Increased sodium requirement following early postnatal surgical correction of congenital uropathies in infants

Serum electrolyte equilibrium and plasma aldosterone concentrations were monitored in 19 infants who had severe obstructive uropathy or grade 5 vesico-ureteral reflux and were undergoing surgical correction in the first 2 months of life. Before surgery high plasma aldosterone levels were observed in 8 patients, but serum sodium and potassium concentrations were normal. Plasma concentrations of aldosterone were elevated in all patients during the week following surgery and 7 patients developed severe hyponatraemia, hyperkalaemia and weight loss despite very high plasma aldosterone concentrations. As a consequence 5 infants were infused with sodium chloride (4 mEq/kg per day) before and for 36h after surgery; this prevented metabolic imbalance. We conclude that infants undergoing surgical correction of uropathies may require a high sodium intake to maintain electrolyte balance and adequate growth.     

血管瘤不同治疗方法的疗效评价

目的　评价四种不同方法治疗血管瘤远期疗效。方法　取 1992～ 1998年共七年间我院门诊及住院分别患有毛细血管瘤、海绵状血管瘤、蔓状血管瘤病人 2 33例 ,分别采取血管瘤营养血管结扎 平阳霉素注射、5 %鱼肝油酸钠注射、平阳霉素 强的松龙注射、平阳霉素 5 %鱼肝油酸钠注射 4种治疗方法 ,并对上述 4种方法血管瘤注射后进行随访及疗效评定。结果　血管瘤营养血管结扎 平阳霉素注射组总有效率及显效率均较其余 3组高 ,而单纯应用鱼肝油酸钠血管瘤注射组较其余 3组无论是总有效率或显效率均低。结论　联合用药较单一用药治疗血管瘤效果好 ,而血管瘤远期疗效与药物在瘤体内存留时间长短有关 ,停留时间愈长 ,其有效率愈高 ,而缝扎血管瘤营养血管后无疑为药物在血管瘤内长时间停留提供条件。     

Comparison of serum fluoride levels after administration of monofluorophosphate-calcium carbonate or sodium fluoride: differences in peak serum concentrations

Fluoride salts are widely used in Europe in the treatment of established osteoporosis with crush fractures for their ability to increase trabecular bone mass. However, in the United States fluorides are still regarded as an experimental drug. In a prospective, randomized study we compared the fluoride pharmacokinetics of enteric-coated sodium fluoride and disodium monofluorophosphate calcium carbonate (MFP-Ca) over the period of 76 h. Twenty subjects (12 females, 8 males), aged 35–80 years, free of gastrointestinal disorders, renal impairment, and liver disease and without prior fluoride intake entered the study. Ten subjects received NaF (11.3 mg fluoride) twice a day and the other ten MFP-Ca (13.2 mg fluoride) twice a day. During the study period of 76 h the patient's usual food intake was not changed. Serum fluoride levels were determined using an ion sensitive electrode. After intake of a single drug preparation of MFPCa or NaF, MFP-Ca showed a significantly shorter lag time of absorption and a significantly higher maximal serum fluoride concentration than NaF (P<0.01). A comparison of fluoride cumulative characteristics of both drugs showed virtually identical serum fluoride levels before intake of the morning dose on all 4 study days, whereas serum fluoride concentrations measured 4 h afterwards were significantly higher for MFP-Ca than for NaF. These data provide evidence of high peak serum fluoride levels for MFP-Ca, whereas only small peak-to-trough fluctuations are seen for NaF.Abbreviations MFP-Ca disodium monofluorophosphate-calcium carbonate - C _max maximum drug concentration - T _max lag time of maximum drug concentration - AUC area under the serum concentration versus time curve Correspondence to: L. Erlacher     

Characterization of [3H]brevetoxin binding to voltage-dependent sodium channels in adrenal medullary cells

We have previously reported that in bovine adrenal chromaffin cells Ptychodiscus brevis toxin-3 (PbTx-3) does not alter the veratridine-induced ²²Na influx when given alone, but increases the influx of ²²Na when co-applied with either - or -scorpion venom (Wada et al. 1992). In the present study, we characterized [³H]PbTx-3 binding in bovine adrenal chromaffin cells. [³H]PbTx-3 binding was saturable, reversible and of high-affinity with an equilibrium dissociation constant (K_d) of 32.0±4.9 nmol/1 and a maximum binding capacity B_max of 6.2 ± 1.2 pmol/4 × 10⁶ cells (4.5 ± 0.9 pmol/mg cell protein). A Hill plot revealed the lack of cooperative interaction among the binding sites. Unlabelled PbTx-3 inhibited [³H]PbTx-3 binding with an IC₅₀ of 31 nmol/l. However, tetrodotoxin, veratridine, - and -scorpion venom, or veratridine in combination with either - or -scorpion venom did not alter [³H]PbTx-3 binding. All these results suggest that PbTx-3 binds to a site (site 5) distinct from the previously known four toxin binding sites, which does not gate voltage-dependent Na channels by itself, but is specifically involved in the allosteric modulation of Na channels in adrenal medullary cells. Correspondence to: A. Wada at the above address     

Stereoselective effects of mexiletine enantiomers on sodium currents and excitability characteristics of adult skeletal muscle fibers

The effects of the enantiomers of mexiletine were tested on sodium currents of frog skeletal muscle fibers recorded by means of the three vaseline gap voltage clamp method and compared with the effects produced by tocainide enantiomers. The R-( – ) mexiletine produced a tonic block of the sodium current, elicited by single depolarizing test pulses from the holding potential of – 100 mV to – 20 mV, with an IC₅₀ of 43.9 ± 1 M, whereas the corresponding S-( + ) enantiomer produced the same effects at about twofold higher concentrations. A similar stereoselectivity was observed with tocainide enantiomers, but at about 5 fold higher concentrations. Both the R-( – ) and S-( + ) enantiomers of mexiletine and tocainide produced a further use-dependent block of sodium currents when the test pulse was applied repetitively at a frequency of 2 Hz. The use dependent behaviour led to a significant lowering of the IC₅₀ values with respect to the tonic block but the eudismic ratios ([IC₅₀S-( + )]/[IC₅₀R( – )]) and the relative potency between mexiletine and tocainide were maintained. All the tested compounds produced a left shift of the steady state inactivation curves (h) , suggesting a high-affinity interaction with the inactivated sodium channels. Again a stronger potency of R-( – ) vs. S-( + ) enantiomers and of mexiletine vs. tocainide was observed. The excitability characteristics recorded from the semitendinosus muscle by the two microelectrode technique were modified by the tested drugs in agreement with their ability to block sodium current. Thus a concentration-related increase in the threshold current required to elicit an action potential was observed along with a decrease in the amplitude and a shortening of the latency of action potential and a decrease in the firing capability of the membrane. Again the R-( – ) isomers were more potent than the S-( + ) ones and mexiletine was more effective than tocainide. These data corroborate the presence of a stereospecific site for these drugs on adult skeletal muscle sodium channels. The constant eudismic ratios between the enantiomers during both tonic and use-dependent block suggest that the increase in the apparent affinity of the receptor during statedependent conformational changes of the channel does not enhance its stereospecificity. The decrease in effective concentration upon high frequency stimulation supports the potential usefulness of low doses of R-( – ) mexiletine in the treatment of the abnormal hyperexcitability of the myotonic muscles, with a likely reduction of unwanted side effects.     

Electrophysiological effects of dridocainide on isolated canine,guinea-pig and human cardiac tissues

The cellular electrophysiological effects of dridocainide (EGIS-3966), a novel class I antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibres and papillary muscle preparations obtained from humans and guinea-pigs. In each preparation, dridocainide (0.6–2 mol/l) decreased the maximum velocity of action potential upstroke (V_max) in a frequency-dependent manner, although marked differences were observed in its effects in Purkinje fibre and ventricular muscle preparations. In canine Purkinje fibres, action potential duration measured at 50% and 90% of repolarization was decreased, while action potential duration measured at 10% of repolarization was increased by dridocainide. In addition, the plateau of the action potential was depressed by the drug. These changes in action potential configuration were not observed in guinea pig or human papillary muscles. The offset kinetics of the dridocainide-induced V _max block were different in Purkinje fibres and in ventricular muscle: the slow time constant of recovery of V _max was estimated to be 2.5 s in dog Purkinje fibre and 5–6 s in human and guinea-pig papillary muscle. In guinea-pig papillary muscle, the rate of onset of the V _max block was 0.15 and 0.2 per action potential in the presence of 0.6 and 2 mol/l dridocainide, respectively. Dridocainide also decreased the force of contraction in this preparation. On the basis of the present results, dridocainide appears to posess mixed class LC and LA properties, with LC predominance in human and guinea-pig ventricular muscle. Present results also indicate that results of conventional classification of class I drugs may depend on the parameters chosen, as well as on the preparation selected.     

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。     

全血活化凝血时间在局部枸橼酸盐抗凝血透中的应用

目的：开展局部枸橼酸抗凝血液透析,监控枸橼酸盐的输注量;方法：采用全血活化凝血时间（ＡＣＴ）监测患者的凝血状态;结果：基础ＡＣＴ值为１１０．５±１０．０９ｓ;透析结束时动脉端ＡＣＴ值为１１５．３±１１．６１ｓ,与基础值相比无明显差异（Ｐ＞０．０５）;透析结束时静脉端ＡＣＴ值为１４６．６±３０．３５ｓ,与基础值相比有显著差异（Ｐ＜０．０５）,枸橼酸钠输注速度为３０～４０ｍｌ／ｈ;结论：静脉端ＡＣＴ值较基础值延长３０％,枸橼酸盐能在体外循环达到有效抗凝效果,不会引起出血并发症     

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.