The Effectiveness of Albumin Combined with Diuretics in Treating Ascites in Cirrhosis

Cirrhosis often leads to various complications during its progression,with ascites being one of the most common.Among these cases,5%to 10%are classified as refractory ascites.In recent years,clinical research on the treatment of cirrhotic ascites has yielded increasingly enriched results.In this paper,a large number of clinical data on the treatment of ascites using albumin combined with diuretics were collected,and it was found that there were more results in group control studies.It was believed that albumin combined with diuretic therapy could effectively improve symptoms,reduce the occurrence of adverse reactions,ensure the safety of patients,and have a good clinical application prospect.This paper reviews the efficacy of albumin combined with diuretics in the treatment of ascites in cirrhosis.

Effects of Different Diuretics on Water Drinking Amount, Urination Volume and Related Blood Indices of Sheep Fed with Cottonseed

[Objective] This study aimed to investigate the effects of three kinds of diuretics on the water drinking amount and urination volume of sheep fed with cottonseed hulls. [Method] The method of self-control was adopted. Five two-year-old male Kazak sheep about 40 kg which never had intake of the feeds containing gossypol were selected. The experiment was divided into five periods, namely the control period, a period with the supplement of 300 mg/d of hydrochlorothiazide, a period with the supplement of 200 mg/d of hydrochlorothiazide, a period with the supplement of 350 mg of GY-01 and a period with the supplement of 200 mg of GY-01. The sheep were fed with the concentrate and the cottonseed hulls in the control period, and corresponding diuretics were supplemented in the rest four periods. The water drinking amount, urination volume and the contents of the hormone and ion in the blood were determined in each period. [Result] After 350 mg GY-01 was supplemented, the water drinking amount of each sheep had an increase of 60.14% compared with that of the sheep in the control period and the urination volume was 2.67 times of that of the latter, and the differences were both significant （P0.01）. The antidiuretic hormone declined by 32.59% compared with that of the sheep in the control period, with the significant difference （P 0.05）. The adrenocorticotropic hormone content increased by 81.93% compared with that of the sheep in the control period and the difference was significant （P0.01）. An increase of 28.04% （P 0.05） and 39.39% （P 0.01） was found in the contents of serum potassium and phosphorus respectively compared with that of sheep in the control period. [Conclusion] The diet with supplement of GY-01 can increase the urination volume of livestock fed with the cottonseed hulls, and the most appropriate supplement amount is 200 mg GY-01.

Ototoxic effects and mechanisms of loop diuretics

Over the past two decades considerable progress has been made in understanding the ototoxic effects and mechanisms underlying loop diuretics. As typical representative of loop diuretics ethacrynic acid or furosemide only induces temporary hearing loss, but rarely permanent deafness unless applied in severe acute or chronic renal failure or with other ototoxic drugs. Loop diuretic induce unique pathological changes in the cochlea such as formation of edematous spaces in the epithelium of the stria vascularis, which leads to rapid decrease of the endolymphatic potential and eventual loss of the cochlear microphonic potential, summating potential, and compound action potential. Loop diuretics interfere with strial adenylate cyclase and Nat/Kt-ATPase and inhibit the Na-K-2Cl cotransporter in the stria vascularis, however recent reports indicate that one of the earliest effects in vivo is to abolish blood flow in the vessels supplying the lateral wall. Since ethacrynic acid does not damage the stria vascularis in vitro, the changes in Nat/Kt-ATPase and Na-K-2Cl seen in vivo may be secondary effects results from strial ischemia and anoxia. Recent observations showing that renin is present in pericytes surrounding stria arterioles suggest that diuretics may induce local vasoconstriction by renin secretion and angiotensin formation. The tight junctions in the blood-cochlea barrier prevent toxic molecules and pathogens from entering cochlea, but when diuretics induce a transient ischemia, the barrier is temporarily disrupted allowing the entry of toxic chemicals or pathogens.

Diuretic and antioxidant activities of the aqueous extract of leaves of Cassia occidentalis(Linn.) in rats

Objective: To assess the putative diuretic and antioxidant properties of Cassia occidentalis(C. occidentalis) leaves' aqueous extract. Methods: Adult rats were administered with C. occidentalis leaves aqueous extract acutely(24-h) and subchronically(7 d), at doses 80, 160, 240, 320, and 400 mg/kg(per os). Negative control group received only an equivalent volume of distilled water, while the two positive control groups received the diuretic drugs furosemide(20 mg/kg, i.p.) and hydrochlorothiazide(HCTZ, 20 mg/kg, i.p.). Urinary elimination of electrolytes in response to treatments was evaluated, together with changes in concentrations of creatinine, urea, aldosterone, glucose, and albumin in urine and plasma. Various urinary indicators of kidney function and plasmatic markers of oxidative stress were also assessed. Results: The acute administration of C. occidentalis increased the urinary excretion of 107.58% at the higher dose tested, compared to negative control. The reference drugs furosemide and HCTZ induced increases of 84.27 % and 48.05 %, respectively. Acutely, the extract induced Na+ and Cl- elimination, whereas subchronically an increase in K+ elimination was also observed. The extract also improved the kidney function indexes and oxidative stress markers. These effects were dose-dependent and comparable with positive control observations. Conclusions: Our i ndings strongly suggest that C. occidentalis aqueous extract has diuretic and antioxidant activities, and deserves further studies considering the potential for the treatment of hypertension.

The use of diuretics in acute heart failure: Evidence based therapy?

The evidence base for the use of diuretics in acute heart failure is limited, with no large double-blind placebo-controlled randomized trials. However, their use as a first line treatment of acute heart failure is firmly established in clinical practice, and endorsed in clinical guidelines. Loop diuretics are typically the first line diuretic strategy for the treatment of acute heart failure. For patients with considerable fluid retention, there is some evidence that initial treatment with continuous infusion or boluses of high dose loop diuretic is superior to an initial lower dose strategy. In patients who are diuretic resistant, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. Intravenous low-dose dopamine has also been used to assist diuresis and preserve renal function in such circumstances, but trials are underway to confirm the clinical value of this agent. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence base is not secure, and its place in clinical practice is yet to be established.

Determination of 8 Diuretics and Probenecid in Human Urine by Gas Chromatography-Mass Spectrometry: Confirmation Procedure

A fast and sensitive method for determination of 8 diuretics (acetazolamide, bendroflumethiazide, bumetanide, chlorthalidone, furosemide, hydrochlorothiazide, metolazone, triamterene) and masking agent (probenecid) in human urine using gas-chromatography with mass spectrometric detection is described. The extraction of the substances as function of the nature of organic solvent, mixing time and pH of aqueous phase was studied. The tandem mass spectrometry was used to increase selectivity of diuretics determination due to elimination of background interferences. Fragmentation reactions were studied for each compound and their collision energies were optimized to obtain the best selectivity. The results of method’s validation demonstrate its suitability in routine analysis for confirmation purposes.

Diuretic window hypothesis in cirrhosis: Changing the point of view

Since the 1970s,non-selective beta-blockers(NSBB)have been used to prevent variceal upper bleeding in advanced cirrhotic patients.However,several recent studies have raised the doubt about the benefit of NSBB in end-stage cirrhotic patients.In fact,they suggested a detrimental effect in these patients that even reduced survival.All of these studies have been assembled to compose the“window therapy hypothesis”,in which NSBB would have traditional indication to be initiated to prevent variceal upper bleeding;however,treatment should be stopped(or not be initiated)in patients with end-stage cirrhosis.NSBB would reduce the cardiac reserve of these patients,worsening systemic perfusion and prognosis.However,it should be emphasized that these studies present important bias issues,and their results also suggested that diuretic treatment may also be behind the effects observed.In this opinion review,we changed the point of view from NSBB to diuretic treatment,based on a physiopathogenic approach of circulatory parameters of cirrhotic patients studied,and based on diuretic effect in blood pressure lowering and in other hypervolemic disease,as heart failure.We suggest a“diuretic window hypothesis”,composed by an open window in hypervolemic phase,an attention window when patient present in a normal plasma volume phase,and a closed window during the plasma hypovolemic phase.

Diuretic Agents in Treatment of Sudden Deafness

Objective To study the role of diuretic agents in treating sudden deafness (SD) and explore the possibility of endolymphatic hydrops as a potential cause of SD. Methods Twenty-eight SD cases were reviewed. In 23 cases, treatment was initiated with routine agents. Diuretic agents were later added in 8 of these cases that failed to respond to routine treatment agents. Diuretic agents were included in the initial treatment in the rest 5 cases. In total, 13 cases received diuretics in addition to routine treatment agents and 15 cases received conventional treatment only. Results In the 8 cases who received diuretics after failed conventional treatments, 4 showed hearing improvement, whereas all 5 cases in which diuretics were included in the initial treatment demonstrated hearing improvement. Conclusion These results suggest a possible role of endolymphatic hydrops in the pathophysiologic course of SD. Diuretics should be considered when clear indications exist with no conflicts to other medical conditions.

Diuretic activity of Phyllanthus niruri (Linn.) in rats

Aqueous extract of Phyllanthus niruri (200 mg/kg and 400 mg/kg. p.o. single dose) was tested for its diuretic activity and compared with the standard drug hydrochlorothiazide (10 mg/ kg p.o.;single dose). Significant increase in the volume of urine and excretion of sodium, potassium and chloride was recorded when aqueous extract of Phyllanthus niruri was administered to hydrated albino rats.

Diuretic Effect of <em>Cymbopogon jwarancusa</em>after Single and Multiple Doses in Rats

Diuretics are efficaciously used in management of various clinical emergencies like hypertension, heart failure, cirrhosis, hypercalciuria, hematuria and nephrotic syndrome. Cymbopogon jwarancusa is an aromatic perennial grass used in both traditional and Unani system of medicine to eradicate diseases like colds, seasonal fever, asthma, tuberculosis, rheumatic pain, back pain, toothache and nervous disorders. C. jwarancusa essential oils are used in perfumery, soap, detergents, medicines and pharmaceutical industry. Monoterpenes and sesquiterpenes constitute the highest composition in essential oil of C. jwarancusa. The present was designed to compare the diuretic activity of C. jwarancusa after single and multi-doses. Furosemide (20 mg/kg) was used as reference drug and 10% DMSO was used as vehicle. Diuretic activity was noticed by measuring urine volume and calculating diuretic and Lipchitz values. Maximum diuretic response was observed at 500 mg/kg of extract after both single and multi-dose administration. On basis of results it may be concluded that C. jwarancusa may be used as diuretic agent.

The Effect of Loop Diuretics on Sarcopenia and Long-Term Prognosis in Patients with Refractory Hepatic Ascites Treated with Tolvaptan

We investigated sarcopenia, focusing on the dose of loop diuretics used in 70 patients with refractory hepatic ascites treated with tolvaptan. Bloating improved in 68.5% of patients, as determined using the Japanese version of the Support Team Assessment Schedule. The psoas muscle index (PMI) was used to define sarcopenia. A statistically significant difference was observed in the PMI between patients receiving low-dose (3.6 ± 1.2 cm2/m2) and high-dose furosemide (3.1 ± 1.2 cm2/m2) before tolvaptan treatment (P = 0.048). The PMI increased from 3.2 ± 1.1 cm2/m2 to 3.5 ± 1.3 cm2/m2 (P = 0.002) in responders, but decreased from 3.4 ± 1.2 cm2/m2 to 3.0 ± 1.0 cm2/m2 (P = 0.106) in non-responders before and after tolvaptan treatment, respectively. The long-term prognosis improved in responders compared with non-responders (mean survival time: 646 days vs. 228 days, P < 0.001). Early introduction of tolvaptan treatment is necessary to prevent the progression of sarcopenia.

Urea transporter inhibitors identified as novel diuretics

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.

GC-MS STUDY ON DIURETICS IN URINE Ⅰ.BETECTION METHOD USING METHYLATION

A reliable and sensitive method is developed for the detection of common diuretics in human urine. diuretics along with probenecid are methylated and subjected to GC-MS analysis.Both chromatographic and mass spectrometric data are obtained in selected ion monitoring and full scanning modes.The average detection limit is 0.1-1.0 ag/mi urine.This method is suitable to large-scale and routine screening or confirmation of diuretics in doping control.

GC-MS STUDY ON DIURETICS IN URINE Ⅱ.DETECTION METHOD USING TRIMETHYLSILYLATION

A reliable method is described for the detection of amitoride,triamterene. canrenone and spironolactone in human urine using GC-MS analysis after trimethytsitytation.The mass spectrometric and metabotic features of the compounds are discussed

Diuretic combinations in critically ill patients with respiratory failure:A systematic review and meta-analysis

BACKGROUND In patients with respiratory failure,loop diuretics remain the cornerstone of the treatment to maintain fluid balance,but resistance is common.AIM To determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure.METHODS We searched MEDLINE,Embase,Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic.A meta-analysis using mean differences(MD)with 95%confidence interval(CI)was performed for the 24-h fluid balance(primary outcome)and the 24-h urine output,while descriptive statistics were used for safety events.RESULTS Nine studies totalling 440 patients from a total of 6510 citations were included.When compared to loop diuretics alone,the addition of a second diuretic is associated with an improved negative fluid balance at 24 h[MD:-1.06 L(95%CI:-1.46;-0.65)],driven by the combination of a thiazide plus furosemide[MD:-1.25 L(95%CI:-1.68;-0.82)],while no difference was observed with the combination of a loop-diuretic plus acetazolamide[MD:-0.40 L(95%CI:-0.96;0.16)]or spironolactone[MD:-0.65 L(95%CI:-1.66;0.36)].Heterogeneity was high and the report of clinical and safety endpoints varied across studies.CONCLUSION Based on limited evidence,the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure,but only when using a thiazide.Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.

Inhibition of Urogenital Chlamydia Trachomatis in Vitro by 12 Diuretic Traditional Chinese Medicines

Objective: To detect the inhibition of urogenitalchlamydia trachomatis (CT) by 12 traditional Chinesemedicines in vitro.Methods: The inhibition of CT isolates by these medicineswas detected by micro-culture technique with McCoy cellsin vitro. Results: All the diuretic traditional Chinese medicinesinhibited urogenital CT The minimum inhibitoryconcentrations (MICs) ranged from 0.122 mg ml^(-1) to 62.5mg ml^(-1). Diathus superbus L., Poria cocos (Shew.) Woft,Polyporus umbellatus (Pers.) Fries, and Artemisia capillariesThunb showed stronger inhibition than the other eighttraditional Chinese medicines. The numbers and sizes ofinclusions bodies reduced gradually and disappeared finallywith the increase of the concentrations. Conclusion: All the 12 diuretic traditional Chinesemedicines inhibited urogenital CT.

Unusual Presentation of COVID-19: Encephalitis and Syndrome of Inappropriate Anti-Diuretic Hormone Secretion

COVID-19 is a new challenge in clinical medicine. Although typical presentations include fever and pneumonia, we describe a case of COVID-19 presenting with neurological symptoms of encephalitis and infectious-related syndrome of inappropriate anti-diuretic hormone secretion. Because of the epidemic health problems, it is crucial to identify these patients as early as possible to follow the isolation procedures. We suggest that unclear neurological clinical presentations of patients should be considered for COVID-19.

参芪益心汤治疗心力衰竭合并利尿剂抵抗患者的临床疗效及对其心功能、NT-proBNP水平的影响

目的 探讨参芪益心汤加减治疗心力衰竭合并利尿剂抵抗患者的疗效。方法 选取2021年12月—2022年12月期间黑龙江中医药大学附属第一医院收治的心力衰竭合并利尿剂抵抗患者100例作为研究对象,按照随机数字表法分为对照组和试验组,每组各50例。对照组予常规治疗,试验组在对照组基础上加用参芪益心汤,两周为1个疗程,两组患者均治疗4周。观察比较两组患者治疗前后心功能指标[左心室舒张末期内径(Left ventricular end-diastolic diameter,LVDD)、左房内径(Left atrial diameter,LAD),计算左室射血分数(Left ventricular ejection fraction,LVEF)]、血清指标[N端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)、肌钙蛋白T(Cardiac troponin T,CTnT)、肌酸磷化脢同功脢(Creatine kinase isoenzyme,Ck-MB)]、中医证候积分,比较两组患者临床疗效及不良反应。结果 治疗后两组患者心功能LVDD、LAD水平均较治疗前降低,LVEF水平均较治疗前升高,差异有统计学意义(P<0.05);且试验组LVDD、LAD水平均明显低于对照组,LVEF水平明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者NT-proBNP、CTnT、Ck-MB水平均较治疗前降低,差异有统计学意义(P<0.05);且试验组NT-proBNP、CTnT、Ck-MB水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者心悸、气短、气喘、胸闷评分均较治疗前降低,差异有统计学意义(P>0.05);且试验组心悸、气短、气喘、胸闷评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后试验组总有效率96.00%(48/50)高于对照组72.00%(36/50),差异有统计学意义(P<0.05)。治疗期间,两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论 应用参芪益心汤能够显著改善心功能,缓解临床症状,疗效显著,值得临床应用。

连续性肾脏替代疗法对难治性心力衰竭伴利尿药抵抗患者预后的影响

目的探讨连续性肾脏替代疗法(continuous renal replacement therapy,CRRT)对难治性心力衰竭(refractory heart failure,RHF)伴利尿药抵抗患者预后的影响,分析其影响因素。方法选取北京市普仁医院2019年1月至2022年1月收治的利尿药抵抗性RHF患者102例开展回顾性研究。患者均采用CRRT治疗,比较患者治疗前、后的左心室射血分数(left ventricular ejection fraction,LVEF)、心脏指数(cardiac index,CI)、心排血量(cardiac output,CO),检测血清氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)、血肌酐(serum creatinine,Scr)、尿酸(uric acid,UA)、血尿素氮(blood urea nitrogen,BUN)浓度,并记录24 h尿量变化。观察患者28 d的预后情况,根据预后分成生存组、死亡组,收集并比较两组患者的临床资料,利用多元Logistic回归模型分析CRRT治疗患者预后的影响因素。结果经治疗后,患者LVEF、CI、CO高于治疗前,血清NT-proBNP浓度低于治疗前,差异有统计学意义(P<0.05)。患者治疗后的血清Scr、UA、BUN浓度低于治疗前,而24 h尿量高于治疗前,差异有统计学意义(P<0.05)。102例患者中病死率为35.29%,生存率为64.71%。死亡组入院后6 h内治疗占比为13.89%,低于生存组的40.91%,且死亡组入院时平均动脉压(mean arterial pressure,MAP)、血红蛋白(hemoglobin,Hb)浓度及24 h尿量低于生存组,血清NT-proBNP浓度高于生存组,差异有统计学意义(P<0.05)。多元Logistic回归分析显示,患者入院后6 h内接受治疗及入院时相对较高的MAP、Hb浓度及24 h尿量是预后保护性因素,入院时血清NT-proBNP浓度过高是预后危险因素(P<0.05)。结论CRRT对利尿药抵抗性RHF患者有一定治疗作用,但早期病死率仍较高,且CRRT治疗的预后与多种因素相关,临床需引起重视。