Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677481 (urinary frequency)
 1,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study of the effect of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in Crl:CD rats during the perinatal and lactational periods. Female rats(thirty-three per dose level) were given NS-21 orally at dose levels of 0 (control), 2, 25 and 300 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. At the 300 mg/kg dosage level, reduced activity, salivation and rales were observed in dams, and five dams died. Decreases in body weight gain, food consumption and water consumption were also observed in the dams at the 300 mg/kg. The number of remaining implantation sites was increased at 300 mg/kg, indicating fetal mortality. The number of live newborns, birth index and survival index at the birth were decreased at the 300 mg/kg dosage level. Reduced activity, paleness in color and/or discoloration were observed for many pups at the 300 mg/kg on lactation day 0. Body weights of male and female offspring at the birth were also decreased at the 300 mg/kg dosage group. Survival index at the 4 days was decreased at the 300 mg/kg dosage level. Body weight gains of male and female offspring were decreased at the 300 mg/kg during the lactational period and after weaning. NS-21 did not affect the postnatal development of the offspring, including physical and functional development, motor activity, emotionality, learning ability and reproductive performance. These results demonstrate that the NOAEL (no observed adverse effect level) of NS-21 is 25 mg/kg for general toxicity and reproductive function in mother rats and 25 mg/kg for developmental toxicity of their offspring.
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PMID:[Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence (4). Perinatal and postnatal study in rats by oral administration]. 917 Jun 12

The mutagenicity of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was investigated by the reverse mutation test in bacteria, the chromosome aberration test in vitro, and the micronucleus test in mice. The reverse mutation test was performed at a dose from 31.3 to 4000 micrograms/plate, at which dose cell killing was observed, using Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2uvrA. NS-21 did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S9 mix). The chromosome aberration test was carried out at a dose from 3.75 to 140 micrograms/ml, at which dose more than 50% cell proliferation was inhibited, using cultured Chinese hamster lung cells (CHL/IU). No significant increases of the frequencies of cells with chromosome aberrations were observed with or without S9 mix. The micronucleus test was conducted in the bone marrow cells of Slc : ddY male mice. Mice were given NS-21 by a single oral administration at doses of 0, 43.8, 87.5, 175, and 350 mg/kg, the geometric mean dose between the maximum tolerated dose and the minimum lethal dose. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes at any dose levels. These results show that NS-21 has no mutagenic activity in vitro or in vivo.
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PMID:[Mutagenicity studies of (+/-)-4-diethylamino-1,1,-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence]. 917 Jun 13

The oncogenic potential of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was assessed when it was administered in the diet of Charles River B6C3F1 mice for 78 weeks in dosages of 0, 30, 100 and 300 mg/kg/day. No drug-related effects occurred on survival, appearance or behavior, or occurrence, location or number of palpable masses. Average food consumption, food efficiency and hematologic values also were apparently unaffected. Statistically significantly low body weights were observed in the 100 and 300 mg/kg/day mice. The plasma concentrations of NS-21 and its active metabolite, RCC-36, in the treated groups were increased in a dose-dependent manner. Histopathological examinations disclosed midzonal hepatocellular vacuolization compatible with lipid vacuoles in both sexes at the 300 mg/kg/day dose level. There were no test article-related effects on the incidence or type of neoplastic lesions. In conclusion, under the conditions of this study, no oncogenic effects were evident in B6C3F1 mice when NS-21 was administered in the diet in concentrations to produce an intake of up to 300 mg/kg/day for 78 weeks.
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PMID:Seventy-eight-week dietary carcinogenicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in mice. 917 Jun 15

The oncogenic potential of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was assessed when it was administered in the diet of Charles River Fischer-344 rats for 2 years in dosages of 0, 10, 30 and 100 mg/kg/day. No drug-related effects occurred on survival, appearance or behavior, or occurrence, location or number of palpable masses. Food efficiency and hematologic values also were apparently unaffected. Statistically significantly low mean weekly body weights and average food consumption values were observed in the all dose groups. The plasma concentrations of NS-21 and its active metabolite, RCC-36, in the treated groups were increased in a dose-dependent manner. Histopathological examinations disclosed test article-related increases in the incidence of periportal hypertrophy and midzonal hepatocellular vacuolization in the livers of the 100 mg/kg/day animals. There were no test article-related effects on the incidence or type of neoplastic lesions. In conclusion, under the conditions of this study, no oncogenic effects were evident in Fischer-344 rats when NS-21 was administered in the diet in concentrations to produce an intake of up to 100 mg/kg/day for 2 years.
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PMID:Two-year dietary carcinogenicity study of (+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in rats. 917 Jun 16

An antigenicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in Hartley guinea pigs and BALB/cAnN mice. The following results were obtained. No active systemic anaphylaxis reactions were found in guinea pigs immunized by subcutaneous injection of NS-21 alone or in combination with Freund's complete adjuvant (FCA). No 24-hr heterologous passive cutaneous anaphylaxis reactions were elicited in rats by sera from mice immunized by intraperitoneal injection of NS-21 alone or in combination with 3% aluminum hydroxide gel. No passive hemagglutination reactions were elicited by sera from mice immunized by subcutaneous injection of NS-21 in combination with FCA. These results show that NS-21 has no antigenicity under the present experimental conditions.
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PMID:[Antigenicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence]. 917 Jun 17

We studied the urological aspects of the tethered cord syndrome before and after untethering. Presenting urological symptoms include incontinence in 10 (38%), voiding difficulty in 8 (30%), stool soilage in 7 (27%), pollakiuria in 8 (30%) and urgency and symptomatic urinary tract infection in 9 patients (34%). All patients had presacral skin lesion. In all cases cystometric study was done preoperatively and postoperatively. In this study, we noted that the overall clinical symptomatology and urodynamic parameters improved in 67.0% and 49.0%, respectively. Although no patient became normal after surgery, we found better improvement in patients treated promptly by neurosurgical intervention.
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PMID:The outcome of urological findings in operated tethered cord patients. 924 43

Lower urinary tract symptoms and disorders are prevalent and bothersome in the rapidly growing aging population. Common symptoms include urinary frequency, nocturia, urgency, and incontinence. Among older men, symptoms of voiding difficulty, such as hesitancy, slow stream, and straining, are also common. A variety of aging changes, as well as age-associated disease, predispose older people to the development of lower urinary tract symptoms. Medications used to treat conditions outside the lower urinary tract also can contribute to these symptoms. Physicians and other health professionals should routinely ask specific questions about lower urinary tract symptoms in their older patients and evaluate them thoroughly when they are present.
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PMID:Aging and the lower urinary tract. 933 58

Medications to treat lower urinary tract dysfunction in older adults are selected to alter specific physiologic parameters. Pharmacotherapy alone results in modest clinical improvement. Because of the high prevalence of adverse drug reactions and polypharmacy in the geriatric population, medication should be used for those conditions that do not respond sufficiently to behavioral therapy. For stress incontinence, medications with alpha-adrenergic agonist properties are the mainstay of pharmacotherapy because they increase outlet resistance. Pharmacotherapy of urinary frequency and urge incontinence aims to decrease detrusor irritability and increase bladder capacity by inhibiting cholinergic stimulation of the bladder. In addition to these medications, in postmenopausal women, estrogen seems to have an additive effect for both urge and stress incontinence. More randomized, placebo-controlled, double-blinded clinical trials are needed that compare various pharmacologic agents and combinations, as well as pharmacotherapy with other forms of treatment for lower urinary tract dysfunction.
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PMID:Pharmacologic treatment of lower urinary tract dysfunction in geriatric patients. 933 66

We constructed a pubovaginal sling using the Gore-tex Soft Tissue Patch and 2-0 polytetrafluoroethylene (PTFE) suspension suture and placed it in 122 consecutive incontinent women with urethral hypermobility and/or intrinsic sphincter deficiency. We performed a retrospective outcome analysis using a questionnaire-based telephone survey. The mean follow-up period was 24.4 months. Stress incontinence was cured in 88% of patients (equally effective in type II and type III incontinence), de novo postoperative urinary frequency occurred in 32% of cases, and preoperative urinary frequency resolved postoperatively in 51% of patients. Significant urinary obstruction occurred in 5% of patients. Vaginal granulation tissue with exposed sling occurred in 4% of patients. There was no urethral or bladder erosion. The treatment of female stress incontinence with a PTFE sling is effective and durable with minimal complications. Furthermore, this technique addresses many of the presumed technical shortcomings of endoscopic needle suspensions.
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PMID:The Gore-tex sling procedure for female sphincteric incontinence: indications, technique, and results. 937 80

The aim of this study was to analyse the effects of radical hysterectomy on urodynamic parameters (urethral resistance, functional urethral length, pressure gradients, bladder capacity, residual urine volume, stress urethral pressure profile), on bladder function (detrusor pressure, urgency sensation, flow pattern) and on continence. We reviewed 33 patients who underwent a radical abdominal hysterectomy as described by Wertheim-Meigs-Okabayashi. They were investigated by urodynamic examination preoperatively and 4 resp. 8 months postoperatively. To ascertain bladder dysfunctions and changes of urinary continence as a long term effect of operative procedure a standardized questionnaire was mailed to all patients. The radical abdominal hysterectomy did not alter significantly the urethral resistance, functional urethral length or pressure gradients. The maximal bladder capacity decreased postoperatively from 615 ml to 503 ml (SD 148.5: p = 0.04). The maximal urine flow and the detrusor pressure decreased temporarily (p = 0.01). The residual urinary increased five-fold (p = 0.01) and the first sensation of bladder filling was recognized later, at 4 as at 8 months postoperatively (p = 0.07). Preoperatively 75% of the patients voided by detrusor activity, postoperatively only 16%. 20% of the preoperative continent patients were incontinent during the second measurement (8 months postoperatively). 47% of the previous continent patients complained about incontinence in the questionnaire (4 years postoperatively). Although the patients complained about pollakiuria, urgency (60%) and urge incontinence (39%), 73% of the patients were content with their situation. Although the urethral pressure profile showed no significant alteration, the clinical situation and the deterioration of the parameters bladder capacity, residual urine and flow pattern verified the postoperative disturbances of the lower urinary tract function and the negative effects on continence behaviour.
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PMID:[Urodynamic parameters and continence after radical Wertheim-Meigs-Okabayashi hysterectomy]. 943 26


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