Dual chamber pacing in a patient of hypertrophic cardiomyopathy with failure to wean from mechanical ventilator

We discuss the case of a 63 years old female who required repeated intubation due to recurrent pulmonary edema. She was found to have hypertrophic cardiomyopathy with a gradient of 82 mmHg across the left ventricular outflow tract. Initially adequate rate control and treatment with negative inotropes did not help her condition. Finally a dual chamber pacemaker implantation and atrioventricular node modification lead to successful extubation.     

玻璃腔内注射曲安奈德联合真武汤加减治疗视盘血管炎继发黄斑水肿的临床疗效观察

目的:探讨玻璃腔内注射曲安奈德结合真武汤加减治疗视盘血管炎继发黄斑水肿的临床疗效及安全性。方法:选择2013年12月到2017年4月在我院诊治的视盘血管炎继发黄斑水肿患者142例(142眼)作为研究对象,根据信封随机抽签法分为观察组与对照组,每组各71例。对照组给予玻璃腔内注射曲安奈德治疗,观察组在对照组治疗的基础上给予真武汤加减治疗。治疗1个月后,比较两组治疗前后视力、黄斑中心凹厚度的变化情况及不良反应的发生情况。结果:治疗后,观察组与对照组的视力均明显优于治疗前(P0.05),且观察组视力明显优于对照组(P0.05)。治疗后,观察组与对照组的黄斑中心凹厚度分别为168.34±22.19μm和267.35±34.11μm,均明显低于治疗前[516.35±45.20μm和522.14±23.01μm](P0.05),且观察组治疗后黄斑中心凹厚度明显低于对照组(P0.05)。两组治疗后发生玻璃体积血、新生血管性青光眼、瞳孔区模性渗出等并发症,发生率对比差异无统计学意义(P0.05)。结论:与单用玻璃腔内注射曲安奈德治疗相比,玻璃腔内注射曲安奈德结合真武汤加减治疗视盘血管炎继发黄斑水肿的安全性更高,且能有效减轻黄斑水肿,缩小黄斑区域,提高视力。     

A mimetic of the mSin3-binding helix of NRSF/REST ameliorates abnormal pain behavior in chronic pain models

The neuron-restrictive silencing factor NRSF/REST binds to neuron-restrictive silencing elements in neuronal genes and recruits corepressors such as mSin3 to inhibit epigenetically neuronal gene expression. Because dysregulation of NRSF/REST is related to neuropathic pain, here, we have designed compounds to target neuropathic pain based on the mSin3-binding helix structure of NRSF/REST and examined their ability to bind to mSin3 by NMR. One compound, mS-11, binds strongly to mSin3 with a binding mode similar to that of NRSF/REST. In a mouse model of neuropathic pain, mS-11 was found to ameliorate abnormal pain behavior and to reverse lost peripheral morphine analgesia. Furthermore, even in the less well epigenetically defined case of fibromyalgia, mS-11 ameliorated symptoms in a mouse model, suggesting that fibromyalgia is related to the dysfunction of NRSF/REST. Taken together, these findings show that the chemically optimized mimetic mS-11 can inhibit mSin3-NRSF/REST binding and successfully reverse lost peripheral and central morphine analgesia in mouse models of pain.     

促红细胞生成素对脑缺血/再灌注损伤的保护作用

目的:探讨促红细胞生成素(Epo)对大鼠脑缺血/再灌注损伤的保护作用。方法:32只SD大鼠,采用夹闭双侧颈总动脉30min再灌注24h制作脑缺血/再灌注模型。随机分为4组(n=8):假手术组、脑缺血/再灌注组、Epo组及阳性对照组(尼莫地平),观察缺血/再灌注后血清一氧化氮(NO)和脑组织匀浆中超氧化歧化酶(SOD)活性、丙二醛(MDA)含量及脑组织含水量的变化。结果:Epo组血清NO和脑组织匀浆中MDA含量显著下降,SOD活性显著升高,脑组织含水量显著下降,与缺血/再灌注组相比有显著性差异。结论:大鼠脑缺血/再灌注后,Epo能减轻脑组织的含水量,减少自由基的生成,减轻脂质过氧化反应,对脑缺血/再灌注损伤有保护作用。     

蝮蛇三龙丹胶囊对大鼠实验性脑血肿的影响

目的探讨蝮蛇三龙丹胶囊对大鼠实验性脑血肿的影响。方法采用大鼠自体血液颅内注入造成大鼠脑血肿模型,观察蝮蛇三龙丹胶囊的作用。结果蝮蛇三龙丹胶囊（０．２ｇ／ｋｇ、０．４ｇ／ｋｇ）可明显降低脑指数、脑组织含水量（Ｐ＜０．０１）及Ｃａ２＋离子含量（Ｐ＜０．０１）,对Ｎａ＋、Ｋ＋离子含量无明显影响（Ｐ＜０．０５）。结论蝮蛇三龙丹胶囊对实验性脑血肿诱发脑水肿有一定防治作用,且对小鼠出、凝血时间无影响,亦未见对大鼠实验性脑血肿发生再出血。本实验为蛇毒制剂治疗高血压性脑出血提供可靠依据。关键词蝮蛇三龙丹胶囊脑血肿脑水肿     

大鼠肢体缺血/再灌注后多器官水肿及丹参的预防作用

目的:探讨大鼠肢体缺血/再灌注(LI/R)导致的多器官水肿及丹参的防治作用。方法:Wistar大鼠24只随机分为3组(n=8):对照组(C组)、缺血/再灌注组(I/R组)和丹参预处理组(SM组)。以止血带法制作大鼠肢体缺血/再灌注模型,SM组在再灌注前30 min经尾静脉推注丹参注射液5 ml/kg。准确留取每只动物的心、肝、肾、肺、脑、肠及骨骼肌组织各1 g,恒温烘干后称其干重并计算各组织的湿干重比值(W/D)。采用ELISA法测定血清白细胞介素1(IL-1)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNFα-)含量;采用生物化学方法测定超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。光镜下观察骨骼肌组织的形态学变化。结果:LI/R后各组织W/D均增加(P<0.05,P<0.01),血浆SOD活性降低而MDA含量增加(P<0.05,P<0.01),血清IL-1、IL-6、TNFα-水平均升高(P<0.05,P<0.01),骨骼肌组织镜下可见炎细胞浸润、肌纤维间隙增宽等病理改变。而SM组与单纯再灌注组比较,血清炎症因子水平下降,氧化损伤程度减轻,镜下组织形态学变化有所改善。结论:大鼠肢体缺血/再灌注可导致多器官水肿,丹参可通过抑制炎症反应、抗氧化等途径在一定程度上预防肢体缺血/再灌注后多器官的水肿。     

Atomic Structures of Anthrax Prechannel Bound with Full-Length Lethal and Edema Factors

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Metabolic manipulation of neural tissue to counter the hypersynchronous excitation of migraine and epilepsy

Very prominent in the large biochemical data bank on epilepsy, is the almost universal finding that a familial or environmental predisposition towards epilepsy, as well as the earliest signs preceding other forms of hypersynchronous excitation, coincide with an altered glutamate metabolism. Hence, it has become increasingly apparent that glutamate occupies a central position in the development of epilepsy or in the onset of a migraine incident. The importance of glutamate is explained by a variety of functions in the CNS: as a dominant constituent of many proteins, by its intermediary role in linking energy metabolism to that of many other amino acids, and as the virtually exclusive precursor of GABA. Moreover, glutamate serves as the primary substrate in ammonia detoxification and the product, glutamine, actively participates in CSF water homeostasis. Finally, by its direct electrophysiological and metabolic actions on neurons and glia, via at least four distinct types of receptor proteins, glutamate is implicated in a number of critical mechanisms of information. These include neuronal excitatory modulation, intracellular Ca²⁺ redistribution, and key metabolic (phosphorylation) mechanisms. The phenomena, when exaggerated due to excessive extracellular glutamate levels, may cause pathological effects such as hypersynchrony-epilepsy, Spreading Depression-migraine, high internal Ca²⁺-damage, impaired phosphorylation/dephosphorylation-necrosis, among others. Not surprising therefore that severe epilepsy may eventually cause CNS cytoarchitectual and metabolic damage, or conversely, that neural tissue trauma not infrequently gives rise to epilepsy many years later. Both conditions are associated with a persistent, excessive leakage or release of glutamate into the extracellular milieu. An electrophysiological and neurochemical commonality between migraine and epilepsy has also been noted. A specific nutritional supplement is proposed, consisting of a combination of taurine (100 mg),l-leucine (75 mg), (acetyl-)l-carnitine (25 mg), and zinc gluconate (10 mg) which is aimed at, principally, normalizing internal Ca²⁺ ionization, and removal of extracellular glutamate by glial amidation to glutamine.Special issue dedicated to Dr. Claude Baxter.     

Amino acid sequence of piratoxin-I, a myotoxin fromBothrops pirajai snake venom, and its biological activity after alkylation withp-bromophenacyl bromide

The complete sequence of the 121 amino acid residues of piratoxin-I (PrTX-I), a phospholipase A₂ (PLA₂)-like myotoxin fromBothrops pirajai snake (Bahia jararacussu) venom, is reported. From the sequence, anM _r of 13,825 and an approximatepI of 8.3 were calculated. PrTX-I shows a high sequence homology with Lys-49 myotoxins from other bothropic (∼95%) and nonbothropic (∼80%) venoms, but only 70–75% homology w hen aligned with the catalytically active Asp-49 PLA₂s. When compared with bothropstoxin-I fromBothrops jararacussu, which is morphologically almost identical toB. pirajai, only two changes out of 121 total amino acid residues have been observed. The approximate minimal lethal doseLD ₅₀ (mice, i.p., 24 hr) of PrTX-I was 8 (6.8–9.1) mg/kg, and the minimal edematogenic dose (MED) in a rat paw model was 39.5±1.8 ug. After alkylation of His-48 withp-bromophenacyl bromide, the MED was 40.1±1.9 ug, but up to 4LD ₅₀ were unable to cause death in any of a group of eight mice after 72 hr. Therefore the edematogenic activity was retained and apparently did not involve His-48, suggesting that at least two biologically active sites are present in PrTX-I.