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OBJECTIVES: To investigate the efficacy of tadalafil for patients with benign prostatic hyperplasia and chronic prostatitis/chronic pelvic pain syndrome. METHODS: Tadalafil 5 mg was given each morning for 12 weeks to patients diagnosed as having either moderate or severe lower urinary tract symptoms. Voiding symptoms were compared between patients with a high (≥4; high group) and low (<4; low group) pain subscore of the National Institutes of Health Chronic Prostatitis Symptom Index before and after tadalafil administration. The correlation between changes in the Chronic Prostatitis Symptom Index and the International Prostate Symptom Score during treatment was also investigated. RESULTS: At baseline, the pain subscore of the Chronic Prostatitis Symptom Index was high (≥4) in 24 of 74 (32.4%) patients. The International Prostate Symptom Score in the group with a high pain subscore was significantly higher than that in the group with a low pain subscore. International Prostate Symptom Score, National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscore were all significantly improved after treatment. The change in the Chronic Prostatitis Symptom Index total score correlated positively with the change in the International Prostate Symptom Score. The decrease in the International Prostate Symptom Score was significantly greater in the group with high versus low pain subscore. CONCLUSIONS: Tadalafil is sufficiently effective in the treatment of patients with benign prostatic hyperplasia and severe chronic prostatitis/chronic pelvic pain syndrome.
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Inibidores da Fosfodiesterase 5/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Prostatite/tratamento farmacológico , Tadalafila/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Prostatite/complicações , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Clinical and pharmacological studies of obsessive-compulsive disorder (OCD) have suggested that the serotonergic systems are involved in the pathogenesis, while structural imaging studies have found some neuroanatomical abnormalities in OCD patients. In the etiopathogenesis of OCD, few studies have performed concurrent assessment of genetic and neuroanatomical variables. METHODS: We carried out a two-way ANOVA between a variable number of tandem repeat polymorphisms (5-HTTLPR) in the serotonin transporter gene and gray matter (GM) volumes in 40 OCD patients and 40 healthy controls (HCs). RESULTS: We found that relative to the HCs, the OCD patients showed significant decreased GM volume in the right hippocampus, and increased GM volume in the left precentral gyrus. 5-HTTLPR polymorphism in OCD patients had a statistical tendency of stronger effects on the right frontal pole than those in HCs. CONCLUSIONS: Our results showed that the neuroanatomical changes of specific GM regions could be endophenotypes of 5-HTTLPR polymorphism in OCD.
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AIM: Although many neuroimaging studies of obsessive-compulsive disorder (OCD) have reported broad abnormalities in gray matter (GM), their results remain inconsistent. One reason for this inconsistency could be the heterogeneity of OCD. In the present study, we aimed to classify alterations in brain anatomy by OCD subtype. METHODS: Magnetic resonance imaging examinations of 37 OCD patients and 37 matched healthy controls were conducted using a 3.0-Tesla scanner. In the voxel-based morphometric procedure, preprocessed GM structural images were used to compare the two groups, and multiple regression analysis was used to investigate the correlation between regional GM volume in OCD patients and the OCD symptom dimension type assessed by using the Dimensional Yale-Brown Obsessive-Compulsive Scale. RESULTS: We found significant reductions in GM volume in broad areas of the left prefrontal, right orbitofrontal, right parietal, right temporal, and right posterior cingulate cortex in the OCD patients compared to healthy controls. In addition, we found specific negative correlations between symptomatic dimension scores and regional GM volumes, mainly as decreased right cerebellum in 'aggression/checking' and decreased right insula in 'contamination/washing'. CONCLUSION: The pathophysiology of OCD may involve widely distributed neural systems. Moreover, there are distinct correlations among symptomatic dimensions and structural abnormalities.
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Encéfalo/patologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/patologia , Adulto , Atrofia/patologia , Estudos de Casos e Controles , Feminino , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Adulto JovemRESUMO
We applied Chrysanthemum flower oil (CFO) to a hyperuricemia model by feeding rats a hyperuricemia-inducing diet (HID) and investigated its effect on serum uric acid (SUA) levels and its mode of action. CFO is the oily fraction that contains polyphenols derived from chrysanthemum flowers. Oral administration of CFO to HID-fed rats significantly decreased their SUA levels. It also inhibited xanthine oxidase activities in the liver and increased urine uric acid levels. The effects of CFO on the renal gene expressions that accompanied the induction of hyperuricemia were comprehensively confirmed by DNA microarray analysis. The analysis showed up-regulation of those genes for uric acid excretion by CFO administration. These results suggest that CFO suppresses the increase in SUA levels via two mechanisms: suppression of uric acid production by inhibition of xanthine oxidase in the liver and acceleration of its excretion by up-regulation of uric acid transporter genes in the kidney.
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Chrysanthemum/química , Flores/química , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Análise de Sequência com Séries de Oligonucleotídeos , Óleos de Plantas/farmacologia , Animais , Bovinos , Hiperuricemia/sangue , Hiperuricemia/enzimologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Óleos de Plantas/administração & dosagem , Óleos de Plantas/uso terapêutico , Ratos , Ácido Úrico/sangue , Xantina Oxidase/metabolismoRESUMO
Declines in estrogen levels occur in women transitioning to menopause. Estrogen hormones play important roles in multiple systems of the body, and estrogen loss is associated with a variety of symptoms that can decrease quality of life. The gut microbiota is involved in regulating endogenous estrogen levels. A portion of estrogen glucuronides can be reactivated in the gut by the microbial enzyme ß-glucuronidase, and the resulting free estrogens can return to the bloodstream. Here, we carried out in vitro screening of ß-glucuronidase activities for 84 strains belonging to 16 different species of lactic acid bacteria and bifidobacteria and found that one and three strains of Levilactobacillus brevis and Lacticasebacillus rhamnosus, respectively, can deconjugate estrogens. Among these strains, L. brevis KABP052 had the highest ß-glucuronidase activity. Moreover, in an exploratory, randomized, double-blind, placebo-controlled trial, we demonstrated that serum estrogen levels in healthy peri- and postmenopausal women given a probiotic formula containing KABP052 were maintained over time, whereas levels significantly decreased in the group given a placebo. Significantly higher levels of estradiol (31.62 ± 7.97 pg/mL vs. 25.12 ± 8.17 pg/mL) and estrone (21.38 ± 8.57 pg/mL vs. 13.18 ± 8.77 pg/mL) were observed in the probiotic versus placebo group after 12 weeks of intervention. This clinical study demonstrated for the first time the estrogen modulation capacity of a probiotic formula containing a bacterial strain having ß-glucuronidase activity in women during the menopausal transition and formed the basis for future investigations using probiotics in the menopausal population.
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Suplementos Nutricionais , Estrogênios , Glucuronidase , Pós-Menopausa , Probióticos , Humanos , Probióticos/farmacologia , Feminino , Glucuronidase/metabolismo , Glucuronidase/sangue , Estrogênios/sangue , Estrogênios/metabolismo , Pessoa de Meia-Idade , Método Duplo-Cego , Microbioma Gastrointestinal/efeitos dos fármacos , Lacticaseibacillus rhamnosus , Perimenopausa/sangue , Adulto , BifidobacteriumRESUMO
Single-wall carbon nanotubes (SWCNTs) are promising materials for electronic applications, such as transparent electrodes and thin-film transistors. However, the dispersion of isolated SWCNTs into solvents remains an important issue for their practical applications. SWCNTs are commonly dispersed in solvents via ultrasonication. However, ultrasonication damages SWCNTs, forming defects and cutting them into short pieces, which significantly degrade their electrical and mechanical properties. Herein, we demonstrate a novel approach toward the large-scale dispersion of long and isolated SWCNTs by using hydrodynamic cavitation. Considering the results of atomic force microscopy and dynamic light-scattering measurements, the average length of the SWCNTs dispersed via the hydrodynamic cavitation method is larger than that of the SWCNTs dispersed by using an ultrasonic homogenizer.
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We investigated whether a blend of probiotics (KABP-021, KABP-022, and KABP-023) improved diarrhea-related problems in healthy Japanese adults who routinely lived under stressful conditions. Twenty-six females and 34 males were divided randomly into the probiotic and placebo groups in this double-blind, placebo-controlled, parallel-group comparison study. All participants ingested 1 capsule of probiotics or placebo per day for 4 weeks. Intervention with probiotics significantly reduced diarrhea-related problems assessed by the Izumo scale compared with placebo treatment (P < 0.001). In the Short Form-8 questionnaire, probiotic intervention improved mental component scores (P = 0.002), role emotional scores (P = 0.002), and mental health scores (P < 0.001). Treatment with probiotics also reduced the effects of diarrhea on daily activities (P < 0.001) and overall working habits (P = 0.010), including missing work (absenteeism) and impaired productivity (presenteeism), as assessed by the Work Productivity and Activity Impairment Questionnaire: General Health. Furthermore, there was a correlation between improved scores for diarrhea on the Izumo scale and increased abundance of Faecalibacterium, a butyric acid-producing bacterium, in the gut in the probiotic group (P = 0.047), whereas no such a correlation or trend was found in the placebo group. Our strategy of supplementation for 4 weeks with a specific blend of probiotics reduced diarrhea-related symptoms and may improve the mental health and daily activities of healthy individuals under stress.
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Sarcopenia is an age-related skeletal muscle atrophy. Exercise is effective in improving sarcopenia via two mechanisms: activation of skeletal muscle satellite cells (SCs) and stimulation of muscle protein synthesis. In contrast, most nutritional approaches for improving sarcopenia focus mainly on muscle protein synthesis, and little is known about SC activation. Here, we investigated the effect of lemon myrtle extract (LM) on SC activation both in vitro and in vivo. Primary SCs or myoblast cell lines were treated with LM or its derived compounds, and incorporation of 5-bromo-2'-deoxyuridine, an indicator of cell cycle progression, was detected by immunocytochemistry. We found that LM significantly activated SCs (p < 0.05), but not myoblasts. We also identified casuarinin, an ellagitannin, as the active compound in LM involved in SC activation. The structure−activity relationship analysis showed that rather than the structure of each functional group of casuarinin, its overall structure is crucial for SC activation. Furthermore, SC activation by LM and casuarinin was associated with upregulation of interleukin-6 mRNA expression, which is essential for SC activation and proliferation. Finally, oral administration of LM or casuarinin to rats showed significant activation of SCs in skeletal muscle (p < 0.05), suggesting that LM and casuarinin may serve as novel nutritional interventions for improving sarcopenia through activating SCs.
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Taninos Hidrolisáveis , Myrtaceae/química , Extratos Vegetais , Células Satélites de Músculo Esquelético , Animais , Células Cultivadas , Taninos Hidrolisáveis/farmacologia , Extratos Vegetais/farmacologia , Ratos , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Células Satélites de Músculo Esquelético/metabolismoRESUMO
OBJECTIVE: To investigate the efficacy and safety of vibegron add-on therapy in men with persistent storage symptoms receiving α-1 blockers or PDE5 inhibitor for benign prostatic hyperplasia and then determine the independent factors affecting the efficacy of vibegron. METHODS: Vibegron 50 mg was administered for 12 weeks to 42 patients (72.0 ± 8.2 years) with persistent storage symptoms who had taken α-1 blockers (22 patients) or PDE5 inhibitor (20 patients). The primary endpoint was change in the overactive Bladder (OAB) Symptom Score from baseline to end of treatment. The secondary endpoints were changes in each question of several questionnaires, maximum flow rate and residual urine volume. Finally, independent factors affecting the efficacy of vibegron were investigated. RESULTS: Total OAB Symptom Score was significantly decreased (6.21 ± 3.12 vs 4.38 ± 2.46; P < .001). Although each score of several questionnaires, especially for storage symptoms, improved significantly, no significant improvement was found in stress incontinence, straining, bladder pain and urethral pain in the Core Lower Urinary Tract Symptom score. Maximum flow rate and residual urine volume did not change, and no patient discontinued vibegron because of adverse events. Multiple regression analysis showed that OAB Symptom Score, Core Lower Urinary Tract Symptom score, prostate volume and monotherapy with α-1 blocker were independent factors affecting the efficacy of vibegron. CONCLUSION: Add-on therapy of vibegron to monotherapy with α-1 blockers or PDE5 inhibitor for patients with benign prostatic hyperplasia and persistent storage symptoms was effective and safe.
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Hiperplasia Prostática/tratamento farmacológico , Pirimidinonas/uso terapêutico , Pirrolidinas/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Antagonistas Adrenérgicos alfa/uso terapêutico , Idoso , Quimioterapia Combinada , Humanos , Masculino , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Prospectivos , Hiperplasia Prostática/complicações , UrodinâmicaRESUMO
Bioassay-guided fractionation of the EtOH extract of licorice (Glycyrrhiza glabra roots), using a GAL-4-PPAR-gamma chimera assay method, resulted in the isolation of 39 phenolics, including 10 new compounds (1-10). The structures of the new compounds were determined by analysis of their spectroscopic data. Among the isolated compounds, 5'-formylglabridin (5), (2R,3R)-3,4',7-trihydroxy-3'-prenylflavane (7), echinatin, (3R)-2',3',7-trihydroxy-4'-methoxyisoflavan, kanzonol X, kanzonol W, shinpterocarpin, licoflavanone A, glabrol, shinflavanone, gancaonin L, and glabrone all exhibited significant PPAR-gamma ligand-binding activity. The activity of these compounds at a sample concentration of 10microg/mL was three times more potent than that of 0.5microM troglitazone.
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Glycyrrhiza/química , PPAR gama/efeitos dos fármacos , Fenóis/farmacologia , Raízes de Plantas/química , Animais , Sítios de Ligação , Linhagem Celular , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Ligantes , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: This study evaluated the 5-year failure rate of naftopidil (NAF) or tamsulosin hydrochloride (TAM) in lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS) and compared the prognostic factor of two alpha(1)-blockers. MATERIAL AND METHODS: A total of 131 patients with International Prostate Symptom Score (IPSS) >or= 8 or IPSS quality of life (IPSS-QOL) >or= 3 with BPH/LUTS receiving treatment with alpha(1)-blockers had been administered NAF or TAM, and failure rates were calculated for 5 years. Age, prostate volume (PV), acute urinary retention (AUR), overactive bladder (OAB), IPSS, IPSS-QOL and postvoiding residual volume (PVR) were evaluated as prognostic factors. RESULTS: No significant differences in failure rate were observed between the drugs. The failure rate was significantly high for patients with a PV >or= 35 ml, PVR >or= 30 ml, a history of AUR or complications of OAB symptoms. The failure rate for patients with a history of AUR was significantly higher than in those without AUR in the NAF group. By contrast, in the TAM group, it was significantly higher in patients who had OAB symptoms than in those without OAB. CONCLUSIONS: No significant differences were observed between the drugs for the failure rate. Each treatment had a unique factor for prognosis, such as history of AUR for NAF and complications of OAB for TAM. Therefore, it will be necessary to use the two alpha(1)-blockers properly, considering the patient's background.
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Antagonistas Adrenérgicos alfa/uso terapêutico , Naftalenos/uso terapêutico , Piperazinas/uso terapêutico , Hiperplasia Prostática/complicações , Prostatismo/tratamento farmacológico , Prostatismo/etiologia , Sulfonamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Retrospectivos , Tansulosina , Fatores de TempoRESUMO
Previous studies have reported clinical characteristics of hoarding disorder (HD), such as early onset, a chronic course, familiality, high unmarried rate, and high rates of comorbidities. However, clinical research targeting Japanese HD patients has been very limited. As a result, there is a low recognition of HD in Japan, leading to insufficient evaluation and treatment of Japanese HD patients. The aim of the current study was to delineate the clinical characteristics of Japanese HD patients. Thirty HD patients, 20 obsessive-compulsive disorder (OCD) patients, and 21 normal controls (NC) were targeted in this study. The HD group had a tendency toward higher familiality, earlier onset, and longer disease duration compared to the OCD group. In addition, the HD group showed a significantly higher unmarried rate than the NC group. The top two comorbidities in the HD group were major depressive disorder (56.7%) and attention-deficit/hyperactivity disorder (26.7%). The HD group had significantly higher scores on hoarding rating scales and lower scores on the Global Assessment of Functioning Scale than the other two groups. The current study showed a clinical trend in Japanese HD patients similar to previous studies in various countries, suggesting that HD may be a universal disease with consistent clinical symptoms.
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Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human health. Turmeric oleoresin, an extract of turmeric, is often used for flavoring and coloring. Curcuminoids and turmeric essential oil are both contained in turmeric oleoresin, and both of these fractions have hypoglycemic effects. In the present study, we comprehensively assessed the effect of turmeric oleoresin on hepatic gene expression in obese diabetic KK-Ay mice using DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR). Female KK-Ay mice aged 6 weeks (n = 6/group) were fed a high-fat diet containing turmeric oleoresin, curcuminoids, and essential oil for 5 weeks. The same diet without any of these fractions was used as a control diet. Ingestion of turmeric oleoresin and essential oil inhibited the development of increased blood glucose and abdominal fat mass, while curcuminoids only inhibited the increase in blood glucose. DNA microarray analysis indicated that turmeric oleoresin ingestion up-regulated the expression of genes related to glycolysis, beta-oxidation, and cholesterol metabolism in the liver of KK-Ay mice, while expression of gluconeogenesis-related genes was down-regulated. Real-time PCR analysis was conducted to assess the contribution of the curcuminoids and essential oil in turmeric oleoresin to the changes in expression of representative genes selected by DNA microarray analysis. This analysis suggested that curcuminoids regulated turmeric oleoresin ingestion-induced expression of glycolysis-related genes and also that curcuminoids and turmeric essential oil acted synergistically to regulate the peroxisomal beta-oxidation-related gene expression induced by turmeric oleoresin ingestion. These changes in gene expression were considered to be the mechanism by which the turmeric oleoresin affected the control of both blood glucose levels and abdominal adipose tissue masses. All of these results suggest that the use of whole turmeric oleoresin is more effective than the use of either curcuminoids or the essential oil alone.
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Curcuma , Hipoglicemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Camundongos , Camundongos Obesos , Análise de Sequência com Séries de Oligonucleotídeos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Óleos de Plantas/administração & dosagem , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Óleos de Plantas/uso terapêutico , RizomaRESUMO
We applied licorice flavonoid oil (LFO) to high-fat diet-induced obese C57BL/6J mice and investigated its effect. LFO contains hydrophobic flavonoids obtained from licorice by extraction with ethanol. The oil is a mixture of medium-chain triglycerides, having glabridin, a major flavonoid of licorice, concentrated to 1.2% (w/w). Obese mice were fed on a high-fat diet containing LFO at 0 (control), 0.5%, 1.0%, or 2.0% for 8 weeks. Compared with mice in the control group, those in the 1% and 2% LFO groups efficiently reduced the weight of abdominal white adipose tissues and body weight gain. A histological examination revealed that the adipocytes became smaller and the fatty degenerative state of the hepatocytes was improved in the 2% LFO group. A DNA microarray analysis of the liver showed up-regulation of those genes for beta-oxidation and down-regulation of those for fatty acid synthesis in the 2% LFO group. These findings suggest that LFO prevented and ameliorated diet-induced obesity via the regulation of lipid metabolism-related gene expression in the liver.
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Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Peso Corporal/efeitos dos fármacos , Flavonoides/farmacologia , Glycyrrhiza/química , Obesidade/tratamento farmacológico , Adipócitos Brancos/efeitos dos fármacos , Ração Animal , Animais , Regulação para Baixo/efeitos dos fármacos , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Regulação para Cima/efeitos dos fármacosRESUMO
We performed four-terminal conductivity measurements on a CoSi2 nanowire (NW) at room temperature by using PtIr-coated carbon nanotube (CNT) tips in a four-tip scanning tunneling microscope. The physical stability and high aspect ratio of the CNT tips made it possible to reduce the probe spacing down to ca. 30 nm. The probe-spacing dependence of resistance showed diffusive transport even at 30 nm and no current leakage to the Si substrate.
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Eletroquímica/instrumentação , Análise de Falha de Equipamento/instrumentação , Irídio/química , Teste de Materiais/instrumentação , Microeletrodos , Nanotubos de Carbono/química , Platina/química , Impedância Elétrica , Eletroquímica/métodos , Desenho de Equipamento , Análise de Falha de Equipamento/métodos , Teste de Materiais/métodos , Nanotubos de Carbono/ultraestruturaRESUMO
AIM: The aim of this study was to compare the efficacy and safety of alpha1-adrenoceptor (alpha1-AR) antagonist monotherapy with combination therapy using alpha1-AR antagonist and anticholinergic agent for benign prostatic hyperplasia (BPH) with storage symptoms as the chief complaint. METHODS: In this prospective comparative study, either 25-75 mg/day of naftopidil monotherapy (monotherapy group) or combination therapy using 25-75 mg/day of naftopidil and an anticholinergic agent (10-20 mg/day of propiverine hydrochloride or 2-6 mg/day of oxybutynin hydrochloride; cotherapy group) were administered for 12 weeks to 101 BPH patients with storage symptoms. RESULTS: International prostate symptom score (IPSS) and quality of life (QOL) index improved significantly in both groups, with no marked differences between groups. Maximum flow rate (Qmax) and residual urine volume (RUV) tended to improve in both groups, again with no marked differences between groups. However, median post-therapeutic RUV was significantly worse for the cotherapy group (45.0 mL) than for the monotherapy group (13.5 mL; P = 0.0210). Ratio of patients with increased RUV was also significantly worse for cotherapy (22.9%) than for monotherapy (5.0%; P = 0.038). CONCLUSIONS: Although the anticholinergic dosage was low, the present results suggest that naftopidil monotherapy was as useful as combination therapy of naftopidil and an anticholinergic agent. Therefore, naftopidil is a useful agent as the first choice in BPH patients with storage symptoms.