BACKGROUND & AIMS: AIM:Itopride is a newly developed prokinetic agent, which enhances gastric motility through both antidopaminergic and anti-acetylcholinesterasic actions. The importance of esophageal motor dysfunction in the pathogenesis of gastro-esophageal reflux disease (GERD) makes it interesting to examine the effect of itopride on esophageal acid exposure. METHODS:The effect of itopride on esophageal acid reflux variables for 24 h was studied in 26 patients with GERD symptoms, pre-entry total acid exposure time (pH<4) of more than 5% and mild esophagitis (Savary-Miller grades I, II) proven by endoscopy. Ambulatory 24-h pH-metry and symptom assessment were performed after treatments with 150 or 300 mg itopride thrice a day (t.i.d.) for 30 d in random order, using an open label method. For evaluating the safety of itopride, blood biochemical laboratory test was performed and the serum prolactin level was also examined before and after treatment. RESULTS:Total symptom score was significantly decreased after treatment in 150- or 300-mg group. Itopride 300 mg was significantly effective than 150 mg on decreasing the total per cent time with pH<4, total time with pH<4 and DeMeester score. No serious adverse effects were observed with administration of itopride in both groups. CONCLUSION:Itopride 100 mg t.i.d. is effective on decreasing pathologic reflux in patient with GERD and therefore it has the potential to be effective in the treatment of this disease.

背景与目标： 目的：伊托必利是一种新开发的促动力剂，可通过抗多巴胺能和抗乙酰胆碱酯酶作用增强胃动力。食管运动功能障碍在胃食管反流病（GERD）发病机理中的重要性使研究伊托必利对食管酸暴露的影响变得有趣。
方法：对26例GERD症状，进入前总酸暴露时间（pH <4）大于5％和轻度食管炎（Savary-Miller等级I，I级，26例）的患者，研究了伊托必利对食管酸反流变量24 h的影响。 II）经内窥镜检查证实。使用开放标签方法，以150或300 mg的伊托必利一天三次（t.i.d.）治疗30天后，进行24小时动态pH测量和症状评估。为了评估伊托必利的安全性，在治疗前后进行了血液生化实验室测试，并检查了血清催乳素水平。
结果：150或300 mg治疗组的总症状评分明显降低。依托必利300毫克比150毫克在减少pH <4的总百分比时​​间，pH <4的总时间和DeMeester分数方面显着有效。两组均未观察到伊托必利的严重不良反应。
结论：依托必利100 mg t.i.d.在减少GERD患者的病理性返流方面有效，因此有可能有效治疗该疾病。

BACKGROUND & AIMS: :Two simple, rapid and sensitive methods, namely, fourth-derivative synchronous spectrofluorimetry (method I) and HPLC with fluorescence detection (method II) were developed for the simultaneous analysis of a binary mixture of itopride HCl (ITP) and domperidone (DOM) without prior separation. The first method was based on measuring the fourth derivative of the synchronous fluorescence spectra of the two drugs at Δλ = 40 nm in methanol. The different experimental parameters affecting the synchronous fluorescence of the studied drugs were carefully optimized. Chromatographic separation was performed in < 6.0 min using a RP C18 column (250 mm × 4.6 mm i.d., 5 µm particle size) with fluorescence detection at 344 nm after excitation at 285 nm. A mobile phase composed of a mixture of 0.02 M phosphate buffer with acetonitrile in a ratio of 55 : 45, pH 4.5, was used at a flow rate of 1 mL/min. Linearity ranges were found to be 0.1-2 µg/mL for ITP in both methods, whereas those for DOM were found to be 0.08-2 and 0.05-1.5 µg/mL in methods I and II, respectively. The proposed methods were successfully applied for the determination of the studied drugs in synthetic mixtures and laboratory-prepared tablets.

背景与目标： ：开发了两种简单，快速和灵敏的方法，即四阶导数同步光谱荧光法（方法I）和带荧光检测的HPLC（方法II），用于同时分析伊托必利HCl（ITP）和多潘立酮（DOM）的二元混合物无需事先分离。第一种方法是基于在甲醇中在Δλ= 40 nm下测量两种药物的同步荧光光谱的四阶导数。仔细优化了影响所研究药物同步荧光的不同实验参数。色谱分离是使用RP C18色谱柱（内径250毫米×4.6毫米，粒径5微米）在6.0 min内进行的，在285 nm激发后，在344 nm处进行了荧光检测。使用流动相，流动相由0.02 M磷酸盐缓冲液和乙腈以55:45的比例（pH约为4.5）的混合物组成，流速为1 mL / min。在两种方法中，ITP的线性范围均为0.1-2μg/ mL，而在方法I和II中，DOM的线性范围分别为0.08-2和0.05-1.5μg/ mL。所提出的方法已成功地用于测定合成混合物和实验室制备的片剂中所研究药物的含量。

BACKGROUND & AIMS: :The present work describes the formulation and evaluation of the gastroretentive system of Itopride hydrochloride. In this research, we have formulated floating hydrogel-based microspheres employing calcium carbonate (CaCO(3)) as a gas forming agent dispersed in alginate matrix. In vitro characterizations such as drug content, particle size, and drug release were carried out. GI motility was determined by administration of charcoal meal to rats. Results demonstrated that prepared microspheres were spherical in shape with smooth surface, good loading efficiency, and excellent buoyancy. The gastro retentive dosage form of itiopride demonstrated significant antacid, anti-ulcer, and anti-GERD activity after 12 hours in comparison with the conventional dosage form.

背景与目标： ：本工作描述了盐酸依托必利胃滞留系统的配方和评估。在这项研究中，我们制定了浮动的基于水凝胶的微球，使用碳酸钙（CaCO（3））作为分散在藻酸盐基质中的气体形成剂。进行了体外表征，例如药物含量，粒径和药物释放。通过向大鼠施用木炭粉确定胃肠动力。结果表明，制备的微球为球形，表面光滑，加载效率好，浮力好。与常规剂型相比，依托必利的胃滞留剂型在12小时后显示出显着的抗酸，抗溃疡和抗GERD活性。

BACKGROUND & AIMS: :A sensitive, selective and simple method using a precipitation of protein with 10% perchloric acid, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was developed for the determination of itopride hydrochloride in human plasma, using levofloxacin as the internal standard (IS). Chromatographic separation was obtained within 7.0 min using a reverse phase Hypersil BDS C(18) (250 mm x 4.6 mm, 5 microm) column and an isocratic mobile phase, constituting of a mixture of 0.1 mol/l ammonium acetate-methanol (30:70, v/v) flowing at 1.1 ml/min. The excitation and emission wavelengths were set at 304 and 344 nm, respectively. The method was validated over the concentration range of 5 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 5 ng/ml. The extractive recovery of itopride hydrochloride from the biological matrix was more than 80.77%. The intra-day accuracy of the drug containing serum samples was more than 82.94% with a precision of 2.81-4.37%. The inter-day accuracy was 82.91% or more, with a precision of 6.89-9.54%. The limit we have used (70-143%) is based on the local regulatory authority (SFDA). The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

背景与目标： ：以左氧氟沙星为内标，开发了一种灵敏，选择性，简单的方法，该方法使用10％高氯酸沉淀蛋白质，然后进行高效液相色谱（HPLC）和荧光检测，用于测定人血浆中的盐酸伊托必利（是）。使用反相Hypersil BDS C（18）（250 mm x 4.6 mm，5 microm）色谱柱和等度流动相，在7.0分钟内完成色谱分离，该流动相由0.1 mol / l乙酸铵-甲醇（30： 70，v / v）以1.1ml / min流动。激发和发射波长分别设置为304和344 nm。该方法在5 ng / ml至1000.0 ng / ml的浓度范围内得到验证。定量下限（LLOQ）为5 ng / ml。从生物基质中提取盐酸伊托必利的回收率超过80.77％。含药物血清样品的日内准确度超过82.94％，准确度为2.81-4.37％。日间精度为82.91％或更高，精度为6.89-9.54％。我们使用的限制（70-143％）基于当地监管机构（SFDA）。验证了所开发的方法，并将其成功应用于健康男性志愿者中盐酸伊托必利的生物等效性研究。

BACKGROUND & AIMS: :Acotiamide hydrochloride (acotiamide; N-[2-[bis(1-methylethyl) amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl) amino] thiazole-4-carboxamide monohydrochloride trihydrate, Z-338) has been reported to improve meal-related symptoms of functional dyspepsia in clinical studies. Here, we examined the gastroprokinetic effects of acotiamide and its antiacetylcholinesterase activity as a possible mechanism of action in conscious dogs. Acotiamide increased postprandial gastric motor activity in conscious dogs with chronically implanted force transducers and, like itopride, mosapride, and cisapride, exhibited gastroprokinetic activity in these dogs. Furthermore, acotiamide improved clonidine-induced hypomotility and delayed gastric emptying. Acotiamide-enhanced postprandial gastroduodenal motility was suppressed completely by pretreatment with atropine, a muscarinic receptor antagonist. In in vitro studies, acotiamide enhanced acetylcholine- but not carbachol-induced contractile responses of guinea pig gastric antrum strips. Moreover, like itopride and neostigmine, acotiamide inhibited recombinant human and canine stomach-derived acetylcholinesterase (AChE) activity in vitro. The mode of the AChE inhibitory action of acotiamide was selective and reversible. Unlike itopride or mosapride, acotiamide showed no affinity for dopamine D(2) or serotonin 5-HT(4) receptors. With regard to cardiovascular side effects, unlike cisapride, acotiamide did not affect myocardial monophasic action potential duration, QT interval, or corrected QT interval in anesthetized dogs. These results suggest that acotiamide stimulates gastric motility in vivo by inhibiting AChE activity without affecting QT interval. Acotiamide thus represents a beneficial new drug for the treatment of functional dyspepsia involving gastric motility dysfunction, with differences from other prokinetic agents.

背景与目标： ：乙酰酰胺盐酸盐（烟酰胺； N- [2- [双（1-（甲基）甲基）氨基]乙基] -2-[（2-羟基-4，5-二甲氧基苯甲酰基）氨基]噻唑-4-羧酰胺一盐酸盐三水合物，Z-338在临床研究中已报道）可以改善膳食相关的功能性消化不良症状。在这里，我们检查了乙酰甲酰胺的胃肠动力作用及其抗乙酰胆碱酯酶活性，作为有意识的犬的一种可能的作用机制。乙酰甲酰胺在长期植入力传感器的清醒犬中增加了餐后胃运动活动，并且如伊托必利，莫沙必利和西沙必利在这些犬中表现出胃肠运动活性。此外，乙酰甲酰胺改善了可乐定诱导的动力不足，并延迟了胃排空。用毒蕈碱受体拮抗剂阿托品预处理可完全抑制乙酰酰胺增强的餐后胃十二指肠运动。在体外研究中，乙酰甲酰胺可增强乙酰胆碱对豚鼠胃窦粘膜条的乙酰胆碱诱导的收缩反应，但不增强。此外，像伊托必利和新斯的明一样，在体外，乙酰甲酰胺抑制重组人和犬胃来源的乙酰胆碱酯酶（AChE）的活性。乙酰甲酰胺对AChE抑制作用的模式是选择性的和可逆的。与伊托必利或莫沙必利不同，乙酰甲酰胺对多巴胺D（2）或5-羟色胺5-HT（4）受体没有亲和力。关于心血管副作用，与西沙必利不同，乙酰甲酰胺不会影响麻醉狗的心肌单相动作电位持续时间，QT间期或校正的QT间期。这些结果表明，烟酰胺在不影响QT间隔的情况下通过抑制AChE活性而在体内刺激胃运动。因此，乙酰甲酰胺代表了一种有益的新药，用于治疗涉及胃动力功能障碍的功能性消化不良，与其他促动力药有所不同。

BACKGROUND & AIMS: PURPOSE:Itopride is an effective gastroprokinetic agent mainly used for the treatment of functional dyspepsia. Flavin-containing monooxygenase 3 (FMO3) has been confirmed to be the key enzyme involved in the main itopride metabolic pathway. We investigated whether the FMO3 genotypes can affect itopride metabolism in Chinese healthy volunteers. METHODS:Twelve healthy volunteers who had been genotyped for FMO3 gene were selected to participate in our study. Volunteers were given 50 mg itopride orally and then blood samples were collected from 0 to 24 h. The plasma concentrations of itopride and itopride N-oxide were determined by HPLC-MS/MS method. RESULTS:Itopride and itopride N-oxide both exhibit FMO3 genotype-dependent pharmacokinetic profiles. The area under the plasma concentration-time curve (AUC) of itopride increased by 127.82 ± 41.99 % (P < 0.001) and the AUC of itopride N-oxide decreased by 30.30 ± 25.70 % (P < 0.05) in homozygous FMO3 hhdd subjects (n = 6) compared with the HHDD group (n = 6). The CL/F value was lower in the hhdd group than that in the HHDD group (36.60 ± 7.06 vs. 80.20 ± 15.34 L/h, P < 0.001). But no significant differences in t1/2 value and tmax of itopride and itopride N-oxide were observed between these two genotypes. CONCLUSION:The FMO3 allele can significantly affect the metabolism of itopride. The pharmacokinetic parameters of both itopride and itopride N-oxide were significantly different between these two genotypes.

背景与目标： 用途：依托必利是一种有效的胃肠动力药，主要用于治疗功能性消化不良。含黄素的单加氧酶3（FMO3）已被证实是主要的伊托必利代谢途径中涉及的关键酶。我们调查了FMO3基因型是否可以影响中国健康志愿者的伊托必利代谢。
方法：选择12名经过FMO3基因基因分型的健康志愿者参加我们的研究。给志愿者口服50mg伊托必利，然后在0至24小时内收集血样。依托必利和依托必利N-氧化物的血浆浓度通过HPLC-MS / MS方法测定。
结果：依托必利和依托必利N-氧化物均表现出FMO3基因型依赖性的药代动力学特征。在纯合子FMO3 hhdd受试者中，伊托必利的血浆浓度-时间曲线下面积（AUC）增加了127.82±±41.99％（P <0.001），伊托必利N-氧化物的AUC减少了30.30±±25.70％（P <0.05）（与HHDD组相比（n = 6）。 hhdd组的CL / F值低于HHDD组（36.60±±7.06 vs. 80.20±±15.34 L / h，P <0.001）。但是在这两种基因型之间，在伊托必利和伊托必利N-氧化物的t1 / 2值和tmax上没有观察到显着差异。
结论：FMO3等位基因可显着影响伊托必利的代谢。在这两种基因型之间，伊托必利和伊托必利N-氧化物的药代动力学参数显着不同。

BACKGROUND & AIMS: BACKGROUND:Prokinetic agents are commonly used in the symptomatic treatment of functional dyspepsia (FD). Safety or efficacy issues associated with the use of available prokinetics, such as metoclopramide, domperidone, cisapride and mosapride, mean there is a need for an effective and well tolerated prokinetic agent. Itopride is a novel prokinetic agent with a dual mode of action, good safety profile and documented efficacy in placebo-controlled trials. OBJECTIVE:The objective of this study was to assess the effectiveness and safety of itopride in the management of FD. METHODS:This was a prospective, multicentre, post-marketing observational study carried out in private outpatient clinics throughout China. The study included patients with symptomatic FD aged ≥18 years. Patients were prescribed itopride 50 mg three times daily before meals for 4 weeks, after which there was a 2-week follow-up period during which they did not take itopride. Effectiveness and tolerability data obtained from patients who completed 4 weeks of therapy were analysed. The treatment response rate after 4 weeks was measured by patient global assessment; scores at the end of treatment were compared with baseline scores. Response rate based on symptom scoring was also measured after 4 weeks, with an effective treatment being defined as a symptom improvement of ≥50%. RESULTS:In total, 587 patients with FD were enrolled. The mean ± SD difference in the total symptom score before and after the 4-week treatment period was -5.62 ± 3.27, corresponding to a 69.23 ± 26.53% reduction from baseline (p < 0.001). The treatment response rates in patients who fulfilled Rome I, II and III criteria for FD were 33.68%, 34.71% and 35.50%, respectively, after 1 week of treatment; 52.82%, 54.61% and 56.51%, respectively, after 2 weeks; 66.67%, 67.23% and 68.64%, respectively, after 3 weeks; and 72.82%, 73.54% and 75.15%, respectively, after 4 weeks. Response rates were significantly different at 1 week versus 4 weeks of treatment. Nine patients (1.54%) had adverse events: four were probably related to the study drug, three were possibly related and two were not related. Of the nine patients with adverse events, two discontinued the study drug, two suspended (i.e. temporarily discontinued the drug until the adverse event subsided) the study drug, and five continued the study drug. Seven of the nine patients with adverse events had adverse reactions (defined as adverse events considered causally related to the study drug): two improved, three recovered and two showed no change. No adverse reactions were serious enough to warrant discontinuation of therapy. CONCLUSION:Itopride was an effective and well tolerated drug in the management of FD in this patient population.

背景与目标： 背景：促动力药通常用于功能性消化不良（FD）的对症治疗。与使用诸如甲氧氯普胺，多潘立酮，西沙必利和莫沙必利等现有的动力学相关的安全性或功效问题，意味着需要一种有效且耐受性良好的促运动剂。依托必利是一种新型的促运动剂，具有双重作用方式，良好的安全性和在安慰剂对照试验中已证明的疗效。
目的：本研究的目的是评估伊托必利在FD治疗中的有效性和安全性。
方法：这是在中国各地的私人门诊进行的一项前瞻性，多中心，上市后的观察性研究。该研究包括年龄≥18岁的有症状FD患者。饭前4周，每天3次给患者开50 mg伊托必利处方，此后有2周的随访期不服用伊托必利。分析从完成4周治疗的患者获得的有效性和耐受性数据。 4周后的治疗反应率通过患者总体评估来衡量；将治疗结束时的得分与基线得分进行比较。在4周后还测量了基于症状评分的缓解率，有效治疗被定义为≥50％的症状改善。
结果：总共587例FD患者入组。 4周治疗前后总症状评分的平均值±SD差异为-5.62±3.27，与基线相比降低了69.23±26.53％（p <0.001）。治疗1周后，符合罗马I，II和III FD标准的患者的治疗反应率分别为33.68％，34.71％和35.50％。 2周后分别为52.82％，54.61％和56.51％； 3周后分别为66.67％，67.23％和68.64％； 4周后分别为72.82％，73.54％和75.15％。治疗1周和4周的缓解率显着不同。 9名患者（1.54％）发生不良事件：4例可能与研究药物有关，3例可能相关，2例无关。在这9名有不良事件的患者中，有2名停用了研究药物，有2名被暂停（即暂时停止使用该药物直到不良事件消退），还有5名继续了该研究药物。在9名发生不良事件的患者中，有7名发生了不良反应（定义为与研究药物因果相关的不良事件）：2例得到改善，3例得到了恢复，2例没有变化。没有不良反应严重到足以终止治疗的程度。
结论：伊托必利是该患者人群FD治疗的有效且耐受性良好的药物。

BACKGROUND & AIMS: :Flavin-containing monooxygenase (FMO) catalyzes the oxygenation of a wide variety of medicines and dietary-derived compounds. However, little information is available regarding drug interactions mediated by FMO3 in vivo. Consequently, we investigated interactions between FMO substrates in humanized-liver mice. Trimethylamine-d9 and itopride were, respectively, intravenously and orally administered to humanized-liver mice (n = 5-7). The pharmacokinetic profiles of itopride (the victim drug) in the presence of trimethylamine (the perpetrator drug) were determined for 24 h after co-administration using liquid chromatography/tandem mass spectrometry. Itopride (10 mg/kg) was extensively oxygenated in humanized-liver mice to its N-oxide. The plasma concentrations of itopride N-oxide after co-administration of itopride and trimethylamine (10 and 100 mg/kg) were significantly suppressed in a dose-dependent manner, but only during the early phase, i.e., up to 2 h after co-administration. With the higher dose of trimethylamine, the areas under the concentration-time curves of itopride and its N-oxide significantly increased (1.6-fold) and decreased (to 60%), respectively; modeling suggested that these modified pharmacokinetics resulted from suppression of the in vivo hepatic intrinsic clearance (to 67%). These results suggest that food-derived trimethylamine may result in interactions with FMO drug substrates immediately after administration; however, the potential for this to occur in vivo may be limited.

背景与目标： ：含黄素的单加氧酶（FMO）催化多种药物和膳食衍生化合物的氧化。但是，关于FMO3在体内的药物相互作用的信息很少。因此，我们调查了人源化肝脏小鼠中FMO底物之间的相互作用。将三甲胺-d9和伊托必利分别静脉内和口服给予人源化肝小鼠（n = 5-7）。在液相色谱/串联质谱联用后24小时内，确定在三甲胺（作恶药）存在下伊托必利（受害药）的药代动力学概况。依托必利（10 mg / kg）在人源化肝小鼠中被广泛氧化成其N-氧化物。依托必利和三甲胺并用后血浆中的依托必利N-氧化物的血浆浓度（10和100 mg / kg）以剂量依赖的方式被显着抑制，但仅在早期阶段，即在合用后直至2小时行政。随着三甲胺剂量的增加，伊托必利及其氮氧化物的浓度-时间曲线下的面积分别显着增加（1.6倍）和减少（至60％）。模型表明这些修饰的药代动力学是由体内肝内在清除率的抑制（至67％）导致的。这些结果表明，食品中的三甲胺可能会在给药后立即与FMO药物底物发生相互作用。但是，这种可能性在体内可能会受到限制。

BACKGROUND & AIMS: :With the aging of the population, the burden of Alzheimer's disease (AD) is rapidly expanding. More than 5 million people in the US alone are affected with AD and this number is expected to triple by 2050. While men may have a higher risk of mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, women are disproportionally affected with AD. One explanation is that men may die of competing causes of death earlier in life, so that only the most resilient men may survive to older ages. However, many other factors should also be considered to explain the sex differences. In this review, we discuss the differences observed in men versus women in the incidence and prevalence of MCI and AD, in the structure and function of the brain, and in the sex-specific and gender-specific risk and protective factors for AD. In medical research, sex refers to biological differences such as chromosomal differences (eg, XX versus XY chromosomes), gonadal differences, or hormonal differences. In contrast, gender refers to psychosocial and cultural differences between men and women (eg, access to education and occupation). Both factors play an important role in the development and progression of diseases, including AD. Understanding both sex- and gender-specific risk and protective factors for AD is critical for developing individualized interventions for the prevention and treatment of AD.

背景与目标： 随着人口的老龄化，阿尔茨海默氏病（AD）的负担正在迅速扩大。仅在美国，就有超过500万人患有AD，预计到2050年，这一数字将增加三倍。尽管男性轻度认知障碍（MCI）的风险较高，轻度认知障碍是正常衰老与痴呆症之间的中间阶段，但女性比例却不成比例。受AD影响。一种解释是，男人可能会在生命的早期死于竞争性死亡原因，因此只有最有韧性的男人才能生存到更高的年龄。但是，还应考虑许多其他因素来解释性别差异。在这篇综述中，我们讨论了男性和女性在MCI和AD的发生率和患病率，大脑的结构和功能以及针对性别的性别和性别特异性风险及保护因素方面的差异。在医学研究中，性别是指生物学差异，例如染色体差异（例如XX与XY染色体），性腺差异或荷尔蒙差异。相反，性别是指男人和女人之间的社会心理和文化差异（例如，获得教育和职业的机会）。这两个因素在包括AD在内的疾病的发生和发展中都起着重要作用。理解针对性别的性别风险和针对性别的风险因素以及保护因素对于开发预防和治疗AD的个性化干预措施至关重要。

BACKGROUND & AIMS: :Gaze-stabilization exercise (GSE) is often conducted in vestibular rehabilitation, but its effect on vestibular function in postural control is not clear. We investigated whether GSE affects vestibular function during static upright standing and vestibulospinal reflex (VSR) in healthy young adults. First, the center of pressure of the total trajectory length (CoP-L) was measured before each GSE task or control (only standing) task (pre), immediately after (post), and 10 min after (post10) in the static standing position on foam rubber with the eyes open or closed (EC). Second, the H-reflex on the soleus muscle was measured after the onset of ipsilateral anodal galvanic vestibular stimulation before and after a GSE or a control task to estimate the amount of VSR induced by electrical vestibular input. CoP-L for the pre, post, and post10 control tasks and the GSE in EC did not differ significantly; the CoP-L for the post and post10 tasks in EC were significantly lower than that for the pretask. The H-reflex was inhibited by galvanic vestibular stimulation in the pre-GSE tasks. The inhibition increased after GSE, but not during control tasks. These findings suggest that GSE immediately improves the postural stability required for vestibular function and can be mediated by VSR improvements.

背景与目标： ：凝视稳定运动（GSE）通常在前庭康复中进行，但对姿势控制中前庭功能的影响尚不清楚。我们调查了健康年轻人在静态直立站立和前庭脊髓反射（VSR）期间，GSE是否会影响前庭功能。首先，在静态站立时，在每个GSE任务或控制（仅站立）任务（前）之前，之后（后）和之后（post10）之后的10分钟内，测量总轨迹长度（CoP-L）的压力中心睁眼或闭眼（EC）将其放在泡沫橡胶上。其次，在GSE或控制任务之前和之后，在同侧肛门电流前庭刺激开始后，测量比目鱼肌的H反射，以估计由前庭电输入引起的VSR量。前，后和后10个控制任务的CoP-L与EC中的GSE并无显着差异。 EC中的post和post10任务的CoP-L显着低于pretask的CoP-L。 GSE之前的任务中，前庭电刺激抑制了H反射。抑制作用在GSE后增加，但在控制任务期间没有增加。这些发现表明，GSE可立即改善前庭功能所需的姿势稳定性，并可通过VSR的改善来介导。

BACKGROUND & AIMS:

背景与目标：

BACKGROUND & AIMS: :Domperidone and Itopride are pro-kinetic agents, regulating the gastric motility and are commonly prescribed as anti emetic drugs. In the present study a simple, rapid and sensitive RP-HPLC/UV method was developed for simultaneous determination of Domperidone and Itopride in pharmaceutical samples and human plasma, using Tenofavir as internal standard. Experimental conditions were optimized and method was validated according to the standard guidelines. Combination of water (pH 3.0) and acetonitrile (65:35 v/v) was used as mobile phase, pumped at the flow rate of 1.5 ml/min. Detector wavelength was set at 210 nm and column oven temperature was 40oC. Unlike conventional liquid-liquid extraction, simple precipitation technique was applied for drug extraction from human plasma using acetonitrile for deprotienation. The method showed adequate separation of both the analytes and best resolution was achieved using Hypersil BDS C8 column (150 mm × 4.6 mm, 5 μm). The method was quite linear in the range of 20-600 ng/ml. Recovery of the method was 92.31% and 89.82% for Domperidone and Itopride, respectively. Retention time of both the analytes and internal standard was below 15 min. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for Domperidone were 5 and 10 ng/ml while for Itopride was 12 and 15 ng/ml, respectively. The developed method was successfully applied for in-vivo analysis of fast dispersible tablets of Domperidone in healthy human volunteer. The proposed method was a part of formulation development study and was efficiently applied for determination of the two drugs in various pharmaceutical products and human plasma.

背景与目标： 多潘立酮和伊托必利是促动剂，可调节胃动力，通常被处方为催吐药。在本研究中，开发了一种简单，快速，灵敏的RP-HPLC / UV方法，以替诺福韦作为内标，同时测定药物样品和人血浆中的多潘立酮和伊托必利。根据标准指南优化了实验条件并验证了方法。将水（pH 3.0）和乙腈（65:35 v / v）的混合物用作流动相，以1.5 ml / min的流速泵送。检测器波长设置为210 nm，柱温箱温度为40oC。与常规液-液萃取不同，简单的沉淀技术被应用于使用乙腈脱去质从人血浆中提取药物。该方法显示了两种分析物的充分分离，使用Hypersil BDS C8色谱柱（150 mm×4.6 mm，5μm）可实现最佳分离度。该方法在20-600 ng / ml范围内呈线性。多潘立酮和伊托必利的方法回收率分别为92.31％和89.82％。分析物和内标物的保留时间均在15分钟以下。多潘立酮的检测下限（LLOD）和定量下限（LLOQ）分别为5和10 ng / ml，而伊托必利的分别为12和15 ng / ml。所开发的方法已成功地用于健康人志愿者中多潘立酮快速分散片的体内分析。所提出的方法是制剂开发研究的一部分，可有效地用于测定各种药品和人体血浆中的两种药物。

BACKGROUND & AIMS:

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The treatment of patients with functional dyspepsia remains unsatisfactory. We assessed the efficacy of itopride, a dopamine D2 antagonist with anti-acetylcholinesterase [corrected] effects, in patients with functional dyspepsia. METHODS:Patients with functional dyspepsia were randomly assigned to receive either itopride (50, 100, or 200 mg three times daily) or placebo. After eight weeks of treatment, three primary efficacy end points were analyzed: the change from baseline in the severity of symptoms of functional dyspepsia (as assessed by the Leeds Dyspepsia Questionnaire), patients' global assessment of efficacy (the proportion of patients without symptoms or with marked improvement), and the severity of pain or fullness as rated on a five-grade scale. RESULTS:We randomly assigned 554 patients; 523 had outcome data and could be included in the analyses. After eight weeks, 41 percent of the patients receiving placebo were symptom-free or had marked improvement, as compared with 57 percent, 59 percent, and 64 percent receiving itopride at a dose of 50, 100, or 200 mg three times daily, respectively (P<0.05 for all comparisons between placebo and itopride). Although the symptom score improved significantly in all four groups, an overall analysis revealed that itopride was significantly superior to placebo, with the greatest symptom-score improvement in the 100- and 200-mg groups (-6.24 and -6.27, vs. -4.50 in the placebo group; P=0.05). Analysis of the combined end point of pain and fullness showed that itopride yielded a greater rate of response than placebo (73 percent vs. 63 percent, P=0.04). CONCLUSIONS:Itopride significantly improves symptoms in patients with functional dyspepsia. (ClinicalTrials.gov number, NCT00272103.).

背景与目标： 背景：功能性消化不良患者的治疗仍不令人满意。我们评估了伊托必利（一种具有抗乙酰胆碱酯酶[校正]作用的多巴胺D2拮抗剂）在功能性消化不良患者中的疗效。
方法：将具有功能性消化不良的患者随机分配为接受伊托必利（每日3次，每次50、100或200毫克）或安慰剂。在治疗八周后，分析了三个主要功效终点：功能性消化不良症状严重程度相对于基线的变化（由利兹消化不良问卷评估），整体疗效评估（无症状或无症状的患者比例）有明显改善），以及疼痛或饱胀的严重程度（以五级量表评分）。
结果：我们随机分配了554例患者。 523有结果数据，可以纳入分析。八周后，接受安慰剂的患者中有41％无症状或有明显改善，而分别以50、100或200 mg的剂量每天3次接受伊托必利的患者分别为57％，59％和64％。 （对于安慰剂和伊托必利之间的所有比较，P <0.05）。尽管在所有四个组中症状评分均显着改善，但总体分析显示，伊托必利明显优于安慰剂，在100和200 mg组中，症状评分改善最大（-6.24和-6.27，而-4.50在安慰剂组中； P ＝ 0.05）。对疼痛和饱胀感综合终点的分析表明，伊托必利产生的反应率高于安慰剂（73％vs. 63％，P = 0.04）。
结论：依托必利可显着改善功能性消化不良患者的症状。 （ClinicalTrials.gov编号，NCT00272103。）。

BACKGROUND & AIMS: :Several methods are used to evaluate gastric motility in rodents, but they all have technical limitations. Recent technical developments enable a convenient method to evaluate gastric motility. The (13)C-acetic acid breath test in rodents is a non-invasive and repeatable method that can be used without physical restraints. The present study aimed to validate the (13)C-acetic acid breath test by measuring the effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice. Loperamide (1-10 mg/kg) and morphine (1.25-10 mg/kg) slowed gastric emptying and decreased the maximum concentration (C(max)) and area under the curve (AUC(90 min)) value in a dose-dependent manner. Mosapride (0.2-5 mg/kg) accelerated gastric emptying and increased C(max) value. Mosapride (20 mg/kg) did not accelerate gastric emptying on the (13)C-breath test. Itopride (30 mg/kg, per os) significantly accelerated gastric emptying compared with the vehicle group. In a comparison with the conventional phenol red test, there was a correlation between the C(max) value of breath test and gastric emptying (%) of phenol red tests in treatment with loperamide or mosapride. These results indicate that the (13)C-acetic acid breath test is an accurate, noninvasive, and simple method for monitoring gastric emptying in mice. This method is useful to assess the effect of drugs and gut function pharmacologically.

背景与目标： ：有几种方法可用于评估啮齿动物的胃动力，但是它们都有技术上的局限性。最近的技术发展为评估胃动力提供了一种方便的方法。啮齿动物的（13）C-乙酸呼气试验是一种无创且可重复的方法，可以在没有物理限制的情况下使用。本研究旨在通过测量洛哌丁胺，吗啡，莫沙必利和伊托必利对小鼠胃排空的影响来验证（13）C-乙酸呼气试验。剂量下的洛哌丁胺（1-10 mg / kg）和吗啡（1.25-10 mg / kg）减慢了胃排空速度，降低了最大浓度（C（max））和曲线下面积（AUC（90 min））值-依赖方式。莫沙必利（0.2-5 mg / kg）加速胃排空并增加C（max）值。莫沙必利（20 mg / kg）在（13）C呼气试验中并未加速胃排空。与媒介物组相比，依托必利（30 mg / kg，口服）显着加速了胃排空。与常规酚红试验比较，在用洛哌丁胺或莫沙必利治疗时，呼气试验的C（max）值与酚红试验的胃排空率（％）之间存在相关性。这些结果表明，（13）C-乙酸呼气试验是一种监测小鼠胃排空的准确，无创且简单的方法。此方法可用于从药理学角度评估药物的作用和肠道功能。