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1.
The efficacy of an association of palmitoylethanolamide and alpha-lipoic acid in patients with chronic prostatitis/chronic pelvic pain syndrome: A randomized clinical trial.
Giammusso, B, Di Mauro, R, Bernardini, R
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2017;(1):17-21
Abstract
BACKGROUND Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition, characterized by uncertain etiology and by limited response to therapy. The definition of CP/CPPS includes genitourinary pain with or without voiding symptoms in the absence of uropathogenic bacteria, as detected by standard microbiological methods, or another identifiable cause such as malignancy. The efficacy of various medical therapies, has been evaluated in clinical studies, but evidence is lacking or conflicting. We compared Serenoa Repens in monotherapy versus Palmitoylethanolamide (PEA) in combination with Alpha-lipoic acid (ALA) and evaluated the efficacy of these treatments in patients with CP/CPPS. METHODS We conducted a randomized, single-blind trial. 44 patients diagnosed with CP/CPPS (mean age 41.32 ± 1.686 years) were randomly assigned to treatment with Palmitoylethanolamide 300 mg plus Alpha-lipoic acid 300 mg (Peanase®), or Serenoa Repens at 320 mg. Three questionnaires (NIH-CPSI, IPSS and IIEF5) were administered at baseline and after 12 weeks of treatment in each group. RESULTS 12 week treatment with Peanase significantly improved the IPSS score compared to the same period of treatment with Serenoa Repens, and significantly reduced NIH-CPSI score. Similar results were observed in the different NIH-CPSI subscores break down. However, the same treatment did not result in significant improvement of the IIEF5 score. Both treatments did not produce undesired effects. CONCLUSIONS The present results document the efficacy of an association of Palmitoylethanolamide (PEA) and Alpha-lipoic acid (ALA) administered for 12 weeks for treating patients with CP/CPPS, compared with Serenoa Repens monotherapy.
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2.
N-palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic eczema: results of a randomized, double-blind, controlled study in 60 patients.
Yuan, C, Wang, XM, Guichard, A, Tan, YM, Qian, CY, Yang, LJ, Humbert, P
Clinical interventions in aging. 2014;:1163-9
Abstract
BACKGROUND Asteatotic eczema (AE) is characterized by itchy, dry, rough, and scaling skin. The treatments for AE are mainly emollients, usually containing urea, lactic acid, or a lactate salt. N-palmitoylethanolamine (PEA) and N-acetylethanolamine (AEA) are both endogenous lipids used as novel therapeutic tools in the treatment of many skin diseases. The purpose of this study was to compare a PEA/AEA emollient with a traditional emollient in the treatment of AE. METHODS A monocentric, randomized, double-blind, comparative trial was conducted in 60 AE patients to evaluate and compare the efficacy of the two emollients. The level of skin dryness among the subjects ranged from mild to moderate. The subjects' skin barrier function and the current perception threshold were tested for 28 days by clinical scoring and bioengineering technology. RESULTS The results showed that, although some aspects were improved in both groups, the group using the emollient containing PEA/AEA presented a better skin surface change in capacitance. However, the most impressive finding was the ability of the PEA/AEA emollient to increase the 5 Hz current perception threshold to a normal level after 7 days, with a significant difference between values at baseline and after 14 days. A current perception threshold of 5 Hz was positively and significantly correlated with skin surface hydration and negatively correlated with transepidermal water loss in the PEA/AEA emollient group. CONCLUSION Compared with traditional emollients, regular application of a topical PEA/AEA emollient could improve both passive and active skin functions simultaneously.
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3.
Singular and combined effects of nebivolol and lifestyle modification on large artery stiffness in hypertensive adults.
Werner, TJ, Boutagy, NE, Osterberg, KL, Rivero, JM, Davy, KP
Therapeutic advances in cardiovascular disease. 2013;(6):285-92
Abstract
BACKGROUND We hypothesized that the combination of nebivolol and lifestyle modification would reduce large artery stiffness in middle-aged and older hypertensive adults more than either intervention alone. METHODS To address this, 45 men and women (age 40-75 years) with stage I hypertension were randomized to receive either nebivolol (NB; forced titration to 10 mg OD; n = 15; age 57.2 ± 11.4 years; body mass index [BMI] 30.8 ± 5.8 kg/m(2)), lifestyle modification (LM; 5-10% weight loss via calorie restriction and physical activity; n = 15; age 52.7 ± 8.5 years; BMI 33.9 ± 7.2 kg/m(2)) or nebivolol plus lifestyle modification (NBLM; n = 15; age 58.9 ± 9.4 years; BMI 32.5 ± 4.9 kg/m(2)) for 12 weeks. β-stiffness index, a blood-pressure-independent measure of arterial stiffness, and arterial compliance were measured via high-resolution ultrasound and tonometry at baseline and after the 12-week intervention. There was no difference between groups in age, body weight or composition, blood pressure, or in β-stiffness index or arterial compliance at baseline (all p > 0.05). RESULTS Following the 12-week intervention, body weight decreased ~5% (p < 0.05) in the LM and NBLM groups but did not change from baseline in the NB group (p > 0.05). Supine brachial and carotid systolic and diastolic blood pressure declined following treatment in each of the groups (p < 0.05). However, the magnitude of reduction was not different (p < 0.05) between groups. β-stiffness index declined (-2.03 ± 0.60, -1.87 ± 0.83 and -2.51 ± 0.90 U) and arterial compliance increased similarly (both p > 0.05) in the NB, LM and NBLM groups, respectively. CONCLUSION In summary, our findings indicate that the combination of nebivolol and lifestyle modification reduced large artery stiffness to a similar degree as either intervention alone in middle-aged and older hypertensive adults.
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4.
24-hour bronchodilator efficacy of single doses of indacaterol in patients with persistent asthma: comparison with placebo and formoterol.
LaForce, C, Korenblat, P, Osborne, P, Dong, F, Higgins, M
Current medical research and opinion. 2009;(10):2353-9
Abstract
OBJECTIVE To assess the 24-h bronchodilator efficacy and safety of single-dose indacaterol in asthma. METHODS This was a five-period, double-blind, double-dummy, crossover study in patients with persistent asthma. On separate study days, patients inhaled a single dose of indacaterol (150, 300 or 600 microg) in the morning via a single-dose dry powder inhaler (SDDPI), formoterol 12 microg twice daily via its proprietary SDDPI, or placebo. Study days were separated by a washout period of at least 6 days. RESULTS Of the 45 patients randomized to treatment, 42 completed the study. The 24-h trough FEV(1) (primary endpoint) was significantly higher than placebo following all doses of indacaterol (mean [95% CI] differences of 0.11 [0.06, 0.16], 0.21 [0.17, 0.26] and 0.22 [0.18, 0.27] L for 150, 300, and 600 microg, respectively) and formoterol (by 0.13 [0.08, 0.18] L). The 24-h trough FEV(1) was significantly higher following indacaterol 300 and 600 microg than indacaterol 150 microg (by 0.11 [0.06, 0.15] and 0.12 [0.07, 0.17] L, respectively) or formoterol (by 0.08 [0.03, 0.13] L vs. 300 microg; by 0.09 [0.04, 0.14] L vs. 600 microg). Most adverse events were mild-to-moderate and transient. Examination of serum potassium, blood glucose, QTc interval, pulse rate, and blood pressure raised no concern over the safety of indacaterol. CONCLUSIONS Single doses of indacaterol provided effective 24-h bronchodilation and were well tolerated in patients with persistent asthma. Safety findings were limited by non-standardized diet conditions in this study but suggest a minimal systemic treatment effect.
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5.
The effect of nebivolol treatment on oxidative stress and antioxidant status in patients with cardiac syndrome-X.
Erdamar, H, Sen, N, Tavil, Y, Yazici, HU, Turfan, M, Poyraz, F, Topal, S, Okuyan, H, Cemri, M, Cengel, A
Coronary artery disease. 2009;(3):238-4
Abstract
BACKGROUND Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several disorders. The aim of this study was to elucidate the effect of treatment with nebivolol on the metabolic state of oxidative stress, and antioxidant status markers in patients with cardiac syndrome-X (CSX), additionally, to compare with the effect of metoprolol treatment. METHODS Thirty patients, 17 female and 13 male, with CSX were enrolled in the study. Nebivolol (5 mg/day) or metoprolol (50 mg/day) was administrated for 12 weeks. Twelve hour fasting blood samples, taken at the initiation and on the third month of therapy, were analyzed for the levels of malondialdehyde (MDA), nitrite+nitrate (NOx), and the activity of myeloperoxidase (MPO), superoxide dismutase (SOD). No patient presented additional risk factors for increased reactive oxygen species levels. RESULTS Compared with sixteen control participants, patients with CSX had significantly higher activity of MPO and levels of MDA, but significantly lower SOD activity and levels of NOx before treatment. After treatment, MPO activity and MDA levels were significantly reduced; SOD activity and NOx levels were significantly increased with nebivolol but remained unchanged with metoprolol. CONCLUSION We have shown that patients with CSX who taken nebivolol have lower serum MPO activity, levels of MDA and higher serum SOD activity, NOx levels when compared with metoprolol treatment. Exercise stress test parameters were also ameliorated in patients who had taken nebivolol in contrast to metoprolol. Nebivolol treatment may be a novel treatment strategy in cases with CSX in the future.
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6.
Long duration of airway but not systemic effects of inhaled formoterol in asthmatic patients.
Lötvall, J, Ankerst, J
Respiratory medicine. 2008;(3):449-56
Abstract
RATIONALE Formoterol is approved as asthma rescue medication in many countries. The exact duration of the airway vs. systemic effects of formoterol compared with another rescue medication, salbutamol, has not been evaluated. OBJECTIVE To assess the duration of airway bronchodilatory effects vs. systemic effects of inhaled formoterol and salbutamol in asthmatic patients. METHODS Twenty-six patients with stable and reversible asthma were given single doses of formoterol dry-powder inhaler (OxisTurbuhaler) 2x9 microg (lower dose; LD) and 6x9 microg (higher dose; HD), salbutamol (VentolinDiskhaler) 3x400 microg (LD) and 9x400 microg (HD), and placebo in a randomized, double-blind, crossover trial. Airway and systemic effects were assessed by forced expiratory volume in 1s (FEV1), serum potassium, blood pressure, corrected QT-interval (QTc), and palpitation and tremor scores. Time with clinically relevant bronchodilation (FEV1 increase 12%) without clinically relevant markers of systemic effects (serum potassium suppression 0.2 mmol/L, QTc-prolongation 20 ms, or heart rate increase 8 beats per minute) was evaluated. RESULTS Bronchodilation was maintained for 24h with both formoterol doses and for 7-11h with salbutamol. Maximum bronchodilation and systemic effects were similar after formoterol and salbutamol, except for statistically significantly larger maximum heart rate and palpitation and tremor scores after salbutamol. Systemic responses were similarly brief for formoterol and salbutamol (7 h). CONCLUSIONS The airway effects of inhaled formoterol are of long duration, whereas the systemic effects are of a similarly short duration as salbutamol. Thus, the time with clinically relevant bronchodilation without systemic effects is substantially longer after formoterol than after salbutamol.
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7.
Traditional and patient-centred outcomes with three classes of asthma medication.
Jenkins, CR, Thien, FC, Wheatley, JR, Reddel, HK
The European respiratory journal. 2005;(1):36-44
Abstract
Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d., then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules, with 6-week treatment periods and 1-week washouts. Individual "traditional" end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and "patient-centred" end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol>fluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class.
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8.
Formoterol (OXIS) Turbuhaler as a rescue therapy compared with salbutamol pMDI plus spacer in patients with acute severe asthma.
Boonsawat, W, Charoenratanakul, S, Pothirat, C, Sawanyawisuth, K, Seearamroongruang, T, Bengtsson, T, Brander, R, Selroos, O
Respiratory medicine. 2003;(9):1067-74
Abstract
Formoterol has a similar onset of effect to salbutamol but a prolonged duration of action. However, the relative efficacy of the two drugs in acute severe asthma is not known. This double-blind, double-dummy study compared the safety and efficacy of the maximum recommended daily dose of formoterol and a predicted equivalent dose of salbutamol in 88 patients presenting to the emergency department with acute severe asthma. Patients were randomized to formoterol 54 microg via Turbuhaler or salbutamol 2400 microg via pressurized metered dose inhaler (pMDI) plus spacer in three equal doses over 1 h. Following the full dose, mean FEV1 at 75 min increased by 37% for formoterol and 28% for salbutamol (P = 0.18). The maximum increase in FEV1 over 4 h was significantly greater with formoterol compared with salbutamol (51% vs. 36%, respectively P < 0.05) and formoterol was as effective as salbutamol at improving symptoms and wellbeing. Both treatments were well tolerated. Formoterol caused a greater decrease in serum potassium (difference -0.2 mmol/l). In severe acute asthma, bronchodilator therapy with high-dose (54 microg) formoterol Turbuhaler provided equally rapid improvements in lung function of greater magnitude over 4 h than high-dose (2400 microg) salbutamol pMDI plus spacer.
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9.
A comparison of the beta1-selectivity of three beta1-selective beta-blockers.
Nuttall, SL, Routledge, HC, Kendall, MJ
Journal of clinical pharmacy and therapeutics. 2003;(3):179-86
Abstract
OBJECTIVE To determine the relative beta1-selectivity of three beta-blockers (nebivolol, bisoprolol and atenolol), administered orally at normal therapeutic doses, by assessing their impact on the beta2-mediated, haemodynamic and biochemical responses to a terbutaline infusion, which decreases serum potassium and increases serum glucose and insulin. METHODS Twenty-four healthy volunteers (14 men, 10 women), with no history of respiratory disease, attended on five separate occasions; beta-blockers (nebivolol 5 mg, bisoprolol 10 mg, atenolol 50 and 100 mg) or placebo were supplied in random order. Three baseline blood samples were collected at 65-85 min post-beta-blocker. A 60-min terbutaline infusion was started 90 min after taking the beta-blocker. Blood samples were taken and blood pressure and heart rate recorded at 15 min intervals up to 30-min post-infusion. Blood samples were analysed for serum potassium, glucose and insulin concentrations. RESULTS Terbutaline increased heart rate. Pretreatment with nebivolol caused a modest and non-significant reduction in terbutaline-induced tachycardia whilst bisoprolol produced a more marked effect. Atenolol at both 50 and 100 mg doses caused a highly significant reduction in terbutaline-induced tachycardia. All active preparations had a comparable impact on the terbutaline-induced increase in systolic blood pressure, but the drugs had no impact on the changes produced in diastolic blood pressure. After pretreatment with placebo, the terbutaline infusion caused a significant decrease in serum potassium and increases in serum glucose and insulin. Pretreatment with nebivolol had no discernible effect on potassium compared with placebo. In contrast, when compared with either placebo or nebivolol, bisoprolol (P < 0.01) and both doses of atenolol (P < 0.001) significantly attenuated the hypokalaemic effect of terbutaline. Treatment with nebivolol and bisoprolol modestly but significantly reduced the terbutaline-induced increases in glucose (P < 0.05). The blocking effects of both doses of atenolol were highly significant (P < 0.001) when compared with placebo and also significant (P < 0.05 and P < 0.01, respectively) when compared with nebivolol and bisoprolol. A similar pattern of responses with the different beta-blocker treatments was observed for the effects on insulin concentrations during the terbutaline infusion. CONCLUSION The beta1-selectivity of three different beta1-blockers has been demonstrated in healthy volunteers using the blocking of biochemical and haemodynamic responses to a beta2 stimulus. Terbutaline alone caused an increase in heart rate, a rise in systolic blood pressure, a fall in serum potassium and a rise in both serum glucose and insulin. In this study, for both haemodynamic and biochemical responses, atenolol 100 mg had the greatest beta2-blocking effect, nebivolol 5 mg the least. Bisoprolol 10 mg and atenolol 50 mg had intermediate effects; bisoprolol was the more beta1-selective of these two.
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10.
Safety of formoterol by Turbuhaler as reliever medication compared with terbutaline in moderate asthma.
Ind, PW, Villasante, C, Shiner, RJ, Pietinalho, A, Böszörményi, NG, Soliman, S, Selroos, O
The European respiratory journal. 2002;(4):859-66
Abstract
The present study compared the safety of 4.5 microg formoterol with 0.5 mg terbutaline, both by Turbuhaler and used as needed, in addition to regular formoterol in moderate asthma. In this double-blind parallel-group study, 357 patients taking a moderate-to-high dose of inhaled corticosteroids and additional terbutaline (2-5 inhalations x day(-1) during run-in) were randomised to either formoterol or terbutaline as needed in addition to formoterol 9 microg b.i.d. over 12 weeks. Adverse events, serum potassium levels, electrocardiogram, vital signs and lung function were assessed monthly; peak expiratory flow and severe asthma exacerbations were recorded daily. Patients used 2.16 (range 0.0-6.3) formoterol and 2.34 (range 0.1-7.5) terbutaline relief inhalations x day(-1). No clinically significant differences in safety variables were found between treatments. Statistically greater increases in cardiac frequency (2.6 beats x min(-1), p=0.03) were found on terbutaline. There were 44 and 52 severe asthma exacerbations with formoterol and terbutaline, respectively, with no significant difference in time to first exacerbation. There was also no difference between treatments for other efficacy measures (peak expiratory flow, forced expiratory volume in one second and morning/evening symptom scores). Formoterol 4.5 microg as needed was at least as safe, well tolerated and effective as terbutaline 0.5 mg in stable patients (requiring up to 6 relief inhalations x day(-1)) taking formoterol plus inhaled corticosteroids regularly over 12 weeks.