Combined with a high-cholesterol diet, endothelial injury of iliac arteries induced arterial occlusive disease in the downstream vessels and consequent bladder ischemia in rats. This model of chronic bladder ischemia showed detrusor overactivity manifested as an increase in voiding frequency.
Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10−5; allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10−11). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10−4). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10−18). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10−7) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension.
TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca(2+) release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca(2+) release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca(2+) sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP(3)Rs) evokes global Ca(2+) transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca(2+) influx, and adversely enhanced IP(3)R-mediated Ca(2+) transients by overloading Ca(2+) stores in VSMCs. Moreover, association analysis identified single-nucleotide polymorphisms (SNPs) around the human TRIC-A gene that increase hypertension risk and restrict the efficiency of antihypertensive drugs. Therefore, TRIC-A channels contribute to maintaining blood pressure, while TRIC-A SNPs could provide biomarkers for constitutional diagnosis and personalized medical treatment of essential hypertension.
Abbreviations & AcronymsAbstract: Robot-assisted radical prostatectomy has been shown to have comparable and possibly improved postoperative continent rates compared with retropubic and laparoscopic radical prostatectomy. However, postoperative urinary incontinence has remained one of the most bothersome postoperative complications. The basic concept of the intraoperative technique to improve postoperative urinary continence is to maintain as normal anatomical and functional structure in the pelvis as possible. Therefore, improved knowledge of the normal structure in the pelvis should lead to a greater understanding of the pathophysiology of urinary incontinence, and further development of intraoperative techniques to improve the outcomes of urinary continence. It might be necessary to carry out three steps to realize improvement of the early return of urinary continence after robot-assisted radical prostatectomy: (i) preservation (bladder neck, neurovascular bundle, puboprostatic ligament, pubovesical complex, and/or urethral length, etc.); (ii) reconstruction (posterior and/or anterior reconstruction, and/or reattachment of the arcus tendineus to the bladder neck, etc.); and (iii) reinforcement (bladder neck plication and/or sling suspension, etc.). On the basis of these steps, further modifications during robot-assisted radical prostatectomy should be developed to improve urinary continence and quality of life after robot-assisted radical prostatectomy.
The aim of this study was to elucidate risk factors associated with postoperative febrile UTI after URS for urinary stones. Data from 153 patients undergoing URS for renal and/or ureteral stones between 2011 and 2013 at a single center were reviewed to detect factors predicting postoperative febrile UTI. URS for residual stones was excluded. Postoperative febrile UTI was defined as body temperature >38 °C and was graded according to the Clavien grading system. The definition of pyuria was 10 or more white blood cells per high power field. Median age of the patients was 57 (range 17-89) years. Of the 153 patients, 98 (64.1 %) were male, 10 (6.5 %) had Eastern Cooperative Oncology Group performance status 2 or greater, 14 (9.2 %) had Charlson comorbidity index 3 or greater. Before URS, 69 (45.1 %) had pyuria, 27 (17.6 %) had acute pyelonephritis, 42 (27.5 %) had ureteral stent, and 50 (32.7 %) were treated with antibiotics. After URS, 28 (18.3 %) developed febrile UTI (Clavien grade I, n = 16; grade II, n = 10; grade III, n = 1; grade IV, n = 1). Preoperative pyuria and acute pyelonephritis were significant factors for postoperative febrile UTI (pyuria: odds ratio 3.62, 95 % CI 1.26-8.11, P value 0.017; pyelonephritis: odds ratio 4.43, 95 % CI 1.06-11.16, P value 0.044). Degree of pyuria was likely to be associated with severity of postoperative febrile UTI, and two cases (1.3 %) with severe pyuria developed sepsis. Careful management is needed for patients with preoperative pyelonephritis or pyuria; risk factors for postoperative febrile UTI to avoid sepsis.
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