Na+ currents near and away from endplates on human fast and slow twitch muscle fibers

Fast and slow twitch muscle fibers have distinct contractile properties. Here we determined that membrane excitability also varies with fiber type. Na⁺ currents (I_NA) were studied with the loose-patch voltage clamp technique on 29 histochemically classified human intercostal skeletal muscle fibers at the endplate border and <200 μm from the endplate (extrajunctional). Fast and slow twitch fibers showed slow inactivation of endplate border and extrajunctional I_NA and had increased I_NA at the endplate border compared to extrajunctional membrane. The voltage dependencies of I_NA were similar on the endplate border and extrajunctional membrane, which suggests thatboth regions have physiclogically similar channels. Fast twitch fibers had larger I_NA on the endplate border and extrajunctional membrane and manifest fast and slow inactivation of I_NA at more negative potentials than slow twitch fibers. For normal muscle, the differences between I_NA on fast and slow twitch fibers might: (1) enable fast twitch fibers to operate at high firing frequencies for brief periods; and (2) enable slow twitch fibers to operate at low firing frequencies for prolonged times. Disorders of skeletal membrane excitability, such as the periodic paralyses and myotonias, may impact fast and slow twitch fibers differently due to the distinctive Na⁺ channel properties of each fiber type. © 1993 John Wiley & Sons, Inc.     

Analgesic profile of the sodium salt of pemedolac

Pemedolac Na, 1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b] indole-1-acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED₅₀ values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall-Selitto model, the ED₅₀ o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ-induced writing in mice with an ED₅₀ of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley-Liss, Inc.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

钠摄入量对心力衰竭大鼠心脏肾素-血管紧张素系统与心钠素的影响

目的　观察钠摄入量对心力衰竭大鼠心脏局部肾素-血管紧张素系统与心钠素的影响 .方法　经动 -静脉分流术造成大鼠充血性心衰模型 ,分为心衰组、心衰限钠组、心衰补钠组 ,假手术大鼠为对照组 ,用放射免疫分析法和原位杂交技术分别测定各组血浆和心肌血管紧张素 、心钠素含量及心肌血管紧张素原 m RNA表达水平 (吸光度 A值 ) ,同时检测心功能 .结果　心衰限钠组心房和心室血管紧张素 含量(2 0 .1± 4 .5 )和 (2 7.3± 5 .9) ng· g- 1、血管紧张素原 m RNA表达 (6 .4± 1.2 )和 (12 .6± 2 .3)显著高于心衰组 (17.5± 3.6 )和 (2 0 .1± 3.7) ng· g- 1 ,(6 .2± 1.9)和 (8.6± 1.7) (P<0 .0 5 ,P<0 .0 1) ,心室心钠素 (42 3± 6 8) ng· g- 1 也显著高于心衰组 (337± 86 ) ng· g- 1 (P<0 .0 5 ) ,心房心钠素 (6 7± 19)μg· g- 1显著低于心衰组 (85± 15 ) μg· g- 1 (P<0 .0 5 ) ;心衰补钠组心房和心室血管紧张素原 m RNA表达水平、心室血管紧张素 和心钠素与心衰组无显著差别 ,心房血管紧张素 与对照组无显著差别 ,心房心钠素 (10 1± 17) μg· g- 1 显著高于心衰组 (P<0 .0 1) .结论　心衰时不同钠摄入量可通过改变心脏局部肾素 -血管紧张素系统与心钠素的平衡状态在心衰发展进程中发挥作用     

Zero-Order Release Formulation of Oxprenolol Hydrochloride with Swelling and Erosion Control

Zero-order release of oxprenolol hydrochloride was obtained by controlling the swelling and erosion of the matrix. This formulation involves only mixing of drug, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC) at the ratio of 1:0.4:1.6, respectively, and compressing the mixture directly into tablets. The in vitro release pattern from this optimized matrix tablet was reproducible. Accelerated stability studies revealed that the optimized formulation remains stable for an approximately 2-year shelf life. This sustained-release (SR) tablet was evaluated in dogs, and for comparison a conventional (CV) formulation was also given at the same dose level. Plasma oxprenolol levels were monitored by a sensitive and specific high-performance liquid chromatographic (HPLC) method. Significant differences in the pharmacokinetic parameters, i.e., lower C _max, higher values of t _max, MRT, AUC, and plasma concentration at 24 hr, and nearly constant plasma levels over 12 hr, indicated that the SR matrix tablet is superior to the CV rapid-releasing formulation. The in vitro release parameters and in vivo pharmacokinetics correlated well.     

Comparative study of renal sodium transport between ouabain-hypertensive rats and ouabain-nonhypertensive rats

Objective: To compare renal sodium transport, using fractional excretions of lithium(FELi) as a marker of proximal tubule sodium reabsorption, between hypertensive and non-hypertensive ouabain-treated rats and further to elucidate the role of ouabain in pathogenesis of hypertension. Methods: Thirty male Sprague-Dawley rats weighting 180-200 g were randomly divided into normal control group and ouabain treated group. Rats were infused with 1 ml/kg·d normal saline or 27. 8μg/kg·d ouabain in-traperitoneally once a day respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Rats were sacrificed 6 weeks after treatment. Blood and 24-hour urine sample were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate(Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated. Ouabain levels of plasma and renal tissue, plasma renin activity, angiotensin I and aldosterone concentration were determined. Results: 65% of the ouabain-treated rats achieved significantly higher SBP after 4 weeks, compared with that of the saline control groups or self baseline (P<0. 01). But in the other 35% of the ouabain-treated rats, their SBP was similar with control group during the experiment (P>0. 05). The body weight, heart rate and food intake between the 3 groups were no significant differences (P> 0. 05). FELi and FDRNa were significantly lower in ouabain-hypertensive group compared with ouabain-non-hypertensive group and control group(P<0. 01 and P<0. 05). The FEu and FDRn, of ouabain-nonhyper-tensive groups were similar with control group(P>0. 05). Ccr and FENa were comparable between the 3 groups (P>0. 05). Plasma and renal tissue ouabain levels, plasma renin activity, angiotensin I and aldosterone contents in ouabain-hypertensive rats were comparable with ouabain-nonhypertensive rats. Conclusion: Increase of proximal tubule sodium reabsorption play an important role in the pathogenesis of ouabain-hypertensive rats. The change of renal sodium transport may result from regulation to renal Na+ , K + -ATPase by ouabain.     

Levocabastine compared with sodium cromoglygate eyedrops in children with both birch and grass pollen allergy

Fifty–five children 6–16 years old with allergic rhinoconjunctivitis due to both birch and grass pollinosis were randomized into 2 parallel groups, treated in double–blind fashion with either levocabastinc (LEV) eye–drops twice daily plus placebo eyedrops twice daily or sodium cromoglycate (SCG) eyedrops 4 times daily for 3 months. Spersallerg® (antazolini chloride + tetryzolini chloride) eyedrops were allowed as rescue medicine. All children received basic treatment with an antihistamine (terfenadine) during the complete trial period, and a local nasal corticosteroid if needed. Eye symptoms were recorded daily by the patients and at 4 visits by the investigator, at start and after 4, 10 and 13 weeks. Pollen counts were performed and a blood sample was collected at start and end of the treatment. The global evaluation of treatment was similar for the 2 groups, and there was no significant difference in any effect parameter except for the symptom, itchy eyes, which had lower score in the SCG group as evaluated by the investigator after 4 weeks. On days with low pollen counts the patients in the SCG group had fewer days with moderate or severe eye symptoms. It is concluded that even though LEV and SCG eyedrops were given in addition to systemic treatment with an antihistamine, no consistently significant differences in clinical effect were found between the 2 treatment groups, but the SCG group experienced slightly less eye symptoms throughout the trial. LEV eye–drops appear safe in long–term treatment in children, and no signs of tachyphylaxis were recorded.     

次氯酸钠和氢氧化钙对牙本质弹性模量和挠曲强度的影响

目的 :评估 5 %次氯酸钠 (NaOCl)溶液和饱和氢氧化钙 [Ca(OH) 2 ]溶液对牙本质弹性模量和挠曲强度的影响 ,以进一步了解根管治疗过程中药物对牙齿机械性能的影响。方法 :取新鲜拔除的完整前磨牙制成标准规格牙本质条 ,经 5 %NaOCl和饱和Ca(OH) 2 溶液处理 ,三点加荷系统测定其弹性模量和挠曲强度。结果 :5 %NaOCl使牙本质弹性模量和挠曲强度显著降低 ;饱和Ca(OH) 2 溶液使牙本质挠曲强度显著降低 ,对弹性模量无显著影响 ;5 %NaOCl处理后再用饱和Ca(OH) 2 溶液处理对牙本质弹性模量和挠曲强度无进一步影响。结论 :5 %NaOCl和饱和Ca(OH) 2 溶液对牙本质的机械性能有一定影响     

Sodium removal and sodium concentration during peritoneal dialysis: effects of three methods of sodium measurement.

BACKGROUND: Sodium removal (NaR) may have a major impact on the survival of peritoneal dialysis patients. The dialysate/plasma sodium concentration ratio (D/P(Na)) is an indirect index of transcellular water transport by aquaporin channels, and thus of ultrafiltration. Sodium concentration can be assessed by means of flame photometry (F), and direct (D-ISE) or indirect ion-selective electrodes (I-ISE), but these methods have different properties. I-ISE is being used increasingly in clinical laboratories. The aim of this study was to evaluate NaR and D/P(Na) using the three different measurement methods. METHODS: We performed peritoneal equilibration tests (PETs) in 44 peritoneal dialysis patients and calculated the NaR. We also calculated D/P(Na) during the test; plasma and dialysate sodium concentrations were measured by F, D-ISE and I-ISE. RESULTS: NaR was lower (P<0.001) with D-ISE (69+/-29 mmol) than with F (81+/-29 mmol) or I-ISE (79+/-28 mmol). D/P(Na) was also lower at baseline (0.92+/-0.02 vs 0.95+/-0.02 and 0.95+/-0.02; P<0.001), after 60 min (0.87+/-0.03 vs 0.90+/-0.03 and 0.90+/-0.03; P<0.001) and at the end of PET (0.88+/-0.04 vs 0.92+/-0.04 and 0.92+/-0.04; P<0.001) when measured by D-ISE in comparison with F and I-ISE, respectively. CONCLUSIONS: NaR and D/P(Na) were lower when measured by the D-ISE method compared with the F and I-ISE methods. NaR and D/P(Na) were similar when measured by F or I-ISE. I-ISE can be used reliably in the evaluation of NaR and D/P(Na) in everyday clinical practice of peritoneal dialysis.