1.Analysis of the nasopharyngeal aspirates in children with different severities of bronchiolitis.
Rui LI ; Ji-An WANG ; Jin-Sheng LIU ; Chun-Juan ZHANG ; Xue-Bin REN
Chinese Journal of Contemporary Pediatrics 2010;12(5):396-397
Bronchiolitis
;
diagnosis
;
microbiology
;
pathology
;
Female
;
Humans
;
Infant
;
Leukotriene D4
;
analysis
;
Male
;
Nasopharynx
;
chemistry
;
microbiology
;
pathology
2.Inhibitory Effect of Rebamipide on Helicobacter pylori Induced Release of Leukotriene D4.
Jung Jin LEE ; Bok Gee HAN ; Mal Nam KIM ; Myung Hee CHUNG
Journal of the Korean Society for Microbiology 1997;32(6):653-658
It has been implicated that leukotrienes play roles in the pathogenesis of gastritis and gastric ulceration associated with Helicobacter pylori (H. pylori). Rebamipide is being used as an antiulcer drug but it's mechanism of action has not been understood well. One possible mechanism of action of this drug is to inhibit the cellular release of leukotrienes by various stimuli, particularly H. pylori. In the present study, attempts were made to test this possibility and the results are as follows. When Kato III cells (gastric adenoma cells) were stimulated by H. pylori, leukotriene D4 (LTD4) was released and rebamipide inhibited this release dose-dependently. Similar experiment was performed on neutrophils because the infilteration of neutrophils is a common phenomenon in H. pylori-infected gasrtric tissues. Neutrophils released LTD4 when these cells were stimulated by H. pylori and rebamipide also inhibited this release. Furthermore, rebamipide inhibited the release of LTD from neutrophils induced by calcium ionophore A23187 and arachidonic acid. The results suggest that rebamipide has the action to inhibit the release of LTD4 from various cells and this action may contribute in part to prevent the ulcerogenesis induced by H. pylori.
Adenoma
;
Arachidonic Acid
;
Calcimycin
;
Calcium
;
Gastritis
;
Helicobacter pylori*
;
Helicobacter*
;
Leukotriene D4*
;
Leukotrienes
;
Neutrophils
;
Stomach Ulcer
3.Leukotriene D4 bronchial provocation test for detection of airway hyper-responsiveness in children.
Fangjun LIU ; Caihui GONG ; Jiangjiao QIN ; Zhou FU ; Sha LIU
Journal of Southern Medical University 2020;40(6):793-798
OBJECTIVE:
To explore the value of leukotriene D4 (LTD4) bronchial provocation test (BPT) in detection of airway hyper-responsiveness (AHR) in children.
METHODS:
A total of 151 children aged 6 to 14 years, including 86 in remission of asthma and 65 with acute bronchitis, who were followed up in our respiratory clinic between November, 2017 and August, 2018. The children were randomly divided into LTD4 group (78 cases) and methacholine (MCH) group (73 cases). In LTD4 group, the 78 children underwent LTD4-BPT, including 46 with asthma and 32 children having re-examination for previous episodes of acute bronchitis; in MCH group, the 73 children underwent MCH-BPT, including 40 with asthma and 33 with acute bronchitis. MCH-BPT was also performed in the asthmatic children in the LTD4 group who had negative responses to LTD4 after an elution period. The major adverse reactions of the children to the two BPT were recorded. The diagnostic values of the two BPT were evaluated using receiver-operating characteristic (ROC) curve.
RESULTS:
There was no significant difference in the results of basic lung function tests between LTD4 group and MCH group (>0.05). The positive rate of BPT in asthmatic children in the LTD4 group was significantly lower than that in the MCH group (26.1% 72.5%; < 0.05). The positive rate of BPT in children with previous acute bronchitis in the LTD4 group was lower than that in the MCH group (3.1% 15.2%). The positive rate of MCH-BPT in asthmatic children had negative BPT results in LTD4 group was 58.8%, and their asthma was mostly mild. The sensitivity was lower in LTD4 group than in MCH group (0.2609 0.725), but the specificity was slightly higher in LTD4 group (0.9688 vs 0.8485).The area under ROC curvein LTD4 group was lower than that in MCH group (0.635 0.787). In children with asthma in the LTD4 group, the main adverse reactions in BPT included cough (34.8%), shortness of breath (19.6%), chest tightness (15.2%), and wheezing (10.9%). The incidence of these adverse reactions was significantly lower in LTD4 group than in MCH group ( < 0.05). Serious adverse reactions occurred in neither of the two groups.
CONCLUSIONS
LTD4-BPT had high safety in clinical application of children and was similar to the specificity of MCH-BPT. However, it had low sensitivity, low diagnostic value, and limited application value in children's AHR detection.
Adolescent
;
Asthma
;
Bronchial Provocation Tests
;
Child
;
Humans
;
Leukotriene D4
;
Methacholine Chloride
;
Respiratory Hypersensitivity
4.Correlations of nasal responses to leukotriene D4 and histamine nasal provocation with quality of life in allergic rhinitis
Zheng ZHU ; Yanqing XIE ; Weijie GUAN ; Yi GAO ; Shu XIA ; Xu SHI ; Jinping ZHENG
Asia Pacific Allergy 2016;6(4):245-252
BACKGROUND: The symptoms of allergic rhinitis (AR) greatly affect the quality of life (QoL) in the patients with AR. The correlations of nasal response to leukotriene D4 (LTD4) and histamine nasal provocation with health related QoL in AR are not clear. OBJECTIVE: To evaluate the correlations of nasal response to LTD4 and histamine nasal challenge with QoL in AR. METHODS: Patients randomly underwent LTD4 and histamine nasal challenge tests, completed the rhinoconjunctivitis quality of life questionnaire (RQoLQ), and rating the symptom severity score (total symptom score 4, TSS4) in the previous week. The correlations between nasal challenge tests induced nasal responses and QoL in RQoLQ were analyzed. RESULTS: A total of 25 eligible AR patients enrolled and finished both LTD4 and histamine nasal challenge and completed the questionnaire of RQoLQ. Histamine nasal challenge induced sneezing, increased nasal resistant were correlated with most of the dimensions (general, practical, nasal, eye problems, and quality of sleep, p < 0.05), while LTD4 nasal challenge induced sneeze, increased nasal resistant only correlated with nasal and ocular problems. On the contrary, the severity of the sneeze assessed by TSS4, was not correlated with QoL, while the severity of rhinorrhea, congestion, and nasal pruritus were correlated with nasal and practical problems, and nasal congestion was also correlated with ocular problems (r = 0.60, p = 0.01). CONCLUSION: LTD4 and histamine nasal challenge induced nasal responses were correlated with different clinical symptoms severity and QoL, which can be used as a good diagnosis and evaluation methods for the management of AR.
Diagnosis
;
Estrogens, Conjugated (USP)
;
Histamine
;
Humans
;
Leukotriene D4
;
Pruritus
;
Quality of Life
;
Rhinitis, Allergic
;
Sneezing
5.The inhibitory effect of eupatilin on Helicobacter pylori-induced release of leukotriene D4 in the human neutrophils and gastric mucosal cells.
Jung Jin LEE ; Bok Gee HAN ; Mal Nam KIM ; Myung Hee CHUNG
The Korean Journal of Physiology and Pharmacology 1997;1(5):573-580
In this report, the inhibitory action of eupatilin was investigated by using leukotriene D4 in the human neutrophils and Kato III cells (Gastric adenoma cells as a substitute for gastric mucosal cells) stimulated by Helicobacter pylori. Leukotriene D4 (LTD4) was released from both neutrophils and Kato III cells when these cells were incubated with H. pylori. The release of LTD4 increased time-dependently and the maximum release of LTD4 was 2.3-2.5 pmol. But in the presence of eupatilin, the release of LTD4 from these cells was inhibited in a dose-dependent manner. In the neutrophils, die release of LTD4 was suppressed to 70% and 50% of the control levels when neutrophils was incubated with 0.01 and 0.1 mM of eupatilin. In the Kato III cells, the release of LTD4 was suppressed to 59% and 27% of the control levels by adding 0.01 and 0.1 mM of eupatilin. We estimated the intracellular Ca2+ levels when Kato III cells and neutrophils were stimulated by H. pylori using 45Ca. But the suppressive effect of eupatilin on Ca2+ influx into these cells was not significant. We also obtained the results that H. pylori induced Ca2+ influx into these cells by confocal microscopy, however there was no differences in the dose level of eupatilin. These results were confirmed by 1H Nuclear Magnetic Resonance(NMR) spectroscopy. The NMR patterns of eupatilin in the absence of Ca2+ was changed compare with when Ca2+ was present, but its effect was not strong.
Adenoma
;
Helicobacter pylori
;
Helicobacter*
;
Humans*
;
Leukotriene D4*
;
Microscopy, Confocal
;
Neutrophils*
;
Spectrum Analysis
6.Method for screening cysteinyl leukotriene receptor 2 antagonists and preliminary screening of compounds.
Bei-Lei CAI ; Xue-Qin HUANG ; Xiao-Wu DONG ; San-Hua FANG ; Yun-Bi LU ; Wei-Ping ZHANG ; Yong-Zhou HU ; Jian-Gen SHEN ; Er-Qing WEI
Journal of Zhejiang University. Medical sciences 2009;38(6):598-604
OBJECTIVETo establish a method for screening cysteinyl leukotriene receptor 2 (CysLT(2)) antagonists and to preliminarily screen a series of synthetic compounds.
METHODSRat glioma cell line (C6 cells) highly expressing CysLT(2) receptor was used. Intracellular calcium concentration was measured after stimulation with the agonist LTD(4),which was used to screen compounds with antagonist activity for CysLT(2) receptor. Bay u9773, a CysLT1/CysLT(2) receptor non-selective antagonist, and AP-100984, a CysLT(2) receptor antagonist, were used as control.
RESULTPT-PCR showed a higher expression of CysLT(2) receptor in C6 cells. LTD(4) at 1 mumol/L significantly increased intracellular calcium in C6 cells; the maximal effect was about 37.5% of ATP, a positive stimulus.LTD(4)-induced increase of intracellular calcium was blocked by CysLT(2) receptor antagonists, but not by CysLT(1) receptor antagonists. Among the synthetic compounds, D(XW-)1,2,13,23,29 and 30 inhibited LTD(4)-induced increase of intracellular calcium.
CONCLUSIONLTD(4)-induced change in intracellular calcium in C6 cells can be used as a screening method for CysLT(2) receptor antagonists. The compounds, D(XW-)1,2,13,23,29 and 30, possess antagonist activity for CysLT(2) receptor.
Animals ; Brain Neoplasms ; pathology ; Cell Line, Tumor ; Drug Evaluation, Preclinical ; methods ; Glioma ; pathology ; Leukotriene Antagonists ; isolation & purification ; Leukotriene D4 ; metabolism ; pharmacology ; Rats ; Receptors, Leukotriene ; chemistry
7.MUC2/5AC Expression and Mucin Secretion through Leukotriene Receptor in Human Airway Epithelial Cells.
Yong Dae KIM ; Jae Euk LEE ; Chang Hoon BAI ; Young Jung SEO ; Sang Baik YE ; Si Yeon SONG
Korean Journal of Otolaryngology - Head and Neck Surgery 2004;47(11):1115-1119
BACKGROUND AND OBJECTIVES: Mucin gene expression and mucin production are highly increased during inflammatory airway disorders such as, asthma, chronic bronchitis and sinusitis. Cytokines, lipopolysaccharides and other inflammatory mediators are related with secretion and production of mucin. However, among of inflammatory mediators, the relation of leukotrienes and mucin genes expression is not clear. The aim of this study is to evaluate MUC2/5AC genes expression and mucin secretion through leukotriene receptor in human airway epithelial cells. SUBJECTS AND METHOD: The effect of Leukotriene D4 and leukotriene receptor antagonist, pranlukast hydrate (ONO-1078) on the regulation of MUC2/5AC gene expression and mucin secretion was observed in the human airway NCI-H292 epithelial cells. The mRNA levels of MUC2/5AC and the amount of mucin protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunoassay. RESULTS: Leukotriene D4 upregulated MUC2/5AC gene expression and mucin secretion on a dose dependent pattern. Pranlukast hydrate (ONO-1078, 100 micrometer) downregulated the leukotriene D4-mediated MUC2/5AC gene expression and mucin secretion. CONCLUSION: These results suggest that the leukotriene receptor system is one of the expression mechanisms of MUC2/5AC genes and mucin secretion.
Asthma
;
Bronchitis, Chronic
;
Cytokines
;
Epithelial Cells*
;
Gene Expression
;
Humans*
;
Immunoassay
;
Leukotriene Antagonists
;
Leukotriene D4
;
Leukotrienes
;
Lipopolysaccharides
;
Mucins*
;
Receptors, Leukotriene*
;
RNA, Messenger
;
Sinusitis
8.Mast Cells and Allergic Rhinitis.
Journal of Rhinology 1998;5(2):85-91
That mast cells play a role in acute allergic inflammation by releasing various inflammatory mediators, including histamine, leukotrienes (LT), such as LTC4 and LTD4, and prostaglandins (PG), such as PGD2, is well known. Additionally, mast cells contribute to the development of allergic inflammation also through the release of multifunctional cytokines. The incidence of intraepithelial mast cells (IEMC) is found to be greater in nasal mucosa exposed to an allergen, and the cells are thought to play an important role in producing the immediate allergic reaction. Lamina propira mast cells (LPMC) are known to be the dominant source of TH2 cytokine and are responsible for development of the late phases of an allergic reaction They may upregulate the expression of adhesion molecules on the endothelial cells and induce basophil and eosinophil recruitment. Based on these consideration it can be proposed that mast cell is a initiating cell of allergic reaction in target organ and IEMC and LPMC have capacity to make major contribution to both immediate or late phase reaction of allergic rhinitis.
Basophils
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Cytokines
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Endothelial Cells
;
Eosinophils
;
Histamine
;
Hypersensitivity
;
Incidence
;
Inflammation
;
Leukotriene C4
;
Leukotriene D4
;
Leukotrienes
;
Mast Cells*
;
Nasal Mucosa
;
Prostaglandin D2
;
Prostaglandins
;
Rhinitis*
9.Cysteinyl leukotriene receptor 1 antagonist pranlukast modulates differentiation of SK-N-SH cells.
Fang PENG ; San-Hua FANG ; Xiao-Liang ZHENG ; Wei-Ping ZHANG ; Yun-Bi LU ; Er-Qing WEI
Journal of Zhejiang University. Medical sciences 2007;36(2):123-128
OBJECTIVETo determine whether cysteinyl leukotriene receptor agonist LTD(4) and cysteinyl leukotriene receptor 1 (CysLT(1)) antagonist pranlukast affect the differentiation of human neuroblastoma SK-N-SH cells.
METHODSSK-N-SH cell morphological changes induced by LTD(4), pranlukast and LTD(4) + pranlukast were observed with retinoid acid (RA) as the positive control. The expressions of CysLT(1) and CysLT(2) receptors were detected by immunoblotting analysis, and the expression of microtubule-associated protein-2 (MAP-2), a neuron marker, was detected by fluorescent immunostaining.
RESULTThe immunoblotting results showed that SK-N-SH cells expressed CysLT(1) receptor moderately, and CysLT(2) receptor highly. The morphological results showed that RA, pranlukast and LTD(4) + pranlukast induced the compaction of the cell bodies and the outgrowth of neurites, while LTD(4) had no significant effect. The immunostaining results showed that MAP-2 was distributed in the cell bodies in control or pranlukast-treated cells; it was distributed in cell bodies and neuritis in RA-treated cells. Pranlukast increased the numbers of MAP-2-positive cells.
CONCLUSIONThe CysLT(1)receptor antagonist pranlukast modulates the differentiation of SK-N-SH cells.
Cell Differentiation ; drug effects ; Cell Line, Tumor ; Chromones ; pharmacology ; Humans ; Immunoblotting ; Immunohistochemistry ; Leukotriene Antagonists ; pharmacology ; Leukotriene D4 ; pharmacology ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Neuroblastoma ; metabolism ; pathology ; Receptors, Leukotriene ; metabolism
10.Effects of cysteinyl receptor agonist and antagonists on rat primary cortical neurons.
Xin HU ; Qiu-Fu GE ; Wei-Ping ZHANG ; Er-Qing WEI
Journal of Zhejiang University. Medical sciences 2007;36(2):117-122
OBJECTIVETo determine the effect of cysteinyl receptor agonist leukotriene D(4) (LTD(4)) and its antagonists on rat primary neurons.
METHODSIn the primarily cultured rat cortical neurons, the neuron injury was evaluated by measuring intracellular calcium, 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) reduction, and propidium iodide (PI) and Hoechst 33258 staining. The in vitro ischemic injury was induced by oxygen-glucose deprivation (OGD) for 1.5 h and reperfusion for 24 h.
RESULTLTD(4) (0.01-1 micromol/L) did not induce the elevation of intracellular calcium, neuron viability changes and neuron death. OGD-induced injury was not significantly ameliorated by the CysLT(1) receptor antagonists, pranlukast (0.2-10 micromol/L) and montelukast (0.2-10 micromol/L), as well as by the CysLT(1)/CysLT(2) receptor non-selective antagonist, BAY u9773 (0.02-1 micromol/L).
CONCLUSIONNeither agonist nor antagonists of cysteinyl receptors have the effects on the viability and ischemic-like injury in rat primary neurons.
Acetates ; pharmacology ; Animals ; Animals, Newborn ; Calcium ; metabolism ; Cell Hypoxia ; Cell Survival ; drug effects ; Cells, Cultured ; Cerebral Cortex ; cytology ; Chromones ; pharmacology ; Glucose ; pharmacology ; Leukotriene Antagonists ; pharmacology ; Leukotriene D4 ; pharmacology ; Neurons ; cytology ; drug effects ; metabolism ; Quinolines ; pharmacology ; Rats ; Receptors, Leukotriene ; agonists