Numerical simulation of the urine flow in a stented ureter

When a stent is implanted in a blocked ureter, the urine passing from the kidney to the bladder must traverse a very complicated flow path. That path consists of two parallel passages, one of which is the bore of the stent and the other is the annular space between the external surface of the stent and the inner wall of the ureter. The flow path is further complicated by the presence of numerous pass-through holes that are deployed along the length of the stent. These holes allow urine to pass between the annulus and the bore. Further complexity in the pattern of the urine flow occurs because the coiled "pig tails," which hold the stent in place, contain multiple ports for fluid ingress and egress. The fluid flow in a stented ureter has been quantitatively analyzed here for the first time using numerical simulation. The numerical solutions obtained here fully reveal the details of the urine flow throughout the entire stented ureter. It was found that in the absence of blockages, most of the pass-through holes are inactive. Furthermore, only the port in each coiled pig tail that is nearest the stent proper is actively involved in the urine flow. Only in the presence of blockages, which may occur due to encrustation or biofouling, are the numerous pass-through holes activated. The numerical simulations are able to track the urine flow through the pass-through holes as well as adjacent to the blockages. The simulations are also able to provide highly accurate results for the kidney-to-bladder urine flow rate. The simulation method presented here constitutes a powerful new tool for rational design of ureteral stents in the future.     

Calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses in the renal pelvis and ureter of rats

Summary The distribution of calcitonin gene-related peptide-immunoreactive nerve fibers in the renal pelvis and ureter was examined by immunohistochemistry using whole-mount preparations and cryostat sections. The patterns of innervation were contrasted between the pelvis and ureter; the immunoreactive nerve fibers in the pelvis ran parallel to the long axis of each of the circular and longitudinal muscle layers, causing a lattice-like appearance of the nerve fibers. In the ureter, the immunoreactive fibers were accumulated in the subepithelial region and the longitudinal muscle. In both the pelvis and ureter, a portion of the nerve fibers of smaller caliber showed a swollen or beaded structure; they were located in the musculature and beneath the epithelium extending for considerable distances. Ligation of the ureter caused a marked decrease in the immunoreactive nerves in the pelvis and the proximal portion of the ureter, suggesting that the axonal flow in the calcitonin gene-related peptide-containing neurons of the ureter runs towards the pelvis.     

A two way fully coupled fluid structure simulation of human ureter peristalsis

Abstract

Numerical simulations of ureter peristalsis have been carried out in the past to understand both the flow field and ureter wall mechanics. The main objective of the current investigations is to have a better understanding of the urine transport due to the peristalsis in the ureter, thus making the information helpful for a better treatment and diagnosis of ureteral complications like urine reflux. In the current study, a numerical simulation is performed using a finite-element-based solver with a two-way fully coupled fluid structure interaction approach between the ureter wall and urine. For the first time, the ureter wall is modeled as an anisotropic hyper-elastic material based on experiments performed in previous literature on the human ureter. Peristalsis in the ureter is modeled as a series of isolated boluses. By observing the flow field it is clear that the peristalsis mechanism has a natural tendency to create a backflow as the isolated bolus moves forward. As a result, the urine can flow back from the bladder to the ureter at the ureterovesical (ureter-bladder) junctions, if the one-way valve starts to malfunction.     

Flow of urine through the ureter: a collapsible, muscular tube undergoing peristalsis

In steady flow through nonuniform collapsible tubes a key concept is the compressive zone, at which flow limitation can occur at both high and low Reynolds numbers. Ureteral peristalsis can be considered as a series of compressive zones, corresponding to waves of active muscular contraction, that move at near-constant speed along the ureter towards the bladder. One-dimensional, lubrication-theory analysis shows that peristalsis can pump urine from kidney into the bladder only at relatively low mean rates of urine flow. Under these circumstances isolated boluses of urine are propelled steadily through the ureter (assumed uniform) by the contraction waves. At higher mean rates of flow the behavior depends on whether the frequency of peristalsis is higher or lower than a critical value. For frequencies above the critical value steady propagation of boluses that are in contact with contraction waves at both ends is possible. As the flow rate rises the urine begins to leak through the contraction waves and steady peristaltic flow breaks down. There is an upper limit to the mean flow rate that can be carried by steady peristalsis, which depends on the mechanical properties of the ureter. At high flow rates the peristaltic contractions do not pump but hinder the flow of urine through the ureter.     

A mathematical simulation of the ureter: effects of the model parameters on ureteral pressure/flow relations

Ureteral peristaltic mechanism facilitates urine transport from the kidney to the bladder. Numerical analysis of the peristaltic flow in the ureter aims to further our understanding of the reflux phenomenon and other ureteral abnormalities. Fluid-structure interaction (FSI) plays an important role in accuracy of this approach and the arbitrary Lagrangian-Eulerian (ALE) formulation is a strong method to analyze the coupled fluid-structure interaction between the compliant wall and the surrounding fluid. This formulation, however, was not used in previous studies of peristalsis in living organisms. In the present investigation, a numerical simulation is introduced and solved through ALE formulation to perform the ureteral flow and stress analysis. The incompressible Navier-Stokes equations are used as the governing equations for the fluid, and a linear elastic model is utilized for the compliant wall. The wall stimulation is modeled by nonlinear contact analysis using a rigid contact surface since an appropriate model for simulation of ureteral peristalsis needs to contain cell-to-cell wall stimulation. In contrast to previous studies, the wall displacements are not predetermined in the presented model of this finite-length compliant tube, neither the peristalsis needs to be periodic. Moreover, the temporal changes of ureteral wall intraluminal shear stress during peristalsis are included in our study. Iterative computing of two-way coupling is used to solve the governing equations. Two phases of nonperistaltic and peristaltic transport of urine in the ureter are discussed. Results are obtained following an analysis of the effects of the ureteral wall compliance, the pressure difference between the ureteral inlet and outlet, the maximum height of the contraction wave, the contraction wave velocity, and the number of contraction waves on the ureteral outlet flow. The results indicate that the proximal part of the ureter is prone to a higher shear stress during peristalsis compared with its middle and distal parts. It is also shown that the peristalsis is more efficient as the maximum height of the contraction wave increases. Finally, it is concluded that improper function of ureteropelvic junction results in the passage of part of urine back flow even in the case of slow start-up of the peristaltic contraction wave.     

Analytical solutions for the specific activities of a traced substance within the component parts of a simulated kidney-ureter system

Two models for a kidney-ureter system are considered: one model of one vessel in which a traced substance, undergoing exchange between the vessel and an external compartment, is emptying into the ureter; the second model of two approximately parallel, identical vessels in which a traced substance, undergoing exchange between each vessel and an external compartment, is emptying into the ureter. A single impulsive input of label into a vessel is assumed. For mathematical simplicity, the major conditions imposed on each system are: (1) rapid mixing transverse to a vessel axis and no mixing longitudinal to a vessel axis within the plasma; (2) small variation of the specific activity within the plasma in the longitudinal direction to a vessel axis; (3) constant flow rate of urine into the ureter and (4) constant exchange coefficients, tubule flow velocity and traced substance concentrations within individual compartments.     

Effects of a long-lasting hyperinsulinemia induced by insulin infusion on the subcellular distribution of liver insulin receptors in the rat

Acute hyperinsulinemia in rats have been shown to cause enhanced endocytosis of liver insulin receptors with little or no change in the total receptor number. To determine whether a similar phenomenon occurs in long-lasting hyperinsulinemia, the subcellular distribution of liver insulin receptors has been studied in rats infused continuously with insulin (0.4 and 0.2 U/h) for 4 days. In rats in which plasma insulin concentration was maintained at 15-20 ng/ml, there was, from 3 to 24 h, a 2-fold decrease in insulin binding to plasma membranes (PM), along with 2 to 4-fold increase in insulin binding to the light (GEI), intermediate (GEi) and heavy (GEh) Golgi-endosomal fractions; concomitantly, there was a 10-fold increase in the insulin content of Golgi-endosomal fractions. After 24 h, the changes in insulin binding to PM and GEI were maintained, but the increase in both insulin binding activity and insulin content of GEi and GEh became progressively less marked, although plasma insulin concentration remained elevated. Throughout infusion, insulin binding to the total particulate fraction was unchanged. In rats, in which plasma insulin was maintained at 6-8 ng/ml, insulin binding to PM was decreased to a lesser degree and insulin binding to Golgi-endosomal fractions was unchanged (GEh) or decreased (GEI and GEi), although the insulin content of these fractions remained high. These results suggest that, while an enhanced receptor endocytosis accounts for the decrease in cell surface receptors observed at an early stage of the hyperinsulinemia, additional regulatory mechanisms are probably involved at a later stage.     

Cytosolic Calcium Measurements in Renal Epithelial Cells by Flow Cytometry

A variety of cellular processes, both physiological and pathophysiological, require or are governed by calcium, including exocytosis, mitochondrial function, cell death, cell metabolism and cell migration to name but a few. Cytosolic calcium is normally maintained at low nanomolar concentrations; rather it is found in high micromolar to millimolar concentrations in the endoplasmic reticulum, mitochondrial matrix and the extracellular compartment. Upon stimulation, a transient increase in cytosolic calcium serves to signal downstream events. Detecting changes in cytosolic calcium is normally performed using a live cell imaging set up with calcium binding dyes that exhibit either an increase in fluorescence intensity or a shift in the emission wavelength upon calcium binding. However, a live cell imaging set up is not freely accessible to all researchers. Alternative detection methods have been optimized for immunological cells with flow cytometry and for non-immunological adherent cells with a fluorescence microplate reader. Here, we describe an optimized, simple method for detecting changes in epithelial cells with flow cytometry using a single wavelength calcium binding dye. Adherent renal proximal tubule epithelial cells, which are normally difficult to load with dyes, were loaded with a fluorescent cell permeable calcium binding dye in the presence of probenecid, brought into suspension and calcium signals were monitored before and after addition of thapsigargin, tunicamycin and ionomycin.     

Effect of compensatory hypertrophy of the kidney on the ability of splenocytes to induce a regional graft versus host reaction

The ability of C57BL/6 mouse splenocytes to induce regional GVHR during uni- and bilateral nephrectomy, ligation of the ureter and sham operations was studied. It was shown that any kidney operation enhances the ability of splenocytes to induce the GVHR in contrast to uni- and bilateral sham operations. This phenomenon was first observed during bilateral nephrectomy (after 5 h), unilateral nephrectomy (after 24 h) and ligation of the ureter (after 72 h). The data indicate that deficiency of the tissue is the main cause of changes in the immunity system status rather than changes in antigen properties and functional insufficiency of the kidneys.     

Assessment of the robustness of a serendipitous zinc binding fold: mutagenesis and protein grafting

Zinc binding motifs have received much attention in the area of protein design. Here, we have tested the suitability of a recently discovered nonnative zinc binding structure as a protein design scaffold. A series of multiple alanine mutants was created to investigate the minimal requirements for folding, and solution structures of these mutants showed that the original fold was maintained, despite changes in approximately 50% of the sequence. We next attempted to transplant binding faces from chosen bimolecular interactions onto one of these mutants, and many of the resulting "chimeras" were shown to adopt a native-like fold. These results both highlight the robust nature of small zinc binding domains and underscore the complexity of designing functional proteins, even using such small, highly ordered scaffolds as templates.     

Characterization of spontaneous electrical activity of the urinary tract: Ureter,bladder, urethra

The study aimed to characterize spontaneous electrical activity of the ureter, urinary bladder and urethra as well as their interrelationship. The basic parameters of pacemaker activity (amplitude, frequency, peak rise rate, peak rise time, peak half-width) were comparatively analyzed in each of the active areas. Out of the three areas compared, the ureteral rhythmogenic zone displayed the maximum amplitude and apex formation rate. Under conditions of urine influx from the ureter into the bladder and isolation of these organs from the urethra, the amplitude and peak rise rate in the latter decreased by almost 20%. At the same time, all the parameters of the ureter and bladder remained intact. Complete block of urine influx into the bladder by transecting the ureter at the appropriate area led to a slight decrease in the amplitude of action potentials, peak rise rate and rhythmogenicity frequency in the bladder, respectively, by 14.2, 12.5 and 16% at the constancy of other parameters of its activity. Subsequent isolation of the bladder from the urethra had no appreciable effect on the altered parameters of the former. The similar tendency towards a reduction of the parameters was observed under the same conditions in the urethra. Thus, a relationship was revealed between autonomous activities of the ureter, bladder and urethra. The regulatory role in this process is provided by the urine flow through these organs.     

Development and differentiation of the ureteric bud into the ureter in the absence of a kidney collecting system

Six1-/- mice were found to have apparently normal ureters in the absence of a kidney, suggesting that the growth and development of the unbranched ureter is largely independent of the more proximal portions of the UB which differentiates into the highly branched renal collecting system. Culture of isolated urinary tracts (from normal and mutant mice) on Transwell filters was employed to study the morphogenesis of this portion of the urogenital system. Examination of the ureters revealed the presence of a multi-cell layered tubule with a lumen lined by cells expressing uroplakin (a protein exclusively expressed in the epithelium of the lower urinary tract). Cultured ureters of both the wild-type and Six1 mutant become contractile and undergo peristalsis, an activity preceded by the expression of alpha-smooth muscle actin (alphaSMA). Treatment with a number of inhibitors of signaling molecules revealed that inhibition of PI3 kinase dissociates the developmental expression of alphaSMA from ureter growth and elongation. Epidermal growth factor also perturbed smooth muscle differentiation in culture. Moreover, the peristalsis of the ureter in the absence of the kidney in the Six1-/- mouse indicates that the development of this clinically important function of ureter (peristaltic movement of urine) is not dependent on fluid flow through the ureter. In keeping with this, isolated ureters cultured in the absence of surrounding tissues elongate, differentiate and undergo peristalsis when cultured on a filter and undergo branching morphogenesis when cultured in 3-dimensional extracellular matrix gels in the presence of a conditioned medium derived from a metanephric mesenchyme (MM) cell line. In addition, ureters of Six1-/- urinary tracts (i.e., lacking a kidney) displayed budding structures from their proximal ends when cultured in the presence of GDNF and FGFs reminiscent of UB budding from the wolffian duct. Taken together with the above data, this indicates that, although the distal ureter (at least early in its development) retains some of the characteristics of the more proximal UB, the growth and differentiation (i.e., development of smooth muscle actin, peristalsis and uroplakin expression) of the distal non-branching ureter are inherent properties of this portion of the UB, occurring independently of detectable influences of either the undifferentiated MM (unlike the upper portion of the ureteric bud) or more differentiated metanephric kidney. Thus, the developing distal ureter appears to be a unique anatomical structure which should no longer be considered as simply the non-branching portion of the ureteric bud. In future studies, the ability to independently analyze and study the portion of the UB that becomes the renal collecting system and that which becomes the ureter should facilitate distinguishing the developmental nephrome (renal ontogenome) from the ureterome.     

Renal response of euryhaline toad (Bufo viridis) to acute immersion in tap water, NaCl, or urea solutions

Green toads (Bufo viridis) were acclimated to either tap water, 230 mOsmol NaCl kg-1 H2O (saline), 500 mOsmol NaCl kg-1 H2O (high saline), or 500 mmol L-1 urea. Renal functions for each acclimation group were studied on conscious animals that had one ureter chronically catheterized. Reciprocal immersion of tap-water- and saline-acclimated toads in the opposite solution did not stress the animals osmotically, and plasma osmolality increased or decreased by no more than 15%. However, urine osmolality and ionic composition changed immediately and profoundly on exposure to the other solution. Exposure of tap-water-acclimated toads to saline decreased urine flow by 30%, whereas the reciprocal immersion led to an increase of 30%. Immersion of tap-water-acclimated toads in high saline led to immediate cessation of urine flow, whereas immersion of 500 NaCl- or urea-acclimated toads in tap water led to a large increase in urine flow, with an overshoot that lasted 10 h (as a result of either salt or urea diuresis). Urine flow then stabilized at a level 5-6 times higher than the value attained at high-salt environment. On immersion of 500 urea-acclimated toads in 500 NaCl, urine flow doubled, accompanied by a change in ion composition, without change in the osmolality. In all experimental conditions, plasma potassium concentration was maintained within a narrow range. The results show that the toad's kidneys contributed efficiently both to osmo- and ionoregulation in a wide range of ambient solutions.     

X-ray endovascular surgery of the right ovarian vein syndrome]

The author analyzes the causes of the disorders in the urodynamics and retention changes in the upper urinary routes of 43 infertile women who suffered from disordered venous reno-ovarian circulation. In chronic phlebostasis of the pelvic organs a compensatory varicose dilatation of the right ovarian vein, mediating the hemodynamic decompression of the venous bed of internal genitals, is responsible for the development of the venous compression syndrome of the right ureter. To correct the vasourethral conflict roentgenoendovascular embolization of the left ovarian vein was carried out. In the remote postembolization period 40 women presented without pain or urodynamic disorders and with normal urinalyses, in 3 women the right ureter dilatation persisted but had not progressed.     

Epithelial-mesenchymal interactions regulate the stage-specific expression of a cell surface proteoglycan, syndecan, in the developing kidney

Morphogenesis of the kidney is regulated by reciprocal tissue interactions between the epithelial ureter bud and the metanephric mesenchyme. The differentiation of the kidney involves profound changes in the extracellular matrix, and therefore matrix receptors may have an important role in this process. We studied the expression of syndecan, a cell surface proteoglycan acting as a receptor for interstitial matrix materials, by using a monoclonal antibody against the core protein of the molecule. Syndecan was not detected in the uninduced metanephric mesenchyme. During the formation of the ureter bud from the Wolffian duct, syndecan appeared in the mesenchymal cells around the invaginating bud. Simultaneously with the first branching of the ureter bud, the whole nephric mesenchyme became syndecan positive, but a 3- to 10-cell-thick layer around the branching ureter bud, representing the presumptive tubular cells, was most intensely stained. During the assembly of the mesenchyme cells into pretubular aggregates, syndecan was detected in these aggregates and, to a lesser degree, in the morphologically undifferentiated mesenchyme. Thereafter syndecan was found only in the differentiating epithelium, from which it was gradually lost during maturation of the nephron. It was last detected in the periphery of the kidney, where tubulogenesis still continued. In transfilter cultures we showed that syndecan appeared in the nephric mesenchyme during the period when the mesenchyme becomes programmed to transform into epithelial structures. By using interspecies recombinations and a species-specific antibody we excluded the possibility that syndecan in the mesenchyme would originate from the inductor. We conclude that syndecan expression is regulated by epithelial-mesenchymal interactions. The findings that syndecan appeared as an early response to induction and that its distribution showed both spatial and temporal correlation with kidney morphogenesis suggest an important role for this molecule in development.     

Studies on the regulation of insulin receptors in cultured BALB/3T3 fibroblasts

The level of [¹²⁵I]insulin binding to BALB/ 3T3 fibroblasts was low in growing cells and high in stationary cells. Since frequent changes of medium (every 2 h) did not modify the hormone binding of the stationary cells, it is unlikely that serum factors directly regulate the number of insulin receptors. Cells were grown to different densities by plating them in different concentrations of serum. Insulin binding was low in dense cultures maintained actively growing by high serum concentration, while binding was high in sparse cultures which were growth-arrested due to serum depletion. Thus, cell density does not directly regulate the insulin receptors. The growth status of the cells is the only factor that explains consistently the variations of insulin binding in these and previous [1, 2] experiments. Synchronization of the cells by two different methods did not show a reproducible cellcycle dependence for the insulin receptors.     

Topography of the neurotensin (NT)(8-9) binding site of human NT receptor-1 probed with NT(8-13) analogs.

A series of neurotensin (NT)(8-13) analogs featuring substitution of the Arg8 and/or Arg9 residues with non-natural cationic amino acids was synthesized and evaluated for binding to the human NT receptor-1 (hNTR-1). The modifications were designed to probe specific steric and electrostatic requirements in the N-terminal cationic region of NT(8-13) for receptor binding as a general evaluation of the feasibility of incorporating minor structural changes into a peptide at a crucial polar receptor binding site. Many of the non-natural amino acids are more or less isosteric to Arg but more lipophilic as a result of addition of alkyl groups or through removal or replacement of NH character with methylene or methyl substituents, whereas others vary the distance between the cation and the alpha-amino acid carbon. Substitution of Arg8 with N(G)-alkylated Arg derivatives or homolysine (Hlys) maintained the subnanomolar affinity of NT(8-13) to the hNTR-1. Position 8 incorporation of Hlys produced the most favorable primary amine side-chain substitution to date. Moderate losses in affinity observed with position 9 substitutions were attributed to adverse steric effects. Doubly substituted [Hlys8, DAB9]NT(8-13), in which DAB is 2,4-diaminobutyric acid, was also prepared and tested as the shorter side-chain of DAB is known to be favored in position 9 of NT(8-13). This analog maintained 60% of NT(8-13) binding affinity making it the most favored des-guanidinium-containing analog known. These results demonstrate that adequate receptor binding affinity can be maintained over a structural range of Arg analogs, thus providing a range of peptides expected to exhibit altered pharmacokinetic properties. From the standpoint of the hNTR-1 cationic binding sites, these results help to map out the structural stringency inherent in the formation of a tight binding complex with NT(8-13) and related analogs.     

Factors influencing the altered thermogenic response of rat brown adipose tissue in streptozotocin-diabetes.

1. Adipocytes were isolated from the interscapular brown fat of male rats maintained at 21 degrees C. These animals were controls, streptozotocin-diabetics or 2-day insulin-treated diabetics. 2. With adipocytes from diabetic animals, maximum rates of noradrenaline-stimulated O2 uptake were decreased by 58%, and the Bmax. of [3H]GDP binding to mitochondria was decreased by 55%. Insulin administration reversed both of these changes. 3. Streptozotocin-diabetes increased basal lipolysis in adipocytes incubated with adenosine deaminase (1 unit/ml), decreased the EC50 (concn. giving 50% of maximum effect) for noradrenaline, but did not change the maximum rate of noradrenaline-stimulated lipolysis. Except for some small differences at very low concentrations (10-100 pM), diabetes or insulin treatment did not alter the sensitivity of noradrenaline-stimulated lipolysis or O2 uptake to the inhibitory effect of N6-phenylisopropyladenosine. It is therefore concluded that the lesion(s) in thermogenesis in diabetes are not attributable to any changes in lipolysis. 4. Blood flow through interscapular brown fat, measured by accumulation of [14C]DDT [14C-labelled 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] was increased by 2.3-fold 70 min after a single administration of insulin to diabetic rats. This treatment decreased blood flow through epididymal white fat by 58%. 5. Propranolol treatment of diabetic rats muted the ability of insulin treatment to increase the maximum rate of noradrenaline-stimulated O2 uptake, suggesting that this action of insulin may be a secondary one rather than a direct effect of the hormone on the adipocytes.     

输尿管囊肿的超声诊断价值探讨

目的:探讨超声显像对输尿管囊肿的诊断价值,提高本病的诊断及鉴别诊断水平。方法:对我院例输尿管囊肿的超声检查资料进行回顾性分析。结果:全部病例均经手术病理证实,右侧11例,左侧11例,双侧2,5例合并重复肾及双输尿管,二维超声可直接显示输尿管囊肿形态、部位大小及其变化,超声诊断合率96%(25/26)。结论:超声显像诊断输尿管囊肿的符合率高,具有方便、快捷、经济、无创伤、无痛苦、重复性好、无需造影剂、可实时动态观察等优点,可迅速发现早期病变,直接观察囊肿部位、大小、形态、输尿管来源、输尿管开口位置、有无尿路出口梗阻及其多种并发症的诊断,可做为本病的常规首选检查项目。     

In vitro autoradiographic localization of [I]-angiotensin II binding sites in the rat and dog kidney

Light microscopic autoradiographic techniques have been utilized to demonstrate specific regions of the rat and dog kidney where angiotensin II receptors exist. Slide mounted tissue sections were labeled with [¹²⁵I]-angiotensin II using conditions which provided for highly specific binding. These angiotensin II binding sites were localized to several distinct renal structures. In the renal cortex, angiotensin II binding sites were found concentrated in all parts of the glomeruli including the vascular components, the macula densa and the juxtaglomerular apparatus. Angiotensin II binding in the medulla was more diffusely associated with the vasa recta, and to a lesser extent, the thick ascending segment of the loop of Henle. Binding sites specific for angiotensin II were also found in the smooth muscle laminae of the ureter. Scatchard analysis of the binding kinetics allowed the demonstration of two subpopulations of binding sites which differ slightly in their affinities for [¹²⁵I]-angiotensin II. These subpopulations appear to be associated with distinct components of the renal structure.