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.

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.

The therapeutical effect and mechanism of tiotropium bromide in patients with chronic obstructive pulmonary disease / 中国医师进修杂志

Objective To investigate the therapeutical effect and mechanism of tiotropium bromide in patients with stable phase midrange and severe chronic obstructive pulmonary disease (COPD). Methods Seventy-eight patients with stable phase midrange and severe COPD were selected, and they were divided into observation group (40 cases) and control group (38 cases) according to treatment method. All patients were given conventional treatment. The patients in observation group were given tiotropium bromide, and the patients in control group were given terbutaline according to the needs for 12 weeks. The changes of dyspnea, 6 min walking distance, pulmonary function, leukotrienes C4 (LTC4), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-ɑ) before and after treatment, and drug adverse reaction were observed. Results The dyspnea score after treatment in observation group was significantly lower than that in control group:(2.9±0.5) scores vs. (3.5±0.7) scores, 6 min walking distance in observation group was significantly longer than that in control group: (427.67±70.36) m vs. (365.41±61.42) m, forced expired volume in 1 second (FEV1) and FEV1/forced vital capacity in observation group were significantly higher than those in control group:(1.76±0.89) L vs. (1.29±0.53) L and (67.43±9.52)%vs. (56.32±8.51)%, LTC4, IL-8 and TNF-αlevels in observation group were significantly lower than those in control group: (397.41± 198.57)μg/L vs. (1 181.95±207.54)μg/L, (434.81±176.05) ng/L vs. (823.37±165.43) ng/L and (0.15±0.02) ng/L vs. (0.25 ±0.02) ng/L, there were significant differences ( P<0.01). Pearson correlation analysis result showed that serum LTC4 level was negatively related to FEV 1 (r=-0.578, P=0.024);and the serum IL-8 level was negatively related to FEV1 (r=-0.542, P=0.019). There was no obvious drug adverse reaction in the two groups. Conclusions Tiotropium bromide can significantly improve the clinical manifestations in patients with COPD. Tiotropium bromide may take effects by blocking various inflammatory factors release in the stable phase of COPD.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cgamma1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-kappaB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

The relationship between LTC4S, ALOX5 genetic polymorphism and clinical efficacy of leukotriene receptor modula-tors in children with asthma / 临床儿科杂志

Objective To study the effect of genetic polymorphism of leukotriene C4 synthase (LTC4S) and 5-lipoxy-genase (ALOX5) on efifcacy of leukotriene receptor antagonist (LTRA) in children with moderate persistent asthma. Methods Seventy-two children with moderate persistent asthma who visited the out-patient clinic of Shanghai Children’s Medical. Center from June 2011 to June 2013 were divided into two groups, each of which ifrst had ICS or LTRA+ICS for twelve weeks and then had the other for another twelve weeks. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to assess the genetic polymorphism of LTC4S RS730012 and ALOX5 RS2115819. Pulmonary function, clinical symptoms and C-ACT score were evaluated before and after treatment. Results After the treatment with LTRA, 75%forced expiratory lfow (FEF75) was improved more signiifcantly in patients with A/C or C/C genotype at LTC4S (RS730012) locus than in patients with A/A genotype. After the treatment with LTRA+ICS, there was no difference of pulmonary function among patients with different genotypes at ALOX5 (RS2115819). Conclusions The SNP of LTC4S (RS730012) is associated with the efifcacy of montelukast in asthmatic patients because of the improvement of small airway function.

Curcumin Inhibits the Activation of Immunoglobulin E-Mediated Mast Cells and Passive Systemic Anaphylaxis in Mice by Reducing Serum Eicosanoid and Histamine Levels

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cgamma1 (PLCgamma1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappaB (NF-kappaB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

Curcumin Inhibits the Activation of Immunoglobulin E-Mediated Mast Cells and Passive Systemic Anaphylaxis in Mice by Reducing Serum Eicosanoid and Histamine Levels

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cgamma1 (PLCgamma1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappaB (NF-kappaB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

Expression of lipoxin A4, leukotriene C4 and lipoxygenase-5 in severe preeclampsia / 中华围产医学杂志

Objective To investigate the expression and clinical significance of lipoxin A4,leukotrienc C4,lipoxygenase-5 in peripheral blood of pregnant women with different types of severe preeclampsia.Methods Forty-five singleton pregnant women who accepted antenatal care and delivered in First Affiliated Hospital of Wenzhou Medical College were enrolled in this study from December 2010 to June 2011.All objects were divided into normal pregnancy group (n=20),early onset severe preeclampsia group (n=10) and late onset severe preeclampsia group (n=15).Enzymelinked immunosorbent assay was used to detect lipoxin A4 and leukotriene C4 levels in peripheral blood.The level of lipoxygenase-5 mRNA in white blood cells was detected by real time fluorescence quantitative reverse transcription-polymerase chain reaction.The differences of lipoxin A4,leukotriene C4 and lipoxygenase-5 mRNA among groups were compared by analysis of variance and LSD-t test;and correlations among their expressions were analyzed by linear regression.Results Lipoxin A4 level in early and late onset severe preeclampsia group was (355.3±116.0) pg/ml and (389.7±117.5) pg/ml,which were both significantly lower than that in normal pregnancy group [(555.0±139.8) pg/ml] (t=-4.03 and-3.77,P＜0.05 respectively).The leukotriene C4 level in early and lateonset severe preeclampsia and normal pregnaney group was (591.3±185.5) pg/ml,(510.3±197.1) pg/ml and (496.9 ± 158.8) pg/ml,no statistical difference were found (F=0.889,P＞0.05) ; neither did the expression of lipoxygenase 5 mRNA,which was 4.2± 1.9 in normal pregnancy group,4.8 ± 2.0 in early onset severe preeclampsia group and 4.4 ± 1.2 in late onset severe preeclampsia group (F=0.311,P＞0.05).There was no correlation among the levels of lipoxin A4,leukotriene C4 and lipoxygenase-5 mRNA in each group (P ＞ 0.05).Conclusions Early and remarkable decreasing of lipoxin A4 level might contribute to the development of early onset severe preeclampsia.

Effects of ATP and LTC4 on hypoxic pulmonary vasoconstriction in isolated rat lungs / 대한마취과학회지

BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary circulation but the mechanism remains elusive. Red blood cells (RBCs) are known to augment HPV and to release more ATP as oxygen content falls. Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. Hence we hypothesized that ATP and leukotrienes are mediators of HPV produced during acute alveolar hypoxia. METHODS: In forty Sprague-Dawley rats, lungs were isolated and perfused. We administered ATP (10 micrometer) to the ATP group (n = 8), the ATP antagonist, suramin (100 micrometer) to the suramin group (n = 8), leukotriene C4 (LTC4, 5 microgram) to the LTC4 group (n = 8), the LTC4 antagonist, LY171883 (20 micrometer) to the LY171883 group (n = 8), and LTC4 (5 microgram) + ATP (10 micrometer) to the LTC4 + ATP group (n = 8) during normoxic ventilation. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. Baseline pulmonary artery pressure change after exposure to each drug and hypoxic pressor response between a period 21% normoxic gas ventilation and that of 3% hypoxic gas ventilation were measured. RESULTS: ATP and LTC4 + ATP increased baseline pulmonary artery pressures but LTC4 did not alter it. ATP did not affect hypoxic pressor response. Suramin, LY171883 and LTC4 + ATP inhibited the pressor response to hypoxia. LTC4 increased hypoxic pressor response. CONCLUSIONS: In isolated rat lungs, HPV may be mediated by ATP and LTC4 appears more likely to be a modulator than a mediator of HPV.

Association study of polymorphism in leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes with phenotype of asthma and clinical parameters in Korean children / 소아과

PURPOSE: Cysteinyl leukotrienes are important proinflammatory mediators in asthma. Recently, it was suggested that a promoter polymorphism in the genes encoding for leukotriene C4 synthase (LTC4S), a key enzyme in the leukotriene synthetic pathway, and cysteinyl leukotriene receptor 1 (CysLTR1) might be associated with aspirin-intolerant asthma. We investigated whether polymorphisms in LTC4S and CysLTR1 genes or their interactions were associated with the asthma phenotype, lung function, or bronchial hyperreactivity (BHR) in Korean children. METHODS: A total of 856 asthmatic children and 254 non-asthmatic controls were enrolled; a skin prick test, lung function test and bronchial provocation test were performed. Of those enrolled, 395 children underwent exercise challenge tests. The LTC4S A(-444)C and CysLTR1 T(+927)C were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of those enrolled, 699 children were classified as having atopic asthma and 277 children, as having exercise-induced asthma (EIA). LTC4S and CysLTR1 polymorphisms were not associated with atopic asthma, EIA, or asthma per se. Lung function and BHR were not significantly different between the wild type (AA or TT) and the variant (AC+CC or TC+CC) genotypes in asthmatics, atopic asthmatics, and EIA (+) asthmatics, while total eosinophil counts were higher in the variant type of LTC4S than in the wild type in atopic asthmatics. There were no associations between the gene-gene interactions of LTC4S and CysLTR1 genotypes and the asthma phenotypes. CONCLUSION: LTC4S A(-444)C and CysLTR1 T(+927)C polymorphisms and their gene-gene interactions are not associated with asthma phenotype, lung function, or BHR in Korean children.

The Effect of Spa Therapy Combined with Dietary Supplementation with n-3 Fatty Acids on Serum Eosinophil Cationic Protein in Asthmatic Subjects / 日本温泉気候物理医学会雑誌

Recently, we have also reported that spa therapy combined with dietary supplementation of perilla seed oil would be effective for patients, and would suppress the generation of leukotriene C4 (LTC4) by peripheral leucocytes. However, it is still unclear how the combination spa therapy and dietary supplementation of perilla seed oil influences on the pathophysiology of bronchial asthma. In the present study, the effects of spa therapy combined with dietary supplementation of perilla seed oil were examined in patients with asthma in relation to the serum eosinophil cationic protein (ECP) levels to investigate the effect on bronchial asthma. Ten adult asthmatic patients with moderate type asthma in terms of severity were taken to have a complex spa therapy and consume perilla seed oil-rich diet for 4 weeks. The generation of LTC4 by peripheral leucocytes, serum ECP level and pulmonary function were measured. Significant decreases were observed for LTC4 and ECP for 4 weeks. Forced vital capacity (FVC), which was one of the pulmonary function tests, improved significantly at 4 weeks (p<0.05). The number of eosinophils decreased for 4 weeks, but the differences were not significant. The results obtained here suggest that spa therapy combined with dietary supplementation of perilla seed oil leads to decrease in LTC4 and ECP and improves pulmonary function and asthma control.

Association of Leukotriene C4 Synthase Gene Polymorphism with Clinical Response to Montelukast in Childhood Asthma / 소아과

PURPOSE: Cysteinyl leukotrienes are important inflammatory mediators in the pathogenesis of asthma; therefore interruption of cysteinyl leukotrienes by leukotriene receptor antagonists improves clinical symptoms in the management of patients with mild to moderate asthma. We evaluated whether clinical response to montelukast, a leukotriene receptor antagonist, in childhood asthma was predicted by genotypes of leukotriene C4 synthase (LTC4S) promoter gene polymorphism. METHODS: An 8-week prospective, open trial of montelukast was carried out in 161 children with mild to moderate asthma. Genotyping of LTC4S gene polymorphism was determined by restriction fragment length polymorphism. RESULTS: The distribution of the LTC4S genotypes AA, AC, and CC was 70.8 percent, 23.6 percent, and 5.6 percent, respectively in asthma group and 74.0 percent, 22.6 percent, and 3.4 percent, respectively in control group. A statistically significant difference in the distribution of LTC4S genotype was not observed between the asthma and the control groups, and there was no significant difference between the LTC4S genotype and asthma severity. The responders to montelukast were significantly prevalent in the mild asthma group (P< 0.05). There was no significant difference in the distribution of the responders compared to non-responders within genotype in the total asthma group or the moderate asthma group. However, the responsiveness for montelukast was significant difference within genotype for both AA and AC/CC in the mild asthma group: The AA genotype was more included in the responder group (P< 0.05). CONCLUSION: In the mild persistent asthma group, the A allele of LTC4S polymorphism may be regarded as a predictable factor for clinical response to montelukast. However, LTC4S polymorphism was not significantly associated with the clinical response to montelukast in asthmatic children.

Effects of Spa Therapy Combined with Dietary Supplementation with n-3 Fatty Acids on Bronchial Asthma / 日本温泉気候物理医学会雑誌

N-3 fatty acids are reportedly effective for asthma. In addition, spa therapy has been reported to be effective for patients with asthma. In the present study, the effects of spa therapy combined with perilla seed oil-rich diet (rich in n-3 fatty acid) were examined on asthma. A total of 14 asthmatic patients had a complex spa therapy and consumed a perilla seed oil-rich diet-rich in α-linolenic acid (α-LNA) for 8 weeks. Generation of leukotriene (LT) C4 by leucocytes, respiratory function were analyzed. The generation of LTC4 by leucocytes decreased significantly for 2, 4 and 8 weeks (P<0.05). Peak expiratory flow (PEF) values increased significantly for 2, 4, 6 and 8 weeks (P<0.05). The values of ventilatory parameters [forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), forced expiratory flow after 25% of expired FVC (FEF₂₅), forced expiratory flow after 75% of expired FVC (FEF₇₅), mean expiratory flow during the middle half of the FVC (FEF_25-75)] revealed a significant increase after 4 and 8 weeks of the modified diet (P<0.05). The results suggest that spa therapy combined with a perilla seed oil-rich diet are effective in the treatment of asthma in terms of its ability to suppress LTC4 generation by leucocytes, and in inducing an improvement of pulmonary function.

The Effects of Nimodipine and Intracisternal Urokinase on the Content of Leukotrience C4 in the Brain Tissue after Experimental Subarachnoid Hemorrhage in Rats

To find out whether early lysis of subarachnoid blood clot with intracisternal urokinase as well as intraperitoneal nimodipine prevents or decrease the breakdown of arachidonic acid(AA) of the brain after subarachnoid hemorrhage(SAH), we have investigated the levels of leukotrience(LT) C4, the metabolite of the lipooxygenase pathway of the AA metabolism, in the brain tissue after experimental SAH in rats. The experimental SAH was induced by an intracisternal autologous blood injection through the catheter which was inserted into the cisterna magna. Experimental animals were assigned to one of four groups as follows. The control group(I) was that intracisternal saline irrigation was done after SAH induction. The second group(II) was treated with an injection of nimodipine(4 times per a day of 1.2 mg/Kg until sacrificed) intraperitoneally after SAH induction, the third group(III) was tried with an intracisternal urokinase irrigation(3 times per a day of 0.1 ml, 1 ml : 20,000 unit urokinase, until sacrificed) and the fourth group(IV) was treated with intraperitoneal nimodipine and intracisternal urokinase(same regimen as above). Average levels of LT C4in each group was determined at 24 hours(subgroup a), 48 hours(subgroup b), 72 hours(subgroup c) after the induction of SAH by the radioimmunoassay method. The result showed that average levels of LT C4was significantly enhanced in the brain tissue at 48 hours after SAH induction in control group(group Ia vs. IB vs. Ic : 43.85+/-15.62 vs. 184.32+/-27.46 vs. 39.29+/-12.79 pg/ml, respectively. group Ia vs. Ib vs. Ic ; p<0.01) and was decreased by intraperitoneal nimodipine, intracisternal urokinase or combination of both at 48 hours after SAH induction (group Ib vs. IIb vs. IIIb vs. IVb : 184.32+/-27.46 vs. 41.99+/-5.94 vs. 37.68+/-10.4 vs.37.38+/-9.27 pg/ml, respectively group Ib vs. IIb vs. IIIb, and IVb ; p<0.05). However, there was no significant differences among the second, the third and the fourth group(group IIa vs. IIIa vs. IVa, group IIb vs. IIIb vs. IVb and group IIc vs. IIIc vs. IVc : 41.07+/-7.06 vs. 37.97+/-4.48 vs. 31.84+/-6.07 pg/ml, 41.99+/-5.94 vs. 37.68+/-10.43 vs. 37.38+/-9.27 pg/mi and 36.41+/-6.76 vs. 37.98+/-3.45 vs. 35.59+/-8.37 pg/ml, respectively). We concluded that the early lysis of subarachnoid blood clot with intracisternal urokinase had some benefits against the damage of neurons in the early period after SAH as much as intraperitoneal injection of nimodipine. However, the benefit of the combined treatment with intraperitoneal nimodipine and intracisternal urokinase, compared to intraperioneal nimodipine or intracisternal urokinase alone, has not been cleary established.

The Cerebrospinal Fluid Levels of Leukotriene C4 in Patients with aneurysmal subarachnoid hemorrhage

We have checked levels of leukotriene(LT) C4, one of the arachidonic acid(AA) metabolites, in the lumbar, cisternal and ventricular cerebrospinal fluid(CSF) of 37 patients admitted with diagnosis of aneurysmal subarachnoid hemorrhage(SAH) and in lumbar CSF of 10 patients without aneurysmal SAH as the control group. We compared the levels of LTC4 in the CSF of the patients with aneurysmal SAH with those of the control group. We observed the changes of levels of LTC4 periodically after the onset of SAH. We devided the data of patients with aneurysmal SAH into 3 groups according to sampling days(respectively 1-4, 5-11, 12-24 days after SAH) and the clinical spasm group was compared with that of the non-spasm group. We also looked for the differences in the sampling sites and the correlation between the white blood cell counts and the levels of LTC4 in the CSF. The results of this study showed that the mean level of CSF LTC4(+/- standard deviation) of the SAH group was significantly higher than that of the control group(215.59+/-94.95 vs. 98.44+/-31.72pg/ml, respectively : P0.05) even though we expected the level in the cisternal CSF to be higher than the lumbar CSF. There was no correlation between the white blood cell counts and the levels of LTC4 in the CSF(correlation coefficient=0.1240). From this study it is concluded that : 1) the AA metabolism via the lipoxygenase pathway is enhanced after SAH ; 2) the LTC4 may play a role in the pathogenesis of cerebral vasospasm, especially in the early days after SAH ; 3) the extraction of CSF via the external ventricular or cisternal drainage may decrease substances such as LTC4 which was thought to be vasoconstrictor material ; and 4) the granulocyte production of the LTC4 accounts for only a small part.