Decreasing electrical resistivity of silver along the melting boundary up to 5 GPa

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Littleton, Joshua A. H.; Secco, Richard A.; Yong, Wenjun

2018-04-01

The electrical resistivity of Ag was experimentally measured at high pressures up to 5 GPa and at temperatures up to ∼300 K above melting. The resistivity decreased as a function of pressure and increased as a function of temperature as expected and is in very good agreement with 1 atm data. Observed melting temperatures at high pressures also agree well with previous experimental and theoretical studies. The main finding of this study is that resistivity of Ag decreases along the pressure- and temperature-dependent melting boundary, in conflict with prediction of resistivity invariance. This result is discussed in terms of the dominant contribution of the increasing energy separation between the Fermi level and 4d-band as a function of pressure. Calculated from the resistivity using the Wiedemann-Franz law, the electronic thermal conductivity increased as a function of pressure and decreased as a function of temperature as expected. The decrease in the high pressure thermal conductivity in the liquid phase as a function of temperature contrasts with the behavior of the 1 atm data.

Protease-resistant prions selectively decrease Shadoo protein.

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Joel C Watts

2011-11-01

Full Text Available The central event in prion diseases is the conformational conversion of the cellular prion protein (PrP(C into PrP(Sc, a partially protease-resistant and infectious conformer. However, the mechanism by which PrP(Sc causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho, a protein that resembles the flexibly disordered N-terminal domain of PrP(C, were found to be reduced in the brains of mice infected with the RML strain of prions [1], implying that Sho levels may reflect the presence of PrP(Sc in the brain. To test this hypothesis, we examined levels of Sho during prion infection using a variety of experimental systems. Sho protein levels were decreased in the brains of mice, hamsters, voles, and sheep infected with different natural and experimental prion strains. Furthermore, Sho levels were decreased in the brains of prion-infected, transgenic mice overexpressing Sho and in infected neuroblastoma cells. Time-course experiments revealed that Sho levels were inversely proportional to levels of protease-resistant PrP(Sc. Membrane anchoring and the N-terminal domain of PrP both influenced the inverse relationship between Sho and PrP(Sc. Although increased Sho levels had no discernible effect on prion replication in mice, we conclude that Sho is the first non-PrP marker specific for prion disease. Additional studies using this paradigm may provide insight into the cellular pathways and systems subverted by PrP(Sc during prion disease.

Microvillus-Specific Protein Tyrosine Phosphatase SAP-1 Plays a Role in Regulating the Intestinal Paracellular Transport of Macromolecules.

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Mori, Shingo; Kamei, Noriyasu; Murata, Yoji; Takayama, Kozo; Matozaki, Takashi; Takeda-Morishita, Mariko

2017-09-01

The stomach cancer-associated protein tyrosine phosphatase 1 (SAP-1) is a receptor-type protein tyrosine phosphatase that is specifically expressed on the apical membrane of the intestinal epithelium. SAP-1 is known to maintain the balance of phosphorylation of proteins together with protein kinases; however, its biological function and impact on pharmacokinetics in the intestine remain unclear. The present study, therefore, aimed at clarifying the relationship between SAP-1 and the intestinal absorption behaviors of typical transporter substrates and macromolecules. The endogenous levels of glucose and total cholesterol in the blood were similar between wild-type and SAP-1-deficient mice (Sap1 -/- ), suggesting no contribution of SAP-1 to biogenic influx. Moreover, in vitro transport study with everted ileal sacs demonstrated that there was no difference in the absorption of breast cancer resistance protein, P-glycoprotein, and peptide transporter substrates between both mice. However, absorptive clearance of macromolecular model dextrans (FD-4 and FD-10) in Sap1 -/- mice was significantly higher than that in wild-type mice, and this was confirmed by the trend of increased FD-4 absorption from colonic loops of Sap1 -/- mice. Therefore, the results of this study suggest the partial contribution of SAP-1 to the regulated transport of hydrophilic macromolecules through paracellular tight junctions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Bacillus anthracis-derived edema toxin (ET counter-regulates movement of neutrophils and macromolecules through the endothelial paracellular pathway

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Nguyen Chinh

2012-01-01

Full Text Available Abstract Background A common finding amongst patients with inhalational anthrax is a paucity of polymorphonuclear leukocytes (PMNs in infected tissues in the face of abundant circulating PMNs. A major virulence determinant of anthrax is edema toxin (ET, which is formed by the combination of two proteins produced by the organism, edema factor (EF, which is an adenyl cyclase, and protective antigen (PA. Since cAMP, a product of adenyl cyclase, is known to enhance endothelial barrier integrity, we asked whether ET might decrease extravasation of PMNs into tissues through closure of the paracellular pathway through which PMNs traverse. Results Pretreatment of human microvascular endothelial cell(ECs of the lung (HMVEC-L with ET decreased interleukin (IL-8-driven transendothelial migration (TEM of PMNs with a maximal reduction of nearly 60%. This effect required the presence of both EF and PA. Conversely, ET did not diminish PMN chemotaxis in an EC-free system. Pretreatment of subconfluent HMVEC-Ls decreased transendothelial 14 C-albumin flux by ~ 50% compared to medium controls. Coadministration of ET with either tumor necrosis factor-α or bacterial lipopolysaccharide, each at 100 ng/mL, attenuated the increase of transendothelial 14 C-albumin flux caused by either agent alone. The inhibitory effect of ET on TEM paralleled increases in protein kinase A (PKA activity, but could not be blocked by inhibition of PKA with either H-89 or KT-5720. Finally, we were unable to replicate the ET effect with either forskolin or 3-isobutyl-1-methylxanthine, two agents known to increase cAMP. Conclusions We conclude that ET decreases IL-8-driven TEM of PMNs across HMVEC-L monolayers independent of cAMP/PKA activity.

Decreased outer membrane permeability in imipenem-resistant mutants of Pseudomonas aeruginosa.

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Trias, J; Dufresne, J; Levesque, R C; Nikaido, H

1989-01-01

The outer membrane of imipenem-resistant mutants of Pseudomonas aeruginosa was shown to have decreased permeability to imipenem but not to cephaloridine. These experiments were performed with intact cells and liposomes containing imipenem-hydrolyzing beta-lactamase derived from Pseudomonas maltophilia, in both cases utilizing an imipenem concentration of 50 microM. In contrast, liposome swelling assays using imipenem at 8 mM detected no significant difference between the imipenem-resistant mu...

In vivo measurement of vocal fold surface resistance.

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Mizuta, Masanobu; Kurita, Takashi; Dillon, Neal P; Kimball, Emily E; Garrett, C Gaelyn; Sivasankar, M Preeti; Webster, Robert J; Rousseau, Bernard

2017-10-01

A custom-designed probe was developed to measure vocal fold surface resistance in vivo. The purpose of this study was to demonstrate proof of concept of using vocal fold surface resistance as a proxy of functional tissue integrity after acute phonotrauma using an animal model. Prospective animal study. New Zealand White breeder rabbits received 120 minutes of airflow without vocal fold approximation (control) or 120 minutes of raised intensity phonation (experimental). The probe was inserted via laryngoscope and placed on the left vocal fold under endoscopic visualization. Vocal fold surface resistance of the middle one-third of the vocal fold was measured after 0 (baseline), 60, and 120 minutes of phonation. After the phonation procedure, the larynx was harvested and prepared for transmission electron microscopy. In the control group, vocal fold surface resistance values remained stable across time points. In the experimental group, surface resistance (X% ± Y% relative to baseline) was significantly decreased after 120 minutes of raised intensity phonation. This was associated with structural changes using transmission electron microscopy, which revealed damage to the vocal fold epithelium after phonotrauma, including disruption of the epithelium and basement membrane, dilated paracellular spaces, and alterations to epithelial microprojections. In contrast, control vocal fold specimens showed well-preserved stratified squamous epithelia. These data demonstrate the feasibility of measuring vocal fold surface resistance in vivo as a means of evaluating functional vocal fold epithelial barrier integrity. Device prototypes are in development for additional testing, validation, and for clinical applications in laryngology. NA Laryngoscope, 127:E364-E370, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

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Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

2017-06-28

Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

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Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil)

2015-03-27

The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

International Nuclear Information System (INIS)

Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C.; Irigoyen, M.C.; De Angelis, K.

2015-01-01

The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation

Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection.

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Ruiz, Joaquim

2003-05-01

Quinolones are broad-spectrum antibacterial agents, commonly used in both clinical and veterinary medicine. Their extensive use has resulted in bacteria rapidly developing resistance to these agents. Two mechanisms of quinolone resistance have been established to date: alterations in the targets of quinolones, and decreased accumulation due to impermeability of the membrane and/or an overexpression of efflux pump systems. Recently, mobile elements have also been described, carrying the qnr gene, which confers resistance to quinolones.

Decreased uptake of cadmium by a resistant strain of Staphylococcus aureus

Energy Technology Data Exchange (ETDEWEB)

Chopra, I

1971-01-01

Penicillinase plasmids, and some related extrachromosomal elements in Staphylococcus aureus, can specify resistance to inorganic ions, including Hg/sup 2 +/ and Cd/sup 2 +/. There is some tentative evidence that resistance to Hg/sup 2 +/ ions is due to the impermeability of the cells to the ions and not to a higher concentration of free -SH groups in resistance to cadmium ions is unknown. Experiments are described which show that there is a markedly decreased rate of uptake of Cd/sup 2 +/ ions by resistant cells when compared with strains that lack the cad-r gene. The uptake of Cd/sup 2 +/ ions has been studied in the cadmium resistant Staphylococcus aureus strain 8325 (..cap alpha...i/sup +/p/sup +/.cad-r.mer-r) and in its cadmium-sensitive derivative, strain 8324(N). Strain 8325(N) was obtained from 8325 (..cap alpha...i/sup +/.cad-r.mer-r) by isolating a variant which had spontaneously lost the ..cap alpha.. penicillinase plasmid specifying resistance to Cd/sup 2 +/ ions. Cadmium uptake was estimated by adding /sup 115m/CdCl/sub 2/ (final concentration: 10/sup -4/M) to exponentially growing cultures of the sensitive and resistant strains and following the uptake of radioactivity.

Experience with dynamic reinforcement rates decreases resistance to extinction.

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Craig, Andrew R; Shahan, Timothy A

2016-03-01

The ability of organisms to detect reinforcer-rate changes in choice preparations is positively related to two factors: the magnitude of the change in rate and the frequency with which rates change. Gallistel (2012) suggested similar rate-detection processes are responsible for decreases in responding during operant extinction. Although effects of magnitude of change in reinforcer rate on resistance to extinction are well known (e.g., the partial-reinforcement-extinction effect), effects of frequency of changes in rate prior to extinction are unknown. Thus, the present experiments examined whether frequency of changes in baseline reinforcer rates impacts resistance to extinction. Pigeons pecked keys for variable-interval food under conditions where reinforcer rates were stable and where they changed within and between sessions. Overall reinforcer rates between conditions were controlled. In Experiment 1, resistance to extinction was lower following exposure to dynamic reinforcement schedules than to static schedules. Experiment 2 showed that resistance to presession feeding, a disruptor that should not involve change-detection processes, was unaffected by baseline-schedule dynamics. These findings are consistent with the suggestion that change detection contributes to extinction. We discuss implications of change-detection processes for extinction of simple and discriminated operant behavior and relate these processes to the behavioral-momentum based approach to understanding extinction. © 2016 Society for the Experimental Analysis of Behavior.

Empagliflozin decreases remnant-like particle cholesterol in type 2 diabetes patients with insulin resistance.

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Hattori, Sachiko

2017-11-28

Remnant lipoproteins are thought to be atherogenic. Remnant-like particle cholesterol (RLP-C), which reflects the levels of various kinds of remnant lipoproteins in the blood, has a significant correlation with insulin resistance. In the present study, we measured the effect of empagliflozin (EMPA) on the levels of RLP-C, and investigated whether EMPA-mediated change in RLP-C is associated with a change in insulin resistance in type 2 diabetes patients who have insulin resistance. Patients were allocated to receive a placebo (n = 51) or EMPA (n = 58) as an add-on treatment. Fasting blood samples were collected before and 12 weeks after this intervention. EMPA significantly decreased glycated hemoglobin, bodyweight, systolic blood pressure, plasma triglycerides, liver transaminases and estimated glomerular filtration rate, and increased high-density lipoprotein cholesterol. Furthermore, EMPA decreased RLP-C and homeostatic model assessment of insulin resistance. In the placebo group, there were no significant changes in these factors except for slight increases in liver transaminases. Multiple regression analysis showed that the change in homeostatic model assessment of insulin resistance (P = 0.0102) and the change in alanine aminotransferase (P = 0.0301) were significantly associated with the change in RLP-C in the EMPA group. The change in RLP-C significantly correlated with the change in homeostatic model assessment of insulin resistance (Pearson correlation coefficient 0.503, 95% confidence interval 0.199-0.719; P = 0.00241). EMPA decreases RLP-C levels, which is closely associated with amelioration of insulin sensitivity in diabetes patients who have insulin resistance. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Decreased expression of LamB and Odp1 complex is crucial for antibiotic resistance in Escherichia coli.

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Lin, Xiang-min; Yang, Man-jun; Li, Hui; Wang, Chao; Peng, Xuan-Xian

2014-02-26

We previously revealed a negative regulation of LamB in chlortetracycline-resistant Escherichia coli strain. In the present study, we first showed that the negative regulation, which was characterized by decreased abundance of LamB with elevated growth of its gene-deleted mutant in medium with antibiotics, was a general response in resistance to different classes of antibiotics using 2-DE based proteomics or/and genetically gene-deletion mutant of LamB. Then, we revealed the interaction of LamB and Odp1 which catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2, and found the decrease of the complex in antibiotic-resistant strains with a minimum inhibitory concentration dose-dependent manner. Further spectrofluorometry assay indicated that LamB served as a porin to influx an antibiotic. Finally, we showed that the decreased expression of LamB and Odp1 was detected in almost of all 34 multidrug-resistant strains, which suggested that LamB and Odp1 were biomarkers for identification of antibiotic-resistant E. coli. Our results indicated that the interaction of an outer membrane protein with an energy metabolic enzyme constructed an efficient pathway to resist antibiotics. These findings provide novel insights into the mechanisms of antibiotic resistance. Our data indicate that the negative regulation by LamB is widely detected in antibiotic-resistant E. coli. LamB serves as a porin to influx an antibiotic and is interacted with Odp1. The complex decreases in antibiotic-resistant strains with a MIC dose-dependent manner. Our findings indicate that interaction of outer membrane protein with energy metabolic enzyme constructs an efficient pathway to resist antibiotics and provides novel insights into the mechanisms of antibiotic resistance. Copyright © 2014 Elsevier B.V. All rights reserved.

Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1β-exposed human intestinal epithelial cells.

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Gentile, C; Perrone, A; Attanzio, A; Tesoriere, L; Livrea, M A

2015-08-01

Dietary approaches to control inflammatory bowel diseases (IBD) may include proanthocyanidin-rich foods. Our previous research showed that a hydrophilic extract from Sicilian pistachio nut (HPE) contains substantial amounts of proanthocyanidins and possesses anti-inflammatory activities. We studied the effects of HPE and of its polymeric proanthocyanidin fraction (PPF) in a cell model that simulated some conditions of IBD, consisting of interleukin (IL)-1β-stimulated Caco-2 cells. HPE was prepared by Pistacia vera L. nuts, and PPF was isolated from HPE by adsorbance chromatography. Proanthocyanidins were quantified as anthocyanidins after acidic hydrolysis. Differentiated Caco-2 cells were pre-incubated with HPE or PPF and then were exposed to IL-1β. Cell viability and parameters associated with nuclear factor-κB (NF-κB) activation were assayed. Adsorption of polymeric proanthocyanidins to the cell membrane was investigated by transepithelial electrical resistance (TEER) measurements. HPE decreased prostaglandin (PG)E2 production, IL-6 and IL-8 release, and cyclooxygenase (COX)-2 expression. HPE also inhibited the increase in paracellular permeability and reduced NF-κB activation. Polymeric proanthocyanidins, tested at a concentration comparable with their content in HPE, produced effects comparable to HPE. Finally, cell exposure to PPF increases TEER of the epithelial monolayers. Our results provide evidence that pistachio nut components inhibit inflammatory response of intestinal epithelial cells in vitro and indicate polymeric proanthocyanidins as the major bioactive nut components. The protection implies inhibition of NF-κB activation and occurs in parallel with the adsorption of polymeric proanthocyanidins to cell membrane. Our findings suggest that intake of small amounts of pistachio nut can exert beneficial effects to gastrointestinal pathophysiology.

Antibiotic Resistance in Haemophilus influenzae Decreased, except for β-Lactamase-Negative Amoxicillin-Resistant Isolates, in Parallel with Community Antibiotic Consumption in Spain from 1997 to 2007▿

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García-Cobos, Silvia; Campos, José; Cercenado, Emilia; Román, Federico; Lázaro, Edurne; Pérez-Vázquez, María; de Abajo, Francisco; Oteo, Jesús

2008-01-01

The susceptibility to 14 antimicrobial agents and the mechanisms of aminopenicillin resistance were studied in 197 clinical isolates of Haemophilus influenzae—109 isolated in 2007 (study group) and 88 isolated in 1997 (control group). Community antibiotic consumption trends were also examined. H. influenzae strains were consecutively isolated from the same geographic area, mostly from respiratory specimens from children and adults. Overall, amoxicillin resistance decreased by 8.4% (from 38.6 to 30.2%). β-Lactamase production decreased by 15.6% (from 33 to 17.4%, P = 0.01), but amoxicillin resistance without β-lactamase production increased by 7.1% (from 5.7 to 12.8%). All β-lactamase-positive isolates were TEM-1, but five different promoter regions were identified, with Pdel being the most prevalent in both years, and Prpt being associated with the highest amoxicillin resistance. A new promoter consisting of a double repeat of 54 bp was detected. Community consumption of most antibiotics decreased, as did the geometric means of their MICs, but amoxicillin-clavulanic acid and azithromycin consumption increased by ca. 60%. For amoxicillin-clavulanic acid, a 14.2% increase in the population with an MIC of 2 to 4 μg/ml (P = 0.02) was observed; for azithromycin, a 21.2% increase in the population with an MIC of 2 to 8 μg/ml (P = 0.0005) was observed. In both periods, the most common gBLNAR (i.e., H. influenzae isolates with mutations in the ftsI gene as previously defined) patterns were IIc and IIb. Community consumption of trimethoprim-sulfamethoxazole decreased by 54%, while resistance decreased from 50 to 34.9% (P = 0.04). Antibiotic resistance in H. influenzae decreased in Spain from 1997 to 2007, but surveillance should be maintained since new forms of resistances may be developing. PMID:18505850

ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells.

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Poppi, Lauren A; Tabatabaee, Hessam; Drury, Hannah R; Jobling, Phillip; Callister, Robert J; Migliaccio, Americo A; Jordan, Paivi M; Holt, Joseph C; Rabbitt, Richard D; Lim, Rebecca; Brichta, Alan M

2018-01-01

In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9 -/- ) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9 -/- mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted

Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

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W. Cui

2010-04-01

Full Text Available The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-α on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-α (10 or 100 ng/mL for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-α treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-α decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-α did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-α increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

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Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

2016-01-01

In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

Science.gov (United States)

Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

2016-04-01

In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

Sixteen weeks of resistance training can decrease the risk of metabolic syndrome in healthy postmenopausal women

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Conceição MS

2013-09-01

Full Text Available Miguel Soares Conceição,1 Valéria Bonganha,1 Felipe Cassaro Vechin,2 Ricardo Paes de Barros Berton,1 Manoel Emílio Lixandrão,1 Felipe Romano Damas Nogueira,1 Giovana Vergínia de Souza,1 Mara Patricia Traina Chacon-Mikahil,1 Cleiton Augusto Libardi2 1Exercise Physiology Laboratory, School of Physical Education, State University of Campinas, Campinas, 2Laboratory of Neuromuscular Adaptation to Strength Training, School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil Background: The postmenopausal phase has been considered an aggravating factor for developing metabolic syndrome. Notwithstanding, no studies have as yet investigated the effects of resistance training on metabolic syndrome in postmenopausal women. Thus, the purpose of this study was to verify whether resistance training could reduce the risk of metabolic syndrome in postmenopausal women. Methods: Twenty postmenopausal women were randomly assigned to a resistance training protocol (n = 10, 53.40 ± 3.95 years, 64.58 ± 9.22 kg or a control group (n = 10, 53.0 ± 5.7 years, 64.03 ± 5.03 kg. In the resistance training protocol, ten exercises were performed, with 3 × 8–10 maximal repetitions three times per week, and the load was increased every week. Two-way analysis of variance was used to evaluate specific metabolic syndrome Z-score, high density lipoprotein cholesterol, fasting blood glucose, triglycerides, waist circumference, blood pressure, strength, and body composition. The level of statistical significance was set at P < 0.05. Results: The main results demonstrated a significant decrease of metabolic syndrome Z-score when the postmenopausal women performed resistance training (P = 0.0162. Moreover, we observed decreases in fasting blood glucose for the resistance training group (P = 0.001, and also significant improvements in lean body mass (P = 0.042, 2.46%, reduction of body fat percentage (P = 0.001, −6.75% and noticeable increases in

Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes

International Nuclear Information System (INIS)

Aspenstroem-Fagerlund, Bitte; Ring, Linda; Aspenstroem, Pontus; Tallkvist, Jonas; Ilbaeck, Nils-Gunnar; Glynn, Anders W.

2007-01-01

Surface active compounds present in food possibly have the ability to enhance the absorption of water soluble toxic agents. Therefore, we investigated whether fatty acids such as oleic acid and docosahexaenoic acid (DHA), both commonly present in food, negatively affect the integrity of tight junctions (TJ) in the intestinal epithelium and thereby increase the absorption of poorly absorbed hydrophilic substances. Caco-2 cells, which are derived from human absorptive enterocytes, were grown on permeable filters for 20-25 days. Differentiated cell monolayers were apically exposed for 90 min to mannitol in emulsions of oleic acid (5, 15 or 30 mM) or DHA (5, 15 or 30 mM) in an experimental medium with or without Ca 2+ and Mg 2+ . Absorption of 14 C-mannitol increased and trans-epithelial electrical resistance (TEER) decreased in cell monolayers exposed to oleic acid and DHA, compared to controls. Cytotoxicity, measured as leakage of LDH, was higher in groups exposed to 30 mM oleic acid and all concentrations of DHA. Morphology of the cell monolayers was studied by using fluorescence microscopy. Exposure of cell monolayers to 5 mM DHA for 90 min resulted in a profound alteration of the cell-cell contacts as detected by staining the cells for β-catenin. Oleic acid (30 mM) treatment also induced dissolution of the cell-cell contacts but the effect was not as pronounced as with DHA. Cell monolayers were also exposed for 180 min to 250 nM cadmium (Cd) in emulsions of oleic acid (5 or 30 mM) or DHA (1 or 5 mM), in an experimental medium with Ca 2+ and Mg 2+ . Retention of Cd in Caco-2 cells was higher after exposure to 5 mM oleic acid but lower after exposure to 30 mM oleic acid and DHA. Absorption of Cd through the monolayers increased after DHA exposure but not after exposure to oleic acid. Our results indicate that fatty acids may compromise the integrity of the intestinal epithelium and that certain lipids in food may enhance the paracellular absorption of poorly

Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat.

Science.gov (United States)

Lasram, Mohamed Montassar; Bouzid, Kahena; Douib, Ines Bini; Annabi, Alya; El Elj, Naziha; El Fazaa, Saloua; Abdelmoula, Jaouida; Gharbi, Najoua

2015-04-01

Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

Enhanced paracellular and transcellular paclitaxel permeation by chitosan-vitamin E succinate- N-acetyl- l-cysteine copolymer on Caco-2 cell monolayer

Science.gov (United States)

Lian, He; Zhang, Tianhong; Sun, Jin; Pu, Xiaohui; Tang, Yilin; Zhang, Youxi; He, Zhonggui

2014-04-01

The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan-vitamin E succinate- N-acetyl- l-cysteine (CS-VES-NAC) nanomicelles from the cellular level. In aqueous solution, CS-VES-NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS-VES-NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS-VES-NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS-VES-NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P app value of PTX-loaded CS-VES-NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS-VES-NAC copolymer, the P app value of PTX was almost increased up to 19.5-fold. All the results indicate that CS-VES-NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation.

(--Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance

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Eleonora Cremonini

2018-04-01

Full Text Available Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (--epicatechin (EC supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2–20 mg/kg body weight mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption. Keywords: Intestinal permeability, (--Epicatechin, Steatosis, Insulin resistance, Endotoxemia, NADPH oxidase

Dietary fructo-oligosaccharides and inulin decrease resistance of rats to salmonelle: protective role of calcium

NARCIS (Netherlands)

Bruggencate, ten S.J.M.; Bovee-Oudenhoven, I.M.J.; Lettink-Wissink, M.L.G.; Katan, M.B.; Meer, van der R.

2004-01-01

Background: We have shown recently that rapid fermentable fructo-oligosaccharides (FOS) decreased resistance of rats towards salmonella. It is not known whether inulin ( which is fermented more gradually) has similar effects or whether buffering nutrients can counteract the adverse effects of rapid

Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure.

Science.gov (United States)

El Asmar, Ramzi; Panigrahi, Pinaki; Bamford, Penelope; Berti, Irene; Not, Tarcisio; Coppa, Giovanni V; Catassi, Carlo; Fasano, Alessio; El Asmar, Rahzi

2002-11-01

Enteric infections have been implicated in the pathogenesis of both food intolerance and autoimmune diseases secondary to the impairment of the intestinal barrier. On the basis of our recent discovery of zonulin, a modulator of small-intestinal tight junctions, we asked whether microorganisms might induce zonulin secretion and increased small-intestinal permeability. Both ex vivo mammalian small intestines and intestinal cell monolayers were exposed to either pathogenic or nonpathogenic enterobacteria. Zonulin production and changes in paracellular permeability were monitored in Ussing chambers and micro-snapwells. Zonula occludens 1 protein redistribution after bacteria colonization was evaluated on cell monolayers. Small intestines exposed to enteric bacteria secreted zonulin. This secretion was independent of either the species of the small intestines or the virulence of the microorganisms tested, occurred only on the luminal aspect of the bacteria-exposed small-intestinal mucosa, and was followed by a decrease in small-intestinal tissue resistance (transepithelial electrical resistance). The transepithelial electrical resistance decrement was secondary to the zonulin-induced tight junction disassembly, as also shown by the disengagement of the protein zonula occludens 1 protein from the tight junctional complex. This zonulin-driven opening of the paracellular pathway may represent a defensive mechanism, which flushes out microorganisms and contributes to the host response against bacterial colonization of the small intestine.

Inhibition of EGFR nuclear shuttling decreases irradiation resistance in HeLa cells.

Science.gov (United States)

Wei, Hong; Zhu, Zijie; Lu, Longtao

2017-01-01

Cervical cancer is a leading cause of mortality in women worldwide. The resistance to irradiation at the advanced stage is the main reason for the poor prognosis and high mortality. This work aims to elucidate the molecular mechanism underlying the radio-resistance. In this study, we determined the pEGFR-T654 and pDNA-PK-T2609 expression level changes in irradiated HeLa cells treated with T654 peptide, a nuclear localization signal (NLS) inhibitor, to inhibit EGFR nuclear transport. Cell viability, cell cycle and migratory capacity were analyzed. Xenograft animal model was used to evaluate the effect of EGFR nuclear transport inhibition on the tumor growth in vivo. The enhanced translocation of nuclear EGFR in the irradiated HeLa cells correlated with the increasing level of pEGFR-T654 and pDNA-PK-T2609. Inhibition of EGFR nuclear translocation by NLS peptide inhibitor attenuated DNA damage repair in the irradiated HeLa cells, decreased cell viability and promoted cell death through arrest at G0 phase. NLS peptide inhibitor impaired the migratory capacity of irradiated HeLa cells, and negatively affected tumorigenesis in xenograft mice. This work puts forward a potential molecular mechanism of the irradiation resistance in cervical cancer cells, providing a promising direction towards an efficient therapy of cervical cancer.

Decrease in electrical resistivity on depletion of islands of mobility during aging of a bulk metal glass

Science.gov (United States)

Aji, Daisman P. B.; Johari, G. P.

2018-04-01

The effect of structural relaxation on electrical resistivity, ρglass, of strain-free Zr46.75Ti8.25Cu7.5Ni10Be27.5 bulk metallic glass was studied during isothermal aging at several temperatures, Tas. Since cooling of a liquid metal increases its resistivity ρliq, one expects ρglass to increase on aging toward ρliq at T = Ta. Instead, ρglass decreased non-exponentially with the aging time. The activation energy of aging kinetics is 189 kJ mol-1, which is higher than the activation energy of the Johari-Goldstein (JG) relaxation. After considering the sample's contraction, phase separation, and crystallization as possible causes of the decrease in ρglass, we attribute the decrease to depletion of islands of atomic mobility, soft spots, or static heterogeneity. Vibrations of the atoms in these local (loosely packed) regions and in the region's interfacial area contribute to electron scattering. As these deplete on aging, the contribution decreases and ρglass decreases, with a concomitant decrease in macroscopic volume, enthalpy, and entropy (V, H, and S). Local regions of faster mobility also decrease on cooling as V, H, and S of a liquid decrease, but structure fluctuations dominate electron scattering of a liquid metal and ρliq increases effectively according to the Ziman-Nagel theory for a homogenously disordered structure. Whether depletion of such local regions initiates the structural relaxation of a glass, or vice versa, may be resolved by finding a glass that physically ages but shows no JG relaxation.

Multidrug resistance in Botrytis cinerea associated with decreased accumulation of the azole fungicide oxpoconazole and increased transcription of the ABC transporter gene BcatrD

NARCIS (Netherlands)

Hayashi, K.; Schoonbeek, H.; Sugiura, H.; Waard, De M.A.

2001-01-01

Azole-resistant mutants of Botrytis cinerea have a multidrug resistance phenotype since they exhibit cross-resistance to unrelated chemicals. These mutants also display resistance to the new azole fungicide oxpoconazole. Resistance to oxpoconazole is associated with decreased accumulation of the

Brush border membrane vesicle and Caco-2 cell line: Two experimental models for evaluation of absorption enhancing effects of saponins, bile salts, and some synthetic surfactants

Directory of Open Access Journals (Sweden)

Eskandar Moghimipour

2016-01-01

Full Text Available The aim of this study was to investigate the influence of absorption enhancers in the uptake of hydrophilic compounds. The permeation of the two hydrophilic drug models gentamicin and 5 (6-carboxyfluorescein (CF across the brush border membrane vesicles and Caco-2 cell lines were evaluated using total saponins of Acanthophyllum squarrosum, Quillaja saponaria, sodium lauryl sulfate, sodium glycocholate, sodium taurodeoxycholate , and Tween 20 as absorption enhancers. Transepithelial electrical resistance (TEER measurement was utilized to assess the paracellular permeability of cell lines. Confocal laser scanning microscopy (CLSM was performed to obtain images of the distribution of CF in Caco-2 cells. These compounds were able to loosen tight junctions, thus increasing paracellular permeability. CLSM confirmed the effect of these absorption enhancers on CF transport across Caco-2 lines and increased the Caco-2 permeability via transcellular route. It was also confirmed that the decrease in TEER was transient and reversible after removal of permeation enhancers.

Ultrasound-guided hydrodissection decreases gliding resistance of the median nerve within the carpal tunnel.

Science.gov (United States)

Evers, Stefanie; Thoreson, Andrew R; Smith, Jay; Zhao, Chunfeng; Geske, Jennifer R; Amadio, Peter C

2018-01-01

The aim of this study was to assess alterations in median nerve (MN) biomechanics within the carpal tunnel resulting from ultrasound-guided hydrodissection in a cadaveric model. Twelve fresh frozen human cadaver hands were used. MN gliding resistance was measured at baseline and posthydrodissection, by pulling the nerve proximally and then returning it to the origin. Six specimens were treated with hydrodissection, and 6 were used as controls. In the hydrodissection group there was a significant reduction in mean peak gliding resistance of 92.9 ± 34.8 mN between baseline and immediately posthydrodissection (21.4% ± 10.5%; P = 0.001). No significant reduction between baseline and the second cycle occurred in the control group: 9.6 ± 29.8 mN (0.4% ± 5.3%; P = 0.467). Hydrodissection can decrease the gliding resistance of the MN within the carpal tunnel, at least in wrists unaffected by carpal tunnel syndrome. A clinical trial of hydrodissection seems justified. Muscle Nerve 57: 25-32, 2018. © 2017 Wiley Periodicals, Inc.

Cluster of Neisseria gonorrhoeae Isolates With High-level Azithromycin Resistance and Decreased Ceftriaxone Susceptibility, Hawaii, 2016.

Science.gov (United States)

Katz, Alan R; Komeya, Alan Y; Kirkcaldy, Robert D; Whelen, A Christian; Soge, Olusegun O; Papp, John R; Kersh, Ellen N; Wasserman, Glenn M; O'Connor, Norman P; O'Brien, Pamela S; Sato, Douglas T; Maningas, Eloisa V; Kunimoto, Gail Y; Tomas, Juval E

2017-09-15

The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 μg/mL and elevated ceftriaxone MICs (≥0.125 μg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. All isolates had azithromycin MICs >16 µg/mL and 5 had ceftriaxone MICs = 0.125 µg/mL by agar dilution. All isolates were β-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

Science.gov (United States)

Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

2017-05-01

Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

A New Ala-122-Asn Amino Acid Change Confers Decreased Fitness to ALS-Resistant Echinochloa crus-galli

Directory of Open Access Journals (Sweden)

Silvia Panozzo

2017-11-01

Full Text Available Gene mutations conferring herbicide resistance may cause pleiotropic effects on plant fitness. Knowledge of these effects is important for managing the evolution of herbicide-resistant weeds. An Echinochloa crus-galli population resistant to acetolactate synthase (ALS herbicides was collected in a maize field in north-eastern Italy and the cross-resistance pattern, resistance mechanism and fitness costs associated to mutant-resistant plants under field conditions in the presence or absence of intra-specific competition were determined. The study reports for the first time the Ala-122-Asn amino-acid change in the ALS gene that confers high levels of cross-resistance to all ALS inhibitors tested. Results of 3-year growth analysis showed that mutant resistant E. crus-galli plants had a delayed development in comparison with susceptible plants and this was registered in both competitive (3, 7, and 20 plants m-2 and non-competitive (spaced plants situations. The number of panicles produced by resistant plants was also lower (about 40% fewer panicles than susceptible plants under no-intraspecific competition. Instead, with the increasing competition level, the difference in panicle production at harvest time decreased until it became negligible at 20 plants m-2. Evaluation of total dry biomass as well as biomass allocation in vegetative parts did not highlight any difference between resistant and susceptible plants. Instead, panicle dry weight was higher in susceptible plants indicating that they allocated more biomass than resistant ones to the reproductive organs, especially in no-competition and in competition situations at lower plant densities. The different fitness between resistant and susceptible phenotypes suggests that keeping the infestation density as low as possible can increase the reproduction success of the susceptible phenotype and therefore contribute to lowering the ratio between resistant and susceptible alleles. If adequately

A New Ala-122-Asn Amino Acid Change Confers Decreased Fitness to ALS-Resistant Echinochloa crus-galli.

Science.gov (United States)

Panozzo, Silvia; Scarabel, Laura; Rosan, Valentina; Sattin, Maurizio

2017-01-01

Gene mutations conferring herbicide resistance may cause pleiotropic effects on plant fitness. Knowledge of these effects is important for managing the evolution of herbicide-resistant weeds. An Echinochloa crus-galli population resistant to acetolactate synthase (ALS) herbicides was collected in a maize field in north-eastern Italy and the cross-resistance pattern, resistance mechanism and fitness costs associated to mutant-resistant plants under field conditions in the presence or absence of intra-specific competition were determined. The study reports for the first time the Ala-122-Asn amino-acid change in the ALS gene that confers high levels of cross-resistance to all ALS inhibitors tested. Results of 3-year growth analysis showed that mutant resistant E. crus-galli plants had a delayed development in comparison with susceptible plants and this was registered in both competitive (3, 7, and 20 plants m -2 ) and non-competitive (spaced plants) situations. The number of panicles produced by resistant plants was also lower (about 40% fewer panicles) than susceptible plants under no-intraspecific competition. Instead, with the increasing competition level, the difference in panicle production at harvest time decreased until it became negligible at 20 plants m -2 . Evaluation of total dry biomass as well as biomass allocation in vegetative parts did not highlight any difference between resistant and susceptible plants. Instead, panicle dry weight was higher in susceptible plants indicating that they allocated more biomass than resistant ones to the reproductive organs, especially in no-competition and in competition situations at lower plant densities. The different fitness between resistant and susceptible phenotypes suggests that keeping the infestation density as low as possible can increase the reproduction success of the susceptible phenotype and therefore contribute to lowering the ratio between resistant and susceptible alleles. If adequately embedded in a

[6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway

Directory of Open Access Journals (Sweden)

Sung Ok Kim

2013-01-01

Full Text Available To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP activities; transepithelial electrical resistance (TER and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO- 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.

Copper pollution decreases the resistance of soil microbial community to subsequent dry-rewetting disturbance.

Science.gov (United States)

Li, Jing; Wang, Jun-Tao; Hu, Hang-Wei; Ma, Yi-Bing; Zhang, Li-Mei; He, Ji-Zheng

2016-01-01

Dry-rewetting (DW) disturbance frequently occurs in soils due to rainfall and irrigation, and the frequency of DW cycles might exert significant influences on soil microbial communities and their mediated functions. However, how microorganisms respond to DW alternations in soils with a history of heavy metal pollution remains largely unknown. Here, soil laboratory microcosms were constructed to explore the impacts of ten DW cycles on the soil microbial communities in two contrasting soils (fluvo-aquic soil and red soil) under three copper concentrations (zero, medium and high). Results showed that the fluctuations of substrate induced respiration (SIR) decreased with repeated cycles of DW alternation. Furthermore, the resistance values of substrate induced respiration (RS-SIR) were highest in non-copper-stressed (zero) soils. Structural equation model (SEM) analysis ascertained that the shifts of bacterial communities determined the changes of RS-SIR in both soils. The rate of bacterial community variance was significantly lower in non-copper-stressed soil compared to the other two copper-stressed (medium and high) soils, which might lead to the higher RS-SIR in the fluvo-aquic soil. As for the red soil, the substantial increase of the dominant group WPS-2 after DW disturbance might result in the low RS-SIR in the high copper-stressed soil. Moreover, in both soils, the bacterial diversity was highest in non-copper-stressed soils. Our results revealed that initial copper stress could decrease the resistance of soil microbial community structure and function to subsequent DW disturbance. Copyright © 2015. Published by Elsevier B.V.

A fish oil diet does not reverse insulin resistance despite decreased adipose tissue TNF-alpha protein concentration in ApoE-3*Leiden mice

NARCIS (Netherlands)

Muurling, Martin; Mensink, Ronald P.; Pijl, Hanno; Romijn, Johannes A.; Havekes, Louis M.; Voshol, Peter J.

2003-01-01

Dietary interventions with fish oil have been found to protect against the development of high-fat diet-induced insulin resistance and to decrease the expression of tumor necrosis factor (TNF)-alpha. However, the effect of fish oil administration on preexisting insulin resistance is subject to

Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin

LENUS (Irish Health Repository)

Boehm, Manja

2012-04-25

AbstractBackgroundCampylobacter jejuni is one of the most important bacterial pathogens causing food-borne illness worldwide. Crossing the intestinal epithelial barrier and host cell entry by C. jejuni is considered the primary reason of damage to the intestinal tissue, but the molecular mechanisms as well as major bacterial and host cell factors involved in this process are still widely unclear.ResultsIn the present study, we characterized the serine protease HtrA (high-temperature requirement A) of C. jejuni as a secreted virulence factor with important proteolytic functions. Infection studies and in vitro cleavage assays showed that C. jejuni’s HtrA triggers shedding of the extracellular E-cadherin NTF domain (90 kDa) of non-polarised INT-407 and polarized MKN-28 epithelial cells, but fibronectin was not cleaved as seen for H. pylori’s HtrA. Deletion of the htrA gene in C. jejuni or expression of a protease-deficient S197A point mutant did not lead to loss of flagella or reduced bacterial motility, but led to severe defects in E-cadherin cleavage and transmigration of the bacteria across polarized MKN-28 cell layers. Unlike other highly invasive pathogens, transmigration across polarized cells by wild-type C. jejuni is highly efficient and is achieved within a few minutes of infection. Interestingly, E-cadherin cleavage by C. jejuni occurs in a limited fashion and transmigration required the intact flagella as well as HtrA protease activity, but does not reduce transepithelial electrical resistance (TER) as seen with Salmonella, Shigella, Listeria or Neisseria.ConclusionThese results suggest that HtrA-mediated E-cadherin cleavage is involved in rapid crossing of the epithelial barrier by C. jejuni via a very specific mechanism using the paracellular route to reach basolateral surfaces, but does not cleave the fibronectin receptor which is necessary for cell entry.

Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin.

Science.gov (United States)

Boehm, Manja; Hoy, Benjamin; Rohde, Manfred; Tegtmeyer, Nicole; Bæk, Kristoffer T; Oyarzabal, Omar A; Brøndsted, Lone; Wessler, Silja; Backert, Steffen

2012-04-25

Campylobacter jejuni is one of the most important bacterial pathogens causing food-borne illness worldwide. Crossing the intestinal epithelial barrier and host cell entry by C. jejuni is considered the primary reason of damage to the intestinal tissue, but the molecular mechanisms as well as major bacterial and host cell factors involved in this process are still widely unclear. In the present study, we characterized the serine protease HtrA (high-temperature requirement A) of C. jejuni as a secreted virulence factor with important proteolytic functions. Infection studies and in vitro cleavage assays showed that C. jejuni's HtrA triggers shedding of the extracellular E-cadherin NTF domain (90 kDa) of non-polarised INT-407 and polarized MKN-28 epithelial cells, but fibronectin was not cleaved as seen for H. pylori's HtrA. Deletion of the htrA gene in C. jejuni or expression of a protease-deficient S197A point mutant did not lead to loss of flagella or reduced bacterial motility, but led to severe defects in E-cadherin cleavage and transmigration of the bacteria across polarized MKN-28 cell layers. Unlike other highly invasive pathogens, transmigration across polarized cells by wild-type C. jejuni is highly efficient and is achieved within a few minutes of infection. Interestingly, E-cadherin cleavage by C. jejuni occurs in a limited fashion and transmigration required the intact flagella as well as HtrA protease activity, but does not reduce transepithelial electrical resistance (TER) as seen with Salmonella, Shigella, Listeria or Neisseria. These results suggest that HtrA-mediated E-cadherin cleavage is involved in rapid crossing of the epithelial barrier by C. jejuni via a very specific mechanism using the paracellular route to reach basolateral surfaces, but does not cleave the fibronectin receptor which is necessary for cell entry.

Horizontal infection control strategy decreases methicillin-resistant Staphylococcus aureus infection and eliminates bacteremia in a surgical ICU without active surveillance.

Science.gov (United States)

Traa, Maria X; Barboza, Lorena; Doron, Shira; Snydman, David R; Noubary, Farzad; Nasraway, Stanley A

2014-10-01

Methicillin-resistant Staphylococcus aureus infection is a significant contributor to morbidity and mortality in hospitalized patients worldwide. Numerous healthcare bodies in Europe and the United States have championed active surveillance per the "search and destroy" model. However, this strategy is associated with significant economic, logistical, and patient costs without any impact on other hospital-acquired pathogens. We evaluated whether horizontal infection control strategies could decrease the prevalence of methicillin-resistant S. aureus infection in the ICU, without the need for active surveillance. Retrospective, observational study in the surgical ICU of a tertiary care medical center in Boston, MA, from 2005 to 2012. A total of 6,697 patients in the surgical ICU. Evidence-based infection prevention strategies were implemented in an iterative fashion, including 1) hand hygiene program with refresher education campaign, 2) chlorhexidine oral hygiene program, 3) chlorhexidine bathing, 4) catheter-associated bloodstream infection program, and 5) daily goals sheets. The prevalence of methicillin-resistant S. aureus infection fell from 2.66 to 0.69 per 1,000 patient days from 2005 to 2012, an average decrease of 21% per year. The biggest decline in rate of infection was detected in 2008, which may suggest that the catheter-associated bloodstream infection prevention program was particularly effective. Among 4,478 surgical ICU admissions over the last 5 years, not a single case of methicillin-resistant S. aureus bacteremia was observed. Aggressive multifaceted horizontal infection control is an effective strategy for reducing the prevalence of methicillin-resistant S. aureus infection and eliminating methicillin-resistant S. aureus bacteremia in the ICU without the need for active surveillance and decontamination.

Anomalous decrease of resistance at 250 K in ultrathin Au-Nb film on single-crystal silicon

International Nuclear Information System (INIS)

Yamamoto, H.; Kawashima, T.; Tanaka, M.

1986-01-01

Ultrathin Au-Nb films as thin as 0.2 about 10 nm were deposited on clean surfaces of single-crystal silicon in order to investigate interfacial excitonic superconductivity. The samples were classified into two types, Nb-Au/Si and Au-Nb-Au/Si. In the latter case, the secondary Au film was deposited on the former sample cooled by liquid nitrogen. In the Nb-Au/ Si type of sample, a sheet resistance, R /SUB s/ at room temperature abruptly increased from 10 3 Ωsq -1 order to about 10 5 Ωsq -1 in several days a few months after the sample preparation. Then the sample showed an anomalous decrease of R /SUB s/ at about 250 K and an approximately null resistance at lower temperatures. This phenomenon was not so stable and was observed only for a few days. The Au-Nb-Au/Si type of sample showed low R /SUB s/ (10 2 about 10 3 Ωsq -1 ) at room temperature. A decrease and disappearance of R /SUB s/ were also observed at about 240 K in the sample with comparatively good reproducibility. These phenomena are discussed qualitatively, based on the excitonic superconductive model for an interface of metal/semiconductor by Allender, Bray, and Bardeen

Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection.

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Pedersen, Niels C; Liu, Hongwei; Durden, Monica; Lyons, Leslie A

2016-03-01

A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4-12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

International Nuclear Information System (INIS)

Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A.; Pinilla, Mabel G.; Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C.; McNerney, Eileen M.; Onate, Sergio A.

2015-01-01

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

Energy Technology Data Exchange (ETDEWEB)

Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Pinilla, Mabel G. [Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C. [Department of Physiopathology, School of Biological Sciences, University of Concepcion, Concepcion (Chile); McNerney, Eileen M. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Onate, Sergio A., E-mail: sergio.onate@udec.cl [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Department of Urology, State University of New York at Buffalo, NY (United States)

2015-11-27

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

Development of a model for functional studies of ABCG2 (breast cancer resistance protein) efflux employing a standard BeWo clone (B24).

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Crowe, Andrew; Keelan, Jeffrey A

2012-10-01

Human choriocarcinoma-derived BeWo cells express high levels of breast cancer resistance protein (BCRP/ABCG2) with no functional P-glycoprotein (P-gp) (ABCB1) activity, making them a potential model to study bidirectional ABCG2-mediated drug transport. However, the original BeWo clone (B24) available to researchers does not form confluent monolayers with tight junctions required by the model. Our aim was to adapt culture conditions to attempt to generate confluent BeWo monolayers for drug transport studies using the standard B24 clone. BeWo cells (B24; American Type Culture collection [ATCC]) were cultured in six-well plates or polycarbonate millicell inserts in a number of media formulations, growth supplements, and basement membrane substitutes. Cells were examined for confluence by microscopy, and transepithelial electrical resistance (TEER) was measured daily; monolayer permeability was assessed when TEER had stabilized. Optimal growth rates were achieved in culture conditions consisting of Medium 199 (M199) supplemented with epidermal growth factor (EGF; 20 ng/mL), vitamin supplements, and 10% fetal calf serum (FCS) with collagen coating. A TEER of 170 Ω in 0.6 cm(2) inserts was achieved 2 weeks after seeding under optimal conditions. The cell-impermeable diffusion marker 5(6) carboxy-2,7dichlorodihydrofluorescein (C-DCDHF) had a permeability coefficient of 3.5×10(-6) cm/s, indicative of minimal paracellular permeability. ABCG2 expression, as determined by immunoblotting, remained unaffected by confluency. In conclusion, we describe culture conditions for the B24 BeWo clone that facilitate the formation of monolayers with tighter junctions and reduced paracellular transport compared to previously published models. These growth conditions provide a good model of ABCG2-mediated drug transport in a human placental cell line.

Dendritic cell CNS recruitment correlates with disease severity in EAE via CCL2 chemotaxis at the blood–brain barrier through paracellular transmigration and ERK activation

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Sagar Divya

2012-10-01

Full Text Available Abstract Background Transmigration of circulating dendritic cells (DCs into the central nervous system (CNS across the blood–brain barrier (BBB has not thus far been investigated. An increase in immune cell infiltration across the BBB, uncontrolled activation and antigen presentation are influenced by chemokines. Chemokine ligand 2 (CCL2 is a potent chemoattractant known to be secreted by the BBB but has not been implicated in the recruitment of DCs specifically at the BBB. Methods Experimental autoimmune encephalomyelitis (EAE was induced in C57BL/6 mice by injection of MOG35–55 peptide and pertussis toxin intraperitoneally. Animals with increasing degree of EAE score were sacrificed and subjected to near-infrared and fluorescence imaging analysis to detect and localize the accumulation of CD11c+-labeled DCs with respect to CCL2 expression. To further characterize the direct effect of CCL2 in DC trafficking at the BBB, we utilized an in vitro BBB model consisting of human brain microvascular endothelial cells to compare migratory patterns of monocyte-derived dendritic cells, CD4+ and CD8+ T cells. Further, this model was used to image transmigration using fluorescence microcopy and to assess specific molecular signaling pathways involved in transmigration. Results Near-infrared imaging of DC transmigration correlated with the severity of inflammation during EAE. Ex vivo histology confirmed the presence of CCL2 in EAE lesions, with DCs emerging from perivascular spaces. DCs exhibited more efficient transmigration than T cells in BBB model studies. These observations correlated with transwell imaging, which indicated a paracellular versus transcellular pattern of migration by DCs and T cells. Moreover, at the molecular level, CCL2 seems to facilitate DC transmigration in an ERK1/2-dependent manner. Conclusion CNS recruitment of DCs correlates with disease severity in EAE via CCL2 chemotaxis and paracellular transmigration across the BBB

The small molecule triclabendazole decreases the intracellular level of cyclic AMP and increases resistance to stress in Saccharomyces cerevisiae.

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Yong Joo Lee

Full Text Available The Ras-adenylyl cyclase-protein kinase A nutrient-sensing pathway controls metabolism, proliferation and resistance to stress in Saccharomyces cerevisiae. The genetic disruption of this pathway increases resistance to a variety of stresses. We show here that the pharmacological inhibition of this pathway by the drug triclabendazole increases resistance to oxidants, heat stress and extends the chronological life. Evidence is presented that triclabendazole decreases the intracellular level of cyclic AMP by inhibiting adenylyl cyclase and triggers the parallel rapid translocation of the stress-resistance transcription factor Msn2 from the cytosol into the nucleus, as deduced from experiments employing a strain in which MSN2 is replaced with MSN2-GFP (GFP, green fluorescent protein. Msn2 and Msn4 are responsible for activating the transcription of numerous genes that encode proteins that protect cells from stress. The results are consistent with triclabendazole either inhibiting the association of Ras with adenylyl cyclase or directly inhibiting adenylyl cyclase, which in turn triggers Msn2/4 to enter the nucleus and activate stress-responsible element gene expression.

Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

Science.gov (United States)

Scheulen, M E; Hoensch, H; Kappus, H; Seeber, S; Schmidt, C G

1987-01-01

From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

IPEC-J2 MDR1, a Novel High-Resistance Cell Line with Functional Expression of Human P-glycoprotein (ABCB1) for Drug Screening Studies

DEFF Research Database (Denmark)

Saaby, Lasse; Helms, Hans Christian Cederberg; Brodin, Birger

2016-01-01

The P-glycoprotein (P-gp) efflux pump has been shown to affect drug distribution and absorption in various organs and to cause drug resistance in cancer therapy. The aim of this work was to develop a cell line to serve as a screening system for potential substrates of P-gp. This requires a cell...... line with high paracellular tightness, low expression of nonhuman ABC transporters, and high expression of functional human P-gp (ABCB1). The porcine intestinal epithelial cell line, IPEC-J2, was selected as a transfection host, due to its ability to form extremely high-resistance monolayers (>10,000 Ω......·cm(2)) and its low endogenous expression of ABC-type efflux transporters. The IPEC-J2 cells were transfected with a plasmid that contained the sequence of the human MDR1 gene, which encodes P-gp, followed by a selection of successfully transfected cells with geneticin and puromycin. The resulting cell...

Decreased antimicrobial resistance and defined daily doses after implementation of a clinical culture-guided antimicrobial stewardship program in a local hospital

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Chang-Teng Wu

2017-12-01

Full Text Available Background: We aimed to report the implementation of an antimicrobial stewardship program (ASP guided by clinically significant cultures in a hospital to assess its pharmaceutical, microbiological, financial, and outcome effects. Methods: A 3-year cohort study of an antimicrobial restriction policy implementation was performed. The ASP with culture-guided de-escalation of antibiotics was instituted in a local hospital since January 1, 2012. The cost of antimicrobials, defined daily dose (DDD, susceptibility to antimicrobials, and outcome of all admitted patients were calculated and evaluated before and after the ASP implementation. Results: Average monthly length of stay of admitted patients decreased from 7.8 ± 0.5 days in 2011 to 6.9 ± 0.3 days in 2013 (p < 0.001. The average monthly cost of antimicrobials decreased 46.9% from US$30,146.8 in 2011 to US$16,021.3 in 2013 (p < 0.001. Total intravenous antimicrobial DDDs per 100 bed-days of the inpatients were 66.9, 54.1 and 48.4 in 2011, 2012 and 2013, respectively. A total of 18.6 DDDs per 100 bed-days of inpatients (27.7% decreased from 2011 to 2013. By comparing data in 2013 to those in 2011, the ASP reduced antimicrobial resistance of Gram-positive bacteria (p = 0.013, Gram-negative bacteria (p < 0.001, and predominant species (all p < 0.05. The yearly mortality also decreased from 1.3% in 2011 to 1.1% in 2012 and 1.0% in 2013. Conclusions: The ASP with a culture-guided de-escalation of antibiotics successfully reduced length of stay, mortality, the cost of antimicrobials, DDDs, and antimicrobial resistance rate, and that is highly recommended for local hospitals. Keywords: antimicrobial resistance, antimicrobial restriction policy, antimicrobial stewardship program, defined daily dose

Resistance Training Combined With Diet Decreases Body Fat While Preserving Lean Mass Independent of Resting Metabolic Rate: A Randomized Trial.

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Miller, Todd; Mull, Stephanie; Aragon, Alan Albert; Krieger, James; Schoenfeld, Brad Jon

2018-01-01

The purpose of this study was to determine the effects of resistance training only (RT; n = 10), dietary intervention only (DIET; n = 10), resistance training plus diet (RT+DIET; n = 10), and control (CON; n = 10) on body composition and resting metabolic rate (RMR) in a cohort of 40 premenopausal female volunteers. Subjects in DIET and RT+DIET were provided with daily macronutrient and calorie goals based on DXA and RMR tests, with protein maintained at 3.1 g/kg/day. Subjects in the RT and RT+DIET groups performed a supervised progressive RT program consisting of exercises for all the major muscle groups of the body. Results showed a significant month-by-group interaction for change in fat mass with no significant linear trend for control. The three treatment groups all showed significant linear decreases in fat mass, but the slope of the decrease became progressively steeper from the RT, to DIET, to RT+DIET. A significant linear increase for lean mass was seen for resistance training only. There was a nonsignificant increase in RMR in all groups from Month 0 to Month 4 but no significant month by group interaction. In conclusion, significant reductions in fat mass were achieved by all experimental groups, but results were maximized by RT+DIET. Only the RT group showed significant increases in lean mass.

Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake

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Angela Oliveira Pisco

2014-10-01

Full Text Available Expression of ABC family transporter proteins that promote drug efflux from cancer cells is a widely observed mechanism of multi-drug resistance of cancer cells. Cell adaptation in long-term culture of HL60 leukemic cells in the presence of chemotherapy leads to induction and maintenance of the ABC transporters expression, preventing further accumulation of drugs. However, we found that decreased accumulation of drugs and fluorescent dyes was also contributed by a reduced uptake by the resistant cells. Confocal time-lapse microscopy and flow cytometry revealed that fluid-phase endocytosis was diminished in drug-resistant cells compared to drug-sensitive cells. Drug uptake was increased by insulin co-treatment when cells were grown in methylcellulose and monitored under the microscope, but not when cultured in suspension. We propose that multi-drug resistance is not solely achieved by enhanced efflux capacity but also by supressed intake of the drug offering an alternative target to overcome drug resistance or potentiate chemotherapy.

A significant reduction in the frequency of HIV-1 drug resistance in Québec from 2001 to 2011 is associated with a decrease in the monitored viral load.

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Hugues Charest

Full Text Available BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL in treatment-naïve (TN and treatment-experienced (TE individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011. METHODS AND FINDINGS: Resistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%], nucleoside [NRTI (from 78% to 37% and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004. CONCLUSIONS: We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant

Does nasal congestion have a role in decreased resistance to regular CPAP usage?

Science.gov (United States)

İriz, Ayşe; Düzlü, Mehmet; Köktürk, Oğuz; Kemaloğlu, Yusuf Kemal; Eravcı, Fakih Cihat; Zorlu, Mehmet Ekrem; Karamert, Recep

2017-11-01

Nasal obstruction is known to cause resistance to continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea syndrome (OSAS). In this paper, short- and long-term nasal congestion in OSAS patients receiving CPAP treatment were evaluated with acoustic rhinometry (AR). A total of 36 patients with moderate-to-severe OSAS, diagnosed with polysomnography were included in the study. Ten healthy subjects without OSAS constituted the control group. Pre-treatment nasal patency were measured with AR in all participants. 26 patients used the recommended CPAP treatment. Ten patients did not accept CPAP treatment. The AR test was repeated for all the subjects after 1 and 3 months except the 3rd month's measurements of the control group. There was no statistically significant difference between the initial minimum cross-sectional area (MCA) measurements of OSAS patients, using or not using CPAP, and the control group (P > 0.05). However, the first month MCA measurements of patients receiving CPAP were found to be significantly decreased compared with the initial values (P CPAP (P > 0.05). No significant difference revealed in the 3rd month MCA measurements of the patients using CPAP compared with the initial values (P > 0.05). In this study, the increased nasal congestion, which is thought to be the cause of CPAP resistance, was objectively demonstrated in OSAS patients using CPAP. In addition, the nasal congestion developing at the first month was shown to disappear over time, supporting the opinion that patient compliance in CPAP treatment is expected to increase after regular device usage.

Decreasing prevalence of multi-drugs resistant Mycobacterium tuberculosis in Nashik City, India

OpenAIRE

More, Arun Punaji; Nagdawane, Ramkrishna Panchamrao; Gangurde, Aniket K

2013-01-01

Objective: In India, increasing prevalence of multi-drug resistant tuberculosis (MDR) has aggravated the control oftuberculosis problem. In many urban and semi-urban regions of India, no surveillance data of multidrug resistance inMycobacterium tuberculosisis available.Methods: A surveillance study on multidrug resistance was carried out in semi-urban and rural regions in and aroundNashik City of Maharashtra, India. The surveillance study was conducted in this region found that the prevalence...

Decreasing prevalence of multi-drugs resistant Mycobacterium tuberculosis in Nashik City, India

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Arun P. More

2013-03-01

Full Text Available Objective: In India, increasing prevalence of multi-drug resistant tuberculosis (MDR has aggravated the control oftuberculosis problem. In many urban and semi-urban regions of India, no surveillance data of multidrug resistance inMycobacterium tuberculosisis available.Methods: A surveillance study on multidrug resistance was carried out in semi-urban and rural regions in and aroundNashik City of Maharashtra, India. The surveillance study was conducted in this region found that the prevalence ofcombined resistance to first and second-line anti-tuberculosis drugs is remarkably high. The isolates of M. tuberculosiswas identified and subjected to drug susceptibility testing. The patterns of drug susceptibility of isolates of M. tuberculosisduring the periods 2000 and 2004 were compared with drug susceptibility patterns of the organisms during theperiod 2008 to 2011.Results: The 260 isolates identified as M. tuberculosis show mean drug resistance prevalence of 45.6% for more than anytwo drugs and the MDR rate as 37% in the years 2000 to 2004 whereas 305 isolates of the organism show mean drugresistance prevalence of 30.2% and the MDR rate as 25% in the years 2008 to 2011.Conclusion: The researcher found that, though the prevalence of multidrug resistance to the drugs tested is remarkablyhigh, it has come down noticeably during the past seven years due to efforts of State Government and strict implementationof treatment guidelines of WHO by the physicians. J Microbiol Infect Dis 2013; 3(1: 12-17Key words: MDR-TB, XDR-TB, DOTS, drug-resistance prevalence rate.

Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

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Carole D Mitnick

Full Text Available A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7 drugs. Cure or completion was achieved in 66.1% (442 of patients; death occurred in 20.8% (139. Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89, compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93.The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

Decrease in the prevalence of extended-spectrum cephalosporin-resistant Salmonella following cessation of ceftiofur use by the Japanese poultry industry.

Science.gov (United States)

Shigemura, Hiroaki; Matsui, Mari; Sekizuka, Tsuyoshi; Onozuka, Daisuke; Noda, Tamie; Yamashita, Akifumi; Kuroda, Makoto; Suzuki, Satowa; Kimura, Hirokazu; Fujimoto, Shuji; Oishi, Kazunori; Sera, Nobuyuki; Inoshima, Yasuo; Murakami, Koichi

2018-06-02

Extended-spectrum cephalosporin (ESC)-resistant Salmonella in chicken meat is a significant food safety concern. We previously reported that the prevalence of ESC-resistant Salmonella in chicken meat, giblets, and processed chicken (chicken meat products) increased in Japan between 2005 and 2010, with 27.9% (17/61) of Salmonella isolated from chicken meat products in 2010 showing resistance to ESC. The aims of the present study were to clarify trends in the prevalence of ESC-resistant Salmonella in chicken meat products in Japan between 2011 and 2015, and to determine the genetic profiles of bla-harboring plasmids, including replicon types, using next-generation sequencing. Our results showed that the prevalence of ESC-resistant Salmonella, mainly consisting of AmpC β-lactamase CMY-2-producing isolates, in chicken meat products had increased to 45.5% (10/22) by 2011. However, following the voluntary cessation of ceftiofur use by the Japanese poultry industry in 2012, the prevalence of ESC-resistant Salmonella steadily decreased each year, to 29.2% (7/24), 18.2% (4/22), 10.5% (2/19), and 10.5% (2/19) in 2012, 2013, 2014, and 2015, respectively. Furthermore, no AmpC β-lactamase CMY-2-producing isolates were identified in 2014 and 2015. However, the prevalence of Salmonella enterica subspecies enterica serovar Manhattan isolates harboring a bla TEM-52 -carrying IncX1 plasmid remained steady even after the cessation of ceftiofur use. Therefore, continuous monitoring of ESC resistance amongst Salmonella isolates from chicken meat products is required for food safety. Copyright © 2018. Published by Elsevier B.V.

Informed switching strongly decreases the prevalence of antibiotic resistance in hospital wards.

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Roger D Kouyos

2011-03-01

Full Text Available Antibiotic resistant nosocomial infections are an important cause of mortality and morbidity in hospitals. Antibiotic cycling has been proposed to contain this spread by a coordinated use of different antibiotics. Theoretical work, however, suggests that often the random deployment of drugs ("mixing" might be the better strategy. We use an epidemiological model for a single hospital ward in order to assess the performance of cycling strategies which take into account the frequency of antibiotic resistance in the hospital ward. We assume that information on resistance frequencies stems from microbiological tests, which are performed in order to optimize individual therapy. Thus the strategy proposed here represents an optimization at population-level, which comes as a free byproduct of optimizing treatment at the individual level. We find that in most cases such an informed switching strategy outperforms both periodic cycling and mixing, despite the fact that information on the frequency of resistance is derived only from a small sub-population of patients. Furthermore we show that the success of this strategy is essentially a stochastic phenomenon taking advantage of the small population sizes in hospital wards. We find that the performance of an informed switching strategy can be improved substantially if information on resistance tests is integrated over a period of one to two weeks. Finally we argue that our findings are robust against a (moderate preexistence of doubly resistant strains and against transmission via environmental reservoirs. Overall, our results suggest that switching between different antibiotics might be a valuable strategy in small patient populations, if the switching strategies take the frequencies of resistance alleles into account.

Biorelevant media resistant co-culture model mimicking permeability of human intestine.

Science.gov (United States)

Antoine, Delphine; Pellequer, Yann; Tempesta, Camille; Lorscheidt, Stefan; Kettel, Bernadette; Tamaddon, Lana; Jannin, Vincent; Demarne, Frédéric; Lamprecht, Alf; Béduneau, Arnaud

2015-03-15

Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. Copyright © 2015. Published by Elsevier B.V.

Apple extract induces increased epithelial resistance and claudin 4 expression in Caco-2 cells

NARCIS (Netherlands)

Vreeburg, R.A.M.; Wezel, van E.E.; Ocana-Calahorro, F.; Mes, J.J.

2012-01-01

BACKGROUND: The small intestinal epithelium functions both to absorb nutrients, and to provide a barrier between the outside, luminal, world and the human body. One of the passageways across the intestinal epithelium is paracellular diffusion, which is controlled by the properties of tight junction

Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis

International Nuclear Information System (INIS)

Van De Walle, Jacqueline; Sergent, Therese; Piront, Neil; Toussaint, Olivier; Schneider, Yves-Jacques; Larondelle, Yvan

2010-01-01

Deoxynivalenol (DON), one of the most common mycotoxin contaminants of raw and processed cereal food, adversely affects the gastrointestinal tract. Since DON acts as a protein synthesis inhibitor, the constantly renewing intestinal epithelium could be particularly sensitive to DON. We analyzed the toxicological effects of DON on intestinal epithelial protein synthesis and barrier integrity. Differentiated Caco-2 cells, as a widely used model of the human intestinal barrier, were exposed to realistic intestinal concentrations of DON (50, 500 and 5000 ng/ml) during 24 h. DON caused a concentration-dependent decrease in total protein content associated with a reduction in the incorporation of [ 3 H]-leucine, demonstrating its inhibitory effect on protein synthesis. DON simultaneously increased the paracellular permeability of the monolayer as reflected through a decreased transepithelial electrical resistance associated with an increased paracellular flux of the tracer [ 3 H]-mannitol. A concentration-dependent reduction in the expression level of the tight junction constituent claudin-4 was demonstrated by Western blot, which was not due to diminished transcription, increased degradation, or NF-κB, ERK or JNK activation, and was also observed for a tight junction independent protein, i.e. intestinal alkaline phosphatase. These results demonstrate a dual toxicological effect of DON on differentiated Caco-2 cells consisting in an inhibition of protein synthesis as well as an increase in monolayer permeability, and moreover suggest a possible link between them through diminished synthesis of the tight junction constituent claudin-4.

Epithelial Fluid Transport is Due to Electro-osmosis (80%), Plus Osmosis (20%).

Science.gov (United States)

Fischbarg, Jorge; Hernandez, Julio A; Rubashkin, Andrey A; Iserovich, Pavel; Cacace, Veronica I; Kusnier, Carlos F

2017-06-01

Epithelial fluid transport, an important physiological process shrouded in a long-standing enigma, may finally be moving closer to a solution. We propose that, for the corneal endothelium, relative proportions for the driving forces for fluid transport are 80% of paracellular electro-osmosis, and 20% classical transcellular osmosis. These operate in a cyclical process with a period of 9.2 s, which is dictated by the decrease and exhaustion of cellular Na + . Paracellular electro-osmosis is sketched here, and partially discussed as much as the subject still allows; transcellular osmosis is presented at length.

Expression of transcellular and paracellular calcium and magnesium transport proteins in renal and intestinal epithelia during lactation.

Science.gov (United States)

Beggs, Megan R; Appel, Ida; Svenningsen, Per; Skjødt, Karsten; Alexander, R Todd; Dimke, Henrik

2017-09-01

Significant alterations in maternal calcium (Ca 2+ ) and magnesium (Mg 2+ ) balance occur during lactation. Ca 2+ is the primary divalent cation mobilized into breast milk by demineralization of the skeleton and alterations in intestinal and renal Ca 2+ transport. Mg 2+ is also concentrated in breast milk, but the underlying mechanisms are not well understood. To determine the molecular alterations in Ca 2+ and Mg 2+ transport in the intestine and kidney during lactation, three groups of female mice consisting of either nonpregnant controls, lactating mice, or mice undergoing involution were examined. The fractional excretion of Ca 2+ , but not Mg 2+ , rose significantly during lactation. Renal 1-α hydroxylase and 24-OHase mRNA levels increased markedly, as did plasma 1,25 dihydroxyvitamin D levels. This was accompanied by significant increases in intestinal expression of Trpv6 and S100g in lactating mice. However, no alterations in the expression of cation-permeable claudin-2, claudin-12, or claudins-15 were found in the intestine. In the kidney, increased expression of Trpv5 and Calb1 was observed during lactation, while no changes in claudins involved in Ca 2+ and Mg 2+ transport (claudin-2, claudin-14, claudin-16, or claudin-19) were found. Consistent with the mRNA expression, expression of both calbindin-D 28K and transient receptor potential vanilloid 5 (TRPV5) proteins increased. Colonic Trpm6 expression increased during lactation, while renal Trpm6 remained unaltered. In conclusion, proteins involved in transcellular Ca 2+ and Mg 2+ transport pathways increase during lactation, while expression of paracellular transport proteins remained unchanged. Increased fractional Ca 2+ excretion can be explained by vitamin D-dependent intestinal hyperabsorption and bone demineralization, despite enhanced transcellular Ca 2+ uptake by the kidney. Copyright © 2017 the American Physiological Society.

Discerning apical and basolateral properties of HT-29/B6 and IPEC-J2 cell layers by impedance spectroscopy, mathematical modeling and machine learning.

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Thomas Schmid

Full Text Available Quantifying changes in partial resistances of epithelial barriers in vitro is a challenging and time-consuming task in physiology and pathophysiology. Here, we demonstrate that electrical properties of epithelial barriers can be estimated reliably by combining impedance spectroscopy measurements, mathematical modeling and machine learning algorithms. Conventional impedance spectroscopy is often used to estimate epithelial capacitance as well as epithelial and subepithelial resistance. Based on this, the more refined two-path impedance spectroscopy makes it possible to further distinguish transcellular and paracellular resistances. In a next step, transcellular properties may be further divided into their apical and basolateral components. The accuracy of these derived values, however, strongly depends on the accuracy of the initial estimates. To obtain adequate accuracy in estimating subepithelial and epithelial resistance, artificial neural networks were trained to estimate these parameters from model impedance spectra. Spectra that reflect behavior of either HT-29/B6 or IPEC-J2 cells as well as the data scatter intrinsic to the used experimental setup were created computationally. To prove the proposed approach, reliability of the estimations was assessed with both modeled and measured impedance spectra. Transcellular and paracellular resistances obtained by such neural network-enhanced two-path impedance spectroscopy are shown to be sufficiently reliable to derive the underlying apical and basolateral resistances and capacitances. As an exemplary perturbation of pathophysiological importance, the effect of forskolin on the apical resistance of HT-29/B6 cells was quantified.

Spontaneous entropy decrease and its statistical formula

OpenAIRE

Xing, Xiu-San

2007-01-01

Why can the world resist the law of entropy increase and produce self-organizing structure? Does the entropy of an isolated system always only increase and never decrease? Can be thermodymamic degradation and self-organizing evolution united? How to unite? In this paper starting out from nonequilibrium entropy evolution equation we proved that a new entropy decrease could spontaneously emerge in nonequilibrium system with internal attractive interaction. This new entropy decrease coexists wit...

Tight junction proteins contribute to barrier properties in human pleura.

Science.gov (United States)

Markov, Alexander G; Voronkova, Maria A; Volgin, George N; Yablonsky, Piotr K; Fromm, Michael; Amasheh, Salah

2011-03-15

The permeability of pleural mesothelium helps to control the volume and composition of the liquid lubricating pleural surfaces. Information on pleural barrier function in health and disease, however, is scarce. Tissue specimens of human pleura were mounted in Ussing chambers for measurement of transmesothelial resistance. Expression of tight junction (TJ) proteins was studied by Western blots and immune fluorescence confocal microscopy. Both visceral and parietal pleura showed barrier properties represented by transmesothelial resistance. Occludin, claudin-1, -3, -5, and -7, were detected in visceral pleura. In parietal pleura, the same TJ proteins were detected, except claudin-7. In tissues from patients with pleural inflammation these tightening claudins were decreased and in visceral pleura claudin-2, a paracellular channel former, became apparent. We report that barrier function in human pleura coincides with expression of claudins known to be key determinants of epithelial barrier properties. In inflamed tissue, claudin expression indicates a reduced barrier function. Copyright © 2010 Elsevier B.V. All rights reserved.

Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression.

Science.gov (United States)

Lyons, Taylor; Carhart-Harris, Robin L

2018-01-01

Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations. Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian-authoritarian political perspective in patients with treatment-resistant depression (TRD). This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian-authoritarian political perspective in patients with moderate to severe TRD ( n=7) versus age-matched non-treated healthy control subjects ( n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7-12 months after the second dosing session. Nature relatedness and libertarian-authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnaire (PPQ-5), respectively. Nature relatedness significantly increased ( t(6)=-4.242, p=0.003) and authoritarianism significantly decreased ( t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7-12 months post-dosing, nature relatedness remained significantly increased ( t(5)=-2.707, p=0.021) and authoritarianism remained decreased at trend level ( t(5)=-1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects. This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.

Electrical resistivity measurements to predict abrasion resistance of ...

Indian Academy of Sciences (India)

WINTEC

increasing expansion of highway and other construction works and decreasing natural aggregate resources in the world, the demand for crushed stone aggregates has in- creased from day-to-day. One of the important properties of rock aggregates is abrasion resistance. The abrasion resistance of aggregates is generally ...

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....... insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant...

Decrease in effective electron mobility in the channel of a metal-oxide-semiconductor transistor as the gate length is decreased

International Nuclear Information System (INIS)

Frantsuzov, A. A.; Boyarkina, N. I.; Popov, V. P.

2008-01-01

Effective electron mobility μ eff in channels of metal-oxide-semiconductor transistors with a gate length L in the range of 3.8 to 0.34 μm was measured; the transistors were formed on wafers of the silicon-oninsulator type. It was found that μ eff decreases as L is decreased. It is shown that this decrease can be accounted for by the effect of series resistances of the source and drain only if it is assumed that there is a rapid increase in these resistances as the gate voltage is decreased. This assumption is difficult to substantiate. A more realistic model is suggested; this model accounts for the observed decrease in μ eff as L is decreased. The model implies that zones with a mobility lower than that in the middle part of the channel originate at the edges of the gate. An analysis shows that, in this case, the plot of the dependence of 1/μ eff on 1/L should be linear, which is exactly what is observed experimentally. The use of this plot makes it possible to determine both the electron mobility μ 0 in the middle part of the channel and the quantity A that characterizes the zones with lowered mobility at the gate’s edges.

Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance.

Science.gov (United States)

Du, Caiqi; Zhang, Cai; Wu, Wei; Liang, Yan; Wang, Anru; Wu, Shimin; Zhao, Yue; Hou, Ling; Ning, Qin; Luo, Xiaoping

2018-04-25

A novel bioactive peptide, mitochondrial-derived peptide (MOTS-c), has recently attracted attention as a potential prevention or therapeutic option for obesity and type 2 diabetes mellitus (T2DM). MOTS-c profiles have not yet been reported in human obesity and T2DM. We aimed to determine circulating MOTS-c levels in obesity and explore the association between MOTS-c levels and various metabolic parameters. In this case-control study, 40 obese children and adolescents (27 males) and 57 controls (40 males) were recruited in the Hubei Province of China in 2017. Circulating MOTS-c levels were measured, clinical data (e.g., glucose, insulin and lipid profile) were recorded, and anthropometric measurements were performed. Finally, we investigated correlations between MOTS-c levels and related variables. MOTS-c levels were significantly decreased in the obese group compared with the control group (472.61 ± 22.83 ng/mL vs. 561.64 ± 19.19 ng/mL, p c levels were significantly decreased in obese male children and adolescents compared to their counterparts (465.26 ± 24.53 ng/mL vs. 584.07 ± 21.18 ng/mL, p 0.05). Further, MOTS-c levels were negatively correlated with body mass index (BMI), BMI standard deviation score, waist circumference, waist-to-hip ratio, fasting insulin level, HOMA-IR, and HbA1c in the male cohort. Circulating MOTS-c levels were decreased in obese male children and adolescents and correlated with markers of insulin resistance and obesity. This article is protected by copyright. All rights reserved.

Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum

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Verónica Gómez Pérez

2016-08-01

Full Text Available Visceral leishmaniasis (VL caused by the protozoan parasite Leishmania infantum, is one of the most important zoonotic diseases affecting dogs and humans in the Mediterranean area. The presence of infected dogs as the main reservoir host of L. infantum is regarded as the most significant risk for potential human infection. We have studied the susceptibility profile to antimony and other anti-leishmania drugs (amphotericin B, miltefosine, paromomycin in Leishmania infantum isolates extracted from a dog before and after two therapeutic interventions with meglumine antimoniate (subcutaneous Glucantime®, 100 mg/kg/day for 28 days. After the therapeutic intervention, these parasites were significantly less susceptible to antimony than pretreatment isolate, presenting a resistance index of 6-fold to SbIII for promastigotes and >3-fold to SbIII and 3-fold to SbV for intracellular amastigotes. The susceptibility profile of this resistant L. infantum line is related to a decreased antimony uptake due to lower aquaglyceroporin-1 expression levels. Additionally, other mechanisms including an increase in thiols and overexpression of enzymes involved in thiol metabolism, such as ornithine decarboxylase, trypanothione reductase, mitochondrial tryparedoxin and mitochondrial tryparedoxin peroxidase, could contribute to the resistance as antimony detoxification mechanisms. A major contribution of this study in a canine L. infantum isolate is to find an antimony-resistant mechanism similar to that previously described in other human clinical isolates.

Aluminum exposure for one hour decreases vascular reactivity in conductance and resistance arteries in rats

International Nuclear Information System (INIS)

Schmidt, Patrícia Medeiros; Escobar, Alyne Goulart; Torres, João Guilherme Dini; Martinez, Caroline Silveira; Rizzetti, Danize Aparecida; Kunz, Simone Noremberg; Vassallo, Dalton Valentim; Alonso, María Jesús; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra

2016-01-01

Aims: Aluminum (Al) is an important environmental contaminant; however, there are not enough evidences of Al-induced cardiovascular dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl 3 ) on blood pressure, vascular reactivity and oxidative stress. Methods and results: Male Wistar rats were divided into two groups: Untreated: vehicle (ultrapure water, ip) and AlCl 3 : single dose of AlCl 3 (100 mg/kg,ip). Concentration-response curves to phenylephrine in the absence and presence of endothelium, the nitric oxide synthase inhibitor L-NAME, the potassium channel blocker tetraethylammonium, and the NADPH oxidase inhibitor apocynin were performed in segments from aortic and mesenteric resistance arteries. NO released was assessed in aorta and reactive oxygen species (ROS), malondialdehyde, non-protein thiol levels, antioxidant capacity and enzymatic antioxidant activities were investigated in plasma, aorta and/or mesenteric arteries. After one hour of AlCl 3 exposure serum Al levels attained 147.7 ± 25.0 μg/L. Al treatment: 1) did not affect blood pressure, heart rate and vasodilator responses induced by acetylcholine or sodium nitroprusside; 2) decreased phenylephrine-induced vasoconstrictor responses; 3) increased endothelial modulation of contractile responses, NO release and vascular ROS production from NADPH oxidase; 4) increased plasmatic, aortic and mesenteric malondialdehyde and ROS production, and 5) decreased antioxidant capacity and affected the antioxidant biomarkers non-protein thiol levels, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymatic activities. Conclusion: AlCl 3 -acute exposure reduces vascular reactivity. This effect is associated with increased NO production, probably acting on K + channels, which seems to occur as a compensatory mechanism against Al-induced oxidative stress. Our results suggest that Al exerts toxic effects to the vascular system. - Highlights: �

Aluminum exposure for one hour decreases vascular reactivity in conductance and resistance arteries in rats

Energy Technology Data Exchange (ETDEWEB)

Schmidt, Patrícia Medeiros; Escobar, Alyne Goulart; Torres, João Guilherme Dini; Martinez, Caroline Silveira; Rizzetti, Danize Aparecida; Kunz, Simone Noremberg [Postgraduate Program in Biochemistry, Universidade Federal do Pampa, Uruguaiana, Rio Grande do Sul (Brazil); Vassallo, Dalton Valentim [Department of Physiological Sciences, Universidade Federal do Espírito Santo, Espirito Santo (Brazil); Alonso, María Jesús [Department of Basic Health Sciences, Universidad Rey Juan Carlos, Alcorcón (Spain); Peçanha, Franck Maciel [Postgraduate Program in Biochemistry, Universidade Federal do Pampa, Uruguaiana, Rio Grande do Sul (Brazil); Wiggers, Giulia Alessandra, E-mail: giuliawp@gmail.com [Postgraduate Program in Biochemistry, Universidade Federal do Pampa, Uruguaiana, Rio Grande do Sul (Brazil)

2016-12-15

Aims: Aluminum (Al) is an important environmental contaminant; however, there are not enough evidences of Al-induced cardiovascular dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl{sub 3}) on blood pressure, vascular reactivity and oxidative stress. Methods and results: Male Wistar rats were divided into two groups: Untreated: vehicle (ultrapure water, ip) and AlCl{sub 3}: single dose of AlCl{sub 3} (100 mg/kg,ip). Concentration-response curves to phenylephrine in the absence and presence of endothelium, the nitric oxide synthase inhibitor L-NAME, the potassium channel blocker tetraethylammonium, and the NADPH oxidase inhibitor apocynin were performed in segments from aortic and mesenteric resistance arteries. NO released was assessed in aorta and reactive oxygen species (ROS), malondialdehyde, non-protein thiol levels, antioxidant capacity and enzymatic antioxidant activities were investigated in plasma, aorta and/or mesenteric arteries. After one hour of AlCl{sub 3} exposure serum Al levels attained 147.7 ± 25.0 μg/L. Al treatment: 1) did not affect blood pressure, heart rate and vasodilator responses induced by acetylcholine or sodium nitroprusside; 2) decreased phenylephrine-induced vasoconstrictor responses; 3) increased endothelial modulation of contractile responses, NO release and vascular ROS production from NADPH oxidase; 4) increased plasmatic, aortic and mesenteric malondialdehyde and ROS production, and 5) decreased antioxidant capacity and affected the antioxidant biomarkers non-protein thiol levels, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymatic activities. Conclusion: AlCl{sub 3}-acute exposure reduces vascular reactivity. This effect is associated with increased NO production, probably acting on K{sup +} channels, which seems to occur as a compensatory mechanism against Al-induced oxidative stress. Our results suggest that Al exerts toxic effects to the vascular

Mild Caloric Restriction Decreases Insulin Requirements in Patients With Type 2 Diabetes and Severe Insulin Resistance.

Science.gov (United States)

Meehan, Cristina Adelia; Cochran, Elaine; Mattingly, Megan; Gorden, Phillip; Brown, Rebecca J

2015-07-01

Type 2 diabetes (T2D) affects ~10% of the US population, a subset of whom have severe insulin resistance (SIR) (>200 units/d). Treatment of these patients with high-dose insulin presents logistical and compliance challenges. We hypothesized that mild caloric restriction would reduce insulin requirements in patients with T2D and SIR.This was a retrospective study at the National Institutes of Health Clinical Center. Inclusion criteria were as follows: T2D, and insulin dose >200 units/d or >2 units/kg/d. The intervention consisted of mild caloric restriction during a 3 to 6-day hospitalization. The major outcomes were change in insulin dose and blood glucose from admission to discharge.Ten patients met inclusion criteria. Baseline glycated hemoglobin A1c was 10.0 ± 1.6% and body mass index 38.8 ± 9.0 kg/m. Food intake was restricted from 2210 ± 371 kcal/d preadmission to 1810 ± 202 during the hospital stay (16.5% reduction). Insulin dose decreased from 486 ± 291 units/d preadmission to 223 ± 127 at discharge (44% reduction, P = 0.0025). Blood sugars decreased nonsignificantly in the fasting state (from 184 ± 85 to 141 ± 42, P = 0.20), before lunch (239 ± 68 to 180 ± 76, P = 0.057), and at bedtime (212 ± 95 to 176 ± 48, P = 0.19), and significantly decreased before dinner (222 ± 92 to 162 ± 70, P = 0.016).Mild caloric restriction, an accessible and affordable intervention, substantially reduced insulin doses in patients with T2D and SIR. Further studies are needed to determine if the intervention and results are sustainable outside of a hospital setting.

Isolation and Biochemical Characterization of Apios Tuber Lectin

Directory of Open Access Journals (Sweden)

Eri Kenmochi

2015-01-01

Full Text Available Apios tuber lectin, named ATL, was isolated from Apios americana Medikus by two chromatography steps, hydrophobic chromatography and anion-exchange chromatography. The minimum concentration required for the hemagglutination activity toward rabbit erythrocytes of ATL was 4 μg/mL. ATL was composed of a homodimer of 28.4 kDa subunits. The amino acid sequence of ATL was similar to those of other legume lectins. The lectin showed moderate stability toward heating and acidic pH, and the binding affinity against several monosaccharides, such as D-glucosamine and D-galactosamine. ATL also bound to desialylated or agalactosylated glycoproteins such as asialo and agalacto transferrin. ATL decreased the transepithelial electrical resistance across human intestinal Caco-2 cell monolayers, suggesting the effect on the tight junction-mediated paracellular transport.

Experimental Studies on the Changes in Resistivity and Its Anisotropy Using Electrical Resistivity Tomography

Directory of Open Access Journals (Sweden)

Tao Zhu

2012-01-01

Full Text Available Three measuring lines were arranged on one of free planes of magnetite cuboid samples. Apparent resistivity data were acquired by MIR-2007 resistivity meter when samples were under uniaxial compression of servocontrol YAW-5000F loadingmachine in laboratory. Then we constructed the residual resistivity images using electrical resistivity tomography (ERT and plotted the diagrams of apparent resistivity anisotropy coefficient (ARAC λ∗ and the included angle α between the major axis of apparent resistivity anisotropy ellipse and the axis of load with pressure and effective depth. Our results show that with increasing pressure, resistivity and the decreased (D region and increased (I region resistivity regions have complex behaviors, but when pressure is higher than a certain value, the average resistivity decrease and the area of D region expand gradually in all time with the increase of pressure, which may be significant to the monitoring and prediction of earthquake, volcanic activities, and large-scale geologic motions. The effects of pressure on λ∗ and α are not very outstanding for dry magnetite samples.

Adriamycin resistance, heat resistance and radiation response in Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Wallner, K.; Li, G.

1985-01-01

Previous investigators have demonstrated synergistic interaction between hyperthermia and radiation or Adriamycin (ADR), using cell lines that are sensitive to heat or ADR alone. The authors investigated the effect of heat, radiation or ADR on Chinese hamster fibroblasts (HA-1), their heat resistant variants and their ADR resistant variants. Heat for ADR resistance did not confer cross resistance to radiation. Cells resistant to heat did show cross resistance to ADR. While cells selected for ADR resistance were not cross resistant to heat, they did not exhibit drug potentiation by hyperthermia, characteristic of ADR sensitive cells. Cytofluorometric measurement showed decreased ADR uptake in both heat and ADR resistant cells. The possibility of cross resistance between heat and ADR should be considered when designing combined modality trials

Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29

International Nuclear Information System (INIS)

Jeong, Chang Hee; Seok, Jin Sil; Petriello, Michael C.; Han, Sung Gu

2017-01-01

Arsenic is a naturally occurring metalloid that often is found in foods and drinking water. Human exposure to arsenic is associated with the development of gastrointestinal problems such as fluid loss, diarrhea and gastritis. Arsenic is also known to induce toxic responses including oxidative stress in cells of the gastrointestinal track. Tight junctions (TJs) regulate paracellular permeability and play a barrier role by inhibiting the movement of water, solutes and microorganisms in the paracellular space. Since oxidative stress and TJ damage are known to be associated, we examined whether arsenic produces TJ damage such as downregulation of claudins in the human colorectal cell line, HT-29. To confirm the importance of oxidative stress in arsenic-induced TJ damage, effects of the antioxidant compound (e.g., N-acetylcysteine (NAC)) were also determined in cells. HT-29 cells were treated with arsenic trioxide (40 μM, 12 h) to observe the modified expression of TJ proteins. Arsenic decreased expression of TJ proteins (i.e., claudin-1 and claudin-5) and transepithelial electrical resistance (TEER) whereas pretreatment of NAC (5–10 mM, 1 h) attenuated the observed claudins downregulation and TEER. Arsenic treatment produced cellular oxidative stress via superoxide generation and lowering glutathione (GSH) levels, while NAC restored cellular GSH levels and decreased oxidative stress. Arsenic increased phosphorylation of p38 and nuclear translocation of nuclear factor-kappa B (NF-κB) p65, while NAC attenuated these intracellular events. Results demonstrated that arsenic can damage intestinal epithelial cells by proinflammatory process (oxidative stress, p38 and NF-κB) which resulted in the downregulation of claudins and NAC can protect intestinal TJs from arsenic toxicity.

Further characterization of porcine Brachyspira hyodysenteriae isolates with decreased susceptibility to tiamulin.

Science.gov (United States)

Karlsson, M; Aspán, A; Landén, A; Franklin, A

2004-04-01

Brachyspira hyodysenteriae is the causative agent of swine dysentery, a severe diarrhoeal disease in pigs. Few drugs are available to treat the disease, owing to both antimicrobial resistance and withdrawal of drugs authorized for use in pigs. Tiamulin is the drug of choice in many countries, but isolates with decreased susceptibility have recently been reported. The mechanism of tiamulin resistance in B. hyodysenteriae is not known and this facet is essential to understand the dissemination of the trait. To study the resistance epidemiology of B. hyodysenteriae, further characterization of a set of isolates from Germany (n = 16) and the UK (n = 6) with decreased susceptibility to tiamulin was performed. The relatedness between the isolates was studied by comparing PFGE patterns, and the in vitro susceptibility to five other antimicrobials (aivlosin, doxycycline, salinomycin, chloramphenicol and avilamycin) was also determined. For comparison of the antimicrobial-susceptibility pattern, Swedish (n = 20) and British (n = 4) tiamulin-susceptible isolates were tested. The German isolates represented several different PFGE patterns, indicating that tiamulin usage has been sufficient to select clones with decreased tiamulin susceptibility at different farms in Germany. The PFGE pattern for the six British isolates with decreased tiamulin susceptibility was identical to that of the German isolates, and they had a similar antimicrobial-susceptibility pattern, except for resistance to aivlosin, which was only found in a few German isolates. No other co-resistance with tiamulin was found.

Decrease of fear avoidance beliefs following person-centered progressive resistance exercise contributes to reduced pain disability in women with fibromyalgia: secondary exploratory analyses from a randomized controlled trial.

Science.gov (United States)

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

2016-05-21

Fibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Women with FM also report disability, in terms of negative consequences on activities of daily living. Our recent randomized controlled trial (RCT) is the first study of resistance exercise to show positive effects on pain disability. The resistance exercise program of our RCT emphasized active involvement of participants in planning and progression of the exercise, using the principles of person-centeredness, to support each participant's ability to manage the exercise and the progress of it. The aim of this sub-study was to investigate explanatory factors for reduced pain disability in women with FM participating in a 15-week person-centered progressive resistance exercise program. A total of 67 women with FM were included in this sub-study of an RCT examining the effects of person-centered progressive resistance exercise performed twice a week for 15 weeks. Tests of physical capacity and health-related questionnaires were assessed at baseline and after the intervention period. Multivariable stepwise regression was used to analyze explanatory factors for improvements in pain disability. Reduced pain disability was explained by higher pain disability at baseline together with decreased fear avoidance beliefs about physical activity (R (2) = 28, p = 0.005). The improvements in the disability domains of recreation and social activity were explained by decreased fear avoidance beliefs about physical activity together with higher baseline values of each disability domain respectively (R (2) = 32, p = 0.025 and R (2) = 30, p = 0.017). The improvement in occupational disability was explained by higher baseline values of occupational disability (R (2) = 19, p = 0.001). The person-centered resistance exercise intervention, based on principles of self-efficacy, had a positive effect on recreational, social and occupational disability

Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people

DEFF Research Database (Denmark)

Fabre, Odile Martine Julie; Breuker, C; Amouzou, C

2014-01-01

Obesity is associated with chronic low-grade inflammation and oxidative stress that blunt insulin response in its target tissues, leading to insulin resistance (IR). IR is a characteristic feature of type 2 diabetes. Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake...... with palmitate, a saturated free fatty acid (FFA) known to induce inflammation and oxidative stress via TLR4 activation. While RNase L and RLI levels remained unchanged, OAS level was decreased in primary myotubes from insulin-resistant obese subjects (OB-IR) compared with myotubes from insulin-sensitive obese......; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Interestingly, some obese people stay insulin-sensitive and metabolically healthy. With the aim of understanding this difference and identifying the mechanisms responsible for insulin sensitivity maintenance...

Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity.

Science.gov (United States)

Paramsothy, Pathmaja; Knopp, Robert H; Kahn, Steven E; Retzlaff, Barbara M; Fish, Brian; Ma, Lina; Ostlund, Richard E

2011-11-01

The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. Plasma sterols were measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (S(I)) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol-cholesterol ratios were as follows: LIS > OIR (P LIR (P OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS sterol concentrations were positively associated with S(I) and negatively associated with obesity, whereas lathosterol correlations were the opposite. Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I) and to decrease cholesterol overproduction in LIR and OIR persons.

Investigation and Treatment of Fusidic Acid Resistance Among Methicillin-Resistant Staphylococcal Isolates from Egypt.

Science.gov (United States)

Abouelfetouh, Alaa; Kassem, Mervat; Naguib, Marwa; El-Nakeeb, Moustafa

2017-01-01

Methicillin resistance among staphylococci isolated from patients in northern Egypt has escalated alarmingly in the past decade. Data about the prevalence of fusidic acid (FA) resistance in Egyptian clinical isolates are limited. This work investigates the prevalence and mechanism of FA resistance among 81 methicillin-resistant staphylococcal isolates from major hospitals of Alexandria, Egypt. Some combinations for treating infections due to resistant isolates were studied. Twenty-six isolates (32.1%) were FA resistant (minimum inhibitory concentrations [MICs] = 2-1,024 μg/ml), and fusB and fusC genes coding for FA resistance were detected in 30.77% and 34.62% of the FA-resistant strains, respectively. One highly resistant isolate, S502 (MIC = 1,024 μg/ml), possessed both genes. Plasmid curing resulted in fusB loss and MIC decrease by 16-64 folds. Conjugation caused acquisition of FA resistance among susceptible isolates. Serial passages in subinhibitory FA concentrations produced mutants with increased MIC by 4-32 folds. The combination of FA with rifampin, gentamicin, or ampicillin/sulbactam, in a subinhibitory concentration, was synergistic against the isolates, including serial passage mutants, decreasing number of survivors by an average of 2-4 logs. A relatively moderate rate of FA resistance was detected in Alexandria hospitals. Combination therapy with gentamicin, rifampin, or ampicillin/sulbactam is crucial to preserve the effectiveness of FA.

Trends in darunavir resistance-associated mutations and phenotypic resistance in commercially tested United States clinical samples between 2006 and 2012.

Science.gov (United States)

Lathouwers, Erkki; Gupta, Soumi; Haddad, Mojgan; Paquet, Agnes; de Meyer, Sandra; Baugh, Bryan

2015-06-01

HIV-1 samples submitted by clinicians from the United States for routine drug susceptibility testing (PhenoSense GT) were evaluated for genotypic and phenotypic resistance to darunavir and other protease inhibitors (PIs). Among these samples (Monogram Biosciences database January 2006-June 2012; N=78,843), isolates harboring zero IAS-USA darunavir resistance-associated mutations (RAMs) increased from 77.7% in 2006 to 92.8% through the first half of 2012 (H1 2012; upward trend, p=0.0008); a downward trend seen for samples with three or more darunavir RAMs (7.5% in 2006 and 2.6% in H1 2012; p=0.002). Among samples with any PI resistance (N=15,932), samples harboring zero darunavir RAMs gradually increased (39.9% in 2006 vs. 55.0% in H1 2012; upward trend, p=0.005), but three or more darunavir RAMs did not change over time (21.7% in 2006 and 19.2% in H1 2012; p=0.27). During this period, the frequency of the 11 individual darunavir RAMs (IAS-USA 2011 list) decreased among all samples. The frequency of each darunavir RAM in PI-resistant samples decreased or remained relatively stable. The prevalence of samples with phenotypic resistance to darunavir (partial-to-full) decreased over time in all samples (8.2% in 2006 vs. 2.3% in H1 2012), as did resistance to other PIs (p<0.006 for all PIs). Phenotypic resistance to darunavir and other PIs also decreased in PI-resistant samples (darunavir: 23.9% in 2006 vs. 17.1% in H1 2012; p<0.013 for all PIs). Since approval of darunavir in 2006, there was a significant decrease in prevalence of samples with genotypic and phenotypic resistance to darunavir in commercially tested HIV-1 isolates. Furthermore, the prevalence of phenotypic resistance to darunavir was lower than all other PIs.

Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.

Science.gov (United States)

Chen, Lin; Cao, Zhao-long; Han, Fang; Gao, Zhan-cheng; He, Quan-ying

2010-02-20

The persistence of sleep disordered breathing (SDB) symptoms after tonsil and/or adenoid (T&A) surgery are common in children with obstructive sleep apnea (OSA). We tested the hypothesis that disturbances of glucose transporters (GLUTs) in intraabdominal adipose tissue caused by chronic intermittent hypoxia (CIH) from the pedo-period could facilitate the appearance of periphery insulin resistance in Sprague-Dawley (SD) rats. We tested the hypothesis that the changes of GLUTs in adipose tissue may be one of the reasons for persistent SDB among clinical OSA children after T&A surgery. Thirty 21-day-old SD rats were randomly divided into a CIH group, a chronic continuous hypoxia (CCH) group, and a normal oxygen group (control group) and exposed for 40 days. The changes of weight, fasting blood glucose and fasting blood insulin levels were measured. Hyperinsulinemic-euglycemic clamp techniques were used to measure insulin resistance in each animal. Real-time quantitative PCR and Western blotting were used to measure GLUT mRNA and proteins in intraabdominal adipose tissue. Additional intraabdomial white adipose tissue (WAT) was also processed into paraffin sections and directly observed for GLUTs1-4 expression. When compared with control group, CIH increased blood fasting insulin levels, (245.07 +/- 53.89) pg/ml vs. (168.63 +/- 38.70) pg/ml, P = 0.038, and decreased the mean glucose infusion rate (GIR), (7.25 +/- 1.29) mg x kg(-1) x min(-1) vs. (13.34 +/- 1.54) mg x kg(-1) x min(-1), P < 0.001. GLUT-4 mRNA and protein expression was significantly reduced after CIH compared with CCH or normal oxygen rats, 0.002 +/- 0.002 vs. 0.039 +/- 0.009, P < 0.001; 0.642 +/- 0.073 vs. 1.000 +/- 0.103, P = 0.035. CIH in young rats could induce insulin resistance via adverse effects on glycometabolism. These findings emphasize the importance of early detection and treatment of insulin insensitivity in obese childhood OSA.

Facile fabrication of carbon brush with reduced graphene oxide (rGO) for decreasing resistance and accelerating pollutants removal in bio-electrochemical systems.

Science.gov (United States)

Cui, Dan; Yang, Li-Ming; Liu, Wen-Zong; Cui, Min-Hua; Cai, Wei-Wei; Wang, Ai-Jie

2018-07-15

Low electrode resistance is crucial for achieving efficient reactions in bio-electrochemical system (BES), especially considering the factors of BES scaling-up and microbial effects. Graphene has revealed a cornucopia of potential applications due to its high conductivity and extraordinary electrochemical properties. Here, significant reduction of electrode resistance and increment of electrochemical activity were achieved by fabricating the three-dimensional carbon brush using reduced graphene oxide (rGO/carbon brush) through one-step electro-deposition without any binder. The rGO/carbon brush was employed as cathode in BES equipped with bio-anode for azo compound (AO7) removal. The charge transfer resistances of cathode part and whole cell were decreased by 89% and 65%, respectively. The reactor showed quickly start-up within 48 h with peak cycle current six fold increase relative to the control. AO7 decolorization efficiency reached 91.1 ± 0.1% at 4 h and 97.6 ± 0.4% at 6 h. Effective decolorization of AO7 was at rate up to 650.7 g AO7/m 3 ·h. The results indicated that the advantages of graphene and three-dimensional carbon brush successfully improved the overall performance of BES and enhanced refractory pollutants removal when applied to specific wastewater. Copyright © 2018 Elsevier B.V. All rights reserved.

Decrease of insecticide resistance over generations without exposure to insecticides in Nilaparvata lugens (Hemipteran: Delphacidae).

Science.gov (United States)

Yang, Yajun; Dong, Biqin; Xu, Hongxing; Zheng, Xusong; Tian, Junce; Heong, Kongleun; Lu, Zhongxian

2014-08-01

The brown planthopper, Nilaparvata lugens (Stål), is one of the most important insect pests on paddy rice in tropical and temperate Asia. Overuse and misuse of insecticides have resulted in the development of high resistance to many different insecticides in this pest. Studies were conducted to evaluate the change of resistance level to four insecticides over 15 generations without any exposure to insecticides in brown planthopper. After 15 generations' rearing without exposure to insecticide, brown planthopper could reverse the resistance to imidacloprid, chlorpyrifos, fipronil, and fenobucarb. The range and style of resistance reversal of brown planthopper differed when treated with four different insecticides. To monitor potential changes in insect physiological responses, we measured the activity of each of the three selected enzymes, including acetylcholinesterases (AChE), general esterases (EST), and glutathione S-transferases. After multiple generations' rearing without exposure to insecticide, AChE and EST activities of brown planthopper declined with the increased generations, suggesting that the brown planthopper population adjusted activities of EST and AChE to adapt to the non-insecticide environment. These findings suggest that the reducing, temporary stop, or rotation of insecticide application could be incorporated into the brown planthopper management.

A decrease in ubiquitination and resulting prolonged life-span of KIT underlies the KIT overexpression-mediated imatinib resistance of KIT mutation-driven canine mast cell tumor cells.

Science.gov (United States)

Kobayashi, Masato; Kuroki, Shiori; Kurita, Sena; Miyamoto, Ryo; Tani, Hiroyuki; Tamura, Kyoichi; Bonkobara, Makoto

2017-10-01

Overexpression of KIT is one of the mechanisms that contributes to imatinib resistance in KIT mutation-driven tumors. Here, the mechanism underlying this overexpression of KIT was investigated using an imatinib-sensitive canine mast cell tumor (MCT) line CoMS, which has an activating mutation in KIT exon 11. A KIT-overexpressing imatinib-resistant subline, rCoMS1, was generated from CoMS cells by their continuous exposure to increasing concentrations of imatinib. Neither a secondary mutation nor upregulated transcription of KIT was detected in rCoMS1 cells. A decrease in KIT ubiquitination, a prolonged KIT life-span, and KIT overexpression were found in rCoMS1 cells. These events were suppressed by withdrawal of imatinib and were re-induced by re‑treatment with imatinib. These findings suggest that imatinib elicited overexpression of KIT via suppression of its ubiquitination. These results also indicated that imatinib-induced overexpression of KIT in rCoMS1 cells was not a permanently acquired feature but was a reversible response of the cells. Moreover, the pan deubiquitinating enzyme inhibitor PR619 prevented imatinib induction of KIT overexpression, suggesting that the imatinib-induced decrease in KIT ubiquitination could be mediated by upregulation and/or activation of deubiquitinating enzyme(s). It may be possible that a similar mechanism of KIT overexpression underlies the acquisition of imatinib resistance in some human tumors that are driven by KIT mutation.

Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity1234

Science.gov (United States)

Knopp, Robert H; Kahn, Steven E; Retzlaff, Barbara M; Fish, Brian; Ma, Lina; Ostlund, Richard E

2011-01-01

Background: The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. Objective: We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. Design: Plasma sterols were measured by gas chromatography–mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (SI) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. Results: The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol–cholesterol ratios were as follows: LIS > OIR (P LIR (P OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS sterol concentrations were positively associated with SI and negatively associated with obesity, whereas lathosterol correlations were the opposite. Conclusions: Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve SI and to decrease cholesterol overproduction in LIR and OIR persons. PMID:21940599

Mutants of Venturia ineaqualis (Cook) Wint. apple scar resistant to fungicides

International Nuclear Information System (INIS)

Bedianashvili, Ts.V.; D'yakov, Yu.T.

1987-01-01

Mutants of apple scab resistant to zineb and bayleton fungicides have been obtained upon action of UV irradiation and nitrosome-thylurea. Using tetrade analysis, two zineb resistence genes have been found. The mutations are pleiotropic and lead to increase in resistance to other fungicides, decrease in growth rate on artificial media, increase in spore size, sporulation, and aggressiveness, decrease in competitiveness at in vitro growth. The resistance is supposed to be determined by decrease in membrane permeability for fungicides

Copper Contamination Impairs Herbivore Initiation of Seaweed Inducible Defenses and Decreases Their Effectiveness.

Directory of Open Access Journals (Sweden)

Alexandria M Warneke

Full Text Available Seaweed-herbivore interactions are often mediated by environmental conditions, yet the roles of emerging anthropogenic stressors on these interactions are poorly understood. For example, chemical contaminants have unknown consequences on seaweed inducible resistance and herbivore response to these defenses despite known deleterious effects of contaminants on animal inducible defenses. Here, we investigated the effect of copper contamination on the interactions between a snail herbivore and a brown seaweed that displays inducible resistance to grazing. We examined seaweed inducible resistance and its effectiveness for organisms exposed to copper at two time points, either during induction or after herbivores had already induced seaweed defenses. Under ambient conditions, non-grazed tissues were more palatable than grazed tissues. However, copper additions negated the preference for non-grazed tissues regardless of the timing of copper exposure, suggesting that copper decreased both how herbivores initiated these inducible defenses and their subsequent effectiveness. Copper decreased stimulation of defenses, at least in part, by suppressing snail grazing pressure-the cue that turns inducible defenses on. Copper decreased effectiveness of defenses by preventing snails from preferentially consuming non-grazed seaweed. Thus, contaminants can potentially stress communities by changing seaweed-herbivore interactions mediated via inducible defenses. Given the ubiquity of seaweed inducible resistance and their potential influence on herbivores, we hypothesize that copper contamination may change the impact of these resistant traits on herbivores.

Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

Science.gov (United States)

Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

2017-07-20

Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

Managing Instructor Cyberanxiety: The Role of Self-Efficacy in Decreasing Resistance to Change.

Science.gov (United States)

George, Gerard; Camarata, M. R.

1996-01-01

Discussion of educational technology innovations focuses on some of the behavioral challenges facing the drive toward multimedia instruction and suggests a method by which instructor resistance to technological change can be lessened or eliminated based on the concept of self-efficacy. A typology of instructors is explained. (Author/LRW)

Decrease in back strength in asymmetric trunk postures

NARCIS (Netherlands)

Vink, P.; Daanen, H. A M; Meijst, W. J.; Ligteringen, J.

1992-01-01

The extension force against resistance was recorded in 23 postures for 12 subjects to find explanations for the decrease in back strength in asymmetric postures. A reduction in muscle force in asymmetric postures was found up to 40%, but was strongly dependent on the plane in which asymmetry

Acibenzolar-S-methyl induces lettuce resistance against ...

African Journals Online (AJOL)

... contributing to the enhancement of plant resistance. The effect was comparable with copper treatment. As a marker of resistance, PR protein activity chitinase showed remarkable increase, depending on decreasing bacterial growth in planta. Key words: Acibenzolar-S-methyl, induced resistance, Xanthomonas campestris ...

Comparison between lactulose/mannitol and 51Cr-ethylenediaminetetraacetic acid/14C-mannitol methods for intestinal permeability

International Nuclear Information System (INIS)

Blomquist, L.; Bark, T.; Hedenborg, G.; Svenberg, T.; Norman, A.

1993-01-01

Urinary excretion of lactulose and mannitol, determined by gas-liquid chromatography, was compared with that of 51 Cr-ethylenediaminetetraacetic acid (EDTA) and 14 C-mannitol for measurement of intestinal permeability in 28 healthy humans. The 0- to 6-h excretion values for unlabelled and labelled mannitol (marker of transcellular permeability) were normally distributed, whereas excretion values for lactulose and 51 Cr-EDTA (markers of paracellular permeability) were shewly distributed, as were the lactulose to mannitol and 51 Cr-EDTA to 14 C-mannitol ratios. Excretion of the transcellular markers, but not of the paracullular markers was significantly correlated to urinary volume; correction for urinary volume resulted in decreased test variability. Significant correlation was found between lactulose and 51 Cr-EDTA excretion and between mannitol and 14 C-mannitol excretion, but not between the lactulose to mannitol and 51 Cr-EDTA to 14 C-mannitol ratios. Inter- and intraindividual test variability was greater for each chemically determined marker than for the corresponding isotope-labelled marker. Similarly, variability was greater for each paracellular marker than for the corresponding transcellular marker and for each paracellular/transcellular marker ratio, than for the transcellular marker alone. Variability of mannitol excretion was increased by the frequent presence of food-derived mannitol in the urine. 23 refs., 5 figs., 2 tabs

Emergence of resistant pathogens against colistin

OpenAIRE

Rakesh Kumar; Baljit Jassal; Bhupinder Kumar

2015-01-01

Emergence of resistant strain to antimicrobials is a growing problem worldwide. Here, we report a case of multidrug-resistant Klebsiella pneumoniae and Acinectobacter baumannii, Gram-negative bacilli, which was only intermediate sensitive to colistin; a polymyxin E. Colistin has attracted more interest recently because of its significant activity against multi-resistant Pseudomonas aeruginosa, A. baumannii and K. pneumoniae, and the low resistance rates to it. The decrease in sensitivity of c...

Resistance exercise performed with repetitions until failure affects nocturnal blood pressure decreases in hypertensive women

Directory of Open Access Journals (Sweden)

Marilia de Almeida Correia

2015-12-01

Full Text Available Studies have shown that resistance exercise reduces 24-hour blood pressure to levels below resting values, although this is not a universal finding. The number of repetitions has been shown to influence this response. Thus, the aim of the study was to analyze the effects of resistance exercise performed until failure (UF on 24-hour blood pressure in hypertensive women. Thirteen hypertensive women underwent three experimental sessions in random order: UF, resistance exercise with repetitions before concentric failure (BF and control (C. Prior to and up to 24 hours after the sessions, cardiovascular variables, as well as the nocturnal fall in blood pressure, the morning surge, and the presence or absence of a blood pressure dip pattern were established using an ambulatory blood pressure monitor. In both wakefulness and sleep there was no significant difference among the three groups. However, after UF and C fewer patients presented a dip in blood pressure (46% and 38%, respectively compared BF (77%, p=0.047. In conclusion, the UF attenuated blood pressure dips at night in hypertensive patients.

Altered membrane permeability in multidrug resistant Escherichia ...

African Journals Online (AJOL)

PRECIOUS

2009-11-02

Nov 2, 2009 ... involvement during the transport of β - lactams in multidrug resistant Escherichia coli isolated from extra-intestinal infections. Also, the ... lactam resistance in multidrug resistant E. coli in ESBL and non-ESBL isolates. .... and decreased susceptibility to carbapenems, particularly ertapenem (Perez et al.,.

Up-Regulation of MicroRNA-190b Plays a Role for Decreased IGF-1 That Induces Insulin Resistance in Human Hepatocellular Carcinoma

Science.gov (United States)

Hung, Tzu-Min; Ho, Cheng-Maw; Liu, Yen-Chun; Lee, Jia-Ling; Liao, Yow-Rong; Wu, Yao-Ming; Ho, Ming-Chih; Chen, Chien-Hung; Lai, Hong-Shiee; Lee, Po-Huang

2014-01-01

Background & Aims Insulin-like growth factor, (IGF)-1, is produced mainly by the liver and plays important roles in promoting growth and regulating metabolism. Previous study reported that development of hepatocellular carcinoma (HCC) was accompanied by a significant reduction in serum IGF-1 levels. Here, we hypothesized that dysregulation of microRNAs (miRNA) in HCC can modulate IGF-1 expression post-transcriptionally. Methods The miRNAs expression profiles in a dataset of 29 HCC patients were examined using illumina BeadArray. Specific miRNA (miR)-190b, which was significantly up-regulated in HCC tumor tissues when compared with paired non-tumor tissues, was among those predicted to interact with 3′-untranslated region (UTR) of IGF-1. In order to explore the regulatory effects of miR-190b on IGF-1 expression, luciferase reporter assay, quantitative real-time PCR, western blotting and immunofluorecence analysis were performed in HCC cells. Results Overexpression of miR-190b in Huh7 cells attenuated the expression of IGF-1, whereas inhibition of miR-190b resulted in up-regulation of IGF-1. Restoration of IGF-1 expression reversed miR-190b-mediated impaired insulin signaling in Huh7 cells, supporting that IGF-1 was a direct and functional target of miR-190b. Additionally, low serum IGF-1 level was associated with insulin resistance and poor overall survival in HCC patients. Conclusions Increased expression of miR-190 may cause decreased IGF-1 in HCC development. Insulin resistance appears to be a part of the physiopathologic significance of decreased IGF-1 levels in HCC progression. This study provides a novel miRNA-mediated regulatory mechanism for controlling IGF-1 expression in HCC and elucidates the biological relevance of this interaction in HCC. PMID:24586785

Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

OpenAIRE

Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

2016-01-01

In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxi...

Adriamycin resistance and radiation response

International Nuclear Information System (INIS)

Belli, J.A.; Harris, J.R.

1979-01-01

Mammalian cells (V79) in culture developed resistance to Adriamycin during continuous exposure to low levels of drug. This resistance was accompanied by change in x-ray survival properties which, in turn, depended upon the isolation of subpopulations from resistant sub lines. These changes in x-ray survival properties were characterized by reduced D/sub Q/ values and a decrease in the D/sub O/. However, these changes were not observed together in the same cell sub line. Adriamycin-resistant cells did not appear to be radiation damage repair deficient. Other phenotypic changes (cell morphology, DNA content and chromosome number) suggested mutational events coincident with the development of Adriamycin resistance

Curious resistivity behaviour of vacuum evaporated Er, Dy and Gd films

International Nuclear Information System (INIS)

Saxena, U.; Kaul, V.K.; Bist, B.M.; Srivastava, O.N.

1976-01-01

The thickness dependence of electrical resistivity of Er, Dy and Gd thin films at room temperature has been studied. The electrical resistivity of these films does not show the usual behaviour expected on the basis of the size affected conduction i.e. Fuchs Sondheimer theory, which always leads to an increase in the resistivity with decreasing film thickness. Instead, the observed resistivity behaviour is characterised mainly by (i) a decrease in resistivity with decreasing film thickness (between 1600-1000 deg A) for Er films and below about 500 deg A for Gd and Dy films), (ii) a thickness independent resistivity behaviour for Er films from 1000-600 deg A, (iii) increase in resistivity of Er films in the thickness region 600-200 deg A, (iv) the resistivity values in certain thickness regions, which are even less than the corresponding bulk value. Analysis reveals that those curious rho-t characteristics arise due to three effects namely, the increase resistivity due to surface scattering the suppression of resistivity due to thickness dependence of structural phase and spin disorder scattering. All the effects are dominant in thickness regions, different in different metals giving rise to the observed characteristics. (author)

Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model.

Science.gov (United States)

Ling, Xiang; Linglong, Peng; Weixia, Du; Hong, Wei

2016-01-01

Zonulin protein is a newly discovered modulator which modulates the permeability of the intestinal epithelial barrier by disassembling intercellular tight junctions (TJ). Disruption of TJ is associated with neonatal necrotizing enterocolitis (NEC). It has been shown bifidobacterium could protect the intestinal barrier function and prophylactical administration of bifidobacterium has beneficial effects in NEC patients and animals. However, it is still unknown whether the zonulin is involved in the gut barrier dysfunction of NEC, and the protective mechanisms of bifidobacterium on intestinal barrier function are also not well understood. The present study aims to investigate the effects of bifidobacterium on intestinal barrier function, zonulin regulation, and TJ integrity both in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. Our results showed bifidobacterium markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS (P zonulin release (P zonulin (P zonulin protein release and improvement of intestinal TJ integrity.

Effect of cAMP derivates on assembly and maintenance of tight junctions in human umbilical vein endothelial cells

Directory of Open Access Journals (Sweden)

Beese Michaela

2010-09-01

Full Text Available Abstract Background Endothelial tight and adherens junctions control a variety of physiological processes like adhesion, paracellular transport of solutes or trafficking of activated leukocytes. Formation and maintenance of endothelial junctions largely depend on the microenvironment of the specific vascular bed and on interactions of the endothelium with adjacent cell types. Consequently, primary cultures of endothelial cells often lose their specific junctional pattern and fail to establish tight monolayer in vitro. This is also true for endothelial cells isolated from the vein of human umbilical cords (HUVEC which are widely used as model for endothelial cell-related studies. Results We here compared the effect of cyclic 3'-5'-adenosine monophosphate (cAMP and its derivates on formation and stabilization of tight junctions and on alterations in paracellular permeability in HUVEC. We demonstrated by light and confocal laser microscopy that for shorter time periods the sodium salt of 8-bromoadenosine-cAMP (8-Br-cAMP/Na and for longer incubation periods 8-(4-chlorophenylthio-cAMP (pCPT-cAMP exerted the greatest effects of all compounds tested here on formation of continuous tight junction strands in HUVEC. We further demonstrated that although all compounds induced protein kinase A-dependent expression of the tight junction proteins claudin-5 and occludin only pCPT-cAMP slightly enhanced paracellular barrier functions. Moreover, we showed that pCPT-cAMP and 8-Br-cAMP/Na induced expression and membrane translocation of tricellulin. Conclusions pCPT-cAMP and, to a lesser extend, 8-Br-cAMP/Na improved formation of continuous tight junction strands and decreased paracellular permeability in primary HUVEC. We concluded that under these conditions HUVEC represent a feasible in vitro model to study formation and disassembly of endothelial tight junctions and to characterize tight junction-associated proteins

Selective response of human airway epithelia to luminal but not serosal solution hypertonicity. Possible role for proximal airway epithelia as an osmolality transducer

DEFF Research Database (Denmark)

Willumsen, Niels J.; Davis, C.W.; Boucher, R.C.

1994-01-01

exposure (10 min) to 430 mosM luminal solution elicited no regulation of any parameter. Optical measurements revealed a reduction in the thickness of preparations only in response to luminal hypertonic solutions. We conclude that (a) airway epithelial cells exhibit asymmetric water transport properties......- secretion; and (d) cell volume loss increases the resistance of the paracellular path. We speculate that these properties configure human nasal epithelium to behave as an osmotic sensor, transducing information about luminal solutions to the airway wall....

Determination of electrical resistivity of dry coke beds

Energy Technology Data Exchange (ETDEWEB)

Eidem, P.A.; Tangstad, M.; Bakken, J.A. [NTNU, Trondheim (Norway)

2008-02-15

The electrical resistivity of the coke bed is of great importance when producing FeMn, SiMn, and FeCr in a submerged arc furnace. In these processes, a coke bed is situated below and around the electrode tip and consists of metallurgical coke, slag, gas, and metal droplets. Since the basic mechanisms determining the electrical resistivity of a coke bed is not yet fully understood, this investigation is focused on the resistivity of dry coke beds consisting of different carbonaceous materials, i.e., coke beds containing no slag or metal. A method that reliably compares the electrical bulk resistivity of different metallurgical cokes at 1500{sup o} C to 1600{sup o}C is developed. The apparatus is dimensioned for industrial sized materials, and the electrical resistivity of anthracite, charcoal, petroleum coke, and metallurgical coke has been measured. The resistivity at high temperatures of the Magnitogorsk coke, which has the highest resistivity of the metallurgical cokes investigated, is twice the resistivity of the Corus coke, which has the lowest electrical resistivity. Zdzieszowice and SSAB coke sort in between with decreasing resistivities in the respective order. The electrical resistivity of anthracite, charcoal, and petroleum coke is generally higher than the resistivity of the metallurgical cokes, ranging from about two to about eight times the resistivity of the Corus coke at 1450{sup o}C. The general trend is that the bulk resistivity of carbon materials decreases with increasing temperature and increasing particle size.

Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

Energy Technology Data Exchange (ETDEWEB)

Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

2010-10-27

Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

Insulin resistance in dairy cows.

Science.gov (United States)

De Koster, Jenne D; Opsomer, Geert

2013-07-01

Glucose is the molecule that drives milk production, and insulin plays a pivotal role in the glucose metabolism of dairy cows. The effect of insulin on the glucose metabolism is regulated by the secretion of insulin by the pancreas and the insulin sensitivity of the skeletal muscles, the adipose tissue, and the liver. Insulin resistance may develop as part of physiologic (pregnancy and lactation) and pathologic processes, which may manifest as decreased insulin sensitivity or decreased insulin responsiveness. A good knowledge of the normal physiology of insulin is needed to measure the in vivo insulin resistance of dairy cows. Copyright © 2013 Elsevier Inc. All rights reserved.

CD44+CD24+ subset of PANC-1 cells exhibits radiation resistance via decreased levels of reactive oxygen species.

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Wang, Lei; Li, Pengping; Hu, Wei; Xia, Youyou; Hu, Chenxi; Liu, Liang; Jiang, Xiaodong

2017-08-01

Emerging evidence has suggested that pancreatic adenocarcinoma is sustained by pancreatic cancer stem cells. The present study aimed to investigate the expression patterns of the pancreatic cancer stem cell surface markers cluster of differentiation CD44 and CD24 in a pancreatic adenocarcinoma cell line, and to investigate the possible mechanisms for their radiation resistance. Flow cytometry was used to analyze the expression patterns of CD44 and CD24 in the pancreatic adenocarcinoma PANC-1 cell line. In addition, a multi-target click model was used to fit cell survival curves and determine the sensitizer enhancement ratio. The apoptosis and cycle distribution of the four cell subsets was determined using flow cytometry, and the level of reactive oxygen species (ROS) was determined using the 2',7'-dichlorofluorescin diacetate probe. The present results identified that the ratios of CD44 + and CD24 + in the sorted PANC-1 cell line were 92.0 and 4.7%, respectively. Prior to radiation, no statistically significant differences were observed among the four groups. Following treatment with 6 MV of X-rays, the rate of apoptosis was decreased in the CD44 + CD24 + group compared with other subsets. The percentage of G0/G1 cells was highest in the CD44 + CD24 + group compared with the three other groups, which exhibited increased radiosensitivity. In addition, the level of ROS in the CD44 + CD24 + group was reduced compared with the other groups. In summary, the results of the present study indicated that CD44 + CD24 + exhibited stem cell properties. The lower level of ROS and apoptosis in CD44 + CD24 + cells may contribute to their resistance to radiation in pancreatic adenocarcinoma.

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.

Science.gov (United States)

Ma, Elise L; Smith, Allen D; Desai, Neemesh; Cheung, Lumei; Hanscom, Marie; Stoica, Bogdan A; Loane, David J; Shea-Donohue, Terez; Faden, Alan I

2017-11-01

Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. Moderate-level TBI was induced in C57BL/6mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed. Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation. These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Fate of antibiotic resistant bacteria and genes during wastewater chlorination: implication for antibiotic resistance control.

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Qing-Bin Yuan

Full Text Available This study investigated fates of nine antibiotic-resistant bacteria as well as two series of antibiotic resistance genes in wastewater treated by various doses of chlorine (0, 15, 30, 60, 150 and 300 mg Cl2 min/L. The results indicated that chlorination was effective in inactivating antibiotic-resistant bacteria. Most bacteria were inactivated completely at the lowest dose (15 mg Cl2 min/L. By comparison, sulfadiazine- and erythromycin-resistant bacteria exhibited tolerance to low chlorine dose (up to 60 mg Cl2 min/L. However, quantitative real-time PCRs revealed that chlorination decreased limited erythromycin or tetracycline resistance genes, with the removal levels of overall erythromycin and tetracycline resistance genes at 0.42 ± 0.12 log and 0.10 ± 0.02 log, respectively. About 40% of erythromycin-resistance genes and 80% of tetracycline resistance genes could not be removed by chlorination. Chlorination was considered not effective in controlling antimicrobial resistance. More concern needs to be paid to the potential risk of antibiotic resistance genes in the wastewater after chlorination.

Resistivity behavior in isothermal annealing of Pd-H(D) alloys around 50 K

International Nuclear Information System (INIS)

Yamakawa, Kohji; Maeta, Hiroshi

2004-01-01

The behavior of electrical resistivity during hydrogen (deuterium) ordering is investigated for Pd-H(D) alloys of various hydrogen concentrations around 50 K. The disordered hydrogen (deuterium) atoms are introduced by quenching from 100 K into liquid helium immediately before isothermal annealings. The disordered atoms order by migration of the atoms during the heating-up of the specimens. On the isothermal curves of the resistivity in the high temperature range, the resistivity increases at first and then adopts a constant value dependent on the annealing temperature. On the other hand, the resistivity increases and then decreases during isothermal annealing in the low temperature range, nevertheless the ordering is progressing. The annealing time, at which the resistivity maximum appears, and the resistivity value of the maximum increase with decreasing annealing temperature. Furthermore, the decreasing resistivity after the maximum saturates to a value dependent on each annealing temperature. Therefore, it becomes clear that an equilibrium amount of ordering depends on the temperature and the resistivity increases in the early stage of hydrogen (deuterium) ordering and decreases in the later stage. The resistivity maximum in the isothermal annealing curve is caused by the nucleation and growth of ordered domains of hydrogen (deuterium) atoms

Sleep Restriction Impairs Blood–Brain Barrier Function

Science.gov (United States)

He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J.; Wang, Yuping

2014-01-01

The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. PMID:25355222

Autolysis of methicillin-resistant and -susceptible Staphylococcus aureus.

Science.gov (United States)

Gustafson, J E; Berger-Bächi, B; Strässle, A; Wilkinson, B J

1992-01-01

The autolytic activities, including unstimulated, Triton X-100-stimulated, and daptomycin-induced, of various sets of methicillin-resistant and related methicillin-susceptible strains were compared. Faster rates of autolysis were noted in two heterogeneous methicillin-resistant transductants than in their methicillin-susceptible parental recipients, in a heterogeneous resistant strain than in a susceptible derivative created by chemical mutagenesis, and in a homogeneous resistant strain than in a derivative that had decreased methicillin resistance and was created by transposon Tn551 mutagenesis. These results suggest that the presence of the methicillin resistance region, mec, either directly or indirectly through an interaction with other host genes, confers a faster rate of autolysis on strains. Various auxilliary genes are known to affect methicillin resistance expression, and one of these genes, femA, was necessary for the expression of this faster rate of autolysis. These differences in autolytic activities were not observed in isolated crude cell walls retaining autolytic activities, suggesting different modes of regulation of autolysins in intact cells and isolated walls. In contrast, one homogeneous, highly resistant strain, DU4916, had a lower autolytic activity than did derived heterogeneous resistant and susceptible strains created by chemical mutagenesis and a strain that had decreased resistance and was created by transposon mutagenesis. Our observations suggest that methicillin resistance expression is associated with an enhanced rate of autolysis, in heterogeneous resistant strains at least. Images PMID:1320363

Major Pathophysiology in Prediabetes and Type 2 Diabetes: Decreased Insulin in Lean and Insulin Resistance in Obese.

Science.gov (United States)

Kabadi, Udaya M

2017-06-01

Lowering of body mass index (BMI) to ≥25 kg/m 2 as obesity by ADA suggests insulin resistance as a major mechanism of impaired glucose metabolism (IGM) in Asians. However, glimepiride, an insulin secretagogue, delayed onset of type 2 diabetes (DM2) from prediabetes (PreDM), indicating decreased insulin secretion (IS) as a major factor in lean (L; BMI DM2. Seventy-five men and 45 women ages 36 to 75 years were divided into six groups: LN, LPreDM, LDM2, ObN, ObPreDM, and ObDM2. Determination of IS by insulinogenic indices (I/G) at fasting (FI/FG), first phase (∆I/∆G), and cumulative responses over 2 hours of OGTT (CRI/CRG), and IR by FIXFG, ∆IX∆G, and CRIXCRG. Changes in IS and IR for PreDM and DM2 were calculated as % fall and % rise, respectively, from levels in N. All indices of IS and IR were lower ( P DM2 ( P < 0.05) in both groups. However, the declines in IS were greater ( P < 0.05) than rises in IR in LPreDM and LDM2. Whereas, the rises in IR were higher ( P < 0.05) than declines in IS in ObPreDM and ObDM2. In L, major mechanism of IGM is declining IS and not rising IR documented among Ob.

Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes

DEFF Research Database (Denmark)

Venkatesan, Meera; Gadalla, Nahla B; Stepniewska, Kasia

2014-01-01

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated...... with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized...

Effect of Chum Salmon Egg Lectin on Tight Junctions in Caco-2 Cell Monolayers

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Ryo Nemoto

2015-05-01

Full Text Available The effect of a chum salmon egg lectin (CSL3 on tight junction (TJ of Caco-2 cell monolayers was investigated. The lectin opened TJ as indicated by the decrease of the transepithelial electrical resistance (TER value and the increase of the permeation of lucifer yellow, which is transported via the TJ-mediated paracellular pathway. The effects of CSL3 were inhibited by the addition of 10 mM L-rhamnose or D-galactose which were specific sugars for CSL3. The lectin increased the intracellular Ca2+ of Caco-2 cell monolayers, that could be inhibited by the addition of L-rhamnose. The fluorescence immunostaining of β-actin in Caco-2 cell monolayers revealed that the cytoskeleton was changed by the CSL3 treatment, suggesting that CSL3 depolymerized β-actin to cause reversible TJ structural and functional disruption. Although Japanese jack bean lectin and wheat germ lectin showed similar effects in the decrease of the TER values and the increase of the intracellular Ca2+, they could not be inhibited by the same concentrations of simple sugars, such as D-glucose and N-acetyl-D-glucosamine.

Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women.

Science.gov (United States)

Ott, Beate; Skurk, Thomas; Hastreiter, Ljiljana; Lagkouvardos, Ilias; Fischer, Sandra; Büttner, Janine; Kellerer, Teresa; Clavel, Thomas; Rychlik, Michael; Haller, Dirk; Hauner, Hans

2017-09-20

Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.

Synthesis and Electrical Resistivity of Nickel Polymethacrylate

Science.gov (United States)

Chohan, M. H.; Khalid, A. H.; Zulfiqar, M.; Butt, P. K.; Khan, Farah; Hussain, Rizwan

Synthesis of nickel polymethacrylate was carried out using methanolic solutions of sodium hydroxide and polymethacrylic acid. The electrical resistivity of the pellets made from Ni-polymethacrylate was measured at different voltages and temperatures. Results showed that the electrical resistivity of Ni-polymethacrylate decreases significantly with voltage in high temperature regions but the decrease is insignificant at temperatures nearing room temperature. The activation energy at low temperatures is approximately 0.8 eV whereas at high temperature it is in the range 0.21-0.27 eV.

Mechanism of quinolone action and resistance.

Science.gov (United States)

Aldred, Katie J; Kerns, Robert J; Osheroff, Neil

2014-03-18

Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone-enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains.

Characterisation of multidrug-resistant Ehrlich ascites tumour cells selected in vivo for resistance to etoposide

DEFF Research Database (Denmark)

Nielsen, D; Maare, C; Eriksen, J

2000-01-01

-extractable immunoreactive topoisomerase IIalpha and beta in EHR2/VP16 was reduced by 30-40% relative to that in EHR2. The multidrug resistance-associated protein (MRP) mRNA was increased 20-fold in EHR2/VP16 as compared with EHR2, whereas the expression of P-glycoprotein was unchanged. In EHR2/VP16, the steady......M. ATPase activity was slightly stimulated by daunorubicin, whereas vinblastine, verapamil, and cyclosporin A had no effect. In conclusion, development of resistance to VP16 in EHR2 is accompanied by a significant reduction in topoisomerase II (alpha and beta) and by increased expression of MRP mRNA (20......-fold). MRP displays several points of resemblance to P-glycoprotein in its mode of action: 1) like P-glycoprotein, MRP causes resistance to a range of hydrophobic drugs; 2) MRP decreases drug accumulation in the cells and this decrease is abolished by omission of energy; and 3) MRP increases efflux...

[Resistance risk and resistance stability of Frankliniella occidentalis to imidacloprid, emamectin benzoate, and phoxim].

Science.gov (United States)

Wang, Sheng-Yin; Yu, Yi; Liu, Yong-Jie; Ma, Jing-Yu

2012-12-01

In order to effectively control the damage of Frankliniella occidentalis (Pergande), Phaseolus vuglaris was dipped with imidacloprid, phoxim, and emamectin benzoate, respectively to select the resistance populations of F. occidentalis from its susceptible population, and the resistance inheritance and resistance risk were analyzed with the resistance reality heredity. After 32, 32, and 24 generations' selection, the F. occidentalis populations obtained 13.8-fold, 29.4-fold and 39.0-fold resistance to imidacloprid, phoxim, and emamectin benzoate, respectively. The resistance reality heritability to imidacloprid, phoxim, and emamectin benzoate was 0.112, 0.166, and 0.259, respectively. The resistance development rate to emamectin benzoate was the fastest, followed by to phoxim, and to imidacloprid. The higher the resistance levels of the selected populations, the lower the differences between the larva and adult susceptibility to imidacloprid, phoxim, and emamectin benzoate. Stopping selection for 12 continuous generations, the resistance level of the selected resistance populations to imidacloprid, phoxim, and emamectin benzoate had definite decline, but it was difficult to regain the original susceptibility. F. occidentalis had a greater potential to gain high level resistance to imidacloprid, phoxim, and emamectin benzoate. Compared with the resistance of F. occidentalis to phoxim and emamectin benzoate, the resistance to imidacloprid increased slower and decreased faster, and thus, imidacloprid was more appropriate to control F. occidentalis in practice.

High chlorpyrifos resistance in Culex pipiens mosquitoes: strong synergy between resistance genes

Science.gov (United States)

Alout, H; Labbé, P; Berthomieu, A; Makoundou, P; Fort, P; Pasteur, N; Weill, M

2016-01-01

We investigated the genetic determinism of high chlorpyrifos resistance (HCR), a phenotype first described in 1999 in Culex pipiens mosquitoes surviving chlorpyrifos doses ⩾1 mg l−1 and more recently found in field samples from Tunisia, Israel or Indian Ocean islands. Through chlorpyrifos selection, we selected several HCR strains that displayed over 10 000-fold resistance. All strains were homozygous for resistant alleles at two main loci: the ace-1 gene, with the resistant ace-1R allele expressing the insensitive G119S acetylcholinesterase, and a resistant allele of an unknown gene (named T) linked to the sex and ace-2 genes. We constructed a strain carrying only the T-resistant allele and studied its resistance characteristics. By crossing this strain with strains harboring different alleles at the ace-1 locus, we showed that the resistant ace-1R and the T alleles act in strong synergy, as they elicited a resistance 100 times higher than expected from a simple multiplicative effect. This effect was specific to chlorpyrifos and parathion and was not affected by synergists. We also examined how HCR was expressed in strains carrying other ace-1-resistant alleles, such as ace-1V or the duplicated ace-1D allele, currently spreading worldwide. We identified two major parameters that influenced the level of resistance: the number and the nature of the ace-1-resistant alleles and the number of T alleles. Our data fit a model that predicts that the T allele acts by decreasing chlorpyrifos concentration in the compartment targeted in insects. PMID:26463842

In vitro cross-resistance profile of nucleoside reverse transcriptase inhibitor (NRTI) BMS-986001 against known NRTI resistance mutations.

Science.gov (United States)

Li, Zhufang; Terry, Brian; Olds, William; Protack, Tricia; Deminie, Carol; Minassian, Beatrice; Nowicka-Sans, Beata; Sun, Yongnian; Dicker, Ira; Hwang, Carey; Lataillade, Max; Hanna, George J; Krystal, Mark

2013-11-01

BMS-986001 is a novel HIV nucleoside reverse transcriptase inhibitor (NRTI). To date, little is known about its resistance profile. In order to examine the cross-resistance profile of BMS-986001 to NRTI mutations, a replicating virus system was used to examine specific amino acid mutations known to confer resistance to various NRTIs. In addition, reverse transcriptases from 19 clinical isolates with various NRTI mutations were examined in the Monogram PhenoSense HIV assay. In the site-directed mutagenesis studies, a virus containing a K65R substitution exhibited a 0.4-fold change in 50% effective concentration (EC50) versus the wild type, while the majority of viruses with the Q151M constellation (without M184V) exhibited changes in EC50 versus wild type of 0.23- to 0.48-fold. Susceptibility to BMS-986001 was also maintained in an L74V-containing virus (0.7-fold change), while an M184V-only-containing virus induced a 2- to 3-fold decrease in susceptibility. Increasing numbers of thymidine analog mutation pattern 1 (TAM-1) pathway mutations correlated with decreases in susceptibility to BMS-986001, while viruses with TAM-2 pathway mutations exhibited a 5- to 8-fold decrease in susceptibility, regardless of the number of TAMs. A 22-fold decrease in susceptibility to BMS-986001 was observed in a site-directed mutant containing the T69 insertion complex. Common non-NRTI (NNRTI) mutations had little impact on susceptibility to BMS-986001. The results from the site-directed mutants correlated well with the more complicated genotypes found in NRTI-resistant clinical isolates. Data from clinical studies are needed to determine the clinically relevant resistance cutoff values for BMS-986001.

Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats.

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Lu Zheng

Full Text Available BACKGROUND: Apolipoprotein M (ApoM is a constituent of high-density lipoproteins (HDL. It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels. AIMS: To assess the effects of increased free fatty acids (FFAs levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression. METHODS: Adult male Sprague-Dawley (SD rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array. RESULTS: Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8 was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin. CONCLUSION: These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes.

LEPTIN RESISTANCE AND TYPE 2 DIABETES

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O. M. Oleshchuk

2017-07-01

Full Text Available Leptin is one of adipocyte-secreted hormones. It signals to the brain and other tissues about the status of body energy reserves. Circulating leptin levels are directly proportional to the amount of the body fat. Leptin concentration increases when surfeit and decreases during fasting. Obese patients are hyperleptinemic compared with thin persons and they are tolerant to the central hypothalamic effects of leptin. The reduced sensitivity toward exogenous and endogenous leptin is commonly referred to as leptin resistance. Alterations in the signaling of the long isoform of the leptin receptor play the crucial role in leptin resistance. Surfeit may induce leptin resistance and other metabolic sequelae of obesity. Leptin insensitivity and insulin resistance play a major role in the development of type 2 diabetes. Metformin remains the preferred first-line pharmacologic agent for the treatment of type 2 diabetes. It reduces hepatic glucose production, increases glucose uptake in peripheral tissue and can lead to weight loss. Metformin decreases both insulin and leptin concentration, restores the sensitivity to these hormones. But some studies have shown poor relationship between metformin action and leptin level. And the mechanism of metformin action on leptin resistance remains unclear. Thus, these issues should be studied as well as polymorphisms in genes encoding metformin action.

The study on corrosion resistance of decorative satin nickel plating

Directory of Open Access Journals (Sweden)

LU Wenya

2012-10-01

Full Text Available This study examined the corrosion resistance of satin nickel plating on conductive plastic.The electrochemical tests were to analyze the corrosion behavior of satin nickel plating with different processes in 3.5% NaCl solution.The results show that,because the satin nickel plating has an organic film on its surface due to process characteristics,the film results in different corrosion resistance.By increasing satin additive dosage,the nickel plating chroma decreases,the microsurface of the plating becomes rough,and the corrosion resistance is followed by decrease.

Antimicrobial resistance 1979-2009 at Karolinska hospital, Sweden: normalized resistance interpretation during a 30-year follow-up on Staphylococcus aureus and Escherichia coli resistance development.

Science.gov (United States)

Kronvall, Göran

2010-09-01

To utilize a material of inhibition zone diameter measurements from disc diffusion susceptibility tests between 1979 and 2009, an objective setting of epidemiological breakpoints was necessary because of methodological changes. Normalized resistance interpretation (NRI) met this need and was applied to zone diameter histograms for Staphylococcus aureus and Escherichia coli isolates. The results confirmed a slow resistance development as seen in Northern countries. The S. aureus resistance levels for erythromycin, clindamycin and fusidic acid in 2009 were 3.2%, 1.8% and 1.4% with denominator correction. A rise in resistance to four antimicrobials in 1983 was probably because of a spread of resistant Methicillin Susceptible Staphylococcus Aureus (MSSA). For E. coli, the denominator-corrected resistance levels in 2009 were 27% for ampicillin, around 3% for third-generation cephalosporins, 0.1% for imipenem, 2.5% for gentamicin, 19% for trimethoprim, 4.5% for co-trimoxazole, 1.2% for nitrofurantoin and 9% for ciprofloxacin. The temporal trends showed a rise in fluoroquinolone resistance from 1993, a parallel increase in gentamicin resistance, a substantial increase in trimethoprim and sulphonamide resistance in spite of decreased consumption, and a steady rise in ampicillin resistance from a constant level before 1989. A short review of global resistance surveillance studies is included.

Spatio-temporal evolution of apparent resistivity during coal-seam hydraulic flushing

Science.gov (United States)

Li, Dexing; Wang, Enyuan; Song, Dazhao; Qiu, Liming; Kong, Xiangguo

2018-06-01

Hydraulic flushing in gas predrainage is widely used, but the hydraulic-flushing effect is evaluated in a traditional way, by determining the desorption volume, moisture content, gas drainage rate and other conventional indices. To verify the rationality and feasibility of the multielectrode resistivity method in the evaluation of coal-seam hydraulic flushing and to research the spatio-temporal evolution of apparent resistivity during hydraulic flushing, a field test was conducted in 17# coal seam at Nuodong Mine, Guizhou. During hydraulic flushing, four stages were defined according to the variation in coal rock resistivity with time, namely, the preparation stage, the sharply decreasing stage, the rapidly increasing stage and the steady stage. The apparent resistivity of the coal rock mass is affected mainly by its own degree of fragmentation and flushing volume. A more serious rupture and a greater flushing volume yield a smaller apparent resistivity during the sharply decreasing stage and a higher resistivity during the stable stage. After three months of gas predrainage, the residual gas content and the gas pressure at different points in the expected affected area decrease below the critical value. Changes in the residual gas content and gas pressure at these points are consistent with the apparent resistivity, which validates the rationality and feasibility of the multielectrode resistivity method in evaluating coal-seam hydraulic flushing.

Monitoring of Leachate Recirculation in a Bioreactor Using Electrical Resistivity

Science.gov (United States)

Grellier, S.; Bureau, N.; Robain, H.; Tabbagh, A.; Camerlynck, C.; Guerin, R.

2004-05-01

The bioreactor is a concept of waste landfill management consisting in speeding up the biodegradation by optimizing the moisture content through leachate recirculation. Electrical resistivity tomography (ERT) is carried out with fast resistivity-meter (Syscal Pro, IRIS Instruments, developed in the framework of the research project CERBERE 01V0665-69, funded by the French Research Ministry) to monitor leachate recirculation. During a recirculation period waste moisture increases, so that electrical resistivity may decrease, but at the same time temperature and mineralization of both waste and leachate become intermixed. If waste temperature is much higher than leachate temperature electrical resistivity will not decrease as much as if the temperature difference was smaller. If leachate mineralization (i.e. leachate conductivity) is higher than that of wet waste in the landfill, electrical resistivity will tend to decrease. Otherwise for example after an addition of rain water into the leachate storage or in case of very wet waste, the resistivities of each medium (leachate and wet waste) can be almost the same, so that leachate mineralization will not have a great influence on waste resistivity. Resistivity measurements were performed during 85 minutes injection trials (with a discharge of 20 m3 h-1) where leachate was injected through a vertical borehole perforated between 1.85 and 4.15 m. Three first measurements are made during the injection (3, 30 and 60 minutes from the beginning of the injection) and the two other after the injection period (8 and 72 minutes after the end of the injection). Apparent and interpreted resistivity variations that occurred during injection trials, expressed as the relative differences (in %) between apparent, respectively interpreted, resistivity during injection and apparent, respectively interpreted, resistivity before injection (reference measurement) show the formation of a plume (a negative anomaly: resistivity decreases with

Reduced expression levels of PTEN are associated with decreased sensitivity of HCC827 cells to icotinib.

Science.gov (United States)

Zhai, Yang; Zhang, Yanjun; Nan, Kejun; Liang, Xuan

2017-05-01

The clinical resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been linked to EGFR T790M resistance mutations or MET amplifications. Additional mechanisms underlying EGFR-TKI drug resistance remain unclear. The present study demonstrated that icotinib significantly inhibited the proliferation and increased the apoptosis rate of HCC827 cells; the cellular mRNA and protein expression levels of phosphatase and tensin homolog (PTEN) were also significantly downregulated. To investigate the effect of PTEN expression levels on the sensitivity of HCC827 cells to icotinib, PTEN expression was silenced using a PTEN-specific small interfering RNA. The current study identified that the downregulation of PTEN expression levels may promote cellular proliferation in addition to decreasing the apoptosis of HCC827 cells, and may reduce the sensitivity of HCC827 cells to icotinib. These results suggested that reduced PTEN expression levels were associated with the decreased sensitivity of HCC827 cells to icotinib. Furthermore, PTEN expression levels may be a useful marker for predicting icotinib resistance and elucidating the resistance mechanisms underlying EGFR-mutated NSCLC.

Risk Factors for Acquisition of Drug Resistance during Multidrug-Resistant Tuberculosis Treatment, Arkhangelsk Oblast, Russia, 2005–2010

Science.gov (United States)

Ershova, Julia; Vlasova, Natalia; Nikishova, Elena; Tarasova, Irina; Eliseev, Platon; Maryandyshev, Andrey O.; Shemyakin, Igor G.; Kurbatova, Ekaterina; Cegielski, J. Peter

2015-01-01

Acquired resistance to antituberculosis drugs decreases effective treatment options and the likelihood of treatment success. We identified risk factors for acquisition of drug resistance during treatment for multidrug-resistant tuberculosis (MDR TB) and evaluated the effect on treatment outcomes. Data were collected prospectively from adults from Arkhangelsk Oblast, Russia, who had pulmonary MDR TB during 2005–2008. Acquisition of resistance to capreomycin and of extensively drug-resistant TB were more likely among patients who received 3 effective drugs (9.4% vs. 0% and 8.6% vs. 0.8%, respectively). Poor outcomes were more likely among patients with acquired capreomycin resistance (100% vs. 25.9%), acquired ofloxacin resistance (83.6% vs. 22.7%), or acquired extensive drug resistance (100% vs. 24.4%). To prevent acquired drug resistance and poor outcomes, baseline susceptibility to first- and second-line drugs should be determined quickly, and treatment should be adjusted to contain >3 effective drugs. PMID:25988954

Bacterial resistance and impetigo treatment trends: a review.

Science.gov (United States)

Bangert, Scott; Levy, Moise; Hebert, Adelaide A

2012-01-01

Impetigo is a common cutaneous infection that is especially prevalent in children. The prevalence of colonization and infection with resistant strains is continually increasing, forcing clinicians to reevaluate treatment strategies. Newer topical agents are effective in treating infections with resistant strains and may help minimize resistance and adverse effects from systemic agents. Use of topical disinfectants to decrease colonization is an important adjunctive measure. Physicians should be aware of local resistance patterns in impetigo to help guide therapy. © 2012 Wiley Periodicals, Inc.

Preventing drug resistance in severe influenza

Science.gov (United States)

Dobrovolny, Hana; Deecke, Lucas

2015-03-01

Severe, long-lasting influenza infections are often caused by new strains of influenza. The long duration of these infections leads to an increased opportunity for the emergence of drug resistant mutants. This is particularly problematic for new strains of influenza since there is often no vaccine, so drug treatment is the first line of defense. One strategy for trying to minimize drug resistance is to apply periodic treatment. During treatment the wild-type virus decreases, but resistant virus might increase; when there is no treatment, wild-type virus will hopefully out-compete the resistant virus, driving down the number of resistant virus. We combine a mathematical model of severe influenza with a model of drug resistance to study emergence of drug resistance during a long-lasting infection. We apply periodic treatment with two types of antivirals: neuraminidase inhibitors, which block release of virions; and adamantanes, which block replication of virions. We compare the efficacy of the two drugs in reducing emergence of drug resistant mutants and examine the effect of treatment frequency on the emergence of drug resistant mutants.

Decreasing Human Trafficking through Sex Work Decriminalization.

Science.gov (United States)

Albright, Erin; D'Adamo, Kate

2017-01-01

In order to decrease human trafficking, health care workers should support the full decriminalization of prostitution. Similar to trafficking in other forms of labor, preventing trafficking in the sex trade requires addressing the different forms of marginalization that create vulnerable communities. By removing punitive laws that prevent reporting of exploitation and abuse, decriminalization allows sex workers to work more safely, thereby reducing marginalization and vulnerability. Decriminalization can also help destigmatize sex work and help resist political, social, and cultural marginalization of sex workers. © 2017 American Medical Association. All Rights Reserved.

Hydraulic resistance of biofilms

KAUST Repository

Dreszer, C.

2013-02-01

after 4 days at a flux of 100Lm-2h-1 (97μm) was in the same order of magnitude as the thickness of a biofilm at a flux of 20Lm-2h-1 (114μm). An increase of flux caused an increased biofilm resistance while a decrease of flux caused a decreased resistance. The effect was reversible. It is suggested that the biofilm resistance is mainly attributed to EPS, probably due to the tortuosity ("hair-in-sink-effect") of the biopolymers to water molecules travelling across the biofilm. The data show clearly that biofilm resistance (6×1012m-1) was high compared to the intrinsic resistance of the employed MF membrane (5×1011m-1). However, in nanofiltration (intrinsic membrane resistance ca. 2×1013m-1) and reverse osmosis membranes (intrinsic resistance ca. 9×1013m-1), the biofilm will not contribute significantly to the overall resistance. © 2012 Elsevier B.V.

Aroclor 1248 exposure leads to immunomodulation, decreased disease resistance and endocrine disruption in the brown bullhead, Ameiurus nebulosus

Science.gov (United States)

Iwanowicz, L.R.; Blazer, V.S.; McCormick, S.D.; Van Veld, P.A.; Ottinger, C.A.

2009-01-01

The brown bullhead Ameiurus nebulosus is a species of the family Ictaluridae commonly used as a sentinel of environmental contamination. While these fish have been utilized for this purpose in areas contaminated with polychlorinated biphenyls (PCBs), few controlled, laboratory-based studies have been designed to document the effects of PCB mixtures in this species. Here, brown bullhead were exposed to the PCB mixture, Aroclor 1248, via intraperitoneal injection and the effects on immune function, plasma hormones and disease resistance were evaluated. Exposure to this mixture led to a decrease in bactericidal activity and circulating antibodies to Edwardsiella ictaluri present from a previous exposure to this pathogen. A subsequent E. ictaluri disease challenge led to significantly higher mortality in A1248 treated fish compared to vehicle-control fish. The mitogenic response to the T-cell mitogen, phytohemaglutinin-P, was increased compared to vehicle-control fish. The steroid hormone, cortisol, and the thyroid hormone, T3, were also significantly lower in A1248 exposed fish. In summary, we have validated a number of functional immune assays for application in brown bullhead immunotoxicity studies. Additionally, we have demonstrated that the PCB mixture (A1248) modulates both immune function and endocrine physiology in brown bullhead. Such data may compliment the interpretation of data yielded from applied field studies conducted in PCB contaminated aquatic ecosystems.

Aroclor 1248 exposure leads to immunomodulation, decreased disease resistance and endocrine disruption in the brown bullhead, Ameiurus nebulosus.

Science.gov (United States)

Iwanowicz, Luke R; Blazer, Vicki S; McCormick, Stephen D; Vanveld, Peter A; Ottinger, Christopher A

2009-06-04

The brown bullhead Ameiurus nebulosus is a species of the family Ictaluridae commonly used as a sentinel of environmental contamination. While these fish have been utilized for this purpose in areas contaminated with polychlorinated biphenyls (PCBs), few controlled, laboratory-based studies have been designed to document the effects of PCB mixtures in this species. Here, brown bullhead were exposed to the PCB mixture, Aroclor 1248, via intraperitoneal injection and the effects on immune function, plasma hormones and disease resistance were evaluated. Exposure to this mixture led to a decrease in bactericidal activity and circulating antibodies to Edwardsiella ictaluri present from a previous exposure to this pathogen. A subsequent E. ictaluri disease challenge led to significantly higher mortality in A1248 treated fish compared to vehicle-control fish. The mitogenic response to the T-cell mitogen, phytohemaglutinin-P, was increased compared to vehicle-control fish. The steroid hormone, cortisol, and the thyroid hormone, T3, were also significantly lower in A1248 exposed fish. In summary, we have validated a number of functional immune assays for application in brown bullhead immunotoxicity studies. Additionally, we have demonstrated that the PCB mixture (A1248) modulates both immune function and endocrine physiology in brown bullhead. Such data may compliment the interpretation of data yielded from applied field studies conducted in PCB contaminated aquatic ecosystems.

Electrical resistivity of sputtered molybdenum films

International Nuclear Information System (INIS)

Nagano, J.

1980-01-01

The electrical resistivity of r.f. sputtered molybdenum films of thickness 5-150 nm deposited on oxidized silicon substrates was resolved into the three electron scattering components: isotropic background scattering, scattering at grain boundaries and scattering at surfaces. It was concluded that the isotropic background scattering is almost equal to that of bulk molybdenum and is not influenced by sputtering and annealing conditions. When the film thickness is sufficient that surface scattering can be ignored, the decrease in film resistivity after annealing is caused by the decrease in scattering at the grain boundaries for zero bias sputtered films, and is caused by an increase of the grain diameter for r.f. bias sputtered films. (Auth.)

Monoamine oxidase A (MAO A) inhibitors decrease glioma progression

Science.gov (United States)

Vaikari, Vijaya Pooja; Kota, Rajesh; Chen, Kevin; Yeh, Tzu-Shao; Jhaveri, Niyati; Groshen, Susan L.; Olenyuk, Bogdan Z.; Chen, Thomas C.; Hofman, Florence M.; Shih, Jean C.

2016-01-01

Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis. PMID:26871599

Decreased UV light resistance of spores of Bacillus subtilis strains deficient in pyrimidine dimer repair and small, acid-soluble spore proteins

International Nuclear Information System (INIS)

Setlow, B.; Setlow, P.

1988-01-01

Loss of small, acid-soluble spore protein alpha reduced spore UV resistance 30- to 50-fold in Bacillus subtilis strains deficient in pyrimidine dimer repair, but gave only a 5- to 8-fold reduction in UV resistance in repair-proficient strains. However, both repair-proficient and -deficient spores lacking this protein had identical heat and gamma-radiation resistance

Pathogenesis of Insulin Resistance in Skeletal Muscle

Directory of Open Access Journals (Sweden)

Muhammad A. Abdul-Ghani

2010-01-01

Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

A Comparison of mucosal surface area and villous histology in small intestines of the Brazilian free-tailed bat (Tadarida brasiliensis) and the mouse (Mus musculus).

Science.gov (United States)

Zhang, Zhi-Qiang; Brun, Antonio; Price, Edwin R; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

2015-01-01

Studies on birds have led to the hypothesis that increased intestinal absorption between enterocytes (paracellular) evolved as a compensation for smaller intestinal size in fliers, which was perhaps selected to minimize the mass of digesta carried. This hypothesis predicts that bats will also exhibit relatively reduced intestinal size and high paracellular absorption, compared with nonflying mammals. Published studies on three bat species indicate relatively high paracellular absorption. One mechanism for increasing paracellular absorption per cm2 small intestine (SI) is increased number of tight junctions (TJs) across which paracellular absorption occurs. To our knowledge, we provide the first comparative analysis of enterocyte size and number in flying and nonflying mammals. Intestines of insectivorous bats Tadarida brasiliensis were compared with Mus musculus using hematoxylin and eosin staining method. Bats had shorter and narrower SIs than mice, and after correction for body size difference by normalizing to mass3/4, the bats had 40% less nominal surface area than the mouse, as predicted. Villous enhancement of surface area was 90% greater in the bat than in the mouse, mainly because of longer villi and a greater density of villi in bat intestines. Bat and mouse were similar in enterocyte diameter. Bats exceeded mice by 54.4% in villous area per cm length SI and by 95% in number of enterocytes per cm2 of the nominal surface area of the SI. Therefore, an increased density of TJs per cm2 SI may be a mechanistic explanation that helps to understand the high paracellular absorption observed in bats compared to nonflying mammals. © 2014 Wiley Periodicals, Inc.

Arterial wave reflection decreases gradually from supine to upright

DEFF Research Database (Denmark)

van den Bogaard, Bas; Westerhof, Berend E; Best, Hendrik

2011-01-01

BACKGROUND. An increase in total peripheral resistance (TPR) usually increases arterial wave reflection. During passive head-up tilt (HUT), however, arterial wave reflection decreases with increasing TPR. This study addressed whether arterial wave reflection gradually decreases during HUT. METHODS....... In 10 healthy volunteers (22-39 years, nine males), we recorded finger arterial pressures in supine position (0°), and 30°and 70°degrees HUT and active standing (90°). Aortic pressure was constructed from the finger pressure signal and hemodynamics were calculated. Arterial wave reflection...... from 0.9 dyn s/cm(5) at 0? to 1.2, 1.4 and 1.4 dyn s/cm(5) at 30°, 70° and 90° (p wave reflection...

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

Energy Technology Data Exchange (ETDEWEB)

Roberts, B. M. [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States); Frye, G. S.; Ahn, B.; Ferreira, L. F. [1864 Stadium Road, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610 (United States); Judge, A.R., E-mail: arjudge@phhp.ufl.edu [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States)

2013-06-07

Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

International Nuclear Information System (INIS)

Roberts, B.M.; Frye, G.S.; Ahn, B.; Ferreira, L.F.; Judge, A.R.

2013-01-01

Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

Impact of restricted amoxicillin/clavulanic acid use on Escherichia coli resistance--antibiotic DU90% profiles with bacterial resistance rates: a visual presentation.

Science.gov (United States)

Mimica Matanovic, Suzana; Bergman, Ulf; Vukovic, Dubravka; Wettermark, Björn; Vlahovic-Palcevski, Vera

2010-10-01

High use of amoxicillin/clavulanic acid (AMC) at the University Hospital Osijek (Croatia) contributed to high rates of resistance in Enterobacteriaceae, in particular Escherichia coli (50%). Thus, in order to decrease bacterial resistance, AMC use was restricted. We present results of the restriction on resistance amongst antibiotics accounting for 90% of antibiotic use [drug utilisation 90% (DU90%)]. Data were analysed on antibiotic use and microbiological susceptibility of E. coli during two 9-month periods, before and after the restriction of AMC use. Drug use was presented as numbers of defined daily doses (DDDs) and DDDs/100 bed-days. Resistance of E. coli to antibiotics was presented as percentages of isolated strains in the DU90% segment. Use of AMC was 16 DDDs/100 bed-days or 30% of all antibiotics before the intervention. Use of AMC fell to 2 DDDs/100 bed-days or 4% after the intervention, and resistance of E. coli fell from 37% to 11%. In conclusion, restricted use of AMC resulted in a significant decrease of E. coli resistance. DU90% resistance profiles are simple and useful tools in highlighting problems in antibiotic use and resistance but may also be useful in long-term follow-up of antibiotic policy. Copyright 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Prevalence of transmitted drug resistance and impact of transmitted resistance on treatment success in the German HIV-1 Seroconverter Cohort.

Directory of Open Access Journals (Sweden)

Barbara Bartmeyer

Full Text Available BACKGROUND: The aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort. METHODS: Genotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008. A genotypic resistance result was obtained for 1,276/1,312 (97.3%. The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml. RESULTS: Prevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N = 158/1,276; 12.4%; CI(wilson 10.7-14.3; p(for trend = 0.25. NRTI resistance was predominant (7.5% but decreased significantly over time (CI(Wilson: 6.2-9.1, p(for trend = 0.02. NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson: 2.6-4.6; p(for trend= 0.07, whereas PI resistance remained stable (PI: 3.0%; CI(Wilson: 2.1-4.0; p(for trend = 0.24. Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%. The majority of NRTI-resistant strains (79.8% carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61. The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%. CONCLUSION: Overall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected

Control of nasal vasculature and airflow resistance in the dog.

Science.gov (United States)

Lung, M A; Phipps, R J; Wang, J C; Widdicombe, J G

1984-01-01

Nasal vascular and airflow resistances have been measured in dogs, simultaneously on both sides separately. Vascular resistance was measured either by constant flow perfusion of the terminal branch of the maxillary artery (which supplies, via the sphenopalatine artery, the nasal septum, most of the turbinates and the nasal sinuses) or by measuring blood flow through this artery, maintained by the dog's own blood pressure. Airflow resistance was assessed by inserting balloon-tipped endotracheal catheters into the back of each nasal cavity via the nasopharynx, and measuring transnasal pressure at constant airflow through each side of the nose simultaneously. Preliminary experiments indicated that there was 5-10% collateral anastomosis between the two sides. Close-arterial injection of drugs showed different patterns of response. Adrenaline, phenylephrine, chlorpheniramine and low doses of prostaglandin F2 alpha increased vascular resistance and lowered airway resistance. Salbutamol, methacholine and histamine lowered vascular resistance and increased airway resistance. Dobutamine decreased airway resistance with a small increase in vascular resistance. Prostaglandins E1, E2 and F2 alpha (high dose) decreased both vascular and airway resistances. Substance P, eledoisin-related peptide and vasoactive intestinal polypeptide lowered vascular resistance with little change in airway resistance. The results are interpreted in terms of possible drug actions on precapillary resistance vessels, sinusoids and venules, and arteriovenous anastomoses. It is concluded that nasal airway resistance cannot be correlated with vascular resistance or blood flow, since the latter has a complex and ill-defined relationship with nasal vascular blood volume. PMID:6204040

Sleep restriction impairs blood-brain barrier function.

Science.gov (United States)

He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong

2014-10-29

The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. Copyright © 2014 the authors 0270-6474/14/3414697-10$15.00/0.

The proteomic signature of insulin-resistant human skeletal muscle reveals increased glycolytic and decreased mitochondrial enzymes

DEFF Research Database (Denmark)

Giebelstein, J; Poschmann, G; Højlund, K

2012-01-01

The molecular mechanisms underlying insulin resistance in skeletal muscle are incompletely understood. Here, we aimed to obtain a global picture of changes in protein abundance in skeletal muscle in obesity and type 2 diabetes, and those associated with whole-body measures of insulin action....

Levels of betatrophin decrease during pregnancy despite increased insulin resistance, beta-cell function and triglyceride levels.

Science.gov (United States)

Zielińska, A; Maciulewski, R; Siewko, K; Popławska-Kita, A; Lipińska, D; Kozłowska, G; Górska, M; Szelachowska, M

2016-12-01

Evidence in support of an association between betatrophin and insulin resistance (IR) is mounting, with studies demonstrating that betatrophin is elevated in patients with type 2 diabetes, obesity and gestational diabetes. The aim of this study was to evaluate the role of betatrophin in IR and physiological proliferation of beta cells during pregnancy in healthy women. Eighty healthy pregnant women were examined at each trimester [T1 (first), T2 (second), T3 (third)], with a subgroup (n=45) that was also examined at 3 months postpartum (3MPP). The controls comprised 30 non-pregnant healthy women (HW) of reproductive age. Also measured were levels of betatrophin (ELISA), glucose (enzymatic method with hexokinase), insulin (IRMA), C-peptide (EASIA) and HbA 1c (HPLC), while HOMA-IR and HOMA-β scores were calculated. Betatrophin concentration was highest at T1, and differed significantly from T2 and T3 (1.84 [Q 1 =1.16, Q 3 =2.67]ng/mL vs 1.46 [Q 1 =0.96, Q 3 =2.21]ng/mL; Pindex scores increased during gestation, peaking at T3 (2.3 [Q 1 =1.66, Q 3 =2.72] and 227.7 [Q 1 =185.49, Q 3 =326.31], respectively) and returning to levels similar to those of HW at 3MPP (1.53 [Q 1 =1.12, Q 3 =2.41] and 88.86 [Q 1 =62.73, Q 3 =130.45] vs 1.35 [Q 1 =1.02, Q 3 =1.62] and 92.5 [Q 1 =74.20, Q 3 =111.47], respectively). Concentrations of betatrophin decrease during pregnancy, suggesting that the hormone does not play a significant role in the expansion of beta-cell mass and IR during pregnancy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Pyrethroid resistance and cross-resistance in the German cockroach, Blattella germanica (L).

Science.gov (United States)

Wei, Y; Appel, A G; Moar, W J; Liu, N

2001-11-01

A German cockroach (Blatella germanica (L)) strain, Apyr-R, was collected from Opelika, Alabama after control failures with pyrethroid insecticides. Levels of resistance to permethrin and deltamethrin in Apyr-R (97- and 480-fold, respectively, compared with a susceptible strain, ACY) were partially or mostly suppressed by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF), suggesting that P450 monooxygenases and hydrolases are involved in resistance to these two pyrethroids in Apyr-R. However, incomplete suppression of pyrethroid resistance with PBO and DEF implies that one or more additional mechanisms are involved in resistance. Injection, compared with topical application, resulted in 43- and 48-fold increases in toxicity of permethrin in ACY and Apyr-R, respectively. Similarly, injection increased the toxicity of deltamethrin 27-fold in ACY and 28-fold in Apyr-R. These data indicate that cuticular penetration is one of the obstacles for the effectiveness of pyrethroids against German cockroaches. However, injection did not change the levels of resistance to either permethrin or deltamethrin, suggesting that a decrease in the rate of cuticular penetration may not play an important role in pyrethroid resistance in Apyr-R. Apyr-R showed cross-resistance to imidacloprid, with a resistance ratio of 10. PBO treatment resulted in no significant change in the toxicity of imidacloprid, implying that P450 monooxygenase-mediated detoxication is not the mechanism responsible for cross-resistance. Apyr-R showed no cross-resistance to spinosad, although spinosad had relatively low toxicity to German cockroaches compared with other insecticides tested in this study. This result further confirmed that the mode of action of spinosad to insects is unique. Fipronil, a relatively new insecticide, was highly toxic to German cockroaches, and the multi-resistance mechanisms in Apyr-R did not confer significant cross-resistance to this compound. Thus, we propose

Bulk and contact resistances of gas diffusion layers in proton exchange membrane fuel cells

Science.gov (United States)

Ye, Donghao; Gauthier, Eric; Benziger, Jay B.; Pan, Mu

2014-06-01

A multi-electrode probe is employed to distinguish the bulk and contact resistances of the catalyst layer (CL) and the gas diffusion layer (GDL) with the bipolar plate (BPP). Resistances are compared for Vulcan carbon catalyst layers (CL), carbon paper and carbon cloth GDL materials, and GDLs with microporous layers (MPL). The Vulcan carbon catalyst layer bulk resistance is 100 times greater than the bulk resistance of carbon paper GDL (Toray TG-H-120). Carbon cloth (CCWP) has bulk and contact resistances twice those of carbon paper. Compression of the GDL decreases the GDL contact resistance, but has little effect on the bulk resistance. Treatment of the GDL with polytetrafluoroethylene (PTFE) increases the contact resistance, but has little effect on the bulk resistance. A microporous layer (MPL) added to the GDL decreases the contact resistance, but has little effect on the bulk resistance. An equivalent circuit model shows that for channels less than 1 mm wide the contact resistance is the major source of electronic resistance and is about 10% of the total ohmic resistance associated with the membrane electrode assembly.

Serendipitous SEU hardening of resistive load SRAMs

International Nuclear Information System (INIS)

Koga, R.; Kirshman, J.F.; Pinkerton, S.D.; Hansel, S.J.; Crawford, K.B.; Crain, W.R.

1996-01-01

High and low resistive load versions of Micron Technology's MT5C1008C (128K x 8) and MT5C2561C (256K x 1) SRAMs were tested for SEU vulnerability. Contrary to computer simulation results, SEU susceptibility decreased with increasing resistive load. A substantially larger number of multiple-bit errors were observed for the low resistive load SRAMs, which also exhibited a 1 → 0 to 0 → 1 bit error ratio close to unity; in contrast, the high resistive load devices displayed a pronounced error bit polarity effect. Two distinct upset mechanisms are proposed to account for these observations

Resistance Switching Characteristics in ZnO-Based Nonvolatile Memory Devices

Directory of Open Access Journals (Sweden)

Fu-Chien Chiu

2013-01-01

Full Text Available Bipolar resistance switching characteristics are demonstrated in Pt/ZnO/Pt nonvolatile memory devices. A negative differential resistance or snapback characteristic can be observed when the memory device switches from a high resistance state to a low resistance state due to the formation of filamentary conducting path. The dependence of pulse width and temperature on set/reset voltages was examined in this work. The exponentially decreasing trend of set/reset voltage with increasing pulse width is observed except when pulse width is larger than 1 s. Hence, to switch the ZnO memory devices, a minimum set/reset voltage is required. The set voltage decreases linearly with the temperature whereas the reset voltage is nearly temperature-independent. In addition, the ac cycling endurance can be over 106 switching cycles, whereas, the dependence of HRS/LRS resistance distribution indicates that a significant memory window closure may take place after about 102  dc switching cycles.

Complementation of a pKM101 derivative that decreases resistance to UV killing but increases susceptibility to mutagenesis

International Nuclear Information System (INIS)

Langer, P.J.; Perry, K.L.; Walker, G.C.

1985-01-01

The drug resistance plasmid pKM101 makes Escherichia coli resistant to the lethal effects of ultraviolet (UV) irradiation and more susceptible to mutagenesis by a variety of agents. The plasmid operon responsible for increasing mutagenesis has been termed mucAB (Mutagenesis, UV and chemical). The authors have isolated a derivative of pKM101 called pGW1975 which makes cells more sensitive to killing by UV but which retains the ability of pKM101 to increase susceptibility to methyl methanesulfonate (MMS) mutagenesis. pGW1975 increases UV mutagenesis less than pKM101 in a uvrA + strain but more than pKM101 in a uvrA - strain. muc - point and insertion mutants of pKM101 and pGW1975 complement to restore the plasmid-mediated: (i) ability to reactivate UV-irradiated phage, (ii) resistance to killing by UV, and (iii) level of susceptibility to UV mutagenesis. They have identified a 2.0 kb region of pKM101 which is responsible for the complementation and which maps counterclockwise of mucAB. (Auth)

Mechanisms of quinolone resistance in Salmonella spp. / Mecanismos de resistência às quinolonas em Salmonella spp.

Directory of Open Access Journals (Sweden)

Tereza Cristina Rocha Moreira de Oliveira

2010-07-01

Full Text Available Salmonellosis is a common and widespread zoonotic disease of humans and a frequent cause of foodborne disease. Treatment of severe and systemic salmonellosis is usually done with fluoroquinolones. In this review resistance mechanisms of Salmonella to quinolones are discussed. Single point mutations in the quinolone resistant determining region (QRDR of the gyrA gene may be sufficient to generate high levels of resistance to non-fluorated quinolones and also may decrease the fluoroquinolones susceptibility. Other resistance mechanisms that should be considered are mutations in parC gene, the possibility of acquiring resistance through plasmidial transference and hyper-expression of efflux pumps. Fluoroquinolones resistance is still relatively uncommon in Salmonella compared to other species belonging to the Enterobacteriaceae family. However, the more careful use of fluoroquinolones in veterinary and human medicine is essential to decrease the selective pressure which can avoid the emergence and spread of resistant clones and consequently maintain the clinical efficacy of this group of antibiotics.A salmonelose é uma zoonose de importância mundial e uma das mais freqüentes doenças de origem alimentar. As fluoroquinolonas são a principal opção para o tratamento de salmoneloses graves ou sistêmicas. Esta revisão de literatura teve como objetivo apresentar os principais mecanismos envolvidos na resistência de Salmonella spp a estes antimicrobianos. Mutações de ponto na Região Determinante de Resistência à Quinolona (QRDR do gene gyrA podem gerar altos níveis de resistência a quinolonas não-fluoradas, além de reduzir a suscetibilidade as fluoroquinolonas. Outros mecanismos de resistência que também precisam ser considerados são as mutações no gene parC, a possibilidade do envolvimento de plasmídios de resistência e o sistema de efluxo ativo. A resistência às fluoroquinolonas ainda é incomum em Salmonella spp., quando

Resisting temptation: decreasing alcohol-related affect and drinking behavior by training response inhibition

NARCIS (Netherlands)

Houben, K.; Nederkoorn, C.; Wiers, R.W.; Jansen, A.

2011-01-01

According to dual-process models, excessive alcohol use emerges when response inhibition ability is insufficient to inhibit automatic impulses to drink alcohol. This study examined whether strengthening response inhibition for alcohol-related cues decreases alcohol intake. Fifty-two heavy drinking

Functional characterization and localization of a gill-specific claudin isoform in Atlantic salmon

DEFF Research Database (Denmark)

Engelund, Morten Buch; Yu, Alan S L; Li, Jiahua

2012-01-01

Claudins are the major determinants of paracellular epithelial permeability in multicellular organisms. In Atlantic salmon (Salmo salar L.), we previously found that mRNA expression of the abundant gill-specific claudin 30 decreases during seawater (SW) acclimation, suggesting that this claudin i...... that claudin 30 functions as a cation barrier between pavement cells in the gill and also has a general role in cell-cell adhesion in deeper layers of the epithelium....

The RESET Mindset Model applied on decreasing antibiotic usage in dairy cattle in the Netherlands

OpenAIRE

Lam, T. J. G. M.; Wessels, R. J.; Jansen, Jolanda

2017-01-01

BACKGROUND: Prudent use of antibiotics is important to prevent antibiotic resistance in humans and in animals. For this reason politicians demanded a decrease of total antibiotic use and of use of critically important antibiotics in animal husbandry in the Netherlands. In the dairy sector the use of antibiotics almost halved in the years 2009-2015, with a decrease of the use of critically important antibiotics to very low levels. THEORY OF BEHAVIOUR CHANGE: To realize a sustainable decrease i...

Insulin decreases atherosclerosis by inducing endothelin receptor B expression

DEFF Research Database (Denmark)

Park, Kyoungmin; Mima, Akira; Li, Qian

2016-01-01

Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1...... induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca(2+)]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1...... overexpression in the endothelia of Aki/ApoE(-/-) mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway...

Rutting and Fatigue Cracking Resistance of Waste Cooking Oil Modified Trinidad Asphaltic Materials

Directory of Open Access Journals (Sweden)

Rean Maharaj

2015-01-01

Full Text Available The influence of waste cooking oil (WCO on the performance characteristics of asphaltic materials indigenous to Trinidad, namely, Trinidad Lake Asphalt (TLA, Trinidad Petroleum Bitumen (TPB, and TLA : TPB (50 : 50 blend, was investigated to deduce the applicability of the WCO as a performance enhancer for the base asphalt. The rheological properties of complex modulus (G∗ and phase angle (δ were measured for modified base asphalt blends containing up to 10% WCO. The results of rheology studies demonstrated that the incremental addition of WCO to the three parent binders resulted in incremental decreases in the rutting resistance (decrease in G∗/sinδ values and increases in the fatigue cracking resistance (decrease in G∗sinδ value. The fatigue cracking resistance and rutting resistance for the TLA : TPB (50 : 50 blends were between those of the blends containing pure TLA and TPB. As operating temperature increased, an increase in the resistance to fatigue cracking and a decrease in the rutting resistance were observed for all of the WCO modified asphaltic blends. This study demonstrated the capability to create customized asphalt-WCO blends to suit special applications and highlights the potential for WCO to be used as an environmentally attractive option for improving the use of Trinidad asphaltic materials.

Effect of Ni Addition on the Wear and Corrosion Resistance of Fe-20Cr-1.7C-1Si Hardfacing Alloy

International Nuclear Information System (INIS)

Lee, Sung Hoon; Kim, Ki Nam; Kim, Seon Jin

2011-01-01

In order to improve the corrosion resistance of Fe-20Cr-1.7C-1Si hardfacing alloy without a loss of wear resistance, the effect of Ni addition was investigated. As expected, the corrosion resistance of the alloy increased with increasing Ni concentration. The wear resistance of the alloy did not decrease, even though the hardness decreased, up to Ni concentration of 5 wt.%. This was attributed to the fact that the decrease in hardness was counterbalanced by the strain-induced martensitic transformation. The wear resistance of the alloy, however, decreased abruptly with increases of the Ni concentration over 5 wt.%.

Cell shunt resistance and photovoltaic module performance

Energy Technology Data Exchange (ETDEWEB)

McMahon, T.J.; Basso, T.S.; Rummel, S.R. [National Renewable Energy Lab., Golden, CO (United States)

1996-05-01

Shunt resistance of cells in photovoltaic modules can affect module power output and could indicate flawed manufacturing processes and reliability problems. The authors describe a two-terminal diagnostic method to directly measure the shunt resistance of individual cells in a series-connected module non-intrusively, without deencapsulation. Peak power efficiency vs. light intensity was measured on a 12-cell, series-connected, single crystalline module having relatively high cell shunt resistances. The module was remeasured with 0.5-, 1-, and 2-ohm resistors attached across each cell to simulate shunt resistances of several emerging technologies. Peak power efficiencies decreased dramatically at lower light levels. Using the PSpice circuit simulator, the authors verified that cell shunt and series resistances can indeed be responsible for the observed peak power efficiency vs. intensity behavior. The authors discuss the effect of basic cell diode parameters, i.e., shunt resistance, series resistance, and recombination losses, on PV module performance as a function of light intensity.

Compound deterioration properties of non-halogen flame-resisting cables

International Nuclear Information System (INIS)

Yamamoto, Yasuaki; Yagyu, Hideki; Onishi, Takao; Kamiharako, Shinji

1984-01-01

Conventional flame-resisting cables release harmful gas such as hydrogen chloride and smoke on burning. To improve this disadvantage, the cables for nuclear power plants using new non-halogen flame-resisting insulating material have been developed. In this experiment, the non-halogen flame-resisting cables were subjected to the environmental test with varying test conditions. The test conditions included the order of exposure (heat treatment, γ-ray irradiation and steam exposure) and dose rate. After the environmental test, the mechanical and electrical properties of the samples were measured. In all test conditions, the samples did not crack in bending, and withstood the bending and withstand-voltage in-water test. The tensile strength and a.c. breakdown voltage did not change, and were stable. The elongation decreased greatly, but maintained the value of about 100 %, and the volumetric resistivity decreased by only one figure. It was confirmed that these cables were able to withstand various environmental tests. (Yoshitake, I.)

Antimicrobial resistance in Shigella spp. causing traveller's diarrhoea (1995-2010): a retrospective analysis.

Science.gov (United States)

Pons, M J; Gomes, C; Martínez-Puchol, S; Ruiz, L; Mensa, L; Vila, J; Gascón, J; Ruiz, J

2013-01-01

Shigellosis is a global human health problem causing an important morbidity among travellers returning from tropical areas. This study was aimed to describe the evolution of antimicrobial resistance profile in Shigella spp. isolated between the years 1995-2010 in patients with traveller's diarrhoea (TD) returning from tropical areas. The levels of antimicrobial resistance were tested in a total of 191 Shigella spp. isolated during the period from 1995 to 2010. A decrease of cases of diarrhoea caused by Shigella has been observed in recent years. A wide spectrum of antibiotic resistance was observed among Shigella spp. These isolates showed high levels of resistance to tetracycline (84%), co-trimoxazole (75.5%), and ampicillin (45.5%). The resistance was low to ciprofloxacin (2.1%), azithromycin (3.9%) and furazolidone (8.4%). According to the period, in the case of ampicillin, amoxicillin plus clavulanic acid, chloramphenicol, values of resistance were significantly decreasing from 1995-2000 to 2001-2010, (62.5% vs. 28.4%, 19.8% vs. 6.6%, 23.4 vs. 10.4%, respectively). Meanwhile in nalidixic acid and tetracycline the evolution of resistance has increased over time. A decrease in the isolation number of Shigella spp. causing TD has been observed. Differential trends in the evolution of the levels of resistance to the tested antibacterial agents have been observed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trends in antimicrobial susceptibility and presence of resistance genes in Staphylococcus hyicus isolated from exudative epidermitis in pigs

DEFF Research Database (Denmark)

Aarestrup, Frank Møller; Jensen, L. B.

2002-01-01

(vat, vga, vga(B), vat(B), vat(D) and vat(E)), streptomycin (aadE) and tetracycline resistance (tet(K), tet(L), tet(M) and tet(O)) were determined in selected isolates. The occurrence of erythromycin resistance increased from 33% in 1996 to a maximum of 62% in 1997 and decreased to 26% in 2001....... Resistance to sulphametazole increased from 17% in 1996 to 30% in 1998 but has since decreased to 4% in 2001. Resistance to trimethoprim increased to 51% in 1997 and decreased to 21% in 2001. Resistance to tetracycline (21-31%) remained relatively constant during 1996-2000, but increased to 47% in 2001...

Mechanisms of drug resistance in cancer cells

International Nuclear Information System (INIS)

Iqbal, M.P.

2003-01-01

Development of drug resist chemotherapy. For the past several years, investigators have been striving hard to unravel mechanisms of drug resistance in cancer cells. Using different experimental models of cancer, some of the major mechanisms of drug resistance identified in mammalian cells include: (a) Altered transport of the drug (decreased influx of the drug; increased efflux of the drug (role of P-glycoprotein; role of polyglutamation; role of multiple drug resistance associated protein)), (b) Increase in total amount of target enzyme/protein (gene amplification), (c) alteration in the target enzyme/protein (low affinity enzyme), (d) Elevation of cellular glutathione, (e) Inhibition of drug-induced apoptosis (mutation in p53 tumor suppressor gene; increased expression of bcl-xl gene). (author)

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

Directory of Open Access Journals (Sweden)

Yanan Gao

2017-12-01

Full Text Available Aflatoxin M1 (AFM1 and ochratoxin A (OTA are mycotoxins commonly found in milk; however, their effects on intestinal epithelial cells have not been reported. In the present study, we show that AFM1 (0.12 and 12 μM and OTA (0.2 and 20 μM individually or collectively increased the paracellular flux of lucifer yellow and fluorescein isothiocyanate (FITC-dextrans (4 and 40 kDa and decreased transepithelial electrical resistance values in differentiated Caco-2 cells after 48 h of exposure, indicating increased epithelial permeability. Immunoblotting and immunofluorescent analysis revealed that AFM1, OTA, and their combination decreased the expression levels of tight junction (TJ proteins and disrupted their structures, namely, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1, and p44/42 mitogen-activated protein kinase (MAPK partially involved in the mycotoxins-induced disruption of intestinal barrier. The effects of a combination of AFM1 and OTA on intestinal barrier function were more significant (p < 0.05 than those of AFM1 and OTA alone, yielding additive or synergistic effects. The additive or synergistic effects of AFM1 and OTA on intestinal barrier function might affect human health, especially in children, and toxin risks should be considered.

Celecoxib decreases growth and angiogenesis and promotes apoptosis in a tumor cell line resistant to chemotherapy

Directory of Open Access Journals (Sweden)

Carlos Rosas

2014-01-01

Full Text Available BACKGROUND: During the last few years it has been shown in several laboratories that Celecoxib (Cx, a non-steroidal anti-inflammatory agent (NSAID normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. However, the effects of this drug on a tumor cell line resistant to chemotherapeutical drugs used in cancer have not been described. Herein we evaluate the angiogenic and antitumor effects of Cx in the development of a drug-resistant mammary adenocarcinoma tumor (TA3-MTXR. RESULTS: Cx reduces angiogenesis in the chick embryonic chorioallantoic membrane assay (CAM, inhibits the growth and microvascular density of the murine TA3-MTXR tumor, reduces microvascular density of tumor metastases, promotes apoptosis and reduces vascular endothelial growth factor (VEGF production and cell proliferation in the tumor. CONCLUSION: The antiangiogenic and antitumor Cx effects correlate with its activity on other tumor cell lines, suggesting that Prostaglandins (PGs and VEGF production are involved. These results open the possibility of using Celecoxib combined with other experimental therapies, ideally aiming to get synergic effects.

Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab

Science.gov (United States)

Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R

2011-01-01

The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical success; however, many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in the activation of EGFR, HER2 and HER3 receptors as well as increased signaling through the MAP K and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared with vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increased rates of apoptosis. The work presented herein suggests that (1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and (2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing rationale

How the nature of the chemical bond governs resistance to amorphization by radiation damage

International Nuclear Information System (INIS)

Trachenko, Kostya; Artacho, Emilio; Dove, Martin T.; Pruneda, J.M.

2005-01-01

We discuss what defines a material's resistance to amorphization by radiation damage. We propose that resistance is generally governed by the competition between the short-range covalent and long-range ionic forces, and we quantify this picture using quantum-mechanical calculations. We calculate the Voronoi deformation density charges and Mulliken overlap populations of 36 materials, representative of different families, including complex oxides. We find that the computed numbers generally follow the trends of experimental resistance in several distinct families of materials: the increase (decrease) of the short-range covalent component in material's total force field decreases (increases) its resistance

MCAM/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelial-mesenchymal transition, decreased ER alpha expression and AKT activation

NARCIS (Netherlands)

Liang, Yuan-Ke; Zeng, De; Xiao, Ying-Sheng; Wu, Yang; Ouyang, Yan-Xiu; Chen, Min; Li, Yao-Chen; Lin, Hao-Yu; Wei, Xiao-Long; Zhang, Yong-Qu; Kruyt, Frank A. E.; Zhang, Guo-Jun

2017-01-01

Tamoxifen resistance presents a prominent clinical challenge in endocrine therapy for hormone sensitive breast cancer. However, the underlying mechanisms that contribute to tamoxifen resistance are not fully understood. In this study, we established a tamoxifen resistant MCF-7 cell line

Temperature influence and reset voltage study of bipolar resistive ...

Indian Academy of Sciences (India)

Moreover, the Cu/ZrO2/ATO device which the ZrO2 thin film annealed at 300 °C can be measured as resistive switching sweeps at 200, 100 and 50 K. It was found that the ratio of off/on reduced when the measured temperature decreased. When the - measurement temperature decreases, on decreases obviously ...

Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae.

OpenAIRE

Dowson, C G; Hutchison, A; Woodford, N; Johnson, A P; George, R C; Spratt, B G

1990-01-01

Penicillin-resistant strains of Streptococcus pneumoniae possess altered forms of penicillin-binding proteins (PBPs) with decreased affinity for penicillin. The PBP2B genes of these strains have a mosaic structure, consisting of regions that are very similar to those in penicillin-sensitive strains, alternating with regions that are highly diverged. Penicillin-resistant strains of viridans groups streptococci (e.g., S. sanguis and S. oralis) that produce altered PBPs have also been reported. ...

Determinants of Growth Hormone Resistance in Malnutrition

Science.gov (United States)

Fazeli, Pouneh K.; Klibanski, Anne

2014-01-01

States of under-nutrition are characterized by growth hormone resistance. Decreased total energy intake, as well as isolated protein-calorie malnutrition and isolated nutrient deficiencies result in elevated growth hormone levels and low levels of IGF-I. We review various states of malnutrition and a disease state characterized by chronic under-nutrition -- anorexia nervosa -- and discuss possible mechanisms contributing to the state of growth hormone resistance, including FGF-21 and SIRT1. We conclude by examining the hypothesis that growth hormone resistance is an adaptive response to states of under-nutrition, in order to maintain euglycemia and preserve energy. PMID:24363451

Antimicrobial resistance programs in canada 1995-2010: a critical evaluation

Directory of Open Access Journals (Sweden)

Conly John M

2012-02-01

Full Text Available Abstract Background In Canada, systematic efforts for controlling antibiotic resistance began in 1997 following a national Consensus Conference. The Canadian strategy produced 27 recommendations, one of which was the formation of the Canadian Committee on Antibiotic Resistance (CCAR. In addition several other organizations began working on a national or provincial basis over the ensuing years on one or more of the 3 identified core areas of the strategy. Critical evaluation of the major programs within Canada which focused on antimicrobial resistance and the identified core components has not been previously conducted. Findings Data was collected from multiple sources to determine the components of four major AMR programs that were considered national based on their scope or in the delivery of their mandates. Assessment of program components was adapted from the report from the International Forum on Antibiotic Resistance colloquium. Most of the programs used similar tools but only the Do Bugs Need Drugs Program (DBND had components directed towards day cares and schools. Surveillance programs for antimicrobial resistant pathogens have limitations and/or significant sources of bias. Overall, there has been a 25.3% decrease in oral antimicrobial prescriptions in Canada since 1995, mainly due to decreases in β lactams, sulphonamides and tetracyclines in temporal association with multiple programs with the most comprehensive and sustained national programs being CCAR and DBND. Conclusions Although there has been a substantial decrease in oral antimicrobial prescriptions in Canada since 1995, there remains a lack of leadership and co-ordination of antimicrobial resistance activities.

Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1-40/42 and Phospho-Tau May Abet Alzheimer Development.

Science.gov (United States)

Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret; Farese, Robert V

2016-07-01

Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat-fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1-40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1-40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1–40/42 and Phospho-Tau May Abet Alzheimer Development

Science.gov (United States)

Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret

2016-01-01

Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat–fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1–40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1–40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. PMID:26895791

Influence of HMB supplementation and resistance training on cytokine responses to resistance exercise.

Science.gov (United States)

Kraemer, William J; Hatfield, Disa L; Comstock, Brett A; Fragala, Maren S; Davitt, Patrick M; Cortis, Cristina; Wilson, Jacob M; Lee, Elaine C; Newton, Robert U; Dunn-Lewis, Courtenay; Häkkinen, Keijo; Szivak, Tunde K; Hooper, David R; Flanagan, Shawn D; Looney, David P; White, Mark T; Volek, Jeff S; Maresh, Carl M

2014-01-01

The purpose of this study was to determine the effects of a multinutritional supplement including amino acids, β-hydroxy-β-methylbutyrate (HMB), and carbohydrates on cytokine responses to resistance exercise and training. Seventeen healthy, college-aged men were randomly assigned to a Muscle Armor™ (MA; Abbott Nutrition, Columbus, OH) or placebo supplement group and 12 weeks of resistance training. An acute resistance exercise protocol was administered at 0, 6, and 12 weeks of training. Venous blood samples at pre-, immediately post-, and 30-minutes postexercise were analyzed via bead multiplex immunoassay for 17 cytokines. After 12 weeks of training, the MA group exhibited decreased interferon-gamma (IFN-γ) and interleukin (IL)-10. IL-1β differed by group at various times. Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-7, IL-8, IL-12p70, IL-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1β) changed over the 12-week training period but did not differ by group. Twelve weeks of resistance training alters the cytokine response to acute resistance exercise, and supplementation with HMB and amino acids appears to further augment this result.

Effect of thiazolidinedione treatment on resistin levels in insulin resistant sprague dawley rats

International Nuclear Information System (INIS)

Yousaf, I.; Hameed, W.; Rajput, T.A.

2015-01-01

Insulin resistance is manifested by decreased effect of fixed quantity of insulin on glucose metabolism leading to type 2 diabetes mellitus. Visceral obesity has been positively correlated with insulin resistance but its mechanism is not fully defined. Insulin resistance may be the consequence of adipocytokines including visfatin and resistin. This study was designed to see the effect of thiazolidinediones on levels of resistin in insulin resistant rats. Methods: Ninety Sprague Dawley rats were randomly divided into three groups. Group I served as control. Rats in Group II and III were made insulin resistant diabetics. Group III was treated with rosiglitazone after development of diabetes. Plasma glucose, serum triglycerides, HDL, TG:HDL ratio and serum resistin levels were analysed. Results: Body weight and plasma glucose were significantly increased (p<0.05) along with TG:HDL ratio (p<0.05) in group II and group III at the end of 4th week. Serum resistin levels also increased significantly (p<0.05) in group II and III at the end of 4th week. Treatment of group III with rosiglitazone led to improvement in insulin resistance with decrease in serum resistin levels (p<0.05). Conclusion: Increased serum resistin level indicates insulin resistance and impending hyperglycaemia. Thiazolidinediones augment sensitivity of insulin to restore normoglycaemia by decreasing serum resistin level. (author)

Effect of fractionated radiation on multidrug resistance in human ovarian cancer

International Nuclear Information System (INIS)

Kong Dejuan; Liu Xiaodong; Liang Bing; Jia Lili; Ma Shumei

2012-01-01

Objective: To investigate the effect of different subtypes of fractionated doses on multidrug resistance in ovarian cancer cells. Methods: The human ovarian cancer cell lines SKOV3 and its drug-resistant subtype SKVCR were divided into four groups i.e., sham-irradiated, single dose (10 Gy), fractionated dose (2 Gy × 5) and multi-fractionated dose (1 Gy × 2 × 5). Cell sensitivity to vincristine (VCR), etoposide (VP-16), pirarubicin (THP) and cisplatin (DDP) was measured by MTT assay. Western blot was applied to detect the expression of P-gp after irradiation. Results: The doubling time of SKVCR was about 1.8-fold of that of SKOV3 cells. P-gp was expressed in SKVCR but not in SKOV3. IC 50 values of SKVCR were higher than those of SKOV3. To SKOV3 cells, single dose irradiation decreased cell sensitivity to THP and DDP and fractionated irradiation decreased cell sensitivity to VCR, THP and VP-16. Multi-fractionated irradiation decreased cell sensitivity to VP-16. In SKVCR cells, all these irradiation treatments increased cell sensitivity to VCR and VP-16 but not to DDP. In addition, single and fractionated irradiation decreased P-gp expression in SKVCR cells. Conclusions: Single, fractionated and multi-fractionated radiation induced chemotherapy resistance in SKOV3 cells, while reversed drug resistance to VCR and VP-16 in SKVCR cells. (authors)

Antibiotic-Impregnated Central Venous Catheters Do Not Change Antibiotic Resistance Patterns.

Science.gov (United States)

Turnbull, Isaiah R; Buckman, Sara A; Horn, Christopher B; Bochicchio, Grant V; Mazuski, John E

2018-01-01

Antibiotic-impregnated central venous catheters (CVCs) decrease the incidence of infection in high-risk patients. However, use of these catheters carries the hypothetical risk of inducing antibiotic resistance. We hypothesized that routine use of minocycline and rifampin-impregnated catheters (MR-CVC) in a single intensive care unit (ICU) would change the resistance profile for Staphylococcus aureus. We reviewed antibiotic susceptibilities of S. aureus isolates obtained from blood cultures in a large urban teaching hospital from 2002-2015. Resistance patterns were compared before and after implementation of MR-CVC use in the surgical ICU (SICU) in August 2006. We also compared resistance patterns of S. aureus obtained in other ICUs and in non-ICU patients, in whom MR-CVCs were not used. Data for rifampin, oxacillin, and clindamycin were available for 9,703 cultures; tetracycline resistance data were available for 4,627 cultures. After implementation of MR-CVC use in the SICU, rifampin resistance remained unchanged, with rates the same as in other ICU and non-ICU populations (3%). After six years of use of MR-CVCs in the SICU, the rate of tetracycline resistance was unchanged in all facilities (1%-3%). The use of MR-CVCs was not associated with any change in S. aureus oxacillin-resistance rates in the SICU (66% vs. 60%). However, there was a significant decrease in S. aureus clindamycin resistance (59% vs. 34%; p resistance of S. aureus isolates to rifampin or tetracyclines.

Annealing Effects on the Normal-State Resistive Properties of Underdoped Cuprates

Science.gov (United States)

Vovk, R. V.; Khadzhai, G. Ya.; Nazyrov, Z. F.; Kamchatnaya, S. N.; Feher, A.; Dobrovolskiy, O. V.

2018-05-01

The influence of room-temperature annealing on the parameters of the basal-plane electrical resistance of underdoped YBa_2Cu_3O_{7-δ } and HoBa_2Cu_3O_{7-δ } single crystals in the normal and superconducting states is investigated. The form of the derivatives dρ (T)/dT makes it possible to determine the onset temperature of the fluctuation conductivity and indicates a nonuniform distribution of the labile oxygen. Annealing has been revealed to lead to a monotonic decrease in the oxygen deficiency, that primarily manifests itself as a decrease in the residual resistance, an increase of T_c, and a decrease in the Debye temperature.

Resistivity dependence of magnetoresistance in Co/ZnO films.

Science.gov (United States)

Quan, Zhi-Yong; Zhang, Li; Liu, Wei; Zeng, Hao; Xu, Xiao-Hong

2014-01-06

We report the dependence of magnetoresistance effect on resistivity (ρ) in Co/ZnO films deposited by magnetron sputtering at different sputtering pressures with different ZnO contents. The magnitude of the resistivity reflects different carrier transport regimes ranging from metallic to hopping behaviors. Large room-temperature magnetoresistance greater than 8% is obtained in the resistivity range from 0.08 to 0.5 Ω · cm. The magnetoresistance value decreases markedly when the resistivity of the films is less than 0.08 Ω · cm or greater than 0.5 Ω · cm. When 0.08 Ω · cm magnetoresistance effect. When ρ > 0.5 Ω · cm, the spin-independent higher-order hopping (N > 2) comes into play and decreases the tunneling magnetoresistance value. For the samples with ρ magnetoresistance is mainly ascribed to the formation of percolation paths through interconnected elongated metallic Co particles. This observation is significant for the improvement of room-temperature magnetoresistance value for future spintronic devices.

Recovery of electrical resistance in copper films on polyethylene terephthalate subjected to a tensile strain

International Nuclear Information System (INIS)

Glushko, O.; Marx, V.M.; Kirchlechner, C.; Zizak, I.; Cordill, M.J.

2014-01-01

Substantial recovery (decrease) of electrical resistance during and after unloading is demonstrated for copper films on polyethylene terephthalate substrates subjected to a tensile strain with different peak values. Particularly, the films strained to 5% exhibit full resistance recovery after unloading despite clearly visible plastic deformation of the film. The recovery of electrical resistance in connection with the mechanical behavior of film/substrate couple is discussed with the help of in situ scanning electron microscopy and X-ray diffraction analysis. - Highlights: • Tensile tests on 200 nm Cu films on PET substrate are performed. • Electrical resistance is recorded in-situ during loading and unloading. • Significant recovery (decrease) of resistance is observed during and after unloading. • Films strained to 5% demonstrate full resistance recovery. • Viscoelastic relaxation of PET is responsible for recovery of Cu film resistance

The depressed central carbon and energy metabolisms is associated to the acquisition of levofloxacin resistance in Vibrio alginolyticus.

Science.gov (United States)

Cheng, Zhi-Xue; Yang, Man-Jun; Peng, Bo; Peng, Xuan-Xian; Lin, Xiang-Min; Li, Hui

2018-06-15

The overuse and misuse of antibiotics lead to bacterial antibiotic resistance, challenging human health and intensive cultivation. It is especially required to understand for the mechanism of antibiotic resistance to control antibiotic-resistant pathogens. The present study characterized the differential proteome of levofloxacin-resistant Vibrio alginolyticus with the most advanced iTRAQ quantitative proteomics technology. A total of 160 proteins of differential abundance were identified, where 70 were decreased and 90 were increased. Further analysis demonstrated that crucial metabolic pathways like TCA cycle were significantly down-regulated. qRT-PCR analysis demonstrated the decreased gene expression of glycolysis/gluconeogenesis, the TCA cycle, and fatty acid biosynthesis. Moreover, Na(+)-NQR complex gene expression, membrane potential and the adenylate energy charge ratio were decreased, indicating that the decreased central carbon metabolism is associated to the acquisition of levofloxacin resistance. Therefore, the reduced central carbon and energy metabolisms form a characteristic feature as fitness costs of V. alginolyticus in resistance to levofloxacin. The overuse and misuse of antibiotics lead to bacterial antibiotic resistance, challenging human health and intensive cultivation. Understanding for the antibiotic resistance mechanisms is especially required to control these antibiotic-resistant pathogens. The present study characterized the differential proteome of levofloxacin-resistant Vibrio alginolyticus using the most advanced iTRAQ quantitative proteomics technology. A total of 160 differential abundance of proteins were identified with 70 decreases and 90 increases by liquid chromatography matrix assisted laser desorption ionization mass spectrometry. Most interestingly, crucial metabolic pathways such as the TCA cycle sharply fluctuated. This is the first report that the reduced central carbon and energy metabolisms form a characteristic feature

Improved corrosion resistance of spin-valve film

International Nuclear Information System (INIS)

Tetsukawa, H.; Hommura, H.; Okabe, A.; Soda, Y.

2007-01-01

We investigated the corrosion behavior and magnetoresistance of spin-valve film in order to improve the corrosion resistance of the spin-valve head for a tape recording system. The conventional spin-valve head (sub./Ta/NiFe/CoFe/Cu/CoFe/PtMn/Ta) with no diamond-like carbon (DLC) protective layer showed poor corrosion resistance. This is because the CoFe for ferromagnetic layer and Cu for spacer in the spin-valve film exhibited poor corrosion resistance. The corrosion resistance of the CoFe film and Cu film improved with the addition of Ni and Au, respectively. The spin-valve film (sub./Ta/NiFe/CoNiFe/CuAu/CoNiFe/PtMn/Ta) showed higher pitting potential than the conventional spin-valve film by +0.45 V. This presents a significant improvement over the conventional spin-valve film. We also investigated the effect of the composition of ferromagnetic layer and spacer on the magnetoresistance of the spin-valve film. The magnetoresistance of the spin-valve film by substitution of CoNiFe for CoFe in ferromagnetic layer decreased slightly. The magnetoresistance of the spin-valve film decreased as the addition of Au of the spacer increased. The diffusion at CoNiFe/CuAu interface has not been observed in annealing process. The quantitative relation between corrosion resistance and magnetoresistance of spin-valve film, and its ferromagnetic layer and spacer's compositions have been clarified. The output voltage at 50 Oe of the corrosion-resistant spin-valve head with CoNiFe ferromagnetic layer and CuAu spacer was about 50% of that of the conventional spin-valve head

Improved corrosion resistance of spin-valve film

Energy Technology Data Exchange (ETDEWEB)

Tetsukawa, H. [Sony Corporation, 6-7-35 Kitashinagawa, Shinagawa-ku, Tokyo 141-0001 (Japan)]. E-mail: tetsukaw@arc.sony.co.jp; Hommura, H. [Sony Corporation, 6-7-35 Kitashinagawa, Shinagawa-ku, Tokyo 141-0001 (Japan); Okabe, A. [Sony Corporation, 6-7-35 Kitashinagawa, Shinagawa-ku, Tokyo 141-0001 (Japan); Soda, Y. [Sony Corporation, 6-7-35 Kitashinagawa, Shinagawa-ku, Tokyo 141-0001 (Japan)

2007-06-15

We investigated the corrosion behavior and magnetoresistance of spin-valve film in order to improve the corrosion resistance of the spin-valve head for a tape recording system. The conventional spin-valve head (sub./Ta/NiFe/CoFe/Cu/CoFe/PtMn/Ta) with no diamond-like carbon (DLC) protective layer showed poor corrosion resistance. This is because the CoFe for ferromagnetic layer and Cu for spacer in the spin-valve film exhibited poor corrosion resistance. The corrosion resistance of the CoFe film and Cu film improved with the addition of Ni and Au, respectively. The spin-valve film (sub./Ta/NiFe/CoNiFe/CuAu/CoNiFe/PtMn/Ta) showed higher pitting potential than the conventional spin-valve film by +0.45 V. This presents a significant improvement over the conventional spin-valve film. We also investigated the effect of the composition of ferromagnetic layer and spacer on the magnetoresistance of the spin-valve film. The magnetoresistance of the spin-valve film by substitution of CoNiFe for CoFe in ferromagnetic layer decreased slightly. The magnetoresistance of the spin-valve film decreased as the addition of Au of the spacer increased. The diffusion at CoNiFe/CuAu interface has not been observed in annealing process. The quantitative relation between corrosion resistance and magnetoresistance of spin-valve film, and its ferromagnetic layer and spacer's compositions have been clarified. The output voltage at 50 Oe of the corrosion-resistant spin-valve head with CoNiFe ferromagnetic layer and CuAu spacer was about 50% of that of the conventional spin-valve head.

Progesterone resistance in endometriosis

DEFF Research Database (Denmark)

Patel, Bansari G; Rudnicki, Martin; Yu, Jie

2017-01-01

Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women...... with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment...... renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone resistant state...

Xylitol prevents NEFA-induced insulin resistance in rats

Science.gov (United States)

Kishore, P.; Kehlenbrink, S.; Hu, M.; Zhang, K.; Gutierrez-Juarez, R.; Koppaka, S.; El-Maghrabi, M. R.

2013-01-01

Aims/hypothesis Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. Methods We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic–hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. Results Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. Conclusions/interpretation We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects. PMID:22460760

Pre-operative antiseptic shower and bath policy decreases the rate of S. aureus and methicillin-resistant S. aureus surgical site infections in patients undergoing joint arthroplasty.

Science.gov (United States)

Colling, Kristin; Statz, Catherine; Glover, James; Banton, Kaysie; Beilman, Greg

2015-04-01

Surgical site infection (SSI) following joint arthroplasty increases length of stay, hospital cost, and leads to patient and healthcare provider dissatisfaction. Due to the presence of non-biologic implants (the prosthetic joint) in these procedures, infection is often devastating and treatment of the infection is more difficult. For this reason, prevention of SSI is of crucial importance in this population. Staphylococcus aureus colonizes the nares of approximately 30-40% of the population, is the most common pathogen causing SSI, and is associated with high morbidity and mortality rate. A pre-operative shower or bath with an antiseptic is an inexpensive and effective method of removal of these transient skin pathogens prior to the procedure and may be used to decrease SSI. We hypothesize that a preoperative antiseptic shower or bath will decrease the rate of SSI. A retrospective review was performed at two affiliated hospitals within the same system, one with a hospital-wide policy enforcing pre-operative antiseptic shower or bath and the other with no policy, with cases included from January 2010 to June 2012. International Classification of Disease-Ninth Revision-Clinical Modification (ICD-9-CM) codes and chart review were used to identify patients undergoing joint arthroplasty and to identify those with SSI. Two thousand three-hundred forty-nine arthroplasties were performed at the University of Minnesota Medical Center, a tertiary-care hospital with a pre-operative antiseptic shower or bath policy in place. An additional 1,693 procedures were performed at Fairview Ridges Hospital, a community hospital with no pre-operative policy. There was no difference in the rate of SSI between the two hospitals (1.96% vs. 1.95%; p=1.0). However, the rate of SSI caused by S. aureus was significantly decreased by pre-operative antiseptic shower/bath (17% vs. 61%; p=0.03), as was the rate of methicillin-resistant S. aureus (MRSA) infections (2% vs. 24% p=0.002). A pre

Decalcification resistance of alkali-activated slag

Energy Technology Data Exchange (ETDEWEB)

Komljenovic, Miroslav M., E-mail: miroslav.komljenovic@imsi.rs [Institute for Multidisciplinary Research, University of Belgrade, Kneza Viseslava 1, 11030 Belgrade (Serbia); Bascarevic, Zvezdana, E-mail: zvezdana@imsi.bg.ac.rs [Institute for Multidisciplinary Research, University of Belgrade, Kneza Viseslava 1, 11030 Belgrade (Serbia); Marjanovic, Natasa, E-mail: natasa@imsi.bg.ac.rs [Institute for Multidisciplinary Research, University of Belgrade, Kneza Viseslava 1, 11030 Belgrade (Serbia); Nikolic, Violeta, E-mail: violeta@imsi.bg.ac.rs [Institute for Multidisciplinary Research, University of Belgrade, Kneza Viseslava 1, 11030 Belgrade (Serbia)

2012-09-30

Highlights: Black-Right-Pointing-Pointer The effects of decalcification on properties of alkali-activated slag were studied. Black-Right-Pointing-Pointer Decalcification was performed by concentrated NH{sub 4}NO{sub 3} solution (accelerated test). Black-Right-Pointing-Pointer Portland-slag cement (CEM II/A-S 42.5 N) was used as a benchmark material. Black-Right-Pointing-Pointer Decalcification led to strength decrease and noticeable structural changes. Black-Right-Pointing-Pointer Alkali-activated slag showed significantly higher resistance to decalcification. - Abstract: This paper analyses the effects of decalcification in concentrated 6 M NH{sub 4}NO{sub 3} solution on mechanical and microstructural properties of alkali-activated slag (AAS). Portland-slag cement (CEM II/A-S 42.5 N) was used as a benchmark material. Decalcification process led to a decrease in strength, both in AAS and in CEM II, and this effect was more pronounced in CEM II. The decrease in strength was explicitly related to the decrease in Ca/Si atomic ratio of C-S-H gel. A very low ratio of Ca/Si {approx}0.3 in AAS was the consequence of coexistence of C-S-H(I) gel and silica gel. During decalcification of AAS almost complete leaching of sodium and tetrahedral aluminum from C-S-H(I) gel also took place. AAS showed significantly higher resistance to decalcification in relation to the benchmark CEM II due to the absence of portlandite, high level of polymerization of silicate chains, low level of aluminum for silicon substitution in the structure of C-S-H(I), and the formation of protective layer of polymerized silica gel during decalcification process. In stabilization/solidification processes alkali-activated slag represents a more promising solution than Portland-slag cement due to significantly higher resistance to decalcification.

Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults.

Science.gov (United States)

Villareal, Dennis T; Aguirre, Lina; Gurney, A Burke; Waters, Debra L; Sinacore, David R; Colombo, Elizabeth; Armamento-Villareal, Reina; Qualls, Clifford

2017-05-18

Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia. In this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs - aerobic training, resistance training, or combined aerobic and resistance training - or to a control group (no weight-management or exercise program). The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance). Secondary outcomes included changes in other frailty measures, body composition, bone mineral density, and physical functions. A total of 141 participants completed the study. The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to 33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively; P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all exercise groups than in the control group (Pexercise groups but did not change significantly in the control group. Lean mass decreased less in the combination and resistance groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1 kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1% decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991 [3% decrease]) (PExercise-related adverse events included musculoskeletal injuries. Of the methods tested, weight loss plus combined aerobic and resistance exercise was the most effective in improving

Effect of heat treatment on the electrical resistance of photoresist as related to radioisotopic thermoelectric generator aging

International Nuclear Information System (INIS)

Johnson, R.T. Jr.

1979-03-01

Photoresist is used in electrical contact definition and processing in radioisotopic thermoelectric generators. Inadequate removal of material during processing could lead to electrical shorting when exposed to the high temperature use environment. This effect has been simulated through studies of the electrical resistance of thin layers of photoresist (Kodak Metal Etch Resist) on glass (Corning 7052) with tungsten electrodes. Results show that both the photoresist and the glass contribute to the resistance. The glass resistance decreases with increasing temperature and becomes significant at high temperatures. Annealing studies on the photoresist show that the resistance of the photoresist decreases by over five orders of magnitude upon annealing to 500 0 C, with a corresponding decrease in activation energy from 0.27 eV (350 0 C anneal) to 0.10 eV (500 0 C anneal). Time dependent decreases in resistance of the photoresist were also measured for up to 8 to 9 days during high temperature anneals. Some electrolytic transport of tungsten may occur through the photoresist at high temperatures. Results are compared with data on thermoelectric generators and show that photoresist could cause the electrical aging (voltage degradation) problem observed in some generators

Resistive foil edge grading for accelerator and other high voltage structures

Science.gov (United States)

Caporaso, George J.; Sampayan, Stephen F.; Sanders, David M.

2014-06-10

In a structure or device having a pair of electrical conductors separated by an insulator across which a voltage is placed, resistive layers are formed around the conductors to force the electric potential within the insulator to distribute more uniformly so as to decrease or eliminate electric field enhancement at the conductor edges. This is done by utilizing the properties of resistive layers to allow the voltage on the electrode to diffuse outwards, reducing the field stress at the conductor edge. Preferably, the resistive layer has a tapered resistivity, with a lower resistivity adjacent to the conductor and a higher resistivity away from the conductor. Generally, a resistive path across the insulator is provided, preferably by providing a resistive region in the bulk of the insulator, with the resistive layer extending over the resistive region.

Conserved Aromatic Residue Confers Cation Selectivity in Claudin-2 and Claudin-10b*

Science.gov (United States)

Li, Jiahua; Zhuo, Min; Pei, Lei; Yu, Alan S. L.

2013-01-01

In tight junctions, both claudin-2 and claudin-10b form paracellular cation-selective pores by the interaction of the first ECL 1 with permeating ions. We hypothesized that a highly conserved aromatic residue near the pore selectivity filter of claudins contributes to cation selectivity by cation-π interaction with the permeating cation. To test this, we generated MDCK I Tet-off cells stably transfected with claudin-2 Tyr67 mutants. The Y67L mutant showed reduced cation selectivity compared with wild-type claudin-2 due to a decrease in Na+ permeability, without affecting the Cl− permeability. The Y67A mutant enlarged the pore size and further decreased the charge selectivity due to an increase in Cl− permeability. The Y67F mutant restored the Na+ permeability, Cl− permeability, and pore size back to wild-type. The accessibility of Y67C to methanethiosulfonate modification indicated that its side chain faces the lumen of the pore. In claudin-10b, the F66L mutant reduced cation selectivity, and the F66A mutant lost pore conductance. We conclude that the conserved aromatic residue near the cation pore domain of claudins contributes to cation selectivity by a dual role of cation-π interaction and a luminal steric effect. Our findings provide new insight into how ion selectivity is achieved in the paracellular pore. PMID:23760508

Experimental study of the complex resistivity and dielectric constant of chrome-contaminated soil

Science.gov (United States)

Liu, Haorui; Yang, Heli; Yi, Fengyan

2016-08-01

Heavy metals such as arsenic and chromium often contaminate soils near industrialized areas. Soil samples, made with different water content and chromate pollutant concentrations, are often needed to test soil quality. Because complex resistivity and complex dielectric characteristics of these samples need to be measured, the relationship between these measurement results and chromium concentration as well as water content was studied. Based on soil sample observations, the amplitude of the sample complex resistivity decreased with an increase of contamination concentration and water content. The phase of complex resistivity takes on a tendency of initially decrease, and then increase with the increasing of contamination concentration and water content. For a soil sample with the same resistivity, the higher the amplitude of complex resistivity, the lower the water content and the higher the contamination concentration. The real and imaginary parts of the complex dielectric constant increase with an increase in contamination concentration and water content. Note that resistivity and complex resistivity methods are necessary to adequately evaluate pollution at various sites.

Resistance of green lacewing, Chrysoperla carnea Stephens to nitenpyram: Cross-resistance patterns, mechanism, stability, and realized heritability.

Science.gov (United States)

Mansoor, Muhammad Mudassir; Raza, Abu Bakar Muhammad; Abbas, Naeem; Aqueel, Muhammad Anjum; Afzal, Muhammad

2017-01-01

The green lacewing, Chrysoperla carnea Stephens (Neuroptera: Chrysopidae) is a major generalist predator employed in integrated pest management (IPM) plans for pest control on many crops. Nitenpyram, a neonicotinoid insecticide has widely been used against the sucking pests of cotton in Pakistan. Therefore, a field green lacewing strain was exposed to nitenpyram for five generations to investigate resistance evolution, cross-resistance pattern, stability, realized heritability, and mechanisms of resistance. Before starting the selection with nitenpyram, a field collected strain showed 22.08-, 23.09-, 484.69- and 602.90-fold resistance to nitenpyram, buprofezin, spinosad and acetamiprid, respectively compared with the Susceptible strain. After continuous selection for five generations (G1-G5) with nitenpyram in the laboratory, the Field strain (Niten-SEL) developed a resistance ratio of 423.95 at G6. The Niten-SEL strain at G6 showed no cross-resistance to buprofezin and acetamiprid and negative cross-resistance to spinosad compared with the Field strain (G1). For resistance stability, the Niten-SEL strain was left unexposed to any insecticide for four generations (G6-G9) and bioassay results at G10 showed that resistance to nitenpyram, buprofezin and spinosad was stable, while resistance to acetamiprid was unstable. The realized heritability values were 0.97, 0.16, 0.03, and -0.16 to nitenpyram, buprofezin, acetamiprid and spinosad, respectively, after five generations of selection. Moreover, the enzyme inhibitors (PBO or DEF) significantly decreased the nitenpyram resistance in the resistant strain, suggesting that resistance was due to microsomal oxidases and esterases. These results are very helpful for integration of green lacewings in IPM programs. Copyright © 2016 Elsevier B.V. All rights reserved.

Antiplatelet therapy: aspirin resistance and all that jazz!

Science.gov (United States)

Divani, Afshin A; Zantek, Nicole D; Borhani-Haghighi, Afshin; Rao, Gundu H R

2013-01-01

Platelets play a crucial role in the pathogenesis of atherosclerosis, thrombosis, and stroke. Aspirin used alone or in combination with other antiplatelet drugs has been shown to offer significant benefit to patients at high risk of vascular events. Resistance to the action of aspirin may decrease this benefit. Aspirin resistance has been defined by clinical and/or laboratory criteria; however, detection by laboratory methods prior to experiencing a clinical event will likely provide the greatest opportunity for intervention. Numerous laboratory methods with different cutoff points have been used to evaluate the resistance. Noncompliance with aspirin treatment has also confounded studies. A single assay is currently insufficient to establish resistance. Combinations of results to confirm compliance and platelet inhibition may identify "at-risk" individuals who truly have aspirin resistance. The most effective strategy for managing patients with aspirin resistance is unknown; however, studies are currently underway to address this issue.

Praziquantel treatment decreases Schistosoma mansoni genetic diversity in experimental infections.

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Regina Coeli

Full Text Available BACKGROUND: Schistosomiasis has a considerable impact on public health in many tropical and subtropical areas. In the new world, schistosomiasis is caused by the digenetic trematode Schistosoma mansoni. Chemotherapy is the main measure for controlling schistosomiasis, and the current drug of choice for treatment is praziquantel (PZQ. Although PZQ is efficient and safe, its repetitive large-scale use in endemic areas may lead to the selection of resistant strains. Isolates less susceptible to PZQ have been found in the field and selected for in the laboratory. The impact of selecting strains with a decreased susceptibility phenotype on disease dynamics and parasite population genetics is not fully understood. This study addresses the impact of PZQ pressure on the genetics of a laboratory population by analyzing frequency variations of polymorphic genetic markers. METHODOLOGY: Infected mice were treated with increasing PZQ doses until the highest dose of 3 × 300 mg/Kg was reached. The effect of PZQ treatment on the parasite population was assessed using five polymorphic microsatellite markers. Parasitological and genetic data were compared with those of the untreated control. After six parasite generations submitted to treatment, it was possible to obtain a S. mansoni population with decreased susceptibility to PZQ. In our experiments we also observed that female worms were more susceptible to PZQ than male worms. CONCLUSIONS: The selective pressure exerted by PZQ led to decreased genetic variability in S. mansoni and increased endogamy. The understanding of how S. mansoni populations respond to successive drug pressure has important implications on the appearance and maintenance of a PZQ resistance phenotype in endemic regions.

Deregulation of apoptotic volume decrease and ionic movements in multidrug-resistant tumor cells: role of chloride channels

DEFF Research Database (Denmark)

Poulsen, Kristian Arild; Andersen, E C; Hansen, C F

2010-01-01

was further reduced. AVD(1) and AVD(2) were coupled to net loss of Cl(-), K(+), Na(+), and amino acids (ninhydrin-positive substances), whereas during AVD(T), Na(+) and Cl(-) were accumulated. MDR EATC was resistant to cisplatin, showing increased viability and less caspase 3 activation. Compared with WT EATC...

Mechanism and degree of chemical elements effect on atmosphere corrosion resistance of steels

International Nuclear Information System (INIS)

Vu Din' Vuj

1991-01-01

It follows from the proposed regression equations that falourable effect of chemical elements on steel resistance to atmospheric corrosion is determined by their ability to increase interatom bond stability in iron crystal lattice and form corrosion products with high protection properties. Element positive influence on steel corrosion resistance decreases in the following order: S, P, Si, Mn, Cu, Cr, Ni, C in semiurban tropical atmosphere and S, Mn, Sr, Cu, Ni, Cr in coastal atmosphere. In the latter case C increases corrosion in a greater degree as compared to P. Small ammounts of Mo decrease steel resistance in semiurban atmosphere and almost do not influence it in the coastal one. Possible mechanisms of individual element influence on steel corrosion resistance are considered

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system.

Science.gov (United States)

Aachmann-Andersen, Niels J; Christensen, Soren J; Lisbjerg, Kristian; Oturai, Peter; Johansson, Pär I; Holstein-Rathlou, Niels-Henrik; Olsen, Niels V

2018-03-01

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high-dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Antimicrobial Resistance in the Food Chain: A Review

Science.gov (United States)

Verraes, Claire; Van Boxstael, Sigrid; Van Meervenne, Eva; Van Coillie, Els; Butaye, Patrick; Catry, Boudewijn; de Schaetzen, Marie-Athénaïs; Van Huffel, Xavier; Imberechts, Hein; Dierick, Katelijne; Daube, George; Saegerman, Claude; De Block, Jan; Dewulf, Jeroen; Herman, Lieve

2013-01-01

Antimicrobial resistant zoonotic pathogens present on food constitute a direct risk to public health. Antimicrobial resistance genes in commensal or pathogenic strains form an indirect risk to public health, as they increase the gene pool from which pathogenic bacteria can pick up resistance traits. Food can be contaminated with antimicrobial resistant bacteria and/or antimicrobial resistance genes in several ways. A first way is the presence of antibiotic resistant bacteria on food selected by the use of antibiotics during agricultural production. A second route is the possible presence of resistance genes in bacteria that are intentionally added during the processing of food (starter cultures, probiotics, bioconserving microorganisms and bacteriophages). A last way is through cross-contamination with antimicrobial resistant bacteria during food processing. Raw food products can be consumed without having undergone prior processing or preservation and therefore hold a substantial risk for transfer of antimicrobial resistance to humans, as the eventually present resistant bacteria are not killed. As a consequence, transfer of antimicrobial resistance genes between bacteria after ingestion by humans may occur. Under minimal processing or preservation treatment conditions, sublethally damaged or stressed cells can be maintained in the food, inducing antimicrobial resistance build-up and enhancing the risk of resistance transfer. Food processes that kill bacteria in food products, decrease the risk of transmission of antimicrobial resistance. PMID:23812024

Human-Finger Electronics Based on Opposing Humidity-Resistance Responses in Carbon Nanofilms

KAUST Repository

Tai, Yanlong

2017-01-09

Carbon nanomaterials have excellent humidity sensing properties. Here, it is demonstrated that multiwalled carbon-nanotube (MWCNT)- and reduced-graphene-oxide (rGO)-based conductive films have opposite humidity/electrical resistance responses: MWCNTs increase their electrical resistance (positive response) and rGOs decrease their electrical resistance (negative response). The authors propose a new phenomenology that describes a

Influence of Compaction Temperature on Resistance Under Monotonic Loading of Crumb-Rubber Modified Hot-Mix Asphalts

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Hugo A. Rondón-Quintana

2012-12-01

Full Text Available The influence of compaction temperature on resistance under mono-tonic loading (Marshall of Crumb-Rubber Modified (CRM Hot-Mix As-phalt (HMA was evaluated. The emphasis of this study was the applica-tion in Bogotá D.C. (Colombia. In this city the compaction temperature of HMA mixtures decreases, compared to the optimum, in about 30°C. Two asphalt cements (AC 60-70 and AC 80-100 were modified. Two particle sizes distribution curve were used. The compaction temperatures used were 120, 130, 140 and 150°C. The decrease of the compaction tempera-ture produces a small decrease in resistance under monotonic loading of the modified mixtures tested. Mixtures without CRM undergo a lineal decrease in its resistance of up to 34%.

Influence of Compaction Temperature on Resistance Under Monotonic Loading of Crumb-Rubber Modified Hot-Mix Asphalts

Directory of Open Access Journals (Sweden)

Hugo A. Rondón-Quintana

2012-12-01

Full Text Available The influence of compaction temperature on resistance under monotonic loading (Marshall of Crumb-Rubber Modified (CRM Hot-Mix Asphalt (HMA was evaluated. The emphasis of this study was the application in Bogotá D.C. (Colombia. In this city the compaction temperature of HMA mixtures decreases, compared to the optimum, in about 30°C. Two asphalt cements (AC 60-70 and AC 80-100 were modified. Two particle sizes distribution curve were used. The compaction temperatures used were 120, 130, 140 and 150°C. The decrease of the compaction temperature produces a small decrease in resistance under monotonic loading of the modified mixtures tested. Mixtures without CRM undergo a lineal decrease in its resistance of up to 34%.

Mechanisms of insulin resistance in obesity

Science.gov (United States)

Ye, Jianping

2014-01-01

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

Capacity for absorption of water-soluble secondary metabolites greater in birds than in rodents.

Science.gov (United States)

Karasov, William H; Caviedes-Vidal, Enrique; Bakken, Bradley Hartman; Izhaki, Ido; Samuni-Blank, Michal; Arad, Zeev

2012-01-01

Plant secondary metabolites (SMs) are pervasive in animal foods and potentially influence feeding behavior, interspecies interactions, and the distribution and abundance of animals. Some of the major classes of naturally occurring SMs in plants include many water-soluble compounds in the molecular size range that could cross the intestinal epithelium via the paracellular space by diffusion or solvent drag. There are differences among species in paracellular permeability. Using Middle Eastern rodent and avian consumers of fruits containing SMs, we tested the hypothesis that avian species would have significantly higher paracellular permeability than rodent species. Permeability in intact animals was assessed using standard pharmacological methodology to measure absorption of two radiolabeled, inert, neutral water-soluble probes that do not interact with intestinal nutrient transporters, L-arabinose (M(r) = 150.1 Da) and lactulose (M(r) = 342.3 Da). We also measured absorption of labeled 3-O-methyl-D-glucose (3OMD-glucose; M(r) = 194.2 Da), which is a nonmetabolized analogue of D-glucose that is passively absorbed through the paracellular space but also transported across the enterocyte membranes. Most glucose was absorbed by all species, but arabinose fractional absorption (f) was nearly three times higher in birds (1.03±0.17, n = 15 in two species) compared to rodents (0.37±0.06, n = 10 in two species) (Pbirds of arabinose exceeded those of 3OMD-glucose. Our findings are in agreement with previous work showing that the paracellular pathway is more prominent in birds relative to nonflying mammals, and suggests that birds may be challenged by greater absorption of water-soluble, dietary SMs. The increased expression of the paracellular pathway in birds hints at a tradeoff: the free energy birds gain by absorbing water-soluble nutrients passively may be offset by the metabolic demands placed on them to eliminate concomitantly absorbed SMs.

Cephalosporin resistance in Neisseria gonorrhoeae

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Manju Bala

2010-01-01

Full Text Available Gonorrhea, a disease of public health importance, not only leads to high incidence of acute infections and complications but also plays a major role in facilitating human immunodeficiency virus (HIV acquisition and transmission. One of the major public health needs for gonorrhea control is appropriate, effective treatment. However, treatment options for gonorrhea are diminishing as Neisseria gonorrhoeae have developed resistance to several antimicrobial drugs such as sulfonamides, penicillin, tetracyclines and quinolones. Antimicrobial resistance (AMR surveillance of N. gonorrhoeae helps establish and maintain the efficacy of standard treatment regimens. AMR surveillance should be continuous to reveal the emergence of new resistant strains, monitor the changing patterns of resistance, and be able to update treatment recommendations so as to assist in disease control. Current treatment guidelines recommend the use of single dose injectable or oral cephalosporins. The emergence and spread of cephalosporin resistant and multi drug resistant N. gonorrhoeae strains, represents a worrying trend that requires monitoring and investigation. Routine clinical laboratories need to be vigilant for the detection of such strains such that strategies for control and prevention could be reviewed and revised from time to time. It will be important to elucidate the genetic mechanisms responsible for decreased susceptibility and future resistance. There is also an urgent need for research of safe, alternative anti-gonococcal compounds that can be administered orally and have effective potency, allowing high therapeutic efficacy (greater than 95.0% cure rate.

Mapping the resistance-associated mobilome of a carbapenem-resistant Klebsiella pneumoniae strain reveals insights into factors shaping these regions and facilitates generation of a 'resistance-disarmed' model organism.

Science.gov (United States)

Bi, Dexi; Jiang, Xiaofei; Sheng, Zi-Ke; Ngmenterebo, David; Tai, Cui; Wang, Minggui; Deng, Zixin; Rajakumar, Kumar; Ou, Hong-Yu

2015-10-01

This study aims to investigate the landscape of the mobile genome, with a focus on antibiotic resistance-associated factors in carbapenem-resistant Klebsiella pneumoniae. The mobile genome of the completely sequenced K. pneumoniae HS11286 strain (an ST11, carbapenem-resistant, near-pan-resistant, clinical isolate) was annotated in fine detail. The identified mobile genetic elements were mapped to the genetic contexts of resistance genes. The blaKPC-2 gene and a 26 kb region containing 12 clustered antibiotic resistance genes and one biocide resistance gene were deleted, and the MICs were determined again to ensure that antibiotic resistance had been lost. HS11286 contains six plasmids, 49 ISs, nine transposons, two separate In2-related integron remnants, two integrative and conjugative elements (ICEs) and seven prophages. Sixteen plasmid-borne resistance genes were identified, 14 of which were found to be directly associated with Tn1721-, Tn3-, Tn5393-, In2-, ISCR2- and ISCR3-derived elements. IS26 appears to have actively moulded several of these genetic regions. The deletion of blaKPC-2, followed by the deletion of a 26 kb region containing 12 clustered antibiotic resistance genes, progressively decreased the spectrum and level of resistance exhibited by the resultant mutant strains. This study has reiterated the role of plasmids as bearers of the vast majority of resistance genes in this species and has provided valuable insights into the vital role played by ISs, transposons and integrons in shaping the resistance-coding regions in this important strain. The 'resistance-disarmed' K. pneumoniae ST11 strain generated in this study will offer a more benign and readily genetically modifiable model organism for future extensive functional studies. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

In Silico Assigned Resistance Genes Confer Bifidobacterium with Partial Resistance to Aminoglycosides but Not to Β-Lactams

Science.gov (United States)

Fouhy, Fiona; O’Connell Motherway, Mary; Fitzgerald, Gerald F.; Ross, R. Paul; Stanton, Catherine; van Sinderen, Douwe; Cotter, Paul D.

2013-01-01

Bifidobacteria have received significant attention due to their contribution to human gut health and the use of specific strains as probiotics. It is thus not surprising that there has also been significant interest with respect to their antibiotic resistance profile. Numerous culture-based studies have demonstrated that bifidobacteria are resistant to the majority of aminoglycosides, but are sensitive to β-lactams. However, limited research exists with respect to the genetic basis for the resistance of bifidobacteria to aminoglycosides. Here we performed an in-depth in silico analysis of putative Bifidobacterium-encoded aminoglycoside resistance proteins and β-lactamases and assess the contribution of these proteins to antibiotic resistance. The in silico-based screen detected putative aminoglycoside and β-lactam resistance proteins across the Bifidobacterium genus. Laboratory-based investigations of a number of representative bifidobacteria strains confirmed that despite containing putative β-lactamases, these strains were sensitive to β-lactams. In contrast, all strains were resistant to the aminoglycosides tested. To assess the contribution of genes encoding putative aminoglycoside resistance proteins in Bifidobacterium sp. two genes, namely Bbr_0651 and Bbr_1586, were targeted for insertional inactivation in B. breve UCC2003. As compared to the wild-type, the UCC2003 insertion mutant strains exhibited decreased resistance to gentamycin, kanamycin and streptomycin. This study highlights the associated risks of relying on the in silico assignment of gene function. Although several putative β-lactam resistance proteins are located in bifidobacteria, their presence does not coincide with resistance to these antibiotics. In contrast however, this approach has resulted in the identification of two loci that contribute to the aminoglycoside resistance of B. breve UCC2003 and, potentially, many other bifidobacteria. PMID:24324818

In silico assigned resistance genes confer Bifidobacterium with partial resistance to aminoglycosides but not to β-lactams.

Directory of Open Access Journals (Sweden)

Fiona Fouhy

Full Text Available Bifidobacteria have received significant attention due to their contribution to human gut health and the use of specific strains as probiotics. It is thus not surprising that there has also been significant interest with respect to their antibiotic resistance profile. Numerous culture-based studies have demonstrated that bifidobacteria are resistant to the majority of aminoglycosides, but are sensitive to β-lactams. However, limited research exists with respect to the genetic basis for the resistance of bifidobacteria to aminoglycosides. Here we performed an in-depth in silico analysis of putative Bifidobacterium-encoded aminoglycoside resistance proteins and β-lactamases and assess the contribution of these proteins to antibiotic resistance. The in silico-based screen detected putative aminoglycoside and β-lactam resistance proteins across the Bifidobacterium genus. Laboratory-based investigations of a number of representative bifidobacteria strains confirmed that despite containing putative β-lactamases, these strains were sensitive to β-lactams. In contrast, all strains were resistant to the aminoglycosides tested. To assess the contribution of genes encoding putative aminoglycoside resistance proteins in Bifidobacterium sp. two genes, namely Bbr_0651 and Bbr_1586, were targeted for insertional inactivation in B. breve UCC2003. As compared to the wild-type, the UCC2003 insertion mutant strains exhibited decreased resistance to gentamycin, kanamycin and streptomycin. This study highlights the associated risks of relying on the in silico assignment of gene function. Although several putative β-lactam resistance proteins are located in bifidobacteria, their presence does not coincide with resistance to these antibiotics. In contrast however, this approach has resulted in the identification of two loci that contribute to the aminoglycoside resistance of B. breve UCC2003 and, potentially, many other bifidobacteria.

Antimicrobial resistance in commensal Escherichia coli isolated from animals at slaughter

Science.gov (United States)

Wasyl, Dariusz; Hoszowski, Andrzej; Zając, Magdalena; Szulowski, Krzysztof

2013-01-01

Monitoring of antimicrobial resistance in commensal Escherichia coli (N = 3430) isolated from slaughtered broilers, laying hens, turkeys, swine, and cattle in Poland has been run between 2009 and 2012. Based on minimal inhibitory concentration (MIC) microbiological resistance to each of 14 tested antimicrobials was found reaching the highest values for tetracycline (43.3%), ampicillin (42.3%), and ciprofloxacin (39.0%) whereas the lowest for colistin (0.9%), cephalosporins (3.6 ÷ 3.8%), and florfenicol (3.8%). The highest prevalence of resistance was noted in broiler and turkey isolates, whereas it was rare in cattle. That finding along with resistance patterns specific to isolation source might reflect antimicrobial consumption, usage preferences or management practices in specific animals. Regression analysis has identified changes in prevalence of microbiological resistance and shifts of MIC values. Critically important fluoroquinolone resistance was worrisome in poultry isolates, but did not change over the study period. The difference (4.7%) between resistance to ciprofloxacin and nalidixic acid indicated the scale of plasmid-mediated quinolone resistance. Cephalosporin resistance were found in less than 3.8% of the isolates but an increasing trends were observed in poultry and MIC shift in the ones from cattle. Gentamycin resistance was also increasing in E. coli of turkey and cattle origin although prevalence of streptomycin resistance in laying hens decreased considerably. Simultaneously, decreasing MIC for phenicols observed in cattle and layers isolates as well as tetracycline values in E. coli from laying hens prove that antimicrobial resistance is multivariable phenomenon not only directly related to antimicrobial usage. Further studies should elucidate the scope of commensal E. coli as reservoirs of resistance genes, their spread and possible threats for human and animal health. PMID:23935596

Antimicrobial resistance in commensal Escherichia coli isolated from animals at slaughter

Directory of Open Access Journals (Sweden)

Dariusz eWasyl

2013-08-01

Full Text Available Monitoring of antimicrobial resistance in commensal Escherichia coli (N = 3430 isolated from slaughtered broilers, laying hens, turkeys, swine, and cattle in Poland has been run between 2009 and 2012. Based on minimal inhibitory concentration (MIC microbiological resistance to each of 14 tested antimicrobials was found reaching the highest values for tetracycline (43.3%, ampicillin (42.3%, and ciprofloxacin (39.0% whereas the lowest for colistin (0.9%, cephalosporins (3.6 ÷ 3.8%, and florfenicol (3.8%. The highest prevalence of resistance was noted in broiler and turkey isolates, whereas it was rare in cattle. That finding along with resistance patterns specific to isolation source might reflect antimicrobial consumption, usage preferences or management practices in specific animals. Regression analysis has identified changes in prevalence of microbiological resistance and shifts of MIC values. Critically important fluoroquinolone resistance was worrisome in poultry isolates, but did not change over the study period. The difference (4.7% between resistance to ciprofloxacin and nalidixic acid indicated the scale of plasmid-mediated quinolone resistance. Cephalosporin resistance were found in less than 3.8% of the isolates but an increasing trends were observed in poultry and MIC shift in the ones from cattle. Gentamycin resistance was also increasing in E. coli of turkey and cattle origin although prevalence of streptomycin resistance in laying hens decreased considerably. Simultaneously, decreasing MIC for phenicols observed in cattle and layers isolates as well as tetracycline values in E. coli from laying hens prove that antimicrobial resistance is multivariable phenomenon not only directly related to antimicrobial usage. Further studies should elucidate the scope of commensal E. coli as reservoirs of resistance genes, their spread and possible threats for human and animal health.

[Changes of resistant phenotype and CRISPR/Cas system of four Shigella strains passaged for 90 times without antibiotics].

Science.gov (United States)

Zhang, B; Hong, L J; Duan, G C; Liang, W J; Yang, H Y; Xi, Y L

2017-02-10

Objective: To explore the stability of resistant phenotypes and changes of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) gene system on four Shigella strains in the absence of antibiotics. Methods: Four clinical isolated Shigella strains that resistant to different antibiotics were consecutive passaged for 90 times without antibiotics. Agar dilution method was used to determine the minimum inhibitory concentration of Shigella strains. After sequence analysis with PCR, CRISPR Finder and Clustal X 2.1 were applied to identify the changes of CRISPR loci in the Shigella strains. Results: After the consecutive transfer of 90 generations, sensitivity to certain antibiotics of four Shigella strains with different drug resistant spectrums increased. Mel-sf1998024/zz resistance to ampicillin, cephalexin, cefotaxime, chloramphenicol decreased, mel-s2014026/sx resistance to norfloxacin, trimethoprim decreased, mel-sf2004004/sx drug resistance to ampicillin, cefuroxime, cefotaxime, chloramphenicol, trimethoprim decreased and mel-sf2013004/bj resistance to chloramphenicol decreased. The spacer of which matched gene codes Cas and its upstream repeat in 3'end of CRISPR3 got lost in mel-sf1998024/zz and mel-sf2013004/bj. Conclusions: Shigella strains could reduce or lose their resistance to some antibiotics after consecutive transfers, without the interference of antibiotics. CRISPR3 locus had dynamic spacers in Shigella strains while CRISPR3 locus and cas genes might have been co-evolved.

Biological changes in Barley mutants resistant to powdery mildew disease

International Nuclear Information System (INIS)

Amer, I. M.; Fahim, M. M.; Moustafa, N. A.

2012-12-01

physiological studies showed that all kinds of chlorophyll (a), (b) and (a + b) content in infected plant were decreased while, the carotenes pigment were increased. Infection generally reduced total sugars content of all resistant mutants. Infected resistant mutant showed more phenols content and peroxidase, polyphenoloxidase activities than healthy ones of the mutants. (Author)

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

Energy Technology Data Exchange (ETDEWEB)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

2013-02-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

International Nuclear Information System (INIS)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

2013-01-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [ 3 H]glucose and 2-deoxy[ 14 C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats

Targeting the HER family with Pan-HER effectively overcomes resistance to cetuximab

Science.gov (United States)

Iida, Mari; Bahrar, Harsh; Brand, Toni M; Pearson, Hannah E; Coan, John P; Orbuch, Rachel A; Flanigan, Bailey G; Swick, Adam D; Prabakaran, Prashanth; Lantto, Johan; Horak, Ivan D.; Kragh, Michael; Salgia, Ravi; Kimple, Randy J; Wheeler, Deric L

2016-01-01

Cetuximab, an antibody against the Epidermal Growth Factor Receptor (EGFR) has shown efficacy in treating head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer and non-small cell lung cancer (NSCLC). Despite the clinical success of cetuximab, many patients do not respond to cetuximab. Furthermore, virtually all patients who do initially respond become refractory, highlighting both intrinsic and acquired resistance to cetuximab as significant clinical problems. To understand mechanistically how cancerous cells acquire resistance, we previously developed models of acquired resistance using the H226 NSCLC and UM-SCC1 HNSCC cell lines. Cetuximab-resistant clones showed a robust upregulation and dependency on the HER family receptors EGFR, HER2 and HER3. Here, we examined Pan-HER, a mixture of six antibodies targeting these receptors on cetuximab-resistant clones. In cells exhibiting acquired or intrinsic resistance to cetuximab, Pan-HER treatment decreased all three receptors’ protein levels and down-stream activation of AKT and MAPK. This correlated with decreased cell proliferation in cetuximab-resistant clones. To determine whether Pan-HER had a therapeutic benefit in vivo, we established de novo cetuximab-resistant mouse xenografts and treated resistant tumors with Pan-HER. This regimen resulted in a superior growth delay of cetuximab-resistant xenografts compared to mice continued on cetuximab. Furthermore, intrinsically cetuximab-resistant HNSCC patient-derived xenograft tumors treated with Pan-HER exhibited significant growth delay compared to vehicle/cetuximab controls. These results suggest that targeting HER family receptors simultaneously with Pan-HER is a promising treatment strategy for tumors displaying intrinsic or acquired resistance to cetuximab. PMID:27422810

A Mathematical Model of Solute Coupled Water Transport in Toad Intestine Incorporating Recirculation of the Actively Transported Solute

DEFF Research Database (Denmark)

Larsen, Erik Hviid; Sørensen, Jakob Balslev; Sørensen, Jens Nørkær

2000-01-01

those of tight junction and interspace basement membrane by convection-diffusion. With solute permeability of paracellular pathway large relative to paracellular water flow, the paracellular flux ratio of the solute (influx/outflux) is small (2-4) in agreement with experiments. The virtual solute......A mathematical model of an absorbing leaky epithelium is developed for analysis of solute coupled water transport. The non-charged driving solute diffuses into cells and is pumped from cells into the lateral intercellular space (lis). All membranes contain water channels with the solute passing...... increases with hydraulic conductance of the pathway carrying water from mucosal solution into lis. Uphill water transport is accomplished, but with high hydraulic conductance of cell membranes strength of transport is obscured by water flow through cells. Anomalous solvent drag occurs when back flux...

Plasmid Conjugation in E. coli and Drug Resistance

African Journals Online (AJOL)

Prof. Ogunji

2Department of Pharmaceutics and Pharmaceutical Microbiology, Ahmadu Bello University, Zaria ... decreasing the emergence of resistant bacteria strains within our environment. ..... Cowan and Steel's Manual for the Identification of Medical.

Decrease of the surface resistance in superconducting niobium resonator cavities by the microwave field

Energy Technology Data Exchange (ETDEWEB)

Ciovati, Gianluigi [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Dhakal, Pashupati [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Gurevich, Alexander V. [Old Dominion University, Norfolk, VA (United States)

2014-03-03

Measurements of the quality factor, Q, of Nb superconducting microwave resonators often show that Q increases by {approx_equal} 10%–30% with increasing radio-frequency (rf) field, H, up to {approx} 15-20 mT. Recent high temperature heat treatments can amplify this rf field-induced increase of Q up to {approx_equal} 50%–100% and extend it to much higher fields, but the mechanisms of the enhancement of Q(H) remain unclear. Here, we suggest a method to reveal these mechanisms by measuring temperature dependencies of Q at different rf field amplitudes. We show that the increase of Q(H) does not come from a field dependent quasi-particles activation energy or residual resistance, but rather results from the smearing of the density of state by the rf field.

Cell surface alteration in Epstein-Barr virus-transformed cells from patients with extreme insulin resistance

International Nuclear Information System (INIS)

Gorden, D.L.; Robert, A.; Moncada, V.Y.; Taylor, S.I.; Muehlhauser, J.C.; Carpentier, J.L.

1990-01-01

An abnormality was detected in the morphology of the cell surface of Epstein-Barr virus-transformed lymphocytes of patients with genetic forms of insulin resistance. In cells from two patients with leprechaunism and two patients with type A extreme insulin resistance, scanning electron microscopy demonstrated a decrease in the percentage of the cell surface occupied by microvilli in cells from the patients with leprechaunism and type A insulin resistance compared with control cells. When cells from a healthy control subject and one of the patients with leprechaunism (Lep/Ark-1) were incubated with 125 I-labeled insulin, there was a decrease in the percentage of 125 I-insulin associated with microvilli on the cell surface. Thus, the decreased localization of insulin receptors with the microvillous region of the cell surface was in proportion to the decrease in microvilli

Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function

Directory of Open Access Journals (Sweden)

Daniele A. Cardinale

2017-12-01

Full Text Available Aim: The current study aimed to examine the effects of resistance exercise with concomitant consumption of high vs. low daily doses of non-steroidal anti-inflammatory drugs (NSAIDs on mitochondrial oxidative phosphorylation in skeletal muscle. As a secondary aim, we compared the effects of eccentric overload with conventional training.Methods: Twenty participants were randomized to either a group taking high doses (3 × 400 mg/day of ibuprofen (IBU; 27 ± 5 year; n = 11 or a group ingesting a low dose (1 × 75 mg/day of acetylsalicylic acid (ASA; 26 ± 4 year; n = 9 during 8 weeks of supervised knee extensor resistance training. Each of the subject's legs were randomized to complete the training program using either a flywheel (FW device emphasizing eccentric overload, or a traditional weight stack machine (WS. Maximal mitochondrial oxidative phosphorylation (CI+IIP from permeabilized skeletal muscle bundles was assessed using high-resolution respirometry. Citrate synthase (CS activity was assessed using spectrophotometric techniques and mitochondrial protein content using western blotting.Results: After training, CI+IIP decreased (P < 0.05 in both IBU (23% and ASA (29% with no difference across medical treatments. Although CI+IIP decreased in both legs, the decrease was greater (interaction p = 0.015 in WS (33%, p = 0.001 compared with FW (19%, p = 0.078. CS activity increased (p = 0.027 with resistance training, with no interactions with medical treatment or training modality. Protein expression of ULK1 increased with training in both groups (p < 0.001. The increase in quadriceps muscle volume was not correlated with changes in CI+IIP (R = 0.16.Conclusion: These results suggest that 8 weeks of resistance training with co-ingestion of anti-inflammatory drugs reduces mitochondrial function but increases mitochondrial content. The observed changes were not affected by higher doses of NSAIDs consumption, suggesting that the resistance training

Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia

NARCIS (Netherlands)

A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); H.B. Beverloo (Berna); A.R.M. von Bergh (Anne); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

2005-01-01

textabstractDrug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7,

Effects of exercise intensity and creatine loading on post-resistance exercise hypotension

Directory of Open Access Journals (Sweden)

Moreno Rodrigues Moreno

2009-09-01

Full Text Available Postexercise hypotension plays an important role in the non-pharmacological treat-ment of hypertension and is characterized by a decrease in blood pressure after a single exercise bout in relation to pre-exercise levels. This study investigated the effects of exercise intensity and creatine monohydrate supplementation on postexercise hypotension, as well as the possible role of blood lactate in this response. Ten normotensive subjects underwent resistance exercise sessions before (BC and after (AC creatine supplementation: 1 muscle endurance (ME consisting of 30 repetitions at 30% of one-repetition maximum; 2 hypertrophy (HP consisting of 8 repetitions at 75% of one-repetition maximum. Blood pressure was measured before and after the exercise bout. Blood lactate was measured after the exercise bout. The HP and ME sessions promoted a decrease in systolic blood pressure (∆ -19 ± 1.0 mmHg; ∆ -15 ± 0.9 mmHg, respectively, P 0.05. In conclusion, resistance exercise intensity did not influence postexercise hypotension. Creatine supplementation attenuated the decrease in blood pressure after resistance exercise. The results suggest the involvement of blood lactate in post-resistance exercise hypotension.

Effects of exercise intensity and creatine loading on post-resistance exercise hypotension

Directory of Open Access Journals (Sweden)

Moreno Rodrigues Moreno

2009-01-01

Postexercise hypotension plays an important role in the non-pharmacological treat-ment of hypertension and is characterized by a decrease in blood pressure after a single exercise bout in relation to pre-exercise levels. This study investigated the effects of exercise intensity and creatine monohydrate supplementation on postexercise hypotension, as well as the possible role of blood lactate in this response. Ten normotensive subjects underwent resistance exercise sessions before (BC and after (AC creatine supplementation: 1 muscle endurance (ME consisting of 30 repetitions at 30% of one-repetition maximum; 2 hypertrophy (HP consisting of 8 repetitions at 75% of one-repetition maximum. Blood pressure was measured before and after the exercise bout. Blood lactate was measured after the exercise bout. The HP and ME sessions promoted a decrease in systolic blood pressure (∆ -19 ± 1.0 mmHg; ∆ -15 ± 0.9 mmHg, respectively, P 0.05. In conclusion, resistance exercise intensity did not influence postexercise hypotension. Creatine supplementation attenuated the decrease in blood pressure after resistance exercise. The results suggest the involvement of blood lactate in post-resistance exercise hypotension.

Influence of smectites on resistivity of rocks and soils; Smectite nendo kobutsu ga ganseki dojo no hi teiko ni oyobosu eikyo

Energy Technology Data Exchange (ETDEWEB)

Takakura, S; Nishizawa, O; Aoki, M [Geological Survey of Japan, Tsukuba (Japan); Kozake, K [University of Tsukuba, Ibaraki (Japan)

1996-10-01

This paper illustrates the measurement results of resistivity for specimens including smectite clay minerals artificially synthesized, and also discusses the influence of smectites on resistivity. Three kinds of bentonites, i.e., KN-1, Kawasaki ore, and Kawasaki Sanhaku, were used for preparing smectites. The KN-1 is Na type smectite, the Kawasaki ore is Ca type smectite, and the Kawasaki Sanhaku is acid clay. It is well known that smectites lower the resistivity of rocks. However, the experimental results suggested that the degree of decreasing the resistivity depends on the kind of smectites. The effect of decreasing the resistivity by the KN-1 was much superior to the other smectites. For the KN-1, a thick electrical double layer was formed by Na ions in the interlayers, which resulted in the larger effect of decreasing the resistivity. Swelling capacity and cation exchange capacity (CEC) of the KN-1 were large, which agreed with the above mentioned consideration. Reversely, it was considered that smectites having larger effect of decreasing the resistivity exhibited larger swelling capacity and CEC. 4 refs., 3 figs.

Insulin resistance in obesity as the underlying cause for the metabolic syndrome.

Science.gov (United States)

Gallagher, Emily J; Leroith, Derek; Karnieli, Eddy

2010-01-01

The metabolic syndrome affects more than a third of the US population, predisposing to the development of type 2 diabetes and cardiovascular disease. The 2009 consensus statement from the International Diabetes Federation, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, and the National Heart, Lung, and Blood Institute defines the metabolic syndrome as 3 of the following elements: abdominal obesity, elevated blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia. Many factors contribute to this syndrome, including decreased physical activity, genetic predisposition, chronic inflammation, free fatty acids, and mitochondrial dysfunction. Insulin resistance appears to be the common link between these elements, obesity and the metabolic syndrome. In normal circumstances, insulin stimulates glucose uptake into skeletal muscle, inhibits hepatic gluconeogenesis, and decreases adipose-tissue lipolysis and hepatic production of very-low-density lipoproteins. Insulin signaling in the brain decreases appetite and prevents glucose production by the liver through neuronal signals from the hypothalamus. Insulin resistance, in contrast, leads to the release of free fatty acids from adipose tissue, increased hepatic production of very-low-density lipoproteins and decreased high-density lipoproteins. Increased production of free fatty acids, inflammatory cytokines, and adipokines and mitochondrial dysfunction contribute to impaired insulin signaling, decreased skeletal muscle glucose uptake, increased hepatic gluconeogenesis, and β cell dysfunction, leading to hyperglycemia. In addition, insulin resistance leads to the development of hypertension by impairing vasodilation induced by nitric oxide. In this review, we discuss normal insulin signaling and the mechanisms by which insulin resistance contributes to the development of the metabolic

A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours.

Science.gov (United States)

Mercado-Lubo, Regino; Zhang, Yuanwei; Zhao, Liang; Rossi, Kyle; Wu, Xiang; Zou, Yekui; Castillo, Antonio; Leonard, Jack; Bortell, Rita; Greiner, Dale L; Shultz, Leonard D; Han, Gang; McCormick, Beth A

2016-07-25

Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics.

Inducible Clindamycin Resistance in Staphylococcus Species

International Nuclear Information System (INIS)

Afridi, F. I.; Zeb, M.; Farooqi, B. J.; Murtaza, G.; Hussain, A.

2014-01-01

Objective: To determine the frequency of inducible clindamycin resistance in clinical isolates of Staphylococcus species by phenotypic D-test. Study Design: Observational study. Place and Duration of Study: Ziauddin University Hospital, Karachi, from July to December 2011. Methodology: Consecutive clinical isolates of Staphylococcus species were collected and identified by conventional microbiological techniques. Antimicrobial susceptibility testing and inducible clindamycin resistance was carried out by performing D-test using CLSI criteria. Methicillin resistance was detected by using Cefoxitin disk as a surrogate marker. Statistical analysis was performed by SPSS version-17. Results: A total of 667 clinical isolates of Staphylococcus species were obtained during the study period. In these isolates, 177 (26.5%) were Staphylococcus aureus, and 490 (73.5%) were coagulase negative Staphylococci. The total frequency of inducible clindamycin resistance among isolates of Staphylococcus species was 120/667 (18%). Frequency of inducible clindamycin resistance among coagulase negative Staphylococci group and Staphylococcus aureus group were 18.57% and 16.38% respectively. Median age of patients in D-test positive group was 19.5 (1 - 54) years. Conclusion: The frequency of inducible clindamycin resistance among Staphylococcus species may differ in different hospital setup. Clinical microbiology laboratories should implement testing simple and effective D-test on all Staphylococcus species. D-test positive isolates should be reported clindamycin resistant to decrease treatment failure. (author)

Roles of inter-SWCNT junctions in resistive humidity response

International Nuclear Information System (INIS)

Zhang, Kang; Zou, Jianping; Zhang, Qing

2015-01-01

As a promising chemiresistor for gas sensing, the single-walled carbon nanotube (SWCNT) network has not yet been fully utilized for humidity detection. In this work, it is found that as humidity increases from 10% to 85%, the resistance of as-grown SWCNT networks first decreases and then increases. This non-monotonic resistive response to humidity limits their sensing capabilities. The competition between SWCNT resistance and inter-tube junction resistance changes is then found to be responsible for the non-monotonic resistive humidity responses. Moreover, creating sp"3 scattering centers on the SWCNT sidewall by monovalent functionalization of four-bromobenzene diazonium tetrafluoroborate is shown to be capable of eliminating the influence from the inter-tube junctions, resulting in a continuous resistance drop as humidity increases from 10% to 85%. Our results revealed the competing resistive humidity sensing process in as-grown SWCNT networks, which could also be helpful in designing and optimizing as-grown SWCNT networks for humidity sensors and other gas sensors. (paper)

Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection

Science.gov (United States)

Dudley, Matthew Z.; Sheen, Patricia; Gilman, Robert H.; Ticona, Eduardo; Friedland, Jon S.; Kirwan, Daniela E.; Caviedes, Luz; Rodriguez, Richard; Cabrera, Lilia Z.; Coronel, Jorge; Grandjean, Louis; Moore, David A. J.; Evans, Carlton A.; Huaroto, Luz; Chávez-Pérez, Víctor; Zimic, Mirko

2016-01-01

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)–positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58–92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures. PMID:27928075

Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE Based Diagnosis and Therapy

Directory of Open Access Journals (Sweden)

Diana P. English

2013-05-01

Full Text Available Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE, a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents.

Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus

International Nuclear Information System (INIS)

Salhanick, A.I.; Amatruda, J.M.

1988-01-01

Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, the authors investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyl-transferase. CMP reduced neuraminidase-releasable [ 14 C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus

Statistical models of a gas diffusion electrode: II. Current resistent

Energy Technology Data Exchange (ETDEWEB)

Proksch, D B; Winsel, O W

1965-07-01

The authors describe an apparatus for measuring the flow resistance of gas diffusion electrodes which is a mechanical analog of the Wheatstone bridge for measuring electric resistance. The flow resistance of a circular DSK electrode sheet, consisting of two covering layers and a working layer between them, was measured as a function of the gas pressure. While the pressure first was increased and then decreased, a hysteresis occurred, which is discussed and explained by a statistical model of a porous electrode.

Pyramiding, alternating or mixing: comparative performances of deployment strategies of nematode resistance genes to promote plant resistance efficiency and durability.

Science.gov (United States)

Djian-Caporalino, Caroline; Palloix, Alain; Fazari, Ariane; Marteu, Nathalie; Barbary, Arnaud; Abad, Pierre; Sage-Palloix, Anne-Marie; Mateille, Thierry; Risso, Sabine; Lanza, Roger; Taussig, Catherine; Castagnone-Sereno, Philippe

2014-02-22

Resistant cultivars are key elements for pathogen control and pesticide reduction, but their repeated use may lead to the emergence of virulent pathogen populations, able to overcome the resistance. Increased research efforts, mainly based on theoretical studies, explore spatio-temporal deployment strategies of resistance genes in order to maximize their durability. We evaluated experimentally three of these strategies to control root-knot nematodes: cultivar mixtures, alternating and pyramiding resistance genes, under controlled and field conditions over a 3-years period, assessing the efficiency and the durability of resistance in a protected crop rotation system with pepper as summer crop and lettuce as winter crop. The choice of the resistance gene and the genetic background in which it is introgressed, affected the frequency of resistance breakdown. The pyramiding of two different resistance genes in one genotype suppressed the emergence of virulent isolates. Alternating different resistance genes in rotation was also efficient to decrease virulent populations in fields due to the specificity of the virulence and the trapping effect of resistant plants. Mixing resistant cultivars together appeared as a less efficient strategy to control nematodes. This work provides experimental evidence that, in a cropping system with seasonal sequences of vegetable species, pyramiding or alternating resistance genes benefit yields in the long-term by increasing the durability of resistant cultivars and improving the long-term control of a soil-borne pest. To our knowledge, this result is the first one obtained for a plant-nematode interaction, which helps demonstrate the general applicability of such strategies for breeding and sustainable management of resistant cultivars against pathogens.

Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster

NARCIS (Netherlands)

Vermeulen, CJ; Van De Zande, L; Bijlsma, R

2005-01-01

There is increasing support for the notion that genetic variation for lifespan, both within and between species, is correlated with variation in the efficiency of the free radical scavenging system and the ability to withstand oxidative stress. In Drosophila, resistance to dietary paraquat, a free

Herbicide resistance and biodiversity: agronomic and environmental aspects of genetically modified herbicide-resistant plants.

Science.gov (United States)

Schütte, Gesine; Eckerstorfer, Michael; Rastelli, Valentina; Reichenbecher, Wolfram; Restrepo-Vassalli, Sara; Ruohonen-Lehto, Marja; Saucy, Anne-Gabrielle Wuest; Mertens, Martha

2017-01-01

Farmland biodiversity is an important characteristic when assessing sustainability of agricultural practices and is of major international concern. Scientific data indicate that agricultural intensification and pesticide use are among the main drivers of biodiversity loss. The analysed data and experiences do not support statements that herbicide-resistant crops provide consistently better yields than conventional crops or reduce herbicide amounts. They rather show that the adoption of herbicide-resistant crops impacts agronomy, agricultural practice, and weed management and contributes to biodiversity loss in several ways: (i) many studies show that glyphosate-based herbicides, which were commonly regarded as less harmful, are toxic to a range of aquatic organisms and adversely affect the soil and intestinal microflora and plant disease resistance; the increased use of 2,4-D or dicamba, linked to new herbicide-resistant crops, causes special concerns. (ii) The adoption of herbicide-resistant crops has reduced crop rotation and favoured weed management that is solely based on the use of herbicides. (iii) Continuous herbicide resistance cropping and the intensive use of glyphosate over the last 20 years have led to the appearance of at least 34 glyphosate-resistant weed species worldwide. Although recommended for many years, farmers did not counter resistance development in weeds by integrated weed management, but continued to rely on herbicides as sole measure. Despite occurrence of widespread resistance in weeds to other herbicides, industry rather develops transgenic crops with additional herbicide resistance genes. (iv) Agricultural management based on broad-spectrum herbicides as in herbicide-resistant crops further decreases diversity and abundance of wild plants and impacts arthropod fauna and other farmland animals. Taken together, adverse impacts of herbicide-resistant crops on biodiversity, when widely adopted, should be expected and are indeed very hard

Faradic resistance of the electrode/electrolyte interface.

Science.gov (United States)

Mayer, S; Geddes, L A; Bourland, J D; Ogborn, L

1992-09-01

A new method is used to measure the direct-current (Faradic) resistance of a single electrode/electrolyte interface. The method employs a constant-current pulse and a potential-sensing electrode. By choosing a sufficiently long pulse duration, the voltage between the test and potential-sensing electrode exhibits a three-phase response. In the steady-state phase, the voltage measured is equal to the current flowing through the electrode Faradic resistance and the resistance of the electrolyte between the test and potential-sensing electrode. By measuring this latter resistance with a high-frequency sinusoidal alternating current, the voltage drop in the electrolyte is calculated and subtracted from the voltage measured between the test and potential-sensing electrode, thereby allowing calculation of the Faradic resistance. By plotting the reciprocal of the Faradic resistance against current density and fitting the data points to a third-order polynomial, it is possible to determine the zero-current density (Faradic) resistance. This technique was used to determine the Faradic resistance of electrodes (0.1 cm2) of stainless-steel, platinum, platinum-iridium and rhodium in 0.9 per cent NaCl at 25 degrees. The zero current Faradic resistance is lowest for platinum (30.3 k omega), slightly higher for platinum-iridium (47.6k omega), much higher for rhodium (111k omega) and highest for type 316 stainless-steel (345k omega). In all cases, the Faradic resistance decreases dramatically with increasing current density.

Fundamentals of EUV resist-inorganic hardmask interactions

Science.gov (United States)

Goldfarb, Dario L.; Glodde, Martin; De Silva, Anuja; Sheshadri, Indira; Felix, Nelson M.; Lionti, Krystelle; Magbitang, Teddie

2017-03-01

High resolution Extreme Ultraviolet (EUV) patterning is currently limited by EUV resist thickness and pattern collapse, thus impacting the faithful image transfer into the underlying stack. Such limitation requires the investigation of improved hardmasks (HMs) as etch transfer layers for EUV patterning. Ultrathin (<5nm) inorganic HMs can provide higher etch selectivity, lower post-etch LWR, decreased defectivity and wet strippability compared to spin-on hybrid HMs (e.g., SiARC), however such novel layers can induce resist adhesion failure and resist residue. Therefore, a fundamental understanding of EUV resist-inorganic HM interactions is needed in order to optimize the EUV resist interfacial behavior. In this paper, novel materials and processing techniques are introduced to characterize and improve the EUV resist-inorganic HM interface. HM surface interactions with specific EUV resist components are evaluated for open-source experimental resist formulations dissected into its individual additives using EUV contrast curves as an effective characterization method to determine post-development residue formation. Separately, an alternative adhesion promoter platform specifically tailored for a selected ultrathin inorganic HM based on amorphous silicon (aSi) is presented and the mitigation of resist delamination is exemplified for the cases of positive-tone and negative-tone development (PTD, NTD). Additionally, original wafer priming hardware for the deposition of such novel adhesion promoters is unveiled. The lessons learned in this work can be directly applied to the engineering of EUV resist materials and processes specifically designed to work on such novel HMs.

Antimicrobial resistance trends among Salmonella isolates obtained from horses in the northeastern United States (2001-2013).

Science.gov (United States)

Cummings, Kevin J; Perkins, Gillian A; Khatibzadeh, Sarah M; Warnick, Lorin D; Aprea, Victor A; Altier, Craig

2016-05-01

OBJECTIVE To describe the antimicrobial resistance patterns of Salmonella isolates obtained from horses in the northeastern United States and to identify trends in resistance to select antimicrobials over time. SAMPLE 462 Salmonella isolates from horses. PROCEDURES Retrospective data were collected for all Salmonella isolates obtained from equine specimens that were submitted to the Cornell University Animal Health Diagnostic Center between January 1, 2001, and December 31, 2013. Temporal trends in the prevalence of resistant Salmonella isolates were investigated for each of 13 antimicrobials by use of the Cochran-Armitage trend test. RESULTS The prevalence of resistant isolates varied among antimicrobials and ranged from 0% (imipenem) to 51.5% (chloramphenicol). During the observation period, the prevalence of resistant isolates decreased significantly for amoxicillin-clavulanic acid, ampicillin, cefazolin, cefoxitin, ceftiofur, chloramphenicol, and tetracycline and remained negligible for amikacin and enrofloxacin. Of the 337 isolates for which the susceptibility to all 13 antimicrobials was determined, 138 (40.9%) were pansusceptible and 192 (57.0%) were multidrug resistant (resistant to ≥ 3 antimicrobial classes). The most common serovar isolated was Salmonella Newport, and although the annual prevalence of that serovar decreased significantly over time, that decrease had only a minimal effect on the observed antimicrobial resistance trends. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that current antimicrobial use in horses is not promoting the emergence and dissemination of antimicrobial-resistant Salmonella strains in the region served by the laboratory.

Inorganic phosphorus decrease after intravenous glucose tolerance test is associated with insulin resistance in dairy cows

OpenAIRE

Cincović, Marko R.; Djoković, Radojica; Belić, Branislavav; Potkonjak, Aleksandar; Toholj, Bojan; Stojanac, Nenad; Stevančević, Ognjen; Starič, Jože

2017-01-01

Inorganic phosphorus (Pi) concentration in blood decreases during an intravenous glucose tolerance test (IVGTT) due to the increase in the level of insulin and glucose. The objective of the present study was to determine the relationship between the intensity of Pi decrease with a dynamic change of insulin and glucose during IVGTT (AUC - total area under curve, AUC increment - area under curve from start of IVGTT to time of maximal response and glucose CR-clearance rate), as well as RQUICKI (...

Increase in cellular concrete resistance to brittle fracture

International Nuclear Information System (INIS)

Chernyshov, E.M.; Krokhin, A.M.

1979-01-01

Considered are theoretical premises of decrease in cellular concrete resistance to brittle fracture at the expense of dispersed reinforcement. It is stated experimentally that the introduction of 3% asbestos fibers permits to increase the ultimate extensibility and strength during cellular concrete tension by 15-30% and to increase in unit rupture work 1.4-1.6 time more and therefore to decrease its brittleness

Development and persistence of resistance to fungicides in Sphaerotheca fuliginea in cucumbers in the Netherlands

NARCIS (Netherlands)

Schepers, H.T.A.M.

1985-01-01

Ergosterol biosynthesis inhibitors (EBIs) have a remarkably broad spectrum of antifungal activity. They belong to the commercial fungicides which exhibit the highest activity known to date. Resistance to EBIs was found in vitro, but the level of resistance and the decreased fitness of resistant

Risk Factors for Emergence of Resistance to Broad-Spectrum Cephalosporins among Enterobacter spp.

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Kaye, Keith S.; Cosgrove, Sara; Harris, Anthony; Eliopoulos, George M.; Carmeli, Yehuda

2001-01-01

Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance. PMID:11502540

Pressure and temperature induced electrical resistance change in nano-carbon/epoxy composites

NARCIS (Netherlands)

Shen, J. T.; Buschhorn, S. T.; De Hosson, J. Th. M.; Schulte, K.; Fiedler, B.

2015-01-01

In this study, we investigate the changes of electrical resistance of the carbon black (CB) and carbon nanotube (CNT) filled epoxy composites upon compression, swelling and temperature variation. For all samples we observe a decrease of electrical resistance under compression, while an increase of

Host range of antibiotic resistance genes in wastewater treatment plant influent and effluent.

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Hultman, Jenni; Tamminen, Manu; Pärnänen, Katariina; Cairns, Johannes; Karkman, Antti; Virta, Marko

2018-04-01

Wastewater treatment plants (WWTPs) collect wastewater from various sources for a multi-step treatment process. By mixing a large variety of bacteria and promoting their proximity, WWTPs constitute potential hotspots for the emergence of antibiotic resistant bacteria. Concerns have been expressed regarding the potential of WWTPs to spread antibiotic resistance genes (ARGs) from environmental reservoirs to human pathogens. We utilized epicPCR (Emulsion, Paired Isolation and Concatenation PCR) to detect the bacterial hosts of ARGs in two WWTPs. We identified the host distribution of four resistance-associated genes (tetM, int1, qacEΔ1and blaOXA-58) in influent and effluent. The bacterial hosts of these resistance genes varied between the WWTP influent and effluent, with a generally decreasing host range in the effluent. Through 16S rRNA gene sequencing, it was determined that the resistance gene carrying bacteria include both abundant and rare taxa. Our results suggest that the studied WWTPs mostly succeed in decreasing the host range of the resistance genes during the treatment process. Still, there were instances where effluent contained resistance genes in bacterial groups not carrying these genes in the influent. By permitting exhaustive profiling of resistance-associated gene hosts in WWTP bacterial communities, the application of epicPCR provides a new level of precision to our resistance gene risk estimates.

The RESET Mindset Model applied on decreasing antibiotic usage in dairy cattle in the Netherlands

NARCIS (Netherlands)

Lam, T. J. G. M.; Wessels, R. J.; Jansen, Jolanda

2017-01-01

BACKGROUND: Prudent use of antibiotics is important to prevent antibiotic resistance in humans and in animals. For this reason politicians demanded a decrease of total antibiotic use and of use of critically important antibiotics in animal husbandry in the Netherlands. In the dairy sector the use of

Minnelide Inhibits Androgen Dependent, Castration Resistant Prostate Cancer Growth by Decreasing Expression of Androgen Receptor Full Length and Splice Variants.

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Isharwal, Sumit; Modi, Shrey; Arora, Nivedita; Uhlrich, Charles; Giri, Bhuwan; Barlass, Usman; Soubra, Ayman; Chugh, Rohit; Dehm, Scott M; Dudeja, Vikas; Saluja, Ashok; Banerjee, Sulagna; Konety, Badrinath

2017-05-01

With almost 30,000 deaths per year, prostate cancer is the second-leading cause of cancer-related death in men. Androgen Deprivation Therapy (ADT) has been the corner stone of prostate cancer treatment for decades. However, despite an initial response of prostate cancer to ADT, this eventually fails and the tumors recur, resulting in Castration Resistant Prostate Cancer (CRPC). Triptolide, a diterpene triepoxide, has been tested for its anti-tumor properties in a number of cancers for over a decade. Owing to its poor solubility in aqueous medium, its clinical application had been limited. To circumvent this problem, we have synthesized a water-soluble pro-drug of triptolide, Minnelide, that is currently being evaluated in a Phase 1 clinical trial against gastrointestinal tumors. In the current study, we assessed the therapeutic potential of Minnelide and its active compound triptolide against androgen dependent prostate cancer both in vitro as well as in vivo. Cell viability was measured by a MTT based assay after treating prostate cancer cells with multiple doses of triptolide. Apoptotic cell death was measured using a caspase 3/7 activity. Androgen Receptor (AR) promoter-binding activity was evaluated by using luciferase reporter assay. For evaluating the effect in vivo, 22Rv1 cells were implanted subcutaneously in animals, following which, treatment was started with 0.21 mg/kg Minnelide. Our study showed that treatment with triptolide induced apoptotic cell death in CRPC cells. Triptolide treatment inhibited AR transcriptional activity and decreased the expression of AR and its splice variants both at the mRNA and the protein level. Our studies show that triptolide inhibits nuclear translocation of Sp1, resulting in its decreased transcriptional activity leading to downregulation of AR and its splice variants in prostate cancer cells. In vivo, Minnelide (0.21 mg/kg) regressed subcutaneous tumors derived from CRPC 22RV1 at our study endpoint. Our animal

Plasmid-Mediated Quinolone Resistance in Shigella flexneri Isolated From Macaques

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Anthony J. Mannion

2018-03-01

Full Text Available Non-human primates (NHPs for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae. In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques. Antibiotic susceptibility testing confirmed resistance or decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, cephalosporins, gentamicin, tetracycline, ciprofloxacin, enrofloxacin, levofloxacin, and nalidixic acid. S. flexneri isolates were susceptible to trimethoprim-sulfamethoxazole, and this drug was used to eradicate infection in two of the macaques. Plasmid DNA from all isolates was positive for the plasmid-encoded quinolone resistance gene qnrS, but not qnrA and qnrB. Conjugation and transformation of plasmid DNA from several S. flexneri isolates into antibiotic-susceptible Escherichia coli strains conferred the recipients with resistance or decreased susceptibility to quinolones and beta-lactams. Genome sequencing of two representative S. flexneri isolates identified the qnrS gene on a plasmid-like contig. These contigs showed >99% homology to plasmid sequences previously characterized from quinolone-resistant Shigella flexneri 2a and Salmonella enterica strains. Other antibiotic resistance genes and virulence factor genes were also identified in chromosome and plasmid sequences in these genomes. The findings from this study indicate macaques harbor pathogenic S. flexneri strains with chromosomally- and plasmid-encoded antibiotic resistance genes. To our knowledge, this is the first report of plasmid-mediated quinolone resistance in S. flexneri isolated from NHPs and warrants

A Consideration of Resistance and Tolerance for Ruminant Nematode Infections

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Steve eBishop

2012-12-01

Full Text Available Debates on the relative merits of resistance (the ability of the host to control the parasite lifecycle and tolerance (the net impact of infection on host performance are often lively and unhindered by data or evidence. Resistance generally shows continuous, heritable variation but data are sparser for tolerance, the utility of which will depend upon the disease prevalence. Prevalence is a function of group mean resistance and infection pressure, which itself is influenced by mean resistance. Tolerance will have most value for endemic diseases with a high prevalence, but will be of little value for low prevalence diseases. The conditionality of tolerance on infection status, and hence resistance, makes it difficult to estimate independently of resistance.Tolerance is potentially tractable for nematode infections, as the prevalence of infection is ca. 100% in animals grazing infected pasture, and infection level can be quantified by faecal egg count (FEC. Whilst individual animal phenotypes for tolerance are difficult to estimate, breeding values are estimable if related animals graze pastures of different contamination levels. Selection for resistance, i.e. FEC, provides both direct and indirect benefits from ever decreased pasture contamination and hence decreased infectious challenge. Modelling and experimental studies have shown that such reductions in pasture contamination may lead to substantially increased performance.It is proposed that selection goals addressing nematode infections should include both resistance and performance under challenging conditions. However, there may be benefits from exploiting large datasets in which sires are used across cohorts differing in infection level, to further explore tolerance. This may help to customise breeding objectives, with tolerance given greater weight in heavily parasitized environments.

Induced resistance to the antimicrobial peptide lactoferricin B in Staphylococcus aureus.

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Samuelsen, Orjan; Haukland, Hanne H; Jenssen, Håvard; Krämer, Manuela; Sandvik, Kjersti; Ulvatne, Hilde; Vorland, Lars H

2005-06-20

This study was designed to investigate inducible intrinsic resistance against lactoferricin B in Staphylococcus aureus. Serial passage of seven S. aureus strains in medium with increasing concentrations of peptide resulted in an induced resistance at various levels in all strains. The induced resistance was unstable and decreased relatively rapidly during passages in peptide free medium but the minimum inhibitory concentration remained elevated after thirty passages. Cross-resistance to penicillin G and low-level cross-resistance to the antimicrobial peptides indolicidin and Ala(8,13,18)-magainin-II amide [corrected] was observed. No cross-resistance was observed to the human cathelicidin LL-37. In conclusion, this study shows that S. aureus has intrinsic resistance mechanisms against antimicrobial peptides that can be induced upon exposure, and that this may confer low-level cross-resistance to other antimicrobial peptides.

Eosinophil inversely associates with type 2 diabetes and insulin resistance in Chinese adults.

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Liying Zhu

Full Text Available CONTEXT: Limited population-based study focused on relationship between eosinophil and type 2 diabetes (T2D. OBJECTIVES: We aimed to evaluate the relationship between peripheral eosinophil percentage and glucose metabolism and insulin resistance in a large sample size of Chinese population aged 40 and older. DESIGN AND METHODS: A cross-sectional study was performed among 9,111 Chinese adults including 3,561 men and 5,550 women. The glucose metabolism status was confirmed by 75-g oral glucose tolerance test. Homeostasis model assessment of insulin resistance index and serum insulin levels were used to evaluate insulin resistance. Homeostasis model assessment-B was used to evaluate β cell function. RESULTS: The average age of participants was 58.5 years. The prevalence of T2D decreased across the tertiles of eosinophil percentage (21.3%, 18.2% and 16.9%, P<0.0001. Each one tertile increase of eosinophil percentage inversely associated with risk of T2D when referred not only to normal glucose tolerance (NGT (odds ratio (OR 0.81, 95% CI 0.76-0.87, P< 0.0001, but also to impaired glucose regulation (OR 0.89, 95% CI 0.83-0.97, P = 0.006, respectively, after adjustment for the confounding factors. Compared with the first tertile, the third tertile of eosinophil percentage associated with a 23% decrease of insulin resistance in NGT participants after full adjustments (P = 0.005. Each 1-standard deviation of increment of eosinophil percentage associated with a 37% decrease of insulin resistance (P = 0.005. CONCLUSIONS: Higher peripheral eosinophil percentage was associated with decreased risk of T2D. The inverse relation to insulin resistance was detected in NGT participants.

Gender differences in factors influencing insulin resistance in elderly hyperlipemic non-diabetic subjects

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Hrebícek Jirí

2002-10-01

Full Text Available Abstract Background The increase in the prevalence of insulin resistance-related metabolic syndrome, a disorder that greatly increases the risk of diabetes, heart attack and stroke, is alarming. One of the most frequent and early symptoms of metabolic syndrome is hypertriglyceridemia. We examined the gender differences between various metabolic factors related to insulin resistance in elderly non-diabetic men and postmenopausal women of comparable age suffering from hypertriglyceridemia, and compared them with healthy subjects of equal age. Results The indexes of insulin resistance HOMA IR and QUICKI were significantly higher in both hyperlipemic men and women than in controls; 95% confidence limits of hyperlipemic subjects did not overlap with controls. In both normolipemic and hyperlipemic men and women serum leptin correlated significantly with insulin resistance, while HDL-cholesterol correlated inversely with HOMA-IR only in women (both normo- and hyperlipemic, and serum tumor necrosis factor α (TNFα only in hyperlipemic women. According to results of multiple regression analysis with HOMA-IR as a dependent variable, leptin played a significant role in determining insulin resistance in both genders, but – aside from leptin – triglycerides, TNFα and decreased HDL-cholesterol were significant determinants in women, while body mass index and decreased HDL-cholesterol were significant determinants in men. The coefficient of determination (R2 of HOMA IR by above mentioned metabolic variables was in women above 60%, in men only about 40%. Conclusion The significant role of serum leptin in determination of insulin resistance in both elderly men and postmenopausal women of equal age was confirmed. However, the study also revealed significant gender differences : in women a strong influence of triglycerides, TNFα and decreased HDL-cholesterol, in men only a mild role of BMI and decreased HDL-cholesterol.

Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

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Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

2017-07-01

Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (Pinsulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanisms of antibiotic resistance in Staphylococcus aureus.

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Pantosti, Annalisa; Sanchini, Andrea; Monaco, Monica

2007-06-01

Staphylococcus aureus can exemplify better than any other human pathogen the adaptive evolution of bacteria in the antibiotic era, as it has demonstrated a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin and methicillin, until the most recent, linezolid and daptomycin. Resistance mechanisms include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes), alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline). Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support to antibiotic susceptibility surveillance in S. aureus.

Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells

International Nuclear Information System (INIS)

Ryu, Chang Seon; Kwak, Hui Chan; Lee, Kye Sook; Kang, Keon Wook; Oh, Soo Jin; Lee, Ki Ho; Kim, Hwan Mook; Ma, Jin Yeul; Kim, Sang Kyum

2011-01-01

Although methionine dependency is a phenotypic characteristic of tumor cells, it remains to be determined whether changes in sulfur amino acid metabolism occur in cancer cells resistant to chemotherapeutic medications. We compared expression/activity of sulfur amino acid metabolizing enzymes and cellular levels of sulfur amino acids and their metabolites between normal MCF-7 cells and doxorubicin-resistant MCF-7 (MCF-7/Adr) cells. The S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in MCF-7/Adr cells decreased to ∼ 10% relative to that in MCF-7 cells, which may have resulted from down-regulation of S-adenosylhomocysteine hydrolase. Expression of homocysteine-clearing enzymes, such as cystathionine beta-synthase, methionine synthase/methylene tetrahydrofolate reductase, and betaine homocysteine methyltransferase, was up-regulated in MCF-7/Adr cells, suggesting that acquiring doxorubicin resistance attenuated methionine-dependence and activated transsulfuration from methionine to cysteine. Homocysteine was similar, which is associated with a balance between the increased expressions of homocysteine-clearing enzymes and decreased extracellular homocysteine. Despite an elevation in cysteine, cellular GSH decreased in MCF-7/Adr cells, which was attributed to over-efflux of GSH into the medium and down-regulation of the GSH synthesis enzyme. Consequently, MCF-7/Adr cells were more sensitive to the oxidative stress induced by bleomycin and menadione than MCF-7 cells. In conclusion, our results suggest that regulating sulfur amino acid metabolism may be a possible therapeutic target for chemoresistant cancer cells. These results warrant further investigations to determine the role of sulfur amino acid metabolism in acquiring anticancer drug resistance in cancer cells using chemical and biological regulators involved in sulfur amino acid metabolism. - Research highlights: → MCF-7/Adr cells showed decreases in cellular GSH

Sesquiterpenes with TRAIL-resistance overcoming activity from Xanthium strumarium.

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Karmakar, Utpal K; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

2015-08-01

The ability of TRAIL to selectively induce apoptosis in cancer cells while sparing normal cells makes it an attractive target for the development of new cancer therapy. In search of bioactive natural products for overcoming TRAIL-resistance from natural resources, we previously reported a number of active compounds. In our screening program on natural resources targeting overcoming TRAIL-resistance, activity-guided fractionations of the extract of Xanthium strumarium led to the isolation of five sesquiterpene compounds (1-5). 11α,13-dihydroxanthinin (2) and 11α,13-dihydroxanthuminol (3) were first isolated from natural resources and xanthinosin (1), desacetylxanthanol (4), and lasidiol p-methoxybenzoate (5) were known compounds. All compounds (1-5) showed potent TRAIL-resistance overcoming activity at 8, 20, 20, 16, and 16 μM, respectively, in TRAIL-resistant AGS cells. Compounds 1 and 5 enhanced the levels of apoptosis inducing proteins DR4, DR5, p53, CHOP, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant AGS cells in a dose-dependent manner. Compound 1 also enhanced the levels of DR4 and DR5 proteins in a time-dependent manner. Thus, compounds 1 and 5 were found to induce both extrinsic and intrinsic apoptotic cell death. Compound 1 also exhibit TRAIL-resistance overcoming activity in DLD1, DU145, HeLa, and MCF7 cells but did not decrease viability in non-cancer HEK293 cells up to 8 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes.

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Wei, Xiang-Bo; Guo, Liang; Liu, Yang; Zhou, Shui-Rong; Liu, Yuan; Dou, Xin; Du, Shao-Yue; Ding, Meng; Peng, Wan-Qiu; Qian, Shu-Wen; Huang, Hai-Yan; Tang, Qi-Qun

2017-09-23

Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM. Copyright © 2017. Published by Elsevier Inc.

Effects of niacin supplementation on the insulin resistance in Holstein cows during early lactation

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Talija Hristovska

2017-01-01

Full Text Available Insulin resistance in early lactation includes low glucose concentration, low insulin release and responsiveness and high lipolysis. Niacin is important antilipolytic agent and leads to increase glucose and insulin concentration. The objectives of this study were to determine the influence of niacin on the insulin resistance in cows during early lactation using the difference of value and regression analysis between blood non-esterified fatty acid (NEFA, glucose and insulin concentrations, revised quantitative insulin sensitivity check index and glucose-to-insulin ratio. Niacin supplementation led to a decrease of NEFA concentration and an increase of glucose and insulin concentrations during the first three weeks after calving. Cows in the niacin group which were more resistant to insulin showed higher concentrations of non-esterified fatty acid in comparison with more sensitive cows from the same group, but still lower than the control. The regression analyses suggest the following characteristics of cows supplemented with niacin in comparison with the control group: the insulin response to glucose was more intense; the antilipolytic effect of insulin was lower; insulin efficiency expressed as glucose-to-insulin ratio increase with a decrease in NEFA. The metabolic changes due to niacin supplementation showed a dual influence on the insulin resistance in dairy cows during early lactation: decreased NEFA concentrations led to a decrease in the insulin resistance (due to an increase in insulin efficiency and insulin sensitivity index, but increased concentrations of insulin and glucose possibly caused an increase in the insulin resistance in dairy cows (due to lower insulin sensitivity index and possibly lower antilipolytic effects of insulin.

Antimicrobial resistance and virulence genes profiling of methicillin-resistant Staphylococcus aureus isolates in a burn center: A 5-year study.

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Jiang, Bei; Yin, Supeng; You, Bo; Gong, Yali; Huang, Guangtao; Yang, Zichen; Zhang, Yulong; Chen, Yu; Chen, Jing; Yuan, Zhiqiang; Hu, Xiaomei; Peng, Yizhi

2018-01-01

Methicillin-resistant S. aureus (MRSA) has attracted more and more attention in recent years, especially in burn medical centers. Here we conducted a 5-year period study to evaluate the MRSA infection in our burn center. The staphylococcal chromosomal cassette mec (SCCmec) typing, antimicrobials susceptibility and virulence profiles were also performed among the MRSA isolates. Of the 259 S. aureus isolates, 239 (92.28%) isolates were identified as MRSA. A decreased trend of MRSA isolation rate over time was found (P = 0.0063). Majority of MRSA isolates in our center belonged to SCCmec type III (230/239, 96.23%). Antimicrobials susceptibility tests of the MRSA isolates revealed significantly decreased resistance to clindamycin (P = 0.0183), and increased resistance to chloramphenicol (P = 0.0020) and minocycline (P Virulence factors profiling showed that most of MRSA isolates in our center carried the virulence factor pattern of cna-clfA-clfB-eno-fib-icaA-icaD-sea-psmα-lukED-hlg-hlgv-hla-hld (214/239, 89.54%). In conclusion, our study suggests that MRSA infection is serious in our burn center, but presented decreased trend over time. Most of MRSA isolates in our center presented the same virulence factor profile. More attention should be attached to nosocomial infection in burn medical center. Antimicrobials susceptibility changing over time was observed. Antimicrobials susceptibility monitoring is necessary and helps to select appropriate drugs against MRSA infections. Copyright © 2017. Published by Elsevier Ltd.

OBESITY-RELATED CARDIOVASCULAR RISK FACTORS AFTER LONG- TERM RESISTANCE TRAINING AND GINGER SUPPLEMENTATION

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Sirvan Atashak

2011-12-01

Full Text Available Obesity and its metabolic consequences are major risk factors for cardiovascular morbidity and mortality. However, lifestyle interventions, including exercise training and dietary components may decrease cardiovascular risk. Hence, this study was conducted to assess the effects of ginger supplementation and progressive resistance training on some cardiovascular risk factors in obese men. In a randomized double-blind design, 32 obese Iranian men (BMI > 30 were assigned in to one of four groups: Placebo (PL, n = 8; ginger group (GI, n = 8 that consumed 1 gr ginger/d for 10 wk; resistance training plus placebo (RTPL, n = 8; and 1gr ginger plus resistance exercise (RTGI, n = 8. Progressive resistance training was performed three days per week for 10 weeks and included eight exercises. At baseline and after 10 weeks, body composition and anthropometric indices were measured. To identify other risk factors, venous blood samples were obtained before and 48-72 hours after the last training session for measurement of blood lipids (LDL-C, HDL-C, TG, systemic inflammation (CRP, and insulin resistance (HOMA-IR. After 10 weeks both RTGI and RTPL groups showed significant decreases in waist circumference (WC, waist-to-hip ratio (WHR, body fat percent, body fat mass, total cholesterol, and insulin resistance (p < 0.05 and a significant increase in fat free mass (FFM (p < 0.05, while it remained unchanged in PL and GI. Further, significant decreases in the mean values of CRP were observed in all groups except PL (p < 0.05. Our results reveal that resistance training is an effective therapeutic strategy to reduce cardiovascular risk in obese Iranian men. Further, ginger supplementation alone or in combination with resistance training, also reduces chronic inflammation. However more research on the efficacy of this supplement to reduce cardiovascular risk in humans is required.

Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells

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Annalucia Carbone

2018-01-01

Full Text Available We previously found that human amniotic mesenchymal stem cells (hAMSCs in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ- mediated intercellular communication (GJIC in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43, a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C, and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells.

Science.gov (United States)

Carbone, Annalucia; Zefferino, Roberto; Beccia, Elisa; Casavola, Valeria; Castellani, Stefano; Di Gioia, Sante; Giannone, Valentina; Seia, Manuela; Angiolillo, Antonella; Colombo, Carla; Favia, Maria; Conese, Massimo

2018-01-01

We previously found that human amniotic mesenchymal stem cells (hAMSCs) in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE) on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ-) mediated intercellular communication (GJIC) in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio) were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43), a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C), and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

An in vitro transport model for rapid screening and predicting the permeability of candidate compounds at blood-brain barrier.

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Yang, Zhi-Hong; Sun, Xiao; Mei, Chao; Sun, Xiao-Bo; Liu, Xiao-Dong; Chang, Qi

2011-12-01

The aim of this study was to design and develop a simple in vitro blood-brain barrier (BBB) permeation model for elementarily and rapidly predicting the permeability of candidate compounds at BBB and further evaluating whether P-glycoprotein (P-gp) affects them across BBB. The model was mainly composed of cultured rat brain microvascular endothelial cells (rBMECs), glass contraption, and micropore membrane. First, we evaluated the model by morphological observation. Second, the restriction effects of paracellular transport were verified by measuring marker probes transport, and monitoring transendothelial electrical resistance (TEER) and leakage. Finally, protein expression and activity of P-gp were confirmed by carrying out Western blot analysis and polarized transport of rhodamine-123 (Rho123) in rBMECs. The rBMECs retained both endothelial cells and BBB features. The rBMECs model reproducibly attained approximately 130 Ω cm² on the steady-state TEER value, and displayed a barrier function to marker probes transport by decreasing the permeability. Protein band of 170 kDa manifested the existence of P-gp in the rBMECs, and the findings of cyclosporin A-sensitive decrease of Rho123 efflux confirmed the presence of P-gp activity. A simple, rapid, and convenient in vitro BBB permeation model was successfully established and applied to evaluate the BBB transport profiles of three natural flavonoids: quercetin, naringenin, and rutin.

Claudins 1, 2, 3, 4, 5 and 7 in solar keratosis and squamocellular carcinoma of the skin

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Hintsala, Hanna-Riikka; Siponen, Maria; Haapasaari, Kirsi-Maria; Karihtala, Peeter; Soini, Ylermi

2013-01-01

Claudins are tight junction proteins regulating the paracellular permeability of cell layers. We investigated the expression of claudins 1, 2, 3, 4, 5 and 7 in a sample set consisting of a total of 93 cases representing normal skin, actinic keratoses and squamous cell carcinomas of the skin. There were several changes found in claudin expression. Claudin 1 appeared to be progressively decreased in solar keratosis and skin squamous cell carcinomas compared to normal skin while expression of claudin 2 was increased. With claudins 3 and 5 occasional immunoreactivity was found in squamous cell carcinomas. Claudins 4 and 7 were variably expressed in skin neoplasia compared to normal skin. According to the results expression of claudins 1 and 2 change in parallel with the severity of the epidermal preneoplastic and neoplastic lesions thus probably influencing the disturbed epithelial polarity characteristic of these lesions. Claudin 1 under- and claudin 2 overexpression also lead to a leakier epithelial barrier function of the skin with a resulting damage to skin epithelial resistance. Other claudins investigated in this study did not show progressive changes even though occasional overexpression of them was found in skin squamous cell carcinoma. PMID:24294371

Trends in antimicrobial susceptibility in relation to antimicrobial usage and presence of resistance genes in Staphylococcus hyicus isolated from exudative epidermitis in pigs

DEFF Research Database (Denmark)

Aarestrup, Frank Møller; Jensen, Lars Bogø

2002-01-01

(vat, vga, vga(B), vat(B), vat(D) and vat(E)), streptomycin (aadE) and tetracycline resistance (tet(K), tet(L), tet(M) and tet(O)) were determined in selected isolates. The occurrence of erythromycin resistance increased from 33% in 1996 to a maximum of 62% in 1997 and decreased to 26% in 2001....... Resistance to sulphametazole increased from 17% in 1996 to 30% in 1998 but has since decreased to 4% in 2001. Resistance to trimethoprim increased to 51% in 1997 and decreased to 21% in 2001. Resistance to tetracycline (21-31%) remained relatively constant during 1996-2000, but increased to 47% in 2001...

Radiation resistance of wide-bandgap semiconductor power transistors

Energy Technology Data Exchange (ETDEWEB)

Hazdra, Pavel; Popelka, Stanislav [Department of Microelectronics, Czech Technical University in Prague (Czech Republic)

2017-04-15

Radiation resistance of state-of-the-art commercial wide-bandgap power transistors, 1700 V 4H-SiC power MOSFETs and 200 V GaN HEMTs, to the total ionization dose was investigated. Transistors were irradiated with 4.5 MeV electrons with doses up to 2000 kGy. Electrical characteristics and introduced defects were characterized by current-voltage (I-V), capacitance-voltage (C-V), and deep level transient spectroscopy (DLTS) measurements. Results show that already low doses of 4.5 MeV electrons (>1 kGy) cause a significant decrease in threshold voltage of SiC MOSFETs due to embedding of the positive charge into the gate oxide. On the other hand, other parameters like the ON-state resistance are nearly unchanged up to the dose of 20 kGy. At 200 kGy, the threshold voltage returns back close to its original value, however, the ON-state resistance increases and transconductance is lowered. This effect is caused by radiation defects introduced into the low-doped drift region which decrease electron concentration and mobility. GaN HEMTs exhibit significantly higher radiation resistance. They keep within the datasheet specification up to doses of 2000 kGy. Absence of dielectric layer beneath the gate and high concentration of carriers in the two dimensional electron gas channel are the reasons of higher radiation resistance of GaN HEMTs. Their degradation then occurs at much higher doses due to electron mobility degradation. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Prevention strategies for antimicrobial resistance: a systematic review of the literature

Directory of Open Access Journals (Sweden)

Whitney P Caron

2010-05-01

Full Text Available Whitney P Caron1, Shaker A Mousa1,21The Pharmaceutical Research Institute, Center of Excellence of Infection Prevention (CEIP, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 2King Saud University, Riyadh, Saudi ArabiaAbstract: Antibiotics offer great benefits by reducing the duration and severity of illnesses and aiding in infection transmission control. With this being said, the inexorable process of antimicrobial drug resistance is to some degree unavoidable. Although drug resistance will likely persist and is to be expected, the overall level can be dramatically decreased with increased attention to antibiotic overuse and the pharmacokinetic and pharmacodynamic properties of different drug formulations, and the use of proper hygiene and protective barriers. Implementation of such practices as microbial surveillance and prophylaxis has been shown to result in decreased hospital length of stay, health care costs and mortality due to drug-resistant infections. This review will summarize current progress in preventative techniques aimed at reducing the incidence of infection by antimicrobial-resistant bacteria and the emergence and spread of antimicrobial-resistant strains. By employing a variety of prevention strategies, including proper personal hygiene, prescreening for carrier status before hospital admission, disinfection of hospital rooms, and careful monitoring of antimicrobial prescribing, marked progress can be achieved in the control of drug-resistant pathogens, which can translate into more effective antimicrobial therapy.Keywords: infection prevention, antibiotic, personal hygiene, disinfection, microbial surveillance, drug-resistant pathogen

Electrical resistivity discontinuity of iron along the melting curve

Science.gov (United States)

Wagle, Fabian; Steinle-Neumann, Gerd

2018-04-01

Discontinuous changes of electrical resistivity ρel (increase), density ϱ and isothermal compressibility βT (decrease) occur across the melting temperature of metals and can be directly related by Ziman's theory in the long-wavelength approximation. By evaluating experimental data at ambient pressure, we show that Ziman's approximation holds for iron and other simple and transition metals. Using a thermodynamic model to determine βT for γ-, ɛ- and liquid Fe and a previously published model for ρel of liquid Fe, we apply Ziman's approximation to calculate ρel of solid Fe along the melting curve. For pure Fe, we find the discontinuity in ρel to decrease with pressure and to be negligibly small at inner core boundary conditions. However, if we account for light element enrichment in the liquid outer core, the electrical resistivity decrease across the inner core boundary is predicted to be as large as 36 per cent.

Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1.

Science.gov (United States)

Zhu, Yinghua; Liu, Yujie; Zhang, Chao; Chu, Junjun; Wu, Yanqing; Li, Yudong; Liu, Jieqiong; Li, Qian; Li, Shunying; Shi, Qianfeng; Jin, Liang; Zhao, Jianli; Yin, Dong; Efroni, Sol; Su, Fengxi; Yao, Herui; Song, Erwei; Liu, Qiang

2018-04-23

Tamoxifen resistance is accountable for relapse in many ER-positive breast cancer patients. Most of these recurrent patients receive chemotherapy, but their chemosensitivity is unknown. Here, we report that tamoxifen-resistant breast cancer cells express significantly more BARD1 and BRCA1, leading to resistance to DNA-damaging chemotherapy including cisplatin and adriamycin, but not to paclitaxel. Silencing BARD1 or BRCA1 expression or inhibition of BRCA1 phosphorylation by Dinaciclib restores the sensitivity to cisplatin in tamoxifen-resistant cells. Furthermore, we show that activated PI3K/AKT pathway is responsible for the upregulation of BARD1 and BRCA1. PI3K inhibitors decrease the expression of BARD1 and BRCA1 in tamoxifen-resistant cells and re-sensitize them to cisplatin both in vitro and in vivo. Higher BARD1 and BRCA1 expression is associated with worse prognosis of early breast cancer patients, especially the ones that received radiotherapy, indicating the potential use of PI3K inhibitors to reverse chemoresistance and radioresistance in ER-positive breast cancer patients.

Calcined Eggshell Waste for Mitigating Soil Antibiotic-Resistant Bacteria/Antibiotic Resistance Gene Dissemination and Accumulation in Bell Pepper.

Science.gov (United States)

Ye, Mao; Sun, Mingming; Feng, Yanfang; Li, Xu; Schwab, Arthur P; Wan, Jinzhong; Liu, Manqiang; Tian, Da; Liu, Kuan; Wu, Jun; Jiang, Xin

2016-07-13

The combined accumulation of antibiotics, heavy metals, antibiotic-resistant bacteria (ARB)/antibiotic resistance genes (ARGs) in vegetables has become a new threat to human health. This is the first study to investigate the feasibility of calcined eggshells modified by aluminum sulfate as novel agricultural wastes to impede mixed contaminants from transferring to bell pepper (Capsicum annuum L.). In this work, calcined eggshell amendment mitigated mixed pollutant accumulation in bell pepper significantly, enhanced the dissipation of soil tetracycline, sulfadiazine, roxithromycin, and chloramphenicol, decreased the water-soluble fractions of antibiotics, and declined the diversity of ARB/ARGs inside the vegetable. Moreover, quantitative polymerase chain reaction analysis detected that ARG levels in the bell pepper fruits significantly decreased to 10(-10) copies/16S copies, indicating limited risk of ARGs transferring along the food chain. Furthermore, the restoration of soil microbial biological function suggests that calcined eggshell is an environmentally friendly amendment to control the dissemination of soil ARB/ARGs in the soil-vegetable system.

Chemosensitivity of irradiated resistant cells of multicellular spheroids in A549 lung adenocarcinoma

International Nuclear Information System (INIS)

Shi Degang; Shi Genming; Huang Gang

2006-01-01

Objective: To investigate the chemosensitivity of irradiated resistant cells of multicellular spheroids in A549 lung adenocarcinoma. Methods: The A549 irradiated resistant cells were the 10th regrowth generations after irradiated with 2.5 Gy of 6 MV X-ray, the control groups were A549 parent cells and MCFY/VCR resistant cells. The 6 kinds of chemotherapeutic drugs were DDP, VDS, 5-FU, HCP, MMC and ADM respectively, with verapamil (VPL) as reverse agent. The treatment effect was compared with MTT assay, and the multidrug resistant gene expressions of mdrl and MRP were measured with RT-PCR method. Results: A549 cells and irradiated resistant cells were resistant to DDP, but sensitivity to VDS,5-FU, HCP, MMC and ADM. The inhibitory rates of VPL to the above two cells were 98% and 25% respectively(P 2 -MG and MRP/β 2 -MG of all A549 cells were about 0 and 0.7 respectively, and those of MCFT/VCR cells were 35 and 4.36. Conclusion: The chemosensitivity of A549 irradiated resistant cells had not changed markedly, the decreased sensitivity to VPL could not be explained by the gene expression of mdrl and MRP. It is conferred that some kinds of changes in the cell membrane and decreased regrowth ability to result in resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to irradiated resistant cells. The new kinds of biological preparation should be sought to combine chemotherapy to treat recurring tumor with irradiated resistance. (authors)

Insecticide control of vector-borne diseases: when is insecticide resistance a problem?

Directory of Open Access Journals (Sweden)

Ana Rivero

Full Text Available Many of the most dangerous human diseases are transmitted by insect vectors. After decades of repeated insecticide use, all of these vector species have demonstrated the capacity to evolve resistance to insecticides. Insecticide resistance is generally considered to undermine control of vector-transmitted diseases because it increases the number of vectors that survive the insecticide treatment. Disease control failure, however, need not follow from vector control failure. Here, we review evidence that insecticide resistance may have an impact on the quality of vectors and, specifically, on three key determinants of parasite transmission: vector longevity, competence, and behaviour. We argue that, in some instances, insecticide resistance is likely to result in a decrease in vector longevity, a decrease in infectiousness, or in a change in behaviour, all of which will reduce the vectorial capacity of the insect. If this effect is sufficiently large, the impact of insecticide resistance on disease management may not be as detrimental as previously thought. In other instances, however, insecticide resistance may have the opposite effect, increasing the insect's vectorial capacity, which may lead to a dramatic increase in the transmission of the disease and even to a higher prevalence than in the absence of insecticides. Either way-and there may be no simple generality-the consequence of the evolution of insecticide resistance for disease ecology deserves additional attention.

Electrical resistivity monitoring of the thermomechanical heater test in Yucca Mountain

International Nuclear Information System (INIS)

Ramirez, A.; Daily, W.; Buettner, M.

1997-01-01

A test is being conducted in the densely welded Topopah Springs tuff within Yucca Mountain, Nevada to study the thermomechanical and hydrological behavior of this horizon when it is headed. A single 4 kW heater, placed in a horizontal borehole, was turned on August, 1996 and will continue to heat the rockmass until April 1997. Of the several thermal, mechanical and hydrological measurements being used to monitor the rockmass response, electrical resistance tomography (ERT) is being used to monitor the movement of liquid water with a special interest in the movement of condensate out of the system. Four boreholes, containing a total of 30 ERT electrodes, were drilled to form the sides of a 30 foot square with the heater at the center and perpendicular to the plane. Images of resistivity change were calculated using data collected before and during the heating episode. The changes recovered show a region of decreasing resistivity approximately centered around the heater. The size this region grows with time and the resistivity decreases become stronger. The changes in resistivity are caused by both temperature and saturation changes. The observed resistivity changes suggest that the rock adjacent to the heater dries as heating progresses. This dry region is surrounded by a region of increased saturation where steam recondenses and imbibes into the rock

Electrical resistivity monitoring of the thermomechanical heater test in Yucca Mountain

International Nuclear Information System (INIS)

Ramirez, A.; Daily, W.; Buettner, M.; LaBrecque, L

1996-01-01

A test is being conducted in the densely welded Topopah Springs tuff within Yucca Mountain, Nevada to study the thermomechanical and hydrological behavior of this horizon when it is heated. A single 4 kW heater, placed in a horizontal borehole, was turned on August, 1996 and will continue to heat the rockmass until April 1997. Of the several thermal, mechanical and hydrological measurements being used to monitor the rockmass response, electrical resistance tomography (ERT) is being used to monitor the movement of liquid water with a special interest in the movement of condensate out of the system. Four boreholes, containing a total of 30 ERT electrodes, were drilled to form the sides of a 30 foot square with the heater at the center and perpendicular to the plane. Images of resistivity change were calculated using data collected before and during the heating episode. The changes recovered show a region of decreasing resistivity approximately centered around the heater. The size this region grows with time and -the resistivity decreases become stronger. The changes in resistivity are caused by both temperature and saturation changes. The observed resistivity changes suggest that the rock adjacent to the heater dries as heating progresses. This dry region is surrounded by a region of increased saturation where steam recondenses and imbibes into the rock

Fasting Ghrelin Levels Are Decreased in Obese Subjects and Are Significantly Related With Insulin Resistance and Body Mass Index

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Dimitrios Papandreou

2017-10-01

CONCLUSION: Obese subjects have low fasting ghrelin levels that they are significantly related to insulin resistance and body mass index. More prospective studies are needed to establish the role of ghrelin in the pathogenesis of human obesity.

The correlation of grain boundary composition in irradiated stainless steel with IASCC resistance

International Nuclear Information System (INIS)

Jacobs, A.J.; Wozadlo, G.P.; Nakata, K.; Kasahara, S.; Okada, T.; Kawano, S.; Suzuki, S.

1993-01-01

Scanning transmission electron microscopy (STEMP) analysis were conducted on a group of irradiated Type-316 stainless steels (SS), in an continuing effort to correlate grain boundary composition with IASCC resistance. The latter property was measured by either one of two means: an in-reactor (boiling water reactor) swelling-mandrel-type test or a laboratory constant extension rate tensile (CERT) test. Possibly because of their basically different nature, the two types of test yielded different correlations with the STEM results. The in-reactor results showed two regimes, one in which IASCC resistance remained essentially unchanged with increasing radiation-induced segregation/depletion (RIS), and another in which IASCC resistance increased with decreasing RIS. The CERT test results, on the other hand, showed a monotonic increase in IASCC resistance with decreasing RIS, with a transition range of RIS in which IASCC resistance was very high or very low. It appeared from the two sets of results that in the reactor environment, a low degree of RIS was necessary but not sufficient for high IASCC resistance, and in the laboratory environment, a low degree of RIS was necessary and sufficient

Mechanisms of antimicrobial resistance among hospital-associated pathogens.

Science.gov (United States)

Khan, Ayesha; Miller, William R; Arias, Cesar A

2018-04-01

The introduction of antibiotics revolutionized medicine in the 20th-century permitting the treatment of once incurable infections. Widespread use of antibiotics, however, has led to the development of resistant organisms, particularly in the healthcare setting. Today, the clinician is often faced with pathogens carrying a cadre of resistance determinants that severely limit therapeutic options. The genetic plasticity of microbes allows them to adapt to stressors via genetic mutations, acquisition or sharing of genetic material and modulation of genetic expression leading to resistance to virtually any antimicrobial used in clinical practice. Areas covered: This is a comprehensive review that outlines major mechanisms of resistance in the most common hospital-associated pathogens including bacteria and fungi. Expert commentary: Understanding the genetic and biochemical mechanisms of such antimicrobial adaptation is crucial to tackling the rapid spread of resistance, can expose unconventional therapeutic targets to combat multidrug resistant pathogens and lead to more accurate prediction of antimicrobial susceptibility using rapid molecular diagnostics. Clinicians making treatment decisions based on the molecular basis of resistance may design therapeutic strategies that include de-escalation of broad spectrum antimicrobial usage, more focused therapies or combination therapies. These strategies are likely to improve patient outcomes and decrease the risk of resistance in hospital settings.

No cross-resistance between imidacloprid and pymetrozine in the brown planthopper: status and mechanisms.

Science.gov (United States)

Yang, Yuanxue; Huang, Lixin; Wang, Yunchao; Zhang, Yixi; Fang, Siqi; Liu, Zewen

2016-06-01

Cross-resistance between insecticides, especially from different groups, can be extremely unpredictable, and it has been a serious concern in pest control. Pymetrozine has been widely used to control Nilaparvata lugens with the suspension of imidacloprid for the resistance, and N. lugens has showed obvious pymetrozine resistance in recent years. To investigate the possible cross-resistance between imidacloprid and pymetrozine is very important to avoid the adverse effects on resistance development and pest control. Bioassays of two field populations in five consecutive years showed that imidacloprid resistance decreased greatly, while pymetrozine resistance increased significantly. The synergist piperonyl butoxide (PBO) could synergize both imidacloprid and pymetrozine in all field populations, which indicated the importance of P450s in the resistance to two insecticides. Imidacloprid resistance was reported to be associated with two P450s, CYP6AY1 and CYP6ER1, which could metabolize imidacloprid efficiently. However, the recombinant proteins of these two P450s did not show any enzymatic activity to metabolize pymetrozine. The pymetrozine susceptibility did not change when CYP6AY1 and CYP6ER1 mRNA levels were reduced by RNA interference (RNAi), although which could obviously decrease imidacloprid resistance. In vivo and in vitro studies provided evidences to demonstrate that there was no cross-resistance between imidacloprid and pymetrozine in N. lugens, which was different from the findings in Bemisia tabaci. Copyright © 2015. Published by Elsevier Inc.

Decrease in electrical contact resistance of Sb-doped n+-BaSi2 layers and spectral response of an Sb-doped n+-BaSi2/undoped BaSi2 structure for solar cells

Science.gov (United States)

Kodama, Komomo; Takabe, Ryota; Yachi, Suguru; Toko, Kaoru; Suemasu, Takashi

2018-03-01

We investigated how the electron concentration n in a 300-nm-thick Sb-doped n+-BaSi2 layer grown by molecular beam epitaxy affected the contact resistance R C to surface electrodes (Al, indium-tin-oxide). As the n of n-BaSi2 increased, R C decreased and reached a minimum of 0.019 Ω cm2 at n = 2.4 × 1018 cm-3 for the Al electrodes. This value was more than 1 order of magnitude smaller than that obtained for Al/B-doped p-BaSi2. We believe that this significant decrease in R C came from Sb segregation. Furthermore, the internal quantum efficiency (IQE) spectrum was evaluated for an Sb-doped n+-BaSi2 (20 nm)/undoped BaSi2 (500 nm)/n+-Si(111) structure. Its IQE reached as high as ˜50% over a wide wavelength range under a small bias voltage of 0.1 V applied between the top and bottom electrodes.

Inactivation Effect of Antibiotic-Resistant Gene Using Chlorine Disinfection

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Takashi Furukawa

2017-07-01

Full Text Available The aim of this study was to elucidate the inactivation effects on the antibiotic-resistance gene (vanA of vancomycin-resistant enterococci (VRE using chlorination, a disinfection method widely used in various water treatment facilities. Suspensions of VRE were prepared by adding VRE to phosphate-buffered saline, or the sterilized secondary effluent of a wastewater treatment plant. The inactivation experiments were carried out at several chlorine concentrations and stirring time. Enterococci concentration and presence of vanA were determined. The enterococci concentration decreased as chlorine concentrations and stirring times increased, with more than 7.0 log reduction occurring under the following conditions: 40 min stirring at 0.5 mg Cl2/L, 20 min stirring at 1.0 mg Cl2/L, and 3 min stirring at 3.0 mg Cl2/L. In the inactivation experiment using VRE suspended in secondary effluent, the culturable enterococci required much higher chlorine concentration and longer treatment time for complete disinfection than the cases of suspension of VRE. However, vanA was detected in all chlorinated suspensions of VRE, even in samples where no enterococcal colonies were present on the medium agar plate. The chlorine disinfection was not able to destroy antibiotic-resistance genes, though it can inactivate and decrease bacterial counts of antibiotic-resistant bacteria (ARB. Therefore, it was suggested that remaining ARB and/or antibiotic-resistance gene in inactivated bacterial cells after chlorine disinfection tank could be discharged into water environments.

[A novel chemo-resistant gene MSX2 discovered by establishment of two pancreatic cancer drug resistant cell lines JF305/CDDP and PANC-1/GEM].

Science.gov (United States)

Yuan, W; Sui, C G; Ma, X; Ma, J

2018-05-23

Objective: To explore new multidrug resistant genes of pancreatic cancer by establishment and characterization of chemo-resistant cell lines. Methods: The cisplatin-resistant cell line JF305/CDDP and the gemcitabine-resistant cell line PANC-1/GEM were induced by high-dose intermittent treatment. CCK-8 assay was used to detect the 50% inhibiting concentration (IC(50)), drug resistance index (R), cross-resistance, and growth difference of different cells. The changes of cell cycle and migration ability of drug-resistant cells were determined by flow cytometry and transwell assay, respectively. And then real-time fluorescence quantitative PCR was used to detect the expression of multidrug resistance-related genes. Results: The drug resistance indexes of JF305/CDDP and PANC-1/GEM were 15.3 and 27.31, respectively, and there was cross-resistance. Compared with the parental cells, the proliferation rate of JF305/CDDP was decreased by 40% on the fourth day ( P PANC-1 cells upregulated MRP2 level ( P PANC-1/GEM, were successfully established. MSX2 might be a new drug resistance related gene in pancreatic cancer cells by up-regulation of MRP2 expression.

Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

Science.gov (United States)

Huntington, M O; Krell, K E; Armour , W E; Liljenquist, J E

2001-06-01

Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

Insulin resistance and mitochondrial function in skeletal muscle

DEFF Research Database (Denmark)

Dela, Flemming; Helge, Jørn Wulff

2013-01-01

are used in the attempt to resolve the mechanisms of insulin resistance. In this context, a dysfunction of mitochondria in the skeletal muscle has been suggested to play a pivotal role. It has been postulated that a decrease in the content of mitochondria in the skeletal muscle can explain the insulin...... resistance. Complementary to this also specific defects of components in the respiratory chain in the mitochondria have been suggested to play a role in insulin resistance. A key element in these mechanistic suggestions is inability to handle substrate fluxes and subsequently an accumulation of ectopic...... intramyocellular lipids, interfering with insulin signaling. In this review we will present the prevailing view-points and argue for the unlikelihood of this scenario being instrumental in human insulin resistance. This article is part of a Directed Issue entitled: Bioenergetic dysfunction....

Re-sensitizing drug-resistant bacteria to antibiotics by designing Antisense Therapeutics

Science.gov (United States)

Courtney, Colleen; Chatterjee, Anushree

2014-03-01

``Super-bugs'' or ``multi-drug resistant organisms'' are a serious international health problem, with devastating consequences to patient health care. The Center for Disease Control has identified antibiotic resistance as one of the world's most pressing public health problems as a significant fraction of bacterial infections contracted are drug resistant. Typically, antibiotic resistance is encoded by ``resistance-genes'' which express proteins that carryout the resistance causing functions inside the bacterium. We present a RNA based therapeutic strategy for designing antimicrobials capable of re-sensitizing resistant bacteria to antibiotics by targeting labile regions of messenger RNAs encoding for resistance-causing proteins. We perform in silico RNA secondary structure modeling to identify labile target regions in an mRNA of interest. A synthetic biology approach is then used to administer antisense nucleic acids to our model system of ampicillin resistant Escherichia coli. Our results show a prolonged lag phase and decrease in viability of drug-resistant E. colitreated with antisense molecules. The antisense strategy can be applied to alter expression of other genes in antibiotic resistance pathways or other pathways of interest.

Tagging of resistance gene(s) to rhizomania disease in sugar beet ...

African Journals Online (AJOL)

The rhizomania disease is one of the most important diseases in Iran and some other parts of the world which potentially could play a role in decreasing sugar yield in fields. One approach to combat with this disease is the use of resistance varieties. This varieties have been identified which are having resistance genes to ...

Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells.

Science.gov (United States)

Gaspar, Nathalie; Sharp, Swee Y; Pacey, Simon; Jones, Chris; Walton, Michael; Vassal, Gilles; Eccles, Suzanne; Pearson, Andrew; Workman, Paul

2009-03-01

Heat shock protein 90 (HSP90) inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), which is currently in phase II/phase III clinical trials, are promising new anticancer agents. Here, we explored acquired resistance to HSP90 inhibitors in glioblastoma (GB), a primary brain tumor with poor prognosis. GB cells were exposed continuously to increased 17-AAG concentrations. Four 17-AAG-resistant GB cell lines were generated. High-resistance levels with resistance indices (RI = resistant line IC(50)/parental line IC(50)) of 20 to 137 were obtained rapidly (2-8 weeks). After cessation of 17-AAG exposure, RI decreased and then stabilized. Cross-resistance was found with other ansamycin benzoquinones but not with the structurally unrelated HSP90 inhibitors, radicicol, the purine BIIB021, and the resorcinylic pyrazole/isoxazole amide compounds VER-49009, VER-50589, and NVP-AUY922. An inverse correlation between NAD(P)H/quinone oxidoreductase 1 (NQO1) expression/activity and 17-AAG IC(50) was observed in the resistant lines. The NQO1 inhibitor ES936 abrogated the differential effects of 17-AAG sensitivity between the parental and resistant lines. NQO1 mRNA levels and NQO1 DNA polymorphism analysis indicated different underlying mechanisms: reduced expression and selection of the inactive NQO1*2 polymorphism. Decreased NQO1 expression was also observed in a melanoma line with acquired resistance to 17-AAG. No resistance was generated with VER-50589 and NVP-AUY922. In conclusion, low NQO1 activity is a likely mechanism of acquired resistance to 17-AAG in GB, melanoma, and, possibly, other tumor types. Such resistance can be overcome with novel HSP90 inhibitors.

Alteration of gene expression and DNA methylation in drug-resistant gastric cancer.

Science.gov (United States)

Maeda, Osamu; Ando, Takafumi; Ohmiya, Naoki; Ishiguro, Kazuhiro; Watanabe, Osamu; Miyahara, Ryoji; Hibi, Yoko; Nagai, Taku; Yamada, Kiyofumi; Goto, Hidemi

2014-04-01

The mechanisms of drug resistance in cancer are not fully elucidated. To study the drug resistance of gastric cancer, we analyzed gene expression and DNA methylation profiles of 5-fluorouracil (5-FU)- and cisplatin (CDDP)-resistant gastric cancer cells and biopsy specimens. Drug-resistant gastric cancer cells were established with culture for >10 months in a medium containing 5-FU or CDDP. Endoscopic biopsy specimens were obtained from gastric cancer patients who underwent chemotherapy with oral fluoropyrimidine S-1 and CDDP. Gene expression and DNA methylation analyses were performed using microarray, and validated using real-time PCR and pyrosequencing, respectively. Out of 17,933 genes, 541 genes commonly increased and 569 genes decreased in both 5-FU- and CDDP-resistant AGS cells. Genes with expression changed by drugs were related to GO term 'extracellular region' and 'p53 signaling pathway' in both 5-FU- and CDDP-treated cells. Expression of 15 genes including KLK13 increased and 12 genes including ETV7 decreased, in both drug-resistant cells and biopsy specimens of two patients after chemotherapy. Out of 10,365 genes evaluated with both expression microarray and methylation microarray, 74 genes were hypermethylated and downregulated, or hypomethylated and upregulated in either 5-FU-resistant or CDDP-resistant cells. Of these genes, expression of 21 genes including FSCN1, CPT1C and NOTCH3, increased from treatment with a demethylating agent. There are alterations of gene expression and DNA methylation in drug-resistant gastric cancer; they may be related to mechanisms of drug resistance and may be useful as biomarkers of gastric cancer drug sensitivity.

Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer.

Science.gov (United States)

Canonici, Alexandra; Gijsen, Merel; Mullooly, Maeve; Bennett, Ruth; Bouguern, Noujoude; Pedersen, Kasper; O'Brien, Neil A; Roxanis, Ioannis; Li, Ji-Liang; Bridge, Esther; Finn, Richard; Siamon, Dennis; McGowan, Patricia; Duffy, Michael J; O'Donovan, Norma; Crown, John; Kong, Anthony

2013-10-01

Trastuzumab has been shown to improve the survival outcomes of HER2 positive breast cancer patients. However, a significant proportion of HER2-positive patients are either inherently resistant or develop resistance to trastuzumab. We assessed the effects of neratinib, an irreversible panHER inhibitor, in a panel of 36 breast cancer cell lines. We further assessed its effects with or without trastuzumab in several sensitive and resistant breast cancer cells as well as a BT474 xenograft model. We confirmed that neratinib was significantly more active in HER2-amplified than HER2 non-amplified cell lines. Neratinib decreased the activation of the 4 HER receptors and inhibited downstream pathways. However, HER3 and Akt were reactivated at 24 hours, which was prevented by the combination of trastuzumab and neratinib. Neratinib also decreased pHER2 and pHER3 in acquired trastuzumab resistant cells. Neratinib in combination with trastuzumab had a greater growth inhibitory effect than either drug alone in 4 HER2 positive cell lines. Furthermore, trastuzumab in combination with neratinib was growth inhibitory in SKBR3 and BT474 cells which had acquired resistance to trastuzumab as well as in a BT474 xenograft model. Innately trastuzumab resistant cell lines showed sensitivity to neratinib, but the combination did not enhance response compared to neratinib alone. Levels of HER2 and phospho-HER2 showed a direct correlation with sensitivity to neratinib. Our data indicate that neratinib is an effective anti-HER2 therapy and counteracted both innate and acquired trastuzumab resistance in HER2 positive breast cancer. Our results suggest that combined treatment with trastuzumab and neratinib is likely to be more effective than either treatment alone for both trastuzumab-sensitive breast cancer as well as HER2-positive tumors with acquired resistance to trastuzumab.

Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed

Directory of Open Access Journals (Sweden)

Schininà Maria

2010-09-01

Full Text Available Abstract Background Several mutations have been described as responsible for rifampicin resistance in Neisseria meningitidis. However, the intriguing question on why these strains are so rare remains open. The aim of this study was to investigate the protein content and to identify differential expression in specific proteins in two rifampicin resistant and one susceptible meningococci using two-dimensional electrophoresis (2-DE combined with mass spectrometry. Results In our experimental conditions, able to resolve soluble proteins with an isoelectric point between 4 and 7, twenty-three proteins have been found differentially expressed in the two resistant strains compared to the susceptible. Some of them, involved in the main metabolic pathways, showed an increased expression, mainly in the catabolism of pyruvate and in the tricarboxylic acid cycle. A decreased expression of proteins belonging to gene regulation and to those involved in the folding of polypeptides has also been observed. 2-DE analysis showed the presence of four proteins displaying a shift in their isoelectric point in both resistant strains, confirmed by the presence of amino acid changes in the sequence analysis, absent in the susceptible. Conclusions The analysis of differentially expressed proteins suggests that an intricate series of events occurs in N. meningitidis rifampicin resistant strains and the results here reported may be considered a starting point in understanding their decreased invasion capacity. In fact, they support the hypothesis that the presence of more than one protein differentially expressed, having a role in the metabolism of the meningococcus, influences its ability to infect and to spread in the population. Different reports have described and discussed how a drug resistant pathogen shows a high biological cost for survival and that may also explain why, for some pathogens, the rate of resistant organisms is relatively low considering the

Role of mitochondrial function in insulin resistance

NARCIS (Netherlands)

Brands, Myrte; Verhoeven, Arthur J.; Serlie, Mireille J.

2012-01-01

The obesity pandemic increases the prevalence of type 2 diabetes (DM2).DM2 develops when pancreatic β-cells fail and cannot compensate for the decrease in insulin sensitivity. How excessive caloric intake and weight gain cause insulin resistance has not completely been elucidated.Skeletal muscle is

Influence of illumination and decay of electrical resistance of ITO nanoscale layers

Energy Technology Data Exchange (ETDEWEB)

Somogyi, K. [MicroVacuum Ltd., Kerekgyarto u.: 10, H-1147 Budapest (Hungary)], E-mail: karoly.somogyi@microvacuum.com; Erdelyi, K.; Szendro, I. [MicroVacuum Ltd., Kerekgyarto u.: 10, H-1147 Budapest (Hungary)

2008-09-30

Indium tin oxide (ITO) is known as a transparent oxide with n-type electrical conductivity. However, the as grown ITO layers have high resistivity and the transparency is also limited. In this work, thin ITO layers were deposited by evaporation and then underwent a post-growth annealing. Annealing leads to a low electrical resistivity and to an enhanced transparency. Annealed samples show n-type conductivity. In this work, ITO layers of typically 10 nm thicknesses were deposited onto Si{sub 1-x}Ti{sub x}O{sub 2} covered glass substrates and then annealed. First the conductivity was evaluated after the annealing. The rough, quick estimation was performed by simple two point direct resistance measurement, and then van der Pauw configuration and collinear four-point probe method were applied. The light sensitivity and storage time dependent stability were studied. It is demonstrated that the resistance decreases due to illumination, though only in a small extent. The measure and speed of the decrease depend on the wavelength of the light and the process is very slow (up to hours). The recovery of the starting resistance is also a slow process.

Collateral methotrexate resistance in cisplatin-selected murine leukemia cells

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Bhushan A.

1999-01-01

Full Text Available Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a >25,000-fold collateral resistance to methotrexate. Given the magnitude of this resistance we elected to investigate this intriguing collateral resistance. From a series of investigations we have identified an alteration in a membrane protein of the resistant cell as compared to the sensitive cells that could be the primary mechanism of resistance. Our studies reviewed here indicate decreased tyrosine phosphorylation of a protein (molecular mass = 66 in the resistant cells, which results in little or no transfer of methotrexate from the medium into the cell. Since this is a relatively novel function for tyrosine phosphorylation, this information may provide insight into possible pharmacological approaches to modify therapeutic regimens by analyzing the status of this protein in tumor samples for a better survival of the cancer patients.

Resistant Hypertension and Obstructive Sleep Apnea

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Akram Khan

2013-01-01

Full Text Available Hypertension (HTN is a modifiable, highly prevalent risk factor for cardiovascular morbidity and renal dysfunction worldwide. In the United States, HTN affects one in three adults, contributes to one out of every seven deaths and to nearly half of all cardiovascular disease-related deaths. HTN is considered resistant when the blood pressure remains above goal despite lifestyle modification and administration of three antihypertensive agents of different classes including a diuretic. Large population-based studies have suggested that obstructive sleep apnea (OSA is a risk factor for resistant HTN. The mechanism proposed is a pattern of intermittent hypoxia associated with hyperaldosteronism, increased sympathetic tone, endothelial dysfunction, and inflammation. In this review we discuss the association between OSA and resistant HTN, the physiologic mechanisms linking OSA with resistant HTN, and the effect of continuous positive airway pressure therapy (CPAP on blood pressure in patients with resistant HTN. While the reduction in blood pressure with CPAP is usually modest in patients with OSA, a decrease of only a few mmHg in blood pressure can significantly reduce cardiovascular risk. Patients presenting to a center specializing in management of hypertension should be screened and treated for OSA as a potentially modifiable risk factor.

Experimental-calculation technique for Ksub(IC) determination using the samples of decreased dimensions

International Nuclear Information System (INIS)

Vinokurov, V.A.; Dymshits, A.V.; Pirusskij, M.V.; Ovsyannikov, B.M.; Kononov, V.V.

1981-01-01

A possibility to decrease the size of samples, which is necessary for the reliable determination of fractUre toughness Ksub(1c), is established. The dependences of crack-resistance caracteristics on the sample dimensions are determined experimentally. The static bending tests are made using the 1251 model of ''Instron'' installation with a specially designed device. The samples of the 20KhNMF steel have been tested. It is shown that the Ksub(1c) value, determined for the samples with the largest netto cross section (50x100 rm), is considerably lower than Ksub(1c) values, determined for the samples with the decreased sizes. it is shown that the developed experimental-calculated method of Ksub(1c) determination can be practically used for the samples of the decreased sizes with the introduction of the corresponding amendment coefficient [ru

Molecular characterization of resistance to Rifampicin in an emerging hospital-associated Methicillin-resistant Staphylococcus aureus clone ST228, Spain

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Liñares Josefina

2010-03-01

Full Text Available Abstract Background Methicillin-resistant S. aureus (MRSA has been endemic in Hospital Universitari de Bellvitge, Barcelona, since 1990. During the 1990-95 period the Iberian clone (ST-247; SCCmec-I was dominant. Isolates of clonal complex 5 (ST-125; SCCmec-IV gradually replaced the Iberian clone from 1996 to 2003. A new multiresistant MRSA phenotype showing rifampicin resistance emerged in 2004 and rapidly increased from 25% in 2004 to 45% in 2006. The aims of this study were i the molecular characterisation of rifampicin resistant MRSA isolates, ii the study of the rifampicin resistance expression by disk diffusion, microdilution and E-test, and iii the analysis of the rpoB gene mutations involved in rifampicin resistance. Results A sample of representative 108 rifampicin-resistant MRSA isolates belonged to a single PFGE genotype, ST-228, SCCmec type I and spa type t041. Of 108 isolates, 104 (96% had a low-level rifampicin resistance (MICs, 2 to 4 mg/L and 4 a high-level rifampicin resistance (MICs, 128 - ≥ 256 mg/L. Disk diffusion and E-test methods failed to identify a low-level rifampicin resistance in 20 and 12 isolates, respectively. A low-level rifampicin resistance was associated with amino acid substitution 481His/Asn in the beta-subunit of RNA polymerase. Isolates with a high-level rifampicin resistance carried additional mutations in the rpoB gene. Conclusions The emergence of MRSA clone ST228-SCCmecI, related to the Southern Germany clone, involved a therapeutical challenge for treating serious MRSA infections. Decreased susceptibility to rifampicin in MRSA strains of ST228-SCCmecI was associated with one or two specific mutations in the rpoB gene. One fifth of isolates with low-level rifampicin-resistance were missed by the diffusion methods.

Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs with different waste load.

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Mailis Laht

Full Text Available Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs, an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs were quantified using qPCR in three WWTPs of decreasing capacity located in Helsinki, Tallinn, and Tartu, respectively: sulphonamide resistance genes (sul1 and sul2, tetracycline resistance genes (tetM and tetC, and resistance genes for extended spectrum beta-lactams (blaoxa-58, blashv-34, and blactx-m-32. To avoid inconsistencies among qPCR assays we normalised the ARG abundances with 16S rRNA gene abundances while assessing if the respective genes increased or decreased during treatment. ARGs were detected in most samples; sul1, sul2, and tetM were detected in all samples. Statistically significant differences (adjusted p<0.01 between the inflow and effluent were detected in only four cases. Effluent values for blaoxa-58 and tetC decreased in the two larger plants while tetM decreased in the medium-sized plant. Only blashv-34 increased in the effluent from the medium-sized plant. In all other cases the purification process caused no significant change in the relative abundance of resistance genes, while the raw abundances fell by several orders of magnitude. Standard water quality variables (biological oxygen demand, total phosphorus and nitrogen, etc. were weakly related or unrelated to the relative abundance of resistance genes. Based on our results we conclude that there is neither considerable enrichment nor purification of antibiotic resistance genes in studied conventional WWTPs.

Arterial Stiffness and Autonomic Modulation After Free-Weight Resistance Exercises in Resistance Trained Individuals.

Science.gov (United States)

Kingsley, J Derek; Mayo, Xián; Tai, Yu Lun; Fennell, Curtis

2016-12-01

Kingsley, JD, Mayo, X, Tai, YL, and Fennell, C. Arterial stiffness and autonomic modulation after free-weight resistance exercises in resistance trained individuals. J Strength Cond Res 30(12): 3373-3380, 2016-We investigated the effects of an acute bout of free-weight, whole-body resistance exercise consisting of the squat, bench press, and deadlift on arterial stiffness and cardiac autonomic modulation in 16 (aged 23 ± 3 years; mean ± SD) resistance-trained individuals. Arterial stiffness, autonomic modulation, and baroreflex sensitivity (BRS) were assessed at rest and after 3 sets of 10 repetitions at 75% 1-repetition maximum on each exercise with 2 minutes of rest between sets and exercises. Arterial stiffness was analyzed using carotid-femoral pulse wave velocity (cf-PWV). Linear heart rate variability (log transformed [ln] absolute and normalized units [nu] of low-frequency [LF] and high-frequency [HF] power) and nonlinear heart rate complexity (Sample Entropy [SampEn], Lempel-Ziv Entropy [LZEn]) were measured to determine autonomic modulation. BRS was measured by the sequence method. A 2 × 2 repeated measures analysis of variance (ANOVA) was used to analyze time (rest, recovery) across condition (acute resistance exercise, control). There were significant increases in cf-PWV (p = 0.05), heart rate (p = 0.0001), normalized LF (LFnu; p = 0.001), and the LF/HF ratio (p = 0.0001). Interactions were also noted for ln HF (p = 0.006), HFnu (p = 0.0001), SampEn (p = 0.001), LZEn (p = 0.005), and BRS (p = 0.0001) such that they significantly decreased during recovery from the resistance exercise compared with rest and the control. There was no effect on ln total power, or ln LF. These data suggest that a bout of resistance exercise using free-weights increases arterial stiffness and reduces vagal activity and BRS in comparison with a control session. Vagal tone may not be fully recovered up to 30 minutes after a resistance exercise bout.

Parallel screening of wild-type and drug-resistant targets for anti-resistance neuraminidase inhibitors.

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Kai-Cheng Hsu

Full Text Available Infection with influenza virus is a major public health problem, causing serious illness and death each year. Emergence of drug-resistant influenza virus strains limits the effectiveness of drug treatment. Importantly, a dual H275Y/I223R mutation detected in the pandemic influenza A 2009 virus strain results in multidrug resistance to current neuraminidase (NA drugs. Therefore, discovery of new agents for treating multiple drug-resistant (MDR influenza virus infections is important. Here, we propose a parallel screening strategy that simultaneously screens wild-type (WT and MDR NAs, and identifies inhibitors matching the subsite characteristics of both NA-binding sites. These may maintain their potency when drug-resistant mutations arise. Initially, we analyzed the subsite of the dual H275Y/I223R NA mutant. Analysis of the site-moiety maps of NA protein structures show that the mutant subsite has a relatively small volume and is highly polar compared with the WT subsite. Moreover, the mutant subsite has a high preference for forming hydrogen-bonding interactions with polar moieties. These changes may drive multidrug resistance. Using this strategy, we identified a new inhibitor, Remazol Brilliant Blue R (RB19, an anthraquinone dye, which inhibited WT NA and MDR NA with IC(50 values of 3.4 and 4.5 µM, respectively. RB19 comprises a rigid core scaffold and a flexible chain with a large polar moiety. The former interacts with highly conserved residues, decreasing the probability of resistance. The latter forms van der Waals contacts with the WT subsite and yields hydrogen bonds with the mutant subsite by switching the orientation of its flexible side chain. Both scaffolds of RB19 are good starting points for lead optimization. The results reveal a parallel screening strategy for identifying resistance mechanisms and discovering anti-resistance neuraminidase inhibitors. We believe that this strategy may be applied to other diseases with high

Effect of nano-TiO{sub 2} particles size on the corrosion resistance of alkyd coating

Energy Technology Data Exchange (ETDEWEB)

Deyab, M.A., E-mail: hamadadeiab@yahoo.com; Keera, S.T.

2014-08-01

The coating system containing various sizes (∼10, 50, 100, 150 nm) of nano-TiO{sub 2} were prepared and investigated for corrosion protection of carbon steel in 1.0 M H{sub 2}SO{sub 4} using polarization, EIS and transmission electron microscopy (TEM) techniques. It was found that nano-TiO{sub 2} particles improved the corrosion resistance of alkyd coatings. The corrosion resistance occurs via physical adhesion on the metal surface. O{sub 2} and H{sub 2}O permeability of coating decreased with decrease in the nano-TiO{sub 2} size. The inhibition efficiency was found to increase with decreasing the size of nano-TiO{sub 2} and with decreasing the temperature. - Highlights: • Nano-TiO{sub 2} coating were prepared and used for corrosion protection of C-steel. • Nano-TiO{sub 2} particles in coating are effective to improve the corrosion resistance. • Nano-TiO{sub 2} coating inhibit both anodic and cathodic reactions. • Corrosion inhibition efficiency increases with decrease in the size of nano-TiO{sub 2}. • O{sub 2} and H{sub 2}O permeability of coating decreased with decrease in the nano-TiO{sub 2} size.

Mechanisms of azole resistance in a clinical isolate of Candida tropicalis.

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Vandeputte, Patrick; Larcher, Gérald; Bergès, Thierry; Renier, Gilles; Chabasse, Dominique; Bouchara, Jean-Philippe

2005-11-01

Azole resistance has been insufficiently investigated in the yeast Candida tropicalis. Here we determined the molecular mechanisms responsible for azole resistance in a clinical isolate of this pathogenic yeast. Antifungal susceptibility testing performed by a disk diffusion method showed resistance or markedly decreased susceptibility to azoles, which was confirmed by determination of MICs. Considering the relationship between azole susceptibility and the respiration reported for other yeast species, the respiratory activity of this isolate was investigated. Flow cytometry using rhodamine 123 and oxygraphy demonstrated an increased respiratory activity, which was not linked to an overexpression or increased number of copies of the mitochondrial genome. Among previously described resistance mechanisms, an increased activity of efflux pumps was investigated by flow cytometry using rhodamine 6G. However, the efflux of rhodamine 6G was lower in the resistant isolate than in susceptible ones. Likewise, real-time reverse transcription-PCR quantification of the expression of C. tropicalis MDR1 (CtMDR1), which encodes an efflux protein belonging to the major facilitator superfamily, did not show overexpression of this gene. In contrast, the resistant isolate overexpressed the CtERG11 gene coding for lanosterol 14alpha-demethylase. This was in agreement with the larger amount of ergosterol found in this isolate. Moreover, sequencing of CtERG11 showed a point mutation leading to a tyrosine substitution in the protein sequence, which might lead to decreased binding affinity for azoles. In conclusion, overexpression of CtERG11 associated with a missense mutation in this gene seemed to be responsible for the acquired azole resistance of this clinical isolate.

Regulation of ion transport via apical purinergic receptors in intact rabbit airway epithelium

DEFF Research Database (Denmark)

Poulsen, Asser Nyander; Klausen, Thomas Levin; Pedersen, Peter Steen

2005-01-01

and unidirectional Cl- fluxes decreased significantly. The results suggest that nucleotides released to the airway surface liquid exert an autocrine regulation of epithelial NaCl absorption mainly by inhibiting the amiloride-sensitive epithelial Na+ channel (ENaC) and paracellular anion conductance via a P2Y......We investigated purinergic receptors involved in ion transport regulation in the intact rabbit nasal airway epithelium. Stimulation of apical membrane P2Y receptors with ATP or UTP (200 microM) induced transient increases in short-circuit current (Isc) of 13 and 6% followed by sustained inhibitions...

Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in the HIV Outpatient Study: 1999–2008

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Kate Buchacz

2012-01-01

Full Text Available Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS who, during 1999–2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI was defined as triple-class exposure (TCE. Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999–2008 (88% to 79%, P=0.05. Resistance to PIs decreased among PI-exposed patients (71% to 46%, P=0.010 as exposure to ritonavir-boosted PIs increased (6% to 81%, P<0.001. Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%, and triple-class-resistance among TCE patients (66% to 41%, but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999–2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs.

Genetics of resistance against lettuce downy mildew

Science.gov (United States)

Lettuce (Lactuca sativa) is one of the most valuable vegetable crops in the U.S. Downy mildew (DM), caused by Bremia lactucae, is the most important foliar disease of lettuce worldwide, which decreases the quality of the marketable portion of the crop. The use of resistant varieties carrying dominan...

Volume Resistivity and Mechanical Behavior of Epoxy Nanocomposite Materials

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M. F. Abdelkarim

2015-04-01

Full Text Available Electrical and mechanical properties of polymer composite materials are investigated through the determination of resistivity and hardness for composites samples. Epoxy composite samples have been prepared with different concentrations of certain inorganic fillers such as; Titanium dioxide (TiO2 and Silica (SiO2, of various size (micro, nano and hybrid to study the electrical and mechanical behavior. The volume resistivity reaches 3.23×1014 ohm.cm for the micro silica composite. Surface of composite material has been mechanically examined by hardness test. The results show that the resistivity of microcomposites and nanocmposites are increased with the decrease of filler concentration. But the resistivity of hybrid composites is increased with the increase of filler concentration. Maximum hardness value was obtained from hybrid silica composite with 0.1% filler concentration.

Effects of grain size on the corrosion resistance of pure magnesium by cooling rate-controlled solidification

Science.gov (United States)

Liu, Yichi; Liu, Debao; You, Chen; Chen, Minfang

2015-09-01

The aim of this study was to investigate the effect of grain size on the corrosion resistance of pure magnesium developed for biomedical applications. High-purity magnesium samples with different grain size were prepared by the cooling rate-controlled solidification. Electrochemical and immersion tests were employed to measure the corrosion resistance of pure magnesium with different grain size. The electrochemical polarization curves indicated that the corrosion susceptibility increased as the grain size decrease. However, the electrochemical impedance spectroscopy (EIS) and immersion tests indicated that the corrosion resistance of pure magnesium is improved as the grain size decreases. The improvement in the corrosion resistance is attributed to refine grain can produce more uniform and density film on the surface of sample.

Resistome diversity in cattle and the environment decreases during beef production.

Science.gov (United States)

Noyes, Noelle R; Yang, Xiang; Linke, Lyndsey M; Magnuson, Roberta J; Dettenwanger, Adam; Cook, Shaun; Geornaras, Ifigenia; Woerner, Dale E; Gow, Sheryl P; McAllister, Tim A; Yang, Hua; Ruiz, Jaime; Jones, Kenneth L; Boucher, Christina A; Morley, Paul S; Belk, Keith E

2016-03-08

Antimicrobial resistant determinants (ARDs) can be transmitted from livestock systems through meat products or environmental effluents. The public health risk posed by these two routes is not well understood, particularly in non-pathogenic bacteria. We collected pooled samples from 8 groups of 1741 commercial cattle as they moved through the process of beef production from feedlot entry through slaughter. We recorded antimicrobial drug exposures and interrogated the resistome at points in production when management procedures could potentially influence ARD abundance and/or transmission. Over 300 unique ARDs were identified. Resistome diversity decreased while cattle were in the feedlot, indicating selective pressure. ARDs were not identified in beef products, suggesting that slaughter interventions may reduce the risk of transmission of ARDs to beef consumers. This report highlights the utility and limitations of metagenomics for assessing public health risks regarding antimicrobial resistance, and demonstrates that environmental pathways may represent a greater risk than the food supply.

In vivo T cell depletion regulates resistance and morbidity in murine schistosomiasis

International Nuclear Information System (INIS)

Phillips, S.M.; Linette, G.P.; Doughty, B.L.; Byram, J.E.; Von Lichtenberg, F.

1987-01-01

These studies assessed the roles of subpopulations of T lymphocytes in inducing and modulating resistance to schistosomiasis and thereby influencing subsequent morbidity. C57BL/6 mice were depleted in vivo of Lyt-1+, Lyt-2+, and L3T4+ cells by the daily administration of monoclonal antibodies. The development of protective immunity, induced by exposure to irradiated Schistosoma mansoni cercariae as expressed in depleted animals, was compared to that demonstrated in undepleted, normal, and congenitally athymic C57BL/6 mice. The development of morbidity was determined by spleen weight, portal pressure and reticuloendothelial system activity. The results indicated that depletion of specific subpopulations of T lymphocytes minimally affected the primary development of parasites; however, depletion strongly influenced the development of resistance to the parasite and subsequent morbidity due to infection. Depletion of T lymphocytes by anti-Lyt-1+ or anti-L3T4+ antibody decreased the development of resistance, antibody and delayed-type hypersensitivity directed against schistosome antigens. Morbidity due to disease was increased. Depletion of Lyt-2+ cells produced opposite changes with augmented resistance and reduced morbidity. Congenitally athymic mice developed minimal resistance and morbidity. Moreover, resistance was inversely related to the morbidity shown by a given animal. These studies indicate that the development of protective immunity to S. mansoni cercariae is regulated by discrete subpopulations of T lymphocytes. The feasibility of decreasing morbidity by increasing specific immunologically mediated resistance is suggested

Improved cell line IPEC-J2, characterized as a model for porcine jejunal epithelium.

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Silke S Zakrzewski

Full Text Available Cell lines matching the source epithelium are indispensable for investigating porcine intestinal transport and barrier properties on a subcellular or molecular level and furthermore help to reduce animal usage. The porcine jejunal cell line IPEC-J2 is established as an in vitro model for porcine infection studies but exhibits atypically high transepithelial resistances (TER and only low active transport rates so that the effect of nutritional factors cannot be reliably investigated. This study aimed to properly remodel IPEC-J2 and then to re-characterize these cells regarding epithelial architecture, expression of barrier-relevant tight junction (TJ proteins, adequate TER and transport function, and reaction to secretagogues. For this, IPEC-J2 monolayers were cultured on permeable supports, either under conventional (fetal bovine serum, FBS or species-specific (porcine serum, PS conditions. Porcine jejunal mucosa was analyzed for comparison. Main results were that under PS conditions (IPEC-J2/PS, compared to conventional FBS culture (IPEC-J2/FBS, the cell height increased 6-fold while the cell diameter was reduced by 50%. The apical cell membrane of IPEC-J2/PS exhibited typical microvilli. Most importantly, PS caused a one order of magnitude reduction of TER and of trans- and paracellular resistance, and a 2-fold increase in secretory response to forskolin when compared to FBS condition. TJ ultrastructure and appearance of TJ proteins changed dramatically in IPEC-J2/PS. Most parameters measured under PS conditions were much closer to those of typical pig jejunocytes than ever reported since the cell line's initial establishment in 1989. In conclusion, IPEC-J2, if cultured under defined species-specific conditions, forms a suitable model for investigating porcine paracellular intestinal barrier function.

Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial.

Science.gov (United States)

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

2017-04-01

Our aim was to investigate the effects and prevalence of nonresponders (NR) to high-intensity interval training (HIIT) and resistance training (RT) in women with insulin resistance on cardiometabolic health parameters. Sedentary overweight/obese insulin-resistant women (age = 33.5 ± 6.5 yr; body mass index = 29.9 ± 3.7 kg/m 2 ) were randomly assigned to a triweekly HIIT program (HIIT; n = 18) or resistance training (RT; n = 17). Anthropometry (body mass, fat mass, muscle mass, waist circumference, and skinfold thickness), cardiovascular (blood pressure), metabolic [fasting glucose, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR)], as well as muscle strength, and endurance performance covariables were measured before and after 12 wk in both intervention groups. The interindividual variability to exercise training of the subjects was categorized as responders and NR using as cut points two times the typical error of measurement in mean outcomes. After intervention, significant reduction in waist circumference, skinfold thicknesses, fat mass, blood pressure, fasting glucose, insulin, and HOMA-IR ( P HIIT and RT group, respectively. Both HIIT and RT groups exhibited a significant decrease in the endurance performance, whereas only RT exhibited increased muscle strength. Significant differences in the NR prevalence between the HIIT and RT groups were identified for a decrease in fat mass (HIIT 33.3% vs. RT 70.5%; P = 0.028), muscle mass (HIIT 100% vs. RT 52.9%; P = 0.001), and tricipital skinfold (HIIT 5.5% vs. RT 29.4%; P HIIT and RT groups (55.5% vs. 94.1; P = 0.009). However, there were no differences in the NR prevalence between HIIT and RT for decreasing fasting glucose. Twelve weeks of HIIT and RT have similar effects and NR prevalence to improve glucose control variables; however, there is different NR prevalence in other anthropometric, cardiovascular, strength, and endurance performance measurements in insulin-resistant women. These

Metabolic changes during development of Walker-256 carcinosarcoma resistance to doxorubicin.

Science.gov (United States)

Todor, I N; Lukyanova, N Yu; Shvets, Yu V; Lozovska, Yu V; Chekhun, V F

2015-03-01

To study indices of energy metabolism, content of K(+) and Mg(++) both in peripheral blood and in Walker-256 carcinosarcoma during development of resistance to doxorubicin. Resistance of Walker-256 carcinosarcoma to doxorubicin has been developed through 12 subsequent transplantations of tumor after the chemotherapy. Parental strain was inhibited by drug by 65%, while transitional resistant substrains - by 30% and 2%, respectively. Determination of biochemical indices in blood serum and homogenates of tumor tissue, level of potassium, magnesium, lactate, glucose, activities of lactate dehydrogenase and glucose-6-phosphate dehydrogenase was performed with the help of biochemical and immune-enzyme analyzer GBG ChemWell 2990 (USA) using standard kits. Polarography was used to determine indices of mitochondrial oxidative phosphorylation. Study of mitochondrial membrane potential was carried out on flow cytometer Beckman Coulter Epics XL using dye JC-1. It has been determined that development of drug resistance causes the decrease of K(+), Mg(++), glucose content in blood serum and increase of these indices in tumor tissue. At the same time, gradual tumor's loss of sensitivity is characterized by decrease of glycolysis activity in it and activation of mitochondrial oxidative phosphorylation and pentose phosphate pathway of glucose degradation, which causes more intensive formation of NADPH. Development of drug resistance of tumor causes certain metabolic changes in organism and tumor. Further study of such changes will make possible to determine tumor and extratumor markers of resistance.

EPSPS variability, gene expression, and enzymatic activity in glyphosate-resistant biotypes of Digitaria insularis.

Science.gov (United States)

Galeano, E; Barroso, A A M; Vasconcelos, T S; López-Rubio, A; Albrecht, A J P; Victoria Filho, R; Carrer, H

2016-08-12

Weed resistance to herbicides is a natural phenomenon that exerts selection on individuals in a population. In Brazil, glyphosate resistance was recently detected in Digitaria insularis. The objective of this study was to elucidate mechanisms of weed resistance in this plant, including genetic variability, allelism, amino acid substitutions, gene expression, and enzymatic activity levels. Most of these have not previously been studied in this species. D. insularis DNA sequences were used to analyze genetic variability. cDNA from resistant and susceptible plants was used to identify mutations, alleles, and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) expression, using real-time quantitative reverse transcription-polymerase chain reaction. In addition, EPSPS activity was measured. We found a decrease in genetic variability between populations related to glyphosate application. Substitutions from proline to threonine and tyrosine to cysteine led to a decrease in EPSPS affinity for the glyphosate. In addition, the EPSPS enzymatic activity was slightly higher in resistant plants, whereas EPSPS gene expression was almost identical in both biotypes, suggesting feedback regulation at different levels. To conclude, our results suggest new molecular mechanisms used by D. insularis to increase glyphosate resistance.

Contrasting effects of specialist and generalist herbivores on resistance evolution in invasive plants.

Science.gov (United States)

Zhang, Zhijie; Pan, Xiaoyun; Blumenthal, Dana; van Kleunen, Mark; Liu, Mu; Li, Bo

2018-04-01

Invasive alien plants are likely to be released from specialist herbivores and at the same time encounter biotic resistance from resident generalist herbivores in their new ranges. The Shifting Defense hypothesis predicts that this will result in evolution of decreased defense against specialist herbivores and increased defense against generalist herbivores. To test this, we performed a comprehensive meta-analysis of 61 common garden studies that provide data on resistance and/or tolerance for both introduced and native populations of 32 invasive plant species. We demonstrate that introduced populations, relative to native populations, decreased their resistance against specialists, and increased their resistance against generalists. These differences were significant when resistance was measured in terms of damage caused by the herbivore, but not in terms of performance of the herbivore. Furthermore, we found the first evidence that the magnitude of resistance differences between introduced and native populations depended significantly on herbivore origin (i.e., whether the test herbivore was collected from the native or non-native range of the invasive plant). Finally, tolerance to generalists was found to be higher in introduced populations, while neither tolerance to specialists nor that to simulated herbivory differed between introduced and native plant populations. We conclude that enemy release from specialist herbivores and biotic resistance from generalist herbivores have contrasting effects on resistance evolution in invasive plants. Our results thus provide strong support for the Shifting Defense hypothesis. © 2018 by the Ecological Society of America.

Treatment of acute otitis media - challenges in the era of antibiotic resistance.

Science.gov (United States)

Dagan, R

2000-12-08

The last decade is characterized by the increase in antibiotic resistance among respiratory bacterial pathogens in the presence of only modest progress in the development of new antibacterial agents to overcome this resistance. A series of recent studies show clearly that the increased resistance among the main AOM pathogens (namely Streptococcus pneumoniae and Haemophilus influenzae) is associated with a dramatic decrease in bacteriologic response to antibiotic treatment, which in turn has an impact on clinical response. Thus, the individual patient is affected by the increasing antibiotic resistance. Moreover, the society as a whole is now also affected because the carriage and spread of antibiotic resistant AOM pathogens is remarkably impacted by antibiotic treatment. New studies show the remarkable ability of antibiotics to rapidly promote nasopharyngeal carriage and spread of antibiotic-resistant AOM pathogens. In these studies, the increase in carriage of antibiotic resistant S. pneumoniae is shown already after 3-4 days from initiation of antibiotic treatment and may last for weeks to months after treatment. Children carrying antibiotic-resistant organisms transmit those organisms to their family and to their day care centers and thus a vicious cycle is created in which increased antibiotic resistance with decreased response leads to increased antibiotic use, which in turn leads to further increase in resistance. New antibiotics are not likely to improve this situation. It is clear that the challenge in the next decade is to prevent AOM rather than to treat it. Efforts to prevent AOM include improved environmental factors, immunization with bacterial and viral vaccines and some creative measures such as prevention of colonization and attachment to epithelium of AOM pathogens. Whether these efforts will prove successful or, even if successful, will only modify the clinical and bacteriologic picture presenting new challenges, only time will tell.

Effect of Air Gap Entrapped in Firefighter Protective Clothing on Thermal Resistance and Evaporative Resistance

Directory of Open Access Journals (Sweden)

He Hualing

2018-03-01

Full Text Available Heat and water vapor transfer behavior of thermal protective clothing is greatly influenced by the air gap entrapped in multilayer fabric system. In this study, a sweating hot plate method was used to investigate the effect of air gap position and size on thermal resistance and evaporative resistance of firefighter clothing under a range of ambient temperature and humidity. Results indicated that the presence of air gap in multilayer fabric system decreased heat and water vapor transfer abilities under normal wear. Moreover, the air gap position slightly influenced the thermal and evaporative performances of the firefighter clothing. In this study, the multilayer fabric system obtained the highest thermal resistance, when the air space was located at position B. Furthermore, the effect of ambient temperature on heat and water vapor transfer properties of the multilayer fabric system was also investigated in the presence of a specific air gap. It was indicated that ambient temperature did not influence the evaporative resistance of thermal protective clothing. A thermographic image was used to test the surface temperature of multilayer fabric system when an air gap was incorporated. These results suggested that a certain air gap entrapped in thermal protective clothing system could affect wear comfort.

The relationship of thioredoxin-1 and cisplatin resistance: its impact on ROS and oxidative metabolism in lung cancer cells.

Science.gov (United States)

Wangpaichitr, Medhi; Sullivan, Elizabeth J; Theodoropoulos, George; Wu, Chunjing; You, Min; Feun, Lynn G; Lampidis, Theodore J; Kuo, Macus T; Savaraj, Niramol

2012-03-01

Elimination of cisplatin-resistant lung cancer cells remains a major obstacle. We have shown that cisplatin-resistant tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here, we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1 and contributed to higher ROS in cisplatin-resistant tumors in vivo and in vitro. By reconstituting TRX1 protein in cisplatin-resistant cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. Cisplatin-resistant cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase mRNA, which contributed to oxidative metabolism (OXMET) when compared with parental cells. Restoring intracellular TRX1 protein in cisplatin-resistant cells resulted in lowering ASS and fumarase mRNAs, which in turn sensitized them to arginine deprivation. Interestingly, cisplatin-resistant cells also had significantly higher basal levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Overexpressing TRX1 lowered ACC and FAS proteins expressions in cisplatin-resistant cells. Chemical inhibition and short interfering RNA of ACC resulted in significant cell death in cisplatin-resistant compared with parental cells. Conversely, TRX1 overexpressed cisplatin-resistant cells resisted 5-(tetradecyloxy)-2-furoic acid (TOFA)-induced death. Collectively, lowering TRX1 expression through increased secretion leads cisplatin-resistant cells to higher ROS production and increased dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin-resistant lung cancer.

The Enhancement of Mg Corrosion Resistance by Alloying Mn and Laser-Melting

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Youwen Yang

2016-03-01

Full Text Available Mg has been considered a promising biomaterial for bone implants. However, the poor corrosion resistance has become its main undesirable property. In this study, both alloying Mn and laser-melting were applied to enhance the Mg corrosion resistance. The corrosion resistance, mechanical properties, and microstructure of rapid laser-melted Mg-xMn (x = 0–3 wt % alloys were investigated. The alloys were composed of dendrite grains, and the grains size decreased with increasing Mn. Moreover, Mn could dissolve and induce the crystal lattice distortion of the Mg matrix during the solidification process. Mn ranging from 0–2 wt % dissolved completely due to rapid laser solidification. As Mn contents further increased up to 3 wt %, a small amount of Mn was left undissolved. The compressive strength of Mg-Mn alloys increased first (up to 2 wt % and then decreased with increasing Mn, while the hardness increased continuously. The refinement of grains and the increase in corrosion potential both made contributions to the enhancement of Mg corrosion resistance.

Increasing Resistance to Extended-Spectrum Cephalosporins, Fluoroquinolone, and Carbapenem in Gram-Negative Bacilli and the Emergence of Carbapenem Non-Susceptibility in Klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System (KARMS) Data From 2013 to 2015.

Science.gov (United States)

Kim, Dokyun; Ahn, Ji Young; Lee, Chae Hoon; Jang, Sook Jin; Lee, Hyukmin; Yong, Dongeun; Jeong, Seok Hoon; Lee, Kyungwon

2017-05-01

National surveillance of antimicrobial resistance becomes more important for the control of antimicrobial resistance and determination of treatment guidelines. We analyzed Korean Antimicrobial Resistance Monitoring System (KARMS) data collected from 2013 to 2015. Of the KARMS participants, 16 secondary or tertiary hospitals consecutively reported antimicrobial resistance rates from 2013 to 2015. Data from duplicate isolates and institutions with fewer than 20 isolates were excluded. To determine the long-term trends, previous KARMS data from 2004 to 2012 were also considered. The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium from 2013 to 2015 was 66-72% and 29-31%, respectively. The resistance rates of Escherichia coli to cefotaxime and cefepime gradually increased to 35% and 31%, respectively, and fluoroquinolone resistance reached 48% in 2015. The resistance rates of Klebsiella pneumoniae to cefotaxime, cefepime, and carbapenem were 38-41%, 33-41%, and carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99.0% and 97.0% in 2015, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenem increased to 35% and the prevalence of carbapenem-resistant Acinetobacter baumannii increased from 77% in 2013 to 85% in 2015. Between 2013 and 2015, the resistance rates of E. coli to third- and fourth-generation cephalosporins increased continuously, while carbapenem-susceptibility gradually decreased, particularly in K. pneumoniae. The prevalence of carbapenem-resistant P. aeruginosa and A. baumannii increased significantly; therefore, few treatment options remain for these resistant strains. © The Korean Society for Laboratory Medicine

Corrosion resistance testing of high-boron-content stainless steels

International Nuclear Information System (INIS)

Petrman, I.; Safek, V.

1994-01-01

Boron steels, i.e. stainless steels with boron contents of 0.2 to 2.25 wt.%, are employed in nuclear engineering for the manufacture of baskets or wells in which radioactive fissile materials are stored, mostly spent nuclear fuel elements. The resistance of such steels to intergranular corrosion and uniform corrosion was examined in the Strauss solution and in boric acid; the dependence of the corrosion rate of the steels on their chemical composition was investigated, and their resistance was compared with that of AISI 304 type steel. Corrosion resistance tests in actual conditions of ''wet'' compact storage (demineralized water or a weak boric acid solution) gave evidence that boron steels undergo nearly no uniform corrosion and, as electrochemical measurements indicated, match standard corrosion-resistant steels. Corrosion resistance was confirmed to decrease slightly with increasing boron content and to increase somewhat with increasing molybdenum content. (Z.S.). 3 tabs., 4 figs., 7 refs

A common variation of the PTEN gene is associated with peripheral insulin resistance

DEFF Research Database (Denmark)

Grinder-Hansen, L; Ribel-Madsen, R; Wojtaszewski, Jørgen

2016-01-01

. RESULTS: The minor G allele of PTEN rs11202614 was associated with elevated fasting plasma insulin levels and a decreased peripheral glucose disposal rate, but not with the hepatic insulin resistance index or insulin secretion measured as the first-phase insulin response and disposition index. The single...... nucleotide polymorphism was not associated with either PI3K or Akt activities. CONCLUSION: A common PTEN variation is associated with peripheral insulin resistance and subsequent risk of developing T2D. However, the association with insulin resistance is not explained by decreased proximal insulin signalling......AIM: Phosphatase and tensin homologue (PTEN) reduces insulin sensitivity by inhibiting the phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (Akt) pathway. This study investigated how a common single nucleotide polymorphism near PTEN, previously associated...

Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration.

Science.gov (United States)

Takemoto, Jody K; Miller, Tracie L; Wang, Jiajia; Jacobson, Denise L; Geffner, Mitchell E; Van Dyke, Russell B; Gerschenson, Mariana

2017-01-02

To identify relationships between insulin resistance (IR) and mitochondrial respiration in perinatally HIV-infected youth. Case-control study. Mitochondrial respiration was assessed in perinatally HIV-infected youth in Tanner stages 2-5, 25 youth with IR (IR+) and 50 without IR (IR-) who were enrolled in the Pediatric HIV/AIDS Cohort Study. IR was defined as a homeostatic model of assessment for IR value at least 4.0. A novel, high-throughput oximetry method was used to evaluate cellular respiration in peripheral blood mononuclear cells. Unadjusted and adjusted differences in mitochondrial respiration markers between IR+ and IR- were evaluated, as were correlations between mitochondrial respiration markers and biochemical measurements. IR+ and IR- youth were similar on age, sex, and race/ethnicity. Mean age was 16.5 and 15.6 years in IR+ and IR-, respectively. The IR+ group had significantly higher mean BMI and metabolic analytes (fasting glucose, insulin, cholesterol, triglycerides, and venous lactate and pyruvate) compared with the IR-. Mitochondrial respiration markers were, on average, lower in the IR+ compared with IR-, including basal respiration (417.5 vs. 597.5 pmol, P = 0.074), ATP production (11 513 vs. 15 202 pmol, P = 0.078), proton leak (584.6 vs. 790.0 pmol, P = 0.033), maximal respiration (1815 vs. 2399 pmol, P = 0.025), and spare respiration capacity (1162 vs. 2017 pmol, P = 0.032). Nonmitochondrial respiration did not differ by IR status. The results did not change when adjusted for age. HIV-infected youth with IR have lower mitochondrial respiration markers when compared to youth without IR. Disordered mitochondrial respiration may be a potential mechanism for IR in this population.

Toughness degradation evaluation of low alloyed steels by electrical resistivity

Energy Technology Data Exchange (ETDEWEB)

Nahm, S H; Yu, K M; Kim, S C [Korea Research Inst. of Standards and Science, Taejon (Korea, Republic of); Kim, A [Department of Mechanical Engineering, Kongju Univ., Kongju, Chungnam (Korea, Republic of)

1997-09-01

Remaining life of turbine rotors with a crack can be assessed by the fracture toughness on the aged rotors at service temperature. DC potential drop measurement system was constructed in order to evaluate material toughness nondestructively. Test material was 1Cr-1Mo-0.25V steel used widely for turbine rotor material. Seven kinds of specimen with different degradation levels were prepared according to isothermal aging heat treatment at 630 deg. C. Electrical resistivity of test material was measured at room temperature. It was observed that material toughness and electrical resistivity decreased with the increase of degradation. The relationship between fracture toughness and electrical resistivity was investigated. Fracture toughness of a test material may be determined nondestructively by electrical resistivity. (author). 13 refs, 7 figs.

Aging and cellular defense mechanisms: age-related changes in resistance of mice to Listeria monocytogenes.

OpenAIRE

Patel, P J

1981-01-01

Age-related changes in resistance of mice to infection with Listeria monocytogenes were investigated. One-month-old mice exhibited the least resistance, and the resistance level increased over the first few months to reach a maximum by 8 months. Increase in age thereafter was accompanied by a slow but progressive decrease in resistance. Thus, 50% lethal doses for 1-, 8-, and 24-month-old mice were 10(4.2), 10(6.6), and 10(5.2), respectively. In spite of differences in resistance, the growth o...

ENZYME RESISTANCE OF GENETICALLY MODIFIED STARCH POTATOES

Directory of Open Access Journals (Sweden)

A. Sh. Mannapova

2015-01-01

Full Text Available Here in this article the justification of expediency of enzyme resistant starch use in therapeutic food products is presented . Enzyme resistant starch is capable to resist to enzymatic hydrolysis in a small intestine of a person, has a low glycemic index, leads to decrease of postprandial concentration of glucose, cholesterol, triglycerides in blood and insulin reaction, to improvement of sensitivity of all organism to insulin, to increase in sense of fulness and to reduction of adjournment of fats. Resistant starch makes bifidogenшс impact on microflora of a intestine of the person, leads to increase of a quantity of lactobacillus and bifidobacterium and to increased production of butyric acid in a large intestine. In this regard the enzyme resistant starch is an important component in food for prevention and curing of human diseases such as diabetes, obesity, colitis, a cancer of large and direct intestine. One method is specified by authors for imitation of starch digestion in a human body. This method is based on the definition of an enzyme resistance of starch in vitro by its hydrolysis to glucose with application of a glucoamylase and digestive enzyme preparation Pancreatin. This method is used in researches of an enzyme resistance of starch, of genetically modified potato, high amylose corn starch Hi-Maize 1043 and HYLON VII (National Starch Food Innovation, USA, amylopectin and amylose. It is shown that the enzyme resistance of the starch emitted from genetically modified potatoes conforms to the enzyme resistance of the high amylose corn starch “Hi-Maize 1043 and HYLON VII starch”, (National Starch Food Innovation, the USA relating to the II type of enzyme resistant starch. It is established that amylopectin doesn't have the enzyme resistant properties. The results of researches are presented. They allow us to make the following conclusion: amylose in comparison with amylopectin possesses higher enzyme resistance and gives to

Impact of colistin sulfate treatment of broilers on the presence of resistant bacteria and resistance genes in stored or composted manure.

Science.gov (United States)

Le Devendec, Laetitia; Mourand, Gwenaelle; Bougeard, Stéphanie; Léaustic, Julien; Jouy, Eric; Keita, Alassane; Couet, William; Rousset, Nathalie; Kempf, Isabelle

2016-10-15

The application of manure may result in contamination of the environment with antimicrobials, antimicrobial-resistant bacteria, resistance genes and plasmids. The aim of this study was to investigate the impact of the administration of colistin and of manure management on (i) the presence of colistin-resistant Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and (ii) the prevalence of various antimicrobial resistance genes in feces and in composted or stored manure. One flock of chickens was treated with colistin at the recommended dosage and a second flock was kept as an untreated control. Samples of feces, litter and stored or composted manure from both flocks were collected for isolation and determination of the colistin-susceptibility of E. coli, K. pneumoniae and P. aeruginosa and quantification of genes coding for resistance to different antimicrobials. The persistence of plasmids in stored or composted manure from colistin-treated broilers was also evaluated by plasmid capturing experiments. Results revealed that colistin administration to chickens had no apparent impact on the antimicrobial resistance of the dominant Enterobacteriaceae and P. aeruginosa populations in the chicken gut. Composting stimulated an apparently limited decrease in genes coding for resistance to different antimicrobial families. Importantly, it was shown that even after six weeks of composting or storage, plasmids carrying antimicrobial resistance genes could still be transferred to a recipient E. coli. In conclusion, composting is insufficient to completely eliminate the risk of spreading antimicrobial resistance through chicken manure. Copyright © 2015 Elsevier B.V. All rights reserved.

Reducing of internal resistance lithium ion battery using glucose addition

Science.gov (United States)

Salim, Andri Pratama; Hafidlullah, Noor; Purwanto, Agus

2016-02-01

There are two indicators of battery performance, i.e : capacity and the internal resistance of battery. In this research, the affect of glucose addition to decrease the internal resistance of lithium battery was investigated. The ratio of glucose addition were varied at weight ratio 1%, 3%, and 5% and one mixtures without glucose addition. Lithium ferri phosphate (LiFePO4), polyvinylidene fluoride (PVDF), acetylene black (AB) and glucose were materials that used in this study. Both of mixtures were mixed in the vacuum mixer until became homogeneous. The slurry was coated on an aluminium foil sheet and the coated thickness was 200 µm. The performance of battery lithium was examined by Eight Channel Battery Analyzer and the Internal resistance was examined by Internal Resistance of Battery Meter. The result from all analyzer were showed that the internal resistance reduced as well as the battery capacity. The best internal resistance value is owned by mixtures with 3wt% ratio glucose addition. It has an internal resistance value about 64 miliohm.

Reducing of internal resistance lithium ion battery using glucose addition

International Nuclear Information System (INIS)

Salim, Andri Pratama; Hafidlullah, Noor; Purwanto, Agus

2016-01-01

There are two indicators of battery performance, i.e : capacity and the internal resistance of battery. In this research, the affect of glucose addition to decrease the internal resistance of lithium battery was investigated. The ratio of glucose addition were varied at weight ratio 1%, 3%, and 5% and one mixtures without glucose addition. Lithium ferri phosphate (LiFePO 4 ), polyvinylidene fluoride (PVDF), acetylene black (AB) and glucose were materials that used in this study. Both of mixtures were mixed in the vacuum mixer until became homogeneous. The slurry was coated on an aluminium foil sheet and the coated thickness was 200 µm. The performance of battery lithium was examined by Eight Channel Battery Analyzer and the Internal resistance was examined by Internal Resistance of Battery Meter. The result from all analyzer were showed that the internal resistance reduced as well as the battery capacity. The best internal resistance value is owned by mixtures with 3wt% ratio glucose addition. It has an internal resistance value about 64 miliohm

Reducing of internal resistance lithium ion battery using glucose addition

Energy Technology Data Exchange (ETDEWEB)

Salim, Andri Pratama; Hafidlullah, Noor; Purwanto, Agus, E-mail: aguspurw@gmail.com [Research Group of Battery & Advanced Material, Department of Chemical Engineering, Sebelas Maret University, Jl. Ir. Sutami 36 A Kentingan, Surakarta Indonesia 57126 (Indonesia)

2016-02-08

There are two indicators of battery performance, i.e : capacity and the internal resistance of battery. In this research, the affect of glucose addition to decrease the internal resistance of lithium battery was investigated. The ratio of glucose addition were varied at weight ratio 1%, 3%, and 5% and one mixtures without glucose addition. Lithium ferri phosphate (LiFePO{sub 4}), polyvinylidene fluoride (PVDF), acetylene black (AB) and glucose were materials that used in this study. Both of mixtures were mixed in the vacuum mixer until became homogeneous. The slurry was coated on an aluminium foil sheet and the coated thickness was 200 µm. The performance of battery lithium was examined by Eight Channel Battery Analyzer and the Internal resistance was examined by Internal Resistance of Battery Meter. The result from all analyzer were showed that the internal resistance reduced as well as the battery capacity. The best internal resistance value is owned by mixtures with 3wt% ratio glucose addition. It has an internal resistance value about 64 miliohm.

Malaria profiles and challenges in artemisinin resistance containment in Myanmar.

Science.gov (United States)

Nwe, Thet Wai; Oo, Tin; Wai, Khin Thet; Zhou, Shuisen; van Griensven, Johan; Chinnakali, Palanivel; Shah, Safieh; Thi, Aung

2017-04-25

This study examined evolving malaria profiles from January, 2010 to December, 2014 to evaluate achievements and challenges of implementing measures to prevent and control spread of artemisinin resistance in Myanmar. Using National Malaria Control Programme (NMCP) data, a cross-sectional descriptive study of 52 townships in artemisinin-resistant containment areas in Myanmar was conducted. Annual program data were analysed, and trends over time are graphically presented. In the 52 study townships populated by 8.7 million inhabitants, malaria incidence showed a decreasing trend from 10.54 per 1 000 population in 2010 to 2.53 in 2014, and malaria mortalities also decreased from 1.83 per 100 000 population in 2010 to 0.17 in 2014. The proportion of confirmed to total tested malaria cases also decreased from 6 to 1%, while identification of cases improved. All cases from all parasites species, including Plasmodium falciparum, decreased. Coverage of LLIN (long-lasting insecticidal net)/ITN (insecticide-treated mosquito nets) and indoor residual spraying (IRS) was high in targeted areas with at-risk persons, even though the total population was not covered. In addition to passive case detection (PCD), active case detection (ACD) was conducted in hard-to-reach areas and worksites where mobile migrant populations were present. ACD improved in most areas from 2012 to 2014, but continues to need to be strengthened. The findings provide useful data on the malaria situation in artemisinin-resistant initiative areas, which may be useful for the NMCP to meet its elimination goal. These profiles could contribute to better planning, implementation, and evaluation of intervention activities.

Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats.

Science.gov (United States)

Durak, Aysegul; Olgar, Yusuf; Tuncay, Erkan; Karaomerlioglu, Irem; Kayki Mutlu, Gizem; Arioglu Inan, Ebru; Altan, Vecdi Melih; Turan, Belma

2017-11-01

Mechanical activity of the heart is adversely affected in metabolic syndrome (MetS) characterized by increased body mass and marked insulin resistance. Herein, we examined the effects of high carbohydrate intake on cardiac function abnormalities by evaluating in situ heart work, heart rate, and electrocardiograms (ECGs) in rats. MetS was induced in male Wistar rats by adding 32% sucrose to drinking water for 22-24 weeks and was confirmed by insulin resistance, increased body weight, increased blood glucose and serum insulin, and increased systolic and diastolic blood pressures in addition to significant loss of left ventricular integrity and increased connective tissue around myofibrils. Analysis of in situ ECG recordings showed a markedly shortened QT interval and decreased QRS amplitude with increased heart rate. We also observed increased oxidative stress and decreased antioxidant defense characterized by decreases in serum total thiol level and attenuated paraoxonase and arylesterase activities. Our data indicate that increased heart rate and a shortened QT interval concomitant with higher left ventricular developed pressure in response to β-adrenoreceptor stimulation as a result of less cyclic AMP release could be regarded as a natural compensation mechanism in overweight rats with MetS. In addition to the persistent insulin resistance and obesity associated with MetS, one should consider the decreased heart work, increased heart rate, and shortened QT interval associated with high carbohydrate intake, which may have more deleterious effects on the mammalian heart.

Centrally administered urocortin 2 decreases gorging on high-fat diet in in both diet induced obesity-prone and -resistant rats

Science.gov (United States)

Cottone, Pietro; Sabino, Valentina; Nagy, Tim R.; Coscina, Donald V.; Levin, Barry E.; Zorrilla, Eric P.

2013-01-01

Objective Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to play a role in obesity risk. The present study tested the hypothesis that i) the microstructure of chronic high-fat diet intake differs between genetically selected Diet-Induced Obesity (DIO) and Diet Resistant (DR) rats, and ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 (CRF2) agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. Design Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 µg). Results Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 µg, suppressing high-fat diet intake by ~40% at the 3 µg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with 2/3rd less water. Conclusions Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically-prone DIO rats, which otherwise show a “gorging” meal pattern. These results open new opportunities of investigation towards treating some forms of diet-induced obesity. PMID:23478425

The causes and consequences of antibiotic resistance evolution in microbial pathogens

DEFF Research Database (Denmark)

Jochumsen, Nicholas

pleiotropy as they conferred a decreased growth rate in the absence of colistin and also rendered the colistin resistant strains susceptible towards all tested classes of β-lactams. The results suggest that colistin/β-lactam combination therapy could be used to reduce the risk of resistance evolution during......The evolution of antimicrobial resistance in bacterial pathogens is a growing global health problem that is gradually making the successful treatment of infectious diseases more difficult. Antimicrobial peptides have been proposed as promising candidates for future drug development as they retain...... activity against bacteria resistant to conventional antibiotics and because resistance evolution is expected to be unlikely since the peptides have complex modes of action due to their interaction with the bacterial membrane. The work presented in this thesis has involved studies to increase our...

Decreased distensibility of resistance vessels of the skin in type 1 (insulin-dependent) diabetic patients with microangiopathy

DEFF Research Database (Denmark)

Kastrup, J; Nørgaard, T; Parving, H H

1987-01-01

The distensibility of the resistance vessels of the skin at the dorsum of the foot was determined in 11 long-term type 1 (insulin-dependent) diabetic patients with nephropathy and retinopathy, nine short-term type 1 diabetic patients without clinical microangiopathy and in nine healthy non-diabetic...... during head-up tilt was only 24% in diabetic subjects with and 48% in diabetic patients without clinical microangiopathy, compared with 79% in normal non-diabetic subjects (P less than 0.0005 and P less than 0.05, respectively). An inverse correlation between microvascular distensibility and degree...

Radiation resistance of ethylene-styrene copolymers

International Nuclear Information System (INIS)

Matsumoto, Kaoru; Ikeda, Masaaki; Ohki, Yoshimichi; Kusama, Yasuo; Harashige, Masahiro; Yazaki, Fumihiko.

1988-01-01

In this paper, the radiation resistance of ethylene-styrene copolymer, a polymeric resin developed newly by the authors, is reported. Resin examined were five kinds of ethylene-styrene copolymers: three random and two graft copolymers with different styrene contents. Low-density polyethylene was used as a reference. The samples were irradiated by 60 Co γ-rays to total absorbed doses up to 10 MGy. The mechanical properties of the smaples were examined. Infrared spectroscopy, differential scanning calorimetry and X-ray scattering techniques were used to examine the morphology of the samples. The random copolymers are soft and easy to extend, because benzene rings which exisist highly at random hinder the crystallization. As for the radiation resistance, they are highly resistant to γ-rays in the aspects of carbonyl group formation, gel formation, and elongation. Further, they show even better radiation resistance when proper additives were compounded in. The graft copolymers are hard to extend, because they consist of segregated polystyrene and polyethylene regions which are connected with each other. The tensile strength of irradiated graft copolymers does not decrease below that of unirradiated copolymers, up to a total dose of 10 MGy. As a consequence, it can be said that ethylene-styrene copolymers have good radiation resistance owing to the so-called 'sponge' effect of benzene rings. (author)

Electrical Resistance Tomography to monitor vadose water movement

International Nuclear Information System (INIS)

Ramirez, A.; Daily, W.; LaBrecque, D.

1991-01-01

We report results of one test in which Electrical Resistance Tomography (ERT) was used to map the changes in electrical resistivity in the vadose zone as a function of time while water infiltration occurred. The ERT images were used to infer shape and movement of the infiltration plume in the unsaturated soil. We supplied a continuous water source at a point about 10 feet below the surface (at the end of a shallow screened hole) for only a short time--2.5 hours. This pulsed source introduced a open-quote slug close-quote of water whose infiltration was followed to about 60 foot depth during a 23 hour period. The ERT images show resistivity decreases as the water content of the vadose zone increased while water was added to the soil; the resistivity of the soil later increased after the supply of water was cut-off and the induced soil moisture began to subside

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats.

Science.gov (United States)

Potikanond, Saranyapin; Rattanachote, Pinyada; Pintana, Hiranya; Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Chattipakorn, Nipon; Chattipakorn, Siriporn

2016-02-01

The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, n=12) or a sham operation (S, n=12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats. © 2016 Society for Endocrinology.

Electrical resistivity anomaly observed in and around the epicentral area prior to the T'angshan Earthquake of 1976

Energy Technology Data Exchange (ETDEWEB)

Chao, Y L; Ch' ien, F Y

1978-07-01

Before the T'angshan earthquake, magnitude 7.8 on 28 July 1976, 9 of the 14 resistivity stations located within the region of Peking, Tientsin, and T'angshan recorded gradual decreases in apparent electrical resistivity for a period of 2 to 3 years. The anomalous region as deduced from the records of these nine stations has a semimajor axis of about 150 km surrounding the epicenter, and yet two of the stations located very close to the epicenter recorded rapidly decreasing apparent resistivity anomaly during a period of more than two months immediately before the earthquake. From results of some field measurements in situ of the apparent resistivity-decrease due to compression of rock or soil layers near the earth's surface, the linear compressional strain of shallow layers in and around the epicentral area was estimated to be about 3 x 10/sup -5/. Compressional strain of much the same order of magnitude was observed by base line survey before the T'angshan earthquake.

Consumption of resistant starch decreases postprandial lipogenesis in white adipose tissue of the rat

Directory of Open Access Journals (Sweden)

Brown Marc A

2006-09-01

Full Text Available Abstract Chronic consumption of diets high in resistant starch (RS leads to reduced fat cell size compared to diets high in digestible starch (DS in rats and increases total and meal fat oxidation in humans. The aim of the present study was to examine the rate of lipogenesis in key lipogenic organs following a high RS or DS meal. Following an overnight fast, male Wistar rats ingested a meal with an RS content of 2% or 30% of total carbohydrate and were then administered an i.p bolus of 50 μCi 3H2O either immediately or 1 hour post-meal. One hour following tracer administration, rats were sacrificed, a blood sample collected, and the liver, white adipose tissue (WAT, and gastrocnemius muscle excised and frozen until assayed for total 3H-lipid and 3H-glycogen content. Plasma triglyceride and NEFA concentrations and 3H-glycogen content did not differ between groups. In all tissues, except the liver, there was a trend for the rate of lipogenesis to be higher in the DS group than the RS group which reached significance only in WAT at 1 h (p

Reduction in mRNA and protein expression of a nicotinic acetylcholine receptor α8 subunit is associated with resistance to imidacloprid in the brown planthopper, Nilaparvata lugens.

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Zhang, Yixi; Wang, Xin; Yang, Baojun; Hu, Yuanyuan; Huang, Lixin; Bass, Chris; Liu, Zewen

2015-11-01

Target-site resistance is commonly caused by qualitative changes in insecticide target-receptors and few studies have implicated quantitative changes in insecticide targets in resistance. Here we show that resistance to imidacloprid in a selected strain of Nilaparvata lugens is associated with a reduction in expression levels of the nicotinic acetylcholine receptor (nAChR) subunit Nlα8. Synergism bioassays of the selected strain suggested resistance was conferred, in part, by a target-site mechanism. Sequencing of N. lugens nAChR subunit genes identified no mutations associated with resistance, however, a decrease in mRNA and protein levels of Nlα8 was observed during selection. RNA interference knockdown of Nlα8 decreased the sensitivity of N. lugens to imidacloprid, demonstrating that a decrease in Nlα8 expression is sufficient to confer resistance in vivo. Radioligand binding assays revealed that the affinity of the high-affinity imidacloprid-binding site of native nAChRs was reduced by selection, and reducing the amount of Nlα8 cRNA injected into Xenopus oocytes significantly decreased imidacloprid potency on recombinant receptors. Taken together, these results provide strong evidence that a decrease in Nlα8 levels confers resistance to imidacloprid in N. lugens, and thus provides a rare example of target-site resistance associated with a quantitative rather than qualitative change. In insects, target-site mutations often cause high resistance to insecticides, such as neonicotinoids acting on nicotinic acetylcholine receptors (nAChRs). Here we found that a quantitative change in target-protein level, decrease in mRNA and protein levels of Nlα8, contributed importantly to imidacloprid resistance in Nilaparvata lugens. This finding provides a new target-site mechanism of insecticide resistance. © 2015 International Society for Neurochemistry.

Evaluation of the corrosion resistance of an epoxy-polyamide coating containing different ratios of micaceous iron oxide/Al pigments

International Nuclear Information System (INIS)

Nikravesh, B.; Ramezanzadeh, B.; Sarabi, A.A.; Kasiriha, S.M.

2011-01-01

Research highlights: → The corrosion resistance of the coating was improved using MIO and Al pigments. → The greatest coating corrosion resistance was observed at MIO/Al ratio of 10/90. → The cathodic disbonded area of the coating was decreased using MIO and Al particles. → The lowest disbonded area was observed at MIO/Al ratio of 10/90. → Al particles had high capability of reacting with the OH - ions. - Abstract: The corrosion resistance of an epoxy coating reinforced with different ratios of MIO/Al pigments was studied. The coatings properties were investigated by an electrochemical impedance spectroscopy (EIS), salt spray test, cathodic disbonding and a scanning electron microscope (SEM). The corrosion resistance of the epoxy coating was improved using MIO (micaceous iron oxide) and Al pigments. The corrosion resistance of the purely Al pigmented coating was considerably greater than the purely MIO pigmented coating. The cathodic disbonded area of coating was decreased using MIO and Al pigments. The decrease in disbonded area was more pronounced in the presence of Al particles.

Individual’s Resistance Regarding BPM Initiative: Case Study of the Insurance Company

Directory of Open Access Journals (Sweden)

Pejić Bach Mirjana

2017-12-01

Full Text Available Though the individual’s resistance is very often considered a significant barrier to BPM success, the literature on that topic is quite scarce. With the aim to shed light on this topic, we have conducted research of a Croatian insurance company. We examined the impact of individual’s resistance regarding BPM initiative using the theory of reasoned action. Structural equation model was developed using the data collected by the survey among company employees. The results indicate that subjective norms are positively related to the individual’s resistance regarding BPM initiative, while positive initial belief regarding BPM initiative tends to decrease the probability of resistance to change.

Physics of lumen growth.

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Dasgupta, Sabyasachi; Gupta, Kapish; Zhang, Yue; Viasnoff, Virgile; Prost, Jacques

2018-05-22

We model the dynamics of formation of intercellular secretory lumens. Using conservation laws, we quantitatively study the balance between paracellular leaks and the build-up of osmotic pressure in the lumen. Our model predicts a critical pumping threshold to expand stable lumens. Consistently with experimental observations in bile canaliculi, the model also describes a transition between a monotonous and oscillatory regime during luminogenesis as a function of ion and water transport parameters. We finally discuss the possible importance of regulation of paracellular leaks in intercellular tubulogenesis.

Effects of photovoltaic module soiling on glass surface resistance and potential-induced degradation

DEFF Research Database (Denmark)

Hacke, Peter; Burton, Patrick; Hendrickson, Alexander

2015-01-01

The sheet resistance of three soil types (Arizona road dust, soot, and sea salt) on glass were measured by the transmission line method as a function of relative humidity (RH) between 39% and 95% at 60°C. Sea salt yielded a 3.5 orders of magnitude decrease in resistance on the glass surface when ...

The study on corrosion resistance of decorative satin nickel plating

OpenAIRE

LU Wenya; CHENG Xianhua

2012-01-01

This study examined the corrosion resistance of satin nickel plating on conductive plastic.The electrochemical tests were to analyze the corrosion behavior of satin nickel plating with different processes in 3.5% NaCl solution.The results show that,because the satin nickel plating has an organic film on its surface due to process characteristics,the film results in different corrosion resistance.By increasing satin additive dosage,the nickel plating chroma decreases,the microsurface of the p...

Influence of regular reporting on local Pseudomonas aeruginosa and Acinetobacter spp. sensitivity to antibiotics on consumption of antibiotics and resistance patterns.

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Djordjevic, Z M; Folic, M M; Jankovic, S M

2017-10-01

Regular surveillance of antimicrobial resistance is an important component of multifaceted interventions directed at the problem with resistance of bacteria causing healthcare-associated infections (HAIs) in intensive care units (ICUs). Our aim was to analyse antimicrobial consumption and resistance among isolates of Pseudomonas aeruginosa and Acinetobacter spp. causing HAIs, before and after the introduction of mandatory reporting of resistance patterns to prescribers. A retrospective observational study was conducted between January 2011 and December 2015, at an interdisciplinary ICU of the Clinical Centre Kragujevac, Serbia. The intervention consisted of continuous resistance monitoring of all bacterial isolates from ICU patients and biannual reporting of results per isolate to prescribers across the hospital. Both utilization of antibiotics and density of resistant isolates of P. aeruginosa and Acinetobacter spp. were followed within the ICU. Resistance densities of P. aeruginosa to all tested antimicrobials were lower in 2015, in comparison with 2011. Although isolates of Acinetobacter spp. had lower resistance density in 2015 than in 2011 to the majority of investigated antibiotics, a statistically significant decrease was noted only for piperacillin/tazobactam. Statistically significant decreasing trends of consumption were recorded for third-generation cephalosporins, aminoglycosides and fluoroquinolones, whereas for the piperacillin/tazobactam, ampicillin/sulbactam and carbapenems, utilization trends were decreasing, but without statistical significance. In the same period, increasing trends of consumption were observed for tigecycline and colistin. Regular monitoring of resistance of bacterial isolates in ICUs and reporting of summary results to prescribers may lead to a significant decrease in utilization of some antibiotics and slow restoration of P. aeruginosa and Acinetobacter spp. susceptibility. © 2017 John Wiley & Sons Ltd.

Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

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Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

2011-11-01

The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

Bacterial mediated alleviation of heavy metal stress and decreased accumulation of metals in plant tissues: Mechanisms and future prospects.

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Etesami, Hassan

2018-01-01

Heavy metal pollution of agricultural soils is one of main concerns causing some of the different ecological and environmental problems. Excess accumulation of these metals in soil has changed microbial community (e.g., structure, function, and diversity), deteriorated soil, decreased the growth and yield of plant, and entered into the food chain. Plants' tolerance to heavy metal stress needs to be improved in order to allow growth of crops with minimum or no accumulation of heavy metals in edible parts of plant that satisfy safe food demands for the world's rapidly increasing population. It is well known that PGPRs (plant growth-promoting rhizobacteria) enhance crop productivity and plant resistance to heavy metal stress. Many recent reports describe the application of heavy metal resistant-PGPRs to enhance agricultural yields without accumulation of metal in plant tissues. This review provides information about the mechanisms possessed by heavy metal resistant-PGPRs that ameliorate heavy metal stress to plants and decrease the accumulation of these metals in plant, and finally gives some perspectives for research on these bacteria in agriculture in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Insulin Resistance of Puberty.

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Kelsey, Megan M; Zeitler, Philip S

2016-07-01

Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity.

Radiation resistance and molecular structure of poly(arylene ether sulphone)s

International Nuclear Information System (INIS)

Hill, D.J.T.; Lewis, D.A.; O'Donnell, J.H.; Pomery, P.J.; Hedrick, J.L.; McGrath, J.E.

1991-01-01

The radiation resistance of a series of aromatic polysulfones comprising alternating units of diphenyl sulfone and various aromatic diols has been investigated by measuring volatile products, soluble fractions and electron spin resonance (ESR) spectra. The yields of radicals at 77 K observed by ESR and of SO 2 at 423 K have indicated that biphenol gives enhanced resistance to γ radiation, and tetramethyl bisphenol-A decreased resistance, relative to bisphenol-A, bisphenol-S and hydroquinone. The protective effect of biphenol was confirmed by lower scission and crosslinking yields determined from the soluble fractions after high doses. (author)

Multi-polar resistance switching and memory effect in copper phthalocyanine junctions

International Nuclear Information System (INIS)

Qiao Shi-Zhu; Kang Shi-Shou; Li Qiang; Zhong Hai; Kang Yun; Yu Shu-Yun; Han Guang-Bing; Yan Shi-Shen; Mei Liang-Mo; Qin Yu-Feng

2014-01-01

Copper phthalocyanine junctions, fabricated by magnetron sputtering and evaporating methods, show multi-polar (unipolar and bipolar) resistance switching and the memory effect. The multi-polar resistance switching has not been observed simultaneously in one organic material before. With both electrodes being cobalt, the unipolar resistance switching is universal. The high resistance state is switched to the low resistance state when the bias reaches the set voltage. Generally, the set voltage increases with the thickness of copper phthalocyanine and decreases with increasing dwell time of bias. Moreover, the low resistance state could be switched to the high resistance state by absorbing the phonon energy. The stability of the low resistance state could be tuned by different electrodes. In Au/copper phthalocyanine/Co system, the low resistance state is far more stable, and the bipolar resistance switching is found. Temperature dependence of electrical transport measurements demonstrates that there are no obvious differences in the electrical transport mechanism before and after the resistance switching. They fit quite well with Mott variable range hopping theory. The effect of Al 2 O 3 on the resistance switching is excluded by control experiments. The holes trapping and detrapping in copper phthalocyanine layer are responsible for the resistance switching, and the interfacial effect between electrodes and copper phthalocyanine layer affects the memory effect. (interdisciplinary physics and related areas of science and technology)

Is pulmonary resistance constant, within the range of tidal volume ventilation, in patients with ARDS?

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Mols, G; Kessler, V; Benzing, A; Lichtwarck-Aschoff, M; Geiger, K; Guttmann, J

2001-02-01

When managing patients with acute respiratory distress syndrome (ARDS), respiratory system compliance is usually considered first and changes in resistance, although recognized, are neglected. Resistance can change considerably between minimum and maximum lung volume, but is generally assumed to be constant in the tidal volume range (V(T)). We measured resistance during tidal ventilation in 16 patients with ARDS or acute lung injury by the slice method and multiple linear regression analysis. Resistance was constant within V(T) in only six of 16 patients. In the remaining patients, resistance decreased, increased or showed complex changes. We conclude that resistance within V(T) varies considerably from patient to patient and that constant resistance within V(T) is not always likely.

A novel resistance gene, lnu(H), conferring resistance to lincosamides in Riemerella anatipestifer CH-2.

Science.gov (United States)

Luo, Hong-Yan; Liu, Ma-Feng; Wang, Ming-Shu; Zhao, Xin-Xin; Jia, Ren-Yong; Chen, Shun; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Chen, Xiao-Yue; Biville, Francis; Zou, Yuan-Feng; Jing, Bo; Cheng, An-Chun; Zhu, De-Kang

2018-01-01

The Gram-negative bacterium Riemerella anatipestifer CH-2 is resistant to lincosamides, having a lincomycin (LCM) minimum inhibitory concentration (MIC) of 128 µg/mL. The G148_1775 gene of R. anatipestifer CH-2, designated lnu(H), encodes a 260-amino acid protein with ≤41% identity to other reported lincosamide nucleotidylyltransferases. Escherichia coli Rosetta TM (DE3) containing the pBAD24-lnu(H) plasmid showed four- and two-fold increases in the MICs of LCM and clindamycin (CLI), respectively. A kinetic assay of the purified Lnu(H) enzyme for LCM and CLI showed that the protein could inactive lincosamides. Mass spectrometry analysis demonstrated that the Lnu(H) enzyme catalysed adenylylation of lincosamides. In addition, an lnu(H) gene deletion strain exhibited 512- and 32-fold decreases in LCM and CLI MICs, respectively. The wild-type level of lincosamide resistance could be restored by complementation with a shuttle plasmid carrying the lnu(H) gene. The transformant R. anatipestifer ATCC 11845 [lnu(H)] acquired by natural transformation also exhibited high-level lincosamide resistance. Moreover, among 175 R. anatipestifer field isolates, 56 (32.0%) were positive for the lnu(H) gene by PCR. In conclusion, Lnu(H) is a novel lincosamide nucleotidylyltransferase that inactivates LCM and CLI by nucleotidylylation, thus conferring high-level lincosamide resistance to R. anatipestifer CH-2. Copyright © 2017. Published by Elsevier B.V.

Effects of endotoxin on mammary secretion of lactating cows

International Nuclear Information System (INIS)

Lengemann, F.W.; Pitzrick, M.

1986-01-01

The objectives were to describe the magnitude and time course of changes in milk pH, Na, K, lactose, and somatic cells and to determine if paracellular pathways were altered after infusion of Escherichia coli endotoxin (serotype 0128:AB12) to produce inflammation in one-half of the udder of the goat. Intramammary infusion of endotoxin increased pH, number of somatic cells, and Na and decreased K and lactose in milk. Sodium and number of somatic cells were increased by as little as .1μg of endotoxin; .25 μg produced changes in most of the other parameters; maximal effect was elicited by 1μg of endotoxin. The gland response peaked from 5 to 7 h after infusion of endotoxin with an increase in milk cellularity as the only significant effect noted in the control gland. Infusion of [ 14 C]lactose into the gland and [/sup 99m/Tc]albumin into the blood demonstrated that large molecules were more able to cross into and out of udder halves after endotoxin treatment. It is suggested that ion interchange rather than bulk flow across paracellular paths is responsible for changes. In addition, endotoxin appeared to reduce lactose secretion and synthesis

[Resistance risk, cross-resistance and biochemical resistance mechanism of Laodelphax striatellus to buprofezin].

Science.gov (United States)

Mao, Xu-lian; Liu, Jin; Li, Xu-ke; Chi, Jia-jia; Liu, Yong-jie

2016-01-01

In order to investigate the resistance development law and biochemical resistance mechanism of Laodelphax striatellus to buprofezin, spraying rice seedlings was used to continuously screen resistant strains of L. striatellus and dipping rice seedlings was applied to determine the toxicity and cross-resistance of L. striatellus to insecticides. After 32-generation screening with buprofezin, L. striatellus developed 168.49 folds resistance and its reality heritability (h2) was 0.11. If the killing rate was 80%-90%, L. striatellus was expected to develop 10-fold resistance to buprofezin only after 5 to 6 generations breeding. Because the actual reality heritability of field populations was usually lower than that of the resistant strains, the production of field populations increasing with 10-fold resistance would need much longer time. The results of cross-resistance showed that resistant strain had high level cross-resistance with thiamethoxam and imidacloprid, low level cross-resistance with acetamiprid, and no cross-resistance with pymetrozine and chlorpyrifos. The activity of detoxification enzymes of different strains and the syergism of synergist were measured. The results showed that cytochrome P450 monooxygenase played a major role in the resistance of L. striatellus to buprofezin, the esterase played a minor role and the GSH-S-transferase had no effect. Therefore, L. striatellus would have high risk to develop resistance to buprofezin when used in the field and might be delayed by using pymetrozine and chlorpyrifos.

Targeting protein kinases to reverse multidrug resistance in sarcoma.

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Chen, Hua; Shen, Jacson; Choy, Edwin; Hornicek, Francis J; Duan, Zhenfeng

2016-02-01

Sarcomas are a group of cancers that arise from transformed cells of mesenchymal origin. They can be classified into over 50 subtypes, accounting for approximately 1% of adult and 15% of pediatric cancers. Wide surgical resection, radiotherapy, and chemotherapy are the most common treatments for the majority of sarcomas. Among these therapies, chemotherapy can palliate symptoms and prolong life for some sarcoma patients. However, sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multidrug resistance (MDR). MDR attenuates the efficacy of anticancer drugs and results in treatment failure for sarcomas. Therefore, overcoming MDR is an unmet need for sarcoma therapy. Certain protein kinases demonstrate aberrant expression and/or activity in sarcoma cells, which have been found to be involved in the regulation of sarcoma cell progression, such as cell cycle, apoptosis, and survival. Inhibiting these protein kinases may not only decrease the proliferation and growth of sarcoma cells, but also reverse their resistance to chemotherapeutic drugs to subsequently reduce the doses of anticancer drugs and decrease drug side-effects. The discovery of novel strategies targeting protein kinases opens a door to a new area of sarcoma research and provides insight into the mechanisms of MDR in chemotherapy. This review will focus on the recent studies in targeting protein kinase to reverse chemotherapeutic drug resistance in sarcoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanism of cisplatin resistance in human urothelial carcinoma cells.

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Yu, Hui-Min; Wang, Tsing-Cheng

2012-05-01

An isogenic pair of cisplatin-susceptible (NTUB1) and -resistant (NTUB1/P) human urothelial carcinoma cell lines was used to elucidate the mechanism of cisplatin resistance. The significantly lower intracellular platinum (IP) concentration, which resulted from the decreased cisplatin uptake, was found in NTUB1/P cells. The enhancement of IP concentration did not increase the susceptibility of NTUB1/P cells to cisplatin treatment. The reduction of IP concentration as well was unable to enhance the cisplatin-resistance in susceptible NTUB1 cells. This indicated that reduction of IP concentration was not the account for the development of cisplatin resistance here. Instead, the over expression of anti-apoptotic Bcl-2, anti-oxidative heme oxygenase-1 (HO-1) and cell cycle regulator p16INK4 seemed to be more important for the gaining of cisplatin in these human urothelial carcinoma cell. Copyright © 2012 Elsevier Ltd. All rights reserved.

Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs) with different waste load

DEFF Research Database (Denmark)

Laht, Mailis; Karkman, Antti; Voolaid, Veiko

2014-01-01

Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs), an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs) were quantified using qPCR in three WWTPs of decreasing capacity located...... abundances with 16S rRNA gene abundances while assessing if the respective genes increased or decreased during treatment. ARGs were detected in most samples; sul1, sul2, and tetM were detected in all samples. Statistically significant differences (adjusted p... in the relative abundance of resistance genes, while the raw abundances fell by several orders of magnitude. Standard water quality variables (biological oxygen demand, total phosphorus and nitrogen, etc.) were weakly related or unrelated to the relative abundance of resistance genes. Based on our results we...

A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance

DEFF Research Database (Denmark)

Kristensen, Jonas Møller; Skov, Vibe; Petersson, Stine Juhl

2014-01-01

Insulin resistance in obesity and type 2 diabetes is related to abnormalities in mitochondrial oxidative phosphorylation (OxPhos) in skeletal muscle. We tested the hypothesis that mitochondrial oxidative metabolism is impaired in muscle of patients with inherited insulin resistance and defective...

Resistant starch and energy balance: impact on weight loss and maintenance.

Science.gov (United States)

Higgins, Janine A

2014-01-01

The obesity epidemic has prompted researchers to find effective weight-loss and maintenance tools. Weight loss and subsequent maintenance are reliant on energy balance--the net difference between energy intake and energy expenditure. Negative energy balance, lower intake than expenditure, results in weight loss whereas positive energy balance, greater intake than expenditure, results in weight gain. Resistant starch has many attributes, which could promote weight loss and/or maintenance including reduced postprandial insulinemia, increased release of gut satiety peptides, increased fat oxidation, lower fat storage in adipocytes, and preservation of lean body mass. Retention of lean body mass during weight loss or maintenance would prevent the decrease in basal metabolic rate and, therefore, the decrease in total energy expenditure, that occurs with weight loss. In addition, the fiber-like properties of resistant starch may increase the thermic effect of food, thereby increasing total energy expenditure. Due to its ability to increase fat oxidation and reduce fat storage in adipocytes, resistant starch has recently been promoted in the popular press as a "weight loss wonder food". This review focuses on data describing the effects of resistant starch on body weight, energy intake, energy expenditure, and body composition to determine if there is sufficient evidence to warrant these claims.

Relationship between insulin resistance and plasma endothelin in hypertension patients

International Nuclear Information System (INIS)

Duan Yongqiang; Wang Zuobing; Yu Hui; Cao Wei; Wang Jing; Li Xiaoqin

2011-01-01

To explore the relationship between plasma endothelin and hypertension insulin resistance, and the improvement of insulin resistance in hypertension patients treated with captopril and l-amlodipine, 25 patients with primary hypertension and impaired glucose tolerance were selected and treated by captopril and l-amlodipine. Systolic pressure, diastolic pressure, fasting blood glucose, insulin and insulin antibody were measured before and after treatment and compared with healthy controls. The results showed that the plasma ET-1 level in hypertension group was significantly higher than that of healthy controls (P<0.01), and he plasma ET-1 level was positively correlated with FPG, FINS, Anti-INS, HOMA-IR. The systolic pressure, diastolic pressure, fasting blood glucose, insulin, insulin antibody and insulin resistance index in hypertension patients were decreased significantly after treatment (P<0.05). There is a good correlation between endothelin and insulin resistance index in hypertension patients. Captopril and l-amlodipine had obvious improvement effect on insulin resistance in hypertension patients. (authors)

Intramuscular Lipid Metabolism in the Insulin Resistance of Smoking

OpenAIRE

Bergman, Bryan C.; Perreault, Leigh; Hunerdosse, Devon M.; Koehler, Mary C.; Samek, Ali M.; Eckel, Robert H.

2009-01-01

OBJECTIVE Smoking decreases insulin action and increases the risk of type 2 diabetes in humans. Mechanisms responsible for smoking-induced insulin resistance are unclear. We hypothesized smokers would have increased intramuscular triglyceride (IMTG) and diacylglycerol (DAG) concentration and decreased fractional synthesis rate (FSR) compared with nonsmokers. RESEARCH DESIGN AND METHODS Nonsmokers (n = 18, aged 20 ± 0.5 years, BMI 22 ± 0.4 kg/m2, body fat 20 ± 2%, 0 cigarettes per day) and smo...

Poverty and prevalence of antimicrobial resistance in invasive isolates.

Science.gov (United States)

Alvarez-Uria, Gerardo; Gandra, Sumanth; Laxminarayan, Ramanan

2016-11-01

To evaluate the association between the income status of a country and the prevalence of antimicrobial resistance (AMR) in the three most common bacteria causing infections in hospitals and in the community: third-generation cephalosporin (3GC)-resistant Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), and 3GC-resistant Klebsiella species. Using 2013-2014 country-specific data from the ResistanceMap repository and the World Bank, the association between the prevalence of AMR in invasive samples and the gross national income (GNI) per capita was investigated through linear regression with robust standard errors. To account for non-linear association with the dependent variable, GNI per capita was log-transformed. The models predicted an 11.3% (95% confidence interval (CI) 6.5-16.2%), 18.2% (95% CI 11-25.5%), and 12.3% (95% CI 5.5-19.1%) decrease in the prevalence of 3GC-resistant E. coli, 3GC-resistant Klebsiella species, and MRSA, respectively, for each log GNI per capita. The association was stronger for 3GC-resistant E. coli and Klebsiella species than for MRSA. A significant negative association between GNI per capita and the prevalence of MRSA and 3GC-resistant E. coli and Klebsiella species was found. These results underscore the urgent need for new policies aimed at reducing AMR in resource-poor settings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Analysis of drug resistance in 1,861 strains of Acinetobacter baumannii.

Science.gov (United States)

Jin, Hao; Qiu, Fan; Ji, Hong Jian; Lu, Qiang

2016-04-01

Acinetobacter baumannii is an emerging human pathogen that causes hospital-acquired infections. The trend in increased antimicrobial resistance limits the choice of effective antimicrobial agents. The present study reports the resistance to Acinetobacter baumannii and analyzes the associations between antibiotic use and resistance rates at a general hospital between 2010 and 2014. A total of 1,861 isolates were obtained from clinical cultures, accounting for 10.33% of all detected bacteria (1,861/18,016). The strains were mainly from respiratory samples (1,628 isolates, 87.5%) and the intensive care unit (696 isolates, 37.4%). The resistance rates of Acinetobacter baumannii to the majority of antibiotics were >50%, particularly the resistance rate to cefoperazone/sulbactam increased from 47.37 in 2011 to 89.25% in 2014. However, the rates of imipenem and cilastatin sodium decreased from 81.03 to 69.44% due to the antibiotic policy. There were Pearson significant associations between the use of three antibiotics and resistance in Acinetobacter baumannii to this drug, piperacillin/tazobactam (r=0.976, Ppolicies are essential to control the emergence of multidrug-resistance Acinetobacter baumannii .

Control of multidrug resistant bacteria in a tertiary care hospital in India

Directory of Open Access Journals (Sweden)

Jaggi Namita

2012-06-01

Full Text Available Abstract Background The objective of this study was to assess the impact of antimicrobial stewardship programs on the multidrug resistance patterns of bacterial isolates. The study comprised an initial retrospective analysis of multidrug resistance in bacterial isolates for one year (July 2007-June 2008 followed by prospective evaluation of the impact of Antimicrobial Stewardship programs on resistance for two years and nine months (July 2008-March 2011. Setting A 300-bed tertiary care private hospital in Gurgaon, Haryana (India Findings Methods Study Design • July 2007 to June 2008: Resistance patterns of bacterial isolates were studied. • July 2008: Phase I intervention programme Implementation of an antibiotic policy in the hospital. • July 2008 to June 2010: Assessment of the impact of the Phase I intervention programme. • July 2010 to March 2011: Phase II intervention programme: Formation and effective functioning of the antimicrobial stewardship committee. Statistical correlation of the Defined daily dose (DDD for prescribed drugs with the antimicrobial resistance of Gram negatives. Results Phase I intervention programme (July 2008 resulted in a decrease of 4.47% in ESBLs (E.coli and Klebsiella and a significant decrease of 40.8% in carbapenem-resistant Pseudomonas. Phase II intervention (July 2010 brought a significant reduction (24.7% in carbapenem-resistant Pseudomonas. However, the resistance in the other Gram negatives (E.coli, Klebsiella, and Acinetobacter rose and then stabilized. A positive correlation was observed in Pseudomonas and Acinetobacter with carbapenems and cefoperazone-sulbactam. Piperacillin-tazobactam showed a positive correlation with Acinetobacter only. E.coli and Klebsiella showed positive correlation with cefoparazone-sulbactam and piperacillin-tazobactam. Conclusion An antimicrobial stewardship programme with sustained and multifaceted efforts is essential to promote the judicious use of antibiotics.

Spironolactone and doxazosin treatment in patients with resistant hypertension.

Science.gov (United States)

Rodilla, Enrique; Costa, José A; Pérez-Lahiguera, Francisco; Baldó, Emilio; González, Carmen; Pascual, José M

2009-02-01

The aim of this study was to evaluate the use of spironolactone and doxazosin as treatment for patients with resistant hypertension. This retrospective study involved 181 outpatients with resistant hypertension (defined as a failure of blood pressure [BP] control despite treatment with three drugs, one of which was a diuretic) who received additional spironolactone (n=88) or doxazosin (n=93). Mean systolic BP in the spironolactone group fell by 28 mmHg (95% confidence interval [CI], 24-32 mmHg; P< .001) and mean diastolic BP fell by 12 mmHg (95% CI, 9-14 mmHg; P< .001). The corresponding falls in the doxazosin group were 16 mmHg (95% CI, 13-20 mmHg; P< .001) and 7 mmHg (95% CI, 5-9 mmHg; P< .001), respectively. The decrease was significantly greater with spironolactone for both systolic (P< .001) and diastolic (P=.003) pressures. At the end of follow-up, 30% of all patients had achieved BP control, with control being more frequent with spironolactone (39%) than doxazosin (23%; P=.02). Multivariate logistic regression analysis showed that the only factors that significantly influenced the achievement of BP control were diabetes (odds ratio=0.17; 95% CI, 0.08-0.39; P< .001) and baseline systolic BP <165 mmHg (odds ratio=2.56; 95% CI, 1.11-5.90; P=.03). In patients with resistant hypertension, the addition of either spironolactone or doxazosin resulted in a significant decrease in BP, though the decrease appeared to be greater with spironolactone. The presence of diabetes complicated BP control.

Investigation of Concrete Electrical Resistivity As a Performance Based Test

OpenAIRE

Malakooti, Amir

2017-01-01

The purpose of this research project was to identify the extent that concrete resistivity measurements (bulk and/or surface) can be used as a performance based lab test to improve the quality of concrete in Utah bridge decks. By allowing UDOT to specify a required resistivity, concrete bridge deck quality will increase and future maintenance costs will decrease. This research consisted of two phases: the field phase and the lab phase. In the field phase, concrete samples were gathered from...

Identification of glycan structure alterations on cell membrane proteins in desoxyepothilone B resistant leukemia cells.

Science.gov (United States)

Nakano, Miyako; Saldanha, Rohit; Göbel, Anja; Kavallaris, Maria; Packer, Nicolle H

2011-11-01

Resistance to tubulin-binding agents used in cancer is often multifactorial and can include changes in drug accumulation and modified expression of tubulin isotypes. Glycans on cell membrane proteins play important roles in many cellular processes such as recognition and apoptosis, and this study investigated whether changes to the glycan structures on cell membrane proteins occur when cells become resistant to drugs. Specifically, we investigated the alteration of glycan structures on the cell membrane proteins of human T-cell acute lymphoblastic leukemia (CEM) cells that were selected for resistance to desoxyepothilone B (CEM/dEpoB). The glycan profile of the cell membrane glycoproteins was obtained by sequential release of N- and O-glycans from cell membrane fraction dotted onto polyvinylidene difluoride membrane with PNGase F and β-elimination respectively. The released glycan alditols were analyzed by liquid chromatography (graphitized carbon)-electrospray ionization tandem MS. The major N-glycan on CEM cell was the core fucosylated α2-6 monosialo-biantennary structure. Resistant CEM/dEpoB cells had a significant decrease of α2-6 linked sialic acid on N-glycans. The lower α2-6 sialylation was caused by a decrease in activity of β-galactoside α2-6 sialyltransferase (ST6Gal), and decreased expression of the mRNA. It is clear that the membrane glycosylation of leukemia cells changes during acquired resistance to dEpoB drugs and that this change occurs globally on all cell membrane glycoproteins. This is the first identification of a specific glycan modification on the surface of drug resistant cells and the mechanism of this downstream effect on microtubule targeting drugs may offer a route to new interventions to overcome drug resistance.

Home-based exercise may not decrease the insulin resistance in individuals with metabolic syndrome.

Science.gov (United States)

Chen, Chiao-Nan; Chuang, Lee-Ming; Korivi, Mallikarjuna; Wu, Ying-Tai

2015-01-01

This study investigated the differences in exercise self-efficacy, compliance, and effectiveness of home-based exercise in individuals with and without metabolic syndrome (MetS). One hundred and ten individuals at risk for diabetes participated in this study. Subjects were categorized into individuals with MetS and individuals without MetS. Metabolic risk factors and exercise self-efficacy were evaluated for all subjects before and after 3 months of home-based exercise. Univariate analysis of variance was used to compare the effectiveness of a home-based exercise program between individuals with and without MetS. The home-based exercise program improved body mass index and lipid profile in individuals at risk for diabetes, regardless of MetS status at baseline. Individuals without MetS had higher exercise self-efficacy at baseline and performed greater exercise volume compared with individuals with MetS during the intervention. The increased exercise volume in individuals without MetS may contribute to their better control of insulin resistance than individuals with MetS. Furthermore, baseline exercise self-efficacy was correlated with exercise volume executed by subjects at home. We conclude that home-based exercise programs are beneficial for individuals at risk for diabetes. However, more intensive and/or supervised exercise intervention may be needed for those with MetS.

Selective insulin resistance in hepatocyte senescence

International Nuclear Information System (INIS)

Aravinthan, Aloysious; Challis, Benjamin; Shannon, Nicholas; Hoare, Matthew; Heaney, Judith; Alexander, Graeme J.M.

2015-01-01

Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance

Selective insulin resistance in hepatocyte senescence

Energy Technology Data Exchange (ETDEWEB)

Aravinthan, Aloysious [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Challis, Benjamin [Institute of Metabolic Sciences, University of Cambridge, Cambridge (United Kingdom); Shannon, Nicholas [Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Hoare, Matthew [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Heaney, Judith [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Foundation for Liver Research, Institute of Hepatology, London (United Kingdom); Alexander, Graeme J.M., E-mail: gja1000@doctors.org.uk [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom)

2015-02-01

Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance.

Resistance to Change of Responding Maintained by Unsignaled Delays to Reinforcement: A Response-Bout Analysis

Science.gov (United States)

Podlesnik, Christopher A.; Jimenez-Gomez, Corina; Ward, Ryan D.; Shahan, Timothy A.

2006-01-01

Previous experiments have shown that unsignaled delayed reinforcement decreases response rates and resistance to change. However, the effects of different delays to reinforcement on underlying response structure have not been investigated in conjunction with tests of resistance to change. In the present experiment, pigeons responded on a…

Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

Science.gov (United States)

Tugizov, Sharof

2016-01-01

Abstract Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

Antimicrobial Resistance Risks of Cholera Prophylaxis for United Nations Peacekeepers.

Science.gov (United States)

Kunkel, Amber; Lewnard, Joseph A; Pitzer, Virginia E; Cohen, Ted

2017-08-01

More than 5 years after a United Nations peacekeeping battalion introduced cholera to Haiti, over 150,000 peacekeepers continue to be deployed annually from countries where cholera is endemic. The United Nations has thus far declined to provide antimicrobial chemoprophylaxis to peacekeepers, a policy based largely on concerns that the risks of drug resistance generation and spread would outweigh the potential benefits of preventing future cholera importations. In this study, we sought to better understand the relative benefits and risks of cholera chemoprophylaxis for peacekeepers in terms of antibiotic resistance. Using a stochastic model to quantify the potential impact of chemoprophylaxis on importation and transmission of drug-resistant and drug-sensitive Vibrio cholerae , we found that chemoprophylaxis would decrease the probability of cholera importation but would increase the expected number of drug-resistant infections if an importation event were to occur. Despite this potential increase, we found that at least 10 drug-sensitive infections would likely be averted per excess drug-resistant infection under a wide range of assumptions about the underlying prevalence of drug resistance and risk of acquired resistance. Given these findings, policymakers should reconsider whether the potential resistance risks of providing antimicrobial chemoprophylaxis to peacekeepers are sufficient to outweigh the anticipated benefits. Copyright © 2017 American Society for Microbiology.

Lack of cross-resistance to fostriecin in a human small-cell lung carcinoma cell line showing topoisomerase II-related drug resistance

NARCIS (Netherlands)

de Jong, Steven; Zijlstra, J G; Mulder, Nanno; de Vries, Liesbeth

1991-01-01

Cells exhibiting decreased topoisomerase II (Topo II) activity are resistant to several drugs that require Topo II as an intermediate. These drugs are cytotoxic due to the formation of a cleavable complex between the drug, Topo II and DNA. Fostriecin belongs to a new class of drugs that inhibit Topo

Global transcriptional response of methicillin-resistant Staphylococcus aureus to thioridazine

DEFF Research Database (Denmark)

Bonde, Mette; Jacobsen, Kirstine; Kolmos, Hans Jørn

Few drugs are available against methicillin-resistant S. aureus (MRSA), and decreased susceptibility among staphylococci to newly introduced agents such as linezolid, daptomycin, and tigecycline has been observed [1-3]. Consequently, new treatment strategies are urgently needed. Thioridazine...

Selective breeding for scrapie resistance in sheep

Directory of Open Access Journals (Sweden)

Cristina Santos Sotomaior

2012-11-01

Full Text Available It is well known that the susceptibility of sheep to scrapie is determined by the host’s prion protein gene (PRNP. PRNP polymorphisms at codons 136 (alanine, A/valine, V, 154 (histidine, H/arginine, R and 171 (glutamine, Q/histidine, H/arginine, R are the main determinants of sheep susceptibility/resistance to classical scrapie. There are four major variants of the wild-type ARQ allele: VRQ, AHQ, ARH and ARR. Breeding programs have been developed in the European Union and the USA to increase the frequency of the resistant ARR allele while decreasing the frequency of the susceptible VRQ allele in sheep populations. In Brazil, little PRNP genotyping data are available for sheep, and thus far, no controlled breeding scheme for scrapie has been implemented. This review will focus on important epidemiological aspects of scrapie and the use of genetic resistance as a tool in breeding programs to control the disease.

Antimicrobial growth promoter ban and resistance to macrolides and vancomycin in enterococci from pigs

DEFF Research Database (Denmark)

Boerlin, P.; Wissing, A.; Aarestrup, Frank Møller

2001-01-01

Ninety-six enterococcus isolates from fecal samples of pigs receiving tylosin as an antimicrobial growth promoter and 59 isolates obtained in the same farms 5 to 6 months after the ban of antimicrobial growth promoters in Switzerland were tested for susceptibility to nine antimicrobial agents....... A clear decrease in resistance to macrolides, lincosamides, and tetracycline was visible after the ban. Vancomycin-resistant Enterococcus faecium belonged to the same clonal lineage as vancomycin-resistant isolates previously isolated from Danish pigs....

p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

Directory of Open Access Journals (Sweden)

Lena Willkomm

Full Text Available Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs. Lactate (La-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3 known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD vs. high intensity RE (HIT. Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

Science.gov (United States)

Willkomm, Lena; Gehlert, Sebastian; Jacko, Daniel; Schiffer, Thorsten; Bloch, Wilhelm

2017-01-01

Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs). Lactate (La)-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK) which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3) known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM) and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC) leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE) associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD) vs. high intensity RE (HIT). Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation.

LENUS (Irish Health Repository)

Noori, S

2014-08-14

Objective:We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine whether echocardiographic indices of impaired myocardial performance were associated with subsequent development of catecholamine-resistant hypotension following ligation.Study Design:A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was >15 μg kg(-1)min(-1). Echocardiograms and cortisol measurements were obtained between 6 and 14 h after the ligation (prior to the presence of catecholamine-resistant hypotension).Result:Forty-five infants were enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration.Conclusion:We speculate that low cortisol levels and impaired vascular tone may have a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension.Journal of Perinatology advance online publication, 14 August 2014; doi:10.1038\\/jp.2014.151.

Telomerase and drug resistance in cancer

OpenAIRE

Lipinska, Natalia; Romaniuk, Aleksandra; Paszel-Jaworska, Anna; Toton, Ewa; Kopczynski, Przemyslaw; Rubis, Blazej

2017-01-01

It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gen...

Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L.

2016-01-01

with the resistance evolved after single-drug exposure. Combination therapy selected for mutants that displayed broad-spectrum resistance, and a major resistance mechanism was mutational inactivation of the repressor gene mexR that regulates the multidrug efflux operon mexAB–oprM. Deregulation of this operon led...... to a broad-spectrum resistance phenotype that decreased susceptibility to the combination of drugs applied during selection as well as to unrelated antibiotic classes. Mutants isolated after single-drug exposure displayed narrow-spectrum resistance and carried mutations in the MexCD–OprJ efflux pump...... regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use...

[Establishment of human multidrug-resistant lung carcinoma cell line (D6/MVP)].

Science.gov (United States)

Ma, Sheng-lin; Feng, Jian-guo; Gu, Lin-hui; Ling, Yu-tian

2003-03-01

To establish human multidrug-resistant lung carcinoma cell line (D6/MVP) with its characteristics studied. Intermittent administration of high-dose MMC, VDS and DDP (MVP) was used to induce human lung carcinoma cell line (D6) to a multidrug-resistant variety (D6/MVP). MTT assay was used to study the multidrug resistance of D6/MVP to multianticarcinogen. Flow cytometry was used to study the cell cycle distribution and the expression of P-gp, multidrug resistance-associated protein (MRP) and GSH/GST. 1. D6/MVP was resistant to many anti-tumor agents, with the IC(50) 13.3 times higher and the drug resistance 2 - 6 times higher than D6, 2. The multiplication time of D6/MVP was prolonged and the cell number of S-phase decreased while that of G1- and G(2)-phase increased and 3. The expression of P-gp and MRP was enhanced significantly (96.2% vs 51.7%), but the expression of GSH/GST kept stable. D6/MVP is a multidrug-resistant cell line possessing the basic characteristics of drug-resistance.

Resistance training, insulin sensitivity and muscle function in the elderly

DEFF Research Database (Denmark)

Dela, Flemming; Kjaer, Michael

2006-01-01

Ageing is associated with a loss in both muscle mass and in the metabolic quality of skeletal muscle. This leads to sarcopenia and reduced daily function, as well as to an increased risk for development of insulin resistance and type 2 diabetes. A major part, but not all, of these changes......, and likewise to improve muscle strength in both elderly healthy individuals and in elderly individuals with chronic disease. The increased strength is coupled to improved function and a decreased risk for fall injuries and fractures. Elderly individuals have preserved the capacity to improve muscle strength...... are associated with an age-related decrease in the physical activity level and can be counteracted by increased physical activity of a resistive nature. Strength training has been shown to improve insulin-stimulated glucose uptake in both healthy elderly individuals and patients with manifest diabetes...

[A new challenge in clinical practice: resistance to directly acting antivirals in hepatitis C treatment].

Science.gov (United States)

Chen, Z W; Hu, P; Ren, H

2016-03-20

Directly acting antivirals (DAAs) is a major treatment of hepatitis C virus (HCV) overseas. But DAAs resistance is getting more and more clinicians' attention. DAAs have not been approved in China to date, even though some of them are in clinical trials. However, a good knowledge of DAAs resistance is important on optimizing HCV treatment regimens, increasing sustained virological response (SVR) and decreasing treatment failure in clinical. In this review, DAAs resistance mechanism and virologic barrier to resistance, the prevalence of pre-existing DAAs resistance-associated variants (RAVs), the impact of RAVs on treatment outcome, the options of treatment regimens after resistance and drug resistance testing are discussed, hoping to provide some help for DAAs' standardized treatment in China in the future.

Does antifouling paint select for antibiotic resistance?

Science.gov (United States)

Flach, Carl-Fredrik; Pal, Chandan; Svensson, Carl Johan; Kristiansson, Erik; Östman, Marcus; Bengtsson-Palme, Johan; Tysklind, Mats; Larsson, D G Joakim

2017-07-15

There is concern that heavy metals and biocides contribute to the development of antibiotic resistance via co-selection. Most antifouling paints contain high amounts of such substances, which risks turning painted ship hulls into highly mobile refuges and breeding grounds for antibiotic-resistant bacteria. The objectives of this study were to start investigate if heavy-metal based antifouling paints can pose a risk for co-selection of antibiotic-resistant bacteria and, if so, identify the underlying genetic basis. Plastic panels with one side painted with copper and zinc-containing antifouling paint were submerged in a Swedish marina and biofilms from both sides of the panels were harvested after 2.5-4weeks. DNA was isolated from the biofilms and subjected to metagenomic sequencing. Biofilm bacteria were cultured on marine agar supplemented with tetracycline, gentamicin, copper sulfate or zinc sulfate. Biofilm communities from painted surfaces displayed lower taxonomic diversity and enrichment of Gammaproteobacteria. Bacteria from these communities showed increased resistance to both heavy metals and tetracycline but not to gentamicin. Significantly higher abundance of metal and biocide resistance genes was observed, whereas mobile antibiotic resistance genes were not enriched in these communities. In contrast, we found an enrichment of chromosomal RND efflux system genes, including such with documented ability to confer decreased susceptibility to both antibiotics and biocides/heavy metals. This was paralleled by increased abundances of integron-associated integrase and ISCR transposase genes. The results show that the heavy metal-based antifouling paint exerts a strong selection pressure on marine bacterial communities and can co-select for certain antibiotic-resistant bacteria, likely by favoring species and strains carrying genes that provide cross-resistance. Although this does not indicate an immediate risk for promotion of mobile antibiotic resistance, the

Radiation response of drug-resistant variants of a human breast cancer cell line

International Nuclear Information System (INIS)

Lehnert, S.; Greene, D.; Batist, G.

1989-01-01

The radiation response of drug-resistant variants of the human tumor breast cancer cell line MCF-7 has been investigated. Two sublines, one resistant to adriamycin (ADRR) and the other to melphalan (MLNR), have been selected by exposure to stepwise increasing concentrations of the respective drugs. ADRR cells are 200-fold resistant to adriamycin and cross-resistant to a number of other drugs and are characterized by the presence of elevated levels of selenium-dependent glutathione peroxidase and glutathione-S-transferase. MLNR cells are fourfold resistant to melphalan and cross-resistant to some other drugs. The only mechanism of drug resistance established for MLNR cells to date is an enhancement of DNA excision repair processes. While the spectrum of drug resistance and the underlying mechanisms differ for the two sublines, their response to radiation is qualitatively similar. Radiation survival curves for ADRR and MLNR cells differ from that for wild-type cells in a complex manner with, for the linear-quadratic model, a decrease in the size of alpha and an increase in the size of beta. There is a concomitant decrease in the size of the alpha/beta ratio which is greater for ADRR cells than for MLNR cells. Analysis of results using the multitarget model gave values of D0 of 1.48, 1.43, and 1.67 Gy for MCF-7 cells are not a consequence of cell kinetic differences between these sublines. Results of split-dose experiments indicated that for both drug-resistant sublines the extent of sublethal damage repair reflected the width of the shoulder on the single-dose survival curve. For MCF-7 cells in the stationary phase of growth, the drug-resistant sublines did not show cross-resistance to radiation; however, delayed subculture following irradiation of stationary-phase cultures increased survival to a greater extent for ADRR and MLNR cells than for wild-type cells

A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections.

Directory of Open Access Journals (Sweden)

Janelle S Ayres

2008-12-01

Full Text Available Organisms evolve two routes to surviving infections-they can resist pathogen growth (resistance and they can endure the pathogenesis of infection (tolerance. The sum of these two properties together defines the defensive capabilities of the host. Typically, studies of animal defenses focus on either understanding resistance or, to a lesser extent, tolerance mechanisms, thus providing little understanding of the relationship between these two mechanisms. We suggest there are nine possible pairwise permutations of these traits, assuming they can increase, decrease, or remain unchanged in an independent manner. Here we show that by making a single mutation in the gene encoding a protease, CG3066, active in the melanization cascade in Drosophila melanogaster, we observe the full spectrum of changes; these mutant flies show increases and decreases in their resistance and tolerance properties when challenged with a variety of pathogens. This result implicates melanization in fighting microbial infections and shows that an immune response can affect both resistance and tolerance to infections in microbe-dependent ways. The fly is often described as having an unsophisticated and stereotypical immune response where single mutations cause simple binary changes in immunity. We report a level of complexity in the fly's immune response that has strong ecological implications. We suggest that immune responses are highly tuned by evolution, since selection for defenses that alter resistance against one pathogen may change both resistance and tolerance to other pathogens.

Thermal stress resistance of ion implanted sapphire crystals

International Nuclear Information System (INIS)

Gurarie, V.N.; Jamieson, D.N.; Szymanski, R.; Orlov, A.V.; Williams, J.S.; Conway, M.

1999-01-01

Monocrystals of sapphire have been subjected to ion implantation with 86 keV Si - and 80 keV Cr - ions to doses in the range of 5x10 14 -5x10 16 cm -2 prior to thermal stress testing in a pulsed plasma. Above a certain critical dose ion implantation is shown to modify the near-surface structure of samples by introducing damage, which makes crack nucleation easier under the applied stress. The effect of ion dose on the stress resistance is investigated and the critical doses which produce a noticeable change in the stress resistance are determined. The critical dose for Si ions is shown to be much lower than that for Cr - ions. However, for doses exceeding 2x10 16 cm -2 the stress resistance parameter decreases to approximately the same value for both implants. The size of the implantation-induced crack nucleating centers and the density of the implantation-induced defects are considered to be the major factors determining the stress resistance of sapphire crystals irradiated with Si - and Cr - ions

Comparison of joint kinetics during free weight and flywheel resistance exercise.

Science.gov (United States)

Chiu, Loren Z F; Salem, George J

2006-08-01

The most common modality for resistance exercise is free weight resistance. Alternative methods of providing external resistance have been investigated, in particular for use in microgravity environments such as space flight. One alternative modality is flywheel inertial resistance, which generates resistance as a function of the mass, distribution of mass, and angular acceleration of the flywheel. The purpose of this investigation was to characterize net joint kinetics of multijoint exercises performed with a flywheel inertial resistance device in comparison to free weights. Eleven trained men and women performed the front squat, lunge, and push press on separate days with free weight or flywheel resistance, while instrumented for biomechanical analysis. Front squats performed with flywheel resistance required greater contribution of the hip and ankle, and less contribution of the knee, compared to free weight. Push presses performed with flywheel resistance had similar impulse requirements at the knee compared to free weight, but greater impulse requirement at the hip and ankle. As used in this investigation, flywheel inertial resistance increases the demand on the hip extensors and ankle plantarflexors and decreases the mechanical demand on the knee extensors for lower extremity exercises such as the front squat and lunge. Exercises involving dynamic lower and upper extremity actions, such as the push press, may benefit from flywheel inertial resistance, due to the increased mechanical demand on the knee extensors.

Progesterone resistance in endometriosis: origins, consequences and interventions.

Science.gov (United States)

Patel, Bansari G; Rudnicki, Martin; Yu, Jie; Shu, Yimin; Taylor, Robert N

2017-06-01

Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment. © 2017 Nordic Federation of

Development of high electrical resistance persistent current switch for high speed energization system

International Nuclear Information System (INIS)

Jizo, Y.; Furuta, Y.; Nakashima, H.

1986-01-01

Japanese National Railways is now developing a superconducting magnetically-levitated train system. A persistent current switch is incorporated in the super-conducting magnet used in the magnetically-levitated train. In recent years, the switch has been required to have higher electrical resistance during its off-state in order to realize the high speed energization/de-energization system of the superconducting magnets. The system aims to decrease evaporation volume of liquid helium during the energization/de-energization of the magnet, by means of energizing the superconducting magnet with high current increasing/decreasing rate. Consequently, it would be possible to decrease the dependence of the on-board magnet system upon the ground cooling system. Through the development of a stable superconductive wire material and a coil structure for the persistent current switch using many small model switches which were produced in order to improve their current carrying capacities, the authors have succeeded in manufacturing the high electrical resistance persistent current switch whose electrical resistance was 5 ohms. The switch, of cylindrical shape, has a diameter of about 100mm, a length of about 100mm. These 5 ohm PCSs are now functioning in stable conditions being incorporated in the superconducting magnets of No.2 vehicle of MLU001 at the JNR's Miyazaki test track. Further, the authors are now developing the PCS of still higher resistance values, such as 50 ohms, through studies for stabilization in structural aspects of the winding and obtaining results therefrom

Insulin Sensitivity Determines Effects of Insulin and Meal Ingestion on Systemic Vascular Resistance in Healthy Subjects.