Evaluation of the relationship of cholinergic metabolites in urine and urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To investigate differences in urine cholinergic metabolites in women with urinary urgency incontinence (UUI) and responders (R) and non-responders (NR) to anti-cholinergic medications (AC). METHODS: Patients with UUI and age-matched controls were evaluated pre- and post-treatment using OABSS, UDI-6 and IIQ-7. Controls were defined as having a cumulative OABSS of zero. Patients with UUI were treated with AC and followed for 12 weeks. Responders were those with a > 50% decrease in the total OABSS score. Urine samples were collected from all participants for evaluation. Metabolite detection was accomplished using commercial assay kits. Wilcoxon-rank sum test and Fisher's exact test were used to express differences between groups. Spearman's rho correlation coefficient was used to determine the relationship between acetylcholine (Ach), choline (Ch), acetylcholinesterase (AchE) and questionnaire scores. RESULTS: We recruited 39 with UUI and 33 controls. We found concentrations of Ch [29.0 (IQR: 24.2-42.5) µmol vs. 15.2 (IQR: 7.5-24.1) µmol] and Ach [65.8 (IQR: 30.4-101.8) nmol and 33.1 (IQR: 11.9-43.8) nmol] were higher in the UUI group compared to controls (p = 0.003 and p < 0.001, respectively] and no differences in AchE concentrations. In the UUI group, 43.6% responded to AC after 12 weeks of therapy. There were no differences in Ch or AchE levels between R and NR; Ach levels were higher in the R group [82.1 nmol (IQR: 54.8-118.1) vs. 50.3 nmol (IQR: 29.9-68.2), p = 0.007]. Ch and Ach were positively associated with pre-treatment OABSS parameters. CONCLUSIONS: Urine Ach is higher in responders to anti-cholinergic therapy, and urine cholinergic metabolites were higher in the UUI patients compared to controls.

Evaluation of Urine Choline Levels in Women With and Without Overactive Bladder Syndrome.

OBJECTIVE: The objective of this study was to determine whether levels of choline (Ch) differ in women with and without overactive bladder (OAB) symptoms. METHODS: New patients were evaluated using the overactive bladder symptom score; Medical, Epidemiologic, and Social Aspects of Aging (MESA) urgency incontinence questionnaire; and Impact Questionnaire 7 and provided a urine sample. Patients were stratified into asymptomatic controls, scoring 0 on overactive bladder symptom score and the MESA questionnaire, and patients with OAB and urgency incontinence (OAB-wet). Patients with conditions predisposing to OAB or had a history of OAB treatment were excluded. Choline detection was accomplished using a commercially available kit. Wilcoxon rank sum test and Fisher exact test were used to express differences between groups. Spearman ρ correlation was used to determine the relationship between Ch and questionnaire scores. Logistic regression was used to identify significant variables associated with OAB. RESULTS: Sixty-three women were included in the final analysis. Patients with OAB-wet were older (P = 0.001), more likely to be obese (P = 0.04), had greater apical descent (P = 0.02), were more likely to be postmenopausal (P = 0.01), and were more likely to have stress incontinence (P = 0.005). Choline was 34.8% lower in OAB compared with the controls (P = 0.014). Lower Ch levels were associated with higher MESA (Spearman ρ = -0.311, P = 0.03). After logistic regression, lower Ch (adjusted odds ratio [aOR], 0.97; 95% confidence interval [CI], 0.96-0.98), age (aOR, 1.12; 95% CI, 1.08-1.18), and body mass index (aOR, 1.09; 95% CI, 1.01-1.18) were significantly associated with OAB-wet. CONCLUSIONS: Choline levels are significantly decreased in women complaining of OAB with urgency incontinence, and lower levels are associated with higher MESA scores.

Evaluation of Choline and Acetylcholine Levels in Responders and Nonresponders to Anticholinergic Therapy for Overactive Bladder Syndrome.

OBJECTIVE: This study aimed to determine whether levels of choline (Ch) and acetylcholine (Ach) differ between responders and nonresponders to anticholinergic therapy. METHODS: Patients prescribed an anticholinergic were evaluated using the Overactive Bladder Symptom Score; Medical, Epidemiologic and Social Aspects of Aging and Incontinence Questionnaire; and Incontinence Impact Questionnaire-7. A 1-day voiding diary and a urine sample were collected. After treatment for 12 weeks, the questionnaires were administered and 1-day voiding diary was completed. Levels of Ach and Ch were measured by liquid chromatography with tandem mass spectrometry. Subjects were divided into responders and nonresponders. Wilcoxon rank sum test and Fisher exact test were used to express differences between groups. Spearman ρ correlation coefficient was used to determine the relationship between Ach and Ch and symptom severity, patient demographics, and questionnaire scores. RESULTS: Thirty-one women were included in the analysis. The treatment response rate was 48.8%. The median age was 67 years (interquartile range, 50-76 years), and median body mass index was 32.3 kg/m2 (27.5-40.6 kg/m2), with 41.2% having an additional complaint of stress incontinence. There were no significant differences in symptom severity or questionnaire scores between groups.The median Ch and Ach levels were higher in responders (28.6 vs 9.2 µL, P = 0.04) and (83.1 vs 18.7 nL, P = 0.02), respectively. Levels of both Ch and Ach had moderate positive correlations with the Medical, Epidemiologic and Social Aspects of Aging and Incontinence Questionnaire urgency urinary incontinence score (ρ = 0.533 [P = 0.002] and ρ = 0.453 [P = 0.01], respectively). CONCLUSION: In women with overactive bladder, urinary Ach and Ch levels are higher in responders to anticholinergic therapy compared with nonresponders.

Plasma proteome analysis reveals overlapping, yet distinct mechanisms of immune activation in chronic HCV and HIV infections.

BACKGROUND: HIV infection contributes to accelerated rates of progression of liver fibrosis during hepatitis C virus (HCV) infection, and HCV liver disease contributes to mortality during HIV infection. Although mechanisms underlying these interactions are not well known, soluble and cellular markers of immune activation associate with disease progression during both infections. METHODS: We identified proteins varying in expression across the plasma proteomes of subjects with untreated HIV infection, untreated HCV infection with low aspartate transaminase/platelet ratio index, untreated HCV infection with high aspartate transaminase/platelet ratio index, HIV-HCV coinfection, and controls. We examined correlations between dysregulated proteins and markers of immune activation to uncover biomarkers specific to disease states. RESULTS: We observed the anticipated higher frequencies of HLA-DRCD38CD4 and CD8 T cells, higher serum soluble CD14 levels, and higher serum interleukin-6 levels for HCV- and HIV-infected groups compared with controls. Plasma proteome analysis identified 2297 peptides mapping to 227 proteins, and quantitative analysis of peptide intensity identified significant changes in 85 proteins across the 5 groups. Abundance for 7 of these proteins was validated by enzyme-linked immunosorbent assay. Forty-three of these proteins correlated with markers of immune activation, including at least 2 proteins that may directly drive T-cell activation. As a functional validation, we tested the enzymatic pathway product (lysophosphatidic acid, LPA) of one such protein, ecotonucleotide pyrophosphatase/phosphodiesterase-2, for ability to activate T cells in vitro. LPA activated T cells to express CD38 and HLA-DR. CONCLUSIONS: These data indicate that elevated levels of ecotonucleotide pyrophosphatase/phosphodiesterase-2 and LPA during advanced HCV disease may play a role in exacerbating immune activation during HCV-HIV coinfection.

Mass drug administration trial to eliminate lymphatic filariasis in Papua New Guinea: changes in microfilaremia, filarial antigen, and Bm14 antibody after cessation.

Laboratory tools to monitor infection burden are important to evaluate progress and determine endpoints in programs to eliminate lymphatic filariasis. We evaluated changes in Wuchereria bancrofti microfilaria, filarial antigen and Bm14 antibody in individuals who participated in a five-year mass drug administration trial in Papua New Guinea. Comparing values before treatment and one year after four annual treatments, the proportion of microfilaria positive individuals declined to the greatest degree, with less marked change in antibody and antigen rates. Considering children as sentinel groups who reflect recent transmission intensity, children surveyed before the trial were more frequently microfilaria and antibody positive than those examined one year after the trial stopped. In contrast, antigen positive rates were similar in the two groups. All infection indicators continued to decline five years after cessation of mass drug administration; Bm14 antibody persisted in the greatest proportion of individuals. These data suggest that Bm14 antibody may be a sensitive test to monitor continuing transmission during and after mass drug administration aimed at eliminating transmission of lymphatic filariasis.