons, and an increment of nest contamination levels via nest materials of birds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bionomics of Asian Citrus Psyllid (Hemiptera: Liviidae) Associated with Orange Jasmine Hedges in Southeast Central Florida, with Special Reference to Biological Control by Tamarixia radiata.

PubMed

Hall, David G; Rohrig, Eric

2015-06-01

The Asian citrus psyllid, Diaphorina citri Kuwayama, is an important pest in Florida because it transmits bacteria responsible for citrus huanglongbing disease. In addition to infesting citrus, orange jasmine (Murraya exotica L.) is one of Asian citrus psyllid's preferred host plants and is widely grown as an ornamental hedge. We report on Asian citrus psyllid bionomics over three years at five urban plantings of orange jasmine and on biological control of Asian citrus psyllid by a parasitoid Tamarixia radiata (Waterston). T. radiata had been released in Florida shortly after Asian citrus psyllid was first found, and the parasitoid was known to be established at each planting. Additionally, three new T. radiata haplotypes were released every 3 wk at three plantings during the first study year (one haplotype per planting, over all releases an average of 17 parasitoids per linear meter of hedge); all three haplotypes were released at a fourth planting beginning midway through the study (over all releases, an average combined total of 202 parasitoids per linear meter of hedge). Asian citrus psyllid populations were present year-round at each planting, often at large levels. Such plantings may pose risk to commercial citrus as Asian citrus psyllid reservoirs. Releases of the new haplotypes did not cause any measurable reduction in Asian citrus psyllid population levels during the study, and ironically percentage parasitism was generally highest at a planting where no releases were made. Higher release rates might have been more effective. The probability is discussed that repetitive pruning of orange jasmine reduced the full potential of T. radiata against Asian citrus psyllid in this study. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

A leukocyte activation test identifies food items which induce release of DNA by innate immune peripheral blood leucocytes.

PubMed

Garcia-Martinez, Irma; Weiss, Theresa R; Yousaf, Muhammad N; Ali, Ather; Mehal, Wajahat Z

2018-01-01

Leukocyte activation (LA) testing identifies food items that induce a patient specific cellular response in the immune system, and has recently been shown in a randomized double blinded prospective study to reduce symptoms in patients with irritable bowel syndrome (IBS). We hypothesized that test reactivity to particular food items, and the systemic immune response initiated by these food items, is due to the release of cellular DNA from blood immune cells. We tested this by quantifying total DNA concentration in the cellular supernatant of immune cells exposed to positive and negative foods from 20 healthy volunteers. To establish if the DNA release by positive samples is a specific phenomenon, we quantified myeloperoxidase (MPO) in cellular supernatants. We further assessed if a particular immune cell population (neutrophils, eosinophils, and basophils) was activated by the positive food items by flow cytometry analysis. To identify the signaling pathways that are required for DNA release we tested if specific inhibitors of key signaling pathways could block DNA release. Foods with a positive LA test result gave a higher supernatant DNA content when compared to foods with a negative result. This was specific as MPO levels were not increased by foods with a positive LA test. Protein kinase C (PKC) inhibitors resulted in inhibition of positive food stimulated DNA release. Positive foods resulted in CD63 levels greater than negative foods in eosinophils in 76.5% of tests. LA test identifies food items that result in release of DNA and activation of peripheral blood innate immune cells in a PKC dependent manner, suggesting that this LA test identifies food items that result in release of inflammatory markers and activation of innate immune cells. This may be the basis for the improvement in symptoms in IBS patients who followed an LA test guided diet.

Pro-Gastrin Releasing Peptide: A New Serum Marker for Endometrioid Adenocarcinoma.

PubMed

Kiseli, Mine; Caglar, Gamze Sinem; Yarci Gursoy, Asli; Tasci, Tolga; Candar, Tuba; Akincioglu, Egemen; Pabuccu, Emre Goksan; Boran, Nurettin; Tulunay, Gokhan; Umudum, Haldun

2018-06-13

Gastrin-releasing peptide (GRP) is thought to play a role in the metastatic process of various malignancies. The more stable precursor of GRP, pro-GRP (ProGRP), has been shown to be secreted by neuroendocrine tumors. This study was designed to assess the validity of ProGRP as a diagnostic marker in endometrioid adenocarcinomas (EAs) of the endometrium. Thirty-seven patients with a diagnosis of EA, 23 patients with endometrial hyperplasia, and 32 age-matched controls with normal endometrial histology were recruited for this study. Serum ProGRP and cancer antigen 125 (CA125) values were compared between groups. Median serum ProGRP levels were significantly higher in the cancer group compared to corresponding levels in both the hyperplasia and control groups (p = 0.008 and p < 0.001 respectively; endometrial cancer: 27.5 pg/mL; hyperplasia: 16.1 pg/mL; controls: 12.9 pg/mL). Age and endometrial thickness were positively correlated with ProGRP levels (r = 0.322, p = 0.006 and r = 0.269, p = 0.023, respectively). Receiver Operating Characteristic curve analyses for EA revealed a threshold of 20.81 pg/mL, with a sensitivity of 60.7% and specificity of 81.4%, positive predictive value of 68% and negative predictive value of 76.1%. Significantly higher ProGRP levels were observed in patients with EA than in controls. Serum ProGRP has good diagnostic sensitivity and specificity for EA. © 2018 S. Karger AG, Basel.

Modified release terbutaline (SKP1052) for hypoglycaemia prevention: a proof-of-concept study in people with type 1 diabetes mellitus.

PubMed

Nosek, L; Cardot, J-M; Owens, D R; Ibarra, P; Bagate, K; Vergnault, G; Kaiser, K; Fischer, A; Heise, T

2012-12-01

In this randomized, single blind, cross-over study 2.5 mg and 5 mg of the modified-release terbutaline formulation (SKP-1052) were compared with conventional immediate-release terbutaline (IRT, 5 mg) and placebo on overnight blood glucose (BG) and hypoglycaemia in 30 subjects with type 1 diabetes mellitus. Subjects received subcutaneous injections of insulin glargine (individualized doses) before dinner. SKP-1052, IRT or placebo was administered around 21:00 hours. BG and terbutaline concentrations were monitored overnight for 10 h post-dosing. Endpoints comprised of the nadir BG (BGn 0-10 h, primary endpoint), mean overnight BG (BGmean), morning BG (BGmorning) and hypoglycaemia rates as well as pharmacokinetic (PK) endpoints. SKP-1052 delayed release of terbutaline by 2 h [PK-tmax (mean ± SD) 5.0 ± 2.1 h (2.5 mg) and 4.7 ± 1.7 h (5 mg) vs. 2.6 ± 1.3 h with IRT, p < 0.01, respectively]. Compared with placebo, no significant differences were observed for BGn 0-10 h across treatments, but both 5 mg formulations showed less hypoglycaemic events [10 (IRT), 16 (SKP-1052) vs. 33], higher BGmean (120, 114 and 95 mg/dl) and BGmorning (126, 126 and 101 mg/dl, all comparisons p < 0.05 vs. placebo). Numerically higher BG-levels between 3 and 8 h post-dosing were observed with 2.5 mg SKP-1052 vs. placebo. Compared with IRT SKP-1052 delays release of terbutaline. 2.5 mg SKP-1052 led to numerically higher BG 3 to 8 h post-dose without fasting hyperglycaemia while 5 mg SKP-1052 resulted in fasting hyperglycaemia vs. placebo. Future studies will investigate optimized doses of SKP-1052 for nocturnal hypoglycaemia prevention. © 2012 Blackwell Publishing Ltd.

Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice.

PubMed

Dolejší, Eva; Liraz, Ori; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; Michaelson, Daniel M

2016-02-01

Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease. We utilized apoE4-targeted replacement mice (approved by the Tel Aviv University Animal Care Committee) to investigate whether cholinergic dysfunction, which increases during aging and is a hallmark of Alzheimer's disease, is accentuated by apoE4. This revealed that levels of the pre-synaptic cholinergic marker, vesicular acetylcholine transporter in the hippocampus and the corresponding electrically evoked release of acetylcholine, are similar in 4-month-old apoE4 and apolipoprotein E3 (apoE3) mice. Both parameters decrease with age. This decrease is, however, significantly more pronounced in the apoE4 mice. The levels of cholinacetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) were similar in the hippocampus of young apoE4 and apoE3 mice and decreased during aging. For ChAT, this decrease was similar in the apoE4 and apoE3 mice, whereas it was more pronounced in the apoE4 mice, regarding their corresponding AChE and BuChE levels. The level of muscarinic receptors was higher in the apoE4 than in the apoE3 mice at 4 months and increased to similar levels with age. However, the relative representation of the M1 receptor subtype decreased during aging in apoE4 mice. These results demonstrate impairment of the evoked release of acetylcholine in hippocampus by apoE4 in 12-month-old mice but not in 4-month-old mice. The levels of ChAT and the extent of the M2 receptor-mediated autoregulation of ACh release were similar in the adult mice, suggesting that the apoE4-related inhibition of hippocampal ACh release in these mice is not driven by these parameters. Evoked ACh release from hippocampal and cortical slices is similar in 4-month-old apoE4 and apoE3 mice but is specifically and significantly reduced in hippocampus, but not cortex, of 12-month-old apoE4 mice. This effect is accompanied by decreased VAChT levels. These findings show that the hipocampal cholinergic nerve terminals are specifically affected by apoE4 and that this effect is age dependent. © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

PubMed

Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

2015-01-01

A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included headache (26%) and nausea (18%). All three hydrocodone ER tablet prototypes (low-, intermediate-, and high-level polymer coating) demonstrated ER pharmacokinetic characteristics. The hydrocodone ER tablet prototype with the high-level coating was selected for development because of its comparable exposure to the hydrocodone IR/APAP formulation and potentially increased ability to resist rapid drug release upon product tampering because of a higher polymer coating level. All study medications were well tolerated in healthy naltrexone-blocked volunteers.

NASA/GEWEX shortwave surface radiation budget: Integrated data product with reprocessed radiance, cloud, and meteorology inputs, and new surface albedo treatment

NASA Astrophysics Data System (ADS)

Cox, Stephen J.; Stackhouse, Paul W.; Gupta, Shashi K.; Mikovitz, J. Colleen; Zhang, Taiping

2017-02-01

The NASA/GEWEX Surface Radiation Budget (SRB) project produces shortwave and longwave surface and top of atmosphere radiative fluxes for the 1983-near present time period. Spatial resolution is 1 degree. The current Release 3.0 (available at gewex-srb.larc.nasa.gov) uses the International Satellite Cloud Climatology Project (ISCCP) DX product for pixel level radiance and cloud information. This product is subsampled to 30 km. ISCCP is currently recalibrating and recomputing their entire data series, to be released as the H product, at 10km resolution. The ninefold increase in pixel number will allow SRB a higher resolution gridded product (e.g. 0.5 degree), as well as the production of pixel-level fluxes. Other key input improvements include a detailed aerosol history using the Max Planck Institute Aerosol Climatology (MAC), and temperature and moisture profiles from nnHIRS.

Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model.

PubMed

Brisbois, Elizabeth J; Bayliss, Jill; Wu, Jianfeng; Major, Terry C; Xi, Chuanwu; Wang, Stewart C; Bartlett, Robert H; Handa, Hitesh; Meyerhoff, Mark E

2014-10-01

Nitric oxide (NO) has many biological roles (e.g. antimicrobial agent, promoter of angiogenesis, prevention of platelet activation) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2±0.7wt.%) and Tecophilic SP-60D-20 (22.5±1.1wt.%)) were doped with 25wt.% DBHD/N2O2 and 10wt.% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with the lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24h (∼4 log reduction). The NO release patches are also able to reduce the level of transforming growth factor-β in comparison to controls, which can enhance re-epithelialization, decrease scarring and reduce migration of bacteria. The combined DBHD/N2O2 and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Correlation of in vitro and in vivo paracetamol availability from layered excipient suppositories.

PubMed

Chicco, D; Grabnar, I; Skerjanec, A; Vojnovic, D; Maurich, V; Realdon, N; Ragazzi, E; Belic, A; Karba, R; Mrhar, A

1999-11-05

An in vivo investigation of paracetamol availability was carried out on eight healthy volunteers, comparing two paracetamol suppository formulations prepared using two different gliceride bases, a fast drug-releasing one and a slow drug-releasing one, i.e. Witepsol H15 and W35, respectively. The formulations were selected on the basis of a previous in vitro drug release study, which showed that, by superimposing the excipients in two layers within the same suppository, the drug release kinetics could be modulated using different ratios between the two layers. The comparison between the two different formulations in terms of plasma profiles and total amounts of drug excreted in urine revealed an increase in the extent of drug absorption from the layered excipient suppository. As the W35 has a higher monoglyceride content than the H15, this improved paracetamol availability could be ascribed to the absorption-enhancing effect of the monoglycerides. Moreover, the W35 has also a higher viscosity, which could possibly cause the suppository to be retained for a longer time in the lower part of the rectum, where the blood is drained directly to the systemic circulation. It was therefore hypothesized that the enhanced paracetamol availability could be also due to a liver bypass mechanism. For a further examination of the paracetamol absorption kinetics after rectal administration, a one-compartment model was fitted to the drug plasma concentration data. This approach allowed to draw absorption versus time profiles, which showed that a retardation actually occurred in paracetamol absorption when using suppositories containing the slow drug releasing excipient W35. These absorption data were then employed for an A level in vitro-in vivo correlation testing, and a linear relationship was found between in vitro release rate and in vivo absorption rate, both for fast releasing and for the layered excipient suppositories.

Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model

PubMed Central

Brisbois, Elizabeth J.; Bayliss, Jill; Wu, Jianfeng; Major, Terry C.; Xi, Chuanwu; Wang, Stewart C.; Bartlett, Robert H.; Handa, Hitesh; Meyerhoff, Mark E.

2014-01-01

Nitric oxide (NO) has many biological roles (e.g., antimicrobial agent, promoter of angiogenesis, prevention of platelet activation, etc.) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2 ± 0.7 wt %) and Tecophillic SP-60D-20 (22.5 ± 1.1 wt%)) were doped with 25 wt% DBHD/N2O2 and 10 wt% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24 h (~4 log reduction). The NO release patches are also able to reduce the TGF-β levels, in comparison to controls, which can enhance reepithelialization, decrease scarring, and reduce migration of bacteria. The combined DBHD/N2O2 and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process. PMID:24980058

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

PubMed Central

Peroni, Cibele N.; Hayashida, Cesar Y.; Nascimento, Nancy; Longuini, Viviane C.; Toledo, Rodrigo A.; Bartolini, Paolo; Bowers, Cyril Y.; Toledo, Sergio P.A.

2012-01-01

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a. PMID:22473409

Pre- and postjunctional inhibitory effects of fenspiride on guinea-pig bronchi.

PubMed

Girard, V; Naline, E; Crambes, O; Malbezin, M; Malmström, R E; Lundberg, J M; Advenier, C

1997-05-01

Fenspiride is a drug with potential benefits in the treatment of obstructive airways disease. It has antibronchoconstriction and anti-inflammatory properties. The aim of this study was to investigate the effect of this drug on the contractions induced in the guinea-pig isolated main bronchus and perfused lung by electrical field stimulation (EFS) or exogenously added agents. Bronchi were stimulated transmurally in the presence of indomethacin 10(-6) M and propranolol 10(-6) M, and isometric tension was measured. In the perfused lung model calcitonin gene-related peptide (CGRP) release was determined in the perfusate fractions as a measure of neuropeptide production. Two successive contractile responses were observed: a rapid cholinergic contraction, followed by a long-lasting contraction due to local release of neuropeptides from C-fibre endings. Fenspiride (10(-6) to 10(-4) M) inhibited the nonadrenergic, noncholinergic (NANC) component of the contraction of the guinea-pig isolated main bronchus induced by EFS. Fenspiride significantly affected contractions induced by exogenously added substance P or [Nle10]-NKA(4-10) only at concentrations higher than 10(-3) M. In the guinea-pig perfused lung, fenspiride inhibited low pH- but not capsaicin-evoked release of CGRP. At higher concentrations (10(-4) M to 3x10(-4) M) fenspiride exhibited a significant inhibitory effect both on the cholinergic component of contractile response induced by EFS in the guinea-pig isolated main bronchus and on exogenously added acetylcholine. In conclusion, the result of this study suggests that fenspiride, in moderate concentrations, reduces the release of neuropeptides, including tachykinins, from sensory nerve endings at a prejunctional level. At higher concentrations, postjunctional actions on bronchial smooth muscle are also present.

Attaining the canopy in dry and moist tropical forests: strong differences in tree growth trajectories reflect variation in growing conditions.

PubMed

Brienen, Roel J W; Zuidema, Pieter A; Martínez-Ramos, Miguel

2010-06-01

Availability of light and water differs between tropical moist and dry forests, with typically higher understorey light levels and lower water availability in the latter. Therefore, growth trajectories of juvenile trees--those that have not attained the canopy--are likely governed by temporal fluctuations in light availability in moist forests (suppressions and releases), and by spatial heterogeneity in water availability in dry forests. In this study, we compared juvenile growth trajectories of Cedrela odorata in a dry (Mexico) and a moist forest (Bolivia) using tree rings. We tested the following specific hypotheses: (1) moist forest juveniles show more and longer suppressions, and more and stronger releases; (2) moist forest juveniles exhibit wider variation in canopy accession pattern, i.e. the typical growth trajectory to the canopy; (3) growth variation among dry forest juveniles persists over longer time due to spatial heterogeneity in water availability. As expected, the proportion of suppressed juveniles was higher in moist than in dry forest (72 vs. 17%). Moist forest suppressions also lasted longer (9 vs. 5 years). The proportion of juveniles that experienced releases in moist forest (76%) was higher than in dry forest (41%), and releases in moist forests were much stronger. Trees in the moist forest also had a wider variation in canopy accession patterns compared to the dry forest. Our results also showed that growth variation among juvenile trees persisted over substantially longer periods of time in dry forest (>64 years) compared to moist forest (12 years), most probably because of larger persistent spatial variation in water availability. Our results suggest that periodic increases in light availability are more important for attaining the canopy in moist forests, and that spatial heterogeneity in water availability governs long-term tree growth in dry forests.

Formula milk feeding does not increase the release of the inflammatory marker calprotectin, compared to human milk.

PubMed

Rosti, L; Braga, M; Fulcieri, C; Sammarco, G; Manenti, B; Costa, E

2011-01-01

Calprotectin is a protein released into stools, used as a marker of inflammation in inflammatory bowel diseases. We tested the hypothesis that cow's milk protein in formula milk may increase the intestinal release of calprotectin, as a consequence of a subclinical inflammatory reaction. At 12 weeks of age, we measured fecal calprotectin by an immunoenzyme assay (Calprest, Eurospital, Trieste, Italy), in 38 exclusively breastfed and in 32 exclusively formula-fed infants. Fecal calprotectin levels were not different in the two groups (p = 0.09), although a trend to higher values in infants with colic, or with family history of allergies was noted. This suggest that, in general, formula milk does not promote activation of an intestinal inflammatory reaction, compared to human milk, although a subclinical activation of the inflammatory response in infants at risk for allergic diseases may be present.

Pavlovian autoshaping procedures increase plasma corticosterone and levels of norepinephrine and serotonin in prefrontal cortex in rats.

PubMed

Tomie, Arthur; Tirado, Aidaluz D; Yu, Lung; Pohorecky, Larissa A

2004-08-12

Pavlovian autoshaping procedures provide for pairings of a small object conditioned stimulus (CS) with a rewarding substance unconditioned stimulus (US), resulting in the acquisition of complex sequences of CS-directed skeletal-motor responses or autoshaping conditioned responses (CRs). Autoshaping procedures induce higher post-session levels of corticosterone than in controls receiving CS and US randomly, and the enhanced post-session corticosterone levels have been attributed to the appetitive or arousal-inducing effects of autoshaping procedures. Enhanced corticosterone release can be induced by aversive stimulation or stressful situations, where it is often accompanied by higher levels of norepinephrine (NE) and serotonin (5-HT) in prefrontal cortex (PFC) but not in striatum (ST). Effects of autoshaping procedures on post-session corticosterone levels, NE contents in PFC, and 5-HT contents in PFC and ST were investigated in male Long-Evans rats. Post-session blood samples revealed higher corticosterone levels in the CS-US Paired group (n = 46) than in the CS-US Random control group (n = 21), and brain samples revealed higher levels of PFC NE and 5-HT in CS-US Paired group. Striatal 5-HT levels were unaltered by the autoshaping procedures. Autoshaping procedures provide for appetitive stimulation and induce an arousal-like state, as well as simultaneous stress-like changes in plasma corticosterone and monoamine levels in PFC. Autoshaping, therefore, may be useful for the study of endocrine and central processes associated with appetitive conditions.

The effects of a mineral trioxide aggregate-based sealer on the production of reactive oxygen species, nitrogen species and cytokines by two macrophage subtypes.

PubMed

Braga, J M; Oliveira, R R; Martins, R C; Ribeiro Sobrinho, A P

2014-10-01

To test the effects of a mineral trioxide aggregate-based sealer (MTA Fillapex(®)) and MTA (MTA-Ângelus(®)) on viability and on the production of cytokines, reactive oxygen species (ROS) and nitrogen species (NO) by M1 and M2 inflammatory macrophages. M1 (from C57BL/6 mice) and M2 (from BALB/c mice) peritoneal inflammatory macrophages were obtained and cultured in vitro in the presence of original and diluted extracts of MTA and MTA Fillapex (FLPX). The cell viability, ROS release and the release of tumour necrosis factor-a, interleukin (IL)-12, IL-10 and NO in response to stimulation with interferon-γ and Fusobacterium nucleatum or Peptostreptococcus anaerobius were evaluated. The data were analysed using the Mann-Whitney test and Student's t-test. Fillapex was cytotoxic at the highest concentrations (1:1;1:2) and decreased the viability (P < 0.05) of both macrophage types (<20%). MTA did not interfere with cellular viability. FLPX inhibited the release of ROS and decreased NO release in F. nucleatum and P. anaerobius -stimulated M1 and M2 macrophages (≤25 μ mol L(-1)). F. nucleatum-stimulated M2 macrophage cultures released lower levels of TNF-α when FLPX was added (≤1 ng mL(-1)). M2 macrophages released higher (>5 ng mL(-1)) levels of IL-10 than M1 macrophages. Only M1 macrophage cultures produced IL-12p70. Fillapex impaired effector immune responses during inflammation (M1 macrophages), as well as during healing (M2 macrophages) responses. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Effect of thiol pendant conjugates on plasmid DNA binding, release, and stability of polymeric delivery vectors.

PubMed

Bacalocostantis, Irene; Mane, Viraj P; Kang, Michael S; Goodley, Addison S; Muro, Silvia; Kofinas, Peter

2012-05-14

Polymers have attracted much attention as potential gene delivery vectors due to their chemical and structural versatility. However, several challenges associated with polymeric carriers, including low transfection efficiencies, insufficient cargo release, and high cytotoxicity levels have prevented clinical implementation. Strong electrostatic interactions between polymeric carriers and DNA cargo can prohibit complete cargo release within the cell. As a result, cargo DNA never reaches the cell's nucleus where gene expression takes place. In addition, highly charged cationic polymers have been correlated with high cytotoxicity levels, making them unsuitable carriers in vivo. Using poly(allylamine) (PAA) as a model, we investigated how pH-sensitive disulfide cross-linked polymer networks can improve the delivery potential of cationic polymer carriers. To accomplish this, we conjugated thiol-terminated pendant chains onto the primary amines of PAA using 2-iminothiolane, developing three new polymer vectors with 5, 13, or 20% thiol modification. Unmodified PAA and thiol-conjugated polymers were tested for their ability to bind and release plasmid DNA, their capacity to protect genetic cargo from enzymatic degradation, and their potential for endolysosomal escape. Our results demonstrate that polymer-plasmid complexes (polyplexes) formed by the 13% thiolated polymer demonstrate the greatest delivery potential. At high N/P ratios, all thiolated polymers (but not unmodified counterparts) were able to resist decomplexation in the presence of heparin, a negatively charged polysaccharide used to mimic in vivo polyplex-protein interactions. Further, all thiolated polymers exhibited higher buffering capacities than unmodified PAA and, therefore, have a greater potential for endolysosomal escape. However, 5 and 20% thiolated polymers exhibited poor DNA binding-release kinetics, making them unsuitable carriers for gene delivery. The 13% thiolated polymers, on the other hand, displayed high DNA binding efficiency and pH-sensitive release.

Development of a microwave assisted extraction method for the analysis of 2,4,6-trichloroanisole in cork stoppers by SIDA-SBSE-GC-MS.

PubMed

Vestner, Jochen; Fritsch, Stefanie; Rauhut, Doris

2010-02-15

The aim of this research work was focused on the replacement of the time-consuming soaking of cork stoppers which is mainly used as screening method for cork lots in connection with sensory analysis and/or analytical methods to detect releasable 2,4,6-trichloroanisole (TCA) of natural cork stoppers. Releasable TCA from whole cork stoppers was analysed with the application of a microwave assisted extraction method (MAE) in combination with stir bar sorptive extraction (SBSE). The soaking of corks (SOAK) was used as a reference method to optimise MAE parameters. Cork lots of different quality and TCA contamination levels were used to adapt MAE. Pre-tests indicated that an MAE at 40 degrees C for 120 min with 90 min of cooling time are suitable conditions to avoid an over-extraction of TCA of low and medium tainted cork stoppers in comparison to SOAK. These MAE parameters allow the measuring of almost the same amounts of releasable TCA as with the application of the soaking procedure in the relevant range (<25 ng L(-1) releasable TCA from one cork) to evaluate the TCA level of cork stoppers. Stable isotope dilution assay (SIDA) was applied to optimise quantification of the released TCA with deuterium-labelled TCA (TCA-d(5)) using a time-saving GC-MS technique in single ion monitoring (SIM) mode. The developed MAE method allows the measuring of releasable TCA from the whole cork stopper under improved conditions and in connection with a low use of solvent and a higher sample throughput. Copyright 2009 Elsevier B.V. All rights reserved.

Electrically responsive microreservoires for controllable delivery of dexamethasone in bone tissue engineering

NASA Astrophysics Data System (ADS)

Paun, Irina Alexandra; Zamfirescu, Marian; Luculescu, Catalin Romeo; Acasandrei, Adriana Maria; Mustaciosu, Cosmin Catalin; Mihailescu, Mona; Dinescu, Maria

2017-01-01

A major concern in orthopedic implants is to decrease the chronic inflammation using specific drug therapies. The newest strategies rely on the controlled delivery of antiinflammatory drugs from carrier biointerfaces designed in the shape of 3D architectures. We report on electrically responsive microreservoires (ERRs) acting as microcontainers for antiinflammatory drugs, as potential biointerfaces in orthopedic implants. The ERRs consist in arrays of vertical microtubes produced by laser direct writing using two photon polymerization effects (2PP_LDW) of a commercially available photoresist, IP-L780. A polypyrrole (conductive)/dexamethasone (drug model) (PPy/Dex) mixture was loaded into the ERRs via a simple immersion process. Then, the ERRs were sealed with a poly(lactic-co-glycolic acid)(PLGA) layer by Matrix Assisted Pulsed Laser Evaporation. ERRs stimulation using voltage cycles between -1 V and +1 V, applied at specific time intervals, at a scan rate of 0.1 V s-1, enabled to control the Dex release. The release time scales were between 150 and 275 h, while the concentrations of Dex released were between 450-460 nM after three applied voltage cycles, for different microreservoires dimensions. The proposed approach was validated in osteoblast-like MG-63 cell cultures. Cell viability and adhesion assays showed that the Dex-loaded ERRs sustained the cells growth and preserved their characteristic polygonal shape. Importantly, for the electrically-stimulated Dex release, the level of the alkaline phosphatase activity increased twice, the osteogenic differentiation surpassed by 1.6 times and the relative level of osteocalcin gene expression was 2.2 times higher as compared with the unstimulated drug release. Overall, the ERRs were able to accelerate the cells osteogenic differentiation via electrically controlled release of Dex.

Effect of centrifugation time on growth factor and MMP release of an experimental platelet-rich fibrin-type product.

PubMed

Eren, Gülnihal; Gürkan, Ali; Atmaca, Harika; Dönmez, Ayhan; Atilla, Gül

2016-07-01

Platelet-rich fibrin (PRF) has a controlled release of growth factors due to the fibrin matrix structure. Different centrifugation protocols were suggested for PRF preparation. Since the derivation method of PRF can alter its contents, in the present study it is aimed to investigate the cell contents and transforming growth factor beta-1 (TGF-β1), platelet-derived growth factor (PDGF-AB), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and-8 release from experimental PRF-type membranes obtained with different centrifugation times at 400 gravity. Three blood samples were collected from 20 healthy non-smoker volunteers. One tube was used for whole blood analyses. The other two tubes were centrifuged at 400 g for 10 minutes (group A) or 12 minutes (group B). Each experimental PRF-type membrane was placed in Dulbecco's Modified Eagle's Medium (DMEM)and at 1, 24 and 72 hours, TGF-β1, PDGF-AB, VEGF, MMP-1 and -8 release amounts were analysed by enzyme-linked immunosorbent assay (ELISA). The blood cell count of membranes was determined by subtracting plasma supernatant and red blood cell (RBC) mixture from the whole blood cell counts. At 72 hours, the VEGF level of group B was statistically higher than that of group A (p = 0.040). The centrifugation time was not found to influence the release of other growth factors, enzymes and cell counts. Within the limits of the present study, it might be suggested that centrifugation time at a constant gravity has a significant effect on the VEGF levels released from experimental PRF-type membrane. It can be concluded that due to the importance of VEGF in the tissue healing process, membranes obtained at 12-minute centrifugation time may show a superior potential in wound healing.

Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation.

PubMed

Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D

2016-01-01

Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

Centrifugal air-assisted melt agglomeration for fast-release "granulet" design.

PubMed

Wong, Tin Wui; Musa, Nafisah

2012-07-01

Conventional melt pelletization and granulation processes produce round and dense, and irregularly shaped but porous agglomerates respectively. This study aimed to design centrifugal air-assisted melt agglomeration technology for manufacture of spherical and yet porous "granulets" for ease of downstream manufacturing and enhancing drug release. A bladeless agglomerator, which utilized shear-free air stream to mass the powder mixture of lactose filler, polyethylene glycol binder and poorly water-soluble tolbutamide drug into "granulets", was developed. The inclination angle and number of vane, air-impermeable surface area of air guide, processing temperature, binder content and molecular weight were investigated with reference to "granulet" size, shape, texture and drug release properties. Unlike fluid-bed melt agglomeration with vertical processing air flow, the air stream in the present technology moved centrifugally to roll the processing mass into spherical but porous "granulets" with a drug release propensity higher than physical powder mixture, unprocessed drug and dense pellets prepared using high shear mixer. The fast-release attribute of "granulets" was ascribed to porous matrix formed with a high level of polyethylene glycol as solubilizer. The agglomeration and drug release outcomes of centrifugal air-assisted technology are unmet by the existing high shear and fluid-bed melt agglomeration techniques. Copyright © 2012 Elsevier B.V. All rights reserved.

Hypoxia-induced angiogenesis is increased by the controlled release of deferoxiamine from gelatin hydrogels.

PubMed

Saito, Takashi; Tabata, Yasuhiko

2014-08-01

The objective of this study is to design biodegradable hydrogels for the controlled release of deferoxiamine (DFO) and evaluate their biological activity. When the DFO was added to human umbilical vein endothelial cells cultured in 5.0% O2, the level of hypoxia-inducible factor-1α and vascular endothelial growth factor significantly increased compared with that without DFO. The expression of angiogenesis-related genes was accordingly increased by the DFO addition. An aqueous solution of mixed gelatin and DFO was freeze-dried, and dehydrothermally treated at 140°C for 24h to prepare a gelatin hydrogel incorporating DFO. In the release test with phosphate-buffered saline solution (PBS) at 37°C, an initial DFO release of 60% was observed, followed by no release. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded with time, and consequently released DFO in a degradation-dependent manner. After the hydrogel incorporating DFO was injected intramuscularly into a mouse model of hind limb ischemia, the number of new blood vessels formed was significantly higher than that with free DFO and DFO-free hydrogel. It is concluded that the DFO-containing hydrogel shows promising for inducing angiogenesis locally. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Floating modular drug delivery systems with buoyancy independent of release mechanisms to sustain amoxicillin and clarithromycin intra-gastric concentrations.

PubMed

Rossi, Alessandra; Conti, Chiara; Colombo, Gaia; Castrati, Luca; Scarpignato, Carmelo; Barata, Pedro; Sandri, Giuseppina; Caramella, Carla; Bettini, Ruggero; Buttini, Francesca; Colombo, Paolo

2016-01-01

Release modules of amoxicillin and clarithromycin combined in a single dosage form designed to float in the gastric content and to sustain the intra-gastric concentrations of these two antibiotics used for the eradication of Helicobacter pylori have been studied. The modules having a disc shape with curved bases were formulated as hydrophilic matrices. Two modules of clarithromycin were assembled by sticking the concave base of one module to the concave base of the other, creating an internal void chamber. The final dosage form was a floating assembly of three modules of clarithromycin and two of amoxicillin in which the drug release mechanism did not interfere with the floatation mechanism. The assembled system showed immediate in vitro floatation at pH 1.2, lasting 5 h. The in vitro antibiotics release profiles from individual modules and assembled systems exhibited linear release rate during buoyancy for at least 8 h. The predicted antibiotic concentrations in the stomach maintained for long time levels significantly higher than the respective minimum inhibitory concentrations (MIC). In addition, an in vivo absorption study performed on beagle dogs confirmed the slow release of clarithromycin and amoxicillin from the assembled system during the assembly's permanence in the stomach for at least 4 h.

Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques.

PubMed

McConville, Christopher; Smith, James M; McCoy, Clare F; Srinivasan, Priya; Mitchell, James; Holder, Angela; Otten, Ron A; Butera, Salvatore; Doncel, Gustavo F; Friend, David R; Malcolm, R Karl

2015-02-01

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82-860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo-in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism.

Poly(ethylene glycol)-containing hydrogels promote the release of primary granules from human blood-derived polymorphonuclear leukocytes

PubMed Central

Cohen, Hannah Caitlin; Lieberthal, Tyler Jacob; Kao, W. John

2014-01-01

Polymorphonuclear leukocytes (PMNs) are recruited to sites of injury and biomaterial implants. Once activated, PMNs can exocytose their granule subsets to recruit monocytes (MCs) and mediate MC/macrophage activation. We investigated the release of myeloperoxidase (MPO), a primary granule marker, and matrix metalloproteinase-9 (MMP-9), a tertiary granule marker, from human blood-derived PMNs cultured on poly(ethylene glycol) (PEG) hydrogels, polydimethylsiloxane (PDMS), tissue culture polystyrene (TCPS) and gelatin-PEG (GP) hydrogels, with and without the presence of the bacterial peptide formyl-Met-Leu-Phe. Supernatants from PMN cultures on PEG-containing hydrogels (i.e., PEG and GP hydrogels) had higher concentrations of MPO than those from PMN cultures on PDMS or TCPS at 2 hours. PMNs on all biomaterials released comparable levels of MMP-9 at 2 hours, indicating that PMNs cultured on PEG-containing hydrogels have different mechanisms of release for primary and tertiary granules. Src family kinases were involved in the release of MPO from PMNs cultured on PEG hydrogels, TCPS and GP hydrogels and in the release of MMP-9 from PMNs cultured on all four materials. The increased release of primary granules from PMNs on PEG-containing hydrogels did not significantly increase MC chemotaxis, indicating that additional co-effectors in the dynamic inflammatory milieu in vivo modulate PMN-mediated MC recruitment. PMID:24497370

Comparison of elastic properties of nickel-titanium orthodontic archwires.

PubMed

Sarul, Michał; Kowala, Beata; Antoszewska, Joanna

2013-01-01

Cognizance of the mechanical properties of nickel-titanium archwires is necessary for the management of orthodontic therapy with fixed appliances. Acting on the periodontium with forces that are too heavy may lead to such complications as: pain, tooth root resorption and destruction of the alveolar bone and may also lead to retardation in tooth movement. The aim of the study was to assess the activation and deactivation forces of nickel-titanium archwires: Titanol Superelastic, Copper NiTi 35oC and NeoSentalloy. The examined material was 90 samples of Titanol Superelastic, Copper NiTi 35oC and NeoSentalloy with diameters of 0.016 and 0.016 x 0.022. All tests were carried out on the Zwick mechanical tests machine at a temperature of 30o C. In the group of archwires with diameters 0.016, the levels of deactivation forces were, respectively, from highest to lowest: Titanol Supertelastic, NeoSentalloy, Copper NiTi 35oC. In the group of rectangular archwires 0.016 x 0.022, the highest deactivation forces were released in Titanol Superelastic. With the high levels of deflection, 0.016 x 0.022 NeoSentalloy archwires released statistically significantly higher levels of force than 0.016 x 0.022 Copper NiTi 35o C, but this force diminished rapidly with lower deflection and below 3 mm of deflection, the highest forces were released by Copper NiTi 35o C. Testing the mechanical properties of the nickel-titanium wires of various diameters, it was found that round section wires release forces which fall within the range of optimal forces.

Release of chlorinated, brominated and mixed halogenated dioxin-related compounds to soils from open burning of e-waste in Agbogbloshie (Accra, Ghana).

PubMed

Tue, Nguyen Minh; Goto, Akitoshi; Takahashi, Shin; Itai, Takaaki; Asante, Kwadwo Ansong; Kunisue, Tatsuya; Tanabe, Shinsuke

2016-01-25

Although complex mixtures of dioxin-related compounds (DRCs) can be released from informal e-waste recycling, DRC contamination in African e-waste recycling sites has not been investigated. This study examined the concentrations of DRCs including chlorinated, brominated, mixed halogenated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs, PBDD/Fs, PXDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in surface soil samples from the Agbogbloshie e-waste recycling site in Ghana. PCDD/F and PBDD/F concentrations in open burning areas (18-520 and 83-3800 ng/g dry, respectively) were among the highest reported in soils from informal e-waste sites. The concentrations of PCDFs and PBDFs were higher than those of the respective dibenzo-p-dioxins, suggesting combustion and PBDE-containing plastics as principal sources. PXDFs were found as more abundant than PCDFs, and higher brominated analogues occurred at higher concentrations. The median total WHO toxic equivalent (TEQ) concentration in open burning soils was 7 times higher than the U.S. action level (1000 pg/g), with TEQ contributors in the order of PBDFs>PCDD/Fs>PXDFs. DRC emission to soils over the e-waste site as of 2010 was estimated, from surface soil lightness based on the correlations between concentrations and lightness, at 200mg (95% confidence interval 93-540 mg) WHO-TEQ over three years. People living in Agbogbloshie are potentially exposed to high levels of not only chlorinated but also brominated DRCs, and human health implications need to be assessed in future studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Involvement of pituitary gonadotropins, gonadal steroids and breeding season in sex change of protogynous dusky grouper, Epinephelus marginatus (Teleostei: Serranidae), induced by a non-steroidal aromatase inhibitor.

PubMed

Garcia, Carlos Eduardo de O; Araújo, Bruno C; Mello, Paulo H; Narcizo, Amanda de M; Rodrigues-Filho, Jandyr A; Medrado, Andreone T; Zampieri, Ricardo A; Floeter-Winter, Lucile M; Moreira, Renata Guimarães

2013-10-01

Two experiments were performed using the aromatase inhibitor (AI) letrozole (100mg/kg) to promote sex change, from female-to-male, in protogynous dusky grouper. One experiment was performed during the breeding season (spring) and the other at the end of the breeding season (summer). During the spring, AI promoted sex change after 9 weeks and the sperm produced was able to fertilize grouper oocytes. During the summer, the sex change was incomplete; intersex individuals were present and sperm was not released by any of the animals. Sex changed gonads had a lamellar architecture; cysts of spermatocytes and spermatozoa in the lumen of the germinal compartment. In the spring, after 4 weeks, 11ketotestosterone (11KT) levels were higher in the AI than in control fish, and after 9 weeks, coincident with semen release, testosterone levels increased in the AI group, while 11KT returned to the initial levels. Estradiol (E2) levels remained unchanged during the experimental period. Instead of decreasing throughout the period, as in control group, 17 α-OH progesterone levels did not change in the AI-treated fish, resulting in higher values after 9 weeks when compared with control fish. fshβ and lhβ gene expression in the AI animals were lower compared with control fish after 9 weeks. The use of AI was effective to obtain functional males during the breeding season. The increase in androgens, modulated by gonadotropins, triggered the sex change, enabling the development of male germ cells, whereas a decrease in E2 levels was not required to change sex in dusky grouper. Copyright © 2013 Elsevier Inc. All rights reserved.

Strong Foundations: The State of State Postsecondary Data Systems--2012 Update on Data Sharing with K-12 and Labor

ERIC Educational Resources Information Center

Garcia, Tanya I.; L'Orange, Hans Peter

2012-01-01

In 2010, the State Higher Education Executive Officers Association released the results of a national study of state level postsecondary student unit record (SUR) data systems in 44 states and the District of Columbia (D.C.). One section of the report, "Strong Foundations: The State of State Postsecondary Data Systems" (Garcia and L'Orange 2010),…

Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity

PubMed Central

Sacchi, Silvia; Novellis, Vito De; Paolone, Giovanna; Nuzzo, Tommaso; Iannotta, Monica; Belardo, Carmela; Squillace, Marta; Bolognesi, Paolo; Rosini, Elena; Motta, Zoraide; Frassineti, Martina; Bertolino, Alessandro; Pollegioni, Loredano; Morari, Michele; Maione, Sabatino; Errico, Francesco; Usiello, Alessandro

2017-01-01

D-aspartate levels in the brain are regulated by the catabolic enzyme D-aspartate oxidase (DDO). D-aspartate activates NMDA receptors, and influences brain connectivity and behaviors relevant to schizophrenia in animal models. In addition, recent evidence reported a significant reduction of D-aspartate levels in the post-mortem brain of schizophrenia-affected patients, associated to higher DDO activity. In the present work, microdialysis experiments in freely moving mice revealed that exogenously administered D-aspartate efficiently cross the blood brain barrier and stimulates L-glutamate efflux in the prefrontal cortex (PFC). Consistently, D-aspartate was able to evoke L-glutamate release in a preparation of cortical synaptosomes through presynaptic stimulation of NMDA, mGlu5 and AMPA/kainate receptors. In support of a potential therapeutic relevance of D-aspartate metabolism in schizophrenia, in vitro enzymatic assays revealed that the second-generation antipsychotic olanzapine, differently to clozapine, chlorpromazine, haloperidol, bupropion, fluoxetine and amitriptyline, inhibits the human DDO activity. In line with in vitro evidence, chronic systemic administration of olanzapine induces a significant extracellular release of D-aspartate and L-glutamate in the PFC of freely moving mice, which is suppressed in Ddo knockout animals. These results suggest that the second-generation antipsychotic olanzapine, through the inhibition of DDO activity, increases L-glutamate release in the PFC of treated mice. PMID:28393897

Fluoride loaded polymeric nanoparticles for dental delivery.

PubMed

Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro; Hiorth, Marianne

2017-06-15

The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33-113ppm, and the entrapment efficiency 3.6-6.2% for chitosan nanoparticles prepared in 0.2-0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic cytotoxic effects of ions released by zinc-aluminum bronze and the metallic salts on osteoblastic cells.

PubMed

Grillo, Claudia A; Morales, María L; Mirífico, María V; Fernández Lorenzo de Mele, Mónica A

2013-07-01

The use of copper-based alloys for fixed dental crowns and bridges is increasingly widespread in several countries. The aim of this work is to study the dissolution of a zinc-aluminum-bronze and the cytotoxic effects of the ions released on UMR-106 osteoblastic cell line. Two sources of ions were used: (1) ions released by the metal alloy immersed in the cell culture and (2) salts of the metal ions. Conventional electrochemical techniques, atomic absorption spectroscopy [to obtain the average concentration of ions (AC) in solution], and energy dispersive X-ray (EDX) spectroscopy analysis were used to study the corrosion process. Corrosion tests revealed a strong influence of the composition of the electrolyte medium and the immersion time on the electrochemical response. The cytotoxicity was evaluated with (a) individual ions, (b) combinations of two ions, and (c) the mixture of all the ions released by a metal disc of the alloy. Importantly, synergistic cytotoxic effects were found when Al-Zn ion combinations were used at concentration levels lower than the cytotoxic threshold values of the individual ions. Cytotoxic effects in cells in the vicinity of the metal disc were also found. These results were interpreted considering synergistic effects and a diffusion controlled mechanism that yields to concentration levels, in the metal surroundings, several times higher than the measured AC value. Copyright © 2013 Wiley Periodicals, Inc.

Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea.

PubMed

Berga, S L; Loucks-Daniels, T L; Adler, L J; Chrousos, G P; Cameron, J L; Matthews, K A; Marcus, M D

2000-04-01

Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.

High resolution monitoring system for IRE stack releases.

PubMed

Deconninck, B; De Lellis, C

2013-11-01

The main activity of IRE (Institute for Radio-Element) is radioisotope production of bulk (99)Mo and (131)I for medical application (diagnosis and therapy). Those isotopes are chemically extracted from HEU (High Enriched Uranium) targets activated in reactors. During this process, fission products are released from the targets, including noble gases isotopes (Xe and Kr). Like any nuclear plant, IRE has release limits which are given by the Belgium authority and moreover IRE is in the process of continuously reducing the level of its releases. To achieve this mission, the need of an accurate tool is necessary and IRE has developed a specific monitoring system using a high resolution detector in order to identify and accurately estimate its gaseous releases. This system has a continuous air sampling system in the plant main stack. The sampled gases cross charcoal cartridges where they are slowed down and concentrated for higher detection efficiency. In front of those cartridges is installed an HPGe detector with a detection chain connected to a specific analysis system allowing on-line spectrum analysis. Each isotope can be separately followed without interferences, especially during the production process where high activity can be released. Due to its conception, the system also allows to measure iodine isotopes by integration on the charcoal cartridges. This device is of great help for accurately estimate IRE releases and to help for understanding specific releases and their origin in the production or maintenance process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of early salmon louse, Lepeophtheirus salmonis, infestation and differences in survival and marine growth of sea-ranched Atlantic salmon, Salmo salar L., smolts 1997–2009

PubMed Central

Skilbrei, O T; Finstad, B; Urdal, K; Bakke, G; Kroglund, F; Strand, R

2013-01-01

The impact of salmon lice on the survival of migrating Atlantic salmon smolts was studied by comparing the adult returns of sea-ranched smolts treated for sea lice using emamectin benzoate or substance EX with untreated control groups in the River Dale in western Norway. A total of 143 500 smolts were released in 35 release groups in freshwater from 1997 to 2009 and in the fjord system from 2007 to 2009. The adult recaptures declined gradually with release year and reached minimum levels in 2007. This development corresponded with poor marine growth and increased age at maturity of ranched salmon and in three monitored salmon populations and indicated unfavourable conditions in the Norwegian Sea. The recapture rate of treated smolts was significantly higher than the controls in three of the releases performed: the only release in 1997, one of three in 2002 and the only group released in sea water in 2007. The effect of treating the smolts against salmon lice was smaller than the variability in return rates between release groups, and much smaller that variability between release years, but its overall contribution was still significant (P < 0.05) and equivalent to an odds ratio of the probability of being recaptured of 1.17 in favour of the treated smolts. Control fish also tended to be smaller as grilse (P = 0.057), possibly due to a sublethal effect of salmon lice. PMID:23311746

Metal ion release from silver soldering and laser welding caused by different types of mouthwash.

PubMed

Erdogan, Ayse Tuygun; Nalbantgil, Didem; Ulkur, Feyza; Sahin, Fikrettin

2015-07-01

To compare metal ion release from samples welded with silver soldering and laser welding when immersed into mouthwashes with different ingredients. A total of 72 samples were prepared: 36 laser welded and 36 silver soldered. Four samples were chosen from each subgroup to study the morphologic changes on their surfaces via scanning electron microscopy (SEM). Each group was further divided into four groups where the samples were submerged into mouthwash containing sodium fluoride (NaF), mouthwash containing sodium fluoride + alcohol (NaF + alcohol), mouthwash containing chlorhexidine (CHX), or artificial saliva (AS) for 24 hours and removed thereafter. Subsequently, the metal ion release from the samples was measured with inductively coupled plasma mass spectrometry (ICP-MS). The metal ion release among the solutions and the welding methods were compared. The Kruskal-Wallis and analysis of variance (ANOVA) tests were used for the group comparisons, and post hoc Dunn multiple comparison test was utilized for the two group comparisons. The level of metal ion release from samples of silver soldering was higher than from samples of laser welding. Furthermore, greater amounts of nickel, chrome, and iron were released from silver soldering. With regard to the mouthwash solutions, the lowest amounts of metal ions were released in CHX, and the highest amounts of metal ions were released in NaF + alcohol. SEM images were in accord with these findings. The laser welding should be preferred over silver soldering. CHX can be recommended for patients who have welded appliances for orthodontic reasons.

Physicochemical Characteristics and Slow Release Performances of Chlorpyrifos Encapsulated by Poly(butyl acrylate-co-styrene) with the Cross-Linker Ethylene Glycol Dimethacrylate.

PubMed

Wang, Yu; Gao, Zideng; Shen, Feng; Li, Yang; Zhang, Sainan; Ren, Xueqin; Hu, Shuwen

2015-06-03

Chlorpyrifos' application and delivery to the target substrate needs to be controlled to improve its use. Herein, poly(butyl acrylate-co-styrene) (poly(BA/St)) and poly(BA/St/ethylene glycol dimethacrylate (EGDMA)) microcapsules loaded with chlorpyrifos as a slow release formulation were prepared by emulsion polymerization. The effects of structural characteristics on the chlorpyrifos microcapsule particle size, entrapment rate (ER), pesticide loading (PL), and release behaviors in ethyl alcohol were investigated. Fourier transform infrared and thermogravimetric analysis confirmed the successful entrapment of chlorpyrifos. The ER and PL varied with the BA/St monomer ratio, chlorpyrifos/monomer core-to-shell ratio, and EGDMA cross-linker content with consequence that suitable PL was estimated to be smaller than 3.09% and the highest ER was observed as 96.74%. The microcapsule particle size (88.36-101.8 nm) remained mostly constant. The extent of sustainable release decreased with increasing content of BA, St, or chlorpyrifos in the oil phase. Specifically, an adequate degree of cross-linking with EGMDA (0.5-2.5%) increased the extent of sustainable release considerably. However, higher levels of cross-linking with EGDMA (5-10%) reduced the extent of sustainable release. Chlorpyrifos release from specific microcapsules (monomer ratio 1:2 with 0.5% EGDMA or 5 g chlopyrifos) tended to be a diffusion-controlled process, while for others, the kinetics probably indicated the initial rupture release.

The influence of photodynamic therapy (PDT) with δ-aminolevulinic acid (ALA) on J-774A.1 macrophage cell line

NASA Astrophysics Data System (ADS)

Kawczyk-Krupka, Aleksandra; Czuba, Zenon; Ledwon, Aleksandra; Latos, Wojciech; Sliszka, Ewelina; Mianowska, Marta; Krol, Wojciech; Sieron, Aleksander

2008-02-01

Introduction. The whole mechanism of the cellular level of tumor destruction by photodynamic therapy (PDT) is still unknown. Despite necrotic and apoptotic ways of cell death, there is a variety of events leading to and magnifying the inactivation of tumor cells. Material and methods. J-774A.1 were incubated with δ-aminolevulinic acid (ALA) at different concentrations (125, 250, 500, 1000 μM) and then irradiated with VIS (400 - 750 nm) at the dose of 5,10 and 30 J/cm2 delivered from the incoherent light source. The effects of the application of ALA-PDT were evaluated on the basis of cell viability, nitric oxide (NO), tumor necrosis factor α- (TNF-α) and interleukin-1β (IL-1β) produced by the J-774A.1 cells. Results. The cell viability (assessed using MTT test) was comparable with control group at 5,10 and 30 J/cm2. At these doses of energy using different concentrations of ALA we have observed that at the higher energy doses, the greater increase of TNF-α release, lowering of the level of IL-1β production and decrease of NO release were observed. There was also observed the dependence of the secretional activity of the cells on the ALA concentrations. Conclusion. The cell viability and production of cytokines depended on ALA concentrations and energy doses of the light. The higher some cytokines' release after PDT could be an additional factor for the complete eradication of tumor.

Depot-dependent effects of adipose tissue explants on co-cultured hepatocytes.

PubMed

Du, Zhen-Yu; Ma, Tao; Lock, Erik-Jan; Hao, Qin; Kristiansen, Karsten; Frøyland, Livar; Madsen, Lise

2011-01-01

We have developed an in vitro hepatocyte-adipose tissue explant (ATE) co-culture model enabling examination of the effect of visceral and subcutaneous adipose tissues on primary rat hepatocytes. Initial analyses of inflammatory marker genes were performed in fractionated epididymal or inguinal adipose tissues. Expressions of inflammation related genes (IL-6, TNF-α, COX-2) were higher in the inguinal than the epididymal ATE. Similarly, expressions of marker genes of macrophage and monocyte (MPEG-1, CD68, F4/80, CD64) were higher in the stromal vascular fraction (SVF) isolated from inguinal ATE than that from epididymal ATE. However, expressions of lipolysis related genes (ATGL, HSL, perilipin-1) were higher in the epididymal adipocytes than inguinal adipocytes. Moreover, secretion of IL-6 and PGE(2) was higher from inguinal ATEs than from epididymal ATEs. There was a trend that the total levels of IL-6, TNF-α and PGE(2) in the media from inguinal ATEs co-cultured with primary rat hepatocytes were higher than that in the media from epididymal ATEs co-cultured with hepatocytes, although the significant difference was only seen in PGE(2). Lipolysis, measured as glycerol release, was similar in the ATEs isolated from inguinal and epididymal adipose tissues when cultured alone, but the glycerol release was higher in the ATEs isolated from epididymal than from inguinal adipose tissue when co-cultured with hepatocytes. Compared to epididymal ATEs, the ATEs from inguinal adipose tissue elicited a stronger cytotoxic response and higher level of insulin resistance in the co-cultured hepatocytes. In conclusion, our results reveal depot-dependent effects of ATEs on co-cultured primary hepatocytes, which in part may be related to a more pronounced infiltration of stromal vascular cells (SVCs), particularly macrophages, in inguinal adipose tissue resulting in stronger responses in terms of hepatotoxicity and insulin-resistance.

A Monte Carlo model reveals independent signaling at central glutamatergic synapses.

PubMed Central

Franks, Kevin M; Bartol, Thomas M; Sejnowski, Terrence J

2002-01-01

We have developed a biophysically realistic model of receptor activation at an idealized central glutamatergic synapse that uses Monte Carlo techniques to simulate the stochastic nature of transmission following release of a single synaptic vesicle. For the a synapse with 80 AMPA and 20 NMDA receptors, a single quantum, with 3000 glutamate molecules, opened approximately 3 NMDARs and 20 AMPARs. The number of open receptors varied directly with the total number of receptors, and the fraction of open receptors did not depend on the ratio of co-localized AMPARs and NMDARs. Variability decreased with increases in either total receptor number or quantal size, and differences between the variability of AMPAR and NMDAR responses were due solely to unequal numbers of receptors at the synapse. Despite NMDARs having a much higher affinity for glutamate than AMPARs, quantal release resulted in similar occupancy levels in both receptor types. Receptor activation increased with number of transmitter molecules released or total receptor number, whereas occupancy levels were only dependent on quantal size. Tortuous diffusion spaces reduced the extent of spillover and the activation of extrasynaptic receptors. These results support the conclusion that signaling is spatially independent within and between central glutamatergic synapses. PMID:12414671

In vitro fluoride release from a different kind of conventional and resin modified glass-ionomer cements

PubMed Central

Selimović-Dragaš, Mediha; Hasić-Branković, Lajla; Korać, Fehim; Đapo, Nermin; Huseinbegović, Amina; Kobašlija, Sedin; Lekić, Meliha; Hatibović-Kofman, Šahza

2013-01-01

Fluoride release is important characteristic of glass-ionomer cements. Quantity of fluoride ions released from the glass-ionomer cements has major importance in definition of their biological activity. The objectives of this study were to define the quantity of fluoride ions released from the experimental glass-ionomer cements and to define the effect of fluoride ions released from the experimental glass-ionomer cements on their cytotoxicity. Concentrations of the fluoride ions released in the evaluated glass-ionomer cements were measured indirectly, by the fluoride-selective WTW, F500 electrode potential, combined with reference R503/D electrode. Statistical analyses of F-ion concentrations released by all glass-ionomers evaluated at two time points, after 8 and after 24 hours, show statistically higher fluoride releases from RMGICs: Vitrebond, Fuji II LC and Fuji Plus, when compared to conventional glass-ionomer cements: Fuji Triage, Fuji IX GP Fast and Ketac Silver, both after 8 and after 24 hours. Correlation coefficient between concentrations of fluoride ion released by evaluated glass-ionomer cements and cytotoxic response of UMR-106 osteoblast cell-line are relatively high, but do not reach levels of biological significance. Correlation between concentrations of fluoride ion released and cytotoxic response of NIH3T3 mouse fibroblast cell line after 8 hours is high, positive and statistically significant for conventional GICs, Fuji Triage and Fuji IX GP Fast, and RMGIC, Fuji II LC. Statistically significant Correlation coefficient between concentrations of fluoride ion released and cytotoxic response of NIH3T3 cell line after 24 hours is defined for RMGIC Fuji II LC only. PMID:23988173

Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

PubMed

Hiremath, Praveen S; Saha, Ranendra N

2008-10-01

The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

Stress-induced release of the S100A8/A9 alarmin is elevated in coronary artery disease patients with impaired cortisol response.

PubMed

Jonasson, L; Grauen Larsen, H; Lundberg, A K; Gullstrand, B; Bengtsson, A A; Schiopu, A

2017-12-13

Psychological stress is thought to be an important trigger of cardiovascular events, yet the involved pathways and mediators are largely unknown. Elevated systemic levels of the pro-inflammatory alarmin S100A8/A9 correlate with poor prognosis in coronary artery disease (CAD) patients. Here, we investigated the links between S100A8/A9 release and parameters of anti-inflammatory glucocorticoid secretion in two different cohorts subjected to a psychological stress test. In the first cohort of 60 CAD patients, psychological stress induced a rapid increase of circulating S100A8/A9. This rapid S100A8/A9 response strongly correlated with elevated evening saliva cortisol levels, suggesting an association with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. In the second cohort of 27 CAD patients and 28 controls, elevated S100A8/A9 levels were still detectable 24 h after stress in 40% of patients and 36% of controls, with a tendency for higher levels in patients. The sustained S100A8/A9 response was associated with a poor rapid cortisol release after stress in patients, but not in the control group. Our findings reveal for the first time that acute psychological stress induces elevated levels of S100A8/A9. We also provide hypothesis-generating evidence that dysregulated cortisol secretion in CAD patients might be associated with an exaggerated pro-inflammatory S100A8/A9 response.

A Systematic Review of Tennis Elbow Surgery: Open Versus Arthroscopic Versus Percutaneous Release of the Common Extensor Origin.

PubMed

Pierce, Todd P; Issa, Kimona; Gilbert, Benjamin T; Hanly, Brian; Festa, Anthony; McInerney, Vincent K; Scillia, Anthony J

2017-06-01

To compare complications, function, pain, and patient satisfaction after conventional open, percutaneous, or arthroscopic release of the extensor origin for the treatment of lateral epicondylitis. A thorough review of 4 databases-PubMed, EBSCOhost, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus, and Scopus-was performed to identify all studies that addressed surgical management of lateral epicondylitis. We included (1) studies published between 2000 and 2015 and (2) studies with clearly defined surgical techniques. We excluded (1) non-English-language manuscripts, (2) isolated case reports, (3) studies with fewer than 10 subjects, (4) animal studies, (5) studies with additional adjunctive procedures aside from release of the extensor origin, (6) clinical or systematic review manuscripts, (7) studies with a follow-up period of 6 months or less, and (8) studies in which less than 80% of patients completed follow-up. Each study was analyzed for complication rates, functional outcomes, pain, and patient satisfaction. Thirty reports were identified that included 848 open, 578 arthroscopic, and 178 percutaneous releases. Patients within each release group had a similar age (46 years vs 46 years vs 48 years; P = .9 and P = .4, respectively), whereas there was a longer follow-up time in patients who underwent surgery by an open technique (49.4 months vs 42.6 months vs 23 months, P < .001). There were no differences in complication rates among these techniques (3.8% vs 2.9% vs 3.9%; P = .5 and P = .9, respectively). However, open techniques were correlated with higher surgical-site infection rates than arthroscopic techniques (0.7% vs 0%, P = .04). Mean Disabilities of the Arm, Shoulder and Hand scores were substantially better with both open and arthroscopic techniques than with percutaneous release (19.9 points vs 21.3 points vs 29 points, P < .001). In addition, there was less pain reported in the arthroscopic and percutaneous release groups as opposed to their open counterparts (1.9 points vs 1.4 points vs 1.3 points, P < .0001). There were no differences among the techniques in patient satisfaction rate (93.7% vs 89% vs 88%; P = .08 and P = .07, respectively). Functional outcomes of open and arthroscopic releases may be superior to those of percutaneous release. In addition, patients may report less pain with arthroscopic and percutaneous techniques. Although the risk of complications is similar regardless of technique, patients may be counseled that their risk of infectious complications may be slightly higher with open releases. However, it is important to note that this statistical difference may not necessarily portend noticeable clinical differences. Level IV, systematic review of Level III and IV evidence. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

NASA Astrophysics Data System (ADS)

Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

Analysis of Silicones Released from Household Items and Baby Articles by Direct Analysis in Real Time-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Gross, Jürgen H.

2015-03-01

Direct analysis in real time-mass spectrometry (DART-MS) enables screening of articles of daily use made of polydimethylsiloxanes (PDMS), commonly known as silicone rubber, to assess their tendency to release low molecular weight silicone oligomers. DART-MS analyses were performed on a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Flexible silicone baking molds, a watch band, and a dough scraper, as baby articles different brands of pacifiers, nipples, and a teething ring have been examined. While somewhat arbitrarily chosen, the set can be regarded as representative of household items, baby articles, and other objects made of silicone rubber. For comparison, two brands of silicone septa and as blanks a glass slide and a latex pacifier were included. Differences between the objects were mainly observed in terms of molecular weight distribution and occasional release of other compounds in addition to PDMS. Other than that, all objects made of silicone rubber released significant amounts of PDMS during DART analysis. To provide a coarse quantification, a calibration based on silicone oil was established, which delivered PDMS losses from 20 μg to >100 μg during the 16-s period per measurement. Also, the extraction of baking molds in rapeseed oil demonstrated a PDMS release at the level of 1 μg mg-1. These findings indicate a potential health hazard from frequent or long-term use of such items. This work does not intend to blame certain brands of such articles. Nonetheless, a higher level of awareness of this source of daily silicone intake is suggested.

A Microparticle/Hydrogel Combination Drug-Delivery System for Sustained Release of Retinoids

PubMed Central

Gao, Song-Qi; Maeda, Tadao; Okano, Kiichiro; Palczewski, Krzysztof

2012-01-01

Purpose. To design and develop a drug-delivery system containing a combination of poly(d,l-lactide-co-glycolide) (PLGA) microparticles and alginate hydrogel for sustained release of retinoids to treat retinal blinding diseases that result from an inadequate supply of retinol and generation of 11-cis-retinal. Methods. To study drug release in vivo, either the drug-loaded microparticle–hydrogel combination was injected subcutaneously or drug-loaded microparticles were injected intravitreally into Lrat−/− mice. Orally administered 9-cis-retinoids were used for comparison and drug concentrations in plasma were determined by HPLC. Electroretinography (ERG) and both chemical and histologic analyses were used to evaluate drug effects on visual function and morphology. Results. Lrat−/− mice demonstrated sustained drug release from the microparticle/hydrogel combination that lasted 4 weeks after subcutaneous injection. Drug concentrations in plasma of the control group treated with the same oral dose rose to higher levels for 6−7 hours but then dropped markedly by 24 hours. Significantly increased ERG responses and a markedly improved retinal pigmented epithelium (RPE)–rod outer segment (ROS) interface were observed after subcutaneous injection of the drug-loaded delivery combination. Intravitreal injection of just 2% of the systemic dose of drug-loaded microparticles provided comparable therapeutic efficacy. Conclusions. Sustained release of therapeutic levels of 9-cis-retinoids was achieved in Lrat−/− mice by subcutaneous injection in a microparticle/hydrogel drug-delivery system. Both subcutaneous and intravitreal injections of drug-loaded microparticles into Lrat−/− mice improved visual function and retinal structure. PMID:22918645

Analysis of silicones released from household items and baby articles by direct analysis in real time-mass spectrometry.

PubMed

Gross, Jürgen H

2015-03-01

Direct analysis in real time-mass spectrometry (DART-MS) enables screening of articles of daily use made of polydimethylsiloxanes (PDMS), commonly known as silicone rubber, to assess their tendency to release low molecular weight silicone oligomers. DART-MS analyses were performed on a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Flexible silicone baking molds, a watch band, and a dough scraper, as baby articles different brands of pacifiers, nipples, and a teething ring have been examined. While somewhat arbitrarily chosen, the set can be regarded as representative of household items, baby articles, and other objects made of silicone rubber. For comparison, two brands of silicone septa and as blanks a glass slide and a latex pacifier were included. Differences between the objects were mainly observed in terms of molecular weight distribution and occasional release of other compounds in addition to PDMS. Other than that, all objects made of silicone rubber released significant amounts of PDMS during DART analysis. To provide a coarse quantification, a calibration based on silicone oil was established, which delivered PDMS losses from 20 μg to >100 μg during the 16-s period per measurement. Also, the extraction of baking molds in rapeseed oil demonstrated a PDMS release at the level of 1 μg mg(-1). These findings indicate a potential health hazard from frequent or long-term use of such items. This work does not intend to blame certain brands of such articles. Nonetheless, a higher level of awareness of this source of daily silicone intake is suggested.

Organic Carbon Release from Groundwater Sediments under Changing Geochemical Conditions

NASA Astrophysics Data System (ADS)

Tinnacher, R. M.; Bhattacharyya, A.; Fox, P. M.; Nico, P. S.

2016-12-01

Due to climate change, local weather patterns are expected to change, especially with respect to precipitation, the frequency of extreme storm water events, and `drought-like' conditions. This in turn, may affect groundwater recharge, the geochemical conditions in natural groundwater systems, and the chemical and microbiological processes involved in organic matter degradation. Besides the complexity of organic matter structures and local limitations in nutrients, the association of organic carbon with sediment minerals can strongly limit organic matter bioaccessability and degradability. In this study, we investigate how variations in groundwater chemistry, e.g. with respect to dissolved CO2 concentrations, may potentially affect the release of natural organic carbon from groundwater sediments, and render organic matter more bioaccessible. In lab-scale experiments under anaerobic conditions, aquifer sediments from the floodplain of the Colorado River (Rifle, USA) were brought into contact with fresh, organic-carbon free groundwater solutions, at natural or reduced CO2 concentration levels. During the repeated exchange of solutions at two temperature settings (room-temperature and 4 °C), supernatant solutions were characterized in terms of pH, dissolved metal and organic carbon (OC) concentrations, and potential changes in released OC characteristics. Sediment samples were evaluated for possible differences in Fe-speciation before and after the experiment based on EXAFS (bulk Fe K-edge). Preliminary results for 20 exchanges of groundwater solutions show a repeated release of low OC concentrations ( 0.5-2 mg OC/g sediment; 0.05-0.2% of sediment-associated OC) without any apparent depletion in the overall source term over 50 days. After 14 days, room-temperature samples released slightly higher OC concentrations than samples kept at 4 °C. An increase in solution pH, after switching to a `CO2-free' groundwater solution, did not trigger a higher OC release. Last, specific UV absorbance measurements for room-temperature samples suggest changes in released OC characteristics due to repeated solution exchanges. Additional sample characterization is ongoing, with the goal to elucidate potential changes in released OC characteristics over the course of the experiment.

A diels-alder modulated approach to control and sustain the release of dexamethasone and induce osteogenic differentiation of human mesenchymal stem cells

PubMed Central

Koehler, Kenneth C.; Alge, Daniel L.; Anseth, Kristi S.; Bowman, Christopher N.

2013-01-01

We report a new approach to controlled drug release based upon exploiting the dynamic equilibrium that exists between Diels-Alder reactants and products, demonstrating the release of a furan containing dexamethasone peptide (dex-KGPQG-furan) from a maleimide containing hydrogel. Using a reaction-diffusion model, the release kinetics were tuned to achieve sustained concentrations conducive to osteogenic differentiation of human mesenchymal stem cells (hMSCs). Efficacy was first demonstrated in a 2D culture model, in which dexamethasone release induced significant increases in alkaline phosphatase (ALP) activity and mineral deposition in hMSCs compared to a dexamethasone-free treatment. The results were similar to that observed with a soluble dexamethasone treatment. More dramatic differences were observed in 3D culture, where co-encapsulation of a dexamethasone releasing hydrogel depot within an hMSC-laden extracellular matrix mimetic poly(ethylene glycol) hydrogel resulted in a local and robust osteogenic differentiation. ALP activity reached levels that were up to six times higher than the dexamethasone free treatment. Interestingly, at 5 and 10 day time points, the ALP activity exceeded the dexamethasone positive control, suggesting a potential benefit of sustained release in 3D culture. After 21 days, substantial mineralization comparable to the positive control was also observed in the hydrogels. Collectively, these results demonstrate Diels-Alder modulated release as an effective and versatile new platform for controlled drug delivery that may prove especially beneficial for sustaining the release of low molecular weight molecules in hydrogel systems. PMID:23465826

Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery.

PubMed

Gu, Zhen; Dang, Tram T; Ma, Minglin; Tang, Benjamin C; Cheng, Hao; Jiang, Shan; Dong, Yizhou; Zhang, Yunlong; Anderson, Daniel G

2013-08-27

A glucose-responsive closed-loop insulin delivery system represents the ideal treatment of type 1 diabetes mellitus. In this study, we develop uniform injectable microgels for controlled glucose-responsive release of insulin. Monodisperse microgels (256 ± 18 μm), consisting of a pH-responsive chitosan matrix, enzyme nanocapsules, and recombinant human insulin, were fabricated through a one-step electrospray procedure. Glucose-specific enzymes were covalently encapsulated into the nanocapsules to improve enzymatic stability by protecting from denaturation and immunogenicity as well as to minimize loss due to diffusion from the matrix. The microgel system swelled when subjected to hyperglycemic conditions, as a result of the enzymatic conversion of glucose into gluconic acid and protonation of the chitosan network. Acting as a self-regulating valve system, microgels were adjusted to release insulin at basal release rates under normoglycemic conditions and at higher rates under hyperglycemic conditions. Finally, we demonstrated that these microgels with enzyme nanocapsules facilitate insulin release and result in a reduction of blood glucose levels in a mouse model of type 1 diabetes.

Particle emissions from laboratory activities involving carbon nanotubes

NASA Astrophysics Data System (ADS)

Lo, Li-Ming; Tsai, Candace S.-J.; Heitbrink, William A.; Dunn, Kevin H.; Topmiller, Jennifer; Ellenbecker, Michael

2017-08-01

This site study was conducted in a chemical laboratory to evaluate nanomaterial emissions from 20-30-nm-diameter bundles of single-walled carbon nanotubes (CNTs) during product development activities. Direct-reading instruments were used to monitor the tasks in real time, and airborne particles were collected using various methods to characterize released nanomaterials using electron microscopy and elemental carbon (EC) analyses. CNT clusters and a few high-aspect-ratio particles were identified as being released from some activities. The EC concentration (0.87 μg/m3) at the source of probe sonication was found to be higher than other activities including weighing, mixing, centrifugation, coating, and cutting. Various sampling methods all indicated different levels of CNTs from the activities; however, the sonication process was found to release the highest amounts of CNTs. It can be cautiously concluded that the task of probe sonication possibly released nanomaterials into the laboratory and posed a risk of surface contamination. Based on these results, the sonication of CNT suspension should be covered or conducted inside a ventilated enclosure with proper filtration or a glovebox to minimize the potential of exposure.

Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype.

PubMed

Mantione, K; Zhu, W; Rialas, C; Casares, F; Cadet, P; Franklin, A L; Tonnesen, J; Stefano, G B

2002-03-01

We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining a receptor displacement analysis, both opiate alkaloids displaced [3H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again suggesting that a novel mu opiate receptor may be present.

Strategies to overcome pH-dependent solubility of weakly basic drugs by using different types of alginates.

PubMed

Gutsche, S; Krause, M; Kranz, H

2008-12-01

Weakly basic drugs demonstrate higher solubility at lower pH, thus often leading to faster drug release at lower pH. The objective of this study was to achieve pH-independent release of weakly basic drugs from extended release formulations based on the naturally occurring polymer sodium alginate. Three approaches to overcome the pH-dependent solubility of the weakly basic model drug verapamil hydrochloride were investigated. First, matrix tablets were prepared by direct compression of drug substance with different types of sodium alginate only. Second, pH-modifiers were added to the drug/alginate matrix systems. Third, press-coated tablets consisting of an inner pH-modifier tablet core and an outer drug/sodium alginate coat were prepared. pH-Independent drug release was achieved from matrix tablets consisting of selected alginates and drug substance only. Alginates are better soluble at higher pH. Therefore, they are able to compensate the poor solubility of weakly basic drugs at higher pH as the matrix of the tablets dissolves faster. This approach was successful when using alginates that demonstrated fast hydration and erosion at higher pH. The approach failed for alginates with less-pronounced erosion at higher pH. The addition of fumaric acid to drug/alginate-based matrix systems decreased the microenvironmental pH within the tablets thus increasing the solubility of the weakly basic drug at higher pH. Therefore, pH-independent drug release was achieved irrespective of the type of alginate used. Drug release from press-coated tablets did not provide any further advantages as compound release remained pH-dependent.

Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release.

PubMed

Formica, S; Roach, T I; Blackwell, J M

1994-05-01

The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic proline/serine-rich putative SH3 binding domain.

Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress

NASA Astrophysics Data System (ADS)

Pangeni, Rudra; Sharma, Shrestha; Mustafa, Gulam; Ali, Javed; Baboota, Sanjula

2014-12-01

Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson’s disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml-1 of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

Release of Phosphorylated HSP27 (HSPB1) from Platelets Is Accompanied with the Acceleration of Aggregation in Diabetic Patients

PubMed Central

Tokuda, Haruhiko; Kuroyanagi, Gen; Tsujimoto, Masanori; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Onuma, Takashi; Kojima, Akiko; Doi, Tomoaki; Tanabe, Kumiko; Akamatsu, Shigeru; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Iwama, Toru; Tanikawa, Takahisa; Ishikawa, Kei; Kojima, Kumi; Kozawa, Osamu

2015-01-01

We investigated the relationship between HSP27 phosphorylation and collagen-stimulated activation of platelets in patients with diabetes mellitus (DM). Platelet-rich plasma was prepared from blood of type 2 DM patients. The platelet aggregation was analyzed in size of aggregates by an aggregometer using a laser scattering method. The protein phosphorylation was analyzed by Western blotting. Phosphorylated-HSP27 and PDGF-AB released from platelets were measured by ELISA. The phosphorylated-HSP27 levels at Ser-78 and Ser-82 induced by collagen were directly proportional to the platelet aggregation. Total HSP27 levels in platelets were decreased concomitantly with the phosphorylation. The released HSP27 levels were significantly correlated with the phosphorylated levels of HSP27 in the platelets stimulated by 0.3 μg/ml collagen. The low dose collagen-stimulated release of HSP27 was detected but relatively small in healthy donors. The released levels of PDGF-AB were in parallel with the levels of released HSP27. Area under the curve (AUC) of small aggregation (9-25 μm) induced by 0.3 μg/ml collagen was inversely proportional to the levels of released HSP27. AUC of large aggregation (50-70 μm) was directly proportional to the levels of released HSP27. Exogenous recombinant phosphorylated- HSP27 hardly affected the aggregation or the released levels of PDGF-AB induced by collagen. These results strongly suggest that HSP27 is released from human platelets accompanied with its phosphorylation induced by collagen, which is correlated with the acceleration of platelet aggregation in type 2 DM patients. PMID:26046355

Release of Phosphorylated HSP27 (HSPB1) from Platelets Is Accompanied with the Acceleration of Aggregation in Diabetic Patients.

PubMed

Tokuda, Haruhiko; Kuroyanagi, Gen; Tsujimoto, Masanori; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Onuma, Takashi; Kojima, Akiko; Doi, Tomoaki; Tanabe, Kumiko; Akamatsu, Shigeru; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Iwama, Toru; Tanikawa, Takahisa; Ishikawa, Kei; Kojima, Kumi; Kozawa, Osamu

2015-01-01

We investigated the relationship between HSP27 phosphorylation and collagen-stimulated activation of platelets in patients with diabetes mellitus (DM). Platelet-rich plasma was prepared from blood of type 2 DM patients. The platelet aggregation was analyzed in size of aggregates by an aggregometer using a laser scattering method. The protein phosphorylation was analyzed by Western blotting. Phosphorylated-HSP27 and PDGF-AB released from platelets were measured by ELISA. The phosphorylated-HSP27 levels at Ser-78 and Ser-82 induced by collagen were directly proportional to the platelet aggregation. Total HSP27 levels in platelets were decreased concomitantly with the phosphorylation. The released HSP27 levels were significantly correlated with the phosphorylated levels of HSP27 in the platelets stimulated by 0.3 μg/ml collagen. The low dose collagen-stimulated release of HSP27 was detected but relatively small in healthy donors. The released levels of PDGF-AB were in parallel with the levels of released HSP27. Area under the curve (AUC) of small aggregation (9-25 μm) induced by 0.3 μg/ml collagen was inversely proportional to the levels of released HSP27. AUC of large aggregation (50-70 μm) was directly proportional to the levels of released HSP27. Exogenous recombinant phosphorylated- HSP27 hardly affected the aggregation or the released levels of PDGF-AB induced by collagen. These results strongly suggest that HSP27 is released from human platelets accompanied with its phosphorylation induced by collagen, which is correlated with the acceleration of platelet aggregation in type 2 DM patients.

24-hour variation in content and release of hypothalamic neuropeptides in the rat.

PubMed

Nicholson, S A; Adrian, T E; Bacarese-Hamilton, A J; Gillham, B; Jones, M T; Bloom, S R

1983-12-01

The tissue content of up to eight neuropeptides, viz bombesin (BOM), cholecystokinin (CCK-8), neurotensin (NT), neuropeptide Y (NPY), peptide histidine isoleucine amide (PHI), somatostatin (SRIF), substance P (SP) and vasoactive intestinal polypeptide (VIP), in rat hypothalami removed at various times of the day, was measured using specific radioimmunoassays. There was significant variation in the content of BOM, CCK-8, NT, PHI, SP and VIP across a 24-h period. The levels of BOM, CCK-8 and NT were lowest around the onset of darkness (1900 h) and rose throughout the night to reach a peak around the time of lights on. Hypothalamic content of all eight peptides fell between 0700 h and 1300 h by an average of 45 +/- 4%. Basal release of these peptides, as well as that in the presence of 48 mM potassium (K+), was measured from hypothalami removed between 0700 and 1900 h and incubated in vitro in a CSF-like medium. Basal secretion of NT significantly increased, whilst that of CCK-8 significantly decreased over the same period. There was no significant change in the basal release of the other neuropeptides. The release in the presence of 48 mM K+ of SP decreased significantly during the day, whilst that of VIP significantly increased. There was also a significant change in the stimulated release of BOM, levels falling during the morning and rising again at 1900 h. 48 mM K+ caused a significant increase in the release of SRIF and SP at all times tested. Whilst 48 mM K+ induced a significantly higher release of CCK-8 and NT in the morning, this stimulus was ineffective in the evening. The contrary was true in the case of BOM, NPY and VIP, where a significant stimulation was induced only at 1900 h. The possible implications of these findings are discussed.

Synthesis and antitumor activity evaluation of a novel combi-nitrosourea prodrug: Designed to release a DNA cross-linking agent and an inhibitor of O(6)-alkylguanine-DNA alkyltransferase.

PubMed

Sun, Guohui; Zhang, Na; Zhao, Lijiao; Fan, Tengjiao; Zhang, Shufen; Zhong, Rugang

2016-05-01

The drug resistance of CENUs induced by O(6)-alkylguanine-DNA alkyltransferase (AGT), which repairs the O(6)-alkylated guanine and subsequently inhibits the formation of dG-dC cross-links, hinders the application of CENU chemotherapies. Therefore, the discovery of CENU analogs with AGT inhibiting activity is a promising approach leading to novel CENU chemotherapies with high therapeutic index. In this study, a new combi-nitrosourea prodrug 3-(3-(((2-amino-9H-purin-6-yl)oxy)methyl)benzyl)-1-(2-chloroethyl)-1-nitrosourea (6), designed to release a DNA cross-linking agent and an inhibitor of AGT, was synthesized and evaluated for its antitumor activity and ability to induce DNA interstrand cross-links (ICLs). The results indicated that 6 exhibited higher cytotoxicity against mer(+) glioma cells compared with ACNU, BCNU, and their respective combinations with O(6)-benzylguanine (O(6)-BG). Quantifications of dG-dC cross-links induced by 6 were performed using HPLC-ESI-MS/MS. Higher levels of dG-dC cross-link were observed in 6-treated human glioma SF763 cells (mer(+)), whereas lower levels of dG-dC cross-link were observed in 6-treated calf thymus DNA, when compared with the groups treated with BCNU and ACNU. The results suggested that the superiority of 6 might result from the AGT inhibitory moiety, which specifically functions in cells with AGT activity. Molecular docking studies indicated that five hydrogen bonds were formed between the O(6)-BG analogs released from 6 and the five residues in the active pocket of AGT, which provided a reasonable explanation for the higher AGT-inhibitory activity of 6 than O(6)-BG. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sphingosine 1-phosphate release from platelets during clot formation: close correlation between platelet count and serum sphingosine 1-phosphate concentration

PubMed Central

2013-01-01

Background Sphingosine 1-phosphate (Sph-1-P), abundantly stored in platelets and released extracellularly upon activation, plays important roles as an extracellular mediator by interacting with specific cell surface receptors, especially in the area of vascular biology and immunology/hematology. Although the plasma Sph-1-P level is reportedly determined by red blood cells (RBCs), but not platelets, this may not be true in cases where the platelets have been substantially activated. Methods and results We measured the Sph-1-P and dihydrosphingosine 1-phosphate (DHSph-1-P) levels in serum samples (in which the platelets had been fully activated) from subjects with (n = 21) and without (n = 33) hematological disorders. We found that patients with essential thrombocythemia exhibited higher serum Sph-1-P and DHSph-1-P concentrations. The serum Sph-1-P concentration was closely correlated with the platelet count but was very weakly correlated with the RBC count. Similar results were obtained for DHSph-1-P. The serum Sph-1-P and DHSph-1-P levels were inversely correlated with the level of autotaxin (ATX), a lysophosphatidic acid-producing enzyme. A multiple regression analysis also revealed that the platelet count had the greatest explanatory impact on the serum Sph-1-P level. Conclusions Our present results showed close correlations between both the serum Sph-1-P and DHSph-1-P levels and the platelet count (but not the RBC count); these results suggest that high concentrations of these sphingoid base phosphates may be released from platelets and may mediate cross talk between platelet activation and the formation of atherosclerotic lesions. PMID:23418753

Biopolymeric mucoadhesive bilayer patch of pravastatin sodium for buccal delivery and treatment of patients with atherosclerosis.

PubMed

Yedurkar, Pramod; Dhiman, Munish Kumar; Petkar, Kailash; Sawant, Krutika

2013-05-01

Mucoadhesive bilayer buccal patch has been developed to improve the bioavailability and therapeutic efficacy along with providing sustained release of pravastatin sodium. Buccal patches comprising of varying composition of Carbopol 934P and HPMC K4M were designed and characterized for surface pH, swelling index, in vitro bioadhesion, mechanical properties, in vitro drug release and in vivo pharmacokinetic and pharmacodynamics performance. All formulations exhibited satisfactory technological parameters and followed non-fickian drug release mechanism. Bilayer buccal patch containing Carbopol 934P and HPMC K4M in 4:6 ratio (PBP5) was considered optimum in terms of swelling, mucoadhesion, mechanical properties and in vitro release profile. Pharmacokinetic studies in rabbits showed significantly higher (p < 0.05) Cmax (75.63 ± 6.98 ng/mL), AUC(0-8) (311.10 ± 5.89 ng/mL/h) and AUC(0-∞) (909.42 ± 5.89 ng/mL/h) than pravastatin oral tablet (Cmax - 67.40 ± 9.23 ng/mL, AUC(0-8)-130.33 ± 10.25 ng/mL/h and AUC(0-∞)-417.17 ± 5.89 ng/mL/h)). While, increased tmax of buccal patch indicated its sustained release property in comparison to oral tablet. Pharmacodynamic studies in rabbits showed statistically significant difference (p < 0.005) in the reduction of TG (131.10 ± 10.23 mg/dL), VLDL (26.00 ± 2.56 mg/dL) and LDL level (8.99 ± 3.01 mg/dL) as compared to oral conventional tablet. In conclusion, bioavailability from the developed buccal patch of pravastatin was 2.38 times higher than the oral dosage form, indicating its therapeutic potential in the treatment of atherosclerosis.

A Comparative Analysis of the Corrosive Effect of Artificial Saliva of Variable pH on DMLS and Cast Co-Cr-Mo Dental Alloy

PubMed Central

Puskar, Tatjana; Jevremovic, Danimir; Williams, Robert J.; Eggbeer, Dominic; Vukelic, Djordje; Budak, Igor

2014-01-01

Dental alloys for direct metal laser sintering (DMLS) are available on the market today, but there is little scientific evidence reported on their characteristics. One of them is the release of ions, as an indicator of the corrosion characteristics of a dental alloy. Within this research, the difference in the elution of metals from DMLS and cast (CM) samples of Co-Cr-Mo dental alloy in saliva-like medium of three different pH was examined by inductively-coupled plasma mass spectrometry (ICP-MS). The obtained results show that the metal elution in artificial saliva from the DMLS alloy was lower than the elution from the CM alloy. The release of all investigated metal ions was influenced by the acidity, both from the DMLS and CM alloy, throughout the investigated period of 30 days. The change in acidity from a pH of 6.8 to a pH of 2.3 for the cast alloy led to a higher increase of the elution of Co, Cr and Mo from CM than from the DMLS alloy. The greatest release out of Co, Cr and Mo was for Co for both tested alloys. Further, the greatest release of all ions was measured at pH 2.3. In saliva of pH 2.3 and pH 4.5, the longer the investigated period, the higher the difference between the total metal ion release from the CM and DMLS alloys. Both alloys showed a safe level of elution according to the ISO definition in all investigated acidic environments. PMID:28788197

A Comparative Analysis of the Corrosive Effect of Artificial Saliva of Variable pH on DMLS and Cast Co-Cr-Mo Dental Alloy.

PubMed

Puskar, Tatjana; Jevremovic, Danimir; Williams, Robert J; Eggbeer, Dominic; Vukelic, Djordje; Budak, Igor

2014-09-11

Dental alloys for direct metal laser sintering (DMLS) are available on the market today, but there is little scientific evidence reported on their characteristics. One of them is the release of ions, as an indicator of the corrosion characteristics of a dental alloy. Within this research, the difference in the elution of metals from DMLS and cast (CM) samples of Co-Cr-Mo dental alloy in saliva-like medium of three different pH was examined by inductively-coupled plasma mass spectrometry (ICP-MS). The obtained results show that the metal elution in artificial saliva from the DMLS alloy was lower than the elution from the CM alloy. The release of all investigated metal ions was influenced by the acidity, both from the DMLS and CM alloy, throughout the investigated period of 30 days. The change in acidity from a pH of 6.8 to a pH of 2.3 for the cast alloy led to a higher increase of the elution of Co, Cr and Mo from CM than from the DMLS alloy. The greatest release out of Co, Cr and Mo was for Co for both tested alloys. Further, the greatest release of all ions was measured at pH 2.3. In saliva of pH 2.3 and pH 4.5, the longer the investigated period, the higher the difference between the total metal ion release from the CM and DMLS alloys. Both alloys showed a safe level of elution according to the ISO definition in all investigated acidic environments.

Developmental changes and day-night expression of the gonadotropin-inhibitory hormone system in the European sea bass: Effects of rearing temperature.

PubMed

Paullada-Salmerón, José A; Loentgen, Guillaume Henri; Cowan, Mairi; Aliaga-Guerrero, María; Rendón-Unceta, María Del Carmen; Muñoz-Cueto, José A

2017-04-01

The role of rearing temperature on fish development, sex differentiation and puberty has been largely addressed, but the impact of water temperature on the ontogeny of the main neuroendocrine systems controlling reproduction has received little attention. Gonadotropin-inhibitory hormone (GnIH) has been shown to act on gonadotropin-releasing hormone (GnRH) neurons and on the pituitary to inhibit gonadotropin release and synthesis in vertebrates, including sea bass, Dicentrarchus labrax. In the present study we investigated the effects of rearing temperature during the thermosensitive period (5-60days post-fertilization, dpf) on the expression of the GnIH gene (gnih) and its receptor (gnihr). Animals were maintained under two different conditions, low temperature (LT, 15°C) or high temperature (HT, 21°C), throughout the thermosensitive period and sampled from 5 to 360dpf at mid-light (ML) and mid-dark (MD). Our results showed significant effects of temperature on gnih and gnihr expression during the thermosensitive period, with higher transcript levels under LT condition. Some differences were also evident after the completion of the sex differentiation process. Moreover, we revealed daily variations in the developmental expression of gnih and gnihr, with higher diurnal mRNA levels at early stages (until 25dpf), and a shift to higher nocturnal expression levels at 300-360dpf, which corresponded with the beginning of the winter (reproductive season). To the best of our knowledge, this work represents the first study reporting the effects of rearing temperature on the transcription of gnih system genes, as well as its daily variations during the development of a fish species. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy.

PubMed

Sattler, Annika; Schaefer, Marion; May, Theodor W

2015-09-01

To evaluate the relationship between serum concentrations of mono-hydroxy-carbazepine (MHD), the main metabolite of oxcarbazepine (OXC), and the occurrence of adverse effects (AE) in a large group of patients on OXC monotherapy. An antiepileptic drug (AED) therapeutic drug monitoring (TDM) database was analyzed especially with regard to OXC dosage, MHD serum concentration, and the occurrence of AE. In total, 893 blood samples of 442 patients were included in this retrospective study. The statistical evaluation was performed by means of Kaplan-Meier estimates, log-rank tests and generalized estimating equations (GEE). At least one AE was reported in 78 (17.6%) of the 442 patients. At MHD serum concentrations of 30.0 μg/ml and 43.7 μg/ml and OXC dosages of 33.1 mg/kg and 62.3 mg/kg, 25% and 75% of patients, respectively, experienced at least one AE. Log-rank tests indicated that younger patients (<18 years) may be able to tolerate higher MHD serum levels (p = 0.006) and higher OXC dosages per body weight (p < 0.001) compared to adult patients (≥ 18 years). Furthermore, AEs occurred at higher body-weight adjusted OXC dosages of extended release formulations compared to immediate-release formulations (p = 0.010), whereas MHD serum levels at which AEs occurred did not differ significantly between formulations (p = 0.125). Multivariate GEE confirmed the results. The occurrence of AEs is significantly (and non-linearly) dependent on MHD serum level, whereas the dependence of OXC dosage is less distinctive. But, tolerability of OXC seems to depend on age of the patients as well as on pharmaceutical formulation of OXC. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Abdominal adipose tissue: early metabolic dysfunction associated to insulin resistance and oxidative stress induced by an unbalanced diet.

PubMed

Rebolledo, O R; Marra, C A; Raschia, A; Rodriguez, S; Gagliardino, J J

2008-11-01

The possible contribution of early changes in lipid composition, function, and antioxidant status of abdominal adipose tissue (AAT) induced by a fructose-rich diet (FRD) to the development of insulin resistance (IR) and oxidative stress (OS) was studied. Wistar rats were fed with a commercial diet with (FRD) or without 10% fructose in the drinking water for 3 weeks. The glucose (G), triglyceride (TG), and insulin (I) plasma levels, and the activity of antioxidant enzymes, lyposoluble antioxidants, total glutathione (GSH), lipid peroxidation as TBARS, fatty acid (FA) composition of AAT-TG as well as their release by incubated pieces of AAT were measured. Rats fed with a FRD have significantly higher plasma levels of G, TG, and I. Their AAT showed a marked increase in content and ratios of saturated to monounsaturated and polyunsaturated FAs, TBARS, and catalase, GSH-transferase and GSH-reductase, together with a decrease in superoxide dismutase and GSH-peroxidase activity, and total GSH, alpha-tocopherol, beta-carotene and lycopene content. Incubated AAT from FRD released in vitro higher amount of free fatty acids (FFAs) with higher ratios of saturated to monounsaturated and polyunsaturated FAs. Our data suggest that FRD induced an early prooxidative state and metabolic dysfunction in AAT that would favor the overall development of IR and OS and further development of pancreatic beta-cell failure; therefore, its early control would represent an appropriate strategy to prevent alterations such as the development of type 2 diabetes.

[The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions. Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients.

Alternative barging strategies to improve survival of salmonids transported from Lower Granite Dam: Final report from the 2006-2008 spring/summer Chinook salmon and Steelhead juvenile migrations

USGS Publications Warehouse

Marsh, Tiffani M.; Muir, William D.; Sandford, Benjamin P.; Smith, Steven G.; Elliott, Diane G.

2012-01-01

We found no evidence of a consistent difference in SARs for fish released at the two barge-release locations. Data were not sufficient to evaluate the effects of fish pathogens on avian predation. There was clear evidence that fish of both species released at Astoria were less vulnerable to avian predators than those released at the customary site at Skamania Landing. Unfortunately, this survival benefit did not translate to higher SARs, as it was offset by higher rates of straying by fish released from Astoria. This was likely a result of greater impairment to homing ability for fish released at Astoria.

Gravitational failure of sea cliffs in weakly lithified sediment

USGS Publications Warehouse

Hampton, M.A.

2002-01-01

Gravitational failure of sea cliffs eroded into weakly lithified sediment at several sites in California involves episodic stress-release fracturing and cantilevered block falls. The principal variables that influence the gravitational stability are tensional stresses generated during the release of horizontal confining stress and weakening of the sediment with increased saturation levels. Individual failures typically comprise less than a cubic meter of sediment, but large areas of a cliff face can be affected by sustained instability over a period of several days. Typically, only the outer meter or so of sediment is removed during a failure episode. In-place sediment saturation levels vary over time and space, generally being higher during the rainy season but moderate to high year-round. Laboratory direct-shear tests show that sediment cohesion decreases abruptly with increasing saturation level; the decrease is similar for all tested sediment if the cohesion is normalized by the maximum, dry-sediment cohesion. Large failures that extend over most or all of the height of the sea cliff are uncommon, but a few large wedge-shaped failures sometimes occur, as does separation of large blocks at sea cliff-gully intersections.

Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients

PubMed Central

Politis, Marios; Wu, Kit; Loane, Clare; Brooks, David J.; Kiferle, Lorenzo; Turkheimer, Federico E.; Bain, Peter; Molloy, Sophie; Piccini, Paola

2014-01-01

Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson’s disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD. PMID:24531549

Total and free iodothyronine changes in response to transport of Equidae (Equus asinus and Equus caballus).

PubMed

Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Ferlazzo, Adriana

2017-03-31

In this study the effects of short distance road transport on total and free iodothyronine changes in 12 stallions (Equus asinus and Equus caballus) were evaluated. Donkeys (n = 6) and horses (n = 6) were transported for a distance of 50 km. Blood samples were collected 1 week before transport in basal conditions, 1 week later immediately before loading, and after transport and unloading. After transport, donkeys showed significant increases in circulating T4 (P≤0.01), fT3 (P≤0.001), and fT4 (P≤0.01) levels; while horses had significant increases in circulating T3, fT3 and fT4 (P≤0.01) levels. Compared to donkeys' values, horses showed lower T4 values in basal condition, before and after transport (P≤0.001); higher fT3 values in basal condition and before (P≤0.001), and lower values (P≤0.001) after transport; higher fT4 values (P≤0.001) in basal condition. The results indicate that short road transport of donkeys and horses induces the activation of the thyroid gland, with the same release of fT3 and fT4 iodothyronines, but with different preferential release of T3 in horses and T4 in donkeys after transport.

Behavioural and hormonal effects of member replacement in captive groups of blue-fronted amazon parrots (Amazona aestiva).

PubMed

Silva de Souza Matos, Laerciana; Palme, Rupert; Silva Vasconcellos, Angélica

2017-05-01

Social species in captivity may face allostatic overload due to artificial grouping and other social constraints. In rescue centres, groups of psittacines are constantly mixed due to the arrival and/or release of individuals; this procedure is potentially harmful to animal welfare. This study aimed at evaluating the possible impacts of mate replacement on the stress levels of captive blue-fronted amazon parrots (Amazona aestiva). During five weeks, we recorded agonistic interactions and dropping-glucocorticoid metabolites (GCM) concentrations of individuals allocated in a group whose members were kept constant and in a group subjected to frequent member replacement. In both groups, non-linear hierarchies developed, without sex differences regarding aggression or hierarchical positions. The replacement of individuals had no effect on the number of agonistic interactions or on the animals' stress levels. In both groups, higher-ranking individuals had higher stress loads than subordinates. Our study, the first to investigate the social dynamics of A. aestiva, indicated that introducing or removing individuals in captive groups does not seem to affect the welfare of the birds in the short term. This information favours release and reintroduction programs and is relevant for conservation management of this, and possibly other parrot species with similar environmental requirements. Copyright © 2017 Elsevier B.V. All rights reserved.

Hair from different ethnic groups vary in elemental composition and nitrogen and phosphorus mineralisation in soil.

PubMed

Malepfane, N M; Muchaonyerwa, P

2017-02-01

Disposal of hair wastes at landfills causes nitrate leaching to ground water, and use of the waste as fertiliser could be a viable option. This study was to determine elemental composition of major hair types in South Africa and their nitrogen (N) and phosphorus (P) release in soil. Wastes of African, White and Indian hair were obtained from local salons and analysed for carbon (C), N and sulphur (S) with the Leco CNS analyzer, and P, bases, aluminium (Al) and micronutrients, with the ICP. We also conducted an incubation study to determine changes in mineral N and P in soil. Hair wastes were added to soil at increasing rates based on N, incubated at 25 °C with destructive sampling after 0, 28, 56 and 84 days and pH, ammonium-N, nitrate-N and extractable P measured. All data were subjected to analysis of variance. Indian and White hair had higher N than African. White hair had higher C and lower potassium (K) than those of other types. The Fe levels in hair were in the order White > African > Indian, whilst those of Al were African > Indian > White. African hair had higher calcium (Ca), manganese (Mn), zinc (Zn) and cobalt (Co) than the other types. Ammonium-N and nitrate-N releases were in the order: Indian > African > White, especially at higher rates. Ammonium-N increased in the first 28 days and declined thereafter, when nitrate-N increased and pH decreased. The findings implied that hair types differ in elemental composition and nitrogen release in soil, with implications on pollution and soil fertility.

Wildlife disease ecology in changing landscapes: Mesopredator release and toxoplasmosis

PubMed Central

Hollings, Tracey; Jones, Menna; Mooney, Nick; McCallum, Hamish

2013-01-01

Changing ecosystem dynamics are increasing the threat of disease epidemics arising in wildlife populations. Several recent disease outbreaks have highlighted the critical need for understanding pathogen dynamics, including the role host densities play in disease transmission. In Australia, introduced feral cats are of immense concern because of the risk they pose to native wildlife through predation and competition. They are also the only known definitive host of the coccidian parasite, Toxoplasma gondii, the population-level impacts of which are unknown in any species. Australia’s native wildlife have not evolved in the presence of cats or their parasites, and feral cats may be linked with several native mammal declines and extinctions. In Tasmania there is emerging evidence that feral cat populations are increasing following wide-ranging and extensive declines in the apex predator, the Tasmanian devil, from a consistently fatal transmissible cancer. We assess whether feral cat density is associated with the seroprevalence of T. gondii in native wildlife to determine whether an increasing population of feral cats may correspond to an increased level of risk to naive native intermediate hosts. We found evidence that seroprevalence of T. gondii in Tasmanian pademelons was lower in the north-west of Tasmania than in the north-east and central regions where cat density was higher. Also, samples obtained from road-killed animals had significantly higher seroprevalence of T. gondii than those from culled individuals, suggesting there may be behavioural differences associated with infection. In addition, seroprevalence in different trophic levels was assessed to determine whether position in the food-web influences exposure risk. Higher order carnivores had significantly higher seroprevalence than medium-sized browser species. The highest seroprevalence observed in an intermediate host was 71% in spotted-tailed quolls (Dasyurus maculatus), the largest mammalian mesopredator, in areas of low cat density. Mesopredator release of cats may be a significant issue for native species conservation, potentially affecting the population viability of many endangered species. PMID:24533323

In situ release rates of Cu and Zn from commercial antifouling paints at different salinities.

PubMed

Lagerström, Maria; Lindgren, J Fredrik; Holmqvist, Albin; Dahlström, Mia; Ytreberg, Erik

2018-02-01

Antifouling paints are environmentally risk assessed based on their biocidal release rates to the water phase. In situ release rates of copper (Cu) and zinc (Zn) were derived for five commercial paints in two recreational marinas with different salinities (5 and 14 PSU) using an X-Ray Fluorescence spectrometer (XRF). Salinity was found to significantly affect the Cu release, with twice the amount of Cu released at the higher salinity, while its influence on the Zn release was paint-specific. Site-specific release rates for water bodies with salinity gradients, e.g. the Baltic Sea, are therefore necessary for more realistic risk assessments of antifouling paints. Furthermore, the in situ release rates were up to 8 times higher than those generated using standardized laboratory or calculation methods. The environmental risk assessment repeated with the field release rates concludes that it is questionable whether the studied products should be allowed on the Swedish market. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Compacted Multiparticulate Systems for Colon-Specific Delivery of Ketoprofen.

PubMed

de Alencar, Rodrigo Gomes; de Oliveira, Aline Carlos; Lima, Eliana Martins; da Cunha-Filho, Marcílio Sérgio Soares; Taveira, Stephânia Fleury; Marreto, Ricardo Neves

2017-08-01

Pellet-containing tablets for colon-specific drug delivery present higher targeting efficiency and lower costs when compared with monolithic tablets and pellet-filled capsules, respectively. In this study, pellets containing ketoprofen were coated with different acrylic polymers and submitted to compaction. The influence of formulation and process factors on film integrity was then evaluated. Pellets were prepared via extrusion-spheronization and coated using two acrylic polymers (Eudragit® FS 30 D and Opadry® 94 k28327, PMMA and PMA, respectively). The resulting pellets were mixed with placebo granules and compressed in a hydraulic press. Multiple regression showed that ketoprofen release from pellet-containing tablets is predominantly influenced by pellet content, hardness, friability, and disintegration time. PMA-containing tablets prepared under low compaction force or with low pellet content showed rapid disintegration (<1 min) and ketoprofen release similar to those of uncompressed coated pellets (∼30% at 360 min of experiment). On the other hand, PMMA-containing tablets showed a higher rupture level, and those prepared with higher pellet content gave rise to a non-disintegrating matrix. Coated pellets were shown to be able to target ketoprofen to the colonic region. Targeting capacity was dependent on the physicochemical characteristics of the tablets.

Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis.

PubMed

Hellström, Per M; Hendolin, Panu; Kaihovaara, Pertti; Kronberg, Leif; Meierjohann, Axel; Millerhovf, Anders; Paloheimo, Lea; Sundelin, Heidi; Syrjänen, Kari; Webb, Dominic-Luc; Salaspuro, Mikko

2017-02-01

Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Administration of L-cysteine increased MTCA (p < .0004) and decreased gastric acetaldehyde concentrations by 68% (p < .0001). The peak L-cysteine level was 7552 ± 2687 μmol/L at 40 min and peak MTCA level 196 ± 98 μmol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.

Effects of new fluorinated analogues of GABA, pregabalin bioisosters, on the ambient level and exocytotic release of [3H]GABA from rat brain nerve terminals.

PubMed

Borisova, T; Pozdnyakova, N; Shaitanova, E; Gerus, I; Dudarenko, M; Haufe, G; Kukhar, V

2017-01-15

Recently, we have shown that new fluorinated analogues of γ-aminobutyric acid (GABA), bioisosters of pregabalin (β-i-Bu-GABA), i.e. β-polyfluoroalkyl-GABAs (FGABAs), with substituents: β-CF 3 -β-OH (1), β-CF 3 (2); β-CF 2 CF 2 H (3), are able to increase the initial rate of [ 3 H]GABA uptake by isolated rat brain nerve terminals (synaptosomes), and this effect is higher than that of pregabalin. So, synthesized FGABAs are structural but not functional analogues of GABA. Herein, we assessed the effects of synthesized FGABAs (100μM) on the ambient level and exocytotic release of [ 3 H]GABA in nerve terminals and compared with those of pregabalin (100μM). It was shown that FGABAs 1-3 did not influence the ambient level of [ 3 H]GABA in the synaptosomal preparations, and this parameter was also not altered by pregabalin. During blockage of GABA transporters GAT1 by specific inhibitor NO-711, FGABAs and pregabalin also did not change ambient [ 3 H]GABA in synaptosomal preparations. Exocytotic release of [ 3 H]GABA from synaptosomes decreased in the presence of FGABAs 1-3 and pregabalin, and the effects of FGABAs 1 &3 were more significant than those of FGABAs 2 and pregabalin. FGABAs 1-3/pregabalin-induced decrease in exocytotic release of [ 3 H]GABA from synaptosomes was not a result of changes in the potential of the plasma membrane. Therefore, new synthesized FGABAs 1 &3 were able to decrease exocytotic release of [ 3 H]GABA from nerve terminals more effectively in comparison to pregabalin. Absence of unspecific side effects of FGABAs 1 &3 on the membrane potential makes these compounds perspective for medical application. Copyright © 2016 Elsevier Ltd. All rights reserved.

New approaches to evaluate sympathoadrenal system activity in experiments on Earth and in space

NASA Astrophysics Data System (ADS)

Kvetnansky, R.; Noskov, V. B.; Blazicek, P.; Macho, L.; Grigoriev, A. I.; Goldstein, D. S.; Kopin, I. J.

In previous studies the activity of the sympathoadrenal system (SAS) in cosmonauts during space flights was evaluated by measuring plasma catecholamines (CA) levels and urinary CA and their metabolites concentrations. Plasma CA levels are accepted indicators of SAS activity, however, they are determined by the plasma clearances as well as the rates of CA release (spillover-SO) into the bloodstream. Nowadays methods are available which evaluate not only plasma levels of CA but also their release, spillover, uptake, reuptake, degradation and also CA synthesis in vivo measured by plasma levels of dihydroxyphenylalanine (DOPA). Plasma concentrations of DOPA, the CA noradrenaline (NE), adrenaline (ADR), and dopamine (DA), the deaminated catechol metabolites dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC), and the O-methylated metabolites methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured during immobilization stress (IMO) in conscious rats. Radiotracer methods were used to measure NE SO. IMO markedly increased arterial NE levels but NE SO was less elevated bacause the NE clearance was slightly reduced in IMO rats. Simultaneous measurements of plasma CA and their metabolites provide another means to obtain information about SAS function. For instance, dissociation between changes of plasma DHPG and NE levels can indicate changes in neuronal reuptake of NE. We found marked parallel increases in plasma NE and DHPG levels during acute IMO; however after repeated IMO, plasma NE levels were increased but DHPG responses were less pronounced suggesting a reduced NE reuptake. DOPA, the CA precursor, circulates in plasma at a concentration higher than NE. During stress, increased sympathoneural outflow stimulates DOPA synthesis and release into the circulation supporting the view that changes in plasma DOPA levels during stress reflect in vivo changes in the rate of CA synthesis. We propose to measure the new plasma indicators of SAS activity in cosmonauts and/or in animals before, during and after space flights.

Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma.

PubMed

Pham, D L; Ban, G-Y; Kim, S-H; Shin, Y S; Ye, Y-M; Chwae, Y-J; Park, H-S

2017-01-01

Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs). Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)-8 (100 ng/mL). Autophagy (light chain 3-II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = -0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups. Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA. © 2016 John Wiley & Sons Ltd.

Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

PubMed Central

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Fà, Mauro; Gessa, Gian Luigi

2005-01-01

Background Previous studies by our group suggest that extracellular dopamine (DA) and noradrenaline (NA) may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC). This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC), occipital cortex (Occ), and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats. Results Twenty min electrical stimulation of the LC, with burst type pattern of pulses, increased NA and DA both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned to baseline within 20 min after the end of the stimulation period, while DA in the Occ reached a maximum increase during 20 min post-stimulation and remained higher than baseline values at 220 min post-stimulation. Local perfusion with tetrodotoxin (TTX, 10 μM) markedly reduced baseline NA and DA in the mPFC and Occ and totally suppressed the effect of electrical stimulation in both areas. A sequence of five 20 min stimulations at 20 min intervals were delivered to the LC. Each stimulus increased NA to the same extent and duration as the first stimulus, whereas DA remained elevated at the time next stimulus was delivered, so that baseline DA progressively increased in the mPFC and Occ to reach about 130 and 200% the initial level, respectively. In the presence of the NA transport (NAT) blocker desipramine (DMI, 100 μM), multiple LC stimulation still increased extracellular NA and DA levels. Electrical stimulation of the LC increased NA levels in the homolateral caudate nucleus, but failed to modify DA level. Conclusion The results confirm and extend that LC stimulation induces a concomitant release of DA and NA in the mPFC and Occ. The different time-course of LC-induced elevation of DA and NA suggests that their co-release may be differentially controlled. PMID:15865626

Ceftaroline modulates the innate immune and host defense responses of immunocompetent cells exposed to cigarette smoke.

PubMed

Bruno, A; Cipollina, C; Di Vincenzo, S; Siena, L; Dino, P; Di Gaudio, F; Gjomarkaj, M; Pace, E

2017-09-05

Cigarette smoke, the principal risk factor for chronic obstructive pulmonary disease (COPD), negatively influences the effectiveness of the immune system's response to a pathogen. The antibiotic ceftaroline exerts immune-modulatory effects in bronchial epithelial cells exposed to cigarette smoke. The present study aims to assess the effects of ceftaroline on TLR2 and TLR4 expression, LPS binding and TNF-α and human beta defensin (HBD2) release in an undifferentiated and PMA-differentiated human monocyte cell line (THP-1) exposed or not to cigarette smoke extracts (CSE). TLR2, TLR4, and LPS binding were assessed by flow cytometry, TNF-α and HBD2 release were evaluated by ELISA. The constitutive expression of TLR2 and TLR4 and LPS binding were higher in differentiated compared to undifferentiated THP-1 cells. In undifferentiated THP-1 cells, CSE increased TLR2 and TLR4 protein levels, LPS binding and TNF-α release and reduced HBD2 release and ceftaroline counteracted all these effects. In differentiated THP-1, CSE did not significantly affect TLR2 and TLR4 expression and LPS binding but reduced HBD2 release and increased TNF-α release. Ceftaroline counteracted the effects of CSE on HBD2 release in differentiated THP-1. Ceftaroline counteracts the effect of CSE in immune cells by increasing the effectiveness of the innate immune system. This effect may also assist in reducing pathogen activity and recurrent exacerbations in COPD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Energy release for the actuation and deployment of muscle-inspired asymmetrically multistable chains

NASA Astrophysics Data System (ADS)

Kidambi, Narayanan; Zheng, Yisheng; Harne, Ryan L.; Wang, K. W.

2018-03-01

Animal locomotion and movement requires energy, and the elastic potential energy stored in skeletal muscle can facilitate movements that are otherwise energetically infeasible. A significant proportion of this energy is captured and stored in the micro- and nano-scale constituents of muscle near the point of instability between asymmetric equilibrium states. This energy may be quickly released to enable explosive macroscopic motions or to reduce the metabolic cost of cyclic movements. Inspired by these behaviors, this research explores modular metastructures of bistable element chains and develops methods to release the energy stored in higher-potential system configurations. Quasi-static investigations reveal the role of state-transition pathways on the overall efficiency of the deployment event. It is shown that sequential, local release of energy from the bistable elements is more efficient than concurrent energy release achieved by applying a force at the free end of the structure. From dynamic analyses and experiments, it is shown that that the energy released from one bistable element can be used to activate the release of energy from subsequent links, reducing the actuation energy required to extend or deploy the chain below that required for quasi-static deployment. This phenomenon is influenced by the level of asymmetry in the bistable constituents and the location of the impulse that initiates the deployment of the structure. The results provide insight into the design and behavior of asymmetrically multistable chains that can leverage stored potential energy to enable efficient and effective system deployment and length change.

Application of enzymes, sodium tripolyphosphate and cation exchange resin for the release of extracellular polymeric substances from sewage sludge. Characterization of the extracted polysaccharides/glycoconjugates by a panel of lectins.

PubMed

Wawrzynczyk, J; Szewczyk, E; Norrlöw, O; Dey, E Szwajcer

2007-06-30

The study describes extraction of extracellular polymeric substances (EPS) from sewage sludge by applying enzymes and enzymes combined with sodium tripolyphosphate (STPP). Additionally, a systematic study of two non-enzymatic extraction agents is described. The assessment of the released products is made by colorimetrical methods and polysaccharides/glycoconjugates identification by the interaction with four immobilized lectins. Bio-sludge from Helsingborg (Sweden) and Damhusåen (Denmark) were used as two case studies for testing enzymatic extractability and thereby to make useful prediction of sludge bio-digestibility. From Helsingborg sludge the enzymes extracted about 40% more of EPS than from Damhusåen. The polysaccharides/glycoconjugates in both sludges maintained the same level, and showed substantial different interaction motifs with lectins panel. Damhusåen enzymatic extracted EPS had an enhanced amount of suspended material that was post-hydrolysed by the use of polygalacturonase and lysozyme resulting in pectin like polymers and petiptidoglycans. Petiptidoglycan is a marker from bacterial cell debris. STPP and cation exchange resin (CER) released different quantities of EPS. The CER released polysaccharides/glycoconjugates had higher molecular weight and stronger affinity towards Concanavalin A than the one released by the action of STPP. Independent of the extraction conditions, STPP released elevated amounts of polyvalent cations and humic substances in contrast to the very low amounts of released by CER.

Evaluation of tumor necrosis factor-alpha (TNF) as an exposure or risk marker in three French coal mining regions.

PubMed

Porcher, J M; Oberson, D; Viseux, N; Sébastien, P; Honnons, S; Auburtin, G

1994-01-01

Several studies have shown the crucial role of the tumor necrosis factor-alpha (TNF) in the fibrosis induced by dusts containing silica and its role in the transition from simple pneumoconiosis (CWSP) to progressive massive fibrosis (PMF). To evaluate the nocivity of dust exposure among coal miners (n = 474) from different mining regions in France (e.g., Nord-Pas de Calais, Lorraine, and Provence), spontaneous and LPS or silica-induced TNF released by peripheral blood monocytes was quantified. The primary aim of this effort was to study the link between the prevalence of coal workers pneumoconiosis (CWP) and TNF release. TNF levels were significantly different between active miners from the three regions. However, after correction for age and region, TNF was found not to be related to dust exposure. Interestingly, a very low, homogeneous expression of TNF was observed in the group from Provence. These results are probably related to the absence of pneumoconiosis in this area. A positive relation between profusion and TNF release was found for all stimulants among retired miners with PMF. Although in retired miners TNF release was consistently higher, the design of the study does not allow this effect to be separated from that of age. Both silica and nonstimulated TNF release were found to increase with increasing radiological symptoms; the opposite was found for LPS-induced release.

Microbial Mineral Weathering for Nutrient Acquisition Releases Arsenic

NASA Astrophysics Data System (ADS)

Mailloux, B. J.; Alexandrova, E.; Keimowitz, A.; Wovkulich, K.; Freyer, G.; Stolz, J.; Kenna, T.; Pichler, T.; Polizzotto, M.; Dong, H.; Radloff, K. A.; van Geen, A.

2008-12-01

Tens of millions of people in Southeast Asia drink groundwater contaminated with naturally occurring arsenic. The process of arsenic release from the sediment to the groundwater remains poorly understood. Experiments were performed to determine if microbial mineral weathering for nutrient acquisition can serve as a potential mechanism for arsenic mobilization. We performed microcosm experiments with Burkholderia fungorum, phosphate free artificial groundwater, and natural apatite. Controls included incubations with no cells and with killed cells. Additionally, samples were treated with two spikes - an arsenic spike, to show that arsenic release is independent of the initial arsenic concentration, and a phosphate spike to determine whether release occurs at field relevant phosphate conditions. We show in laboratory experiments that phosphate-limited cells of Burkholderia fungorum mobilize ancillary arsenic from apatite as a by-product of mineral weathering for nutrient acquisition. The released arsenic does not undergo a redox transformation but appears to be solubilized from the apatite mineral lattice as arsenate during weathering. Apatite has been shown to be commonly present in sediment samples from Bangladesh aquifers. Analysis of apatite purified from the Ganges, Brahamputra, Meghna drainage basin shows 210 mg/kg of arsenic, which is higher than the average crustal level. Finally, we demonstrate the presence of the microbial phenotype that releases arsenic from apatite in Bangladesh sediments. These results suggest that microbial weathering for nutrient acquisition could be an important mechanism for arsenic mobilization.

Oxygen transport of hemoglobin in high-altitude animals (Camelidae).

PubMed

Reynafarje, C; Faura, J; Villavicencio, D; Curaca, A; Reynafarje, B; Oyola, L; Contreras, L; Vallenas, E; Faura, A

1975-05-01

To clarify the mechanisms by which high-altitude Camelidae can adapt to hypoxia, the study of some blood characteristics were carried out in apacas and llamas. The results show that there is a peculiar dissociation curve of hemoglobin in alpacas which permits great affinity of hemoglobin for oxygen at lung level and the release of oxygen at the tissue level with a facility similar to that in man. Fetal hemoglobin was found high in adult alpacas (55 percent). Electrophoretic studies of hemoglobin showed that this pigment has two components, both of which have a very low mobility. Lactic dehydrogenase was found six times higher than in humans. RBC glucose-6-phosphate dehydrogenase was two times higher than in man living at the same altitude. Myoglobin was found to be higher than in man living at altitude. Alpacas have erythrocytes in which the amount of 2,3-DPG is approximately the same as in man. RBC are more resistent to hypotonic solutions than humans. The amount of lactic dehydrogenase, myoglobin, and glucose-6-phosphate dehydrogenase dimishes when alpacas are bought down to sea level.

Differential effects of tetracaine on two kinetic components of calcium release in frog skeletal muscle fibres.

PubMed Central

Pizarro, G; Csernoch, L; Uribe, I; Ríos, E

1992-01-01

1. Intramembrane charge movements and changes in intracellular calcium concentration were recorded simultaneously in voltage clamped cut skeletal muscle fibres of the frog in the presence and absence of tetracaine. 2. Extracellular application of 20 microM tetracaine reduced the increase in myoplasmic [Ca2+]. The effect on the underlying calcium release flux from the sarcoplasmic reticulum was to suppress the peak of the release while sparing the steady level attained at the end of 100 ms clamp depolarizations. 3. While the peak of the release flux at corresponding voltages was reduced by 62% after the addition of tetracaine, the rate of inactivation was the same when the pulses elicited release fluxes of similar amplitude. 4. Higher concentrations of tetracaine, 0.2 mM, abolished the calcium signal in stretched fibres whereas in slack fibres this concentration left a non-inactivating calcium release flux. 5. Lowering the extracellular pH antagonized the effect of the drug both on charge movements and on calcium signals. The permanently charged analogue tetracaine methobromide lacked effects on excitation-contraction coupling. 6. These results imply that the two kinetic components of calcium release flux have very different tetracaine sensitivities. They are also consistent with an intracellular site of action of the drug at low concentration. Taken together they strongly suggest that the inactivating and non-inactivating components of calcium release correspond to different pathways: one that inactivates, is sensitive to tetracaine and is controlled by calcium, and another that does not inactivate, is much less sensitive to tetracaine and is directly controlled by voltage. PMID:1297844

Effects of articaine on [3H]noradrenaline release from cortical and spinal cord slices prepared from normal and streptozotocin-induced diabetic rats and compared to lidocaine.

PubMed

Végh, D; Somogyi, A; Bányai, D; Lakatos, M; Balogh, M; Al-Khrasani, M; Fürst, S; Vizi, E S; Hermann, P

2017-10-01

Since a significant proportion of diabetic patients have clinical or subclinical neuropathy, there may be concerns about the use of local anaesthetics. The present study was designed to determine and compare the effects of articaine, a widely used anaesthetic in dental practice, and lidocaine on the resting and axonal stimulation-evoked release of [ 3 H]noradrenaline ([ 3 H]NA) in prefrontal cortex slices and the release of [ 3 H]NA in spinal cord slices prepared from non-diabetic and streptozocin (STZ)-induced diabetic (glucose level=22.03±2.31mmol/l) rats. The peak of allodynia was achieved 9 weeks after STZ-treatment. Articaine and lidocaine inhibited the stimulation-evoked release in a concentration-dependent manner and increased the resting release by two to six times. These effects indicate an inhibitory action of these anaesthetics on Na + - and K + -channels. There was no difference in clinically important nerve conduction between non-diabetic and diabetic rats, as measured by the release of transmitter in response to axonal stimulation. The uptake and resting release of NA was significantly higher in the brain slices prepared from diabetic rats, but there were no differences in the spinal cord. For the adverse effects, the effects of articaine on K + channels (resting release) are more pronounced compared to lidocaine. In this respect, articaine has a thiophene ring with high lipid solubility, which may present potential risks for some patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Trajectories of psychological distress after prison release: implications for mental health service need in ex-prisoners.

PubMed

Thomas, E G; Spittal, M J; Heffernan, E B; Taxman, F S; Alati, R; Kinner, S A

2016-02-01

Understanding individual-level changes in mental health status after prison release is crucial to providing targeted and effective mental health care to ex-prisoners. We aimed to describe trajectories of psychological distress following prison discharge and compare these trajectories with mental health service use in the community. The Kessler Psychological Distress Scale (K10) was administered to 1216 sentenced adult prisoners in Queensland, Australia, before prison release and approximately 1, 3 and 6 months after release. We used group-based trajectory modeling to identify K10 trajectories after release. Contact with community mental health services in the year following release was assessed via data linkage. We identified five trajectory groups, representing consistently low (51.1% of the cohort), consistently moderate (29.8%), high increasing (11.6%), high declining (5.5%) and consistently very high (1.9%) psychological distress. Mood disorder, anxiety disorder, history of self-harm and risky drug use were risk factors for the high increasing, very high and high declining trajectory groups. Women were over-represented in the high increasing and high declining groups, but men were at higher risk of very high psychological distress. Within the high increasing and very high groups, 25% of participants accessed community mental health services in the first year post-release, for a median of 4.4 contact hours. For the majority of prisoners with high to very high psychological distress, distress persists after release. However, contact with mental health services in the community appears low. Further research is required to understand barriers to mental health service access among ex-prisoners.

Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria

PubMed Central

White, Phillipa C.; Milward, Michael R.; Cooper, Paul R.

2017-01-01

ABSTRACT Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii, stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated. PMID:28947649

Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria.

PubMed

Hirschfeld, Josefine; White, Phillipa C; Milward, Michael R; Cooper, Paul R; Chapple, Iain L C

2017-12-01

Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii , stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated. Copyright © 2017 American Society for Microbiology.

Interactions of Stress and CRF in Ethanol-Withdrawal Induced Anxiety in Adolescent and Adult Rats

PubMed Central

Wills, Tiffany A.; Knapp, Darin J.; Overstreet, David H.; Breese, George R.

2010-01-01

Background Repeated stress or administration of corticotropin-releasing factor (CRF) prior to ethanol exposure sensitizes anxiety-like behavior in adult rats. Current experiments determined whether adolescent rats were more sensitive to these challenges in sensitizing ethanol withdrawal-induced anxiety and altering CRF levels in brain during withdrawal. Methods Male adult and adolescent Sprague–Dawley rats were restraint stressed (1 hour) twice 1 week apart prior to a single 5-day cycle of ethanol diet (ED; stress/withdrawal paradigm). Other rats received control diet (CD) and three 1-hour restraint stress sessions. Rats were then tested 5, 24, or 48 hours after the final withdrawal for anxiety-like behavior in the social interaction (SI) test. In other experiments, adolescent rats were given two microinjections of CRF icv 1 week apart followed by 5-days of either CD or ED and tested in social interaction 5 hours into withdrawal. Finally, CRF immunoreactivity was measured in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) after rats experienced control diet, repeated ethanol withdrawals, or stress/withdrawal. Results Rats of both ages had reduced SI following the stress/withdrawal paradigm, and this effect recovered within 24 hours. Higher CRF doses were required to reduce SI in adolescents than previously reported in adults. CRF immunohistochemical levels were higher in the PVN and CeA of CD-exposed adolescents. In adolescent rats, repeated ethanol withdrawals decreased CRF in the CeA but was not associated with decreased CRF cell number. There was no change in CRF from adult treatments. Conclusions In the production of anxiety-like behavior, adolescent rats have equal sensitivity with stress and lower sensitivity with CRF compared to adults. Further, adolescents had higher basal levels of CRF within the PVN and CeA and reduced CRF levels following repeated ethanol withdrawals. This reduced CRF within the CeA could indicate increased release of CRF, and future work will determine how this change relates to behavior. PMID:20586753

β2-adrenergic stimulation enhances Ca2+ release and contractile properties of skeletal muscles, and counteracts exercise-induced reductions in Na+-K+-ATPase Vmax in trained men.

PubMed

Hostrup, M; Kalsen, A; Ortenblad, N; Juel, C; Mørch, K; Rzeppa, S; Karlsson, S; Backer, V; Bangsbo, J

2014-12-15

The aim of the present study was to examine the effect of β2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca(2+) release and uptake, and Na(+)-K(+)-ATPase activity before and after fatiguing exercise in trained men. The study consisted of two experiments (EXP1, n = 10 males, EXP2, n = 20 males), where β2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction (MVC) of m. quadriceps was measured, followed by exercise to fatigue at 120% of maximal oxygen uptake (V̇O2, max ). A muscle biopsy was taken after MVC (non-fatigue) and at time of fatigue. In EXP2, contractile properties of m. quadriceps were measured with electrical stimulations before (non-fatigue) and after two fatiguing 45 s sprints. Non-fatigued MVCs were 6 ± 3 and 6 ± 2% higher (P < 0.05) with terbutaline than placebo in EXP1 and EXP2, respectively. Furthermore, peak twitch force was 11 ± 7% higher (P < 0.01) with terbutaline than placebo at non-fatigue. After sprints, MVC declined (P < 0.05) to the same levels with terbutaline as placebo, whereas peak twitch force was lower (P < 0.05) and half-relaxation time was prolonged (P < 0.05) with terbutaline. Rates of SR Ca(2+) release and uptake at 400 nm [Ca(2+)] were 15 ± 5 and 14 ± 5% (P < 0.05) higher, respectively, with terbutaline than placebo at non-fatigue, but declined (P < 0.05) to similar levels at time of fatigue. Na(+)-K(+)-ATPase activity was unaffected by terbutaline compared with placebo at non-fatigue, but terbutaline counteracted exercise-induced reductions in maximum rate of activity (Vmax) at time of fatigue. In conclusion, increased contractile force induced by β2-adrenergic stimulation is associated with enhanced rate of Ca(2+) release in humans. While β2-adrenergic stimulation elicits positive inotropic and lusitropic effects on non-fatigued m. quadriceps, these effects are blunted when muscles fatigue. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Soft-Template-Synthesized Mesoporous Carbon for Oral Drug Delivery

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

Saha, Dipendu; Warren, Kaitlyn E; Naskar, Amit K

Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride. Captopril and furosemide exhibited desorption kinetics over 30 40 h, and ranitidine HCl had a complete release time of 5 10 h. As evident from the slow release kinetics, we contend that our mesoporous carbon is an improved drug-delivery medium compared to state-of-the-art porous silica-based substrates. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200 400 m2 g-1 and pore volume of 0.2 0.6 cm3 g-1.more » The phloroglucinol-based carbon has narrower pore widths and higher pore volume than the lignin-derived counterpart and maintains a longer release time. Numerical modeling of the release kinetics data reveals that the diffusivities of all the drugs from lignin-based carbon media are of equivalent magnitude (10-22 to 10-24 m2 s-1). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecules (captopril) by an order of magnitude. Thus, engineered pore morphology in our synthesized carbon sorbent, along with its potential to tailor the chemistry of its interaction with sorbet, can be exploited for optimal delivery system of a preferred drug within its therapeutic level and below the level of toxicity.« less

Isolation and Role of PmRGL2 in GA-mediated Floral Bud Dormancy Release in Japanese Apricot (Prunus mume Siebold et Zucc.)

PubMed Central

Lv, Lin; Huo, Ximei; Wen, Luhua; Gao, Zhihong; Khalil-ur-Rehman, Muhammad

2018-01-01

Bud dormancy release is regulated by gibberellins (GAs). DELLA proteins are highly conserved and act as negative regulators in GA signaling pathway. The present study established a relationship between PmRGL2 in Japanese apricot and GA4 levels during dormancy release of floral buds. Overexpression of PmRGL2 in poplar delayed the onset of bud dormancy and resulted in dwarf plants, relative to wild-type trees. PmRGL2 exhibited higher expression during ecodormancy and relatively lower expression during endodormancy. The relative level of GA4 exhibited an increasing trend at the transition from endodormancy to ecodormancy and displayed a similar expression pattern of genes related to GA metabolism, PmGA20ox2, PmGA3ox1, PmGID1b, in both Japanese apricot and transgenic poplar. These results suggests that PmRGL2 acts as an integrator and negative regulator of dormancy via a GA-signaling pathway. Moreover, an interaction between RGL2 and SLY1 in a yeast two hybrid (Y2H) system further suggests that SCF E3 ubiquitin ligases, such as SLY1, may be a critical factor in the regulation of RGL2 through an SCFSLY1-proteasome pathway. Our study demonstrated that PmRGL2 plays a negative role in bud dormancy release by regulating the GA biosynthetic enzymes, GA20ox and GA3ox1 and the GA receptor, GID1b. PMID:29434610

Lack of circadian regulation of melatonin rhythms in the sockeye salmon (Oncorhynchus nerka) in vivo and in vitro.

PubMed

Iigo, Masayuki; Azuma, Teruo; Iwata, Munehico

2007-01-01

Melatonin profiles were determined in the plasma in vivo and in the pineal organ in vitro of the sockeye salmon (Oncorhynchus nerka) under various light conditions to test whether they are under circadian regulation. When serial blood samples were taken at 4-h intervals for 3 days via a cannula inserted into the dorsal aorta, plasma melatonin exhibited significant fluctuation under a light-dark cycle, with higher levels during the dark phase than during the light phase. No rhythmic fluctuations persisted under either constant dark or constant light, with constant low and high levels, respectively. Melatonin release from the pineal organ in flow-through culture exhibited a similar pattern in response to the change in light conditions, with high and low release associated with the dark and light phases, respectively. These results indicate that melatonin production in the sockeye salmon is driven by light and darkness but lacks circadian regulation.

Comparison of effects of ingested medium- and long-chain triglyceride on gallbladder volume and release of cholecystokinin and other gut peptides.

PubMed

Isaacs, P E; Ladas, S; Forgacs, I C; Dowling, R H; Ellam, S V; Adrian, T E; Bloom, S R

1987-05-01

In a double-blind, crossover study of the effect of ingested medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) in six normal subjects, the gallbladder did not contract after ingestion of MCT but instead had significantly increased in volume at 2 hr after the meal. Plasma cholecystokinin (CCK) increased after the MCT meal, but gastrin, motilin, pancreatic polypeptide (PP), and GIP were unaffected. The long-chain triglyceride meal evoked a brisk and sustained gallbladder contraction, higher levels of CCK, and a significant increase in plasma PP and GIP levels.

Expression of intra- and extracellular granzymes in patients with typhoid fever.

PubMed

de Jong, Hanna K; Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J; Parry, Christopher M; Maude, Rapeephan R; Dondorp, Arjen M; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-07-01

Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.

Expression of intra- and extracellular granzymes in patients with typhoid fever

PubMed Central

Garcia-Laorden, Maria Isabel; Hoogendijk, Arie J.; Parry, Christopher M.; Maude, Rapeephan R.; Dondorp, Arjen M.; Faiz, Mohammed Abul; van der Poll, Tom; Wiersinga, Willem Joost

2017-01-01

Background Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. Methods and principal findings We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. Conclusion The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease. PMID:28749963

Effect of Mobile Phone Usage on Nickel Ions Release and pH of Saliva in Patients Undergoing Fixed Orthodontic Treatment.

PubMed

Nanjannawar, Lalita Girish; Girme, Tejashree Suresh; Agrawal, Jiwanasha Manish; Agrawal, Manish Suresh; Fulari, Sangamesh Gurunath; Shetti, Shraddha Subhash; Kagi, Vishwal Ajith

2017-09-01

Hand held mobile phones are presently the most popular means of communication worldwide and have transformed our lives in many aspects. The widespread use of such devices have resulted in growing concerns regarding harmful effects of radiations emitted by them. This study was designed to evaluate the effects of mobile phone usage on nickel ion release as well as pH of saliva in patients with fixed orthodontic appliances. To assess the level of nickel ions in saliva and pH of saliva in mobile phone users undergoing fixed orthodontic treatment using inductively coupled plasma atomic emission spectrometry. A total of 42 healthy patients with fixed orthodontic appliance in mouth for a duration of six to nine months were selected for the study. They were divided into experimental group (n=21) consisting of mobile phone users and control group (n=21) of non mobile phone users. Saliva samples were collected from both the groups and nickel ion levels were measured using inductively coupled plasma-mass spectroscopy. The pH values were also assessed for both groups using pH meter. Unpaired t-test was used for the data analysis. Statistical analysis revealed that though the pH levels were reduced and the nickel ion levels were higher in the experimental group compared to the control group, the results were non significant. Mobile phone usage may affect the pH of saliva and result in increased release of nickel ions in saliva of patients with fixed orthodontic appliances in the oral cavity.

Increase in work productivity of depressed individuals with improvement in depressive symptom severity.

PubMed

Trivedi, Madhukar H; Morris, David W; Wisniewski, Stephen R; Lesser, Ira; Nierenberg, Andrew A; Daly, Ella; Kurian, Benji T; Gaynes, Bradley N; Balasubramani, G K; Rush, A John

2013-06-01

The authors sought to identify baseline clinical and sociodemographic characteristics associated with work productivity in depressed outpatients and to assess the effect of treatment on work productivity. Employed depressed outpatients 18-75 years old who completed the Work Productivity and Activity Impairment scale (N=1,928) were treated with citalopram (20-40 mg/day) in the Sequenced Treatment Alternatives to Relieve Depression study. For patients who did not remit after an initial adequate antidepressant trial (level 1), either a switch to sertraline, sustained-release bupropion, or extended-release venlafaxine or an augmentation with sustained-release bupropion or buspirone was provided (level 2). Participants' clinical and demographic characteristics and treatment outcomes were analyzed for associations with baseline work productivity and change in productivity over time. Education, baseline depression severity, and melancholic, atypical, and recurrent depression subtypes were all independently associated with lower benefit to work productivity domains. During level 1 treatment, work productivity in several domains improved with reductions in depressive symptom severity. However, these findings did not hold true for level 2 outcomes; there was no significant association between treatment response and reduction in work impairment. Results were largely confirmed when multiple imputations were employed to address missing data. During this additional analysis, an association was also observed between greater impairment in work productivity and higher levels of anxious depression. Patients with clinically significant reductions in symptom severity during initial treatment were more likely than nonresponders to experience significant improvements in work productivity. In contrast, patients who achieved symptom remission in second-step treatment continued to have impairment at work. Patients who have demonstrated some degree of treatment resistance are more prone to persistent impairment in occupational productivity, implying a need for additional, possibly novel, treatments.

Sodium selenite increases the transcript levels of iodothyronine deiodinases I and II in ovine and bovine fetal thyrocytes in vitro.

PubMed

Foroughi, Mohammad Ali; Dehghani, Hesam; Mahdavi-Shahri, Naser; Bassami, Mohammad Reza

2013-07-01

Selenium is essential for thyroid hormone homeostasis. Selenium is co-translationally incorporated into the protein backbone of 5' deiodinase enzymes, which are responsible for the intra- and extra-thyroidal activation of thyroid hormones. The objective of this study was to evaluate the effects of sodium selenite on the transcript levels of type I (DIO1) and II (DIO2) deiodinases in the primary culture of ovine and bovine fetal thyroid. By culture of fetal thyrocytes in the presence or absence of sodium selenite, and quantification of DIO1 and DIO2 transcripts using real-time reverse transcription polymerase chain reaction (RT-qPCR), we found that sodium selenite is able to increase the abundance of transcripts for DIO1 and DIO2 genes. We also found that cultured thyrocytes in the presence of sodium selenite compared to control cultured thyrocytes release more T3 into the culture medium. This indicates that in the presence of sodium selenite higher levels of DIO1 and DIO2 enzymes are produced, which are able to convert T4 to T3. In conclusion, we have shown that sodium selenite is increasing the abundance of DIO1 and DIO2 transcripts and increasing the production and release of T3 from cultured fetal thyrocytes. This finding emphasizes the role of selenium in transcriptional and expression processes during development and suggests that selenium deficiency during pregnancy in sheep and cattle may lead to the lower levels of DIO1 and DIO2 transcription in fetal thyroid, and thus, lower level of thyroidal T3 release into the fetal serum. Copyright © 2013 Elsevier GmbH. All rights reserved.

Patients with chronic insomnia have selective impairments in memory that are modulated by cortisol.

PubMed

Chen, Gui-Hai; Xia, Lan; Wang, Fang; Li, Xue-Wei; Jiao, Chuan-An

2016-10-01

Memory impairment is a frequent complaint in insomniacs; however, it is not consistently demonstrated. It is unknown whether memory impairment in insomniacs involves neuroendocrine dysfunction. The participants in this study were selected from the clinical setting and included 21 patients with chronic insomnia disorder (CID), 25 patients with insomnia and comorbid depressive disorder (CDD), and 20 control participants without insomnia. We evaluated spatial working and reference memory, object working and reference memory, and object recognition memory using the Nine Box Maze Test. We also evaluated serum neuroendocrine hormone levels. Compared to the controls, the CID patients made significantly more errors in spatial working and object recognition memory (p < .05), whereas the CDD patients performed poorly in all the assessed memory types (p < .05). In addition, the CID patients had higher levels (mean difference [95% CI]) of corticotrophin-releasing hormone, cortisol (31.98 [23.97, 39.98] μg/l), total triiodothyronine (667.58 [505.71, 829.45] μg/l), and total thyroxine (41.49 [33.23, 49.74] μg/l) (p < .05), and lower levels of thyrotropin-releasing hormone (-35.93 [-38.83, -33.02] ng/l), gonadotropin-releasing hormone (-4.50 [-5.02, -3.98] ng/l) (p < .05), and adrenocorticotropic hormone compared to the CDD patients. After controlling for confounding variables, the partial correlation analysis revealed that the levels of cortisol positively correlated with the errors in object working memory (r = .534, p = .033) and negatively correlated with the errors in object recognition memory (r = -.659, p = .006) in the CID patients. The results suggest that the CID patients had selective memory impairment, which may be mediated by increased cortisol levels. © 2016 Society for Psychophysiological Research.

Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca2+ signaling in ventricular myocytes.

PubMed

Park, Seon-Ah; Hong, Bing-Zhe; Ha, Ki-Chan; Kim, Uh-Hyun; Han, Myung-Kwan; Kwak, Yong-Geun

2017-06-02

Cyclic ADP-ribose (cADPR) releases Ca 2+ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca 2+ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca 2+ ([Ca 2+ ] i ) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca 2+ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca 2+ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.

Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro, ex vivo and in vivo characterizations.

PubMed

Mahjub, Reza; Radmehr, Moojan; Dorkoosh, Farid Abedin; Ostad, Seyed Naser; Rafiee-Tehrani, Morteza

2014-12-01

The purpose of this research was the development, in vitro, ex vivo and in vivo characterization of lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan. Insulin nanoparticles were prepared from methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4 pyridinyl) and methylated N-(benzyl). Insulin nanoparticles containing non-modified chitosan and also trimethyl chiotsan (TMC) were also prepared as control. The effects of the freeze-drying process on physico-chemical properties of nanoparticles were investigated. The release of insulin from the nanoparticles was studied in vitro. The mechanism of the release of insulin from different types of nanoparticles was determined using curve fitting. The secondary structure of the insulin released from the nanoparticles was analyzed using circular dichroism and the cell cytotoxicity of nanoparticles on a Caco-2 cell line was determined. Ex vivo studies were performed on excised rat jejunum using Frantz diffusion cells. In vivo studies were performed on diabetic male Wistar rats and blood glucose level and insulin serum concentration were determined. Optimized nanoparticles with proper physico-chemical properties were obtained. The lyophilization process was found to cause a decrease in zeta potential and an increase in PdI as well as and a decrease in entrapment efficiency (EE%) and loading efficiency (LE%) but conservation in size of nanoparticles. Atomic force microscopy (AFM) images showed non-aggregated, stable and spherical to sub-spherical nanoparticles. The in vitro release study revealed higher release rates for lyophilized compared to non-lyophilized nanoparticles. Cytotoxicity studies on Caco-2 cells revealed no significant cytotoxicity for prepared nanoparticles after 3-h post-incubation but did show the concentration-dependent cytotoxicity after 24 h. The percentage of cumulative insulin determined from ex vivo studies was significantly higher in nanoparticles prepared from quaternized aromatic derivatives of chitosan. In vivo data showed significantly higher insulin intestinal absorption in nanoparticles prepared from methylated N-(4-N, N-dimethylaminobenzyl) chitosan nanoparticles compared to trimethyl chitosan. These data obtained demonstrated that as the result of optimized physico-chemical properties, drug release rate, cytotoxicity profile, ex vivo permeation enhancement and increased in vivo absorption, nanoparticles prepared from N-aryl derivatives of chitosan can be considered as valuable method for the oral delivery of insulin.

Effects of different supplemental soya bean oil levels on the performance of prepubertal Saanen goats: Oestrogen and progesterone release.

PubMed

Bomfim, G F; Merighe, G K F; de Oliveira, S A; Rodrigues, A D; Augusto, L; Teixeira, I A M A; de Resende, K T; Negrao, J A

2016-12-01

The aim of this study was to investigate the effects of different levels of soya bean oil in the total diet on the growth rate, metabolic changes, and oestrogen and progesterone release in Saanen goats. After dietary adaptation, 21 prepubertal goats (weight of 29.12 ± 0.91 kg, 230 days old) were randomly distributed among three diets of D2: inclusion of 2% soya bean oil in the total diet; D3: basal diet - inclusion of 3% soya bean oil in the total diet; and D4: inclusion of 4% soya bean oil in the total diet. The basal diet (D3) was formulated to promote a daily gain of 0.140 kg. The goats were weighed, and their blood samples were collected weekly. Glucose, cholesterol, triglycerides, total protein, urea, non-esterified fatty acids, beta-hydroxybutyrate, oestrogen and progesterone in the plasma were measured. Prepubertal goats that were fed D4 exhibited a significantly lower dry matter intake, urea and cholesterol levels compared with the goats that were fed D2 and D3. Indeed, goats that were fed D4 displayed a significantly lower final weight than goats that were fed D2 and D3. In contrast, the inclusion of soya bean oil in the diet increased the progesterone and oestrogen concentrations, and goats that were fed D4 released a significantly higher concentration of progesterone than those that were fed D2 and D3. Furthermore, the percentage of goats with a progesterone level greater than 1 ng/ml (functional Corpus luteum) was significantly higher among the goats that were fed D3 and D4 than among those that were fed D2. In this study, although the inclusion of 4% soya bean oil in the diet decreased dry matter intake and growth rate, it increased progesterone concentration and the percentage of goats with a functional Corpus luteum, suggesting that the inclusion of soya bean oil accelerated puberty in prepubertal goats. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Forecasting of future earthquakes in the northeast region of India considering energy released concept

NASA Astrophysics Data System (ADS)

Zarola, Amit; Sil, Arjun

2018-04-01

This study presents the forecasting of time and magnitude size of the next earthquake in the northeast India, using four probability distribution models (Gamma, Lognormal, Weibull and Log-logistic) considering updated earthquake catalog of magnitude Mw ≥ 6.0 that occurred from year 1737-2015 in the study area. On the basis of past seismicity of the region, two types of conditional probabilities have been estimated using their best fit model and respective model parameters. The first conditional probability is the probability of seismic energy (e × 1020 ergs), which is expected to release in the future earthquake, exceeding a certain level of seismic energy (E × 1020 ergs). And the second conditional probability is the probability of seismic energy (a × 1020 ergs/year), which is expected to release per year, exceeding a certain level of seismic energy per year (A × 1020 ergs/year). The logarithm likelihood functions (ln L) were also estimated for all four probability distribution models. A higher value of ln L suggests a better model and a lower value shows a worse model. The time of the future earthquake is forecasted by dividing the total seismic energy expected to release in the future earthquake with the total seismic energy expected to release per year. The epicentre of recently occurred 4 January 2016 Manipur earthquake (M 6.7), 13 April 2016 Myanmar earthquake (M 6.9) and the 24 August 2016 Myanmar earthquake (M 6.8) are located in zone Z.12, zone Z.16 and zone Z.15, respectively and that are the identified seismic source zones in the study area which show that the proposed techniques and models yield good forecasting accuracy.

Differential release and deposition of S100A8/A9 proteins in inflamed upper airway tissue.

PubMed

Van Crombruggen, Koen; Vogl, Thomas; Pérez-Novo, Claudina; Holtappels, Gabriele; Bachert, Claus

2016-01-01

Intracellular Ca(2+)-binding S100A8/A9 proteins gain novel functions when released during inflammation. The exact outcome of their extracellular function depends on the local tissue environment in which they are released; both anti-inflammatory and pro-inflammatory responses are described, modulating the immune system by binding Toll-like receptor (TLR)-4 or the receptor for advanced glycation end-products (RAGE). However, the contribution of the proteins in the pathophysiology of chronic rhinosinusitis (CRS) remains unclear.Homomeric S100A8 and S100A9, and heteromeric S100A8/A9 proteins were evaluated in CRS with/without nasal polyps (CRSw/sNP) and controls. Functional responses were assessed in polyp tissue stimulated with S100 proteins in the presence of TLR-4 and RAGE blocking antibodies.S100A8, S100A9 and S100A8/A9 protein levels were significantly higher in CRSwNP patients, showing increased deposition on extracellular matrix (ECM) structures of CRSwNP tissue in contrast to CRSsNP and controls. In the presence of Staphylococcus aureus, S100A8/A9 is released from neutrophils and from the ECM. Extracellular S100A8 and S100A9 proteins induced increased levels of diverse inflammatory mediators via TLR-4 engagement.The inflammatory/remodelling characteristics of CRSwNP specifically allow increased retention of S100A8, S100A9 and S100A8/A9 proteins in the ECM of CRSwNP tissue. Upon release, homodimeric proteins act as a local danger signal inducing inflammatory mediators, predominantly via TLR-4 activation. Copyright ©ERS 2016.

Sweat Allergy.

PubMed

Hiragun, Takaaki; Hide, Michihiro

2016-01-01

For many years, sweat has been recognized as an exacerbation factor in all age groups of atopic dermatitis (AD) and a trigger of cholinergic urticaria (CholU). Recently, we reported the improvement of AD symptoms by spray with tannic acid, which suppresses basophil histamine release by semipurified sweat antigens in vitro, and showering that removes antigens in sweat from the skin surface. We finally identified MGL_1304 secreted by Malassezia globosa as a major histamine-releasing antigen in human sweat. MGL_1304 is detected as a 17-kDa protein in sweat and exhibits almost the highest histamine-release ability from basophils of patients with AD and CholU among antigens derived from Malassezia species. Moreover, serum levels of anti-MGL_1304 IgE of patients with AD and CholU were significantly higher than those of normal controls. Desensitization therapy using autologous sweat or MGL_1304 purified from culture of M. globosa or its cognates might be beneficial for patients with intractable CholU due to sweat allergy. © 2016 S. Karger AG, Basel.

Effectiveness of a Releasing Exercise Program on Anxiety and Self-Efficacy Among Nurses.

PubMed

Chen, Huei-Mein; Wang, Hsiu-Hung; Chiu, Min-Hui

2016-02-01

The purpose of this study was to evaluate the effectiveness of a releasing exercise program (REP) on anxiety and exercise self-efficacy among nurses. The REP consisted of warm-up and tension-releasing exercises and mood adjustment. Ninety-nine nurses (age = 33.38 ± 7.38 years) experiencing anxiety (average Visual Analog Scale for Anxiety [VASA] score of 5.63 ± 1.44 at baseline) were randomly assigned to an experimental group (n = 50) that received 50-min REP sessions 3 times a week or a control group (n = 49) that did not attend REP sessions. The outcome measures were VASA, the Chinese Version of the Beck Anxiety Inventory, and Exercise Self-Efficacy Scale scores. At Weeks 12 and 24, the experimental group had significantly lower anxiety levels and higher exercise self-efficacy scores than the control group. Therefore, the REP effectively reduces anxiety and enhances self-confidence in exercise capability. © The Author(s) 2014.

An Evaluation of iPad as a Learning Tool in Higher Education within a Rural Catchment: A Case Study at a South African University

ERIC Educational Resources Information Center

Wario, Ruth Diko; Ireri, Bonface Ngari; De Wet, Lizette

2016-01-01

Since Apple released the iPad in 2010, it has been widely adopted for teaching and learning. Its graphical user interface combined with touch screen features engages users by attracting their attention. However, the level of engagement that would influence learning is not well understood. This case study investigated the use of iPads when engaging…

Occurrence of pharmaceuticals and personal care products in effluent-dominated Saudi Arabian coastal waters of the Red Sea.

PubMed

Ali, Aasim M; Rønning, Helene Thorsen; Alarif, Walied; Kallenborn, Roland; Al-Lihaibi, Sultan S

2017-05-01

The occurrence of selected pharmaceuticals and personal care products (PPCPs) and the pesticide atrazine were investigated in seawater samples collected from stations located at effluent dominated sites in the Saudi Arabian coastal waters of the Red Sea. PPCPs were analysed using solid phase extraction (SPE) followed by high performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). A multi component method for the ultra-trace level quantification of 13 target PPCPs in Seawater was developed and validated for the here performed study. The method procedure is described in detail in the supplementary material section. 26 samples from 7 distinct locations (2 directly influenced by continuous sewage release) were chosen for the sampling of surface seawater. Based upon local sales information, 25 target substances (20 PPCPs, 4 pesticides and 1 stimulant) were chosen for the here reported method development. Thirteen PPCPs were detected and quantified in a total of 26 seawater samples. Metformin, diclofenac, acetaminophen, and caffeine were identified as the most abundant PPCPs, detected in maximum concentration higher than 3 μg/L (upper quantification limit for the here developed method). Concentrations were in the range of 7- >3000 (metformin), 3000 ng/L (caffeine). The contribution of direct sewage release on the PPCP levels detected was obvious, the target PPCPs were detected in the Al-Arbaeen and Al-Shabab coastal lagoons in high concentrations due to the low water exchange with the open sea and still ongoing sewage releases in the lagoons. Also, substantial amounts of antibiotics were detected in all samples. Levels and distribution profile of the detected PPCPs revealed high level release rates and give raise to concern on potential environmental risks associated with the here document long term exposure on the fragile coastal marine environment of the region but particularly in the nearby protected coral reef environment outside the harbour region of Jeddah. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neural correlates of binaural masking level difference in the inferior colliculus of the barn owl (Tyto alba).

PubMed

Asadollahi, Ali; Endler, Frank; Nelken, Israel; Wagner, Hermann

2010-08-01

Humans and animals are able to detect signals in noisy environments. Detection improves when the noise and the signal have different interaural phase relationships. The resulting improvement in detection threshold is called the binaural masking level difference. We investigated neural mechanisms underlying the release from masking in the inferior colliculus of barn owls in low-frequency and high-frequency neurons. A tone (signal) was presented either with the same interaural time difference as the noise (masker) or at a 180 degrees phase shift as compared with the interaural time difference of the noise. The changes in firing rates induced by the addition of a signal of increasing level while masker level was kept constant was well predicted by the relative responses to the masker and signal alone. In many cases, the response at the highest signal levels was dominated by the response to the signal alone, in spite of a significant response to the masker at low signal levels, suggesting the presence of occlusion. Detection thresholds and binaural masking level differences were widely distributed. The amount of release from masking increased with increasing masker level. Narrowly tuned neurons in the central nucleus of the inferior colliculus had detection thresholds that were lower than or similar to those of broadly tuned neurons in the external nucleus of the inferior colliculus. Broadly tuned neurons exhibited higher masking level differences than narrowband neurons. These data suggest that detection has different spectral requirements from localization.

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes.

PubMed

Na, Yong-Jin; Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Wang, Ji-Won; Jin, Jun-O; Kwak, Jong-Young; Lee, Kyu-Sup

2011-06-01

Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. There was a positive correlation between the levels of MCP-1 and MIP-1α in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1α when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1α released by neutrophils and between the levels of MCP-1 and MIP-1α released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1α in response to stimulation with ePF.

Neural nitric oxide gene inactivation affects the release profile of oxytocin into the blood in response to forced swimming.

PubMed

Orlando, G F; Langnaese, K; Landgraf, R; Spina, M G; Wolf, G; Engelmann, M

2007-02-01

This study was undertaken to examine the importance of nitric oxide (NO) generated by the neural isoform of the nitric oxide synthase (nNOS) on the activity of the hypothalamic neurohypophyseal system in neural nitric oxide synthase knock-out (KO) and wild-type (WT) mice under basal conditions and in response to forced swimming. The intensity of the hybridisation signal for vasopressin (AVP) in the hypothalamic supraoptic nucleus (SON) was significantly higher in KO mice when compared with WT, whereas oxytocin (OXT) basal mRNA levels were similar in both groups. Although the basal peripheral release of AVP and OXT was equivalent in both genotypes, we observed in KO mice a significant drop of AVP and OXT plasma values 15 min after stressor onset and a robust increase in the OXT plasma concentration at 60 min. These findings suggest that in the male mouse, NO inhibits AVP gene transcription in magnocellular neurones of the SON and collaborates in maintaining constant AVP and OXT plasma levels following acute stressor exposure, exerting a bimodal regulatory action on OXT secretion. We conclude that NO is involved in the regulation of magnocellular neurones of the SON, and it is preferentially implicated in the attenuation of the peripheral release of OXT induced by acute stressor exposure.

The mid-Cretaceous super plume, carbon dioxide, and global warming

NASA Technical Reports Server (NTRS)

Caldeira, Ken; Rampino, Michael R.

1991-01-01

Carbon-dioxide releases associated with a mid-Cretaceous super plume and the emplacement of the Ontong-Java Plateau have been suggested as a principal cause of the mid-Cretaceous global warming. A carbonate-silicate cycle model is developed to quantify the possible climatic effects of these CO2 releases, utilizing four different formulations for the rate of silicate-rock weathering as a function of atmospheric CO2. CO2 emissions resulting from super-plume tectonics could have produced atmospheric CO2 levels from 3.7 to 14.7 times the modern preindustrial value of 285 ppm. Based on the temperature sensitivity to CO2 increases used in the weathering-rate formulations, this would cause a global warming of from 2.8 to 7.7 C over today's glogal mean temperature. Altered continental positions and higher sea level may have been contributed about 4.8 C to mid-Cretaceous warming. Thus, the combined effects of paleogeographic changes and super-plume related CO2 emissions could be in the range of 7.6 to 12.5 C, within the 6 to 14 C range previously estimated for mid-Cretaceous warming. CO2 releases from oceanic plateaus alone are unlikely to have been directly responsible for more than 20 percent of the mid-Cretaceous increase in atmospheric CO2.

Mimicking the Impact of Infant Tongue Peristalsis on Behavior of Solid Oral Dosage Forms Administered During Breastfeeding.

PubMed

Scheuerle, Rebekah L; Kendall, Richard A; Tuleu, Catherine; Slater, Nigel K H; Gerrard, Stephen E

2017-01-01

An in vitro simulation system was developed to study the effect of an infant's peristaltic tongue motion during breastfeeding on oral rapidly disintegrating tablets in the mouth, for use in rapid product candidate screening. These tablets are being designed for use inside a modified nipple shield worn by a mother during breastfeeding, a proposed novel platform technology to administer drugs and nutrients to breastfeeding infants. In this study, the release of a model compound, sulforhodamine B, from tablet formulations was studied under physiologically relevant forces induced by compression and rotation of a tongue mimic. The release profiles of the sulforhodamine B in flowing deionized water were found to be statistically different using 2-way ANOVA with matching, when tongue mimic rotation was introduced for 2 compression levels representing 2 tongue strengths (p = 0.0013 and p < 0.0001 for the lower and higher compression settings, respectively). Compression level was found to be a significant factor for increasing model compound release at rotational rates representing nonnutritive breastfeeding (p = 0.0162). This novel apparatus is the first to simulate the motion and pressures applied by the tongue and could be used in future infant oral product development. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A Novel Method for Characterizing Fatigue Delamination Growth Under Mode I Using the Double Cantilever Beam Specimen

NASA Technical Reports Server (NTRS)

Carvalho, Nelson; Murri, G.

2014-01-01

A novel method is proposed to obtain Mode I delamination growth rate from a Double Cantilever Beam (DCB) specimen. In the proposed method, Unidirectional (UD) DCB specimens are tested in fatigue at different initial maximum energy release rates levels. The growth rate data obtained in the first increments of crack growth at each maximum energy release rate level are used to generate a Paris Law equation, which characterizes delamination growth rate without fiber-bridging, and can also be used to determine a delamination onset curve. The remaining delamination growth rate data from each test are used to determine a modified Paris law, which characterizes the delamination growth rate in a DCB specimen, explicitly accounting for fiber-bridging. The proposed expression captures well the scatter in experimental data obtained using the DCB specimens, suggesting its adequacy. The Paris Law characterizing delamination growth rate without fiber-bridging predicts higher delamination growth rates for the same maximum energy release rate applied, leading to a conservative estimate for delamination growth. This is particularly relevant, since in generic ply interfaces, fiber-bridging is less predominant than in UD DCB specimens. Failing to account for fiber-bridging in UD DCB specimens may underestimate the delamination growth rate, yielding non-conservative predictions.

Real time imaging of live cell ATP leaking or release events by chemiluminescence microscopy

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

Zhang, Yun

The purpose of this research was to expand the chemiluminescence microscopy applications in live bacterial/mammalian cell imaging and to improve the detection sensitivity for ATP leaking or release events. We first demonstrated that chemiluminescence (CL) imaging can be used to interrogate single bacterial cells. While using a luminometer allows detecting ATP from cell lysate extracted from at least 10 bacterial cells, all previous cell CL detection never reached this sensitivity of single bacteria level. We approached this goal with a different strategy from before: instead of breaking bacterial cell membrane and trying to capture the transiently diluted ATP with themore » firefly luciferase CL assay, we introduced the firefly luciferase enzyme into bacteria using the modern genetic techniques and placed the CL reaction substrate D-luciferin outside the cells. By damaging the cell membrane with various antibacterial drugs including antibiotics such as Penicillins and bacteriophages, the D-luciferin molecules diffused inside the cell and initiated the reaction that produces CL light. As firefly luciferases are large protein molecules which are retained within the cells before the total rupture and intracellular ATP concentration is high at the millmolar level, the CL reaction of firefly luciferase, ATP and D-luciferin can be kept for a relatively long time within the cells acting as a reaction container to generate enough photons for detection by the extremely sensitive intensified charge coupled device (ICCD) camera. The result was inspiring as various single bacterium lysis and leakage events were monitored with 10-s temporal resolution movies. We also found a new way of enhancing diffusion D-luciferin into cells by dehydrating the bacteria. Then we started with this novel single bacterial CL imaging technique, and applied it for quantifying gene expression levels from individual bacterial cells. Previous published result in single cell gene expression quantification mainly used a fluorescence method; CL detection is limited because of the difficulty to introduce enough D-luciferin molecules. Since dehydration could easily cause proper size holes in bacterial cell membranes and facilitate D-luciferin diffusion, we used this method and recorded CL from individual cells each hour after induction. The CL light intensity from each individual cell was integrated and gene expression levels of two strain types were compared. Based on our calculation, the overall sensitivity of our system is already approaching the single enzyme level. The median enzyme number inside a single bacterium from the higher expression strain after 2 hours induction was quantified to be about 550 molecules. Finally we imaged ATP release from astrocyte cells. Upon mechanical stimulation, astrocyte cells respond by increasing intracellular Ca 2+ level and releasing ATP to extracellular spaces as signaling molecules. The ATP release imaged by direct CL imaging using free firefly luciferase and D-luciferin outside cells reflects the transient release as well as rapid ATP diffusion. Therefore ATP release detection at the cell surface is critical to study the ATP release mechanism and signaling propagation pathway. We realized this cell surface localized ATP release imaging detection by immobilizing firefly luciferase to streptavidin beads that attached to the cell surface via streptavidin-biotin interactions. Both intracellular Ca 2+ propagation wave and extracellular ATP propagation wave at the cell surface were recorded with fluorescence and CL respectively. The results imply that at close distances from the stimulation center (<120 μm) extracellular ATP pathway is faster, while at long distances (>120 μm) intracellular Ca 2+ signaling through gap junctions seems more effective.« less

Preparation and characterization of intravaginal vardenafil suppositories targeting a complementary treatment to boost in vitro fertilization process.

PubMed

Gomaa, Eman; Abu Lila, Amr S; Hasan, Azza A; Ghazy, Fakhr-Eldin S

2018-01-01

Vaginal route has been recently considered as a potential route for systemic delivery of drugs with poor oral bioavailability. Vardenafil (VDF) is a relatively new phosphodiesterase-5 inhibitor that exhibits a limited oral bioavailability (≈15%) due to extensive first-pass metabolism. In this study, we attempted to enhance the systemic bioavailability of VDF via its formulation within vaginal suppositories. Witepsol H15 and Suppocire NA50 were adopted as lipophilic suppository bases while polyethylene glycol 4000/400 and glycerogelatin were used as hydrophilic suppository bases. The effect of different base types and/or the incorporation of bioadhesive polymer on in vitro release of VDF were evaluated. The in vivo fate and organ biodistribution of VDF following intravaginal (IVG) administration were also investigated. VDF release from water-soluble bases was higher than that from lipophilic bases. The incorporation of bioadhesive polymers, such as Na alginate, remarkably sustained drug release from suppository base. The organ biodistribution study showed a higher C max (32 times) and AUC 0-4h (20 times) of VDF in uterus following IVG administration of conventional suppositories, compared to oral administration of VDF suspension. In addition, cyclic guanosine monophosphate (cGMP) serum levels, used as an indicator of the in vivo activity of VDF, in animals were higher following IVG administration rather than oral administration. This study suggests that IVG administration of VDF might represent a potential alternative to oral route with superior therapeutic benefits especially when targeting the uterus. Copyright © 2017 Elsevier B.V. All rights reserved.

Ambient ammonia measurements using laser photo-acoustic spectroscopy

NASA Technical Reports Server (NTRS)

Aldridge, M. D., III; Copeland, G. E.; Harward, C. N.

1981-01-01

Ammonia concentrations reached minimal levels (approximately 0.1 ppb) in early winter, followed by a sudden later winter increase. A direct relationship between ambient ammonia levels and air temperature was inferred from the data (linear correlation coefficient r=0.53). Ammonia concentrations were determined to be directly related to the absolute humidity of the air (r=0.72); a weaker relationship between ammonia concentrations and relative humidity was discovered (r=0.37). The data also indicated that ammonia levels were generally higher within continental air masses than those of maritime origin. Soil parameters such as pH and moisture content were found to have a major bearing on the release of gaseous ammonia from soils in the region.

Reservoir water level drawdown as a novel, substantial, and manageable control on methane release to the atmosphere

NASA Astrophysics Data System (ADS)

Harrison, J.; Deemer, B. R.; Birchfield, M. K.

2014-12-01

Reservoirs constitute a globally important source of atmospheric methane (CH4). Although it is reasonably well-established that hydrostatic and barometric pressure can influence rates of CH4 release from lake and tidal sediments, the relationship between water-level manipulation and CH4 release from man-made impoundments has not been quantified or characterized. Furthermore, cross-system controls on CH4 production and release to the atmosphere have not been established. We collected CH4 emission (diffusion and ebullition) data for 8 reservoirs in the U.S. Pacific Northwest that are subject to a range of trophic conditions and water level management regimes. Our aim was to: (1) characterize CH4 emissions from these systems, and (2) quantify effects of water level management and eutrophication on CH4 fluxes. Results indicate very high fluxes, in some cases the highest reported reservoir emission rates, and a strong correspondence between lake level reduction and CH4 emissions, including quantitatively important bursts of CH4 bubbling. In one reservoir, drawdown-associated CH4 fluxes accounted for over 25% of annual CH4 emissions in a period of just 16 days (4% of the year). Average CH4 ebullition rates in a reservoir managed for hydropower peaking were nearly three-fold higher than in a paired upstream reservoir managed to maintain a constant water level (528 mg CH4 m-2 d-1 and 187 mg CH4 m-2 d-1 respectively). Highest gas fluxes were observed during the water level drawdown component of the hydropower peaking cycle (14.3 g CH4 m-2 d-1). In addition we observe a strong, positive relationship between eutrophication (as indicated by surface Chl a concentrations) and CH4 production (r2 = 0.88; P<0.001) and between eutrophication and the sensitivity of CH4 emissions to drawdown (r2 = 0.84; P<0.001). This work suggests that manipulation of water levels can significantly affect CH4 emissions from reservoirs to the atmosphere, and that sampling programs that miss drawdown periods may substantially underestimate CH4 fluxes. It also suggests that controlling nutrient loading may reduce greenhouse gas fluxes from surface waters to the atmosphere.

Radiation Monitoring Equipment Dosimeter Experiment

NASA Technical Reports Server (NTRS)

Hardy, Kenneth A.; Golightly, Michael J.; Quam, William

1992-01-01

Spacecraft crews risk exposure to relatively high levels of ionizing radiation. This radiation may come from charged particles trapped in the Earth's magnetic fields, charged particles released by solar flare activity, galactic cosmic radiation, energetic photons and neutrons generated by interaction of these primary radiations with spacecraft and crew, and man-made sources (e.g., nuclear power generators). As missions are directed to higher radiation level orbits, viz., higher altitudes and inclinations, longer durations, and increased flight frequency, radiation exposure could well become a major factor for crew stay time and career lengths. To more accurately define the radiological exposure and risk to the crew, real-time radiation monitoring instrumentation, which is capable of identifying and measuring the various radiation components, must be flown. This presentation describes a radiation dosimeter instrument which was successfully flown on the Space Shuttle, the RME-3.

Elemental composition and optical properties reveal changes in dissolved organic matter along a permafrost thaw chronosequence in a subarctic peatland

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

Hodgkins, Suzanne B.; Tfaily, Malak M.; Podgorski, David C.

2016-08-01

The fate of carbon stored in permafrost-zone peatlands represents a significant uncertainty in global climate modeling. Given that the breakdown of dissolved organic matter (DOM) is often a major pathway for decomposition in peatlands, knowledge of DOM reactivity under different permafrost regimes is critical for determining future climate feedbacks. To explore the effects of permafrost thaw and resultant plant succession on DOM reactivity, we used a combination of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), UV/Vis absorbance, and excitation-emission matrix spectroscopy (EEMS) to examine the DOM elemental composition and optical properties of 27 pore water samples gathered frommore » various sites along a permafrost thaw sequence in Stordalen Mire, a thawing subarctic peatland in northern Sweden. The presence of dense Sphagnum moss, a feature that is dominant in the intermediate thaw stages, appeared to be the main driver of variation in DOM elemental composition and optical properties at Stordalen. Specifically, DOM from sites with Sphagnum had greater aromaticity, higher average molecular weights, and greater O/C, consistent with a higher abundance of phenolic compounds that likely inhibit decomposition. These compounds are released by Sphagnum and may accumulate due to inhibition of phenol oxidase activity by the acidic pH at these sites. In contrast, sites without Sphagnum, specifically fully-thawed rich fens, had more saturated, more reduced compounds, which were high in N and S. Optical properties at rich fens were indicated the presence of microbially-derived DOM, consistent with the higher decomposition rates previously measured at these sites. These results indicate that Sphagnum acts as an inhibitor of rapid decomposition and CH4 release in thawing subarctic peatlands, consistent with lower rates of CO2 and CH4 production previously observed at these sites. However, this inhibitory effect may disappear if Sphagnumdominated bogs transition to more waterlogged rich fens that contain very little to no living Sphagnum. Release of this inhibition allows for higher levels of microbial activity and potentially greater CH4 release, as has been observed in these fen sites.« less

Elemental composition and optical properties reveal changes in dissolved organic matter along a permafrost thaw chronosequence in a subarctic peatland

NASA Astrophysics Data System (ADS)

Hodgkins, Suzanne B.; Tfaily, Malak M.; Podgorski, David C.; McCalley, Carmody K.; Saleska, Scott R.; Crill, Patrick M.; Rich, Virginia I.; Chanton, Jeffrey P.; Cooper, William T.

2016-08-01

The fate of carbon stored in permafrost-zone peatlands represents a significant uncertainty in global climate modeling. Given that the breakdown of dissolved organic matter (DOM) is often a major pathway for decomposition in peatlands, knowledge of DOM reactivity under different permafrost regimes is critical for determining future climate feedbacks. To explore the effects of permafrost thaw and resultant plant succession on DOM reactivity, we used a combination of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), UV/Vis absorbance, and excitation-emission matrix spectroscopy (EEMS) to examine the DOM elemental composition and optical properties of 27 pore water samples gathered from various sites along a permafrost thaw sequence in Stordalen Mire, a thawing subarctic peatland in northern Sweden. The presence of dense Sphagnum moss, a feature that is dominant in the intermediate thaw stages, appeared to be the main driver of variation in DOM elemental composition and optical properties at Stordalen. Specifically, DOM from sites with Sphagnum had greater aromaticity, higher average molecular weights, and greater O/C, consistent with a higher abundance of phenolic compounds that likely inhibit decomposition. These compounds are released by Sphagnum and may accumulate due to inhibition of phenol oxidase activity by the acidic pH at these sites. In contrast, sites without Sphagnum, specifically fully-thawed rich fens, had more saturated, more reduced compounds, which were high in N and S. Optical properties at rich fens indicated the presence of microbially-derived DOM, consistent with the higher decomposition rates previously measured at these sites. These results indicate that Sphagnum acts as an inhibitor of rapid decomposition and CH4 release in thawing subarctic peatlands, consistent with lower rates of CO2 and CH4 production previously observed at these sites. However, this inhibitory effect may disappear if Sphagnum-dominated bogs transition to more waterlogged rich fens that contain very little to no living Sphagnum. Release of this inhibition allows for higher levels of microbial activity and potentially greater CH4 release, as has been observed in these fen sites.

Investigation of a new pH-responsive nanoparticulate pore former for controlled release enteric coating with improved processability and stability.

PubMed

Chen, Kuan; Chang, Hao Han R; Shalviri, Alireza; Li, Jason; Lugtu-Pe, Jamie Anne; Kane, Anil; Wu, Xiao Yu

2017-11-01

Water-soluble polymers are often used as pore formers to tailor permeability of film-forming hydrophobic polymers on coated dosage forms. However, their addition to a coating formulation could significantly increase the viscosity thus making the coating process difficult. Moreover, the dissolution of pore formers after oral administration could compromise film integrity resulting in undesirable, inconsistent release profiles. Therefore, a non-leaching, pH-responsive nanoparticulate pore former is proposed herein to preserve film integrity and maintain pH-dependent permeability. Poly(methacrylic acid)-polysorbate 80-grafted-starch terpolymer nanoparticles (TPNs) were incorporated within an ethylcellulose (EC) film (TPN-EC) by casting or spray coating. TPNs at 10%wt (pore former level) only increased viscosity of EC coating suspension slightly while conventional pore formers increased the viscosity by 490-11,700%. Negligible leaching of TPNs led to superior mechanical properties of TPN-EC films compared to Eudragit® L-EC films. As pH increased from 1.2 to 6.8, TPN-EC films with 10% pore former level exhibited an 8-fold higher diltiazem permeability compared to Eudragit® L-EC films. The pH-dependent drug release kinetics of diltiazem HCl beads coated with TPN-EC films was tunable by adjusting the pore former level. These results suggest that the TPNs are promising pH-sensitive nanoparticulate pore formers in EC-coated dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlling the Release of Indomethacin from Glass Solutions Layered with a Rate Controlling Membrane Using Fluid-Bed Processing. Part 2: The Influence of Formulation Parameters on Drug Release.

PubMed

Dereymaker, Aswin; Pelgrims, Jirka; Engelen, Frederik; Adriaensens, Peter; Van den Mooter, Guy

2017-04-03

This study aimed to investigate the pharmaceutical performance of an indomethacin-polyvinylpyrrolidone (PVP) glass solution applied using fluid bed processing as a layer on inert sucrose spheres and subsequently top-coated with a release rate controlling membrane consisting of either ethyl cellulose or Eudragit RL. The implications of the addition of a pore former (PVP) and the coating medium (ethanol or water) on the diffusion and release behavior were also considered. In addition, the role of a charge interaction between drug and controlled release polymer on the release was investigated. Diffusion experiments pointed to the influence of pore former concentration, rate controlling polymer type, and coating solvent on the permeability of the controlled release membranes. This can be translated to drug release tests, which show the potential of diffusion tests as a preliminary screening test and that diffusion is the main factor influencing release. Drug release tests also showed the effect of coating layer thickness. A charge interaction between INDO and ERL was demonstrated, but this had no negative effect on drug release. The higher diffusion and release observed in ERL-based rate controlling membranes was explained by a higher hydrophilicity, compared to EC.

Attaining the canopy in dry and moist tropical forests: strong differences in tree growth trajectories reflect variation in growing conditions

PubMed Central

Zuidema, Pieter A.; Martínez-Ramos, Miguel

2009-01-01

Availability of light and water differs between tropical moist and dry forests, with typically higher understorey light levels and lower water availability in the latter. Therefore, growth trajectories of juvenile trees—those that have not attained the canopy—are likely governed by temporal fluctuations in light availability in moist forests (suppressions and releases), and by spatial heterogeneity in water availability in dry forests. In this study, we compared juvenile growth trajectories of Cedrela odorata in a dry (Mexico) and a moist forest (Bolivia) using tree rings. We tested the following specific hypotheses: (1) moist forest juveniles show more and longer suppressions, and more and stronger releases; (2) moist forest juveniles exhibit wider variation in canopy accession pattern, i.e. the typical growth trajectory to the canopy; (3) growth variation among dry forest juveniles persists over longer time due to spatial heterogeneity in water availability. As expected, the proportion of suppressed juveniles was higher in moist than in dry forest (72 vs. 17%). Moist forest suppressions also lasted longer (9 vs. 5 years). The proportion of juveniles that experienced releases in moist forest (76%) was higher than in dry forest (41%), and releases in moist forests were much stronger. Trees in the moist forest also had a wider variation in canopy accession patterns compared to the dry forest. Our results also showed that growth variation among juvenile trees persisted over substantially longer periods of time in dry forest (>64 years) compared to moist forest (12 years), most probably because of larger persistent spatial variation in water availability. Our results suggest that periodic increases in light availability are more important for attaining the canopy in moist forests, and that spatial heterogeneity in water availability governs long-term tree growth in dry forests. Electronic supplementary material The online version of this article (doi:10.1007/s00442-009-1540-5) contains supplementary material, which is available to authorized users. PMID:20033820

Influence of 2% chlorhexidine on pH, calcium release and setting time of a resinous MTA-based root-end filling material.

PubMed

Jacinto, Rogério Castilho; Linhares-Farina, Giane; Sposito, Otávio da Silva; Zanchi, César Henrique; Cenci, Maximiliano Sérgio

2015-01-01

The addition of chlorhexidine (CHX) to a resinous experimental Mineral Trioxide Aggregate (E-MTA) based root-end filling material is an alternative to boost its antimicrobial activity. However, the influence of chlorhexidine on the properties of this material is unclear. The aim of this study was to evaluate the influence of 2% chlorhexidine on the pH, calcium ion release and setting time of a Bisphenol A Ethoxylate Dimethacrylate/Mineral Trioxide Aggregate (Bis-EMA/MTA) based dual-cure experimental root-end filling material (E-MTA), in comparison with E-MTA without the addition of CHX and with conventional white MTA (W-MTA). The materials were placed in polyethylene tubes, and immersed in deionized water to determine pH (digital pH meter) and calcium ion release (atomic absorption spectrometry technique). The setting time of each material was analyzed using Gilmore needles. The data were statistically analyzed at a significance level of 5%. E-MTA + CHX showed an alkaline pH in the 3 h period of evaluation, the alkalinity of which decreased but remained as such for 15 days. The pH of E-MTA + CHX was higher than the other two materials after 7 days, and lower after 30 days (p < 0.05). All of the materials were found to release calcium ions throughout the 30 days of the study. The addition of CHX increased the calcium ion release of E-MTA to levels statistically similar to W-MTA. E-MTA showed shorter initial and final setting time, compared with W-MTA (p < 0.05). The addition of 2% CHX to MTA prevented setting of the material. The addition of CHX to E-MTA increased its pH and calcium ion release. However, it also prevented setting of the material.

PELA microspheres with encapsulated arginine-chitosan/pBMP-2 nanoparticles induce pBMP-2 controlled-release, transfected osteoblastic progenitor cells, and promoted osteogenic differentiation.

PubMed

Xu, Xiaolong; Qiu, Sujun; Zhang, Yuxian; Yin, Jie; Min, Shaoxiong

2017-03-01

Repair of the bone injury remains a challenge in clinical practices. Recent progress in tissue engineering and therapeutic gene delivery systems have led to promising new strategies for successful acceleration of bone repair process. The aim of this study was to create a controlled-release system to slowly release the arginine-chitosan/plasmid DNA nanoparticles encoding BMP-2 gene (Arg-CS/pBMP-2 NPs), efficiently transfect osteoblastic progenitor cells, secrete functional BMP-2 protein, and promote osteogenic differentiation. In this study, chitosan was conjugated with arginine to generate arginine-chitosan polymer (Arg-CS) for gene delivery. Mix the Arg-CS with pBMP-2 to condense pBMP-2 into nano-sized particles. In vitro transfection assays demonstrated that the transfection efficiency of Arg-CS/pBMP-2 nanoparticles and the expression level of BMP-2 was obviously exceed control groups. Further, PELA microspheres as the controlled-release carrier for the nanoparticles were used to encapsulate Arg-CS/pBMP-2 NPs. We demonstrated that the Arg-CS/pBMP-2 NPs could slowly release from the PELA microspheres at least for 42 d. During the co-culture with the PELA microspheres, the content of BMP-2 protein secreted by MC3T3-E1 reached the peak at 7 d. After 21d, the secretion of BMP-2 protein still maintain a higher level. The alkaline phosphatase activity, alizarin red staining, and osteogenesis-related gene expression by real-time quantitative PCR analysis all showed the PELA microspheres entrapping with Arg-CS/pBMP-2 NPs can obviously induce the osteogenic differentiation. The results indicated that the Arg-CS is a suitable gene vector which can promote the gene transfection. And the novel PELA microspheres-nanoparticle controlled-release system has potential clinical application in the future after further research.

Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

PubMed

Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

2017-12-01

Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

Preparation and evaluation of a timolol maleate drug-resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo.

PubMed

Qin, Fuhong; Zeng, Li; Zhu, Yongtao; Cao, Jingjing; Wang, Xiaohui; Liu, Wei

2016-01-01

The aim of this work was to assess the performance of resin as an ocular delivery system. Timolol maleate (TM) was chosen as the model drug and an ion exchange resin (IER) as the carrier. The drug-resin complex was prepared using an oscillation method and then characterized regarding particle size, zeta potential, morphology, and drug content. After in vitro drug release study and corneal permeation study were performed, in vivo studies were performed in New Zealand albino rabbits using a suspension with particles sized 4.8 ± 1.2 μm and drug loading at 43.00 ± 0.09%. The results indicate that drug released from the drug-resin ophthalmic suspension permeated the cornea and displayed a sustained-release behavior. Drug levels in the ocular tissues after administration of the drug-resin ophthalmic suspension were significantly higher than after treatment with an eye drop formulation but were lower in body tissues and in the plasma. In conclusion, resins have great potential as effective ocular drug delivery carriers to increase ocular bioavailability of timolol while simultaneously reducing systemic drug absorption.

Alginate Beads as Synthetic Inoculant Carriers for Slow Release of Bacteria That Affect Plant Growth †‡

PubMed Central

Bashan, Yoav

1986-01-01

Uniform synthetic beads were developed as carriers for the bacterial inoculation of plants. The beads are made of sodium alginate and skim milk and contain a large reservoir of bacterial culture which releases the bacteria at a slow and constant rate. The beads are biodegradable and produce no environmental pollution. The strength of the beads, the rate of bacterial release, and the time of their survival in the soil can be controlled by several hardening treatments. The final product, lyophilized beads, is simple to use and is applied to the seeds concomitantly with sowing. The released bacteria are available for root colonization immediately at seed germination. Dry beads containing bacteria can be stored at ambient temperature over a long period without loss of bacterial content; storage requires a limited space, and the quality control of a number of bacteria in the bead is simple. The level of plant inoculation with beads was similar to that with previously used peat inoculants, but the former method yielded more consistent results, as the frequency of inoculated plants was much higher. The former method provides a different approach for inoculation of plants with beneficial rhizosphere bacteria. Images PMID:16347055

Study on the rheological properties and volatile release of cold-set emulsion-filled protein gels.

PubMed

Mao, Like; Roos, Yrjö H; Miao, Song

2014-11-26

Emulsion-filled protein gels (EFP gels) were prepared through a cold-set gelation process, and they were used to deliver volatile compounds. An increase in the whey protein isolate (WPI) content from 4 to 6% w/w did not show significant effect on the gelation time, whereas an increase in the oil content from 5 to 20% w/w resulted in an earlier onset of gelation. Gels with a higher WPI content had a higher storage modulus and water-holding capacity (WHC), and they presented a higher force and strain at breaking, indicating that a more compact gel network was formed. An increase in the oil content contributed to gels with a higher storage modulus and force at breaking; however, this increase did not affect the WHC of the gels, and gels with a higher oil content became more brittle, resulting in a decreased strain at breaking. GC headspace analysis showed that volatiles released at lower rates and had lower air-gel partition coefficients in EFP gels than those in ungelled counterparts. Gels with a higher WPI content had lower release rates and partition coefficients of the volatiles. A change in the oil content significantly modified the partition of volatiles at equilibrium, but it produced a minor effect on the release rate of the volatiles. The findings indicated that EFP gels could be potentially used to modulate volatile release by varying the rheological properties of the gel.

Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility

PubMed Central

2017-01-01

Purpose We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. Materials and Methods Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were estimated. Results Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. Conclusions Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model. PMID:29076302

A mesoporous nanocontainer gated by a stimuli-responsive peptide for selective triggering of intracellular drug release

NASA Astrophysics Data System (ADS)

Lee, Jeonghun; Oh, Eun-Taex; Yoon, Haerry; Kim, Hyunmi; Park, Heon Joo; Kim, Chulhee

2016-04-01

Mesoporous silica nanocontainers (MSNs) with biologically responsive gatekeepers have great potential for effective delivery of cargo molecules to the desired sites. For that purpose, peptides could be effective candidates as gatekeepers because of their bioresponsiveness and targeting capability. Taking advantage of the zinc finger domain peptide (CXXC), we designed a biocompatible all-peptide gatekeeper (WCGKC) with on-off gatekeeping capability through stimulus-responsive conformational conversion and the steric bulkiness of the tryptophan unit. The turn structure induced by an intramolecular disulfide bond of the peptide gatekeeper (WCGKC-SS) completely inhibited the release of the entrapped doxorubicin (DOX). However, upon reduction of the disulfide bond by glutathione (GSH), the peptide conformation was converted to a random structure, which opened the orifice of the mesopore leading to the release of DOX. The amine moiety of the lysine of the peptide gatekeeper was PEGylated to enhance dispersion stability and biocompatibility of the nanocontainer. Furthermore, the MSNs with the peptide gatekeeper (PEG-WCGKC-SS-Si) selectively released the entrapped DOX in A549 human lung cancer cells in a controlled manner triggered by intracellular GSH, but not in CCD normal lung cells containing a low intracellular GSH level. In A549 cells, DOX-loaded PEG-WCGKC-SS-Si exhibited about 10-times higher cytotoxicity induced by apoptosis than that in CCD cells.Mesoporous silica nanocontainers (MSNs) with biologically responsive gatekeepers have great potential for effective delivery of cargo molecules to the desired sites. For that purpose, peptides could be effective candidates as gatekeepers because of their bioresponsiveness and targeting capability. Taking advantage of the zinc finger domain peptide (CXXC), we designed a biocompatible all-peptide gatekeeper (WCGKC) with on-off gatekeeping capability through stimulus-responsive conformational conversion and the steric bulkiness of the tryptophan unit. The turn structure induced by an intramolecular disulfide bond of the peptide gatekeeper (WCGKC-SS) completely inhibited the release of the entrapped doxorubicin (DOX). However, upon reduction of the disulfide bond by glutathione (GSH), the peptide conformation was converted to a random structure, which opened the orifice of the mesopore leading to the release of DOX. The amine moiety of the lysine of the peptide gatekeeper was PEGylated to enhance dispersion stability and biocompatibility of the nanocontainer. Furthermore, the MSNs with the peptide gatekeeper (PEG-WCGKC-SS-Si) selectively released the entrapped DOX in A549 human lung cancer cells in a controlled manner triggered by intracellular GSH, but not in CCD normal lung cells containing a low intracellular GSH level. In A549 cells, DOX-loaded PEG-WCGKC-SS-Si exhibited about 10-times higher cytotoxicity induced by apoptosis than that in CCD cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr09280a

Cytokine release from alveolar macrophages exposed to ambient particulate matter: Heterogeneity in relation to size, city and season

PubMed Central

Hetland, Ragna B; Cassee, Flemming R; Låg, Marit; Refsnes, Magne; Dybing, Erik; Schwarze, Per E

2005-01-01

Background Several studies have demonstrated an association between exposure to ambient particulate matter (PM) and respiratory and cardiovascular diseases. Inflammation seems to play an important role in the observed health effects. However, the predominant particle component(s) that drives the inflammation is still not fully clarified. In this study representative coarse (2.5–10 μm) and fine (0.1–2.5 μm) particulate samples from a western, an eastern, a northern and a southern European city (Amsterdam, Lodz, Oslo and Rome) were collected during three seasons (spring, summer and winter). All fractions were investigated with respect to cytokine-inducing potential in primary macrophages isolated from rat lung. The results were related to the physical and chemical parameters of the samples in order to disclose possible connections between inflammatory potential and specific characteristics of the particles. Results Compared on a gram-by gram basis, both site-specific and seasonal variations in the PM-induced cytokine responses were demonstrated. The samples collected in the eastern (Lodz) and southern (Rome) cities appeared to be the most potent. Seasonal variation was most obvious with the samples from Lodz, with the highest responses induced by the spring and summer samples. The site-specific or seasonal variation in cytokine release could not be attributed to variations in any of the chemical parameters. Coarse fractions from all cities were more potent to induce the inflammatory cytokines interleukin-6 and tumour necrosis factor-α than the corresponding fine fractions. Higher levels of specific elements such as iron and copper, some polycyclic aromatic hydrocarbons (PAHs) and endotoxin/lipopolysaccaride seemed to be prevalent in the coarse fractions. However, variations in the content of these components did not reflect the variation in cytokine release induced by the different coarse fractions. Addition of polymyxin B did not affect the particle-induced cytokine release, indicating that the variations in potency among the coarse fractions are not explained by endootoxin. Conclusion The inflammatory potential of ambient PM demonstrated heterogeneity in relation to city and season. The coarse particle fractions were consistently more potent than the respective fine fractions. Though a higher level of some elements, PAH and endotoxin was found in the coarse fractions, the presence of specific components was not sufficient to explain all variations in PM-induced cytokine release. PMID:16105184

Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients

PubMed Central

Tokuda, Haruhiko; Kuroyanagi, Gen; Tsujimoto, Masanori; Matsushima-Nishiwaki, Rie; Akamatsu, Shigeru; Enomoto, Yukiko; Iida, Hiroki; Otsuka, Takanobu; Ogura, Shinji; Iwama, Toru; Kojima, Kumi; Kozawa, Osamu

2016-01-01

It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of thrombin receptor-activating protein (TRAP) on the release of HSP27 in platelets in type 2 diabetes mellitus (DM) patients. The phosphorylated-HSP27 levels induced by TRAP were directly proportional to the aggregation of platelets. The levels of phosphorylated-HSP27 (Ser-78) were correlated with the levels of phosphorylated-p38 MAP kinase and phosphorylated-Akt in the platelets stimulated by 10 µM TRAP but not with those of phosphorylated-p44/p42 MAP kinase. The levels of HSP27 released from the TRAP (10 µM)-stimulated platelets were correlated with the levels of phosphorylated-HSP27 in the platelets. The released platelet-derived growth factor-AB (PDGF-AB) levels were in parallel with the HSP27 levels released from the platelets stimulated by 10 µM TRAP. Although the area under the curve (AUC) of small aggregates (9–25 µm) induced by 10 µM TRAP showed no significant correlation with the released HSP27 levels, AUC of medium aggregates (25–50 µm), large aggregates (50–70 µm) and light transmittance were significantly correlated with the released HSP27 levels. TRAP-induced phosphorylation of HSP27 was truly suppressed by deguelin, an inhibitor of Akt, in the platelets from a healthy subject. These results strongly suggest that TRAP-induced activation of Akt in addition to p38 MAP kinase positively regulates the release of phosphorylated-HSP27 from human platelets, which is closely related to the platelet hyper-aggregation in type 2 DM patients. PMID:27187380

Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients.

PubMed

Tokuda, Haruhiko; Kuroyanagi, Gen; Tsujimoto, Masanori; Matsushima-Nishiwaki, Rie; Akamatsu, Shigeru; Enomoto, Yukiko; Iida, Hiroki; Otsuka, Takanobu; Ogura, Shinji; Iwama, Toru; Kojima, Kumi; Kozawa, Osamu

2016-05-14

It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of thrombin receptor-activating protein (TRAP) on the release of HSP27 in platelets in type 2 diabetes mellitus (DM) patients. The phosphorylated-HSP27 levels induced by TRAP were directly proportional to the aggregation of platelets. The levels of phosphorylated-HSP27 (Ser-78) were correlated with the levels of phosphorylated-p38 MAP kinase and phosphorylated-Akt in the platelets stimulated by 10 µM TRAP but not with those of phosphorylated-p44/p42 MAP kinase. The levels of HSP27 released from the TRAP (10 µM)-stimulated platelets were correlated with the levels of phosphorylated-HSP27 in the platelets. The released platelet-derived growth factor-AB (PDGF-AB) levels were in parallel with the HSP27 levels released from the platelets stimulated by 10 µM TRAP. Although the area under the curve (AUC) of small aggregates (9-25 µm) induced by 10 µM TRAP showed no significant correlation with the released HSP27 levels, AUC of medium aggregates (25-50 µm), large aggregates (50-70 µm) and light transmittance were significantly correlated with the released HSP27 levels. TRAP-induced phosphorylation of HSP27 was truly suppressed by deguelin, an inhibitor of Akt, in the platelets from a healthy subject. These results strongly suggest that TRAP-induced activation of Akt in addition to p38 MAP kinase positively regulates the release of phosphorylated-HSP27 from human platelets, which is closely related to the platelet hyper-aggregation in type 2 DM patients.

Subthreshold concentration of endothelin-1-enhanced, capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs.

PubMed

Kanazawa, H; Fujiwara, H; Hirata, K; Yoshikawa, J

1998-12-01

An increasing number of studies have been performed to address a possible role for endothelin-1 (ET-1) as a significant mediator in asthma. However, the effects of subthreshold concentrations of ET-1, which cannot elicit bronchial smooth muscle contraction itself, in asthma has yet to be determined. This study determined these effects of ET-1 on capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs. Aerosolized ET-1 administered at doses of 10(-9) M and higher induced a dose-dependent increase in pulmonary resistance, but ET-1 at 10(-10) M did not have any bronchoconstrictive effect. However, this subthreshold concentration of ET-1 potentiated capsaicin-induced bronchoconstriction. In addition, the potentiation of capsaicin-induced bronchoconstriction by this subthreshold concentration of ET-1 was completely abolished by BQ788 (ET(B) receptor antagonist), but not BQ123 (ET(A) receptor antagonists). Immunoreactive substance P (SP) levels in bronchoalveolar lavage fluid after capsaicin administration were significantly higher than those after solvent administration. However, ET-1 alone did not significantly stimulate immunoreactive SP release and ET-1 (10(-10) M) did not potentiate capsaicin-induced immunoreactive SP release. In contrast, ET-1 (10(-10) M) potentiated exogenous neurokinin A- and SP-induced bronchoconstriction. These findings suggest that a subthreshold concentration of endothelin-1 does not potentiate the tachykinin release induced by capsaicin but the airway smooth muscle contraction through endothelin-B receptors.

In vitro and in vivo evaluation of gastro-retentive carvedilol loaded chitosan beads using Gastroplus™.

PubMed

Praveen, Radhakrishnan; Prasad Verma, Priya Ranjan; Venkatesan, Jayachandran; Yoon, Dong-Han; Kim, Se-Kwon; Singh, Sandeep Kumar

2017-09-01

The objective of present investigation was to develop gastro-retentive controlled release system of carvedilol using biological macromolecule, chitosan. 3 2 full factorial design was adopted for optimization of tripolyphosphate (X 1 ) and curing time (X 2 ). Bead stability in 0.1N HCl, buoyancy duration, density, drug loading, dissolution efficiency and cumulative percentage release at 8th hour were evaluated as dependent variables. The levels of X 1 and X 2 of optimized formulation having maximum desirability was found to 2.0% w/v and 62.66min, respectively. The in silico predicted responses and observed response were found to be in good agreement (percent bias error: -13.295 to +13.269). SEM images showed numerous pores in the cross sectional image that renders buoyancy. AUC 0-∞ of optimized formulation was 1.47 times higher as compared to suspension corroborating enhanced extent of absorption. T max and mean residence time were significantly higher from optimized formulation vis a vis suspension. In silico study indicated maximum regional absorption from the duodenum (94.1%) followed by jejunum (5.6%). Wagner-Nelson and Loo-Reigelman method were the preferred deconvolution approach over numerical deconvolution to establish IVIVC. In conclusion, the study showed that gastro-retentive controlled release system prepared using chitosan could be a potential drug carrier of carvedilol with improved bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuropeptide Y - an early biomarker for cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

PubMed

Schebesch, Karl-Michael; Brawanski, Alexander; Bele, Sylvia; Schödel, Petra; Herbst, Andreas; Bründl, Elisabeth; Kagerbauer, Simone Maria; Martin, Jan; Lohmeier, Anette; Stoerr, Eva-Maria; Proescholdt, Martin

2013-12-01

In the human brain, the potent vasoconstrictive neuropeptide Y (NPY) is abundantly expressed. Neuropeptide Y, which is stored in perivascular nerve fibers of the cerebral arteries, regulates the cerebral vascular diameter as well as cerebral blood flow. However, the role of NPY in the pathogenesis of cerebral vasospasm (CV) related to subarachnoid hemorrhage (SAH) is unclear. We prospectively analyzed and compared the release of endogenous NPY in the cerebrospinal fluid (CSF) of 66 patients with SAH to NPY release in a control group. Additionally, we correlated the levels of NPY with CV and consecutive ischemic stroke. Sixty-six consecutive patients (40 women, 26 men; mean age 53·1 years) with aneurysmal SAH were included. In the SAH group, CSF was drawn daily from day 1 to day 10 after the onset of SAH. The CSF of 29 patients undergoing spinal anesthesia for orthopedic surgery served as control samples. The NPY levels were determined in duplicate CSF samples by means of a competitive enzyme immunoassay (EIA). The levels of NPY in CSF were correlated with the development of CV over the 10-day period after the onset of SAH and to the occurrence of consecutive ischemic stroke. To evaluate CSF NPY levels as a predictive biomarker for vasospasm, we calculated the sensitivity and specificity as well as the positive and negative predictive values. The NPY levels were significantly higher in the SAH group than in the control group (p < 0·001). The treatment modality (clip versus coil) did not influence the level of NPY in CSF (p > 0·05). Patients with CV showed significantly higher NPY levels than patients without CV during the entire observation period. The NPY levels of the non-CV group dissipated over time, whereas the CV group showed continuously increasing values. The NPY levels from day 4 to 10 were significantly higher in patients with CV-related stroke than in non-stroke patients. Using 0·3 ng/ml as a cut-off value, NPY levels on day 3 predicted the occurrence of CV with a sensitivity and specificity of 82% and 72%, respectively. High NPY levels, starting on day 4, significantly correlated with poor Glasgow Outcome Score grading at the follow-up (p < 0·05). Our data indicate that NPY is involved in the pathogenesis of SAH-related CV and ischemia. Neuropeptide Y represents an early and reliable biomarker for the prediction of CV and consecutive stroke due to aneurysmal SAH.

Conductive plastics: comparing alternative nanotechnologies by performance and life cycle release probability

NASA Astrophysics Data System (ADS)

Neubauer, Nicole; Wohlleben, Wendel; Tomović, Željko

2017-03-01

Nanocomposites can be considered safe during their life cycle as long as the nanofillers remain embedded in the matrix. Therefore, a possible release of nanofillers has to be assessed before commercialization. This report addresses possible life cycle release scenarios for carbon nanotubes (CNT), graphene, and carbon black (CB) from a thermoplastic polyurethane (TPU) matrix. The content of each nanofiller was adjusted to achieve the same conductivity level. The nanofillers reduced the rate of nanoscale releases during mechanical processing with decreasing release in the order neat TPU, TPU-CNT, TPU-graphene, and TPU-CB. Released fragments were dominated by the polymer matrix with embedded or surface-protruding nanofillers. During electron microscopy analysis, free CB was observed, however, there was no free CNT or graphene. Quantitatively, the presence of free nanofillers remained below the detection limit of <0.01% of generated dust. Further, both the production process and type of mechanical processing showed a significant impact with higher release rates for injection-molded compared to extruded and sanded compared to drilled materials. Due to its optimal performance for further development, extruded TPU-CNT was investigated in a combined, stepwise worst case scenario (mechanical processing after weathering). After weathering by simulated sunlight and rain, CNT were visible at the surface of the nanocomposite; after additional sanding, fragments showed protruding CNT, but free CNT were not detected. In summary, this preliminary exposure assessment showed no indication that recommended occupational exposure limits for carbonaceous nanomaterials can be exceeded during the life cycle of the specific TPU nanocomposites and conditions investigated in this study.

Comparative endocrinological responses to short transportation of Equidae (Equus asinus and Equus caballus).

PubMed

Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Aveni, Francesca; Ferlazzo, Adriana

2013-03-01

In order to evaluate the effects of short transportation on β-endorphin, adrenocorticotropic hormone (ACTH) and cortisol changes, 12 healthy stallions of Equidae (Equus asinus and Equus caballus) were studied before and after transportation of 50 km. Blood samples were collected 1 week before transportation in basal conditions, immediately before loading and after transportation and unloading, on their arrival at the breeding station. Compared to basal and before values, donkeys showed an increase in circulating ACTH (P < 0.001) and cortisol (P < 0.0005) levels after transportation and higher ACTH (P < 0.01) levels than horses after transportation. A positive and significant correlation (r = 0.885; P < 0.01) between ACTH and cortisol levels after transportation was found. No significant differences were observed for β-endorphin levels. Compared to basal and before values, horses showed higher cortisol (P < 0.005) levels after transportation and no significant differences were observed for ACTH and β-endorphin levels in donkeys. Horses facing forward (direction of travel) showed higher (P < 0.01) β-endorphin levels after transportation than donkeys; horses facing backward (the opposite direction of travel) showed lower (P < 0.05) ACTH levels after transportation. The results indicate that short transportation induces a preferential activation of the hypothalamus-pituitary-axis (HPA), with significant release of ACTH and cortisol in donkeys and only of cortisol in horses, suggesting that transportation for donkeys may be more stressful than horses. © 2012 The Authors Animal Science Journal © 2012 Japanese Society of Animal Science.

Investigation of drug loading and in vitro release mechanisms of insulin-lauryl sulfate complex loaded PLGA nanoparticles.

PubMed

Shi, K; Cui, F; Yamamoto, H; Kawashima, Y

2008-12-01

Insulin, a water soluble peptide hormone, was hydrophobically ion-paired with sodium lauryl sulfate (SDS) at the stoichiometric molar ratio of 6:1. The obtained insulin-SDS complex precipitation was subsequently formulated in biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles by a modified spontaneous emulsion solvent diffusion method. Compared with a conventional method for free insulin encapsulation, direct dissolution of SDS-paired insulin in the non-aqueous organic phase led to an increase in drug recovery from 42.5% to 89.6%. The more hydrophobic complex contributes to the improved affinity of insulin to the polymer matrix, resulting in a higher drug content in the nanoparticles. The drug loading was investigated by determining initial burst release at the first 30 min. The results showed that 64.8% of recovered drug were preferentially surface bound on complex loaded nanoparticles. The in vitro drug release was characterized by an initial burst and subsequent delayed release in dissolution media of deionized water and phosphate buffer saline (PBS). Compared with that in PBS, nanoparticles in deionized water medium presented very low initial burst release (15% vs. 65%) and incomplete cumulative release (25% vs. 90%) of the drug. In addition, dialysis experiments were performed to clarify the form of the released insulin in the dissolution media. The results suggested that the ion-pair complex was sensitive to ionic strength, insulin was released from the particular matrix as complex form and subsequently suffered dissociation from SDS in buffer saline. Moreover, the in vivo bioactivity of the SDS-paired insulin and nanoparticulate formulations were evaluated in mice by estimation of their blood sugar levels. The results showed that the bioactivity of insulin was unaltered after the ion-pairing process.

Synergistic effect between 5-HT4 receptor agonist and phosphodiesterase 4-inhibitor in releasing acetylcholine in pig gastric circular muscle in vitro.

PubMed

Lefebvre, Romain A; Van Colen, Inge; Pauwelyn, Vicky; De Maeyer, Joris H

2016-06-15

5-HT4 receptor agonists have a gastroprokinetic effect by facilitating acetylcholine release from cholinergic nerves innervating gastrointestinal smooth muscle. The role of phosphodiesterase (PDE) 4 in the signal transduction pathway of the 5-HT4 receptors located on the cholinergic neurons towards the circular muscle layer in pig stomach was investigated by analysis of acetylcholine release. Circular muscle strips were prepared from pig proximal stomach and tritium outflow, induced by electrical field stimulation, was studied as a marker for acetylcholine release after incubation with [(3)H]-choline. The PDE4-inhibitor roflumilast concentration-dependently (0.1-1µM) enhanced the facilitating effect of a submaximally effective concentration of the 5-HT4 receptor agonist prucalopride (0.01µM) on electrically induced acetylcholine release. Roflumilast (0.3µM) enhanced acetylcholine release per se but in the combined presence of roflumilast and prucalopride, acetylcholine release was enhanced more than the sum of the effect of the 2 compounds alone. The 5-HT4 receptor agonist velusetrag concentration-dependently (0.01-0.1µM) enhanced acetylcholine release; the effect of the minimally effective concentration (0.01µM) was significantly enhanced by 1µM of the PDE4-inhibitor rolipram, again to a level higher than the sum of the effect of the 2 compounds alone. The synergistic effect between 5-HT4 receptor agonists and PDE4-inhibitors demonstrates that the intracellular pathway of the 5-HT4 receptors located on cholinergic neurons towards pig gastric circular muscle is controlled by PDE4. Combining a 5-HT4 receptor agonist with a PDE4-inhibitor might thus enhance its gastroprokinetic effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Modeling Patterns of Total Dissolved Solids Release from Central Appalachia, USA, Mine Spoils.

PubMed

Clark, Elyse V; Zipper, Carl E; Daniels, W Lee; Orndorff, Zenah W; Keefe, Matthew J

2017-01-01

Surface mining in the central Appalachian coalfields (USA) influences water quality because the interaction of infiltrated waters and O with freshly exposed mine spoils releases elevated levels of total dissolved solids (TDS) to streams. Modeling and predicting the short- and long-term TDS release potentials of mine spoils can aid in the management of current and future mining-influenced watersheds and landscapes. In this study, the specific conductance (SC, a proxy variable for TDS) patterns of 39 mine spoils during a sequence of 40 leaching events were modeled using a five-parameter nonlinear regression. Estimated parameter values were compared to six rapid spoil assessment techniques (RSATs) to assess predictive relationships between model parameters and RSATs. Spoil leachates reached maximum values, 1108 ± 161 μS cm on average, within the first three leaching events, then declined exponentially to a breakpoint at the 16th leaching event on average. After the breakpoint, SC release remained linear, with most spoil samples exhibiting declines in SC release with successive leaching events. The SC asymptote averaged 276 ± 25 μS cm. Only three samples had SCs >500 μS cm at the end of the 40 leaching events. Model parameters varied with mine spoil rock and weathering type, and RSATs were predictive of four model parameters. Unweathered samples released higher SCs throughout the leaching period relative to weathered samples, and rock type influenced the rate of SC release. The RSATs for SC, total S, and neutralization potential may best predict certain phases of mine spoil TDS release. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Optimal killing for obligate killers: the evolution of life histories and virulence of semelparous parasites.

PubMed Central

Ebert, D; Weisser, W W

1997-01-01

Many viral, bacterial and protozoan parasites of invertebrates first propagate inside their host without releasing any transmission stages and then kill their host to release all transmission stages at once. Life history and the evolution of virulence of these obligately killing parasites are modelled, assuming that within-host growth is density dependent. We find that the parasite should kill the host when its per capita growth rate falls to the level of the host mortality rate. The parasite should kill its host later when the carrying capacity, K, is higher, but should kill it earlier when the parasite-independent host mortality increases or when the parasite has a higher birth rate. When K(t), for parasite growth, is not constant over the duration of an infection, but increases with time, the parasite should kill the host around the stage when the growth rate of the carrying capacity decelerates strongly. In case that K(t) relates to host body size, this deceleration in growth is around host maturation. PMID:9263465

The contribution of autochthonous microflora on free fatty acids release and flavor development in low-salt fermented fish.

PubMed

Xu, Yanshun; Li, Lin; Regenstein, Joe Mac; Gao, Pei; Zang, Jinhong; Xia, Wenshui; Jiang, Qixing

2018-08-01

To investigate the contribution of autochthonous microflora on free fatty acids (FFA) release and flavor development in low-salt fermented fish, three groups of processed fish, including bacteriostatic-acidification group (BAG), bacteriostatic group (BG), and spontaneous fermented fish (CG) were established. Results showed that addition of NaN 3 reduced microbial load in BAG and BG below 3.5 log CFU/g after 3 weeks of incubation. Activities of lipases and lipoxygenase declined markedly with increasing time, where BG had the highest activities, followed by CG and BAG. There is a 36.3% higher in the total FFA content in CG than that in BAG, indicating both microbial and endogenous lipases contributed to the FFA liberation in fermented fish while endogenous lipases play a major role. However, compared to BAG and BG, largely higher levels of volatile compounds were observed in CG, suggesting that autochthonous microflora dominated the generation of volatile flavor compounds in fermented fish. Copyright © 2018 Elsevier Ltd. All rights reserved.

Saccharification of ozonated sugarcane bagasse using enzymes from Myceliophthora thermophila JCP 1-4 for sugars release and ethanol production.

PubMed

de Cassia Pereira, Josiani; Travaini, Rodolfo; Paganini Marques, Natalia; Bolado-Rodríguez, Silvia; Bocchini Martins, Daniela Alonso

2016-03-01

The saccharification of ozonated sugarcane bagasse (SCB) by enzymes from Myceliophthora thermophila JCP 1-4 was studied. Fungal enzymes provided slightly higher sugar release than commercial enzymes, working at 50°C. Sugar release increased with temperature increase. Kinetic studies showed remarkable glucose release (4.99 g/L, 3%w/w dry matter) at 60°C, 8 h of hydrolysis, using an enzyme load of 10 FPU (filter paper unit). FPase and β-glucosidase activities increased during saccharification (284% and 270%, respectively). No further significant improvement on glucose release was observed increasing the enzyme load above 7.5 FPU per g of cellulose. Higher dry matter contents increased sugars release, but not yields. The fermentation of hydrolysates by Saccharomyces cerevisiae provided glucose-to-ethanol conversions around to 63%. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of extended-release niacin with laropiprant in high-risk patients.

PubMed

Landray, Martin J; Haynes, Richard; Hopewell, Jemma C; Parish, Sarah; Aung, Theingi; Tomson, Joseph; Wallendszus, Karl; Craig, Martin; Jiang, Lixin; Collins, Rory; Armitage, Jane

2014-07-17

Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) cholesterol level, but its clinical efficacy and safety are uncertain. After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants' ability to take extended-release niacin without clinically significant adverse effects, we randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization). During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower and an HDL cholesterol level that was an average of 6 mg per deciliter (0.16 mmol per liter) higher than the levels in those assigned to placebo. Assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events (13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29). Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious (absolute excess as compared with placebo, 3.7 percentage points; P<0.001) and with an increased incidence of diabetes diagnoses (absolute excess, 1.3 percentage points; P<0.001), as well as increases in serious adverse events associated with the gastrointestinal system (absolute excess, 1.0 percentage point; P<0.001), musculoskeletal system (absolute excess, 0.7 percentage points; P<0.001), skin (absolute excess, 0.3 percentage points; P=0.003), and unexpectedly, infection (absolute excess, 1.4 percentage points; P<0.001) and bleeding (absolute excess, 0.7 percentage points; P<0.001). Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.).

[Behavior of soluble L-selectin in HIV infected children].

PubMed

Gaddi, E; Balbaryski, J; Cantisano, C; Barboni, G; Candi, M; Quiroz, H; Giraudi, V

2001-01-01

L-selectin is an adhesion molecule that is responsible for the initial attachment of leukocytes to endothelium. After leukocyte activation L-selectin is endoproteolytically released from the cell surface. In order to analyze the relationship between soluble L-selectin (sL-selectin) and parameters of immune activation and disease progression, 51 HIV infected children and 15 healthy controls were studied. Serum L-selectin concentrations were significantly higher in HIV infected children than in the control group. Levels of sL-selectin were higher in HIV infected patients with severe immunologic suppression than in those with moderate or no evidence of suppression. A positive correlation between sL-selectin levels and LTCD8 counts, sL-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) and immunogobulin A (IgA) levels was detected. On the contrary sL-selectin concentration did not correlate with plasmatic viral load. The correlation with parameters of immune activation may implicate involvement of sL-selectin in the immunopathogenesis of HIV infection.

In vitro effects of the dicyclohexylammonium salt of hyperforin on interleukin-6 release in different experimental models.

PubMed

Gobbi, Marco; Moia, Manuela; Funicello, Marcella; Riva, Antonella; Morazzoni, Paolo; Mennini, Tiziana

2004-07-01

Cytokine hypersecretion might be involved in the onset and maintenance of depressive disorders and it has been suggested that St. John's wort extracts (Hypericum perforatum, SJW) might exert their antidepressant-like effects by affecting peripheral interleukin-6 (IL6) expression. We found that hyperforin, one putative active principle of SJW, and its dicyclohexylammonium salt (hyperforin-DCHA), inhibited the substance P (SP)-induced [L6 release inhuman astrocytoma cells (U373MG) with an Cs50 of 1.6 pM, indicating that hyperforin is likely to account for the inhibitory effect previously found in the same experimental model with SJW ex-tracts. [3H]SP binding experiments in parallel on the same intact cells indicate that hyperforin-DCHA does not interact with neuro-kinin-I receptors but very likely interacts with some intracellular steps leading to the synthesis and/or release of IL6. Hyperforin-DCHA also inhibited, with a similar IC50, the IL6 release induced in U373MG cells by two other classic proinflammatory stimuli,ILl and lipopolysaccharide (LPS), as well as the LPS-induced IL6 release in whole rat blood. Hyperforin-DCHA was less active in whole human blood. The concentrations required in vitro to inhibit LPS-induced IL6 release from rat and human whole blood are about one order of magnitude higher than the hyperforin levels measured in the plasma of rats or humans treated with pharmaco-logically active doses of SJW or hyperforin-DCHA.

The Interaction of Steroid Hormones and Oncogene in Breast Cancer.

DTIC Science & Technology

1998-10-01

fragment [3] at the 5’ end of our regulator under the control of the MMTV promoter and the bovine growth hormone polyadenylation signal (Figure 6A...appeared swollen exhibiting a classic case of mastitis due to the failure to release milk that is produced. A couple of unique wart-like structures... mastitis ). As previously mentioned, it was most likely that the levels of int- 2/fgf-3 expression are enormously higher than that needed for

Leaching of cadmium and tellurium from cadmium telluride (CdTe) thin-film solar panels under simulated landfill conditions

PubMed Central

Ramos-Ruiz, Adriana; Wilkening, Jean V.; Field, James A.; Sierra-Alvarez, Reyes

2017-01-01

A crushed non-encapsulated CdTe thin-film solar cell was subjected to two standardized batch leaching tests (i.e., Toxicity Characteristic Leaching Procedure (TCLP) and California Waste Extraction Test (WET)) and to a continuous-flow column test to assess cadmium (Cd) and tellurium (Te) dissolution under conditions simulating the acidic- and the methanogenic phases of municipal solid waste landfills. Low levels of Cd and Te were solubilized in both batch leaching tests (<8.2% and <3.6% of added Cd and Te, respectively). On the other hand, over the course of 30 days, 73% of the Cd and 21% of the Te were released to the synthetic leachate of a continuous-flow column simulating the acidic landfill phase. The dissolved Cd concentration was 3.24-fold higher than the TCLP limit (1 mg L-1), and 650-fold higher than the maximum contaminant level established by the US-EPA for this metal in drinking water (0.005 mg L-1). In contrast, the release of Cd and Te to the effluent of the continuous-flow column simulating the methanogenic phase of a landfill was negligible. The remarkable difference in the leaching behavior of CdTe in the columns is related to different aqueous pH and redox conditions promoted by the microbial communities in the columns, and is in agreement with thermodynamic predictions. PMID:28472709

Crystal structures of different substrates of bacteriorhodopsin's M intermediate at various pH levels.

PubMed

Yamamoto, Masataka; Hayakawa, Naoki; Murakami, Midori; Kouyama, Tsutomu

2009-10-30

The hexagonal P622 crystal of bacteriorhodopsin, which is made up of stacked membranes, is stable provided that the precipitant concentration in the soaking solution is higher than a critical value (i.e., 1.5 M ammonium sulfate). Diffraction data showed that the crystal lattice shrank linearly with increasing precipitant concentration, due primarily to narrowing of intermembrane spaces. Although the crystal shrinkage did not affect the rate of formation of the photoreaction M intermediate, its lifetime increased exponentially with the precipitant concentration. It was suggested that the energetic barrier of the M-to-N transition becomes higher when the motional freedom of the EF loop is reduced by crystal lattice force. As a result of this property, the M state accumulated predominantly when the crystal that was soaked at a high precipitant concentration was illuminated at room temperature. Structural data obtained at various pH levels showed that the overall structure of M is not strongly dependent on pH, except that Glu194 and Glu204 in the proton release complex are more separated at pH 7 than at pH 4.4. This result suggests that light-induced disruption of the paired structure of Glu194 and Glu204 is incomplete when external pH is lower than the pK(a) value of the proton release group in the M state.

Analysis of Factors Influencing Soil Salinity, Acidity, and Arsenic Concentration in a Polder in Southwest Bangladesh

NASA Astrophysics Data System (ADS)

Ayers, J. C.; Patton, B.; Fry, D. C.; Goodbred, S. L., Jr.

2017-12-01

Soil samples were collected on Polder 32 in the coastal zone of SW Bangladesh in wet (October) and dry (May) seasons from 2013-2017 and analyzed to characterize the problems of soil salinization and arsenic contamination and identify their causes. Soils are entisols formed from recently deposited, predominantly silt-sized sediments with low carbon concentrations typical of the local mangrove forests. Soluble (DI extract) arsenic concentrations were below the Government of Bangladesh limit of 50 ppb for drinking water. Soil acidity and extract arsenic concentrations exhibit spatial variation but no consistent trends. In October soil extract As is higher and S and pH are lower than in May. These observations suggest that wet season rainwater oxidizes pyrite, reducing soil S and releasing H+, causing pH to decrease. Released iron is oxidized to form Hydrous Ferric Oxyhydroxides (HFOs), which sorb As and increase extractable As in wet season soils. Changes in pH are small due to pH buffering by soil carbonates. Soil and rice paddy water salinities are consistently higher in May than October, reaching levels in May that reduce rice yields. Rice grown in paddies should be unaffected by salt concentrations in the wet season, while arsenic concentrations in soil may be high enough to cause unsafe As levels in produced rice.

Combined alkaline and ultrasonic pretreatment of sludge before aerobic digestion.

PubMed

Jin, Yiying; Li, Huan; Mahar, Rasool Bux; Wang, Zhiyu; Nie, Yongfeng

2009-01-01

Alkaline and ultrasonic sludge disintegration can be used as the pretreatment of waste activated sludge (WAS) to promote the subsequent anaerobic or aerobic digestion. In this study, different combinations of these two methods were investigated. The evaluation was based on the quantity of soluble chemical oxygen demand (SCOD) in the pretreated sludge as well as the degradation of organic matter in the subsequent aerobic digestion. For WAS samples with combined pretreatment, the released COD levels were higher than those with ultrasonic or alkaline pretreatment alone. When combined with the ultrasonic treatment, NaOH treatment was more efficient than Ca(OH)2 for WAS solubilization. The COD levels released in various sequential options of combined NaOH and ultrasonic treatments were in the the following descending order: simultaneous treatment > NaOH treatment followed by ultrasonic treatment > ultrasonic treatment followed by NaOH treatment. For simultaneous treatment, low NaOH dosage (100 g/kg dry solid), short duration (30 min) of NaOH treatment, and low ultrasonic specific energy (7500 kJ/kg dry solid) were suitable for sludge disintegration. Using combined NaOH and ultrasonic pretreatment with optimal parameters, the degradation efficiency of organic matter was increased from 38.0% to 50.7%, which is much higher than that with ultrasonic (42.5%) or with NaOH pretreatment (43.5%) in the subsequent aerobic digestion at the same retention time.

Modular Integrated Stackable Layers (MISL) 1.1 Design Specification. Design Guideline Document

NASA Technical Reports Server (NTRS)

Yim, Hester J.

2012-01-01

This document establishes the design guideline of the Modular Instrumentation Data Acquisition (MI-DAQ) system in utilization of several designs available in EV. The MI- DAQ provides the options to the customers depending on their system requirements i.e. a 28V interface power supply, a low power battery operated system, a low power microcontroller, a higher performance microcontroller, a USB interface, a Ethernet interface, a wireless communication, various sensor interfaces, etc. Depending on customer's requirements, the each functional board can be stacked up from a bottom level of power supply to a higher level of stack to provide user interfaces. The stack up of boards are accomplished by a predefined and standardized power bus and data bus connections which are included in this document along with other physical and electrical guidelines. This guideline also provides information for a new design options. This specification is the product of a collaboration between NASA/JSC/EV and Texas A&M University. The goal of the collaboration is to open source the specification and allow outside entities to design, build, and market modules that are compatible with the specification. NASA has designed and is using numerous modules that are compatible to this specification. A limited number of these modules will also be released as open source designs to support the collaboration. The released designs are listed in the Applicable Documents.

Lead toxicity: An overview of prevalence in Indians.

PubMed

Iyer, Sandhya; Sengupta, Caesar; Velumani, A

2015-12-07

Elements form a basic and natural constituent of the Earth's crust and are released into the atmosphere due to many human activities like mining and manufacturing. Of all, the elements, lead toxicity is a prevailing as well as a growing concern the world over because of its ability to affect multiple clinical functions. Blood lead levels have been analyzed in a large pan-India cohort of 222,668 comprising of 121,115 males and 101,553 females respectively. The cohort included all age groups from <2 to >55 years old. The analytical platform of Inductively Coupled Plasma-Mass Spectrometry has been used to assess lead levels. Blood lead levels of ≥150 μg/L was considered high for analysis. The total frequency of high lead levels detected in our study was 1.16%. The frequency of males affected were higher than females, with the difference being statistically significant.. Lead being ubiquitous in its presence and also serving no biological function, has grown today to become a serious threat to human health. The high frequency of affected detected in our study raises a cause for concern. Determining its presence and the most affected geography in any country will aid in charting guidelines on controlling its release as well as exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

DNA repair phenotype and dietary antioxidant supplementation.

PubMed

Guarnieri, Serena; Loft, Steffen; Riso, Patrizia; Porrini, Marisa; Risom, Lotte; Poulsen, Henrik E; Dragsted, Lars O; Møller, Peter

2008-05-01

Phytochemicals may protect cellular DNA by direct antioxidant effect or modulation of the DNA repair activity. We investigated the repair activity towards oxidised DNA in human mononuclear blood cells (MNBC) in two placebo-controlled antioxidant intervention studies as follows: (1) well-nourished subjects who ingested 600 g fruits and vegetables, or tablets containing the equivalent amount of vitamins and minerals, for 24 d; (2) poorly nourished male smokers who ingested 500 mg vitamin C/d as slow- or plain-release formulations together with 182 mg vitamin E/d for 4 weeks. The mean baseline levels of DNA repair incisions were 65.2 (95 % CI 60.4, 70.0) and 86.1 (95 % CI 76.2, 99.9) among the male smokers and well-nourished subjects, respectively. The male smokers also had high baseline levels of oxidised guanines in MNBC. After supplementation, only the male smokers supplemented with slow-release vitamin C tablets had increased DNA repair activity (27 (95 % CI 12, 41) % higher incision activity). These subjects also benefited from the supplementation by reduced levels of oxidised guanines in MNBC. In conclusion, nutritional status, DNA repair activity and DNA damage are linked, and beneficial effects of antioxidants might only be observed among poorly nourished subjects with high levels of oxidised DNA damage and low repair activity.

Active suppression of vortex-driven combustion instability using controlled liquid-fuel injection

NASA Astrophysics Data System (ADS)

Pang, Bin

Combustion instabilities remain one of the most challenging problems encountered in developing propulsion and power systems. Large amplitude pressure oscillations, driven by unsteady heat release, can produce numerous detrimental effects. Most previous active control studies utilized gaseous fuels to suppress combustion instabilities. However, using liquid fuel to suppress combustion instabilities is more realistic for propulsion applications. Active instability suppression in vortex-driven combustors using a direct liquid fuel injection strategy was theoretically established and experimentally demonstrated in this dissertation work. Droplet size measurements revealed that with pulsed fuel injection management, fuel droplet size could be modulated periodically. Consequently, desired heat release fluctuation could be created. If this oscillatory heat release is coupled with the natural pressure oscillation in an out of phase manner, combustion instabilities can be suppressed. To identify proper locations of supplying additional liquid fuel for the purpose of achieving control, the natural heat release pattern in a vortex-driven combustor was characterized in this study. It was found that at high Damkohler number oscillatory heat release pattern closely followed the evolving vortex front. However, when Damkohler number became close to unity, heat release fluctuation wave no longer coincided with the coherent structures. A heat release deficit area was found near the dump plane when combustor was operated in lean premixed conditions. Active combustion instability suppression experiments were performed in a dump combustor using a controlled liquid fuel injection strategy. High-speed Schlieren results illustrated that vortex shedding plays an important role in maintaining self-sustained combustion instabilities. Complete combustion instability control requires total suppression of these large-scale coherent structures. The sound pressure level at the excited dominant frequency was reduced by more than 20 dB with controlled liquid fuel injection method. Scaling issues were also investigated in this dump combustor to test the effectiveness of using pulsed liquid fuel injection strategies to suppress instabilities at higher power output conditions. With the liquid fuel injection control method, it was possible to suppress strong instabilities with initial amplitude of +/-5 psi down to the background noise level. The stable combustor operating range was also expanded from equivalence ratio of 0.75 to beyond 0.9.

Maternal and neonatal copeptin levels at cesarean section and vaginal delivery.

PubMed

Foda, Ashraf A; Abdel Aal, Ibrahim A

2012-12-01

The objective of the study was to measure the copeptin levels in maternal serum and umbilical cord serum at cesarean section and vaginal delivery in normotensive pregnancy and pre-eclamptic women. This was a prospective study at Mansoura University Hospital, Egypt. Ninety cases were included. They were divided into six groups: (1) normal pregnancy near term, as a control group, (2) primiparas who had vaginal delivery, (3) primiparas who had vaginal delivery and mild preeclampsia, (4) elective repeat cesarean section, (5) intrapartum cesarean section for indications other than fetal distress, and (6) intrapartum cesarean section for fetal distress. Serum copeptin concentrations were quantified with an enzyme-linked immunosorbent assay (ELISA). Mean, standard deviation, and paired t-test were used to test for significant change in quantitative data. The vaginal delivery groups had higher levels of maternal serum copeptin than the elective cesarean section group (P<0.01). Higher maternal serum copeptin levels were found in cases with pre-eclampsia as compared with the normotensive cases. The maternal copeptin levels during intrapartum cesarean section were higher than that during elective repeat cesarean section. There was a significant correlation between maternal copeptin levels and the duration of the first stage. In the presence of fetal distress, umbilical cord serum copeptin levels were significantly higher than other groups. Vaginal delivery can be very painful and stressful, and is accompanied by a marked increase of maternal serum copeptin. Increased maternal levels of serum copeptin were found in cases with pre-eclampsia as compared with the normotensive cases, and it may be helpful in assessing the disease. Intrauterine fetal distress is a strong stimulus to the release of copeptin into the fetal circulation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Influence of thinning style on stand structure and growth in upland oaks: a 58-year case study

Treesearch

Jeffery S. Ward

2003-01-01

In 1937, a study comparing low and high thinning (partial crop tree release) was established in northwestern Connecticut. Oaks accounted for 65 percent of the crop trees that were partially released at stand ages 17, 26, and 42 years. Sawtimber trees had greater diameters, higher volumes, and higher tree grades on thinned than unmanaged plots. The higher oak density on...

Vanadium release in whole blood, serum and urine of patients implanted with a titanium alloy hip prosthesis.

PubMed

Catalani, S; Stea, S; Beraudi, A; Gilberti, M E; Bordini, B; Toni, A; Apostoli, P

2013-08-01

Vanadium (V) is a minor constituent of the Titanium-Aluminum-Vanadium (TiAlV) alloy currently used in cementless hip prostheses. Present study aimed at verifying the correlation of vanadium levels among different matrices and assessing reference levels of the ion in a population of patients wearing a well-functioning hip prosthesis. Vanadium was measured using Inductive Coupled Plasma Mass Spectrometry (ICP-MS) in whole blood, serum and urine of 129 patients implanted with a TiAlV-alloy hip prosthesis. The values in the serum were above the upper limit of the reference values in 42% of patients (29% in urine and 13% in whole blood). A good correlation among matrices was observed (p < 0.001). The cohort of patients (N = 32) complaining of pain or in which a loosening or damage to the prosthesis was assessed showed a significantly higher excretion of vanadium in urine as compared with the remaining asymptomatic patients (p = 0.001). The 95th percentile distribution of vanadium in the cohort of patients with a well-functioning prosthesis was 0.3 μg/L in whole blood, 0.5 μg/L in serum and 2.8 μg/L in urine, higher that in the unexposed population, especially for urine. The presence of a prosthesis, even though well-functioning, may cause a possible release of vanadium into the blood and a significant urinary excretion. The reference values of vanadium of the asymptomatic patients with titanium alloy hip prostheses supplied information regarding the background exposure level of the ions and their lower and upper limits.

Simulated responses of soil organic carbon stock to tillage management scenarios in the Northwest Great Plains

USGS Publications Warehouse

Tan, Z.; Liu, S.; Li, Z.; Loveland, Thomas R.

2007-01-01

Background: Tillage practices greatly affect carbon (C) stocks in agricultural soils. Quantification of the impacts of tillage on C stocks at a regional scale has been challenging because of the spatial heterogeneity of soil, climate, and management conditions. We evaluated the effects of tillage management on the dynamics of soil organic carbon (SOC) in croplands of the Northwest Great Plains ecoregion of the United States using the General Ensemble biogeochemical Modeling System (GEMS). Tillage management scenarios included actual tillage management (ATM), conventional tillage (CT), and no-till (NT). Results: Model simulations show that the average amount of C (kg C ha-1yr-1) released from croplands between 1972 and 2000 was 246 with ATM, 261 with CT, and 210 with NT. The reduction in the rate of C emissions with conversion of CT to NT at the ecoregion scale is much smaller than those reported at plot scale and simulated for other regions. Results indicate that the response of SOC to tillage practices depends significantly on baseline SOC levels: the conversion of CT to NT had less influence on SOC stocks in soils having lower baseline SOC levels but would lead to higher potentials to mitigate C release from soils having higher baseline SOC levels. Conclusion: For assessing the potential of agricultural soils to mitigate C emissions with conservation tillage practices, it is critical to consider both the crop rotations being used at a local scale and the composition of all cropping systems at a regional scale. ?? 2007 Tan et al; licensee BioMed Central Ltd.

Cyclic AMP agonist inhibition increases at low levels of histamine release from human basophils

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

Tung, R.S.; Lichtenstein, L.M.

1981-09-01

The relationship between the intensity of the signal for antigen-induced immunoglobulin E-mediated histamine release from human basophils and the concentration of agonist needed to inhibit release has been determined. The agonists, prostaglandin E1, dimaprit, fenoterol, isobutylmethylxanthine and dibutyryl cyclic AMP, all act by increasing the cyclic AMP level. Each agonist was 10- to 1000-fold more potent (relative ID50) at low levels of histamine release (5-10% of total histamine) than at high levels (50-80%). Thus, the inhibitory potential of a drug is a function of the concentration of antigen used to initiate the response. Our results are now more in accordmore » with the inhibitory profile of these drugs in human lung tissue. It is suggested that in vivo release is likely to be low and that this is the level at which to evaluate drugs in vitro.« less

Australia’s first national level quantitative environmental justice assessment of industrial air pollution

NASA Astrophysics Data System (ADS)

Chakraborty, Jayajit; Green, Donna

2014-04-01

This study presents the first national level quantitative environmental justice assessment of industrial air pollution in Australia. Specifically, our analysis links the spatial distribution of sites and emissions associated with industrial pollution sources derived from the National Pollution Inventory, to Indigenous status and social disadvantage characteristics of communities derived from Australian Bureau of Statistics indicators. Our results reveal a clear national pattern of environmental injustice based on the locations of industrial pollution sources, as well as volume, and toxicity of air pollution released at these locations. Communities with the highest number of polluting sites, emission volume, and toxicity-weighted air emissions indicate significantly greater proportions of Indigenous population and higher levels of socio-economic disadvantage. The quantities and toxicities of industrial air pollution are particularly higher in communities with the lowest levels of educational attainment and occupational status. These findings emphasize the need for more detailed analysis in specific regions and communities where socially disadvantaged groups are disproportionately impacted by industrial air pollution. Our empirical findings also underscore the growing necessity to incorporate environmental justice considerations in environmental planning and policy-making in Australia.

Mineralogical and chemical interactions of soils eaten by chimpanzees of the Mahale Mountains and Gombe Stream National Parks, Tanzania.

PubMed

Aufreiter, S; Mahaney, W C; Milner, M W; Huffman, M A; Hancock, R G; Wink, M; Reich, M

2001-02-01

Termite mound soils eaten by chimpanzees of the Mahale Mountains and Gombe National Parks, Tanzania, have mineralogical and geochemical compositions similar to many soils eaten by higher primates, but release very low levels of either toxic or nutritional inorganic elements to solution at acid pH. Comparison with control (uneaten) soils from the same areas showed lower levels of carbon and nitrogen in the eaten soils, a relationship confirmed by surface analysis. Surface analysis also revealed lower levels of iron on particle surfaces versus interiors, and higher levels of iron on ingested versus control soil particle surfaces. The soils can adsorb dietary toxins, present in the plant diet or those produced by microorganisms. Taking the toxic alkaloids quinine, atropine, sparteine, and lupanine as examples, it is evident that soils from Mahale have a very good adsorptive capacity. A new adaptive advantage of geophagy is proposed, based on the prevention of iron uptake. The behavior of the soils in vitro is consistent with the theory that geophagy has a therapeutic value for these chimpanzees.

Investigation of factors affecting in vitro doxorubicin release from PEGylated liposomal doxorubicin for the development of in vitro release testing conditions.

PubMed

Shibata, Hiroko; Izutsu, Ken-Ichi; Yomota, Chikako; Okuda, Haruhiro; Goda, Yukihiro

2015-01-01

Establishing appropriate drug release testing methods of liposomal products for assuring quality and performance requires the determination of factors affecting in vitro drug release. In this study, we investigated the effects of test conditions (human plasma lot, pH/salt concentration in the test media, dilution factor, temperature, ultrasound irradiation, etc.), and liposomal preparation conditions (pH/concentration of ammonium sulfate solution), on doxorubicin (DXR) release from PEGylated liposomal DXR. Higher temperature and lower pH significantly increased DXR release. The evaluation of DXR solubility indicated that the high DXR release induced by low pH may be attributed to the high solubility of DXR at low pH. Ultrasound irradiation induced rapid DXR release in an amplitude-dependent manner. The salt concentration in the test solution, human plasma lot, and dilution factor had a limited impact on DXR-release. Variations in the ammonium sulfate concentration used in solutions for the formation/hydration of liposomes significantly affected DXR release behavior, whereas differences in pH did not. In addition, heating condition in phosphate-buffered saline at lower pH (<6.5) exhibited higher discriminative ability for the release profiles from various liposomes with different concentrations of ammonium sulfate than did ultrasound irradiation. These results are expected to be helpful in the process of establishing appropriate drug release testing methods for PEGylated liposomal DXR.

The effects of alpha tocopherol supplementation on monocyte function. Decreased lipid oxidation, interleukin 1 beta secretion, and monocyte adhesion to endothelium.

PubMed Central

Devaraj, S; Li, D; Jialal, I

1996-01-01

Low levels of alpha tocopherol are related to a higher incidence of cardiovascular disease and increased intake appears to afford protection against cardiovascular disease. In addition to decreasing LDL oxidation, alpha tocopherol may exert intracellular effects on cells crucial in atherogenesis, such as monocytes. Hence, the aim of this study was to test the effect of alpha tocopherol supplementation on monocyte function relevant to atherogenesis. Monocyte function was assessed in 21 healthy subjects at baseline, after 8 wk of supplementation with d-alpha tocopherol (1,200 IU/d) and after a 6-wk washout phase. The release of reactive oxygen species (superoxide anion, hydrogen peroxide), lipid oxidation, release of the potentially atherogenic cytokine, interleukin 1 beta, and monocyte-endothelial adhesion were studied in the resting state and after activation of the monocytes with lipopolysaccharide at 0, 8, and 14 wk. There was a 2.5-fold increase in plasma lipid-standardized and monocyte alpha tocopherol levels in the supplemented phase. After alpha tocopherol supplementation, there were significant decreases in release of reactive oxygen species, lipid oxidation, IL-1 beta secretion, and monocyte-endothelial cell adhesion, both in resting and activated cells compared with baseline and washout phases. Studies with the protein kinase C inhibitor, Calphostin C, suggest that the inhibition of reactive oxygen species release and lipid oxidation is due to an inhibition of protein kinase C activity by alpha tocopherol. Thus, this study provides novel evidence for an intracellular effect of alpha tocopherol in monocytes that is antiatherogenic. PMID:8698868

Influence of freezing and thawing on the hydration characteristics, quality, and consumer acceptance of whole muscle beef injected with solutions of salt and phosphate.

PubMed

Pietrasik, Z; Janz, J A M

2009-03-01

Effects of salt/phosphate injection level (112% or 125% pump), salt level (0.5% or 1.5% salt), and freezing/thawing on hydration characteristics, quality, and consumer acceptance of beef semitendinosus were investigated. All enhancement treatments decreased shear force by 25-35%, but negatively affected colour. Increased salt concentration yielded lower purge and cooking losses, and higher water holding capacity. The higher injection level reduced water binding properties, however, the loss in functionality with higher water addition was overcome with increased salt content. Freezing and subsequent thawing was generally detrimental to colour and water binding properties and tended to increase shear force. Freezing and subsequent thawing did not affect fluid release in steaks held for 1 day before analysis, but resulted in decreased water retention in samples held for 7 days. Holding vacuum packaged steaks for 7 days generally increased package purge and negatively affected colour parameters, although water binding characteristics were improved. Consumer panel results demonstrated a negative effect on juiciness and tenderness where meat subject to low salt/high injection was frozen then thawed - the low salt level was insufficient to maintain any positive effect of injection treatment. In general, salt/phosphate injection improved product acceptability and increased willingness to purchase.

Adenoviral vector tethering to metal surfaces via hydrolysable cross-linkers for the modulation of vector release and transduction

PubMed Central

Fishbein, Ilia; Forbes, Scott P.; Chorny, Michael; Connolly, Jeanne M.; Adamo, Richard F.; Corrales, Ricardo; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

The use of arterial stents and other medical implants as a delivery platform for surface immobilized gene vectors allows for safe and efficient localized expression of therapeutic transgenes. In this study we investigate the use of hydrolysable cross-linkers with distinct kinetics of hydrolysis for delivery of gene vectors from polyallylamine bisphosphonate-modified metal surfaces. Three cross-linkers with the estimated t1/2 of ester bonds hydrolysis of 5, 12 and 50 days demonstrated a cumulative 20%, 39% and 45% vector release, respectively, after 30 days exposure to physiological buffer at 37°C. Transgene expression in endothelial and smooth muscles cells transduced with substrate immobilized adenovirus resulted in significantly different expression profiles for each individual cross-linker. Furthermore, immobilization of adenoviral vectors effectively extended their transduction effectiveness beyond the initial phase of release. Transgene expression driven by adenovirus-tethered stents in rat carotid arteries demonstrated that a faster rate of cross-linker hydrolysis resulted in higher expression levels at day 1, which declined by day 8 after stent implantation, while inversely, slower hydrolysis was associated with increased arterial expression at day 8 in comparison with day 1. In conclusion, adjustable release of transduction-competent adenoviral vectors from metallic surfaces can be achieved, both in vitro and in vivo, through surface immobilization of adenoviral vectors using hydrolysable cross-linkers with structure-specific release kinetics. PMID:23777912

Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress.

PubMed

Santana, Magda M; Rosmaninho-Salgado, Joana; Cortez, Vera; Pereira, Frederico C; Kaster, Manuella P; Aveleira, Célia A; Ferreira, Marisa; Álvaro, Ana Rita; Cavadas, Cláudia

2015-10-01

Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Electrical Stimuli Are Anti-Apoptotic in Skeletal Muscle via Extracellular ATP. Alteration of This Signal in Mdx Mice Is a Likely Cause of Dystrophy

PubMed Central

Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

2013-01-01

ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies. PMID:24282497

Electrical stimuli are anti-apoptotic in skeletal muscle via extracellular ATP. Alteration of this signal in Mdx mice is a likely cause of dystrophy.

PubMed

Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

2013-01-01

ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies.

Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.

PubMed

Louiset, Estelle; Duparc, Céline; Young, Jacques; Renouf, Sylvie; Tetsi Nomigni, Milène; Boutelet, Isabelle; Libé, Rossella; Bram, Zakariae; Groussin, Lionel; Caron, Philippe; Tabarin, Antoine; Grunenberger, Fabienne; Christin-Maitre, Sophie; Bertagna, Xavier; Kuhn, Jean-Marc; Anouar, Youssef; Bertherat, Jérôme; Lefebvre, Hervé

2013-11-28

Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands. We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients. The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion. Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of steroidogenic cells in the hyperplastic adrenals. Thus, the hypercortisolism associated with bilateral macronodular adrenal hyperplasia appears to be corticotropin-dependent. (Funded by the Agence Nationale de la Recherche and others.).

Effect of Mobile Phone Usage on Nickel Ions Release and pH of Saliva in Patients Undergoing Fixed Orthodontic Treatment

PubMed Central

Girme, Tejashree Suresh; Agrawal, Jiwanasha Manish; Agrawal, Manish Suresh; Fulari, Sangamesh Gurunath; Shetti, Shraddha Subhash; Kagi, Vishwal Ajith

2017-01-01

Introduction Hand held mobile phones are presently the most popular means of communication worldwide and have transformed our lives in many aspects. The widespread use of such devices have resulted in growing concerns regarding harmful effects of radiations emitted by them. This study was designed to evaluate the effects of mobile phone usage on nickel ion release as well as pH of saliva in patients with fixed orthodontic appliances. Aim To assess the level of nickel ions in saliva and pH of saliva in mobile phone users undergoing fixed orthodontic treatment using inductively coupled plasma atomic emission spectrometry. Materials and Methods A total of 42 healthy patients with fixed orthodontic appliance in mouth for a duration of six to nine months were selected for the study. They were divided into experimental group (n=21) consisting of mobile phone users and control group (n=21) of non mobile phone users. Saliva samples were collected from both the groups and nickel ion levels were measured using inductively coupled plasma-mass spectroscopy. The pH values were also assessed for both groups using pH meter. Unpaired t-test was used for the data analysis. Results Statistical analysis revealed that though the pH levels were reduced and the nickel ion levels were higher in the experimental group compared to the control group, the results were non significant. Conclusion Mobile phone usage may affect the pH of saliva and result in increased release of nickel ions in saliva of patients with fixed orthodontic appliances in the oral cavity. PMID:29207841

In Vivo and In Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland.

PubMed

Ronchetti, Sonia A; Bianchi, María S; Duvilanski, Beatriz H; Cabilla, Jimena P

2016-07-01

Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status. © The Author(s) 2016.

VGluT2 expression in painful Achilles and patellar tendinosis: evidence of local glutamate release by tenocytes.

PubMed

Scott, Alexander; Alfredson, Håkan; Forsgren, Sture

2008-05-01

The pathogenesis of chronic tendinopathy is unclear. We have previously measured high intratendinous levels of glutamate in patients with tendinosis, suggesting potential roles of glutamate in the modulation of pain, vascular function, and degenerative changes including apoptosis of tenocytes. However, the origin of free glutamate found in tendon tissue is completely unknown. Surgical biopsies of pain-free normal tendons and tendinosis tendons (Achilles and patellar) were examined immunohistochemically using antibodies against vesicular glutamate transporters (VGluT1 and VGluT2), as indirect markers of glutamate release. In situ hybridization for VGluT2 mRNA was also conducted. Specific immunoreactions for VGluT2, but not VGluT1, could be consistently detected in tenocytes. However, there were interindividual variations in the levels of immunoreactivity. The level of immunoreaction for VGluT2 was higher in tendinosis tendons compared to normal tendons (p < 0.05). In situ hybridization of VGluT2 demonstrated that mRNA was localized in a similar pattern as the protein, with marked expression by certain tenocytes, particularly those showing abnormal appearances. Reactivity for VGluT1 and -2 was absent from nerves and vessel structures in both normal and painful tendons. The current data demonstrate that tenocytes may be involved in the regulation of extracellular glutamate levels in tendons. Specifically, the observations suggest that free glutamate may be locally produced and released by tenocytes, rather than by peripheral neurons. Excessive free glutamate is expected to impact a variety of autocrine and paracrine functions important in the development of tendinosis, including tenocyte proliferation and apoptosis, extracellular matrix metabolism, nociception, and blood flow. (c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Sustained Release of Green Tea Polyphenols from Liposomal Nanoparticles; Release Kinetics and Mathematical Modelling.

PubMed

Prakash Upputuri, Ravi Theaj; Azad Mandal, Abul Kalam

2017-01-01

Background: Green tea polyphenols (GTP) are known to have several health benefits. In spite of these benefits, its application as a therapeutic agent is limited due to some of its limitations such as stability, bioavailability, and biotransformation. To overcome these limitations, liposomal nanoparticles have been used as a carrier of the GTP. Objective: Encapsulation of GTP to the liposomal nanoparticles in order to achieve a sustained release of the GTP and to determine the drug release kinetics and the mechanism of the release. Materials and Methods: GTP encapsulated liposomal nanoparticles were prepared using phosphatidyl choline and cholesterol. The synthesized particles were characterized for their particle size and morphology. In vitro release studies were carried out, followed by drug release kinetics, and determining the mechanism of release. In vitro , antioxidant assay was determined following 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Results: Atomic force microscope (AFM) and high resolution scanning electron microscope (HR SEM) images showed spherical particles of the size of 64.5 and 252 nm. An encapsulation efficiency as high as 77.7% was observed with GTP concentration of 5 mg.mL -1 . In vitro release studies showed that the loading concentrations of GTP were independent to the cumulative percentage of the drug release. GTP release by varying the pH and temperature showed a direct correlation between the release parameter and the percentage of drug release. The higher the pH and temperature, the higher was the percentage of the drug release. The release data showed a good correlation with Zero order kinetics and the mechanism of the release being anomalous mode. Radical scavenging activity of the released GTP showed a potent scavenging activity. Conclusion: GTP encapsulated liposomal nanoparticles could be used as a delivery vehicle for achieving a sustained release.

Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum.

PubMed

Prins, J M; Kuijper, E J; Mevissen, M L; Speelman, P; van Deventer, S J

1995-06-01

The concentration and accessibility of endotoxin can increase following antibiotic killing of gram-negative bacteria. There are indications that antibiotics may differ in this respect. We measured endotoxin levels in RPMI 1640 and tumor necrosis factor alpha (TNF-alpha) and interleukin-6 production in whole blood ex vivo after exposure of log-phase Escherichia coli to antibiotics belonging to different classes, in a final concentration of 0.5, 5, or 50 times the MIC. After 4 h of incubation at 50 times the MIC, ceftazidime and ciprofloxacin treatment resulted in levels of endotoxin, TNF-alpha, and interleukin-6 significantly higher than those of imipenem and gentamicin (P < 0.001). Similar differences in cytokine induction were measured after 8 h of incubation. At 0.5 times the MIC, the differences between the antibiotics in measured endotoxin and cytokine levels were small, with levels comparable to the levels in untreated cultures. Polymyxin B and, to a lesser degree, recombinant bactericidal/permeability-increasing protein 21 (rBPI-21) were found to be potent inhibitors of TNF-alpha release, supporting the concept that the differences between the antibiotics in cytokine production were indeed due to differences in amounts of biologically active endotoxin. The presence of serum from patients suffering from untreated sepsis decreased TNF-alpha production significantly, in a concentration-dependent manner.

Pharmacological management of persistent hostility and aggression in persons with schizophrenia spectrum disorders: a systematic review.

PubMed

Victoroff, Jeff; Coburn, Kerry; Reeve, Alya; Sampson, Shirlene; Shillcutt, Samuel

2014-01-01

The incidence of aggressive behaviors is higher among persons with schizophrenia spectrum disorders (SSDs) than among persons without such disorders. This phenomenon represents a risk to the well-being of patients, their families, and society. The authors undertook a systematic review of the English language literature to determine the efficacy of neuropharmacological agents for the management of hostility and aggression among persons with SSDs. The search combined findings from the Medline, EMBASE, and PsycINFO databases. Ninety-two full text articles were identified that reported relevant findings. The American Academy of Neurology criteria were used to determine levels of evidence. Paliperidone-extended release is probably effective for the management of hostility among inpatients with SSDs who have not been preselected for aggression (Level B). Clozapine is possibly more effective than haloperidol for the management of overt aggression and possibly more effective than chlorpromazine for the management of hostility among inpatients with SSDs who have not been preselected for aggression (Level C). Clozapine is also possibly more effective than olanzapine or haloperidol for reducing aggression among selected physically assaultive inpatients (Level C). Adjunctive propranolol, valproic acid, and famotidine are possibly effective for reducing some aspects of hostility or aggression among inpatients with SSDs (Level C). Paliperidone-extended release currently appears to be the agent for the management of hostility among inpatients with SSDs for which there is the strongest evidence of efficacy.

Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity.

PubMed

Varamini, Pegah; Rafiee, Amirreza; Giddam, Ashwini Kumar; Mansfeld, Friederike M; Steyn, Frederik; Toth, Istvan

2017-10-26

Gonadotropin-releasing hormone (GnRH) agonists (e.g., triptorelin) are used for androgen suppression therapy. They possess improved stability as compared to the natural GnRH, yet they suffer from a poor pharmacokinetic profile. To address this, we used a GnRH peptide-modified dendrimer platform with and without lipidation strategy. Dendrimers were synthesized on a polylysine core and bore either native GnRH (1, 2, and 5) or lipid-modified GnRH (3 and 4). Compound 3, which bore a lipidic moiety in a branched tetramer structure, showed approximately 10-fold higher permeability and metabolic stability and 39 times higher antitumor activity against hormone-resistant prostate cancer cells (DU145) relative to triptorelin. In gonadotropin-release experiments, dendrimer 3 was shown to be the most potent construct. Dendrimer 3 showed similar luteinizing hormone (LH)-release activity to triptorelin in mice. Our findings indicate that dendrimer 3 is a promising analog with higher potency for the treatment of hormone-resistant prostate cancer than the currently available GnRH agonists.

Recovery of Retained Tritium from Graphite Tile of JT-60U

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

Takeishi, Toshiharu; Katayama, Kazunari; Nishikawa, Masabumi

Tritium thermal release and full combustion with oxygen were performed on isotropic graphite tiles used for plasma facing material of JT-60U. Approximately 50-80 % of tritium was released by dry argon gas purge and 20-50 % of tritium was released by humid argon gas purge up to 800-1200 deg. C within one day, respectively. Further several percent of tritium was released by full combustion with oxygen. It was experimentally confirmed that all retained tritium is not released by thermal dry gas purge and by use of isotope exchange reaction at high temperature in such a short period. In the fullmore » combustion operation, isotropic graphite begins to combust at higher temperature than 650 deg. C, but effective combustion temperature was higher than 700 deg. C. Since it is very difficult to heat the graphite tile attached on the wall of vacuum vessel at higher than 700 deg. C, it is considered to be not easy to recover all the tritium retained in the graphite while in the vacuum vessel.« less

Fuel use and metabolic response to endurance exercise: a wind tunnel study of a long-distance migrant shorebird.

PubMed

Jenni-Eiermann, Susanne; Jenni, Lukas; Kvist, Anders; Lindström, Ake; Piersma, Theunis; Visser, G Henk

2002-08-01

This study examines fuel use and metabolism in a group of long-distance migrating birds, red knots Calidris canutus (Scolopacidae), flying under controlled conditions in a wind tunnel for up to 10 h. Data are compared with values for resting birds fasting for the same time. Plasma levels of free fatty acids, glycerol and uric acid were elevated during flight, irrespective of flight duration (1-10 h). Triglyceride levels, the estimated concentration of very-low-density lipoproteins (VLDLs) and beta-hydroxybutyrate levels were lower during flight, while glucose levels did not change. In flying birds, plasma levels of uric acid and lipid catabolites were positively correlated with the residual variation in body mass loss, and lipid catabolites with energy expenditure (as measured using the doubly labelled water method), after removing the effect of initial body mass. The plasma metabolite levels indicate: (i) that the rates of catabolism of lipids from adipose tissue and of protein are higher during flight; (ii) that low ketone body concentrations probably facilitate fatty acid release from adipose tissue; (iii) that low triglyceride and VLDL levels do not indicate the use of an additional pathway of fatty acid delivery, as found in small birds; and (iv) that the relationships between energy expenditure, body mass loss and metabolic pattern suggest that a higher individual energy expenditure entails a higher rate of catabolism of both lipids and protein and not a shift in fuel substrate.

Colostrum proinflammatory cytokines as biomarkers of bovine immune response to bovine tuberculosis (bTB).

PubMed

Sánchez-Soto, Eduardo; Ponce-Ramos, Rosa; Hernández-Gutiérrez, Rodolfo; Gutiérrez-Ortega, Abel; Álvarez, Angel H; Martínez-Velázquez, Moisés; Absalón, Angel E; Ortiz-Lazareno, Pablo; Limón-Flores, Alberto; Estrada-Chávez, Ciro; Herrera-Rodríguez, Sara E

2017-02-01

Bovine colostrum contains compounds, which provide passive immune protection from mother to newborn calves. Little is known about cytokine levels and their role in bovine colostrum. Moreover, the capacity of bovine colostrum cells to mount specific immune responses after natural exposure to bovine tuberculosis (bTB) antigens in dairy herds has not been studied, thus far. The purpose of this study was to identify biomarkers for bTB infection measurable in bovine colostrum. The present study reveals that isolated-immune colostrum cells can mount a specific immune response against bTB antigens, by measuring the novo IFN-γ release in cell culture. We found that IFN-γ levels in the responders (Bov + ) to bTB antigen were higher than in non-responders (Bov - ). On the other hand, proinflammatory cytokines contained in colostrum's whey were tested in Tuberculin Skin Test (TST) reactor (TST + ) and non-reactor (TST - ) animals to assess their potential role as biomarker. We observed that IFN-γ levels were lower or undetectable, as opposed to IL4 levels were measurable, the TNF-α level was higher in TST - than TST + , while IL-6 levels showed the opposite reaction and with no statistical significance. Moreover, IL-1α mRNA expression levels were higher in colostrum mononuclear cells (CMC) in Bov + cattle. Collectively, these data suggest that the differential expression of pro and anti-inflammatory cytokines could have relevant value to diagnose bTB in cattle. Copyright © 2016 Elsevier Ltd. All rights reserved.

Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

PubMed Central

2010-01-01

Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone) at 10 pM (representing pre-development levels), and 1 nM (representing higher cycle-dependent and pregnancy levels) in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2) phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER) were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively). Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation) of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are vulnerable to very low concentrations of these structurally related xenoestrogens. Because of their non-classical dose-responses, they must be studied in detail to pinpoint effective concentrations and the directions of response changes. PMID:20950447

The Persistence of HIV Risk Behaviors Among Methamphetamine-Using Offenders†

PubMed Central

Cartier, Jerome J.; Greenwell, Lisa; Prendergast, Michael L.

2012-01-01

Studies have shown that methamphetamine (MA) is rapidly becoming the drug of choice for a large number of substance-abusing offenders and is associated with significantly higher levels of HIV risk behaviors prior to their incarceration. Despite these findings, there has been little follow-up research to determine whether these patterns persist among recently paroled offenders after attendance in an in-prison treatment program. This study uses the self-reported data from 812 substance-abusing offenders in a multisite NIDA-funded project to determine whether, either before incarceration or nine months after release from an in-prison substance abuse program, MA use in the past 30 days was associated with increased HIV risk behaviors. The findings indicate that offenders who used MA prior to and after incarceration and treatment report higher levels of HIV risk behaviors compared with offenders with no MA use. Clinical and policy implications of the findings are discussed. PMID:19283948

Consecutive Food and Respiratory Allergies Amplify Systemic and Gut but Not Lung Outcomes in Mice.

PubMed

Bouchaud, Gregory; Gourbeyre, Paxcal; Bihouée, Tiphaine; Aubert, Phillippe; Lair, David; Cheminant, Marie-Aude; Denery-Papini, Sandra; Neunlist, Michel; Magnan, Antoine; Bodinier, Marie

2015-07-22

Epidemiological data suggest a link between food allergies and the subsequent development of asthma. Although this progression may result from the additional effects of exposure to multiple allergens, whether both allergies amplify each other's effects remains unknown. This study investigated whether oral exposure to food allergens influences the outcomes of subsequent respiratory exposure to an asthma-inducing allergen. Mice were sensitized and orally challenged with wheat (FA) and then exposed to house dust mite (HDM) extract (RA). Immunoglobulin (Ig), histamine, and cytokine levels were assayed by ELISA. Intestinal and lung physiology was assessed. Ig levels, histamine release, and cytokine secretion were higher after exposure to both allergens than after separate exposure to each. Intestinal permeability was higher, although airway hyper-responsiveness and lung inflammation remained unchanged. Exposure to food and respiratory allergens amplifies systemic and gut allergy-related immune responses without any additional effect on lung function and inflammation.

Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols.

PubMed

Bomar, Lindsey; Brugger, Silvio D; Yost, Brian H; Davies, Sean S; Lemon, Katherine P

2016-01-05

Bacterial interspecies interactions play clinically important roles in shaping microbial community composition. We observed that Corynebacterium spp. are overrepresented in children free of Streptococcus pneumoniae (pneumococcus), a common pediatric nasal colonizer and an important infectious agent. Corynebacterium accolens, a benign lipid-requiring species, inhibits pneumococcal growth during in vitro cocultivation on medium supplemented with human skin surface triacylglycerols (TAGs) that are likely present in the nostrils. This inhibition depends on LipS1, a TAG lipase necessary for C. accolens growth on TAGs such as triolein. We determined that C. accolens hydrolysis of triolein releases oleic acid, which inhibits pneumococcus, as do other free fatty acids (FFAs) that might be released by LipS1 from human skin surface TAGs. Our results support a model in which C. accolens hydrolyzes skin surface TAGS in vivo releasing antipneumococcal FFAs. These data indicate that C. accolens may play a beneficial role in sculpting the human microbiome. Little is known about how harmless Corynebacterium species that colonize the human nose and skin might impact pathogen colonization and proliferation at these sites. We show that Corynebacterium accolens, a common benign nasal bacterium, modifies its local habitat in vitro as it inhibits growth of Streptococcus pneumoniae by releasing antibacterial free fatty acids from host skin surface triacylglycerols. We further identify the primary C. accolens lipase required for this activity. We postulate a model in which higher numbers of C. accolens cells deter/limit S. pneumoniae nostril colonization, which might partly explain why children without S. pneumoniae colonization have higher levels of nasal Corynebacterium. This work narrows the gap between descriptive studies and the needed in-depth understanding of the molecular mechanisms of microbe-microbe interactions that help shape the human microbiome. It also lays the foundation for future in vivo studies to determine whether habitat modification by C. accolens could be promoted to control pathogen colonization. Copyright © 2016 Bomar et al.

PLGA nanoparticles for the oral delivery of nuciferine: preparation, physicochemical characterization and in vitro/in vivo studies.

PubMed

Liu, Ying; Wu, Xin; Mi, Yushuai; Zhang, Bimeng; Gu, Shengying; Liu, Gaolin; Li, Xiaoyu

2017-11-01

This article reports a promising approach to enhance the oral delivery of nuciferine (NUC), improve its aqueous solubility and bioavailability, and allow its controlled release as well as inhibiting lipid accumulation. NUC-loaded poly lactic-co-glycolic acid nanoparticles (NUC-PLGA-NPs) were prepared according to a solid/oil/water (s/o/w) emulsion technique due to the water-insolubility of NUC. PLGA exhibited excellent loading capacity for NUC with adjustable dosing ratios. The drug loading and encapsulation efficiency of optimized formulation were 8.89 ± 0.71 and 88.54 ± 7.08%, respectively. NUC-PLGA-NPs exhibited a spherical morphology with average size of 150.83 ± 5.72 nm and negative charge of -22.73 ± 1.63 mV, which are suitable for oral administration. A sustained NUC released from NUC-PLGA-NPs with an initial exponential release owing to the surface associated drug followed by a slower release of NUC, which was entrapped in the core. In addition, ∼77 ± 6.67% was released in simulating intestinal juice, while only about 45.95 ± 5.2% in simulating gastric juice. NUC-PLGA-NPs are more efficient against oleic acid (OA)-induced hepatic steatosis in HepG 2 cells when compared to naked NUC (n-NUC, *p < 0.05). The oral bioavailability of NUC-PLGA-NPs group was significantly higher (**p < 0.01) and a significantly decreased serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as a higher concentration of high-density lipoprotein cholesterol (HDL-C) was observed, compared with that of n-NUC treated group. These findings suggest that NUC-PLGA-NPs hold great promise for sustained and controlled drug delivery with improved bioavailability to alleviating lipogenesis.

Protective activities of Vaccinium antioxidants with potential relevance to mitochondrial dysfunction and neurotoxicity.

PubMed

Yao, Yu; Vieira, Amandio

2007-01-01

Both the neurotransmitter dopamine (DA) and a neurotoxic metabolite, 6-hydroxy DA, can be oxidized to generate hydrogen peroxide and other reactive species (ROS). ROS promote oxidative stress and have been implicated in dopaminergic neurodegeneration, e.g., Parkinson's disease (PD). There is also evidence for a relation between catecholamine-mediated oxidative damage in dopaminergic neurons and the effects of these neurotransmitters on the redox state of cytochrome c (Cytc). In neurons and other cells, oxidative stress may be enhanced by abnormal release of Cytc and other mitochondrial proteins into the cytoplasm. Cytc release can result in apoptosis; but sub-apoptogenic-threshold release can also occur, and may be highly damaging in the presence of DA metabolites. Loss of mitochondrial membrane integrity, a pathological situation of relevance to several aging-related neurodegenerative disorders including PD, contributes to release of Cytc; and the level of such release is known to be indicative of the extent of mitochondrial dysfunction. In this context, we have used a Cytc-enhanced 6-hydroxy DA oxidation reaction to gauge dietary antioxidant activities. Anthocyanin-rich preparations of Vaccinium species (Vaccinium myrtillus, Vaccinium corymbosum, and Vaccinium oxycoccus) as well as a purified glycosylated anthocyanidin were compared. The most potent inhibition of oxidation was observed with V. myrtillus preparation: 50% inhibition with 7 microM of total anthocyanins. This activity was 1.5-4 times higher than that for the other preparations or for the purified anthocyanin. Ascorbate (Vitamin C), at up to 4-fold higher concentrations, did not result in significant inhibition in this assay. Antioxidant activity in the assay correlated strongly (r2>0.91, P<0.01) with reported Vaccinium content of anthocyanins and total cyanidins, but not quercetin or myricetin. The results provide evidence for the high potency of anthocyanins towards a potentially neurotoxic reaction, and provide a basis for in vivo testing of these flavonoids and their physiological metabolites in the context of neuro- and mitochondrio-protective effects.

Progesterone receptor knockout mice have an improved glucose homeostasis secondary to -cell proliferation

NASA Astrophysics Data System (ADS)

Picard, Frédéric; Wanatabe, Mitsuhiro; Schoonjans, Kristina; Lydon, John; O'Malley, Bert W.; Auwerx, Johan

2002-11-01

Gestational diabetes coincides with elevated circulating progesterone levels. We show that progesterone accelerates the progression of diabetes in female db/db mice. In contrast, RU486, an antagonist of the progesterone receptor (PR), reduces blood glucose levels in both female WT and db/db mice. Furthermore, female, but not male, PR-/- mice had lower fasting glycemia than PR+/+ mice and showed higher insulin levels on glucose injection. Pancreatic islets from female PR-/- mice were larger and secreted more insulin consequent to an increase in -cell mass due to an increase in -cell proliferation. These findings demonstrate an important role of progesterone signaling in insulin release and pancreatic function and suggest that it affects the susceptibility to diabetes.

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

PubMed

Warren, W B; Gurewitsch, E D; Goland, R S

1995-02-01

We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

Arginine potentiates the GHRH- but not the pyridostigmine-induced GH secretion in normal short children. Further evidence for a somatostatin suppressing effect of arginine.

PubMed

Ghigo, E; Bellone, J; Mazza, E; Imperiale, E; Procopio, M; Valente, F; Lala, R; De Sanctis, C; Camanni, F

1990-06-01

To investigate the mechanism underlying the GH-releasing effect of arginine (ARG), we studied the interactions of ARG (0.5 g/kg infused i.v. over 30 min) with GHRH (1 microgram/kg i.v.) and with pyridostigmine (PD, 60 mg orally) on GH secretion in 15 children and adolescents with familial short stature (5.1-15.4 years). In a group of eight subjects ARG induced a GH increase not statistically different to that observed after GHRH (peak, mean +/- SEM: 38.0 +/- 10.4 vs 64.0 +/- 14.4 mU/l). The combined administration of ARG and GHRH led to GH levels (101 +/- 15.2 mU/l) higher than those observed after GHRH (P less than 0.025) or ARG alone (P less than 0.001) and overlapping with those recorded after combined PD and GHRH administration (111 +/- 22.4 mU/l). In the other seven subjects, ARG and PD administration induced a similar GH response either when administered alone (25.2 +/- 13.6 and 27.8 +/- 4.0 mU/l, respectively) or in combination (33.8 +/- 5.4 mU/l). In conclusion, our results show that in children ARG administration potentiates GHRH- but not PD-induced GH increase. These findings agree with the hypothesis that the GH-releasing effect of both ARG and PD is mediated via the same mechanism, namely, by suppression of endogeneous somatostatin release. Combined administration of either ARG or PD with GHRH has a similar striking GH-releasing effect which is clearly higher than that of GHRH alone.

Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

NASA Astrophysics Data System (ADS)

Nahire, Rahul Rajaram

Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image guided, targeted delivery of anticancer drugs.

Association of serum glypican-4 levels with cardiovascular risk predictors in women with polycystic ovary syndrome - a pilot study.

PubMed

Jędrzejuk, Diana; Lwow, Felicja; Kuliczkowska-Płaksej, Justyna; Hirnle, Lidia; Trzmiel-Bira, Anna; Lenarcik-Kabza, Agnieszka; Kolackov, Katarzyna; Łaczmański, Łukasz; Milewicz, Andrzej

2016-01-01

Glypican-4 (Gpc4) is an adipokine which interacts with the insulin receptor and affects insulin sensitivity in proteoglycans. Insulin resistance plays a crucial role in the etiology of polycystic ovary syndrome (PCOS). PCOS is associated with metabolic disturbances such as abdominal obesity, dyslipidemia and type 2 diabetes. Thus, higher levels of Gpc4 released from visceral adipose tissue in women with PCOS may suggest an increased risk of cardiovascular disease (CVD). The aim of this pilot study was to determine whether the serum Gpc4 level is associated with cardiovascular risk predictors in women with PCOS. Sixty-two women with PCOS according to the Rotterdam criteria (20-35 years old) and 43 healthy controls were studied. Cardiovascular risk predictors such as obesity indices, fat deposits according to dual-energy X-ray absorptiometry, biochemical lipid profile parameters and Homeostasis Model Assessment were estimated. The serum Gpc4 level in PCOS women was significantly higher (2.61 ± 1.17 ng/ml) than in the control group (1.55 ± 0.47 ng/ml) and correlated with waist circumference, waist-to-hip ratio, total fat and android fat deposit to gynoid fat deposit ratio only in the PCOS group. The Gpc4 level was higher in the PCOS group and correlated with CVD risk predictors, especially fat distribution.

Tritium release during nuclear power operation in China.

PubMed

Yang, D J; Chen, X Q; Li, B

2012-06-01

Overviews were evaluated of tritium releases and related doses to the public from airborne and liquid effluents from nuclear power plants on the mainland of China before 2009. The differences between tritium releases from various nuclear power plants were also evaluated. The tritium releases are mainly from liquid pathways for pressurised water reactors, but tritium releases between airborne and liquid effluents are comparable for heavy water reactors. The airborne release from a heavy water reactor is obviously higher than that from a pressurised water reactor.

NOS-based biopolymers; towards novel thromboresistant NO-release materials

NASA Astrophysics Data System (ADS)

Abou Diwan, Charbel

Nitric Oxide releasing biopolymers have the potential to prolong vascular graft and stent potency without adverse systemic vasodilation. It was reported in literature that eNOS-overexpressing endothelial cell seeding of synthetic small diameter vascular grafts decreased human platelet aggregation by 46% and bovine aortic smooth muscle cell proliferation by 67.2% in vitro. We hypothesized that incorporating the enzyme nitric oxide synthase (NOS) in biocompatible polymeric matrix will provide a source of NO that utilizes endogenous compounds to maintain an unlimited supply of NO. To test this hypothesis, we have incorporated the enzyme nitric oxide synthase into a polyethyleneimine film using a layer-by-layer electrostatic deposition. This approach will provide a source of NO that utilizes endogenous compounds available in the blood matrix to maintain a constant supply of NO at the blood/device interface. When coated onto the surface of various blood-contacting implantable medical devices, it will provide NO fluxes at levels equal or greater than the normal endothelial cells, and for extended time periods. This configuration will help solve the issues of both thrombosis and stenosis that occur as side effects for several types of biomedical implants. Our results indicate a proof of principle of a new approach for making antithrombotic coatings for medical devices and implants based on NO release. We have demonstrated that NOS-based polymetric films successfully generate NO under physiologic conditions at small levels equal to and higher than those observed for endothelial cells. The level of NO release can be fine-tuned through varying the number of NOS layers in the film buildup. We have shown that NO fluxes from our NOS-based PEI films are sustained for prolonged periods of time, which has the potential of producing efficient, short and long-term, antithrombotic coatings for medical devices and blood-contacting tools such as stents and catheters. We also show that NO release from these coatings successfully decrease platelet adhesion at the surface by 60%. This, and other properties are key for the desired thromboresistivity needed for blood-contacting medical devices.

Simulating future water temperatures in the North Santiam River, Oregon

NASA Astrophysics Data System (ADS)

Buccola, Norman L.; Risley, John C.; Rounds, Stewart A.

2016-04-01

A previously calibrated two-dimensional hydrodynamic and water-quality model (CE-QUAL-W2) of Detroit Lake in western Oregon was used in conjunction with inflows derived from Precipitation-Runoff Modeling System (PRMS) hydrologic models to examine in-lake and downstream water temperature effects under future climate conditions. Current and hypothetical operations and structures at Detroit Dam were imposed on boundary conditions derived from downscaled General Circulation Models in base (1990-1999) and future (2059-2068) periods. Compared with the base period, future air temperatures were about 2 °C warmer year-round. Higher air temperature and lower precipitation under the future period resulted in a 23% reduction in mean annual PRMS-simulated discharge and a 1 °C increase in mean annual estimated stream temperatures flowing into the lake compared to the base period. Simulations incorporating current operational rules and minimum release rates at Detroit Dam to support downstream habitat, irrigation, and water supply during key times of year resulted in lower future lake levels. That scenario results in a lake level that is above the dam's spillway crest only about half as many days in the future compared to historical frequencies. Managing temperature downstream of Detroit Dam depends on the ability to blend warmer water from the lake's surface with cooler water from deep in the lake, and the spillway is an important release point near the lake's surface. Annual average in-lake and release temperatures from Detroit Lake warmed 1.1 °C and 1.5 °C from base to future periods under present-day dam operational rules and fill schedules. Simulated dam operations such as beginning refill of the lake 30 days earlier or reducing minimum release rates (to keep more water in the lake to retain the use of the spillway) mitigated future warming to 0.4 and 0.9 °C below existing operational scenarios during the critical autumn spawning period for endangered salmonids. A hypothetical floating surface withdrawal at Detroit Dam improved temperature control in summer and autumn (0.6 °C warmer in summer, 0.6 °C cooler in autumn compared to existing structures) without altering release rates or lake level management rules.

Effect of naltrexone treatment on the treadmill exercise-induced hormone release in amenorrheic women.

PubMed

Botticelli, G; Bacchi Modena, A; Bresciani, D; Villa, P; Aguzzoli, L; Florio, P; Nappi, R E; Petraglia, F; Genazzani, A R

1992-12-01

The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, beta-endorphin) and adrenal (cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (VO2) every 20 min) was used as physical stressor. While mean +/- SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p < 0.01), no significant differences of basal plasma hormonal levels were observed between amenorrheic and eumenorrheic women, both before and after naltrexone treatment. Physical exercise at 90% VO2 induced a significant increase in plasma GH, ACTH, beta-endorphin, cortisol, androstenedione and testosterone levels in controls before naltrexone treatment (p < 0.01). The mean increase in plasma androstenedione and testosterone levels in control women was significantly higher after naltrexone treatment (p < 0.01). In amenorrheic patients before naltrexone, physical exercise induced an increase in plasma prolactin and GH levels, but not in plasma ACTH, beta-endorphin, cortisol, testosterone and androstenedione. After naltrexone treatment, the exercise induced a significant plasma ACTH, beta-endorphin and cortisol levels, while the increase of plasma prolactin levels was significantly higher than before treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Primary hypothyroidism in dogs is associated with elevated GH release.

PubMed

Lee, W M; Diaz-Espineira, M; Mol, J A; Rijnberk, A; Kooistra, H S

2001-01-01

The pulsatile secretion patterns of GH were investigated in seven beagle bitches by collecting blood samples every 10 min for 6 h during euthyroidism and 1.5 years after induction of primary hypothyroidism. Hypothyroidism was induced by surgical removal of the thyroid gland and subsequent destruction of any remnant thyroid tissue by oral administration of sodium [(131)I]iodide. Some of the physical changes observed in the dogs with primary hypothyroidism mimicked those of acromegaly. During both euthyroidism and hypothyroidism GH was secreted in a pulsatile fashion. The mean (+/-s.e.m. ) basal plasma GH concentration was significantly higher (P=0.003) in the hypothyroid state (4.1+/-1.6 microg/l) than in the euthyroid state (1.2+/-0.4 microg/l). Likewise, the mean area under the curve (AUC) for GH above the zero-level during hypothyroidism (27.0+/-10.0 microg/lx6 h) was significantly higher (P=0.004) than that during euthyroidism (11.7+/-2.0 microg/l x 6 h). The mean AUC for GH above the baseline was significantly lower (P=0.008) during hypothyroidism (2.4+/-0.8 microg/l x 6 h) than during euthyroidism (4.5+/-1.8 microg/lx6 h), whereas there was no significant difference in GH pulse frequency. The mean plasma IGF-I level was significantly higher (P<0.01) in the hypothyroid state (169+/-45 microg/l) than in the euthyroid (97+/-15 microg/l). The results of this study demonstrate that primary hypothyroidism in dogs is associated with elevated basal GH secretion and less GH secreted in pulses. This elevated GH secretion has endocrine significance as illustrated by elevated plasma IGF-I levels and some physical changes mimicking acromegaly. It is discussed that the increased GH release in hypothyroid dogs may be the result of the absence of a response element for thyroid hormone within the canine pituitary GH gene and alterations in supra-pituitary regulation.

Short-term nutritional folate deficiency in rats has a greater effect on choline and acetylcholine metabolism in the peripheral nervous system than in the brain, and this effect escalates with age

PubMed Central

Crivello, Natalia A.; Blusztajn, Jan K.; Joseph, James A.; Shukitt-Hale, Barbara; Smith, Donald E.

2010-01-01

The hypothesis of this study is that a folate-deficient diet (FD) has a greater effect on cholinergic system in the peripheral nervous system than in the brain, and that this effect escalates with age. It was tested by comparing choline and acetylcholine levels in male Sprague Dawley rats fed either control or folate-deficient diets for 10 weeks, starting at age 4 weeks (the young group) or 9 months (the adult group). FD consumption resulted in depletion of plasma folate in both age groups. In young folate-deficient rats, liver and lung choline levels were significantly lower than those in the respective controls. No other significant effects of FD on choline and acetylcholine metabolism were found in young rats. In adult rats, FD consumption markedly decreased choline levels in the liver, kidneys, and heart; furthermore, choline levels in the cortex and striatum were moderately elevated, although hippocampal choline levels were not affected. Acetylcholine levels were higher in the heart, cortex, and striatum but lower in the hippocampus in adult folate-deficient rats, as compared to controls. Higher acetylcholine levels in the striatum in adult folate-deficient rats were also associated with higher dopamine release in the striatal slices. Thus, both age groups showed higher cholinergic metabolic sensitivity to FD in the peripheral nervous system than in the brain. However, compensatory abilities appeared to be better in the young group, implicating the adult group as a preferred model for further investigation of folate-choline-acetylcholine interactions and their role in brain plasticity and cognitive functions. PMID:21056288

Short-term nutritional folate deficiency in rats has a greater effect on choline and acetylcholine metabolism in the peripheral nervous system than in the brain, and this effect escalates with age.

PubMed

Crivello, Natalia A; Blusztajn, Jan K; Joseph, James A; Shukitt-Hale, Barbara; Smith, Donald E

2010-10-01

The hypothesis of this study is that a folate-deficient diet (FD) has a greater effect on cholinergic system in the peripheral nervous system than in the brain, and that this effect escalates with age. It was tested by comparing choline and acetylcholine levels in male Sprague Dawley rats fed either control or folate-deficient diets for 10 weeks, starting at age 4 weeks (the young group) or 9 months (the adult group). Folate-deficient diet consumption resulted in depletion of plasma folate in both age groups. In young folate-deficient rats, liver and lung choline levels were significantly lower than those in the respective controls. No other significant effects of FD on choline and acetylcholine metabolism were found in young rats. In adult rats, FD consumption markedly decreased choline levels in the liver, kidneys, and heart; furthermore, choline levels in the cortex and striatum were moderately elevated, although hippocampal choline levels were not affected. Acetylcholine levels were higher in the heart, cortex, and striatum but lower in the hippocampus in adult folate-deficient rats, as compared to controls. Higher acetylcholine levels in the striatum in adult folate-deficient rats were also associated with higher dopamine release in the striatal slices. Thus, both age groups showed higher cholinergic metabolic sensitivity to FD in the peripheral nervous system than in the brain. However, compensatory abilities appeared to be better in the young group, implicating the adult group as a preferred model for further investigation of folate-choline-acetylcholine interactions and their role in brain plasticity and cognitive functions. Copyright © 2010 Elsevier Inc. All rights reserved.

GnRH mRNA levels in male three-spined sticklebacks, Gasterosteus aculeatus, under different reproductive conditions.

PubMed

Shao, Yi Ta; Tseng, Yung Che; Chang, Chia-Hao; Yan, Hong Young; Hwang, Pung Pung; Borg, Bertil

2015-02-01

In vertebrates, reproduction is regulated by the brain-pituitary-gonad (BPG) axis, where the gonadotropin-releasing hormone (GnRH) is one of the key components. However, very little is known about the possible role of GnRH in the environmental and feedback control of fish reproduction. To investigate this, full-length gnrh2 (chicken GnRH II) and gnrh3 (salmon GnRH) sequences of male three-spined sticklebacks (Gasterosteus aculeatus), which are clustered with the taxa of the same GnRH type as other Euteleostei, were cloned and annotated. gnrh1 is absent in this species. The mRNA levels of gnrh2 and gnrh3 in the sticklebacks' brain were measured under breeding and post-breeding conditions as well as in castrated and sham-operated breeding fish and castrated/sham-operated fish kept under long-day (LD 16:8) and short-day (LD 8:16) conditions. Fully breeding males had considerably higher mRNA levels of gnrh2 and gnrh3 in the thalamus (Th) and in the telencephalon and preoptic area (T+POA), respectively, than post-breeding males. Sham-operated breeding males have higher gnrh3 mRNA levels than the corresponding castrated males. Moreover, higher gnrh2 mRNA levels in the Th and higher gnrh3 mRNA levels in the T+POA and hypothalamus (HypTh) were also found in long-day sham-operated males than in sham-operated fish kept under an inhibitory short day photoperiod. Nevertheless, gnrh2 and gnrh3 mRNA levels were not up-regulated in castrated males kept under long-day photoperiod, which suggests that positive feedbacks on the brain-pituitary-gonad axis are necessary for this response. Copyright © 2014 Elsevier Inc. All rights reserved.

[Secretion of growth hormone in hyperthyroidism].

PubMed

Hervás, F; Morreale de Escobar, G; Escobar Del Rey, F; Pozuelo, V

1976-01-01

The authors studied growth hormone (GH) secretion in a group of adult controls and another group of hyperthyroid patients after stimulation with intravenous insulin-induced (0,1 IU/kg) hypoglycemia, aiming to clear out the problem of discrepancies in literature concerning GH secretion in hyperthyroidism. They concluded that in this syndrome, GH levels are significantly higher than those of controls. The GH releasing response is normal, though it could be expected to be decreased due to decreased pituitary GH contents as a result of permanent somatotrophic cell stimulation.

Cisplatin-Conjugated Porous Gelatin Particles: Assessment of Optimal Conditions for Binding and Release

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

Ohta, Shinichi, E-mail: junryuhei@yahoo.co.jp; Nitta, Norihisa; Sonoda, Akinaga

2010-08-15

This study was designed to evaluate the optimal conditions for binding cisplatin and porous gelatin particles (PGPs) and to establish in vivo drug release pharmacokinetics. PGPs were immersed in cisplatin solutions under different conditions: concentration, immersion time, and temperature. Thereafter, PGPs were washed in distilled water to remove uncombined cisplatin and were then freeze-dried. The platinum concentration (PC) in the PGPs was then measured. For the in vivo release test, 50 mg/kg of the cisplatin-conjugated PGPs was implanted subcutaneously in the abdominal region of two rabbits. PCs in the blood were measured at different time intervals. PCs significantly increased inmore » direct proportion to the concentration and immersion time (p < 0.01). Although PC increased at higher solution temperature, it was not a linear progression. For the in vivo release test, platinum was released from cisplatin-conjugated PGPs after 1 day, and the peak PC was confirmed 2 days after implantation. Platinum in the blood was detected until 7 days after implantation in one rabbit and 15 days after administration in the other rabbit. Platinum binding with PGPs increased with a higher concentration of cisplatin solution at a higher temperature over a longer duration of time. Release of cisplatin from cisplatin-conjugated PGPs was confirmed in vivo.« less

Serum soluble CD163 levels in patients with influenza-associated encephalopathy.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Takahara, Midori; Kajimoto, Madoka; Momonaka, Hiroshi; Ishida, Chiemi; Tanaka, Saya; Morishima, Tsuneo; Ichiyama, Takashi

2013-08-01

Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Seasonal arsenic accumulation in stream sediments at a groundwater discharge zone.

PubMed

MacKay, Allison A; Gan, Ping; Yu, Ran; Smets, Barth F

2014-01-21

Seasonal changes in arsenic and iron accumulation rates were examined in the sediments of a brook that receives groundwater discharges of arsenic and reduced iron. Clean glass bead columns were deployed in sediments for known periods over the annual hydrologic cycle to monitor changes in arsenic and iron concentrations in bead coatings. The highest accumulation rates occurred during the dry summer period (July-October) when groundwater discharges were likely greatest at the sample locations. The intermediate flow period (October-March), with higher surface water levels, was associated with losses of arsenic and iron from bead column coatings at depths below 2-6 cm. Batch incubations indicated iron releases from solids to be induced by biological reduction of iron (oxy)hydroxide solids. Congruent arsenic releases during incubation were limited by the high arsenic sorption capacity (0.536 mg(As)/mg(Fe)) of unreacted iron oxide solids. The flooded spring (March-June) with high surface water flows showed the lowest arsenic and iron accumulation rates in the sediments. Comparisons of accumulation rates across a shoreline transect were consistent with greater rates at regions exposed above surface water levels for longer times and greater losses at locations submerged below surface water. Iron (oxy)hydroxide solids in the shallowest sediments likely serve as a passive barrier to sorb arsenic released to pore water at depth by biological iron reduction.

Investigation of drug release and matrix degradation of electrospun poly(DL-lactide) fibers with paracetanol inoculation.

PubMed

Cui, Wenguo; Li, Xiaohong; Zhu, Xinli; Yu, Guo; Zhou, Shaobing; Weng, Jie

2006-05-01

This study was aimed at assessing the potential use of electrospun fibers as drug delivery vehicles with focus on the different diameters and drug contents to control drug release and polymer fiber degradation. A drug-loaded solvent-casting polymer film was made with an average thickness of 100 microm for comparative purposes. DSC analysis indicated that electrospun fibers had a lower T(g) but higher transition enthalpy than solvent-casting polymer film due to the inner stress and high degree of alignment and orientation of polymer chains caused by the electrospinning process. Inoculation of paracetanol led to a further slight decrease in the T(g) and transition enthalpy. An in vitro drug release study showed that a pronounced burst release or steady release phase was initially observed followed by a plateau or gradual release during the rest time. Fibers with a larger diameter exhibited a longer period of nearly zero order release, and higher drug encapsulation led to a more significant burst release after incubation. In vitro degradation showed that the smaller diameter and higher drug entrapment led to more significant changes of morphologies. The electrospun fiber mat showed almost no molecular weight reduction, but mass loss was observed for fibers with small and medium size, which was characterized with surface erosion and inconsistent with the ordinarily polymer degrading form. Further wetting behavior analysis showed that the high water repellent property of electrospun fibers led to much slower water penetration into the fiber mat, which may contribute to the degradation profiles of surface erosion. The specific degradation profile and adjustable drug release behaviors by variation of fiber characteristics made the electrospun nonwoven mat a potential drug delivery system rather than polymer films and particles.

Impulsive behavior and nicotinic acetylcholine receptors.

PubMed

Ohmura, Yu; Tsutsui-Kimura, Iku; Yoshioka, Mitsuhiro

2012-01-01

Higher impulsivity is thought to be a risk factor for drug addiction, criminal involvement, and suicide. Excessive levels of impulsivity are often observed in several psychiatric disorders including attention-deficit/hyperactivity disorder and schizophrenia. Previous studies have demonstrated that nicotinic acetylcholine receptors (nAChRs) are involved in impulsive behavior. Here, we introduce recent advances in this field and describe the role of the following nAChR-related brain mechanisms in modulating impulsive behavior: dopamine release in the ventral striatum; α4β2 nAChRs in the infralimbic cortex, which is a ventral part of the medial prefrontal cortex (mPFC); and dopamine release in the mPFC. We also suggest several potential therapeutic drugs to address these mechanisms in impulsivity-related disorders and explore future directions to further elucidate the roles of central nAChRs in impulsive behavior.

Impact production of CO2 by the Cretaceous/Tertiary extinction bolide and the resultant heating of the earth

NASA Technical Reports Server (NTRS)

O'Keefe, John D.; Ahrens, Thomas J.

1989-01-01

Various observations and data demonstrate that sea level at the end of the Cretaceous was 150-200 m higher than at present, suggesting the possibility that the extinction bolide struck a shallow marine carbonate-rich sedimentary section. It is shown here that the impact of such a bolide (about 5 km in radius) onto a carbonate-rich terrane would increase the CO2 content of the atmosphere by a factor of two to ten. Additional dissolution of CO2 from the ocean's photic zone could release much larger quantities of CO2. The impact-induced release of CO2, by itself, would enhance atmospheric greenhouse heating and give rise to a worldwide increase in temperature from 2 K to 10 K for periods of 10,000 to 100,000 years.

Ion release from dental casting alloys as assessed by a continuous flow system: Nutritional and toxicological implications.

PubMed

López-Alías, José F; Martinez-Gomis, Jordi; Anglada, Josep M; Peraire, Maria

2006-09-01

The aims of this study were to quantify the metallic ions released by various dental alloys subjected to a continuous flow of saliva and to estimate the nutritional and toxicological implications of such a release. Four pieces of three nickel-based, one noble, one high-noble and two copper-aluminum alloys were cast and then immersed in a continuous flow of artificial saliva for 15 days. To simulate three meals a day, casts were subjected to thrice-daily episodes, lasting 30 min each and consisting of pH decreases and salinity increases. After 15 days, the metallic ions in the artificial saliva were analyzed. Data were expressed as averaged release rate: microg/cm2/day of ion released for each alloy. The highest value of 95% Cl of each ion was adapted to a hypothetical worst scenario of a subject with 100 cm2 of exposed metal surface. The results were compared with the tolerable upper daily intake level of each ion. The copper-aluminum alloys released copper, aluminum, nickel, manganese and iron. The nickel-based alloys essentially released nickel and chromium, while the beryllium-containing alloy released beryllium and significantly more nickel. The noble and high-noble alloys were very resistant to corrosion. The amount of ions released remained far below the upper tolerable intake level, with the exception of nickel, released by beryllium-containing nickel-based alloy, whose levels approach 50% of this threshold. The daily amount of ions released seems to be far below the tolerable upper intake levels for each ion.

Surgical injury: comparing open surgery and laparoscopy by markers of tissue damage.

PubMed

Máca, Jan; Peteja, Matúš; Reimer, Petr; Jor, Ondřej; Šeděnková, Věra; Panáčková, Lucie; Ihnát, Peter; Burda, Michal; Ševčík, Pavel

2018-01-01

Major abdominal surgery (MAS) is high-risk intervention usually accompanied by tissue injury leading to a release of signaling danger molecules called alarmins. This study evaluates the surgical injury caused by two fundamental types of gastrointestinal surgical procedures (open surgery and laparoscopy) in relation to the inflammation elicited by alarmins. Patients undergoing MAS were divided into a mixed laparoscopy group (LPS) and an open surgery group (LPT). Serum levels of alarmins (S100A8, S100A12, HMGB1, and HSP70) and biomarkers (leukocytes, C-reactive protein [CRP], and interleukin-6 [IL-6]) were analyzed between the groups. The secondary objectives were to compare LPT and LPS cancer subgroups and to find the relationship between procedure and outcome (intensive care unit length of stay [ICU-LOS] and hospital length of stay [H-LOS]). A total of 82 patients were analyzed. No significant difference was found in alarmin levels between the mixed LPS and LPT groups. IL-6 was higher in the LPS group on day 2 ( p =0.03) and day 3 ( p =0.04). Significantly higher S100A8 protein levels on day 1 ( p =0.02) and day 2 ( p =0.01) and higher S100A12 protein levels on day 2 ( p =0.03) were obtained in the LPS cancer subgroup. ICU-LOS and H-LOS were longer in the LPS cancer subgroup. The degree of surgical injury elicited by open MAS as reflected by alarmins is similar to that of laparoscopic procedures. Nevertheless, an early biomarker of inflammation (IL-6) was higher in the laparoscopy group, suggesting a greater inflammatory response. Moreover, the levels of S100A8 and S100A12 were higher with a longer ICU-LOS and H-LOS in the LPS cancer subgroup.

Individual differences in pavlovian autoshaping of lever pressing in rats predict stress-induced corticosterone release and mesolimbic levels of monoamines.

PubMed

Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

2000-03-01

Pavlovian autoshaping CRs are directed and reflexive consummatory responses targeted at objects repeatedly paired with rewarding substances. To evaluate the hypothesis that autoshaping may provide an animal learning model of vulnerability to drug abuse, this study relates individual differences in lever-press autoshaping CR performance in rats to stress-induced corticosterone release and tissue monoamine levels in the mesolimbic dopamine tract. Long-Evans rats (n = 14) were given 20 sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of food US. Large between-subjects differences in lever-press autoshaping CR performance were observed, with group high CR frequency (n = 5) performing many more lever press CRs than group low CR frequency (n = 9). Tail-blood samples were obtained before and after the 20th autoshaping session, then 24 h later the rats were sacrificed and dissection yielded tissue samples of nucleus accumbens (NAC), prefrontal cortex (PFC), caudate putamen (CP), and ventral tegmental area (VTA). Serum levels of postsession corticosterone were elevated in group high CR frequency. HPLC revealed that group high CR frequency had higher tissue levels of dopamine and DOPAC in NAC, lower levels of DOPAC/DA turnover in CP, and lower levels of 5-HIAA and lower 5-HIAA/5-HT turnover in VTA. The neurochemical profile of rats that perform more autoshaping CRs share some features of vulnerability to drug abuse.

Possible environmental chemical cues affecting behaviour of the mangrove gastropod Cerithidea decollata

NASA Astrophysics Data System (ADS)

Lazzeri, Anna Marta

2017-03-01

The Indo-West Pacific mangrove gastropod Cerithidea decollata feeds on the ground at low tide and climbs the trees (Avicennia marina) two hours before the arrival of water, settling well above the level that the incoming tide will reach at high tide (from 0 to 80 cm, depending on the tidal phase). In addition, it has been shown that these snails climb twice as high when translocated to lower shore sites (dominated by Rhizophora mucronata), where C. decollata is missing and the high water can reach 1.6 m instead of about 80 cm as within the snail home environment. The study assesses the possible role of chemical cues in the afore-mentioned behaviours. The hypothesis that snails may foresee the periodical tide level variation thanks to airborne chemical cues, possibly released by trees or sediments, has been rejected. On the other hand, airborne chemical cues released by R. mucronata may play a role in inducing snails translocated to low shore sites to climb much higher than control, allowing them to avoid submersion.

ATP release from bladder urothelium and serosa in a rat model of partial bladder outlet obstruction.

PubMed

Shiina, Kazuhiro; Hayashida, Ken-Ichiro; Ishikawa, Kazuo; Kawatani, Masahito

2016-01-01

Overactive bladder is one of the major health problem especially in elderly people. Adenosine triphosphate (ATP) is released from urinary bladder cells and acts as a smooth muscle contraction and sensory signal in micturition but little is known about the role of ATP release in the pathophysiology of overactive bladder. To assess the relationship between ATP and overactive bladder, we used a partial bladder outlet obstruction (pBOO) model in rats. The bladder caused several changes by pBOO: An increase in bladder weight, hypertrophy of sub-urothelium and sub-serosal area, and frequent non-voiding bladder contraction during urine storage. Basal ATP release from urothelium and serosa of pBOO rats was significantly higher than that of normal rats. Distentioninduced ATP release from urothelium of normal and pBOO rats had no significant change. However, distention-induced ATP release from serosa of pBOO rats was higher than that of normal. These findings may identify ATP especially released from serosa as one of causes of non-voiding contractions and overactive bladder symptoms.

Candida albicans-induced inflammatory response in human keratinocytes.

PubMed

Wollina, U; Künkel, W; Bulling, L; Fünfstück, C; Knöll, B; Vennewald, I; Hipler, U-C

2004-06-01

Candida albicans strains 3153a, ATCC 48867, CBS 2730, DSM 70014, and Vir 13 were cultivated and sterile C. albicans filtrates were produced. The interaction of soluble Candida factors of these infiltrates with human HaCaT keratinocytes was assayed in vitro. The following parameters were analyzed: cell proliferation, protein synthesis, nuclear matrix protein (NMP) 41 release, cytokine release (IL-1beta, soluble IL-2 receptor, IL-6, and IL-8), and reactive oxygen species (ROS). Cell counts at 1, 12, and 24 h were significantly lower for C. albicans strains CBS 2730 and VIR 13 (P < 0.05). There was no significant change for the remaining strains. Neither the protein synthesis nor the NMP-41 release was significantly affected. IL-6 and IL-8 were stimulated by C. albicans filtrates to different amounts with higher levels in strains of low virulence. There was no effect on the other cytokines. The production of ROS by HaCaT keratinocytes was suppressed. The induction of an inflammatory keratinocyte response by soluble C. albicans factors may play a role among the host-yeast interactions.

Emergence and fate of cyclic volatile polydimethylsiloxanes (D4, D5) in municipal waste streams: release mechanisms, partitioning and persistence in air, water, soil and sediments.

PubMed

Surita, Sharon C; Tansel, Berrin

2014-01-15

Siloxane use in consumer products (i.e., fabrics, paper, concrete, wood, adhesive surfaces) has significantly increased in recent years due to their excellent water repelling and antimicrobial characteristics. The objectives of this study were to evaluate the release mechanisms of two siloxane compounds, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5), which have been detected both at landfills and wastewater treatment plants, estimate persistence times in different media, and project release quantities over time in relation to their increasing use. Analyses were conducted based on fate and transport mechanisms after siloxanes enter waste streams. Due to their high volatility, the majority of D4 and D5 end up in the biogas during decomposition. D5 is about ten times more likely to partition into the solid phase (i.e., soil, biosolids). D5 concentrations in the wastewater influent and biogas are about 16 times and 18 times higher respectively, in comparison to the detected levels of D4. © 2013 Elsevier B.V. All rights reserved.

Percutaneous Trigger Finger Release: A Cost-effectiveness Analysis.

PubMed

Gancarczyk, Stephanie M; Jang, Eugene S; Swart, Eric P; Makhni, Eric C; Kadiyala, Rajendra Kumar

2016-07-01

Percutaneous trigger finger releases (TFRs) performed in the office setting are becoming more prevalent. This study compares the costs of in-hospital open TFRs, open TFRs performed in ambulatory surgical centers (ASCs), and in-office percutaneous releases. An expected-value decision-analysis model was constructed from the payer perspective to estimate total costs of the three competing treatment strategies for TFR. Model parameters were estimated based on the best available literature and were tested using multiway sensitivity analysis. Percutaneous TFR performed in the office and then, if needed, revised open TFR performed in the ASC, was the most cost-effective strategy, with an attributed cost of $603. The cost associated with an initial open TFR performed in the ASC was approximately 7% higher. Initial open TFR performed in the hospital was the least cost-effective, with an attributed cost nearly twice that of primary percutaneous TFR. An initial attempt at percutaneous TFR is more cost-effective than an open TFR. Currently, only about 5% of TFRs are performed in the office; therefore, a substantial opportunity exists for cost savings in the future. Decision model level II.

Passive Avoidance Training and Recall are Associated With Increased Glutamate Levels in the Intermediate Medial Hyperstriatum Ventrale of the Day-Old Chick

PubMed Central

Daisley, Jonathan N.; Gruss, Michael; Rose, Steven P. R.; Braun, Katharina

1998-01-01

In the young chick, the intermediate medial hyperstriatum ventrale is involved in learning paradigms, including imprinting and passive avoidance learning. Biochemical changes in the intermediate medial hyperstriatum ventrale following learning include an up-regulation of amino-acid transmitter levels and receptor activity. To follow the changes of extracellular amino acid levels during passive avoidance training, we used an in vivo microdialysis technique. Probes were implanted in chicks before training the animals, either on a methyl- anthranylate-or water-coated bead. One hour later, recall was tested in both groups by presenting a similar bead. An increase of extra-cellular glutamate levels accompanied training and testing in both groups; during training, glutamate release was higher in methylanthranylate- trained than in water-trained chicks. When compared with the methylanthranylate-trained chicks during testing, the water-trained chicks showed enhanced extra-cellular glutamate levels. No other amino acid examined showed significant changes. After testing, the chicks were anesthetized and release- stimulated with an infusion of 50 mM potassium. Extra-cellular glutamate and taurine levels were significantly increased in both methylanthranylate-and water-trained chicks. The presentation of methylanthranylate as an. olfactory stimulus significantly enhanced glutamate levels, especially in methylanthranylate-trained chicks. The results suggest that such changes in extra-cellular glutamate levels in the intermediate medial hyperstriatum ventrale accompany pecking at either the water- or the methylanthranylate-bead. The taste of the aversant may be responsible for the greater increases found in methylanthranylate-trained birds. PMID:9920682

Effect of particle size on calcium release and elevation of pH of endodontic cements.

PubMed

Saghiri, Mohammad Ali; Asatourian, Armen; Orangi, Jafar; Lotfi, Mehrdad; Soukup, Jason W; Garcia-Godoy, Franklin; Sheibani, Nader

2015-06-01

Elevation of pH and calcium ion release are of great importance in antibacterial activity and the promotion of dental soft and hard tissue healing process. In this study, we evaluated the effect of particle size on the elevation of pH and the calcium ion release from calcium silicate-based dental cements. Twelve plastic tubes were divided into three groups, filled with white mineral trioxide aggregate (WMTA), WMTA plus 1% methylcellulose, and nano-modified WMTA (nano-WMTA), and placed inside flasks containing 10 ml of distilled water. The pH values were measured using a pH sensor 3, 24, 72, and 168 h after setting of the cements. The calcium ion release was measured using an atomic absorption spectrophotometer with same sample preparation method. Data were subjected to two-way analysis of variance (anova) followed by post hoc Tukey tests with significance level of P < 0.05. Nano-WMTA showed significant pH elevation only after 24 h (P < 0.05) compared with WMTA, and after 3, 24, and 72 h compared with WMTA plus 1% methylcellulose (P < 0.05). Nano-WMTA showed significantly higher calcium ion release values compared to the other two groups (P < 0.05). Nano-modification of WMTA remarkably increased the calcium ion release at all time intervals postsetting, which can significantly influence the osteogenic properties of human dental pulp cells and as a consequence enhance mineralized matrix nodule formation to achieve desirable clinical outcomes. However, the increase in pH values mainly occurred during the short time postsetting. Addition of 1% methylcellulose imposed a delay in elevation of pH and calcium ion release by WMTA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mechanical properties and ion release from bioactive restorative composites containing glass fillers and calcium phosphate nano-structured particles.

PubMed

Chiari, Marina D S; Rodrigues, Marcela C; Xavier, Tathy A; de Souza, Eugen M N; Arana-Chavez, Victor E; Braga, Roberto R

2015-06-01

To evaluate the effect of the replacement of barium glass by dicalcium phosphate dihydrate (DCPD) particles on the mechanical properties and degree of conversion (DC) of composites. Additionally, calcium and hydrogen phosphate (HPO4(2-)) release were followed for 28 days. Nine composites containing equal parts (in mols) of BisGMA and TEGDMA and 40, 50 or 60 vol% of total filler were manipulated. Filler phase was constituted by silanated barium glass and 0%, 10% or 20% of DCPD particles. DC was determined by near-FTIR. Biaxial flexural strength (BFS) and modulus (E) were tested using the "piston on three balls" method, while fracture toughness (KIc) used the "single edge notched beam" method. Specimens were tested after 24h and 28 days in water. Ion release was determined using inductively coupled plasma optical emission spectrometry (ICP-OES). Data were analyzed by ANOVA/Tukey (DC and ion release) or Kruskal-Wallis/Mann-Whitney (mechanical properties; alpha: 5%). DC was not affected by DCPD. The presence of DCPD reduced BFS for both storage times, while differences in E became evident after 28 days. After 24h, KIc increased with the addition of DCPD; after 28 days, however, KIc decreased only for DCPD-containing composites. Calcium release was similar for both DCPD contents and remained fairly constant during the 28-day period. Overall, HPO4(2-) release was higher at 7 days and did not decrease after 14 days. The composite with the highest filler level and 10% DCPD represented the best compromise between mechanical properties after aging in water and ion release. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

ATP during early bladder stretch is important for urgency in detrusor overactivity patients.

PubMed

Cheng, Y; Mansfield, K J; Allen, W; Chess-Williams, R; Burcher, E; Moore, K H

2014-01-01

ATP is an important mediator of urgency in women with detrusor overactivity (DO). In order to understand how different degrees of bladder stretch elicited ATP release in DO patients compared with controls, sequential aliquots were collected during cystometry and ATP release was measured at each degree of bladder filling, in female patients with DO and controls. In both DO and control groups, ATP release was induced during bladder filling, suggesting that stretch stimulated further ATP release. However, the luminal ATP concentrations were already high at early filling stage (200 mL), which was even greater than those at the later filling stages (400 mL and maximum cystometric capacity, MCC), indicating that a substantial ATP release has been induced during early filling (200 mL) in both DO and controls. In DO, ATP release at 200 mL was significantly higher in those with low first desire to void (FDV) (≤ 200 mL) than in those with higher FDV (> 200 mL); this may suggest that ATP release at early stretch may play an important role in urgency (early sensation) in DO. ATP concentrations remained unchanged after voiding, suggesting that voiding did not further induce ATP release into intraluminal fluid.

Temperature-Induced Increase in Methane Release from Peat Bogs: A Mesocosm Experiment

PubMed Central

van Winden, Julia F.; Reichart, Gert-Jan; McNamara, Niall P.; Benthien, Albert; Damsté, Jaap S. Sinninghe.

2012-01-01

Peat bogs are primarily situated at mid to high latitudes and future climatic change projections indicate that these areas may become increasingly wetter and warmer. Methane emissions from peat bogs are reduced by symbiotic methane oxidizing bacteria (methanotrophs). Higher temperatures and increasing water levels will enhance methane production, but also methane oxidation. To unravel the temperature effect on methane and carbon cycling, a set of mesocosm experiments were executed, where intact peat cores containing actively growing Sphagnum were incubated at 5, 10, 15, 20, and 25°C. After two months of incubation, methane flux measurements indicated that, at increasing temperatures, methanotrophs are not able to fully compensate for the increasing methane production by methanogens. Net methane fluxes showed a strong temperature-dependence, with higher methane fluxes at higher temperatures. After removal of Sphagnum, methane fluxes were higher, increasing with increasing temperature. This indicates that the methanotrophs associated with Sphagnum plants play an important role in limiting the net methane flux from peat. Methanotrophs appear to consume almost all methane transported through diffusion between 5 and 15°C. Still, even though methane consumption increased with increasing temperature, the higher fluxes from the methane producing microbes could not be balanced by methanotrophic activity. The efficiency of the Sphagnum-methanotroph consortium as a filter for methane escape thus decreases with increasing temperature. Whereas 98% of the produced methane is retained at 5°C, this drops to approximately 50% at 25°C. This implies that warming at the mid to high latitudes may be enhanced through increased methane release from peat bogs. PMID:22768100

Boar semen controlled delivery system: storage and in vitro spermatozoa release.

PubMed

Torre, M L; Faustini, M; Norberti, R; Stacchezzini, S; Maggi, L; Maffeo, G; Conte, U; Vigo, D

2002-12-13

Swine spermatozoa were encapsulated in barium alginate and protamine-barium alginate membranes to lengthen their preservation time and to provide a means of controlling their release. Precocious acrosome reactions and secondary anomalies were measured as indices of semen quality. These characteristics were observed for two forms of encapsulated spermatozoa when stored at 18 and 38 degrees C for 24 h and for semen diluted in a classical extender at both temperatures. The results indicate that encapsulation enhances semen preservation, providing protection against membrane damage upon dilution. The effect is even more evident at the higher temperature (38 degrees C), where cell metabolism is higher. An in vitro release test of spermatozoa showed a massive cell delivery from barium alginate capsules within 6 h, and a slow release from protamine-barium alginate capsules. The properties of spermatozoa 24 h after release did not differ from the semen stored at the same temperature in capsules, indicating that the release process does not impair semen quality.

Investigating the in-vitro and in-vivo flavour release from 21 fresh-cut apples.

PubMed

Ting, Valentina J L; Romano, Andrea; Soukoulis, Christos; Silcock, Patrick; Bremer, Phil J; Cappellin, Luca; Biasioli, Franco

2016-12-01

In-vitro and in-vivo flavour release from 21 different apple cultivars was studied using proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) with a focus on the relationship between texture and volatile organic compound (VOC) emission. Generally, firm-juicy cultivars had a shorter time to first swallow (Tswal) and a higher number of swallows (Nswal), while softer-mealy cultivars had a longer Tswal and a lower Nswal. Firm-juicy cultivars containing high VOC concentrations had a short time to maximum intensity (Tmax) owing to a shorter Tswal and a higher Nswal as juice was released during mastication. Swallowing increased VOC flow through the nasal cavity. These results differ from previous flavour release studies with gel/gel-like model systems as juiciness/release of fluids is not a factor in such matrices. The current study, therefore, highlights the benefits of using in-vivo analysis to gain a better understanding of flavour release in real food products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Temperature affects brain and pituitary gene expression related to reproduction and growth in the male blue gouramis, Trichogaster trichopterus.

PubMed

David, Dalia; Degani, Gad

2011-04-01

This study examined the effect of temperature on reproduction and growth-related factors in blue gourami males under nonreproductive and reproductive conditions. Males that were maintained under nonreproductive conditions did not build nest and the gonado-somatic index (% GSI) was significantly higher in fish maintained at 27°C compared with fish maintained at 23°C. The relative mRNA levels of brain gonadotropin-releasing hormone 3 (GnRH3), pituitary adenylate cyclase-activating polypeptide (PACAP), insulin-like growth factor-1(IGF-1), pituitary β-luteinizing hormone (βLH), and prolactin were significantly higher when the fish were maintained at 27°C than at 23°C or 31°C. β-Follicle-stimulating hormone (βFSH) mRNA levels were significantly lower when maintained at 31°C than at the other temperatures. Nests were observed only in males under reproductive conditions. In these fish, higher mRNA levels of GnRH3, PACAP, βFSH, βLH and prolactin were detected at 27°C, and higher mRNA levels of IGF-1 were detected at 23°C, when compared with other temperature of maintenance or with fish that did not build nest. In conclusion, we propose that temperature has more effect on the transcription of genes, associated with reproduction, than on those pertaining to growth. Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.

Effect of Disinfectant Exposure on Legionella pneumophila Associated with Simulated Drinking Water Biofilms: Release, Inactivation, and Infectivity.

PubMed

Shen, Yun; Huang, Conghui; Lin, Jie; Wu, Wenjing; Ashbolt, Nicholas J; Liu, Wen-Tso; Nguyen, Thanh H

2017-02-21

Legionella pneumophila, the most commonly identified causative agent in drinking water associated with disease outbreaks, can be harbored by and released from drinking water biofilms. In this study, the release of biofilm-associated L. pneumophila under simulated drinking water flow containing a disinfectant residual was examined. Meanwhile, the inactivation and infectivity (to amoebae) of the released L. pneumophila were studied. To simulate drinking water system conditions, biofilms were prepared under either disinfectant exposure (predisinfected biofilms) or disinfectant-free (untreated biofilms) conditions, respectively. For experiments with water flow containing a disinfectant to release the biofilm-associated L. pneumophila from these two types of biofilms, the L. pneumophila release kinetics values from predisinfected and untreated biofilms under flow condition were not statistically different (one-way ANOVA, p > 0.05). However, inactivation of the L. pneumophila released from predisinfected biofilms was 1-2 times higher and amoeba infectivity was 2-29 times lower than that from untreated biofilms. The higher disinfectant resistance of L. pneumophila released from untreated biofilms was presumably influenced by the detachment of a larger amount of biofilm material (determined by 16S rRNA qPCR) surrounding the released L. pneumophila. This study highlights the interaction among disinfectant residual, biofilms, and L. pneumophila, which provides guidelines to assess and control pathogen risk.

Arginase-II Promotes Tumor Necrosis Factor-α Release From Pancreatic Acinar Cells Causing β-Cell Apoptosis in Aging.

PubMed

Xiong, Yuyan; Yepuri, Gautham; Necetin, Sevil; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

2017-06-01

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L -arginine-ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II -/- ) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin release, larger islet size and β-cell mass, and more proliferative and less apoptotic β-cells compared with the age-matched wild-type (WT) controls. Moreover, Arg-II is mainly expressed in acinar cells and is upregulated with aging, which enhances p38 mitogen-activated protein kinase (p38 MAPK) activation and release of tumor necrosis factor-α (TNF-α). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II -/- ) mice contains higher TNF-α levels than the young mice and stimulates β-cell apoptosis and dysfunction, which are prevented by a neutralizing anti-TNF-α antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-α release through p38 MAPK leading to β-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice. © 2017 by the American Diabetes Association.

Comparison of short-term in vitro fluoride release and recharge from four different types of pit-and-fissure sealants.

PubMed

Koga, Hiroshi; Kameyama, Atsushi; Matsukubo, Takashi; Hirai, Yoshito; Takaesu, Yoshinori

2004-08-01

The purpose of this in vitro study was to assess the effects of four commercial fluoride-containing pit-and-fissure sealants on caries prevention. Four sealants containing fluoride, Fuji III, Fuji III LC (GC Co., Tokyo), Teethmate F-1 (Kuraray Medical Co., Osaka) and Helioseal F (Vivadent Co., Liechtenstein) were used to investigate fluoride release and recharge. Disk-shaped specimens prepared from each material were immersed in distilled water at a temperature of 37 degrees C. After seven days, acidulated phosphate fluoride solution (APF) was applied to each specimen, and it was then again immersed in distilled water for 14 days. We then determined how much fluoride had been released into the immersing water. Fuji III LC was used with APF solution to investigate the fluoride uptake. Fuji III had the highest fluoride release, and Fuji III LC had the highest fluoride recharge. Helioseal F and Teethmate F-1 had almost no fluoride recharge. Fuji III LC/APF had a higher fluoride uptake to enamel than Fuji III LC. These results suggest that GIC-sealants in the oral cavity can serve as a fluoride reservoir and contribute to retaining a low fluoride level in oral fluids, thereby preventing caries.

Stimulatory effect of exogenous diadenosine tetraphosphate on insulin and glucagon secretion in the perfused rat pancreas

PubMed Central

Silvestre, Ramona A; Rodríguez-Gallardo, Jovita; Egido, Eva M; Marco, José

1999-01-01

Diadenosine triphosphate (AP3A) and diadenosine tetraphosphate (AP4A) are released by various cells (e.g. platelets and chromaffin cells), and may act as extracellular messengers. In pancreatic B-cells, AP3A and AP4A are inhibitors of the ATP-regulated K+ channels, and glucose increases intracellular levels of both substances.We have studied the effect of exogenous AP3A and AP4A on insulin and glucagon secretion by the perfused rat pancreas.AP3A did not significantly modify insulin or glucagon release, whereas AP4A induced a prompt, short-lived insulin response (≈4 fold higher than basal value; P<0.05) in pancreases perfused at different glucose concentrations (3.2, 5.5 or 9 mM). AP4A-induced insulin release was abolished by somatostatin and by diazoxide. These two substances share the capacity to activate ATP-dependent K+ channels, suggesting that these channels are a potential target for AP4A in the B-cell.AP4A stimulated glucagon release at both 3.2 and 5.5 mM glucose. This effect was abolished by somatostatin.The results suggest that extracellular AP4A may play a physiological role in the control of insulin and glucagon secretion. PMID:10516664

Stimulatory effect of exogenous diadenosine tetraphosphate on insulin and glucagon secretion in the perfused rat pancreas.

PubMed

Silvestre, R A; Rodríguez-Gallardo, J; Egido, E M; Marco, J

1999-10-01

1. Diadenosine triphosphate (AP3A) and diadenosine tetraphosphate (AP4A) are released by various cells (e.g. platelets and chromaffin cells), and may act as extracellular messengers. In pancreatic B-cells, AP3A and AP4A are inhibitors of the ATP-regulated K+ channels, and glucose increases intracellular levels of both substances. 2. We have studied the effect of exogenous AP3A and AP4A on insulin and glucagon secretion by the perfused rat pancreas. 3. AP3A did not significantly modify insulin or glucagon release, whereas AP4A induced a prompt, short-lived insulin response ( approximately 4 fold higher than basal value; P<0.05) in pancreases perfused at different glucose concentrations (3.2, 5.5 or 9 mM). AP4A-induced insulin release was abolished by somatostatin and by diazoxide. These two substances share the capacity to activate ATP-dependent K+ channels, suggesting that these channels are a potential target for AP4A in the B-cell. 4. AP4A stimulated glucagon release at both 3.2 and 5.5 mM glucose. This effect was abolished by somatostatin. 5. The results suggest that extracellular AP4A may play a physiological role in the control of insulin and glucagon secretion.

Meletin sustained-release gliadin nanoparticles prepared via solvent surface modification on blending electrospraying

NASA Astrophysics Data System (ADS)

Yang, Yao-Yao; Zhang, Man; Liu, Zhe-Peng; Wang, Ke; Yu, Deng-Guang

2018-03-01

Almost all electrospraying processes are carried out under an air-solution interface, thereby overlooking the potential influence of an additional solvent surface modification between air and the working solution. A pure solvent was explored to temporarily and dynamically surround the solutions utilized for blending electrospraying, which contained a guest drug meletin and a protein drug carrier gliadin. The new modified processes created protein-based medicated nanoparticles (P2) with higher quality than their counterparts (P1) from blending processes, as demonstrated by the SEM and TEM images. Although the particles from the two processes were similar (nanocomposites), and the particles P1 were larger than P2, the later provided a better meletin sustained-release profile than the former. This finding was verified by the smaller initial burst release, longer sustained-release time period, and shorter late leveling-off stage. These unanticipated results were attributed to the rounder surface, the more uniform size distribution, and the smaller total surface area of particles P2 than P1. The microformation mechanism of the modified coaxial process was suggested. The protocols reported here paved a new way for the development of new kinds of functional nanoparticles by modifying the interfaces of working fluids during electrospraying.

Photolytic Release of Dissolved Vanadium and Copper from Resuspended Coastal Marine Sediments

NASA Astrophysics Data System (ADS)

Skrabal, S. A.; Hammaker, S. N.; McBurney, A. W.; Avery, G. B., Jr.; Kieber, R. J.; Mead, R. N.

2016-02-01

Sunlight photolysis engenders release of dissolved vanadium (V), copper (Cu), and dissolved organic carbon (DOC) from a wide variety of resuspendable coastal marine sediments. Net photoreleases after 6 h of simulated sunlight were as high as 12 nM for Cu and as high as 15 nM for V. Release of Cu significantly correlated with sediment Cu. Photoreleased Cu (but not V) correlated with sediment Fe content, suggesting that photoreduction of Fe oxide carrier phases may be an important photoproduction mechanism for Cu. Longer term experiments showed continued release of metals that were not immediately readsorbed back onto sediments after 24 h of irradiation suggesting that photoproduced metals persist in the dissolved phase and are not immediately scavenged onto particles. Experiments utilizing differing total suspended sediment (TSS) levels show that, although higher TSS causes more photoproduction of Cu and V, the amount produced per mass of sediment is greatest at the lowest TSS. Vanadium photoproduction increased in Macondo oil-amended sediments compared to controls after a one-month incubation period suggesting that the oil may be a source of this metal to the water column. These results imply that photoproduction is an unrecognized source of the micronutrient metals Cu and V to coastal waters.

The involvement of mitochondrial phosphate transporter in accelerating bud dormancy release during chilling treatment of tree peony (Paeonia suffruticosa).

PubMed

Huang, Xin; Zhu, Wei; Dai, Silan; Gai, Shupeng; Zheng, Guosheng; Zheng, Chengchao

2008-09-01

A cDNA clone was isolated from tree peony (Paeonia suffruticosa) subtractive cDNA library of burst buds and characterized with regard to its sequence, expression in response to chilling treatment during the release of bud dormancy, and its function in transgenic Arabidopsis thaliana. The clone, designated as PsMPT, contains 1,615 nucleotides with an open reading frame of 1,119 nucleotides, and the deduced amino acid sequence shows high homology with mitochondrial phosphate transporters (MPTs) from various organisms. The mRNA accumulation of PsMPT in tree peony was strongly induced by chilling treatment during the release of bud dormancy. When the treated plants were transferred to normal growth conditions, the level of PsMPT transcripts induced by sufficient chilling could be maintained high, whereas that induced by insufficient chilling decreased sharply. The transgenic Arabidopsis plants that overexpress PsMPT showed rapid growth and earlier flowering than wild-type plants. ATP contents in the transgenic plants were much higher than that in wild-type plants through various developmental stages. Together, these results suggest that the product of PsMPT is a MPT and might play an important role during the release of bud dormancy in tree peony.

Influence of irradiation on release of endothelial microparticles (EMP) in vitro.

PubMed

Neuber, Christin; Pufe, Johanna; Pietzsch, Jens

2015-01-01

Survivors of Hodgkin's disease as well as of breast and lung cancer are at risk of radiation-associated cardiovascular disease. Recent studies demonstrated a correlation between cardiovascular risk factors and circulating endothelial microparticles (EMP) and thereby suggest increased EMP levels in circulation to be an early biomarker of endothelial dysfunction and cardiovascular risk. This prompted us to analyze the amount of EMP released by human aortic endothelial cells (HAEC) after exposure to different doses of X-ray (0.4, 2, 4, 6, and 20 Gy) using antibodies against the endothelial cell markers CD31, CD144, and CD146 by flow cytometry. In this pilot experiment only CD146 proved appropriate for quantification of HAEC-derived EMP. Exposure of HAEC to different doses of X-ray did not significantly influence formation of CD146-positive EMP. However, low doses (0.4 Gy) tended to decrease EMP formation, whereas higher doses (2 or 4 Gy) slightly increased release of CD146-positive EMP. By contrast, inflammatory activation of HAEC by TPA significantly increased EMP release about 15-fold (P <  0.01). In conclusion, under the present experimental conditions EMP did not prove a suitable biomarker for radiation-induced endothelial dysfunction in vitro.

Remote loading of doxorubicin into liposomes driven by a transmembrane phosphate gradient.

PubMed

Fritze, Andreas; Hens, Felicitas; Kimpfler, Andrea; Schubert, Rolf; Peschka-Süss, Regine

2006-10-01

This study examines a new method for the remote loading of doxorubicin into liposomes. It was shown that doxorubicin can be loaded to a level of up to 98% into large unilamellar vesicles composed of egg phosphatidylcholine/cholesterol (7/3 mol/mol) with a transmembrane phosphate gradient. The different encapsulation efficiencies which were achieved with ammonium salts (citrate 100%, phosphate 98%, sulfate 95%, acetate 77%) were significantly higher as compared to the loading via sodium salts (citrate 54%, phosphate 52%, sulfate 44%, acetate 16%). Various factors, including pH-value, buffer capacity, solubility of doxorubicin in different salt solutions and base counter-flow, which likely has an influence on drug accumulation in the intraliposomal interior are taken into account. In contrast to other methods, the newly developed remote loading method exhibits a pH-dependent drug release property which may be effective in tumor tissues. At physiological pH-value doxorubicin is retained in the liposomes, whereas drug release is achieved by lowering the pH to 5.5 (approximately 25% release at 25 degrees C or 30% at 37 degrees C within two h). The DXR release of liposomes which were loaded via a sulfate gradient showed a maximum of 3% at pH 5.5.

Experimental and modeling studies showing the effect of lipid type and level on flavor release from milk-based liquid emulsions.

PubMed

Roberts, Deborah D; Pollien, Philippe; Watzke, Brigitte

2003-01-01

The purpose of this work was to study two key parameters of the lipid phase that influence flavor release-lipid level and lipid type-and to relate the results to a mass balance partition coefficient-based mathematical model. Release of 10 volatile compounds from milk-based emulsions at 10, 25, and 50 degrees C was monitored by 1-min headspace sampling with a solid-phase microextraction fiber, followed by GC-MS analysis. As compared to the observations for milk fat, changing to a lipophilic lipid (medium-chain triglycerides, MCT) and adding a monoglyceride-based surfactant did not influence the volatiles release. However, increasing the solid fat content was found to increase the release. At 25 degrees C, and even more so at 10 degrees C, concurrent with an increase in their solid fat content, hydrogenated palm fat emulsions showed increased flavor release over that observed for emulsions made with coconut oil, coconut oil with surfactant, milk fat, and MCT. However, at 50 degrees C, when hydrogenated palm fat emulsions had zero solid fat content, there was no difference in flavor release from that observed for milk fat emulsions. Varying milk fat at nine levels between 0 and 4.5% showed a systematic dependence of the release on the lipid level, dependent on compound lipophilicity. Close correlations were found between the experimental and model predictions with lipid level and percent liquid lipid as variables.

Antagonistic effects of beta-phenylethylamine on quinpirole- and (-)-sulpiride-induced changes in evoked dopamine release from rat striatal slices.

PubMed

Yamada, S; Harano, M; Tanaka, M

1998-02-19

To assess the role of beta-phenylethylamine in aspects of dopamine release, we measured the level of beta-phenylethylamine in the rat striatum after killing the rats by microwave irradiation. We then investigated the effect of beta-phenylethylamine on electrically evoked dopamine release from rat striatal slices in vitro. The striatal beta-phenylethylamine level was 46.5 +/- 3.5 ng/g wet tissue, equivalent to 0.3 micromol/l. Superfusion with low concentrations of beta-phenylethylamine up to 1 micromol/l had no effect on spontaneous or electrically evoked dopamine release from striatal slices. Quinpirole reduced the evoked dopamine release from slices in a concentration-dependent manner. The quinpirole-induced reduction of evoked dopamine release was attenuated 30% by superfusion with 0.3 micromol/l beta-phenylethylamine. Moreover, the (-)-sulpiride (0.1 micromol/l)-induced increase in evoked dopamine release was also attenuated by superfusion with 0.3 micromol/l beta-phenylethylamine. These data indicate that submicromolar levels of beta-phenylethylamine could modify the dopamine autoreceptor mediated changes in evoked dopamine release from rat striatal slices.

Physiological response of wild rainbow trout to angling: Impact of angling duration, fish size, body condition, and temperature

USGS Publications Warehouse

Meka, Julie M.; McCormick, S.D.

2005-01-01

This study evaluated the immediate physiological response of wild rainbow trout to catch-and-release angling in the Alagnak River, southwest Alaska. Information was recorded on individual rainbow trout (n = 415) captured by angling including landing time and the time required to remove hooks (angling duration), the time to anesthetize fish in clove oil and withdraw blood, fish length and weight, and water temperature at capture locations. Plasma cortisol, glucose, ions (sodium, potassium, chloride), and lactate were analyzed to determine the effects of angling duration, fish size, body condition, and temperature. Levels of plasma ions did not change significantly during the observed physiological response and levels of plasma glucose were sometimes influenced by length (2000, 2001), body condition (2001), or temperature (2001). Levels of plasma cortisol and lactate in extended capture fish (angling duration greater than 2 min) were significantly higher than levels in rapid capture fish (angling duration less than 2 min). Rapid capture fish were significantly smaller than extended capture fish, reflecting that fish size influenced landing and handling times. Fish size was related to cortisol and lactate in 2002, which corresponded to the year when larger fish were captured and there were longer landing times. Body condition (i.e., weight/length regression residuals index), was significantly related to lactate in 2000 and 2001. Water temperatures were higher in 2001 (mean temperature ± S.E., 13 ± 2oC) than in 2002 (10 ± 2oC), and fish captured in 2001 had significantly higher cortisol and lactate concentrations than fish captured in 2002. The pattern of increase in plasma cortisol and lactate was due to the amount of time fish were angled, and the upper limit of the response was due to water temperature. The results of this study indicate the importance of minimizing the duration of angling in order to reduce the sublethal physiological disturbances in wild fish subjected to catch-and-release angling, particularly during warmer water temperatures. It is also important to note that factors such as fish size may influence both the duration of angling and subsequent physiological response. 

The Effect of Formulation Excipients and Thermal Treatment on the Release Properties of Lisinopril Spheres and Tablets.

PubMed

Amador Ríos, Zoriely; Ghaly, Evone Shehata

2015-01-01

Multiparticulate systems are used in the development of controlled release systems. The objective of this study was to determine the effect of the wax level, the type of excipient, and the exposure of the tablets to thermal treatment on drug release. Spheres from multiparticulate system with different wax levels and excipients were developed using the drug Lisinopril and compressed into tablets; these tablets were analyzed to determine the drug release. All tablets contained constant level of Lisinopril (10% w/w) and Compritol (30% and 50% w/w). Also, as a diluent, all of them contained 30% w/w Avicel and 30% w/w dibasic calcium phosphate or lactose, or 60% Avicel. Tablets compacted from spheres prepared by extruder/marumerizer and using 30% w/w lipid and 60% Avicel released 84% of drug at six hours of dissolution testing, while tablets of the same composition but prepared using 30% dibasic calcium phosphate and 30% Avicel released 101%. When the tablets were thermally treated, the drug release reduced. As the percent of lipid increased in the formulation, the drug release decreased. Compaction of tablets prepared from spheres with wax has potential for controlling the drug release.

Dissolution effect and cytotoxicity of diamond-like carbon coatings on orthodontic archwires.

PubMed

Kobayashi, Shinya; Ohgoe, Yasuharu; Ozeki, Kazuhide; Hirakuri, Kenji; Aoki, Hideki

2007-12-01

Nickel-titanium (NiTi) has been used for implants in orthodontics due to the unique properties such as shape memory effect and superelasticity. However, NiTi alloys are eroded in the oral cavity because they are immersed by saliva with enzymolysis. Their reactions lead corrosion and nickel release into the body. The higher concentrations of Ni release may generate harmful reactions. Ni release causes allergenic, toxic and carcinogenic reactions. It is well known that diamond-like carbon (DLC) films have excellent properties, such as extreme hardness, low friction coefficients, high wear resistance. In addition, DLC film has many other superior properties as a protective coating for biomedical applications such as biocompatibility and chemical inertness. Therefore, DLC film has received enormous attention as a biocompatible coating. In this study, DLC film coated NiTi orthodontic archwires to protect Ni release into the oral cavity. Each wire was immersed in physiological saline at the temperature 37 degrees C for 6 months. The release concentration of Ni ions was detected using microwave induced plasma mass spectrometry (MIP-MS) with the resolution of ppb level. The toxic effect of Ni release was studied the cell growth using squamous carcinoma cells. These cells were seeded in 24 well culture plates and materials were immersed in each well directly. The concentration of Ni ions in the solutions had been reduced one-sixth by DLC films when compared with non-coated wire. This study indicated that DLC films have the protective effect of the diffusion and the non-cytotoxicity in corrosive environment.

Clostridium butyricum MIYAIRI 588 shows antitumor effects by enhancing the release of TRAIL from neutrophils through MMP-8.

PubMed

Shinnoh, Masahide; Horinaka, Mano; Yasuda, Takashi; Yoshikawa, Sae; Morita, Mie; Yamada, Takeshi; Miki, Tsuneharu; Sakai, Toshiyuki

2013-03-01

Bacillus Calmette-Guérin (BCG) intravesical therapy against superficial bladder cancer is one of the most successful immunotherapies in cancer, though the precise mechanism has not been clarified. Recent studies have demonstrated urinary tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels to be higher in BCG-responsive patients than non-responders and shown that polymorphonuclear neutrophils (PMNs) migrating to the bladder after BCG instillation release large amounts of TRAIL. To establish a safer and more effective intravesical therapy than BCG, we examined whether other bacteria induced similar effects. We stimulated PMNs or peripheral blood mononuclear cells (PBMCs) with BCG or other bacteria, and then aliquots of the culture supernatants or cell lysates were assayed for TRAIL. We examined the signaling pathway regulating the release of TRAIL from PMNs and evaluated the antitumor effects of BCG or other bacteria in vitro and in vivo. We have found that Clostridium butyricum MIYAIRI 588 (CBM588) induces the release of endogenous TRAIL from PMNs as well as BCG. In addition, we have shown that matrix metalloproteinase 8 (MMP-8) is one of the key factors responsible for the release. Interestingly, TLR2/4 signaling pathway has been suggested to be important for the release of TRAIL by MMP-8. CBM588 has been proven to be as effective as BCG against cancer cells by inducing apoptosis in vivo as well as in vitro. Taken together, these results strongly suggest that CBM588 is promising for a safer and more effective therapy against bladder cancer.

Predicting the size-dependent tissue accumulation of agents released from vascular targeted nanoconstructs

NASA Astrophysics Data System (ADS)

de Tullio, Marco D.; Singh, Jaykrishna; Pascazio, Giuseppe; Decuzzi, Paolo

2014-03-01

Vascular targeted nanoparticles have been developed for the delivery of therapeutic and imaging agents in cancer and cardiovascular diseases. However, at authors' knowledge, a comprehensive systematic analysis on their delivery efficiency is still missing. Here, a computational model is developed to predict the vessel wall accumulation of agents released from vascular targeted nanoconstructs. The transport problem for the released agent is solved using a finite volume scheme in terms of three governing parameters: the local wall shear rate , ranging from to ; the wall filtration velocity , varying from to ; and the agent diffusion coefficient , ranging from to . It is shown that the percentage of released agent adsorbing on the vessel walls in the vicinity of the vascular targeted nanoconstructs reduces with an increase in shear rate , and with a decrease in filtration velocity and agent diffusivity . In particular, in tumor microvessels, characterized by lower shear rates () and higher filtration velocities (), an agent with a diffusivity (i.e. a 50 nm particle) is predicted to deposit on the vessel wall up to of the total released dose. Differently, drug molecules, exhibiting a smaller size and much higher diffusion coefficient (), are predicted to accumulate up to . In healthy vessels, characterized by higher and lower , the largest majority of the released agent is redistributed directly in the circulation. These data suggest that drug molecules and small nanoparticles only can be efficiently released from vascular targeted nanoconstructs towards the diseased vessel walls and tissue.