Urinary Tract Urothelium Research Articles

Additive Effects of Arsenic and Aristolochic Acid in Chemical Carcinogenesis of Upper Urinary Tract Urothelium.

Aristolochic acids (AA) and arsenic are chemical carcinogens associated with urothelial carcinogenesis. Here we investigate the combined effects of AA and arsenic toward the risk of developing upper tract urothelial carcinoma (UTUC). Hospital-based (n = 89) and population-based (2,921 cases and 11,684 controls) Taiwanese UTUC cohorts were used to investigate the association between exposure to AA and/or arsenic and the risk of developing UTUC. In the hospital cohort, AA exposure was evaluated by measuring aristolactam-DNA adducts in the renal cortex and by identifying A>T TP53 mutations in tumors. In the population cohort, AA exposure was determined from prescription health insurance records. Arsenic levels were graded from 0 to 3 based on concentrations in well water and the presence of arseniasis-related diseases. In the hospital cohort, 43, 26, and 20 patients resided in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Aristolactam-DNA adducts were present in >90% of these patients, indicating widespread AA exposure. A>T mutations in TP53 were detected in 28%, 44%, and 22% of patients residing in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Population studies revealed that individuals who consumed more AA-containing herbs had a higher risk of developing UTUC in both arseniasis-endemic and nonendemic areas. Logistic regression showed an additive effect of AA and arsenic exposure on the risk of developing UTUC. Exposure to both AA and arsenic acts additively to increase the UTUC risk in Taiwan. This is the first study to investigate the combined effect of AA and arsenic exposure on UTUC.

The impact of cathelicidin, the human antimicrobial peptide LL-37 in urinary tract infections

BackgroundThe defense mechanisms of the urinary tract are attributed mainly to the innate immune system and the urinary tract urothelium which represent the first line of defense against invading pathogens and maintaining sterility of the urinary tract. There are only a few publications regarding cathelicidin (LL-37) and a urinary tract infection (UTI). This study was done to investigate the plasma and urine levels of human LL-37 in patients with UTI.MethodsA case-control study was conducted at Omdurman Hospital, Sudan during the period from August 2014 to May 2017. The cases were patients with confirmed UTI and the controls were healthy volunteers without UTI. Sociodemographic and clinical data were obtained from each participant using questionnaires. Urine cultures and antimicrobial susceptibility were tested. Plasma and urine levels of LL-37 were determined using an enzyme-linked immunosorbent assay (ELISA) kit. SPSS (version 16.0) was used for analyses.ResultsCases and controls (87 in each arm) were matched according to their basic characteristics. Compared with controls, the median (inter-quartile) LL-37 level in plasma [2.100 (1.700–2.700) vs. 1.800 (1.000–2.200) ng/ml, P = 0.002] and in urine [0.900 (0.300–1.600) vs. 0.000 (0.000–1.000) ng/mg creatinine, P < 0.001] was significantly higher in cases. There was no significant difference in the median plasma [2.1 (1.7–2.9) vs. 2.000 (1.700–2.400) ng/ml, P = 0.561] and urine [0.850 (0.275–2.025) vs. 0.900 (0.250–1.350) ng/mg creatinine, P = 0.124]. The uropathogenic Escherichia coli (UPEC) was the predominant isolate, n = 38 (43.7%). LL-37 levels between the E. coli isolates and the other isolated organisms. There was no significant correlation between plasma and urine LL-37 levels (r = 0.221), even when the data of the cases were analyzed separately.ConclusionLL-37 is notably increased among patients with UTI compared with normal control subjects. Severity of UTI increases the levels of LL-37. The increased level was not only in the patient’s urine, but has also been observed in the patient’s plasma. Detection of increased levels of LL-37 could help to differentiate subjects with suspected UTI. Accordingly, LL-37 could act as a good marker for diagnosing UTIs.

Technique of thulium laser in managing bladder cuff in nephroureterectomy for upper urinary tract urothelium carcinoma

To explore the application of thulium laser (2 µm laser) in managing bladder cuff in nephroureterectomy for upper urinary tract urothelium carcinoma (UUT-UC). The medical records of 56 patients undergoing nephroureterectomy at our hospital were reviewed retrospectively. The operative indicators, oncologic outcomes and clinicopathologic data were compared among the groups of open surgery (Group A), electric coagulation (Group B) and thulium laser technique (Group C). Furthermore a model of burst pressure measurement was built to measure the different burst pressures of sealing distal ureter. The follow-up results: when the indicators of operative duration, intraoperative blood loss volume, removal time of drainage tube, removal time of catheter and hospital stays were compared among three groups, Group A had no statistical differences with Group B/C in terms of removal time of drainage tube and removal time of catheter. But significant statistical differences existed in terms of operative duration, intraoperative blood loss volume and hospital stays ((232 ± 52) vs (148 ± 47) and (130 ± 49) min, (358 ± 81) vs (136 ± 74) and (145 ± 70) ml, (13 ± 3) vs (11 ± 4) and (10 ± 3) d, all P < 0.05). No statistical differences existed between Groups B and C in terms of all the above indicators. Burst pressure measurement results: no statistical differences existed between Group C and B ((116 ± 21) vs (139 ± 32) cm H2O, P > 0.05). For the surgical treatment of UUT-UC, thulium laser technique has no difference in operation indicators and oncologic outcomes compared to open surgery. Besides, it has the advantages of improved spatial beam quality and more precise tissue incision.

UT-B1 urea transporter is expressed along the urinary and gastrointestinal tracts of the mouse

Selective transporters account for rapid urea transport across plasma membranes of several cell types. UT-B1 urea transporter is widely distributed in rat and human tissues. Because mice exhibit high urea turnover and are the preferred species for gene engineering, we have delineated UT-B1 tissue expression in murine tissues. A cDNA was cloned from BALB/c mouse kidney, encoding a polypeptide that differed from C57BL/6 mouse UT-B1 by one residue (Val-8-Ala). UT-B1 mRNA was detected by RT-PCR in brain, kidney, bladder, testis, lung, spleen, and digestive tract (liver, stomach, jejunum, colon). Northern blotting revealed seven UT-B1 transcripts in mouse tissues. Immunoblots identified a nonglycosylated UT-B1 protein of 29 kDa in most tissues and of 36 and 32 kDa in testis and liver, respectively. UT-B1 protein of gastrointestinal tract did not undergo N-glycosylation. Immunohistochemistry and in situ hybridization localized UT-B1 in urinary tract urothelium (papillary surface, ureter, bladder, and urethra), prominently on plasma membranes and restricted to the basolateral area in umbrella cells. UT-B1 was found in endothelial cells of descending vasa recta in kidney medulla and in astrocyte processes in brain. Dehydration induced by water deprivation for 2 days caused a tissue-specific decrease in UT-B1 abundance in the urinary bladder and the ureter.