Urea transporters （UT）, including isoforms of UT-A endothelia and erythrocytes, play an important role in the urine in kidney tubule epithelia and UT-B in vasa recta concentration mechanism by mediated an intrarenal...Urea transporters （UT）, including isoforms of UT-A endothelia and erythrocytes, play an important role in the urine in kidney tubule epithelia and UT-B in vasa recta concentration mechanism by mediated an intrarenalurea recycling, suggesting that functional inhibition of these proteins could have therapeutic use as diuretic. By in- tegrated cell based high throughput screening and in silico methods, a class of small-molecule drug-like compounds with thienoquinolin core structure was found to have inhibition activity on both UT-A and UT-B. The structure and activity relationship analysis showed a compound PU-48, named chemically as methyl 3-amino-6-methoxythieno[ 2, 3-b] quinoline-2-carboxylate, had the best UT-A and UT-B inhibition activity. IC50s of PU-48 on UT-B facilitated as determined by erythrocyte lysis assay. In vivo urea transport were micromole level in human, rat, and mouse, activity of PU-48 on urinary concentrating function was evaluated in rats fed ad libitum in metabolic cages. Urine output significantly increased in a dose-dependent manner in rats subcutaneously administered PU-48. Urinary os- molality and urea concentration were significantly decreased. The peak changes of urine output, urinary osmolality and urinary urea concentration occurred between 2 and 4 h after PU/18 administration, with values returning to was subcutaneously injected every 6 h the 24 h urine output in baseline by 10 h. When PU-48 at 50 mg · kg^-1 PU-48 treated rats was significantly higher than that in vehicle control rats. Urinary osmolality and urea concentra- tion in PU-48 treated rats were significantly lower than in vehicle control rats. The excretion of Na ＋ , K ＋ , C1- was PU-48 treated rats had significantly higher urea excre- similar in PU-48 treated and vehicle control rats. However, tion than vehicle control rats. The data suggest that PU-48 caused a urea-selective diuresis without disturbing elec- TGs, and LDL-C in PU-48-treated rats were similar with those trolyte metabolism. Notably, blood urea, T-CHO, in vehicle control rats, which are normal levels. These data indicate that the diuretic effect of PU-14 does not cause electrolyte imbalance and abnormal metabolism. It is predicated that UT inhibitors have potential clinical applica- tions as sodium-sparing diuretics in edema from different etiologies, such as congestive heart failure and cirrhosis.展开更多
Objective:To detect the inhibition of urogenital chlamydia trachomatis (CT) by 12 traditional Chinese medicines in vitro. Methods: The inhibition of CT isolates by these medicines was detected by micro-culture techniq...Objective:To detect the inhibition of urogenital chlamydia trachomatis (CT) by 12 traditional Chinese medicines in vitro. Methods: The inhibition of CT isolates by these medicines was detected by micro-culture technique with McCoy cells in vitro. Results: All the diuretic traditional Chinese medicines inhibited urogenital CT. The minimum inhibitory concentrations (MICs) ranged from 0.122 mg ml^-1 to 62.5mg ml^-1. Diathus superbus L., Poria cocos (Shcw.) Woft, Polyporus umbellatus (Pers.) Fries, and Artemisia capillaries Thunb showed stronger inhibition than the other eight traditional Chinese medicines. The numbers and sizes of inclusions bodies reduced gradually and disappeared finally with the increase of the concentrations. Conclusion: All the 12 diuretic traditional Chinese medicines inhibited urogenital CT.展开更多
Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination ther...Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.展开更多
目的比较缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性的治疗作用。方法 80例老年高血压患者随机分为2组,分别给予缬沙坦联合氨氯地平(氨氯地平组)或缬沙坦联合氢氯噻嗪(氢氯噻嗪组)降压治疗,监测2组24 h动态血压,观察治疗...目的比较缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性的治疗作用。方法 80例老年高血压患者随机分为2组,分别给予缬沙坦联合氨氯地平(氨氯地平组)或缬沙坦联合氢氯噻嗪(氢氯噻嗪组)降压治疗,监测2组24 h动态血压,观察治疗前、治疗第6周和第12周,2组血压及血压变异性的变化。同时观察2组6周末血压达标率。记录治疗过程中的不良反应情况。结果 2组治疗6周和12周的24 h平均收缩压(SBP)、白昼SBP、夜间SBP、晨峰SBP、24 h收缩压变异性(SBPV)均较治疗前降低(P<0.05)。24 h SBP、白昼SBP、夜间SBP、24 h SBPV及白昼SBPV分组因素与时间因素存在交互作用(P<0.05)。治疗第6周和第12周,氨氯地平组24 h SBP、白昼SBP、夜间SBP及白昼SBPV较氢氯噻嗪组降低(P<0.05),治疗第12周,氨氯地平组24 h SBPV低于氢氯噻嗪组(P<0.01)。2组血压达标率和不良反应发生率差异均无统计学意义。结论缬沙坦联合氨氯地平或氢氯噻嗪均能有效控制老年高血压患者血压变异性,而缬沙坦联合氨氯地平在降低血压和血压变异性方面作用更强。展开更多
文摘Urea transporters （UT）, including isoforms of UT-A endothelia and erythrocytes, play an important role in the urine in kidney tubule epithelia and UT-B in vasa recta concentration mechanism by mediated an intrarenalurea recycling, suggesting that functional inhibition of these proteins could have therapeutic use as diuretic. By in- tegrated cell based high throughput screening and in silico methods, a class of small-molecule drug-like compounds with thienoquinolin core structure was found to have inhibition activity on both UT-A and UT-B. The structure and activity relationship analysis showed a compound PU-48, named chemically as methyl 3-amino-6-methoxythieno[ 2, 3-b] quinoline-2-carboxylate, had the best UT-A and UT-B inhibition activity. IC50s of PU-48 on UT-B facilitated as determined by erythrocyte lysis assay. In vivo urea transport were micromole level in human, rat, and mouse, activity of PU-48 on urinary concentrating function was evaluated in rats fed ad libitum in metabolic cages. Urine output significantly increased in a dose-dependent manner in rats subcutaneously administered PU-48. Urinary os- molality and urea concentration were significantly decreased. The peak changes of urine output, urinary osmolality and urinary urea concentration occurred between 2 and 4 h after PU/18 administration, with values returning to was subcutaneously injected every 6 h the 24 h urine output in baseline by 10 h. When PU-48 at 50 mg · kg^-1 PU-48 treated rats was significantly higher than that in vehicle control rats. Urinary osmolality and urea concentra- tion in PU-48 treated rats were significantly lower than in vehicle control rats. The excretion of Na ＋ , K ＋ , C1- was PU-48 treated rats had significantly higher urea excre- similar in PU-48 treated and vehicle control rats. However, tion than vehicle control rats. The data suggest that PU-48 caused a urea-selective diuresis without disturbing elec- TGs, and LDL-C in PU-48-treated rats were similar with those trolyte metabolism. Notably, blood urea, T-CHO, in vehicle control rats, which are normal levels. These data indicate that the diuretic effect of PU-14 does not cause electrolyte imbalance and abnormal metabolism. It is predicated that UT inhibitors have potential clinical applica- tions as sodium-sparing diuretics in edema from different etiologies, such as congestive heart failure and cirrhosis.
文摘Objective:To detect the inhibition of urogenital chlamydia trachomatis (CT) by 12 traditional Chinese medicines in vitro. Methods: The inhibition of CT isolates by these medicines was detected by micro-culture technique with McCoy cells in vitro. Results: All the diuretic traditional Chinese medicines inhibited urogenital CT. The minimum inhibitory concentrations (MICs) ranged from 0.122 mg ml^-1 to 62.5mg ml^-1. Diathus superbus L., Poria cocos (Shcw.) Woft, Polyporus umbellatus (Pers.) Fries, and Artemisia capillaries Thunb showed stronger inhibition than the other eight traditional Chinese medicines. The numbers and sizes of inclusions bodies reduced gradually and disappeared finally with the increase of the concentrations. Conclusion: All the 12 diuretic traditional Chinese medicines inhibited urogenital CT.
基金supported by a grant from the Chinese Ministry of Sciences and Technology (2016YFC1300100)
文摘Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.
文摘目的比较缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性的治疗作用。方法 80例老年高血压患者随机分为2组,分别给予缬沙坦联合氨氯地平(氨氯地平组)或缬沙坦联合氢氯噻嗪(氢氯噻嗪组)降压治疗,监测2组24 h动态血压,观察治疗前、治疗第6周和第12周,2组血压及血压变异性的变化。同时观察2组6周末血压达标率。记录治疗过程中的不良反应情况。结果 2组治疗6周和12周的24 h平均收缩压(SBP)、白昼SBP、夜间SBP、晨峰SBP、24 h收缩压变异性(SBPV)均较治疗前降低(P<0.05)。24 h SBP、白昼SBP、夜间SBP、24 h SBPV及白昼SBPV分组因素与时间因素存在交互作用(P<0.05)。治疗第6周和第12周,氨氯地平组24 h SBP、白昼SBP、夜间SBP及白昼SBPV较氢氯噻嗪组降低(P<0.05),治疗第12周,氨氯地平组24 h SBPV低于氢氯噻嗪组(P<0.01)。2组血压达标率和不良反应发生率差异均无统计学意义。结论缬沙坦联合氨氯地平或氢氯噻嗪均能有效控制老年高血压患者血压变异性,而缬沙坦联合氨氯地平在降低血压和血压变异性方面作用更强。
