脑震荡大鼠海马CA1区P-CREB的表达

目的观察磷酸化CREB（p-CREB）在脑震荡大鼠海马区的表达。方法在多聚甲醛固定的海马脑薄片上，用免疫组化法观察p-CREB在海马CA1区的表达。结果p-CREB在脑震荡大鼠海马结构CA1区的表达，1～72h增多（P〈0．05），7d后降至正常。结论p-CREB在脑震荡大鼠海马内伤后早期表达增多，P-CREB可能具有神经保护因子的作用。     

慢律升颗粒对慢性心律失常模型大鼠血浆环磷酸腺苷和环磷酸鸟苷的影响

目的:研究慢律升颗粒对慢性心律失常模型大鼠血浆环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)的影响。方法:将30只SD大鼠随机分为对照组、普萘洛尔组、乙酰胆碱组、普萘洛尔联合慢律升组、乙酰胆碱联合慢律升组,每组各6只。对照组大鼠灌胃0.9%氯化钠溶液,普萘洛尔组大鼠灌胃盐酸普萘洛尔,乙酰胆碱组大鼠灌胃乙酰胆碱,普萘洛尔联合慢律升组灌胃普萘洛尔、慢律升颗粒,乙酰胆碱联合慢律升组大鼠灌胃乙酰胆碱、慢律升颗粒。各组大鼠均连续灌胃7 d。治疗后记录各组大鼠的肛温、心率以及血清中cAMP、cGMP水平。结果:与对照组比较,普萘洛尔组、乙酰胆碱组大鼠的肛温均低(均P<0.05),普萘洛尔联合慢律升组、乙酰胆碱联合慢律升组的肛温均高(均P<0.05)。与对照组比较,普萘洛尔组、乙酰胆碱组大鼠的心率均低,普萘洛尔联合慢律升组、乙酰胆碱联合慢律升组的心率均高(均P<0.05)。与对照组比较,普萘洛尔组和乙酰胆碱组大鼠的cAMP均降低,而cGMP均高、cAMP/cGMP比值均低(均P<0.05)。与对照组比较,普萘洛尔联合慢律升组、乙酰胆碱联合慢律升组的cAMP均高、cGMP均低、cAMP/cGMP比值均高(均P<0.05)。结论:慢律升颗粒对普萘洛尔和乙酰胆碱诱导的慢性心律失常模型大鼠的肛温、心率及血清中cAMP、cGMP水平具有良好的改善作用。     

Treatment of Lesch–Nyhan disease with S-adenosylmethionine: Experience with five young Malaysians,including a girl

Background: Lesch–Nyhan disease (LND) is a rare X-linked recessive neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8) which is responsible for recycling purine bases into purine nucleotides. Affected individuals have hyperuricemia leading to gout and urolithiasis, accompanied by a characteristic severe neurobehavioural phenotype with compulsive self-mutilation, extrapyramidal motor disturbances and cognitive impairment. Aim: For its theoretical therapeutic potential to replenish the brain purine nucleotide pool, oral supplementation with S-adenosylmethionine (SAMe) was trialed in 5 Malaysian children with LND, comprising 4 related Malay children from 2 families, including an LND girl, and a Chinese Malaysian boy. Results: Dramatic reductions of self-injury and aggressive behaviour, as well as a milder reduction of dystonia, were observed in all 5 patients. Other LND neurological symptoms did not improve during SAMe therapy. Discussion: Molecular mechanisms proposed for LND neuropathology include GTP depletion in the brain leading to impaired dopamine synthesis, dysfunction of G-protein-mediated signal transduction, and defective developmental programming of dopamine neurons. The improvement of our LND patients on SAMe, particularly the hallmark self-injurious behaviour, echoed clinical progress reported with another purine nucleotide depletion disorder, Arts Syndrome, but contrasted lack of benefit with the purine disorder adenylosuccinate lyase deficiency. This first report of a trial of SAMe therapy in LND children showed remarkably encouraging results that warrant larger studies.     

注射用单磷酸阿糖腺苷细菌内毒素检查法的建立

目的:建立注射用单磷酸阿糖腺苷的细菌内毒素检查方法。方法:按照2010年版《中国药典》(二部)附录细菌内毒素检查法,采用2个厂家的鲎试剂对5个厂家的5批样品,通过预干扰和干扰试验确定样品最大无干扰质量浓度,并进行细菌内毒素检查。结果:将供试品溶液稀释至质量浓度为50 mg/ml时,不干扰细菌内毒素试验;确定其细菌内毒素限值为0.5 EU/mg。结论:采用细菌内毒素检查法检查注射用单磷酸阿糖腺苷中的细菌内毒素是可行的。     

Nitroglycerin rebound associated with vascular, rather than platelet, hypersensitivity

OBJECTIVES

The purpose of this study was to determine whether acute withdrawal of nitroglycerin (NTG) during hemodynamic tolerance is associated with platelet hypersensitivity.

BACKGROUND

Nitroglycerin is an effective antianginal medication but its use is limited by the development of tolerance and rebound. We have previously demonstrated a sustained inhibition of platelet function during continued use of NTG, but whether cessation of NTG is associated with an increase in platelet function that may contribute to rebound is unknown.

METHODS

Normal porcine aortic media were exposed to flowing arterial blood from pigs (n = 8) treated continuously with NTG patches (Nitrodur 0.8 mg/h) for 48 h. Platelet function, blood pressure and the responses to angiotensin II infusion were evaluated before, during and after NTG treatment.

RESULTS

Mean arterial pressure fell by 15% after 3 h of treatment compared with control, returned to baseline by 48 h and increased significantly 2 h after drug removal. Autologous ⁵¹Cr-labelled platelet deposition on the aortic media was reduced by 30% after 48 h of continuous NTG administration compared with baseline (p = 0.02) and remained decreased 2 h after cessation of NTG therapy. Platelet aggregation to thrombin decreased in parallel to the decrease in platelet deposition. Blood pressure increase after intravenous injection of 10 μg of angiotensin II was blunted during treatment with NTG but increased significantly 2 h after cessation of nitrate therapy when compared with baseline.

CONCLUSIONS

Supersensitivity of the vessel wall to vasoconstrictors such as angiotensin 11, but not platelet hyperactivity, may contribute to the rebound phenomenon after acute nitrate withdrawal.     

Ammonia metabolism,the brain and fatigue; revisiting the link

This review addresses the ammonia fatigue theory in light of new evidence from exercise and disease studies and aims to provide a view of the role of ammonia during exercise. Hyperammonemia is a condition common to pathological liver disorders and intense or exhausting exercise. In pathology, hyperammonemia is linked to impairment of normal brain function and the onset of the neurological condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise due to a diminished capacity for removal via the liver and lead to increased exposure of organs, such as the brain, to the toxic effects of ammonia. High levels of brain ammonia can lead to deleterious alterations in astrocyte morphology, cerebral energy metabolism and neurotransmission, which may in turn impact on the functioning of important signalling pathways within the neuron. Such changes are believed to contribute to the disturbances in neuropsychological function, in particular the learning, memory, and motor control deficits observed in animal models of liver disease and also patients with cirrhosis. Hyperammonemia in exercise occurs as a result of an increased production by contracting muscle, through adenosine monophosphate (AMP) deamination (the purine nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to oxidation. Plasma concentrations of ammonia during exercise often achieve or exceed those measured in liver disease patients, resulting in increased cerebral uptake. In this article we propose that exercise-induced hyperammonemia may lead to concomitant disturbances in brain function, potentially through similar mechanisms underpinning pathology, which may impact on performance as fatigue or reduced function, especially during extreme exercise.     

硫酸软骨素酶ABC和环磷酸腺苷缓释组织工程 支架的构建

目的:制备一种可生物降解有效安全的硫酸软骨素酶ABC(ChABC)和环磷酸腺苷(cAMP)缓释组织工程支架,使药物缓慢稳定释放,降低局部应用时对神经的刺激,促进中枢神经系统损伤后神经的修复和轴突的再生。方法:应用电纺丝技术制作的含ChABC及cAMP的聚碳酸亚丙酯及壳聚糖缓释组织工程支架,分析支架直径、载药量、包封率等参数,然后以磷酸盐缓冲液为体外释药介质观察组织工程支架的药物释放速度、药物的失活率及支架的降解速度。结果:ChABC和cAMP缓释组织工程支架在聚碳酸亚内酯质量浓度为8%、电压为10～15 kV、距离为15～20 cm时可以纺出纤维直径约3μm的平滑支架,单纯聚碳酸盐内酯纤维光滑,直径均一,壳聚糖微球光滑,聚碳酸亚内酯与壳聚糖混合后电纺丝形成的支架呈串珠样结构,其能缓慢持续释放有活性ChABC和cAMP,12 d后支架降解失重率约7%。结论:应用电纺丝方法成功制备含ChABC及cAMP的聚碳酸盐内酯及壳聚糖组织工程支架,其药物稳定释放,局部应用无神经刺激,可生物降解。