Septal innervation of mossy cells in the hilus of the rat dentate gyrus: an anterograde tracing and intracellular labeling study

 Mossy cells in the hilus of the rat dentate gyrus are the main cells of origin of the dentate commissural and associational projections. They project along the septotemporal axis of the dentate gyrus and may thus influence the hippocampal signal flow in a longitudinal direction. To analyze the septal innervation of these hilar neurons, anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHAL) was used in combination with intracellular labeling of mossy cells (Lucifer yellow). Anterogradely labeled septal fibers impinge on proximal and distal dendrites of hilar mossy cells but spare the cell body. In contrast, numerous aspiny hilar neurons, presumably GABAergic interneurons, receive a septal innervation on their somata and proximal primary dendrites. These data demonstrate that septal fibers show a specificity for the dendritic segments of hilar mossy cells. Since mossy cells project predominantly to adjacent hippocampal lamellae, the activity of adjacent portions of the dentate gyrus may be influenced by the septal input onto these neurons. Received: 22 July 1996 / Accepted: 24 October 1996     

Control of locomotion in marine mollusc — Clione limacina. V. Photoinactivation of efferent neurons

Summary Efferent neurons in isolated pedal ganglia of the pteropodial mollusc Clione limacina were filled with Lucifer Yellow through the wing nerves. Then the ganglia were illuminated with intense blue light which resulted in the complete inactivation of these neurons. After inactivation of efferent neurons, interneurons of the pedal ganglia continued to generate the locomotor rhythm.     

从心身同治角度针灸对乳腺癌关节痛患者生命质量改善的临床研究

目的:评价基于《黄帝内经》心身疾病病因的整体选穴与乳腺癌芳香化酶抑制剂(AI)关节痛局部配穴相结合的针灸方法,对乳腺癌康复期AI关节痛患者生命质量及局部关节症状的临床疗效。方法:选取2019年1月至2021年5月南京医科大学第一附属医院乳腺外科筛选使用唑来膦酸的乳腺癌AI患者232例作为研究对象,依据针灸意愿分为对照组(n=19)和观察组(n=16),对照组采用唑来膦酸常规镇痛,观察组在唑来膦酸的基础上采用整体及局部取穴相结合的方法针灸治疗,共治疗4周,分别评价治疗前、治疗2周、4周、8周时的乳腺癌患者生命质量量表(FACT-B)生命质量评分以及简明疼痛评估量表(BPI-SF)关节痛评分,同时评估针灸治疗的安全性。结果:治疗4周以及8周时观察组FACT-B生命质量评分较对照组高,治疗4周时观察组BPI-SF疼痛评分较对照组低,差异有统计学意义(P<0.05)。结论:采用整体配穴调和心身与局部选穴缓急止痛相结合的针灸方法对乳腺癌康复期AI患者的生命质量以及局部关节症状有较好的临床疗效。     

Next generation live-attenuated yellow fever vaccine candidate: Safety and immuno-efficacy in small animal models

Yellow fever (YF) remains a threat to human health in tropical regions of Africa and South America. Live-attenuated YF-17D vaccines have proven to be safe and effective in protecting travellers and populations in endemic regions against YF, despite very rare severe reactions following vaccination — YF vaccine-associated viscerotropic disease (YEL-AVD) and neurological disease (YEL-AND). We describe the generation and selection of a live-attenuated YF-17D vaccine candidate and present its preclinical profile. Initially, 24 YF-17D vaccine candidate sub-strains from the Stamaril® and YF-VAX® lineage were created through transfection of viral genomic RNA into Vero cells cultured in serum-free media to produce seed lots. The clone with the ‘optimal’ preclinical profile, i.e. the lowest neurovirulence, neurotropism and viscerotropism, and immunogenicity at least comparable with Stamaril and YF-VAX in relevant animal models, was selected as the vaccine candidate and taken forward for assessment at various production stages. The ‘optimal’ vaccine candidate was obtained from the YF-VAX lineage (hence named vYF-247) and had five nucleotide differences relative to its parent, with only two changes that resulted in amino acid changes at position 480 of the envelope protein (E) (valine to leucine), and position 65 of the non-structural protein 2A (NS2A) (methionine to valine). vYF-247 was less neurovirulent in mice than Stamaril and YF-VAX irrespective of production stage. Its attenuation profile in terms of neurotropism and viscerotropism was similar to YF-VAX in A129 mice, a ‘worst case’ animal model lacking type-I IFN receptors required to initiate viral clearance. Thus, vYF-247 would not be expected to have higher rates of YEL-AVD or YEL-AND than Stamaril and YF-VAX. In hamsters, vYF-247 was immunogenic and protected against high viremia and death induced by a lethal challenge with the hamster-adapted Jimenez P10 YF virus strain. Our data suggests that vYF-247 would provide robust protection against YF disease in humans, similar to currently marketed YF vaccines.     

Electrical coupling, without dye coupling, between mammalian astrocytes and oligodendrocytes in cell culture

Evidence of electrical and dye coupling between oligodendrocytes and astrocytes was sought in cultures of mouse spinal cord. Cell identity was verified using cell specific antigenic markers. In most experiments current was injected into oligodendrocytes while recording voltage in nearby astrocytes. Nine of 17 oligodendrocyte-astrocyte cell pairs showed weak electrical coupling; the average estimated coupling ratio was 0.03 +/- 0.06 (cf. 0.11 for oligodendrocyte-oligodendrocyte and 0.44 for astrocyte-astrocyte pairs; Kettenmann and Ransom: Glia, 1: 64-73, 1988). Application of 0.5 mM BaCl2 or 44.6 mM CsCl depolarized astrocytes and oligodendrocytes and was estimated to increase the coupling ratio between these cells 3-5-fold; these effects were rapid in onset and completely reversible. In 5 of 7 cases, oligodendrocyte-astrocyte pairs that appeared uncoupled in normal solution exhibited coupling during Ba++ or Cs+ exposure. The actions of these cations are believed to be mediated by blockade of glial K+ channels. Depolarization, per se, as induced by increasing [K+]o, did not increase coupling ratio. The fluorescent dye lucifer yellow (LY) was injected into 10 oligodendrocytes, 8 of which were electrically coupled to nearby astrocytes, and never passed into astrocytes in detectable quantities. Likewise, astrocytes injected with LY stained other astrocytes, but never oligodendrocytes. These findings document the presence of weak electrical coupling between astrocytes and oligodendrocytes, in the absence of dye coupling. Weak coupling of this sort could subserve metabolic interactions between these cells mediated by the passage of small but important molecules such as cyclic AMP, but would not allow strong electrical interactions. If such coupling among glial cells is widespread, it would constitute a "metabolic syncytium" that could serve to coordinate glial behavior.     

Endothelins Inhibit Junctional Permeability in Cultured Mouse Astrocytes

Endothelins, a family of potent vasoconstrictor peptides initially characterized in peripheral tissues, have also been reported to be synthesized in the brain. In this structure several cell types, including astrocytes, endothelial cells and certain neurons, are potential targets for these peptides. In astrocytes, endothelins induce changes in the concentration of several second messengers (calcium, diacylglycerol, arachidonic acid, cAMP) known to be involved in the regulation of gap junction channels. Using the scrape loading/dye transfer technique we have observed that two isoforms of endothelin, endothelin-1 and endothelin-3, strongly inhibit the extent of dye-coupling between confluent astrocytes, suggesting that gap junction permeability was reduced. This inhibitory effect on dye coupling was reproduced by the snake venom sarafotoxin. When used at 10⁻⁷ M, these three compounds had inhibitory effects on gap junction channels which were comparable to those induced by the well known uncoupling agents octanol and halothane. In the absence of extracellular calcium, the effects of endothelins were largely prevented, suggesting that second messengers linked to the activation of phospholipases C and/or A₂, which both are dependent on external calcium, could be involved in the uncoupling mechanism.     

Innervation of Entorhinal Principal Cells by Neurons of the Nucleus Reuniens Thalami. Anterograde PHA-L Tracing Combined with Retrograde Fluorescent Tracing and Intracellular Injection with Lucifer Yellow in the Rat

The innervation of dendrites of identified entorhinal principal cells by fibres originating in the nucleus reuniens thalami was studied in the rat. The lectin Phaseolus vulgaris-leucoagglutinin (PHA-L, anterograde tracer) was injected into the nucleus reuniens and the fluorescent dye Fast Blue (retrograde tracer) into the hippocampus. After survival, perfusion-fixation and the preparation of brain slices, entorhinal neurons retrogradely labelled with Fast Blue were intracellularly injected with the dye Lucifer yellow to introduce a specific marker into their dendrites. The transported PHA-L and the injected Lucifer yellow were visualized through dual peroxidase immunohistochemistry. Varicosities on PHA-L labelled reuniens fibres abut ascending and descending Lucifer yellow-filled secondary dendrites of multipolar and pyramidal principal entorhinal neurons that possess either spiny or sparsely spiny dendrites, but they do not appose the perikarya of these cells. In the electron microscope, PHA-L labelled boutons in the entorhinal cortex were observed forming asymmetrical synaptic contacts with dendritic spines (50%) or shafts (50%). The results indicate that direct thalamic input occurs on dendrites of neurons in the entorhinal cortex which project to the hippocampus.     

《内经》针刺禁忌理论的人文观与自然观探讨

用人文与自然的观点，对《内经》关于针刺禁忌的理论进行分析，用中医的整体观念，将针刺禁忌理论，从具体的部位、具体的疾病升华到人神与自然的高度。论述了精神对气血的导引作用以及体内阴阳之气的运动规律，同时阐明了逆时逆势而刺后患无穷，反为针害的重要道理，并强调了针灸治疗要关注人的精神，关注自然环境的绿色医学思想。     

《内经》所蕴含的中医肾病证治思路探讨

邹氏肾科医术非物质文化遗产团队根据《内经》相关理论结合团队临床实践对常见肾病的中医证治思路进行探讨,认为肾气不足为肾病发病之因,肾元衰竭是发病之本。临床中需注意未病先防、既病防变,强调治病必求于本。根据临床实际情况,分别提出从脾肾、从肝肾、从肺论治肾病,常用治法有健脾温肾、扶正渗利、清肝解毒、养肝滋阴、平肝潜阳、疏肝活络、疏风宣肺、清热宣肺、清热利咽、和法缓治、活血化瘀、疏滞泄浊等法。      

Yellow fever live attenuated vaccine: A very successful live attenuated vaccine but still we have problems controlling the disease

Yellow fever (YF) is regarded as the original hemorrhagic fever and has been a major public health problem for at least 250 years. A very effective live attenuated vaccine, strain 17D, was developed in the 1930s and this has proved critical in the control of the disease. There is little doubt that without the vaccine, YF virus would be considered a biosafety level 4 pathogen. Significantly, YF is currently the only disease where an international vaccination certificate is required under the International Health Regulations. Despite having a very successful vaccine, there are occasional issues of supply and demand, such as that which occurred in Angola and Democratic Republic of Congo in 2016 when there was insufficient vaccine available. For the first time fractional dosing of the vaccine was approved on an emergency basis. Thus, continued vigilance and improvements in supply and demand are needed in the future.