Urodynamic and gait analyses in multiple system atrophy.

BACKGROUND: Limited attention has been paid to the relationship between bladder dysfunction and motor disorder in multiple system atrophy (MSA). OBJECTIVE: We aimed to correlate pressure-flow urodynamic parameters with video-gait analysis parameters in MSA. METHODS: We recruited 34 patients with MSA: 20 men, 14 women; age 64.0 + - 7.9 years; disease duration 2 years (1-4 years). Nineteen cases had the cerebellar form, and 15 had the parkinsonian form; the patients were taking levodopa 300 mg/day (100-400 mg). All patients underwent pressure-flow urodynamics (parameters: detrusor overactivity [noted in 72%] and Watts factor) and video-gait analysis (parameters: time and the number of strides taken to walk 5 m (simple task) and time for timed up and go (complex task). Statistical analysis was done using Student's t-test to analyze the relation between detrusor overactivity and gait, and Spearman's rank correlation coefficient test to analyze the relation between the remaining parameters and gait. RESULTS: We found no relation between filling-phase urodynamics (detrusor overactivity) and video-gait analysis parameters. Also, we found no relation between voiding-phase urodynamics (Watts factor, reflecting detrusor power) and all three video-gait analysis parameters in our MSA patients. CONCLUSION: The fact that neither detrusor overactivity nor the Watts factor was related with motor disorders in the present study suggests that bladder dysfunction occurs independently from motor disorder in MSA.

Imidafenacin on bladder and cognitive function in neurologic OAB patients.

OBJECTIVE: To explore imidafenacin's effects on bladder and cognitive function in neurologic overactive bladder (OAB) patients. METHODS: Sixty-two subjects (25 men, 37 women; mean age 70 years (25-86) with OAB due to neurologic diseases) were enrolled in the study. We conducted a urinary symptom survey and cognitive tests (MMSE, FAB, ADAS-cog) in all patients. We performed urodynamics in 35 patients and measured real-time near-infrared spectroscopy (NIRS)-urodynamics in eight patients before and after the administration of imidafenacin, an anticholinergic agent, for 3 months at 0.2 mg/day. RESULTS: Imidafenacin significantly ameliorated urinary urgency, nighttime urinary frequency, and quality of life index (p < 0.05). Three cognitive measures did not change significantly. Urodynamics showed increased bladder capacity (p < 0.05) but detrusor overactivity did not change significantly. NIRS showed that the subtraction of oxyhemoglobin between the start of filling and the first sensation increased in the bilateral prefrontal area but without statistical significance. CONCLUSIONS: Imidafenacin ameliorated bladder sensation without cognitive worsening, with a trend of prefrontal activation. Regarding cognitive function, imidafenacin is safely used in OAB patients due to neurologic diseases. SYNOPSIS: In order to explore imidafenacin (anticholinergic agent)'s effects on bladder and brain function, we performed urinary questionnaire, cognitive tests, urodynamics and near-infrared spectroscopy (selected cases) in 62 overactive bladder (OAB) patients due to various neurologic diseases. As a result, imidafenacin ameliorated bladder sensation without cognitive worsening, with a trend of prefrontal activation. Imidafenacin seems safe in treating OAB patients due to neurologic diseases.

Inhibitory control task is decreased in vascular incontinence patients.

OBJECTIVE: 'Vascular incontinence' is a part of elderly incontinence due to cerebral white matter change (WMC). We studied the relationship between performance on several cognitive tasks and urodynamic detrusor overactivity (DO) in patients with vascular incontinence. METHODS: We recruited 40 patients with lower urinary tract symptoms due to WMC [20 male, 20 female; mean age 77 years (60-89 years)]. Other neurologic, urologic, and systemic causes of LUT dysfunction were excluded. All patients underwent urodynamics tests and two sets of cognitive tasks, i.e., the Mini-Mental State Examination (MMSE) (general cognitive tasks), and the Frontal Assessment Battery (FAB) (frontal lobe tasks). RESULTS: The most common urinary symptom was urinary urgency (27 patients), followed by urinary incontinence (26) and nocturnal urinary frequency (25). The urodynamic testing revealed DO in 22 patients. The cognitive testing revealed that the patients' mean MMSE score was 25.8 (range 15-30), and their mean FAB score was 13.6 (4-18). There was no relationship between DO and the total MMSE or FAB score, but our analysis of the relationship between DO and the six subdomains of the FAB (conceptualization, mental flexibility, programming, sensitivity to interference, inhibitory control, and environmental autonomy) revealed a significant relationship between DO and the inhibitory control task (p < 0.005). CONCLUSIONS: The results of the present study showed that performance on an inhibitory control task is decreased in vascular incontinence patients with DO.

Weak detrusor contractility correlates with motor disorders in Parkinson's disease.

Limited attention has been paid to the relationship between urinary symptoms or urodynamic findings and motor disorders in Parkinson's disease (PD). We aimed to correlate pressure-flow urodynamic parameters with video-gait analysis parameters in PD. We recruited 41 patients with PD (25 men and 16 women; age, 70.6 ± 8.5 years; H & Y motor grading: 2 [range, 1-3]; disease duration: 4 years [range, 1-7]; taking levodopa 300 mg/day [range, 100-400]). All patients underwent pressure-flow urodynamics (parameters: first sensation, bladder capacity, detrusor overactivity [noted in 24 patients], and Watts factor [WF]) and video-gait analysis (parameters: time and number of strides for 5-m gait [simple task] and time for timed up and go [complex task]). Statistical analysis was made by Mann-Whitney's U-test for analyzing the relation between detrusor overactivity and gait as well as Spearman's rank-correlation coefficient test for analyzing the relation between the remaining parameters and gait. We found no relation between filling-phase urodynamics (detrusor overactivity, first sensation, and bladder capacity) and video-gait analysis parameters. By contrast, we found a significant relation between voiding-phase urodynamics (WF, reflecting detrusor power) and all three video-gait analysis parameters (reflecting lower-half bradykinesia and loss of postural reflex) in our PD patients (P < 0.01). The close relation between the WF and motor disorders in the present study suggests that, though clinically mild, a weak detrusor in PD might have a central origin. We should follow postvoid residual volume carefully in PD patients with advanced gait disorder, because postvoid residual volume might increase in such patients.

Engineering the substrate specificity of Alcaligenes D-aminoacylase useful for the production of D-amino acids by optical resolution.

D-Aminoacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6 (AxD-NAase) offers a novel biotechnological application, the production of D-amino acid from the racemic mixture of N-acyl-DL-amino acids. However, its substrate specificity is biased toward certain N-acyl-D-amino acids. To construct mutant AxD-NAases with substrate specificities different from those of wild-type enzyme, the substrate recognition site of the AxD-NAase was rationally manipulated based on computational structural analysis and comparison of its primary structure with other D-aminoacylases with distinct substrate specificities. Mutations of amino acid residues, Phe191, Leu298, Tyr344, and Met346, which interact with the side chain of the substrate, induced marked changes in activities toward each substrate. For example, the catalytic efficiency (k(cat)/K(m)) of mutant F191W toward N-acetyl-D-Trp and N-acetyl-D-Ala was enhanced by 15.6- and 1.5-folds, respectively, compared with that of the wild-type enzyme, and the catalytic efficiency (k(cat)/K(m)) of mutant L298A toward N-acetyl-D-Trp was enhanced by 4.4-folds compared with that of the wild-type enzyme. Other enzymatic properties of both mutants, such as pH and temperature dependence, were the same as those of the wild-type enzyme. The F191W mutant in particular is considered to be useful for the enzymatic production of D-Trp which is an important building block of some therapeutic drugs.