Hypoxia-Induced Suppression of Antiapoptotic Bcl-2 Expression in Human Bladder Tumor Cells Is Regulated by Caveolin-1-Dependent Adenosine Monophosphate-Activated Protein Kinase Activity / 대한배뇨장애요실금학회지

Purpose@#Adenosine monophosphate-activated protein kinase (AMPK) is thought to inhibit cell proliferation or promote cell death, but the details remain unclear. In this study, we propose that AMPK inhibits the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) by relying on the hypoxia-inducible factor 1 alpha (HIF-1α)-induced caveolin-1 (Cav-1) expression pathway in noninvasive human bladder tumor (RT4) cells. @*Methods@#In cells exposed to a hypoxic environment (0.5% oxygen), the levels of expression and phospho-activity of the relevant signaling enzymes were examined via Western blots and reverse transcription-polymerase chain reaction. Cell proliferation was assessed using a Cell Counting Kit-8 assay. @*Results@#The level of expression of Cav-1 was very low or undetectable in RT4 cells. Hypoxia was associated with significantly decreased cell growth, along with marked induction of HIF-1α and Cav-1 expression; additionally, it suppressed the expression of the antiapoptotic marker Bcl-2 while leaving AMPK activity unchanged. Under hypoxic conditions, HIF-1α acts as a transcription factor for Cav-1 mRNA gene expression. The cell growth and Bcl-2 expression suppressed under hypoxia were reversed along with decreases in the induced HIF-1α and Cav-1 levels by AMPK activation with metformin (1mM) or phenformin (0.1mM). In addition, pretreatment with AMPK small interfering RNA not only increased the hypoxia-induced expression of HIF-1α and Cav-1, but also reversed the suppression of Bcl-2 expression. These results suggest that HIF-1α and Cav-1 expression in hypoxic environments is regulated by basal AMPK activity; therefore, the inhibition of Bcl-2 expression cannot be expected when AMPK activity is suppressed, even if Cav-1 expression is elevated. @*Conclusions@#For the first time, we find that AMPK activation can regulate HIF-1α induction as well as HIF-1α-induced Cav1 expression, and the hypoxia-induced inhibitory effect on the antiapoptotic pathway in RT4 cells is due to Cav-1-dependent AMPK activity.

Hypoxia-Induced Suppression of Antiapoptotic Bcl-2 Expression in Human Bladder Tumor Cells Is Regulated by Caveolin-1-Dependent Adenosine Monophosphate-Activated Protein Kinase Activity / 대한배뇨장애요실금학회지

Purpose@#Adenosine monophosphate-activated protein kinase (AMPK) is thought to inhibit cell proliferation or promote cell death, but the details remain unclear. In this study, we propose that AMPK inhibits the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) by relying on the hypoxia-inducible factor 1 alpha (HIF-1α)-induced caveolin-1 (Cav-1) expression pathway in noninvasive human bladder tumor (RT4) cells. @*Methods@#In cells exposed to a hypoxic environment (0.5% oxygen), the levels of expression and phospho-activity of the relevant signaling enzymes were examined via Western blots and reverse transcription-polymerase chain reaction. Cell proliferation was assessed using a Cell Counting Kit-8 assay. @*Results@#The level of expression of Cav-1 was very low or undetectable in RT4 cells. Hypoxia was associated with significantly decreased cell growth, along with marked induction of HIF-1α and Cav-1 expression; additionally, it suppressed the expression of the antiapoptotic marker Bcl-2 while leaving AMPK activity unchanged. Under hypoxic conditions, HIF-1α acts as a transcription factor for Cav-1 mRNA gene expression. The cell growth and Bcl-2 expression suppressed under hypoxia were reversed along with decreases in the induced HIF-1α and Cav-1 levels by AMPK activation with metformin (1mM) or phenformin (0.1mM). In addition, pretreatment with AMPK small interfering RNA not only increased the hypoxia-induced expression of HIF-1α and Cav-1, but also reversed the suppression of Bcl-2 expression. These results suggest that HIF-1α and Cav-1 expression in hypoxic environments is regulated by basal AMPK activity; therefore, the inhibition of Bcl-2 expression cannot be expected when AMPK activity is suppressed, even if Cav-1 expression is elevated. @*Conclusions@#For the first time, we find that AMPK activation can regulate HIF-1α induction as well as HIF-1α-induced Cav1 expression, and the hypoxia-induced inhibitory effect on the antiapoptotic pathway in RT4 cells is due to Cav-1-dependent AMPK activity.

Korean medical students' attitudes toward academic misconduct: a cross-sectional multicenter study / 한국의학교육

PURPOSE: This study investigated medical students' attitudes toward academic misconduct that occurs in the learning environment during the pre-clinical and clinical periods. METHODS: Third-year medical students from seven medical schools were invited to participate in this study. A total of 337 of the 557 (60.5%) students completed an inventory assessing their attitudes toward academic misconduct. The inventory covered seven factors: scientific misconduct (eight items), irresponsibility in class (six items), disrespectful behavior in patient care (five items), dishonesty in clerkship tasks (four items), free riding on group assignments (four items), irresponsibility during clerkship (two items), and cheating on examinations (one item). RESULTS: Medical students showed a strict attitude toward academic misconduct such as cheating on examinations and disrespectful behavior in patient care, but they showed a less rigorous attitude toward dishonesty in clerkship tasks and irresponsibility in class. There was no difference in students' attitudes toward unprofessional behaviors by gender. The graduate medical school students showed a stricter attitude toward some factors of academic misconduct than the medical college students. This difference was significant for irresponsibility in class, disrespectful behavior in patient care, and free riding on group assignments. CONCLUSION: This study indicates a critical vulnerability in medical students' professionalism toward academic integrity and responsibility. Further study evidence is needed to confirm whether this professionalism lapse is confined only to this population or is pervasive in other medical schools as well.

Korean medical students' attitudes toward academic misconduct: a cross-sectional multicenter study / 한국의학교육

PURPOSE@#This study investigated medical students' attitudes toward academic misconduct that occurs in the learning environment during the pre-clinical and clinical periods.@*METHODS@#Third-year medical students from seven medical schools were invited to participate in this study. A total of 337 of the 557 (60.5%) students completed an inventory assessing their attitudes toward academic misconduct. The inventory covered seven factors: scientific misconduct (eight items), irresponsibility in class (six items), disrespectful behavior in patient care (five items), dishonesty in clerkship tasks (four items), free riding on group assignments (four items), irresponsibility during clerkship (two items), and cheating on examinations (one item).@*RESULTS@#Medical students showed a strict attitude toward academic misconduct such as cheating on examinations and disrespectful behavior in patient care, but they showed a less rigorous attitude toward dishonesty in clerkship tasks and irresponsibility in class. There was no difference in students' attitudes toward unprofessional behaviors by gender. The graduate medical school students showed a stricter attitude toward some factors of academic misconduct than the medical college students. This difference was significant for irresponsibility in class, disrespectful behavior in patient care, and free riding on group assignments.@*CONCLUSION@#This study indicates a critical vulnerability in medical students' professionalism toward academic integrity and responsibility. Further study evidence is needed to confirm whether this professionalism lapse is confined only to this population or is pervasive in other medical schools as well.

Near-Normalized Gene Expression Profiles in Bladder With Detrusor Overactivity in Rats With Bladder Outlet Obstruction After Deobstruction / 대한배뇨장애요실금학회지

PURPOSE: The pathophysiological role of detrusor overactivity (DO) in the bladder, which is commonly observed in various bladder diseases, is not well understood. DO appears in bladder outlet obstruction (BOO), and may continue even after subsequent deobstruction. DO therefore provides an excellent opportunity to observe molecular biological changes. METHODS: In this study, to understand the molecular effects of persistent DO after BOO induction and deobstruction, we performed awake cystometry on female Sprague-Dawley rats divided into 4 groups: a sham group, a BOO group, a deobstructed group with DO after BOO (DDO), and a deobstructed group without DO after BOO (non-DDO). Total RNA was extracted from the bladder samples, and gene expression profiles were compared between the sham and model groups. RESULTS: DO was observed in 5 of the 6 rats (83%) in the BOO group, and in 6 of the 13 rats (46%) in the deobstructed group. The non-DDO group showed a significantly greater residual volume than the DDO group. Through a clustering analysis of gene expression profiles, we identified 7,532 common upregulated and downregulated genes, the expression of which changed by more than 2 fold. In the BOO group, 898 upregulated and 2,911 downregulated genes were identified. The non-DDO group showed 3,472 upregulated and 4,025 downregulated genes, whereas in the DDO group, only 145 and 72 genes were upregulated and downregulated, respectively. CONCLUSIONS: Abnormal function and gene expression profiles in bladders after BOO were normalized in the BOO rats with DO after deobstruction, whereas in those without DO, abnormal function persisted and the gene expression profile became more abnormal. DO may play a protective role against the stress to the bladder induced by BOO and deobstruction as a form of adaptive neuroplasticity.

Extracellular Vesicles as a Source of Urological Biomarkers: Lessons Learned From Advances and Challenges in Clinical Applications to Major Diseases / 대한배뇨장애요실금학회지

Extracellular vesicles (EVs) not only eliminate unwanted molecular components, but also carry molecular cargo essential for specific intercellular communication mechanisms. As the molecular characteristics and biogenetical mechanisms of heterogeneous EVs are different, many studies have attempted to purify and characterize EVs. In particular, exosomal molecules, including proteins, lipids, and nucleic acids, have been suggested as disease biomarkers or therapeutic targets in various diseases. However, several unresolved issues and challenges remain despite these promising results, including source variability before the isolation of exosomes from body fluids, the contamination of proteins during isolation, and methodological issues related to the purification of exosomes. This paper reviews the general characteristics of EVs, particularly microvesicles and exosomes, along with their physiological roles and contribution to the pathogenesis of major diseases, several widely used methods to isolate exosomes, and challenges in the development of disease biomarkers using the molecular contents of EVs isolated from body fluids.

Anti-interleukin-33 Reduces Ovalbumin-Induced Nephrotoxicity and Expression of Kidney Injury Molecule-1 / 대한배뇨장애요실금학회지

PURPOSE: To evaluate the effect of anti-interleukin-33 (anti-IL-33) on a mouse model of ovalbumin (OVA)-induced acute kidney injury (AKI). METHODS: Twenty-four female BALB/c mice were assigned to 4 groups: group A (control, n=6) was administered sterile saline intraperitoneally (i.p.) and intranasally (i.n.); group B (allergic, n=6) was administered i.p./i.n. OVA challenge; group C (null treatment, n=6) was administered control IgG i.p. before OVA challenge; and group D (anti-IL-33, n=6) was pretreated with 3.6 µg of anti-IL-33 i.p. before every OVA challenge. The following were evaluated after sacrifice: serum blood urea nitrogen and creatinine levels, Kidney injury molecule-1 gene (Kim-1) and protein (KIM-1) expression in renal parenchyma, and expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phosphorylated endothelial NOS (p-eNOS), and phosphorylated AMP kinase (p-AMPK) proteins in renal parenchyma. RESULTS: After OVA injection and intranasal challenge, mice in groups B and C showed significant increases in the expression of Kim-1 at both the mRNA and protein levels. After anti-IL-33 treatment, mice in group D showed significant Kim-1 down-regulation at the mRNA and protein levels. Group D also showed significantly lower COX-2 protein expression, marginally lesser iNOS expression than groups B and C, and p-eNOS and p-AMPK expression at baseline levels. CONCLUSIONS: Kim-1 could be a useful marker for detecting early-stage renal injury in mouse models of OVA-induced AKI. Further, anti-IL-33 might have beneficial effects on these mouse models.

Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

Controls of Nuclear Factor-Kappa B Signaling Activity by 5’-AMP-Activated Protein Kinase Activation With Examples in Human Bladder Cancer Cells / 대한배뇨장애요실금학회지

Generally, both lipopolysaccharide (LPS)- and hypoxia-induced nuclear factor kappa B (NF-κB) effects are alleviated through differential posttranslational modification of NF-κB phosphorylation after pretreatment with 5'-AMP-activated protein kinase (AMPK) activators such as 5'-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or the hypoglycemic agent metformin. We found that AICAR or metformin acts as a regulator of LPS/NF-κB-or hypoxia/NF-κB-mediated cyclooxygenase induction by an AMPK-dependent mechanism with interactions between p65-NF-κB phosphorylation and acetylation, including in a human bladder cancer cell line (T24). In summary, we highlighted the regulatory interactions of AMPK activity on NF-κB induction, particularly in posttranslational phosphorylation and acetylation of NF-κB under inflammatory conditions or hypoxia environment.

What is the Clinical Significance of Cerebrospinal Fluid Biomarkers in Parkinson's disease? Is the Significance Diagnostic or Prognostic?

The clinical diagnostic criteria of Parkinson's disease (PD) have limitations in detecting the disease at early stage and in differentiating heterogeneous clinical progression. The lack of reliable biomarker(s) for early diagnosis and prediction of prognosis is a major hurdle to achieve optimal clinical care of patients and efficient design of clinical trials for disease-modifying therapeutics. Numerous efforts to discover PD biomarkers in CSF were conducted. In this review, we describe the molecular pathogenesis of PD and discuss its implication to develop PD biomarkers in CSF. Next, we summarize the clinical utility of CSF biomarkers including alpha-synuclein for early and differential diagnosis, and prediction of PD progression. Given the heterogeneity in the clinical features of PD and none of the CSF biomarkers for an early diagnosis have been developed, research efforts to develop biomarkers to predict heterogeneous disease progression is on-going. Notably, a rapid cognitive decline followed by the development of dementia is a risk factor of poor prognosis in PD. In connection to this, CSF levels of Alzheimer's disease (AD) biomarkers have received considerable attention. However, we still need long-term longitudinal observational studies employing large cohorts to evaluate the clinical utility of CSF biomarkers reflecting Lewy body pathology and AD pathology in the brain. We believe that current research efforts including the Parkinson's Progression Markers Initiative will resolve the current needs of early diagnosis and/or prediction of disease progression using CSF biomarkers, and which will further accelerate the development of disease-modifying therapeutics and optimize the clinical management of PD patients.

Flow Starting Point and Voiding Mechanisms Measured by Simultaneous Registrations of Intravesical, Intra-abdominal, and Intraurethral Pressures in Awake Rats / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to apply a new surgical procedure that allows for the successful monitoring of intraurethral pressure (IUP) changes in the cystometry of awake Sprague-Dawley rats. METHODS: Twenty-six female Sprague-Dawley rats were grouped according to the catheterization method (bladder only; bladder and urethra; or bladder, urethra, and abdomen). Using an arbitrarily determined initial point of the first phase among four rat micturition phases on the simultaneous curves as a reference point, we compared the time differences to the points on an intravesical pressure (IVP) and those on IUP or a detrusor pressure (DP) curve from intra-abdominal pressure (IAP). RESULTS: In awake rat, the start of urethral flow on IUP curve corresponded to the initial point of the second phase, which is same to the results on the anesthetized rat. However, certain results, such as micturition pressure (MP) and intraluminal pressure high-frequency oscillations (IPHFOs), differed between awake and anesthetized rats. Most MP values were checked after the end of urethral flow on the IUP curve, which is due to the peculiar methodology such as transvesical catheterization. Urethral flow was not completely interrupted during the IPHFOs, which suggests the presence of urethral wall tension against the flow during voiding. After removal of the superimposed effects of IAP from IVP, the DP curve clearly showed a peculiar shape, highlighting the possibility of using IAP in place of IUP to detect the flow starting point on the IVP curve. CONCLUSIONS: Awake rat cystometry results have been interpreted based on those in anesthetized rats. However, our awake cystometry data were substantially different in terms of voiding time compared to those of anesthetized rats. This discovery warrants careful interpretation of the voiding parameters in awake rat cystometry.

Effect of Anti-Siglec-F Antibody and Reactive Oxygen Species Blocking on Histamine Release in Urinary Bladder of Ovalbumin-Treated Mice / 대한배뇨장애요실금학회지

PURPOSE: Sialic acid-binding Ig-like lectin (Siglec) is an immune inhibitory receptor that plays a role in the negative regulation of the activation of immune cells. This study aimed to evaluate the effects of anti-Siglec-F on plasma and urinary histamine levels in ovalbumin (OVA)-challenged urinary bladder in mice. METHODS: Thirty BALB/c mice were used. In group I (control group, n=5), mice were sensitized with OVA and challenged with saline. In group II (OVA challenge group, n=5), OVA was used for intraperitoneal sensitization and intravesical challenge. The challenged mice in group III (control immunoglobulin G [IgG] group, n=5) and those in group IV (anti-Siglec-F group, n=5) were intraperitoneally pretreated with rabbit control IgG or anti-Siglec-F antibody, respectively. In groups V (N-acetylcysteine [NAC] in OVA challenge group, n=5) and VI (control NAC only, n=5), mice were pretreated with NAC. RESULTS: Urinary histamine concentrations were significantly higher 7 days after intravesical OVA challenge (P<0.01), whereas plasma histamine levels were not. Pretreatment with anti-Siglec-F antibody significantly prevented the increase in urinary histamine release (P<0.05), whereas pretreatment with the IgG antibody control did not. Also, pretreatment of the OVA challenge group with NAC did not affect the histamine concentration in either urine or plasma. CONCLUSIONS: Systemic anti-Siglec-F treatment showed anti-allergic effects at least on local histamine release, particularly in the lower urinary bladder.

Erratum: Urodynamic Findings in an Awake Chemical Cystitis Rat Model Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

No abstract available.

Development and Changes with Age of Detrusor Overactivity in Spontaneous Hypertensive Rats as Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

PURPOSE: Overactive bladder is especially common in the elderly, although it is not regarded as a normal part of aging. Thus, we investigated how aging alters the cystometric and detrusor overactivity (DO) parameters and the density of nerve growth factor (NGF) in awake spontaneous hypertensive rats (SHRs) of different ages. METHODS: Three age groups of 12- (n=5), 17- (n=6), and 21- (n=6) week-old SHRs (Oriental Bio Inc.) were used. A catheter was implanted into the bladder to record the intravesical pressure (IVP), and a balloon-fitted catheter was positioned in the abdominal cavity to record the intraabdominal pressure (IAP). Of the IVP elevations above 2 cm H2O, DO was defined as a rise in IVP without a simultaneous change in IAP and was counted during the filling phase. We measured the expression of NGF in the bladders by enzyme-linked immunosorbent assay. RESULTS: Both the body and bladder weights significantly increased with age, but the normalized ratio between those was not changed. As for DO, none of the12-week-old rats showed DO, whereas the other groups did. DO increased significantly with age (P=0.0045 by Mantel-Haenszel trend test), although no significant differences were found in DO frequency or pressure between the 17- and 21-week-old age groups. NGF did not show any significant differences among the three groups. CONCLUSIONS: Our results showed that SHRs begin to shows DO after a certain age, such as 12 weeks of age, and that the occurrence of DO has a close relationship with aging. However, NGF, which is known to be increased in the bladder wall of patients with overactive bladder, did not show any relationship with aging in this study.

Potential Targeting of Siglecs, Mast Cell Inhibitory Receptors, in Interstitial Cystitis / 대한배뇨장애요실금학회지

Mast cell increases and activation are detected in the chronic inflammatory bladder disease interstitial cystitis (IC), and their proinflammatory mediators are felt to contribute to regional pelvic pain and inflammatory pathophysiology. The immunoreceptor tyrosine-based inhibition motif-containing sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed in mast cells could be evaluated as in vivo signaling regulators capable of inhibiting IC-related mast cell activation.

Time-Related Changes in Detrusor Overactivity in Awake Rats with Spinal Cord Injury Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

PURPOSE: To compare the physical characteristics of detrusor overactivity (DO) induced by intravesical infusion of saline in awake, sham rats and rats with chronic spinal cord injury (SCI), by simultaneous registrations of intravesical and intraabdominal pressures. METHODS: Male Sprague-Dawley rats, normal or with a spinal vascular clip at the level of Th9, were investigated cystometrically 1 and 4 weeks after SCI. Intra-vesical pressure (IVP) and intra-abdominal pressure (IAP) were recorded simultaneously to evaluate true DO. During the filling phase, the event of IVP rises, defined as increments that exceeded 2 cmH2O from baseline, were determined as DO according to the absence of simultaneous changes in IAP. RESULTS: All SCI rats exhibited DO during the filling phase, which was not shown in sham rats. The frequency and pressure of DO had a tendency to decrease with time. The DO frequency of SCI rats after 4 weeks (0.9+/-0.2 min(-1)) was decreased compared with that after 1 week (2.1+/-0.4 min(-1); P0.05). CONCLUSIONS: Cystometric studies in awake male SCI rats showed some significant changes in bladder function after SCI. All SCI rats exhibited DO during the filling phase, and showed different physical characteristics of DO over the course of time. The neurological basis of these time-related changes remains poorly understood, but may provide important prognostic information about long-term urological management in SCI patients.

Dissimilar Effects of Tolterodine on Detrusor Overactivity in Awake Rats with Chemical Cystitis and Partial Bladder Outlet Obstruction / 대한배뇨장애요실금학회지

PURPOSE: We investigated bladder function, with a special focus on nonvoiding contractions (NVCs), in awake rats with chronic chemical cystitis and bladder outlet obstruction (BOO) by use of simultaneous registrations of intravesical and intraabdominal pressures. In addition, we tested the effects of tolterodine on the NVCs in these models. METHODS: A total of 20 female Sprague-Dawley rats were used in this study. In eight rats, chemical cystitis was induced by intravesical instillation of HCl. Twelve rats were subjected to sham instillations or partial BOO. Four weeks after intravesical instillation or 2 weeks after partial BOO, cystometrograms were obtained by use of simultaneous recording of intravesical and intraabdominal pressure in all unanesthetized, unrestrained rats in metabolic cages. RESULTS: A total of 17 rats survived. In the rats with acute injury by HCl, 50% showed detrusor overactivity (DO), which was not seen in the sham group. The cystitis group had lower DO pressure without a difference in DO frequency compared with the BOO group. After the administration of tolterodine, the cystitis group showed no difference in DO frequency or pressure, whereas the BOO group showed decreased values for both parameters. CONCLUSIONS: Our study showed that toleterodine produced no effect on DO during the filling phase in rats with chronic chemical cystitisbut decreased the frequency and pressure of DO in rats with BOO. Clinically, studies are needed to improve the treatment effect of anticholinergic drugs ininterstitial cystitis patients with overactive bladder.

Early Sequential Changes in Bladder Function after Partial Bladder Outlet Obstruction in Awake Sprague-Dawley Rats: Focus on the Decompensated Bladder

PURPOSE: We investigated bladder function, with special focus on initial functional changes, by objective report of decompensated bladder according to the percentage of residual urine volume to bladder capacity in awake, obstructed rats. MATERIALS AND METHODS: Thirty rats were randomly subjected to sham operations (n=10) or partial bladder outlet obstruction (BOO, n=20). Cystometric investigations were performed without anesthesia 1 or 2 weeks after BOO surgery. To reduce the influence of confounding factors in awake cystometry, we used simultaneous recordings of intravesical and intraabdominal pressures. Decompensated bladder was defined as the bladder with more than 20% of residual volume compared with bladder capacity. RESULTS: Compared with that in sham animals, basal pressure was elevated in both BOO groups. Threshold pressure was higher in the 2 week BOO (p<0.01) group. Compliance was decreased in the 1 week BOO group (p<0.01) and increased in the 2 week BOO group (p<0.001). Bladder capacity was not increased in the 1 week BOO group, but was increased in the 2 week BOO group (p<0.01). Decompensation was found in 62.5% of the 1 week BOO group and in 33.3% of the 2 week BOO group. CONCLUSIONS: From the earlier phase, the bladders exhibited serial changes in pressure and volume parameters, and decompensated bladders defined by the percentage of residual volume to bladder capacity could be seen. During the later phase, there was an increasing tendency of compensated bladders, accompanied by the bladders being enlarged and more compliant.

Urodynamic Findings in an Awake Chemical Cystitis Rat Model Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to investigate the effect of urinary bladder inflammation on bladder function in a rat chemical cystitis model. We also histologically confirmed the effects of inflammation in the detrusor on chronically inflamed bladder in rats. MATERIALS AND METHODS: A total of 13 female Sprague-Dawley rats were used in this study. In seven rats, intravesical instillation of HCl induced chemical cystitis, and the other rats with intravesical instillation of saline were used as the sham. After 2 weeks, cystometrograms were obtained with additional intraabdominal pressure measurements in all unanesthetized, unrestrained rats in metabolic cages. The rats were killed just after cystometry. The bladders were removed and examined histologically for mast cells and inflammatory changes. RESULTS: The rats with acute injury by HCl showed no differences in pressure parameters, including basal pressure, threshold pressure, and maximum bladder pressure, compared with the sham rats. They showed significantly increased bladder capacity, micturition volume, residual volume, and micturition interval compared with the sham group. They also showed an increased frequency of detrusor overactivity compared with the sham group. The percent of detrusor overactivity was 56.3% among the total intravesical pressure rises above 2 cmH2O. The histological findings of the rats with acute injury by HCl were consistent with chemical cystitis. CONCLUSIONS: Overlapping patterns of lower urinary tract symptoms and pelvic pain are common disease characteristics among interstitial cystitis patients. The situation in an animal model of interstitial cystitis is similar, as observed in this study by the histologic and awake cystometric examinations. However, the interstitial cystitis model showed detrusor overactivity during the filling phase without a decrease in bladder capacity and micturition intervals, which differs from the characteristics of overactive bladder patients.

Intravesical PGE2 Administration in Conscious Rats as an Experimental Model of Detrusor Overactivity Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

PURPOSE: The urodynamic effects of intravesical PGE2 instillation on bladder function and detrusor overactivity (DO) during the filling phase were investigated in rats by measuring intraabdominal and intravesical pressures simultaneously. MATERIALS AND METHODS: Continuous cystometry was performed inconscious, female and male Sprague- Dawley rats. We investigated pressure-, volume-, and DO-related parameters. RESULTS: Intravesical instillation of PGE2 increased all pressure-related parameters and decreased volume-related ones, compared to the control cystometric ones. However, among the total number of intravesical pressure rises (IVPRs) above 2 cmH2O during the filling phase, only 33% in female rats and 38% in male rats after PGE2 instillation were identified as true DO during the filling phase. CONCLUSIONS: Our findings suggest that the rat model with intravesical PGE2 is inappropriate for observing the effects of some drugs or mechanisms on DO, because only approximately 30% of IVPRs were confirmed as true DO. However, this model of intravesical PGE2 instillation has some advantages for the observation of changes in pressure and volume parameters rather than in DO-related ones.