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Although sympathetic suppression is considered one of the mechanisms for cardioprotection afforded by sodium–glucose cotransporter 2 (SGLT2) inhibitors, whether SGLT2 inhibition acutely modifies sympathetic arterial pressure (AP) regulation remains unclear. We examined the acute effect of an SGLT2 inhibitor, empagliflozin (10 mg/kg), on open-loop baroreflex static characteristics in streptozotocin (STZ)-induced type 1 diabetic and control (CNT) rats (n = 9 each). Empagliflozin significantly increased urine flow [CNT: 25.5 (21.7–31.2) vs. 55.9 (51.0–64.5), STZ: 83.4 (53.7–91.7) vs. 121.2 (57.0–136.0) μL·min−1·kg−1, median (1st–3rd quartiles), P < 0.001 for empagliflozin and STZ]. Empagliflozin decreased the minimum sympathetic nerve activity (SNA) [CNT: 15.7 (6.8–18.4) vs. 10.5 (2.9–19.0), STZ: 36.9 (25.7–54.9) vs. 32.8 (15.1–37.5) %, P = 0.021 for empagliflozin and P = 0.003 for STZ], but did not significantly affect the peripheral arc characteristics assessed by the SNA–AP relationship. Despite the significant increase in urine flow and changes in several baroreflex parameters, empagliflozin preserved the overall sympathetic AP regulation in STZ-induced diabetic rats. The lack of a significant change in the peripheral arc may minimize reflex sympathetic activation, thereby enhancing a cardioprotective benefit of empagliflozin. [ABSTRACT FROM AUTHOR]

The effect of side holes morphology changes in double J stent (DJS) on encrustation was analyzed using computational fluid dynamics (CFD). We analyzed DJS side holes with inner diameter of 1 mm and outer diameters of 1 (type A), 1.2 (type B) and 1.4 (type C) mm, respectively. Concentric stenosis with three intraureteral degree (0%, 12%, and 88%) was analyzed. The flow rate, shear stress and wall shear stress (WSS) distribution were investigated. Urine flow through SH1 before the ureteropelvic junction (UPJ) differed based on the ureteral stenosis degree. The sum of flow rates through the SHs increased with diameter. In the stented ureter with 12% stenosis, the flow rate through SH1 approximately doubled than that without ureteral stenosis, and the flow rate through SH1 was maximal for the type 'C' stent in both 12% and 88% ureteral stenosis. The mean shear stress in the SHs increased with the degree of stenosis. The WSS around the SHs was higher for type 'C' than types A and B. From the flow rates and shear stresses in and around the SHs, the larger SH diameter of the DJS from the UPJ to mid-ureter is expected to induce encrustation reduction, especially in patients with urinary lithiasis. [ABSTRACT FROM AUTHOR]

Aim: Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis. Methods: UTI was induced in 8–10 w female BALB/cJ‐mice by surgically injecting Escherichia coli (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24‐h post‐infection. In vitro bacterial growth (OD600) was determined in urine from mice or from human volunteers. Results: Gel feeding increased urine output (1.40 ± 0.77 μL min−1, p < 0.01) and diluted the urine (668.7 ± 177 mOsmol kg−1, p < 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 μL min−1, osmolality: 1439 ± 473.5 mOsmol kg−1). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg−1 tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg−1, p < 0.01). Correspondingly, the growth of E. coli was markedly reduced at osmolalities above 1200 mOsmol kg−1 compared to 600 mOsmol kg−1 and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 μg mL−1, p < 0.01) compared to controls (24.65 ± 2.70 μg mL−1). Conclusion: Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for E. coli. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake. [ABSTRACT FROM AUTHOR]

Objectives: Uroflowmetry (UFM) is the first‐line noninvasive screening test employed in the diagnosis of lower urinary tract dysfunction (LUTD). The purpose of this study was to determine normal UFM values in healthy Turkish children among our local population. Methods: A total of 100 healthy girls and 62 healthy boys aged 5–15 years, who applied to İnönü University Turgut Özal Medical Center Pediatrics Polyclinic between February 2021 and January 2022, were included in the present study. The UFM parameters, including maximum flow rate (Qmax), average flow rate (Qavg), voided volume (VV), time to maximum flow, and voiding time, were measured using the Inoflow Smart System UFM Device and the resulting urine flow curve was recorded. The children were compared in terms of the UFM parameters based on their gender and age groups (5–10 years and 11–15 years). Results: The mean Qmax value in healthy female children aged 5–15 years (21.8 ± 8.6 mL/s) was significantly higher than in male children (17.98 ± 6.1 mL/s) (p =.003). VV, Qmax, and Qavg values of the children in the 11–15 age group were significantly higher than those in the age group of 5–10 years (p >.05 for each). VV, Qmax, and Qavg values were directly proportional to age (p =.0001, for each). Conclusions: We believe that this study adds to the limited knowledge base regarding normal flow patterns in healthy children. [ABSTRACT FROM AUTHOR]

Purpose: Urine oxygen partial pressure (PuO2) may be useful for assessing acute kidney injury (AKI) risk. The primary purpose of this study was to quantify the ability of a novel urinary oxygen monitoring system to make real-time PuO2 measurements intraoperatively which depends on adequate urine flow. We hypothesized that PuO2 data could be acquired with enough temporal resolution to provide real-time information in both AKI and non-AKI patients. Methods: PuO2 and urine flow were analyzed in 86 cardiac surgery patients. PuO2 data associated with low (< 0.5 ml/kg/hr) or retrograde urine flow were discarded. Patients were excluded if > 70% of their data were discarded during the respective periods, i.e., during cardiopulmonary bypass (CPB), before CPB (pre-CPB), and after CPB (post-CPB). The length of intervals of discarded data were recorded for each patient. The median length of intervals of discarded data were compared between AKI and non-AKI patients and between surgical periods. Results: There were more valid PuO2 data in CPB and post-CPB periods compared to the pre-CPB period (81% and 90% vs. 31% of patients included, respectively; p < 0.001 and p < 0.001). Most intervals of discarded data were < 3 minutes during CPB (96%) and post-CPB (98%). The median length was < 25 s during all periods and there was no significant difference in the group median length of discarded data intervals for AKI and non-AKI patients. Conclusions: PuO2 measurements were acquired with enough temporal resolution to demonstrate real-time PuO2 monitoring during CPB and the post-CPB period. ClinicalTrials.gov Identifier: NCT03335865, First Posted Date: Nov. 8th, 2017. [ABSTRACT FROM AUTHOR]

This study investigated which sizes of double-J stents are more effective in achieving an acceptable urine flow through stenotic and stented ureters. Sixty four computational fluid dynamics models of the combinations of two different gauge ureters (4.57 mm and 5.39 mm in diameter) with four different levels of ureteral and four different sizes of double-J stents were developed for the numerical analysis of urine flow in the ureter. Luminal, extraluminal, and total flow rates along the ureter were measured, and the flow patterns around the ports and side holes were investigated. For the 4.57-mm ureter, the total flow rate for each gauge of stent was 23–63 mL/h (5 Fr), 20–47 mL/h (6 Fr), 17–35 mL/h (7 Fr), and 16–26 mL/h (8 Fr) and for the 5.39-mm ureter, the total flow rate for each gauge of stent was 43–147 mL/h (5 Fr), 36–116 mL/h (6 Fr), 29–92 mL/h (7 Fr), and 26–71 mL/h (8 Fr). With a 74% stenosis, all stents allowed a low flow rate, and the differences in flow rates between the stents were small. At the other levels of stenosis, 5 Fr stents allowed greater flow rates than the 8 Fr stents. The luminal flow rate increased just before the area of stenosis and decreased after the stenosis because of the increase and decrease in the luminal flow through the side holes before and after the stenosis. Therefore, a larger double-J stent is not favorable in achieving an acceptable urine flow through the stenotic and stented ureters. The results in this study could not be necessarily correlated with clinical situation because peristalsis, viscosity of the urine and real format of the ureter were not considered in our model. In vivo experiments are necessary for confirmation of our findings. Double J stents are commonly used in the ureteral stenosis or occlusion, especially due to ureter stones which obstruct the flow of urine. Clinicians choose the size of double J stent on the basis of their clinical experience. Here, we tried to know which sizes of double J stents are better for sufficient urine flow. According to various documents that try to determine the optimal shape of double J stents to increase the urine flow through the ureter, mostly bigger stent is recommended to occur maximum urine flow. However, in case of ureter with stenosis or occlusion, the right size of the double J stent may vary depending on the degree of stenosis in the ureter. To find appropriate stent size for the ureter with stenosis, computational fluid dynamics was conducted. This study shows that smaller diameter stents are more appropriate than larger diameter stents depending on the situation. [ABSTRACT FROM AUTHOR]

This study investigated which sizes of double-J stents are more effective in achieving an acceptable urine flow through stenotic and stented ureters. Sixty four computational fluid dynamics models of the combinations of two different gauge ureters (4.57 mm and 5.39 mm in diameter) with four different levels of ureteral and four different sizes of double-J stents were developed for the numerical analysis of urine flow in the ureter. Luminal, extraluminal, and total flow rates along the ureter were measured, and the flow patterns around the ports and side holes were investigated. For the 4.57-mm ureter, the total flow rate for each gauge of stent was 23–63 mL/h (5 Fr), 20–47 mL/h (6 Fr), 17–35 mL/h (7 Fr), and 16–26 mL/h (8 Fr) and for the 5.39-mm ureter, the total flow rate for each gauge of stent was 43–147 mL/h (5 Fr), 36–116 mL/h (6 Fr), 29–92 mL/h (7 Fr), and 26–71 mL/h (8 Fr). With a 74% stenosis, all stents allowed a low flow rate, and the differences in flow rates between the stents were small. At the other levels of stenosis, 5 Fr stents allowed greater flow rates than the 8 Fr stents. The luminal flow rate increased just before the area of stenosis and decreased after the stenosis because of the increase and decrease in the luminal flow through the side holes before and after the stenosis. Therefore, a larger double-J stent is not favorable in achieving an acceptable urine flow through the stenotic and stented ureters. The results in this study could not be necessarily correlated with clinical situation because peristalsis, viscosity of the urine and real format of the ureter were not considered in our model. In vivo experiments are necessary for confirmation of our findings. Double J stents are commonly used in the ureteral stenosis or occlusion, especially due to ureter stones which obstruct the flow of urine. Clinicians choose the size of double J stent on the basis of their clinical experience. Here, we tried to know which sizes of double J stents are better for sufficient urine flow. According to various documents that try to determine the optimal shape of double J stents to increase the urine flow through the ureter, mostly bigger stent is recommended to occur maximum urine flow. However, in case of ureter with stenosis or occlusion, the right size of the double J stent may vary depending on the degree of stenosis in the ureter. To find appropriate stent size for the ureter with stenosis, computational fluid dynamics was conducted. This study shows that smaller diameter stents are more appropriate than larger diameter stents depending on the situation.

Competing Interests: None

Ureteral stenosis presents with a narrowing in the ureter, due to an intrinsic or extrinsic ureteral disease, such as ureter cancer or retroperitoneal fibrosis. The placement of a double J stent in the upper urinary system is one of the most common treatments of ureteral stenosis, along with the insertion of a percutaneous nephrostomy tube into the renal pelvis. The effect that the side holes in a double J stent have on urine flow has been evaluated in a few studies using straight ureter models. In this study, urine flow through a double J stent's side holes was analyzed in curved ureter models, which were based on human anatomy. In ureteral stenosis, especially in severe ureteral stenosis, a stent with side holes had a positive effect on the luminal and total flow rates, compared with the rates for a stent without side holes. The more side holes a stent has, the greater the luminal and total flow rates. However, the angular positions of the side holes did not affect flow rate. In conclusion, the side holes in a double J stent had a positive effect on ureteral stenosis, and the effect became greater as the ureteral stenosis became more severe. [ABSTRACT FROM AUTHOR]

Uncommon bacteria, such as Delftia tusurhatensis have been isolated from CAUTIs in combination with well-established pathogenic bacteria such as Escherichia coli . Nonetheless, the reason why E. coli coexists with other bacteria instead of outcompeting and completely eliminating them is unknown. As such, a flow cell reactor simulating the hydrodynamic conditions found in CAUTIs (shear rate of 15 s −1 ) was used to characterize the microbial physiology of E. coli and D. tsuruhatensis individually and in consortium, in terms of the growth kinetics and substrate uptake. Single-species biofilms showed that up to 48 h the cultivable cell counts significantly increased for both species ( p < 0.05). When in dual-species biofilm, E. coli outnumbered D. tsuruhatensis up to 16 h and then D. tsuruhatensis gained a fitness advantage. However, the assessment of the spatial distribution of the dual-species biofilm by LNA/2′OMe-FISH revealed that E. coli and D. tsuruhatensis coexist and tend to co-aggregate over time, which suggests that both bacteria are able to cooperate synergistically. Substrate uptake measurements revealed that D. tsuruhatensis metabolized citric acid more rapidly, presumably leaving more uric acid available in the medium to be used by E. coli . In conclusion, E. coli and uncommon bacteria seem to cooperate, when sharing the same environment under dynamic conditions, leading to the persistence of both bacteria in a stable microbial community. [ABSTRACT FROM AUTHOR]

• Urine flow in the urethra was simulated based on patient-specific urethra models. • Wake flow causes total pressure loss, resulting in high bladder pressure. • Outcome of BPH surgery varies depending on the urethra models. • Bladder pressure increases as a quadratic function with increase in voided flow rate. Conventional practice includes a limited depiction of urethral pressure and flows based on fragmented gross clinical observations. However, with technological advancements in simulations, computational fluid dynamics (CFD) can provide an alternative approach to predict the bladder pressure with a concordant quantitative flow field in the urethra. Thus, this study aims to comprehensively analyze the urine flow characteristics in various urethra models using simulations. Three-dimensional urethra models were constructed for seven specific subjects based on clinical radiographs. Simulations with Reynolds averaged Navier-Stokes model were performed to quantitatively investigate the urine flow under various volume flow rate of voided urine. Under benign prostatic hyperplasia, the spindle shape of the prostatic urethra (PRU) generates wake flow. The wake flow was also observed in several regions downstream of the PRU, depending on the urethra shape. This wake flow resulted in total pressure loss and urinary tract dysfunction. When comparing pre- and post-operative urethra models, the bladder pressure decreased by 14.98% in P04 and 4.67% in P06. Thus, we identified variability between surgical results of patients. The bladder pressure according to the volume flow rate of voided urine was investigated using simulations and the theoretical consideration based on hydrodynamics. In theoretical consideration, the bladder pressure was expressed as a second-order polynomial for volume flow rate. These results concur with the simulation results. Numerical simulation can describe the urine flow field in the urethra, providing the possibility to predict the bladder pressure without requiring painful, invasive interventions, such as cystoscopy. Furthermore, effective treatments to improve urination function can be formulated to be patient-specific, by detecting causes and problem regions based on quantitative analysis and predicting post-surgical outcomes. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Interruption of urine flow during micturition has been used as an assessment of ability to voluntarily contract the pelvic floor muscles (PFM). However, the PFM are also activated during specific abdominal manoeuvres. This study aimed to assess the effect of similar abdominal manoeuvres on urine flow and compare this with the effect of PFM contraction. Methods: Eight healthy women, of mixed parity, contracted the abdominal muscles and the PFM during urine flow on separate occasions. Differences in urine flow were compared using paired t tests. Results: All participants were able to interrupt the urine stream using both muscle activation patterns. There was no difference in the time taken to interrupt urine flow ( p = 0.78) between the two patterns. Conclusions: These data provide evidence that specific abdominal muscle manoeuvres influence urethral closure in continent women, and this is probably mediated by concurrent activation of PFM during the abdominal task. [ABSTRACT FROM AUTHOR]

Angiotensin (ANG) II-dependent hypertension is characterized by increases in intrarenal ANG II levels, derangement in renal hemodynamics, and augmented tubular sodium reabsorptive capability. Increased nephron expression of renin-angiotensin system components, such as angiotensinogen by proximal tubule cells and renin by collecting duct principal cells, has been associated with an augmented ability of the kidney to form ANG II in hypertensive states. However, the contribution of de novo intrarenal ANG II production to the development and maintenance of ANG II-dependent hypertension remains unclear. The present study was performed to determine the effects of selective intrarenal renin inhibition on whole kidney hemodynamics and renal excretory function in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension in the absence of the confounding influence of associated reductions in mean arterial pressure (MAP). Male Cyp1a1-Ren2 transgenic rats were induced to develop malignant hypertension, anesthetized, and surgically prepared for intrarenal administration of the direct renin inhibitor aliskiren (0.01 mg/kg). Following acute aliskiren treatment, urine flow and sodium excretion increased (10.5 ± 1.1 to 15.9 ± 1.9 μl/min, P < 0.001; 550 ± 160 to 1,370 ± 320 neq/min, P < 0.001, respectively) and ANG II excretion decreased (120 ± 30 to 63 ± 17 fmol/h, P < 0.05). There were no significant changes in MAP, glomerular filtration rate, estimated renal plasma flow, plasma ANG II levels, or protein excretion. The present findings demonstrate that selective renal renin inhibition elicits diuretic and natriuretic responses in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension. Elevated intraluminal ANG II levels likely act to augment tubular reabsorptive function and, thereby, contribute to the elevated blood pressure in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension. [ABSTRACT FROM AUTHOR]

There is evidence that in cardiac failure, there is defective baroreceptor reflex control of sympathetic nerve activity. Often, cardiac failure is preceded by a state of cardiac hypertrophy in which there may be enhanced performance of the heart. This study investigated whether in two different models of cardiac hypertrophy, there was an increased contribution of nitric oxide (NO) to the low-pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA) and nerve-dependent excretory function. Administration of a volume load, 0.25* body wt/min saline for 30 min, in normal rats decreased RSNA by 40* and increased urine flow by some 9-fold. Following nitro-l-arginine methyl ester (l-NAME) administration, 10 μg·kg-1·min-1 for 60 min, which had no effect on blood pressure, heart rate, or RSNA, the volume load-induced renal sympathoinhibitory and excretory responses were markedly enhanced. In cardiac hypertrophy states induced by 2 wk of isoprenaline/caffeine or 1 wk thyroxine administration, the volume challenge failed to suppress RSNA, and there were blunted increases in urine flow in the innervated kidneys, but following l-NAME infusion, the volume load decreased RSNA by 30-40* and increased urine flow by some 20-fold in the innervated kidneys, roughly to the same extent as observed in normal rats. These findings suggest that the blunted renal sympathoinhibition and nerve-dependent diuresis to the volume load in cardiac hypertrophy are related to a heightened production or activity of NO within either the afferent or central arms of the reflex. [ABSTRACT FROM AUTHOR]

Flow sensing by primary cilia of the epithelial cells is involved in cystogenesis in polycystic kidney disease. We investigate whether a similar mechanism applies to the pathogenesis of cyst-like tubular dilatation induced by ureteral obstruction in mice. Robust proliferation occurs in the obstructed tubules when urine flow is interrupted as well as in the repairing tubules when urine flow is reestablished after relief of the obstruction, suggesting a urine flow-independent mechanism of proliferation. In the urothelium, proliferation is only detected above the obstruction, although urine flow ceased both above and below the obstruction. Our results support mechanical strain- rather than flow-mediated proliferation in obstructive uropathy. To understand the mechanism of cell proliferation leading to increased tubular diameter in cyst-like tubular dilatation, we examine planar cell polarity (PCP), which is necessary for oriented cell division and maintenance of tubular diameter. In dilated tubules, the orientation of cell division is randomized, atypical PKC (aPKC) is mislocalized, and the pattern of the expression of a core PCP protein, Frizzled3 (Fz3), is altered. In addition, the level of Fz3 expression is increased. These results indicate that aberrant PCP may contribute to cyst-like tubular dilatation in obstructive uropathy. Interestingly, the orientation of cell division, localization of aPKC, and Fz3 expression return to normal when obstruction is relieved, which suggest a role of normal PCP signaling in tubular repair. [ABSTRACT FROM AUTHOR]

The article presents a study on the effects of caffeine ingestion on thermoregulation and fluid-electrolyte balance during arduous exercise in hot environment. The study which conforms to the Declaration of Helsinki and sanctioned by the local Hospital Research Ethics Committee involves seven heat-adapted and light caffeine consumer cyclists who accomplished an uninterrupted nine consecutive days of cycling to volitional exhaustion to determine their VO2max. It determined that caffeine ingestion did not change heat production, forearm skin blood flow and sweat rate but increased loses of sodium, chloride and potassium. It concludes that caffeine ingestion before cycling in hot environment do not have thermogenic effect.

Cyclophosphamide (CP) is an alkylating agent classified as a human carcinogen. Health care workers handling this drug may be exposed during, e.g., preparation or administration. Cyclophosphamide is readily absorbed by inhalation and by dermal uptake. A biomarker, CP in urine, has frequently been used to assess the occupational exposure to CP, but has not been fully validated. The aim of this study was to investigate if the proportion of the CP dose that is excreted in urine (renal clearance) is constant over different plasma drug concentrations and other pharmacokinetic parameters, e.g., urine flow. Pharmacokinetics of CP were studied in 16 breast cancer patients that were treated with postoperative adjuvant chemotherapy including CP. Plasma and urine from the patients were collected at different occasions up to 12 days after the dose. Urine was collected during 4-h periods and blood was sampled at the end of each period. Analysis of CP was performed by liquid chromatography tandem mass spectrometry. The limit of detection for CP in urine and plasma was 0.01 and 0.02 ng/ml, respectively. The precisions of the developed methods were determined to ≤8%. The administered doses of CP in absolute amounts ranged between 800 and 2,240 mg. Mean renal clearance of CP was 8.6 (confidence interval 6.5–10.7) ml/min and was not significantly dependent of the plasma drug concentration. However, a significant correlation between renal clearance and urine flow was observed. There was a large inter-individual variation in the plasma and urine concentrations even when the same doses were given. Cyclophosphamide in urine can be continued to be used as a biomarker to monitor occupational exposure to CP, however the inter-individual variability of excretion of CP in urine, and its dependency on urine flow must be taken into consideration in future applications. [ABSTRACT FROM AUTHOR]

Increasing the extravascular fluid of the airways acutely by obstructing pulmonary lymph drainage causes a reflex diuresis mediated by neuronal nitric oxide synthase in the renal medulla. The authors examined this reflex in rabbits with a chronic increase in extravascular fluid of the airways resulting from surgically induced mitral regurgitation. Intact rabbits served as controls. Renal neuronal (nNOS) and endothelial (eNOS) nitric oxide synthase expressions were also examined. The reflex was absent in rabbits with mitral regurgitation. There were significant increases in medullary and cortical nNOS mRNA compared to controls. The observed changes in mRNA levels correlated with nNOS protein levels. eNOS mRNA was unaffected. [ABSTRACT FROM AUTHOR]