A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

哮喘患儿血清嗜酸性粒细胞阳离子蛋白改变及其意义

目的：评价变应性哮喘患儿血清嗜酸性粒细胞阳离子蛋白（S-ECP）水平改变及其意义。方法：测定25例哮喘发作期患儿糖皮质激素吸入治疗12周前后，及20例未予糖皮质激素吸入治疗的哮喘缓解期患儿S-ECP水平，并对发作期患儿S-ECP水平变化与血嗜酸性粒细胞计数（B-EOS）、肺功能一秒用力呼气量（FEV1）、一秒用力呼气量比用力肺活量（FEV1/FVC）及症状评分的关系作相关性分析。结果：哮喘发作组治疗后S-ECP水平较治疗前显著降低，与对照组（健康儿童10名）比较差异无显著性；哮喘缓解组S-ECP水平明显高于发作组治疗后，但明显低于发作组治疗前。哮喘发作组治疗前S-ECP水平变化与B-EOS无相关性，与FEV1、FEV1/FVC呈负相关，与症状评分呈正相关。结论：监测S-ECP水平可作为评价哮喘气道炎症程度、病情预后和指导抗炎治疗的有效指标。     

Characteristics of the Nonselective Cation Current （NSCCs） in Rabbit Left Ventricular Epicardial, Midmyocardial and Endocardial Myocytes

Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventricular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current (INa-Ca) and late INa in M region (deep subepicardial to midmyocardial). Studies from our laboratory have found a new repolarization current-nonselective cation current (NSCCs) existing in rabbit right ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp techniques. The permeability to Na , K , Li , Cs but not to Cl- indicating that it was a nonselective cation current. Gd3 (0.1 mmol/l) and La3 (0.1 mmol/l) can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to -80 mV, INs current density was (-0.44±0.05) PA/PF in endocardial cells, (-0.12±0.05) PA/PF in M cells and (-0.28±0.07) PA/PF in epicardial cells; and with repolarization to 30 mV, INs current density was (1.09±0.29) PA/PF in endocardial cells, (0.38±0.09) PA/PF in M cells and (0.91±0.32) PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias.     

酸性成纤维细胞生长因子的分离纯化及活性鉴定

目的：从牛脑中分离纯化酸性成纤维细胞生长因子（aFGF)并鉴定生物活性，方法：根据DenisGOSPODAROW-ICZ的方法，新鲜牛脑匀浆，三步硫酸铵盐析。最后沉淀物溶解透析后予离子交换层析及琼脂糖胶亲和层析，促3T3细胞DNA合成率鉴定生物活性。结果：用1.0mol/LNaCl的缓冲液洗脱得到分子量为13600的多肽，得率为610μg/kg牛脑，氨基酸组成分析与已知的aFGF相同，促3T3细胞DNA合成的最低浓度为0.5ng/ml，最大效应浓度50ng/ml，ED50值为8ng/ml。结论：aFGF具有强烈的促细胞增殖作用。     

巴戟天枯萎病对寄主显微构造及成分的影响

枯萎病能显著影响巴戟天肉质根的显微构造,并显著影响巴戟天营养器官B,Mn等元素的转运以及根、茎的β-谷甾醇含量,使肉质根总糖含量下降5.42%～15.29%。     

大鼠下丘脑弓状核的形态计量研究

为了探讨急性癫痫弓状核形态改变与可复性，我们采用光、电镜技术和形态计量方法对下丘脑弓状核进行了形态定量研究。结果显示：弓状核切面面积为317500±6460um2，神经元胞体和胞核的等效直径分别为12.94±0.34um和8.54±0.43um，暗细胞内线粒体、粗面内质网、高尔基复合体、溶酶体、游离核相体和分泌颗粒的面积分数分别是5.87±1.98％、3.53±0.25％、0.81±0.49％、2.13±0.42％、10.53±0.46％和0.86±0.35％，其面数密度（单位面积为30um2）分别为15.68±1.14um-2、21.29±3.52um-2、10.20±0.42um-2、5.62±067um-2、101.35±7.55um-2和5.22±0.77um-2.本文还对弓状核的形态结构、神经元类型及其功能进行了讨论。     

定坤丹的显微鉴定研究

对定坤丹(蜜丸)进行了显微鉴定研究,将29种组成药物全部检出,对各组成药物的显微鉴别特征作了简明描述,并附显微特征图。     

Cobalt-dependent potentiation of net inward current density in Helix aspersa neurons.

A low concentration of transition metal ions Co2+ and Ni2+ increases the inward current density in neurons from the land snail Helix aspersa. The currents were measured using a single electrode voltage-clamp/internal perfusion method under conditions in which the external Na+ was replaced by Tris+, the predominant external current carrying cation was Ca2+, and the internal perfusate contained 120 mM Cs+/0 K+; 30 mM tetraethylammonium (TEA) was added externally to block K+ current. In the presence of Co2+ (3 mM) or Ni2+ (0.5 mM) inward Ca2+ currents were stimulated normally by voltage-dependent activation of Ca2+ channels. There was a 5-10% decrease in the rate of rise of the inward current. The principal effect of Co2+ and Ni2+ in increasing the current density seems to be a decrease in the rate at which the inward currents decline during a depolarizing voltage pulse. The results may be due to a decrease in a voltage-dependent or Ca(2+)-dependent outward current and/or an inhibition of Ca2+ channel inactivation. Outward current under these conditions (zero internal K+) was significant and most likely due to Cs+ efflux through the voltage-activated or Ca(2+)-activated nonspecific cation channels. Co2+ is an extremely effective blocker of this outward current. These results are not an artifact of internal perfusion or the special ionic conditions. Intracellular recording of unperfused neurons in normal Helix Ringer's solution showed that the Ca(2+)-dependent action potential duration was increased significantly by low concentrations of Co2+. This result is consistant with the Co(2+)-dependent increase in inward (depolarizing) current seen in voltage-clamp experiments.     

Ultrastuctural studies of the primate lateral geniculate nucleus: Morphology and spatial relationships of axon terminals arising from the retina,visual cortex (area 17), superior colliculus,parabigminal nucleus,and pretectum of Galago crassicaudatus

The electron microscopic autoradiographic tracing method has been used to examine the morphology and postsynaptic relationships of five projections (retina, cortical area 17, superior colliculus (tectal), parabigeminal nucleus, and pretectum) to the dorsal lateral geniculate nucleus of the greater bush baby galago crassicaudatus. Retinal terminals have been examined in the contralaterally innervated layer of each of the three matched pairs [parvi-(X-cell), magno- (Y--cell), and koniocellular (small, W-cell)] of geniculate layers. These terminals are large and contain pale mitochondria and round vesicles (RLPs). RLPs are presynaptic to juxtasomatic regions of parvi-and magnocellular neurons. In contrast, RLPs innervate more distal regions of konicellular neurons. Labeled cortical, tectal, and parabigeminal terminals are relatively small and contain round vesicles na dark mitochondria. Cortical terminals in each of the three representative layers are presynaptic to small diameter dendrites. No convergence of cortical and retinal terminals has been seen in any layer. Labeled tectal and parabigminal terminals are found primarily in the koniocellular layers, but the latter are also seen in all other layers. Tectal and parabigeminal terminals have been observed converging with retinal terminals on dendrites of some koniocellular neurons. Labeled pretectogeniculate terminals contain densely packed pleomorphic vesicles, dark mitochondria, and a dark cytoplasmic matric. These terminals, which are present in each of the representative layers, are presynaptic to conventional dendrites and profiles containing loosely despersed pleomorphic vesicles and a pale cytoplasmic matrix. © 1994 Wiley-Liss, Inc.