染料法术中标记34例大肠癌前哨淋巴结的意义

目的探索前哨淋巴结活检（SI。NB）技术在早期大肠癌中的应用及前哨淋巴结（SI。N）微转移检测的临床意义。方法应用染料法对34例大肠癌患者，在根治术中于肿瘤周围或基底部浆膜下注射亚甲蓝溶液2mL左右，识别和定位蓝染的淋巴结（即前哨淋巴结），术后行常规HE病理和鼠抗人细胞角蛋白单克隆抗体AE1／AE3免疫组化染色法（ELIVISION二步法）检查。结果34例大肠癌患者中33例检出SLN，检出率为97．1％。由SLN状态预测其周淋巴结转移情况的准确率为93．9％（31／33），敏感性为88．9％（16／18），特异性为100．0％（16／16），假阴性率为11．1％（2／18）。免疫组化与常规HE对SLN转移的检出率相比较，差异有统计学意义（P=0．034），免疫组化法共检出12枚18例SLN存在微转移现象。结论SLN能够较准确反映早期大肠癌的淋巴转移状况，免疫组化法较常规HE病理检查更为敏感，AE1／AE3免疫组化发能提高SLN微转移的检测，对确定临床分期诊疗及判断预后有积极临床意义。     

胃癌组织芯片中Ezrin蛋白的表达及意义

目的探讨细胞骨架蛋白Ezrin在胃癌组织芯片中的表达及临床意义。方法利用组织芯片技术和免疫组化Envision法检测Ezrin蛋白在385例胃癌（包括114例淋巴结未转移的胃癌和271例淋巴结转移的胃癌）及40例距肿瘤7cm的正常胃组织中Ezrin蛋白的表达情况。所有患者均经外科手术治疗,病理诊断明确,术前未经放、化疗。结果Ezrin蛋白在胃癌中的阳性率为64．9％（250／385）,而在正常胃黏膜组织中的阳性表达率为5．0％（2／40）,P〈0．05;在淋巴结未转移者中的阳性率为16．6％（64／114）,在淋巴结转移者中的阳性率为48．3％（186／271）,P〈0．05。Ezrin蛋白在淋巴结转移性胃癌中的高表达高于非转移性胃癌[40．0％（154／385）比14．8％（57／385）,P〈0．05];与胃癌仅侵犯至肌层者相比,胃癌侵犯至浆膜及浆膜外者Ezrin蛋白呈高表达[44．4％（171／385）比9．4％（36／385）,P〈0．05]。结论胃癌组织中Ezrin蛋白的阳性表达明显高于正常胃组织,并与胃癌的浸润及转移相关。     

肺癌淋巴结分子生物学分期的初步研究

目的应用荧光定量聚合酶链反应（PCR）及免疫组织化学方法对行根治性非小细胞肺癌手术患者的阴性淋巴结进行检测和分析，形成分子生物学分期。方法共34例非小细胞肺癌患者根治术中193枚常规病理阴性淋巴结．进行CEAmRNA的荧光定量PCR及P53和角蛋白（AE1／AE3）免疫组织化学定性检测。根据检测结果重新确定患者的TNM分期．形成分子生物学分期，并进行平均40个月的随访。结果肺癌阴性淋巴结CEAmRNA荧光定量PCR检测显示21．7％（42／193）阴性淋巴结阳性，共17例（17／34，50％）患者；8例患者常规病理分期上调；9例患者淋巴结阳性数目增加。肺癌阴性淋巴结P53免疫组织化学检测显示9．8％（19／193）阴性淋巴结阳性，共11例（11／34，32．4％）患者，2例患者常规病理分期上调；7例患者淋巴结阳性数目增加。肺癌阴性淋巴结AE1／AE3免疫组织化学检测显示18．6％（36／193）阴性淋巴结阳性．共15例患者（15／34，44．1％），4例患者常规病理分期上调；11例患者淋巴结阳性数目增加。三者之间差异有统计学意义（P〈0．05）。结论分子生物学技术及标记物可以更敏感的检出肺癌微转移，形成分子生物学分期。这种分期及微转移与非小细胞肺癌预后相关。     

CK(AE1/AE3)在喉鳞癌淋巴结微转移诊断中的应用

目的 研究细胞角蛋白广谱抗体CK(AE1/AE3)作为免疫标志物在喉鳞癌淋巴结微转移诊断中的应用与临床病理意义.方法 对50例喉鳞癌患者喉标本及其常规病理报告为阳性的140个淋巴结和阴性的756个淋巴结重新切片,以CK(AE1/AE3)作为免疫标志物,采用免疫组化PV9000两步法检测.结果 在50例喉鳞癌原发灶和病理检查阳性淋巴结中,CK AE1/AE3全部表达,和临床T分期、病理分级无明显相关(P>0.05),756个阴性淋巴结标本中,有9例(18.0%)16个淋巴结(2.1%)发现了微转移灶.结论 CK(AE1/AE3)免疫组化法是检测喉鳞癌淋巴结转移的敏感而便捷的方法,特别对筛选组织学检查淋巴结阴性但存在微转移的患者有一定实用价值.     

CK18和PNA受体在大肠癌淋巴结微转移中的表达及意义

目的探讨CK18和PNA受体在大肠癌淋巴结微转移(micrometastases)中的表达及其意义。方法应用免疫组织化学法(S-P法)和亲和组织化学法(ABC)检测CX18和PNA受体在60例大肠癌患者淋巴结微转移灶中的表达。分析其与HE染色的关系,两者表达之间的相关性和检出的淋巴结微转移与大肠癌患者的年龄、性别、病理类型、分化程度、临床分期之间的关系。结果(1)60例大肠癌患者的234枚淋巴结中,共有22例患者(36．67％)39枚(16．70％)淋巴结存在微转移,主要以单个散在和小团状分布于淋巴结的边缘窦内。(2)CKl8蛋白表达阳性率为14．10％(33／234),除1枚淋巴结外,HE染色阳性者CKl8染色均阳性;PNA受体表达阳性率为13．25％(31／234),HE染色阳性者PNA染色均阳性。CK18蛋白和PNA受体阳性表达与HE染色阳性比较,差异有极显著性(P＜O．01)。(3)CKl8和PNA受体共同表达阳性率为10．68％(25／234);(K18表达阳性而PNA受体阴性的淋巴结8枚,占3．42％;PNA受体表达阳性而cKl8表达阴性的淋巴结6枚,占2．56％;两者之间比较,差异无显著性(P＞O．05)。(4)淋巴结微转移灶的检出率与患者年龄、性别、病理类型、分化程度无关(P＞O．05),与临床Dukes’分期有关(P＜O．01),C期患者淋巴结微转移灶的检出率明显高于A和B期患者。结论(1)淋巴结微转移主要以单个散在和小团状分布于边缘窦内。(2)CK18和PNA受体同样敏感,二者联合应用,可提高淋巴结微转移的检出率。(3)淋巴结微转移与大肠癌惠者年龄、性别、病理类型、分化程度无关,而与临床Dukes’分期有关,C期患者淋巴结微转多灶的检出率明显高于A和B期患者。     

胃窦癌第三组淋巴结转移灶以远前哨淋巴结示踪

目的：探讨进展期胃窦癌第三组淋巴结转移灶以远前哨淋巴结转移状态，为进展期胃窦癌淋巴结清扫提供科学依据。方法：手术中将砭甲蓝抗癌混合溶液2～4ml注射至转移第三组淋巴结内或结节边缘，然后于5-10分钟寻找及切取首先着色并距第三组淋巴结转移结节最近的淋巴结即二级前哨淋巴结。通过标本常规病理学检查分析转移状况。结果：38例进展期胃窦癌成功找到二级前哨淋巴结31例，检出率81．6％（31／38）。病理检查二级前哨淋巴结转移26例，阳性率83．9％（26131）。总二级前哨淋巴结52枚，平均每例1．67枚，阳性35枚，总阳性率67．3％（35/52）。分布特点为二级前哨淋巴结的检出淋巴个数、阳性个数（阳性率）分别是第七组：35枚、18枚（60．0％）；第五组：14枚、13枚（92．8％）、；第四组：3枚、1枚（33．3％）；第六组：3枚、3枚（100％）；第九组：1枚、0枚（0）；第八组：1枚、0枚（0）。临床病理特征为肿瘤大于5cm及分化程度低者SSLN的阳性例数及阳性率较高。结论：在进展期胃窦癌根治术中采用二级前哨淋巴结示踪技术可以了解淋巴结转移的终末状态，对术中淋巴结清扫具有指导意义。     

凝集素受体在胃癌及其淋巴结转移癌中的分布

目的：探讨凝集素受体分布与胃癌及其淋巴结转移癌的关系。方法：应用生物素标记的3种凝集素（Biotin-PHA,Biotin-PNA,Biotin-DBA)对人体胃癌66例,淋巴结转移癌32例,正常胃粘膜10例,进行亲合组织化学法（ABC法）研究。结果：发现PHA、PNA受体的分布与胃癌组织学类型及分化程度有关。PHA、PNA在胃癌中标记阳性率较高,对于胃癌的诊断是一个十分有用的探针。81．3％淋巴结转移癌与其原发胃癌在凝集素标记的量上存在着差异,并且比原发肿瘤获得更多的PHA受体。PHA、PNA在淋巴结转移癌中的标记阳性率较高,对于识别淋巴结是否转移具有一定的应用价值。结果：胃癌中凝集素受体分布与其组织学类型及淋巴结转移癌有关。     

胃癌患者外周血CEAmRNA和CK20mRNA联合检测及意义

目的探讨胃癌患者外周血中CEAmRNA和CK20mRNA表达情况及临床意义。方法应用RT—PCR方法检测56例胃癌患者,20例胃良性病变患者外周血CEAmRNA和CK20mRNA。结果胃癌组,CEAmRNA及CK20mRNA的阳性率与良性组比较,差异有统计学意义（P〈0．05）;二者联合检测阳性率为76．8％,较单项阳性率高组差异无统计学意义（P〉0．05）;肿瘤不同分化程度,组织类型,临床分期及淋巴结转移的CEAmRNA的阳性表达间差异有统计学意义（P〈0．05）;不同肿瘤组织类型,临床分期及淋巴结转移CK20mRNA的阳性表达间差异有统计学意义（P〈0．05）。结论联合检测有助于提高肿瘤微转移检出率,其表达与临床分期及淋巴结转移明显相关。可作预后参考指标。     

联合使用蓝染料和Tc同位素测定胃癌前哨淋巴结的临床意义

目的探讨胃癌中前哨淋巴结（sentinel lymphnode，SLN）概念的适用性，评估前哨淋巴结活检预测胃癌区域淋巴结转移状态的价值及其指导胃癌淋巴结清扫范围的临床意义。方法46例胃癌患者，术前经胃镜于病灶周围黏膜下注入锝标记的锡胶体，术中于病灶周同浆膜下分点注入亚甲蓝，待亚甲蓝显示淋巴结后，将γ探测仪检测到的放射活性最高的淋巴结视为胃癌前哨淋巴结，行术中冰冻免疫组化和常规病理检查或进一步行常规免疫组化染色，分别计算前哨淋巴结诊断胃癌淋巴结转移状态的准确性、敏感性、阴性预测值。结果胃癌前哨淋巴结的检出成功率为100％（46／46）。联合法测定SLN诊断胃癌周围淋巴结转移状态的准确性为100％．敏感性为100％，阴性预测值为100％。结论前哨淋巴结概念适合于胃癌；联合使用蓝染料和锝标锡胶体示踪检测胃癌前哨淋巴结可准确预测胃癌周围淋巴结的转移状态，并可能用于指导胃癌的淋巴结清扫范围。     

乳腺癌化疗后前哨淋巴结活检术的临床探讨

目的探讨乳腺癌化疗后前哨淋巴结活检术（SLNB）的准确性及临床意义。方法用美蓝作为示踪剂，对90例临床分期为Ⅱ、Ⅲ期，并已行化疗后临床检查腋窝淋巴结阴性的乳腺癌患者进行SLNB，术中均同时行腋窝淋巴结清扫术。结果90例中前哨淋巴结成功检出82例，检出率91．1％。每例检出前哨淋巴结的数量为1～4枚，平均1．6枚。82例前哨淋巴结成功检出的患者中。45例患者有腋窝淋巴结转移，其中前哨淋巴结有转移者40例，前哨淋巴结未发现转移而非前哨淋巴结有转移者5例，8例只有前哨淋巴结为阳性淋巴结，前哨淋巴结预测腋窝淋巴结状态准确率为93．9％（77／82）。灵敏度为88．9％（40／45），阳性预测值为100％，阴性预测值为88．1％，假阴性率为11．1％（5／45）。原发肿瘤为T2、T3／T4组检出率分别为96．1％（49／51）、84．6％（33／39）；假阴性率分别为5．3％（1／19）、15．4％（4／26），差异无统计学意义。肿瘤对化疗反应为完全缓解（CR）、部分缓解（PR）、稳定（SD）的前哨淋巴结检出率分别为92．3％、93．1％、84．2％，差异无统计学意义；假阴性5例均发生在PR、SD患者。结论化疗后腋窝淋巴结阴性的Ⅱ、Ⅲ期乳腺癌患者，行SLNB可获得与早期未行新辅助化疗乳腺癌SLNB相似的结果；化疗前原发肿瘤为T2的乳腺癌患者，SLNB能较准确预测腋窝淋巴结的状态。     

EFFECTS OF AE0047 ON RENAL HAEMODYNAMICS AND FUNCTION IN ANAESTHETIZED DOGS

1. The effects of AE0047, a newly developed calcium channel blocker, on renal haemodynamics and function were investigated and compared with those of nicardipine in anaesthetized dogs. 2. Intravenous injection of AE0047 (10 and 30 μg/kg) caused a dose-related fall in blood pressure (BP). The AE0047-induced fall in BP was of slow onset and long lasting. AE0047 at 10 μg/kg elicited a slight increase in renal blood flow (RBF) and urine formation. 3. When AE0047 was infused intrarenally at non-hypotensive doses (25 and 50 ng/kg per min), there was no significant increase in RBF. However, the glomerular filtration rate increased significantly after drug infusion. Intrarenal arterial (i.r.a.) infusion of AE0047 led to dose-related increases in urine flow (UF), urinary excretion of electrolytes (Na⁺, K⁺ and Cl^-) and fractional excretion of electrolytes. The AE0047-induced increase in urine formation was of very slow onset and progressed even after the cessation of the AE0047 infusion. 4. The intrarenal arterial infusion of nicardipine at same doses as AE0047 produced significant increases in urine formation, but these effects were immediately restored to the control values after cessation of the nicardipine infusion. 5. It was shown that AE0047 has a long-lasting diuretic effect and that AE0047-induced diuresis may be due to inhibitory effects on sodium and water reabsorption in the renal tubules.     

253例莲必治注射液不良反应/事件文献分析

目的探讨莲必治注射液致不良反应/事件(ADR/AE)发生的发生类型、特点及相关风险因素,为临床安全用药提供参考。方法检索中国期刊全文数据库、万方数据、维普医药信息资源系统等期刊数据库(1978年1月~2012年3月),以"莲必治注射液"、"不良反应"、"治疗"、"病例报道"等为检索词,检索文献全文136篇,纳入分析的文献36篇,进行统计学分析。结果该药不良反应可累积多个系统-器官,以皮肤损害、过敏反应、胃肠道损害最为常见,严重者可致过敏性休克,急性肾功能衰竭;男女比例各占53.23%、41.94%,19～60岁占比为43.48%,不良反应发生在30分钟以内的占45.05%,1小时内占51.37%,联合用药时占70.36%,结论莲必治注射液的不良反应以速发型为主兼具迟发型,多发于青壮年,并且联合用药时不良反应发生率较高。     

PREVENTATIVE AND THERAPEUTIC EFFECTS OF AE0047 ON RENAL INJURY IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1. The present study was designed to investigate the preventative and therapeutic effects of AE0047 on renal injury compared with those of nitrendipine in stroke-prone spontaneously hypertensive rats (SHRSP). 2. In the preventative study, drug administration was started before the appearance of renal injury, such as proteinuria. Treatment for 6 weeks with AE0047 (1 and 3 mg/kg, p.o.) led to a dose-related reduction in systolic blood pressure (SBP). Nitrendipine, at doses of 10 and 30 mg/kg, also lowered SBP to a similar degree to that seen with AE0047 at 1 and 3 mg/kg, respectively. 3. In the vehicle-administered SHRSP group, urinary excretion of protei. (U_proteinV) increased progressively from 14 weeks of age for another 6 weeks. AE0047 at both doses maintained U_proteinV within normal levels throughout the experimental period. However, the elevation of U_proteinV was only inhibited in the 30 mg/kg nitrendipine-treated group. Urinary N-acetyl-β-D-glucosaminide (NAG) activity in the vehicle-treated SHRSP group was elevated. Urinary NAG activity remained at a low level only in AE0047-treated groups. 4. Histopathological examination revealed severe lesion. (i.e. fibrinoid necrosis, proliferative vasculitis and glomerular lesions) of the kidney in SHRSP. AE0047 treatment at each dose attenuated the development of renal lesions in SHRSP. In contrast, nitrendipine, at 10 mg/kg, was ineffective against the development of renal lesions. Although nitrendipine at 30 mg/kg suppressed the development of renal lesions, this effect was still weaker than that seen with AE0047 at 1 mg/kg. 5. In the therapeutic study, drugs were administered to 17-week-old SHRSP with moderate renal damage for 10 days. Treatment with AE0047 (1 and 3 mg/kg) produced dose-dependent decreases in U_proteinV. In the nitrendipine-treated group, U_proteinV tended to decrease but the changes were not significant. 6. Histopathological studies revealed that 3 mg/kg AE0047 improved renal lesions, such as fibrinoid necrosis, proliferative vasculitis and glomerular lesions, whereas 30 mg/kg nitrendipine di. not. 7. Taken together, the results indicate that AE0047 is capable of preventing proteinuria as well as renal lesions, in part via a mechanism independent of its depressor action on SBP. Furthermore, AE0047 improves proteinuria and renal lesions in proteinuria-established SHRSP. Thus, AE0047 may have therapeutic potential in suppressing either the development or the progression of renal disease in hypertensive patients.     

POSSIBLE MECHANISM FOR THE ANTI-ATHEROSCLEROTIC ACTION OF THE CALCIUM CHANNEL BLOCKER AE0047 IN CHOLESTEROL-FED RABBITS

1. The present study was designed to investigate the anti-atherosclerotic effect of AE0047, a calcium channel blocker, and to compare it with that of nilvadipine in cholesterol-fed rabbits. Furthermore, the effects of AE0047 on low-density lipoprotein (LDL) oxidation were studied in vitro. 2. A 7 week treatment period with AE0047 (3 and 10 mg/kg, p.o.) led to a dose-dependent reduction in the lipid deposition area by Oil Red-O staining (surface index) without affecting serum lipid levels. There was no reduction in the surface index following treatment with the same dose of nilvadipine (10 mg/kg). 3. In a vehicle-administered high-fat diet group of rabbits, levels of total cholesterol (TC) and esterified cholesterol (EC) and calcium content in the aorta were increased approximately two- to three-fold over those of the normal diet group. Increased levels of TC and EC and calcium content were reduced to the same levels as the normal diet group by AE0047 treatment, whereas nilvadipine did not affect TC and EC levels. 4. In an in vitro study, AE0047 (10 μol/L) inhibited LDL oxidation and the aggregation of apolipoprotein (Apo) B-100 induced by Cu²⁺. Furthermore, AE0047 inhibited the degradation of oxidized LDL by macrophages. In contrast, the same dose of nilvadipine (10 μol/L) did not inhibit either LDL oxidation or the aggregation of ApoB-100. 5. In summary, AE0047 inhibited LDL oxidation, resulting in a decrease of its uptake into macrophages and an inhibition of cholesterol esterification. This leads to an anti-atherosclerotic effect of AE0047. Thus, AE0047 may have therapeutic potential in preventing cardiovascular disease in hypertensive patients.     

CALCIUM CHANNEL BLOCKING AND VASODILATING ACTIONS OF THE NOVEL DIHYDROPYRIDINE DERIVATIVE AE0047

1. The pharmacological characteristics of AE0047, a newly synthesized dihydropyridine (DHP) derivative, were investigated in vitro. 2. In bovine aortic membrane, AE0047 and other DHP calcium channel blockers (nitrendipine, nicardipine) displayed concentration-dependent antagonism to specific [3H]-PN200-110 binding sites with the following values for inhibition constants (K1) obtained: 20.8±8.9, 12.3±4.5 and 3.9±1.0nmol/L for AE0047, nitrendipine and nicardipine, respectively. 3. In guinea-pig ventricular myocytes, AE0047 blocked the L-type calcium current, with values for the dissociation constant (Kd) and Hill coefficient of 11.4±5.7nmol/L and 0.852±0.061, respectively, indicating in the terms of Hill's hypothesis that one drug molecule blocks one calcium channel molecule. 4. In rat aorta, AE0047 inhibited 45Ca uptake induced by high K+(100mmol/L)by55%. 5. AE0047 and nitrendipine concentration dependently relaxed rat aortic strips contracted with 30 mmol/L KC1. The response to nitrendipine reached a plateau within 60 min and disappeared after drug washing. Interestingly, AE0047 required 5 h or more to produce a plateau of response, with no effect of drug washing. This confirmed the slow onset and long duration of its vasodilating action. 6. With AE0047, tissue content in rat aorta increased more slowly than with nitrendipine and release of AE0047 from tissue was also slower. 7. The data suggest that AE0047 is incorporated slowly into smooth muscle membranes, approaches receptors slowly through the membrane bilayer and accumulates in the membrane because of its high lipophilicity, resulting in an antihypertensive action that is slow in onset and of long duration.     

Effects of the calcium channel blocker AE0047 on renal function in conscious spontaneously hypertensive rats: Focus on renal proximal tubules

The hypotension induced by peripheral vasodilators is occasionally accompanied by diminished urine formation induced via various anti-diuretic mechanisms. The question of whether an antihypertensive agent has diuretic action is therefore relevant to its usefulness. In the present study, conducted in conscious, spontaneously hypertensive rats (SHR), the lithium clearance technique was used to investigate the effect of intravenously administered AE0047 on renal function; the effect of orally administered AE0047 on uric acid excretion was also investigated. Intravenous injection of AE0047 (10 and 30 μg/kg) produced potent hypotension, accompanied by diuresis and natriuresis. The diuretic action was accompanied by an elevation of FE_Na and FE_Li levels, with minimal change in GFR. Oral administration of AE0047 (1 and 3 mg/kg) led to a dose-related increase in urine volume and in urinary excretion of sodium and uric acid (U_UAV). Simultaneous administration of pyrazinamide, an inhibitor of uric acid secretion in proximal tubules, mitigated the increase in U_UAV. These findings indicate that systemically administered AE0047 produces diuresis and natriuresis, in part via an inhibition of sodium and water reabsorption in the proximal tubules. The action of AE0047 at renal proximal tubular sites thus offers benefit in hypertension therapy. Drug Dev. Res. 41:91–98, 1997. © 1997 Wiley-Liss, Inc.     

AE 941

AE 941 [Arthrovas, Neoretna, Psovascar] is shark cartilage extract that inhibits angiogenesis. AE 941 acts by blocking the two main pathways that contribute to the process of angiogenesis, matrix metalloproteases and the vascular endothelial growth factor signalling pathway. When initial development of AE 941 was being conducted, AEterna assigned the various indications different trademarks. Neovastat was used for oncology, Psovascar was used for dermatology, Neoretna was used for ophthalmology and Arthrovas was used for rheumatology. However, it is unclear if these trademarks will be used in the future and AEterna appears to only be using the Neovastat trademark in its current publications regardless of the indication. AEterna Laboratories signed commercialisation agreements with Grupo Ferrer Internacional SA of Spain and Medac GmbH of Germany in February 2001. Under the terms of the agreement, AEterna has granted exclusive commercialisation and distribution rights to AE 941 in oncology to Grupo Ferrer Internacional for the Southern European countries of France, Belgium, Spain, Greece, Portugal and Italy. It also has rights in Central and South America. Medac GmbH will have marketing rights in Germany, the UK, Scandinavia, Switzerland, Austria, Ireland, the Netherlands and Eastern Europe. In October 2002, AEterna Laboratories announced that it had signed an agreement with Australian healthcare products and services company Mayne Group for marketing AE 941 (as Neovastat) in Australia, New Zealand, Canada and Mexico. In March 2003, AEterna Laboratories announced it has signed an agreement with Korean based LG Life Sciences Ltd for marketing AE 941 (as Neovastat) in South Korea. The agreement provides AEterna with upfront and milestone payments, as well as a return on manufacturing and sales of AE 941. AEterna Laboratories had granted Alcon Laboratories an exclusive worldwide licence for AE 941 for ophthalmic products. However, this licence has been terminated. In 1999, AEterna secured funding for AE 941, part of which is from Technology Partnerships Canada (TPC), a research support programme run by Canada's federal government. Industry Canada will contribute $Can 1 for every $Can3 spent by AEterna on the development of AE 941, up to a total figure of $Can29.4 million. AEterna will reimburse TPC upon commercialisation of AE 941-derived products as a royalty on income generated. In January 2004 AEterna announced that development of AE 941 would be focusing on non-small cell lung cancer and that development for renal cell carcinoma would be discontinued. AEterna had previously announced in January 2003, following its acquisition of Zentaris, that development of AE 941 would be "strictly focused" on renal and non-small cell lung cancer, suggesting that development for all other indications has been discontinued, at least for the foreseeable future.     

Action mechanism of anticonvulsant and anti-immobility (forced swim) effects of 3', 4'-dihydro-N, N-dimethylspiro-[9H-fluorene-9, 2' (5'H) furane]-3'-methanamine (AE37F)

AE37F, a new aminotetrahydrofuranic derivative, exhibited, at 10-30 mg/Kg (po) or 1-10 mg/Kg (ip), antagonism of tonic convulsions, induced by pentetrazole (130 mg/Kg, ip), and of forced swin immobility, in mice. At these doses AE37F induced a considerable (100-250%) increase of serotonin (5-HT) and its main metabolite, 5-hydroxyindolacetic acid (5-HIAA), in the rat nucleus reticularis pontis oralis (NRPO), antagonized by amantadine, which also increased 5-HT and 5-HIAA levels in the NRPO. It is suggested: a) that the anti-immobility effect of AE37F is related to its antimuscarinic properties, b) that the rate of 5-HT release in the NRPO, calculated here by a new approach (from the 5-HT and 5-HIAA brain levels) is increased by AE37F and decreased by amantadine, in the NRPO, c) that the anti-convulsant action, observed with AE37F, could be related to a NMDA-sigma mediated stimulation of serotoninergic, GABAergic and glycinergic brain neurones, antagonized by the NMDA-sigma inhibition induced by amantadine.     

改变原料配比提高头孢曲松钠收率

目的：提高头孢曲松钠收率。方法：调整原料配比,减少原料消耗提高头孢曲松钠收率。结果：根据实验原料AE活性酯对收率的影响很明显。结论：减少AE活性酯的投入量可以使收率稳定。