Introduction: A nationwide survey was conducted to investigate the prevalence of upper urinary calculi in Taiwan. Materials and Methods: A postal questionnaire was mailed to 27,758 people, 0.2% of the adults in Taiwan. Results: Of the 4,588 valid respondents, 440 had at least one episode of upper urinary calculus disease. The overall prevalence was 9.6% (14.5% in males and 4.3% in females). Men were more prone to nephrolithiasis than women (age-adjusted prevalence of 12.2% in men and 3.1% in women, p = 0). The ‘stone belt’ was localized in the Midwest region of Taiwan. A gender- and age-adjusted multivariate analysis revealed that alcohol consumption and family history of kidney stone were significant risk factors for stone occurrence. Compared with general population, the odds ratios for stone disease in inhabitants whose father, mother and both parents with stone history were 3.44 [95% confidence interval (CI), 2.33–5.07], 4.79 (95% CI, 2.85–8.07) and 10.40 (95% CI, 3.75–28.84), respectively. The subtropical temperature and gradually higher socioeconomic standards of living may contribute to the high prevalence. Inhabitants in the Midwest region have higher risk to develop stones. Conclusions: Further studies are needed to investigate the exact cause of these regional variations of stone prevalence. Nevertheless, the present study provides an additional piece of information on worldwide epidemiology of urolithiasis.

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Mast cells, neutrophils, and macrophages are important inflammatory cells that have been implicated in the pathogenesis of acute and chronic inflammatory diseases. To explore a novel antiinflammatory agent, we have synthesized two types of acridines, 9-anilinoacridine and 9-phenoxyacridine derivatives, for evaluation on the grounds that acridine is a versatile heterocycle possessing a wide variety of biological properties. The title compounds were synthesized by reaction of 9-chloroacridine with appropriate Ar-NH(2) and Ar-OH, and their antiinflammatory activities on inhibitory effects on the activation of mast cells, neutrophils, and macrophages were studied. Three acridine derivatives 4, 10, and 11 were proved to be more potent than the reference inhibitor mepacrine for the inhibition of rat peritoneal mast cell degranulation with similar IC(50) values (16-21 microM). Compound 3 also showed potent inhibitory activity (IC(50) = 8.2 and 4.4 microM, respectively) for the secretion of lysosomal enzyme and beta-glucuronidase from neutrophils. Moreover, compounds 5 and 9 were shown to be efficacious inhibitors of TNF-alpha production in macrophage-like cell lines RAW 264.7. Compounds 2 and 12 were the potent inhibitors of TNF-alpha production in murine microglial cell lines N9. To further explore the cytotoxic properties of these acridine derivatives, (E)-12 was selected for NCI's in vitro disease-oriented tumor cells screen. The results indicated that this compound had no significant cytotoxicity with a mean GI(50) of 58.0 microM. These results indicated that the antiinflammatory effects of acridine derivatives were mediated, at least in part, through the suppression of chemical mediators released from mast cells, neutrophils, and macrophages and that these compounds have the potential to be novel antiinflammatory agents with no significant cytotoxicity.

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The present report describes the synthesis and antiproliferative evaluation of certain indolo[3,2-c]quinoline derivatives. For the C(6) anilino-substituted derivatives, (11H-indolo[3,2-c]quinolin-6-yl)phenylamine (6a) was inactive. Structural optimization of 6a by the introduction of a hydroxyl group at the anilino-moiety resulted in the enhancement of antiproliferative activity in which the activity decreased in an order of para-OH, 7a>meta-OH, 8a>ortho-OH, 9a. For the C(6) alkylamino-substituted derivatives, 11a, 12a, 13a, 14a, and 15a exhibited comparable antiproliferative activities against all cancer cells tested and the skin Detroit 551 normal fibroblast cells. Three cancer cells, HeLa, A549, and SKHep, are very susceptible with IC(50) of less than 2.17 microM while PC-3 is relatively resistant to this group of indolo[3,2-c]quinolines. For the 2-phenylethylamino derivatives, compound 20a is active against the growth of HeLa with an IC(50) of 0.52 microM, but is less effective against the growth of Detroit 551 with an IC(50) of 19.32 microM. For the bis-indolo[3,2-c]quinolines, N,N-bis-[3-(11H-indolo[3,2-c]quinolin-6-yl)aminopropyl]amine hydrochloride (25) is more active than its N-methyl derivative 26 and the positive Doxorubicin. Mechanism studies indicated 25 can induce caspase-3 activation, gamma-H2AX phosphorylation, cleavage of poly(ADP-ribose)polymerase and DNA fragmentation. These results provide evidence that DNA, topo I, and topo II are the primary targets of indolo[3,2-c]quinoline derivatives and that consequently inhibits proliferation and causes apoptosis in cancer cells.

Background Inconsistent results for coffee consumption and bladder cancer (BC) risk have been shown in epidemiological studies. This research aims to increase the understanding of the association between coffee consumption and BC risk by bringing together worldwide case-control studies on this topic. Methods Data were collected from 13 case-control comprising of 5,911 cases and 16,172 controls. Pooled multivariate odds ratios (ORs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel logistic regression models. Furthermore, linear dose-response relationships were examined using fractional polynomial models. Results No association of BC risk was observed with coffee consumption among smokers. However, after adjustment for age, gender, and smoking, the risk was significantly increased for never smokers (ever vs. never coffee consumers: OR model2 1.30, 95% CI 1.06-1.59; heavy (> 4 cups/day) coffee consumers vs. never coffee consumers: OR model2 1.52, 95% CI 1.18-1.97, p trend = 0.23). In addition, dose-response analyses, in both the overall population and among never smokers, also showed a significant increased BC risk for coffee consumption of more than four cups per day. Among smokers, a significant increased BC risk was shown only after consumption of more than six cups per day. Conclusion This research suggests that positive associations between coffee consumption and BC among never smokers but not smokers.

BackgroundLow-abundance proteins are difficultly observed on the two-dimensional gel electrophoresis (2-DE) maps of urine proteome, because they are usually obscured by high-abundance proteins such as albumin and immunoglobulin. In this study, a novel fractionation method was developed for enriching low-abundance proteins by removing high-abundance proteins and progressive elution with salts of various concentrations.ResultsStepwise weak anion exchange (WAX) chromatography, which applied DEAE-Sephacel resin with non-fixed volume elution, was used to fractionate urine proteome prior to performing 2-DE. Urine proteome was separated into four fractions by progressively eluting the column with 0 M, 50 mM, 100 mM, and 1 M NaCl solutions. Most of the heavy and light immunoglobulin chains appeared in the eluent. After the high-abundance proteins were removed, various low-abundance proteins were enriched and could be easily identified. The potential of this method for obtaining diversified fractionations was demonstrated by eluting the column separately with Na2SO4 and MgCl2 solutions. The 2-DE maps of the fractions eluted with these different salt solutions of identical ionic strength revealed markedly different stain patterns.ConclusionThe present study demonstrated that this fractionation method could be applied for purposes of enriching low-abundance proteins and obtaining diversified fractionations of urine, and potentially other proteomes.