Riboflavin prophylaxis in pediatric and adolescent migraine

Migraine is a common disorder in childhood and adolescence. Studies on adults show the effectiveness and tolerability of riboflavin in migraine prevention, while data on children are scarce. This retrospective study reports on our experience of using riboflavin for migraine prophylaxis in 41 pediatric and adolescent patients, who received 200 or 400 mg/day single oral dose of riboflavin for 3, 4 or 6 months. Attack frequency and intensity decreased (P < 0.01) during treatment, and these results were confirmed during the follow-up. A large number of patients (77.1%) reported that abortive drugs were effective for controlling ictal events. During the follow-up, 68.4% of cases had a 50% or greater reduction in frequency of attacks and 21.0% in intensity. Two patients had vomiting and increased appetite, respectively, most likely for causes unrelated to the use of riboflavin. In conclusion, riboflavin seems to be a well-tolerated, effective, and low-cost prophylactic treatment in children and adolescents suffering from migraine.     

舒马普坦与散利痛治疗偏头痛急性发作疗效比较

目的比较舒马普坦与散利痛治疗偏头痛急性发作的疗效。方法57例偏头痛患者随机单盲分为舒马普坦与散利痛组,头痛开始发作时分别服用舒马普坦50 mg及散利痛1片,分别观察患者服药后起效的时间,服药后4小时的治疗有效率,各组服药后0.5、1、2、4小时头痛消失的比例及VAS评分,服药后24小时内完全止痛维持的时间,药物不良反应。结果起效时间散利痛组(1.02±0.67)小时,舒马普坦组(0.79±0.49)小时;服药后4小时治疗有效率分别为89.29%、93.10%;不良反应发生率分别为14.29%、10.34%;舒马普坦组服药后1小时头痛消失率(62.09%)高于散利痛组(32.14%),P=0.024。结论舒马普坦与散利痛均能有效治疗偏头痛急性发作,舒马普坦1小时头痛消失率高于散利痛。     

A comparison of preference for and efficacy of tablet formulations of sumatriptan (50 mg and 100 mg), naratriptan (2.5 mg), rizatriptan (10 mg), and zolmitriptan (2.5 mg) in the acute treatment of migraine

Abstract This randomized, multicenter, open-label, five-way crossover study was conducted to assess patients preference for tablet formulations of sumatriptan (50 mg and 100 mg), naratriptan (2.5 mg), rizatriptan (10 mg), and zolmitriptan (2.5 mg) in the acute treatment of migraine and to identify determinants of preference. Patients treated one mild, moderate, or severe migraine with each triptan. The results show that sumatriptan 100 mg was significantly preferred over the random preference rate of 20% (p<0.001) whereas sumatriptan 50 mg, naratriptan, rizatriptan, and zolmitriptan were not. Patients primary reason for preferring a medication was best relief of migraine pain, and the treatment that patients preferred corresponded to the medication that was most likely to confer for them a pain-free response 2 hours postdose. Across all patients, efficacy 2 hours postdose was comparable among triptans with the exception of naratriptan, which was slightly less effective than the other medications (pain-free response 2 hours postdose: 40% sumatriptan 100 mg, 37% sumatriptan 50 mg, 28% naratriptan 2.5 mg, 38% rizatriptan 10 mg, 36% zolmitriptan 2.5 mg). The medications were also similarly well-tolerated. These data demonstrate that information on patients medication preference supplements and does not duplicate data from traditional efficacy measures. Patient preference data are useful in tailoring migraine therapy to the needs of the individual patient.     

Parenteral vs. oral sumatriptan and naratriptan: plasma levels and efficacy in migraine. A comment

The clinical efficacy in migraine was compared for oral and subcutaneous sumatriptan and naratriptan. Doses of the two administration forms were chosen as resulting in comparable blood concentrations. Subcutaneous administrations of the drugs were superior for efficacy than the oral forms. This most likely due to a quicker rise in blood concentrations after subcutaneous injections.. In designing new therapies for migraine one should aim at a quick absorption of the drug, which will probably result in an increased efficacy.     

Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine

A controlled study was performed to assess the involvement of the nitric oxide pathway in migraine pathophysiology. Thirteen patients with migraine without aura and seven clinically healthy subjects (C) were selected. All of the migraine patients were studied both before, during an asymptomatic phase (t ₀), and 1 h after the administration of 5 mg isosorbide dinitrate, a nitric oxide donor able to induce an experimental migraine attack (t ₁). The nitric oxide levels were analyzed as nitrite accumulation in serum samples, in peripheral blood mononuclear cell extracts, and culture supernatants. Basal nitrite levels in serum samples and peripheral blood mononuclear cell culture supernatants of migraine patients and healthy subjects indicated that migraine patients possess an activated nitric oxide synthesis pathway (t ₀ vs. C F=8.16,P<0.01 and F=16.2,P<0.01, respectively). As expected, in the migraine patients treated with the nitric oxide donor, a marked increase of nitrite levels was observed in sera (t ₁ vs.t ₀ P<0.05,t=3.05). In contrast, during the nitric oxide donor-induced migraine attacks a statistically significant decrease of nitrite levels in peripheral blood mononuclear cell culture supernatants was observed (t ₁ vs.t ₀ P<0.01,t=−4.03), whereas a significant increase of nitrite in total cell extracts was detected (t ₁ vs.t ₀ P<0.001,t=−6.89). These preliminary data suggest that nitric oxide could be involved in the neurovascular modifications leading to a migraine attack.     

Treatment with sumatriptan 50 mg in the mild phase of migraine attacks in patients with infrequent attacks: a randomised, double-blind, placebo-controlled study

Most migraine patients with infrequent attacks are currently not treated with migrainespecific medication such as triptans. The response of these patients to triptans is unknown. The objective of this study was to investigate the efficacy and tolerability of sumatriptan 50 mg vs. placebo in migraine patents with infrequent migraine attacks when medication is taken during the mild phase of an attack. The study design was double-blind, placebocontrolled, parallel-group and randomised. Migraine patients were recruited by general practitioners and referred to one of 4 study centres. Additional patients were recruited by advertising. The patients were eligible for the study if they had between 6 and 12 migraine attacks with or without aura per year. The patients were instructed to take the medication during the mild phase of a single attack. The primary efficacy measure was the percentage of patients pain-free after 2 h. Fortysix percent of treated attacks were moderate or severe. In the intention-to-treat analysis, sumatriptan was superior (20/51 patients were pain-free) to placebo (8/47 patients pain-free) (p=0.03). Adverse events (AEs) occurred more frequently after sumatriptan (40%) than after placebo (13%) (p=0.003) and most AEs were mild or moderate. In this migraine population with infrequent attacks, sumatriptan was superior to placebo and was generally well tolerated.     

高压氧对大鼠脑缺血后NOS阳性神经元的影响

目的　探讨一氧化氮合酶 (NOS)阳性细胞在大鼠急性局灶性脑缺血 /再灌注损伤和高压氧 (HBO)治疗后表达的变化。方法　应用血管内细丝栓堵大脑中动脉 (MCA)的局灶性脑缺血大鼠模型 ,利用黄递酶 -NADPH组织化学方法 ,观察MCA缺血 1h ,再灌注 4、11、2 3、71hNOS阳性细胞在视交叉平面梗死区皮层、视前区、纹状体外侧区和纹状体内侧区域分布的变化 ,在以上期间应用 0 2 5MPaHBO于开始缺血后 2、9、2 1、4 5和 6 9h分别治疗 1次 (1h)。结果　脑缺血后 ,在上述区域形态改变的NOS阳性细胞数随着再灌注时间的延长逐渐增多。HBO治疗后 ,各时间点在皮层、视前区和纹状体内侧区 ,形态改变的NOS阳性细胞数明显减少 (P <0 0 5 ) ,而纹状体外侧区无明显变化 (P >0 0 5 )。结论　HBO可明显抑制大鼠急性局灶性脑缺血 /再灌注损伤区NOS阳性细胞的变性     

发育期大鼠反复惊厥后海马组织NO、NOS变化及川芎嗪的干预研究

目的 探讨发育期大鼠反复惊厥后海马组织一氧化氮（NO）、一氧化氮合酶（NOS）的变化及川芎嗪对其的影响，方法 三氟乙醚反复吸入（连续6次，每天1次）制成发育期大鼠惊厥动物模型，观察川芎嗪对反复惊厥后6h、1d、3d、7d海马组织NO含量、NOS活性及光镜下海马组织病理变化的影响。结果 ①反复惊厥后6h、ld、3d海马组织NO含量及NOS活性明显升高，与对照组相比有显著性差异（P〈0．01），第7天已恢复正常。②反复惊厥后6h海马神经细胞即有轻度水肿，第1～3天水肿、变性坏死明显，第7天有大量炎性细胞浸润、胶质细胞增生明显。③川芎嗪干预组海马组织病理变化明显改善．NO含量及NOS活性明显低于惊厥组，两组相比在第6h、1d、3d有显著差异（P〈0．01）。结论 反复惊厥发作可导致大鼠海马组织损伤，可能与NO大量生成，NOS活性明显增高有关。川芎嗪能改善惊厥后脑组织病理损伤，其机制可能与降低NO含量及NOS活性有关。     

大鼠局灶性脑缺血再灌注损伤脑组织中NO、NOS变化及雷公藤多甙的影响

目的 观察大鼠局灶性脑缺血再灌注损伤后一氧化氮(NO)和一氧化氮合酶(NOS)活性的变化及雷公藤多甙(GTW)对其的影响。方法 用线栓法建立大鼠脑缺血再灌注动物模型，灌胃法给药，硝酸银还原法测定NO含量。结果 脑缺血再灌注损伤后，大鼠脑组织中NOS活性、NO含量随时间延长而进行性升高，GTW能抑制NOS活性的升高，减少NO的产生。结论 GTW可能对大鼠局灶性脑缺血再灌注损伤有保护作用。     

失血性休克再灌注大鼠血液NO、NOS的改变和丹参的作用

目的探讨失血性休克再灌注大鼠血液中一氧化氮(NO)、一氧化氮合酶(NOS)含量的变化及丹参对其的影响。方法健康SD大鼠30只,随机平分成正常对照组(NC组)、失血性休克再灌注组(HS-R组)和丹参治疗组(SM组)。分别测定三组血清NO、NOS含量。结果与NC组相比较,HS-R组血清NO、NOS含量明显增高(P<0.01)。SM组的血清NO、NOS含量明显低于HS-R组(P<0.01)。结论失血性休克再灌注时NOS大量激活,使NO产生增多,NO介导了失血性休克再灌注损伤,大量释放的NO参与休克再灌注损伤的脂质过氧化反应;丹参通过减少NO的生成,抗脂质过氧化反应而发挥其保护作用。     

The effect of sumatriptan on nitric oxide synthase enzyme production after iatrogenic inflammation in the brain stem of adolescent rats: A randomized, controlled, experimental study

Background: Migraine is a common disabling disorder of childhood and adolescence. Despite advances in the understanding of migraine pathophysiology, treatment remains a challenge.Objectives: The aims of this study were to investigate the production of nitric oxide synthase (NOS) enzymes in the brain stem of adolescent rats, using an experimental model of migraine, and the effect of sumatriptan pretreatment on the production of the NOS enzymes.Methods: Male adolescent (aged ~2 months) Wistar rats were used in the study. The animals were anesthetized using pentobarbital. The trigeminovascular system was stimulated by injecting a proinflammatory molecule, carrageenan, into the cis-terna magna of the anesthetized rats. The animals were divided into 3 groups of equal size: (1) the study group, in which the rats were treated with sumatriptan succinate 2 hours before intracisternal carrageenan injection; (2) the sham group, in which the rats were not administered intracisternal carrageenan injection or sumatriptan pretreatment; and (3) the control group, in which the rats were administered intracisternal carrageenan injection but were not pretreated with sumatriptan. In the control and study groups, the rats were euthanized using ether anesthesia 1 hour after intracisternal carrageenan injection. Rats in the sham group were euthanized 1 hour after intracisternal catheterization. Brain tissue was removed and endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS) immunohistochemistry was performed.Results: Twenty-one rats were randomized into 3 groups of 7. The mean values of the immunolabeling intensities for eNOS, nNOS, and iNOS enzymes in the brain stem were significantly lower in the sham group compared with the control group (P = 0.001, P = 0.002, and P = 0.001, respectively). The mean values of the immunolabeling intensities of eNOS, nNOS, and iNOS in the brain stem were significantly lower in the study group compared with the control group (P = 0.001, P = 0.025, and P = 0.005, respectively).Conclusions: In this experimental model of migraine in adolescent rats, intracisternal injection of carrageenan was associated with a significant increase in the production of NOS enzymes in the brain stem. Pretreatment with sumatriptan was associated with a decrease in NOS production.     

急性一氧化碳中毒患者血清NO和NOS水平及其临床意义

目的探讨一氧化氮（NO）及一氧化氮合酶（NOS）的水平与急性一氧化碳中毒患者病情的关系,寻找表达急性一氧化碳中毒（ACMP）患者病情变化的理想生物学标志。方法应用比色法（colorimetric method）测定40例ACMP患者血清NO及NOS水平,并与38例正常对照进行比较。结果AC-MP组患者血清NO及NOS水平明显高于正常对照组（P〈0．05）。结论NO—NOS系统水平异常在AC-MP引起的缺血缺氧性疾病发生中起重要作用。     

Headache induced by a nitric oxide donor (nitroglycerin) responds to sumatriptan. A human model for development of migraine drugs

Experimental "vascular" headache in humans may be used in characterizing new migraine drugs. The effects of sumatriptan on nitroglycerin-(NTG)-induced headache and arterial responses were therefore studied. Following a double-blind randomized crossover design, 10 healthy volunteers received sumatriptan 6 mg s.c. or placebo succeeded by 20 min NTG (0.12 mg/kg/min) infusion. Headache was rated on a 10 points scale. Temporal and radial artery diameters and velocity in the middle cerebral artery (MCA) were measured with ultrasound. Sumatriptan reduced the NTG-induced headache, median score 1.5 versus 4 after placebo ( p <0.01) and decreased temporal and radial artery diameters 75±3 and 86±3% of baseline respectively ( p <0.05), Blood velocity in the MCA was unaffected. The NTG model may prove to be a valuable tool in the development of future migraine drugs. The results suggest that NTG headache in non-migraineurs may share mechanisms with migraine headache.     

The central analgesia induced by antimigraine drugs is independent from Gi proteins: superiority of a fixed combination of indomethacin, prochlorperazine and caffeine, compared to sumatriptan, in an in vivo model

A hypofunctionality of Gi proteins has been found in migraine patients. The fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) is a drug of well-established use in the acute treatment of migraine and tension-type headache. The aim of this study was to investigate if Indoprocaf was able to exert its central antinociceptive action when Gi proteins activity is abolished by pertussis toxin (PTX), compared to its single active ingredients and to sumatriptan. The mice model of abdominal constriction test induced by an i.p. injection of a 0.6% solution of acetic acid was used. The study showed that Indoprocaf (a fixed combination of indomethacin 1 mg/kg, prochlorperazine 1 mg/kg and caffeine 3 mg/kg, s.c.) and sumatriptan (20 mg/kg, s.c.) exert their central antinociceptive action independently from the Gi proteins. In addition, the antinociceptive efficacy of Indoprocaf in this study was statistically superior to that of sumatriptan. This study also showed that the single active ingredients of Indoprocaf, indomethacin (1 mg/kg, s.c.), prochlorperazine (1 mg/kg, s.c.) and caffeine (3 mg/kg, s.c.), were able to exert their central antinociceptive action independently from the Gi proteins. However, Indoprocaf at analgesic doses was able to abolish almost completely the abdominal constrictions, with a statistically higher efficacy compared to the single active ingredients, showing an important synergic effect of Indoprocaf. This synergic effect was evident not only when Gi proteins activity was abolished by PTX, but also under control condition, when Gi proteins were active. This study suggests that the central antinociceptive action induced by antimigraine drugs is independent from Gi proteins.     

肝硬化门脉高压症患者肝功能分级、与肝组织中一氧化氮和一氧化氮合酶含量的探讨

目的探讨肝硬化门脉高压症患者肝组织中一氧化氮（NO）和一氧化氮合酶（NOS）与肝功能分级的关系。方法用硝酸还原酶化学比色法,检测56例肝硬化门脉高压症患者（按肝功能Child分级标准分为A、B、C级三组）及19例正常对照组肝组织中的NO含量和NOS活性,分析其与肝功能分级的相关性。结果肝硬化门脉高压组肝组织中NO含量分别为（0．851±0．141）μmol／g．plot、（1．059±0．211）p．mol／g．prot、（1．987±0．566）μmol／g．prot。？NOS活性分别为（0．701±0．105）U／mg．prot,（0．861±0．118）U／mg．prot,（1．414±0．241）U／mg．prot,均高于正常对照组[（0．211±0．099）μmol／g．pmt,（0．282±0．086）U／mg．prot],且与肝功能Child分级呈正相关（r=0．847）。结论肝硬化门脉高压组患者肝组织中NO含量较正常对照组明显增加,NOS活性显著增强,与肝功能Child分级呈正相关。     

Effect of CGRP and sumatriptan on the BOLD response in visual cortex

To test the hypothesis that calcitonin gene-related peptide (CGRP) modulates brain activity, we investigated the effect of intravenous CGRP on brain activity in response to a visual stimulus. In addition, we examined if possible alteration in brain activity was reversed by the anti-migraine drug sumatriptan. Eighteen healthy volunteers were randomly allocated to receive CGRP infusion (1.5 μg/min for 20 min) or placebo. In vivo activity in the visual cortex was recorded before, during and after infusion and after 6 mg subcutaneous sumatriptan by functional magnetic resonance imaging (3 T). 77% of the participants reported headache after CGRP. We found no changes in brain activity after CGRP (P = 0.12) or after placebo (P = 0.41). Sumatriptan did not affect brain activity after CGRP (P = 0.71) or after placebo (P = 0.98). Systemic CGRP or sumatriptan has no direct effects on the BOLD activity in visual cortex. This suggests that in healthy volunteers both CGRP and sumatriptan may exert their actions outside of the blood–brain barrier.     

血清NO及NOS在雷公藤多甙治疗复发性口疮的疗效评价中的应用

目的 通过对运用雷公藤多甙（TWP）治疗复发性口疮（RAU）的临床观察,探讨血清一氧化氮（NO）、一氧化氮合酶（NOS）水平的变化及其在临床疗效和预后判断中的应用价值。方法 用常规治疗方案和TWP联合治疗方案治疗RAU患者108例及135例。观察治疗前后血清NO、NOS水平变化,分别作治疗期疗效和治疗后疗效变化评价。结果 TWP联合治疗组,近期疗效有效率为91．11％,远期疗效有效率为94．07％,常规治疗组近期疗效有效率为70．37％,远期疗效有效率为68．52％。结论 血清NO、NOS水平变化可用于治疗RAU的疗效评价和预后判断。     

硝基精氨酸-赖氨酸三肽对感染性休克大鼠血压的影响并机制探讨

目的　用合成的硝基精氨酸 赖氨酸三肽 (以下简称新化合物 )在大鼠感染性休克模型上检测其对血压的影响 ,并对其作用机制作一探讨。方法 :1.盲肠结扎穿孔法 (CLP)建立大鼠感染性休克模型 ,检测新化合物对血压、血清一氧化氮 (NO)的影响。 2 .大鼠腹腔巨噬细胞培养 ,检测新化合物对诱导型一氧化氮合酶 (iNOS)的抑制程度。 3 .大鼠离体主动脉条孵育 ,检测新化合物对结构型一氧化氮合酶 (cNOS)的抑制程度。结果 :1.新化合物 ( 0 0 1mmol/kg)明显升高感染性休克大鼠血压至接近假手术组水平 ;注射新化合物、NG- 硝基 左旋精氨酸(L NNA)可使大鼠血清NO水平下降 ,新化合物较L NNA作用更明显。 2 .新化合物 ( 10 4mol/L)可显著抑制大鼠腹腔巨噬细胞产生NO (P <0 0 1) ,较L NNA作用增强 (P <0 0 1)。 3 .与L NNA相比 ,新化合物 ( 1 5× 10 4mol/L)对大鼠主动脉壁cNOS的抑制程度减小 (P <0 0 5)。结论 :硝基精氨酸 赖氨酸三肽对感染性休克大鼠血压有优越的升高作用 ,其机制在于选择性地抑制iN OS     

内皮素-1、一氧化氮、一氧化氮合酶、B型内皮肽受体及移动抑制因子在大鼠肝肺综合征作用中的初步研究

目的 探讨内皮素-1（ET-1）、内皮素B（ETB）受体、NOS、NO及巨噬细胞游走抑制因子（MIF）在大鼠肝肺综合征（HPS）作用中的机制.方法 将雄性Wistar大鼠共48只随机分为正常对照组（Control组）、胆总管结扎组（CBDL组）、肝前门静脉高压组（PVL组）及CBDL＋抗MIF组四组.分别对Control组和PVL组术后5周,以及CBDL组和CBDL＋抗MIF组术后2周、3周和5周进行：门静脉压力、血气分析、肝功能以及血清NO、ET-1、肺组织内ETB受体、一氧化氮合酶诱导型（iN-OS）、一氧化氮合酶内皮型（eNOS）蛋白表达及MIF水平进行检测,检查肝、肺病理,并使用激光多普勒血流仪检测肝、肺微循环差异.结果 CBDL组和Control组相比肝功能检测中白蛋白降低,胆红素、AST均升高;血气分析中PaO2降低,AaPO2增大;肝脏毛细血管血流量降低（P＜0.05）;肺脏毛细血管血流量增大（P＜0.05）;血浆内ET-1、NO及MIF水平增高;肺脏组织内eNOS、ETB受体蛋白表达增高（P＜0.05）;且病理检查CBDL组大鼠的肝脏组织可见胆汁性纤维化表现,肺组织可见肺毛细血管扩张、充血,证实HPS大鼠模型制成.PVL组大鼠与Control组相比,除门静脉压力和组织内ETB受体蛋白表达增高外（P＜0.05）,其余指标的差异无统计学意义.CBDL＋抗MIF组在各项指标及病理检测中,血浆内ET-1、NO及MIF水平较CBDL组相比有所降低,肝、肺病理变化较CBDL组减轻.肺脏组织内iNOS蛋白表达在四组间的表达差异无统计学意义.结论 在CBDL建立的HPS大鼠模型中,可能是ET-1可被肝脏过量生成,进入血液循环,与肺脏血管内皮细胞上的ETB受体结合,增加eNOS的表达和活性,NO产生增多,引起肺内血管扩张,进一步引起HPS,抗MIF抗体通过抑制MIF在对抗CBDL引起HPS的发生中发挥一定的作用.     

毫米波对大鼠血清中活性氧,一氧化氮及其相关酶？…

目的 观察低功率毫米波经皮肤辐射能还引起大血中活性氧、一氧化氮及其相关酶的改变,以探索其作用机制。方法 应用波长５．６ｍｍ、功率密度１０ｍＷ／ｃｍ＾２极高频电磁波辐射大鼠腰背部皮肤,每天１ｈ,连续７ｄ,采集心血４ｍｌ,测定其血清中总超氧化物歧化酶（Ｔ－ＳＯＤ）、氮 氧合酶（ＮＯＳ）活性以及脂质过氧化物丙二醛（ＭＤＡ）和一氧化氮（ＮＯ）含量。结果 辐射组Ｔ－ＳＯＤ、ＮＯＳ活性下降,ＮＯ含量减少,ＭＤ