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.     

Spectral characteristics of early receptor potential in congenital red-green color blindness

The spectral response curve (amplitude versus wavelength) of the R₂ of the early receptor potential (ERP) was studied in normal, protan, and deutan subjects. The R₂ amplitude peaked at 520nm in most normal subjects. The R₂ at long wavelengths was smaller than normal in protans and larger than normal in deutans when the maximum amplitudes were normalized to 100% at the peak. The ratio of the R₂ amplitude at 460 nm to that at 600 nm clearly differed between protans and deutans. The ERP and the rapid off-response, which is mainly due to the cessation of the late receptor potential, were recorded in the same subjects. The ratio of the sensitivity of the rapid off-response at 500 nm to that at 600 nm was correlated with the ratio of the R₂ amplitude at 460 nm to that at 600nm (correlation coefficient, 0.823, p < 0.001). This study, in conjunction with our previous study, indicates that the abnormality is in the outer segments of the cones in protans and deutans.     

碘杂环化合物对离体豚鼠心乳头肌动作电位和收缩力的作用

采用细胞内微电极记录技术,同步观察了3,6-[二甲氨基]-二苯并碘因甲酸盐(IHC-64)对豚鼠心乳头肌细胞动作电位和收缩力的作用。50μmol/L IHC-64抑制心肌收缩力,而不影响快反应动作电位。增加IHC-64浓度,动作电位0相最大峰值(APA)、除极速率(dp/dt_(max))和复极50％和90％时程(APD_(50)、APD_(90))被明显抑制。IHC-64抑制慢反应动作电位,提高细胞外钙浓度可拮抗这种抑制。结果提示,IHC-64主要抑制慢Ca~(2+)内流,同时也部分抑制快Na~+内流,它可能是一种新型B类钙通道阻滞剂。     

合并心律失常的心力衰竭56例治疗评价

目的探讨心力衰竭并发心律失常的发病规律及治疗方法。方法回顾性分析了93例慢性心力衰竭病人的临床资料，包括临床特点、诊断治疗方法以及预后。结果心律失常发生率为60．2％，以室性早搏发生率最高32．1％，其次是房性早搏26．8％，心房纤颤21．4％，其他19．7％，经治疗有效71例，总有效率76．3％。结论纠正心功能不全是治疗的关键，应根据具体情况选择性地应用抗心律失常药。     

Computerised and technical navigation in total knee-arthroplasty

Abstract The objective of the study was to evaluate the precision, concordance, practicability and the early clinical outcome of the use of a computerised navigation system in a comparative study with a group of 100 patients. Two groups of 50 patients each underwent implantation of a bicondylar knee prosthesis either by means of the freehand navigation system or by means of technical instrumentation. We found that the computerised navigation system provided a higher precision than the technically instrumented implantation: 94% of the prostheses implanted with the navigation system have an alignment within a range of -3° to 3° on of the Mikulicz line. Only 46% of the patients operated by means of the technical instrumentation reached this aspired result. Furthermore, the navigation system showed smaller ranges in the deviation of the aspired alignment. The radiological and computer-modeled alignment values differed both pre- and postoperatively, but to a larger extent before surgery. The varus or valgus deviations of the axis were more distinct radiologically under the weight of the patient’s body than in the computer model. The clinical outcome examined by the use of the HSS score after a mean followup of 7 months is good in both groups, and without significant differences. On average, the duration of surgery was 13 minutes longer in the computerised navigation group. We conclude that the benefit of the computerised navigation system is represented by the high improvement of precision. Achieving early clinical results identical to those in the technical instrumentation group, we expect a reduction of aseptic loosening in the computerised navigation group.     

Gating modifier peptides as probes of pancreatic beta-cell physiology.

Pancreatic beta-cells depolarize in response to glucose and fire calcium-dependent actions potentials that trigger insulin secretion. The major current responsible for action potential repolarization in these cells is a delayed rectifier and Kv2.1 subunits are thought be a major contributor of the delayed rectifier channels. Hence, blockers of Kv2.1 channels might prolong action potentials and enhance calcium influx and insulin secretion. However, the lack of specific small molecule Kv2.1 inhibitors has hindered the testing of this mechanism. Importantly, several gating modifier peptides inhibit Kv2.1 channels in a relatively specific fashion. Hanatoxin (HaTX) and guangxitoxin-1 (GxTX-1) are examples that have been used to probe the role of Kv2.1 channels in beta-cell physiology. Both HaTX and GxTX-1 strongly inhibit the Kv current of beta-cells from various species, arguing that Kv2.1 subunits contribute significantly to the beta-cell delayed rectifier. GxTX-1 prolongs glucose-triggered action potentials, enhances glucose-dependent intracellular calcium elevations and augments glucose-dependent insulin secretion. Taken together, these data suggest that blockers of Kv2.1 channels may be a useful approach to the design of novel therapeutic agents for the treatment of type 2 diabetes. These studies highlight the utility of gating modifier peptides in the study of physiological systems.     

2型糖尿病患者的智能障碍

目的：调查没有临床神经损害体征的2型糖尿病患者早期的高级神经功能改变，方法：分别对52例2型糖尿病患者和32名健康对照者进行了韦氏智力量表的相似、数字广度、数字符号、木块图等4项分测验测定，采用二合一(相似、木块图)的方法计算简式智商，同时进行事件相关电位检查，结果：糖尿病患者组的相似、木块图分测验成绩和简式智商明显较健康对照组低下，ERP检查发现病人组N2、P3潜伏期较对照组明显延长，结论：2型糖尿病可导致高级神经功能损害。并且这种损害可能要早于周围神经损害。     

A neosynthesis of sodium channels is involved in the evolution of the sodium current in isolated adult DUM neurons

Short-term culture of isolated adult dorsal unpaired median (DUM) neurons of the cockroach Periplaneta americana has been used to study the evolution of the sodium current during the time in culture after axotomy and deafferentation treatment. An increase in the maximum peak amplitude of the sodium current recorded under voltage-clamp conditions with the patch-clamp technique in the whole-cell recording configuration, was only observed between 24h and 72h (75%) without any modification of the kinetics and the voltage-dependence of the current. A decrease in the level of foetal calf serum in the culture medium reduces the amplitude of the sodium current on all days but does not affect its time-course of development which was on the contrary completely abolished by both protein synthesis inhibitors, actinomycin D and cycloheximide. The results obtained in these neurons strongly suggest that a neosynthesis of sodium channel proteins is involved in the evolution of the sodium current induced by axotomy and deafferentation.     

Repetitive firing properties in subpopulations of the chick Edinger Westphal nucleus.

The avian Edinger Westphal nucleus, through the ciliary ganglion, controls accommodation, iris constriction, and blood flow through the choroid. In live brainstem slices, the nucleus is easily identifiable as an olive-shaped cluster of neurons dorsal to the oculomotor nerve and nucleus. Intracellular recordings from neurons in the nucleus identified two classes of responses to sustained (300 to 500 ms) injections of depolarizing current. One set of cells fired action potentials for the duration of the pulse while a second set of cells fired action potentials only transiently, during the first 50 to 100 ms, after which they remained silent regardless of the size of the depolarization. Intracellular recordings followed by injections of the fluorescent dye lucifer yellow revealed that repetitively firing cells were located in the lateral half of the nucleus while non-repetitively or transiently firing cells were located in the medial half. These locations correspond to different Edinger Westphal subdivisions which have distinct inputs and target populations. The varying firing patterns are discussed with reference to the known functions of the subdivisions in which they occur. Replacement of calcium by magnesium in the extracellular medium had no effect on the number of action potentials fired by non-repetitively firing cells, suggesting that a calcium-activated potassium current is not responsible for suppressing repetitive firing in these cells. In contrast, in repetitively firing cells removal of extracellular calcium increased the frequency of action potential discharge and decreased the amplitude of afterhyperpolarizations following single action potentials. Addition of cadmium to the bath medium had similar effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Introducing expert systems to medical students using esta, Expert System Teaching Aid

Medical students are allocated little curriculum time for exposure to expert systems. ESTA, a computer model of an expert system, was developed to make best use of this time. The nature of the students' interaction with ESTA is described, and their reactions to the expert system concepts and the place of expert systems in medicine are presented. A discussion of these reactions draws some conclusions about teaching expert systems in particular, and computers in general, in the basic medical course.