The Effect of Amiloride on Proteinuria in Patients with Proteinuric Kidney Disease.

INTRODUCTION: Proteinuric kidney diseases share an aggressive clinical course of developing end-stage renal disease. However, the treatment is limited. Amiloride, an epithelial sodium channel (ENaC) inhibitor, was reported to reduce proteinuria in animal studies and case reports independent of ENaC inhibition. We hypothesized that amiloride not triamterene (an analog of amiloride) would reduce proteinuria in the patients with proteinuric kidney disease. METHODS: Patients with proteinuria >1.0 g/day and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 on a maximum tolerable dose of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were randomized to receive amiloride 5 mg twice daily or triamterene 50 mg twice daily for 8 weeks, followed by 4 weeks of washout, and then crossed over to the other drug for 8 weeks. The primary outcome was 24-h urine protein reduction. Secondary outcomes were changes in body weight, blood pressure (BP), serum potassium, and eGFR. Data were analyzed by analysis of variance. RESULTS: A total of 12 patients completed the study. Amiloride reduced 24-h urine protein by 38.7% (p = 0.002) and decreased systolic BP by 12.3 mm Hg (p = 0.04). Interestingly, triamterene reduced 24 h urine protein as well, by 32.8% (p = 0.02). Triamterene lowered eGFR by 9.0 mL/min/1.73 m2 (p = 0.007), but it was reversible. The average weight change was insignificant in both groups (p = 0.40 and 0.34 respectively). Three patients withdrew the study due to hyperkalemia. CONCLUSIONS: Both amiloride and triamterene significantly reduced proteinuria in patients with proteinuric kidney disease. The anti-proteinuric effect was additive to renin-angiotensin-aldosterone system (RAAS) blockade, given all patients were on RAAS blockade. Hyperkalemia was a safety concern. Larger trials might be needed to examine the antiproteinuric effects of ENaC inhibitors.

Triamterene in lithium-induced nephrogenic diabetes insipidus: a case report.

Lithium-induced nephrogenic diabetes insipidus (NDI) is a rare and difficult-to-treat condition. We describe the case of an 81-year-old woman with bipolar treated with lithium and no previous history of diabetes insipidus. She was hospitalized due to disturbance of consciousness and was diagnosed with, hypercalcemia, hyperparathyroidism, and NDI. Parathyroidectomy was contraindicated and parathyroid hormone level was improved insufficiently after cinacalcet initiation, percutaneous ethanol injection therapy was performed for the enlarged parathyroid gland. After improvement in hypercalcemia and unsuccessful indapamide treatment, triamterene was administrated to control polyuria. Lithium is one of the indispensable maintenance treatment options for bipolar disorder, but it has the side effect of NDI. Lithium enters the collecting duct's principal cells mainly via the epithelial sodium channel (ENaC) located on their apical membranes, ENaC shows high selectivity for both sodium and lithium, is upregulated by aldosterone, and inhibited by triamterene. To our knowledge, this is the first publication on triamterene use in lithium-induced NDI patients.

Severe Acquired Hypokalemic Paralysis in a Bodybuilder After Self-Medication With Triamterene/Hydrochlorothiazide.

BACKGROUND: Severe hypokalemia with severe neurological impairment and electrocardiogram (ECG) abnormalities due to the misuse of triamterene/hydrochlorothiazide (HCTZ) in a bodybuilder has not yet been reported. CASE REPORT: A 22-year-old bodybuilder developed acute generalized muscle cramps, sensory disturbance of the distal lower and upper limbs, quadriparesis, and urinary retention. These abnormalities were attributed to severe hypokalemia of 1.8 mmol/L (normal range 3.4-4.5 mmol/L) due to misuse of triamterene/HCTZ together with fluid restriction. He was cardiologically asymptomatic, but ECG revealed a corrected QT (QTc) interval of 625 ms. On intravenous application of fluids along with intravenous and oral substitution of potassium, his condition rapidly improved, such that the sensory disturbances, quadriparesis, and bladder dysfunction completely resolved within 2 days after admission. CONCLUSIONS: Self-medication with diuretics along with fluid restriction may result in severe hypokalemia, paralysis, and ECG abnormalities. Those responsible for the management of bodybuilding studios and competitions must be aware of the potential severe health threats caused by self-medication with diuretics and anabolic steroids. Although triamterene is potassium-sparing, it may enhance the potassium-lowering effect of HCTZ.

Evaluation of the suitability of a fluidized bed process for the coating of drug-eluting stents.

Drug-eluting stents are often coated using single-stent coating techniques. In pharmaceutical industry, single-tablet coating is unthinkable. Instead large batches of tablets are coated in fluidized bed apparatuses or pan coaters. Therefore, it was the aim of this work to evaluate whether stents can be coated using a fluidized bed process. For this purpose stents were coated with the model fluorescent drug triamterene embedded in ammonium methacrylate copolymer. Different stent lengths as well as different coating yields were assessed and also a drug-free topcoat was evaluated. The coated stents were analysed regarded coating layer mass, drug content, surface structure, coating thickness and drug release. Furthermore, coating yield and stent defect rate were examined. Except for one stent configuration good results were obtained without optimization of process parameters which indicates the suitability of the method to coat large amounts of stents simultaneously in principle. Drug release was tuneable over a wide range of time spans and a wide range of drug loadings was produced. Further work will be necessary to transform the results of this study from a model stent to a clinically relevant product.

Investigation of triamterene as an inhibitor of the TGR5 receptor: identification in cells and animals.

BACKGROUND: G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) has been shown to participate in glucose homeostasis. In animal models, a TGR5 agonist increases incretin secretion to reduce hyperglycemia. Many agonists have been developed for clinical use. However, the effects of TGR5 blockade have not been studied extensively, with the exception of studies using TGR5 knockout mice. Therefore, we investigated the potential effect of triamterene on TGR5. METHODS: We transfected the TGR5 gene into cultured Chinese hamster ovary cells (CHO-K1 cells) to express TGR5. Then, we applied a fluorescent indicator to examine the glucose uptake of these transfected cells. In addition, NCI-H716 cells that secrete incretin were also evaluated. Fura-2, a fluorescence indicator, was applied to determine the changes in calcium concentrations. The levels of cyclic adenosine monophosphate (cAMP) and glucagon-like peptide (GLP-1) were estimated using enzyme-linked immunosorbent assay kits. Moreover, rats with streptozotocin (STZ)-induced type 1-like diabetes were used to investigate the effects in vivo. RESULTS: Triamterene dose dependently inhibits the increase in glucose uptake induced by TGR5 agonists in CHO-K1 cells expressing the TGR5 gene. In cultured NCI-H716 cells, TGR5 activation also increases GLP-1 secretion by increasing calcium levels. Triamterene inhibits the increased calcium levels by TGR5 activation through competitive antagonism. Moreover, the GLP-1 secretion and increased cAMP levels induced by TGR5 activation are both dose dependently reduced by triamterene. However, treatment with KB-R7943 at a dose sufficient to block the Na+/Ca2+ exchanger (NCX) failed to modify the responses to TGR5 activation in NCI-H716 cells or CHO-K1 cells expressing TGR5. Therefore, the inhibitory effects of triamterene on TGR5 activation do not appear to be related to NCX inhibition. Blockade of TGR5 activation by triamterene was further characterized in vivo using the STZ-induced diabetic rats. CONCLUSION: Based on the obtained data, we identified triamterene as a reliable inhibitor of TGR5. Therefore, triamterene can be developed as a clinical inhibitor of TGR5 activation in future studies.

Liddle syndrome: clinical and genetic profiles.

Liddle syndrome is a rare autosomal dominant monogenic form of hypertension. The authors analyzed clinical and genetic features of 12 cases of Liddle syndrome, the largest sample size ever reported. Clinical data were studied retrospectively. The exon 13 of the ß and γ subunits of the epithelial sodium channel were amplified and sequenced in the peripheral blood leukocytes of the patients. The onset age of the 12 patients was 15.5±3.3 years. Their blood pressures were poorly controlled, and serum potassium levels in most patients were <3.0 mmol/L. Upright plasma renin activity and plasma aldosterone concentration were suppressed in all patients. All patients were treated with triamterene, and blood pressures were well controlled and serum potassium levels returned to normal. The serum creatinine level rose to 124 and 161 µmol/L, respectively, in two patients upon triamterene treatment, and returned to normal soon after treatment was discontinued. Eight mutation alleles were identified, and three mutations were newly identified.

A practical approach for measurement of antihypertensive medication adherence in patients with resistant hypertension.

Confirmation of medication adherence is a challenge in clinical practice and essential for the accurate diagnosis of resistant hypertension. Although it is well established that drug adherence is critical for controlling blood pressure, there are still difficulties applying a simple, inexpensive, and reliable assessment of adherence in the clinical setting. We aimed to test a simple method to assess adherence in resistant hypertensive (RH) patients. A pilot study with normotensives or mild/moderate hypertensive subjects was performed to provide a fluorescence cutoff point for adherence. After that, 21 patients referred to the Resistant Hypertension Clinic had triamterene prescribed and were monitored for a 30-day period. We conducted two unannounced randomly selected home visits for urine collection to test drug intake that day. Office, home and 24-hour ambulatory blood pressure, biochemical data, and the 8-item Morisky Medication Adherence Scale (MMAS-8) were systematically acquired. According to adherence indicated by urine fluorescence, subjects were divided into adherent and nonadherent groups. We found 57% of nonadherence. No differences were found between groups regarding baseline characteristics or prescribed medications; Kappa's test showed concordance between adherence through MMAS-8 items and fluorescence (kappa = 0.61; 95% confidence interval: 0.28-0.94; P = .005). Nonadherent patients had higher office (81 ± 11 vs. 73 ± 6 mm Hg, P = .03), 24-hour ambulatory blood pressure monitoring (75 ± 9 vs. 66 ± 7 mm Hg, P = .01), and home blood pressure measurement (77 ± 9 vs. 67 ± 8 mm Hg, P = .01) diastolic blood pressure than their counterparts. Nonadherence to antihypertensive therapy is high in patients with RH, even when assessed in clinics specialized in this condition. Fluorometry to detect a drug in the urine of RH patients is safe, easy, and reliable method to assess adherence.

Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serum potassium: systematic review and meta-analyses.

BACKGROUND: Potassium-sparing diuretics (PSDs) are valuable antihypertensives with additional benefits unrelated to control of systolic blood pressure (SBP). However, their key parameters affecting SBP and serum potassium are poorly defined, fostering underutilization. METHOD: Consequently, we conducted systematic reviews and meta-analyses, yielding 3668 articles and ultimately 84 randomized comparisons. RESULTS: For office SBP, overall placebo-adjusted changes were triamterene -1.9 (low dose only), amiloride -9.9, spironolactone -13.2, and eplerenone -9.2. Differences in antihypertensive effect were due to potency rather than efficacy. Doubling amiloride, eplerenone, and spironolactone doses reduced SBP (95% confidence limits) on average by -2.3 (-3.1, -1.5). Relative antihypertensive potencies were spironolactone>amiloride>eplerenone. Spironolactone had significantly greater antihypertensive potency than amiloride, -4.0 (-7.4, -0.6), and eplerenone, -5.5 (-7.4, -3.6). Dose equivalencies were eplerenone-spironolactone 4.5-to-1 (e.g., eplerenone 125∼spironolactone 25), amiloride-spironolactone 3.3-to-1, and eplerenone-amiloride 1.4-to-1. Increases in serum potassium from amiloride and spironolactone at commonly used doses averaged 0.14-0.29 mEq/l; the dose doubling effect was 0.16 (0.10, 0.22). Spironolactone caused greater hyperkalemia than amiloride across their dose ranges: 0.14, P = 0.043. Seven features make important bias unlikely: a comprehensive literature search, adjustment for covariates, all models explaining 95-100% of the between-study variability, similar dose doubling effects among PSDs, two different methods giving the same potency sequence, similar results from double blind comparisons, and similar results for eplerenone versus spironolactone from analysing direct comparison data (i.e., no meta-regression) for office and 24-h SBP. CONCLUSION: This synthesis accomplishes for PSDs what has already been achieved for thiazide-type diuretics and other antihypertensives and can guide the application of these underutilized medicines.

Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in Patients with Hypertension.

BACKGROUND: Triamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied. OBJECTIVE: To determine if triamterene provides an effect to further lower BP in patients treated with HCTZ. DESIGN: We conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012. MAIN MEASURES: BP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses. KEY RESULTS: The mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was similarly lower for patients taking triamterene with other medication combinations. Systolic BP reduction was consistently observed for different medication combinations. The range of systolic BP reduction was between 1 and 4 mm Hg, depending on the concurrently used medications. CONCLUSIONS: In the present study, triamterene was found to enhance the effect of HCTZ to lower BP. In addition to its potassium-sparing action, triamterene's ability to lower BP should also be considered.

Triamterene crystalline nephropathy.

Medications can cause a tubulointerstitial insult leading to acute kidney injury through multiple mechanisms. Acute tubular injury, a dose-dependent process, occurs due to direct toxicity on tubular cells. Acute interstitial nephritis characterized by interstitial inflammation and tubulitis develops from drugs that incite an allergic reaction. Other less common mechanisms include osmotic nephrosis and crystalline nephropathy. The latter complication is rare but has been associated with several drugs, such as sulfadiazine, indinavir, methotrexate, and ciprofloxacin. Triamterene crystalline nephropathy has been reported only rarely, and its histologic characteristics are not well characterized. We report 2 cases of triamterene crystalline nephropathy, one of which initially was misdiagnosed as 2,8-dihydroxyadenine crystalline nephropathy.

Investigation of the inclusion interaction of p-sulfonatocalix[6]arene with triamterene.

The inclusion complexation behavior of p-sulfonatocalix[6]arene (SCX6) with triamterene (TA) was investigated by fluorescence spectroscopy, UV-Vis spectroscopy, (1)H and 2D NMR, FT-IR, SEM and DSC. The results indicate that TA is able to form an inclusion complex with SCX6. The inclusion complex has a stoichiometry of 1:1 at pH 6.50. In addition, the water solubility of TA was obviously increased in the inclusion complex with SCX6.

Blood pressure lowering efficacy of potassium-sparing diuretics (that block the epithelial sodium channel) for primary hypertension.

BACKGROUND: Potassium-sparing diuretics, which block the epithelial sodium channel (ENaC), are widely prescribed for hypertension as a second-line drug in patients taking other diuretics (e.g. thiazide diuretics) and much less commonly prescribed as monotherapy. Therefore, it is essential to determine the effects of ENaC blockers on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAEs) when given as a first-line or second-line therapy. OBJECTIVES: To quantify the dose-related reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) of ENaC blocker therapy as a first-line or second-line drug in patients with primary hypertension. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2012), MEDLINE (1950 to August 2012), EMBASE (1980 to August 2012) and reference lists of articles. SELECTION CRITERIA: Double-blind, randomized, controlled trials in patients with primary hypertension that evaluate, for a duration of 3 to 12 weeks, the BP lowering efficacy of: 1) fixed-dose monotherapy with an ENaC blocker compared with placebo; or 2) an ENaC blocker in combination with another class of anti-hypertensive drugs compared with the respective monotherapy (without an ENaC blocker). DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. Study authors were contacted for additional information. WDAE information was also collected from the trials. MAIN RESULTS: No trials evaluating the BP lowering efficacy of ENaC blockers as monotherapy in patients with primary hypertension were identified. Only 6 trials evaluated the BP lowering efficacy of low doses of amiloride and triamterene as a second drug in 496 participants with a baseline BP of 151/102 mm Hg. The additional BP reduction caused by the ENaC blocker as a second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. The addition of low doses of amiloride and triamterene in these trials did not reduce BP. An estimate of the dose-related BP lowering efficacy for ENaC blockers was not possible because of a lack of trial data at higher doses. AUTHORS' CONCLUSIONS: ENaC blockers do not have a statistically or clinically significant BP lowering effect at low doses but trials at higher doses are not available. The review did not provide a good estimate of the incidence of harms associated with ENaC blockers.

Bioavailability study of triamterene and xipamide using urinary pharmacokinetic data following single oral dose of each drug or their combination.

An efficient chromatographic method for the simultaneous determination of triamterene (TRI) and xipamide (XIP) in urine samples, based on high performance liquid chromatography with photodiode array detector (HPLC-DAD) has been developed. The HPLC separation was performed on a RP stainless-steel C-18 analytical column (250 mm × 4.6 mm, 5 µm) with a gradient elution system of 0.05 M phosphate buffer adjusted to pH 4.0 and methanol as the mobile phase. The method was used to determine the urinary excretion profile and to calculate different urinary pharmacokinetic parameters following oral dose of their combination compared with single oral doses of each drug and hence comparing their bioavailability. Quantitation was performed using chlorthalidone as internal standard. The calibration graphs of each drug were rectilinear in the range of 0.2-40 µg/mL urine for TRI and 0.2-15 µg/mL urine for XIP. An HPLC-DAD method was also successfully developed for the simultaneous determination of the investigated drugs in pharmaceutical preparations. The methods were validated in terms of linearity, accuracy, precision, selectivity, limits of detection and quantitation and other aspects of analytical validation.

Long-term efficacy and tolerability of a fixed-dose combination of antihypertensive agents: an open-label surveillance study in China.

BACKGROUND: A fixed-dose combination (FDC) of four compounds, hydrochlorothiazide 12.5 mg, triamterene 12.5 mg, dihydralazine 12.5 mg and reserpine 0.1 mg (HTDR), is widely used as an antihypertensive treatment in China. Although HTDR has been used in China for more than 30 years, there have been few comprehensive evaluations of this treatment. OBJECTIVE: The aim of this study was to investigate the long-term efficacy and tolerability of HTDR in Chinese patients with essential hypertension. METHODS: This was a 36-month, community-based, open-label surveillance study, conducted in the Huangpu District (Shanghai, China). The study was based in local primary healthcare settings. Subjects were recruited if they had essential hypertension, were aged ≥35 years at the time of enrolment, were expected to remain in the area for 3 years, and were able to provide informed consent. Patients who had secondary hypertension, myocardial infarction or stroke within 6 months of screening, impaired renal or hepatic function, history of cardiomyopathy or chronic heart failure, or were pregnant or lactating were excluded. HTDR was administered as one or two tablets per day in the morning. If necessary, additional hydrochlorothiazide was added. Blood pressure (BP) was measured at baseline and throughout the 36-month surveillance period every 3 months. Biochemical indicators (e.g. fasting blood glucose, plasma lipid parameters, plasma sodium and potassium, plasma uric acid and serum creatinine) were also measured, and adverse events were noted. BP reductions and the rate at which patients achieved BP targets (systolic BP [SBP] <140 mmHg and diastolic BP [DBP] <90 mmHg) throughout the period were determined. Subgroup analyses by sex and age were also conducted. RESULTS: A total of 1529 patients (550 male, 979 female; mean age 65.7 years) entered the study. After the 36-month treatment period, 93.1% of patients had achieved the SBP target, 97.9% had achieved the DBP target, and 92.1% had achieved both. The mean decreases in SBP and DBP were 15.3 mmHg and 9.9 mmHg, respectively. Overall, 127 adverse events in 119 patients (7.8%) occurred during the follow-up period, most of which were mild to moderate. Plasma lipid profiles were improved after 24 months of treatment. In addition, a significant increase in plasma potassium and a significant reduction in plasma uric acid were seen. CONCLUSION: HTDR was found to have good long-term efficacy and tolerability in Chinese patients with essential hypertension.

Bioequivalence evaluation of a triamterene-hydrochlorothiazide generic product: a new bioequivalence index for fixed-dose combinations.

In this study, an open, double-blind, randomized, two-period, two-group crossover design was conducted in 14 healthy volunteers to study the bioequivalence of a fixed-dose generic product. After administration of test or reference products to each volunteer, both active ingredients were determined simultaneously in plasma samples using a developed and validated HPLC-UV method, and pharmacokinetic parameters, including C(max), T(max), AUC(0-t) , AUC(0∞), terminal elimination rate constant (λz), volume of distribution in steady state (Vd(ss)), mean residence time (MRT), clearance (Cl), terminal elimination rate constant (Kel) were determined in each subject using the standard non-compartmental approach. Statistical comparison showed that the test and reference products were bioequivalent in terms of both the rate and extent of bioavailability of both active ingredients. Finally, a new parameter named range overlap index (ROI) was introduced for the first time in this study in order to judge about the overall bioequivalence of the combination products. This parameter indicates the extent in which the two CI90% ranges of each parameter for two active ingredients overlap with each other. The ROI is suggested to be equal or more than 50% for two combination products in order to be known as bioequivalent. The ROI values of the bioequivalence-indicating parameters were 61.90%, 84.6%, and 76.0% for C(max), AUC(0--->12), and AUC(0--->∞), respectively, which are indicative for bioequivalence in all the cases.

Blood pressure lowering efficacy of potassium-sparing diuretics (that block the epithelial sodium channel) for primary hypertension.

BACKGROUND: Potassium-sparing diuretics, which block the epithelial sodium channel (ENaC), are widely prescribed for hypertension as a second-line drug in patients taking other diuretics (e.g. thiazide diuretics) and much less commonly prescribed as monotherapy. Therefore, it is essential to determine the effects of ENaC blockers on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAEs) when given as a first-line or second-line therapy. OBJECTIVES: To quantify the dose-related reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) of ENaC blocker therapy as a first-line or second-line drug in patients with primary hypertension. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (1950 to August 2009), EMBASE (1980 to August 2009) and reference lists of articles. SELECTION CRITERIA: Double-blind, randomized, controlled trials in patients with primary hypertension that evaluate, for a duration of 3 to 12 weeks, the BP lowering efficacy of: 1) fixed-dose monotherapy with an ENaC blocker compared with placebo; or 2) an ENaC blocker in combination with another class of anti-hypertensive drugs compared with the respective monotherapy (without an ENaC blocker). DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. Study authors were contacted for additional information. WDAE information was also collected from the trials. MAIN RESULTS: No trials evaluating the BP lowering efficacy of ENaC blockers as monotherapy in patients with primary hypertension were identified. Only 6 trials evaluated the BP lowering efficacy of low doses of amiloride and triamterene as a second drug in 496 participants with a baseline BP of 151/102 mm Hg. The additional BP reduction caused by the ENaC blocker as a second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. The addition of low doses of amiloride and triamterene in these trials did not reduce BP. An estimate of the dose-related BP lowering efficacy for ENaC blockers was not possible because of a lack of trial data at higher doses. AUTHORS' CONCLUSIONS: ENaC blockers do not have a statistically or clinically significant BP lowering effect at low doses but trials at higher doses are not available. The review did not provide a good estimate of the incidence of harms associated with ENaC blockers.

[Asynchronous lumbar synovial cysts after surgical resection: a case report]. / Asynchrone Facettgelenks-Zyste nach Facettgelenks-Punktion: eine Falldemonstration.

Lumbar synovial cysts represent a rare condition, they are believed to arise from defects of the joint capsule due to degeneration, trauma, rheumatoid arthritis or spondylosis. The symptom spectrum ranges from neural claudication to neurological deficits. We report the case of a contralateral asynchronous facet joint cyst after surgical resection and review the literature.

Prolonged exercise after diuretic-induced hypohydration: effects on substrate turnover and oxidation.

To determine the influence of a diuretic-induced reduction in plasma volume (PV) on substrate turnover and oxidation, 10 healthy young males were studied during 60 min of cycling exercise at 61% peak oxygen uptake on two separate occasions > or =1 wk apart. Exercise was performed under control conditions (CON; placebo), and after 4 days of diuretic administration (DIU; Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide). DIU resulted in a calculated reduction of PV by 14.6 +/- 3.3% (P < 0.05). Rates of glucose appearance (R(a)) and disappearance (R(d)) and glycerol R(a) were determined by using primed constant infusions of [6,6-(2)H]glucose and [(2)H(5)]glycerol, respectively. No differences in oxygen uptake during exercise were observed between trials. Main effects for condition (P < 0.05) were observed for plasma glucose and glycerol, such that the values observed for DIU were higher than for CON. No differences were observed in plasma lactate and serum free fatty acid concentrations either at rest or during exercise. Hypohydration led to lower (P < 0.05) glucose R(a) and R(d) at rest and at 15 and 30 min of exercise, but by 60 min, the effects were reversed (P < 0. 05). Hypohydration had no effect on rates of whole body lipolysis or total carbohydrate or fat oxidation. A main effect for condition (P < 0.05) was observed for plasma glucagon concentrations such that larger values were observed for DIU than for CON. A similar decline in plasma insulin occurred with exercise in both conditions. These results indicate that diuretic-induced reductions in PV decreases glucose kinetics during moderate-intensity dynamic exercise in the absence of changes in total carbohydrate and fat oxidation. The specific effect on glucose kinetics depends on the duration of the exercise.