Carnosine inhibits pentylenetetrazol-induced seizures by histaminergic mechanisms in histidine decarboxylase knock-out mice

In the present study, we used both histidine decarboxylase-deficient (HDC-KO) mice and wild-type (WT) mice to elucidate the possible role of carnosine in pentylenetetrazol (PTZ)-induced seizures. In the acute PTZ challenge study, PTZ (75 mg/kg) was injected intraperitoneally (i.p.) to induce seizures. Carnosine (200, 500 or 1000 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latency for myoclonic jerks in WT mice in a dose-dependent manner. The effects of carnosine (500 mg/kg) were time-dependent and reached a peak at 1 h. However, it had no significant effect on HDC-KO mice. Carnosine (500 mg/kg) also significantly elevated the thresholds in WT mice but not HDC-KO mice following intravenous (tail vein) administration of PTZ. We also found that α-fluoromethylhistidine substantially reversed the protective effects of carnosine in WT mice. In addition, carnosine pretreatment reduced the cortical EEG activity induced by PTZ (75 mg/kg, i.p.). These results indicate that carnosine can protect against PTZ-induced seizures and its action is mainly through the carnosine–histidine–histamine metabolic pathway. This suggests that carnosine may be an endogenous anticonvulsant factor in the brain and may be used as a new antiepileptic drug in the future.     

健康男性前列腺健康指数各年龄段分布曲线特征及临床意义

目的综合对比前列腺特异抗原(PSA)各指标,探讨健康男性各年龄段前列腺健康指数(PHI)指标潜在价值及意义。方法对238名10⁹0岁年龄段马鞍山地区健康男性统一检测tPSA、fPSA、p2PSA等指标,按每10岁一组共分为8组,分别计算各组均值及其95%可信区间(CI),综合对比tPSA、fPSA、%fPSA、p2PSA、%p2PSA及PHI指标,绘制各指标年龄相关分布曲线并统计分析曲线特征。结果与其他曲线趋势不同,PHI指标终生随年龄变化特征相当显著:PHI曲线在1090岁年龄段马鞍山地区健康男性统一检测tPSA、fPSA、p2PSA等指标,按每10岁一组共分为8组,分别计算各组均值及其95%可信区间(CI),综合对比tPSA、fPSA、%fPSA、p2PSA、%p2PSA及PHI指标,绘制各指标年龄相关分布曲线并统计分析曲线特征。结果与其他曲线趋势不同,PHI指标终生随年龄变化特征相当显著:PHI曲线在10²9岁期间相对平稳,但随后出现2个高峰和1个低谷,分别为青春期高峰于3029岁期间相对平稳,但随后出现2个高峰和1个低谷,分别为青春期高峰于30³9岁,PHI=31.83±10.29(95%CI 10.2939岁,PHI=31.83±10.29(95%CI 10.29⁵3.37);老年期最高峰于6053.37);老年期最高峰于60⁶9岁,PHI=42.85±9.06(95%CI 23.9669岁,PHI=42.85±9.06(95%CI 23.96⁶1.75);中年期低谷于4061.75);中年期低谷于40⁴9岁,PHI=9.16±2.05(95%CI 8.1949岁,PHI=9.16±2.05(95%CI 8.19¹6.76)。与fPSA终生持续缓慢上升不同,PHI与tPSA两者均在老年期转向下,但PHI转折点(6016.76)。与fPSA终生持续缓慢上升不同,PHI与tPSA两者均在老年期转向下,但PHI转折点(60⁶9岁)较tPSA提早约10年。结论 PHI与年龄的相关性较PSA单一指标更敏感更超前,似能更准确反映前列腺总体功能在男性各年龄段的生理或病理动态变化特征。同时综合计算多指标而获取的PHI新指标,可能较以往PSA单一肿瘤标记物具有更多的潜在研究价值。     

内源性组胺参与吗啡调节戊四唑癫痫易感性过程

目的:研究吗啡对戊四唑(PTZ)癫痫易感性的调节作用,同时探讨内源性组胺在该调节过程中的作用。方法:在组氨酸脱羧酶(组胺合成关键酶)基因敲除及其相应野生型小鼠皮下注射不同剂量的吗啡,1h后以0.3ml/min的恒定速度尾静脉注射1.5%的化学致痫剂戊四唑,观察达到肌阵挛及全身性阵挛发作的阈值。结果:吗啡可以剂量依赖性地降低野生型小鼠达到肌阵挛及全身性阵挛发作的阈值,基因敲除型小鼠注射10mg/kg的吗啡后,达到肌阵挛发作的阈值从生理盐水组的(38.6±2.9)mg/kg降低到(32.5±0.7)mg/kg,具有显著性差异,而达到全身性阵挛发作的阈值从生理盐水组的(51.8±2.1)mg/kg降低到(47.6±1.2)mg/kg,没有统计学差异。另外,基因敲除鼠达到肌阵挛发作阈值的降低幅度(15.8±1.4)%及全身性阵挛发作阈值的降低幅度(8.3±0.9)%,都比野生型小鼠明显减少,分别为(26.1±2.5)%和(20.8±2.4)%。结论:吗啡可以降低戊四唑癫痫发作的阈值,从而增加癫痫的易感性,而内源性组胺参与了该过程。     

CT监控下立体定向颅内血肿抽吸术的临床应用

目的 探讨在CT监控下立体定向脑内血肿清除术的临床应用价值。方法 将定向仪安装在CT床头侧并与CT坐标中心校验为同步，病人在手术室或直接在CT室钻孔，手术全过程在CT床上进行，至少行术前、术中和术毕3次监控扫描，并根据需要随时扫描观察动态效果或调整靶点。本组共860例，包括基底节血肿408例、丘脑－内囊后肢血肿136例、外囊血肿105例、脑叶血肿156例、脑干血肿40例、小脑血肿5例及脑室出血10例；抽吸术距发病时间自3h至14d。结果 血肿可随意抽出者586例，血肿较馥稠但可清除率大于50％者202例，可清除率在50％以下者68例，完全无法抽出4例；手术时间25－120min，平均45min；存活693例，死亡167例，对生存者进行日常生活能力测评（active day life,ADL),ADL 1-2级者378例，ADL3级者166例，ADL4级者107例，ADL5级者28例，失访14例。结论 CT监控下立体定向脑内血肿抽吸术，是1种值得推广的安全、精确和简捷的脑内血肿治疗方法。     

神经导航系统在颅脑手术中的应用体会

目的探讨神经导航技术在颅内病变显微神经外科手术中的应用价值。方法22例颅内肿瘤和血管性病变患者，经术前MRI和(或)fMRI检查，将影像数据输入计算机工作站进行三维重建和术前计划，标记病灶及其临近重要结构。术中神经导航引导下以显微神经外科技术切除病变，进行手术前后的临床和影像学评价。22例患者中，脑膜瘤9例，胶质瘤3例，胆脂瘤1例，海绵状血管瘤5例，动静脉畸形3例，转移瘤1例。结果18例病灶全切除，4例次全切除；1例术后发生偏瘫，其余无新增加神经功能障碍。结论神经导航能有效指导手术入路．对术前计划和显微手术的术中引导有价值。     

小儿外伤性硬膜外血肿的诊治

目的 探讨小儿外伤性硬膜外血肿的临床特点、手术方法及治疗效果。方法 对本院自1944年1月至2002年5月收治的5(例小儿外伤性EDH，进行回顾性分析。手术治疗49例，保守1例。结果 全部病例中存活49例，死亡1例。其中重残1例，死亡率2％。结论 早期诊断、及时正确的治疗，是小儿外伤性硬膜外血肿患降低死亡率致残率、提高治愈率的关键。     

表现为慢性脑内血肿的脑血管畸形诊断与治疗

目的：探索CT表现为慢性脑内血肿的脑血管畸形的诊断和外科治疗。方法：回顾性分析10例CT表现为慢性脑内血肿的脑血管畸形，主要症状表现为癫痫，轻瘫和头痛，所有病例均经CT检查，5例经MRI检查，4例经全脑DSA检查，所有病人均经手术治疗，并取得相应资料。结果：术前6例误诊囊性胶质瘤或肿瘤卒中，术后是诊断均为脑血管畸形伴慢性脑内血肿，全组无死亡，除1例轻瘫外均恢复正常；8例临床和影像学随访5月－6年无异常发现。结论：表现慢性脑内血肿的脑血管畸形易误诊为脑胶质瘤，MRI，DSA检查对确诊和治疗有重要意义。     

立体定向~（32）P内放疗和甲氨喋呤内化疗联合治疗脑深部神经胶质瘤

报道４４例脑深部神经胶质瘤采用ＣＴ导向立体定向技术，用放射性胶体磷酸铬（３２Ｐ）进行瘤内放射治疗，其中３０例联合甲氨蝶呤（ＭＴＸ）瘤内化疗。术后经临床和ＣＴ随访６～４８月，结果：临床症状和体征消失１３例，改善２２例，无效或恶化９例。ＣＴ证实显效４例，有效２７例，微效４例，无变化４例，恶化５例。囊性较实质性效果为好，联合治疗较单纯内放疗效果好。作者认为，此法操作简单，效果确定，特别适用于深部和重要功能区的囊性神经胶质瘤，并对联合作用的机理和并发症进行了讨论。     

Unilateral low-frequency stimulation of central piriform cortex delays seizure development induced by amygdaloid kindling in rats

Low-frequency stimulation of the kindling site interferes with the course of kindling epileptogenesis. The present study examined the effect of unilateral low-frequency stimulation of the central piriform cortex on seizure development induced by amygdaloid kindling in rats. The ipsilateral or contralateral central piriform cortex received low-frequency stimulation (15 min train of 0.1 ms pulses at 1 Hz and 50-150 muA) immediately after termination of once daily kindling stimulation (2 s train of 1 ms pulses at 60 Hz and 150-300 microA) in the right amygdala for 30 days. Low-frequency stimulation of either the ipsilateral or contralateral central piriform cortex significantly suppressed the progression of seizure stages and reduced afterdischarge duration throughout the course of amygdaloid kindling. The marked suppression induced by low-frequency stimulation of the central piriform cortex on either side was predominantly due to the significant retardation of progression from stage 0 to stage 1 and stage 3 to stage 4 seizures. In addition, the suppressive effect of low-frequency stimulation did not disappear when the stimulation was stopped; it could persist for at least 10 days. These findings indicate that brain areas other than the kindling focus, such as the central piriform cortex on both sides, can also be used as reasonable targets for low-frequency stimulation to retard seizure development induced by amygdaloid kindling. Secondly, like the ipsilateral central piriform cortex, the contralateral central piriform cortex may also participate in the progression and secondary generalization of focal seizures. The study suggests that unilateral low-frequency stimulation of the central piriform cortex may have a significant antiepileptogenic effect, and may be helpful for exploring effective and long-lasting therapies for human temporal lobe epilepsy.