High isoprostane level in cardinal ligament-derived fibroblasts and urine sample of women with uterine prolapse.

We studied the isoprostane level, a well-recognised biomarker of oxidative stress, from women with uterine prolapse and age-matched female controls without prolapse. Cardinal ligament-derived fibroblasts explanted from women with prolapse showed a significant increased level of isoprostane production (P < 0.05) compared with those derived from controls. This concurs with elevated urinary isoprostane levels identified among women with prolapse (P < 0.001) compared with controls. In addition, the matrix metalloproteinase 2 mRNA was significantly increased (P= 0.004) among women with uterine prolapse. Parallel findings of increased isoprostane in cardinal ligament and urine sample among women with prolapse suggest that oxidative stress might be involved in the development of uterine prolapse.

Quantitative determination of progesterones and corticosteroids in human urine using gas chromatography/mass spectrometry: application to pelvic organ prolapse patients.

A quantitative analytical method using gas chromatography/mass spectrometry (GC/MS) to determine urinary concentrations of eight progesterones and corticosteroids has been developed. After enzymatic hydrolysis with beta-glucouronidase/arylsulfatase, urine samples were extracted by simple one-step solid-phase extraction. Obtained extracts were derivatized with a mixture of N-methyl-N-(trimethylsilyl)trifluoroacetamide/ammonium iodide/dithiothreitol and determined by GC/MS in selected ion monitoring mode to increase the sensitivity. d(4)-Cortisol and d(9)-progesterone were used as internal standards for two different steroid groups. The linear correlation coefficient was in the range of 0.9913 to 0.9998 and recoveries were over 80% for all compounds. Precision and accuracy were in the range of 0.9-18.1 and 84.1-118.7%, respectively. The limit of quantitation (LOQ) was 10 ng/mL for 11-deoxycorticosterone and 21-deoxycortisol and 5 ng/mL for all other analytes. The developed method was successfully applied on pelvic organ prolapsed patients (n = 10, age: 67.9 +/- 4.9) and post-menopausal (n = 10, age: 63.6 +/- 5.5) control women. Urinary levels of most progesterones and corticosteroids except 11-deoxycorticosterone decreased but only that of 17 alpha-hydroxyprogesterone significantly decreased in patients compared with the control groups. Thus, it is concluded that progesterones could be a factor in the pathogenesis of pelvic organ prolapse, and, among them, 17 alpha-hydroxyprogesterone could be a biomarker for pelvic organ prolapse.

Steroid hormone metabolism in women with pelvic organ prolapse.

OBJECTIVE: To identify whether endogenous steroid hormone metabolism in women with pelvic organ prolapse (POP) is different from that in normal women and the relationship between endogenous steroid hormone metabolites and POP stage. STUDY DESIGN: Twenty postmenopausal women who were clinically diagnosed as having POP and 20 volunteer postmenopausal women without prolapse were included in the study. We compared the urinary profiles of endogenous steroids between the two groups and investigated the relationship between urinary profiles of endogenous steroids and degree of prolapse. Urinary profiles of endogenous steroids were assayed by gas chromatography/mass spectrometry. RESULTS: The ages of the patients and control group were 64.6 +/- 6.5 and 63.5 +/- 3.9 years, and the body mass index was 23.96 +/- 3.14 and 24.11 +/- 2.73 kg/m2 in patients and normal subjects, respectively. The number of patients were 4 at stage I, 4 at stage II, 6 at stage III and 6 at stage IV. 5-Androstene-3 beta,16 beta,17 beta-triol (5-AT), 11 beta-hydroxy an and 17 beta-estradiol were significantly increased in the POP group as compared with the control group (0.76 +/- 0.67 vs. 0.06 +/- 0.03 mumol/g creatinine, P = .002, 1.16 +/- 0.83 vs. 0.65 +/- 0.23 mumol/g creatinine, P = .04; and 15.08 +/- 9.81 vs. 8.53 +/- 6.19 mumol/g creatinine, P = .04). However, tetrahydrocortisone (THE) was significantly increased in the control group as compared with the patient group (9.80 +/- 6.21 vs. 5.22 +/- 4.89 mumol/g creatinine, P = .04). Androgen metabolites 5-AT and THE significantly correlated with the pelvic organ prolapse quantitation (POP-Q) stage (R = .418; P = .027; R = .46, P = .016). Among the estrogen metabolites, 17 beta-estradiol correlated with POP-Q stage, but not significantly so (R = .38, P = .05), and the 17 beta-estradiol/estrone ratio weakly correlated with stage (R = .14, P = .49). CONCLUSION: The metabolites of endogenous steroid hormones could be contributing factors in the pathogenesis of POP.

Presence of urokinase-type plasminogen activator receptor in urine of cancer patients and its possible clinical relevance.

High levels of urokinase-type plasminogen activator receptor (uPAR) are expressed in various types of cancer. Recent studies showed that cancer patients may have increased levels of soluble (s)uPAR in their serum. In the present study, we show that urine samples from healthy volunteers contain measurable amounts of suPAR. suPAR/creatinine levels from healthy controls showed only little variation over the day and were even stable during a month of continued monitoring. Importantly, urinary suPAR/creatinine levels were highly correlated with serum suPAR concentrations. Urinary suPAR levels were elevated in patients with different types of cancer. Interestingly, part of the urinary suPAR seemed to be present in a cleaved form, as has been found in tumor tissue extracts. Together with the recently established, cell migration-promoting effect of certain cleaved fragments of suPAR, the present data suggest that the measurement of urinary suPAR and/or its cleaved forms might have clinical implications.