Objective: To evaluate the impact of empagliflozin on peak oxygen uptake (VO₂peak) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: In this randomized controlled trial, consecutive HFmrEF patients admitted to the Department of Cardiology of China-Japan Friendship Hospital from September 2019 to October 2020 were screened, and randomly assigned to empagliflozin group (EG) or conventional group (CG) using a random number table. The enrolled patients were treated according to the guidelines, and patients in the empagliflozin group received additional empagliflozin (10 mg, once a day, orally) on top of the conventional treatment. The primary end points were VO₂peak at 6 months after treatment, and the secondary end points included other parameters of cardiopulmonary exercise test (CPET), 6-minute walking distance, N-terminal B-type pro-natriuretic peptide (NT-proBNP) level, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score. Results: A total of 112 patients were included (mean age 69 (57, 78) years, 84 male (75.0%)). There were 55 cases in CG group and 57 cases in EG group. There were no significant differences in baseline data including age, sex, body mass index, left ventricular ejection fraction, systolic blood pressure, heart rate, estimated glomerular filtration rate, glycosylated hemoglobin, hemoglobin, NT-proBNP, daily dose of tolasemi, combined medication, CPET parameters, the proportion of New York Heart Association heart function Ⅲ/Ⅳ, history of coronary heart disease, history of hypertension, history of diabetes (all P>0.05). At 6 months after treatment, VO₂peak was significantly higher in EG group than in CG group(P=0.023). VE/VCO₂ slope was significantly lower in EG group than in CG group(P=0.034). Oxygen uptake efficiency slope was significantly higher in EG group than in CG group(P=0.038). The level of NT-proBNP was significantly lower in EG group than in CG group(P=0.020). Six-minute walking distance was significantly higher in EG group than in CG group(P=0.037). KCCQ score was significantly higher in EG group than in CG group(P=0.048). Exercise oscillatory ventilation decreased in both groups (1 case in each group, P>0.05). Conclusion: Empagliflozin can significantly improve VO₂peak in patients with HFmrEF.
Aged ; Benzhydryl Compounds ; Glucosides ; Heart Failure/drug therapy* ; Humans ; Male ; Natriuretic Peptide, Brain ; Oxygen/therapeutic use* ; Peptide Fragments ; Stroke Volume/physiology* ; Ventricular Dysfunction, Left ; Ventricular Function, Left

PURPOSE: To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. MATERIALS AND METHODS: This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. RESULTS: Urinary levels of NGF/Cr (OAB: 1.13+/-0.9 pg/mg; control: 0.5+/-0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73+/-6.55 pg/mg; control: 4.45+/-2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13+/-0.08 pg/mg; 16 weeks: 0.60+/-0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73+/-6.55 pg/mg; 16 weeks: 4.72+/-2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores. CONCLUSION: Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.
Adult ; Benzhydryl Compounds/pharmacology/*therapeutic use ; Biological Markers/urine ; Case-Control Studies ; Creatinine/urine ; Female ; Heparin-binding EGF-like Growth Factor/*urine ; Humans ; Male ; Middle Aged ; Nerve Growth Factor/*urine ; Questionnaires ; Treatment Outcome ; Urinary Bladder, Overactive/*drug therapy/physiopathology/*urine ; Urodynamics

OBJECTIVETo evaluate the influence of an extract of Genista tinctoria L. herba (GT) or methylparaben (MP) on histopathological changes and 2 biomarkers of oxidative stress in rats subchronicly exposed to bisphenol A (BPA).

METHODSAdult female Wistar rats were orally exposed for 90 d to BPA (50 mg/kg), BPA+GT (35 mg isoflavones/kg) or BPA+MP (250 mg/kg). Plasma and tissue samples were taken from liver, kidney, thyroid, uterus, ovary, and mammary gland after 30, 60, and 90 d of exposure respectively. Lipid peroxidation and in vivo hydroxyl radical production were evaluated by histological analysis along with malondialdehyde and 2,3-dihydroxybenzoic acid detection.

RESULTSThe severity of histopathological changes in liver and kidneys was lower after GT treatment than after BPA or BPA+MP treatment. A minimal thyroid receptor antagonist effect was only observed after BPA+MP treatment. The abnormal folliculogenesis increased in a time-dependent manner, and the number of corpus luteum decreased. No significant histological alterations were found in the uterus. The mammary gland displayed specific estrogen stimulation changes at all periods. Both MP and GT revealed antioxidant properties reducing lipid peroxidation and BPA-induced hydroxyl radical generation.

CONCLUSIONGT L. extract ameliorates the toxic effects of BPA and is proved to have antioxidant potential and antitoxic effect. MP has antioxidant properties, but has either no effect or exacerbates the BPA-induced histopathological changes.

Animals ; Benzhydryl Compounds ; toxicity ; Chemical and Drug Induced Liver Injury ; pathology ; prevention & control ; Endocrine Disruptors ; toxicity ; Female ; Genista ; Hydroxyl Radical ; blood ; Lipid Peroxidation ; drug effects ; Liver ; pathology ; Oxidative Stress ; drug effects ; Parabens ; toxicity ; Phenols ; toxicity ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the effectiveness of the monotherapy of Cardura and the combination therapy of Cardura and Tolterodine L-Tartrate Tablets for II° ? benign prostate hyperplasia (BPH) with overactive bladder (OAB).

METHODSThis study included 87 cases of BPH with OAB, with a disease course > or = 3 months, daily urination > or = 8 times, nocturnal urination > or = 2 times, urine volume < 200 ml per time, International Prostate Symptom Score (IPSS) > or = 8, OAB symptom score (OABS) > or = 3, quality of life score (QOL) > or = 3, post-void residual (PVR) < or = 100 ml, maximum urinary flow (Qmax) > or = 5 ml/s, prostate weight 25-50 g, and PSA < 4 microg/L. We randomized the patients to a monotherapy group (n = 44) and combination group (n = 43), the former treated with Cardura 4 mg qd, and the latter with Cardura 4 mg + Tolterodine L-Tartrate Tablets 4 mg qd, both for 8 weeks. Then we recorded the IPSS, OABS, Qmax, PVR, PSA, and adverse events.

RESULTSThe baseline parameters showed no significant differences between the two groups (P > 0.05). In comparison with the baseline, both the monotherapy group and the combination therapy group showed significant decreased in the IPSS (16.50 +/- 4.27 vs 13.68 +/- 3.69 and 15.51 +/- 3.80 vs 11.49 +/- 2.75), urine storage symptom score (10.48 +/- 2.75 vs 7.98 +/- 2.34 and 9.47 +/- 2.31 vs 5.74 +/- 1.66), OABS (8.55 +/- 2.69 vs 6.32 +/- 1.97 and 8.21 +/- 2.55 vs 4.44 +/- 1.62), urgent micturition score (4.25 +/- 1.06 vs 3.23 +/- 0.99 and 4.07 +/- 0.83 vs 2.26 +/- 1.05), QOL (5.36 +/- 0.72 vs 3.43 +/- 0.66 and 5.07 +/- 0.86 vs 2.37 +/- 0.76) and PVR ([44.55 +/- 22.39] vs [38.30 +/- 20.20] ml and [36.19 +/- 21.21] vs [24.98 +/- 17.60] ml) (P < 0.01). All the six parameters were significantly more improved in the combination therapy group than in the monotherapy group (P < 0.01), but there were no remarkable differences between the groups in Qmax and voiding symptom score (P > 0.05). Neither group exhibited significant changes in the PSA level and prostate weight after treatment as compared with the baseline (P > 0.05). No acute urinary retention and other severe adverse reactions were observed during the medication.

CONCLUSIONBoth Cardura monotherapy and the combination therapy of Cardura + Tolterodine L-Tartrate Tablets can improve II ? BPH with OAB, and the latter has an even better efficacy than the former.

Aged ; Benzhydryl Compounds ; therapeutic use ; Cresols ; therapeutic use ; Doxazosin ; therapeutic use ; Drug Therapy, Combination ; Humans ; Male ; Middle Aged ; Phenylpropanolamine ; therapeutic use ; Prostatic Hyperplasia ; complications ; drug therapy ; Tolterodine Tartrate ; Treatment Outcome ; Urinary Bladder, Overactive ; complications ; drug therapy

OBJECTIVETo evaluate the therapeutic effect of Parkinson's disease combined with overactive bladder syndrome (GAB) treated with combined therapy of oral administration of Tolterodine with low dose and electroacuponcture.

METHODSSixty cases of Parkinson's disease combined with GAB were randomly divided into a combined acupuncture and medication group (group A) and a medication group (group B), 30 cases in each group. In both groups, Madopar basic doses were same, and anticholinergic agents such as Artane were stopped. In group A, Tolterodine was orally taken for 1 mg, twice a day; Baihui (GV 20), Sishengcong (EX-HN 1) and Yintang (EX-HN 3) were punctured with electroacupuncture, once a day. In group B, Tolterodine was orally taken for 2 mg, twice a day. After 6 weeks, the changes of urination and UPDRS III scores were observed, and the adverse reactions were recorded in both groups.

RESULTSAfter treatment, the frequency of average urination of 24 hours, frequency of incontinence of 24 hours and average urine volume at a time were obviously improved (all P < 0. 01), of which, the above items in group A were superior to those in group B (all P < 0. 05) the UPDRSIII score in group A was superior to that in group B (P < 0.05). The adverse reactions in group A were less than those in group B.

CONCLUSIONThe therapeutic effect of Parkinson' s disease combined with GAB treated with combined therapy of Tolterodine with low dose and electroacupuncture is superior to that of complete dose of Tolterodine with oral administration, with less adverse reactions. And it also can improve the motor symptom of Parkinson's disease patients.

Adult ; Aged ; Benzhydryl Compounds ; therapeutic use ; Combined Modality Therapy ; Cresols ; therapeutic use ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease ; drug therapy ; therapy ; Phenylpropanolamine ; therapeutic use ; Tolterodine Tartrate ; Urinary Bladder, Overactive ; drug therapy ; therapy

OBJECTIVETo evaluate the therapeutic effect of overactive bladder after transurethral resection of prostate (TURP) preventively treated with electroacupuncture and Tolterodine.

METHODSOne hundred and twenty cases of benign prostate hyperplasia of TURP were randomly divided into an electroacupuncture and medicine group, an electroacupuncture group, a medicine group and a control group, 30 cases in each group. All the patients were treated with TURP under the continuous epidural anesthesia, and the catheter was retained for 5-7 days. In electroacupuncture group, before the surgery of the same day, Huiyang (BL 35), Ciliao (BL 32), Qugu (CV 2) and Huiyin (CV 1) were acupunctured with electroacupuncture for 30 min, once a day, 5-7 days' treatment was applied. In medicine group, Tolterodine Tartrate tablet was taken for 2 mg in the morning of surgery day, twice a day and treatment was applied for 5-7 days. In electroacupuncture and medicine group, the comprehensive therapies above in both electroacupuncture group and medicine group were applied. In control group, Pethidine of 50 mg was given by intramuscular injection when bladder was overactive, combined with Anisodamine injection of 10 mg according to the symptoms. The frequency and lasting time of bladder overactivity were compared within 72 hours after TURP in each group.

RESULTSAfter TURP, the frequency of bladder overactivity were 2-4 times a day, and lasted for 5-15 min each time in control group. The frequency and lasting time of bladder overactivity in treatment groups at different time were less than those in control group (P < 0.01, P < 0.001). There was no significant difference in comparison of frequency and lasting time of bladder overactivity between electroacupuncture and medicine group (all P > 0.05). The frequency and lasting time of bladder hyperactivity in electroacupuncture and medicine group were less than those in the electroacupuncture group and the medicine group at 24 hours, 24-48 hours, 48-72 hours after TUPR (P < 0.05, P < 0.01, P < 0.001).

CONCLUSIONAfter TURP, early prevention of combined therapy of electroacupuncture and Tolterodine with oral administration is superior to that of electroacupuncture therapy or Tolterodine for overactive bladder treatment, and it is the safe and effective method to treat overactive bladder.

Aged ; Aged, 80 and over ; Benzhydryl Compounds ; therapeutic use ; Combined Modality Therapy ; Cresols ; therapeutic use ; Electroacupuncture ; Humans ; Male ; Middle Aged ; Phenylpropanolamine ; therapeutic use ; Postoperative Complications ; drug therapy ; etiology ; physiopathology ; therapy ; Prostate ; surgery ; Tolterodine Tartrate ; Transurethral Resection of Prostate ; adverse effects ; Urinary Bladder, Overactive ; drug therapy ; etiology ; physiopathology ; therapy

OBJECTIVETo compare the efficacy and safety of tolterodine and oxybutynin in the treatment of idiopathic overactive bladder in children.

METHODSA total of 204 children with idiopathic overactive bladder were randomly divided into three groups (n=68 each): placebo, tolterodine-treated and oxybutynin-treated. The efficacy and safety were evaluated two weeks after treatment.

RESULTSThe effective rate was 25% in the placebo group, 89% in the tolterodine-treated group, and 92% in the oxybutynin-treated group. The effective rate in the two treatment groups was significantly higher than that in the placebo group (P<0.05). There was a similar efficacy between the two treatment groups. The incidence of adverse events in the tolterodine-treated group (28%) was significantly lower than that in the oxybutnin-treated group (57%) (P<0.05).

CONCLUSIONSTolterodine has a similar efficacy to oxybutynin in the treatment of idiopathic overactive bladder in children, with better safety in pharmacotherapy.

Adolescent ; Benzhydryl Compounds ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Cresols ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Mandelic Acids ; adverse effects ; therapeutic use ; Muscarinic Antagonists ; therapeutic use ; Phenylpropanolamine ; adverse effects ; therapeutic use ; Tolterodine Tartrate ; Urinary Bladder, Overactive ; drug therapy

OBJECTIVETo evaluate the efficacy and safety of Tolterodine Tartrate combined with the alpha-receptor blocker in the treatment of benign prostatic hyperplasia with detrusor overactivity (BPH-DO).

METHODSA total of 113 patients with BPH-DO were randomly assigned to receive Tolterodine Tartrate combined with Cardura (Group A) and Cardura alone (Group B), both for 12 weeks. Then we recorded and compared their average 24 h urinary frequency, IPSS and QOL score, maximum urinary flow rate, residual urine volume and urinary retention times before and after the treatment.

RESULTSAfter the treatment, Group A showed significantly better improvement in the average 24 h urinary frequency and scores on IPSS and QOL than Group B. No significant differences were found between the two groups in the maximum urinary flow rate and residual urine volume. No acute urinary retention occurred in either group.

CONCLUSIONThe combined use of Tolterodine Tartrate and the alpha-receptor blocker can effectively relieve the symptoms of dysuria, urinary frequency and urinary urgency in patients with BPH-DO, with neither significant adverse effects on the maximum flow rate and residual urine volume nor increase in the incidence of acute urinary retention.

Adrenergic alpha-Antagonists ; therapeutic use ; Aged ; Benzhydryl Compounds ; therapeutic use ; Cresols ; therapeutic use ; Humans ; Male ; Muscarinic Antagonists ; therapeutic use ; Phenylpropanolamine ; therapeutic use ; Prostatic Hyperplasia ; complications ; drug therapy ; Tolterodine Tartrate ; Treatment Outcome ; Urinary Bladder, Overactive ; complications ; drug therapy

OBJECTIVETo evaluate and compare the clinical efficacy and safety of the highly selective alpha receptor antagonist tamsulosin and its combination with the M receptor antagonist tolterodine in the treatment of refractory lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).

METHODSWe included in this study 184 BPH patients with refractory LUTS with the disease course of 4 weeks to 2 years, whose LUTS were not alleviated after a week's treatment with tamsulosin. The patients were randomly divided into Groups A and B, the former (n=89) treated with tamsulosin at 0.2 mg qd and the latter (n=95) given tolterodine at 2 mg bid in addition to tamsulosin medication, both for 4 weeks. Scores on IPSS, QOL and Qmax were obtained before and after the treatment, and the improvement of LUTS evaluated after the medication.

RESULTSThe tamsulosin group showed no significant differences before and after the treatment in the scores on IPSS (13.23 +/- 4.39 vs. 12.21 +/- 4.07), QOL (4.23 +/- 1.27 vs 3.53 +/- 0.95) and Qmax ([12.3 +/- 8.39] ml/s vs. [14.1 +/- 8.62] mls) (P > 0.05), while the combination group exhibited significantly higher scores on IPSS and QOL and lower score on Qmax after the medication than before it (IPSS: 14.45 +/- 5.31 vs. 6.56 +/- 2.03, P < 0.05; QOL: 4.45 +/- 0.79 vs. 2.34 +/- 0.73, P < 0.05; Qmax: [11.4 +/- 9.21] ml/s vs. [15.5 +/- 8.35] ml/s, P < 0.01). No severe complications were found in any of the cases.

CONCLUSIONCombination of tamsulosin and tolterodine can significantly alleviate refractory LUTS and improve QOL without causing serious adverse events in BPH patients.

Adrenergic alpha-1 Receptor Antagonists ; therapeutic use ; Aged ; Aged, 80 and over ; Benzhydryl Compounds ; therapeutic use ; Cresols ; therapeutic use ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Phenylpropanolamine ; therapeutic use ; Prostatic Hyperplasia ; drug therapy ; Sulfonamides ; therapeutic use ; Tolterodine Tartrate ; Treatment Outcome

OBJECTIVEOveractive bladder may coexist with bladder outlet obstruction induced by benign prostatic hyperplasia (BPH). This study aimed to evaluate the efficacy of the combined use of tolterodine and tamsulosin in the treatment of BPH accompanied by overactive bladder.

METHODSWe selected 53 cases of clinically diagnosed BPH, and randomly assigned them to a tamsulosin group (n = 25) to receive 0.2 mg of tamsulosin once a day and a tamsulosin + tolterodine group (n = 28) to be treated with 0.2 mg of tamsulosin once a day plus 2 mg of tolterodine twice a day, both for 12 weeks. Before and after the treatment, we obtained the International Prostate Symptoms Score (IPSS), quality of life (QOL) score and Qmax, and recorded the adverse events.

RESULTSAll the patients accomplished the 12-week treatment. The tamsulosin group showed a significant decrease in IPSS and QOL from 21.50 +/- 5.42 and 4.58 +/- 0.94 before the treatment to 14.80 +/- 4.21 and 2.78 +/- 0.91 after it (P < 0.05), but a significant increase in Qmax from (12.20 +/- 6.60) ml/s to (16.40 +/- 5.13) ml/s (P < 0.05). In the tamsulosin + tolterodine group, IPSS and QOL were decreased from 20.90 +/- 5.15 and 4.61 +/- 0.86 at the baseline to 14.90 +/- 5.32 and 2.12 +/- 0.87 after the medication (P < 0.05), Qmax was increased from (13.30 +/- 7.80) ml/s to (16.70 +/- 6.32) ml/s (P < 0.05), and the score on the urinary storage phase symptoms was reduced from 10.12 +/- 3.10 to 4.77 +/- 0.75 (P < 0.05).

CONCLUSIONTamsulosin could quickly relieve BPH-induced lower urinary tract symptoms (LUTS) , while the combined use of tolterodine and tamsulosin could even better alleviate the LUTS and improve the QOL of BPH patients.

Aged ; Benzhydryl Compounds ; therapeutic use ; Cresols ; therapeutic use ; Drug Therapy, Combination ; Humans ; Male ; Middle Aged ; Phenylpropanolamine ; therapeutic use ; Prostatic Hyperplasia ; drug therapy ; Sulfonamides ; therapeutic use ; Tolterodine Tartrate ; Treatment Outcome