Neuronal connections between the cerebellar nuclei and hypothalamus in Macaca fascicularis: cerebello-visceral circuits.

The purpose of this study was to identify the basic pattern of interconnections between the cerebellar nuclei and hypothalamus in Macaca fascicularis. The distribution of retrogradely labeled cells and anterogradely filled cerebellofugal axons in the hypothalamus of M. fascicularis was investigated after pressure injections of a horseradish peroxidase mixture (HRP + WGA-HRP) in the cerebellar nuclei. Following injections in the lateral, anterior, and posterior interposed cerebellar nuclei retrogradely labeled cells were present in the following areas (greatest to least concentration): lateral and dorsal hypothalamic areas, dorsomedial nucleus, griseum periventriculare hypothalami, supramammillary and tuberomammillary nuclei, posterior hypothalamic area, ventromedial nucleus and periventricular hypothalamus, around the medial mammillary nucleus, lateral mammillary nucleus, and infundibular nucleus. Cell labeling was bilateral with an ipsilateral preponderance. In these same experiments anterogradely labeled cerebellar efferent fibers terminated in the contralateral posterior, dorsal and lateral hypothalamic areas, and the dorsomedial nucleus. In these regions retrogradely labeled hypothalamic cells were occasionally found in areas that also contained anterogradely filled cerebellar axons. This suggests a partial reciprocity in this system. In addition, sparse numbers of labeled cerebellar fibers recross in the hypothalamus to distribute to homologous areas ipsilateral to the injection site. Subsequent to an injection in the medial cerebellar nucleus (NM), cell labeling was present in more rostral hypothalamic levels including the lateral and dorsal hypothalamic areas, the dorsomedial nucleus, around or in fascicles of the column of the fornix, and in the periventricular hypothalamic area. Although no fastigiohypothalamic fibers were seen in this study, on the basis of information available from the literature it is likely that such a connection exists in primates. In summary, hypothalamic projections to NM originated mainly from rostral to midhypothalamic levels, whereas those projections to the lateral three cerebellar nuclei came from mid and more caudal levels. The existence of direct hypothalamic projections to cerebellar nuclei in M. fascicularis and of cerebellofugal projection to some hypothalamic centers indicates that circuitry is present through which the cerebellum may influence visceral functions. Furthermore, the fact that projections to NM versus the other cerebellar nuclei originate from somewhat different regions of the hypothalamus would suggest that the visceral functions modulated by each pathway is not the same.     

The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord

By application of the anterograde transport technique ofPhaseolus vulgaris leuco-agglutinin the descending autonomic projection of the paraventricular hypothalamic nucleus was investigated. ThePhaseolus lectin technique allowed the detection of the cells of origin in the paraventricular PVN, the precise position of two distinct descending axon pathways and the detailed morphology of terminal structures in midbrain, medulla oblongata and spinal cord.     

专科-社区诊疗路径中不稳定型心绞痛患者功能状态及满意度评价

目的评价专科．社区诊疗路径对冠心痫不稳定型心绞患者的治疗效果、可行性和可推广性。方法采用同期非随机对照试验。选择同期住院的冠心病不稳定型心绞痛患者：试验组34例，住院期间按照专科．社区诊疗路径进行管理；对照组34例，住院期间采用常规治疗。整体健康状态、身体疼痛、体能状况、情绪状态、日常生活、社交及健康状况作为患者功能状态的观察指标：治疗过程、照顾结果、信息提供程度、费用接受程度作为专科路径满意度评价指标。结果总观察时间为3个月。功能状态方面。试验组在整体健康方面、体能方面、情绪状态和社交生活方面与对照组比较差异有统计学意义（P〈0．05）；而在身体疼痛、日常生活和健康变化方面与对照组比较差异无统计学意义。患者满意度方面，治疗过程、照顾结果、信息提供程度、费用接受程度等方面与对照组比较差异有统计学意义（P〈0．05）。结论专科，社区照顾路径有效提高了冠心病不稳定型心绞痛患者的生活质量，增加了患者对治疗的满意度，有很好的推广意义。     

Characterization of the spinal adrenergic receptors mediating the spinal effects produced by the microinjection of morphine into the periaqueductal gray

After the microinjection of morphine (5 micrograms/0.5 microliter) into the periaqueductal gray resulted in an increase in the hot-plate and tail-flick response latency of the unanesthetized rat, the alpha-adrenergic antagonists yohimbine, rauwolscine and corynanthine were given intrathecally. This treatment resulted in a dose-dependent reversal of the inhibition of the thermally evoked tail-flick reflex. The relative potency of these stereoisomers was: yohimbine = rauwolscine greater than corynanthine. Given the reported affinity of these agonists for the alpha 2 (yohimbine/rauwolscine) and alpha 1 (corynanthine) receptors, these observations suggest that the spinopetal noradrenergic systems are acting on alpha 2-adrenergic receptors. Prazosin, an agent with several orders of magnitude higher affinity for the alpha 1 than the alpha 2-receptor, was at best only equiactive with yohimbine. None of the intrathecal treatments produced a significant reversal of the effects of periaqueductal gray morphine on the hot-plate response. This suggests that the activation of spinopetal noradrenergic pathways alone cannot account for the suppression by morphine in the periaqueductal gray of this response which is organized at the supraspinal level.     

Migration of neuroblasts by perikaryal translocation: role of cellular elongation and axonal outgrowth in the acoustic nuclei of the chick embryo medulla

The neuroblasts forming nucleus magnocellularis, the avian homologue of the mammalian ventral cochlear nucleus, migrate by growth and elongation of their leading processes and by perikaryal translocation through these processes from the matrix zone of the rhombic lip to the acoustico-vestibular anlage. Golgi methods were used on staged chick embryos to reconstruct the morphogenetic phases of migration and early differentiation in situ. Fluorescence labeling of the living cells in vitro elucidated the role of axonal growth in the migratory process. In situ, branching cochlear nerve fibers, tipped with growth cones, enter the acoustico-vestibular anlage at E4.5-5.5 before migration of the magnocellularis neuroblasts at E.5.5-6.5. The premigratory neuroblasts in the matrix zone of the rhombic lip resemble primitive epithelial cells, which extend branched, curving processes into a characteristic formation, the rhombic whorl. The leading process of the migrating magnocellularis neuroblasts gives rise to a bifurcating axon at the interface between the matrix and mantle zones. The lateral branch becomes the recurrent ipsilateral collateral; the medial branch crosses the midline, heading toward the contralateral target site in the region of the presumptive nucleus laminaris. The cell bodies of the migratory neuroblasts appear in intermediate locations along the migration route as they translocate radially through their leading processes past the axonal bifurcation and then tangentially and obliquely into the mantle zone. Neuroblasts destined for nucleus laminaris migrate coincidentally with magnocellularis neuroblasts. Nucleus angularis neuroblasts migrate later in development, after E6.5. In vitro, injections of a nontoxic fluorescent dye (diI) were made into explants of the medulla in the region of the contralateral target area at the time of neuroblast migration. DiI retrogradely labeled the cell bodies of premigratory magnocellularis neuroblasts in the matrix zone and of migratory neuroblasts in the mantle zone through their medial, crossing axonal branches. The morphology of the living neuroblasts in the explants resembled that in the Golgi impregnations at the corresponding stages of migration. Anterograde axonal transport also occurred. These results demonstrate migration by perikaryal translocation and early axon extension of a specific group of neuroblasts in the central nervous system. The morphology of the migrating neuroblasts is such that a simple radial arrangement of cellular guides, glial or otherwise, would not account for their configurations. The available evidence supports the proposition that cellular elongation and perikaryal translocation constitute the general mode of neuronal migration in the central nervous system. The early extension of axons into their target sites may play a critical role in migration and early development of specific types of neurons.     

Computer Model of the Atrioventricular Node Predicts Reentrant Arrhythmias

Introduction: Following atrial premature beats, the AV node may exhibit sustained reentrant tachyarrhyth-mias, isolated echo beats, or discontinuities in the recovery curve (the plot of conduction time versus atrial cycle length). A computer model was used to examine the hypothesis that spatial variation of AV nodal passive electrical resistance may account for these phenomena. Methods and Results: A computer model of a rectangular lattice of elecirotonically linked elements whose ionic kinetics simulated nodal ionic flux was developed. the model showed that there exists a resistance value that minimizes the effective refractory period, because high resistance prevents depolarization of distal elements, while low resistance allows leakage of depolarizing current by electrotonic transmission, preventing activation of proximal elements. High resistances stabilized reentry by slowing conduction. Simulations incorporating equal resistance values between elements predicted increased AV nodal conduction times with increasing prematurity of atrial impulses. A model with a gradual change in resistance between fibers produced discontinuities and tachycardia, but not both simultaneously. Uniform anisotropy produced preferential transverse block, leading to echo beats and “fast-slow” tachycardia, but not recovery curve discontinuities. Nonuniform anisotropy could produce reentry, but tachycardia often occurred without discontinuities. Dividing the lattice into two electrotonically linked parallel pathways with different resistance values (“dual pathway model”) predicted recovery curve discontinuities, echo beats, and tachycardia. At critical atrial cycle lengths, only the (high resistance) slow pathway conducted antegradely, while the fast pathway conducted retrogradely, to generate the typical “slow-fast” tachycardia. Responses of the dual pathway model to ablation were consistent with clinical data, including the previous observation of a decrease in fast pathway effective refractory period after slow pathway ablation. Conclusion: Differences in passive electrical resistance of electrotonically linked dual pathways within the AV node may account for functional longitudinal dissociation, reentrant arrhythmias, and responses to catheter ablation therapy.     

胍丁胺对皮质酮致原代培养大鼠海马神经元损伤的保护作用

目的前期证明胍丁胺作为一种新型神经递质具有抗抑郁作用，本实验通过观察胍丁胺对皮质酮致原代培养海马神经元损伤的保护作用及作用机制，探讨其抗抑郁作用的细胞分子机制。方法体外培养新生大鼠海马神经元，加入不同浓度皮质酮（50～300μmol·L^-1），采用CCK-8试剂盒比色法检测对神经元存活的影响；培养体系内加入胍丁胺，观察对神经元损伤的保护作用；加入H89（PKA特异性抑制剂）或PD98059（MEK特异性抑制剂），观察胍丁胺的神经元保护作用及可能的相关信号通路。结果皮质酮（50～300μmol·L^-1）能够浓度依赖地抑制原代培养海马神经元的存活；同时胍丁胺（5μmol·L^-1）对此损伤具有保护作用；胍丁胺的保护作用可以被H89（20μmol·L^-1）和PD98059（20μmol·L^-1）取消。结论胍丁胺具有神经元保护作用，此作用与cAMP-PKA-CREB通路和MEK-ERK-CREB通路密切相关。     

抑制PI3K/Akt信号通路拮抗胰岛素诱导的子宫内膜癌细胞增殖

目的:研究抑制磷脂酰肌醇3激酶(PI3K)/Akt信号通路对胰岛素诱导的子宫内膜癌细胞增殖的拮抗作用。方法:将无血清饥饿的子宫内膜癌Ishikawa3-H-12细胞分为空白对照组、10-6mol/L胰岛素单独刺激组以及不同剂量PI3K抑制剂-LY294002预处理后再用胰岛素刺激组。Western blot检测各组Akt磷酸化(p-Akt)水平,MTT试验观察细胞增殖情况。结果:胰岛素可引起内膜癌细胞Akt活化,刺激15min后p-Akt/Akt比值显著高于空白对照组(68.68%vs 26.21%,P<0.001)。LY294002以浓度依赖方式抑制胰岛素引起的Akt磷酸化。MTT试验显示,在药物处理24h,48h和72h 3个时间点,不同组别570nm吸光度值(OD570nm)均有显著差异(F=156.329,700.973,812.224,均P<0.001)。胰岛素组OD570nm值均高于同时间点的空白对照组(均P<0.001),胰岛素促内膜癌细胞增殖作用于48h时最为显著。LY294002可抑制胰岛素的增殖促进作用,此抑制作用具有浓度依赖性。不同剂量LY294002抑制作用的时间依赖性不同,48h时小剂量(0.1、1、10μmol/L)的抑制作用最为显著,72h时胰岛素重新呈现一定的促增殖作用;而50μmol/L LY294002可以持久抑制胰岛素的促增殖作用。结论:PI3K抑制剂LY294002可以通过抑制Akt磷酸化阻断胰岛素信号传导,拮抗后者促子宫内膜癌细胞增殖的作用。