Efficacy of montelukast sodium combined with methylprednisolone in the treatment of allergic purpura in children and its effects on inflammatory factors and immune function / 中国基层医药

Objective:To investigate the efficacy of montelukast sodium combined with methylprednisolone in the treatment of pediatric allergic purpura and its effects on inflammatory factors and immune function.Methods:A total of 94 children with allergic purpura who received treatment in Taizhou Women and Children's Hospital and Taizhou Hospital Medical Center (Group) Enze Hospital from March 2019 to March 2021 were included in this study. They were randomly divided into observation and control groups ( n = 47/group). The control group was treated with methylprednisolone. The observation group was treated with montelukast sodium combined with methylprednisolone. The course of treatment was 2 weeks in both groups. Efficacy and changes in inflammatory factors and immune function post-treatment relative to those pre-treatment were compared between the two groups. Results:Total response rate in the observation group [93.62% (44/47)] was significantly higher than that in the control group [74.47% (35/47), Z = 2.15, P < 0.05)]. After treatment, interleukin (IL-4), IL-6, and IL-18 levels in each group were significantly decreased compared with those before treatment ( tobservation group = 21.19, 22.26, 27.20, tcontrol group = 11.10, 13.21, 14.86, all P < 0.05). After treatment, IL-4, IL-6, and IL-8 levels in the observation group were (48.98 ± 5.21) ng/L, (34.10 ± 6.42) ng/L, and (53.29 ± 5.67) ng/L, respectively, which were significantly lower than (65.38 ± 7.08) ng/L, (47.83 ± 4.71) ng/L, (67.83 ± 7.10) ng/L in the control group ( t = 12.79, 11.82, 10.97, all P < 0.05). After treatment, CD3 +, CD4 +, and CD4 +/CD8 + in each group were significantly increased compared with those before treatment ( tobservation group = 14.27, 14.41, 17.61, tcontrol group = 6.90, 5.12, 7.40, all P < 0.05). After treatment, CD3 +, CD4 +, and CD4 +/CD8 + in the observation group were (68.94 ± 2.89)%, (39.94 ± 2.15)%, and (1.79 ± 0.13), respectively, which were significantly higher than (63.86 ± 3.28)%, (35.65 ± 2.31)%, and (1.53 ± 0.16) in the control group ( t = 7.96, 9.32, 8.64, all P < 0.05). After treatment, serum IgG and IgM levels in each group were significantly decreased compared with those before treatment ( tobservation group = 21.00, 7.99, tcontrol group = 8.38, 5.76, both P < 0.05). After treatment, serum IgG and IgM levels in the observation group were (1.43 ± 0.19) g/L and (9.74 ± 0.78) g/L, respectively, which were significantly lower than (1.95 ± 0.37) g/L and (10.89 ± 0.85) g/L in the control group ( t = 8.57, 6.83, both P < 0.05). Conclusion:Montelukast sodium combined with methylprednisolone is highly effective on allergic purpura in children. The combined therapy can reduce inflammatory responses and improve immune function in children.

Efficacy of Guanqiao Zhengqi holistic therapy for chronic rhinosinusitis / 中国基层医药

Objective:To investigate the efficacy of Guanqiao Zhengqi holistic therapy in the treatment of chronic rhinosinusitis. Methods:A total of 200 patients with chronic rhinosinusitis who received treatment in the Department of Otolaryngology, Shanxi Provincial Integrated Traditional Chinese Medicine and Western Medicine Hospital ( n = 72) and Shanxi Yishengtang Traditional Chinese Medicine Center ( n = 128) from January 2021 to January 2022 were included in this study. These patients were randomly assigned to undergo treatment either with mometasone furoate nasal spray and levocetirizine hydrochloride tablets (control group, n = 100) or Guanqiao Zhengqi holistic therapy combined with mometasone furoate nasal spray and levocetirizine hydrochloride tablets (observation group). All patients were treated for 4 weeks and followed up for 3 months. Clinical efficacy, modified Visual Analogue Scale score, Lund-Kennedy endoscopy scoring system score, and duration of glucocorticoid and anti-leukotriene use were compared between the two groups. Results:The total response rate in the observation group was significantly higher than that in the control group [92.00% (92/100) vs. 73.00% (73/100), χ2 = 18.45, P < 0.001). There was no significant difference in the modified Visual Analogue Scale score between the two groups before treatment ( Z = 1.37, P = 0.170). There was a significant difference in the modified Visual Analogue Scale score between the two groups after treatment ( Z = -5.27, P < 0.001). Before treatment, there was no significant difference in the Lund-Kennedy endoscopy scoring system score between the two groups ( Z = -1.65, P = 0.098) and the Lund-Kennedy endoscopy scoring system score differed significantly between the two groups after treatment ( Z = -6.03, P < 0.001). The duration of glucocorticoid and anti-leukotriene use in the observation group was significantly shorter than that in the control group [10.00 (10.00, 14.00) days vs. 42.00 (28.00, 70.00) days, 7.00 (7.00, 7.00) days vs. 21.00 (14.00, 26.25) days, Z = -11.27, P < 0.001, Z = -12.31, P < 0.001). Conclusion:Based on the conventional treatment with western medicine, Guanqiao Zhengqi holistic therapy for the treatment of chronic rhinosinusitis can effectively reduce clinical symptoms, reduce the dose of hormones and anti-leukotriene used, shorten the use cycle, and improve the therapeutic efficacy.

Leukotriene B4 Loaded in Microspheres Inhibits Osteoclast Differentiation and Activation

Abstract To investigate osteoclast formation in vivo and if leukotriene B4 (LTB4) loaded in microspheres (MS) could be used as a therapeutical strategy to promote a sustained delivery of the mediator and prevent osteoclast differentiation. Methods: In vivo, apical periodontitis was induced in mice to investigate osteoclast differentiation and signaling in absence of 5-lipoxygenase (5-LO). In vitro, LTB4-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process. Characterization and efficiency of LTB4 encapsulation were investigated. J774A.1 macrophages were cultured in the presence of monocyte colony-stimulating factor (M-CSF) and ligand for receptor activator of nuclear factor kappa B (RANKL) and then stimulated with LTB4-MS. Cytotoxicity, in vitro MS-LTB4 uptake, osteoclast formation and gene expression were measured. Results: We found that 5-LO negatively regulates osteoclastic formation in vivo during apical periodontitis development. In vitro, LTB4-MS were up-taken by macrophages and were not cytotoxic to the cells. LTB4-MS inhibited osteoclast formation and the synthesis of osteoclastogenic genes Acp5, Mmp9, Calcr and Ctsk. LTB4-MS inhibited differentiation of macrophages into an osteoclastic phenotype and cell activation under M-CSF and RANKL stimulus.

Resumo O objetivo deste trabalho foi Investigar a formação de osteoclastos in vivo e se o leucotrieno B4 (LTB4) incorporado em microesferas (MS) poderia ser usado como estratégia terapêutica para promover uma entrega sustentada do mediador e prevenir a diferenciação dos osteoclastos. Métodos: In vivo, a periodontite apical foi induzida em camundongos para investigar a diferenciação e sinalização de osteoclastos na ausência de 5-lipoxigenase (5-LO). In vitro, LTB4-MS foi preparado usando um processo de evaporação e extração de solvente de emulsão de óleo em água. A caracterização e a eficiência do encapsulamento do LTB4 foram investigadas. Macrófagos J774A.1 foram cultivados na presença de fator estimulador de colônia de monócitos (M-CSF) e ligante para o receptor ativador do fator nuclear kappa B (RANKL) e, então, estimulados com LTB4-MS. Citotoxicidade, captação in vitro de MS-LTB4, formação de osteoclastos e expressão gênica foram avaliadas. Resultados: A via 5-LO regula negativamente a formação de osteoclastos in vivo durante o desenvolvimento da periodontite apical. In vitro, LTB4-MS foram fagocitadas pelos macrófagos e não foram citotóxicos para as células. LTB4-MS inibiu a formação de osteoclastos e a síntese dos genes pró-osteoclastogênicos Acp5, Mmp9, Calcr e Ctsk. Conclusões: LTB4-MS inibiu a diferenciação de macrófagos em um fenótipo osteoclástico e a ativação celular sob estímulo de M-CSF e RANKL.

Prognostic implications and functional enrichment analysis of LTB4R in patients with acute myeloid leukemia / 南方医科大学学报

OBJECTIVE@#To explore the expression patterns, prognostic implications, and biological role of leukotriene B4 receptor (LTB4R) in patients with acute myeloid leukemia (AML).@*METHODS@#We collected the data of mRNA expression levels and clinical information of patients with AML from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database for mRNA expression analyses, survival analyses, Cox regression analyses and correlation analyses using R studio to assess the expression patterns and prognostic value of LTB4R. The correlation of LTB4R expression levels with clinical characteristics of the patients were analyzed using UALCAN. The co-expressed genes LTB4R were screened from Linkedomics and subjected to functional enrichment analysis. A protein-protein interaction network was constructed using STRING. GSEA analyses of the differentially expressed genes (DEGs) were performed based on datasets from TCGA-LAML stratified by LTB4R expression level. We also collected peripheral blood mononuclear cells (PBMCs) from AML patients and healthy donors for examination of the mRNA expression levels of LTB4R and immune checkpoint genes using qRT-PCR. We also examined serum LTB4R protein levels in the patients using ELISA.@*RESULTS@#The mRNA expression level of LTB4R was significantly increased in AML patients (4.898±1.220 vs 2.252±0.215, P < 0.001), and an elevated LTB4R expression level was correlated with a poor overall survival (OS) of the patients (P=0.004, HR=1.74). LTB4R was identified as an independent prognostic factor for OS (P=0.019, HR=1.66) and was associated with FAB subtypes, cytogenetic risk, karyotype abnormalities and NPM1 mutations. The co- expressed genes of LTB4R were enriched in the functional pathways closely associated with AML leukemogenesis, including neutrophil inflammation, lymphocyte activation, signal transduction, and metabolism. The DEGs were enriched in differentiation, activation of immune cells, and cytokine signaling. Examination of the clinical serum samples also demonstrated significantly increased expressions of LTB4R mRNA (P=0.044) and protein (P=0.008) in AML patients, and LTB4R mRNA expression was positively correlated with the expression of the immune checkpoint HAVCR2 (r= 0.466, P=0.040).@*CONCLUSION@#LTB4R can serve as a novel biomarker and independent prognostic indicator of AML and its expression patterns provide insights into the crosstalk of leukemogenesis signaling pathways involving tumor immunity and metabolism.

Correlation between hand-arm vibration disease and vasoactive factors / 环境与职业医学

Background Hand-arm vibration disease (HAVD) is a chronic progressive disease caused by long-term exposure to hand-transmitted vibration, but the mechanism by which vibration affects peripheral vascular function of fingers is not completely clear. Objective To study the association between vasoactive factors and HAVD, and to screen specific indicators for its early diagnosis and prevention. Methods Judgmental sampling method was used to select workers with (HAVD group) and without HAVD (vibration contact group), and non-hand-transmitted vibration operation workers (control group), with 60 workers in each group. The levels of leukotriene B4 (LTB4), vascular endothelial growth factor (VEGF), 5-hydroxy tryptamine (5-HT), interleukin-1β (IL-1β), and calcitonin gene-related peptide (CGRP) in plasma of the three groups were measured by enzyme-linked immunosorbent assay. The association between vasoactive factors and HAVD was analyzed using logistic regression, and the diagnostic HAVD indicators were screened by receiver operator characteristic (ROC) curve of a multivariate model indicator \begin{document}$ \widehat{Y} $\end{document}. Results The hand symptom rates of the HAVD group, the vibration contact group, and the control group were 26.7%, 66.7%, and 96.7% respectively, with a significant difference (P<0.05). The levels of LTB4, 5-HT, IL-1β, and CGRP in the HAVD group were the highest followed by the vibration contact group, and lowest levels were in the control group (P<0.05). There was no significant difference in the VEGF level among the three groups (P>0.05). The logistic regression results showed that higher levels of LTB4 (OR=1.048, 95%CI: 1.022-1.076), 5-HT (OR=1.011, 95%CI: 1.004-1.018), IL-1β (OR=1.148, 95%CI: 1.071-1.230), and CGRP (OR=1.055, 95%CI: 1.008-1.104) were associated with a higher risk of HAVD (P<0.05). The order of the potential indicators' area under the ROC curve from high to low was:\begin{document}$ \widehat{Y} $\end{document} (0.969) > IL-1β (0.907) > LTB4 (0.876) > 5-HT (0.858) > CGRP (0.836). Conclusion The expression levels of LTB4, 5-HT, IL-1β, and CGRP are altered with occupational exposure in hand-transmitted vibration operations and may be associated with HAVD; VEGF is not found to be associated with HAVD. The accuracy of early screening for HAVD can be improved by combining the monitoring of various biochemical indicators.

Efficacy of inhalation therapy with montelukast sodium, budesonide and formoterol in combination in the treatment of bronchial asthma in adult patients and its effects on cytokines / 中国基层医药

Objective:To investigate the efficacy of combination treatment with montelukast sodium, budesonide and formoterol in the treatment of bronchial asthma in adults and its effects on cytokines.Methods:A total of 100 adult patients with bronchial asthma who received treatment in The First People's Hospital of Yongkang from January 2019 to December 2020 were included in this study. They were randomly assigned to receive either budesonide inhalation alone (control group, n = 50) or combination inhalation of montelukast sodium, budesonide and formoterol (observation group, n = 50) for 12 weeks. Efficacy was compared between the two groups. Lung function [forced expiratory volume in one second (FEV 1), peak expiratory flow (PEF) and FEV 1/forced vital capacity (FVC) ratio], cytokines [interleukin (IL)-2, IL-4, IL-6], Asthma Quality of Life Questionnaire (AQLQ) score, and Asthma Control Test (ACT) score measured before and 12 weeks after treatment were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [92.00% (46/50) vs. 72.00% (36/50), χ2 = 6.77, P < 0.05). After 12 weeks of treatment, FEV 1, PEF and FEV1/FVC in the observation group were (2.17 ± 0.23) L, (246.56 ± 17.86) L/s, and (83.86 ± 3.98)%, respectively, which were significantly higher than (1.86 ± 0.17) L, (203.12 ± 20.10) L/s, (74.82 ± 5.67)% in the control group ( t = 7.66, 11.42, 9.22, P < 0.05). Serum IL-2 level in the observation group was significantly higher than that in the control group [(10.85 ± 0.86) ng/L vs. (8.94 ± 1.03) ng/L, t = 10.06, t < 0.05]. Serum IL-4 and IL-6 in the observation group were (24.98 ± 3.08) ng/L and (98.46 ± 9.76) μg/L, respectively, which were significantly lower than (36.75 ± 4.34) ng/L and (125.84 ± 13.19) μg/L in the control group ( t =15.63, 11.79, both P < 0.05). AQLQ score and ACT score in the observation group were (121.03 ± 8.69) points and (22.08 ± 1.35) points, respectively, which were significantly higher than (110.93 ± 7.86) points and (19.74 ± 1.76) points in the control group ( t = 6.095, 7.460, both P < 0.05). Conclusion:Inhalation therapy with montelukast sodium, budesonide and formoterol produces obvious therapeutic effects on bronchial asthma in adult patients and the combined therapy can reduce inflammatory reactions.

Reacciones adversas a montelukast: de la teoría a la práctica. Serie de casos / Adverse drug reactions of montelukast: from theory to practice. Case report

El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.

Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.

The role of montelukast in the prevention and treatment of bronchopulmonary dysplasia in premature infants / 国际儿科学杂志

Bronchopulmonary dysplasia is one of the most common chronic respiratory diseases in premature infants, especially in very low birth weight infants.Lung immaturity, inflammatory injury, oxidative stress and abnormal repair after injury are the important factors.Leukotriene is an inflammatory mediator of 5-lipoxygenase pathway and participates in the occurrence of bronchopulmonary dysplasia.Montelukast, as a leukotriene receptor antagonist, may play a role in the treatment of bronchopulmonary dysplasia through anti-inflammation, anti-oxidation and anti-fibrosis.This article will review the potential mechanism and related clinical researches of montelukast which is used in treating bronchopulmonary dysplasia.

Root canal contamination or exposure to lipopolysaccharide differentially modulate prostaglandin E 2 and leukotriene B 4 signaling in apical periodontitis

Abstract Purpose To evaluate the kinetics of apical periodontitis development in vivo , induced either by contamination of the root canals by microorganisms from the oral cavity or by inoculation of bacterial lipopolysaccharide (LPS) and the regulation of major enzymes and receptors involved in the arachidonic acid metabolism. Methodology Apical periodontitis was induced in C57BL6 mice (n=96), by root canal exposure to oral cavity (n=48 teeth) or inoculation of LPS (10 µL of a suspension of 0.1 µg/µL) from E. coli into the root canals (n= 48 teeth). Healthy teeth were used as control (n=48 teeth). After 7, 14, 21 and 28 days the animals were euthanized and tissues removed for histopathological and qRT-PCR analyses. Histological analysis data were analyzed using two-way ANOVA followed by Sidak's test, and qRT-PCR data using two-way ANOVA followed by Tukey's test (α=0.05). Results Contamination by microorganisms led to the development of apical periodontitis, characterized by the recruitment of inflammatory cells and bone tissue resorption, whereas inoculation of LPS induced inflammatory cells recruitment without bone resorption. Both stimuli induced mRNA expression for cyclooxygenase-2 and 5-lipoxygenase enzymes. Expression of prostaglandin E 2 and leukotriene B 4 cell surface receptors were more stimulated by LPS. Regarding nuclear peroxisome proliferator-activated receptors (PPAR), oral contamination induced the synthesis of mRNA for PPARδ, differently from inoculation of LPS, that induced PPARα and PPARγ expression. Conclusions Contamination of the root canals by microorganisms from oral cavity induced the development of apical periodontitis differently than by inoculation with LPS, characterized by less bone loss than the first model. Regardless of the model used, it was found a local increase in the synthesis of mRNA for the enzymes 5-lipoxygenase and cyclooxygenase-2 of the arachidonic acid metabolism, as well as in the surface and nuclear receptors for the lipid mediators prostaglandin E2 and leukotriene B4.

Leukotriene D4 bronchial provocation test for detection of airway hyper-responsiveness in children / 南方医科大学学报

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.

Effect of Zelen' s Guige Lingxian Decoction Combined with Moxibustion at Neck Jiaji Acupoint in Treatment of Cervical Spondylotic radiculopathy of Wind-cold-dampness Arthralgia Syndrome / 中国实验方剂学杂志

Objective::To investigate the clinical efficacy and mechanism of Guige Lingxian decoction combined with moxibustion at neck Jiaji acupoint on cervical spondylotic radiculopathy (CSR) of wind-cold-dampness arthralgia syndrome. Method::Totally 120 cases of cervical spondylotic radiculopathy with wind-cold-dampness syndrome were randomly divided into two groups: traditional Chinese medicine(TCM) group and combination group, with 60 cases in each group. The TCM group was treated with Guige Lingxian Tang 150 mL/time, twice a day. The combination group was treated with moxibustion at neck Jiaji acupoint in addition to the therapy of the TCM group, 30 minutes/time, once a day. Both groups were treated for 8 weeks. CSR 20 subscale score, SF-36 scale score, typical symptoms and signs remission time were recorded. The total effective rate and the cure rate were recorded after treatment. Serum levels of leukotriene B4(LTB4), leukotriene C4(LTC4), leukotriene D4 (LTD4), chitinase protein 40 (YKL-40), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay(ELISA) before and after treatment. Result::The total effective rate was 98.11%(52/53), and the cure rate was 43.39%(23/53) in the combination group, which were higher than 91.04%(61/67) and 20.89%(14/67) in the TCM group (P<0.05). Compared with the TCM group, the scores of CSR 20 subscale and SF-36 scale in combination group were increased (P<0.05), and the remission time of typical symptoms and signs was shortened. Serum levels of LTB4, LTC4, LTD4, YKL-40, IL-1β and TNF-α were decreased (P<0.05). Conclusion::Moxibustion at neck Jiaji acupoint combined with Guige Lingxian decoction is effective in treating CSR of wind-cold-dampness arthralgia syndrome, which is worthy of clinical promotion. Its mechanism may be related to the inhibition of the expression of LT, and the reduction of the content of IL-1β and TNF-α in serum, thus promoting the repair of cervical cartilage and increasing the pain threshold.

Pathogenic role leukotriene B4 in lung injury induced by lung-protective mechanical ventilation in rabbits / 南方医科大学学报

OBJECTIVE@#To elucidate the pathogenic role of leukotriene B4 (LTB4) in pulmonary hyper-permeability and inflammation induced by lung-protective mechanical ventilation (LPMV) in rabbits.@*METHODS@#Thirty-two healthy Japanese white rabbits were randomized into 4 groups for treatment with vehicle or bestatin (a leukotriene A4 hydrolase inhibitor that inhibits LTB4 production) administered intragastrically at the daily dose of 8 mg/kg for 5 days, followed by sham operation (group S and group BS, respectively, in which the rabbits were anesthetized only) or LPMV (group PM and group BPM, respectively, in which the rabbits received ventilation with 50% oxygen at a tidal volume of 8 mL/kg for 5 h). The concentrations of LTB4 and cyclic adenosine monophosphate (cAMP) in the lung tissues were analyzed by ELISA. cAMP content, protein kinase A (PKA) protein expression and the Rap1-GTP protein to total Rap1 protein ratio were determined to assess the activities of cAMP/PKA and Rap1 signaling pathways. The lung injury was evaluated by assessing lung permeability index, lung wet/dry weight ratio, polymorphonuclear leukocyte (PMN) count in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity and lung histological scores.@*RESULTS@#None of the examined parameters differed significantly between group S and group BS. All the parameters with the exception of lung histological score increased significantly in group PM and group BPM as compared to those in group S (@*CONCLUSIONS@#LPMV can induce LTB4 overproduction to down-regulate cAMP/PKA and Rap1 signaling pathways in the lungs of rabbits, which results in lung hyper-permeability and inflammation. Bestatin can inhibit LTB4 production in the lungs to protect against LPMV-induced lung hyper-permeability and inflammation.

Leukotriene B4 in equine asthma syndrome: what do we know so far? / Leucotrieno B4 na síndrome asmática equina: o que sabemos até o momento?

The term "equine asthma syndrome" (EAS) was recently proposed due to the resemblance of the equine disease to human asthma. Leukotrienes cause constriction of the bronchi, especially in the lower airways and increase mucus secretion in the respiratory system. Leukotriene B4 (LTB4) has been discovered as a strong chemotactic factor, which plays a role in neutrophil migration. The immunologic background of EAS remains not fully elucidated despite many studies on the pathogenesis. This study aimed to evaluate the LTB4 concentration in the bronchoalveolar lavage fluid (BALF) of horses with and without pulmonary inflammatory disease. Thirty-five mixed breed horses were studied and LTB4 was determined by using specific ELISA Kit. The horses were grouped by 2 different criteria for statistical analysis of data: 1) according to the values for BALF citology and 2) according to the detection of LTB4 in BALF. There was significant difference of effect of age on the LTB4 detection in equine BALF. Younger animals were the majority where it was possible to detect LTB4 values in LBA. In conclusion, there was an effect of age on the detection of LTB4 in equine BALF, where LTB4 levels were more easily detected in younger animals than older animals and the results of this study raise the possibility of considering future studies with the objective of establishing the real role and the best moment to detect LTB4 in BALF of the equine asthma syndrome.(AU)

Recentemente, o termo "síndrome da asma equina" (SAE) foi proposto devido à semelhança da doença equina à asma humana. Os leucotrienos causam constrição dos brônquios, especialmente nas vias aéreas posteriores e aumentam a secreção de muco no sistema respiratório. O leucotrieno B4 (LTB4) foi descoberto como um forte fator quimiotático, que desempenha um papel na migração de neutrófilos. O fundo imunológico do SAE permanece não completamente elucidado apesar de muitos estudos sobre a patogênese. Este estudo teve como objetivo avaliar a concentração de LTB4 no lavado broncoalveolar (LBA) de equinos com e sem doença inflamatória pulmonar. Trinta e cinco cavalos de raças mistas foram estudados e o LTB4 foi determinado usando o kit ELISA específico. Os animais foram agrupados por dois critérios diferentes para análise estatística dos dados: 1) de acordo com os valores para citologia do LBA e 2) de acordo com a detecção do LTB4 no LBA. Houve diferença significativa do efeito da idade na detecção do LTB4 no LBA equino. Os animais mais jovens foram a maioria onde foi possível detectar os valores de LTB4 no LBA. Em conclusão, houve um efeito da idade na detecção de LTB4 em LBA equino, onde os níveis de LTB4 foram mais facilmente detectados em animais jovens do que em animais mais velhos e foi possível detectar a concentração de LTB4 no LBA equino e os resultados deste estudo levantam a possibilidade de considerar futuros estudos com o objetivo de estabelecer o real papel e o melhor momento para detectar LTB4 no LBA da síndrome asmática equina.(AU)

Efectos adversos neuropsiquiátricos de montelukast / Neuropsychiatric adverse effects of montelukast / Reações psiquiátricas adversas do montelucaste

Resumen: En la última década se ha registrado un aumento en la prescripción de antileucotrienos, en particular montelukast. A partir del año 2007 comenzaron los primeros reportes efectos adversos de esfera neuropsiquiátrica en la edad pediátrica. Los efectos reportados incluían trastornos del sueño y del humor hasta una posible asociación con ideación suicida y suicidio consumado. En el presente trabajo se realiza una revisión de la seguridad de montelukast tema con objetivo de establecer o descartar una eventual asociación entes los fenómenos mencionados y la administración de antileucotrienos.

Summary: In the last decade there has been an increase in the prescription of antileukotrienes, specifically montelukast. The first pediatric reports discussing adverse neuropsychiatric effects go back to 2007. The reported effects included a range from sleep and mood disorders, to even a possible association with suicidal ideation and consummated suicide. In the present paper we carry out a review of the safety of using montelukast in order to confirm or rule out an eventual association between such adverse effects and the administration of antileukotrienes.

Resumo: Na última década, houve um aumento na prescrição de antileucotrienos, em particular do montelucaste. A partir de 2007, começaram a surgir os primeiros reportes relativos aos efeitos neuropsiquiátricos adversos na idade pediátrica. Os efeitos relatados incluíram desde distúrbios do sono e do humor até uma possível associação com ideação suicida e suicídio consumado. No presente paper realizamos uma revisão da segurança no uso do montelucaste com o objetivo de confirmar ou descartar uma eventual associação entre os seus efeitos adversos e a administração de antileucotrienos.

Advances on the mechanism of leukotrienes in children with airway allergic inflammation / 国际儿科学杂志

The guideline for "allergic rhinitis and its impact on asthma" in 2001 pointed out that allergic rhinitis and asthma are " one airway, one disease" , both in terms of epidemiology, histopathology, pathophysiology and immune mechanisms, which was a certain similarity.Leukotrienes which as an inflammatory mediator play an important role in the development of upper and lower airway allergic diseases.

Clinical effect of mometasone furoate nasal spray combined with montelukast in the treatment of children with obstructive sleep apnea hypopnea syndrome / 中国基层医药

Objective@#To explore the clinical effect of mometasone furoate nasal spray combined with montelukast in the treatment of children with obstructive sleep apnea hypopnea syndrome (OSAHS), and to analyze its feasibility and clinical application value.@*Methods@#From August 2017 to March 2019, 64 children with OSAHS who were treated in the People's Hospital of Jinhua were selected in the study.According to the random number table method, they were divided into the observation group and the control group, with 32 cases in each group.The observation group was treated with mometasone furoate nasal spray combined with montelukast for 12 weeks.The control group was treated with surgical treatment to remove hypertrophic tonsils and/or adenoids.The clinical symptom scores, polysomnography(PSG) monitoring index, adenoid and tonsil size index, and the efficacy after 12 weeks of treatment were compared between the two groups.@*Results@#There were no statistically significant differences in symptom scores and minimum arterial oxygen saturation(LSaO2) between the two groups before treatment(all P>0.05). After treatment, the symptom scores and LSaO2 of the control group were (1.90±0.53)points and (94.74±1.54)%, respectively, which of the observation group were (4.00±1.50)points and (85.34±10.57)%, respectively, the differences between the two groups were statistically significant(t=-7.416, 4.972, all P<0.05). There were statistically significant differences in the apnea hypopnea index(AHI) and obstructive apnea index(OAI) between the two groups(all P<0.05). After treatment, the A/N of the adenoids in the observation group was significantly decreased, and the difference in the tonsil classification was statistically significant(Z=-2.602, P<0.05). The effective rate of the observation group was 56.25%(18/32), which was significantly lower than that of the control group [100.00%(32/32)], the difference was statistically significant(χ2=17.920, P<0.05).@*Conclusion@#In summary, non-surgical treatment can alleviate OSAHS-related symptoms, reduce the size of tonsils and adenoids, and achieve the purpose of remission or cure.Non-surgical treatment can be selected when patients' families are reluctant to choose surgical treatment.

Effect of mizolastine conventional dose combined with momestasone furoate in the treatment of allergic rhinitis caused by pollen allergy / 中国基层医药

Objective To compare the effects of mizolastine intensive dose and mizolastine conventional dose+momestasone furoate on symptom score and laboratory index of patients with allergic rhinitis caused by pollen allergy.Methods From June 2016 to January 2018,one hundred and fifty allergic rhinitis patients caused by pollen allergy were chosen in the First People＇s Hospital of Taizhou and randomly divided into two groups according to the digital table,with 75 patients in each group.A group was treated with mizolastine intensive dose scheme,and B group was treated with mizolastine conventional dose +momestasone furoate. The short -term efficacy,rhinitis symptoms score,the levels of histamine,leukotrienes C4,IL-6,IL-8 and TNF-α before and after treatment,the incidence of adverse reactions and daily treatment cost of the two groups were compared.Results The short-term efficacy of B group was significantly better than that of A group(93.33% vs.81.33% ,χ2 =9.15,P<0.05).The rhinitis symptoms scores of B group[(0.49 ± 0.19)points,(1.02 ± 0.20) points,(0.95 ± 0.28) points,(0.84 ± 0.20)points] after treatment were significantly lower than those of A group [(0.87 ± 0.21) points,(1.40 ± 0.24) points,(1.63 ± 0.36)points,(1.19 ± 0.27) points] and before treatment[(3.13 ± 1.06) points,(2.88 ± 0.57) points,(2.81 ± 0.79)points,(2.85 ± 0.61)points](t=2.45,2.71,2.66,2.89,3.78,3.75,3.44,4.53,all P<0.05).The levels of histamine,leukotrienes C4,IL-6,IL-8 and TNF-α of B group[(15.76 ± 3.54) mg/L,(12.17 ± 3.58) mg/L, (1.23 ± 0.19)mg/L,(3.27 ± 0.62)mg/L,(3.96 ± 1.05)mg/L] after treatment were significantly lower than those of A group [(19.58 ± 5.25) mg/L,(15.44 ± 4.14) mg/L,(1.96 ± 0.33)mg/L,(5.40 ± 0.88) mg/L,(5.01 ± 1.40)mg/L] and before treatment[(24.57 ± 7.67) mg/L,(18.90 ± 6.33) mg/L,(2.58 ± 0.54) mg/L,(7.66 ± 1.17)mg/L,(6.81 ± 1.67)mg/L](t=2.31,2.50,2.53,2.39,3.05,3.60,3.10,3.57,3.90,all P<0.05).There was no statistically significant difference in the incidence rate of adverse reactions between the two groups ( P >0.05).The daily treatment cost of B group after treatment was significantly less than that of A group and before treatment[(7.56 ± 1.02)CNY vs.(6.88 ± 0.80)CNY,t=3.12,P<0.05].Conclusion Compared with mizolas-tine intensive dose scheme,mizolastine conventional dose + momestasone furoate in the treatment of patients with allergic rhinitis caused by pollen allergy can efficiently relieve the nasal symptoms, down - regulate the levels of histamine,leukotriene C4 and inflammatory cytokines,reduce the treatment cost and has the approved safety.

Comparison of effect of desloratadine citrate disodium tablets and loratadine dispersible tablets in treatment of patients with allergic rhinitis / 中国基层医药

Objective To compare the efficacy and adverse reactions of desloratadine citrate disodium tablets and loratadine dispersible tablets in treatment of patients with allergic rhinitis,and their influence on leukotriene B4(LTB4),interleukin-4 (IL-4),interleukin-10 (IL-10) and interferon gamma (INF-γ).Methods From June 2015 to June 2016,a total of 110 patients with allergic rhinitis in the Second People's Hospital of Cangnan County were selected and randomly divided into control group and observation group according to the digital table,with 55 cases in each group.The control group was given loratadine dispersible tablets,while the observation group was given desloratadine citrate disodium tablets.Both two groups were treated for 14 days.The clinical efficacy,adverse reactions and changes of LTB4,IL-4,IL-10,INF-γ levels before and after treatment were compared between the two groups.Results The total effective rate of the observation group was 94.5 ％,which was significantly higher than 80.0％ of the control group(x2 =6.310,P ＜ 0.05).The incidence rate of adverse reactions in the observation group was 16.4％,which was similar to 20.0％ in the control group.Before treatment,there were no statistically significant differences in LTB4,IL-4,IL-10,INF-γ levels between the two groups (all P ＞ 0.05).After 2 weeks of treatment,the levels of LTB4,IL-4,IL-10 and INF-γ in the observation group were (67.74 ±10.15) ng/L,(52.37 ± 5.12) μg/L,(81.26 ± 11.78) μg/L,(94.47 ± 7.87) μg/L,respectively,which in the control group were (80.32 ± 9.97) ng/L,(62.95 ± 5.45) μg/L,(96.32 ± 11.57) μg/L,(86.74 ± 7.63) μg/L,respectively,there were statistically significant differences between the two groups (t =7.124,5.262,4.654,3.718,all P ＜ 0.05).Conclusion Both desloratadine citrate disodium tablets and loratadine dispersible tablets can effectively treat patients with allergic rhinitis,improve the symptoms and physical signs,reduce the levels of LTB4,IL-4 and IL-10,increase the level of INF-γ,and the adverse reactions are less and slight,but the efficacy of desloratadine citrate disodium tablets is better than loratadine dispersible tablets.

Advances on the mechanism of leukotrienes in children with airway allergic inflammation / 国际儿科学杂志

The guideline for"allergic rhinitis and its impact on asthma" in 2001 pointed out that aller-gic rhinitis and asthma are " one airway, one disease", both in terms of epidemiology, histopathology, pathophysiology and immune mechanisms, which was a certain similarity. Leukotrienes which as an inflamma-tory mediator play an important role in the development of upper and lower airway allergic diseases.

NO donor V-PYRRO/NO inhibits expression of leukotriene C4 synthase in early stage of hepatic ischemia/reperfusion injury in rats / 基础医学与临床

Objective To explore the mechanism underlying a selective liver nitric oxide donor V-PYRRO/NO effects on the gene expression of LTC4 synthase(LTC4S) during hepatic ischemia reperfusion(I/R).Methods Adult male SD rats were divided into 3 groups:control group(sham),ischemic-reperfusion group(I/R) and V-PYRRO/NO group. Liver subjected to 1 hour of partial hepatic ischemia followed by 5 hours of reperfusion, saline or V-PYRRO/NO[1.06 mmol/(kg·h)] administered intravenously. The mRNA expression of LTC4S in rat liver was examined by RT-PCR method,the protein expressions of NF-κB p65,p50 and IκB in liver cell lysates and nu-clear extracts were detected by Western blot analysis. Results Hepatic mRNA expression of LTC4S in I/R group was higher than that in sham group(P<0.05), whereas it was lower in V-PYRRO/NO group than that in I/R group(P<0.05). Moreover,compared with sham group,the protein expressions of NF-κB p65 and p50 in nucleus extract were markedly increased(P<0.01) but significantly decreased in cytoplasm(P<0.01) in I/R group. V-PYRRO/NO reversed completely the increase of these protein expressions in nucleus extract (P<0.05) and the decrease of them in cytoplasm(P<0.01,P<0.05) during hepatic I/R injury.However,IκB protein in three groups did not change. Immunohistochemistry staining revealed that no marked positive staining for NF-κB p65 was found in sham liver,I/R liver exhibited strong cytoplasmic and nuclear positive staining for NF-κB p65,but V-PYRRO/NO I/R group liver presented slight cytoplasmic and nuclear staining. Conclusions V-PYRRO/NO may down-regulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκB during hepatic I/R injury.