Effect of FLAP antagonist MK-0591 on leukotriene production and ozone-induced airway responses in dogs

1994 ◽  
Vol 76 (4) ◽  
pp. 1583-1588 ◽  
Author(s):  
W. H. Stevens ◽  
C. G. Lane ◽  
M. J. Woolley ◽  
R. Ellis ◽  
P. Tagari ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Whole Blood ◽  
Airway Hyperresponsiveness ◽  
Calcium Ionophore ◽  
The Other ◽  
Continuous Intravenous Infusion ◽  
Before And After ◽  
Ltb4 Production ◽  
The Mean ◽  
Airway Responses

We used the 5-lipoxygenase-activating protein (FLAP) antagonist MK-0591 to investigate the importance of leukotrienes (LT) in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs. Six random source dogs were studied. On one day, dogs were treated with MK-0591 (2 mg/kg iv) followed by a continuous intravenous infusion of 8 micrograms.kg-1.min-1. On the other day, the diluent was infused. Acetylcholine airway responsiveness was measured before and 1 h after ozone inhalation (3 ppm for 30 min). On each day, whole blood and bronchoalveolar lavage (BAL) cells were challenged with calcium ionophore to stimulate LTB4 production. Urinary LTE4 levels were measured before and after ozone. MK-0591 inhibited LTB4 production in whole blood by 96% (P = 0.001) and that from BAL cells by 91% (P = 0.001). By contrast, MK-0591 had no effect on ozone-induced bronchoconstriction, airway hyperresponsiveness, or influx of neutrophils into BAL. The mean log difference of the pre- to post-acetylcholine provocative concentration was 0.64 +/- 0.40 during MK-0591 treatment and 0.68 +/- 0.40 during diluent treatment (P = 0.71). These results indicate that peptidoleukotrienes are produced during ozone inhalation and that MK-0591 inhibits LT production in dogs. However, LTs do not play a role in ozone-induced bronchoconstriction, airway inflammation, or airway hyperresponsiveness in dogs.

Effect of thromboxane antagonists on ozone-induced airway responses in dogs

1990 ◽  
Vol 69 (3) ◽  
pp. 880-884 ◽  
Author(s):  
G. L. Jones ◽  
C. G. Lane ◽  
P. M. O'Byrne
Keyword(s):  
Airway Hyperresponsiveness ◽  
The Other ◽  
Receptor Antagonists ◽  
Thromboxane Receptor ◽  
Before And After ◽  
The Mean ◽  
Airway Responses ◽  
Control Infusion

Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness.

Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. airway hyperresponsiveness

2015 ◽  
Vol 309 (8) ◽  
pp. L789-L800 ◽  
Author(s):  
Akihiko Taniguchi ◽  
Nobuaki Miyahara ◽  
Koichi Waseda ◽  
Etsuko Kurimoto ◽  
Utako Fujii ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Allergic Airway Inflammation ◽  
T Helper ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Group 2 ◽  
Airway Responses

The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE−/−) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE−/− mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE+/+ mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE−/− mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

Short-term stability of free metanephrines in plasma and whole blood

2020 ◽  
Vol 58 (5) ◽  
pp. 753-757 ◽  
Author(s):  
Elisa Danese ◽  
Martina Montagnana ◽  
Claudio Brentegani ◽  
Giuseppe Lippi
Keyword(s):  
Whole Blood ◽  
Repeated Measures ◽  
Sample Collection ◽  
Short Term ◽  
Total Change ◽  
Term Stability ◽  
Before And After ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
The Stability

AbstractBackgroundAnalysis of plasma metanephrine (MN) and normetanephrine (NMN) with liquid chromatography tandem mass spectrometry (LC-MS/MS) is the gold standard for the screening of pheochromocytomas and paragangliomas (PPGLs). As scarce information is available on the stability of MNs in diagnostic samples, this study was aimed at analyzing the short-term stability of plasma free MNs in whole blood and plasma, using LC-MS/MS.MethodsThe stability of plasma MNs was evaluated after sample collection at 1, 2 and 3 h in whole blood, and at 2, 4 and 6 h in centrifuged samples. Both studies were performed while maintaining the samples at room temperature (RT) and at 4 °C. The ClinMass Complete Kit (Recipe, Munchen, Germany) was used for measuring MNs with LC-MS/MS (Nexera X2 UHPLC-4500MD Sciex). Differences from the baseline (T0) were assessed using repeated measures one-way ANOVA, Students’ paired t-test and a comparison of the mean percentage changes with the total change limit (TCL).ResultsStatistically significant differences from T0 were found for both MNs (p < 0.001) in whole blood stored at RT, and for NMN (p = 0.028) but not MN (p = 0.220) at 4 °C. The mean difference exceeded the TCL after 1 h and 3 h at RT for MN, and after 1 h at RT for NMN. Statistically significant differences from T0 were only observed in the plasma samples for NMN at RT (p = 0.012), but the variation was within the TCL.ConclusionsMN and NMN displayed different patterns of stability before and after centrifugation. Even short-time storage at RT in whole blood should hence be avoided.

Effect of an anti-Mo1 MAb on ozone-induced airway inflammation and airway hyperresponsiveness in dogs

1992 ◽  
Vol 263 (6) ◽  
pp. L723-L726 ◽  
Author(s):  
Z. Li ◽  
E. E. Daniel ◽  
C. G. Lane ◽  
M. A. Arnaout ◽  
P. M. O'Byrne
Keyword(s):  
Neutrophil Count ◽  
Airway Hyperresponsiveness ◽  
Leukocyte Adhesion ◽  
Neutrophil Migration ◽  
Leukocyte Adhesion Molecule ◽  
Neutrophil Influx ◽  
Dry Air ◽  
Airway Lumen ◽  
Before And After ◽  
Airway Responses

Ozone inhalation causes neutrophil migration into the airway and airway hyperresponsiveness in dogs. The leukocyte adhesion molecule Mo1 (CD11b/CD18) is a heterodimeric glycoprotein the expression of which is necessary for neutrophil adhesion to endothelium. To evaluate the contribution of Mo1 to ozone-induced neutrophil influx and airway hyperresponsiveness, six dogs were treated intravenously with an Anti-Mo1 monoclonal antibody (3.75 mg/kg in normal saline) that binds to both human and canine Mo1, or the diluent alone, 1.5 h before inhaling ozone (3 ppm for 30 min), or dry air. Airway responses to doubling doses of inhaled acetylcholine (ACh) were measured before and after inhalation of ozone. Neutrophil influx was assessed by bronchoalveolar lavage (BAL) performed after the second ACh inhalation. Treatment with anti-Mo1 prevented the ozone-induced influx of neutrophils into BAL. After diluent and inhaled dry air, the neutrophil count in BAL was 1.49 +/- 1.26 (SE) x 10(4) (5.0% of total cells). After diluent and inhaled ozone, the neutrophil count increased to 7.27 +/- 3.22 (SE) x 10(4) (22.6% of total cells) (P < 0.05). After anti-Mo1 and inhaled ozone, the neutrophil count was 1.48 +/- 0.62 (SE) x 10(4) (8.5% of total cells). Treatment with anti-Mo1 also significantly reduced the number of eosinophils in BAL after ozone. Ozone-induced ACh airway hyperresponsiveness was not prevented by treatment with anti-Mo1. These results indicate that expression of Mo1 is necessary for ozone-induced neutrophil migration into the airway lumen.

Efficacy of Gabapentin in the Treatment of SUNCT Syndrome

Cephalalgia ◽  
2008 ◽  
Vol 28 (12) ◽  
pp. 1339-1342 ◽  
Author(s):  
M Etemadifar ◽  
AH Maghzi ◽  
M Ghasemi ◽  
A Chitsaz ◽  
M Kaji Esfahani
Keyword(s):  
Side Effects ◽  
Case Reports ◽  
The Other ◽  
Side Effect Profile ◽  
Open Label ◽  
Mean Intensity ◽  
Sunct Syndrome ◽  
Before And After ◽  
The Mean ◽  
Pre Treatment

This study was designed to evaluate the efficacy of gabapentin (GBP) in the treatment of SUNCT syndrome on a relatively large sample of Persian patients. Eight patients with SUNCT syndrome underwent a 4-week, open-label, daily treatment of 600-900 mg GBP. The frequency, intensity and duration of attacks were compared before and after the trial. After 4 weeks of treatment, intensity, duration and frequency of headaches were significantly ( P< 0.05) reduced. In addition, five patients (62.5±) were completely relieved from headaches, and in the other three patients the mean intensity, frequency and duration of headaches were decreased notably. In this study, GBP was well tolerated and no unfavourable side-effects were reported. After the end of the trial all patients continued the medication, and after 3 months none reported undesired side-effects or return of the headaches to the pre-treatment status. Our patients had a significant response to GBP, and considering other case reports on the effectiveness of GBP in the treatment of SUNCT syndrome, we propose that, taking into account the good side-effect profile and lack of interactions of GBP, this drug could be considered as an option for the treatment of SUNCT.

scholarly journals Assessment of eutrophication and nitrogen and phosphorus carrying capacity before and after removing pen culture (2013–2018) in Lake Changhu, China

2021 ◽  
Author(s):  
Xuemei Li ◽  
Tingbing Zhu ◽  
Yongfeng He ◽  
Xingbing Wu ◽  
Yongjiu Zhu ◽  
...  
Keyword(s):  
Oxygen Demand ◽  
Total Suspended Solid ◽  
Suspended Solid ◽  
The Other ◽  
Nitrogen And Phosphorus ◽  
Chl A ◽  
Before And After ◽  
The Mean ◽  
Inform Decision Making ◽  
Trophic Level Index

Abstract In this study, the eutrophication levels and nitrogen and phosphorus carrying capacities of Lake Changhu in Jingzhou city, Hubei province, China, were measured using the trophic level index (TLI) and Dillon model. The measurements were taken before (2013 and 2015) and after (2017 and 2018) the removal of pen aquaculture from the lake. The lake was divided into three districts: Lake Haizihu, Mahongtai Channel and Lake Dahu. The results showed total nitrogen (TN), chemical oxygen demand (COD), chlorophyll a (Chl-a), and total suspended solid (TSS) values were significantly higher in 2017 than in the other years. The Lake Haizihu district was predicted to be more seriously polluted than the other districts. In the sediment, the organic matter, STN (TN in sediment) and STP (TP in sediment) contents increased from 2013 to 2018. The mean TLI values ranged from 62.99 to 78.93 in the studied years, and the eutrophication level was highest in 2017. According to the Dillon model, when the target water quality was level III (GB 3838 − 2002, Ministry of Environmental Protection of China, 2002), the remaining TN and TP loading capacities were − 1470.72 t/a and − 182.74 t/a, respectively, in 2015, and 320.03 t/a and − 111.14 t/a, respectively, in 2018. The study provide valuable information about the actual water conditions of Lake Changhu, which will help to inform decision-making for the management of water environments.

The Contribution of Dental Amalgam to Mercury in Blood

1989 ◽  
Vol 68 (5) ◽  
pp. 780-785 ◽  
Author(s):  
K.R. Snapp ◽  
D.B. Boyer ◽  
L.C. Peterson ◽  
C.W. Svare
Keyword(s):  
Whole Blood ◽  
Daily Intake ◽  
Dental Amalgam ◽  
Blood Levels ◽  
Half Time ◽  
Occlusal Surfaces ◽  
Before And After ◽  
Blood Mercury ◽  
The Mean ◽  
Amalgam Removal

We determined the exposure to mercury from dental amalgam by comparison of blood levels of mercury before and after removal of all amalgams from ten subjects. Baseline concentrations of mercury in whole blood were measured weekly for four to 18 weeks (median = 6.6 weeks) prior to removal. All amalgams were removed in a single appointment. The subjects had an average of 14 surfaces of amalgam, seven of which were occlusal surfaces. Weekly blood sampling was continued for five to 18 weeks (median=7.6 weeks) after the amalgams were removed. The mean baseline concentration of total mercury in whole blood of the ten subjects was 2.18 (SD = 0.90) ng Hgl mL before the amalgams were removed. The baseline mercury levels were related to the number of amalgam surfaces. The linear correlation coefficient was 0.724 with number of occlusal surfaces, and 0.433 with total number of surfaces. After removal of the amalgams, nine of the ten subjects exhibited a statistically significant decrease in blood mercury at the 95% level of confidence. The mean decrease in mercury was 1.13 (SD = 0.60) ng Hg/mL. The half-time for elimination of mercury from blood after amalgam removal was 30.2 (SD = 5.8) days. Removal of the amalgams provided an additional exposure of 1. 46 (SD = 1.17) ng HglmL that was rapidly cleared from the blood with a half-time of 2.9 days. The daily intake of mercury from amalgam in the subjects was estimated to be at least 1.3 μg.

scholarly journals Lung hyperinflation, perception of bronchoconstriction and airway hyperresponsiveness

2007 ◽  
Vol 30 (1) ◽  
pp. 2 ◽  
Author(s):  
Louis-Philippe Boulet ◽  
Helene Turcotte
Keyword(s):  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Adenosine Monophosphate ◽  
Mild Asthma ◽  
Chest Tightness ◽  
Lung Hyperinflation ◽  
Cell Counts ◽  
Symptom Scores ◽  
Maximum Decrease ◽  
The Mean

Purpose: To compare the influence of underlying airway inflammation and lung hyperinflation on dyspnea during induced bronchoconstriction in subjects with mild asthma (or asymptomatic airway hyperresponsiveness (AAHR). Methods: Fourteen mild asthmatic and 14 AAHR subjects had methacholine and 5'-adenosine monophosphate (AMP) challenges, and induced sputum analysis. Changes in inspiratory capacity (IC) and respiratory symptom scores were measured after challenges. Perception of respiratory symptoms was recorded on a modified Borg scale. Results: The mean baseline FEV1, IC, mean provocative concentration of methacholine inducing a 20% decrease in FEV1 (PC20), the mean PC20 AMP and median inflammatory cell counts were similar in both groups. After methacholine, mean (±SD) reductions in FEV1 were 24.7±10.3% in mild asthma and 35.6±19.1% in AAHR (P>0.05); reductions in IC were, respectively, 10±12% and 24±20% (P>0.05); mean breathlessness scores at PC20 were 1.1 in mild asthma and 0 in AAHR P=0.003), and mean chest tightness scores were 1.2 in mild asthma and 0.8 in AAHR (P>0.05). Maximum chest tightness scores following MC correlated with the maximum decrease in IC in mild asthma (rs=0.75,P=0.009) and with the maximum decrease in FEV1 in AAHR (rs=0.60,P=0.04). After AMP, symptom scores were not significantly correlated with decreases in FEV1 or IC. The number of inflammatory cells was not correlated with decreases in IC after methacholine, AMP or with their PC20s, although inflammation was minimal in both groups. Conclusion: Lower breathlessness scores in AAHR compared to mild asthma were not explained by differences in lung hyperinflation nor in airway inflammation.

Cellular LTB4 production differs in allergic sheep with and without late airway responses

1990 ◽  
Vol 259 (2) ◽  
pp. L136-L143 ◽  
Author(s):  
G. A. Chapman ◽  
F. Signoretti ◽  
I. T. Lauredo ◽  
P. Torrealba ◽  
M. W. Sielczak ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Peripheral Blood ◽  
High Performance ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Cyclooxygenase Activity ◽  
Ltb4 Production ◽  
Airway Responses

We tested the hypothesis that allergic sheep that develop both early and late airway responses to inhaled Ascaris suum antigen (late responders) have an increased capacity to generate leukotrienes (LTs) compared with allergic sheep that show only early responses to inhaled antigen (acute responders). To test this hypothesis, we measured LTB4 production, in vitro, by granulocytes isolated from peripheral blood and by macrophages isolated from bronchoalveolar lavage (BAL) from both groups of sheep greater than or equal to 2 wk after the animal's last antigen challenge; LTB4 production by granulocytes isolated from BAL from both groups of sheep 6 and 48 h after local airway challenge with A. suum antigen was also measured. LTB4 production was induced by incubating cells (i.e., either granulocytes or macrophages) with calcium ionophore (A23187, 2 microM) and arachidonic acid (30 microM). LTB4 production was quantitated by high-performance liquid chromatography and verified by radioimmunoassay (RIA). On stimulation peripheral blood granulocytes from late responders (n = 7) produced (means +/- SD/10(6) cells) 13.3 +/- 5.2 ng LTB4 compared with 5.3 +/- 1.5 ng LTB4 (P less than 0.05) for acute responders (n = 7). This increased LTB4 production did not result from variations in granulocyte differential or cyclooxygenase activity (as indicated by RIA measurements of prostaglandin E2 production).(ABSTRACT TRUNCATED AT 250 WORDS)

THE EFFECT OF LOCAL TEMPERATURE ON THE REACTIVITY TO NORADRENALINE OF DIGITAL VESSELS

1967 ◽  
Vol 45 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Peter Gaskell ◽  
David L. Hoeppner
Keyword(s):  
Intravenous Infusion ◽  
The Other ◽  
Local Temperature ◽  
Continuous Intravenous Infusion ◽  
Opening Pressure ◽  
Simultaneous Measurements ◽  
Critical Opening ◽  
Short Period ◽  
The Mean

The effect of local temperature on the in vivo reactivity of vascular smooth muscle was studied. Reactivity was measured as the increase in critical opening pressure (COP) of digital vessels caused by intravenous infusion of 5 μg of noradrenaline per minute. With one hand cool (22 °C) and the other warm (34 °C) in test experiments or both hands either cool or warm in control experiments, simultaneous measurements were made of the increase in COP of vessels in both middle fingers in response to the noradrenaline. In control experiments the mean increase in COP was similar in right and left fingers, but in test experiments the mean increase was greater in the warm finger than in the cool one. Warm vessels were more reactive to noradrenaline than cool ones (p < 0.01). Because a short period of ischemia is involved in the measurement of COP, other experiments were performed in which the effect of duration of ischemia on the COP, with and without a continuous intravenous infusion of noradrenaline, was ascertained. They suggested that the estimated COP would, in most cases, be about 3 mm Hg less than the COP existing just before the measurement. These results also indicated that although the rate of fall of COP during ischemia was slightly greater for a higher initial COP, the ischemia involved did not invalidate the comparison of the increases in COP caused by noradrenaline in warm and cool fingers, as an index of relative arteriolar reactivity in the test reactivity experiments.

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