改变督导方式促进临床教学质量

目的:发挥教学督导的作用,提高医学院校临床教学的质量.方法:对教学督导工作进行了大胆的改革:①督导前移,加强了教学的环节质量;②疏通反馈通道,保证教学督导效果;③言传身教,加强对青年教师的培养和指导;④扩大督导范围,促进各层次教学质量;⑤全程随机评价,客观评价教学效果.结果:保证了教学效果,使教学质量有了明显的提高.结论:加速我军现代化建设,培养高素质医学人才,教学督导的作用显的尤其重要.     

五味子酚对大鼠嗜中性白细胞功能与形态的作用(英文)

目的:探讨五味子酚(Sal)对大鼠嗜中性白细胞(Neu)功能的调节作用.结果:Sal 1,10,100μmol·L~(-1)剂量依赖性抑制Neu功能,Sal 100μmol·L~(-1)使Neu表面伪足和皱褶消失,并可降低细胞内钙离子浓度、升高细胞内cAMP水平.结论:Sal可通过影响细胞内钙离子浓度、cAMP水平及细胞表面形态抑制Neu的功能.     

Long-Term Depression in Rat Cerebellum Requires both NO Synthase and NO-sensitive Guanylyl Cyclase

Long-term depression (LTD) of synaptic transmission between parallel fibres and Purkinje cells is a well-known example of synaptic plasticity taking place in the cerebellum. Nitric oxide (NO) has been implicated in synaptic plasticity in other brain areas, but its function in cerebellar LTD is controversial. Even when an involvement is suggested, the NO signal transduction pathway is unclear. One candidate is the cyclic GMP-synthesizing enzyme, soluble guanylyl cyclase, whose activity in the brain and elsewhere is powerfully stimulated by NO. By recording intracellularly from Purkinje cells in cerebellar slices, we demonstrate that blockade of NO synthase completely inhibits LTD induced by pairing parallel fibre stimulation with postsynaptic Ca²⁺ spike firing. LTD was also blocked by intracellular application of 1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxalin-1-one, a recently identified potent and selective inhibitor of soluble guanylyl cyclase. These findings indicate that soluble guanylyl cyclase is required for cerebellar LTD and suggest that this enzyme, located within Purkinje cells, transduces the NO signal in this form of synaptic plasticity.     

Modulation of guanylate cyclase and phosphodiesterase by monovalent cations and nucleoside triphosphates in light-sensitive excised patches of rod outer segments

Excised inside-out patches of vertebrate rod outer segment can support phototransduction. I have examined how ionic and metabolic conditions influence the functional properties of light-sensitive patches fromGekko gekko. I find that such patches retain a variable level of basal phosphodiesterase activity, which lowers the cyclic guanosine monophosphate (cGMP) concentration reaching the channels and reduces the dark current. The dose/response relationship for channel opening by cGMP varies among patches and this variability is only reduced by working in darkness with the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX), suggesting that it is only partially due to phosphodiesterase activity. MgATP or MgGTP, but not Mg or ATP separately, increase this activity but a kinase does not appear to be involved. Intracellular monovalent cations also influence dark current intensity and light response kinetics. With 5 mM MgGTP, 1 mM IBMX, and 144 mM Li⁺, Na⁺, K⁺, or Rb⁺, dark current intensity and recovery time follow the respective sequences K⁺>Rb⁺>Na⁺>Li⁺ and K⁺<Rb⁺<Li⁺<Na⁺. Without IBMX, a dark current develops with K⁺ but not with Na⁺. These effects are not due to altered channel permeability (P) = 0.841.00 1.011.090.42], or differential Mg²⁺ block, but to modulation of guanylate cyclase, which overcomes phosphodiesterase when the major cation is K⁺ but not when it is Na⁺.     

N G-nitro-l-arginine antagonizes endothelium-dependent dilator responses by inhibiting endothelium-derived relaxing factor release in the isolated rabbit heart

The effects of a recently described inhibitor of endothelial NO synthesis, N ^G-nitro-l-arginine (l-NNA), on the vasomotor responses to endothelium-dependent and independent vasodilators, and on the release of endothelium-derived relaxing factor (EDRF), were studied in the isolated saline-perfused rabbit heart. Infusion of l-NNA (30 M) resulted in a 52±12% increase in basal coronary perfusion pressure. The vasomotor responses to 1 M acetylcholine (ACh) and serotonin after l-NNA became biphasic, showing a small transient dilation followed by a pronounced vasoconstriction. In contrast, the dilation observed with sodium nitroprusside was not affected by l-NNA. None of the above-mentioned effects was elicited by the Stereo-isomer d-NNA. Similarly, an increase in the basal coronary perfusion pressure by endothelin-1 (0.3 nM) to the same level as observed with l-NNA did not alter the vasomotor responses to ACh and sodium nitroprusside. The increase in cyclic GMP (cGMP) in platelets passing through the coronary vascular bed was used as an index of EDRF release. Platelet cGMP amounted to 0.50±0.10 pmol/mg protein after passage through the coronary bed of the unstimulated heart. When platelets were injected during an ACh infusion (1 M), a 2.7 fold increase in cGMP was observed (P<0.01). After a 30-min infusion with l-NNA, the cGMP content of platelets passing through the unstimulated heart was reduced by 62%. Likewise, the ACh-induced increase in platelet cGMP was totally blocked. These results show that l-NNA inhibits EDRF release, and is thus a potent and selective inhibitor of EDRF-mediated dilation in the isolated rabbit heart.     

Levels of quality management of blood transfusion services in Europe

The European blood legislation has defined several key quality elements to achieve Good Manufacturing Practice (GMP) in the field of blood transfusion. During the recent years, the blood legislation is in the process of implementation throughout its member states. Following the Directive 2002/98/EC, Directive 2005/62/EC has given further requirements for quality-management systems to be fulfilled by blood establishments. In addition, GMP/Good Laboratory Practice (GLP) and ISO standards are used inter alia by blood establishments. In order to support the implementation of the blood legislation, the European Public Health Work Plan (2005/2007) has cofunded two projects, led by the German Red Cross and supported by the European Blood Alliance, delivering a common European Standard Operating Procedure (SOP) methodology (EU-Q-Blood-SOP) and criteria and standards for the inspection of blood establishments (EUBIS). The EU-SOP manual will assist blood establishments in preparing for the inspection of their services related to the implementation of quality relevant elements required by the EU Directive 2002/98/EC and its technical annexes. The standards and criteria for inspection of blood establishments will cross-reference existing quality standards to the directive requirements and define requirements for the structure of quality-management systems based on the directive 2002/98/EC and its technical annexes. Based on these requirements, inspection standards and criteria are developed to assist in the independent assessment of quality systems established by individual blood establishments. These assessments are done in relation to the requirements defined by the European Union legislation on blood, in order to safeguard the quality of blood and to achieve continuous improvement of its quality throughout Europe.     

Cytochemical localization of 5'-nucleotidase activity in retinal photoreceptor cells

Further cytochemical studies on the ultrastructural localization of 5'-nucleotidase in the rat retina have revealed activity to be associated with the complex synapses formed by the rod spherules of the receptors and the bipolar and horizontal cell processes. Activity was also seen on the axolemma of receptor fibers. In the rod inner segment strong reaction product is located intracellularly. In the rod outer segment the enzyme appears to be located only on the cytoplasmic side of the disc membrane and not intradiscally . Retinal pigment cells are rich in 5'-nucleotidase. Their microvilli accompany the tips of the receptor cells and show enzyme activity in an ecto position. A role for 5'-nucleotidase is possible in the metabolism of guanylate and adenylate nucleotides both of which are important for visual transduction processes.     

Synaptic efficacy of inhibitory synapses in hypoglossal motoneurons after transection of the hypoglossal nerves

In cat hypoglossal motoneurons after axotomy the synaptic efficacy of inhibitory synapses made by the lingual nerve afferent fibers was studied. The amplitude of the short- and the long-lasting inhibitory postsynaptic potential produced in tongue protruder motoneurons 24 days after axotomy by stimulation of the lingual nerve was significantly reduced in size as compared with the control on the unoperated side. In most protruder motoneurons 40 days after axotomy a large excitatory postsynaptic potential and a spike was produced by stimulation of either the ipsilateral or the contralateral lingual nerve. We have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was more prominent than that for the long-lasting inhibitory potential in the motoneuron 24 days after axotomy. After the cut axons of protruder motoneurons were re-united to tongue muscles, we have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was less prominent than that in axotomized protruder motoneurons.     

The pharmacology of fever

The ability to minimise, if not prevent, large variations in deep body temperature that would otherwise result from some environmental conditions is a homeostatic function of unquestioned benefit that is demonstrated only by the more highly evolved animals. Nevertheless, body temperature is raised above normal values in many pathological conditions. This increase in temperature or fever is an active and co-ordinated response, which indicates the involvement of the CNS. Central injection and lesion studies have shown that the brain, in particular the PO/AH, is the site of action of fever-inducing agents, termed pyrogens. Electrophysiological data show that pyrogens modify the activity of central thermosensitive neurones as if to increase heat gain and decrease heat loss. The common response of fever to pyrogens of diverse origins is attributable to fever being mediated by an endogenous pyrogen released by phagocytic cells in the host. The mechanism by which central neuronal function is disturbed by pyrogens present in the periphery is not known. Tracer studies have yet to demonstrate the passage of a pyrogen across the blood-brain barrier. The possible involvement of several putative neuro- transmitters and modulators in fever has been reviewed here, but most compounds have not been studied sufficiently to allow firm conclusions to be drawn. Much of the data is limited to the effects of the putative mediators on normal thermoregulation but, even when the effect is hyperthermia, such observations do not necessarily indicate a role for the endogenous material in fever. Dose-response curves for agonists and the effects of antagonists are often undetermined. This shortfall in data is due to some extent to the nature of fever; a central response in vivo over several hours. Although fever may enhance other host reactions to combat infection and inflammation, neither this benefit nor the undesirability of antipyretic therapy has been demonstrated unequivocally in either homeothermic laboratory animals or humans. Consequently, antipyretic drugs continue to be used clinically to alleviate the fever, malaise and/or pain commonly associated with disease. The drugs in common usage are the nonsteroidal antipyretic analgesics, many of which also have an anti-flammatory effect. The primary mode of action of these drugs as antipyretics appears at present to be the inhibition of cyclo-oxygenase and a consequent reduction of prostanoid material in pyrogen-sensitive areas of the brain. PGEs in the PO/AH have received most study to date, but other mediators in other parts of the CNS, where the density of pyrogen receptors may be sparse, cannot be discounted and await further investigation.     

Dissociation of acetylcholine- and cyclic GMP-induced currents inXenopu oocytes

InXenopus follicular oocytes, activation of muscarinic receptors evokes a slow potassium current (H-response); a similar current is evoked by intracellular injection of cyclic guanosine 3,5-monophosphate, cGMP (Dascal et al. 1984). We have tested the hypothesis that cGMP may be the second messenger that mediates the opening of K channel by acetylcholine (ACh). ACh elevated the intracellular level of cGMP with a time course similar to that of the development of the muscarinic H-response; maximal increase in cGMP concentration above the control was about 0.2 pmole/oocyte. The amount of injected cGMP that produced a detectable K current (threshold dose) varied between 0.5 and 3 pmole/oocyte. At low doses of cGMP, the slope of log dose-log response curve was about 2.5, suggesting involvement of a biochemical process with a positive cooperativity of at least 3. Higher doses of cGMP evoked, in addition to the outward current, an irregular, rapidly developing, long-lasting inward current, that never reached amplitudes comparable to those of ACh-evoked Cl currents. The K current elicited by cGMP was insensitive to elevation or depletion of external Ca. It was potentiated by isobutylmethylxanthine (IBMX). ACh strongly inhibited the cGMP-evoked K current when applied at the plateau of the latter. 4-Phorbol 12,13-dibutyrate (PDBu) (1 M) rapidly and completely inhibited the cGMP response. It is concluded, that most of the results presented in this report contradict the hyothesis that cGMP is the intracellular mediator of ACh-induced changes in membrane conductance in the oocytes.Abbreviations ACh acetylcholine - cAMP cyclic adenosine 3,5-monophosphate - cGMP cyclic guanosine 3,5-monophosphate - EGTA ethylenediaminetetraacetic acid - Hepes N-2-hydroxyethyl-piperazinc-N-2-hydroxypropanesulphonic acid - IBMX 3-isobutyl-l-methylxanthine - IP₃ inositol 1,4,5-trisphosphate - PDBu 4-phorbol 12,13-dibutyrate