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Prospective study to compare antibiosis versus the association of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract in preventing urinary tract infections in patients submitted to urodynamic investigation.
Palleschi, G, Carbone, A, Zanello, PP, Mele, R, Leto, A, Fuschi, A, Al Salhi, Y, Velotti, G, Al Rawashdah, S, Coppola, G, et al
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2017;(1):45-50
Abstract
BACKGROUND The abuse of antimicrobical drugs has increased the resistance of microorganisms to treatments, thus to make urinary tract infections (UTIs) more difficult to eradicate. Among natural substances used to prevent UTI, literature has provided preliminary data of the beneficial effects of D-mannose, N-acetylcysteine, and Morinda citrifolia fruit extract, due to their complementary mechanism of action which contributes respectively to limit bacteria adhesion to the urothelium, to destroy bacterial pathogenic biofilm, and to the anti-inflammatory and analgesic activity. The purpose of this study was to compare the administration of an association of D-mannose, N-acetylcysteine (NAC) and Morinda citrifolia extract versus antibiotic therapy in the prophylaxis of UTIs potentially associated with urological mini-invasive diagnostics procedures, in clinical model of the urodynamic investigation. METHODS 80 patients eligible for urodynamic examination, 42 men and 38 women, have been prospectively enrolled in the study and randomised in two groups (A and B) of 40 individuals. Patients of group A followed antibiotic therapy with Prulifloxacine, by mouth 400 mg/day for 5 days, while patients of the group B followed the association of mannose and NAC therapy, two vials/day for 7 days. Ten days after the urodynamic study, the patients were submitted to urine examination and urine culture. RESULTS The follow up assessment didn't show statistical significant difference between the two groups regarding the incidence of UTI. CONCLUSIONS The association of mannose and NAC therapy resulted similar to the antibiotic therapy in preventing UTIs in patients submitted to urodynamic examination. This result leads to consider the possible use of these nutraceutical agents as a good alternative in the prophylaxis of the UTI afterwards urological procedures in urodynamics.
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Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV.
Proetel, U, Pletsch, N, Lauseker, M, Müller, MC, Hanfstein, B, Krause, SW, Kalmanti, L, Schreiber, A, Heim, D, Baerlocher, GM, et al
Annals of hematology. 2014;(7):1167-76
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Abstract
The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874
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Nutlin-3a, an MDM2 antagonist and p53 activator, helps to preserve the replicative potential of cancer cells treated with a genotoxic dose of resveratrol.
Zajkowicz, A, Krześniak, M, Matuszczyk, I, Głowala-Kosińska, M, Butkiewicz, D, Rusin, M
Molecular biology reports. 2013;(8):5013-26
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Resveratrol is a natural compound that has been intensely studied due to its role in cancer prevention and potential as an anti-cancer therapy. Its effects include induction of apoptosis and senescence-like growth inhibition. Here, we report that two cancer cell lines (U-2 OS and A549) differ significantly in their molecular responses to resveratrol. Specifically, in U-2 OS cells, the activation of the p53 pathway is attenuated when compared to the activation in A549 cells. This attenuation is accompanied by a point mutation (458: CGA→TGA) in the PPM1D gene and overexpression of the encoded protein, which is a negative regulator of p53. Experimentally induced knockdown of PPM1D in U-2 OS cells resulted in slightly increased activation of the p53 pathway, most clearly visible as stronger phosphorylation of p53 Ser37. When treated with nutlin-3a, a non-genotoxic activator of p53, U-2 OS and A549 cells both responded with substantial activation of the p53 pathway. Nutlin-3a improved the clonogenic survival of both cell lines treated with resveratrol. This improvement was associated with lower activation of DNA-damage signaling (phosphorylation of ATM, CHK2, and histone H2AX) and higher accumulation of cells in the G1 phase of the cell cycle. Thus, the hyperactivation of p53 by nutlin-3a helps to preserve the replicative potential of cells exposed to resveratrol.
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Atorvastatin improves erectile dysfunction in patients initially irresponsive to Sildenafil by the activation of endothelial nitric oxide synthase.
El-Sisi, AA, Hegazy, SK, Salem, KA, AbdElkawy, KS
International journal of impotence research. 2013;(4):143-8
Abstract
This study aimed at comparing the effects of atorvastatin and vitamin E on erectile dysfunction in patients initially irresponsive to sildenafil, with investigation into the underlying possible mechanisms. Sixty patients were randomly divided into three groups: the atorvastatin group received 80 mg daily, the vitamin E group received 400 IU daily and the control group received placebo capsules. Patients were examined both before and after 6 weeks of treatment for biochemical tests; Superoxide dismutase (SOD), glutathione peroxidase (GPO), C-reactive protein (CRP), interleukin-6 (IL-6), nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) and for erectile function tests; International index of erectile function (IIEF-5) scores and Rigiscan. Both atorvastatin and vitamin E showed a statistically significant GPO increase (P<0.05) and a statistically significant IL-6 decrease (P<0.05). Only atorvastatin showed a statistically significant increase in NO (15.19%, P<0.05), eNOS (20.58%, P<0.01), IIEF-5 score (53.1%, P<0.001) and Rigiscan rigidity parameters (P<0.01), in addition to a statistically significant decrease in CRP (57.9%, P<0.01). However, SOD showed a statistically significant increase only after vitamin E intake (23.1%, P<0.05). Both atorvatstain and vitamin E had antioxidant and anti-inflammatory activities. Although activating eNOS by atorvastatin was the real difference, and expected to be the main mechanism for NO increase and for improving erectile dysfunction. Atorvastatin, but not vitamin E, is a promising drug for sildenafil nonresponders.
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Effects of ranolazine on exercise tolerance and angina frequency in patients with severe chronic angina receiving maximally-tolerated background therapy: analysis from the Combination Assessment of Ranolazine In Stable Angina (CARISA) randomized trial.
Sendón, JL, Lee, S, Cheng, ML, Ben-Yehuda, O, ,
European journal of preventive cardiology. 2012;(5):952-9
Abstract
BACKGROUND Ranolazine has been previously shown to improve exercise capacity and symptoms in patients with severe chronic angina treated with standard doses of beta-blockers and calcium-channel blockers, without a significant effect on heart rate or blood pressure. OBJECTIVE The purpose of this study was to assess whether the benefit of ranolazine extends to the subgroup of angina patients treated with maximally-tolerated doses of beta-blockers or calcium blockers. METHODS AND RESULTS In this post-hoc analysis, 258 patients from the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial were considered as treated with maximally-tolerated doses of beta-blockers or calcium-channel blockers (systolic blood pressure (SBP) ≤ 100 mm Hg, and/or a resting heart rate ≤ 60 beats per minute, and/or an ECG PR interval ≥ 200 msec). Change from baseline in total exercise duration after 12 weeks compared to placebo were 34.5 (95% CI 0.8; 68.1) sec (p = 0.045) with ranolazine (750/1000 mg bid) at trough drug levels and 46.3 (13.5; 79.1) (p = 0.006) at peak drug levels. The number of angina attacks per week compared to baseline were reduced compared to placebo (-2.3 ± 0.3 vs -0.9 ± 0.6 (p < 0.001)). The effects of ranolazine 750 mg bid and 1000 mg bid were similar and the beneficial effects of ranolazine in this subgroup of maximally-treated patients were consistent with those not on maximally-tolerated doses of the background therapy. CONCLUSION Ranolazine is effective for the symptomatic treatment of patients with stable angina on background therapy with maximally-tolerated doses of first line anti-anginal therapies.
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Double-blind comparison of the safety and efficacy of lurasidone and ziprasidone in clinically stable outpatients with schizophrenia or schizoaffective disorder.
Potkin, SG, Ogasa, M, Cucchiaro, J, Loebel, A
Schizophrenia research. 2011;(2-3):101-7
Abstract
BACKGROUND Lurasidone is a new atypical antipsychotic agent with high affinity for D(2), 5-HT(2A) and 5-HT(7) receptors. The current study evaluated the safety and efficacy of lurasidone and ziprasidone in stable outpatients diagnosed with schizophrenia or schizoaffective disorder. METHODS Adult outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder that was chronic (≥6 months duration) and stable were randomized to 21 days of double-blind treatment with a fixed dose of lurasidone 120 mg once daily (N=150) or ziprasidone 80 mg BID (N=151). Changes from baseline in efficacy measures were evaluated using mixed model for repeated measures (MMRM) analyses. RESULTS The proportion of patients who discontinued from the study was similar for lurasidone and ziprasidone (32.5% vs. 30.7%); the proportion who discontinued due to adverse events was similar (10.4% vs. 11.1%). Treatment with lurasidone and ziprasidone was associated with a small endpoint reduction in median weight (-0.65 kg vs. -0.35 kg) and median total cholesterol (-6.4 vs. -4.4 mg/dL); no endpoint change was observed in median triglycerides (0.0 vs. 0.0 mg/dL). There were no clinically significant changes in other laboratory or ECG parameters. Improvement was observed on an MMRM analysis of the PANSS total score for lurasidone and ziprasidone at Week 1 (-4.1 vs. -1.6; P=0.020), Week 2, (-6.1 vs. -3.6; P=0.074), and Week 3 (-6.3 vs. -4.5; P=0.229). CONCLUSION In this double-blind, fixed-dose comparison of lurasidone 120 mg and ziprasidone 160 mg, treatment with lurasidone was well-tolerated and safe, and was not associated with clinically significant changes from baseline in weight, metabolic parameters, or QTc interval. Study limitations include the relatively short trial duration and lack of placebo control.
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Comparison of prophylactic naftopidil, tamsulosin, and silodosin for 125I brachytherapy-induced lower urinary tract symptoms in patients with prostate cancer: randomized controlled trial.
Tsumura, H, Satoh, T, Ishiyama, H, Tabata, K, Kotani, S, Minamida, S, Kimura, M, Fujita, T, Matsumoto, K, Kitano, M, et al
International journal of radiation oncology, biology, physics. 2011;(4):e385-92
Abstract
PURPOSE To compare the efficacy of three α(1A)/α(1D)-adrenoceptor (AR) antagonists--naftopidil, tamsulosin, and silodosin--that have differing affinities for the α(1)-AR subtypes in treating urinary morbidities in Japanese men with (125)I prostate implantation (PI) for prostate cancer. METHODS AND MATERIALS This single-institution prospective randomized controlled trial compared naftopidil, tamsulosin, and silodosin in patients undergoing PI. Patients were randomized and received either naftopidil, tamsulosin, or silodosin. Treatment began 1 day after PI and continued for 1 year. The primary efficacy variables were the changes in total International Prostate Symptom Score (IPSS) and postvoid residual urine (PVR). The secondary efficacy variables were changes in IPSS storage score and IPSS voiding score from baseline to set points during the study (1, 3, 6, and 12 months). RESULTS Two hundred twelve patients were evaluated in this study between June 2006 and February 2009: 71, 70, and 71 patients in the naftopidil, tamsulosin, and silodosin groups, respectively. With respect to the primary efficacy variables, the mean changes in the total IPSS at 1 month after PI in the naftopidil, tamsulosin, and silodosin groups were +10.3, +8.9, and +7.5, respectively. There were significantly greater decreases with silodosin than naftopidil at 1 month in the total IPSS. The mean changes in the PVR at 6 months were +14.6, +23.7, and +5.7 mL in the naftopidil, tamsulosin, and silodosin groups, respectively; silodosin showed a significant improvement in the PVR at 6 months vs. tamsulosin. With respect to the secondary efficacy variables, the mean changes in the IPSS voiding score at 1 month in the naftopidil, tamsulosin, and silodosin groups were +6.5, +5.6, and +4.5, respectively; silodosin showed a significant improvement in the IPSS voiding score at 1 month vs. naftopidil. CONCLUSIONS Silodosin has a greater impact on improving PI-induced lower urinary tract symptoms than the other two agents.
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Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial.
Fleischhacker, WW, Heikkinen, ME, Olié, JP, Landsberg, W, Dewaele, P, McQuade, RD, Loze, JY, Hennicken, D, Kerselaers, W
The international journal of neuropsychopharmacology. 2010;(8):1115-25
Abstract
Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk. Outpatients who met DSM-IV-TR criteria for schizophrenia, who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or =2.5 kg while taking clozapine, were randomized (n=207) to aripiprazole at 5-15 mg/d or placebo, in addition to a stable dose of clozapine. The primary endpoint was mean change from baseline in body weight at week 16 (last observation carried forward). Secondary endpoints included clinical efficacy, body mass index (BMI) and waist circumference. A statistically significant difference in weight loss was reported for aripiprazole vs. placebo (-2.53 kg vs. -0.38 kg, respectively, difference=-2.15 kg, p<0.001). Aripiprazole-treated patients also showed BMI (median reduction 0.8 kg/m(2)) and waist circumference reduction (median reduction 2.0 cm) vs. placebo (no change in either parameter, p<0.001 and p=0.001, respectively). Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein (LDL) cholesterol. There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator's Assessment Questionnaire scores favoured aripiprazole over placebo. Safety and tolerability were generally comparable between groups. Combining aripiprazole and clozapine resulted in significant weight, BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine. Improvements may reduce metabolic risk factors associated with clozapine treatment.
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Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study.
Sacchetti, E, Galluzzo, A, Valsecchi, P, Romeo, F, Gorini, B, Warrington, L, ,
Schizophrenia research. 2009;(1):112-21
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This 18-week, randomized, flexible-dose, double-blind, double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients. Patients had a DSM-IV diagnosis of schizophrenia, a history of resistance and/or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses, PANSS score >or= 80, and CGI-S score >or= 4. Patients were randomized to ziprasidone (80-160 mg/day, n = 73) or clozapine (250-600 mg/day, n = 74). On the primary ITT-LOCF analysis, baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone (- 25.0 +/- 22.0, 95% CI - 30.2 to - 19.8) and clozapine (- 24.5 +/- 22.5, 95% CI - 29.7 to - 19.2) groups. A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms. There were also significant improvements on PANSS subscales, CGI-S, CG-I, CDSS, and GAF, without between-drug differences. The two treatment groups had similar rates of early discontinuations due to AEs. AEs were mostly of similar mild-moderate severity in the two groups. There were also no detrimental effects on prolactin, renal and liver function, hematology, and cardiovascular parameters. However, ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores. Moreover, when compared with clozapine, ziprasidone also had a more favorable metabolic profile, with significant endpoint differences in weight, fasting glucose, total cholesterol, LDL cholesterol, and triglycerides. In conclusion, this trial indicates that both ziprasidone and clozapine, having comparable efficacy coupled with satisfactory general safety and tolerability, may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and/or intolerance to antipsychotics. The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians, at least in the presence of patients at high risk for metabolic disorders.
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A 28-week, randomized, double-blind study of olanzapine versus aripiprazole in the treatment of schizophrenia.
Kane, JM, Osuntokun, O, Kryzhanovskaya, LA, Xu, W, Stauffer, VL, Watson, SB, Breier, A
The Journal of clinical psychiatry. 2009;(4):572-81
Abstract
OBJECTIVE To evaluate the effectiveness of olanzapine versus aripiprazole in patients with schizophrenia. METHOD Patients aged 18 to 65 years with schizophrenia (diagnosed according to DSM-IV-TR criteria) were randomly assigned to either olanzapine (n = 281) or aripiprazole (n = 285) for 28 weeks of double-blind treatment. The primary outcome was time to all-cause discontinuation. Efficacy was measured by Positive and Negative Syndrome Scale (PANSS) total change from baseline. Time-to-event data were analyzed via the Kaplan-Meier method. The study was conducted from October 2003 to July 2007. RESULTS Treatment groups did not differ significantly in time to all-cause discontinuation (p = .067) or all-cause discontinuation rate (olanzapine, 42.7% vs. aripiprazole, 50.2%; p = .053). Olanzapine-treated patients had significantly longer time to efficacy-related discontinuation (p < .001) and a significantly lower efficacy-related discontinuation rate (olanzapine, 8.9% vs. aripiprazole, 16.8%; p = .006). Olanzapine-treated patients had a significantly greater mean decrease (last observation carried forward) in PANSS total score (-30.2) than did aripiprazole-treated patients (-25.9, p = .014). Olanzapine-treated patients had a mean weight change of +3.4 kg (vs. +0.3 kg for aripiprazole-treated patients; p < .001) and a significantly greater incidence of >or= 7% body weight gain at any time (40.3% vs. 16.4%; p < .001). Fasting mean glucose change was +4.87 mg/dL for olanzapine and +0.90 mg/dL for aripiprazole (p = .045). Incidence of baseline glucose < 100 mg/dL and >or= 126 mg/dL at any time was 1.7% for olanzapine and 0.6% for aripiprazole (p = .623). Fasting mean total cholesterol change was +4.09 mg/dL for olanzapine and -9.85 mg/dL for aripiprazole (p < .001). Incidence of baseline total cholesterol < 200 mg/dL and >or= 240 mg/dL at any time was 9.2% for olanzapine and 1.5% for aripiprazole (p = .008). Fasting mean triglycerides change was +25.66 mg/dL for olanzapine and -17.52 mg/dL for aripiprazole (p < .001). Treatment groups did not significantly differ on measures of extrapyramidal symptoms. CONCLUSION Treatment groups did not differ significantly on the primary outcome. Olanzapine-treated patients had significantly greater improvement in symptom efficacy at 28 weeks as well as significantly greater mean increases in weight and glucose and significantly greater worsening on lipids parameters. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00088049.