不同诱饵配制成的敌鼠钠盐毒饵杀灭旅客列车拒食残存鼠效果观察

本文报告了0.1％敌鼠钠盐配制成的不同毒饵在旅客列车上对急性灭鼠毒饵拒食残存鼠的杀灭试验效果。采用间隔投饵饱和投药法,投毒14天便有效地杀灭了旅客列车上对急性灭鼠毒饵拒食残存鼠,粉迹法考核灭效达100％。敌鼠钠盐配制的毒饵适口性好,灭效高,现阶段列车灭鼠中,仍有较好的应用价值。     

Ionic mechanism of 4-aminopyridine action on leech neuropile glial cells

Extracellular 4-aminopyridine (4-AP), tetraethylammonium chloride (TEA) and quinine depolarized the neuropile glial cell membrane and decreased its input resistance. As 4-AP induced the most pronounced effects, we focused on the action of 4-AP and clarified the ionic mechanisms involved. 4-AP did not only block glial K+ channels, but also induced Na+ and Ca2+ influx via other than voltage-gated channels. The reversal potential of the 4-AP-induced current was -5 mV. Application of 5 mM Ni2+ or 0.1 mM d-tubocurarine reduced the 4-AP-induced depolarization and the associated decrease in input resistance. We therefore suggest that 4-AP mediates neuronal acetylcholine release, apparently by a presynaptic mechanism. Activation of glial nicotinic acetylcholine receptors contributes to the depolarization, the decrease in input resistance, and the 4-AP-induced inward current. Furthermore, the 4-AP-induced depolarization activates additional voltage-sensitive K+ and Cl- channels and 4-AP-induced Ca2+ influx could activate Ca2+-sensitive K+ and Cl- channels. Together these effects compensate and even exceed the 4-AP-mediated reduction in K+ conductance. Therefore, the 4-AP-induced depolarization was paralleled by a decreasing input resistance.     

Focal cerebral ischaemia induces a decrease in activity and a shift in ouabain affinity of Na+, K+-ATPase isoforms without modifications in mRNA and protein expression

In a mouse model of focal cerebral ischaemia, we observed after 1 h of ischaemia, that the total Na+, K+-ATPase activity was decreased by 39.4%, and then did not vary significantly up to 6 h post-occlusion. In the sham group, the dose-response curves for ouabain disclosed three inhibitory sites of low (LA), high (HA) and very high (VHA) affinity. In ischaemic animals, we detected the presence of only two inhibitory sites for ouabain. After 1 h of permanent occlusion, the first site exhibited a low affinity while the second site presented an affinity intermediate between those of HA and VHA sites, which evolved after 3 h and 6 h of occlusion towards that of the VHA site. The presence of only two ouabain sites for Na+, K+-ATPase after ischaemia could result from a change in ouabain affinity of both HA and VHA sites (alpha2 and alpha3 isoforms, respectively) to form a unique component. Irrespective of the duration of ischaemia, the smaller activity of this second site accounted entirely for the loss in total activity. Surprisingly, no modifications in protein and mRNA expression of any alpha or beta isoforms of the enzyme were observed, thus suggesting that ischaemia could induce intrinsic modifications of the Na+, K+-ATPase.     

Aprindine blocks the sodium current in guinea-pig ventricular myocytes

Summary Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na⁺ current using whole cell voltage clamp (tip resistance = 0.5 , [Na]_i and_o = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kd_rest = 37.7 µmol/l, Kd_i = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na⁺ current by 3 mmol/l tosylchloramide sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = –100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4).The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na⁺ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule. Send offprint requests to: R. Sato at the above address     

Effects of sodium and temperature on tension in isolated canine coronary artery

The effects of sodium and temperature on tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the strength of tension was inversely related to the Na concentration. At 37°C, the tension was significantly increased at 70mEq·l ^–1 Na and below. The tension was gradually suppressed by lowering of the temperature from 37°C to 10°C. At 10°C, tension did not developed significantly at Na concentrations between 127mEq·l ^–1 and 12mEq·l ^–1.It was concluded that the decrease in Na concentrations increased the tension of the canine coronary artery and the lowering of temperature supressed the tension inducted by the decrease in Na concentrations.(Yoshida K, Fujii Y, Ina H, et al.: Effects of sodium and temperature on tension in isolated canine coronary artery. J Anesth 5: 56–59, 1991)     

Comparative cardiovascular effects of SNP,ATP and phentolamine during norepinephrine-induced hypertension in dogs

There has been no study comparing the advantage and disadvantage of various antihypertensive agents during surgery for pheochromocytomas because the study is difficult in clinical setting. In the present experiments using dogs, after increasing the arterial blood pressure with norepinephrine, we decreased it to the baseline with sodium nitroprusside (SNP), adenosine triphosphate (ATP), or phentolamine (PE) and compared the hemodynamic changes. A hyperdynamic state was found with ATP and with PE, but not with SNP. The norepinephrine-induced pulmonary hypertension could be successfully treated with SNP, but not with ATP or PE. The reason for these differences are thought to be the different vasodilative properties on peripheral arteries and veins. We conclude that agents that dilates the arteries and veins should be used to regulate the arterial pressure during surgical removal of a pheochromocytoma.(Murata K, Takahashi H, Ikeda K: Comparative cardiovascular effects of SNP, ATP and phentolamine during norepinephrine-induced hypertension in dogs. J Anesth 5: 396–403, 1991)     

The effect of sodium thiosulfate on ototoxicity and pharmacokinetics after cisplatin treatment in guinea pigs

The effect of sodium thiosulfate (STS) on the pharmacokinetics and ototoxicity of cisplatin (CDDP) was investigated in guinea pigs. Animals received three intramuscular injections of 7.5 mg/kg CDDP separated by intervals of 5 days with or without STS (1,000 mg/kg) administered intraperitoneally immediately and 1 h after each injection of CDDP or 3 and 6 h later. When administered alone, CDDP caused total outer hair cell (OHC) loss in the basal and second turns of the cochlea. In the group administered CDDP and STS, damage to the OHCs was mild when STS was given concurrently, but was severe when STS was given 3 and 6 h later. Pharmacokinetics measured as free and total platinum (Pt) concentrations in plasma and total Pt concentration in perilymph was not affected after administration of STS with CDDP. These results suggest that an inactive Pt-thiosulfate complex is formed in plasma and is measured as a free Pt component which enters the perilymph via the blood-cochlear barrier. Two possible mechanisms are proposed by which STS reduces ototoxicity: entry of CDDP into target cells such as OHCs and striai marginal cells or binding to intracellular macromolecules of these cells is prevented.     

Effect of a neuronal sodium channel blocker on magnetic resonance derived indices of brain water content during global cerebral ischemia

Diffusion-weighted magnetic resonance imaging (DWI) with calculation of the apparent diffusion coefficient (ADC) of water is a widely used noninvasive method to measure movement of water from the extracellular to the intracellular compartment during cerebral ischemia. Lamotrigine, a neuronal Na(+) channel blocker, has been shown to attenuate the increase in extracellular concentrations of excitatory amino acids (EAA) during ischemia and to improve neurological and histological outcome. Because of its proven ability to reduce EAA levels during ischemia, lamotrigine should also minimize excitotoxic-induced increases in intracellular water content and therefore attenuate changes in the ADC. In this study, we sought to determine the effect of lamotrigine on intra- and extracellular water shifts during transient global cerebral ischemia. Fifteen New Zealand white rabbits were anesthetized and randomized to one of three groups: a control group, a lamotrigine-treated group, or a sham group. After being positioned in the bore of the magnet, a 12-min 50-s period of global cerebral ischemia was induced by inflating a neck tourniquet. During ischemia and early reperfusion there was a similar and significant decrease of the ADC in both the lamotrigine and control group. The ADC in the sham ischemia group remained at baseline throughout the experiment. Lamotrigine-mediated blockade of voltage-gated sodium channels did not prevent the intracellular movement of water during 12 min 50 s of global ischemia, as measured by the ADC, suggesting that the ADC decline may not be mediated by voltage-gated sodium influx and glutamate release.     

A possible role for nerve growth factor in the augmentation of sodium channels in models of chronic pain

Inflammation induces an upregulation of sodium channels in sensory neurons. This most likely occurs as a result of the retrograde transport of cytochemical mediators released during the inflammatory response. The purpose of this study was to determine the effect of the subcutaneous administration of one such mediator, nerve growth factor (NGF), on the production of sodium channels in neurons of the rat dorsal root ganglion. For this, hindpaw withdrawal from either a thermal or mechanical stimulus was measured in rats at selected intervals for up to 2 weeks following injections of NGF. Sodium channel augmentation was then examined in dorsal root ganglia using site-specific, anti-sodium channel antibodies. Both thermal and mechanical allodynia was observed between 3 and 12 h post-injection. The hyperalgesic response returned to baseline by approximately 24 h post-injection. Sodium channel labeling was found to increase dramatically in the small neurons of the associated dorsal root ganglia beginning at 23 h, reached maximum intensity by 1 week, and persisted for up to 3 months post-injection. Pre-blocking NGF with anti-NGF prevented the NGF-induced decrease in paw withdrawal latencies and significantly reduced the intensity of sodium channel labeling. The results indicate that NGF is an important mediator both in the development of acute hyperalgesia and in the stimulation of sodium channel production in dorsal root ganglia during inflammation.     

Directed sampling for electrolyte analysis and water content of micro-punch samples shows large differences between normal and ischemic rat brain cortex

Changes in sodium, potassium, and water content in brain tissue are important in the progression of pathology that follows ischemic stroke. Determining these parameters regionally in rodent models of experimental ischemia has been limited because typical tissue weights of more than 35 mg are too large. Identifying ischemic tissue to direct tissue sampling towards ischemic cortex is also represents a difficult generally unresolved area. We suggest that larger differences between normal and ischemic cortex of sodium, potassium, and water content than previously observed can be obtained from directed sampling of 2-mg brain tissue in a model of focal cerebral ischemia. In five rats, the middle cerebral artery and both common carotid arteries were occluded for 4.9+/-0.13 h (mean+/-SEM). Punch-sampling of 1-mm diameter tissue cores for water content (H(2)O%) by the wet-dry method, and [Na(+)] and [K(+)] by flame photometry, was guided by the observation of a subtle change in the surface reflectivity of ischemic cortex of quickly dried, 20-microm frozen brain sections, that was confirmed by MAP2 immunohistochemistry. The ratio of the lesion areas as determined by the reflective change and MAP2 immunoreactivity was 0.96+/-0.03 (n=5). In ischemic cortex H(2)O% was 79.9%+/-0.8%, [Na(+)] was 550+/-25 mEq/kg dry-weight, and [K(+)] 94.2+/-19.2 mEq/kg dry-weight (n=5), all significantly different from the values in border zone cortex, and in cortex contralateral to ischemic cortex and border zone (for all samples n=60, mean wet weight 2.037+/-0.046 mg). Differences between ischemic and normal cortex were 5.4+/-1.1%, 317+/-21 mEq/kg dry-weight, -304+/-27 mEq/kg dry-weight (n=5) for H(2)O%, [Na(+)], and [K(+)]. These differences between ischemic and normal cortex are 1.4-2.5, 1-3.11, and 1.4-3.5 times greater, respectively, than previous results obtained using samples weighing 35 mg or more. These results extend the association of sodium and potassium with ischemic brain edema in the rodent model, and show that these classical measurements can keep pace with the regionality of histochemical and morphological methods.