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)

The clinical significance of the combined detection of IL-6 and LTB4 on early diagnosis of children with allergic purpura and its effect on prognosis / 国际检验医学杂志

Objective To investigate the clinical significance of interleukin-6 (IL-6) and leukotriene B4 (LTB4) in the early diagnosis of allergic purpura(HSP) in children and its effect on prognosis.Methods A total of 68 children with Henoch-Schonlein purpura enrolled in our hospital from May 2014 to May 2016 were selected.The levels of IL-6 and LTB4 in the early stage and early recovery stage of children were detected.The significance of early diagnosis and the impact on prognosis were analyzed.Results Compared with the control group,the levels of IL-6 and LTB4 in acute and early recovery stage of children with Henoch-Schonlein purpura were significantly higher(P＜0.05),and those in the acute stage of children were higher than those in the early recovery stage(P＜0.05).The higher the level of IL-6 and LTB4 in the serum,the greater the possibility of renal damage in patients,and the difference was statistically significant (P＜0.05).The higher the level of serum IL-6 and LTB4,the higher the cure rate(P＜0.05) and the lower the recurrence rate(P＜0.05).The AUC of the combined detection of HSP was 0.894 and the sensitivity was 0.811,which were better than those of IL-6 and LTB4(P＜0.05).Conclusion Combined detection of IL-6 and LTB4 is of great clinical significance in the early diagnosis and prognosis of HSP.

The value of combined detection of LTB4 and LTFA in early diagnosis of renal involvement in children with henoch schonlein purpura and its influence on prognosis / 国际检验医学杂志

Objective To investigate the value of leukotriene B4(LTB4)and leukotriene E4(LTFA)in early diagnosis of renal involvement in children with Henoch Schonlein purpura(HSPN)and its influence on prognosis.Methods A total of 185 children with HSPN were enrolled in our hospital from January 2014 to October 2016.A total of 50 healthy children were selected as control group at the same period.The serum levels of LTB4 and LTFA in all subjects were detected,and their value in early diagnosis of HSPN and its influence on prognosis were analyzed.Results Compared with the control group,the serum levels of LTB4 and LT-FA in children with HSPN were significantly higher(P<0.05),the contents were 987.6 ng/L and 896.3 ng/L,respectively.The AUC of the combined detection of HSPN was 0.899 and the sensitivity was 0.810,which was better than that of LTB4 and LTB4 alone(P<0.05).The average follow-up was(28.4 ± 10.3)months,with grade A prognosis in 133 cases(71.9%),B grade in 47 ca-ses(25.4%),and C grade in 5 cases(2.7%).The rank sum test showed,the prognosis of children with LTB4<987.6 ng/L was better than that of children with LTB4≥987.6 ng/L,the prognosis of children with LTFA<896.3 ng/L was better than that of children with LTFA≥896.3 ng/L.Spearman analysis showed that the content of LTB4 and LTFA was negatively correlated with prognosis(Rs= -0.693 and -0.637,P<0.05).The higher contents of LTB4 and LTFA,the worse the prognosis.Conclusion Combined detection of LTB4 and LTFA has important clinical significance for early diagnosis and prognosis of HSPN.

Effects of Kechuanning Capsules on Airway Inflammatory Cells and Infammatory Mediators in Patients with Stable Chronic Obstructive Pulmonary Disease / 中国中医药信息杂志

Objective To observe the effects of Kechuanning capsules on airway inflammation cells and inflammatory mediators in patients with COPD.Methods Totally 110 patients with stable COPD were randomly divided into therapy group and control group, 55 cases in each group. Both of the groups were given compound ipratropium bromide solution for inhalation, at the same time, patients in the therapy group took Kechuanning capsules orally, 4 softgels each time, 3 times a day, and patients in the control group took the same amount of placebo capsules. The treatment lasted three months. Differential counting of inflammatory cells and levels of inflammatory factors in serum and sputum supernatant were observed.Results In terms of differential counting of inflammatory cells, the sputum neutrophils of the therapy group decreased significantly (P0.05) in two groups before and after treatment;IL-6, IL-8, LTB4 levels in the sputum supernatant of the therapy group were lower than those before treatment (P<0.05), with statistical significance compared with the control group (P<0.05). Conclusion Kechuanning capsules have an obvious inhibitory effect on airway inflammatory cells in patients with stable COPD as well as the release of inflammatory mediators.

Experimental study on the mechanism of anti-anaphylaxis effect of ethyl acetate extraction of Jing-fang powder / 中国药学杂志

OBJECTIVE: To investigat the mechanism of anti-anaphylaxis effect of Jing-fang powder(traditional Chinese medicines) by using initiative systemic anaphylaxis model in mice. METHODS: The model of initiative systemic anaphylaxis in mice was induced by intraperitoneal injection with ovalbumin and DPT vaccine, and the ethyl acetate extraction of Jing-fang powder was intragastricly administrated for 14 d. ELISAs methods were used to measure the levels of total IgE and LTB4 in serum, and the levels of NO, iNOS and LTB4 in lung tissues in model mice. Ultraviolet spectrophotometry was used to measure the PGE2 level in lung tissue, and the index of thymus and spleen were also evaluated. RESULTS: At the dose of 6.67 g·g-1, the ethyl acetate extraction of Jing-fang powder decreased the index of thymus and spleen(P<0.05), as well as suppressed the production of total IgE and LTB4 in serum(P<0.05, and reduced the levels of NO, iNOS, LTB4 and PGE2 in lung tissue in model mice(P<0.05). Meanwhile, the extraction also suppressed the activity of iNOS in lung tissue under the dose of 6.67 and 10.01 g·g-1(P<0.05). CONCLUSION: These results suggest that the ethyl acetate extraction of Jing-fang Powder has potential anti-allergic effect, which the mechanism may be related to reduce the production of IgE, and inhibit the release of metabolic products of arachidonic acid, for example LTB4 and PGE2, and decrease the release of inflammatory allergy mediators NO.

Amelioration of inflammatory responses by Chlorogenic acid via suppression of pro-inflammatory mediators.

The premise of the present investigation was to evaluate the detailed anti-inflammatory properties of chlorogenic acid (CGA) and to delineate the possible mode of action. To explore the anti-inflammatory profile, we evaluated the effect of CGA on TNF-alpha expression (in vitro); carrageenan induced rat paw edema and carrageenan induce pleurisy (in vivo). In our studies, CGA significantly inhibited the TNF-alpha expression, paw edema and antioxidant enzymes in livers of rats in pre-treatment schedule but failed to exert any effect when administered 1 h after carrageenan injection. CGA was also found to be safe, as confirmed by the results of acute toxicity studies and MTT assay. CGA also caused reduction in total leucocytes count most probably by inhibiting neutrophils, but could not alter mononuclear cells count in carrageenan induced pleurisy. Inhibition of exudation was evidenced by the less exudate formation in CGA treated animals, which may be due to decrease in vascular permeability which was further confirmed in acetic acid induced vascular permeability model in mice where significant decrease in vascular permeability was observed. CGA was highly effective in reducing the arachidonic acid metabolites, nitric oxide and pro-inflammatory cytokines production in a dose dependent manner and in some conditions effect observed was almost comparable to ibuprofen. Result of the present investigation shows the anti-inflammatory effects of CGS in different models.

Up-regulation of BLT2 is critical for the survival of bladder cancer cells

The incidence rates of urinary bladder cancer continue to rise yearly, and thus new therapeutic approaches and early diagnostic markers for bladder cancer are urgently needed. Thus, identifying the key mediators and molecular mechanisms responsible for the survival of bladder cancer has valuable implications for the development of therapy. In this study, the role of BLT2, a receptor for leukotriene B4 (LTB4) and 12(S)-hydroxyeicosatetraenoic acid (HETE), in the survival of bladder cancer 253J-BV cells was investigated. We found that the expression of BLT2 is highly elevated in bladder cancer cells. Also, we observed that blockade of BLT2 with an antagonist or BLT2 siRNA resulted in cell cycle arrest and apoptotic cell death, suggesting a role of BLT2 in the survival of human bladder cancer 253J-BV cells. Further experiments aimed at elucidating the mechanism by which BLT2 mediates survival revealed that enhanced level of reactive oxygen species (ROS) are generated via a BLT2-dependent up-regulation of NADPH oxidase members NOX1 and NOX4. Additionally, we observed that inhibition of ROS generation by either NOX1/4 siRNAs or treatment with an ROS-scavenging agent results in apoptotic cell death in 253J-BV bladder cancer cells. These results demonstrated that a 'BLT2-NOX1/4-ROS' cascade plays a role in the survival of this aggressive bladder cancer cells, thus pointing to BLT2 as a potential target for anti-bladder cancer therapy.

Low-dose UVB irradiation stimulates matrix metalloproteinase-1 expression via a BLT2-linked pathway in HaCaT cells

Skin exposure to low-dose ultraviolet B (UVB) light up-regulates the expression of matrix metalloproteinase-1 (MMP-1), thus contributing to premature skin aging (photo-aging). Although cyclooxygenase-2 (COX-2) and its product, prostaglandin E2 (PGE2), have been associated with UVB-induced signaling to MMP expression, very little are known about the roles of lipoxygenases and their products, especially leukotriene B4 (LTB4) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), in MMP-1 expression in skin keratinocytes. In the present study, we demonstrate that BLT2, a cell surface receptor for LTB4 and 12(S)-HETE, plays a critical role in UVB-mediated MMP-1 upregulation in human HaCaT keratinocytes. Moreover, our results demonstrated that BLT2-mediated MMP-1 upregulation occurs through a signaling pathway dependent on reactive oxygen species (ROS) production and the subsequent stimulation of ERK. Blockage of BLT2 via siRNA knockdown or with the BLT2-antagonist LY255283 completely abolished the up-regulated expression of MMP-1 induced by low-dose UVB irradiation. Finally, when HaCaT cells were transiently transfected with a BLT2 expression plasmid, MMP-1 expression was significantly enhanced, along with ERK phosphorylation, suggesting that BLT2 overexpression alone is sufficient for MMP-1 up-regulation. Together, our results suggest that the BLT2-ROS-ERK-linked cascade is a novel signaling mechanism for MMP-1 upregulation in low-dose UVB-irradiated keratinocytes and thus potentially contributes to photo-aging.

Therapeutic Effect of Arbutin Combined with Glycyrrhizin on Immune-inflammation / 中国中医药信息杂志

Objective To study the therapeutic effect of arbutin combined with glycyrrhizin on immune-inflammation. Methods The effect of arbutin combined with glycyrrhizin on adjuvant arthritis and on oxzolone induced mice ear swelling were investigated. PGE2 level in inflammatory tissue and LTB4 content from peritoneal macrophage of rat treated with arbutin and glycyrrhizin were determined. Results Arbutin combined with glycyrrhizin could inhibit Freund's complete adjuvant induced rat primary and secondary foot swelling. The combined group could also inhibit oxazolone induced mice ear swelling and decrease CD4+ T cell in blood. Compared with control group,PGE2 level in combined group was remarkable lower,and there was no difference between combined group and GL 400 mg/kg group. Arbutin combined with glycyrrhizin could inhibit LTB4 release from rat peritoneal macrophage. Conclusion Arbutin and glycyrrhizin has synergetic therapeutic effect on immune-inflammation.

Effect of Pingchuanning on the Levels of LTB4 and sICAM-1 of Guinea Pigs with Asthma / 中国中医药信息杂志

Objective To observe the effect of Pingchuanning on the levels of LTB4 and sICAM-1 of guinea pigs with asthma. Methods The model guinea pigs of asthma were sensitized with ovalbumin (OVA),the changes of the delitescence of asthma was observed. The levels of LTB4 in serum and sICAM-1 in bronchoalveolar lavage fluid (BALF) were also observed by means of enzyme-linked immunosorbent (ELISA). Result Comparing with the model group,the delitescence of asthma was obviously prolonged in guinea pigs treated by Pingchuanning. The levels of LTB4 and sICAM-1 of guinea pigs with asthma treated by Pingchuanning were significantly lowered (P

The Effects of Spa Therapy on Asthma. Relationship to the generation of leukotrienes B4 (LTB4) and C4 (LTC4) and bronchial hyperresponsiveness / 日本温泉気候物理医学会雑誌

Effects of spa therapy on asthma were studied in 64 patients with asthma in relation to the generation of leukotrienes B4 (LTB4) and C4 (LTC4) and bronchial hyperresponsiveness. 1. The efficacy of spa therapy was marked in 12 (18.8%), and moderate in 45 (70.3%) of 64 patients with asthma, and slight or no efficacy of the therapy was observed in the residual 7 patients (10.9%). 2. Bronchial hyperresponsiveness to methacholine was the highest in patients with slight or no efficacy of spa therapy, however, there were no significant differences among the three groups classified by clinical efficacy. 3. The generation of LTC4 by leucocytes was significantly higher in patients with slight or no efficacy compared with the generation in those with marked (p<0.01) and moderate efficacy (p<0.001). However, there were no significant differences in the generation of LTB4 among them. 4. The generation of LTC4 before spa therapy significantly decreased in patients with marked (p<0.001) and moderate efficacy (p<0.01) after spa therapy, but not in those with slight or no efficacy. The generation of LTB4 was not significantly different before and after spa therapy among patients with marked, moderate, and slight or no efficacy. These results show that the efficacy of spa therapy for patients with asthma is closely related to the generation of LTC4 by leucocytes, and that the generation of LTC4 significantly decreases after spa therapy in patients with spa efficacy.

Analysis of TMJ status in the patients with mandibular fractures: preliminary study arthroscopic examination, histomorphology and joint fluid analysis

The purpose of this study is to validate the potential etiologic factors for temporomandibular disorder(TMD). TMJ arthroscopic examination was performed in upper joint compartment of 32 joints from 20 patients with mandibular fractures. Synovial fluid was collected from the upper joint space during pumping manipulation with normal saline. Cytologic smearing and histomorphologic exam of synovial fluid were performed in 15 joints. Prostaglandin E2(PGE2) concentration was measured in 11 joints. Leukotriene B4(LTB4) concentration was measured in 8 joints. There were several arthroscopic variables such as ecchymosis, fibrillation, and adhesion. Histomorphologic exam showed a variety of findings such as bloody smears, cellular cluster, degenerated cells and cartilage, undifferentiated crystal. Mean PGE2 concentrations were 316.5 pg/ml. Mean LTB4 concentrations were 45.9pg/ml. This study demonstrated a variety of findings on inflammatory and degenerative changes of TMJ. Because acute trauma such as mandibular fracture is a major etiologic factor in cartilage degradation and biochemical and intraarticular pathology, clinicians must identify and address TMJ signs and symptoms during follow-up periods in the long term.

The Effect of DA-6034, Eupatilin Derivatives of Flavonoids, on the Rats with Trinitrobenzene Sulfonic Acid (TNBS) - Induced Colitis / 대한내과학회지

OBJECTIVE: In traditional medicine, Artemisia capillaris has been used for treatment of chronic diarrhea. Previously we found Artemisia capillaris had an effect on rats with TNBS-induced colitis. Eupatilin, a kind of flavonoids, may be a probable effective component. To evaluate the effect of a eupatilin derivative compound DA-6034 on the rat with TNBS-induced colitis, we perfomed this study. METHODS: Colitis was induced with 1ml of 50 mg/ml TNBS mixed with 60 % ethanol (vol/vol) in Sprague- Dawley rats. From the next day, 1ml methylcellulose, 1 mg/kg prednisolone, 0.3 or 3 mg/kg of DA-6017 and DA-6034 were administered through rectum once daily for 2 weeks. At 2days, 1week, and 2weeks later, we evaluated the effect by gross damage score (0-10) and measured myeloperoxidase, PGE2, and LTB4 from the damaged mucosa. RESULTS: The mean gross damage scores of prednisolone and 3 mg/kg of DA-6034 groups were significantly lower than that of a placebo group at 2weeks (0.8, 0.9 vs. 4.0, p<0.05). Myeloperoxidase activities also seemed to be lower in those effective groups but were not statistically significant. LTB4 levels were lower in prednisolone and, 0.3 and 3 mg/kg of DA-6034 groups than in a placebo group at 2weeks (7.91, 7.23, and 7.13 vs. 13.90 ng/mg protein, p<0.05). PGE2 levels were decreased in prednisolone and 0.3 mg/kg of DA-6034 groups at 2days. DA-6017 showed no effects. CONCLUSIONS: Eupatilin derivative compound, DA- 6034 was effective in rats with TNBS-induced colitis. In that LTB4 level is lowered with some decrease of PGE2 level, this agent probably has an inhibitory effect on arachidonic acid metabolism.

Ia + Keratinocyte / 대한피부과학회지

Ia antigen (HLA-DR in rnan) is confined to the Langerhans cells and indeterminate cells in the normal epidermis in man. However the keratinocyte express la antigen in a variety of dermatoses. IFN-r (irnmune interfcron), known as macrophage activating factor, has been shown to induce Ia antigen expression in a wide variety of cell types. However the Ia antigen induced by 1FN-r is inhibited PGE2, a product of cyclooxygenase pathway of arachidonic acid metabolism. LTB4, a product of lipoxygenase pathway, can replace the IL-2 requirement for IFN-r production in the lymphocytes. There are three main morphalogical patterns of Ia antigen staining in the epidennis. Staining of the basal cells, staining in the mid epidermis in Malphigian layer and staining throughout the epidermis. The staining of Ia' keratinocyte was found to be confined to the lesional area of contact hypersensitivity reaction, graft vs host disease, and lichen planus. la+staining to extend beyond the lesional area was also seen in the study on turberculosis and leporsy.

THE DETERMINATION OF THE CONTENT OF LTB_4 IN SKIN INCISIONS / 中国法医学杂志

The Content of LT B_4 in the edge of 36 SD rats were determined by HPLC. It was found that the content of LTB_4 in the anternortem wounds is markedly increased, and has certain linear relationship with time of injury within one hour. No increasing of LTB_4 could be found in the postmortem wounds. It indicates that it is very valuable to estimate time of injury by determining LT B_4 content in wound edge, The content of LTB_4 in wound edge can be determined rapidly and accurately with HPLC.