血清UA、Hcy、LDL-C联合监测对急性脑梗死患者阿替普酶静脉溶栓治疗后脑出血性转化的预测价值

摘要 目的：探讨血清尿酸（UA）、同型半胱氨酸（Hcy）和低密度脂蛋白胆固醇（LDL-C）联合监测对急性脑梗死（ACI）患者阿替普酶静脉溶栓治疗后脑出血性转化（HT）的预测价值。方法：选取2018年1月～2020年12月西南医科大学附属成都三六三医院收治的173例接受阿替普酶静脉溶栓治疗的ACI患者,根据静脉溶栓后是否发生HT分为HT组和非HT组。对比两组的临床资料和血清UA、Hcy、LDL-C水平,采用多因素Logistic回归分析ACI患者阿替普酶静脉溶栓治疗后发生HT的影响因素,采用受试者工作特征（ROC）曲线分析血清UA、Hcy、LDL-C联合监测对ACI患者阿替普酶静脉溶栓治疗后发生HT的预测价值。结果：173例患者中有47例发生HT,发生率为27.17％。与非HT组比较,HT组年龄更大,收缩压、舒张压、美国国立卫生研究院卒中量表（NIHSS）评分、溶栓前随机血糖以及Hcy水平更高,而LDL-C及UA水平更低（P＜0.05）。多因素Logistic回归分析结果显示：收缩压、NIHSS评分、溶栓前随机血糖以及Hcy水平为ACI患者阿替普酶静脉溶栓治疗后发生HT的危险因素,而UA、LDL-C水平为保护因素。ROC曲线分析结果显示：血清UA、Hcy、LDL-C单独与联合监测预测ACI患者阿替普酶静脉溶栓治疗后HT的曲线下面积（AUC）分别为0.764、0.794、0.674、0.888,联合监测时的AUC明显更高。结论：血清UA、LDL-C低水平和Hcy高水平是ACI患者阿替普酶静脉溶栓治疗后HT的影响因素,联合监测能提高对HT发生的预测价值。     

Solitaire AB支架机械取栓联合阿替普酶静脉溶栓对急性缺血性脑卒中患者的临床研究

目的:探讨急性缺血性脑卒中患者运用阿替普酶静脉溶栓联合Solitaire AB支架机械取栓对其神经保护因子、血液流变学及免疫功能的影响。方法:将我院于2017年4月~2019年3月期间收治的急性缺血性脑卒中患者113例以双色球随机分组法分为研究组(Solitaire AB支架机械取栓联合阿替普酶静脉溶栓)和对照组(阿替普酶静脉溶栓),分别为57例和56例。比较两组患者疗效、神经功能、血管再通率、神经保护因子、血液流变学及免疫功能,并记录两组治疗期间不良反应状况。结果:研究组治疗后3个月的总有效率为91.22%(52/57),高于对照组的76.79%(43/56)(P<0.05)。研究组的血管再通率高于对照组(P<0.05)。两组不良反应发生率对比未见统计学差异(P>0.05)。两组治疗后3个月的CD8⁺、美国国立卫生研究所卒中量表(NIHSS)评分、纤维蛋白原、全血黏度、神经胶质原纤维酸性蛋白(GFAP)及血浆黏度均较治疗前降低,且研究组低于对照组(P<0.05)。CD3⁺、CD4⁺、CD4⁺/CD8⁺、胰岛素样生长因子-1(IGF-1)、脑源性神经营养因子(BDNF)均升高,且研究组高于对照组(P<0.05)。结论:急性缺血性脑卒中患者在阿替普酶静脉溶栓治疗的基础上联合Solitaire AB支架机械取栓治疗,安全有效,能够改善机体的免疫功能及血液流变学,减轻神经功能损害,并提高患者血管再通率。     

No Relation between Body Temperature and Arterial Recanalization at Three Days in Patients with Acute Ischaemic Stroke

Background

Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization.

Methods

We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1°Celsius increase in admission body temperature and recanalization at three days.

Results

Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1°Celsius, 0.99; 95% confidence interval, 0.94–1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same.

Conclusions

Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase.     

局部动脉注射阿替普酶溶栓治疗急性缺血性脑卒中的临床效果

目的分析局部动脉注射阿替普酶溶栓治疗急性缺血性脑卒中的临床效果。方法本溪市中心医院从2011年1月至2013年10月期间共收治90例急性缺血性脑卒中患者,患者在入院的6 h内接受了阿替普酶溶栓的局部动脉注射治疗,观察总结患者接受治疗24 h和3个月内的疗效,并依据临床观察和NHISS评分结果来评价患者的神经功能恢复情况。结果 90例患者当中有58例前循环缺血患者和32例后循环缺血患者,在接受溶栓治疗的24 h内有64例患者神经功能得到良好恢复,占总数的71.11%,还有26例患者神经功能不良,占总数的28.89%;3个月后通过随访了解到有82例患者神经功能良好,占总数的91.11%,8例患者功能仍然处于不良状态,占总数的8.89%,治疗前后患者的神经功能恢复比较差异具有统计学意义（P〈0.05%）。结论局部动脉注射阿替普酶溶栓治疗急性缺血性脑卒中,患者能够得到有效恢复,疗效显著,值得在临床上推广使用。     

Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor

Hereditary angioedema is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic types are both caused by mutations within the complement C1 inhibitor gene. A recently described new type does not show a deficiency of C1 inhibitor and affects almost exclusively women. We screened twenty unrelated index patients with this new type of hereditary angioedema for mutations in the coagulation factor XII gene. Two different missense mutations were identified in exactly the same position within exon 9 of the F12 gene. 'Mutation 1' (1032C-->A), encountered in five patients, predicts a threonine-to-lysine substitution (Thr309Lys). 'Mutation 2' (1032C-->G), observed in one patient, results in a threonine-to-arginine substitution (Thr309Arg). The predicted structural and functional impact of the mutations, their absence in 145 healthy controls, and their co-segregation with the phenotype in five families provide strong support that they cause disease.     

Polymorphisms in IL12A and cockroach allergy in children with asthma

Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation. Subnormal levels of C1-inhibitor are associated with the inappropriate activation of a number of pathways – including, in particular, the complement and contact systems, and to some extent, the fibrinolysis and coagulation systems. Current findings indicate bradykinin, a product of contact system activation, as the primary mediator of angioedema in patients with C1-inhibitor deficiency. However, other systems may play a role in bradykinin's rapid and excessive generation by depleting available levels of C1-inhibitor. There are currently no effective therapies in the United States to treat acute attacks of hereditary angioedema, and currently available agents used to treat hereditary angioedema prophylactically are suboptimal. Five new agents are, however, in Phase III development. Three of these agents replace C1-inhibitor, directly addressing the underlying cause of hereditary angioedema and re-establishing regulatory control of all pathways and proteases involved in its pathogenesis. These agents include a nano-filtered C1-inhibitor replacement therapy, a pasteurized C1-inhibitor, and a recombinant C1-inhibitor isolated from the milk of transgenic rabbits. All C1-inhibitors are being investigated for acute angioedema attacks; the nano-filtered C1-inhibitor is also being investigated for prophylaxis of attacks. The other two agents, a kallikrein inhibitor and a bradykinin receptor-2 antagonist, target contact system components that are mediators of vascular permeability. These mediators are formed by contact system activation as a result of C1-inhibitor consumption.     

丁苯酞联合低剂量阿替普酶治疗急性脑梗死的疗效及对患者神经内分泌因子的影响

目的:探讨丁苯酞联合低剂量阿替普酶治疗急性脑梗死的疗效及对患者神经内分泌因子的影响。方法:按照随机数表法将105例患者分为对照组(n=52)和研究组(n=53)。对照组患者采用低剂量阿替普酶治疗,研究组患者在对照组基础上加用丁苯酞治疗。评价并比较两组临床疗效,比较两组治疗前后美国国立卫生研究院卒中量表(NIHSS)评分和血清S-100蛋白(S100B)、神经元特异性烯醇化酶(NSE)、髓鞘碱性蛋白(MBP)水平,比较两组治疗14 d内的颅内出血发生率和病死率。结果:研究组的临床总有效率为94.34%(50/53),明显高于对照组的76.92%(40/52),且差异具有统计学意义(x2=6.502,P=0.011)。与治疗前相比,两组治疗后NIHSS评分均明显降低,且研究组治疗后的NIHSS评分明显低于对照组,差异有统计学意义(P<0.05)。与治疗前相比,两组治疗后血清S100B、NSE及MBP水平均明显降低(P<0.05),且研究组治疗后血清S100B、NSE及MBP水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗14 d内,研究组的颅内出血发生率和死亡率均明显低于对照组,差异有统计学意义(P<0.05)。结论:丁苯酞联合低剂量阿替普酶治疗急性脑梗死的疗效显著,能够明显改善神经功能,降低神经内分泌因子水平,且安全性较好。     

阿替普酶联合依达拉奉治疗急性缺血性卒中的疗效及神经功能缺损与时间窗的关系研究

目的:探讨阿替普酶联合依达拉奉治疗急性缺血性卒中的疗效及神经功能缺损与时间窗的关系。方法:选取大连医科大学附属大连市中心医院于2016年3月~2018年10月间收治的急性缺血性卒中患者117例,根据随机数字表法将患者分为对照组(n=58,阿替普酶治疗)和研究组(n=59,阿替普酶联合依达拉奉治疗),比较两组患者临床疗效、神经功能缺损情况、基质金属蛋白酶-9(MMP-9)、白介素-6(IL-6)水平、头颅CT梗死面积,观察两组治疗期间不良反应发生情况。结果:研究组的总有效率为84.75%(50/59),高于对照组的63.79%(37/58)(P<0.05)。两组患者治疗2周后MMP-9、IL-6、美国国立卫生研究院卒中量表(NIHSS)评分均较治疗前降低,且研究组低于对照组(P<0.05)。研究组治疗24h、48h、72h的头颅CT梗死面积小于对照组(P<0.05)。治疗后研究组发病72h内、发病48h内患者NIHSS评分、头颅CT梗死面积高于发病24h内,且发病72h内高于发病48h内(P<0.05)。两组患者不良反应发生率比较无差异(P>0.05)。结论:阿替普酶联合依达拉奉治疗急性缺血性卒中,疗效确切,可有效改善患者过氧化损伤,降低细胞因子水平,且越早的时间窗内接受治疗的患者,其神经功能缺损、脑梗死面积改善效果越好。     

银杏叶提取物注射液联合阿替普酶静脉溶栓治疗急性脑梗死的疗效及对血液流变学和炎症因子的影响

摘要 目的：观察急性脑梗死（ACI）在溶栓治疗的基础上联合银杏叶提取物注射液治疗后的疗效,并分析该治疗方案对炎症因子、血液流变学的影响。方法：选择2019年6月到2020年10月期间来我院接受诊治的ACI患者60例,按照入院奇偶顺序法将患者分为对照组（奇,30例,阿替普酶静脉溶栓治疗）和观察组（偶,30例,银杏叶提取物注射液联合阿替普酶静脉溶栓治疗）,疗程为7 d。对比两组治疗7 d后的疗效,对比两组治疗前、治疗7 d后的血液流变学、美国国立卫生研究院卒中量表（NIHSS）评分、炎症因子、日常生活能力量表（ADL）评分,观察两组治疗期间不良反应发生情况。结果：观察组的临床总有效率较对照组高（P<0.05）。观察组治疗7 d后NIHSS评分低于对照组,ADL评分高于对照组（P<0.05）。观察组治疗7 d后超敏C-反应蛋白（hs-CRP）、白细胞介素-6（IL-6）水平低于对照组（P<0.05）。观察组治疗7 d后血小板压积、血小板分布宽度、纤维蛋白原低于对照组（P<0.05）。两组不良反应发生率对比,差异无统计学意义（P>0.05）。结论：银杏叶提取物注射液联合阿替普酶静脉溶栓治疗ACI患者疗效明确,可改善血液流变学,减少神经功能损伤,降低炎症因子水平,提高患者生活自理能力,且安全性好。     

The Impact of Duration of Treatment on Reported Time-to-Onset in Spontaneous Reporting Systems for Pharmacovigilance

Within pharmacovigilance, knowledge of time-to-onset (time from start of drug administration to onset of reaction) is important in causality assessment of drugs and suspected adverse drug reactions (ADRs) and may indicate pharmacological mechanisms involved. It has been suggested that time-to-onset from individual case reports can be used for detection of safety signals. However, some ADRs only occur during treatment, while those that do occur later are less likely to be reported. The aim of this study was to investigate the impact of treatment duration on the reported time-to-onset. Case reports from the WHO Global ICSR database, VigiBase, up until February 5^th 2010 were the basis of this study. To examine the effect of duration of treatment on reported time-to-onset, angioedema and hepatitis were selected to represent short and long latency ADRs, respectively. The reported time-to-onset for each of these ADRs was contrasted for a set of drugs expected to be used short- or long-term, respectively. The study included 2,980 unique reports for angioedema and 1,159 for hepatitis. Median reported time-to-onset for angioedema in short-term treatments ranged 0-1 days (median 0.5), for angioedema in long-term treatments 0-26 days (median 8), for hepatitis in short-term treatments 4-12 days (median 7.5) and for hepatitis in long term treatments 19-73 days (median 28). Short-term treatments presented significantly shorter reported time-to-onset than long-term treatments. Of note is that reported time-to-onset for angioedema for long-term treatments (median value of medians being 8 days) was very similar to that of hepatitis for short-term treatments (median value of medians equal 7.5 days). The expected duration of treatment needs to be considered in the interpretation of reported time-to-onset and should be accounted for in signal detection method development and case evaluation.     

脑心通胶囊联合阿替普酶治疗急性脑梗死的疗效及对凝血功能、血液流变学和认知功能的影响

摘要 目的：探究脑心通胶囊联合阿替普酶治疗急性脑梗死（ACI）的疗效,并观察该治疗方案对凝血功能、血液流变学和认知功能的影响。方法：选取我院于2016年6月~2020年12月期间收治的137例ACI患者。按照随机数字表法将患者分为对照组和观察组,其中对照组68例,接受阿替普酶治疗,观察组69例,接受脑心通胶囊联合阿替普酶治疗,两组均治疗10 d。比较两组治疗10 d后的临床总有效率,观察两组治疗前、治疗10d后的凝血功能、血液流变学和认知功能变化情况,记录两组肝肾功能、血常规异常情况及药物不良反应。结果：两组临床总有效率组间对比有明显差异（P＜0.05）。与治疗前比较,两组患者治疗10 d后活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、凝血酶时间（TT）均延长,D-二聚体（D-D）、全血低切黏度、全血高切黏度、血浆黏度、红细胞比容均降低（P＜0.05）,且与对照组相比,观察组以上指标改善均更为显著（P＜0.05）。与治疗前比较,治疗10 d后两组患者美国国立卫生研究院卒中量表（NIHSS）评分均降低,日常生活能力量表（ADL）评分均升高（P＜0.05）,且与对照组相比,观察组以上评分改善均更为显著（P＜0.05）。两组用药期间血常规、肝肾功能均无异常情况,未见严重不良反应发生。与治疗前比较,两组患者治疗10d后老年快速认知筛查量表（QCST-E）各维度评分均升高（P＜0.05）,且与对照组相比,观察组改善更为显著（P＜0.05）。结论：在阿替普酶治疗基础上联合脑心通胶囊治疗ACI,可改善患者神经功能,提高患者日常生活能力,并促进凝血功能、血液流变学和认知功能改善。     

Chronic urticaria.

Urticaria affects 15% to 20% of the population once or more during a lifetime. Chronic urticaria is a frequent recurrent eruption over a period greater than 6 weeks; the cause remains a mystery in more than 75% of cases. Urticaria and angioedema may be produced by immunologic or nonimmunologic means. Urticarial vasculitis, contact urticaria, mastocytosis, physical urticarias, dermatographism, cholinergic urticaria, localized heat urticaria, cold urticaria, aquagenic urticaria, and vibratory angioedema all require specific evaluation and treatment. Chronic idiopathic urticaria is usually controlled by antihistamines; depending on the circadian rhythm of the eruption, sedative or nonsedative antihistamines are prescribed. Some patients will require a combination of H1 and H2 antagonists, or even parenteral corticosteroids.     

A point mutation in exon 7 of the C1-inhibitor gene causing type I hereditary angioedema

The polymerase chain reaction and nucleotide sequence analysis have been used to characterize a point mutation in the seventh exon of one allele of the C1-inhibitor gene in a family with type I hereditary angioedema. A single base change (C→T) at nucleotide 1482 in C1-inhibitor converted the codon for Gln-339 to a premature translation termination codon, TAG. Family studies suggest that this mutation is reponsible for type I hereditary angioedema in a studied pedigree. Received: 19 March 1996     

Autoimmune progesterone dermatitis in a patient with endometriosis: case report and review of the literature

Autoimmune progesterone dermatitis (APD) is a condition in which the menstrual cycle is associated with a number of skin findings such as urticaria, eczema, angioedema, and others. In affected women, it occurs 3-10 days prior to the onset of menstrual flow, and resolves 2 days into menses. Women with irregular menses may not have this clear correlation, and therefore may be missed. We present a case of APD in a woman with irregular menses and urticaria/angioedema for over 20 years, who had not been diagnosed or correctly treated due to the variable timing of skin manifestations and menses. In addition, we review the medical literature in regards to clinical features, pathogenesis, diagnosis, and treatment options.     

Cleavage of kininogen and subsequent bradykinin release by the complement component: mannose-binding lectin-associated serine protease (MASP)-1

Bradykinin (BK), generated from high-molecular-weight kininogen (HK) is the major mediator of swelling attacks in hereditary angioedema (HAE), a disease associated with C1-inhibitor deficiency. Plasma kallikrein, activated by factor XIIa, is responsible for most of HK cleavage. However other proteases, which activate during episodes of angioedema, might also contribute to BK production. The lectin pathway of the complement system activates after infection and oxidative stress on endothelial cells generating active serine proteases: MASP-1 and MASP-2. Our aim was to study whether activated MASPs are able to digest HK to release BK. Initially we were trying to find potential new substrates of MASP-1 in human plasma by differential gel electrophoresis, and we identified kininogen cleavage products by this proteomic approach. As a control, MASP-2 was included in the study in addition to MASP-1 and kallikrein. The proteolytic cleavage of HK by MASPs was followed by SDS-PAGE, and BK release was detected by HPLC. We showed that MASP-1 was able to cleave HK resulting in BK production. MASP-2 could also cleave HK but could not release BK. The cleavage pattern of MASPs is similar but not strictly identical to that of kallikrein. The catalytic efficiency of HK cleavage by a recombinant version of MASP-1 and MASP-2 was about 4.0×10(2) and 2.7×10(2) M(-1) s(-1), respectively. C1-inhibitor, the major inhibitor of factor XIIa and kallikrein, also prevented the cleavage of HK by MASPs. In all, a new factor XII- and kallikrein-independent mechanism of bradykinin production by MASP-1 was demonstrated, which may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in HAE patients.     

影响阿替普酶治疗急性缺血性卒中早期疗效的临床研究

目的:探讨影响阿替普酶静脉溶栓治疗急性缺血性卒中早期疗效的因素。方法:回顾性分析2010年11月至2014年11月我院接受阿替普酶静脉(rt-PA)溶栓治疗的49例急性缺血性卒中患者的临床数据,根据美国国立卫生研究院神经功能缺损评分(NIHSS评分),溶栓后24h评分减少超过3分为溶栓早期有效组(24例),否则为溶栓早期无效组(25例),比较两组各临床数据的差异。结果:两组患者性别、年龄、吸烟史、酗酒史、高血压病史、糖尿病史、溶栓前血糖、血生化、血压等均无差异(P0.05);早期有效组患者房颤发生率、脑白质病变发生率和溶栓前NIHSS评分较早期无效组低,差异均有统计学意义(P0.05);早期有效组患者90天生活自理率较早期无效组高,差异有统计学意义(P0.05)。结论:阿替普酶静脉溶栓后早期疗效好者3个月预后好;溶栓前无房颤、无白质疏松患者溶栓后早期疗效好。     

Helicobacter pylori infection as a triggering factor of attacks in patients with hereditary angioedema

BACKGROUND: Helicobacter pylori infection is considered among the causative factors of urticaria and angioedema. Having conducted a study on 65 patients, Hungarian authors reported in 2001 that successful eradication of H. pylori is followed by a significant reduction in the number of attacks in patients with hereditary angioedema (HAE). The present study aimed to reinvestigate the relationship between H. pylori infection and the attack rate in the framework of an international collaborative study. MATERIALS AND METHODS: Within the framework of the PREHAEAT project launched by the European Union, further 152 patients were studied in seven collaborating centers, and participants of the earlier study were followed up in order to detect any relationship between H. pylori infection and the occurrence of attacks in patients suffered from HAE. RESULTS: The proportion of patients experiencing frequent (> or = 5 per year) abdominal attacks was higher (p = .002) among the H. pylori-infected participants of the international study who underwent eradication as compared to the rest of patients. Successful eradication of H. pylori significantly (p = .0006) reduced the number of attacks in these patients as well. Nine subjects of the previous Hungarian study who underwent eradication therapy for dyspepsia were followed up for an additional 4 years. In these patients, attack frequency remained consistently low. CONCLUSIONS: As shown by experience from the Hungarian and the international trial, the number of frequent, edematous abdominal attacks may decrease substantially following the eradication of H. pylori from HAE patients infected with this pathogen. Therefore, screening of patients with HAE for H. pylori infection seems warranted. Eradication of H. pylori may lead to a marked reduction in disease severity.     

Anti-cholesterol antibody levels in hereditary angioedema

Hereditary angioedema (HAE) is a rare disorder caused by the deficiency of the C1-inhibitor gene (C1INH) and characterized by recurrent bouts of angioedema. Autoimmune disorders frequently occur in HAE. Previously we found, that danazol has an adverse effect on serum lipid profile: reduced high-density lipoprotein (HDL) and elevated low-density lipoprotein (LDL) cholesterol levels are associated with long-term prophylactic use, whereas total cholesterol levels are unchanged. Our aim was to study the anti-cholesterol antibody (ACHA) production in HAE patients and compare it with those of healthy blood donors, and to investigate the possible associations between ACHA levels and serum lipid profile alterations caused by danazol. Anti-cholesterol IgG levels were measured by ELISA and their correlation with serum concentrations of total cholesterol, HDL, LDL, triglycerides was determined in HAE patients receiving/not receiving danazol. Serum ACHA levels were significantly higher in HAE patients, compared to healthy blood donors (P<0.0001). Longterm danazol prophylaxis had no effect on serum ACHA levels in HAE patients. However, we found a significant, negative correlation between ACHA levels and serum total cholesterol (r=-0.4033, P=0.0200), LDL (r=-0.4565, P=0.0076) and triglyceride (r=-0.4230, P=0.0121) levels only in danazol-treated patients, but not in HAE patients who did not receive long-term prophylaxis. Patients with HAE have higher baseline ACHA levels compared to healthy subjects, and this might reflect polyclonal B-cell activation. The latter would be a potential explanation for the lack of an increased incidence of infectious diseases in HAE patients, but might lead to increased autoimmunity.     

In vitro effect of the potent poly(ADP-ribose) polymerase (PARP) inhibitor INO-1001 alone and in combination with aspirin, eptifibatide, tirofiban, enoxaparin or alteplase on haemostatic parameters

It has been shown that PARP inhibition is protective in several models of ischemia-reperfusion injury including cardiac, cerebral and renal ones. Due to their ability to reduce myocardial necrosis and to improve myocardial function PARP inhibitors emerged as candidates for treating various cardiovascular diseases including acute myocardial ischemia. Since the pathophysiology of acute ischemic cardiac diseases involves haemostatic impairment and the therapeutic regimen includes antithrombotic drugs, we investigated the effect of the potent poly(ADP-ribose) polymerase (PARP) inhibitor INO-1001 alone and in combination with platelet aggregation inhibitors (aspirin, eptifibatide and tirofiban), unfractionated heparin, low molecular weight heparin (enoxaparin) or the recombinant fibrinolytic drug (alteplase), on various haemostatic parameters in vitro. ADP- and epinephrine-induced platelet aggregation was evaluated by optical aggregometry in the presence or absence of different concentrations of INO-1001, in combination with aspirin, tirofiban, eptifibatide or saline on ten healthy volunteers' platelet rich plasma (PRP). Activated partial thromboplastin time, Anti-Xa activity and euglobulin lysis time were determined in the presence or absence of different concentrations of INO-1001, in combination with sodium heparin, enoxaparin or alteplase, respectively. INO-1001, on its own does not affect the measured platelet, and haemostatic functions, i.e. does not reduce the respective anti-platelet, anti-coagulant and thrombolytic activity of therapeutically relevant concentrations of aspirin, tirofiban, eptifibatide, enoxaparin and alteplase in vitro. INO-1001 enhanced the effects of heparins above therapeutic ranges; the magnitude of this effect was negligible. Consequently, the PARP inhibitor INO-1001 can be safely applied together with the drugs tested.     

Adverse reactions to acetylcysteine and effects of overdose.

Since the introduction in 1979 of intravenous acetylcysteine (Parvolex) as an antidote for overdosage of paracetamol the National Poisons Information Service and the manufacturer have been notified of 38 adverse reactions that were anaphylactoid in nature and 19 accidental overdoses. The most common feature of the anaphylactoid reaction to normal dosage was rash; other features reported included angioedema, hypotension, and bronchospasm; all the patients recovered. The features associated with an overdose of acetylcysteine were similar but more severe; two patients died, but the extent to which the overdose of acetylcysteine may have been implicated was not clear in either case.