托伐普坦治疗顽固性心力衰竭中严重利尿剂抵抗疗效观察

目的：观察托伐普坦治疗顽固性心力衰竭中严重利尿剂抵抗的疗效。方法对经大剂量利尿剂（速尿大于200mg/d）治疗效果不佳,且不伴有严重低钠血症的顽固性心力衰竭患者3例给予托伐普坦15mg/d治疗,观察治疗后体重、尿量、血肌酐、肝功能、电解质的变化。结果治疗1d后体重平均减轻3.16kg;尿量平均增加5540ml;治疗3~5d后血肌酐指标2例降至正常,另外1例较前有轻度改善;肝功能、电解质无明显变化。结论托伐普坦能有效治疗严重利尿剂抵抗,有助于心肾功能改善,疗效较好,无明显不良反应发生。     

The antinociceptive activity of Polygonatumverticillatum rhizomes in pain models

Aim of the study

The current study was designed to establish the pharmacological rationale for the traditional use of the rhizomes of Polygonatum verticillatum in the treatment of painful conditions and as a plant diuretic.

Materials and methods

The crude methanolic extract of the rhizomes of Polygonatumverticillatum (PR) was tested in various established pain models in rodents at 50, 100 and 200 mg/kg i.p. while the diuretic activity was assessed at 300 and 600 mg/kg p.o. in rats.

Results

PR demonstrated significant reduction (14–72%) in the number of writhes induced by acetic acid in a dose-dependent manner. When nociceptive threshold was measured in the formalin test, PR strongly attenuated the formalin-induced flinching behaviour in both phases (6–30% in first phase while 12–72% in second phase). Central involvement in the analgesic profile of PR was confirmed by the hot plate test, in which PR elicited a significant (P < 0.01) analgesic activity by increasing latency time. However, an opioid receptor antagonist, naloxone (2 mg/kg s.c.) strongly antagonized the antinociceptive activity of PR. As a plant diuretic, PR showed mild but statistically insignificant diuretic activity at 300 mg/kg. The crude extract and solvent fractions of the plant contained reasonable quantity of total saponin and alkaloid contents.

Conclusions

The mechanisms underlying the analgesic action of PR shows that the opioid dependant central mediation has synergistic effect by enforcing the peripheral analgesic effects. Interestingly, our findings not only substantiated the folk use of the plant as an analgesic but also reported for the first time in the whole genus.     

Evaluation of the diuretic and analgesic activities of the rhizomes of Rumex abyssinicus Jacq in mice

Aim of the study

Rumex abyssinicus Jacq (Polygonaceae) has been used traditionally for treatment of hypertension, inflammatory and painful conditions in Ethiopia. The present study aimed to evaluate the diuretic and analgesic activities of extracts of Rumex abyssinicus at different doses in mice.

Materials and methods

The effect on urine volume and urinary electrolyte (Na⁺, K⁺ and Cl⁻) was assessed for a period of 5 h following oral administration of aqueous (500 mg/kg, 750 mg/kg or 1000 mg/kg) or 80% methanolic (250 mg/kg, 500 mg/kg or 750 mg/kg) extract or furosemide (10 mg/kg). Acetic acid-induced writhing and hot-plate tests were employed to study the analgesic effect of 80% methanolic extracts (250 mg/kg, 500 mg/kg or 1000 mg/kg, P.O.) and compared with that of aspirin (100 mg/kg, P.O.) or morphine (10 mg/kg, sc).

Results

The extracts displayed dose-dependent diuretic and analgesic effects. The highest doses of both extracts markedly and significantly increased (P < 0.001) urine volume and urinary electrolytes, qualitatively similar to that of furosemide. 1000 mg/kg of the extract reduced the number of writhing by 67.6% (P < 0.001) and conferred more than 70% protection against thermally induced pain stimuli after 45 min of treatment comparable to that of aspirin and morphine, respectively.

Conclusion

These findings collectively indicate that the extracts exhibited significant diuretic and analgesic activities, providing evidence, at least in part, for its folkloric use.     

利尿合剂联合生脉注射液治疗慢性心力衰竭合并低钠血症56例

目的观察利尿合剂联合生脉注射液治疗慢性心力衰竭合并低钠血症的临床疗效。方法将慢性心力衰竭合并低钠血症112例随机分为2组,对照组56例予常规西医治疗,治疗组56例在对照组基础上予羟乙基淀粉20氯化钠注射液、多巴酚丁胺注射液、门冬氨酸钾镁注射液、呋塞米注射液缓慢静脉滴注,同时予生脉注射液静脉滴注,2组均以5d为1个疗程。观察治疗前后6min步行距离(6MWT)、左室射血分数(LVEF)、B型尿钠肽(BNP)、24h尿量及血清电解质指标。结果 2组治疗后6MWT、LVEF、24h尿量、BNP及血清电解质浓度与本组治疗前比较差异均有统计学意义(P0.05),2组治疗后6MWT、LVEF、24h尿量、血清电解质浓度组间比较差异有统计学意义(P0.05),治疗组优于对照组。结论利尿合剂联合生脉注射液治疗慢性心力衰竭合并低钠血症疗效确切。     

The pharmacological activities of Compound Salvia Plebeia Granules on treating urinary tract infection

Aim of the study

Compound Salvia Plebeia Granules (CSPG) had been used for treating urinary tract infection (UTI) for more than 20 years in Drum Tower hospital, but there were lack of sufficient pharmacology studies. The aim of this study was to testify the effects of CSPG on UTI, namely to prove its diuretic, antiblastic, antipyretic and antidynous activities.

Materials and methods

This study evaluated the diuretic effect of CSPG on water load Sprague–Dawley (SD) male rats by the method of metabolic cage, and then analysed the contents of Na⁺, K⁺, and Cl⁻ in urine. The antiblastic activity of CSPG was testified by various kinds of strains in vitro. The antipyretic effect was evaluated by carrageenan-induced fever model in mice. Antidynous activity was demonstrated by the method of acetic acid-induced writhing.

Results

Intragastric (i.g.) administration of CSPG (20–40 g/kg) (equivalent to crude herb) produced a dose-related diuretic effect on water load mice and promoted excreting of Na⁺, K⁺, and Cl⁻ in urine. In addition, the minimal inhibitory concentrations (MICs) of CSPG on Escherichia coli and Staphylococcus aureus were separately 0.25 g/ml and 0.5 g/ml. Moreover, i.g. the doses of CSPG ranging from 25.2 to 50.4 g/kg showed significantly antipyretic effect on carrageenan-induced fever in mice. CSPG (12.6–50.4 g/kg) can also produce dose-related antidynous effects on acetic acid-induced writhing in mice.

Conclusions

The results described the integrity report of pharmacological studies of CSPG and indicated that it had significantly diuretic, antiblastic, antipyretic, anti-inflammatory and antidynous activities which support its folk medicine use on UTI.     

The blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure

Aims

Diuretic response in heart failure is blunted when compared to healthy individuals, but the pathophysiology underlying this phenomenon is unclear. We aimed to investigate whether the diuretic resistance mechanism is related to insufficient furosemide tubular delivery or low tubular responsiveness.

Methods and results

We conducted a prospective, observational study of 50 patients with acute heart failure patients divided into two groups based on previous furosemide use (furosemide naïve: n = 28 [56%] and chronic furosemide users: n = 22 [44%]). Each patient received a protocol-derived, standardized furosemide dose based on body weight. We measured diuretic response and urine furosemide concentrations. The furosemide naïve group had significantly higher urine volumes and natriuresis when compared to chronic users at all timepoints (all p < 0.05). Urine furosemide delivery was similar in furosemide naïve versus chronic users after accounting for differences in estimated glomerular filtration rate (28.02 [21.03–35.89] vs. 29.70 [18.19–34.71] mg, p = 0.87). However, the tubular response to delivered diuretic was dramatically higher in naïve versus chronic users, that is the urine volume per 1 μg/ml of urine furosemide at 2 h was 148.6 ± 136.1 versus 50.6 ± 56.1 ml (p = 0.005).

Conclusions

Patients naïve to furosemide have significantly better diuresis and natriuresis when compared to chronic furosemide users. The blunted diuretic response in patients with chronic loop diuretic exposure is driven by decreased tubular responsiveness rather than insufficient furosemide tubular delivery.     

络风宁2号方对慢性心力衰竭利尿剂抵抗患者的临床研究

目的：观察络风宁2号方对慢性心力衰竭利尿剂抵抗患者的心功能及尿液水通道蛋白2（AQP2）表达的影响。方法：选取2019年1月至2021年1月北京中医医院顺义医院收治的慢性心力衰竭合并利尿剂抵抗患者70例作为研究对象，按照随机数字表法分为对照组和观察组，每组35例。将24 h尿量、血浆氨基末端脑钠肽前体（NT-proBNP）、尿液水通道蛋白2（AQP2）水平以及心力衰竭患者的疗效评价标准作为评价指标，分别于治疗前、治疗2周后进行评估。结果：治疗前2组患者24 h尿量、血浆NT-proBNP、尿液AQP2水平比较，差异无统计学意义（P>0.05）。治疗2周后，与治疗前比较,2组患者24 h尿量、血浆NT-proBNP、尿液AQP2水平均有所改善，差异有统计学意义（P<0.01或P<0.05）；治疗后观察组24 h尿量明显高于对照组（P<0.05），NT-proBNP水平、尿液AQP2水平均较对照组下降（P<0.05）。2组总有效率比较，差异无统计学意义（P>0.05），但体现出观察组较优的趋势。结论：络风宁2号方能够增加慢性心力衰竭患者的尿量、减轻水钠潴留状态、改善利尿剂抵抗情况，改善心功能；同时本研究也表明联合监测血浆NT-proBNP及尿液AQP2水平，可作为慢性心力衰竭患者水液失衡的新靶点。