Excitation of locus coeruleus neurons by an adenosine 3',5'-cyclic monophosphate-activated inward current: extracellular and intracellular studies in rat brain slices

The firing rate of locus coeruleus (LC) neurons in rat brain slices was increased reversibly by agents that either elevate intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) or mimic its actions (e.g., forskolin, and activator of adenylate cyclase, 8-Br-cAMP, a membrane permeable analog of cAMP, and Ro20-1724, a preferential inhibitor of cAMP-phosphodiesterase). Intracellular recordings showed that 8-Br-cAMP and forskolin induce a depolarization of LC neurons, accompanied by a decrease in input resistance. The 8-Br-cAMP- and forskolin-elicited depolarization persisted in the presence of cobalt, a calcium channel blocker. Steady-state current-voltage curves revealed that in the voltage range of -50 to -120 mV, 8-Br-cAMP and forskolin induced an inward current, which did not reverse at the potassium equilibrium potential and could not be blocked by tetrodotoxin. Partial replacement of sodium with Tris or choline markedly reduced the depolarization elicited by 8-Br-cAMP. We conclude that 8-Br-cAMP and forskolin act through a common mechanism to increase the firing rate of locus coeruleus neurons by inducing a cAMP-activated inward current, carried out at least in part by sodium ions.     

Spinal entry route for ventral root afferent fibers in the cat

Twelve anesthetized and paralyzed cats were used to study the spinal entry routes of ventral root afferent fibers. In all animals, the spinal cord was transected at two different levels, L5 and S2. The L5 through S2 dorsal roots were cut bilaterally, making spinal cord segments L5-S2 neurally isolated from the body except for the L5-S2 ventral roots. From this preparation, a powerful excitation of the discharge rate of motor neurons and dorsal horn cells within the isolated spinal segments was observed after intraarterial injection of bradykinin (50 micrograms in 0.5 ml saline). This excitation of the spinal neurons can be considered the most convincing evidence of the potential physiologic role of the ventral root afferent fibers entering the spinal cord directly through the ventral root, because the apparent route of neuronal input from the periphery is through the ventral roots. However, additional control experiments conducted in the present study showed that the excitation persisted even after cutting all ventral roots within the isolated spinal segments, indicating that excitation was not mediated by the ventral roots. Furthermore, direct application of bradykinin on the dorsal surface of the spinal cord also increased the motoneuronal discharge rate, suggesting that excitation of spinal neurons produced by intraarterial injection of bradykinin is due to a direct action of bradykinin on the spinal cord. Thus, we provided an alternate explanation for the most convincing evidence indicating that physiologically important ventral root afferent fibers enter the spinal cord directly through the ventral root. Based on existing experimental evidence, it is likely that the majority of physiologically active ventral root afferent fibers travel distally toward the dorsal root ganglion and then enter the spinal cord through the dorsal root.     

The interaction between the activator agents batrachotoxin and veratridine and the gating processes of neuronal sodium channels

The depolarization of frog sciatic nerves by the Na channel-activating toxins, batrachotoxin and veratridine, was studied using the sucrose-gap technique. To study the interaction between the activators and the gating processes of Na channels, we measured the depolarizations of unstimulated nerves, of nerves during repetitive stimulation, and of nerves whose Na channel inactivation process had been pharmacologically modified. Stimulation enhanced the rates of depolarization by the activators but did not effect the steady state depolarization values. Of the three inhibitors of Na channel inactivation that were tested (Leiurus alpha-scorpion toxin, chloramine T, and Ni2+), only Leiurus toxin enhanced the potencies of the activators. Neither chloramine T nor Ni2+ had any effect on the steady state level of depolarization produced by either activator. Both chloramine T and Ni2+, however, enhanced the rate of batrachotoxin action, although neither affected the rate of veratridine action. Leiurus toxin also potentiated the effects of the activators in chloramine T-treated nerves. We tested the interaction between the Na channel activators and a class of agents, local anesthetics, that stabilize a non-conducting state of the Na channel. The presence of lidocaine inhibited the depolarization produced by addition of either activator, although the addition of lidocaine subsequent to the development of batrachotoxin-induced depolarization produced repolarization very weakly and slowly. We also found that the lidocaine homologue, RAC 109I, was about 3 times as potent as its stereoisomer, RAC 109II, in its ability both to reduce the compound action potential amplitude and to inhibit the veratridine-induced depolarization.     

电视传媒在健康知识传播中的作用

电视传媒已成为人类生活中不可缺少的一部分，承担着传播知识与文化的重要任务。电视传媒对一个民族的思想文化影响力、提高该民族在国际社会中的整体形象，都具有不可替代的作用。20世纪80年代，许多健康教育机构就已经开始利用影视传媒手段为健康教育服务，并取得了明显成效。     

COMPARATIVE STUDY OF AMINO ACID CONTENTS AND LDH ISOZYME BY ELECTROPHORESIS AND SLAB-PAGE IN ADULT WORMS OF ASCARIS LUMBRICOIDES, ASCARIS SUUM AND TOXOCARA CANIS^

Comparative studies are made on the relative percentages of amino acid content and LDH isozyme by electrophoresis and Slab-PAGE in adult worms of Ascaris lumbricoides, Ascaris suum and Toxocara canis. The results show that there are remarkable differences of Arg and His of 17 amino acids bet. ween Toxocara canis and human intestinal ascaris, human biliary ascaris and pig ascaris; there are also obvious differences of band positions of LDH isozyme electrophoretic patterns and band position and amount of slab-PAGE patterns among them, whereas no marked differences are found in these three indices in human intestinal ascaris, human biliary ascaris and pig ascaris.     

重型颅脑损伤后凝血功能变化的研究

目的研究重型颅脑损伤后凝血功能的变化及临床意义。方法对本院2005年3月至2006年2月收治的26例重型单纯性颅脑损伤患者（GCS≤8分）进行前瞻性研究，监测其入院当时、入院第2天、第3天及第7天的部分凝血活酶时间（APTT），凝血酶原时间（PT），纤维蛋白原（FIB）及凝血时间（TT）的变化。并检测14例单纯头部外伤患者在入院时的APTT、PT、FIB和TT值。结果APTT在入院3天明显升高。1周后仍未达到正常（P〈0．05）；PT在入院当天即升高（P〈0．05），1周左右逐步恢复正常；FIB在入院当天即升高，第3天下降（P〈0．05），1周左右逐步恢复正常。有3例按照DIC诊断标准诊断为DIC，结果在观察期间均死亡。结论重型颅脑损伤后可发生凝血功能异常，且外凝性凝血途径的启动早于内源性凝血途径。伤后早期即可发生高凝状态，至第3天左右向低凝状态转变，1周左右恢复正常。     

Local Inflammation in Rat Dorsal Root Ganglion Alters Excitability and Ion Currents in Small-diameter Sensory Neurons

Background: Chronic pain conditions may result from peripheral nerve injury, chronic peripheral inflammation, or sensory ganglia inflammation. However, inflammatory processes may also contribute to peripheral nerve injury responses. To isolate the contribution of local inflammation of sensory ganglia to chronic pain states, the authors previously developed a rat model in which long-lasting pain is induced by inflaming sensory ganglia without injuring the neurons. This results in prolonged mechanical pain, local increases in proinflammatory cytokines, increased neuronal hyperexcitability, and abnormal spontaneous activity.

Methods: The authors used whole cell patch clamp in acutely isolated small-diameter neurons to determine how localized inflammation (3-5 days) of L4 and L5 ganglia altered voltage-gated K+ and Na+ currents.

Results: Tetrodotoxin-sensitive Na+ currents increased twofold to threefold in neurons from inflamed ganglia. Tetrodotoxin-resistant Na+ currents increased more than twofold, but only in cells that bound isolectin B4. These increases occurred without shifts in voltage dependence of activation and inactivation. Similar results are seen in models of peripheral inflammation, except for the large magnitudes. Unlike most pain models, localized inflammation increased rather than decreased voltage-gated K+ currents, due to increased amplitudes of the sustained (delayed rectifier) and fast-inactivating transient components. The overall effect in current clamp experiments was an increase in excitability as indicated by decreased rheobase and lower action potential threshold.