Bronchial effects of leukotriene D4 inhalation in normal human lung

DEFF Research Database (Denmark)

Bisgaard, H; Groth, S

1987-01-01

airways in asthmatic patients out of attack. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900-7000 times more potent......The aim of the study was to investigate whether inhaled leukotriene (LT) D4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD4 were...... than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial...

Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

DEFF Research Database (Denmark)

Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard

2012-01-01

Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and ...

Development of a sensitive and specific radioreceptor assay for leukotriene B4

International Nuclear Information System (INIS)

Kohi, F.; Agrawal, D.K.; Cheng, J.B.; Bewtra, A.; Townley, R.G.; Olesch, J.W.

1988-01-01

To establish a simple and sensitive quantitation of leukotriene B 4 (LTB 4 ), they developed a radioreceptor assay (RRA) using a highly specific [ 3 H]leukotriene B 4 ([ 3 H]LTB 4 ) binding to a guinea pig spleen homogenate. The assay detected LTB 4 levels as low as 0.12 pmol per tube. 50% inhibition of bound [ 3 H]LTB 4 was obtained by 2.5 nM of unlabeled LTB 4 . [ 3 H]LTB 4 competition studies indicated that 20-hydroxy-LTB 4 was 8 times, 6 trans-LTB 4 was 640 times and 20-carboxy-LTB 4 was 1000 times less effective than LTB 4 . The peptide leukotrienes C 4 , D 4 and E 4 showed no effect on [ 3 H]LTB 4 binding. Recovery rates averaged 97% after ethanol extraction and evaporation of known amounts of LTB 4 . The intra-assay coefficients of variation for three samples were 2.4%, 7.2% and 8.4%, respectively. This assay was validated by measuring LTB 4 released from human granulocytes stimulated with calcium ionophore A23187. The LTB 4 level was maximal at 10 min and decreased rapidly after 15 min. This radioreceptor assay for leukotriene B 4 is highly sensitive and is comparable to the reported sensitivity by radioimmunoassay. The method is simpler and less expensive than other methods such as high pressure liquid chromatography and is suitable for routine measurement of leukotriene B 4

Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig

International Nuclear Information System (INIS)

Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

1987-01-01

Experiments on the metabolism and excretion of i.v. administered selectively labeled [ 3 H 8 ]leukotriene C 4 in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D 4 . By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D 4 endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D 4 concentrations from 10 +/- 1 to 86 +/- 10 nM. When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D 4 in bile increased from 0.88 +/- 0.16 before 3.18 +/- 0.38 pmol x min -1 x kg -1 after challenge. It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C 4

Upregulation of Leukotriene Receptors in Gastric Cancer

Energy Technology Data Exchange (ETDEWEB)

Venerito, Marino [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Kuester, Doerthe [Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Harms, Caroline [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Schubert, Daniel [Department of General, Visceral and Vascular Surgery, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, Magdeburg 39120 (Germany); Wex, Thomas, E-mail: thomas.wex@med.ovgu.de; Malfertheiner, Peter [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany)

2011-08-08

Leukotrienes (LT) mediate allergic and inflammatory processes. Previously, we identified significant changes in the expression pattern of LT receptors in the gastric mucosa after eradication of Helicobacter pylori infection. The aim of the present study was to evaluate the expression of 5-lipoxygenase (5-LOX) and LT receptors in gastric cancer (GC). The expression of 5-LOX and receptors for LTB4 (BLT-1, BLT-2) and cysteinyl-LT (CysLT-1, CysLT-2) were analyzed by immunohistochemistry (IHC) in GC samples of 35 consecutive patients who underwent gastrectomy and in 29 tumor-free tissue specimens from gastric mucosa. Male-to-female ratio was 24:11. The median age was 70 years (range 34–91). Twenty-two patients had GC of intestinal, six of diffuse, six of mixed and one of undifferentiated type. The IHC analysis showed a nearly ubiquitous expression of studied proteins in GC (88–97%) and in tumor-free specimens as well (89–100%). An increase in the immunoreactive score of both BLT receptors and CysLT-1 was observed in GC compared to tumor-free gastric mucosa (p < 0.001 for BLT-1; p < 0.01 for BLT-2 and CysLT-1, Mann-Whitney U-test). No differences in the IHC expression of 5-LOX and CsyLT-2 were observed between GC and tumor-free mucosa. The expression of BLT-2, CysLT-1 and CysLT-2 was increased in GC of intestinal type when compared to the diffuse type (p < 0.05; Mann-Whitney U-test). LTB4 receptors and CysLT-1 are up-regulated in GC tissue implying a role in gastric carcinogenesis.

(3H)leukotriene B4 binding to the guinea pig spleen membranes: a rich tissue source for a high affinity leukotriene B4 receptor site

International Nuclear Information System (INIS)

Cheng, J.B.; Kohi, F.; Townley, R.G.

1986-01-01

To select a tissue rich for the high affinity leukotriene (LT)B 4 receptor site, they compared binding of 1 nM ( 3 H)LTB 4 (180 Ci/mmol) to the crude membrane preparations of guinea pig spleen, thymus, lung, uterus, bladder, brain, adrenal gland, small intestine, liver, kidney and heart. They found that the membrane preparations from spleen contained the highest binding activity per mg protein. They characterized the LTB 4 binding to the spleen preparation in detail. LTB 4 binding was rapid, reversible, stereoselective and saturable. The data from equilibrium experiments showed a linear Scatchard plot with a K/sub d/ of 1.6 nM and a binding site density of 259 fmol/mg prot. The rank order of agents competing for spleen ( 3 H)LTB 4 binding at 25 0 C was: LTB 4 (K/sub i/ = 2.8 nM) > 20-OH-LTB 4 (23 nM) > LTA 4 (48 nM) > LTA 4 methyl ester (0.13 μM) > 20-COOH-LTB 4 (> 6.6 μM) ≥ arachidonic acid (0.15 mM) similarly ordered FPL-55,712 (0.11 mM). At 4 0 C, LTB 4 (2.3 nM) competed at least 10x more effectively than 20-OH-LTB 4 (29 nM) and 20-COOH-LTB 4 (> 6.6 μM). HPLC analysis indicated that incubation of 84 ng LTB 4 with the spleen membrane at 25 0 C did not result in the formation of 20-OH-LTB 4 ( 3 H)LTB 4 receptor binding sites

Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines.

Science.gov (United States)

Salimi, Maryam; Stöger, Linda; Liu, Wei; Go, Simei; Pavord, Ian; Klenerman, Paul; Ogg, Graham; Xue, Luzheng

2017-10-01

Group 2 innate lymphoid cells (ILC2s) are a potential innate source of type 2 cytokines in the pathogenesis of allergic conditions. Epithelial cytokines (IL-33, IL-25, and thymic stromal lymphopoietin [TSLP]) and mast cell mediators (prostaglandin D 2 [PGD 2 ]) are critical activators of ILC2s. Cysteinyl leukotrienes (cysLTs), including leukotriene (LT) C 4 , LTD 4 , and LTE 4 , are metabolites of arachidonic acid and mediate inflammatory responses. Their role in human ILC2s is still poorly understood. We sought to determine the role of cysLTs and their relationship with other ILC2 stimulators in the activation of human ILC2s. For ex vivo studies, fresh blood from patients with atopic dermatitis and healthy control subjects was analyzed with flow cytometry. For in vitro studies, ILC2s were isolated and cultured. The effects of cysLTs, PGD 2 , IL-33, IL-25, TSLP, and IL-2 alone or in combination on ILC2s were defined by using chemotaxis, apoptosis, ELISA, Luminex, quantitative RT-PCR, and flow cytometric assays. The effect of endogenous cysLTs was assessed by using human mast cell supernatants. Human ILC2s expressed the LT receptor CysLT 1 , levels of which were increased in atopic subjects. CysLTs, particularly LTE 4 , induced migration, reduced apoptosis, and promoted cytokine production in human ILC2s in vitro. LTE 4 enhanced the effect of PGD 2 , IL-25, IL-33, and TSLP, resulting in increased production of type 2 and other proinflammatory cytokines. The effect of LTE 4 was inhibited by montelukast, a CysLT 1 antagonist. Interestingly, addition of IL-2 to LTE 4 and epithelial cytokines significantly amplified ILC2 activation and upregulated expression of the receptors for IL-33 and IL-25. CysLTs, particularly LTE 4 , are important contributors to the triggering of human ILC2s in inflammatory responses, particularly when combined with other ILC2 activators. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Low expression of CysLT1R and high expression of CysLT2R mediate good prognosis in colorectal cancer

DEFF Research Database (Denmark)

Magnusson, Cecilia; Mezhybovska, Maryna; Lörinc, Ester

2010-01-01

Colorectal cancer is the third most common cancer type in the Western world. In search of new treatment possibilities, the inflammation mediators, know as cysteinyl leukotrienes (CysLTs), have been shown to regulate intestinal epithelial cell survival and proliferation via the CysLT(1)R, and cell...... microarray of 329 colorectal patients. We found that high nuclear expression of CysLT(1)R is associated with a poor prognosis, whereas high nuclear expression of CysLT(2)R is associated with a good prognosis. We also observed that patients with colorectal tumours characterised by high CysLT(1)R but low Cys...

Characterization of arachidonate 5-lipoxygenase and leukotriene A4 synthetase from RBL-1 cells

International Nuclear Information System (INIS)

Cook, M.; Hogaboom, G.K.; Sarau, H.M.; Foley, J.J.; Crooke, S.T.

1986-01-01

5-lipoxygenase (LO) and leukotriene (LT) A4 synthetase from RBL-1 high speed (105,000 x g for 60 min) supernatants were partially purified by protein-high performance liquid chromatography (HPLC) and characterized in detail. The partially purified preparation contained only 5-LO and LTA4 synthetase and was isolated from 12-LO, peroxidase and LTA4 hydrolase activities. Reaction products were separated by reversed phase HPLC and quantitated by absorption spectrophotometry and radiochemical detection. The enzyme preparation rapidly converted [ 14 C]arachidonate to [ 14 C]5-hydroperoxyeicosatetraenoic acid (HPETE) and [ 14 C]5,12-dihydroperoxyeicosatetraenoic acids (diHETEs). The 5,12-diHETEs were primarily non-enzymatic breakdown products of LTA4 (e.g., 6-trans-LTB4 and 6-trans-12-epi-LTB4). Both the 5-LO and LTA4 synthetase activities were Ca 2+- and ATP-dependent. For both enzyme activities, the CA 2+ stimulation required the presence of ATP. The fatty acid hydroperoxides, 5-,12-, and 15-HPETE, both stimulated ([ 3 μM]) 5-LO and LTA4 synthetase activities. The rapid isolation and subsequent characterization of 5-LO and LTA4 synthetase provide the bases for the further understanding of the role of the LO pathway in biological processes

Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

Science.gov (United States)

Levy, Bruce D; Lukacs, Nicholas W; Berlin, Aaron A; Schmidt, Birgitta; Guilford, William J; Serhan, Charles N; Parkinson, John F

2007-12-01

Cellular recruitment during inflammatory/immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At 50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation.

Determination of thromboxanes, leukotrienes and lipoxins using high-temperature capillary liquid chromatography-tandem mass spectrometry and on-line sample preparation

DEFF Research Database (Denmark)

Dahl, Sandra Rinne; Kleiveland, Charlotte Ramstad; Kassem, Moustapha

2009-01-01

An on-line strong cation-exchange (SCX)-reversed-phase (RP) capillary liquid chromatographic (cLC) method with ion-trap tandem mass spectrometric (IT-MS/MS) detection for the simultaneous determination of thromboxane (TX) B(2), TXB(3), leukotriene (LT) B(4), LTD(4) and lipoxin (LX) A(4) in cell...

Pharmacological modulation of human platelet leukotriene C4-synthase.

Science.gov (United States)

Sala, A; Folco, G; Henson, P M; Murphy, R C

1997-03-21

The aim of this study was to test if human platelet leukotriene C4-synthase (LTC4-S) is pharmacologically different from cloned and expressed LTC4-S and, in light of the significant homologies between 5-lipoxygenase activating protein (FLAP) and LTC4-S, if different potencies of leukotriene synthesis inhibitors acting through binding with FLAP (FLAP inhibitors) reflect in different potencies as LTC4-S inhibitors. Leukotriene C4 (LTC4) synthesis by washed human platelets supplemented with synthetic leukotriene A4 (LTA4) was studied in the absence and presence of two different, structurally unrelated FLAP inhibitors (MK-886 and BAY-X1005) as well as a direct 5-lipoxygenase inhibitor (zileuton). LTC4 production was analyzed by RP-HPLC coupled to diode array detection. We report that human platelet LTC4-S was inhibited by MK-886 and BAY-X1005 (IC50 of 4.7 microM and 91.2 microM, respectively), but not by zileuton (inactive up to 300 microM); all 3 compounds were able to inhibit 5-lipoxygenase metabolite biosynthesis in intact human polymorphonuclear leukocytes (IC50 of 0.044 microM, 0.85 microM, and 1.5 microM, respectively). Platelet LTC4-S does not appear pharmacologically different from expression cloned LTC4-S. LTC4-S inhibition by FLAP inhibitors is in agreement with the significant homology reported for expression-cloned LTC4-S with FLAP, Furthermore, functional homology of the binding sites for inhibitors on LTC4-S and FLAP is suggested by the conservation of the relative potencies of MK-886 and BAY-X1005 vs FLAP-dependent 5-lipoxygenase activity and LTC4-S inhibition: MK-886 was 19.3-fold more potent than BAY-X1005 as FLAP inhibitor and 19.6-fold more potent than BAY-X1005 as LTC4-S inhibitor.

Expression of cysLT1 and cysLT2 Receptor in Chronic Hyperplastic Eosinophilic Sinusitis

International Nuclear Information System (INIS)

Ouyang, Yuhui; Kamijo, Atsushi; Murata, Shin-ichi; Okamoto, Atsushi; Endo, Shuichiro; Katoh, Ryohei; Masuyama, Keisuke

2009-01-01

Elevated production of cysteinyl leukotrienes (cysLTs) from sinus tissues and abundant sinus eosinophils are characteristic features of chronic hyperplastic eosinophilic sinusitis (CHS). CysLTs exert their action through G-protein-coupled receptors named cysLTs receptor type I (cysLT1R) and type II (cysLT2R). These expressions of cysLT receptors in the sinus mucosa have yet to be clarified and the relationship between eosinophilia and the expression of these receptors remains obscure. We compared the expressions of cysLT1R and cysLT2R in the sinus mucosa in patients with CHS, non-eosinophilic chronic sinusitis (NECS), and control sinus tissues; and analyzed the correlation between the expression of CysLTRs and the presence of sinus eosinophils by immunohistochemistry and real-time PCR. A significantly higher percentage of eosinophils expressing cysLT2R protein was observed in patients with CHS compared with NECS and controls. In addition, cysLT2R mRNA expression in CHS was significantly higher than in NECS and controls. Furthermore, a positive correlation was observed between cysLT2R mRNA expression and the number of infiltrated eosinophils. In contrast, the cysLT1R mRNA expression did not differ significantly among these groups. The effect of cysLTs on sinus eosinophils may be mediated through the cysLT2R in patients with CHS. These results may suggest the therapeutic benefit of cysLT2R antagonists in CHS

Combination L-T3 and L-T4 therapy for hypothyroidism.

Science.gov (United States)

Wartofsky, Leonard

2013-10-01

Because of the longstanding controversy regarding whether hypothyroid patients can be optimally replaced by treatment with levothyroxine (L-T4) alone, numerous studies have addressed potential benefits of combined therapy of triiodothyronine (T3) with L-T4. Results of these studies have failed to support a potential benefit of combined therapy. A strong argument for the addition of L-T3 to L-T4 monotherapy has been lacking until recent genetic studies indicated a rationale for such therapy among a small fraction of the hypothyroid patient population. Interest in this issue has focused on the importance of the deiodinases in maintaining the euthyroid state and the role of genetic polymorphisms in the deiodinase genes that would affect thyroid hormone concentrations in both blood and tissues. One such polymorphism in the D2 gene, Thr92Ala, is associated with reduced T4 to T3 activation in skeletal muscle and thyroid, linked to obesity and alterations in thyroid-pituitary feedback, and in responses to thyroid hormone treatment. Although our professional organizations continue to recommend L-T4 alone for the treatment of hypothyroidism, the possibility of a D2 gene polymorphism should be considered in patients on L-T4 monotherapy who continue to complain of fatigue in spite of dosage achieving low normal serum thyroid stimulating hormone levels. A suggestive clue to the presence of this polymorphism could be a higher than normal free T4/free T3 ratio. Clinicians could consider adding T3 as a therapeutic trial in selected patients. Future well controlled clinical trials will be required to more fully resolve the controversy.

Role of leukotrienes in asthma pathophysiology

DEFF Research Database (Denmark)

Bisgaard, H

2000-01-01

Inflammation is an essential component of asthma pathophysiology. While beta(2)-agonists are often used for short-term relief of acute bronchospasm, anti-inflammatory agents are required for the long-term management of chronic inflammation in this disease. Corticosteroids have emerged as the first......-line anti-inflammatory therapy for asthma management. However, in some patients, especially children, the high doses of corticosteroids that may be required to control features of hyperresponsiveness, including exercise-induced asthma, raise safety concerns. Thus, there is a need for complementary anti......-inflammatory, steroid-sparing agents in asthma therapy. Several inflammatory mediators have been targeted in an attempt to thwart this inflammatory process, but so far with little success. The cysteinyl leukotrienes (CysLT), LTC(4), LTD(4), and LTE(4), have been shown to be essential mediators in asthma, making them...

Leukotrienes and leukotriene modifiers in pediatric allergic diseases

African Journals Online (AJOL)

Ehab

... 12(1):3-12. 3. Leukotrienes and leukotriene modifiers in pediatric allergic diseases ... childhood allergic diseases. This review ... produce cysteinyl-LTs and LTB4 spontaneously in vitro.8. Although nonleukocyte cells generally do not have sufficient 5-LO and FLAP to synthesize .... uninterrupted sleep in these patients.55.

Cold injury, blood-brain barrier changes, and leukotriene synthesis: Inhibition by phenidone

International Nuclear Information System (INIS)

Robichaud, L.J.; Marcoux, F.W.

1990-01-01

Transcranial cold injury in rats and guinea pigs induced cerebral extravasation of albumin labeled with Evans blue dye or 125 I, respective indicators of the area and amount of blood-brain barrier (BBB) disruption. Radioimmunoassay of brain extracts showed that cold injury induced leukotriene (LT)C4 in rat and guinea pig brains 15 min after injury. In guinea pigs, the LT synthesis inhibitor phenidone (30 mg/kg, i.p.) completely blocked cold-induced LTC4 in brain. Phenidone (30 and 100 mg/kg) also inhibited cerebral tissue accumulation of 125 I-albumin and dye in rats and guinea pigs. Phenidone is reported to show antioxidant properties and selective lipoxygenase inhibition of arachidonic acid metabolism compared to cyclooxygenase inhibitors, meclofenamate sodium, and other nonsteroidal anti-inflammatory agents. Since several oxygen and hydroxyl radical scavengers and the cyclooxygenase inhibitor, meclofenamate sodium, did not inhibit protein extravasation, the findings support a role for LT as a mediator of cold-induced changes in BBB permeability in rats and guinea pigs and suggest that the inhibitory effects of phenidone on BBB permeability may be due to inhibition of LT production

Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin-intolerant asthma.

Science.gov (United States)

Ono, Emiko; Taniguchi, Masami; Higashi, Noritaka; Mita, Haruhisa; Yamaguchi, Hiromichi; Tatsuno, Sayaka; Fukutomi, Yuma; Tanimoto, Hidenori; Sekiya, Kiyoshi; Oshikata, Chiyako; Tsuburai, Takahiro; Tsurikisawa, Naomi; Otomo, Mamoru; Maeda, Yuji; Hasegawa, Maki; Miyazaki, Eishi; Kumamoto, Toshihide; Akiyama, Kazuo

2011-03-01

Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a considerable role in the pathophysiology of aspirin-intolerant asthma (AIA). Saliva has recently been validated as novel, simple, and noninvasive method for investigating inflammation in patients with asthma. The aim of this study is to clarify the molecular species of CysLT in saliva and to evaluate the CysLT and LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT concentration in saliva reflects that of their corresponding urinary metabolite. We preformed an analytical cross-sectional study. CysLT and LTB4 concentrations in saliva were quantified by enzyme immunoassay (EIA) following purification by high-performance liquid chromatography (HPLC). 1. When analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4, LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects), both the concentrations of CysLTs and LTB4 were significantly higher in AIA patients than in ATA patients and healthy subjects. 3. We found significant correlations between CysLT concentration and LTB4 concentration in saliva in each group. 4. No significant correlation was found between the concentration of LTE4 in urine and that of CysLTs in saliva. In this study, we found higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in saliva from ATA patients, suggesting that the quantification of CysLT and LTB4 concentrations in saliva may be another diagnostic strategy for AIA.

Tritium-labelled leukotriene B4 binding to the guinea-pig spleen membrane preparation: a rich tissue source for a high-affinity leukotriene B4 receptor site

International Nuclear Information System (INIS)

Cheng, J.B.; Cheng, E.I.; Kohi, F.; Townley, R.G.

1986-01-01

Intact human granulocytes contain a leukotriene (LT) B4 receptor binding site, but the limited supply of these cells could adversely affect further progress of the study of this receptor. To select a tissue homogenate rich for this site, we have characterized the binding of highly specific [ 3 H]LTB4 to guinea-pig spleen membranes and we have determined the ability of LTB4 to compete with [ 3 H]LTB4 for binding sites in the membranes of 10 nonspleen tissues. In the spleen membrane, MgCl2 and CaCl2 enhanced [ 3 H]LTB4 binding, but NaCl and KCl decreased it. Spleen [ 3 H] LTB4 binding was a function of protein concentration and was rapid, reversible, stereoselective and saturable. Kinetic analyses showed that the rate constant for association and dissociation at 25 0 C was 0.47 nM-1 min-1 and 0.099 min-1, respectively. A Scatchard plot of the data of the equilibrium experiment resulted a straight line with a dissociation constant of 1.8 nM and a density of 274 fmol/mg of protein. Moreover, the LTB4/[ 3 H]LTB4 competition study performed at 4 or 25 0 C revealed the inhibitory constant (Ki) of LTB4 to be in the nanomolar range. The rank order of agents competing for spleen [ 3 H]LTB4 binding was: LTB4 (Ki = 2.8 nM) greater than 20-hydroxy-LTB4 (23 nM) greater than LTA4 (48 nM) greater than LTA4 methyl ester (0.13 microM) greater than 20-carboxy-LTB4 (greater than 6.6 microM) greater than or equal to arachidonic acid (0.15mM) = FPL-55,712 and FPL-57,231 (0.1-0.2 mM). Competition studies further indicated that felodipine, a 1,4-dihyropyridine Ca++ channel blocker, exhibited micromolar inhibition of spleen [ 3 H]LTB4 binding

Characterization of guinea pig myocardial leukotriene C4 binding sites. Regulation by cations and sulfhydryl-directed reagents

International Nuclear Information System (INIS)

Hogaboom, G.K.; Mong, S.; Stadel, J.M.; Crooke, S.T.

1985-01-01

Using [ 3 H]leukotriene C4 (LTC4) and radioligand-binding techniques, specific leukotriene C4 binding sites have been identified in membranes derived from guinea pig ventricular myocardium. High performance liquid chromatography analyses indicated that, in the presence of the gamma-glutamyl transpeptidase inhibitor L-serine-borate (80 mM), less than 2% of membrane-bound [ 3 H]LTC4 was converted at 20 degrees to [ 3 H]leukotriene D4 or [ 3 H]leukotriene E4. The specific binding of 4 nM [ 3 H]LTC4, in the presence of 80 mM L-serine-borate, reached a stable steady state within 15 min at 20 degrees (pH 7.5). A monophasic Scatchard plot of saturation binding data yielded a dissociation constant (Kd) of 27.5 +/- 6.0 nM and a maximum number of binding sites (Bmax) of 19.9 +/- 5.2 pmol/mg of membrane protein. Competition binding studies of [ 3 H]LTC4 with synthetic leukotriene C4, leukotriene D4, and leukotriene E4 and the putative peptidoleukotriene antagonists FPL 55712, SKF 88046, and 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid revealed an order of potency of leukotriene C4 much greater than 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid greater than SKF 88046 greater than LTE4 greater than LTD4 greater than FPL 55712. The specific [ 3 H]LTC4 binding was stimulated by the divalent cations Ca2+, Mg2+, and Mn2+ and to a lesser degree by the monovalent cations Na+, K+, Li+, and NH4+. CaCl2 (3 mM) and NaCl (150 mM) stimulated the LTC4 binding by increasing the Bmax to 42.6 +/- 5.9 and 35.0 +/- 2.0 pmol/mg, respectively, but had minimal effects on Kd

Leukotriene C4 synthase and ischemic cardiovascular disease and obstructive pulmonary disease in 13,000 individuals

DEFF Research Database (Denmark)

Freiberg, Jacob J; Dahl, Morten; Tybjaerg-Hansen, Anne

2009-01-01

Ischemic cardiovascular disease and obstructive pulmonary disease involve inflammation. Leukotrienes may be important pro-inflammatory mediators. We tested the hypothesis that the (-1072)G > A and (-444)A > C promoter polymorphisms of leukotriene C4 synthase confer risk of transient ischemic atta...... with risk of asthma or COPD. Leukotriene C4 synthase promoter genotypes influence risk of TIA and ischemic stroke, but not risk of IHD/coronary atherosclerosis, asthma, or COPD....

Leukotrienes are upregulated and associated with human T-lymphotropic virus type 1 (HTLV-1-associated neuroinflammatory disease.

Directory of Open Access Journals (Sweden)

Bruno Caetano Trindade

Full Text Available Leukotrienes (LTs are lipid mediators involved in several inflammatory disorders. We investigated the LT pathway in human T-lymphotropic virus type 1 (HTLV-1 infection by evaluating LT levels in HTLV-1-infected patients classified according to the clinical status as asymptomatic carriers (HACs and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP patients. Bioactive LTB(4 and CysLTs were both increased in the plasma and in the supernatant of peripheral blood mononuclear cell cultures of HTLV-1-infected when compared to non-infected. Interestingly, CysLT concentrations were increased in HAM/TSP patients. Also, the concentration of plasma LTB(4 and LTC(4 positively correlated with the HTLV-1 proviral load in HTLV-1-infected individuals. The gene expression levels of LT receptors were differentially modulated in CD4(+ and CD8(+ T cells of HTLV-1-infected patients. Analysis of the overall plasma signature of immune mediators demonstrated that LT and chemokine amounts were elevated during HTLV-1 infection. Importantly, in addition to CysLTs, IP-10 was also identified as a biomarker for HAM/TSP activity. These data suggest that LTs are likely to be associated with HTLV-1 infection and HAM/TSP development, suggesting their putative use for clinical monitoring.

Concentrations of cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid of cats with experimentally induced asthma.

Science.gov (United States)

Norris, Carol R; Decile, Kendra C; Berghaus, Londa J; Berghaus, Roy D; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2003-11-01

To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. 19 cats with experimentally induced asthma and 5 control cats. Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

Cysteinyl leukotrienes in the urine of patients with liver diseases.

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Uemura, M; Buchholz, U; Kojima, H; Keppler, A; Hafkemeyer, P; Fukui, H; Tsujii, T; Keppler, D

1994-10-01

The significance of cysteinyl leukotrienes was investigated in patients with liver diseases by measurements of leukotriene E4 and N-acetyl-leukotriene E4 in urine. A marked increase of renal cysteinyl leukotriene excretion was observed in patients with cirrhosis without and with ascites, intrahepatic cholestasis, and obstructive jaundice as compared with healthy subjects (leukotriene E4: means 82, 264, 221 and 142 versus 40 nmol/mol creatinine, respectively; N-acetyl-leukotriene E4: means 25, 64, 61 and 47 versus 13 nmol/mol creatinine, respectively). The urinary concentration of leukotriene E4 was positively correlated with the one of N-acetyl-leukotriene E4 (r = 0.81, p jaundice, the excretion of leukotriene E4 plus N-acetyl-leukotriene E4 was positively correlated with total serum bilirubin. In patients with cirrhosis and in those with obstructive jaundice, the cysteinyl leukotrienes in urine were negatively correlated with creatinine clearance. The elevated renal excretion of cysteinyl leukotrienes decreased after biliary drainage in patients with obstructive jaundice. These data support the concept that increased urinary excretion of cysteinyl leukotrienes in patients with cirrhosis is due to a reduced functional liver mass and that in patients with cholestasis it is mainly due to an impaired elimination into the biliary tract that results in a diversion to renal excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukotriene Receptor Antagonists in the Treatment of Asthma: Implications for Eosinophilic Inflammation

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Redwan Moqbel

1999-01-01

Full Text Available Recent advances in the treatment and management of asthma have suggested that leukotriene (LT receptor antagonists may be very beneficial as a second generation therapy with steroid-sparing properties and negligible side effects. These agents have shown interesting effects on peripheral blood and sputum eosinophils. A major contributor to the damage in the airway of asthmatic patients is the eosinophil, which, upon activation, releases a battery of granule-associated cytotoxic, cationic proteins, including the major basic protein and eosinophil peroxidase, and membrane-derived de novo-synthesized bioactive lipid mediators, including LTC4, LTD4 and LTE4, as well as platelet activating factor. These products have deleterious effects on the airway tissue including mucosal and smooth muscle layers. Accumulating evidence suggests that these agents may also influence the accumulation and maintenance of eosinophilic responses at the site of inflammation. This article reviews the possible anti-inflammatory mode of action of these therapies. It also discusses where there may be a gap in the knowledge regarding the potential direct and indirect effects of LT modifiers on eosinophil function and recruitment.

Leukotriene formation by purified 5-lipoxygenase from rat basophilic leukemia cells

International Nuclear Information System (INIS)

Hogaboom, G.K.; Cook, M.; Sarau, H.M.; Newton, J.F.; Crooke, S.T.

1986-01-01

Arachidonate 5-lipoxygenase (5-LO) from rat basophilic leukemia (RBL-1) cell high speed (105,000 x g for 60 min) supernatants was purified to electrophoretic homogeneity by gel filtration and anion-exchange protein-high pressure liquid chromatography (HPLC). The 5-LO rapidly converted [ 14 C]arachidonate at 20 0 C to [ 14 C]5-hydroperoxyeicosate-traenoic acid (HPETE) as determined by reversed phase-HPLC, scanning spectrophotometry and radiochemical detection. In addition, 5-LO converted both 5-HPETE and arachidonate to 5,12-dihydroxyeicosatetraenoic acids (diHETEs). The 5,12-diHETEs were identified as 6-trans-leukotriene (LT) B4 and 6-trans-12-epi-LTB4 as determined by reversed phase HPLC, scanning spectrophotometry and gas chromatography-mass spectrometry. These data indicate that the RBL-1 5-LO and LTA4 synthetase activities reside on the same protein and that it catalyzes the bioconversion of arachidonate to not only 5-HPETE but also to LTA4. The results suggest that a critical regulatory step in LT biosynthesis in mammalian systems involves the intricate coupling of the enzymes 5-LO and LTA4 synthetase and the interactions of their respective cofactors, substrates and reaction products

A role for inflammatory mediators in heterologous desensitization of CysLT1 receptor in human monocytes

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Capra, Valérie; Accomazzo, Maria Rosa; Gardoni, Fabrizio; Barbieri, Silvia; Rovati, G. Enrico

2010-01-01

Cysteinyl-leukotrienes (cysteinyl-LT) are rapidly generated at sites of inflammation and, in addition to their role in asthma, rhinitis, and other immune disorders, are increasingly regarded as significant inflammatory factors in cancer, gastrointestinal, cardiovascular diseases. We recently demonstrated that in monocyte/macrophage–like U937 cells, extracellular nucleotides heterologously desensitize CysLT1 receptor (CysLT1R)-induced Ca2+ transients. Given that monocytes express a number of other inflammatory and chemoattractant receptors, this study was aimed at characterizing transregulation between these different stimuli. We demonstrate that in U937 cells and in primary human monocytes, a series of inflammatory mediators activating Gi-coupled receptor (FPR1, BLT1) desensitize CysLT1R-induced Ca2+ response unidirectionally through activation of PKC. Conversely, PAF-R, exclusively coupled to Gq, cross-desensitizes CysLT1R without the apparent involvement of any kinase. Interestingly, Gs-coupled receptors (β2AR, H1/2R, EP2/4R) are also able to desensitize CysLT1R response through activation of PKA. Heterologous desensitization seems to affect mostly the Gi-mediated signaling of the CysLT1R. The hierarchy of desensitization among agonists may be important for leukocyte signal processing at the site of inflammation. Considering that monocytes/macrophages are likely to be the major source of cysteinyl-LT in many immunological and inflammatory processes, shedding light on how their receptors are regulated will certainly help to better understand the role of these cells in orchestrating this complex network of integrated signals. PMID:19965602

A novel formulation of L-thyroxine (L-T4) reduces the problem of L-T4 malabsorption by coffee observed with traditional tablet formulations.

Science.gov (United States)

Vita, Roberto; Saraceno, Giovanna; Trimarchi, Francesco; Benvenga, Salvatore

2013-02-01

The purpose of this work is to evaluate if the coffee-associated malabsorption of tablet levothyroxine (L-T4) is reduced by soft gel capsule. We recruited 8 patients with coffee-associated L-T4 malabsorption including one hypothyroid patient. For 6 months, the patients were switched to the capsule maintaining the L-T4 daily dose. Patients took the capsule with water, having coffee 1 h later (proper habit, PH) on days 1-90, or with coffee ≤ 5 min later (improper habit, IH) on days 91-180. After 6 months, 2 patients volunteered for an acute loading test of 600 μg L-T4 (capsule) ingested with water (PH) or with coffee (IH). In the single hypothyroid patient, the post-switch TSH ranged 0.06-0.16 mU/L (PH) versus 5.8-22.4 mU/L pre-switch (PH) and 0.025-0.29 mU/L (IH) versus 26-34 mU/L pre-switch (IH). In the other 7 patients, post-switch TSH was 0.41 ± 0.46 (PH) versus 0.28 ± 0.20 pre-switch (PH) (P = 0.61) and 0.34 ± 0.30 (IH) versus 1.23 ± 1.47 pre-switch (IH) (P coffee influenced L-T4 pharmacokinetics minimally. Soft gel capsules can be used in patients who are unable/unwilling to change their IH of taking L-T4.

A convenient synthesis of deuterated leukotriene A sub 4 methyl ester

Energy Technology Data Exchange (ETDEWEB)

Bestmann, H.J.; Roeder, T. (Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. fuer Organische Chemie); Meese, C.O. (Fischer-Bosch-Inst. fuer Klinische Pharmakologie, Stuttgart (Germany, F.R.))

1989-11-01

2,2,3,3-({sup 2}H{sub 4})-1-Iodopentane was prepared in four steps from propargyl alcohol and used in the C-alkylation of the THP-protected 3-butyne-1-ol. Subsequent protective group removal, semi-deuteration of the acetylenic alcohol and further transformation by known methods afforded the labelled key reagent 3,4,6,6,7,7-({sup 2}H{sub 6})-(Z)-(3-nonen-1-yl)triphenylphosphonium iodide. Wittig olefination of epoxy dienal with the ylide generated from the latter completed the convenient synthesis of hexadeuterated leukotriene A{sub 4} methyl ester. (author).

Effects of menadione, a reactive oxygen generator, on leukotriene secretion from RBL-2H3 cells.

Science.gov (United States)

Kawamura, Fumio; Nakanishi, Mamoru; Hirashima, Naohide

2010-01-01

Reactive oxygen species (ROS) are produced in various cells and affect many biological processes. We previously reported that 2-methyl-1,4-naphtoquinone (menadione) inhibited Ca(2+) influx from the extracellular medium and exocytosis evoked by antigen stimulation in the mast cell line, RBL-2H3. Mast cells release various inflammatory mediators such as leukotrienes (LTs) and cytokines in addition to the exocytotic secretion of histamine. In this study, we investigated the effects of menadione on LT release in RBL-2H3. Treatment of RBL cells with menadione inhibited LTC(4) secretion induced by antigen stimulation. To elucidate the mechanism of this inhibition, we examined the effects of menadione on the activation process of 5-lipoxygenase that is responsible for the synthesis of LTs from arachidonic acid. Menadione did not affect the phosophorylation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, which regulates phosphorylation of 5-lipoxygenase. However, menadione inhibited the translocation of 5-lipoxygenase from the cytoplasm to the nuclear membrane. Together with the result that LT secretion was severely impaired in the absence of extracellular Ca2(2+), it is suggested that ROS produced by menadione inhibited LT secretion through impaired Ca2(2+) influx and 5-lipoxygenase translocation to the nuclear membrane.

Resveratrol, a Red Wine Polyphenol, Suppresses Pancreatic Cancer by Inhibiting Leukotriene A4 Hydrolase

Science.gov (United States)

Oi, Naomi; Jeong, Chul-Ho; Nadas, Janos; Cho, Yong-Yeon; Pugliese, Angelo; Bode, Ann M.; Dong, Zigang

2016-01-01

The anticancer effects of red wine have attracted considerable attention. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a well-known polyphenolic compound of red wine with cancer chemopreventive activity. However, the basis for this activity is unclear. We studied leukotriene A4 hydrolase (LTA4H) as a relevant target in pancreatic cancer. LTA4H knockdown limited the formation of leukotriene B4 (LTB4), the enzymatic product of LTA4H, and suppressed anchorage-independent growth of pancreatic cancer cells. An in silico shape similarity algorithm predicted that LTA4H might be a potential target of resveratrol. In support of this idea, we found that resveratrol directly bound to LTA4H in vitro and in cells and suppressed proliferation and anchorage-independent growth of pancreatic cancer by inhibiting LTB4 production and expression of the LTB4 receptor 1 (BLT1). Notably, resveratrol exerted relatively stronger inhibitory effects than bestatin, an established inhibitor of LTA4H activity, and the inhibitory effects of resveratrol were reduced in cells where LTA4H was suppressed by shRNA-mediated knockdown. Importantly, resveratrol inhibited tumor formation in a xenograft mouse model of human pancreatic cancer by inhibiting LTA4H activity. Our findings identify LTA4H as a functionally important target for mediating the anticancer properties of resveratrol. PMID:20952510

Cysteinyl-Leukotriene Receptors and Cellular Signals

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G. Enrico Rovati

2007-01-01

Full Text Available Cysteinyl-leukotrienes (cysteinyl-LTs exert a range of proinflammatory effects, such as constriction of airways and vascular smooth muscle, increase of endothelial cell permeability leading to plasma exudation and edema, and enhanced mucus secretion. They have proved to be important mediators in asthma, allergic rhinitis, and other inflammatory conditions, including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. The classification into subtypes of the cysteinyl-LT receptors (CysLTRs was based initially on binding and functional data, obtained using the natural agonists and a wide range of antagonists. CysLTRs have proved remarkably resistant to cloning. However, in 1999 and 2000, the CysLT1R and CysLT2R were successfully cloned and both shown to be members of the G-protein coupled receptors (GPCRs superfamily. Molecular cloning has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Recombinant CysLTRs couple to the Gq/11 pathway that modulates inositol phospholipids hydrolysis and calcium mobilization, whereas in native systems, they often activate a pertussis toxin-insensitive Gi/o-protein, or are coupled promiscuously to both G-proteins. Interestingly, recent data provide evidence for the existence of an additional receptor subtype that seems to respond to both cysteinyl-LTs and uracil nucleosides, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Finally, a cross-talk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize recent data derived from studies on the molecular and cellular pharmacology of CysLTRs.

Stereoselective semi-hydrogenation and deuteration of a diacetylenic precursor of leukotriene B4 methyl ester

International Nuclear Information System (INIS)

Pontikis, R.; Le Merrer, Y.; Depezay, J.-C.; Petillot, Y.; Rousseau, B.; Beaucourt, J.P.

1990-01-01

[6,7,14,15- 2 H4]-Leukotriene B4 methyl ester was prepared by reduction with deuterium gas of a suitable precursor (deuterium incorporation > 90%). Several catalytic semi-hydrogenations were affected in order to determine the best conditions for the labeling step. (author)

A Systematic Review of Clinical Practice Guidelines' Recommendations on Levothyroxine Therapy Alone versus Combination Therapy (LT4 plus LT3) for Hypothyroidism.

Science.gov (United States)

Kraut, Eyal; Farahani, Pendar

2015-12-04

Patients with hypothyroidism are increasingly enquiring about the benefit of using combination therapy of levothyroxine (LT4) and liothyronine (LT3) as a potential treatment for hypothyroidism. Combination therapy, however, remains controversial. The purpose of this study was to systematically review available hypothyroidism treatment recommendations from clinical practice guidelines from around the world to identify the consensus regarding combination therapy. Clinical practice guidelines were obtained from searches of PubMed, EMBASE, and MEDLINE, using several combinations of MeSH terms. The search was limited to clinical guidelines in English-language publications, published between January 1, 1990 and May 1, 2015. A quantitative approach was utilized for data synthesis. Thirteen guidelines were identified, including three regarding pregnancy, two regarding pediatric populations and eight regarding adult populations. There were six guidelines from North America, four guidelines from Europe and three guidelines from South America. Twelve of the guidelines were published after 2010. Nine guidelines addressed combination therapy of LT4 plus LT3, and all nine concluded that LT4 therapy alone is the standard of care, with insufficient evidence to recommend widespread combination therapy. Only the 2012 ETA Guidelines and the 2015 BTA Guidelines concluded that combination therapy could be used, although only in certain circumstances and as an experimental treatment. This systematic review illustrates that clinical practice guidelines worldwide do not recommend and do not support routine use of combination LT4 and LT3 therapy to treat hypothyroidism.

The Role of Leukotriene B4 in Allergic Diseases

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Hiroshi Ohnishi

2008-01-01

Full Text Available Leukotriene B4 (LTB4 is a lipid mediator with potent chemoattractant properties and that is rapidly generated from activated innate immune cells such as neutrophils, macrophages, and mast cells. Elevated levels of LTB4 have been reported in various allergic diseases and these levels have been related to disease activity and response to treatment. Recent studies using LTB4 receptor-1 (BLT1 antagonists or BLT1-deficient mice have revealed that ligation of BLT1 by LTB4 is important for the activation and recruitment of inflammatory cells including neutrophils, eosinophils, monocytes/macrophages, mast cells, dendritic cells, and more recently, effector T cells to inflamed tissues in various inflammatory diseases. The LTB4/BLT1 pathway appears to play an important role in the pathogenesis of severe persistent asthma, aspirin- and exercise-induced asthma, allergic rhinitis, and atopic dermatitis together with other mediators including cysteinyl leukotrienes, cytokines, and chemokines. LTB4 production is in general resistant to corticosteroid treatment. In fact, corticosteroids can upregulate BLT1 expression on corticosteroid-resistant inflammatory cells such as neutrophils, monocytes, and effector memory CD8+ T cells. As a result, this corticosteroid-resistant LTB4/BLT1 pathway may contribute to the development of inflammation in allergic diseases that do not respond to the introduction of corticosteroids. Inhibition of this pathway has potential therapeutic benefit in various allergic diseases that have involvement of corticosteroid-insensitivity.

Significance of production of peptide leukotrienes in murine traumatic shock

International Nuclear Information System (INIS)

Craft, D.V.; Lefer, D.J.; Hock, C.E.; Lefer, A.M.

1986-01-01

The authors studied the formation of a leukotriene metabolite in plasma and bile during traumatic shock. Anesthetized rats subjected to Noble-Collip drum trauma developed a lethal shock state characterized by a survival time of 1.9 +/- 0.3h, a 4.5-fold increase in plasma cathepsin D activity, and a reduction in mean arterial blood pressure to 45 +/- 2 mmHg compared with 108 +/- 5 mmHg in sham-shock controls. Plasma and bile samples were analyzed by reverse-phase high-pressure liquid chromatography (HPLC) for peptide leukotrienes, and their retention times were confirmed by co-elution with radioactive standards, radioimmunoassay (RIA), and UV spectrophotometry. No leukotrienes or metabolites were found in plasma. The major peptide leukotriene from bile was eluted between LTC 4 and LTD 4 and corresponds to a metabolite of LTE 4 , N-acetyl-LTE 4 , which is also produced during endotoxin shock. The metabolite increased nearly sevenfold in traumatic shock compared with sham trauma. The identity of the metabolite was confirmed by UV scan, which revealed a spectrum consistent with a peptide leukotriene and similar to that of previously reported spectra for N-acetyl-LTE 4 . In conclusion, peptide leukotrienes are rapidly cleared from the blood and appear in the bile as N-acetyl-LTE 4 , a metabolite of the peptide leukotrienes. These findings support a role of the peptide leukotrienes in the pathogenesis of traumatic shock

Kinetic studies on binding of thyroid hormones (L-T3 and L-T4) to the receptors of lymphocyte cells isolated from uraemia subjects

International Nuclear Information System (INIS)

Al-Sultani, A.S.J.

1989-01-01

The levels of L-T 3 , L-T 4 and TSH in uremic sera have been measured by (RIA), and shown to have a decrease in both L-T 3 and L-T 4 levels with normal level of TSH for most specimens used in this study. Kinetics properties for binding of thyroid hormones L-T 3 and L-T 4 with nuclear receptors of human lymphocyte cells extracted from uremic patient have been studied and compared this result with control and hypothyroidism subjects and we obtained that uremic condition have a large effect on these nuclear receptors properties. Dissociation constant (K d ) and maximal binding capacity (MBC) of both L-T 3 and L-T 4 with these nuclear receptors have been determined, and we obtained that uremic condition did not affect on (K d ) values for both L-T 3 and L-T 4 but it affected on (MBC) values compared with normal subject. 8 tabs.; 25 figs.; 203 refs

In vivo formation of beta-oxidized metabolites of leukotriene E4 in the rat

International Nuclear Information System (INIS)

Perrin, P.; Zirrolli, J.; Stene, D.O.; Lellouche, J.P.; Beaucourt, J.P.; Murphy, R.C.

1989-01-01

Intraperitoneal administration of [ 3 H]-leukotriene E4 in the rat resulted in the appearance of radiolabel in urine and feces. Separation of polar urinary metabolites and chromatographic comparison of synthetic metabolites indicated the in vivo formation of omega-oxidized metabolites of LTE4 with sequential beta-oxidation. Furthermore, the metabolite identified as 16-carboxy-17,18,19,20-tetranor-14,15-dihydro-N-acetyl-LTE4 substantiates the biochemical pathway of beta-oxidation in vivo involving the 2,4-dienoyl CoA reductase as an integral step. These results substantiate beta-oxidation of sulfidopeptide leukotrienes in vivo and these metabolites account for some of the major urinary metabolites of this class of lipid mediator

A possible role for cysteinyl-leukotrienes in non-ionic contrast media induced adverse reactions

International Nuclear Information System (INIS)

Boehm, Ingrid; Speck, Ulrich; Schild, Hans

2005-01-01

Purpose: To test whether mono- or dimeric X-ray contrast media (CM) may induce the de novo production of cysteinyl-leukotriens (cys-LT), that could contribute to allergic/allergy-like side effects. Materials and methods: Leukocytes from 39 patients receiving iopromide or iotrolan for routine CT-examination were analyzed for the production of cys-LT. Histamine levels were analyzed in plasma specimens. One patient with a positive history of a previous CM-reaction did not receive CM-injection. Results: Three patients of the iopromide and five of the iotrolan group showed adverse reactions. Reactors had increased cys-LT values in samples obtained before CM-injection induced by the positive control (anti-FcεRI antibodies) (6763.7 pg/ml ± 1367.3 versus 2299.8 pg/ml ± 399.2; p < 0.007). Patients with versus without CM-reaction did not differ significantly with respect to their histamine values before CM-administeration. In vitro iopromide (p < 0.0002) and iotrolan (p < 0.0008) induced significant cys-LT production as compared to IL-3 stimulation. In vivo both CM induced a significant increase 6 h after CM administration (p < 0.05). Conclusion: Our findings suggest that both CM seem to induce cys-LT production. As to whether the observed increased values in pre-dose samples of patients with as compared to those without reactions could contribute to identify high risk patients should be investigated in larger patient groups in future

A possible role for cysteinyl-leukotrienes in non-ionic contrast media induced adverse reactions

Energy Technology Data Exchange (ETDEWEB)

Boehm, Ingrid [Department of Radiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany)]. E-mail: i.boehm@uni-bonn.de; Speck, Ulrich [Department of Radiology, Humboldt University (Charite) of Berlin (Germany); Schild, Hans [Department of Radiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany)

2005-09-01

Purpose: To test whether mono- or dimeric X-ray contrast media (CM) may induce the de novo production of cysteinyl-leukotriens (cys-LT), that could contribute to allergic/allergy-like side effects. Materials and methods: Leukocytes from 39 patients receiving iopromide or iotrolan for routine CT-examination were analyzed for the production of cys-LT. Histamine levels were analyzed in plasma specimens. One patient with a positive history of a previous CM-reaction did not receive CM-injection. Results: Three patients of the iopromide and five of the iotrolan group showed adverse reactions. Reactors had increased cys-LT values in samples obtained before CM-injection induced by the positive control (anti-Fc{epsilon}RI antibodies) (6763.7 pg/ml {+-} 1367.3 versus 2299.8 pg/ml {+-} 399.2; p < 0.007). Patients with versus without CM-reaction did not differ significantly with respect to their histamine values before CM-administeration. In vitro iopromide (p < 0.0002) and iotrolan (p < 0.0008) induced significant cys-LT production as compared to IL-3 stimulation. In vivo both CM induced a significant increase 6 h after CM administration (p < 0.05). Conclusion: Our findings suggest that both CM seem to induce cys-LT production. As to whether the observed increased values in pre-dose samples of patients with as compared to those without reactions could contribute to identify high risk patients should be investigated in larger patient groups in future.

Stereoselective semi-hydrogenation and deuteration of a diacetylenic precursor of leukotriene B sub 4 methyl ester

Energy Technology Data Exchange (ETDEWEB)

Pontikis, R.; Le Merrer, Y.; Depezay, J.-C. (U.D.C. CNRS-INSERM (URA 400), 75, Paris (France). Lab. de Chimie et Biochimie Pharamacologiques et Toxicologiques); Petillot, Y.; Rousseau, B.; Beaucourt, J.P. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service des Molecules Marquees)

1990-10-01

(6,7,14,15-{sup 2}H4)-Leukotriene B4 methyl ester was prepared by reduction with deuterium gas of a suitable precursor (deuterium incorporation > 90%). Several catalytic semi-hydrogenations were affected in order to determine the best conditions for the labeling step. (author).

Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children

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Barnes Peter J

2005-10-01

Full Text Available Abstract Background The role of leukotriene (LT B4, a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB4 in exhaled breath condensate (EBC has hampered its quantitative assessment in this biological fluid. We sought to measure LTB4 in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO was measured as an independent marker of airway inflammation. Methods Fifteen healthy children, 20 atopic nonasthmatic children, 25 steroid-naïve atopic asthmatic children, and 22 atopic asthmatic children receiving inhaled corticosteroids were studied. The study design was of cross-sectional type. Exhaled LTB4 concentrations were measured using liquid chromatography/mass spectrometry-mass spectrometry (LC/MS/MS with a triple quadrupole mass spectrometer. Exhaled NO was measured by chemiluminescence with a single breath on-line method. LTB4 values were expressed as the total amount (in pg of eicosanoid expired in the 15-minute breath test. Kruskal-Wallis test was used to compare groups. Results Compared with healthy children [87.5 (82.5–102.5 pg, median and interquartile range], exhaled LTB4 was increased in steroid-naïve atopic asthmatic [255.1 (175.0–314.7 pg, p 4 than steroid-naïve asthmatics [125.0 (25.0–245.0 pg vs 255.1 (175.0–314.7 pg, p Conclusion In contrast to exhaled NO concentrations, exhaled LTB4 values are selectively elevated in steroid-naïve atopic asthmatic children, but not in atopic nonasthmatic children. Although placebo control studies are warranted, inhaled corticosteroids seem to reduce exhaled LTB4 in asthmatic children. LC/MS/MS analysis of exhaled LTB4 might provide a non-invasive, sensitive, and quantitative method for airway inflammation assessment in asthmatic children.

Vascular effects of leukotriene D4 in human skin

DEFF Research Database (Denmark)

Bisgaard, H

1987-01-01

Leukotriene D4 (LTD4) increased the blood flow rate in human skin, equipotent to histamine in the dose range of 3.1-200 pmol. The vasodilatation lasted for up to 60 min, and no late reactions occurred. Indomethacin did not affect the LTD4-induced blood flow rate. H1 and H2 antagonists reduced...... as a mediator of the axon reflex, and show that LTD4 causes a direct vasodilatory effect that is not mediated via histamine or cyclooxygenase products. The laser-Doppler flowmeter was applied for dynamic studies of the vasopressor response in the skin during a Valsalva maneuver, and the relative changes...

Elevated Plasma Level of Leukotrienes in Bronchial Asthma Patients: A Possible Clinical Relevance

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Mahmoud Mansour

1994-01-01

Full Text Available Plasma from bronchial asthma patients and healthy controls was investigated for the content of lipoxygenase products. After lipid extraction using SEP-PAK C18 Cartridges, the lipoxygenase products were measured by Enzyme-Immunoassay. Elevated chemotactic B4 was found in plasma from asthmatic patients with mean value (483±75 pmoUL, while the mean value in normal healthy donors was (140± 12.1 pmol/L (M±SE. The levels of spasmogenic cysteinyl containing leukotrienes were also very high in the bronchial asthma patients. Elevations of leukotriene B4 and cysteinyl containing leukotrienes were detected during attacks of bronchial asthma. These results suggest that leukotriene B4 may be important in the pathogenesis of bronchial asthma and confirmed that peptidoleukotrienes playa role as chemical mediators during the asthmatic attack.

Identification of leukotriene D4 specific binding sites in the membrane preparation isolated from guinea pig lung

International Nuclear Information System (INIS)

Mong, S.; Wu, H.L.; Clark, M.A.; Stadel, J.M.; Gleason, J.G.; Crooke, S.T.

1984-01-01

A radioligand binding assay has been established to study leukotriene specific binding sites in the guinea pig and rabbit tissues. Using high specific activity [ 3 H]-leukotriene D4 [( 3 H]-LTD4), in the presence or absence of unlabeled LTD4, the diastereoisomer of LTD4 (5R,6S-LTD4), leukotriene E4 (LTE4) and the end-organ antagonist, FPL 55712, the authors have identified specific binding sites for [ 3 H]-LTD4 in the crude membrane fraction isolated from guinea pig lung. The time required for [ 3 H]-LTD4 binding to reach equilibrium was approximately 20 to 25 min at 37 degrees C in the presence of 10 mM Tris-HCl buffer (pH 7.5) containing 150 mM NaCl. The binding of [ 3 H]-LTD4 to the specific sites was saturable, reversible and stereospecific. The maximal number of binding sites (Bmax), derived from Scatchard analysis, was approximately 320 +/- 200 fmol per mg of crude membrane protein. The dissociation constants, derived from kinetic and saturation analyses, were 9.7 nM and 5 +/- 4 nM, respectively. The specific binding sites could not be detected in the crude membrane fraction prepared from guinea pig ileum, brain and liver, or rabbit lung, trachea, ileum and uterus. In radioligand competition experiments, LTD4, FPL 55712 and 5R,6S-LTD4 competed with [ 3 H]-LTD4. The metabolic inhibitors of arachidonic acid and SKF 88046, an antagonist of the indirectly-mediated actions of LTD4, did not significantly compete with [ 3 H]-LTD4 at the specific binding sites. These correlations indicated that these specific binding sites may be the putative leukotriene receptors in the guinea-pig lung

Leukotriene B4—leukotriene B4 receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8+ T cells

Science.gov (United States)

Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui

2015-01-01

Leukotriene B4 (LTB4) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8+ T cells. The role of the LTB4–BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8+ T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8+ T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8+ T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4–BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8+ T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. PMID:25959240

Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism.

LENUS (Irish Health Repository)

Adrees, M

2012-02-01

CONTEXT: Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short-term L-T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of L-T4 replacement in SCH are poorly understood. OBJECTIVES: To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of L-T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. DESIGN: Fifty-six women with SCH before and after L-T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin-C] in women with SCH before and after 18 months of l-T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after L-T4 in a subgroup of women with SCH. RESULTS: Systolic and diastolic BP, total cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0.05), and following L-T4 replacement decreased (P < 0.05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized following L-T4. Following L-T4 replacement the carotid artery baseline diameter increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12.5% and following endothelium-dependent vasodilatation by 17.5% (P < 0.05). However, the increment following reactive hyperaemia did not differ before or following L-T4 replacement. CONCLUSION: Normalization of

Increasing doses effect of L-T4 and L-T3 in the hypothalamus - hypophysis - thyroid in patients carrier of congenital and acquired hypothyroidism

International Nuclear Information System (INIS)

Cavaliere, H.

1987-01-01

The pituitary and peripheral response to L-T4 and L-T3 therapy were studied in 12 patients with congenital goitrous hypothyroidism, in 10 patients with an ectopic thyroid and onset of hypothyroidism at 3-8 years of age, and in 6 patients with adult-onset hypothyroidism, after they had had their chronic thyroid hormone replacement therapy discontinued for 30 days. They were first treated with increasing L-T4 (0.1, 0.2, and 0.4 mg daily) followed by L-T3 (0.05 and 0.2 mg daily) after stopping thyroid medication for another month. Ten normal subjects were treated identically. Since all patients received similar doses of thyroid hormones (μg/Kg of body weight) and had similar serum levels of T4 and T3 on each dose of L-T4 or L-T3, this paper concludes that congenitally hypothyroid patients have persistent pituitary resistance, but no peripheral resistance, to thyroid hormone. (author)

Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

Czech Academy of Sciences Publication Activity Database

Pelclová, D.; Fenclová, Z.; Vlčková, Š.; Lebedová, J.; Syslová, K.; Pecha, O.; Běláček, J.; Navrátil, Tomáš; Kuzma, Marek; Kačer, P.

2012-01-01

Roč. 50, č. 4 (2012), s. 299-306 ISSN 0019-8366 Institutional support: RVO:61388955 ; RVO:61388971 Keywords : leukotrienes * Lung fibrosis * exhaled breath condensate Subject RIV: CG - Electrochemistry Impact factor: 0.870, year: 2012

Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease

DEFF Research Database (Denmark)

Freiberg, J.J.; Tybjaerg-Hansen, A.; Sillesen, H.

2008-01-01

OBJECTIVE: Cysteinyl leukotrienes are involved in inflammation and possibly in early carotid atherosclerosis. We tested the hypothesis that the -444 A/C and -1072 G/A polymorphisms of the leukotriene C(4) synthase associate with risk of ischemic cerebrovascular disease. METHODS AND RESULTS: We...... genotyped 10 592 individuals from the Danish general population, the Copenhagen City Heart Study. During 24 years of follow-up, 557 individuals developed ischemic cerebrovascular disease. The allele frequency was 0.07 for -1072 A and 0.29 for -444 C. Cumulative incidence for ischemic cerebrovascular disease...... was higher for -1072 AA versus GG genotype (log-rank: P=0.002), and lower for -444 CC versus AA genotype (log-rank: P=0.008). Combined genotypes showed corresponding cumulative incidence differences (log-rank: P=0.003). Multifactorially adjusted hazard ratios for ischemic cerebrovascular disease were 2...

Simultaneous initiation of degranulation and inhibition of leukotriene release by soman in human basophils

Energy Technology Data Exchange (ETDEWEB)

Meier, H.L.; Warner, J.; MacGlashan, D.W.

1995-12-31

Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.

Influence of leukotriene gene polymorphisms on chronic rhinosinusitis

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Duval Melanie

2008-03-01

Full Text Available Abstract Background Chronic rhinosinusitis (CRS is increasingly viewed as an inflammatory condition of the sinonasal mucosa interacting with bacteria and/or fungi. However, factors conferring susceptibility to disease remain unknown. Advances in genomics offer powerful tools to explore this disorder. The goal of this study was to evaluate the effect of single nucleotide polymorphisms (SNP on CRS in a panel of genes related to cysteinyl leukotriene metabolism. Methods Severe cases of CRS and postal code match controls were recruited prospectively. A total of 206 cases and 200 controls were available for the present study. Using a candidate gene approach, five genes related to cysteinyl leukotriene metabolism were assessed. For each gene, we selected the maximally informative set of common SNPs (tagSNPs using the European-derived (CEU HapMap dataset. These SNPs are in arachidonate 5-lipoxygenase (ALOX5, arachidonate 5-lipoxygenase-activating protein (ALOX5AP, leukotriene C4 synthase (LTC4S, cysteinyl leukotriene receptor 1 (CYSLTR1 and cysteinyl leukotriene receptor 2 (CYSLTR2 genes. Results A total of 59 SNPs were genotyped to capture the common genetic variations within these genes. Three SNPs located within the ALOX5, CYSLTR1 and ALOX5AP genes reached the nominal p-value threshold (p Conclusion While these initial results do not support that polymorphsims in genes assessed involved in the leukotriene pathways are contributing to the pathogenesis of CRS, this initial study was not powered to detect polymorphisms with relative risk of 2.0 or less, where we could expect many gene effects for complex diseases to occur. Thus, despite this lack of significant association noted in this study, we believe that validation with external populations and the use of better-powered studies in the future may allow more conclusive findings.

2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

DEFF Research Database (Denmark)

Nygaard, Birte

2012-01-01

. Results: Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues...

A radiochemical assay for detection of leukotriene B4 production from isolated cells

International Nuclear Information System (INIS)

Aharony, D.; Dobson, P.; Krell, R.D.

1984-01-01

A radiochemical procedure for quantitating the effect of inhibitors of leukotriene B4 (LTB4) biosynthesis is described. Rat peritoneal cells were labeled with 3 H-arachidonic acid and stimulated with the calcium ionophore A23187. 3 H-LTB4 was isolated by processing on C18-Sep Pak cartridges followed by reverse-phase high pressure liquid chromatography (HPLC). The identity of this product, as well as other arachidonic acid metabolites, was verified by using silicic acid column chromatography followed by straight-phase HPLC and thin layer chromatography. Using this assay, LTB4 release by ionophore A23187 has been shown to be both time- and concentration-dependent. Indomethacin enhanced, while NDGA and ETYA inhibited, the A23187-induced production of LTB4. This procedure is both simple and direct and is capable of assessing the ability of novel compounds to alter LTB4 production

CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

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Capra Valérie

2006-03-01

Full Text Available Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC proliferation. We used human ASMC (HASMC to identify the signal transduction pathway(s of the leukotriene D4 (LTD4-induced DNA synthesis. Methods Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS was estimated by measuring dichlorodihydrofluorescein (DCF oxidation. Results We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX and phosphoinositide 3-kinase (PI3K inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Conclusion Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF

Sesquiterpene glucosides from anti-leukotriene B4 release fraction of Taraxacum officinale.

Science.gov (United States)

Kashiwada, Y; Takanaka, K; Tsukada, H; Miwa, Y; Taga, T; Tanaka, S; Ikeshiro, Y

2001-01-01

Chemical examination of the MeOH extract of the root of Taraxacum officinale, which exhibited inhibitory activity on the formation of leukotriene B4 from activated human neutrophils, has resulted in the isolation of 14-O-beta-D-glucosyl-11,13-dihydro-taraxinic acid (1) and 14-O-beta-D-glucosyl-taraxinic acid (2). The absolute stereostructure of 1 has been established by X-ray chrystallographic examination.

A new practical method for the preparation of [3H6]-leukotrienes C4 and D4

International Nuclear Information System (INIS)

Belley, M.L.; Gareau, Y.; Zamboni, R.J.; Ahern, D.G.; Yang Hong

1995-01-01

A new method for the synthesis of highly deuterated or tritiated leukotrienes was developed. The higher reactivity of a terminal alkene compared to a 1,2-disubstituted one permitted the selective deuteration or tritiation of the diyne 14,15,19,19,20,20-hexadehydro LTC 4 troester 1. After hydrolysis, LTC 4 was obtained in 36% overall yield. An average of seven deuterium or tritium atoms was incorporated and the specific activity of the tritiated LTC 4 was greater than 180Ci/mmol. 1 was obtained from the addition of glutathione to 14,15,19,19,20,20-hexadehydro LTA 4 ethyl ester which was the product of a Wittig reaction between (3,8-nonanediyn-1-yl) triphenylphosphonium iodide and 5(S), 6(S), 7(E), 9(E) ethyl 5,6-epoxy-11-oxo-7,9-undecadienoate. (Author)

The Role of PPAR Receptors and Leukotriene B4 Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer

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Thomas E. Adrian

2008-01-01

Full Text Available Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPAR pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B4 receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPAR agonist activity in addition to its effects on the 5-lipoxygenase pathway. This raises the question of which of the two targets is of greatest importance with regard to the anticancer effects of this agent. The evidence to date is not conclusive, but suggests that the effects of LY293111 may be mediated by both LTB4 receptors and PPAR.

CysLT2 receptor activation is involved in LTC4-induced lung air-trapping in guinea pigs.

Science.gov (United States)

Sekioka, Tomohiko; Kadode, Michiaki; Yonetomi, Yasuo; Kamiya, Akihiro; Fujita, Manabu; Nabe, Takeshi; Kawabata, Kazuhito

2017-01-05

CysLT 1 receptors are known to be involved in the pathogenesis of asthma. However, the functional roles of CysLT 2 receptors in this condition have not been determined. The purpose of this study is to develop an experimental model of CysLT 2 receptor-mediated LTC 4 -induced lung air-trapping in guinea pigs and use this model to clarify the mechanism underlying response to such trapping. Because LTC 4 is rapidly converted to LTD 4 by γ-glutamyltranspeptidase (γ-GTP) under physiological conditions, S-hexyl GSH was used as a γ-GTP inhibitor. In anesthetized artificially ventilated guinea pigs with no S-hexyl GSH treatment, i.v. LTC 4 -induced bronchoconstriction was almost completely inhibited by montelukast, a CysLT 1 receptor antagonist, but not by BayCysLT 2 RA, a CysLT 2 receptor antagonist. The inhibitory effect of montelukast was diminished by treatment with S-hexyl GSH, whereas the effect of BayCysLT 2 RA was enhanced with increasing dose of S-hexyl GSH. Macroscopic and histological examination of lung tissue isolated from LTC 4 -/S-hexyl-GSH-treated guinea pigs revealed air-trapping expansion, particularly at the alveolar site. Inhaled LTC 4 in conscious guinea pigs treated with S-hexyl GSH increased both airway resistance and airway hyperinflation. On the other hand, LTC 4 -induced air-trapping was only partially suppressed by treatment with the bronchodilator salmeterol. Although montelukast inhibition of LTC 4 -induced air-trapping was weak, treatment with BayCysLT 2 RA resulted in complete suppression of this air-trapping. Furthermore, BayCysLT 2 RA completely suppressed LTC 4 -induced airway vascular hyperpermeability. In conclusion, we found in this study that CysLT 2 receptors mediate LTC 4 -induced bronchoconstriction and air-trapping in S-hexyl GSH-treated guinea pigs. It is therefore believed that CysLT 2 receptors contribute to asthmatic response involving air-trapping. Copyright © 2016 Elsevier B.V. All rights reserved.

Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update.

Science.gov (United States)

Fallahi, Poupak; Ferrari, Silvia Martina; Ruffilli, Ilaria; Ragusa, Francesca; Biricotti, Marco; Materazzi, Gabriele; Miccoli, Paolo; Antonelli, Alessandro

2017-05-01

The most recent advance concerning levothyroxine (L-T4) therapy is the development of novel oral formulations: the liquid preparation, and the soft gel capsule. Areas covered: This review evaluates the most recent clinical studies about these new formulations. The liquid formulation has been shown to overcome: the food and beverages intereference with L-T4 tablets absorption, caused by food or coffee at breakfast; malabsorption induced by the increased gastric pH, resulting from atrophic gastritis, or due to proton-pump inhibitors; and malabsorption after bariatric surgery. The use of liquid L-T4 has been studied also in pregnancy, newborns and infants, suggesting a better bioequivalence than tablets. Finally, liquid L-T4 is more active than tablets in the control of thyroid-stimulating hormone (TSH) in hypothyroid patients without malabsorption, drug interference, or gastric disorders, leading to a hypothesized higher absorption of liquid L-T4 also in these patients. Few studies have evaluated soft gel L-T4 with promising results in patients with malabsorption related to coffee or gastritis. Expert opinion: Liquid L-T4 (and soft gel capsules) are more active than the tablet L-T4 in the control of TSH in hypothyroid patients with gastric disorders, malabsorption, or drug interference, but also in patients without absorption disorders.

Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma

DEFF Research Database (Denmark)

Bisgaard, H

2001-01-01

, exudation of macromolecules and edema. The cysteinyl leukotrienes also have potent chemoattractant properties for eosinophils, causing an influx of eosinophils into the airway mucosa, which further fuels the inflammatory process. In addition, the cysteinyl leukotrienes are potent secretagogues and reduce...... and pranlukast inhibit bronchoconstriction in asthmatic patients undergoing allergen, exercise, cold air or aspirin challenge. They attenuate the hallmarks of asthmatic inflammation, including eosinophilia in the airway mucosa and peripheral blood. Moreover, exhaled nitric oxide concentrations, another correlate...

A study of the photodegradation of leukotriene B4 by ultraviolet irradiation (UVB, UVA)

International Nuclear Information System (INIS)

Millar, B.; Green, C.; Ferguson, J.; Raffle, E.J.; Macleod, T.M.

1989-01-01

In view of the presence of the polymorphonuclear leukocyte (PMN) chemoattractant Leukotriene B 4 (LTB 4 ) in surface scale of the psoriatic lesion and the known therapeutic effect of phototherapy in psoriasis, the photostability of LTB 4 was investigated. LTB 4 was irradiated with UVB (290-320 nm) from 100-1500 mJ cm -2 and UVA (320-400 nm) from 5-40 J cm -2 . Topical application of UVB irradiated LTB 4 to forearm skin of normal volunteers showed marked reduction in cutaneous erythema, paralleled by reduced transepidermal PMN migration compared with sites of application of unirradiated and UVA irradiated LTB 4 . High performance liquid chromatography (HPLC) demonstrated a dose-dependent photodegradation of LTB 4 by UVB irradiation. UVA irradiation produced no such effect. The wavelengths responsible lie within the absorption spectrum of LTB 4 . In vitro chemotaxis studies, using an under agarose technique, showed a statistically significant reduction in the migration of PMN from psoriatic and non-psoriatic subjects to the UVB irradiated LTB 4 compared with unirradiated LTB 4 , whilst UVA irradiated LTB 4 produced a normal PMN chemotactic response. (author)

Urinary Leukotriene E4 Is Associated with Renal Function but Not with Endothelial Function in Type 2 Diabetes

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Arnar Rafnsson

2013-01-01

Full Text Available Leukotrienes are inflammatory and vasoactive mediators implicated in endothelium-dependent relaxations and atherosclerosis. Urinary leukotriene E4 (U-LTE4 is a validated disease marker of asthma and increases also in diabetes and acute coronary syndromes. The aim of the present study was to evaluate the association of U-LTE4 and CRP with endothelial function. Urine samples were obtained from 30 subjects (80% males; median age 65 with type 2 diabetes of at least two years duration and a median glomerular filtration rate (eGFR of 71 (14–129 mL/min. Reactive hyperemia index (RHI was used as a measure of microvascular endothelial function, whereas macrovascular endothelial function was determined be means of flow-mediated dilatation of the brachial artery (FMD. Decreased renal function was associated with lower concentrations of U-LTE4. In addition, U-LTE4 was correlated with serum creatinine (R=−0.572; P=0.001 and eGFR (R=0.517; P=0.0036. A stepwise multiple linear regression analysis identified eGFR as an independent predictor of U-LTE4 concentrations. In conclusion, the present results did not establish an association of U-LTE4 with endothelial dysfunction. However, eGFR was an independent predictor of U-LTE4, but not CRP, in this cohort, suggesting that GFR should be considered in biomarker studies of U-LTE4.

COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

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José Wander BREGANÓ

2014-09-01

Full Text Available Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be

Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes.

Science.gov (United States)

Shak, S; Goldstein, I M

1984-08-25

Leukotriene B4 (LTB4), formed by the 5-lipoxygenase pathway in human polymorphonuclear leukocytes (PMN), may be an important mediator of inflammation. Recent studies suggest that human leukocytes can convert LTB4 to products that are less biologically active. To examine the catabolism of LTB4, we developed (using high performance liquid chromatography) a sensitive, reproducible assay for this mediator and its omega-oxidation products (20-OH- and 20-COOH-LTB4). With this assay, we have found that human PMN (but not human monocytes, lymphocytes, or platelets) convert exogenous LTB4 almost exclusively to 20-OH- and 20-COOH-LTB4 (identified by gas chromatography-mass spectrometry). Catabolism of exogenous LTB4 by omega-oxidation is rapid (t1/2 approximately 4 min at 37 degrees C in reaction mixtures containing 1.0 microM LTB4 and 20 X 10(6) PMN/ml), temperature-dependent (negligible at 0 degrees C), and varies with cell number as well as with initial substrate concentration. The pathway for omega-oxidation in PMN is specific for LTB4 and 5(S),12(S)-dihydroxy-6,8,10,14-eicosatetraenoic acid (only small amounts of other dihydroxylated-derivatives of arachidonic acid are converted to omega-oxidation products). Even PMN that are stimulated by phorbol myristate acetate to produce large amounts of superoxide anion radicals catabolize exogenous leukotriene B4 primarily by omega-oxidation. Finally, LTB4 that is generated when PMN are stimulated with the calcium ionophore, A23187, is rapidly catabolized by omega-oxidation. Thus, human PMN not only generate and respond to LTB4, but also rapidly and specifically catabolize this mediator by omega-oxidation.

Urinary leukotriene E4 at 12 months and influencing factors

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K Stencel-Gabriel

2016-01-01

• 3.        Department of Gynecology, Obstetrics and Oncological Gynecology, Bytom, Medical University of Silesia       Corresponding author: Krystyna Stencel-Gabriel ul. Batorego 15 41-902 Bytom   Keywords: leukotriene E4, infants, allergy, urine.   Summary Objective LTE4 is the end point of cysLTs pathway and its only stable product. Its role was discussed in asthma and AEDS. We aimed to investigate the impact of genetic and environmental factors ( sex, maternal positive family atopy history, breastfeeding, passive smoking and pet exposure . 60 newborns ( including 30 boys were enrolled in the study. Each child was examined at 12 months and urine samples for urinary LTE4 measurement were collected. All samples were processed using ACETM Enzyme Immunoassay Kit ( Cayman Chemical, Ann Arbor, MI, USA . The mean level of urinary LTE4 at 12 months was 186,99 pg/ml ( median: 159,0; CI 95%: 157,79- 221,59 . The Shapiro- Wilk test showed that the distribution of the levels of urinary LTE4 were abnormal. 12- month- old girls had higher urinary LTE4 levels than boys ( mean: 270,50 vs. 193,55 , but maternal positive atopy history, pet exposure, tobacco smoking or length of breastfeeding had no impact on urinary LTE4 excretion. Conclusions In conclusion, most of genetic or environmental factors do not change levels of urinary LTE4 in infants.

Modulation of the heterogeneous membrane potential response of neutrophils to N-formyl-methionyl-leucyl-phenylalanine (FMLP) by leukotriene B4: evidence for cell recruitment

International Nuclear Information System (INIS)

Fletcher, M.P.

1986-01-01

Individual human neutrophils (PMN) isolated by Hypaque-Ficoll gradient sedimentation, dextran sedimentation, or buffy coat preparation were assessed for the effects of leukotriene B4 (5S,12R dihydroxy 6,14-cis-8, 10 trans eicosatetraenoic acid (LTB4)-pretreatment on N-formylmethionyl-leucyl-phenylalanine (FMLP)-mediated membrane potential or oxidative responses by using flow cytometry and a lipophilic probe of membrane potential (di-pentyl-oxacarbocyanine, di-O-C(5)3), or the nitroblue tetrazolium dye (NBT) reduction test, respectively. Although exposure to LTB4 (10(-7) M) had no effect on the membrane potential of resting PMN and little effect on oxidant production, pretreating PMN with LTB4 followed by FMLP (10(-6) M) demonstrated a significant enhancement in the proportion of depolarizing PMN over that seen with FMLP alone (p = 0.0014, N = 9). This recruitment of previously unresponsive cells by LTB4 was dose and time dependent, with the maximal relative increase in the proportion of depolarizing cells occurring at LTB4 concentrations of 10(-8) to 10(-7) M and within 1 min of LTB4 addition. The recruitment effect persisted despite vigorous washing of the cells. LTB4 also increased the proportion of NBT-positive PMN in response to FMLP. Although LTB4 alone did not depolarize PMN it did induce a light scatter shift indicative of cell activation. 3 H-FMLP binding studied at 0 degree C comparing buffer and LTB4-treated PMN indicated no significant change in the number or affinity of FMLP binding. The data provide evidence for the recruitment of a greater proportion of cells into a FMLP-responsive state as a mechanism for the enhanced functional response of PMN pretreated with LTB4, as well as for a dissociation of the membrane potential and light scattering responses of cells to this pro-inflammatory LT

A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

International Nuclear Information System (INIS)

Ismail, Norazren; Jambari, Nuzul Nurahya; Zareen, Seema; Akhtar, Mohamad Nadeem; Shaari, Khozirah; Zamri-Saad, Mohamad; Tham, Chau Ling; Sulaiman, Mohd Roslan; Lajis, Nordin Hj; Israf, Daud Ahmad

2012-01-01

Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics. -- Highlights: ► Safer and effective anti-asthmatic drugs are in great demand. ► tHGA is a new 5-LO/cysLT inhibitor that inhibits allergic asthma in mice. ► tHGA is a natural compound that can be synthesized. ► Doses as low as 2 mg/kg alleviate lung pathology in experimental asthma. ► tHGA is a potential drug lead for the treatment of allergic asthma.

The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

Science.gov (United States)

Barden, Anne E; Shinde, Sujata; Burke, Valerie; Puddey, Ian B; Beilin, Lawrence J; Irish, Ashley B; Watts, Gerald F; Mori, Trevor A

2018-03-22

Neutrophils release leukotriene (LT)B 4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB 5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB 4 . This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB 5 (P n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB 5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

4-Hydroxynonenal enhances MMP-9 production in murine macrophages via 5-lipoxygenase-mediated activation of ERK and p38 MAPK

International Nuclear Information System (INIS)

Lee, Seung J.; Kim, Chae E.; Yun, Mi R.; Seo, Kyo W.; Park, Hye M.; Yun, Jung W.; Shin, Hwa K.; Bae, Sun S.; Kim, Chi D.

2010-01-01

Exaggerated levels of 4-hydroxynonenal (HNE) and 5-lipoxygenase (5-LO) co-exist in macrophages in atherosclerotic lesions, and activated macrophages produce MMP-9 that degrades atherosclerotic plaque constituents. This study investigated the effects of HNE on MMP-9 production, and the potential role for 5-LO derivatives in MMP-9 production in murine macrophages. Stimulation of J774A.1 cells with HNE led to activation of 5-LO, as measured by leukotriene B 4 (LTB 4 ) production. This was associated with an increased production of MMP-9, which was blunted by inhibition of 5-LO with MK886, a 5-LO inhibitor or with 5-LO siRNA. A cysteinyl-LT 1 (cysLT 1 ) receptor antagonist, REV-5901 as well as a BLT 1 receptor antagonist, U-75302, also attenuated MMP-9 production induced by HNE. Furthermore, LTB 4 and cysLT (LTC 4 and LTD 4 ) enhanced MMP-9 production in macrophages, suggesting a pivotal role for 5-LO in HNE-mediated production of MMP-9. Among the MAPK pathways, LTB 4 and cysLT enhanced phosphorylation of ERK and p38 MAPK, but not JNK. Linked to these results, a p38 MAPK inhibitor as well as an ERK inhibitor blunted MMP-9 production induced by LT. Collectively, these data suggest that 5-LO-derived LT mediates HNE-induced MMP-9 production via activation of ERK and p38 MAPK pathways, consequently leading to plaque instability in atherosclerosis.

Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist

Directory of Open Access Journals (Sweden)

James P Kemp

2009-11-01

Full Text Available James P KempClinical Professor of Pediatrics, Division of Immunology and Allergy, University of California School of Medicine, San Diego, CA, USAAbstract: Exercise-induced bronchoconstriction (EIB is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for patients with this condition. A better understanding of EIB will allow the physician to direct the patient towards a type of exercise and medications that can result in a more active lifestyle without the same concern for resulting symptoms. This is especially important for schoolchildren who are usually enrolled in physical education classes and elite athletes who may desire to participate in competitive sports. Fortunately several medications (short- and long-acting β2-agonists, cromolyn, nedocromil, inhaled corticosteroids, and more recently leukotriene modifiers have been shown to be effective in preventing or attenuating the effects of exercise in many patients. In addition, inhaled β2-agonists have been shown to quickly reverse the airway obstruction that develops in patients and continue to be the reliever medications of choice. Inhaled corticosteroids are increasingly being recommended as regular therapy now that the role of inflammation and airway injury has been identified in EIB. With the discovery that there is a release of mediators such as histamine and leukotrienes from cells in the airway following exercise with resulting airway obstruction in susceptible individuals, interest has turned to attenuating their effects with mediator antagonists especially those that block the effects of leukotrienes. Studies with an oral leukotriene antagonist, montelukast, have shown beneficial effects in adults and children aged as young as 6 years with EIB

Association between the clinical classification of hypothyroidism and reduced TSH in LT4 supplemental replacement treatment for pregnancy in China.

Science.gov (United States)

Zhang, Lyu; Zhang, Zhaoyun; Ye, Hongying; Zhu, Xiaoming; Li, Yiming

2016-01-01

The study was aimed to evaluate the effects of levothyroxine (LT4) supplemental replacement treatment for pregnancy and analyze the associations between the clinical classification of hypothyroidism and reduced thyroid-stimulating hormone (TSH) in LT4 therapy. Totally, 195 pregnant women with hypothyroidism receiving routine prenatal care were enrolled. They were categorized into three groups: overt hypothyroidism (OH), subclinical hypothyroidism (SCH) with negative thyroperoxidase antibody (TPOAb), and SCH with positive TPOAb. The association between the clinical classification and reduced TSH in LT4 supplemental replacement treatment was assessed. The results indicated that reduced TSH was significantly different among the groups according to the clinical classifications (p = 0.043). The result was also significantly different between patients with OH and patients with SCH and negative TPOAb (p = 0.036). Similar result was reported for the comparison between patients with OH and patients with SCH and positive TPOAb (p = 0.016). Multiple variable analyses showed that LT4 supplementation, gestational age and the variable of clinical classifications were associated with reduced TSH independently. Our data suggested that the therapeutic effect of substitutive treatment with LT4 was significantly associated with different clinical classifications of hypothyroidism in pregnancy and the treatment should begin as soon as possible after diagnosis.

Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

Science.gov (United States)

Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

2015-06-16

Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Staphylococcus aureus and influenza A virus stimulate human bronchoalveolar cells to release histamine and leukotrienes

DEFF Research Database (Denmark)

Clementsen, P; Bisgaard, H; Pedersen, M

1989-01-01

persons were stimulated with Staph. aureus no release of leukotriene C4 was found. The mediator release caused by bacteria and virus might be of importance for the exacerbation of bronchial asthma in upper respiratory tract infections, since histamine is assumed to increase the epithelial permeability...

Interpretation of the CABRI LT1 test with SAS4A-code analysis

International Nuclear Information System (INIS)

Sato, Ikken; Onoda, Yu-uichi

2001-03-01

In the CABRI-FAST LT1 test, simulating a ULOF (Unprotected Loss of Flow) accident of LMFBR, pin failure took place rather early during the transient. No fuel melting is expected at this failure because the energy injection was too low and a rapid gas-release-like response leading to coolant-channel voiding was observed. This channel voiding was followed by a gradual fuel breakup and axial relocation. With an aid of SAS4A analysis, interpretation of this test was performed. Although the original SAS4A model was not well fitted to this type of early pin failure, the global behavior after the pin failure was reasonably simulated with temporary modifications. Through this study, gas release behavior from the failed fuel pin and its effect on further transient were well understood. It was also demonstrated that the SAS4A code has a potential to simulate the post-failure behavior initiated by a very early pin failure provided that necessary model modification is given. (author)

Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis

DEFF Research Database (Denmark)

Hillingsø, Jens; Kjeldsen, J; Laursen, L S

1995-01-01

dialysis fluid, ex vivo biosynthesis of LTB4 in whole blood, and urinary excretion of leukotriene E4 (LTE4) from 16 patients with mild to moderately active distally located ulcerative colitis were measured by use of radioimmunoassays in a double-blind, placebo-controlled parallel-design study before...... was unchanged. In whole blood, MK-0591 decreased ex vivo biosynthesis of LTB4 (p LTE4 was reduced by more than 85% (p

Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B4 induces an OKT8(+), radiosensitive suppressor cell from resting, human OKT8(-) T cells

International Nuclear Information System (INIS)

Atluru, D.; Goodwin, J.S.

1984-01-01

We report that leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of arachidonic acid, is a potent suppressor of polyclonal Ig production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood lymphocytes, while LTC4 and LTD4 have little activity in this system. Preincubation of T cells with LTB4 in nanomolar to picomolar concentrations rendered these cells suppressive of Ig production in subsequent PWM-stimulated cultures of fresh, autologous B + T cells. This LTB4-induced suppressor cell was radiosensitive, and its generation could be blocked by cyclohexamide but not by mitomycin C. The LTB4-induced suppressor cell was OKT8(+), while the precursor for the cell could be OKT8(-). The incubation of OKT8(-) T cells with LTB4 for 18 h resulted in the appearance of the OKT8(+) on 10-20% of the cells, and this could be blocked by cyclohexamide but not by mitomycin C. Thus, LTB4 in very low concentrations induces a radiosensitive OKT8(+) suppressor cell from OKT8(-) cells. In this regard, LTB4 is three to six orders of magnitude more potent than any endogenous hormonal inducer of suppressor cells previously described. Glucocorticosteroids, which block suppressor cell induction in many systems, may act by inhibiting endogenous production of LTB4

Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children

DEFF Research Database (Denmark)

Bisgaard, H; Nielsen, K G

2000-01-01

We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5...

Hypothyroid Patients Encoding Combined MCT10 and DIO2 Gene Polymorphisms May Prefer L-T3 + L-T4 Combination Treatment - Data Using a Blind, Randomized, Clinical Study

DEFF Research Database (Denmark)

Carlé, Allan; Faber, Jens; Steffensen, Rudi

2017-01-01

on the cellular membrane transport-facilitating monocarboxylate transporter (MCT10) gene (rs17606253), and asked in which of the 2 treatment periods patients felt better (i.e., which treatment was preferred). RESULTS: 27 out of 45 patients (60%) preferred the combination therapy. Two polymorphisms (rs225014 (DIO2......, Thr92Ala) and rs17606253 (MCT10)) were combined yielding 3 groups: none vs. 1 of 2 vs. both SNPs present, and 42 vs. 63 vs. 100% of our patients in the 3 groups preferred the combined treatment (Jongheere-Terpstra trend test, p = 0.009). CONCLUSION: The present study indicates that the combination...... of polymorphisms in DIO2 (rs225014) and MCT10 (rs17606253) enhances hypothyroid patients' preference for L-T4 + L-T3 replacement therapy. In the future, combination therapy may be restricted or may be even recommended to individuals harbouring certain polymorphisms....

The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.

Science.gov (United States)

Bagattini, Brunella; Cosmo, Caterina Di; Montanelli, Lucia; Piaggi, Paolo; Ciampi, Mariella; Agretti, Patrizia; Marco, Giuseppina De; Vitti, Paolo; Tonacchera, Massimo

2014-11-01

Levothyroxine (l-T4) is commonly employed to correct hormone deficiency in children with congenital hypothyroidism (CH) and in adult patients with iatrogenic hypothyroidism. To compare the daily weight-based dosage of the replacement therapy with l-T4 in athyreotic adult patients affected by CH and adult patients with thyroid nodular or cancer diseases treated by total thyroidectomy. A total of 36 adult patients (27 females and nine males) aged 18-29 years were studied; 13 patients (age: 21.5±2.1, group CH) had athyreotic CH treated with l-T4 since the first days of life. The remaining 23 patients (age: 24±2.7, group AH) had hypothyroidism after total thyroidectomy (14 patients previously affected by nodular disease and nine by thyroid carcinoma with clinical and biochemical remission). Patient weight, serum free thyroid hormones, TSH, thyroglobulin (Tg), anti-Tg, and anti-thyroperoxidase antibodies were measured. Required l-T4 dosage was evaluated. At the time of the observations, all patients presented free thyroid hormones within the normal range and TSH between 0.8 and 2 μIU/ml. Patients had undetectable Tg and anti-thyroid antibodies. The daily weight-based dosage of the replacement therapy with l-T4 to reach euthyroidism in patients of group CH was significantly higher than that in those of group AH (2.16±0.36 vs 1.73±0.24 μg/kg, Phypothyroidism, patients of group CH required a daily l-T4 dose/kg higher than group AH patients, despite higher levels of TSH. The different requirement of replacement therapy between adult patients with congenital and those with surgical athyroidism could be explained by a lack of thyroid hormones since fetal life in CH, which could determine a different set point of the hypothalamus-pituitary-thyroid axis. © 2014 European Society of Endocrinology.

Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

Science.gov (United States)

Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

2015-01-01

Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils.

Science.gov (United States)

Hallstrand, Teal S; Lai, Ying; Hooper, Kathryn A; Oslund, Rob C; Altemeier, William A; Matute-Bello, Gustavo; Gelb, Michael H

2016-01-01

Phospholipase A2s mediate the rate-limiting step in the formation of eicosanoids such as cysteinyl leukotrienes (CysLTs). Group IVA cytosolic PLA2α (cPLA2α) is thought to be the dominant PLA2 in eosinophils; however, eosinophils also have secreted PLA2 (sPLA2) activity that has not been fully defined. To examine the expression of sPLA2 group X (sPLA2-X) in eosinophils, the participation of sPLA2-X in the formation of CysLTs, and the mechanism by which sPLA2-X initiates the synthesis of CysLTs in eosinophils. Peripheral blood eosinophils were obtained from volunteers with asthma and/or allergy. A rabbit polyclonal anti-sPLA2-X antibody identified sPLA2-X by Western blot. We used confocal microscopy to colocalize the sPLA2-X to intracellular structures. An inhibitor of sPLA2-X (ROC-0929) that does not inhibit other mammalian sPLA2s, as well as inhibitors of the mitogen-activated kinase cascade (MAPK) and cPLA2α, was used to examine the mechanism of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated formation of CysLT. Eosinophils express the mammalian sPLA2-X gene (PLA2G10). The sPLA2-X protein is located in the endoplasmic reticulum, golgi, and granules of eosinophils and moves to the granules and lipid bodies during fMLP-mediated activation. Selective sPLA2-X inhibition attenuated the fMLP-mediated release of arachidonic acid and CysLT formation by eosinophils. Inhibitors of p38, extracellular-signal-regulated kinases 1/2 (p44/42 MAPK), c-Jun N-terminal kinase, and cPLA2α also attenuated the fMLP-mediated formation of CysLT. The sPLA2-X inhibitor reduced the phosphorylation of p38 and extracellular-signal-regulated kinases 1/2 (p44/42 MAPK) as well as cPLA2α during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leading to the formation of CysLT via cPLA2α. We further demonstrate that sPLA2-X is activated before secretion from the cell during activation. Short-term priming with IL-13 and TNF/IL-1β increased the

Analysis of Exhaled Leukotrienes in Nonasthmatic Adult Patients with Seasonal Allergic Rhinitis

Czech Academy of Sciences Publication Activity Database

Čáp, P.; Pehal, F.; Malý, Marek; Chládek, J.

2005-01-01

Roč. 60, č. 2 (2005), s. 171-176 ISSN 0105-4538 Source of funding: V - iné verejné zdroje Keywords : allergic rhinitis * asthma * breath condensate * gas-chromatography/mass spectrometry analysis * leukotrienes Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 4.120, year: 2005

The effect of the leukotriene antagonist pranlukast on pediatric acute otitis media.

Science.gov (United States)

Nakamura, Yoshihisa; Hamajima, Yuki; Suzuki, Motohiko; Esaki, Shinichi; Yokota, Makoto; Oshika, Masanori; Takagi, Ippei; Yasui, Keiko; Miyamoto, Naoya; Sugiyama, Kazuko; Nakayama, Meiho; Murakami, Shingo

2016-08-01

Conventional treatment for acute otitis media mainly targets bacteria with antibiotics, neglecting to control for mediators of inflammation. Mediators of inflammation, such as leukotrienes, have been identified in patients with acute otitis media (AOM) or subsequent secretory otitis media (SOM). They can cause functional eustachian tube dysfunction or increase mucous in the middle ear, causing persistent SOM following AOM. The objective of the present study was to evaluate whether or not administration of pranlukast, a widely used leukotriene C4, D4, and E4 antagonist, together with antibiotics could inhibit the progression to SOM. Children with AOM, who were from two to 12 years old, were randomly divided into two groups as follows: a control group in which 50 patients received antibiotic-based conventional treatment according to guidelines for treating AOM proposed by the Japan Otological Society (version 2006); and a pranlukast group, in which 52 patients were administered pranlukast for up to 28 days as well as given conventional treatment. Cases were regarded as persistent SOM when a tympanogram was type B or C2 four weeks after treatment was initiated. Two patients in the pranlukast group and 3 patients in the control group were excluded because they relapsed AOM within 28 days after initial treatment. Therefore, the analysis included 50 and 47 subjects in the pranlukast and control groups, respectively. The percentage of patients diagnosed with persistent SOM (22.0%) was significantly smaller in the pranlukast group compared with the control group (44.7%) (p = 0.018, chi-squared test). The results indicate that combined treatment of AOM with antibiotics and a leukotriene antagonist to control inflammation is useful for preventing progression to persistent SOM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bloqueio do receptor de leucotrieno CysLT1 em pacientes com fenômeno de Raynaud: evidência capilaroscópica do papel do leucotrieno CysLT1 receptor inhibition in patients with Raynaud's phenomenon: capillaroscopic evidence of the role of leukotriene

Directory of Open Access Journals (Sweden)

Mario Newton Leitão de Azevedo

2012-02-01

Full Text Available OBJETIVO: Avaliar a ação do medicamento inibidor do receptor de leucotrieno CysLT1 (montelucaste nas alterações vasculares das mãos em pacientes com fenômeno de Raynaud. MÉTODOS: Foram selecionadas pacientes com fenômeno de Raynaud secundário à doença inflamatória do tecido conjuntivo, excluindo tabagismo, hipertensão arterial e diabetes mellitus. As pacientes mantiveram a medicação prévia e iniciaram o uso de montelucaste 10 mg/dia por 60 dias. Foi realizada capilaroscopia periungueal dos dedos das mãos antes do uso da medicação e após 30 e 60 dias. A análise estatística foi feita por meio de porcentagem, média, desvio-padrão e teste exato de Fisher, com intervalo de confiança de 95%. RESULTADOS: Foram estudadas cinco pacientes mulheres, brancas, com fenômeno de Raynaud secundário a doenças do tecido conjuntivo, das quais três apresentavam esclerodermia e duas apresentavam doença mista do tecido conjuntivo. A média de idade foi de 42,4 ± 12,4 anos, e a média de tempo de doença foi de 9,6 ± 4,8 anos. As pacientes estavam em uso de até 20 mg/dia de prednisona (pacientes com doença mista do tecido conjuntivo, nifedipina, pentoxifilina. As medicações foram mantidas. Após o uso de inibidor de receptor de leucotrieno por dois meses, o controle com capilaroscopia ungueal demonstrou diminuição do edema e da palidez e normalização do número, tamanho e distribuição dos capilares. CONCLUSÃO: O uso do montelucaste modificou as alterações capilares observadas na capilaroscopia periungueal de pacientes com fenômeno de RaynaudOBJECTIVE: To assess the effect of the leukotriene receptor inhibitor (montelukast on vascular alterations in fingers of patients with Raynaud's phenomenon. METHODS: Patients with Raynaud's phenomenon of the hands secondary to inflammatory connective tissue disease were selected, and those with the following characteristics were excluded: smokers, arterial hypertension, and diabetes

Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics

Science.gov (United States)

2013-01-01

Background Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders. Methods The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes. Results Supplementation with several EO/BO combinations increased circulating 20–22 carbon (20–22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%. Conclusions This study shows that dietary supplementation with BO/EO alters 20–22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation. PMID:24088297

Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Partial purification and identification as a cytochrome P-450.

Science.gov (United States)

Shak, S; Goldstein, I M

1985-09-01

Human polymorphonuclear leukocytes (PMN) not only synthesize and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by omega-oxidation. To characterize the enzyme(s) responsible for omega-oxidation of LTB4, human PMN were disrupted by sonication and subjected to differential centrifugation to yield membrane, granule, and cytosol fractions (identified by biochemical markers). LTB4 omega-hydroxylase activity was concentrated (together with NADPH cytochrome c reductase activity) only in the membrane fraction (specific activity increased 10-fold as compared to whole sonicates, 41% recovery). Negligible activity was detected in granule or cytosol fractions. LTB4 omega-hydroxylase activity in isolated PMN membranes was linear with respect to duration of incubation and protein concentration, was maximal at pH 7.4, had a Km for LTB4 of 0.6 microM, and was dependent on oxygen and on reduced pyridine nucleotides (apparent Km for NADPH = 0.5 microM; apparent Km for NADH = 223 microM). The LTB4 omega-hydroxylase was inhibited significantly by carbon monoxide, ferricytochrome c, SKF-525A, and Triton X-100, but was not affected by alpha-naphthoflavone, azide, cyanide, catalase, and superoxide dismutase. Finally, isolated PMN membranes exhibited a carbon monoxide difference spectrum with a peak at 452 nm. Thus, we have partially purified the LTB4 omega-hydroxylase in human PMN and identified the enzyme as a membrane-associated, NADPH-dependent cytochrome P-450.

Leukotriene B₄-leukotriene B₄ receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8⁺ T cells.

Science.gov (United States)

Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui

2015-09-01

Leukotriene B4 (LTB4 ) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8(+) T cells. The role of the LTB4 -BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8(+) T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8(+) T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8(+) T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4 -BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8(+) T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. © 2015 John Wiley & Sons Ltd.

Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning

Czech Academy of Sciences Publication Activity Database

Zakharov, S.; Kotíková, K.; Nurieva, O.; Hlušička, J.; Kačer, P.; Urban, P.; Vaněčková, M.; Seidl, Z.; Diblík, P.; Kuthan, P.; Navrátil, Tomáš; Pelclová, D.

2017-01-01

Roč. 55, č. 4 (2017), s. 249-259 ISSN 1556-3650 Institutional support: RVO:61388955 Keywords : brain damage * leukotrienes * methanol poisoning * Neuroinflammation * nontraumatic brain injury * sequelae of poisoning Subject RIV: CG - Electrochemistry OBOR OECD: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis) Impact factor: 3.677, year: 2016

A SEARCH FOR L/T TRANSITION DWARFS WITH PAN-STARRS1 AND WISE. II. L/T TRANSITION ATMOSPHERES AND YOUNG DISCOVERIES

International Nuclear Information System (INIS)

Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Chambers, K. C.; Flewelling, H.; Hodapp, K. W.; Kaiser, N.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.; Deacon, Niall R.; Redstone, Joshua; Burgett, W. S.; Draper, P.; Metcalfe, N.

2015-01-01

The evolution of brown dwarfs from L to T spectral types is one of the least understood aspects of the ultracool population, partly for lack of a large, well-defined, and well-characterized sample in the L/T transition. To improve the existing census, we have searched ≈28,000 deg 2 using the Pan-STARRS1 and Wide-field Infrared Survey Explorer surveys for L/T transition dwarfs within 25 pc. We present 130 ultracool dwarf discoveries with estimated distances ≈9–130 pc, including 21 that were independently discovered by other authors and 3 that were previously identified as photometric candidates. Seventy-nine of our objects have near-IR spectral types of L6–T4.5, the most L/T transition dwarfs from any search to date, and we have increased the census of L9–T1.5 objects within 25 pc by over 50%. The color distribution of our discoveries provides further evidence for the “L/T gap,” a deficit of objects with (J − K) MKO  ≈ 0.0–0.5 mag in the L/T transition, and thus reinforces the idea that the transition from cloudy to clear photospheres occurs rapidly. Among our discoveries are 31 candidate binaries based on their low-resolution spectral features. Two of these candidates are common proper motion companions to nearby main sequence stars; if confirmed as binaries, these would be rare benchmark systems with the potential to stringently test ultracool evolutionary models. Our search also serendipitously identified 23 late-M and L dwarfs with spectroscopic signs of low gravity implying youth, including 10 with vl-g or int-g gravity classifications and another 13 with indications of low gravity whose spectral types or modest spectral signal-to-noise ratio do not allow us to assign formal classifications. Finally, we identify 10 candidate members of nearby young moving groups (YMG) with spectral types L7–T4.5, including three showing spectroscopic signs of low gravity. If confirmed, any of these would be among the coolest known YMG members and would

Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration.

Science.gov (United States)

Pazos, Michael A; Pirzai, Waheed; Yonker, Lael M; Morisseau, Christophe; Gronert, Karsten; Hurley, Bryan P

2015-02-01

Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4). We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response. Copyright © 2015 by The American Association of Immunologists, Inc.

Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis

DEFF Research Database (Denmark)

Kjeldsen, J; Laursen, L S; Hillingsø, Jens

1995-01-01

5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response of several inflammatory diseases, including ulcerative colitis. FPL 64170XX is a selective inhibitor of the enzyme 5-lipoxygenase. Concentrations...... containing 0.5% of FPL 64170XX. Repeated measures analysis of leukotriene B4, after adjusting for baseline, showed a significant treatment effect (P = 0.0014). The concentration of leukotriene B4 from rectal dialysates in patients receiving the active drug dropped to 15% (95% confidence interval 5......-40%) of the placebo level in the second dialysis following administration of FPL 64170XX 0.5%. By contrast, prostaglanding E2 concentrations doubled (P = 0.0068) in patients receiving FPL 64170XX 0.5% with no change in the placebo group. These findings demonstrate that a single dose of FPL 64170XX 0.5% enema...

Prostaglandin E2/leukotriene B4 balance induced by Lutzomyia longipalpis saliva favors Leishmania infantum infection.

Science.gov (United States)

Araújo-Santos, Théo; Prates, Deboraci Brito; França-Costa, Jaqueline; Luz, Nívea F; Andrade, Bruno B; Miranda, José Carlos; Brodskyn, Claudia I; Barral, Aldina; Bozza, Patrícia T; Borges, Valéria Matos

2014-12-20

Eicosanoids and sand fly saliva have a critical role in the Leishmania infection. Here, we evaluated the effect of Lutzomyia longipalpis salivary gland sonicate (SGS) on neutrophil and monocyte recruitment and activation of eicosanoid production in a murine model of inflammation. C57BL/6 mice were inoculated intraperitonealy with Lutzomyia longipalpis SGS or Leishmania infantum or both, followed by analyses of cell recruitment, parasite load and eicosanoid production. Intraperitoneal injection of Lutzomyia longipalpis SGS together with Leishmania infantum induced an early increased parasite viability in monocytes and neutrophils. L. longipalpis SGS increased prostaglandin E2 (PGE2), but reduced leukotriene B4 (LTB4) production ex vivo in peritoneal leukocytes. In addition, the pharmacological inhibition of cyclooxygenase 2 (COX-2) with NS-398 decreased parasite viability inside macrophages during Leishmania infection in the presence of L. longipalpis SGS arguing that PGE2 production is associated with diminished parasite killing. These findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE2/LTB4 axis, which may represent an important mechanism on establishment of the infection.

Metabolism of leukotriene B4 to dihydro and dihydro-oxo products by porcine leukocytes

International Nuclear Information System (INIS)

Powell, W.S.; Gravelle, F.

1989-01-01

Porcine leukocytes contain a novel pathway for the metabolism of leukotriene B4 (LTB4) which results in reduction of the conjugated triene chromophore to a conjugated diene. These cells converted LTB4 to two major metabolites, both of which exhibited maximal absorbance at 230 nm in their UV spectra. These products were purified by high pressure liquid chromatography and identified as 10, 11-dihydro-LTB4 and 10,11-dihydro-12-oxo-LTB4 on the basis of the mass spectra of various derivatives. The position of the double bond of LTB4 which had been reduced was established by cleaving the remaining double bonds of 10, 11-dihydro-LTB4 with ozone followed by oxidation or reduction of the resulting ozonide and analysis of the products by mass spectrometry. Experiments with deuterium-labeled substrate indicated that LTB4 could be directly converted to 10, 11-dihydro-LTB4 without the prior oxidation of either of its hydroxyl groups, as is required for the formation of dihydro metabolites of prostaglandins. Incubation of porcine leukocytes with 10, 11-dihydro-LTB4 and 10, 11-dihydro-12-oxo-LTB4 indicated that these two products can be interconverted and are in equilibrium with one another. The dihydro-oxo metabolite can therefore be formed from 10, 11-dihydro-LTB4, although we have not ruled out the possibility that it is also produced via 12-oxo-LTB4, which could be a transitory intermediate. These results indicate that porcine leukocytes contain a novel reductase/dehydrogenase pathway distinct from the pathway responsible for the metabolism of prostaglandins. This pathway is also different from the pathway in human polymorphonuclear leukocytes which converts 6-trans-isomers of LTB4 to dihydro products, since the latter pathway involves 5-oxo intermediates and results in a shift in the positions of the remaining double bonds

Leukotrienes and 8-isoprostane in exhaled breath condensate in bronchoprovocation tests with occupational allergens

Czech Academy of Sciences Publication Activity Database

Klusáčková, P.; Lebedová, J.; Kačer, P.; Kuzma, Marek; Brabec, Marek; Pelclová, D.; Fenclová, Z.; Navrátil, Tomáš

2008-01-01

Roč. 78, 4-5 (2008), s. 281-292 ISSN 0952-3278 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z10300504; CEZ:AV0Z40400503 Keywords : occupational allergens * leukotrienes * 8-isoprostane Subject RIV: CC - Organic Chemistry Impact factor: 1.366, year: 2008

Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse

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Fugazzola Maria

2012-09-01

Full Text Available Abstract Background Glucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO in horses via systemic as well as local (inhalative administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung slices (PCLS. PCLS were used to analyze ex-vivo effects of beclomethasone on inhibiting bronchoconstriction in the horse. The inhibiting effect was measured through instillation of a known mediator of inflammation and bronchoconstriction, leukotriene C4. For this, the accessory lobes of 13 horses subjected to euthanasia for reasons unrelated to the respiratory apparatus were used to obtain viable lung slices. Results After 30 minutes of PCLS incubation, beclomethasone showed to significantly inhibit the contraction of the bronchioles after instillation with leukotriene C4. The EC50 values of the two contraction curves (LTC4 with and without BDP differed significantly from each other (p = 0.002. The possibility of a non-genomic rapid mechanism of action seems likely since transcriptional activities require a longer lag period. Conclusions In human neuroendocrinology, high levels of glucocorticoids have been proven to function via a non-genomic mechanism of membrane receptors. The concentration of beclomethasone used on the lung slices in our study can be considered as high. This allows speculation about similar rapid non-genomic mechanisms of high-dosage inhaled glucocorticoids in the lower airways of horses. However, further assessment on a molecular basis is needed to confirm this.

Effects of Xingbi gel on leukotriene E4 and immunoglobulin E production and nasal eosinophilia in a guinea pig model for allergic rhinitis.

Science.gov (United States)

Ai, Si; Zheng, Jian; Chu, Ke-Dan; Zhang, Hong-Sheng

2015-06-01

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal airways.Many therapies do not have immediate effects,even which have side-effects.However,the effects of Xingbi gel for the treatment of AR was investigated. We investigated the effects of Xingbi gel on serum levels of leukotriene E4 (LTE4) and immunoglobulin E (IgE), as well as eosinophil counts in the nasal mucosa using a guinea pig model of allergic rhinitis (AR). In addition to a healthy control group without AR, guinea pigs with AR were randomly divided into untreated AR control group, low-dose Xingbi gel (0.2483 g/mL) group, high-dose Xingbi gel (0.4966 g/mL) group, and budesonide group. Compared to the healthy controls, untreated AR guinea pigs had significantly higher ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts (p guinea pigs (p production and reducing eosinophilia in the nasal mucosa.

Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Suicidal inactivation by acetylenic fatty acids.

Science.gov (United States)

Shak, S; Reich, N O; Goldstein, I M; Ortiz de Montellano, P R

1985-10-25

Human polymorphonuclear leukocytes (PMN) not only generate and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by omega-oxidation (probably due to the action of a cytochrome P-450 enzyme). To develop pharmacologically useful inhibitors of the LTB4 omega-hydroxylase in human PMN, we devised a general scheme for synthesizing terminal acetylenic fatty acids based on the "acetylenic zipper" reaction. We found that the LTB4 omega-hydroxylase in intact PMN and in PMN sonicates is inactivated in a concentration-dependent fashion by terminal acetylenic analogues of lauric, palmitic, and stearic acids (i.e. 11-dodecynoic, 15-hexadecynoic, and 17-octadecynoic acids). Consistent with a suicidal process, inactivation of the LTB4 omega-hydroxylase requires molecular oxygen and NADPH, is time-dependent, and follows pseudo-first-order kinetics. Inactivation of the omega-hydroxylase by acetylenic fatty acids also is dependent on the terminal acetylenic moiety and the carbon chain length. Saturated fatty acids lacking a terminal acetylenic moiety do not inactivate the omega-hydroxylase. In addition, the two long-chain (C16, C18) acetylenic fatty acids inactivate the omega-hydroxylase at much lower concentrations (less than 5.0 microM) than those required for inactivation by the short-chain (C12) terminal acetylenic fatty acid (100 microM). Potent suicidal inhibitors of the LTB4 omega-hydroxylase in human PMN will help elucidate the roles played by LTB4 and its omega-oxidation products in regulating PMN function and in mediating inflammation.

Implementation of LT codes based on chaos

International Nuclear Information System (INIS)

Zhou Qian; Li Liang; Chen Zengqiang; Zhao Jiaxiang

2008-01-01

Fountain codes provide an efficient way to transfer information over erasure channels like the Internet. LT codes are the first codes fully realizing the digital fountain concept. They are asymptotically optimal rateless erasure codes with highly efficient encoding and decoding algorithms. In theory, for each encoding symbol of LT codes, its degree is randomly chosen according to a predetermined degree distribution, and its neighbours used to generate that encoding symbol are chosen uniformly at random. Practical implementation of LT codes usually realizes the randomness through pseudo-randomness number generator like linear congruential method. This paper applies the pseudo-randomness of chaotic sequence in the implementation of LT codes. Two Kent chaotic maps are used to determine the degree and neighbour(s) of each encoding symbol. It is shown that the implemented LT codes based on chaos perform better than the LT codes implemented by the traditional pseudo-randomness number generator. (general)

Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation

DEFF Research Database (Denmark)

Sampson, Anthony P; Pizzichini, Emilio; Bisgaard, Hans

2003-01-01

mediators in a wide range of diseases, implying that their biological activities reach far beyond acute bronchoconstriction, the activity traditionally ascribed to them. The validity of examining sputum for "biomarkers" has improved the understanding of asthma pathophysiology, optimization of asthma......The understanding that asthma pathophysiology includes an inflammatory component has spurred the more aggressive use of anti-inflammatory therapies and created a need for effective tools to measure inflammation. Biomarkers of airway inflammation proposed are obtained by methods that are direct...... but highly invasive (bronchial biopsy, bronchoalveolar lavage), moderately direct, and less invasive (indirect sputum, exhaled air, breath condensate) or indirect and least invasive (blood, urine). Several studies described in this review have implicated the cysteinyl leukotrienes (CysLTs) as inflammatory...

Molecular mechanisms of the synergy between cysteinyl-leukotrienes and receptor tyrosine kinase growth factors on human bronchial fibroblast proliferation

Directory of Open Access Journals (Sweden)

Hajime Yoshisue

2006-12-01

Full Text Available We have reported that cysteinyl-leukotrienes (cys-LTs synergise not only with epidermal growth factor (EGF but also with platelet-derived growth factor (PDGF and fibroblast growth factor (FGF to induce mitogenesis in human bronchial fibroblasts. We now describe the molecular mechanisms underlying this synergism. Mitogenesis was assessed by incorporation of [3H]thymidine into DNA and changes in protein phosphorylation by Western blotting. Surprisingly, no CysLT receptor antagonists (MK-571, montelukast, BAY u9773 prevented the synergistic mitogenesis. LTD4 did not cause phosphorylation of EGFR nor did it augment EGF-induced phosphorylation of EGFR, and the synergy between LTD4 and EGF was not blocked by the metalloproteinase inhibitor GM6001 or by an HB-EGF neutralising antibody. The EGFR-selective kinase inhibitor, AG1478, suppressed the synergy by LTD4 and EGF, but had no effect on the synergy with PDGF and FGF. While inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase and protein kinase C (PKC prevented the synergy, these drugs also inhibited mitogenesis elicited by EGF alone. In contrast, pertussis toxin (PTX efficiently inhibited the potentiating effect of LTD4 on EGF-induced mitogenesis, as well as that provoked by PDGF or FGF, but had no effect on mitogenesis elicited by the growth factors alone. Whereas LTD4 alone did not augment phosphorylation of extracellular signal-regulated kinase (Erk-1/2 and Akt, it increased phosphorylation of PKC in a Gi-dependent manner. Addition of LTD4 prolonged the duration of EGF-induced phosphorylation of Erk-1/2 and Akt, both of which were sensitive to PTX. The effect of cys-LTs involves a PTX-sensitive and PKC-mediated intracellular pathway leading to sustained growth factor-dependent phosphorylation of Erk-1/2 and Akt.

Churg-Strauss syndrome and leukotriene antagonist use: a respiratory perspective.

LENUS (Irish Health Repository)

Nathani, N

2008-10-01

Churg-Strauss syndrome (CSS) is a rare granulomatous small vessel vasculitis that occurs against a background of longstanding asthma. Leukotriene antagonists (LTAs) are used in the management of asthma and may facilitate a reduction in steroid dosage. Reports of the development of CSS in patients with asthma following the initiation of LTA therapy suggest either a causal association or an unmasking of latent CSS as steroid doses fall. We have undertaken a systematic review to establish whether evidence of a drug induced syndrome exists.

Leukotriene-B4 concentrations in exhaled breath condensate and lung function after thirty minutes of breathing technically dried compressed air.

Science.gov (United States)

Neubauer, Birger; Struck, Niclas; Mutzbauer, Till S; Schotte, Ulrich; Langfeldt, Norbert; Tetzlaff, Kay

2002-01-01

In previous studies it had been shown that leukotriene-B4 [LTB4] concentrations in the exhaled breath mirror the inflammatory activity of the airways if the respiratory tract has been exposed to occupational hazards. In diving the respiratory tract is exposed to cold and dry air and the nasopharynx, as the site of breathing-gas warming and humidification, is bypassed. The aim of the present study was to obtain LTB4-concentrations in the exhaled breath and spirometric data of 17 healthy subjects before and after thirty minutes of technically dried air breathing at normobar ambient pressure. The exhaled breath was collected non-invasively, via a permanently cooled expiration tube. The condensate was measured by a standard enzyme immunoassay for LTB4. Lung function values (FVC, FEV1, MEF 25, MEF 50) were simultaneously obtained by spirometry. The measured pre- and post-exposure LTB4- concentrations as well as the lung function values were in the normal range. The present data gave no evidence for any inflammatory activity in the subjects' airways after thirty minutes breathing technically dried air.

Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase

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Xiao-Feng Lai

2014-11-01

Full Text Available Aims: Neutrophils can synthesize leukotriene B4 (LTB4 by activating the 5-lipoxygenase (5-LOsignaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils. Methods/Results: Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, MβCD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059. Conclusion: Hypercholesterolemia increases LTB4 production in neutrophils by increasing the nuclear localization of 5-LO, which is the result of its phosphorylation by activated ERK1/2.

Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

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Przemysław Rzodkiewicz

2016-10-01

Full Text Available Objectives : Esculetin (6,7-dihydroxycoumarin is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9. Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods : The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose and experimental (treated with esculetin – 10 mg/kg ip.. The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4 in plasma was determined by a competitive enzyme immunoassay. Results : The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively. Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01. Conclusions : LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834. Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive

Bronislaw Malinowski’nin Kültür Teorisi

OpenAIRE

Aman, Fatih

2014-01-01

Bir toplumu anlamak o toplumun kültürünü anlamaya bağlıdır. Özellikle “her toplumun kendine özgü olduğu” gerçeği kültür konusunda birçok araştırmanın yapılmasını sağlamış ve kültürel araştırmaları daha da ilginç kılmıştır. Bu araştırmalardan birisi de Bronislaw Malinowski’ye aittir. O, kültürün kökeniyle ilgilenmiş, kültürün fonksiyonlarını tanımlamış, kültürel araştırma tekniklerini ilk defa bilimsel ölçütlerle ortaya koymuş ve eleştirileriyle toplamda bir kültür teorisi oluşturmuştur. Malin...

A new method to evaluate anti-allergic effect of food component by measuring leukotriene B4 from a mouse mast cell line.

Science.gov (United States)

Takasugi, Mikako; Muta, Emi; Yamada, Koji; Arai, Hirofumi

2018-02-01

Leukotrienes (LTs), chemical mediators produced by mast cells, play an important role in allergic symptoms such as food allergies and hay fever. We tried to construct an evaluation method for the anti-LTB 4 activity of chemical substances using a mast cell line, PB-3c. PB-3c pre-cultured with or without arachidonic acid (AA) was stimulated by calcium ionophore (A23187) for 20 min, and LTB 4 production by the cells was determined by HPLC with UV detection. LTB 4 was not detected when PB-3c was pre-cultured without AA. On the other hand, LTB 4 production by PB-3c pre-cultured with AA was detectable by HPLC, and the optimal conditions of PB-3c for LTB 4 detection were to utilize the cells pre-cultured with 50 µM AA for 48 h. MK-886 (5-lipoxygenase inhibitor) completely inhibited LTB 4 production, but AACOCF 3 (phospholipase A 2 inhibitor) slightly increased LTB 4 production, suggesting that LTB 4 was generated from exogenous free AA through 5-lipoxygenase pathway. We applied this technique to the evaluation of the anti-LTB 4 activity of food components. PB-3c pre-cultured with 50 µM AA for 48 h was stimulated with A23187 in the presence of 50 µM soybean isoflavones (daidzin, genistin, daidzein, and genistein), equol, quercetin, or kaempferol. Genistein, equol, quercetin, and kaempferol strongly inhibited LTB 4 production without cytotoxicity. These results suggest that a new assay system using PB-3c is convenient to evaluate LTB 4 inhibition activity by food components. This method could be utilized for elucidation of the mechanisms of LTB 4 release suppression by food components such as flavonoids and the structure-activity relationship.

Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

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Cui Zhi-Hua

2012-03-01

Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

The leukotriene B{sub 4} receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis

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Kihara, Yasuyuki, E-mail: kihara-yasuyuki@umin.net [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yokomizo, Takehiko [Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Core Research for Embryonic Science and Technology (CREST), Japan Science and Technology Agency (Japan); Kunita, Akiko; Morishita, Yasuyuki; Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033 (Japan); Ishii, Satoshi; Shimizu, Takao [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

2010-04-09

Leukotriene B{sub 4} (LTB{sub 4}) is a potent chemoattractant and activator of neutrophils, macrophages and T cells. These cells are a key component of inflammation and all express BLT1, a high affinity G-protein-coupled receptor for LTB{sub 4}. However, little is known about the neuroimmune functions of BLT1. In this study, we describe a distinct role for BLT1 in the pathology of experimental autoimmune encephalomyelitis (EAE) and T{sub H}1/T{sub H}17 immune responses. BLT1 mRNA was highly upregulated in the spinal cord of EAE mice, especially during the induction phase. BLT1{sup -/-} mice had delayed onset and less severe symptoms of EAE than BLT1{sup +/+} mice. Additionally, inflammatory cells were recruited to the spinal cord of asymptomatic BLT1{sup +/+}, but not BLT1{sup -/-} mice before the onset of disease. Ex vivo studies showed that both the proliferation and the production of IFN-{gamma}, TNF-{alpha}, IL-17 and IL-6 were impaired in BLT1{sup -/-} cells, as compared with BLT1{sup +/+} cells. Thus, we suggest that BLT1 exacerbates EAE by regulating the migration of inflammatory cells and T{sub H}1/T{sub H}17 immune responses. Our findings provide a novel therapeutic option for the treatment of multiple sclerosis and other T{sub H}17-mediated diseases.

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

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D. Carlos

2011-04-01

Full Text Available It is well known that eosinophilia is a key pathogenetic component of toxocariasis. The objective of the present study was to determine if there is an association between peritoneal and blood eosinophil influx, mast cell hyperplasia and leukotriene B4 (LTB4 production after Toxocara canis infection. Oral inoculation of 56-day-old Wistar rats (N = 5-7 per group with 1000 embryonated eggs containing third-stage (L3 T. canis larvae led to a robust accumulation of total leukocytes in blood beginning on day 3 and peaking on day 18, mainly characterized by eosinophils and accompanied by higher serum LTB4 levels. At that time, we also noted increased eosinophil numbers in the peritoneal cavity. In addition, we observed increased peritoneal mast cell number in the peritoneal cavity, which correlated with the time course of eosinophilia during toxocariasis. We also demonstrated that mast cell hyperplasia in the intestines and lungs began soon after the T. canis larvae migrated to these compartments, reaching maximal levels on day 24, which correlated with the complete elimination of the parasite. Therefore, mast cells appear to be involved in peritoneal and blood eosinophil infiltration through an LTB4-dependent mechanism following T. canis infection in rats. Our data also demonstrate a tight association between larval migratory stages and intestinal and pulmonary mast cell hyperplasia in the toxocariasis model.

PHARMACOGENOMICS OF PROSTAGLANDIN AND LEUKOTRIENE RECEPTORS

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José Antonio Cornejo-García

2016-09-01

Full Text Available Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs, have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs and leukotrienes (LTs are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesised through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2; mast cell maturation, eosinophil recruitment and allergic responses (PTGD2; vascular and respiratory smooth muscle contraction (PTGF2, and inhibition of platelet aggregation (PTGI2. LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs (LTC4, LTD4 and LTE4 induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.

Resolution of Toll-like receptor 4-mediated acute lung injury is linked to eicosanoids and suppressor of cytokine signaling 3.

Science.gov (United States)

Hilberath, Jan N; Carlo, Troy; Pfeffer, Michael A; Croze, Roxanne H; Hastrup, Frantz; Levy, Bruce D

2011-06-01

The purpose of this study was to investigate roles for Toll-like receptor 4 (TLR4) in host responses to sterile tissue injury. Hydrochloric acid was instilled into the left mainstem bronchus of TLR4-defective (both C3H/HeJ and congenic C.C3-Tlr4(Lps-d)/J) and control mice to initiate mild, self-limited acute lung injury (ALI). Outcome measures included respiratory mechanics, barrier integrity, leukocyte accumulation, and levels of select soluble mediators. TLR4-defective mice were more resistant to ALI, with significantly decreased perturbations in lung elastance and resistance, resulting in faster resolution of these parameters [resolution interval (R(i)); ∼6 vs. 12 h]. Vascular permeability changes and oxidative stress were also decreased in injured HeJ mice. These TLR4-defective mice paradoxically displayed increased lung neutrophils [(HeJ) 24×10(3) vs. (control) 13×10(3) cells/bronchoalveolar lavage]. Proresolving mechanisms for TLR4-defective animals included decreased eicosanoid biosynthesis, including cysteinyl leukotrienes (80% mean decrease) that mediated CysLT1 receptor-dependent vascular permeability changes; and induction of lung suppressor of cytokine signaling 3 (SOCS3) expression that decreased TLR4-driven oxidative stress. Together, these findings indicate pivotal roles for TLR4 in promoting sterile ALI and suggest downstream provocative roles for cysteinyl leukotrienes and protective roles for SOCS3 in the intensity and duration of host responses to ALI.

Isolated Subclinical Hyperthyrotropinemia in Obese Children: Does Levothyroxine (LT4 Improve Weight Reduction during Combined Behavioral Therapy?

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Pawel Matusik

2015-01-01

Full Text Available Objective. The study aim was to analyze whether anthropometrical parameters and TSH values in obese children with isolated subclinical hypothyroidism (IsHT treated with levothyroxine (LT4 and weight reduction program differ from those managed by dietary and behavior counselling only. Material and Methods. 51 obese children with IsHT, who were treated according to the same weight reduction program, were retrospectively analyzed. They were divided into two groups: Group 1, n=26, and Group 2, n=25, without or with LT4 therapy, respectively. Changes in anthropometrical (delta BMI z-score and hormonal (delta TSH status were analyzed at the first follow-up visit. Results. In both groups significant decrease of TSH and BMI z-score values were noted. TSH normalized in 80.9% of children from Group 1 versus 90.5% from Group 2, p = NS. Delta BMI z-score was insignificantly higher in Group 1 compared to Group 2. Delta TSH was significantly related to initial TSH level in children treated by lifestyle intervention program only. Conclusions. In obese children with sHT dietary-behavioral management intervention contributed to reduction of body mass index, irrespective of levothyroxine use. This finding suggests that moderately elevated levels of TSH are a consequence rather than cause of overweight and pharmacological treatment should be avoided.

Introducing Leo LT - the "three-headed lion"

Index Scriptorium Estoniae

2008-01-01

Leedu valitsus kiitis heaks seaduseparandused, mille tulemusena saab võtta tuumajaama ehitaja, investeerimis- ja energiafirma Leo LT strateegilise tähtsusega firmade hulka. Kui parlament valitsuse ettepanekud heaks kiidab, saab riik 61,7% Leo LT ja 38,3% NDX Energija aktsiatest

TEO LT hakkab kaotama atraktiivsust / Romet Kreek

Index Scriptorium Estoniae

Kreek, Romet, 1972-

2011-01-01

Autori sõnul on Leedu telekomiettevõtte TEO LT puhul raske oodata, et käive ja kasum kasvaksid, parimal juhul on need stabiilsed. Osalt on selle põhjuseks tehnoloogilised muutused, osalt suuromaniku poliitika. TEO LT I kvartali majandusnäitajatest

Rotavirus 2/6 Viruslike Particles Administered Intranasally with Cholera Toxin, Escherichia coli Heat-Labile Toxin (LT), and LT-R192G Induce Protection from Rotavirus Challenge

Science.gov (United States)

O’Neal, Christine M.; Clements, John D.; Estes, Mary K.; Conner, Margaret E.

1998-01-01

We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced protection from rotavirus challenge, as measured by virus shedding. Since it is unclear if CT will be approved for human use, we evaluated the adjuvanticity of Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated intranasally with 10 μg of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced equivalent geometric mean titers of rotavirus-specific serum antibody and intestinal immunoglobulin G (IgG). Mice inoculated with 2/6-VLPs with LT produced significantly higher titers of intestinal IgA than mice given CT as the adjuvant. All mice inoculated with 2/6-VLPs mixed with LT and LT-R192G were totally protected (100%) from rotavirus challenge, while mice inoculated with 2/6-VLPs mixed with CT showed a mean 91% protection from challenge. The availability of a safe, effective mucosal adjuvant such as LT-R192G will increase the practicality of administering recombinant vaccines mucosally. PMID:9525668

A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis

DEFF Research Database (Denmark)

Bisgaard, Hans

2003-01-01

Infants often develop reactive airway disease after respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl-leukotrienes (cys-LT) are released during RSV infection and may contribute to the inflammation. We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease...... subsequent to RSV bronchiolitis. One hundred and thirty infants who were 3 to 36 months old, hospitalized with acute RSV bronchiolitis, were randomized into a double-blind, parallel comparison of 5-mg montelukast chewable tablets or matching placebo given for 28 days starting within 7 days of symptom debut...

Feedback in LT codes for prioritized and non-prioritized data

DEFF Research Database (Denmark)

Sørensen, Jesper Hemming; Popovski, Petar; Østergaard, Jan

2012-01-01

In this paper feedback in LT codes is investigated. The considered type of feedback is acknowledgments, where information on which symbols have been decoded is given to the transmitter. Our analysis reveals that acknowledgments has a very low potential in LT codes with standard degree distributions....... Motivated by this, we analyze the impact of acknowledgments on multi-layer LT codes. In this case, feedback proves advantageous. By using only a single feedback message, it is possible to achieve a significant performance improvement compared to traditional LT codes....

Gas Chromatography/mass Spectrometry Analysis of Exhaled Leukotrienes in Asthmatic Patients

Czech Academy of Sciences Publication Activity Database

Čáp, P.; Chládek, J.; Pehal, F.; Malý, Marek; Petrů, V.; Barnes, P.J.; Montuschi, P.

2004-01-01

Roč. 59, č. 6 (2004), s. 465-470 ISSN 0040-6376 Source of funding: V - iné verejné zdroje Keywords : asthma * breath condensate * gas chromatography/mass spectrometry * leukotrienes Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 5.040, year: 2004

Leukotriene D4 activates distinct G-proteins in intestinal epithelial cells to regulate stress fibre formation and to generate intracellular Ca2+ mobilisation and ERK1/2 activation

International Nuclear Information System (INIS)

Nielsen, Christian Kamp; Massoumi, Ramin; Sonnerlind, Maria; Sjoelander, Anita

2005-01-01

We have shown that the pro-inflammatory mediator LTD 4 , via its G-protein-coupled receptor CysLT 1 , signals through both pertussis-toxin-sensitive and -insensitive G-proteins to induce various cellular responses. To further characterise the initial step of the different signalling pathways emanating from the CysLT 1 receptor, we transfected intestinal epithelial cells, Int 407, with different mini vectors that each express a specific inhibitory peptide directed against a unique α subunit of a specific heterotrimeric G-protein. Our results revealed that LTD 4 -induced stress fibre formation is inhibited approximately 80% by a vector expressing an inhibitory peptide against the pertussis-toxin-insensitive Gα 12 -protein in intestinal epithelial Int 407 cells. Control experiments revealed that the LPA-induced stress fibre formation, mediated via the Gα 12 -protein in other cell types, was blocked by the same peptide in intestinal Int 407 cells. Furthermore, the CysLT 1 -receptor-mediated calcium signal and activation of the proliferative ERK1/2 kinase are blocked in cells transfected with a vector expressing an inhibitory peptide against the Gα i3 -protein, whereas in cells transfected with an empty ECFP-vector or vectors expressing inhibitory peptides against the Gα i1-2 -, Gα 12 -, Gα R -proteins these signals are not significantly affected. Consequently, the CysLT 1 receptor has the capacity to activate at least two distinctly different heterotrimeric G-proteins that transduce activation of unique downstream cellular events

Low temperature solid oxide electrolytes (LT-SOE): A review

Science.gov (United States)

Singh, B.; Ghosh, S.; Aich, S.; Roy, B.

2017-01-01

Low temperature solid oxide fuel cell (LT-SOFC) can be a source of power for vehicles, online grid, and at the same time reduce system cost, offer high reliability, and fast start-up. A huge amount of research work, as evident from the literature has been conducted for the enhancement of the ionic conductivity of LT electrolytes in the last few years. The basic conduction mechanisms, advantages and disadvantages of different LT oxide ion conducting electrolytes {BIMEVOX systems, bilayer systems including doped cerium oxide/stabilised bismuth oxide and YSZ/DCO}, mixed ion conducting electrolytes {doped cerium oxides/alkali metal carbonate composites}, and proton conducting electrolytes {doped and undoped BaCeO3, BaZrO3, etc.} are discussed here based on the recent research articles. Effect of various material aspects (composition, doping, layer thickness, etc.), fabrication methods (to achieve different microstructures and particle size), design related strategies (interlayer, sintering aid etc.), characterization temperature & environment on the conductivity of the electrolytes and performance of the fuel cells made from these electrolytes are shown in tabular form and discussed. The conductivity of the electrolytes and performance of the corresponding fuel cells are compared. Other applications of the electrolytes are mentioned. A few considerations regarding the future prospects are pointed.

CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

Science.gov (United States)

Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

2013-01-01

The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

Bone infected/inflamed conditions: Clinical experience with RP517, a Tc99m-leukotriene B4 receptor antagonist

International Nuclear Information System (INIS)

Soroa, V.; Nicolini, J.; Camin, L.; Ughetti, R.; Velasquez, M.

2003-01-01

Full text: Objectives: Tc 99m- RP517- is a receptor antagonist of Leukotriene B4 (LTB4) labelling predominantly neutrophils, in whole blood. The aim of this clinical trial was to obtain the best acquisition protocol and performance of this agent in detecting bone, joint and soft tissue infected / inflamed pathologies. Methods: RP517 was labelled with 15-20 mCi (555-740MBq) Tc99m per doses. Twenty-six patients studied (F 14, M 12) with range ages 19- 93, suspected of bone, joint and soft tissue infection (25) and one with fever of unknown origin (FUO). Laboratory data, anatomical images and one other scintiscan (MDP, Ga-67 or Tc99m- ciprofloxacin) were evaluated. Acquisition protocol: flow, 30 min, 1, 2, 3, 4 - 24h planar or Spect images as required. Results documented with histology, cultures or clinical follow up. Scans were classified as positive when abnormal uptake persisted in the 24h images or negative when positivity faded, or not detected in later images. Results: Labeling efficiency 86-90%. No adverse reactions encountered. Image protocol modified to a flow, 30 min, 4 and 24h images. Ten-fifteen % of in vivo leucocyte labelling at 1h. Early bile and intestinal excretion did not improve with cleansing enemas or food restrain. Late bone marrow activity is less visible than with in vitro leucocyte labeling. Only 16 patients had proven biopsies and cultures with coincident images in 8 True Positive; other 6 cases were True Negative, 2 False Negative (with positive Ga-67 and Tc99m-ciprofloxacin) and no False Positive. Sensitivity 80%, Specificity 100%. Conclusions: A kit should be produced in order to make it easily available. Pharmaceutically manipulation altering the excretion route could validate studies in abdominal infections and FUO that are now disesteemed. Protocol images must include 24h scans. Advantage of RP517 is the lack of cell labeling manipulation. Larger series must be studied to obtain statistics on joint bone and soft tissue infection

Thermoelectric coefficient L(T) of polycrystalline silver doped BSCCO samples

International Nuclear Information System (INIS)

Rodriguez, J.E.; Marino, A.

1998-01-01

We present a study of the thermoelectric coefficient L(T) of polycrystalline silver doped BSCCO samples. The quantity L(T) relates the thermoelectric coefficient S(T) with the electrical conductivity σ (T) and gives an indication of the influence of the order parameter fluctuations (OPF) on S(T) in the mean field region (Mfr). The results of L(T) indicate that the critical behavior of S(T) above the superconducting transition is not only driven by σ (T). These results suggest that in the Mfr, L(T) is affected by thermodynamic fluctuations of the superconducting order parameter (OPF). The OPF effects show a two-dimensional (2D) character in the entire Mfr. (Author)

Leukotriene signaling in the extinct human subspecies Homo denisovan and Homo neanderthalensis. Structural and functional comparison with Homo sapiens.

Science.gov (United States)

Adel, Susan; Kakularam, Kumar Reddy; Horn, Thomas; Reddanna, Pallu; Kuhn, Hartmut; Heydeck, Dagmar

2015-01-01

Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.

Science.gov (United States)

Danz, Henning; Stoyanova, Stefka; Thomet, Olivier A R; Simon, Hans-Uwe; Dannhardt, Gerd; Ulbrich, Holger; Hamburger, Matthias

2002-10-01

The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.

Lower leukotriene C4 levels in bronchoalveolar lavage fluid of asthmatic subjects after 2.5 years of inhaled corticosteroid therapy

Directory of Open Access Journals (Sweden)

Y. Oosterhoff

1995-01-01

Full Text Available Long-term treatment with inhaled corticosteroids has been shown to result in improvement of symptoms and lung function in subjects with asthma. Arachidonic acid (AA metabolites are thought to play a role in the pathophysiology of asthma. It was assessed whether differences could be found in bronchoalveolar lavage (BAL AA metabolite levels between subjects with asthma who were treated for 2.5 years with inhaled bronchodilators alone or in combination with inhaled corticosteroids. Prostaglandin (PGD2, PGF2α, 6-keto-PGF1α, thromboxane B2, leukotriene (LTC4 and LTB4 levels and cell numbers were assessed in BAL fluid from 22 non-smoking asthmatic subjects. They were participating in a randomized, double-blind multicentre drug trial over a period of 2.5 years. Results of the group treated with inhaled corticosteroids (CS+: beclomethasone 200 μg four times daily were compared with the other group (CS− which was treated with either ipratropium bromide (40 μg four times daily or placebo. BAL LTC4 levels of asthmatic subjects were significantly lower after 2.5 years inhaled corticosteroid therapy (CS+, 9(1–17 pg/ml vs. CS−, 16(6-53 pg/ml; p = 0.01. The same trend was observed for the PGD2 levels. The results suggest that inhaled corticosteroids may exert their beneficial effect on lung function via a mechanism in which inhibition of LTC4 synthesis in the airways is involved.

The anti-inflammatory effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against estradiol-induced nonbacterial inflammation in the rat prostate.

Science.gov (United States)

Said, Mahmoud M; Bosland, Maarten C

2017-02-01

There is no standard treatment of chronic nonbacterial prostatitis in humans. The current study was aimed to investigate the effect of montelukast, an antagonist of cysteinyl leukotriene receptor-1, against estrogen-induced, nonbacterial lateral lobe-specific prostate inflammation in rats. Male Wistar rats were randomized into five groups of six rats, including sham controls (group 1) and castrated rats (group 2), whereas nonbacterial prostatitis (NBP) was induced in groups 3-5 by castration followed by a daily subcutaneous injection of estradiol (0.25 mg/kg body weight) for 30 days. The rats were left otherwise untreated (group 3) or received a daily oral administration of montelukast (1 and 10 mg/kg body weight for groups 4 and 5, respectively) from the 17th day after castration for two consecutive weeks. Compared with sham controls, induction of NBP led to a significant increase in serum leukotriene B 4 (LTB4), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels, along with a significant upregulation in the transcript level of proinflammatory molecules (nuclear factor kappa beta [NF-κβ] and inducible nitric oxide synthase [iNOS]), chemokines (monocyte chemoattractant protein-1 [MCP-1] and eotaxin), and E-selectin in the lateral prostate. Histological examination revealed intense inflammation in the prostate with leukocyte infiltration and acinar degeneration following estradiol treatment of castrated rats. Montelukast significantly suppressed the increase in serum and prostate proinflammatory mediators/chemokines expression and abolished the histologically inflammatory changes in the lateral prostate. These findings indicate that montelukast inhibits estradiol-induced NBP in a rat model through anti-inflammatory mechanisms, suggesting its future beneficial effect for the treatment of clinical chronic NBP.

Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G

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Christelle Basset

2010-08-01

Full Text Available LT-R192G, a mutant of the thermolabile enterotoxin of E. coli, is a potent adjuvant of immunization. Immune responses are generally analyzed at the end of protocols including at least 2 administrations, but rarely after a prime. To investigate this point, we compared B and T cell responses in mice after one and two intrarectal immunizations with 2/6 rotavirus-like particles (2/6-VLP and LT-R192G. After a boost, we found, an unexpected lower B cell expansion measured by flow cytometry, despite a secondary antibody response. We then analyzed CD4+CD25+Foxp3+ regulatory T cells (Tregs and CD4+CD25+Foxp3− helper T cells after in vitro (restimulation of mesenteric lymph node cells with the antigen (2/6-VLP, the adjuvant (LT-R192G or both. 2/6-VLP did not activate CD4+CD25+Foxp3− nor Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice, whereas they did activate both subsets from mice immunized with 2/6-VLP in the presence of adjuvant. LT-R192G dramatically decreased CD4+CD25+Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice but not from mice immunized with 2/6-VLP and adjuvant. Moreover, in this case, LT-R192G increased Foxp3 expression on CD4+CD25+Foxp3+ cells, suggesting specific Treg activation during the recall. Finally, when both 2/6-VLP and LT-R192G were used for restimulation, LT-R192G clearly suppressed both 2/6-VLP-specific CD4+CD25+Foxp3− and Foxp3+ T cells. All together, these results suggest that LT-R192G exerts different effects on CD4+CD25+Foxp3+ T cells, depending on a first or a second contact. The unexpected immunomodulation observed during the recall should be considered in designing vaccination protocols.

Rotavirus 2/6 Viruslike Particles Administered Intranasally with Cholera Toxin, Escherichia coli Heat-Labile Toxin (LT), and LT-R192G Induce Protection from Rotavirus Challenge

OpenAIRE

O’Neal, Christine M.; Clements, John D.; Estes, Mary K.; Conner, Margaret E.

1998-01-01

We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced protection from rotavirus challenge, as measured by virus shedding. Since it is unclear if CT will be approved for human use, we evaluated the adjuvanticity of Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated intranasally with 10 μg of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced ...

Characterization of LT-LiXO1-YNIYO2 electrodes for rechargeable lithium cells

CSIR Research Space (South Africa)

Gummow, RJ

1993-12-01

Full Text Available -spinel in character and that LT- Li0.4Co0.sNi0.102 is a defect spinel with spinel notation {Li0.s\\[:\\]0.2}sa \\[Co, 6Nio.2D0.2104. Electrochemical data.--The charge and discharge pro- files for the first four cycles of Li/LT-LiCoO2, Li... on the B sites of an A\\[B2104 spinel structure. The spinel phase is significantly more stable to lithium insertion/extraction reactions than the quasi-spinel phase. It is believed that by optimizing the processing conditions...

Design and Analysis of LT Codes with Decreasing Ripple Size

DEFF Research Database (Denmark)

Sørensen, Jesper Hemming; Popovski, Petar; Østergaard, Jan

2012-01-01

In this paper we propose a new design of LT codes, which decreases the amount of necessary overhead in comparison to existing designs. The design focuses on a parameter of the LT decoding process called the ripple size. This parameter was also a key element in the design proposed in the original...... work by Luby. Specifically, Luby argued that an LT code should provide a constant ripple size during decoding. In this work we show that the ripple size should decrease during decoding, in order to reduce the necessary overhead. Initially we motivate this claim by analytical results related...... to the redundancy within an LT code. We then propose a new design procedure, which can provide any desired achievable decreasing ripple size. The new design procedure is evaluated and compared to the current state of the art through simulations. This reveals a significant increase in performance with respect...

Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase?

Science.gov (United States)

Cheng, Yuanyuan; Tse, Hung Fat; Le, X. Chris; Rong, Jianhui

2015-01-01

Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol-induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil-mediated myocardial injury. PMID:26265982

Identification and characterization of luekotriene C4 and D4 receptors on a cultured smooth muscle cell line, BC3H-1

International Nuclear Information System (INIS)

Tamura, N.; Agrawal, D.K.; Townley, R.G.

1987-01-01

The authors studied the characteristics of the leukotriene (LT) C 4 and D 4 receptors on a cultured smooth muscle cell line, BC3H-1. Specific [ 3 H]LTC 4 binding to the cell membrane was greater than 80% of total binding and saturable at a density of 3.96 +/- 0.39 pmol/mg protein, with an apparent dissociation constant(Kd) of 14.3 +/- 2.0 nM (n=9). The association and dissociation of [ 3 H]LTC 4 binding were rapid and apparent equilibrium conditions were established within 5 min. Calculated Kd value of [ 3 H]LTC binding from the kinetic analysis was 9.9 nM. From the competition analysis, calculated Ki value of unlabeled LTC 4 to compete for the specific binding of [ 3 H]LTC 4 was 9.2 nM and was in good agreement with the Kd value obtained from the Scatchard plots or kinetic analysis. The maximum number of binding sites (Bmax) of [ 3 H]LTD 4 in the membrane of BC3H-1 cell line was about 11 times lower than that of the [ 3 H]LTC 4 . The calculated values of Kd and Bmax of [ 3 H]LTD 4 binding were 9.3 +/- 0.8 nM and 0.37 +/- 0.04 pmol/mg proteins, respectively (n=3). These findings demonstrate that BC3H-1 cell line possess both LTC 4 and LTD 4 receptors with a predominance of LTC 4 receptors. Thus, BC3H-1 cell line is a good model to study the regulation of LTC 4 and LTD 4 receptors. 34 references, 5 figures, 1 table

Trigon Farming ostis Kaiu LT / Margus Mikomägi

Index Scriptorium Estoniae

Mikomägi, Margus, 1956-

2006-01-01

Raplamaalt suuruselt neljas põllumajandusühistu Kaiu LT müüdi üldkoosoleku otsusega ühel häälel firmale Trigon Farming. Kaiu LT nõukogu esimees on viimased kolm aastat olnud Riigikogu liige Tiit Tammsaar. Lisa: Trigon Tarming investeerib põllumajandusse

Discovery of a visual T-dwarf triple system and binarity at the L/T transition

Energy Technology Data Exchange (ETDEWEB)

Radigan, Jacqueline [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Jayawardhana, Ray [Department of Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, ON M5S 3H4 (Canada); Lafrenière, David [Département de Physique, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC H3C 3J7 (Canada); Dupuy, Trent J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Liu, Michael C. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); Scholz, Alexander, E-mail: radigan@stsci.edu [School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews, KY169SS (United Kingdom)

2013-11-20

We present new high contrast imaging of eight L/T transition brown dwarfs (BDs) using the NIRC2 camera on the Keck II telescope. One of our targets, the T3.5 dwarf 2MASS J08381155+1511155, was resolved into a hierarchal triple with projected separations of 2.5 ± 0.5 AU and 27 ± 5 AU for the BC and A(BC) components, respectively. Resolved OSIRIS spectroscopy of the A(BC) components confirms that all system members are T dwarfs. The system therefore constitutes the first triple T-dwarf system ever reported. Using resolved photometry to model the integrated-light spectrum, we infer spectral types of T3 ± 1, T3 ± 1, and T4.5 ± 1 for the A, B, and C components, respectively. The uniformly brighter primary has a bluer J – K{sub s} color than the next faintest component, which may reflect a sensitive dependence of the L/T transition temperature on gravity, or alternatively divergent cloud properties among components. Relying on empirical trends and evolutionary models we infer a total system mass of 0.034-0.104 M {sub ☉} for the BC components at ages of 0.3-3 Gyr, which would imply a period of 12-21 yr assuming the system semimajor axis to be similar to its projection. We also infer differences in effective temperatures and surface gravities between components of no more than ∼150 K and ∼0.1 dex. Given the similar physical properties of the components, the 2M0838+15 system provides a controlled sample for constraining the relative roles of effective temperature, surface gravity, and dust clouds in the poorly understood L/T transition regime. For an age of 3 Gyr we estimate a binding energy of ∼20 × 10{sup 41} erg for the wide A(BC) pair, which falls above the empirical minimum found for typical BD binaries, and suggests that the system may have been able to survive a dynamical ejection during formation. Combining our imaging survey results with previous work we find an observed binary fraction of 4/18 or 22{sub −8}{sup +10}% for unresolved spectral types

Breath condensate levels of 8-isoprostane and leukotriene B4 after ozone inhalation are greater in sensitive versus nonsensitive subjects.

Science.gov (United States)

Alfaro, Mario F; Walby, William F; Adams, William C; Schelegle, Edward S

2007-01-01

Ozone (O3) inhalation induces pulmonary function decrements and inflammation. The present study was designed to determine if a relationship exists between O3 induced pulmonary function changes and the presence of inflammatory markers as measured in exhaled breath condensates (EBCs) obtained from O3-sensitive and nonsensitive human subjects. Eight healthy adult volunteers (4 males/4 females, age 18 to 30 years) were studied, characterized as to their ozone sensitivity and placed into 2 groups (sensitive and nonsensitive) with each group having 2 males and 2 females. Subjects completed a 20-minute EBC collection and pulmonary function test (PFT) prior to a single 60-minute bout of cycle ergometer exercise (V(E) = 50-55 L/min) while breathing filtered air (FA) or 0.35 ppm O3. Subjective symptom scores (SSSs) were collected at 6, 20, 40, and 60 minutes during exposure. An immediate postexposure PFT was performed followed by an EBC collection. Subjective symptom scores, EBCs, and PFTs were collected at 1, 4 and 8 hours post exposure. EBCs were analyzed for prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 8-isoprostane, and total nitric oxide (NO) metabolites (nitrate + nitrite content). Sensitive subjects, breathing O3, had significantly greater functional decrements in PFTs, increased SSSs, and increased rapid shallow breathing as well as elevated levels of 8-isoprostane and LTB4 in EBCs compared to those breathing FA. In addition, there were significant increases in nitrate + nitrite content in both sensitive and nonsensitive subjects breathing O3 compared to FA. These results indicate that sensitive subjects have elevated arachidonic acid metabolites in EBCs compared to nonsensitive subjects after O3 inhalation.

MAC-1 Glycoprotein Family mediates adherence of neutrophils to endothelial cells stimulated by leukotriene B/sub 4/ and platelet activating factor

Energy Technology Data Exchange (ETDEWEB)

Tonnesen, M.G.; Anderson, D.C.; Springer, T.A.; Knedler, A.; Avdi, N.; Henson, P.M.

1986-03-01

The process of neutrophil (N) adhesion to and migration through endothelium (EC), an early event in the induction of the acute inflammatory response, has been attributed to the generation of extravascular chemoattractant peptides and lipids. Although both leukotriene B/sub 4/ (LTB/sub 4/) and platelet activating factor (PAF) enhance N adherence to EC, the mechanisms involved in this interaction are still not completely understood. Since the MAC-1 Glycoprotein (GP) Family has recently been shown to be required for a variety of adherence-dependent functions of stimulated N, the authors questioned whether these adherence-associated GP might be involved in N adherence to EC stimulated by LTB/sub 4/ or PAF. Using a microtiter adherence assay with /sup 111/In labeled N, they assessed the ability of N from patients with MAC-1, LFA-1 Deficiency to adhere to monolayers of human omental microvascular or umbilical vein EC as well as to serum-coated plastic. Patient N exhibited markedly diminished adherence in response to LTB/sub 4/ or PAF compared to normal controls. LTB/sub 4/ and PAF enhanced expression of the MAC-1 GP Family on the surface of normal N as determined by flow cytofluorimetry using a monoclonal antibody (TS1/18) to the GP common beta subunit. In addition TS1/18 (20 ..mu..g/ml) completely inhibited N adherence stimulated by either LTB/sub 4/ (10/sup -8/M) or PAF(10/sup -11/M). Thus, the MAC-1 GP Family appears to be important in chemotactic factor regulation of N adherence to EC.

8-Isoprostane and leukotrienes in exhaled breath condensate in czech subjects with silicosis

Czech Academy of Sciences Publication Activity Database

Pelclová, D.; Fenclová, Z.; Kačer, P.; Navrátil, Tomáš; Kuzma, Marek; Lebedová, J.; Klusáčková, P.

2007-01-01

Roč. 45, č. 6 (2007), s. 766-774 ISSN 0019-8366 Grant - others:GA MZd NR8107 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z50200510 Keywords : silica * silicosis * 8-isoprostane * leukotrienes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.792, year: 2007

Leukotriene B4 induces EMT and vimentin expression in PANC-1 pancreatic cancer cells: Involvement of BLT2 via ERK2 activation.

Science.gov (United States)

Kim, You Ri; Park, Mi Kyung; Kang, Gyeong Jin; Kim, Hyun Ji; Kim, Eun Ji; Byun, Hyun Jung; Lee, Moo-Yeol; Lee, Chang Hoon

2016-12-01

Leukotriene B 4 (LTB 4 ) is a leukocyte chemoattractant and plays a major role controlling inflammatory responses including pancreatitis. LTB 4 is known to be correlated with cancer progression. LTB 4 induces keratin phosphorylation and reorganization by activating extracellular regulated kinase (ERK) in PANC-1 pancreatic cancer cell lines. However, the role of LTB 4 in epithelial mesenchymal transition (EMT) and vimentin expression in pancreatic cancer cells is unknown. We examined whether LTB 4 induces EMT and vimentin expression by Western blot, si-RNA, and RT-PCR. LTB 4 induced morphological change, decreased E-cadherin expression and increased N-cadherin and vimentin expression. LTB4 increased migration and invasion of PANC-1 cancer cells. LTB 4 dose-dependently upregulated expression of vimentin in PANC-1 cancer cells. LTB 4 -induced vimentin expression was suppressed by LY255283 (BLT2 antagonist). Comp A, a BLT2 agonist, further increased vimentin expression. Gene silencing of BLT2 suppressed LTB 4 -or Comp A-induced vimentin expression in PANC-1 cells. The MEK inhibitor, PD98059 suppressed Comp A-induced vimentin expression. Comp A or transfection of plasmid containing BLT2 cDNA (pC BLT2 ) activated ERK, and BLT2 gene silencing suppressed Comp A-induced ERK activation. ERK2 siRNA abrogated Comp A-induced vimentin expression and ERK2 overexpression enhanced vimentin expression. One of well-known cause of ras mutation, cigarette smoke extracts increased BLT2 expression in PANC-1 cancer cells. Taken together, these results suggest that BLT2 is involved in LTB 4 -induced vimentin expression through ERK2 in PANC-1 cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Survival properties of ETEC surface-displayed K88ac-LT(B) on Lactobacillus casei].

Science.gov (United States)

Wei, Chunhua; Liu, Jiankui; Hou, Xilin; Wang, Guihua; Yu, Liyun

2009-01-01

K88ac-LT(B) gene derived from pQE30-K88ac-LT(B) was cloned into the expression vector pLA and then the recombinant vector was transformed into the competent cells Lactobacillus casei 525. The recombinant bacteria were grown at 37 degrees C, in MRS broth. Western blotting analysis with rabbit-anti-K88ac-LT(B) polyclonal serum indicated that the recombinant protein reacted with the specific antibodies. The results showed that the molecular weight of the recombinant protein was about 71.2 kD. The K88ac-LT(B) fusion protein on the cell surface was confirmed by immunofluorescence mciroscopy and flow cytometric analysis. In addition, the survival of recombinant Lactobacillus casei 525 was studied in imitative gastrointestinal environments such as artificial gastro fluid (pH 1.5-5.5), artificial intestinal fluid, bile(0.3-3.0 g/L). The results indicated that the recombinant strain survived well in artificial gastric fluids at pH 2.5-4.5 in 5 h. The recombinant Lactobacillus casei 525 could slowly grow in the artificial intestinal fluid for different time, and could survive in 0.3% bile.

Immunomagnetic molecular probe with UHPLC-MS/MS: A promising way for reliable bronchial asthma diagnostics based on quantification of cysteinyl leukotrienes

Czech Academy of Sciences Publication Activity Database

Syslová, K.; Boehmová, A.; Demirbag, E.; Šimková, K.; Kuzma, Marek; Pelclová, D.; Sedlák, V.; Čáp, P.; Martásek, P.; Kačer, P.

81-82, AUG 2013 (2013), s. 108-117 ISSN 0731-7085 Institutional support: RVO:61388971 Keywords : Cysteinyl leukotrienes * Immunomagnetic separation * UHPLC-MS Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.829, year: 2013

Exhaled Leukotrienes and Bronchial Responsiveness to Methacholine in Patients with Seasonal Allergic Rhinitis

Czech Academy of Sciences Publication Activity Database

Čáp, P.; Malý, Marek; Pehal, F.; Pelikán, Z.

2009-01-01

Roč. 102, č. 2 (2009), s. 103-109 ISSN 1081-1206 Grant - others:GA MZd(CZ) NL7024 Institutional research plan: CEZ:AV0Z10300504 Keywords : allergic rhinitis * asthma * breath condensate * leukotrienes * gas chromatography * mass spectrometry analysis Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 2.457, year: 2009

Mainosideoista sähköisiin sisältöihin : sisältöstrategian merkitys mainostoimistojen digitaalisissa palveluissa

OpenAIRE

Pasanen, Riikka

2012-01-01

Sisältöstrategia on suunnittelukäytäntö, jonka tähtää liiketoiminnallisiin tavoitteisiin vaikuttavan verkkosisällön avulla. Tutkimuksessa tarkastellaan hyvän verkkosisällön kriteerejä ja pohditaan, voisiko mainostoimisto ottaa oppia sisältöstrategian käytännöistä ja tarjota sen avulla parempaa palvelua asiakkailleen. Tutkimusta varten on haastateltu neljää mainonnan strategisen suunnittelun ja asiakasjohdon ammattilaista, joiden näkemyksiä on peilattu tutkijan pitkään kokemukseen alalta sekä ...

Genetic influences on ovulation of primary oocytes in LT/Sv strain mice.

Science.gov (United States)

Everett, Clare A; Auchincloss, Catherine A; Kaufman, Matthew H; Abbott, Catherine M; West, John D

2004-11-01

A high proportion of LT/Sv strain oocytes arrest in meiotic metaphase I (MI) and are ovulated as diploid primary oocytes rather than haploid secondary oocytes. (Mus musculus castaneus x LT/SvKau)F1 x LT/SvKau backcross females were analysed for the proportion of oocytes that arrested in MI and typed by PCR for a panel of microsatellite DNA sequences (simple sequence repeat polymorphisms) that differed between strain LT/SvKau and M. m. castaneus. This provided a whole genome scan of 86 genetic markers distributed over all 19 autosomes and the X chromosome, and revealed genetic linkage of the MI arrest phenotype to markers on chromosomes 1 and 9. Identification of these two chromosomal regions should facilitate the identification of genes involved in mammalian oocyte maturation and the control of meiosis.

Determination of cysteinyl leukotrienes in exhaled breath condensate: Method combining immunoseparation with LC-ESI-MS/MS

Czech Academy of Sciences Publication Activity Database

Syslová, K.; Kačer, P.; Vilhanová, B.; Kuzma, Marek; Lipovová, P.; Fenclová, Z.; Lebedová, J.; Pelclová, D.

2011-01-01

Roč. 879, č. 23 (2011), s. 2220-2228 ISSN 1570-0232 R&D Projects: GA MZd NS10298 Keywords : Cysteinyl leukotriene * Exhaled breath condensate * Immunoseparation Subject RIV: CE - Biochemistry Impact factor: 2.888, year: 2011

The Application of LT-Table in TRIZ Contradiction Resolving Process

Science.gov (United States)

Wei, Zihui; Li, Qinghai; Wang, Donglin; Tian, Yumei

TRIZ is used to resolve invention problems. ARIZ is the most powerful systematic method which integrates all of TRIZ heuristics. Definition of ideal final result (IFR), identification of contradictions and resource utilization are main lines of ARIZ. But resource searching of ARIZ has fault of blindness. Alexandr sets up mathematical model of transformation of the hereditary information in an invention problem using the theory of catastrophes, and provides method of resource searching using LT-table. The application of LT-table on contradiction resolving is introduced. Resource utilization using LT-table is joined into ARIZ step as an addition of TRIZ, apply this method in separator paper punching machine design.

Mechanisms of aspirin-sensitive asthma

Directory of Open Access Journals (Sweden)

Sun Ying

2004-01-01

Full Text Available It is now widely accepted that aspirin, along with other non-steroidal anti-inflammatory drugs (NSAIDs, may precipitate asthma attacks in a minority of susceptible individuals. The syndrome is part of a mucosal inflammatory disease that typically affects the nasal, as well as the bronchial, mucosa and sometimes the gut and skin also. Although the mucosal cellular infiltrate in aspirin-sensitive asthma and rhinitis resembles that of asthma and rhinitis in general, there is evidence of increased expression of asthma-relevant cytokines, such as interleukin-5 and granulocyte–macrophage colony stimulating factor, and a more intense infiltrate of mast cells and eosinophils. One key feature of aspirin-sensitive asthma is thought to be the overproduction of cysteinyl leukotrienes, principally by these local mast cells and eosinophils, but whether this represents a fundamental abnormality or is simply a consequence of greater numbers and activation of inflammatory cells is unclear. Genetic polymorphisms of the leukotriene C4 synthase gene, which result in elevated expression of this enzyme, may also play a role. In addition, overexpression of cysteinyl leukotriene receptors, particularly CysLT1, may contribute to an enhanced response of local inflammatory and structural cells to cysteinyl leukotrienes. Aspirin challenge in these patients is accompanied by acute further elevation of the already elevated baseline cysteinyl leukotriene synthesis, a phenomenon that is most closely related to the ability of aspirin and related NSAIDs to inhibit the cyclooxygenase enzyme COX-1. The reason for this is unknown, although it has been suggested that the COX-1 product prostaglandin E2 (PGE2 serves as a ‘brake’ to leukotriene synthesis and that somehow this mechanism is deficient in aspirin-sensitive asthmatics. A better understanding of the pathogenesis of aspirin-sensitive asthma will undoubtedly lead to better approaches to treatment. Aside from the use of

Contempt-LT: a computer program for predicting containment pressure-temperature response to a loss-of-coolant accident

International Nuclear Information System (INIS)

Wheat, L.L.; Wagner, R.J.; Niederauer, G.F.; Obenchain, C.F.

1975-06-01

CONTEMPT-LT is a digital computer program, written in FORTRAN IV, developed to describe the long-term behavior of water-cooled nuclear reactor containment systems subjected to postulated loss-of-coolant accident (LOCA) conditions. The program calculates the time variation of compartment pressures, temperatures, mass and energy inventories, heat structure temperature distributions, and energy exchange with adjacent compartments. The program is capable of describing the effects of leakage on containment response. Models are provided to describe fan cooler and cooling spray engineered safety systems. Up to four compartments can be modeled with CONTEMPT-LT, and any compartment except the reactor system may have both a liquid pool region and an air-vapor atmosphere region above the pool. Each region is assumed to have a uniform temperature, but the temperatures of the two regions may be different. CONTEMPT-LT can be used to model all current boiling water reactor pressure suppression systems, including containments with either vertical or horizontal vent systems. CONTEMPT-LT can also be used to model pressurized water reactor dry containments, subatmospheric containments, and dual volume containments with an annulus region, and can be used to describe containment responses in experimental containment systems. The program user defines which compartments are used, specifies input mass and energy additions, defines heat structure and leakage systems, and describes the time advancement and output control. CONTEMPT-LT source decks are available in double precision extended-binary-coded-decimal-interchange-code (EBCDIC) versions. Sample problems have been run on the IBM360/75 computer. (U.S.)

Mastering Autodesk Inventor 2015 and Autodesk Inventor LT 2015

CERN Document Server

Waguespack, Curtis

2014-01-01

A comprehensive guide to Autodesk Inventor and Inventor LT This detailed reference and tutorial provides straightforward explanations, real-world examples, and practical tutorials that focus squarely on teaching Autodesk Inventor tips, tricks, and techniques. The book also includes a project at the beginning to help those new to Inventor quickly understand key interface conventions and capabilities. In addition, there is more information on Inventor LT, new practice drawings at the end of each chapter to reinforce lessons learned, and thorough coverage of all of Inventor's new features. The au

Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia

DEFF Research Database (Denmark)

Benfield, T L; van Steenwijk, R; Nielsen, T L

1995-01-01

(PG) and leukotrienes (LT)] are pro-inflammatory mediators released from arachidonic acid by action of phospholipase A2 (PLA2) and have been implicated in the host response to micro-organisms. Bronchoalveolar lavage (BAL) was performed on patients with PCP as part of a randomized study of adjuvant...... of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear....

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1.

Science.gov (United States)

Silva, Viviane Carvalho da; Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Martins, Conceição da Silva; Freire, Gildenio Estevam; Aragão, Karoline Saboia; Wanderley, Carlos Wagner de Souza; Freitas, Marcos Rabelo de

2017-09-01

To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

Comparison Results on the Basic Phenomena between CAP and CONTEMPT-LT

Energy Technology Data Exchange (ETDEWEB)

Choo, Yeon Joon; Hong, Soon Joon; Hwang, Su Hyun; Kim, Min Ki; Lee, Byung Chul [FNC Tech., SNU, Seoul (Korea, Republic of); Ha, Sang Jun; Choi, Hoon [KHNP Central Research Institute, Daejeon (Korea, Republic of)

2011-10-15

A development project for the domestic design code was launched to be used for the safety and performance analysis of pressurized light water reactors. As a part of this project, CAP (Containment Analysis Package) code has been developing for the containment safety and performance analysis side by side with SPACE. CAP Beta version has been released lately and validation processes are under way currently. Code by code comparison activity is scheduled in the validation processes and the first comparable code is CONTEMPT-LT. CONTEMPT-LT was developed to predict the longterm behavior of water-cooled nuclear reactor containment systems subjected to postulated loss-ofcoolant accident (LOCA) conditions. CONTEMPT-LT calculates the time variation of compartment pressures, temperatures, mass and energy inventories, heat structure temperature distributions, and energy exchange with adjacent compartments, leakage on containment response. Models are provided for fan cooler and cooling spray as engineered safety systems. Any compartment may have both a liquid pool region and an air-vapor atmosphere region above the pool. Each region is assumed to have a uniform temperature, but the temperatures of the two regions may be different. As mentioned above, CONTEMP-LT has the similar code features and it, therefore, is expected to show the similar analysis performance with CAP. In this study, the code performances were compared for the same phenomena between CAP and CONTEMPT-LT. Code comparison is carried out through two stages; separate and integral effect comparison

Comparison Results on the Basic Phenomena between CAP and CONTEMPT-LT

International Nuclear Information System (INIS)

Choo, Yeon Joon; Hong, Soon Joon; Hwang, Su Hyun; Kim, Min Ki; Lee, Byung Chul; Ha, Sang Jun; Choi, Hoon

2011-01-01

A development project for the domestic design code was launched to be used for the safety and performance analysis of pressurized light water reactors. As a part of this project, CAP (Containment Analysis Package) code has been developing for the containment safety and performance analysis side by side with SPACE. CAP Beta version has been released lately and validation processes are under way currently. Code by code comparison activity is scheduled in the validation processes and the first comparable code is CONTEMPT-LT. CONTEMPT-LT was developed to predict the longterm behavior of water-cooled nuclear reactor containment systems subjected to postulated loss-ofcoolant accident (LOCA) conditions. CONTEMPT-LT calculates the time variation of compartment pressures, temperatures, mass and energy inventories, heat structure temperature distributions, and energy exchange with adjacent compartments, leakage on containment response. Models are provided for fan cooler and cooling spray as engineered safety systems. Any compartment may have both a liquid pool region and an air-vapor atmosphere region above the pool. Each region is assumed to have a uniform temperature, but the temperatures of the two regions may be different. As mentioned above, CONTEMP-LT has the similar code features and it, therefore, is expected to show the similar analysis performance with CAP. In this study, the code performances were compared for the same phenomena between CAP and CONTEMPT-LT. Code comparison is carried out through two stages; separate and integral effect comparison

Passively Q-switched mode-locked Nd3+:LuVO4 laser by LT-GaAs saturable absorber

International Nuclear Information System (INIS)

Li, M; Zhao, S; Li, Y; Yang, K; Li, G; Li, D; An, J; Li, T; Yu, Z

2009-01-01

By using LT-GaAs as saturable absorber, we have demonstrated the stable Q-switched and mode-locked (QML) Nd:LuVO 4 laser run in a Z-type folded cavity. Nearly 100% modulation depth of mode locking can be obtained as long as the pump power reaches the oscillation threshold. The repetition rate of the passively Q-switched pulse envelops ranges from 37.5 to 139 kHz as the pump power increased from 1.7 to 8.2 W. The mode-locked pulse inside the Q-switched envelop has an estimated pulse width of about 220 ps and a repetition rate of 111 MHz. Under an incident pump power of 8.2 W, the highest pulse energy of 6 μJ of each Q-switched envelope, and the highest peak power about 2.73 kW of Q-switched mode-locked pulses can be obtained

Montelukast prevents vascular endothelial dysfunction from internal combustion exhaust inhalation during exercise.

Science.gov (United States)

Rundell, Kenneth W; Steigerwald, Michelle D; Fisk, Michelle Z

2010-08-01

Associations between high particulate matter (PM) pollution and increased morbidity and mortality from coronary heart disease have been identified. This study assessed leukotriene (LT) participation in PM-induced vascular endothelial dysfunction. Ten healthy males exercised 4 times for 30 min in both high PM (550,286 +/- 42,004 particles x cm(-3)) and low PM (4571 +/- 1922 particles x cm(-3)) after ingesting placebo (PL) or 10 mg montelukast (MK; half-life 3-6 h), a leukotriene receptor antagonist. Brachial artery flow-mediated dilation (FMD) was measured pre- and 30 min, 4 h, 24 h post-exercise. No basal brachial artery vascoconstriction was evident from high PM exercise. High PM blunted FMD, whereas high PM MK, low PM PL, and low PM MK demonstrated normal FMD (p < .003). Change in FMD (pre- to post-exercise) for high PM PL was different than for high PM MK, low PM PL, and low PM MK at 30 min post-exercise (p < .007). At 4 h, high PM MK FMD blunting increased (p = .1). At 24 h, high PM FMD blunting persisted (p < .05); no difference was observed between high PM PL or MK treatment, but was different that low PM PL/MK treatments (p < .05). MK blocked high PM post-exercise FMD blunting and maintained normal response, suggesting that leukotrienes are involved in PM-initiated vascular endothelial dysfunction.

Diode-pumped passively mode-locked Nd:LuVO4 laser with LT-In0.25Ga0.75As saturable absorber

International Nuclear Information System (INIS)

Li, T; Zhao, S; Li, Y; Zhuo, Z; Yang, K; Li, G; Li, D; Yu, Z

2009-01-01

A diode pumped passively mode-locked Nd:LuVO 4 laser with a low temperature (LT) In 0.25 Ga 0.75 As absorber is realized in this paper. An In 0.25 Ga 0.75 As single-quantum-well absorber, which is grown by use of the metal-organic chemical-vapor deposition technique, acts as nonlinear absorber and output coupler simultaneously. A special cavity is designed to keep the power density on In 0.25 Ga 0.75 As under its damage threshold. Both the Q-switched and continuous-wave (cw) mode locking operation are experimentally realized. An average output power of 5.9 W with pulse width of 4.9 ps is achieved at the pump power of 22 W, corresponding to an optical conversion efficiency of 26.8%

SNAP23-Dependent Surface Translocation of Leukotriene B4 (LTB4) Receptor 1 Is Essential for NOX2-Mediated Exocytotic Degranulation in Human Mast Cells Induced by Trichomonas vaginalis-Secreted LTB4.

Science.gov (United States)

Min, Arim; Lee, Young Ah; Kim, Kyeong Ah; El-Benna, Jamel; Shin, Myeong Heon

2017-01-01

Trichomonas vaginalis is a sexually transmitted parasite that causes vaginitis in women and itself secretes lipid mediator leukotriene B 4 (LTB 4 ). Mast cells are important effector cells of tissue inflammation during infection with parasites. Membrane-bridging SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes are critical for fusion during exocytosis. Although T. vaginalis-derived secretory products (TvSP) have been shown to induce exocytosis in mast cells, information regarding the signaling mechanisms between mast cell activation and TvSP is limited. In this study, we found that SNAP23-dependent surface trafficking of LTB 4 receptor 1 (BLT1) is required for nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-mediated exocytotic degranulation of mast cells induced by TvSP. First, stimulation with TvSP induced exocytotic degranulation and reactive oxygen species (ROS) generation in HMC-1 cells. Next, TvSP-induced ROS generation and exocytosis were strongly inhibited by transfection of BLT1 small interfering RNA (siRNA). TvSP induced trafficking of BLT1 from the cytosol to the plasma membrane. We also found that knockdown of SNAP23 abrogated TvSP-induced ROS generation, exocytosis, and surface trafficking of BLT1 in HMC-1 cells. By coimmunoprecipitation, there was a physical interaction between BLT1 and SNAP23 in TvSP-stimulated HMC-1 cells. Taken together, our results suggest that SNAP23-dependent surface trafficking of BLT1 is essential for exocytosis in human mast cells induced by T. vaginalis-secreted LTB 4 Our data collectively demonstrate a novel regulatory mechanism for SNAP23-dependent mast cell activation of T. vaginalis-secreted LTB 4 involving surface trafficking of BLT1. These results can help to explain how the cross talk mechanism between parasite and host can govern deliberately tissue inflammatory responses. Copyright © 2016 American Society for Microbiology.

Simulation-Based e-Learning Tools for Science,Engineering, and Technology Education(SimBeLT)

Science.gov (United States)

Davis, Doyle V.; Cherner, Y.

2006-12-01

The focus of Project SimBeLT is the research, development, testing, and dissemination of a new type of simulation-based integrated e-learning set of modules for two-year college technical and engineering curricula in the areas of thermodynamics, fluid physics, and fiber optics that can also be used in secondary schools and four-year colleges. A collection of sophisticated virtual labs is the core component of the SimBeLT modules. These labs will be designed to enhance the understanding of technical concepts and underlying fundamental principles of these topics, as well as to master certain performance based skills online. SimBeLT software will help educators to meet the National Science Education Standard that "learning science and technology is something that students do, not something that is done to them". A major component of Project SimBeLT is the development of multi-layered technology-oriented virtual labs that realistically mimic workplace-like environments. Dynamic data exchange between simulations will be implemented and links with instant instructional messages and data handling tools will be realized. A second important goal of Project SimBeLT labs is to bridge technical skills and scientific knowledge by enhancing the teaching and learning of specific scientific or engineering subjects. SimBeLT builds upon research and outcomes of interactive teaching strategies and tools developed through prior NSF funding (http://webphysics.nhctc.edu/compact/index.html) (Project SimBeLT is partially supported by a grant from the National Science Foundation DUE-0603277)

Effects of doping on ferroelectric properties and leakage current behavior of KNN-LT-LS thin films on SrTiO3 substrate

Science.gov (United States)

Abazari, M.; Safari, A.

2009-05-01

We report the effects of Ba, Ti, and Mn dopants on ferroelectric polarization and leakage current of (K0.44Na0.52Li0.04)(Nb0.84Ta0.1Sb0.06)O3 (KNN-LT-LS) thin films deposited by pulsed laser deposition. It is shown that donor dopants such as Ba2+, which increased the resistivity in bulk KNN-LT-LS, had an opposite effect in the thin film. Ti4+ as an acceptor B-site dopant reduces the leakage current by an order of magnitude, while the polarization values showed a slight degradation. Mn4+, however, was found to effectively suppress the leakage current by over two orders of magnitude while enhancing the polarization, with 15 and 23 μC/cm2 remanent and saturated polarization, whose values are ˜70% and 82% of the reported values for bulk composition. This phenomenon has been associated with the dual effect of Mn4+ in KNN-LT-LS thin film, by substituting both A- and B-site cations. A detailed description on how each dopant affects the concentrations of vacancies in the lattice is presented. Mn-doped KNN-LT-LS thin films are shown to be a promising candidate for lead-free thin films and applications.

UEP LT Codes with Intermediate Feedback

DEFF Research Database (Denmark)

Sørensen, Jesper Hemming; Popovski, Petar; Østergaard, Jan

2013-01-01

We analyze a class of rateless codes, called Luby transform (LT) codes with unequal error protection (UEP). We show that while these codes successfully provide UEP, there is a significant price in terms of redundancy in the lower prioritized segments. We propose a modification with a single inter...... intermediate feedback message. Our analysis shows a dramatic improvement on the decoding performance of the lower prioritized segment....

Evidence for autocrine and paracrine regulation of allergen-induced mast cell mediator release in the guinea pig airways.

Science.gov (United States)

Yu, Li; Liu, Qi; Canning, Brendan J

2018-03-05

Mast cells play an essential role in immediate type hypersensitivity reactions and in chronic allergic diseases of the airways, including asthma. Mast cell mediator release can be modulated by locally released autacoids and circulating hormones, but surprisingly little is known about the autocrine effects of mediators released upon mast cell activation. We thus set out to characterize the autocrine and paracrine effects of mast cell mediators on mast cell activation in the guinea pig airways. By direct measures of histamine, cysteinyl-leukotriene and thromboxane release and with studies of allergen-evoked contractions of airway smooth muscle, we describe a complex interplay amongst these autacoids. Notably, we observed an autocrine effect of the cysteinyl-leukotrienes acting through cysLT 1 receptors on mast cell leukotriene release. We confirmed the results of previous studies demonstrating a marked enhancement of mast cell mediator release following cyclooxygenase inhibition, but we have extended these results by showing that COX-2 derived eicosanoids inhibit cysteinyl-leukotriene release and yet are without effect on histamine release. Given the prominent role of COX-1 inhibition in aspirin-sensitive asthma, these data implicate preformed mediators stored in granules as the initial drivers of these adverse reactions. Finally, we describe the paracrine signaling cascade leading to thromboxane synthesis in the guinea pig airways following allergen challenge, which occurs indirectly, secondary to cysLT 1 receptor activation on structural cells and/ or leukocytes within the airway wall, and a COX-2 dependent synthesis of the eicosanoid. The results highlight the importance of cell-cell and autocrine interactions in regulating allergic responses in the airways. Copyright © 2017. Published by Elsevier B.V.

Human LT-alpha-mediated resistance to autoimmune diabetes is induced in NOD, but not NOD-scid, mice and abrogated by IL-12.

Science.gov (United States)

Miyaguchi, S; Satoh, J; Takahashi, K; Sakata, Y; Nakazawa, T; Miyazaki, J; Toyota, T

2001-01-01

Systemic administration of human lymphotoxin-alpha (hLT-alpha) made NOD mice resistant not only to spontaneous autoimmune type 1 diabetes mellitus but also to cyclophosphamide (CY)-induced diabetes and diabetes transfer by diabetic NOD spleen cells (triple resistance). In this study we analyzed the mechanisms of hLT-alpha-induced resistance, focusing on (1) hLT-alpha-induced resistance in the pancreatic beta cell, (2) CY-resistant suppressor cells, (3) suppression of induction or function of effector cells for beta cell destruction, or (4) others. To examine the first possibility in vitro, a NOD-derived beta cell line (MIN6N) was pretreated with hLT-alpha and then mixed with diabetic NOD spleen cells and MIN6N cell viability was measured. Treatment with hLT-alpha did not protect MIN6N cells but rather enhanced cytotoxicity. Next NOD-scid mice were pretreated with hLT-alpha and then transferred with diabetic NOD spleen. All the recipients developed diabetes. These results excluded the first possibility. The second possibility was also excluded by a cotransfer experiment, in which diabetic NOD spleen cells were cotransferred to NOD-scid mice with nontreated or hLT-alpha-treated nondiabetic NOD spleens. There was no significant difference in diabetes incidence between the two groups. To observe the third possibility, spleen cells of hLT-alpha-treated triple-resistant NOD mice were transferred to NOD-scid mice. Diabetes developed in the recipients, although the onset of diabetes was slightly delayed. Finally, hLT-alpha-treated triple-resistant NOD mice developed diabetes 1 week after daily IL-12 treatment. In summary, hLT-alpha administration made NOD mice resistant to effector cells for beta cell destruction. This resistance was induced in NOD, but not in NOD-scid, mice, indicating that lymphocytes were obligatory for the resistance. However, it was not mediated by transferable suppressor cells. Because effector cells were present in hLT-alpha-treated NOD spleen and

AutoCAD 2015 and AutoCAD LT 2015 bible

CERN Document Server

Finkelstein, Ellen

2014-01-01

The perfect reference for all AutoCAD users AutoCAD 2015 and AutoCAD LT 2015 Bible is the book you want to have close at hand to answer those day-to-day questions about this industry-leading software. Author and Autodesk University instructor Ellen Finkelstein guides readers through AutoCAD 2015 and AutoCAD LT 2015 with clear, easy-to-understand instruction and hands-on tutorials that allow even total beginners to create a design on their very first day. Although simple and fundamental enough to be used by those new to CAD, the book is so comprehensive that even Autodesk power u

Leucocyte labeling: Preliminary clinical evaluation of RP517, the 99mTc-Leukotriene B4 receptor antagonist for infection/inflammation

International Nuclear Information System (INIS)

Soroa, V.E.; Velasquez, M.H.; Nicolini, J.; Ughetti, R.; Camin, L.

2002-01-01

99mTc- Leukotriene B4 (LTB4) is a receptor antagonist RP517 that labels predominantly neutrophils, in whole blood. This new radiopharmaceutical has been developed for imaging infection and inflammation. Aim: We conducted this clinical trial to obtain the best protocol imaging and the efficacy of this novel agent in the detection of suspected infected/inflamed patients. Materials and Methods: RP517 was labelled with 15-20 mCi (555-740 MBq) 99mTc for each patient, with a labeling efficiency of 86-95%. Nine patients studied (F 3, M 6) with ages 45-83, suspected of bone, joint and soft tissue infection (8) and one with fever of unknown origin (FUO). Laboratory, anatomical images and one other scintiscan (MDP, Gallium or 99mTc-ciprofloxacin) were used for evaluation. Acquisition protocol: flow, 30 min, 1, 2, 3, 4 - 24h planar or SPECT images if required. Results were compared to histology, cultures, the clinical derivation and follow up. Scans were classified as positive if abnormal uptake persisted through the 24h images or negative when absent pathological uptake or when positivity faded in later images. Results: No adverse reaction encountered. Image protocol modified to a flow, 30 min, 4 and 24h acquisitions. Early bladder excretion and intestinal activity requires previous cleansing enemas and food restrain. Late bone marrow activity is less visible than with in vitro leucocyte labeling. Coincident images were obtained in 3 True Positive, in 5 True Negative except in a hip prosthesis where Gallium and 99mTc-ciprofloxacin showed positivity and RP517 was False negative. Conclusions: A kit should be produced in order to make it available for Nuclear Medicine Departments. Known advantages of RP517 is the lack of in vitro cell labeling manipulation. We do not recommend investigation of FUO or abdominal pathologies. A larger series must be studied in order to be able to obtain statistics on joint bone and soft tissue infection/inflammation where this compound seems to be

LT^2C^2: A language of thought with Turing-computable Kolmogorov complexity

Directory of Open Access Journals (Sweden)

Santiago Figueira

2013-03-01

Full Text Available In this paper, we present a theoretical effort to connect the theory of program size to psychology by implementing a concrete language of thought with Turing-computable Kolmogorov complexity (LT^2C^2 satisfying the following requirements: 1 to be simple enough so that the complexity of any given finite binary sequence can be computed, 2 to be based on tangible operations of human reasoning (printing, repeating,. . . , 3 to be sufficiently powerful to generate all possible sequences but not too powerful as to identify regularities which would be invisible to humans. We first formalize LT^2C^2, giving its syntax and semantics, and defining an adequate notion of program size. Our setting leads to a Kolmogorov complexity function relative to LT^2C^2 which is computable in polynomial time, and it also induces a prediction algorithm in the spirit of Solomonoff’s inductive inference theory. We then prove the efficacy of this language by investigating regularities in strings produced by participants attempting to generate random strings. Participants had a profound understanding of randomness and hence avoided typical misconceptions such as exaggerating the number of alternations. We reasoned that remaining regularities would express the algorithmic nature of human thoughts, revealed in the form of specific patterns. Kolmogorov complexity relative to LT^2C^2 passed three expected tests examined here: 1 human sequences were less complex than control PRNG sequences, 2 human sequences were not stationary showing decreasing values of complexity resulting from fatigue 3 each individual showed traces of algorithmic stability since fitting of partial data was more effective to predict subsequent data than average fits. This work extends on previous efforts to combine notions of Kolmogorov complexity theory and algorithmic information theory to psychology, by explicitly proposing a language which may describe the patterns of human thoughts.Received: 12

Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in childhood asthma: a pilot study

Directory of Open Access Journals (Sweden)

Kharitonov Sergei A

2006-04-01

Full Text Available Abstract Background It has been suggested that cysteinyl leukotrienes (cysLTs play an important role in airway remodeling. Previous reports have indicated that cysLTs augment human airway smooth muscle cell proliferation. Recently, cysLTs have been measured in exhaled breath condensate (EBC. The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM thickening, in endobronchial biopsies in children. Methods 29 children, aged 4–15 years, with moderate to severe persistent asthma, who underwent bronchoscopy as part of their clinical assessment, were included. Subjects underwent spirometry and EBC collection for cysLTs analysis, followed by bronchoscopy and endobronchial biopsy within 24 hours. Results EBC cysLTs were significantly lower in asthmatic children who were treated with montelukast than in those who were not (median (interquartile range 36.62 (22.60–101.05 versus 249.1 (74.21–526.36 pg/ml, p = 0.004. There was a significant relationship between EBC cysLTs and RBM thickness in the subgroup of children who were not treated with montelukast (n = 13, r = 0.75, p = 0.003. Conclusion EBC cysLTs appear to be associated with RBM thickening in asthma.

The Saccharomyces boulardii CNCM I-745 Strain Shows Protective Effects against the B. anthracis LT Toxin

Directory of Open Access Journals (Sweden)

Rodolphe Pontier-Bres

2015-10-01

Full Text Available The probiotic yeast Saccharomyces boulardii (S. boulardii has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax.

The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin.

Science.gov (United States)

Pontier-Bres, Rodolphe; Rampal, Patrick; Peyron, Jean-François; Munro, Patrick; Lemichez, Emmanuel; Czerucka, Dorota

2015-10-30

The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax.

Clinical experience with EDAP LT-01+ extracorporeal shock wave lithotripsy for radiolucent stones; a report of 27 cases

International Nuclear Information System (INIS)

Rim, Hee Kwan; Kim, Ho Sung; Rim, Joung Sik

1994-01-01

Between February 1990 and February 1993, Radiolucent stones of 27 renal units in 22 patients were treated by extracorporeal shock wave lithotripsy (ESWL) using the EDAP LT-01+. Intravenous urography was done in all patients for the diagnosis of radiolucent stones. Retrograde pyelography, ultrasonography and/or computed tomography was done, if needed. The locations of stones were kidney in 11(40.7 %), upper ureter in 8(29.6 %), lower ureter in 6(22.2 %), bladder in 1(3.7 %), ureteropelvic junction in 1(3.7 %). The average stone size was 10.9mm with a range of 5 to 32mm in maximum diameter. The average numbers of treatment were 2.7 sessions and average storage required was 34.8 in one session. The average treatment time was 40.4 minutes. All the patients showed complete removal of all calculous materials. Of 17 urinary stones analysed by chemical method, 8(47.1 %) were composed of uric acid, 5(29.4 %) of uric acid and calcium, 3 of phosphate and 1 of carbonate and phosphate. Therefore, we conclude that ESWL with EDAP LT-01+ lithotriptor is considered to be an effective noninvasive procedure for treatment of radiolucent stones. (Author)

Marker-Assisted Selection of Xa21 Conferring Resistance to Bacterial Leaf Blight in indica Rice Cultivar LT2

Institute of Scientific and Technical Information of China (English)

Hue Thi NGUYEN; Trung Nguyen DINH; Nakano TOSHITSUGU; Liet Van VU; Quang Hong VU; Tan Van MAI; Thu Thi NGUYEN; Lam Duc VU; Tung Thanh NGUYEN; Long Viet NGUYEN; Hien Thu Thi VU; Hue Thi NONG

2018-01-01

Bacterial leaf blight of rice (BLB), caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases in Asian rice fields. A high-quality rice variety, LT2, was used as the recipient parent. IRBB21, which carries the Xa21 gene, was used as the donor parent. The resistance gene Xa21 was introduced into LT2 by marker-assisted backcrossing. Three Xoo races were used to inoculate the improved lines following the clipping method. Eleven BC3F3lines carrying Xa21 were obtained based on molecular markers and agronomic performance. The 11 lines were then inoculated with the three Xoo races. All the 11 improved lines showed better resistance to BLB than the recipient parent LT2. Based on the level of resistance to BLB and their agronomic performance, five lines (BC3F35.1.5.1, BC3F35.1.5.12, BC3F38.5.6.44, BC3F3 9.5.4.1 and BC3F39.5.4.23) were selected as the most promising for commercial release. These improved lines could contribute to rice production in terms of food security.

LT COL F.F. PIENAAR'S BOER WAR DIARY

African Journals Online (AJOL)

LT COL F.F. PIENAAR'S BOER WAR DIARY. (PART II). Brig J.H. Picard, SM*. FREE STATE TO ..... bing up and down on his master's spare horse. ... Jantjie and his master turned out of the road, and ..... on a list which burghers could afford to.

Persistence of Salmonella Typhimurium LT2 in Soil Enhanced after Growth in Lettuce Medium

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Kornelia Smalla

2017-04-01

Full Text Available The persistence of Salmonella in the environment is influenced by a multitude of biotic and abiotic factors. In addition, its persistence can be influenced by preadaptation before the introduction into the environment. In order to study how preadaptation changes the survival of Salmonella in soil and therefore its potential to colonize the phytosphere, we developed a new medium based on lettuce material [lettuce medium (LM]. Salmonella enterica serovar Typhimurium strain LT2 was used as a model for Salmonella in this study. LT2 was inoculated into soil microcosms after pregrowth in Luria Bertani (LB broth or in LM. Survival of LT2 in soil was monitored over 56 days by plate counts and quantification of the Typhimurium-specific gene STM4497 using qPCR in total community DNA for which primers and TaqMan probe were designed in this study. Significantly enhanced persistence was observed for LT2 pregrown in LM compared to LT2 pregrown in LB, indicating a preadaptation effect. Surprisingly, no improved survival could be observed for S. Typhimurium strain 14028s and S. enterica serovar Senftenberg after pregrowth on LM. This indicates a high strain specificity of preadaptation. Results from previous studies suggested that biofilm formation could enhance the survival of human pathogens in various environments and might contribute to enhanced survival on plants. In vitro biofilm assays with several Salmonella strains revealed a strain-specific effect of LM on the biofilm formation. While LM significantly improved the biofilm formation of S. Senftenberg, the biofilm formation of LT2 was better in LB. This indicates that the better survival of LM-pregrown LT2 in soil was not linked to an improved ability to form biofilms but was likely due to other factors. Most importantly, this study showed that the medium used to pregrow Salmonella can influence its survival in soil and its biofilm formation which might influence the fate of Salmonella in soil.

[Treatment of ASS-Associated Polyposis (ASSAP) with a cysteinyl leukotriene receptor antagonist - a prospective drug study on its antiinflammatory effects].

Science.gov (United States)

Grundmann, T; Töpfner, M

2001-10-01

In a high rate of cases with recurrent polyposis an association with ASS-intolerance is detectable despite missing pulmonary symptoms. New examinations of a disturbed arachidonic acid metabolism lead to the development of new therapeutical options. Treatment with leukotriene-receptor antogonists (LTA) showed primarily good results in therapy of ASS-associated asthma. 18 patients with ASS-intolerance trias - diagnosed by oral provocation - were treated with the LTA Montelukast, after undergoing sinus surgery. Patients underwent a diagnostic pathway of provocation including four groups: recurrent chronic sinusitis, excessive polyposis, polyposis associated with asthma and anaphylactic symptoms after oral ASS-intake. Clinically we examined the following parameters periodically after sinus surgery: nasal and pulmonal symptoms by scoring levels, recurrency of polypoid hyperplasia by endoscopic follow-ups and serum ECP-levels. To evaluate antiinflammatory tissue effects of LTA EG1/EG2 labelled cells and cytokine levels of Interleukin 5 in mucosa samples of the lower turbinate were analysed under LTA-therapy. Under therapy with LTA we saw a beneficial effect on nasal and pulmonary symptoms and a significant reduction of recurrent polyposis in endoscopic examinations in relation to the untreated group. Results were proven by a permanent reduction of serum ECP-level. A reduction of the rate of EG2-positive cells according to decreased Interleukin 5 levels in the nasal mucosa unter LTA-treatment assumed antiinflammatory effects on ASS-associated polyposis. We could demonstrate antiinflammatory effects of Leukotriene-Receptor-Antagonists primarily during postoperative treatment of patients with ASS-associated nasal polyps.

Yoğurt Yapımında Saf Kültürün Kullanımı

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Sevda Kılıç

2015-02-01

Full Text Available Yoğurt, sütün L. bulgaricus ve S. thermophilus bakterilerini belirli oranlarda içeren kültürle aşılanması sonucu elde edilen bir süt mamülüdür. Yoğurt teknolojisinde yaklaşık 70 yıldır kültür kullanılmaktadır. Kültürün hazırlanmasında yararlanılan bakteriler, belirli özellikleri dikkate alınarak seçilmektedir. Daha sonra yağsız süt tozundan hazırlanan süte aşılanarak 42-44 oC’de inkübasyona bırakılmakta ve pH 4.7 olduğunda inkübasyona son verilerek çoğaltımı ve aktifleşmeleri sağlanmaktadır. Günümüzde diğer ülkelerde olduğu gibi ülkemizde de kültür kullanımı gıda maddeleri tüzüğünün 51. maddesine göre zorunlu tutulmaktadır. Ancak buna rağmen kültür, tam anlamıyla bilinmemekte veya bilinçli olarak kullanılmamaktadır. Yoğurt teknolojisinde kültür, kullanımı ile daha kaliteli yoğurt yapılmaktadır. Uzun süre tat, aroma ve yapısı bozulmadan saklanabilmekte, raf ömrü uzamaktadır. Normal sertlikte olan yoğurtta asitlik istenilen düzeyde olduğu için su salmada görülmez.

Structural characterization of the Salmonella typhimurium LT2 umu operon

International Nuclear Information System (INIS)

Thomas, S.M.; Crowne, H.M.; Pidsley, S.C.; Sedgwick, S.G.

1990-01-01

The umuDC operon of Escherichia coli encodes functions required for mutagenesis induced by radiation and a wide variety of chemicals. The closely related organism Salmonella typhimurium is markedly less mutable than E. coli, but a umu homolog has recently been identified and cloned from the LT2 subline. In this study the nucleotide sequence and structure of the S. typhimurium LT2 umu operon have been determined and its gene products have been identified so that the molecular basis of umu activity might be understood more fully. S. typhimurium LT2 umu consists of a smaller 417-base-pair (bp) umuD gene ending 2 bp upstream of a larger 1,266-bp umuC gene. The only apparent structural difference between the two operons is the lack of gene overlap. An SOS box identical to that found in E. coli is present in the promoter region upstream of umuD. The calculated molecular masses of the umuD and umuC gene products were 15.3 and 47.8 kilodaltons, respectively, which agree with figures determined by transpositional disruption and maxicell analysis. The S. typhimurium and E. coli umuD sequences were 68% homologous and encoded products with 71% amino acid identity; the umuC sequences were 71% homologous and encoded products with 83% amino acid identity. Furthermore, the potential UmuD cleavage site and associated catalytic sites could be identified. Thus the very different mutagenic responses of S. typhimurium LT2 and E. coli cannot be accounted for by gross differences in operon structure or gene products. Rather, the ability of the cloned S. typhimurium umuD gene to give stronger complementation of E. coli umuD77 mutants in the absence of a functional umuC gene suggests that Salmonella UmuC protein normally constrains UmuD protein activity

Tissue distribution of a leukotriene antagonist 14C-LY170680, following inhalation exposure in the rat

International Nuclear Information System (INIS)

Pohland, R.C.; Beck, J.M.; Carlson, K.H.; Herman, D.R.; Hoppes, J.L.; Vavrek, M.T.; Wolff, R.K.

1991-01-01

Dissection and whole-body autoradiographic techniques were used to determine the tissue distribution profile of a leukotriene antagonist, 14 C-LY170680, following nose-only inhalation exposure in the rat. Liquid scintillation spectrometry and whole-body autoradiography indicated that highest concentrations of radiocarbon were present in stomach and small intestine at all time points. Radiocarbon reached maximum levels in stomach (2,259 ng-eq/g) and small intestine (2,399 ng-eq/g) 2 to 4 hours postexposure, respectively, and declined with time. In contrast, maximum radiocarbon concentrations in the head (146 ng-eq/g), trachea (408 ng-eq/g), and lung (534 ng-eq/g) occurred at 0 hours postexposure and steadily declined with time. Low concentrations of radiocarbon were detected in the liver ( 14 C-LY170680 were deposited in the head and within the lung following inhalation exposure. However, higher levels of radiocarbon present in the stomach and small intestine suggested significant nasal deposition followed by rapid clearance and ingestion of inhaled radioactive material. Distribution of radiocarbon limited to the respiratory and gastrointestinal tracts demonstrated minimal systemic absorption and exposure over the time course of this study

A new avian fauna from the early-middle Eocene Lillebælt Clay Formation of Denmark

DEFF Research Database (Denmark)

Lindow, Bent Erik Kramer

A number of hitherto undescribed fossil bird remains have been recovered from the Lillebælt Clay Formation of central Denmark, which is early-middle Eocene in age (~50 to 43 mya). The core of the material consists of fossils acquired through the Danish ‘Danekræ' fossil treasure trove legislation......, a member of the extinct 'pseudo-toothed birds' and the first representative of this group known from Denmark. Other taxa present include remains of Lithornithidae and a new taxon possessing a massive, psittacid-like beak. The Lillebælt Clay Formation birds are temporally placed just after the Early Eocene...

Ripple design of LT codes for AWGN channel

DEFF Research Database (Denmark)

Sørensen, Jesper Hemming; Koike-Akino, Toshiaki; Orlik, Philip

2012-01-01

In this paper, we present an analytical framework for designing LT codes in additive white Gaussian noise (AWGN) channels. We show that some of analytical results from binary erasure channels (BEC) also hold in AWGN channels with slight modifications. This enables us to apply a ripple-based design...

Marker-Assisted Selection of Xa21 Conferring Resistance to Bacterial Leaf Blight in indica Rice Cultivar LT2

Directory of Open Access Journals (Sweden)

Hue Thi Nguyen

2018-01-01

Full Text Available Bacterial leaf blight of rice (BLB, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases in Asian rice fields. A high-quality rice variety, LT2, was used as the recipient parent. IRBB21, which carries the Xa21 gene, was used as the donor parent. The resistance gene Xa21 was introduced into LT2 by marker-assisted backcrossing. Three Xoo races were used to inoculate the improved lines following the clipping method. Eleven BC3F3 lines carrying Xa21 were obtained based on molecular markers and agronomic performance. The 11 lines were then inoculated with the three Xoo races. All the 11 improved lines showed better resistance to BLB than the recipient parent LT2. Based on the level of resistance to BLB and their agronomic performance, five lines (BC3F3 5.1.5.1, BC3F3 5.1.5.12, BC3F3 8.5.6.44, BC3F3 9.5.4.1 and BC3F3 9.5.4.23 were selected as the most promising for commercial release. These improved lines could contribute to rice production in terms of food security.

Containment pressure analysis model using CONTEMPT-LT

International Nuclear Information System (INIS)

Gupta, R.N.

1975-09-01

An analytical model for evaluating the reactor containment pressure transient following a loss-of-coolant accident (LOCA) is presented. The model uses the CONTEMPT-LT computer program developed by Aerojet Nuclear Company. The sample problem studied is the containment response following the most severe postulated LOCA at the Yankee Rowe Nuclear Power Station. The results show good agreement with the response predicted by Westinghouse Electric Corporation. (auth)

Characterization and Validation of the LT-SYS Copper Assay on a Roche Cobas 8000 c502 Analyzer.

Science.gov (United States)

Kraus, F Bernhard; Mischereit, Marlies; Eller, Christoph; Ludwig-Kraus, Beatrice

2017-02-01

Validation of the LT-SYS quantitative in vitro copper assay on a Roche Cobas 8000 c502 analyzer and comparison with a BIOMED assay on a Roche Cobas Mira analyzer. Imprecision and bias were quantified at different concentration levels (serum and plasma) over a 20-day period. Linearity was assessed covering a range from 4.08 µmol/L to 33.8 µmol/L. Limit of blank (LoB) and limit of detection (LoD) were established based on a total of 120 blank and low-level samples. The method comparison was based on 58 plasma samples. Within-run imprecision ranged from 0.7% to 1.2% and within-laboratory imprecision from 1.4% to 3.3%. Relative bias for the 2 serum pools with known target values was less than 2.5%. The assay did not deviate from linearity over the tested measuring range. LoB and LoD were 0.12 µmol/L and 0.23 µmol/L, respectively. The method comparison revealed an average deviation of 11.5% (2.016 µmol/L), and the linear regression fit was y = 1.464 + 0.795x. The LT-SYS copper assay characterized in this study showed a fully acceptable performance with good degrees of imprecision and bias, no deviation from linearity in the relevant measuring rangem, and very low LoB and LoD. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Production of arachidonic and linoleic acid metabolites by guinea pig tracheal epithelial cells

International Nuclear Information System (INIS)

Oosthuizen, M.J.; Engels, F.; Van Esch, B.; Henricks, P.A.; Nijkamp, F.P.

1990-01-01

Pulmonary epithelial cells may be responsible for regulating airway smooth muscle function, in part by release of fatty acid-derived mediators. Incubation of isolated guinea pig tracheal epithelial cells with radiolabeled arachidonic acid (AA) leads to the production of 5- and 15-hydroxyeicosatetraenoic acid (5- and 15-HETE) and smaller amounts of leukotriene (LT) B4 and C4 and 12-hydroxyheptadecatrienoic acid (HHT). Epithelial cells also are able to release linoleic acid (LA) metabolites. Incubation with radiolabeled linoleic acid leads to the formation of 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE). The biological significance of these mediators produced by epithelial cells is discussed

Corrections and additions to CONTEMPT-LT computer codes for containment analysis

International Nuclear Information System (INIS)

Eerikaeinen, Lauri.

1980-01-01

The report presents a new version of CONTEMPT-LT/26 tainment code. The corrections and additions are applicable also to other CONTEMPT-LT versions. Thermodynamical background of corrections are shortly described, and in addition, some essential points which should be taken into account in the analysis of a pressure suppression containment have been pointed out. The results obtained by the corrected version have been compared to those calculated by the original program, and to the measured data in the Marviken containment experiment No 10. Finally, it has been indicated that for reliable pressure suppression analysis a wide ranging condensation model for air-steam mixture is necessary. (author)

Variability of Two Young L/T Transition Brown Dwarfs

Science.gov (United States)

Allers, Katelyn; Biller, Beth; Gallimore, Jack; Crossfield, Ian

2015-10-01

We propose for photometric monitoring observations of WISEP J004701.06+680352 (hereinafter W0047) and 2MASSWJ2244316+204343 (hereinafter 2M2244) using Spitzer/IRAC. Both objects are kinematically confirmed L7 members of the 150 Myr old AB Doradus moving group and show remarkable spectral similarity in both the near-IR and optical. The WoW survey found that L/T transition brown dwarfs having detected mid-IR variability are redder than the typical J - K color for their spectral type. A Cycle 11 exploration program (P.I. Metchev) is investigating the geometrical dependence of color and variability by expanding the original WoW sample. If inclination and J - K color are correlated (as predicted by Metchev et al.), then the spectral and photometric diversity seen across the L/T transition could be explained by geometry rather than diversity in atmospheric chemistry and dynamics. This would have wide ranging implications for the way we model cloud dissipation for brown dwarfs and extrasolar planets. Our proposed observations will provide an important test of the Metchev et al. prediction complementary to their Cycle 11 program. W0047 and 2M2244 are the same age, and have remarkably similar colors (J - K = 2.55 and 2.46 mags, respectively) and underlying spectra. Thus, if Metchev's prediction about the correlation of inclination and spectral morphology holds true, we would expect that W0047 and 2M2244 should have similar inclinations. However, the measured v sin(i) values for W0047 and 2M2244 are quite different. This difference in v sin(i) could be due to spin-axis inclination (with W0047 having a smaller i) or orbital period (with W0047 having a longer period), both of which we will determine from our proposed observations. This test is a unique opportunity, as there are no other free-floating L/T transition dwarfs known to be both coeval and spectrally similar. Our proposed observations will also extend the spectral type range for young objects surveyed for variability

Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children.

Science.gov (United States)

Wojnarowski, C; Halmerbauer, G; Mayatepek, E; Gartner, C; Frischer, T; Forster, J; Kuehr, J

2001-09-01

Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in

Type II heat-labile enterotoxins from 50 diverse Escherichia coli isolates belong almost exclusively to the LT-IIc family and may be prophage encoded.

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Michael G Jobling

Full Text Available Some enterotoxigenic Escherichia coli (ETEC produce a type II heat-labile enterotoxin (LT-II that activates adenylate cyclase in susceptible cells but is not neutralized by antisera against cholera toxin or type I heat-labile enterotoxin (LT-I. LT-I variants encoded by plasmids in ETEC from humans and pigs have amino acid sequences that are ≥ 95% identical. In contrast, LT-II toxins are chromosomally encoded and are much more diverse. Early studies characterized LT-IIa and LT-IIb variants, but a novel LT-IIc was reported recently. Here we characterized the LT-II encoding loci from 48 additional ETEC isolates. Two encoded LT-IIa, none encoded LT-IIb, and 46 encoded highly related variants of LT-IIc. Phylogenetic analysis indicated that the predicted LT-IIc toxins encoded by these loci could be assigned to 6 subgroups. The loci corresponding to individual toxins within each subgroup had DNA sequences that were more than 99% identical. The LT-IIc subgroups appear to have arisen by multiple recombinational events between progenitor loci encoding LT-IIc1- and LT-IIc3-like variants. All loci from representative isolates encoding the LT-IIa, LT-IIb, and each subgroup of LT-IIc enterotoxins are preceded by highly-related genes that are between 80 and 93% identical to predicted phage lysozyme genes. DNA sequences immediately following the B genes differ considerably between toxin subgroups, but all are most closely related to genomic sequences found in predicted prophages. Together these data suggest that the LT-II loci are inserted into lambdoid type prophages that may or may not be infectious. These findings raise the possibility that production of LT-II enterotoxins by ETEC may be determined by phage conversion and may be activated by induction of prophage, in a manner similar to control of production of Shiga-like toxins by converting phages in isolates of enterohemmorhagic E. coli.

Alkaline pH Is a signal for optimal production and secretion of the heat labile toxin, LT in enterotoxigenic Escherichia coli (ETEC.

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Lucia Gonzales

Full Text Available Enterotoxigenic Escherichia coli (ETEC cause secretory diarrhea in children and travelers to endemic areas. ETEC spreads through the fecal-oral route. After ingestion, ETEC passes through the stomach and duodenum before it colonizes the lower part of the small intestine, exposing bacteria to a wide range of pH and environmental conditions. This study aimed to determine the impact of external pH and activity of the Cyclic AMP receptor protein (CRP on the regulation of production and secretion of heat labile (LT enterotoxin. ETEC strain E2863wt and its isogenic mutant E2863ΔCRP were grown in LBK media buffered to pH 5, 7 and 9. GM1 ELISA, cDNA and cAMP analyses were carried out on bacterial pellet and supernatant samples derived from 3 and 5 hours growth and from overnight cultures. We confirm that CRP is a repressor of LT transcription and production as has been shown before but we show for the first time that CRP is a positive regulator of LT secretion both in vitro and in vivo. LT secretion increased at neutral to alkaline pH compared to acidic pH 5 where secretion was completely inhibited. At pH 9 secretion of LT was optimal resulting in 600 percent increase of secreted LT compared to unbuffered LBK media. This effect was not due to membrane leakage since the bacteria were viable at pH 9. The results indicate that the transition to the alkaline duodenum and/or exposure to high pH close to the epithelium as well as activation of the global transcription factor CRP are signals that induce secretion of the LT toxin in ETEC.

Quantum-well exciton dipolar interaction: Polarization-dependence and Z-LT splitting

International Nuclear Information System (INIS)

Nguyen Ba An.

1996-12-01

We calculate the exciton dipolar interaction in a semiconductor quantum well. The explicit polarization-dependence, i.e, the dependence on both the exciton dipole moment μ-vector and its inplane wavevector k-vector is derived. The obtained results for the three modes (L, T and Z modes) of the long-range part of the dipolar interaction satisfy the polarization sum rule for any parameters. In the long wavelength limit there is a Z-LT splitting which decreases as the well width increases reflecting a crossover from strict 2D to quasi-2D. A rough crossover from quasi-2D to 3D is also described. (author). 18 refs, 4 figs

Investigation of Public Charging Infrastructure : Case study Gränby sportfält

OpenAIRE

Dahl, Emma; Hedström, Andreas; Lindgren, Anna

2017-01-01

The municipal company Sportfastigheter AB is currently renovating and developing Gränby sportfält, a sports field in Uppsala. Adjacent to the sports field, a parking lot for 700 vehicles is located, where Sportfastigheter AB is preparing to install charging points for electric vehicles (EVs) at some of the places. This bachelor thesis aims to investigate how a public charging solution should be modeled, with the parking lot at Gränby sportfält as a case study. The investigation involves estim...

Designing an efficient LT-code with unequal error protection for image transmission

Science.gov (United States)

S. Marques, F.; Schwartz, C.; Pinho, M. S.; Finamore, W. A.

2015-10-01

The use of images from earth observation satellites is spread over different applications, such as a car navigation systems and a disaster monitoring. In general, those images are captured by on board imaging devices and must be transmitted to the Earth using a communication system. Even though a high resolution image can produce a better Quality of Service, it leads to transmitters with high bit rate which require a large bandwidth and expend a large amount of energy. Therefore, it is very important to design efficient communication systems. From communication theory, it is well known that a source encoder is crucial in an efficient system. In a remote sensing satellite image transmission, this efficiency is achieved by using an image compressor, to reduce the amount of data which must be transmitted. The Consultative Committee for Space Data Systems (CCSDS), a multinational forum for the development of communications and data system standards for space flight, establishes a recommended standard for a data compression algorithm for images from space systems. Unfortunately, in the satellite communication channel, the transmitted signal is corrupted by the presence of noise, interference signals, etc. Therefore, the receiver of a digital communication system may fail to recover the transmitted bit. Actually, a channel code can be used to reduce the effect of this failure. In 2002, the Luby Transform code (LT-code) was introduced and it was shown that it was very efficient when the binary erasure channel model was used. Since the effect of the bit recovery failure depends on the position of the bit in the compressed image stream, in the last decade many e orts have been made to develop LT-code with unequal error protection. In 2012, Arslan et al. showed improvements when LT-codes with unequal error protection were used in images compressed by SPIHT algorithm. The techniques presented by Arslan et al. can be adapted to work with the algorithm for image compression

Clinical evaluation of leukotriene receptor antagonists in preventing common cold-like symptoms in bronchial asthma patients.

Science.gov (United States)

Horiguchi, Takahiko; Ohira, Daisuke; Kobayashi, Kashin; Hirose, Masahiro; Miyazaki, Junichi; Kondo, Rieko; Tachikawa, Soichi

2007-09-01

We investigated the possibility of preventing common cold-like symptoms as a previously unknown benefit of leukotriene receptor antagonists (LTRAs). A total of 279 adult patients with bronchial asthma referred to our hospital between June and December 2004 were retrospectively analyzed. Patients were divided into LTRA treated and untreated groups. Frequency of acute exacerbations and number of visits to emergency rooms and of hospital admissions were analyzed as indicators of frequency of infections and asthma exacerbation over the previous 12 months. Irrespective of inhaled corticosteroid (ICS) use, frequency of infections was significantly lower in the LTRA treated group (0.3 +/- 0.7 times/year) than in the LTRA untreated group (1.6 +/- 4.2 times/year) (P cold-like symptoms. Frequency of acute exacerbations and number of hospital admissions were significantly lower in the LTRA treated versus LTRA untreated group (0.4 +/- 0.8 versus 2.7 +/- 4.3 times/year and 0.0 +/- 0.2 versus 0.4 +/- 0.7 times/year, respectively; both P cold-like symptoms than those not receiving LTRAs. LTRAs play an important role in reducing the incidence of common cold-like symptoms among asthma patients and in suppressing exacerbation of asthma symptoms possibly associated with these symptoms.

Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

Science.gov (United States)

Yeh, D Y-W; Yang, Y-C; Wang, J-J

2015-05-01

Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils. Copyright © 2015 Elsevier Inc. All rights reserved.

Study on characterization of interaction layer between U-10wt%Mo alloy and LT24Al

International Nuclear Information System (INIS)

Chen Jiangang; Yin Changgeng; Sun Changlong; Pang Xiaoxuan; Liu Yunming

2009-01-01

The characterization of interaction layer(IL) between U-10wt%Mo alloy and LT24 Al was studied in detail in this paper. Sandwich structured U-Mo/LT24 Al diffusion couples were hot pressed at different temperature and pressure for different time. Then they were analyzed by Optical Microscope (OM) and Scanning Electron Microscope (SEM) to observe the width of the IL. The distribution of the diffusion elements and the phases in the IL were determined by Energy Dispersive Spectroscopy (EDS) and X Ray Diffraction (XRD). Analysis results are as follows: the diffusion manner was reaction diffusion, and diffusion direction mainly was that Al atoms diffused to U-Mo alloy; diffusion mechanism was vacancy diffusion and growth kinetics showed reaction was controlled by the diffusion speed; the IL containing single phase was constituted mainly by (U, Mo) Al 3 ; the IL containing two phases or more was constituted mainly by (U, Mo) Al 3 and (U, Mo) Al 4 and Al 20 Mo 2 U; and Si impurity in the LT24 Al was easy to enrich in the IL which showed Si added to Al could play positive role on improve compatibility between U-Mo and Al. (authors)

Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity.

Science.gov (United States)

Ruan, Xiaosai; Sack, David A; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent

Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen and a toxoid fusion of heat-stable toxin (STa and heat-labile toxin (LT of enterotoxigenic Escherichia coli (ETEC retain broad anti-CFA and antitoxin antigenicity.

Directory of Open Access Journals (Sweden)

Xiaosai Ruan

Full Text Available Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs and two distinct enterotoxins [heat-labile toxin (LT and heat-stable toxin type Ib (STa or hSTa]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2:243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3, CFA/IV (CS4, CS5, CS6] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5:1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in

The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

OpenAIRE

Falf?n-Valencia, Ramc?s; Pav?n-Romero, Gandhi F.; Camarena, Angel; Garc?a, Mar?a de la Luz; Galicia-Negrete, Gustavo; Negrete-Garc?a, Mar?a Cristina; Teran, Luis Manuel

2011-01-01

Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to th...

Novel UEP LT Coding Scheme with Feedback Based on Different Degree Distributions

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Li Ya-Fang

2016-01-01

Full Text Available Traditional unequal error protection (UEP schemes have some limitations and problems, such as the poor UEP performance of high priority data and the seriously sacrifice of low priority data in decoding property. Based on the reasonable applications of different degree distributions in LT codes, this paper puts forward a novel UEP LT coding scheme with a simple feedback to compile these data packets separately. Simulation results show that the proposed scheme can effectively protect high priority data, and improve the transmission efficiency of low priority data from 2.9% to 22.3%. Furthermore, it is fairly suitable to apply this novel scheme to multicast and broadcast environments since only a simple feedback introduced.

Development and preclinical evaluation of safety and immunogenicity of an oral ETEC vaccine containing inactivated E. coli bacteria overexpressing colonization factors CFA/I, CS3, CS5 and CS6 combined with a hybrid LT/CT B subunit antigen, administered alone and together with dmLT adjuvant.

Science.gov (United States)

Holmgren, J; Bourgeois, L; Carlin, N; Clements, J; Gustafsson, B; Lundgren, A; Nygren, E; Tobias, J; Walker, R; Svennerholm, A-M

2013-05-07

A first-generation oral inactivated whole-cell enterotoxigenic Escherichia coli (ETEC) vaccine, comprising formalin-killed ETEC bacteria expressing different colonization factor (CF) antigens combined with cholera toxin B subunit (CTB), when tested in phase III studies did not significantly reduce overall (generally mild) ETEC diarrhea in travelers or children although it reduced more severe ETEC diarrhea in travelers by almost 80%. We have now developed a novel more immunogenic ETEC vaccine based on recombinant non-toxigenic E. coli strains engineered to express increased amounts of CF antigens, including CS6 as well as an ETEC-based B subunit protein (LCTBA), and the optional combination with a nontoxic double-mutant heat-labile toxin (LT) molecule (dmLT) as an adjuvant. Two test vaccines were prepared under GMP: (1) A prototype E. coli CFA/I-only formalin-killed whole-cell+LCTBA vaccine, and (2) A "complete" inactivated multivalent ETEC-CF (CFA/I, CS3, CS5 and CS6 antigens) whole-cell+LCTBA vaccine. These vaccines, when given intragastrically alone or together with dmLT in mice, were well tolerated and induced strong intestinal-mucosal IgA antibody responses as well as serum IgG and IgA responses to each of the vaccine CF antigens as well as to LT B subunit (LTB). Both mucosal and serum responses were further enhanced (adjuvanted) when the vaccines were co-administered with dmLT. We conclude that the new multivalent oral ETEC vaccine, both alone and especially in combination with the dmLT adjuvant, shows great promise for further testing in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of a umuDC locus in Salmonella typhimurium LT2

International Nuclear Information System (INIS)

Smith, C.M.; Eisenstadt, E.

1989-01-01

The umuDC operon of Escherichia coli is required for efficient mutagenesis by UV light and many other DNA-damaging agents. The existence of a umuDC analog in Salmonella typhimurium has been questioned. With DNA probes to the E. coli umuD and umuC genes, we detected, by Southern blot hybridization, sequences similar to both of these genes in S. typhimurium LT2. We also confirmed that the presence of cloned E. coli umuD enhances the UV mutability and resistance of S. typhimurium. Our data strongly suggest that S. typhimurium contains a functional umuDC operon

Potential probiotic of Lactobacillus johnsonii LT171 for chicken ...

African Journals Online (AJOL)

The objective of this research was to investigate the potential probiotic of Lactobacillus johnsonii LT171. It had aggregation (60 min) and antibacterial effects against Salmonella Enteritidis, Salmonella Typhimurium and Escherichia coli O78:K80. It showed amylase and protease activity and high clear zone in culture medium ...

Nanoscale characterization and local piezoelectric properties of lead-free KNN-LT-LS thin films

Energy Technology Data Exchange (ETDEWEB)

Abazari, M; Safari, A [Glenn Howatt Electroceramics Laboratories, Department of Materials Science and Engineering, Rutgers-The state University of New Jersey, Piscataway, NJ 08854 (United States); Choi, T; Cheong, S-W [Rutgers Center for Emergent Materials, Department of Physics and Astronomy, Rutgers-The state University of New Jersey, Piscataway, NJ 08854 (United States)

2010-01-20

We report the observation of domain structure and piezoelectric properties of pure and Mn-doped (K{sub 0.44},Na{sub 0.52},Li{sub 0.04})(Nb{sub 0.84},Ta{sub 0.1},Sb{sub 0.06})O{sub 3} (KNN-LT-LS) thin films on SrTiO{sub 3} substrates. It is revealed that, using piezoresponse force microscopy, ferroelectric domain structure in such 500 nm thin films comprised of primarily 180{sup 0} domains. This was in accordance with the tetragonal structure of the films, confirmed by relative permittivity measurements and x-ray diffraction patterns. Effective piezoelectric coefficient (d{sub 33}) of the films were calculated using piezoelectric displacement curves and shown to be {approx}53 pm V{sup -1} for pure KNN-LT-LS thin films. This value is among the highest values reported for an epitaxial lead-free thin film and shows a great potential for KNN-LT-LS to serve as an alternative to PZT thin films in future applications.

Nanoscale characterization and local piezoelectric properties of lead-free KNN-LT-LS thin films

Science.gov (United States)

Abazari, M.; Choi, T.; Cheong, S.-W.; Safari, A.

2010-01-01

We report the observation of domain structure and piezoelectric properties of pure and Mn-doped (K0.44,Na0.52,Li0.04)(Nb0.84,Ta0.1,Sb0.06)O3 (KNN-LT-LS) thin films on SrTiO3 substrates. It is revealed that, using piezoresponse force microscopy, ferroelectric domain structure in such 500 nm thin films comprised of primarily 180° domains. This was in accordance with the tetragonal structure of the films, confirmed by relative permittivity measurements and x-ray diffraction patterns. Effective piezoelectric coefficient (d33) of the films were calculated using piezoelectric displacement curves and shown to be ~53 pm V-1 for pure KNN-LT-LS thin films. This value is among the highest values reported for an epitaxial lead-free thin film and shows a great potential for KNN-LT-LS to serve as an alternative to PZT thin films in future applications.

Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4-henanthraquinone from tuberous roots of yam (Dioscorea batatas) through inhibition of prostaglandin D₂ and leukotriene C₄ production in mouse bone marrow-derived mast cells.

Science.gov (United States)

Jin, Meihua; Lu, Yue; Yang, Ju Hye; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil; Park, Sang-Jo; Son, Kun Ho; Chang, Hyeun Wook

2011-09-01

6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 μM and 0.27 μM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX-1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 μM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 μM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases.

Resuscitation of the viable but non-culturable state of Salmonella enterica serovar Oranienburg by recombinant resuscitation-promoting factor derived from Salmonella Typhimurium strain LT2.

Science.gov (United States)

Panutdaporn, N; Kawamoto, K; Asakura, H; Makino, S-I

2006-02-15

A gene encoding the resuscitation-promoting factor (Rpf) from Salmonella Typhimurium LT2 was cloned and characterized. The amino acid sequence encoded by S. Typhimurium LT2 rpf gene shares 24.2% homology with Micrococcus luteus Rpf, which is secreted by growing cells, and required to resuscitate from viable but non-culturable (VNC) state. The S. Typhimurium LT2 rpf gene is 696 bp long, and shared a conserved segment with Salmonella enterica serovar Oranienburg (99.4%). Recombinant Rpf (rRpf) proteins of S. Typhimurium LT2 after expression in E. coli BL21 harboring the pET15-b plasmid was approximately 25 kDa. Since S. Oranienburg cells are relatively quick to enter the VNC state just after incubating in the presence of 7% NaCl at 37 degrees C for 3 days, we evaluated the biological effect of rRpf by using S. Oranienburg VNC cells. The rRpf not only promoted proliferation but also induced resuscitation of VNC cells to the culturable state in a dose-dependent manner. Therefore, rRpf may be useful for detection of bacterial contaminants present in the VNC form in food samples and the environment.

Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock

International Nuclear Information System (INIS)

Cook, J.A.; Li, E.J.; Spicer, K.M.; Wise, W.C.; Halushka, P.V.

1990-01-01

Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock. In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat. Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.). Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization. Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle. In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5). Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold) by endotoxin compared to vehicle controls. Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin. LY reduced the mesenteric permeability index by 70%. Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment. Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds

LT-CFB. Further development and commercialization. Final report. [Low Temperature Circulating Fluid Bed gasifier]; LT-CFB. Videreudvikling og kommercialisering. Slutrapport

Energy Technology Data Exchange (ETDEWEB)

Stoholm, P. [DFBT, Roskilde (Denmark); Birk Henriksen, U.; Ahrentfeldt, J. [Technical Univ. of Denmark. DTU Chemical Engineering, CHEC Research Centre, Roskilde (Denmark); Cramer, J.; Dietrich, J.; Christiansen, Knud [FORCE Technology, Kgs. Lyngby (Denmark); Krogh, J. [Anhydro A/S, Soeborg (Denmark)

2011-12-15

The starting point for the project was the good results achieved in a previous project, in which a series of experiments were carried out with a 500 kW pilot plant at teh Technical University of Denmark. The main task was then to find a way forward towards further scale-up, demonstration and commercialization. The project's partners chose to study three possible sites for demonstration. However, during the project both framework conditions as well as DONG Energy's strategy changed, which resulted in the company taking over the LT-CFB technology in December 2009. As a first step a 6 MW demonstration plant will now be set up at the Asnaes power plant expected to start in spring 2011. The project has also been buit a new mobile 100 kW LT-CFB plant for the further optimization of the process and for short-term trials of new fuels. At the new plant a number of successful trials were performed with straw and residual fibers. Furthermore, it is experimentally demonstrated that it is possible to cool the tar-containing gas to approx. 300 degrees C and purify the gas in a bag filter, so it can be used in natural gas-fired power plant boilers. With the new mobile system, it will now be easier to perform experiments with a number of new fuels such as unsorted municipal waste, bone meal and dried sewage sludge. (LN)

Kültür ve Sanat Ekonomisi Kapsamında Talep Analizleri Yardımı ile Kültür Politikasına Teorik Yaklaşım: Türkiye Örneği

Directory of Open Access Journals (Sweden)

Duygu BÜYÜKYAZICI

2016-08-01

Full Text Available Kültür-sanat ekonomisinin bağımsız bir disiplin olarak ortaya çıkmasını sağlayantemel tez, devletin sanatı desteklemesi gerektiği önermesidir. Gösteri sanatı formlarınıniktisadi araçlarla incelenmesi sonucunda ortaya konan maliyet hastalığı argümanı, devletsanatları desteklemezse sanatların yok olacağı öngörüsünü içerir. Söz konusu analizlerdenönce devlet-sanat ilişkisi farklı disiplinlerin gözlem alanında iken, bu değişkenlerin yanınaekonomi teriminin eklenmesi tartışmaları bilimsel zemine çekmiş ve engin incelemeleriberaberinde getirmiştir. Devletin finansal ve kurumsal anlamda sanatı desteklemesi politikayapıcıların nezdinde erdemli mallar varsayımı ile gerçekleşirken, literatürdekitemellendirmeler büyük ölçüde piyasa başarısızlıkları ekseninde olmuş ve maliyet hastalığıargümanı çürütülmüştür. Devletin sanatı destekleme formu ve miktarına yönelik tercihlerkültür politikasının önemli payını oluştururken, söz konusu politikaların edinilmiş başarısıancak talep analizleri ile tartılabilir. Türkiye’nin kültür politikasına hem teorik biryaklaşımda bulunmayı hem de ulaşılmış başarısını araştırmayı amaçlayan buçalışmada, kültür-sanat ekonomisindeki mikroekonomik talep analizlerinden yola çıkarak,talep profilinin kültür politikasındaki önemi vurgulanmakta ve devletin kültür-sanata olandesteği kadar biçiminin öneminin de altı çizilmektedir. Talep analizlerinin gelişmesidoğrultusunda, talebin profiline yönelik farklı kültür politikaları gerekecek, kültür-sanatayönelik çoğunlukla yetersiz veri ve analiz ile tespit edilen destek, üretim vesübvansiyonların içerik ve miktarı farklılaşarak optimal düzeye yakınsanacaktır. Piyasabaşarısızlıklar da kültür politikasının temellendiği teorik faz olarak analize eklenmiş, pozitifdışsallıklar özelinde devletin sanatı desteklemesinin sebepleri

The effect of triiodothyronine (L-T3) and weight loss on sex-hormone binding globulin (SHBG) in hirsute obese women

International Nuclear Information System (INIS)

Cavaliere, H.; Medeiros Neto, G.A.

1984-01-01

The effect of a 60-day period of treatment with L-T 3 (200 μg/day) was evaluated in hirsute obese women and normal controls. The obese patients were also submitted to a low calorie high protein. Mean initial weight significantly declined with a significant lowering of the mean DHEA-S leves. There was changes in serum T 3 rose in both obese and normal patients. Serum sex-hormone binding globulin levels at baseline studies were significantly higher in normal controls than in obese patients. At the end of de 60-day period of L-T 3 administration it was observed in both groups a 2-4 fold increase in serum SHBG levels but normal controls had significantly higher mean values than obese individuals. (M.A.C.) [pt

Leukotriene B4 catabolism: quantitation of leukotriene B4 and its omega-oxidation products by reversed-phase high-performance liquid chromatography.

Science.gov (United States)

Shak, S

1987-01-01

LTB4 and its omega-oxidation products may be rapidly, sensitively, and specifically quantitated by the methods of solid-phase extraction and reversed-phase high-performance liquid chromatography (HPLC), which are described in this chapter. Although other techniques, such as radioimmunoassay or gas chromatography-mass spectrometry, may be utilized for quantitative analysis of the lipoxygenase products of arachidonic acid, only the technique of reversed-phase HPLC can quantitate as many as 10 metabolites in a single analysis, without prior derivatization. In this chapter, we also reviewed the chromatographic theory which we utilized in order to optimize reversed-phase HPLC analysis of LTB4 and its omega-oxidation products. With this information and a gradient HPLC system, it is possible for any investigator to develop a powerful assay for the potent inflammatory mediator, LTB4, or for any other lipoxygenase product of arachidonic acid.

Comparison of “Morning Olifera Seed Extract and Magnafloc LT25” in Removal of Water Turbidity Case Study: Tehran’s Jalalieh (1 Water Treatment Plant

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Mehdi Khan ahmadi

2013-08-01

Full Text Available Coagulation-flocculation is one of the most important processes for water treatment, commonly used all over the world. The use of synthetic polymers known as “Polyelectrolytes as a coagulant aid is now wide spread in water treatment plants. Tehran’s “Jalalieh WTP” has been using an anionic polyelectrolyte under the trade name of “Magna Floc LT25” for a number of years MagnaFloc LT25 (MF-LT25 is a synthetic coagulant with high molecular weight, produced in granular and powder form. The application of this coagulant aid is known to be most effective if injected to water after addition of main coagulant (Ferric Chloride in Tehran’s WTP.  However the use of synthetic polymers in treatment of drinking water has always been under question due to extract of MO seed contains proteins soluble in water which have high coagulating properties. This pilot scale study was performed to compare the coagulating properties of seed extract of MO to MF-LT25, The tests were carried out on Tehran’s raw water in Jalalieh treatment plant. Several turbidity ranges such as 5, 20, 100, and 200 NTU were used representing real seasonal turbidities of influent water to treatment plant. Optimum concentration of the coagulant and coagulant aid was determined within water pH values of 6, 7 and 8, using common “Jar Test” technique. The extract of Moringa Oleifera seed in optimum concentration of 10, 14,25,35 mg/L and optimum pH of 8 is capable in removal of 96.5, 97.4, 98.5 and 99% of water turbidity range of 5, 20, 100, and 200 NTU respectively. Under similar conditions, MF-LT25 removal efficiency were found 97, 98.1, 98.4 and 99.4% of water turbidity range of 5, 20, 100, and 200 NTU at optimum concentrations of 0.015, 0.02, 0.025, 0.03 mg/L respectively. The results also showed that the extract of Moringa Oleifera seed is a powerful coagulating agent, at alkalinity pH values, and is more effective for high turbid waters. It compared well with synthetic

AutoCAD / AutoCAD LT 2014 fundamentals metric

CERN Document Server

ASCENT center for technical knowledge

2014-01-01

The objective of AutoCAD/AutoCAD LT 2014 Fundamentals is to enable students to create a basic 2D drawing in the AutoCAD software. Even at this fundamental level, the AutoCAD software is one of the most sophisticated computer applications that you are likely to encounter. Therefore learning to use it can be challenging. To make the process easier and provide flexibility for instructors and students, the training guide is divided into two parts that can be taken independently.

Polarized Structure Function $\\sigma_{LT'}$ for $p({\\vec e},e'K^+)\\Lambda$ in the Nucleon Resonance Region

Energy Technology Data Exchange (ETDEWEB)

Nasseripour, Rakhsha; Raue, Brian; Ambrozewicz, Pawel; Carman, Daniel; Amaryan, Moscov; Amaryan, Moskov; Anciant, Eric; Anghinolfi, Marco; Asavapibhop, Burin; Asryan, Gegham; Audit, Gerard; Auger, Thierry; Avagyan, Harutyun; Baghdasaryan, Hovhannes; Baillie, Nathan; Ball, J.P.; Ball, Jacques; Ball, J.P.; Ball, Jacques; Ball, J.P.; Ball, Jacques; Ball, J.P.; Ball, Jacques; Baltzell, Nathan; Barrow, Steve; Battaglieri, Marco; Beard, Kevin; Bedlinskiy, Ivan; Bektasoglu, Mehmet; Bellis, Matthew; Benmouna, Nawal; Berman, Barry; Biselli, Angela; Blaszczyk, Lukasz; Bonner, Billy; Bouchigny, Sylvain; Boyarinov, Sergey; Bradford, Robert; Branford, Derek; Briscoe, William; Brooks, William; Burkert, Volker; Butuceanu, Cornel; Calarco, John; Careccia, Sharon; Casey, Liam; Cetina, Catalina; Chen, Shifeng; Cheng, Lu; Cole, Philip; Collins, Patrick; Coltharp, Philip; Cords, Dieter; Corvisiero, Pietro; Crabb, Donald; Crede, Volker; Dale, Daniel; Dashyan, Natalya; De Masi, Rita; De Vita, Raffaella; De Sanctis, Enzo; Degtiarenko, Pavel; Dennis, Lawrence; Deur, Alexandre; Dhuga, Kalvir; Dickson, Richard; Djalali, Chaden; Dodge, Gail; Doughty, David; Dragovitsch, Peter; Dugger, Michael; Dytman, Steven; Dzyubak, Oleksandr; Egiyan, Hovanes; Egiyan, Kim; Elfassi, Lamiaa; Elouadrhiri, Latifa; Eugenio, Paul; Fatemi, Renee; Fedotov, Gleb; Feldman, Gerald; Feuerbach, Robert; Forest, Tony; Fradi, Ahmed; Funsten, Herbert; Garcon, Michel; Gavalian, Gagik; Gevorgyan, Nerses; Gilfoyle, Gerard; Giovanetti, Kevin; Girard, Pascal; Girod, Francois-Xavier; Goetz, John; Gothe, Ralf; Gothe, Ralf; Griffioen, Keith; Guidal, Michel; Guillo, Matthieu; Guler, Nevzat; Guo, Lei; Gyurjyan, Vardan; Hafidi, Kawtar; Hakobyan, Hayk; Hanretty, Charles; Hardie, John; Heddle, David; Hersman, F.; Hicks, Kenneth; Hleiqawi, Ishaq; Holtrop, Maurik; Hu, Jicun; Hyde, Charles; Ilieva, Yordanka; Ireland, David; Ishkhanov, Boris; Isupov, Evgeny; Ito, Mark; Jenkins, David; Jo, Hyon-Suk; Johnstone, John; Joo, Kyungseon; Juengst, Henry; Kalantarians, Narbe; Kellie, James; Khandaker, Mahbubul; Kim, Kui; Kim, Kyungmo; Kim, Wooyoung; Klein, Andreas; Klein, Franz; Kossov, Mikhail; Krahn, Zebulun; Kramer, Laird; Kubarovsky, Valery; Kuhn, Joachim; Kuhn, Sebastian; Kuleshov, Sergey; Kuznetsov, Viacheslav; Lachniet, Jeff; Laget, Jean; Langheinrich, Jorn; Lawrence, David; Livingston, Kenneth; Lu, Haiyun; Lukashin, Konstantin; MacCormick, Marion; Manak, Joseph; Markov, Nikolai; Mattione, Paul; McAleer, Simeon; McKinnon, Bryan; McNabb, John; Mecking, Bernhard; Mestayer, Mac; Meyer, Curtis; Mibe, Tsutomu; Mikhaylov, Konstantin; Minehart, Ralph; Mirazita, Marco; Miskimen, Rory; Mokeev, Viktor; Moreno, Brahim; Moriya, Kei; Morrow, Steven; Moteabbed, Maryam; Mueller, James; Munevar Espitia, Edwin; Mutchler, Gordon; Nadel-Turonski, Pawel; Niccolai, Silvia; Niculescu, Gabriel; Niculescu, Maria-Ioana; Niczyporuk, Bogdan; Niroula, Megh; Niyazov, Rustam; Nozar, Mina; Osipenko, Mikhail; Ostrovidov, Alexander; Park, Kijun; Pasyuk, Evgueni; Paterson, Craig; Pereira, Sergio; Peterson, Gerald; Philips, Sasha; Pierce, Joshua; Pivnyuk, Nikolay; Pocanic, Dinko; Pogorelko, Oleg; Pozdnyakov, Sergey; Preedom, Barry; Price, John; Procureur, Sebastien; Prok, Yelena; Protopopescu, Dan; Qin, Liming; Riccardi, Gregory; Ricco, Giovanni; Ripani, Marco; Ritchie, Barry; Rosner, Guenther; Rossi, Patrizia; Rubin, Philip; Sabatie, Franck; Salamanca, Julian; Salgado, Carlos; Santoro, Joseph; Sapunenko, Vladimir; Sayre, Donald; Schumacher, Reinhard; Serov, Vladimir; Shafi, Aziz; Sharabian, Youri; Sharov, Dmitri; Shvedunov, Nikolay; Simionatto, Sebastio; Skabelin, Alexander; Smith, Elton; Smith, Lee; Sober, Daniel; Sokhan, Daria; Stavinsky, Aleksey; Stepanyan, Samuel; Stepanyan, Stepan; Stokes, Burnham; Stoler, Paul; Strakovski, Igor; Strauch, Steffen; Taiuti, Mauro; Taylor, Shawn; Tedeschi, David; Thoma, Ulrike; Thompson, Richard; Tkabladze, Avtandil; Tkachenko, Svyatoslav; Ungaro, Maurizio; Vineyard, Michael; Vlassov, Alexander; Wang,

2008-06-01

The first measurements of the polarized structure function $\\sigma_{LT'}$ for the reaction $p(\\vec e,e'K^+)\\Lambda$ in the nucleon resonance region are reported. Measurements are included from threshold up to $W$=2.05 GeV for central values of $Q^2$ of 0.65 and 1.00 GeV$^2$, and nearly the entire kaon center-of-mass angular range. $\\sigma_{LT'}$ is the imaginary part of the longitudinal-transverse response and is expected to be sensitive to interferences between competing intermediate s-channel resonances, as well as resonant and non-resonant processes. The results for $\\sigma_{LT'}$ are comparable in magnitude to previously reported results from CLAS for $\\sigma_{LT}$, the real part of the same response. An intriguing sign change in $\\sigma_{LT'}$ is observed in the high $Q^2$ data at $W\\approx 1.9$ GeV. Comparisons to several existing model predictions are shown.

A specific assay for leukotriene B4 in human whole blood

DEFF Research Database (Denmark)

Fogh, J; Poulsen, L K; Bisgaard, H

1992-01-01

between standard and sample dilution curves. Purification was, therefore, extended by combinations of the following steps: 1) protein precipitation, 2) lipid extractions, and 3) high-performance liquid chromatography (HPLC). One of two commercially available LTB4 standards was found to contain multiple...... components, several of which were immunoreactive in RIA. Even for the standard containing pure LTB4, interference was demonstrated by lack of parallelism between sample and standard dilution curves. Testing eight combinations of varying purification steps, we found that only a three-step purification...

CONTEMPT-LT/028: a computer program for predicting containment pressure-temperature response to a loss-of-coolant accident

International Nuclear Information System (INIS)

Hargroves, D.W.; Metcalfe, L.J.; Wheat, L.L.; Niederauer, G.F.; Obenchain, C.F.

1979-03-01

CONTEMPT-LT is a digital computer program, written in FORTRAN IV, developed to describe the long-term behavior of water-cooled nuclear reactor containment systems subjected to postulated loss-of-coolant accident (LOCA) conditions. The program calculates the time variation of compartment pressures, temperatures, mass and energy inventories, heat structure temperature distributions, and energy exchange with adjacent compartments. The program is capable of describing the effects of leakage on containment response. Models are provided to describe fan cooler and cooling spray engineered safety systems. An annular fan model is also provided to model pressure control in the annular region of dual containment systems. Up to four compartments can be modeled with CONTEMPT-LT, and any compartment except the reactor system may have both a liquid pool region and an air--vapor atmosphere region above the pool. Each region is assumed to have a uniform temperature, but the temperatures of the two regions may be different

Toxicity and immunogenicity of Enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion 3xSTa(A14Q-LT(S63K/R192G/L211A in a murine model.

Directory of Open Access Journals (Sweden)

Chengxian Zhang

Full Text Available Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT and heat-stable type Ib toxin (STa disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STa(P13F fused at the N- or C-terminus, or inside the A subunit of LT(R192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011. In this study, we generated a different STa toxoid (STa(A14Q and a triple-mutant LT toxoid (LT(S63K/R192G/L211A, tmLT, constructed a toxoid fusion (3xSTa(A14Q-tmLT that carried 3 copies of STa(A14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTa(A14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea.

Leukotriene B4 receptors on guinea pig alveolar eosinophils

International Nuclear Information System (INIS)

Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P.

1991-01-01

The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 x 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 ± 0.22 nM; Bmax1 = 966 ± 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 ± 8.9 nM; Bmax2 = 5557 ± 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of [3H]LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 ± 0.14 and 18.14 ± 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 x 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 x 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions

The linkage between Churg-Strauss syndrome and leukotriene receptor antagonists: fact or fiction?

Science.gov (United States)

McDanel, Deanna L; Muller, Barbara A

2005-01-01

Epidemiologic evidence has shown that the worldwide prevalence of asthma is increasing. The leukotriene receptor antagonists (LTRAs) represent a new class of therapy for asthma. They have been developed in the last decade and play a pivotal steroid-sparing role in treating the inflammatory component of asthma. Consequently, reports of Churg-Strauss syndrome (CSS), a rare form of systemic vasculitis, have been recognized as a potential side effect in individuals with moderate to severe asthma on LTRA therapy. The serious nature of this disorder is worthy of prompt recognition by clinicians and aggressive therapy to avoid the subsequent longstanding effects of vasculitis. To validate the postulated linkage between the LTRAs and CSS, this review comprehensively evaluates reported cases in the literature and supports a pathophysiological relationship between the LTRAs and the development of CSS. PMID:18360552

Starter Kültür Kullanılarak Yapılan Tulum Peynirlerinin Bazı Özellikleri

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Zübeyde Öner

2015-02-01

Full Text Available Bu çalışmada, tulum peyniri kalitesi üzerinde starter kültür kullanımının etkileri ve tulum peyniri üretimine uygun starter kültür karışımı araştırılmıştır. Bu amaçla çiğ sütten ve starter kültür olarak Lactobacillus plantarum 1, Lb. plantarum 48, Lactococcus lactis 57, Enterococcus faecalis 40’ın farklı oranlardaki karışımları kullanılarak 3 farklı peynir üretilmiştir. 90 günlük olgunlaşma sonunda toplam kurumadde %57,85-61,09, SH 79,5-94 olgunlaşma katsayısı 51,48-136,32, kurumaddede tuz %4,03-5,26 kurumaddede yağ %54,42-57,29, toplam azot % 2,67-3,43 suda çözünen azot % 1,73-3,64 duyusal değerlendirme sonucu 52-72,81 toplam puan arasında değişmiştir. Mikrobiyolojik analiz sonuçlarına göre 90 günlük olgunlaşma sonunda toplam mezofil aerob bakteri sayısı 7,25-7,97 log kob/g, laktobasil 7,32-7,5 log kob/g, laktokok 7,71-8,15 log kob/g, koliform 1,73-5,02 log kob/g, S. aureus <10-2,35 log kob/g, enterokok 6,71-7,38 log kob/g, psikrofilik mikroorganizma <10 log kob/g, maya ve küf 4,22-5,49 log kob/g arasında değişmiştir.

High performance ceria-bismuth bilayer electrolyte low temperature solid oxide fuel cells (LT-SOFCs) fabricated by combining co-pressing with drop-coating

KAUST Repository

Hou, Jie

2015-03-24

The Sm0.075Nd0.075Ce0.85O2-δ-Er0.4Bi1.6O3 bilayer structure film, which showed an encouraging performance in LT-SOFCs, was successfully fabricated by a simple low cost technique combining one-step co-pressing with drop-coating.

High performance ceria-bismuth bilayer electrolyte low temperature solid oxide fuel cells (LT-SOFCs) fabricated by combining co-pressing with drop-coating

KAUST Repository

Hou, Jie; Bi, Lei; Qian, Jing; Zhu, Zhiwen; Zhang, Junyu; Liu, Wei

2015-01-01

The Sm0.075Nd0.075Ce0.85O2-δ-Er0.4Bi1.6O3 bilayer structure film, which showed an encouraging performance in LT-SOFCs, was successfully fabricated by a simple low cost technique combining one-step co-pressing with drop-coating.

The use of the laryngeal tube disposable (LT-D) by paramedics during out-of-hospital resuscitation-an observational study concerning ERC guidelines 2005.

Science.gov (United States)

Wiese, C H R; Semmel, T; Müller, J U; Bahr, J; Ocker, H; Graf, B M

2009-02-01

In the current guidelines of the European Resuscitation Council (ERC), tracheal intubation, as an instrument for securing the airway during resuscitation, has become less important for persons not trained in this method. For those persons, different supraglottic airway devices are recommended by the ERC. The present investigation deals with the application of the laryngeal tube disposable (LT-D) during pre-hospital resuscitation by paramedics. During a period of 2 years (2006-2008), we registered all cardiac arrest situations in which the LT-D had been applied according to the ERC guidelines 2005. Therefore, we investigated one emergency medical system in Germany. During the defined period, 92 resuscitation attempts, recorded on standardised data sheets, were included. The LT-D was used in 46% of all cardiac arrest situations. Overall, the LT-D was successfully inserted in more than 90% of all cases on first attempt. In 95% of all cases, no problems concerning ventilation of the patient were described. As an alternative airway device recommended by the ERC in 2005, the LT-D may enable airway control rapidly and effectively. Additionally, by using the LT-D, a reduced "no-flow-time" and a better outcome may be possible.

Relationship between leukotriene-modifying agent prescriptions dispensed and rate of suicide deaths by county in the US

Directory of Open Access Journals (Sweden)

Schumock GT

2011-09-01

Full Text Available Glen T Schumock1, Robert D Gibbons2, Todd A Lee1,3,4,6, Min J Joo4, Robert J Valuck5, Leslie T Stayner61Center for Pharmacoeconomic Research, and Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 2Center for Health Statistics, and Departments of Medicine and Health Studies, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 3Center for Management of Complex Chronic Care, Hines VA Hospital, Hines, IL, USA; 4Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 5Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, CO, USA; 6Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USABackground: The US Food and Drug Administration has issued warnings about a potential link between leukotriene receptor-modifying agents (LTMA and suicide. These warnings are based on case reports and there is controversy about the association. While spontaneous reporting of suicide-related events attributed to LTMA has risen dramatically, these data may be biased by the warnings. The objective of this study was to explore the relationship between LTMA and suicide deaths using event data preceding the Food and Drug Administration warnings.Methods: We conducted a mixed-effects Poisson regression analysis of the association between LTMA prescriptions dispensed and suicide deaths at the county level. Counts of suicide deaths in each US county, stratified by race, age group, gender, and year were obtained from the National Center for Health Statistics for the period January 1, 1999 to December 31, 2006. Counts of LTMA prescriptions dispensed in each US county were obtained from IMS Health Incorporated. The model estimated the overall suicide rate conditional on LTMA use, adjusted for age, gender, race, year

Measurement of tumor necrosis factor-α, leukotriene B4, and interleukin 8 in the exhaled breath condensate in patients with acute exacerbations of chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

Fanny WS Ko

2008-12-01

Full Text Available Fanny WS Ko1, Ting-Fan Leung2, Gary WK Wong2, Jenny Ngai1, Kin W To1, Susanna Ng1, David SC Hui11Department of Medicine and Therapeutics; 2Department of Pediatrics, The Chinese University of Hong Kong, Hong KongBackground: Assessment of airway inflammation in the clinical course of acute exacerbations of chronic obstructive pulmonary disease (AECOPD may advance our understanding of the pathogenesis and treatment.Objectives: To assess airway inflammation in patients during the course of AECOPD by serial analyses of their exhaled breath condensates (EBC.Methods: Twenty-six patients with AECOPD (22 males, mean[SD] percentage predicted forced expiratory volume in one second (FEV1 44.8 [14.3], 11 with stable COPD, and 14 age and sex-matched healthy controls were studied. Patients with AECOPD were treated with systemic steroid and antibiotic for 7 days. EBC was collected from each patient with AECOPD on Day 5, 14, 30, and 60 post-hospitalization using EcoScreen (VIASYS Healthcare, USA during tidal breathing over 10 minutes. Concentrations of tumor necrosis factor-α (TNF-α, leukotriene B4 (LTB4, and interleukin-8 (IL-8 were measured by enzyme-linked immunosorbent assay.Results: The median (IQR of TNF-α level on Day 5 was 5.08 (3.80–6 .32 pg/ml, which was lower than on Day 14 (5.84 [4.91–9.14] pg/ml, p = 0.017, Day 30 (6.14 [3.82–7.67] pg/ml, p = 0.045, and Day 60 (5.60 [4.53–8.80] pg/ml, p = 0.009. On Day 60, subjects receiving inhaled corticosteroid (ICS had a lower level of TNF-α than those who were not (4.82 [4.06–5.65] vs 7.66 [5.48–10.9] pg/ml, p = 0.02. EBC LTB4 level did not change significantly during recovery from AECOPD whereas IL-8 was mostly undetectable.Conclusions: EBC TNF-α level was low in patients receiving systemic steroid and antibiotic therapy for AECOPD. These findings suggest a potential role for serial EBC TNF-α for noninvasive monitoring of disease activity.Keywords: COPD, exacerbation, exhaled breath

Autodesk Inventor 2012 and Inventor LT 2012 Essentials

CERN Document Server

Tremblay, Thom

2011-01-01

Essential guide to learning Autodesk Inventor and Inventor LT The new Essentials books from Sybex are beautiful, task-based, full-color Autodesk Official Training Guides that help you get up to speed on Autodesk topics quickly and easily. Inventor Essentials thoroughly covers core features and functions of Autodesk's industry-leading 3D mechanical design software, teaching you what you need to become quickly productive with the software. By following the book's clear explanations, practical tutorials, and step-by-step exercises, you'll cover all the bases. Topics include drawing, modeling part

The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis.

Science.gov (United States)

Kopp, Matthias Volkmar; Brauburger, Jens; Riedinger, Frank; Beischer, Dorothee; Ihorst, Gabriele; Kamin, Wolfgang; Zielen, Stefan; Bez; Friedrichs, Frank; Von Berg, Andrea; Gerhold, Kerstin; Hamelmann, Eckard; Hultsch; Kuehr, Joachim

2002-11-01

Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1

MaLT - Combined Motor and Language Therapy Tool for Brain Injury Patients Using Kinect.

Science.gov (United States)

Wairagkar, Maitreyee; McCrindle, Rachel; Robson, Holly; Meteyard, Lotte; Sperrin, Malcom; Smith, Andy; Pugh, Moyra

2017-03-23

The functional connectivity and structural proximity of elements of the language and motor systems result in frequent co-morbidity post brain injury. Although rehabilitation services are becoming increasingly multidisciplinary and "integrated", treatment for language and motor functions often occurs in isolation. Thus, behavioural therapies which promote neural reorganisation do not reflect the high intersystem connectivity of the neurologically intact brain. As such, there is a pressing need for rehabilitation tools which better reflect and target the impaired cognitive networks. The objective of this research is to develop a combined high dosage therapy tool for language and motor rehabilitation. The rehabilitation therapy tool developed, MaLT (Motor and Language Therapy), comprises a suite of computer games targeting both language and motor therapy that use the Kinect sensor as an interaction device. The games developed are intended for use in the home environment over prolonged periods of time. In order to track patients' engagement with the games and their rehabilitation progress, the game records patient performance data for the therapist to interrogate. MaLT incorporates Kinect-based games, a database of objects and language parameters, and a reporting tool for therapists. Games have been developed that target four major language therapy tasks involving single word comprehension, initial phoneme identification, rhyme identification and a naming task. These tasks have 8 levels each increasing in difficulty. A database of 750 objects is used to programmatically generate appropriate questions for the game, providing both targeted therapy and unique gameplay every time. The design of the games has been informed by therapists and by discussions with a Public Patient Involvement (PPI) group. Pilot MaLT trials have been conducted with three stroke survivors for the duration of 6 to 8 weeks. Patients' performance is monitored through MaLT's reporting facility

Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse

International Nuclear Information System (INIS)

Kozubik, A.; Hofmanova, J.; Pospisil, M.; Netikova, J.; Hola, J.; Lojek, A.

1994-01-01

Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granuloctyes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. (author)

Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse

Energy Technology Data Exchange (ETDEWEB)

Kozubik, A.; Hofmanova, J.; Pospisil, M.; Netikova, J.; Hola, J.; Lojek, A. (Ceskoslovenska Akademie Ved, Brno (Czech Republic). Biofysikalni Ustav)

1994-03-01

Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granuloctyes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. (author).

Autodesk Inventor 2013 and Autodesk Inventor LT 2013 essentials

CERN Document Server

Tremblay, Thom

2012-01-01

Get up to speed with Autodesk Inventor, the leading manufacturing design program This Autodesk Official Training Guide thoroughly covers the fundamentals of Autodesk Inventor 2013 and Inventor LT 2013. Focusing on basics such as using the interface, creating parts and assemblies, applying standards and styles, creating 2D drawings from 3D data, and more, it teaches you everything you need to become quickly productive with the software. Whether you're a new student learning CAD, preparing for certification, or updating your Inventor skills, this is the fast, thorough grounding you need. Featu

Ion heating at the disruptive instability in the LT-3 Tokamak

International Nuclear Information System (INIS)

Bell, M.G.; Hutchinson, I.H.

1976-01-01

Measurements of the ion temperature and the toroidal current density and electric field during the disruptive instability in LT-3 are presented. Rapid ion heating and strong current inhibition have been observed. Fluctuation measurements suggest that these effects may be attributable to the excitation of ion cyclotron drift waves in the plasma

Sewage sludge amendment and inoculation with plant-parasitic nematodes do not facilitate the internalization of Salmonella Typhimurium LT2 in lettuce plants.

Science.gov (United States)

Fornefeld, Eva; Baklawa, Mohamed; Hallmann, Johannes; Schikora, Adam; Smalla, Kornelia

2018-05-01

Contamination of fruits and vegetables with Salmonella is a serious threat to human health. In order to prevent possible contaminations of fresh produce it is necessary to identify the contributing ecological factors. In this study we investigated whether the addition of sewage sludge or the presence of plant-parasitic nematodes foster the internalization of Salmonella enterica serovar Typhimurium LT2 into lettuce plants, posing a potential threat for human health. Greenhouse experiments were conducted to investigate whether the amendment of sewage sludge to soil or the presence of plant-parasitic nematodes Meloidogyne hapla or Pratylenchus crenatus promote the internalization of S. Typhimurium LT2 from soil into the edible part of lettuce plants. Unexpectedly, numbers of cultivable S. Typhimurium LT2 decreased faster in soil with sewage sludge than in control soil but not in root samples. Denaturing gradient gel electrophoresis analysis revealed shifts of the soil bacterial communities in response to sewage sludge amendment and time. Infection and proliferation of nematodes inside plant roots were observed but did not influence the number of cultivable S. Typhimurium LT2 in the root samples or in soil. S. Typhimurium LT2 was not detected in the leaf samples 21 and 49 days after inoculation. The results indicate that addition of sewage sludge, M. hapla or P. crenatus to soil inoculated with S. Typhimurium LT2 did not result in an improved survival in soil or internalization of lettuce plants. Copyright © 2017. Published by Elsevier Ltd.

A SEARCH FOR L/T TRANSITION DWARFS WITH Pan-STARRS1 AND WISE: DISCOVERY OF SEVEN NEARBY OBJECTS INCLUDING TWO CANDIDATE SPECTROSCOPIC VARIABLES

International Nuclear Information System (INIS)

Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J.; Deacon, Niall R.; Dupuy, Trent J.; Redstone, Joshua; Price, P. A.

2013-01-01

We present initial results from a wide-field (30,000 deg 2 ) search for L/T transition brown dwarfs within 25 pc using the Pan-STARRS1 and Wide-field Infrared Survey Explorer (WISE) surveys. Previous large-area searches have been incomplete for L/T transition dwarfs, because these objects are faint in optical bands and have near-infrared (near-IR) colors that are difficult to distinguish from background stars. To overcome these obstacles, we have cross-matched the Pan-STARRS1 (optical) and WISE (mid-IR) catalogs to produce a unique multi-wavelength database for finding ultracool dwarfs. As part of our initial discoveries, we have identified seven brown dwarfs in the L/T transition within 9-15 pc of the Sun. The L9.5 dwarf PSO J140.2308+45.6487 and the T1.5 dwarf PSO J307.6784+07.8263 (both independently discovered by Mace et al.) show possible spectroscopic variability at the Y and J bands. Two more objects in our sample show evidence of photometric J-band variability, and two others are candidate unresolved binaries based on their spectra. We expect our full search to yield a well-defined, volume-limited sample of L/T transition dwarfs that will include many new targets for study of this complex regime. PSO J307.6784+07.8263 in particular may be an excellent candidate for in-depth study of variability, given its brightness (J = 14.2 mag) and proximity (11 pc)

Raman evidence of the formation of LT-LiCoO 2 thin layers on NiO in molten carbonate at 650°C

Science.gov (United States)

Mendoza, L.; Baddour-Hadjean, R.; Cassir, M.; Pereira-Ramos, J. P.

2004-03-01

The structural evolution of thin layers of Co 3O 4 elaborated on nickel-based substrates in the Li 2CO 3-Na 2CO 3 carbonate eutectic at 650 °C as a function of time immersion is reported. Raman microspectrometry has been applied in order to provide more information on the nature of the protective cobalt oxide layers. The typical Raman fingerprint of the LT-LiCoO 2 compound has been obtained, with four well defined bands at 449, 484, 590 and 605 cm -1, while XRD data are unable to distinguish the layered phase (HT) from the spinel one (LT). The mechanical stability of such films does not exceed 10 h in direct contact with the molten carbonate bulk at 650 °C; nevertheless, these conditions are much more corrosive than in a molten carbonate fuel cell (MCFC).

Rotational-mode component of the density of levels of nuclei with A approx-lt 150

International Nuclear Information System (INIS)

Rastopchin, E.M.; Svirin, M.I.; Smirenkin, G.N.

1992-01-01

Some difficulties which arise in the use of the generalized superfluid model to describe the density of levels in the region A approx-lt 150, as the result of an imperfect understanding of collective nuclear excitations, are discussed. One possible way to overcome these difficulties is examined. The idea is to depart from the conventional classification of collective nuclear properties and make use of small static deformations predicted theoretically and a corresponding rotational-mode component of the density of levels of these nuclei

Mastering Autodesk Inventor 2014 and Autodesk Inventor LT 2014

CERN Document Server

Waguespack, Curtis

2013-01-01

An Autodesk Official Press guide to the powerful mechanical design software Autodesk Inventor has been used to design everything from cars and airplanes to appliances and furniture. This comprehensive guide to Inventor and Inventor LT features real-world workflows and work environments, and is packed with practical tutorials that focus on teaching Inventor tips, tricks, and techniques. Additionally, you can download datasets to jump in and practice on any exercise. This reference and tutorial explains key interface conventions, capabilities, tools, and techniques, including desi

A SEARCH FOR L/T TRANSITION DWARFS WITH Pan-STARRS1 AND WISE: DISCOVERY OF SEVEN NEARBY OBJECTS INCLUDING TWO CANDIDATE SPECTROSCOPIC VARIABLES

Energy Technology Data Exchange (ETDEWEB)

Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J. [Institute for Astronomy, University of Hawaii at Manoa, Honolulu, HI 96822 (United States); Deacon, Niall R. [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Dupuy, Trent J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Redstone, Joshua [Facebook, 335 Madison Ave, New York, NY 10017-4677 (United States); Price, P. A., E-mail: wbest@ifa.hawaii.edu [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States)

2013-11-10

We present initial results from a wide-field (30,000 deg{sup 2}) search for L/T transition brown dwarfs within 25 pc using the Pan-STARRS1 and Wide-field Infrared Survey Explorer (WISE) surveys. Previous large-area searches have been incomplete for L/T transition dwarfs, because these objects are faint in optical bands and have near-infrared (near-IR) colors that are difficult to distinguish from background stars. To overcome these obstacles, we have cross-matched the Pan-STARRS1 (optical) and WISE (mid-IR) catalogs to produce a unique multi-wavelength database for finding ultracool dwarfs. As part of our initial discoveries, we have identified seven brown dwarfs in the L/T transition within 9-15 pc of the Sun. The L9.5 dwarf PSO J140.2308+45.6487 and the T1.5 dwarf PSO J307.6784+07.8263 (both independently discovered by Mace et al.) show possible spectroscopic variability at the Y and J bands. Two more objects in our sample show evidence of photometric J-band variability, and two others are candidate unresolved binaries based on their spectra. We expect our full search to yield a well-defined, volume-limited sample of L/T transition dwarfs that will include many new targets for study of this complex regime. PSO J307.6784+07.8263 in particular may be an excellent candidate for in-depth study of variability, given its brightness (J = 14.2 mag) and proximity (11 pc)

The Akashi Kaikyo Bridge and the Storebælt Bridge

DEFF Research Database (Denmark)

Gimsing, Niels Jørgen

1999-01-01

With the completion of the Akashi Kaikyo Bridge and the Storebælt East Bridge the development of the suspension bridge technology in the 20th century has manifested itself in two impressive structures. With the present echnology may bridges of similar (and also more modest) dimensions...... will undoubtedly be built far into the next century. For bridges going beyond the spans of existing bridges it is, however, likely that new concepts will be developed....

Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

Science.gov (United States)

Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

2015-10-01

Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

Düşey Toplum Kuramı Yaklaşımıyla Japon Çalışma Kültürünü Anlamak

OpenAIRE

Aca, Zeynep

2015-01-01

Japon çalışma kültürünün temel felsefesini anlayabilmenin yolu, Japon toplumunun kültürel özelliklerini anlayabilmekten geçmektedir. Ancak kültürü oluşturan her bir özellik elbetteki Japon çalışma kültürünü aynı ölçüde etkilememektedir. İşte bu noktadan hareketle, bu çalışmada, Japon çalışma kültürü, Japon çalışma kültürünün temel felsefi belirleyicilerinden biri olduğunu düşündüğümüz ve Nakane tarafından Düşey Toplum Kuramı olarak adlandırılan Japon aile yapısı ekseninde ele alınmaya çalışıl...

Clonal relatedness of enterotoxigenic Escherichia coli (ETEC) strains expressing LT and CS17 isolated from children with diarrhoea in La Paz, Bolivia.

Science.gov (United States)

Rodas, Claudia; Klena, John D; Nicklasson, Matilda; Iniguez, Volga; Sjöling, Asa

2011-01-01

Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveller's and infantile diarrhoea in the developing world. ETEC produces two toxins, a heat-stable toxin (known as ST) and a heat-labile toxin (LT) and colonization factors that help the bacteria to attach to epithelial cells. In this study, we characterized a subset of ETEC clinical isolates recovered from Bolivian children under 5 years of age using a combination of multilocus sequence typing (MLST) analysis, virulence typing, serotyping and antimicrobial resistance test patterns in order to determine the genetic background of ETEC strains circulating in Bolivia. We found that strains expressing the heat-labile (LT) enterotoxin and colonization factor CS17 were common and belonged to several MLST sequence types but mainly to sequence type-423 and sequence type-443 (Achtman scheme). To further study the LT/CS17 strains we analysed the nucleotide sequence of the CS17 operon and compared the structure to LT/CS17 ETEC isolates from Bangladesh. Sequence analysis confirmed that all sequence type-423 strains from Bolivia had a single nucleotide polymorphism; SNP(bol) in the CS17 operon that was also found in some other MLST sequence types from Bolivia but not in strains recovered from Bangladeshi children. The dominant ETEC clone in Bolivia (sequence type-423/SNP(bol)) was found to persist over multiple years and was associated with severe diarrhoea but these strains were variable with respect to antimicrobial resistance patterns. The results showed that although the LT/CS17 phenotype is common among ETEC strains in Bolivia, multiple clones, as determined by unique MLST sequence types, populate this phenotype. Our data also appear to suggest that acquisition and loss of antimicrobial resistance in LT-expressing CS17 ETEC clones is more dynamic than acquisition or loss of virulence factors.

Clonal Relatedness of Enterotoxigenic Escherichia coli (ETEC) Strains Expressing LT and CS17 Isolated from Children with Diarrhoea in La Paz, Bolivia

Science.gov (United States)

Rodas, Claudia; Klena, John D.; Nicklasson, Matilda; Iniguez, Volga; Sjöling, Åsa

2011-01-01

Background Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveller's and infantile diarrhoea in the developing world. ETEC produces two toxins, a heat-stable toxin (known as ST) and a heat-labile toxin (LT) and colonization factors that help the bacteria to attach to epithelial cells. Methodology/Principal Findings In this study, we characterized a subset of ETEC clinical isolates recovered from Bolivian children under 5 years of age using a combination of multilocus sequence typing (MLST) analysis, virulence typing, serotyping and antimicrobial resistance test patterns in order to determine the genetic background of ETEC strains circulating in Bolivia. We found that strains expressing the heat-labile (LT) enterotoxin and colonization factor CS17 were common and belonged to several MLST sequence types but mainly to sequence type-423 and sequence type-443 (Achtman scheme). To further study the LT/CS17 strains we analysed the nucleotide sequence of the CS17 operon and compared the structure to LT/CS17 ETEC isolates from Bangladesh. Sequence analysis confirmed that all sequence type-423 strains from Bolivia had a single nucleotide polymorphism; SNPbol in the CS17 operon that was also found in some other MLST sequence types from Bolivia but not in strains recovered from Bangladeshi children. The dominant ETEC clone in Bolivia (sequence type-423/SNPbol) was found to persist over multiple years and was associated with severe diarrhoea but these strains were variable with respect to antimicrobial resistance patterns. Conclusion/Significance The results showed that although the LT/CS17 phenotype is common among ETEC strains in Bolivia, multiple clones, as determined by unique MLST sequence types, populate this phenotype. Our data also appear to suggest that acquisition and loss of antimicrobial resistance in LT-expressing CS17 ETEC clones is more dynamic than acquisition or loss of virulence factors. PMID:22140423

AutoCAD 2012 and AutoCAD LT 2012 Bible

CERN Document Server

Finkelstein, Ellen

2011-01-01

The latest version of this perennial favorite, in-depth, reference-tutorial This top-selling book has been updated by AutoCAD guru and author Ellen Finkelstein to provide you with the very latest coverage of both AutoCAD 2012 and AutoCAD LT 2012. It begins with a Quick Start tutorial, so you start creating right away. From there, the book covers so much in-depth material on AutoCAD that it is said that even Autodesk employees keep this comprehensive book at their desks. A DVD is included that features before-and-after drawings of all the tutorials and plenty of great examples from AutoCAD prof

Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates.

Science.gov (United States)

Dierschke, Katrin; Isaxon, Christina; Andersson, Ulla B K; Assarsson, Eva; Axmon, Anna; Stockfelt, Leo; Gudmundsson, Anders; Jönsson, Bo A G; Kåredal, Monica; Löndahl, Jakob; Pagels, Joakim; Wierzbicka, Aneta; Bohgard, Mats; Nielsen, Jörn

2017-07-01

Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m 3 ) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).

Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils.

Science.gov (United States)

Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Shima, Yoshihito; Ohshima, Shiro; Fujimoto, Minoru; Yamadori, Tomoki; Kawase, Ichiro; Tanaka, Toshio

2004-06-01

We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases. Copyright 2004 S. Karger AG, Basel

Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset diabetes mellitus after liver transplantation in a Chinese population.

Science.gov (United States)

Zhang, Tao; Liu, Yuan; Hu, Yibo; Zhang, Xiaoqing; Zhong, Lin; Fan, Junwei; Peng, Zhihai

2017-09-05

New-onset diabetes mellitus (NODM) is a common complication after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphism has been reported to be associated with type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the association of donor and recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences of NODM after LT. A total of 126 liver transplant patients were enrolled in the study. One single nucleotide polymorphism, SUMO4 rs237025, was genotyped in both donors and recipients. Both donor and recipient SUMO4 rs237025 polymorphisms were found to be significantly associated with NODM after LT. In multivariate analysis, recipient age>50 years, tacrolimus trough concentrations>10ng/mL at 1month after LT, donor and recipient rs237025 genetic variant, and the combined donor and recipient rs237025 genetic variant were independent predictive factors of NODM. Area under the receiver operating characteristic curve (AUROC) analysis indicated the higher predictive ability of the model containing combined donor and recipient rs237025 polymorphisms than the clinical model (p=0.046). Furthermore, Kaplan-Meier survival analysis demonstrated that NODM was related to significantly poorer patient survival in comparison with non-NODM patients (p=0.041). Both donor and recipient SUMO4 rs237025 polymorphisms contribute to the development of NODM after LT and NODM is a frequent complication that negatively affects patient survival. Copyright © 2017. Published by Elsevier B.V.

Karzai nõuab USA-lt võitu, ähvardades muidu rahu teha / Heiki Suurkask

Index Scriptorium Estoniae

Suurkask, Heiki, 1972-

2008-01-01

Afganistani president Hamid Karzai nõuab USA-lt ajakava selle kohta, millal NATO kavatseb Talibani üle võidu saavutada. Afganistanis visiidil viibinud USA president George W. Bush avaldas toetust Barack Obama kavale keskenduda veelgi enam Afganistanis sõdimisele

A Novel Bifunctional Amino Acid Racemase With Multiple Substrate Specificity, MalY From Lactobacillus sakei LT-13: Genome-Based Identification and Enzymological Characterization

Directory of Open Access Journals (Sweden)

Shiro Kato

2018-03-01

Full Text Available The Lactobacillus sakei strain LK-145 isolated from Moto, a starter of sake, produces potentially large amounts of three D-amino acids, D-Ala, D-Glu, and D-Asp, in a medium containing amylase-digested rice as a carbon source. The comparison of metabolic pathways deduced from the complete genome sequence of strain LK-145 to the type culture strain of Lactobacillus sakei strain LT-13 showed that the L- and D-amino acid metabolic pathways are similar between the two strains. However, a marked difference was observed in the putative cysteine/methionine metabolic pathways of strain LK-145 and LT-13. The cystathionine β-lyase homolog gene malY was annotated only in the genome of strain LT-13. Cystathionine β-lyase is an important enzyme in the cysteine/methionine metabolic pathway that catalyzes the conversion of L-cystathionine into L-homocysteine. In addition to malY, most genome-sequenced strains of L. sakei including LT-13 lacked the homologous genes encoding other putative enzymes in this pathway. Accordingly, the cysteine/methionine metabolic pathway likely does not function well in almost all strains of L. sakei. We succeeded in cloning and expressing the malY gene from strain LT-13 (Ls-malY in the cells of Escherichia coli BL21 (DE3 and characterized the enzymological properties of Ls-MalY. Spectral analysis of purified Ls-MalY showed that Ls-MalY contained a pyridoxal 5′-phosphate (PLP as a cofactor, and this observation agreed well with the prediction based on its primary structure. Ls-MalY showed amino acid racemase activity and cystathionine β-lyase activity. Ls-MalY showed amino acid racemase activities in various amino acids, such as Ala, Arg, Asn, Glu, Gln, His, Leu, Lys, Met, Ser, Thr, Trp, and Val. Mutational analysis revealed that the -amino group of Lys233 in the primary structure of Ls-MalY likely bound to PLP, and Lys233 was an essential residue for Ls-MalY to catalyze both the amino acid racemase and β-lyase reactions. In

Airpower Leadership on the Front Line: Lt Gen George H. Brett and Combat Command

Science.gov (United States)

2006-09-01

was assigned the additional duty of unit photographer and historian, bequeathing a photo album depicting his adventures to his oldest daughter.10 Lt...his fellow residents with piano music when the men were off duty.21 At the close of the war Brett was a temporary major and listed among officers who

Inhibition of common cold-induced aggravation of childhood asthma by leukotriene receptor antagonists.

Science.gov (United States)

Yoshihara, Shigemi; Fukuda, Hironobu; Abe, Toshio; Nishida, Mitsuhiro; Yamada, Yumi; Kanno, Noriko; Arisaka, Osamu

2012-09-01

Virus infection is an important risk factor for aggravation of childhood asthma. The objective of this study was to examine the effect of drugs on aggravation of asthma induced by a common cold. Asthma control was examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma. The occurrence of common cold, asthma control, and drugs used for asthma control were investigated using a modified Childhood Asthma Control Test (C-ACT) for patients aged cold and aggravation of asthma were significantly higher in patients aged cold-induced aggravation was significantly less effective in patients aged cold, asthma control was significantly more effective for those treated with leukotriene receptor antagonists (LTRAs) compared to treatment without LTRAs. Asthma control did not differ between patients who did or did not take inhaled corticosteroids or long-acting β2 stimulants. These findings showed a high prevalence of common cold in younger patients with childhood asthma and indicated that common cold can induce aggravation of asthma. LTRAs are useful for long-term asthma control in very young patients who develop an asthma attack due to a common cold.

Population-based open-label clinical effectiveness assessment of the cysteinyl leukotriene receptor antagonist pranlukast

Directory of Open Access Journals (Sweden)

Gen Tamura

2000-01-01

Full Text Available Although the efficacy of cysteinyl leukotriene receptor antagonists in asthma therapy has been established through controlled clinical trials, there are no data concerning the effectiveness of their use in clinical practice, in which there is no rigid selection based on specific inclusion and exclusion criteria. The aim of the present study was to evaluate the effectiveness of pranlukast in clinical practice. More than 2500 outpatients with mild to severe persistent asthma answered an input questionnaire, which consisted of 33 items assessing asthma symptoms in terms of six activities of daily living during the previous 2 weeks. Of these patients, 1138 received treatment with pranlukast and answered the same questionnaire 4–6 weeks after the start of treatment. In 923 of these 1138 patients, we examined the impact of concomitantly used inhaled steroids, β2-adrenergic agonists or sustained-release theophylline on the effectiveness of pranlukast treatment. One hundred and sixty-seven control patients completed the questionnaire twice but did not receive pranlukast treatment. We found a significant decrease in the number of asthma symptoms reported among both the 1138 patients treated with pranlukast and the 167 control patients. However, the magnitude of the decrease in symptoms was significantly (P < 0.001 greater with pranlukast treatment. Moreover, pranlukast was equally efficacious in the presence and absence of concomitantly used inhaled steroids, β2-adrenergic agonists or sustained-release theophylline. In conclusion, pranlukast was shown to have clinical effectiveness in the treatment of mild to severe persistent asthma symptoms.

Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection.

Directory of Open Access Journals (Sweden)

William J B Vincent

Full Text Available Immune cells sense and react to a multitude of factors including both host and microbe-derived signals. Understanding how cells translate these cues into particular cellular behaviors is a complex yet critical area of study. We have previously shown that both neutrophils and macrophages are important for controlling the fish pathogen Streptococcus iniae. Here, we report both host and bacterial determinants leading to the formation of organized macrophage aggregates as part of the host inflammatory response in a subset of infected larvae. Streptococcal capsule was a required signal for aggregate formation. Macrophage aggregation coincided with NFκB activity, and the formation of these aggregates is mediated by leukotriene B4 (LTB4 produced by neutrophils. Depletion, inhibition, or genetic deletion of leukotriene A4 hydrolase (Lta4h, which catalyzes the last step in LTB4 synthesis, resulted in the absence of macrophage aggregation. Larvae with impaired neutrophil function also had impaired macrophage aggregation; however, aggregate formation was partially rescued with the addition of exogenous LTB4. Neutrophil-specific expression of lta4h was sufficient to rescue macrophage aggregation in Lta4h-deficient larvae and increased host survival following infection. In summary, our findings highlight a novel innate immune response to infection in which specific bacterial products drive neutrophils that modulate macrophage behavior through eicosanoid signaling.

Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: an isobolographic analysis.

Science.gov (United States)

Fleck, Juliana; Marafiga, Joseane Righes; Jesse, Ana Cláudia; Ribeiro, Leandro Rodrigo; Rambo, Leonardo Magno; Mello, Carlos Fernando

2015-04-01

Although leukotrienes have been implicated in seizures, no study has systematically investigated whether the blockade of CysLT1 receptors synergistically increases the anticonvulsant action of classic antiepileptics. In this study, behavioral and electroencephalographic methods, as well as isobolographic analysis, are used to show that the CysLT1 inverse agonist montelukast synergistically increases the anticonvulsant action of phenobarbital against pentylenetetrazole-induced seizures. Moreover, it is shown that LTD4 reverses the effect of montelukast. The experimentally derived ED50mix value for a fixed-ratio combination (1:1 proportion) of montelukast plus phenobarbital was 0.06±0.02 μmol, whereas the additively calculated ED50add value was 0.49±0.03 μmol. The calculated interaction index was 0.12, indicating a synergistic interaction. The association of montelukast significantly decreased the antiseizure ED50 for phenobarbital (0.74 and 0.04 μmol in the absence and presence of montelukast, respectively) and, consequently, phenobarbital-induced sedation at equieffective doses. The demonstration of a strong synergism between montelukast and phenobarbital is particularly relevant because both drugs are already used in the clinics, foreseeing an immediate translational application for epileptic patients who have drug-resistant seizures. Copyright © 2015 Elsevier Ltd. All rights reserved.

ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT LASER TOUCH AND TECHNOLOGIES, LLC LASER TOUCH MODEL LT-B512

Science.gov (United States)

The Environmental Technology Verification report discusses the technology and performance of Laser Touch model LT-B512 targeting device manufactured by Laser Touch and Technologies, LLC, for manual spray painting operations. The relative transfer efficiency (TE) improved an avera...

’When You Get a Job to Do, Do It.’ The Airpower Leadership of Lt Gen William H. Tunner

Science.gov (United States)

2008-01-01

PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Air University Stephen R. Lorenz, Lt Gen, Commander Air Force Doctrine...Collier, Richard. Bridge across the Sky. New York: Mc Graw - Hill, 1978. Combined Airlift Task Force. A Report on the Airlift Berlin Mis- sion. 572.101B, 26

Cloud Atlas: Rotational Modulations in the L/T Transition Brown Dwarf Companion HN Peg B

Science.gov (United States)

Zhou, Yifan; Apai, Dániel; Metchev, Stanimir; Lew, Ben W. P.; Schneider, Glenn; Marley, Mark S.; Karalidi, Theodora; Manjavacas, Elena; Bedin, Luigi R.; Cowan, Nicolas B.; Miles-Páez, Paulo A.; Lowrance, Patrick J.; Radigan, Jacqueline; Burgasser, Adam J.

2018-03-01

Time-resolved observations of brown dwarfs’ rotational modulations provide powerful insights into the properties of condensate clouds in ultra-cool atmospheres. Multi-wavelength light curves reveal cloud vertical structures, condensate particle sizes, and cloud morphology, which directly constrain condensate cloud and atmospheric circulation models. We report results from Hubble Space Telescope/Wide Field Camera 3 near-infrared G141 taken in six consecutive orbits observations of HN Peg B, an L/T transition brown dwarf companion to a G0V type star. The best-fit sine wave to the 1.1–1.7 μm broadband light curve has an amplitude of 1.206% ± 0.025% and period of 15.4 ± 0.5 hr. The modulation amplitude has no detectable wavelength dependence except in the 1.4 μm water absorption band, indicating that the characteristic condensate particle sizes are large (>1 μm). We detect significantly (4.4σ) lower modulation amplitude in the 1.4 μm water absorption band and find that HN Peg B’s spectral modulation resembles those of early T type brown dwarfs. We also describe a new empirical interpolation method to remove spectral contamination from the bright host star. This method may be applied in other high-contrast time-resolved observations with WFC3.

Development of a high-performance composite cathode for LT-SOFC

Science.gov (United States)

Lee, Byung Wook

carried out to develop a high-performance composite cathode, in particular, for LT-SOFC operating 650°C and below since stability and compatibility of the materials in interest are secured at low temperatures. First, a nano-sized pyrochlore bismuth ruthenate (Bi2Ru 2O7 or BRO7 shortly), one of the promising cathode materials, was successfully synthesized using glycine-nitrate combustion (GNC) route. Stoichiometric Bi2Ru2O7 without any impurity phase was achieved with considerably improved processing condition, leading to the crystallite size of ~24nm in diameter. Even though the resulting powder tends to agglomerate, resulting in overall 200~400nm size range, it still showed better quality than the one prepared by solid state (SS) reaction route followed by extra milling steps such as vibro-milling and sonication for further particle size reduction. Glycine-to-nitrate (G/N) ratio was found to play a critical role in determining the reaction temperature and reaction duration, thus phase purity and particle morphology (particle size, shape, and agglomeration etc). Composite cathodes of such prepared BRO7 (GNC BRO7) combined with SS erbia-stabilized bismuth oxide, Bi1.6Er0.4O3 or ESB, showed better electrochemical performance than vibro-milled BRO7 (VM BRO7)-SS ESB. ASR values of 0.123Ocm2 at 700°C and 4.59cOm 2 at 500°C, respectively, were achieved, which follows well the trend of particle size effect on performance of composite cathodes. Additionally, the number of processing steps (thus time) was reduced by GNC route. Several issues in regard to synthesis process and characteristics of BRO7 material itself will be addressed in this dissertation. Secondly, a unique in-situ composite cathode synthesis was successfully developed and applied for BRO7-ESB composite cathodes to improve percolation and to reduce agglomeration of each phase inside the cathode so that the effective triple phase boundary (TPB) length was extended. To disperse and stabilize ESB powder in de

Trace fossils from the eocene Lillebælt clay formation, Røsnæs Peninsula, Denmark

DEFF Research Database (Denmark)

Nielsen, Jan Kresten; Milàn, Jesper; Mesfun, Daniel

2015-01-01

A cliff exposure of the Eocene Lillebælt Clay Formation, on the Røsnæs peninsula of Zealand, Denmark, has yielded a diverse trace-fossil assemblage. The trace fossils are described formally for the first time and assigned to Phymatoderma melvillensis, unnamed clusters of small burrows, Ophiomorpha...

Cloud Atlas: Rotational Modulations in the L/T Transition Brown Dwarf Companion HN Peg B

Science.gov (United States)

Zhou, Yifan; Apai, Daniel; Metchev, Stanimir; Lew, Ben W. P.; Schneider, Glenn; Marley, Mark S.; Karalidi, Theodora; Manjavacas, Elena; Bedin, Luigi R.; Cowan, Nicolas B.;

Homotopy perturbation method with Laplace Transform (LT-HPM) for solving Lane-Emden type differential equations (LETDEs).

Science.gov (United States)

Tripathi, Rajnee; Mishra, Hradyesh Kumar

2016-01-01

In this communication, we describe the Homotopy Perturbation Method with Laplace Transform (LT-HPM), which is used to solve the Lane-Emden type differential equations. It's very difficult to solve numerically the Lane-Emden types of the differential equation. Here we implemented this method for two linear homogeneous, two linear nonhomogeneous, and four nonlinear homogeneous Lane-Emden type differential equations and use their appropriate comparisons with exact solutions. In the current study, some examples are better than other existing methods with their nearer results in the form of power series. The Laplace transform used to accelerate the convergence of power series and the results are shown in the tables and graphs which have good agreement with the other existing method in the literature. The results show that LT-HPM is very effective and easy to implement.

Kefir Kültürünün Beyaz Peynir Yapımında Kullanılması Üzerine bir Araştırma

Directory of Open Access Journals (Sweden)

Hasan Yaygın

2015-02-01

Full Text Available Beyaz peynir yapımında kullanılacak saf kültürde yer alması gereken mikroorganizmaları saptamak amacı ile bazı çalışmalar yapılmıştır. Araştırıcıların çoğunluğu saf kültürde S. lactis, S. cremoris ve L. casei’ nin bulunması gerektiğini belirtmişlerdir. Bu çalışmada beyaz peynir yapımında saf kültür olarak kefir kültürü kullanılmıştır. Kefir kültüründe söz konusu bakterilerle beraber bazı maya ve bakteriler de bulunmaktadır. Araştırma sonuçları kefir kültürü katılan sütten yapılan beyaz peynirde asitlik gelişiminin istenilen düzeyde olduğu; tat ve aroma ile yapının tüketiciler tarafından beğenildiğini ortaya çıkarmıştır.

Quadruplex genotype analysis at HumTH01, HumTPOX, HumCSF1PO and amelogenin Loci by FoLT-PCR

Energy Technology Data Exchange (ETDEWEB)

Lee, Y.H.; Lim, S.K.; Kang, P.W.; Choi, D.H.; Yoon, S.R.; Han, M.S. [National Institute of Scientific Investigation, Seoul (Korea)

1999-06-01

A simple and rapid procedure, called FoLT-PCR(Formamide Low Temperature-Polymerase Chain Reaction) was applied to amplifying DNA directly from various forensic biological evidences including human blood, saliva, hair root, or semen without any DNA preparative steps. We added washing step with non-ionic detergent, 1% Triton X-100, and used Taq DNA polymerase instead of Tth DNA polymerase to amplify 3 STR loci and gender allele simultaneously. Optimal concentration of formamide and annealing temperature were determined empirically to 8%(v/v), and 48{sup o} C respectively. We also compared this method with standard PCR. 8 refs., 4 figs.

Kültürel Farklılıkların Yönetiminde İnsan Kaynakları Stratejilerinin Rolü : IKEA Örneği

OpenAIRE

Helvacıoğlu, Nuray; Özutku, Hatice

2010-01-01

Günümüzde işletmelerin küreselleşme eğilimleri, işgören çeşitliliğinin ve kültürel farklılıkların artmasına neden olmaktadır. İşletmelerin rekabet üstünlüğü elde edebilmeleri için kültürel farklılıkların etkin bir biçimde yönetilmesi gerekmektedir. Bu çalışmanın amacı, kültürel farklılıkların yönetiminde insan kaynakları yönetiminin rolünün belirlenmesidir. Bu kapsamda, kültürel farklılıkların yönetiminde ön plana çıkan İsveç kökeni IKEA firmasını konu alan nitel bir araş...

Solubilization and cleavage of human neutrophil (N) affinity-labeled receptors for leukotriene B4 (LTB4)

International Nuclear Information System (INIS)

Marotti, T.; Young, R.N.; Gifford, L.A.; Goldman, D.W.; Goetzl, E.J.

1986-01-01

LTB 4 chemotactic receptors in purified N plasma membranes (PMs) have been affinity-labeled with [ 3 H]-C-1 aminopropylamide-LTB 4 ([ 3 H]APA-LTB 4 ) by disuccinimidyl suberate (DSS) cross-linking. Intact Ns were pretreated with diisopropylfluorophosphate, suspended at 10 7 /ml in Hanks' solution-10 mM HEPES (pH 7.4), incubated for 30 min at 4 0 C with 30 nM [ 3 H]APA-LTB 4 and 25 min with 1 mM bis[2-(succinimidooxycarbonyloxy)-ethyl] sulfone, an impermeant analog of DSS, and sonified for 30 sec at 4 0 C. The 10,000 g supernatant of the sonicate was centrifuged at 40,000 g for 30 min at 4 0 C on a discontinuous gradient of 10-50 g % sucrose, from which a mean of 78% of the radiolabel was recovered with PM markers. The extent and specificity of labeling of intact N receptors were similar to those of receptors in PMs. The radioactively-labeled receptors appeared as a single band of 35-40 kd in sodium dodecyl sulfate (SDS) 10 g % polyacrylamide gel electrophoresis. Cleavage of radiolabeled receptors with 1 mg/ml of cyanogen bromide in 70% formic acid for 18 hr at room temperature or with 30 mM HCl under N 2 for 4 hr at 105 0 C converted a mean of 18-32% of the radioactivity to a band of 14 kd in SDS-15 g % PAGE. N receptors for LTB 4 , thus, are localized in the PM and can be isolated for structural studies

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis.

Science.gov (United States)

Laurent, Irakoze; Tang, Siying; Astère, Manirakiza; Wang, Kan Ran; Deng, Shuhua; Xiao, Ling; Li, Qi Fu

2018-03-23

To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L-T4 in patients on L-T4 replacement or suppressive therapy. The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or suppressive therapy were included in the analysis. Overall, the initial search of the four databases identified 1278 published studies; of these, eight studies were ultimately included in the meta-analysis. TSH (thyroid stimulating hormone) levels were significantly suppressed in patients on liquid L-T4 compared with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4 malabsorption (Mean Difference (MD) = -2.26, 95% Confidence Interval (CI): -3.59, -0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 suppressive therapy without malabsorption (MD = 0.08, 95% CI: -0.31, 0.47; P = 0.69). TSH levels were significantly normalized in patients on liquid L-T4 compared with those on tablet L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = -3.20, 95% CI: -5.08, -1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 replacement therapy without malabsorption (MD = 0.91, 95% CI: -0.03, 1.86; P = 0.06). Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4 replacement or suppressive therapy with malabsorption. No significant differences were observed in patients without malabsorption. Further studies should be conducted to verify these findings.

Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

Energy Technology Data Exchange (ETDEWEB)

Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Roelofs, Hennie M.J.; Morsche, Rene H.M. te [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marian, Brigitte [Institute of Cancer Research, Wien University, Vienna (Austria); Nagengast, Fokko M.; Peters, Wilbert H.M. [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

2012-04-15

Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

International Nuclear Information System (INIS)

Heumen, Bjorn W.H. van; Roelofs, Hennie M.J.; Morsche, René H.M. te; Marian, Brigitte; Nagengast, Fokko M.; Peters, Wilbert H.M.

2012-01-01

Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14–17%, p < 0.01). A more pronounced decrease (23–27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to ‘artificial bile’ enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with ‘artificial bile’ enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: ► Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. ► UDCA enriched ‘artificial bile’ decreases LT-97 cell growth only in presence of celecoxib. ► PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

PREFACE: Proceedings of the 25th International Conference on Low Temperature Physics (LT25) (Amsterdam, The Netherlands, 6-13 August 2008) Proceedings of the 25th International Conference on Low Temperature Physics (LT25) (Amsterdam, The Netherlands, 6-13 August 2008)

Science.gov (United States)

Kes, Peter; Jochemsen, Reijer

2009-04-01

This issue forms part I of the Proceedings of the 25th International Conference on Low Temperature Physics (LT25) (Amsterdam, The Netherlands, 67-13 August 2008). The majority of the special invited lectures, such as the London prize lectures, the international union of pure and applied physics (IUPAP) young scientist award lectures, the plenary, half-plenary and public lectures, and the historical lectures presented at the LT25 conference, are included. The papers relating to the oral and poster presentations will appear in part II of the proceedings in a dedicated open access issue of Journal of Physics: Conference Series (2009 J. Phys.: Conf. Ser. 150). In addition to the organizer's report and a summary of the new developments in low temperature physics, which can also be found in this issue, part II provides useful information about LT25, such as an overview of committees, sponsors, exhibitors, and some conference statistics. To ensure the high publication standard mandated by Journal of Physics: Condensed Matter and Journal of Physics: Conference Series every paper was reviewed by at least one referee before it was accepted for publication. The editors are indebted to many colleagues for invaluable assistance in the preparation and review of 900 papers appearing in both parts I and II of these proceedings. In particular, we would like to thank Carlo Beenakker, Jeroen van den Brink, Hans Brom, Jos de Jongh, Horst Rogalla, Fons de Waele, and Jan Zaanen.

Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

International Nuclear Information System (INIS)

Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

1986-01-01

EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A 4 hydrolase activity, plasma renin activity (PRA), urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ and aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P 4 hydrolase activity was inhibited. PRA and urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ were not changed. Similarly, there was no change in aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function

Effects of acrolein on leukotriene biosynthesis in human neutrophils.

Science.gov (United States)

Berry, Karin A Zemski; Henson, Peter M; Murphy, Robert C

2008-12-01

Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase (5-LO) products in addition to small amounts of cyclooxygenase (COX) products were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 microM) was present with almost complete inhibition at > or = 25 microM acrolein. The production of COX products was not affected by acrolein in these cells. The effect of acrolein was examined on key parts of the eicosanoid pathway, such as arachidonic acid release, intracellular calcium ion concentration, and adenosine production. In addition, the direct effect of acrolein on 5-LO enzymatic activity was probed using a recombinant enzyme. Some of these factors were affected by acrolein but did not completely explain the almost complete inhibition of 5-LO product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the effect of acrolein on different stimuli that initiate the 5-LO pathway [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and A23187] was examined. Acrolein had no significant effect on the leukotriene production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. Additionally, 50% inhibition of the 5-LO pathway was observed in A23187-stimulated neutrophils. Our results suggest that acrolein has a profound effect on the 5-LO pathway in neutrophils, which may have implications in disease states, such as chronic obstructive pulmonary disease and other pulmonary disease, where both activated neutrophils and acrolein are

The effects of LT-SN on energy dissipation and lifetime in wireless sensor networks

Directory of Open Access Journals (Sweden)

Zeydin Pala

2016-11-01

Full Text Available Wireless sensor networks (WSNs still attract the attention of researchers, users and the private sector despite their low power and low range tendency for malfunction. This attraction towards WSNs results from their low cost structure and the solutions they offer for many prevalent problems. Many conditions, which remain unforeseen or unexpected during the design of the system, may arise after the initialization of the system. Similarly, many situations where security vulnerabilities take place may emerge in time in WSNs operating normally. In this study, we called nodes which enter sleeping mode without any further waking up and causing a sparser number of nodes in the network without any function in data transmission as Long-Term Sleep Nodes (LT-SN; and considered energy spaces caused by such nodes as a problem; and established two Linear Programming (LP models based on the efficiency of the present nodes. We offered two different models which present the effect of sensor nodes, which were initially operating in wireless sensor network environment and did not wake up following sleep mode, on network lifetime. The results of the present study report that as the number of LT-SN increases, the lifetime of the network decreases.

Rigid'' skeleton dynamics of Li sub 3 In sub 2 (PO sub 4 ) sub 3 superionic conductor

Energy Technology Data Exchange (ETDEWEB)

Naganovsky, Y K; Sigaryov, S E [Inst. of Crystallography, Academy of Sciences, Moscow (USSR)

1992-01-01

The effect studied is made by the thermal prehistory of the Li{sub 3}In{sub 2}(PO{sub 4}){sub 3} ceramics on their structural and electrophysical characteristics. Annealing at T>1290 K is shown to result in a monoclinic (HT) and at T<1230 K, rhombohedral (LT) modifications of the crystal structure of Li{sub 3}In{sub 2}(PO{sub 4}){sub 3}. At the same temperature the ionic conductivity ({sigma}) of the HT-modification is found to be higher than that of LT-modification. Annealing of LT-ceramics at {proportional to}985 K leads to a decrease of {sigma} by as much as two order of magnitude seems due to Li{sup +}-ions redistribution in the (In{sub 2}P{sub 3}O{sub 12}){sub 3{infinity}}{sup 3-} skeleton cavities. In the 290-650 K temperature range phase transitions both in LT- and HT-Li{sub 3}In{sub 2}(PO{sub 4}){sub 3} are observed. (orig.).

Bronchial effects of leukotriene D4 inhalation in normal human lung

DEFF Research Database (Denmark)

Bisgaard, H; Groth, S

1987-01-01

obstruction had decreased by 50% of the maximum effect, and no delayed reaction was observed within 10 h. The reactivity of the airways did not change during 10 h after inhalation of LTD4 as tested by repeated exercise challenges. Pretreatment with ipratropium bromide prevented the effect of LTD4 on FEV1, yet...

Oenothera paradoxa defatted seeds extract and its bioactive component penta-O-galloyl-β-D-glucose decreased production of reactive oxygen species and inhibited release of leukotriene B4, interleukin-8, elastase, and myeloperoxidase in human neutrophils.

Science.gov (United States)

Kiss, Anna K; Filipek, Agnieszka; Czerwińska, Monika; Naruszewicz, Marek

2010-09-22

In this study, we analyzed ex vivo the effect of an aqueous extract of Oenothera paradoxa defatted seeds on the formation of neutrophil-derived oxidants. For defining active compounds, we also tested lypophilic extract constituents such as gallic acid, (+)-catechin, ellagic acid, and penta-O-galloyl-β-D-glucose and a hydrophilic fraction containing polymeric procyanidins. The anti-inflammatory potential of the extract and compounds was tested by determining the release from activated neutrophils of elastase, myeloperoxidase, interleukin-8 (IL-8), and leukotriene B4 (LTB4), which are considered relevant for the pathogenesis of cardiovascular diseases. The extract of O. paradoxa defatted seeds displays potent antioxidant effects against both 4β-phorbol-12β-myristate-α13-acetate- and formyl-met-leu-phenylalanine-induced reactive oxygen species production in neutrophils with IC50 values around 0.2 μg/mL. All types of polyphenolics present in the extract contributed to the extract antioxidant activity. According to their IC50 values, penta-O-galloyl-β-D-glucose was the more potent constituent of the extract. In cell-free assays, we demonstrated that this effect is partially due to the scavenging of O2- and H2O2 oxygen species. The extract and especially penta-O-galloyl-β-D-glucose significantly inhibit elastase, myeloperoxidase IL-8, and LTB4 release with an IC50 for penta-O-galloyl-β-D-glucose of 17±1, 15±1, 6.5±2.5, and around 20 μM, respectively. The inhibition of penta-O-galloyl-β-D-glucose on reactive oxygen species and especially on O2- production, myeloperoxidase, and chemoattractant release may reduce the interaction of polymorphonuclear leukocyte with the vascular endothelium and by that potentially diminish the risk of progression of atherosclerosis development.

SWAAM-LT: The long-term, sodium/water reaction analysis method computer code

International Nuclear Information System (INIS)

Shin, Y.W.; Chung, H.H.; Wiedermann, A.H.; Tanabe, H.

1993-01-01

The SWAAM-LT Code, developed for analysis of long-term effects of sodium/water reactions, is discussed. The theoretical formulation of the code is described, including the introduction of system matrices for ease of computer programming as a general system code. Also, some typical results of the code predictions for available large scale tests are presented. Test data for the steam generator design with the cover-gas feature and without the cover-gas feature are available and analyzed. The capabilities and limitations of the code are then discussed in light of the comparison between the code prediction and the test data

Intranasal Administration of 2/6-Rotavirus-Like Particles with Mutant Escherichia coli Heat-Labile Toxin (LT-R192G) Induces Antibody-Secreting Cell Responses but Not Protective Immunity in Gnotobiotic Pigs

Science.gov (United States)

Yuan, Lijuan; Geyer, Annelise; Hodgins, Douglas C.; Fan, Zhiqian; Qian, Yuan; Chang, Kyeong-Ok; Crawford, Sue E.; Parreño, Viviana; Ward, Lucy A.; Estes, Mary K.; Conner, Margaret E.; Saif, Linda J.

2000-01-01

We investigated the immunogenicity of recombinant double-layered rotavirus-like particle (2/6-VLPs) vaccines derived from simian SA11 or human (VP6) Wa and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were administered to gnotobiotic pigs intranasally (i.n.) with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT), as mucosal adjuvant. Pigs were challenged with virulent Wa (P1A[8],G1) human rotavirus at postinoculation day (PID) 21 (two-dose VLP regimen) or 28 (three-dose VLP regimen). In vivo antigen-activated antibody-secreting cells (ASC) (effector B cells) and in vitro antigen-reactivated ASC (derived from memory B cells) from intestinal and systemic lymphoid tissues (duodenum, ileum, mesenteric lymph nodes [MLN], spleen, peripheral blood lymphocytes [PBL], and bone marrow lymphocytes) collected at selected times were quantitated by enzyme-linked immunospot assays. Rotavirus-specific immunoglobulin M (IgM), IgA, and IgG ASC and memory B-cell responses were detected by PID 21 or 28 in intestinal and systemic lymphoid tissues after i.n. inoculation with two or three doses of 2/6-VLPs with or without mLT. Greater mean numbers of virus-specific ASC and memory B cells in all tissues prechallenge were induced in pigs inoculated with two doses of SA11 2/6-VLPs plus mLT compared to SA11 2/6-VLPs without mLT. After challenge, anamnestic IgA and IgG ASC and memory B-cell responses were detected in intestinal lymphoid tissues of all VLP-inoculated groups, but serum virus-neutralizing antibody titers were not significantly enhanced compared to the challenged controls. Pigs inoculated with Wa-RF 2/6-VLPs (with or without mLT) developed higher anamnestic IgA and IgG ASC responses in ileum after challenge compared to pigs inoculated with SA11 2/6-VLPs (with or without mLT). Three doses of SA 11 2/6-VLP plus mLT induced the highest mean numbers of IgG memory B cells in MLN, spleen, and PBL among all groups postchallenge. However, no significant protection against

Synthesis of leukotrienes labelled with deuterium: [11,12,14,15-2H4]-LTA4, -LTC4, -LTD4 and -LTE4

International Nuclear Information System (INIS)

Lellouche, J.P.; Aubert, F.; Noel, J.P.; Boullais, C.; Beaucourt, J.P.

1989-01-01

Semi-hydrogenation by D 2 gas on Lindlar catalyst of an acetylenic precursor led to [11,12,14,15- 2 H 4 ]-LTA 4 methyl ester. Nucleophilic opening of the epoxide ring by amino thioacids accorded, after saponification, the corresponding deuterated peptidoleukotrienes LTC 4 , LTD 4 and LTE 4 . (author)

Mast cells in citric acid-induced cough of guinea pigs

International Nuclear Information System (INIS)

Lai, Y.-L.; Lin, T.-Y.

2005-01-01

It was demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. To investigate the role of mast cells in CA-induced cough, three experiments were carried out in this study. In the first experiment, 59 guinea pigs were employed and we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit leukotriene synthesis, pyrilamine to antagonize histamine H 1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, 56 compound 48/80-pretreated animals were divided into two parts; the first one was used to test the role of exogenous leukotriene (LT) C 4 , while the second one to test the role of exogenous histamine in CA-induced cough. Each animal with one of the above pretreatments was exposed sequentially to saline (baseline) and CA (0.6 M) aerosol, each for 3 min. Then, cough was recorded for 12 min using a barometric body plethysmograph. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining arterial plasma histamine concentration in 17 animals. Exposure to CA induced a marked increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced cough. Injection of LTC 4 or histamine caused a significant increase in CA-induced cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in plasma histamine concentration, which was blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced cough via perhaps mediators LTs and histamine

Lumbar lordosis restoration following single-level instrumented fusion comparing 4 commonly used techniques.

Science.gov (United States)

Dimar, John R; Glassman, Steven D; Vemuri, Venu M; Esterberg, Justin L; Howard, Jennifer M; Carreon, Leah Y

2011-11-09

A major sequelae of lumbar fusion is acceleration of adjacent-level degeneration due to decreased lumbar lordosis. We evaluated the effectiveness of 4 common fusion techniques in restoring lordosis: instrumented posterolateral fusion, translumbar interbody fusion, anteroposterior fusion with posterior instrumentation, and anterior interbody fusion with lordotic threaded (LT) cages (Medtronic Sofamor Danek, Memphis, Tennessee). Radiographs were measured preoperatively, immediately postoperatively, and a minimum of 6 months postoperatively. Parameters measured included anterior and posterior disk space height, lumbar lordosis from L3 to S1, and surgical level lordosis.No significant difference in demographics existed among the 4 groups. All preoperative parameters were similar among the 4 groups. Lumbar lordosis at final follow-up showed no difference between the anteroposterior fusion with posterior instrumentation, translumbar interbody fusion, and LT cage groups, although the posterolateral fusion group showed a significant loss of lordosis (-10°) (Plordosis and showed maintenance of anterior and posterior disk space height postoperatively compared with the other groups. Instrumented posterolateral fusion produces a greater loss of lordosis compared with anteroposterior fusion with posterior instrumentation, translumbar interbody fusion, and LT cages. Maintenance of lordosis and anterior and posterior disk space height is significantly better with anterior interbody fusion with LT cages. Copyright 2011, SLACK Incorporated.

Tüketim kültüründe etkili bir araç olarak reklamın işlevlerine dair genel bir değerlendirme

OpenAIRE

Elmasoğlu, Kamile

2017-01-01

Betimsel analiz yönteminin kullanıldığı bu çalışmada, tüketim kültürünün yayılmasında etkili bir araç olarak görülen reklamın rolüne dair genel bir değerlendirme sunmak hedeflenmektedir. Bu hedef dâhilinde, tüketim toplumu, tüketim kültürü ve reklamın tüketim kültürü içindeki işlevleri; çeşitli düşünürlerin görüşlerinden istifade edilerek tartışılmıştır. Tüketim kültürünün hakim olduğu bir toplumda reklama ilişkin çeşitli fikirlerin benimsendiği görülmektedir. Çalışma genel olarak değerlendir...

Käyttäjien tuottama sisältö markkinoinnissa : Opas

OpenAIRE

Koskenseppä, Mikko

2016-01-01

Markkinoijien ja kuluttajien roolit ovat muuttunut 2000-luvun aikana, jonka takia yritykset eivät voi enää pitää markkinointia yksisuuntaisena viestintänä. Nykyään yrityksien pitää saada kuluttajat mukaan markkinointiin, ja käyttäjien tuottama sisältö onkin yksi ratkaisu tähän ongelmaan. Tämä opinnäytetyö oli toiminnallinen työ. Sen tavoitteena oli luoda ohjeistus käyttäjien tuottaman sisällön käyttämisestä markkinoinnissa. Työn muut tavoitteet oli selvittää sen tuomat hyödyt ja ominaisuu...

USA kohus nõuab LHV-lt, Lepikult ja Peegilt kiiresti ligi 14 miljonit krooni / Lauri Matsulevitsh

Index Scriptorium Estoniae

Matsulevitsh, Lauri

2005-01-01

USA kohus kinnitas investeerimispangaga LHV eelkokkuleppe ning muutis esialgset hagi tagamise määrust, millega nõuab LHV-lt sealt välja viidud raha USA kohturegistri kontole tagasi viie päeva jooksul. Lisa: Kontodelt nõutakse 13,8 mln krooni. Vt. samas: Advokaat: SEC kasutab jõupositsiooni

Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial

NARCIS (Netherlands)

Appelhof, Bente C.; Fliers, Eric; Wekking, Ellie M.; Schene, Aart H.; Huyser, Jochanan; Tijssen, Jan G. P.; Endert, Erik; van Weert, Henk C. P. M.; Wiersinga, Wilmar M.

2005-01-01

Controversy remains about the value of combined treatment with levothyroxine (LT4) and liothyronine (LT3), compared with LT4 alone in primary hypothyroidism. We compared combined treatment with LT4 and LT3 in a ratio of 5: 1 or 10: 1 with LT4 monotherapy. We conducted a double-blind, randomized,

UV induction of the LT-Toxin operon with respect to the genes lexA, recA, and umuD

International Nuclear Information System (INIS)

Tiganova, I.G.; Rusina, O.Yu.; Andreeva, I.V.; Brukhanskii, G.V.; Skavronskaya, A.G.

1994-01-01

UV induction of the elt operon (the LT-toxin operon in Escherichia coli) was demonstrated in experiments using fusion of elt::lac operons with the help of Mud1(Ap lac) phage. UV induction of the elt operon is lexA-dependent; thus, the possibility of SOS regulation of this process may be assumed. However, UV induction of the elt operon turned out to be recA-independent, which makes it impossible to consider this induction as a typical SOS response. UV induction of the elt operon is also observed in Salmonella typhimurium, which differs from E. coli in the product of umuD, which suggests that the UV induction of the elt operon is umuD independent

Türk Sucuklarında Ticari Starter Kültür Kullanımı Üzerine Araştırmalar II. Duyusal ve Mikrobiyolojik Analizler

Directory of Open Access Journals (Sweden)

Halil Vural

2015-02-01

Full Text Available Bu çalışmada; işletme düzeyinde kontrollü koşullarda Türk sucuğu üretiminde ticari starter kültürlerin kullanımı incelenmiştir. Bu amaçla, starter kültür katılmayan örnek kontrol grubu olarak alınarak, 7 farklı ticari starter kültürle hazırlanan 8 sucuk örneği aynı koşullarda denemeye alınmıştır. Sucuklara üretimin 7 kritik noktasına mezofilik aerobik bakteri, Lactobacillus-Pedicoccus ve patojen olmayan Staphylococcus-Micrococcus sayımı analizleri ile ürün bazında duyusal analizlerle starter kültür katılarak üretilen sucukların kontrol grubuna göre belirgin üstünlük sağladıkları belirlenmiş, kimyasal, mikrobiyolojik ve duyusal analiz bulgularının birlikte değerlendirilmesi; Türk sucuğu özelliklerine en uygun sonuçları Flora Carn SL ve Flora Carn SP starter kültürleri ile yapılan sucukların verdiğini göstermiştir.

Inducible pathway is required for mutagenesis in Salmonella typhimurium LT2

International Nuclear Information System (INIS)

Orrego, C.; Eisenstadt, E.

1987-01-01

UV mutability of Salmonella typhimurium LT2 was eliminated in the presence of a multicopy plasmid carrying the Escherichia coli lexA + gene. This result suggests that inducible, SOS-like functions are required for UV mutagenesis in S. typhimurium. S. typhimurium strains carrying either point or deletion mutations in topA had previously been shown to lose their mutability by UV or methyl methanesulfonate. Mitomycin C induction of the Phi(mucB'-lacZ') fusion (a DNA damage-inducible locus carried on plasmid pSE205) in S. typhimurium topA was normal, suggesting that RecA is activated in topA mutants. These observations lead the authors deduce that S. typhimurium has at least one DNA damage-inducible locus in addition to recA that is required for UV mutability

Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils.

Science.gov (United States)

Qiu, F H; Devchand, P R; Wada, K; Serhan, C N

2001-12-01

Aspirin-triggered 15-epi-lipoxin A4 (ATL) is an endogenous lipid mediator that mimics the actions of native lipoxin A4, a putative "stop signal" involved in regulating resolution of inflammation. A metabolically more stable analog of ATL, 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4 analog (ATLa), inhibits neutrophil recruitment in vitro and in vivo and displays potent anti-inflammatory actions. ATLa binds with high affinity to the lipoxin A4 receptor, a G protein-coupled receptor on the surface of leukocytes. In this study, we used freshly isolated human neutrophils to examine ATLa's potential for initiating rapid nuclear responses. Using differential display reverse transcription polymerase chain reaction, we identified a subset of genes that was selectively up-regulated upon short exposure of polymorphonuclear leukocytes to ATLa but not to the chemoattractant leukotriene B4 or vehicle alone. We further investigated ATLa regulation of one of the genes, NAB1, a transcriptional corepressor identified previously as a glucocorticoid-responsive gene in hamster smooth muscle cells. Treatment of human neutrophils with pertussis toxin blocked ATLa up-regulation of NAB1. In addition, ATLa stimulated NAB1 gene expression in murine lung vascular smooth muscle in vivo. These findings provide evidence for rapid transcriptional induction of a cassette of genes via an ATLa-stimulated G protein-coupled receptor pathway that is potentially protective and overlaps with the anti-inflammatory glucocorticoid regulatory circuit.

Development of 125I-leukotriene B4 radio-immunoassay and its clinical applications

International Nuclear Information System (INIS)

Wang Zhaoyue; He Yang; Chen Dechun; Ruan Changgeng

1992-11-01

LTB 4 was extracted from porcine blood with the help of HPLC. The antiserum was raised by immunizing rabbits with LTB 4 which has been conjugated with bovine serum albumin by mixed anhydride method method. The titer of the anti-body was 1:7000 and the affinity coefficient was 2.1 x 10 9 L/M. Its cross reactions with LTA 4 , LTC 4 , LTD 4 and other arachidonic acid metabolites were 0.4 ∼ 6.4%.The 125 I-histamine-LTB 4 was prepared by using chloramine T procedure. The minimum detectable limit was 25 pg/tube. The recovery rate was 84.2 ∼ 113%. The intra- and inter-assay coefficient of variation were 5.2% and 9.7% respectively. The amount of LTB 4 produced by normal human PMNL which were stimulated by ionophore A23187 and arachidonic acid was 695.5 ± 329.7 pg/10 6 cells. PMNL of patients with various acute leukemias and CML generated an increased quantities of LTB 4 , TXB 2 and 6-keto-PGF 1α . LTB 4 produced by PMNL also showed an increasing tendency in both cerebral thrombosis and acute myocardial infarction, but was not altered in cerebral hemorrhage of non-infarction coronary disease

FIRST 5-DAYS FOLLOW-UP AND CORRELATION STUDY BETWEEN URINARY CYSTEINYL LEUKO TRIENES AND EDEMA VALUES IN PRIMARY SPONTANEOUS SUPRATENTORIAL INTRACEREBRAL HEMO RRHAGE

Directory of Open Access Journals (Sweden)

Dolnenec-Baneva Natalia

2014-07-01

Full Text Available Background: After intracerebral hemorrhage cysteinyl leukotrienes (C4, D4, E4 are synthetisized in the contact brain parenchyma-extravasated blood and participate in producing of edema formation. The study aim is a 5-days follow up (admittance/3thday/5thday of urinary cysteinyl leukotrienes, hematoma and edema volume in patients with primary spontaneous supratentorial intracerebral hemorrhage and to determine the relationship: edema/haematoma and edema/leuko trienes. Methods: An enzyme immunoassay for leukotrienes measuring in the urine samples from 62 patients with hemorrhage during the first 5 days ( admittance/3thday/5thday and 80 health controls is used. Hematoma and edema volume is visualised and measured by computed-tomography. Results: Admission values of leukotrienes were significantly higher in the hemorrhagic patients (min =268.61; max = 5787.36; mean = 1842.20 ± 1413.19 pg/ml/mg creatinine versus control subjects (min =297.8; max = 1684.2; mean = 918.6 ± 332 (p 0.05. The edema (mean: 12.86 ±13.52; 22.38 ± 21.10; 28.45 ± 29.41 cm3 showed very high significance (p 0.05 of moderate strength is found between edema and hematoma; and significant positive correlation (r = 0.6; p 0.05 at admittance, r = – 0.05 (p >0.05 on the 3th day (nonexistence of linear correlation, the sign minus presents their tendency for the opposite movement in their values and r = 0.2 (p > 0.05 on the 5thday are found (positive linear nonsignificant correlation of slight strength. Conclusion: Significant urinary leukotrienes excretion (a brain capacity for significant leukotrienes synthesis and significant edema progression versus constant haematoma are found. The edema size followed the hematoma size of moderate extent. The edema showed an inverse dependence of the leukotrienes (atendency for opposite movement of their values, the high leukotrienes values at admittance bring to greater edema volume on the third/the fifth day, respectively. Elevated cysteinyl

VizieR Online Data Catalog: L/T transition dwarfs search with PS1 & WISE. II. (Best+, 2015)

Science.gov (United States)

Best, W. M. J.; Liu, M. C.; Magnier, E. A.; Deacon, N. R.; Aller, K. M.; Redstone, J.; Burgett, W. S.; Chambers, K. C.; Draper, P.; Flewelling, H.; Hodapp, K. W.; Kaiser, N.; Metcalfe, N.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.

2016-03-01

We used the new Pan-STARRS1 Survey (PS1; Kaiser et al. 2010SPIE.7733E..0EK) detections through 2012 January cross-matched with the Wide-field Infrared Survey Explorer (WISE; Wright et al. 2010AJ....140.1868W) All-sky Release using a 3" matching radius. In Best et al. (2013ApJ...777...84B; Paper I), we presented seven initial discoveries from our search, all bright L/T transition dwarfs within 15pc. In this paper, we present the complete results of our search, including 79 total L/T transition dwarfs and 23 young or potentially young late-M and L dwarfs. The PS1 3π survey (K. C. Chambers et al. 2016AAS...22732407C) has obtained an average of ~12 epochs of imaging in five optical bands (gP1, rP1, iP1, zP1, yP1) with a 1.8-m wide-field telescope on Haleakala, Maui, covering the entire sky north of -30° declination. Imaging began in 2010 May and concluded in 2014 March. The WISE All-sky Source Catalog (Cutri et al. 2012, II/311) comprises data taken between 2010 January and August in four mid-infrared bands: W1 (3.6um), W2 (4.5um), W3 (12um), and W4 (22um). We searched the UKIDSS Data Release 9 (DR9; Lawrence et al. 2013, II/319) and VISTA Hemisphere Survey (Cross et al. 2012A&A...548A.119C) catalogs for JHK photometry of our candidates on the Mauna Kea Observatories (MKO) filter system. For objects not found in either survey, we obtained follow-up images using WFCAM on the 3.8m United Kingdom InfraRed Telescope (UKIRT) as part of the UKIRT Service Program. Observations took place on multiple nights spanning 2010 September to 2013 December. We obtained low-resolution near-IR spectra for our 142 candidates between 2012 July and 2014 January using the NASA IRTF/SpeX spectrograph (details of our observations are listed in table 3). (7 data files).

Effekten af hydraulisk kontrol på den vertikale fordeling og sammensætning af fytoplankton og zooplanktonsamfundene i Lillebælt

DEFF Research Database (Denmark)

Nielsen, Erik Haar; Christensen, Jens Tang; Lund-Hansen, Lars Chresten

Effekten af strømbetinget opblanding på fytoplankton og zooplankton sammensætningen i en lagdelt vandsøjle blev undersøgt i Lillebælt i april 2015. De hydrografiske forhold blev kortlagt gennem kontinuerlige målinger med ADCP og undulerende CTD (Scanfish III) langs et transekt fra Tragten nord...... for Fredericia til det centrale Lillebælt. Vandprøver til analyse af fytoplankton blev taget fra tre strata med CTD forsynet med en rosette med Niskin -vandhentere og zooplankton blev indsamlet med et Multinet-maxi (HydroBios, Kiel) fra 9 strata i vandsøjlen. Under kraftig sydgående strøm viste hydrografien...

Leukotriene B4 (LTB4) induces formation of inositol-phosphates (IP's) in rat peritoneal polymorphonuclear leukocytes (PMN's)

International Nuclear Information System (INIS)

Chi-Rosso, G.; Crooke, S.T.; Mong, S.

1986-01-01

LTB 4 induced rapid breakdown of prelabeled inositol-phospholipids (PI) in rat PMN. Formation of [ 3 H]-inositol-trisphosphate ([ 3 H]-IP 3 ) was rapid, with a peak of 250-300% of the control level, after 5-15 sec of stimulation with LTB 4 . Accumulation of [ 3 H]-inositol-bisphosphate ([ 3 H]-IP 2 ) was rapid, peaking after 30 sec of stimulation. [ 3 H]-inositol-monophosphate ([ 3 H]-IP 1 ) accumulated gradually in the presence of LiCl. The kinetics of [ 3 H]-IP 3 , [ 3 H]-IP 2 and [ 3 H]-IP 1 accumulation suggested that LTB 4 may interact with receptors in PMNs, activate phospholipase C which, in turn, induces hydrolysis of PI. The agonist activities of several LTB 4 analogs were employed to investigate the structure activity relationship of LTB 4 receptor mediated activation of PI hydrolysis. Increases in [ 3 H]-IP 3 formation were dependent upon the concentration of LTB 4 and the agonist analogs. The rank order potency of these analogs were equivalent to that of the pharmacological activity of LTB 4 agonists in the chemotaxis assay. Furthermore, the Islet activation protein (IAP) inhibited LTB 4 induced [ 3 H]-IP 3 formation. The tumor promoting phorbomyristate ester also inhibited LTB 4 induced [ 3 H]-IP 3 formation. These results suggest LTB 4 may interact with receptors in rat PMNs, activate G/sub i/ protein regulated phospholipase C and induce [ 3 H]-IP 3 formation

Role of leukotrienes in NSAID induced gastric ulceration and inflammation in wistar rats

Directory of Open Access Journals (Sweden)

Maulik N Gandhi

2012-06-01

Full Text Available Objective: To evaluate the effects of Montelukast and Curcumin against indomethacin induced gastric damage in rats in order to assess the role of leukotriene (LTs if any, in non steroidal antiinflammatory drug (NSAID induced gastroinflammation. Methods: The effects of Montelukast (10 mg/kg and Curcumin (100 mg/kg were observed on gastric lesion induced by Indomethacin. The blood samples were analyzed for neutrophil adhesion and lipid peroxide levels in gastric tissue measured spectrophotometrically. The skin vascular permeability study was performed by using compound 48/80 induced vascular permeability model. Results: Montelukast and Curcumin significantly reduced Indomethacin induced gastric lesion score. Pretreatment with Montelukast and Curcumin significantly counteracted Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence, through decrease in related production of free radicals that disrupts integrity of stomach mucosa and decrease in vascular permeability as compared to Indomethacin group. The results of the present study further indicates the role of 5-LOX metabolites in NSAIDs induced gastro inflammation and suggests that Montelukast and Curcumin counteracted the Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence and through decrease in related production of free radicals that disrupts integrity of stomach mucosa. Conclusions: Experimental data clearly demonstrated the role of LTs was indomethacin induced gastric ulcers. However, inhibition of ulcerogenic events by Montelukast and Curcumin is suggestive of an important balance between COX and 5-LOX products.

The effect of rider weight and additional weight in Icelandic horses in tölt: part II. Stride parameters responses.

Science.gov (United States)

Gunnarsson, V; Stefánsdóttir, G J; Jansson, A; Roepstorff, L

2017-09-01

This study investigated the effects of rider weight in the BW ratio (BWR) range common for Icelandic horses (20% to 35%), on stride parameters in tölt in Icelandic horses. The kinematics of eight experienced Icelandic school horses were measured during an incremental exercise test using a high-speed camera (300 frames/s). Each horse performed five phases (642 m each) in tölt at a BWR between rider (including saddle) and horse starting at 20% (BWR20) and increasing to 25% (BWR25), 30% (BWR30), 35% (BWR35) and finally 20% (BWR20b) was repeated. One professional rider rode all horses and weight (lead) was added to saddle and rider as needed. For each phase, eight strides at speed of 5.5 m/s were analyzed for stride duration, stride frequency, stride length, duty factor (DF), lateral advanced placement, lateral advanced liftoff, unipedal support (UPS), bipedal support (BPS) and height of front leg action. Stride length became shorter (Y=2.73-0.004x; P0.05). In conclusion, increased BWR decreased stride length and increased DF proportionally to the same extent in all limbs, whereas BPS increased at the expense of decreased UPS. These changes can be expected to decrease tölt quality when subjectively evaluated according to the breeding goals for the Icelandic horse. However, beat, symmetry and height of front leg lifting were not affected by BWR.

Regulation of the cellular content of the organic osmolyte taurine in mammalian cells

DEFF Research Database (Denmark)

Lambert, Ian H.

2004-01-01

regulatory volume decrease, iPLA2, cPLA2, leukotriene D4, reactive oxygen species, NADPH oxidase, protein tyrosine phosphatase, lysophosphatidyl choline......regulatory volume decrease, iPLA2, cPLA2, leukotriene D4, reactive oxygen species, NADPH oxidase, protein tyrosine phosphatase, lysophosphatidyl choline...

On the Solution of the Rational Matrix Equation X=Q+LX−1LT

Directory of Open Access Journals (Sweden)

Heike Faßbender

2007-01-01

Full Text Available We study numerical methods for finding the maximal symmetric positive definite solution of the nonlinear matrix equation X=Q+LX−1LT, where Q is symmetric positive definite and L is nonsingular. Such equations arise for instance in the analysis of stationary Gaussian reciprocal processes over a finite interval. Its unique largest positive definite solution coincides with the unique positive definite solution of a related discrete-time algebraic Riccati equation (DARE. We discuss how to use the butterfly SZ algorithm to solve the DARE. This approach is compared to several fixed-point and doubling-type iterative methods suggested in the literature.

Improving containment mass and energy releases for CONTEMPT-LT/028 TU with RELAP5/MOD3

International Nuclear Information System (INIS)

DaSilva, H.C.; Choe, W.G.

1996-01-01

In order to obtain boundary conditions for RELAP5/MOD3 best estimate (BE) large break (LB) loss-of-coolant accident (LOCA) calculations, it is necessary to utilize a separate containment analysis code CONTEMPT-LT/028 TU, which in turn accepts mass and energy releases from the RELAP5/MOD3 calculation. When these boundary conditions are obtained, they are observed to be significantly lower than those reported in FSAR containment analyses. This motivates the present study, where RELAP5/MOD3 mass and energy releases are generated using the same assumptions listed in the FSAR containment calculations. Then CONTEMPT-LT/028 TU pressures and temperatures calculated with both sets of mass and energy releases are compared. It is seen that those obtained with the RELAP5/MOD3 input are still significantly lower, indicating a level of conservatism in the FSAR mass and energy releases that is even above that explicitly listed and also incorporated into the RELAP5/MOD3 calculation. An important conclusion from this finding is that Environmental Qualification (EQ) issues requiring containment re-analyses are likely to be easily resolved if new mass and energy releases are calculated with state-of-the-art LOCA codes modeling the entire reactor coolant system, even when conservative assumptions are incorporated

Clinical benefits of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease are not related to urinary eicosanoid release and are accompanied with decreased urine creatinine.

Science.gov (United States)

Makowska, Joanna S; Olszewska-Ziąber, Agnieszka; Bieńkiewicz, Barbara; Lewandowska-Polak, Anna; Kurowski, Marcin; Woźniakowski, Bartłomiej; Rotkiewicz, Arkadiusz; Kowalski, Marek L

2016-05-01

Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

Captain Nemo/Lt-General Pitt Rivers and Cleopatra’s Needle — A Story of Flagships

Directory of Open Access Journals (Sweden)

Christopher Evans

2005-11-01

Full Text Available Recently re-reading Verne’s 20,000 Leagues Beneath the Sea for our children I was struck by the marked similarities between the novel’s elusive protagonist, Captain Nemo, and the renowned later 19th century British archaeologist, Lt.-General Pitt Rivers. Could they have been the same person? How could something so seemingly blatant have gone unnoticed? These questions are, of course, only raised in a spirit of academic tongue-in-check. Yet, in an ethos of ‘learning through amusement’ (itself directly relevant to the themes of this study, exploring the parallels between these two ‘heroic’ individuals provides insights into the nature of 19th century science, Victorian edification and disciplinary institutionalisation (e.g. Levine 1986. This eclectic contribution will, moreover, be introduced with the third component of its headline title – Cleopatra’s Needle – as this provides an appropriately quasinautical parable on the project of 19th century archaeology and the problem of ‘deep time’ (Murray 1993.

Experimental plans for LMFBR cavity liner sodium spill test LT-1

International Nuclear Information System (INIS)

Hilliard, R.K.; Newell, G.A.

1976-01-01

Reinforced concrete is an important material of construction in LMFBR cavities and cells. Steel liners are often installed on the concrete surfaces to provide a gastight seal for minimizing air inleakage to inerted cell atmospheres and to protect the concrete from direct contact with sodium in the event of a sodium spill. In making safety assessment analyses, it is of interest to determine the adequacy of the liners to maintain their leaktightness during postulated accidents involving large sodium spills. However, data for basing analytical assessments of cell liners are very meager and an experimental program is underway at HEDL to provide some of the needed information. The HEDL cell liner evaluation program consists of both bench-scale feature tests and large-scale sodium spill demonstration tests. The plans for the first large-scale sodium spill test (LT-1) are the subject of this paper

Çokkültürlülük Bağlamında Türkiye’de Çokkültürcü Medya ve TRT Kürdi / Özet: Çokkültürlülük kavramı uzun bir geçmişe sahip olsa da çokkültürcü anlayış ve politikalar anlamında modern sonrası zamana denk gelmektedir. Etnik azınlıklara ve yerlilere yönelik geçmiş politikaların artık etkisini yitirdiği bir dönemde ortaya çıkan çokkültürcülük yaklaşımı, günümüz açısından, alternatif yaklaşımlarla birlikte halen anılmakta ve uygulanmaktadır. Türkiye’de de, 1990’lı yıllarda çeşitli nedenlerle dile getirilen, ancak uygulama açısından 2000’li yıllarda örneklerini gördüğümüz çokkültürcü liberal politikalar, medyaya da yansımıştır. Bu nedenle çalışmada söz konusu çokkültürcü politikaların Türkiye özelinde, medya örneklerine, kamu hizmeti yayıncılık anlayışı çerçevesinde değinilecektir. Bu bağlamda Türkiye’deki ilk çokkültürlü kamu hizmeti yayıncılık örneği olan TRT KÜRDİ’nin açılmasıyla sonuçlanan sürece dikkat çekilecektir. Anahtar kelimeler: Çokkültürlülük, Çokkültürcülük, Türkiye, TRT, KÜRDİ. Multiculturalist Media and TRT Kurdi in Turkey in the Contex of Multiculturalism

Directory of Open Access Journals (Sweden)

Filiz AYDOĞAN BOSCHELE

2016-07-01

Full Text Available Çokkültürlülük kavramı uzun bir geçmişe sahip olsa da çokkültürcü anlayış ve politikalar anlamında modern sonrası zamana denk gelmektedir. Etnik azınlıklara ve yerlilere yönelik geçmiş politikaların artık etkisini yitirdiği bir dönemde ortaya çıkan çokkültürcülük yaklaşımı, günümüz açısından, alternatif yaklaşımlarla birlikte halen anılmakta ve uygulanmaktadır. Türkiye’de de, 1990’lı yıllarda çeşitli nedenlerle dile getirilen, ancak uygulama açısından 2000’li yıllarda örneklerini gördüğümüz çokkültürcü liberal politikalar, medyaya da yansımıştır. Bu nedenle çalışmada söz konusu çokkültürcü politikaların Türkiye özelinde, medya örneklerine, kamu hizmeti yayıncılık anlayışı çerçevesinde değinilecektir. Bu bağlamda Türkiye’deki ilk çokkültürlü kamu hizmeti yayıncılık örneği olan TRT KÜRDİ’nin açılmasıyla sonuçlanan sürece dikkat çekilecektir. / Multiculturalism notion has coincided with postmodern era with respect to multicultural sense and policies in the world, even though the notion itself has a long historical background. Emerged in an era where old policies toward ethnic minorities and natives have become obsolete, multicultural view is still recognized and applied hand in hand with alternative views. As a matter of debate in 1990s, while not put into practice until 2000s in Turkey, multicultural liberal policies have found themselves wide media coverage in recent years. Therefore this study aims to shed a light on the process of launching TRT KURDI as the first multiculturalist broadcasting example in Turkey through investigating media examples from Turkey within the public broadcasting frame.

The Antiaircraft Journal. Volume 97, Number 4, July-August 1954

Science.gov (United States)

1954-08-01

Col. Wood- row L. Nelson, Executive; Major Harry E. Bock, Jr., S2 and S3; Capt. Jesse N. Worsham, TI&E Officer; Lt. Bernard E. Reiter, Assistant S3; Lt...Major William J. Fling, S4, leaves for Hq. Fifth Army in July; Major Alfred H. Fierke, S2, for the 17th AAA Group; Major Bernard A. Gilman, for .USAR...USAFFE. {:onerly, U. E., to 758th FA Bn., Ft. Bragg. Cornwell , B. R., to AA&GM Qr., Ft. Bliss. Crews, D. J., to USAR Adv. Gp., Rock Islane, Illinois

Esnek ve Rijit Yol Üst Yapılarında Gürültü Seviyelerinin Eş Zamanlı Ölçümü ve Analizi

Directory of Open Access Journals (Sweden)

Hakan Yıldırım

2014-06-01

Full Text Available Beton yollar dünyada yaygın olarak kullanılmasına karşın ülkemizde gelişim gösterememiş, bu nedenle de genel olarak bitümlü sıcak karışım asfalt yollar tercih edilmiştir.Bu çalışmada, Türkiye'de yaygın olarak kullanılan bitümlü sıcak karışım asfalt yollar ve henüz yaygınlaşmamış olan beton yollar arasında gürültü seviyeleri yönünden bir karşılaştırma yapılmıştır. Bunun için Afyonkarahisar-Emirdağ arasında inşa edilmiş 2 km'lik beton yol ile bu yolun devamı olan bitümlü sıcak karışım asfalt yol arasındaki geçiş noktası çalışma koridoru olarak kullanılmıştır.Bu koridordaki beton yol ve bitümlü sıcak karışım asfalt yolun kenarlarına, ses girişimlerini en aza indirecek şekilde, ayrı ayrı gürültü ölçüm cihazı ve kamera düzenekleri yerleştirilmiş, yol yapım malzemesine bağlı olarak değişen gürültü seviyeleri eş zamanlı olarak kaydedilmiş, bulunan değerler analiz edilerek kaplama türleri ile gürültü seviyeleri arasındaki ilişki araştırılmıştır. Bu aşamada, kurulan düzenekler arasındaki mesafe trafik yoğunluğunun ve akış hızının değişimini engellemek için mümkün olduğunca kısa tutulmuştur.Yapılan ölçüm ve analizler sonunda beton yolların bitümlü sıcak karışım asfalt yollara göre ortalama gürültü seviyesinin aynı taşıt kompozisyonu ve trafik hacmi için yaklaşık 4 dB(A daha düşük olduğu ortaya konmuş ve ülkemizde de beton yolların gelişim göstermesi gerektiği vurgulanmıştır.

Çokkültürlü Eğitim ve Öğretim Yeterliğine İlişkin Teorik Bir Çözümleme

OpenAIRE

KILIÇOĞLU, Gökhan

2015-01-01

Yirminci yüzyılın yılların başlarından bu yana göç hareketleriyle etnik çeşitliliği artan dünya günümüzde küreselleşmekte ve birçok farklılığı içerisinde barındırır hale gelmektedir. Dolayısıyla küreselleşen dünya, öğretmenlerin farklı kültürel geçmişe sahip olan öğrencilerin geçmişlerini ve deneyimlerini göz önünde bulundurarak çokkültürlü ve evrensel bakış açısına sahip olmalarını gerektirmektedir. Özellikle farklı kültürleri içerisinde barındıran toplumlar, farklılıklara sahip öğrenciler a...

Diagnostic Usefulness of APRI and FIB-4 for the Prediction of Liver Fibrosis After Liver Transplantation in Patients Infected with Hepatitis C Virus.

Science.gov (United States)

Imai, H; Kamei, H; Onishi, Y; Ishizu, Y; Ishigami, M; Goto, H; Ogura, Y

2018-06-01

Aspartate transaminase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) are well known as representative indirect serum biomarkers related to liver fibrosis. The usefulness of these markers for the diagnosis of liver fibrosis after liver transplantation (LT) in hepatitis C virus (HCV)-infected patients and the influence of splenectomy were investigated. From June 2003 to May 2014, 31 HCV-infected patients who underwent LT and postoperative follow-up liver biopsies were included in this study. The association between liver fibrosis and serum biomarkers and the influence of splenectomy on APRI and FIB-4 were also investigated. A total of 195 biopsy specimens were collected, and liver fibrosis was identified as: F0, 59.7%; F1, 34.1%; and F2, 6.3%. Both APRI and FIB-4 were significantly higher in patients who showed F1 and F2 in liver biopsy specimen than F0 (P values, .009 and .022, respectively); sensitivity and specificity of APRI were, respectively, 63.4% and 66.7%, and those of FIB-4 were 57.7% and 69.6%. In 11 patients (35.5%) who underwent splenectomy at the time of LT, the cutoff values for APRI and FIB-4 were 0.61 and 1.41, which were significantly lower than the corresponding values (1.00 and 3.64) of patients without splenectomy. APRI and FIB-4 could effectively estimate liver fibrosis after LT for HCV-related liver disease. For LT patients with splenectomy, APRI and FIB-4 were also useful to estimate liver fibrosis, but the standard values should be adjusted lower than those for patients without splenectomy. Copyright © 2018 Elsevier Inc. All rights reserved.

Preliminary calculation with code CONTEMPT-LT for spray cooling tests with JAERI model containment vessel

International Nuclear Information System (INIS)

Tanaka, Mitsugu

1978-01-01

LWR plants have a containment spray system to reduce the escape of radioactive material to the environment in a loss-of-coolant accident (LOCA) by washing out fission products, especially radioiodine, and condensing the steam to lower the pressure. For carrying out the containment spray tests, pressure and temperature behaviour of the JAERI Model Containment Vessel in spray cooling has been calculated with computer program CONTEMPT-LT. The following could be studied quantitatively: (1) pressure and temperature raise rates for steam addition rate and (2) pressure fall rate for spray flow rate and spray heat transfer efficiency. (auth.)

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study.

Science.gov (United States)

Kaminski, Juliana; Miasaki, Fabíola Yukiko; Paz-Filho, Gilberto; Graf, Hans; Carvalho, Gisah Amaral de

2016-01-01

To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism. This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16. Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged. The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms.

Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

International Nuclear Information System (INIS)

Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

2010-01-01

Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT TM , a commercially available full-thickness human skin equivalent. CEES (100-1000 μM) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 μM), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE 2 synthases, leukotriene (LT) A 4 hydrolase and LTC 4 synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics.

Inhibition of histamine and eicosanoid release from dispersed human lung cells in vitro by quinotolast.

Science.gov (United States)

Okayama, Y; Hiroi, J; Lau, L C; Church, M K

1995-12-01

We have examined the effects of a new anti-allergic drug, quinotolast [sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido) yetrazolate monohydrate], in inhibiting the release of histamine and the generation of leukotriene (LT) C4 and prostaglandin (PG) D2 from dispersed human lung cells and compared this with those of its active metabolite in the rat, hydroxy quinotolast, and reference drugs, tranilast and sodium cromoglycate (SCG). Quinotolast in the concentration range of 1-100 micrograms/ml inhibited histamine and LTC4 release in a concentration-dependent manner. The inhibitory effect of quinotolast on histamine release from dispersed lung cells was largely independent of the preincubation period, no tachyphylaxis being observed. Hydroxy quinotolast and tranilast showed a weak inhibition of histamine release only when the drugs were added to the cells simultaneously with anti-IgE challenge. Quinotolast, 100 micrograms/ml, and SCG, 1 mM, significantly inhibited PGD2 and LTC4 release. Quinotolast inhibited PGD2 release by 100% and LTC4 release by 54%, whereas SCG inhibited PDG2 release by 33% and LTC4 release by 100%. No cross-tachyphylaxis between quinotolast and SCG was observed. The results demonstrated that quinotolast showed a significant inhibition of inflammatory mediators from human dispersed lung cells, suggesting that quinotolast is a good candidate for a clinical anti-allergic drug.

4. FIELU REGI~E~T

African Journals Online (AJOL)

and were absorbed as one complete battery into I Field Brigade under Capt J. L. Gordon-. Gray. After a course at the Military College Maj. Mackenzie was promoted to Lt Col from 1. Feb 1940. Owing to disagreement about se- niorities 1 Field Brigade became 4 Field Bri- gade, comprising: 10 Field Battery, late 1 Field Battery.

LT-CFB. Applications and follow-up. CP Kelco. Appendix 1. [Low Temperature Circulating Fluid Bed gasifier]; LT-CFB. Anvendelsesmuligheder og opfoelgning. CP Kelco. Bilag 1

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-04-15

This appendix describes how LT-CFB advantageously can gasify residual products at the company CP Kelco's factory. CP Kelco produces the gelation, thickeners and stabilizers carrageenan and pectin from seaweed and citrus peel. Residues from the production consist of a fiber-containing biological material, which has a calorific value of dry matter about 15 to 20 MJ / kg. In addition, there are waste products from the wastewater treatment plant, which are also proposed re-used in the project. The report describes the economic analyses, the overall data and system design for two scenarios, whereas the description of the plant capacities, sizes and detailed data etc. are described only for one scenario. In addition to savings in the purchase of natural gas the gas production also results in a significant reduction in CO{sub 2} emissions, the product gas being characterized as CO{sub 2} neutral. Since CP Kelco is subject to the CO{sub 2} quota system the saved amount of CO{sub 2} emissions represents a significant value. In the economic analyses, the value of 1 ton of CO{sub 2} is set at DKK 100. (LN)

The Collaborative Lithium Trials (CoLT: specific aims, methods, and implementation

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Hooper Stephen R

2008-08-01

Full Text Available Abstract Background Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity. Methods Under the auspices of the Best Pharmaceuticals for Children Act (BPCA, a Written Request (WR pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA to the National Institute of Child Health and Human Development (NICHD in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies. Results The Collaborative Lithium Trials (CoLT investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1 establish evidence-based dosing strategies for lithium; (2 characterize the pharmacokinetics and biodisposition of lithium; (3 examine the acute efficacy of lithium in pediatric bipolarity; (4 investigate the long-term effectiveness of lithium treatment; and (5 characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR, the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1 an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2 a 16-week Long-Term Effectiveness Phase; (3 a 28-week double-blind Discontinuation Phase; and (4 an 8-week open-label Restabilization Phase. The second study consists of: (1 an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2 an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase; (3 a 28-week double

Mardin Süryanilerinde Belleğin Teolojik-Kültürel Çerçevesi / Theological - Cultural Framework of Memory in Mardin Syriacs

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Tahir Pekasil

2016-05-01

Full Text Available Theological - Cultural Framework of Memory in Mardin Syriacs Abstract In this article, “theological/ritual-cultural framework of memory”, "memory participation tools" "recall figures" will be examined in the case of Mardin Syriac Orthodox Church. "Ritual participation" and "rhythmic repetition" which enables "theological-social inclusion" and "integration", also mobilizes remembering instruments and guarantees protection, revival and transfer of cultural memory. This also ensures continuation of sense of belonging. Priests who are accepted as "vicarious memory" enable participation to memory in church which is a "memory space" mediating to the "transmission of blessing and grace by ritual representation". Priests also by institutionalizing ceremonies and rituals which integrated with music, makes cultural meanings functional. The theme is discussed from the perspective of cultural memory and supported by face to face interviews. Mardin Süryanilerinde Belleğin Teolojik-Kültürel Çerçevesi Öz Bu yazıda, Mardin Süryani Ortodoks Kilisesi örneğinden hareketle “belleğin teolojik/ritüel- kültürel çerçevesi”, “belleğe katılım araçları”, “hatırlama figürleri” ele alınacaktır. “Teolojik ve toplumsal katılımı”, “bütünleşmeyi” sağlayan “ritüel katılım” ve “ritmik tekrar”, hatırlama araçlarını harekete geçirerek kültürel belleğin korunmasını, canlandırılmasını ve aktarılmasını garanti etmekte, aidiyetin devamını sağlamaktadır. Belleğe katılımı sağlayan “vekil hafıza” olarak kabul edilen papazlar, bir “hafıza mekânı” olan kilisede, “inayetin ritüel temsille aktarımına” aracılık yapmakta; “ritüel tasarım” yoluyla müzikle bütünleştirdikleri ayin ve ritüelleri kurumsallaştırarak kültürel anlamlara işlerlik kazandırmaktadırlar. Çalışma konusu, kültürel bellek perspektifinden ele alınmış ve mülakat örnekleri ile desteklenmiştir.

Enterotoxigenic Escherichia coli Adhesin-Toxoid Multiepitope Fusion Antigen CFA/I/II/IV-3xSTaN12S-mnLTG192G/L211A-Derived Antibodies Inhibit Adherence of Seven Adhesins, Neutralize Enterotoxicity of LT and STa Toxins, and Protect Piglets against Diarrhea.

Science.gov (United States)

Nandre, Rahul; Ruan, Xiaosai; Lu, Ti; Duan, Qiangde; Sack, David; Zhang, Weiping

2018-03-01

Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of children's diarrhea and travelers' diarrhea. Vaccines inducing antibodies to broadly inhibit bacterial adherence and to neutralize toxin enterotoxicity are expected to be effective against ETEC-associated diarrhea. 6×His-tagged adhesin-toxoid fusion proteins were shown to induce neutralizing antibodies to several adhesins and LT and STa toxins (X. Ruan, D. A. Sack, W. Zhang, PLoS One 10:e0121623, 2015, https://doi.org/10.1371/journal.pone.0121623). However, antibodies derived from His-tagged CFA/I/II/IV-2xSTa A14Q -dmLT or CFA/I/II/IV-2xSTa N12S -dmLT protein were less effective in neutralizing STa enterotoxicity and were not evaluated in vivo for efficacy against ETEC diarrhea. Additionally, His-tagged proteins are considered less desirable for human vaccines. In this study, we produced a tagless adhesin-toxoid MEFA (multiepitope fusion antigen) protein, enhanced anti-STa immunogenicity by including a third copy of STa toxoid STa N12S , and examined antigen immunogenicity in a murine model. Moreover, we immunized pregnant pigs with the tagless adhesin-toxoid MEFA protein and evaluated passive antibody protection against STa + or LT + ETEC infection in a pig challenge model. Results showed that tagless adhesin-toxoid MEFA CFA/I/II/IV-3xSTa N12S -mnLT R192G/L211A induced broad antiadhesin and antitoxin antibody responses in the intraperitoneally immunized mice and the intramuscularly immunized pigs. Mouse and pig serum antibodies significantly inhibited adherence of seven colonization factor antigen (CFA) adhesins (CFA/I and CS1 to CS6) and effectively neutralized both toxins. More importantly, suckling piglets born to the immunized mothers acquired antibodies and were protected against STa + ETEC and LT + ETEC diarrhea. These results indicated that tagless CFA/I/II/IV-3xSTa N12S -mnLT R192G/L211A induced broadly protective antiadhesin and antitoxin antibodies and demonstrate that this adhesin

Tüketim, Tüketim Toplumu ve Tüketim Kültürü: Karşılaştırmalı Bir Analiz / Consumption, Consumption Society and Consumption Culture: A Comparative Analysis

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Olkan SENEMOĞLU

2017-05-01

Full Text Available Bu makale, tüketim, tüketim toplumu ve tüketim kültürü kavramlarına odaklanmak¬tadır. Bu kavramların literatürde nasıl tanımlandığına değinerek, karşılaştırmalı bir analizi¬ni sunmayı amaçlamaktadır. Ayrıca bu makalede tüketim olgusu başta olmak üzere, tüketim toplumu ve tüketim kültürünün günümüzde ne ifade ettiğine odaklanılmaktadır. Bu bağlamda ihtiyaçların manipülasyonu tezi, gösteri toplumu kuramı, reklamın bir tüketim propagandası olduğu yönündeki iddia ve tüketimin fazla ürüne sahip olmayla herhangi bir bağlantısının olmadığını ileri süren düşünce ele alınmaktadır. Tüketim olgusunun iktisadi, sosyal ve kültürel olmak üzere çeşitli boyutlarını ele alan literatürün karşılaştırmalı bir analizi üzerine kurulan bu çalışmada, sadece bir şeyler satın almanın insanları tüketici yapmadığına, insanın ihti¬yacına tekabül eden nesneleri tüketmesinin onu tüketiciye dönüştürmediğine değinilmektedir. Tüketim toplumunda, tüketimin artık ihtiyaçtan dolayı gerçekleşmediğine aksine bizzat tüketi¬min kendisinin bir ihtiyaç haline geldiğine odaklanılmaktadır. Böyle olduğu için de insanların artık kültür yaratmadıklarına “tüketim kültürü”nün nesnelerine eklemlenerek kendilerini var ettiklerine dikkat çekilmektedir. Bu doğrultuda genel olarak çağımızın artık tüketim kültürü¬nün hüküm sürdüğü bir çağ olduğu iddia edilmektedir. Bireyin artık tüketimle, kültürüne dair bir ifade biçimi ortaya koymadığı tam tersine artık tüketim nesnesinin kendisinin birey için bir imaj ve mesaj iletimi halini almış olduğu tartışılmaktadır. Bu anlamda tüketim kültürünün, kendi kültürünü her yere sirayet ettirmiş olduğu gösterilmektedir. / This paper centres on the notions of consumption, consumption society and consumption culture. It seeks to present a comparative analysis by addressing

Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.

Science.gov (United States)

Byrd, Wyatt; Boedeker, Edgar C

2013-03-15

Although enterotoxigenic Escherichia coli (ETEC) infections are important causes of infantile and traveler's diarrhea there is no licensed vaccine available for those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We used an attenuated E. coli strain (O157:H7, Δ-intimin, Stx1-neg, Stx2-neg) as a vector (ZCR533) to prepare two vaccine strains, one strain expressing colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric immunization with the vaccine strains, serum IgG and IgA antibodies were measured to the CFA/I antigen, however, only serum IgG antibodies were detected to the heat-labile enterotoxin. Intranasal administration of the vaccine strains induced respiratory and intestinal antibody responses to the CFA/I and LT antigens, while intragastric administration induced only intestinal antibody responses with no respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized intranasally with the vaccine strains showed enhanced clearance of wild-type (wt) ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically with the vaccine strains were protected from intestinal colonization following oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine following challenge with ETEC wt bacteria or with purified LT as compared to the sham mice indicating that the immunized mice were protected from LT-induced intestinal fluid accumulation. Thus, mice intragastrically immunized with the ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the activity of the LT enterotoxin. However, no difference in intestinal fluid accumulation was detected in the mice immunized intranasally with the vaccine strain as compared to the sham

Recommendations for treatment of hypothyroidism with levothyroxine and levotriiodothyronine: a 2016 position statement of the Italian Society of Endocrinology and the Italian Thyroid Association.

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Biondi, B; Bartalena, L; Chiovato, L; Lenzi, A; Mariotti, S; Pacini, F; Pontecorvi, A; Vitti, P; Trimarchi, F

2016-12-01

Levothyroxine (L-T4) is recommended as lifelong replacement therapy for hypothyroidism. Recent clinical and experimental data support the addition of levotriiodothyronine (L-T3) treatment in some selected hypothyroid patients when their symptoms persist and their quality of life remains impaired despite adequate L-T4 monotherapy. An increase in L-T3 prescriptions has been recently observed in Italy due to availability of different L-T3 formulations, making it possible to clinicians to prescribe L-T3 alone or in combination with L-T4. The aim of the present position statement was to define the correct clinical indications, schedule, duration of treatment and contraindications of combined treatment with L-T4 and L-T3 in hypothyroid patients in an attempt to guide clinicians and to avoid potential adverse effects of overtreatment.

Effects of thyroid hormone analogue and a leukotrienes pathway-blocker on renal ischemia/reperfusion injury in mice

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Hadi Najah R

2011-12-01

Full Text Available Abstract Background Acute renal failure (ARF is an important clinical problem with a high mortality and morbidity. One of the primary causes of ARF is ischemia/reperfusion (I/R. Inflammatory process and oxidative stress are thought to be the major mechanisms causing I/R. MK-886 is a potent inhibitor of leukotrienes biosynthesis which may have anti-inflammatory and antioxidant effects through inhibition of polymorphonuclear leukocytes (PMNs infiltration into renal tissues. 3, 5-diiodothyropropionic acid (DITPA have evidences of improving effects on I/R in heart through modulation of cellular signaling in response to ischemic stress. The objective of present study was to assess the effects of MK-886 and DITPA on renal I/R injury. Methods A total of 24 Adult males of Swiss albino mice were randomized to four groups: I/R group (n = 6, mice underwent 30 minute bilateral renal ischemia and 48 hr reperfusion. Sham group (n = 6, mice underwent same anesthetic and surgical procedures except for ischemia induction. MK-886-treated group: (n = 6, I/R + MK-886 (6 mg/kg by intraperitoneal injection. DITPA-treated group: (n = 6, I/R + DITPA (3.75 mg/kg by intraperitoneal injection. After the end of reperfusion phase mice were sacrificed, blood samples were collected directly from the heart for determination of serum TNF-a, IL-6, urea and Creatinine. Both kidney were excised, the right one homogenized for oxidative stress parameters (MDA and GSH measurements and the left kidney fixed in formalin for histological examination. Results Serum TNF-α, IL-6, urea and Creatinine, kidney MDA levels and scores of histopathological changes were significantly (P 0.05 changes in levels of all study parameters as compared with that of I/R group. Conclusion The results of the present study show that MK-886 significantly ameliorated kidney damage that resulted from I/R. For DITPA, as its administration might not be successful, administration using a different protocol may

Timing and processes for exhumation of HP/LT rocks of the southern Brooks Range (AK): Insight from combined geochemistry and 40Ar/39Ar thermochronology of white mica

Science.gov (United States)

O'Brien, T.; Miller, E. L.; Grove, M. J.; Hayden, L. A.

2015-12-01

The obduction of an island arc onto the Arctic Alaska continental margin in the Jura-Cretaceous led to southward subduction of continental crust and high-pressure/low-temperature (HP/LT) epidote-blueschist facies metamorphism in the southern Brooks Range (BR). A regionally developed greenschist facies normal-sense shear zone system along the southern margin of the BR suggests that extensional faulting had an influential role in the exhumation of the metamorphic core. To better constrain the exhumation history of the metamorphic core of the BR, samples were collected from a N-S transect through the metamorphic core of the orogen. Electron microprobe (EMP) analyses of white micas reveal that they are composed of phengite (Si > 3.0 pfu) or a combination of phengite + paragonite. Si-content of phengites reveal a southward increase in Si from 3.1 to 3.4 pfu (corresponding to an increase in pressure). Si-contents in higher-P phengites are scattered, reflecting subsequent muscovite growth. The Si trend is matched by a southward increase in the 40Ar/39Ar total gas ages of white micas. Phengite from the north are characterized by younger ages (~115 Ma) and flatter 40Ar/39Ar spectra. Farther south, phengites and paragonites yield older 40Ar/39Ar ages. These samples yield convex, staircase 40Ar/39Ar spectra that initiate ~115-120 Ma and flatten-out ~130-138 Ma. Modeling using MacArgon proposes that an initial cooling of HP/LT metamorphism occurred ~130-138 Ma, recorded in the high-Si phengites and paragonites. Following initial cooling, modeling suggests HP/LT rocks stalled in the greenschist facies field before subsequent exhumation, resulting in the staircase 40Ar/39Ar spectra. Flatter 40Ar/39Ar spectra recorded by the northern samples and modeling of 40Ar/39Ar results from the southern samples suggest that these rocks from metamorphic core of the BR were exhumed to temperatures < 300°C by ~115 Ma.

Saiboku-to, a Kampo herbal medicine, inhibits LTC4 release from eosinophils

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Koichi Hirai

1998-01-01

Full Text Available Saiboku-to (TJ-96, a traditional Kampo herbal formation, has been used in the treatment of bronchial asthma in Japan as an anti-allergy herbal medicine. We investigated the effect of TJ-96 on leukotriene (LTC4 release from eosinophils and basophils isolated from healthy volunteers. Pre-incubation of eosinophils with TJ-96 inhibited ionophore- or formyl-methionyl-leucyl-phenylalanine (FMLP-induced LTC4 generation by eosinophils in a dose-dependent fashion. The TJ-96 was more potent in the release by ionophore (IC50 = 60 mg/mL than the release induced by FMLP (IC50 = 300 mg/mL. Maximal inhibition was observed when eosinophils were pretreated with TJ-96 for 5 min. Although TJ-96 at high concentrations inhibited IgE-mediated histamine release from human basophils, inhibition of IgE-mediated LTC4 release was not statistically significant. The potent inhibitory activity was found in the extract of Glycyrrhiza root, one of the herbal components of TJ-96, but the inhibitory effects were not due to either glycyrrhizin or liquiritin, the main elements of the Glycyrrhiza root. These results raise the possibility that the clinical efficacy of TJ-96 is derived, at least in part, from its potent inhibitory effect on LTC4 release from eosinophils.

Sigma Theta Tau, DAaL/Texas Nurse Association, 2017 South Texas Nurse Imagemaker, Lt Col Jacqueline Killian

Science.gov (United States)

2018-04-28

ENDORSEMENT (59 MDW/SGVU Use Only) 43. REVIEWER SIGNATURE 32. DATE 38. DATE 44. DATE April 11 , 20 17 45. DATE RECEIVED 1 46. SENIOR AUTHOR NOTIFIED BY...EBP mentors to facilitate the growing number of EBP projects underway in our organization. 1 Lt Col Killian serves as research consultant to chief...for helping others. The first project is focused on enhancing resil ience in our military families--the " Mentors Offering Maternal Support (M-0-M

The Antiaircraft Journal. Volume 94, Number 4, July-August 1953

Science.gov (United States)

1953-08-01

JOHN A. 1\\lATTAS TIle writer of the following received _his commissioll from Virgillia Polytech- nic Institllte in 1939. Dllrillg "Varld \\Var II he...officer of Leaders Course. Other members of the staff include Lt. Robert G. Mangum, S3 officer, and Lt. Sam H. Biddle , Ad- jutant. Lt. Mangum has the

An estimation of uncertainties in containment P/T analysis using CONTEMPT/LT code

International Nuclear Information System (INIS)

Kang, Y.M.; Park, G.C.; Lee, U.C.; Kang, C.S.

1991-01-01

In a nuclear power plant, the containment design pressure and temperature (P/T) have been established based on the unrealistic conservatism with suffering from a drawback in the economics. Thus, it is necessary that the uncertainties of design P/T values have to be well defined through an extensive uncertainty analysis with plant-specific input data and or models used in the computer code. This study is to estimate plant-specific uncertainties of containment design P/T using the Monte Carlo method in Kori-3 reactor. Kori-3 plant parameters and Uchida heat transfer coefficient are selected to be treated statistically after the sensitivity study. The Monte Carlo analysis has performed based on the response surface method with the CONTEMPT/LT code and Latin Hypercube sampling technique. Finally, the design values based on 95 %/95 % probability are compared with worst estimated values to assess the design margin. (author)

Bacillus sp. LT3 improves the survival of gnotobiotic brine shrimp (Artemia franciscana) larvae challenged with Vibrio campbellii by enhancing the innate immune response and by decreasing the activity of shrimp-associated vibrios.

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Niu, Yufeng; Defoirdt, Tom; Baruah, Kartik; Van de Wiele, Tom; Dong, Shuanglin; Bossier, Peter

2014-10-10

Bacteria belonging to the genus Bacillus are amongst the most intensively studied group of bacteria for use as probiotics in aquaculture. However, the exact mechanism of action of these bacteria is often not well described, and the microbiota that are naturally present in cultures of test organisms often compromise the interpretation of the results. The present study aimed to evaluate the putative probiotic effect of Bacillus sp. LT3 in a model system with gnotobiotic brine shrimp Artemia franciscana larvae. The strain significantly increased the survival of brine shrimp larvae challenged with Vibrio campbellii when administered 6h before the challenge. Under these conditions, LT3 was able to colonize the brine shrimp gastrointestinal tract and to decrease the in vivo pathogen activity as indicated by the bioluminescence of the V. campbellii associated with brine shrimp larvae. In order to investigate the effect of the Bacillus strain on the innate immune system of the brine shrimp larvae, prophenoloxidase and transglutaminase mRNA levels were monitored, while heat shock protein 70 mRNA levels were measured as an indicator of physiological stress. Interestingly, 12h after challenge, the prophenoloxidase mRNA level in the larvae pre-treated with LT3 and challenged with V. campbellii was approximately 8-fold higher than in the other treatments. Further, a decreased mRNA level of transglutaminase gene and heat shock protein 70 gene suggested that pretreatment with LT3 results in less stress and tissue damage in the brine shrimp larvae upon V. campbellii challenge. These results indicated that Bacillus sp. LT3 could improve the survival of brine shrimp larvae when challenged with pathogenic V. campbellii, both by decreasing the in vivo activity of the pathogen and by priming the innate immune response through activating the prophenoloxidase system. Copyright © 2014 Elsevier B.V. All rights reserved.

Kültürel Farkındalık Yaratma Açısından Sanat Eleştirisi Öğretimi

OpenAIRE

Tuna, Serdar

2011-01-01

Bu çalışmanın amacı, özellikle ilk ve ortaöğretim görsel sanatlar dersi içerisinde sanat eleştirisi öğretiminin öğrencilere görsel algı geliştirme, tasarım ilke ve elemanlarını öğrenme ve saptama, sözel ve yazınsal ifadeyi geliştirme gibi yararlarının yanı sıra, sanat yapıtlarında kullanılan imgeler ve simgelerden yararlanarak kendi kültürünün farkına varma ve farklı kültürlerin yaşam tarzlarını öğrenme konusunda da son derece faydalı olacağını ortaya koymaktır. İletişim araçlarının gelişmesi...

Exhaled breath condensate pH and cysteinyl leukotriens in patients with chronic cough secondary to acid gastroesophageal reflux.

Science.gov (United States)

Heffler, Enrico; Crimi, Claudia; Brussino, Luisa; Nicola, Stefania; Sichili, Stefania; Dughera, Luca; Rolla, Giovanni; Crimi, Nunzio

2016-12-22

Chronic cough is one of the most common clinical problems and it may be secondary to different stimuli and diseases, including low-level physical and chemical stimulation of the esophageal-bronchial reflex, suggestive of cough-reflex hyperresponsiveness, in patients with gastroesophageal reflux; however, it is still debated whether gastroesophageal reflux could induce airway inflammation and acidification. The aim of this study was to investigate airway pH and cysteynil-leukotrienes (Cys-LTs) concentration (a marker of airway inflammation) in exhaled breath condensate (EBC). Patients with chronic cough and for which all known causes, excluding gastroesophageal reflux, had been investigated and ruled out, were enrolled in the study. All patients underwent 24 h pH monitoring, and EBC was collected to assess pH and Cys-LTs concentration. Forty-five patients were included in the study and those with gastroesophageal reflux had significantly lower EBC-pH and higher concentration of EBC-Cys-LTs. There was a linear inverse correlation between EBC-pH values and EBC-Cys-LTs logarithmically transformed, and a multivariate analysis confirmed that the only significant determinat variable of EBC-Cys-LTs was the presence of gastroesophageal reflux. This study adds knowledge on possible mechanisms related to chronic cough associated with gastroesophageal reflux, which seems to be strictly dependent on airway acidification and the production of Cys-LTs, therefore suggesting an underlying neurogenic inflammation with tachykinins involvement.

Role of LTB4 in the pathogenesis of elastase-induced murine pulmonary emphysema

Science.gov (United States)

Paige, Mikell; Hanna, Halim; Kim, Su H.; Burdick, Marie D.; Strieter, Robert M.

2010-01-01

Exaggerated levels of the leukotriene B4 (LTB4) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB4 pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB4 were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB4 in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA4 hydrolase−/− mice (LTB4 deficient, LTA4H−/−) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB4 in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA4H−/− mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH2O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA4H−/− mice were found to have significantly delayed influx of the CD45highCD11bhighLy6Ghigh leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA4H−/− mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB4 played an important role in

Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis

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Laura R. R. Ribeiro

2015-01-01

Full Text Available Cysteinyl leukotrienes (CysLTs and lipoxins (LXs are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J and susceptible (B10.A mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages.

An aspirin-triggered lipoxin A4 stable analog displays a unique topical anti-inflammatory profile.

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Schottelius, Arndt J; Giesen, Claudia; Asadullah, Khusru; Fierro, Iolanda M; Colgan, Sean P; Bauman, John; Guilford, William; Perez, Hector D; Parkinson, John F

2002-12-15

Lipoxins and 15-epi-lipoxins are counter-regulatory lipid mediators that modulate leukocyte trafficking and promote the resolution of inflammation. To assess the potential of lipoxins as novel anti-inflammatory agents, a stable 15-epi-lipoxin A(4) analog, 15-epi-16-p-fluorophenoxy-lipoxin A(4) methyl ester (ATLa), was synthesized by total organic synthesis and examined for efficacy relative to a potent leukotriene B(4) (LTB(4)) receptor antagonist (LTB(4)R-Ant) and the clinically used topical glucocorticoid methylprednisolone aceponate. In vitro, ATLa was 100-fold more potent than LTB(4)R-Ant for inhibiting neutrophil chemotaxis and trans-epithelial cell migration induced by fMLP, but was approximately 10-fold less potent than the LTB(4)R-Ant in blocking responses to LTB(4). A broad panel of cutaneous inflammation models that display pathological aspects of psoriasis, atopic dermatitis, and allergic contact dermatitis was used to directly compare the topical efficacy of ATLa with that of LTB(4)R-Ant and methylprednisolone aceponate. ATLa was efficacious in all models tested: LTB(4)/Iloprost-, calcium ionophore-, croton oil-, and mezerein-induced inflammation and trimellitic anhydride-induced allergic delayed-type hypersensitivity. ATLa was efficacious in mouse and guinea pig skin inflammation models, exhibiting dose-dependent effects on edema, neutrophil or eosinophil infiltration, and epidermal hyperproliferation. We conclude that the LXA(4) and aspirin-triggered LXA(4) pathways play key anti-inflammatory roles in vivo. Moreover, these results suggest that ATLa and related LXA(4) analogs may have broad therapeutic potential in inflammatory disorders and could provide an alternative to corticosteroids in certain clinical settings.

Case report: When measured free T4 and free T3 may be misleading. Interference with free thyroid hormones measurements on Roche® and Siemens® platforms

Directory of Open Access Journals (Sweden)

Lewandowski Krzysztof C

2012-10-01

Full Text Available Abstract A 59-year old female patient presented with apathy and 6 kg weight gain. Investigations revealed severe primary hypothyroidism (TSH>100 μIU/ml. L-thyroxine (L-T4 was started and titrated up to 75 μg, once daily, with clinical improvement. Other investigations revealed very high titres of anti-thyroid peroxidase (anti-TPO and anti-thyroglobulin (anti-Tg antibodies. After three months, there was a fall in TSH to 12.74 μIU/ml, however, with unexpectedly high free T4 (FT4 - 6.8 ng/ml and free T3 (FT3 - 6.7 pg/ml concentrations [reference range (rr: 0.8-1.9 ng/ml and 1.5-4.1 pg/ml (Siemens®, respectively]. At this stage L-T4 was stopped, and this was followed by a rapid increase in TSH (to 77.76 μIU/ml and some decrease in FT4 and FT3, however FT4 concentration remained elevated (2.1 ng/ml. Following this, L-T4 was restarted. On admission to our Department, she was clinically euthyroid on L-T4, 88 μg, once daily. Investigations on Roche® platform confirmed mildly elevated TSH - 5.14 (rr: 0.27-4.2 μIU/ml with high FT4 [4.59 (rr: 0.93-1.7 ng/ml] and FT3 [4.98 (rr: 2.6-4.4 pg/ml] concentrations. Other tests revealed hypoechogenic ultrasound pattern typical for Hashimoto thyroiditis. There was no discrepancy in calculated TSH value following TSH dilution (101% recovery. Concentrations of FT4 and FT3 were assessed on the day of discontinuation of L-T4 and after four days by the means of Abbott® Architect I 1000SR platform. These revealed FT4 and FT3 concentrations within the reference range [e.g., FT4 - 1.08 ng/ml (rr: 0.7-1.48] vs 4.59 ng/ml (rr: 0.93-1.7, Roche®, FT3 - 3.70 pg/ml (rr: 1.71-3.71 vs 4.98 (rr: 2.6-4.4, Roche®], confirming assay interference. Concentrations of ferritin and SHBG were normal. Conclusions Clinicians must be aware of possible assay interference, including the measurements of FT4 and FT3 in the differential diagnosis of abnormal results of thyroid function tests that do not fit the patient clinical

High Frontier, The Journal for Space & Missile Professionals. Volume 4, Number 4

Science.gov (United States)

2008-08-01

the Hidden Story of America’s Space Espionage (New York, NY: Simon & Schuster, 2003), 364. 2 Dwayne A. Day, John M. Logsdon, and Brian Latell, Eye...is lengthy but includes folks like Lt Gen Mike Hamel, Lt Gen Tom Sheridan, Maj Gen Jimmy Morrell, Maj Gen Jim Armour , Maj Gen Mitch Mitchell, Brig...Security: Security was very tight. For example, shortly af- ter I was appointed DDNRO I was visited by Clarence “Kel- ly” Johnson , with whom I had worked

CYP4F18-Deficient Neutrophils Exhibit Increased Chemotaxis to Complement Component C5a

Directory of Open Access Journals (Sweden)

Rachel Vaivoda

2015-01-01

Full Text Available CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4. CYP4F18 has an unusual expression in neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild-type and Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response to LTB4, but the response to complement component C5a increased 1.9–2.25-fold in knockout cells compared to wild-type (P < 0.01. This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes in expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences in activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent chemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue myeloperoxidase between wild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to use LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges of CYP knockout studies.

Numerical modelling of the processes in the WWER-1000 containment building during cold leg LOCA using the CONTEMPT-LT/026 code

International Nuclear Information System (INIS)

Kolev, N.I.; Sybotinov, L.S.

1984-01-01

The CONTEMPT-LT/026 code has been used to produce numerical results for the processes in a WWER-1000 containment building during cold leg LOCA with break at the reactor vessel. The objective of the analysis is to estimate the maximal loads on the containment in case of LOCA. Available design data for the geometry and for the operational characteristics of the low-pressure ECC system and the sprinkler system have been used. Boundary conditions such as mass flow and enthalpies at the breach are given by a RELAP4/MOD6 computation. Hydrogen explosions in the containment are not considered. It is found that in case of normal functioning of the low-pressure ECC system the maximal pressure is 3,26±0,44 bar. In the case of malfunctioning of the low-pressure ECC system, the predicted maximal pressure is 4±0,44 bar, when: a) only 50% of the heat transfer surface of the heat exchanger is effectively used due to pollution; b) the main pipeline of the sprinkler is broken; c) the pipeline to the heat exchanger is partially broken so that the mass flow through the exchanger is only 50% of the nominal; and d) ECC low-pressure ECC system attains its maximal efficiency within 3 min, the predicted maximal pressure is 4±0,44 bar

Structure, chain conformation and antitumor activity of a novel polysaccharide from Lentinus edodes.

Science.gov (United States)

Yu, Zhang; Ming, Gu; Kaiping, Wang; Zhixiang, Chen; Liquan, Dai; Jingyu, Liu; Fang, Zeng

2010-12-01

A water-soluble polysaccharide LT1 was isolated from the basidiocarps of Lentinus edodes by hot water extraction and ethanol precipitations, further purified by gel chromatography. The Mw of LT1 was estimated to be 642 kDa by using HPGPC. Chemical and spectroscopic studies illustrated that LT1 has a backbone chain composed of 1 → 4-linked and 1 → 3-linked glucopyranosyl residues and has branches of single glucosyl stubs at C-6 of β-(1 → 4)-linked glucopyranosyl. AFM and Congo-red test revealed that LT1 existed as triple helix chain in 0.10 M NaOH solution or distilled water. Our studies showed that LT1 presented significant antitumor bioactivities on Sarcoma180 solid tumor cell implanted in BALB/c mice, which implies that LT1 could be potentially applied as a natural antitumor drug. Copyright © 2010 Elsevier B.V. All rights reserved.

Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms

DEFF Research Database (Denmark)

Medici, Bjarke Borregaard; la Cour, Jeppe Lerche; Michaelsson, Luba Freja

2017-01-01

BACKGROUND: Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). Combination therapy and the appropriate choice of blood tests to m...

An atlas of L-T transition brown dwarfs with VLT/XShooter

Science.gov (United States)

Marocco, F.; Day-Jones, A. C.; Jones, H. R. A.; Pinfield, D. J.

In this contribution we present the first results from a large observing campaign we are carrying out using VLT/Xshooter to obtain spectra of a large sample (˜250 objects) of L-T transition brown dwarfs. Here we report the results based on the first ˜120 spectra already obtained. The large sample, and the wide spectral coverage (300-2480 nm) given by Xshooter, will allow us to do a new powerful analysis, at an unprecedent level. By fitting the absorption lines of a given element (e.g. Na) at different wavelengths we can test ultracool atmospheric models and draw for the first time a 3D picture of stellar atmospheres at temperatures down to 1000K. Determining the atmospheric parameters (e.g. temperature, surface gravity and metallicity) of a big sample of brown dwarfs, will allow us to understand the role of these parameters on the formation of their spectra. The large number of objects in our sample also will allow us to do a statistical significant test of the birth rate and initial mass function predictions for brown dwarfs. Determining the shape of the initial mass function for very low mass objects is a fundamental task to improve galaxy models, as recent studies tep{2010Natur.468..940V} have shown that low-mass objects dominate in massive elliptical galaxies.

Double symmetry breaking in TmFe{sub 4}Ge{sub 2} compared to RFe{sub 4}Ge{sub 2} (R=Y, Lu, Er, Ho, Dy) magnetic behaviour

Energy Technology Data Exchange (ETDEWEB)

Schobinger-Papamantellos, P., E-mail: Schobinger@mat.ethz.ch [Laboratory of Crystallography, ETH-Zürich, 8093 Zürich (Switzerland); Buschow, K.H.J. [Van der Waals-Zeeman Institute, University of Amsterdam, NL-1018 XE (Netherlands); Rodríguez-Carvajal, J. [Institut Laue-Langevin, 156X, 38042 Grenoble Cédex (France)

2014-04-15

TmFe4Ge{sub 2} undergoes a double magneto-elastic first order transition at T{sub N},T{sub c} where the high temperature (HT) tetragonal phase disproportionate into two distinct orthorhombic low temperature (LT) phases with commensurate and incommensurate magnetic wave vectors respectively: P4{sub 2}/mnm(HT)T{sub N},T{sub c}→Cmmmq{sub 1}=(0,1/2 ,0)+Pnnm(q{sub 2}=(0,q{sub y},0),q{sub y}≈2/11(LT) Neutron diffraction shows the relative portions of the LT Cmmm and Pnnm competing phases change linearly with T. The amount of the majority HT phase Pnnm (54% at 30 K) decreases linearly to 30% down to 10 K in favour of the Cmmm phase that dominates the range 26–1.5 K. The Tm moments point along the c-axis in both phases while the Fe moments have canted arrangements. The μ{sub Tm}=3.54(3) μ{sub B}/atom at 1.5 K is strongly reduced below the Tm{sup 3+} free ion value g{sub J}J=7 μ{sub B} for the q{sub 1} phase. The q{sub 2} phase corresponds to a 3D canted sinusoidal arrangement. The results are summarised on a phase diagram and compared to the findings in RFe{sub 4}Ge{sub 2} (R=Y, Lu, Er, Ho, Dy) that are reviewed. The multitude of transition paths occurring in those systems arise from the competing magnetoelastic mechanisms involving the R-crystal field anisotropy, the exchange interactions R–R, R–Fe, Fe–Fe of the two sublattices and their coupling to the lattice strain. The geometrical frustration emerging from the compact tetrahedral Fe arrangement with antiferromagnetic interactions leads to 2D and 3D canted, incommensurate and non-magnetic states. The Cmmm transition is triggered by dominating R–R and R–Fe interactions becoming stronger at LT while the Pnnm phase is promoted by Fe–Fe and R–Fe interactions that prevail at HT. Included is also the magnetic structure of the ferromagnetic impurity phase Fe{sub 3}Ge. - Highlights: • Magnetic phase diagram of tetragonal TmFe{sub 4}Ge{sub 2} compound studied by neutron diffraction. • Unusual first

“Distributed hybrid” MH–CGH2 system for hydrogen storage and its supply to LT PEMFC power modules

Energy Technology Data Exchange (ETDEWEB)

Lototskyy, M., E-mail: mlototskyy@uwc.ac.za [HySA Systems Competence Centre, South African Institute for Advanced Materials Chemistry, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville 7535 (South Africa); Tolj, I.; Davids, M.W.; Bujlo, P. [HySA Systems Competence Centre, South African Institute for Advanced Materials Chemistry, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville 7535 (South Africa); Smith, F. [Impala Platinum Ltd, Springs (South Africa); Pollet, B.G. [HySA Systems Competence Centre, South African Institute for Advanced Materials Chemistry, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville 7535 (South Africa)

2015-10-05

Highlights: • Prototype hydrogen storage and supply system for LTPEMFC applications was developed. • Combination of MH and CGH2 tanks with common gas manifold was used. • Thermal coupling of fuel cell stack and MH tank was applied. • The system uses AB2-type MH; H2 equilibrium pressure ∼10 bar at room temperature. • Shorter H2 charge time and stable H2 supply at a fluctuating load were observed. - Abstract: This paper describes the layout and presents the results of the testing of a novel prototype “distributed hybrid” hydrogen storage and supply system that has the potential to be used for Low Temperature Proton Exchange Membrane Fuel Cell (LT-PEMFC) applications. The system consists of individual Metal Hydride (MH) and Compressed Gas (CGH2) tanks with common gas manifold, and a thermal management system where heat exchanger of the liquid heated-cooled MH tank is integrated with the cooling system of the LT-PEMFC BoP. The MH tank is filled with a medium-stability AB{sub 2}-type MH material (H{sub 2} equilibrium pressure of about 10 bar at room temperature). This innovative solution allows for (i) an increase in hydrogen storage capacity of the whole gas storage system and the reduction of H{sub 2} charge pressure; (ii) shorter charging times in the refuelling mode and smoother peaks of H{sub 2} consumption during its supply to the fuel cell stack; (iii) the use of standard parts with simple layout and lower costs; and (iv) adding flexibility in the layout and placement of the components of the hydrogen storage and supply system.

“Distributed hybrid” MH–CGH2 system for hydrogen storage and its supply to LT PEMFC power modules

International Nuclear Information System (INIS)

Lototskyy, M.; Tolj, I.; Davids, M.W.; Bujlo, P.; Smith, F.; Pollet, B.G.

2015-01-01

Highlights: • Prototype hydrogen storage and supply system for LTPEMFC applications was developed. • Combination of MH and CGH2 tanks with common gas manifold was used. • Thermal coupling of fuel cell stack and MH tank was applied. • The system uses AB2-type MH; H2 equilibrium pressure ∼10 bar at room temperature. • Shorter H2 charge time and stable H2 supply at a fluctuating load were observed. - Abstract: This paper describes the layout and presents the results of the testing of a novel prototype “distributed hybrid” hydrogen storage and supply system that has the potential to be used for Low Temperature Proton Exchange Membrane Fuel Cell (LT-PEMFC) applications. The system consists of individual Metal Hydride (MH) and Compressed Gas (CGH2) tanks with common gas manifold, and a thermal management system where heat exchanger of the liquid heated-cooled MH tank is integrated with the cooling system of the LT-PEMFC BoP. The MH tank is filled with a medium-stability AB 2 -type MH material (H 2 equilibrium pressure of about 10 bar at room temperature). This innovative solution allows for (i) an increase in hydrogen storage capacity of the whole gas storage system and the reduction of H 2 charge pressure; (ii) shorter charging times in the refuelling mode and smoother peaks of H 2 consumption during its supply to the fuel cell stack; (iii) the use of standard parts with simple layout and lower costs; and (iv) adding flexibility in the layout and placement of the components of the hydrogen storage and supply system

Antalya-Korkuteli Yöresinde Üretilen Kültür Mantarlarının (Agaricus bisporus) Beslenme Durumlarının Belirlenmesi

OpenAIRE

SÖNMEZ, Sahriye; ÜRAS, Dilek Saadet; DEMİR, Erbil; ÖZEN, Nil; KILIÇ, Ezgi

2018-01-01

Kültür mantarcılığı; üretim odalarında sene boyunca üretim yapılabilmesi, diğer tarım kollarındaki gibi ekolojik şartlara bağlılığının olmaması ve uygun koşulların sağlanmasıyla yılda aynı alandan altı defa ürün alınabilmesi nedeniyle çok karlı bir tarımsal faaliyet alanıdır.Türkiye'de mantarcılık faaliyetlerinin yoğun olarak yürütüldüğü Antalya-Korkuteli yöresinde yetiştirilen kültür mantarlarının besin içeriklerinin araştırıldığı bu çalışmada; ilçede faaliyet gösteren 11 farklı işletme...

Phase I Studies of Acebilustat: Pharmacokinetics, Pharmacodynamics, Food Effect, and CYP3A Induction.

Science.gov (United States)

Elborn, J S; Bhatt, L; Grosswald, R; Ahuja, S; Springman, E B

2017-01-01

Acebilustat is a new once-daily oral antiinflammatory drug in development for treatment of cystic fibrosis (CF) and other diseases. It is an inhibitor of leukotriene A4 hydrolase; therefore, production of leukotriene B4 (LTB4) in biological fluids provides a direct measure of the pharmacodynamic (PD) response to acebilustat treatment. Here we compare the pharmacokinetics (PK) and PD between CF patients and healthy volunteers, and investigate the food effect and CYP3A4 induction in healthy volunteers. No significant differences between study populations were observed for peak plasma level (C max ) or exposure (AUC). In healthy volunteers, a shift in time to C max (T max ) was observed after a high-fat meal, but there was no change in AUC. LTB4 production was reduced in the blood of both populations and in sputum from CF patients. Acebilustat did not induce CYP3A4. These results support continued clinical study of once-daily oral acebilustat in CF at doses of 50 and 100 mg. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Human eosinophils express, relative to other circulating leukocytes, large amounts of secretory 14-kD phospholipase A2

NARCIS (Netherlands)

Blom, M.; Tool, A. T.; Wever, P. C.; Wolbink, G. J.; Brouwer, M. C. [=Maria Clara; Calafat, J.; Egesten, A.; Knol, E. F.; Hack, C. E.; Roos, D.; Verhoeven, A. J.