방광근육수축의 발달과정에서 칼슘민감성수축의 역할 및 관련 분자경로

Dept. of Medicine/박사This study was carried out to analyze the developmental changes of bladder response to cholinergic stimulation in detail, highlighting calcium sensitization (CS) and its related pathways. Rats were divided into three groups in accordance with reported time of developmental milestones (newborn: day 1-4, youngster: day 5-14 and grown-up: day 15-28). Following cholinergic stimulation (carbachol 5 uM) the contractile response to detrusor were analyzed with respect to three phases (initial phasic, tonic and superimposed phasic contractions). Contractile responses were analyzed by dynamic and kinetic aspects. The responses were further compared in varying external calcium concentrations and in the presence of inhibitors of protein kinase C (PKC) and Rho kinase (ROCK), which are involved in CS. The responses of newborns were contrasted to the others by the short and brisk initial phasic contractions, prominent tonic contractions and delayed participation of irregular superimposed phasic contractions. With development, phasic contractions became prominent and tonic contractions diminished. These developmental changes of phasic contractions were reproduced when exposed to increasing calcium concentrations. Application of specific inhibitors and molecular phasic analysis revealed that PKC was functional in tonic contractions of the newborn, whereas ROCK took over its role with development. Within a few days of birth, rats’ bladders experienced drastic changes of contractile mechanisms. These included dominance of phasic contractions from tonic contractions due to increased calcium dependence and the maturational shift of calcium sensitivity mechanism from PKC to ROCK. 소아의 배뇨과정의 발달은 아직 충분히 알려져 있지 않지만 방광근육수축의 발달과 밀접한 관련이 있다. 방광수축은 평활근내의 myosin light chain의 인산화로 결정되며 이는 세포내 칼슘농도에 의존하는 기전과 세포내의 칼슘농도의 변화가 거의 없이도 지속적 방광수축을 가능하게 하는 소위 칼슘민감성수축으로 구분된다. 본 연구는 현재까지 연구가 잘 이루어지지 않은 칼슘민감성수축과 이와 관련된 분자경로에 주목하여, 방광근육수축이 연령에 따라 어떻게 변화하는 지를 분석하였다. 백서를 발달시기별로 세 군으로 나누어 (신생아기: 1-4일, 유아기: 5-14일, 청소년기: 15-28일) 콜린성자극 (carbachol 5μM)에 대한 방광근육의 수축을 세가지 단계별 (초기 상동성 수축, 긴장성 수축, 적재성 상동성 수축)로 분석하였다. 실험은 방광근육절편을 이용하였으며, 다양한 세포외 칼슘농도 및 칼슘민감성수축에 관여하는 분자경로인 protein kinase C (PKC)와 Rho-kinase (ROCK)의 길항제의 유무에 따른 수축반응의 변화를 비교 분석하였다. 신생아 백서의 방광근육수축의 특징은 짧고 빠른 초기 상동성 수축, 뚜렷한 긴장성 수축 및 지연되어 나타나는 불규칙적인 적재성 상동성 수축이었다. 이러한 신생아기의 특징은 연령이 증가함에 따라, 상동성 수축이 더 뚜렷해지고 긴장성 수축은 감소하는 경향을 나타냈다. 세포외 칼슘농도를 변화시키며 분석한 결과 신생아기의 백서에서는 상대적으로 낮은 세포외 칼슘농도에서도 방광근육수축이 유발되어 다른 연령군에 비해 칼슘민간성수축이 더 두드러지는 것을 확인할 수 있었다. 칼슘민감성수축과 연관된 분자경로의 분석결과 신생아기의 긴장성 수축에는 PKC가 주요 역할을 하며, 연령이 증가함에 따라 ROCK가 그 역할을 대체하는 것으로 나타났다. 생 후 수일안에, 백서의 방광수축기전은 다음과 같은 급격한 변화를 보였다. 긴장성 수축 우위에서 칼슘의존성 증가에 따른 상동성 수축 우위로 바뀌었으며, 칼슘민감성 기전은 PKC에서 ROCK로 성숙에 따른 변화를 나타냈다.ope

Determinants of Corporate Loans and Bonds before and After Economic Crisis in Korea

The paper suggests that there has been a shift in the allocation of bank credit from large firms to small firms before and after the economic crisis. The paper also suggests that the improved lending practices of financial institutions, at least partiall1. Introduction 　2. The Firm-level Data 　3. Dynamic Patterns in the Allocation of Credit across Large and Small Firms: Loans and Bonds 　4. Determinants of Corporate Loans and Bonds 　5. Concluding Remark

Efficacy and tolerability of anticholinergics in Korean children with overactive bladder: a multicenter retrospective study.

We investigated the efficacy and tolerability of various anticholinergics in Korean children with non-neurogenic overactive bladder (OAB). A total of 326 children (males:females= 157:169) aged under 18 yr (mean age 7.3±2.6 yr) who were diagnosed with OAB from 2008 to 2011 were retrospectively reviewed. The mean duration of OAB symptoms before anticholinergic treatment was 16.9±19.0 months. The mean duration of medication was 5.6±7.3 months. Urgency urinary incontinence episodes per week decreased from 1.9±3.1 to 0.4±1.5 times (P<0.001). The median voiding frequency during daytime was decreased from 9.2±5.4 to 6.3±4.2 times (P<0.001). According to 3-day voiding diaries, the maximum and average bladder capacity were increased from 145.5±66.9 to 196.8±80.3 mL and from 80.8±39.6 to 121.8±56.5 mL, respectively (P<0.001). On uroflowmetry, maximum flow rate was increased from 17.6±8.4 to 20.5±8.2 mL/sec (P<0.001). Adverse effects were reported in 14 (4.3%) children and six children (1.8%) discontinued medication due to adverse effects. Our results indicate that anticholinergics are effective to improve OAB symptoms and tolerability was acceptable without severe complications in children.ope

Is a secondary procedure necessary in every case of failed endoscopic treatment for vesicoureteral reflux?

PURPOSE: Endoscopic treatment (ET) has become a widely accepted procedure for treating vesicoureteral reflux (VUR). However, patients followed up after ET over long periods have reported persistent or recurrent VUR. We evaluated the natural course of failed ET in patients who required further treatments to help physicians in making decisions on the treatment of VUR. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who were diagnosed with VUR and underwent ET from January 2006 to December 2009. A total of 165 patients with 260 ureters underwent ET. We compared the parameters of the patients according to ET success or failure and evaluated the natural course of the patients after ET failure. RESULTS: Mean VUR grade and positive photon defect were higher in the failed ET group than in the successful ET group. Six months after the operation, persistent or recurrent VUR was observed in 76 ureters (29.2%), and by 16.3 months after the operation, VUR resolution was observed in 18 ureters (23.7%). Twenty-five ureters (32.9%) without complications were observed conservatively. Involuntary detrusor contraction was found in 1 of 9 (11.1%) among the secondary ET success group, whereas in the secondary ET failure group, 4 of 6 (66.7%) had accompanying involuntary detrusor contraction. CONCLUSIONS: Patients in whom ET fails can be observed for spontaneous resolution of VUR unless they have febrile urinary tract infection or decreased renal function. Urodynamic study may be helpful in deciding whether a secondary procedure after ET failure is necessary.ope

Is It Necessary to Repeat Videourodynamic Studies on Spina Bifida Children?.

PURPOSE: A videourodynamic study is useful for examining the functional and structural problems of the urinary tract simultaneously. Due to its invasiveness, however, it is important to obtain as much information as is possible as the study is being conducted. The purpose of this study was to evaluate the results of a repeated videourodynamic examination in spina bifida children. MATERIALS AND METHODS: Between January 2005 and July 2006, a total of 48 patients who were diagnosed with spina bifida and underwent repeated videourodynamic studies were enrolled in this study. We compared variables including compliance, involuntary detrusor contraction (IDC), cystometric bladder capacity (CBC), maximum detrusor pressure, and post-voiding residual urine (PVR) between the initial and repeated studies. RESULTS: During the repeated studies, cases of IDC decreased significantly (p<0.05) compared with the initial studies. No other significant differences were found in terms of compliance, CBC, maximum detrusor pressure, and PVR. CONCLUSIONS: There were no significant differences in terms of compliance, CBC, maximum detrusor pressure, and PVR between initial and repeated studies. However, the number of patients who had IDC decreased significantly in the second study. Nevertheless, we conclude that the first examination in this study was enough to evaluate the overall function and structure of the urinary tract. We believe that repeat studies are not necessary in children with spina bifida.ope

Urodynamic Evaluation in Patients with Anorectal Malformation: According to Spinal Cord Abnormalities

Purpose: Anorectal malformation (ARM) is often accompanied by spinal cord abnormality or neurovesical dysfunction. However, only a few studies have comparatively assessed spinal cord abnormality and urodynamic data. We evaluated the effect of spinal cord abnormalities on perioperative neurovesical dysfunction and investigated the necessity of urodynamic study in patients with ARM. Materials and Methods: From 1993 to 2007, 219 patients with ARM were newly diagnosed at our institution; A retrospective study was conducted on 20 patients who underwent preoperative and postoperative urodynamic examinations. Results: Of 20 patients, 10 had abnormal spinal cords. Fourteen (70%) presented abnormal urodynamic findings (detrusor overactivity, dysfunctional voiding, detrusor sphincter dyssynergia, combined overactivity and dyssynergia, or detrusor acontractility). Preoperative urodynamic abnormalities were reported in 6 of 10 patients with abnormal spinal cords and 8 of 10 patients with normal spinal cords. New postoperative urodynamic abnormalities were reported in 2 patients in the abnormal spinal cord group, while 2 preoperative cases were resolved. In the normal spinal cord group, 2 preoperative cases were converted to other forms of urodynamic abnormality. Conclusions: We advocate routine preoperative and follow-up urodynamic assessment of all patients with anorectal malformation, regardless of spinal cord abnormality.ope

Vesicoureteral reflux and bladder dysfunction

The relationship between vesicoureteral reflux and bladder dysfunction is inseparable and has long been emphasized. However, the primary concern of all physicians treating patients with vesicoureteral reflux is the prevention of renal scarring and eventual deterioration of renal function. Bladder dysfunction, urinary tract infection and vesicoureteral reflux are the three important factors which are closely related to each other and contribute to the formation of renal scar. Especially, there is ongoing discussion regarding the role of bladder dysfunction in the prognosis of both medically and surgically treated vesicoureteral reflux. The effect of bladder dysfunction on VUR is mostly via inadequate sphincter relaxation during infancy which is closer to immature bladder dyscoordination rather than true dysfunction. But after toilet training, functional obstruction caused by voluntary sphincter constriction during voiding is responsible through elevation in bladder pressure, thus distorting the architecture of bladder and ureterovesical junction. Reports suggest that voiding phase abnormalities in lower urinary tract dysfunction contributes to lower spontaneous resolution rate of VUR. However, filling phase abnormalities such as involuntary detrusor contraction can also cause VUR even in the absence of dysfunctional voiding. With regards to the effect of bladder dysfunction on treatment, meta-analysis reveals that the cure rate of VUR following endoscopic treatment is less in children with bladder bowel dysfunction but there is no difference for open surgery.ope

Cellular mesoblastic nephroma with liver metastasis in a neonate: Prenatal and postnatal diffusion-weighted MR imaging

Congenital mesoblastic nephroma (CMN) is the most common renal tumor in the first year of life. Here, we present unique findings of cellular variant CMN seen on prenatal and postnatal MRI with diffusion-weighted imaging (DWI).The mass was well-visualized on prenatal MR DWI with diffusion restriction in the solid portions. After excision of the mass, follow-up whole body MRI with DWI helped identify local tumor recurrence with suspicious liver metastasis. This hepatic lesion also showed diffusion restriction.ope

Delayed redo pyeloplasty fails to recover lost renal function after failed pyeloplasty: early sonographic changes that correlate with a loss of differential renal function

PURPOSE: To evaluate changes in differential renal function (DRF), as a functional outcome, in children who underwent redo pyeloplasty for management of failed pyeloplasty and to examine the factors that affect functional outcomes. MATERIALS AND METHODS: Between January 2002 and November 2010, a total of 18 patients who underwent redo pyeloplasty for persistent ureteropelvic junction obstruction after failed pyeloplasty were enrolled in this study. We assessed perioperative factors and evaluated changes in renal cortical thickness (RCT), renal function, and hydronephrosis by use of serial ultrasound and diuretic renography. RESULTS: The mean follow-up period was 44.83±28.86 months. After redo pyeloplasty, prevention of further functional deterioration was observed in only 12 of the 18 patients. After dividing the patients according to this observation, we discovered significant differences in both change in DRF (dDRF) and change in RCT (dRCT) (difference between before and after initial pyeloplasty) between the two groups (p<0.001). Additionally, we noted a significant positive correlation between dRCT and dDRF. All patients showed improvements in hydronephrosis grade and relief of symptoms compared with before redo pyeloplasty. CONCLUSIONS: Redo pyeloplasty should be considered in cases of failed pyeloplasty to preserve renal function and obtain relief from symptoms. If patients show severe deterioration of DRF or a decrease in RCT after initial pyeloplasty, preservation of DRF in these patients after redo pyeloplasty could be difficult. Therefore, redo pyeloplasty should be performed before severe deterioration of DRF or decrease in RCT.ope

Shear wave velocity measurements using acoustic radiation force impulse in young children with normal kidneys versus hydronephrotic kidneys

PURPOSE: To measure shear wave velocities (SWVs) by acoustic radiation force impulse (ARFI) ultrasound elastography in normal kidneys and in hydronephrotic kidneys in young children and to compare SWVs between the hydronephrosis grades. METHODS: This study was approved by an institutional review board, and informed consent was obtained from the parents of all the children included. Children under the age of 24 months were prospectively enrolled. Hydronephrosis grade was evaluated on ultrasonography, and three valid ARFI measurements were attempted using a high-frequency transducer for both kidneys. Hydronephrosis was graded from 0 to 4, and high-grade hydronephrosis was defined as grades 3 and 4. RESULTS: Fifty-one children underwent ARFI measurements, and three valid measurements for both kidneys were obtained in 96% (49/51) of the patients. Nineteen children (38.8%) had no hydronephrosis. Twenty-three children (46.9%) had unilateral hydronephrosis, and seven children (14.3%) had bilateral hydronephrosis. Seven children had ureteropelvic junction obstruction (UPJO). Median SWVs in kidneys with high-grade hydronephrosis (2.02 m/sec) were higher than those in normal kidneys (1.75 m/sec; P=0.027). However, the presence of UPJO did not influence the median SWVs in hydronephrotic kidneys (P=0.362). CONCLUSION: Obtaining ARFI measurements of the kidney is feasible in young children with median SWVs of 1.75 m/sec in normal kidneys. Median SWVs increased in high-grade hydronephrotic kidneys but were not different between hydronephrotic kidneys with and without UPJO.ope