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Objectives To examine whether the epithelial sodium channel (ENaC) is expressed in the human urinary bladder and how its expression changes in association with outlet obstruction. Detrusor instability occurs in association with bladder outlet obstruction. The increase of afferent activity is one of the possible mechanisms for this detrusor instability. The ENaC expressed in mammals has been implicated in various mechanosensory functions. Methods Specimens of urinary bladder mucosa were obtained from 9 controls and 9 patients with bladder outlet obstruction verified by the International Prostate Symptom Score, prostate volume, and urodynamic tests. In 7 patients with outlet obstruction, involuntary detrusor contraction was demonstrated. The expression and localization of ENaC proteins was examined using immunofluorescent staining. The quantification of ENaC gene expression was assessed by real-time reverse transcriptase-polymerase chain reaction. Results The alpha-ENaC, beta-ENaC, and gamma-ENaC proteins were expressed in human urinary bladder epithelium with outlet obstruction, and the alpha-ENaC and gamma-ENaC proteins were virtually unstained in the control bladders. Alpha-ENaC, beta-ENaC, and gamma-ENaC mRNA were detected in 1, 6, and 4 of 9 control bladders, respectively. Each ENaC mRNA was clearly present in all obstructed bladders. The expression levels of each subunit in the obstructed bladders were significantly greater than those in controls. The quantified ENaC expression correlated significantly with the storage symptom score. Conclusions The ENaC expressed in the bladder epithelium might be implicated in the mechanosensory transduction in the bladder afferent pathways, thereby inducing detrusor instability by outlet obstruction.

Many reports indicate that a high homocysteine (Hcy) level is a potential risk factor for such thrombotic diseases as arteriosclerosis, myocardial infarction, and cerebral infarction in healthy individuals or hemodialysis (HD) patients. The methylentetrahydrofolate reductase (MTHFR) C677T polymorphism has been reported to be closely related to plasma Hcy level.Using a cross-sectional design in this study, the relationship between arteriovenous fistula (AVF) obstruction and the MTHFR C677T point mutation was examined in 337 HD patients.Results of multivariate analysis showed no significant influence of age, HD therapy duration, sex, or the presence of diabetes mellitus, cerebral infarction, or myocardial infarction. Only the presence of the MTHFR C677T polymorphism yielded a significant difference. Percentages of patients who experienced AVF obstruction were as follows: CC (12.6%), CT (20.3%), and TT (31.8%). The number of those who experienced obstruction was significantly larger with the TT than CC (P0.01). Moreover, total obstruction episode ratios were as follows: CC, 1 in 107.21 episodes/patient-month; CT, 1 in 74.08 episodes/patient-month; and TT, 1 in 50.33 episodes/patient-month. Episode percentages tended to be greater when the degree of mutation was greater, and a significant difference was observed between the CC and TT alleles (P0.01).Although AVF obstruction is affected by numerous factors, there was a strong relationship between MTHFR C677T mutation and AVF obstruction. These findings suggest that the MTHFR C677T point mutation could serve as an important indicator in identifying susceptibility to AVF obstruction.

Localization and regulation of renal Na + /myo-inositol cotransporter in diabetic rats. We have examined theeffect of diabetes on sodium/myo-inositol cotransporter (SMIT) mRNA levels and myo-inositol content in the kidney to test the hypothesis that diabetes-induced changes in renal myo-inositol levels are due to the regulation of SMIT mRNA levels.In streptozotocin-induced diabetic rats, after 3, 7 and 28 days of diabetes, SMIT mRNA levels in the whole kidney were increased three- to fivefold, and remained increased by about twofold after six months of diabetes. Insulin treatment of diabetic rats normalized blood glucose levels and prevented the increase in SMIT mRNA levels. Treating diabetic rats with sorbinil, an aldose reductase inhibitor,corrected the abnormal accumulation of sorbitol but had no effect on the diabetes-induced increase in renal SMIT mRNA levels. The regional distribution of SMIT mRNA from normal rats showed a relative abundance in cortex, outer medulla, and inner medulla of 1.0:3.4:7.0. After seven days of diabetes, the levels of SMIT mRNA and myo-inositol content were significantly increased only in the outer medulla. In situ hybridization studies revealed that SMIT mRNA in the outer medulla was predominately localized to the medullary thick ascending limbs of Henle's loop and was not localized to any specific cell in the inner medulla. This distribution pattern was unchanged in diabetic rats. These studies show that diabetes causes an increase in renal SMIT mRNA, which is primarily localized to the outer medulla. Accumulation of myo-inositol by the thick ascending limb of Henle's loop may account for most of the increase caused by diabetes.

Editor: For patients undergoing hemodialysis treatment who have a rigid stricture of an arteriovenous fistula, it is extremely difficult to achieve sufficient dilation even if a highpressure resistant balloon catheter is used. In such cases, the parallel wire technique (1,2) has been a better alternative to achieve arteriovenous fistula dilation. The effectiveness of the parallel wire technique has been explained as being a result of the guide wire indwelling between the balloon and the stricture causing a cracked or cut intima, by which the vessel is extended. In other words, the cutting balloon’s blade is replaced with the guide wire. Eventually, the intimal injury is limited to the cracked area. It is speculated that the recurrence of strictures at these points will be less frequent. In the parallel wire technique, there are three alternative ways to indwell the guide wire, as shown in Figure 1: the conventional method passes another wire through the sheath of larger size (Fig 1a); the wire can also be passed through another puncture (Fig 1b); and finally, the selfreversed parallel wire technique, described herein, can be used (Fig 1c). Disadvantages of the conventional technique are that the sheath is required to be thicker than the optimum size and that blood is lost from the point at which the sheath is applied (2). It was reported that 200 mL of blood is generally lost with this method, and use of a Y-shaped connector was recommended (2). The disadvantage of the second method is that a new vein puncture is required and another guide wire is needed. To improve upon these techniques, we chose the method illustrated in Figure 1c: the self-reversed parallel wire technique. In this method, only one guide wire is passed through the sheath, so a sheath of appropriate size is sufficient and a connector preventing blood loss will not be needed. In our hospital, initial implementation of this method used two wires for conventional parallel wire technique (1,2), but this method presented problems such as blood loss from the sheath and required the use of an oversized sheath. Self-reversed parallel wire technique is a simple modification of the conventional one. Details of its implementation and effectiveness are reported herein. Between January 1999 and September 2001, blood access intervention therapy was carried out in 163 patients undergoing hemodialysis treatment. All these patients also had native arteriovenous fistulae. For these cases, we usually used noncompliant balloon catheters (balloon diameter: 4–6 mm) with a rated burst pressure of 15 atm and inflation times of 2 minutes for each dilation. Ultra-short braidedtype sheaths were used (5 F, 3 cm long; Medikit, Tokyo, Japan). In our experience, insufficient dilation was achieved in 22 cases (13%) in which only the high-pressure resistant balloon was used. The self-reversed parallel wire technique was applied in these cases. Figure 2 shows the self-reversed parallel wire technique procedure. A sheath of the required size (5 F) was inserted, through which a flexible-tipped guide-wire with an angleshaped tip (Radifocus; Terumo, Tokyo, Japan) was passed. The tip was then turned in a 180° curve by pushing the tip Figure 1. There are three alternative parallel wire techniques. (a) The conventional method requires an oversized sheath; (b) another puncture can be made to insert the guide wire; or (c) the self-reversed parallel wire technique can be employed.