Urolithiasis in Kidney Transplant Patients: A Multicenter KSER Research Series.

Background and Objectives: Urolithiasis occurrence is uncommon in kidney transplantation patients, though it has serious implications, including acute kidney injury in the transplanted kidney. This study investigates the leading causes of urolithiasis in kidney transplantation patients, the diagnostic process, and the outcomes of multimodal management. Materials and Methods: Data collection spanned from January 1997 to December 2021, involving kidney transplantation patients with urolithiasis from the database of the Korean Society of Endourology and Robotics (KSER) research committee. Analysis encompassed factors triggering urolithiasis, the diagnostic process, stone attributes, treatment methods, and outcomes. Results: Our analysis included 58 kidney transplantation patients with urolithiasis from eight medical centers. Of these patients, 37 were male and 4 had previous urolithiasis diagnoses. The mean age was 59.09 ± 10.70 years, with a mean duration from kidney transplantation to diagnosis of 76.26 ± 183.14 months. The most frequent method of stone detection was through asymptomatic routine check-ups (54.7%). Among the 58 patients, 51 underwent stone treatment. Notably, 95.3% of patients with ureter stones received treatment, a significantly higher rate than the 66.7% of patients with renal stones (p = 0.010). Success rates showed no significant differences between renal (70%) and ureter stone (78.0%) groups (p = 0.881). Conclusions: Urolithiasis in transplanted kidneys constitutes an acute condition requiring emergency intervention. Endo-urological interventions are effective for kidney transplantation patients with urolithiasis. To ensure prevention and early detection, diligent follow-up and routine imaging tests are necessary.

Korean sexually transmitted infection guidelines 2023 revision, guideline update of viral infections: Genital herpes and anogenital warts.

The Korean Association of Urogenital Tract Infection and Inflammation and the Korea Disease Control and Prevention Agency regularly update, revise, and develop new content for the Korean sexually transmitted infection (STI) guidelines. These professional bodies respond to changing epidemiological trends and evolving scientific evidence, and consider advances in laboratory diagnostics and research. The principal recommendations of the 2023 Korean STI guidelines in terms of viral infection follow: 1) If genital herpes recurs more than 4-6 times annually, suppressive therapy with acyclovir 400 mg orally 2 times/day or famciclovir 250 mg orally 2 times/day or valacyclovir 500 mg orally once a day (for patients with <10 episodes/year) or valacyclovir 1 g orally once daily (for patients with ≥10 episodes/year) is recommended to prevent recurrence; 2) molecular human papillomavirus (HPV) testing is not recommended as a routine test for STI status, nor for determination of HPV vaccination status; and 3) patients should inform their current sexual partners about anogenital warts because the types of HPV that cause such warts can be passed to partners. These guidelines will be updated every 5 years and will be revised when new knowledge on STIs becomes available and there is a reasonable need to improve the guidelines. Physicians and other healthcare providers can use the guidelines to assist in the prevention and treatment of STIs.

Neocortical synaptic engrams for remote contextual memories.

While initial encoding of contextual memories involves the strengthening of hippocampal circuits, these memories progressively mature to stabilized forms in neocortex and become less hippocampus dependent. Although it has been proposed that long-term storage of contextual memories may involve enduring synaptic changes in neocortical circuits, synaptic substrates of remote contextual memories have been elusive. Here we demonstrate that the consolidation of remote contextual fear memories in mice correlated with progressive strengthening of excitatory connections between prefrontal cortical (PFC) engram neurons active during learning and reactivated during remote memory recall, whereas the extinction of remote memories weakened those synapses. This synapse-specific plasticity was CREB-dependent and required sustained hippocampal signals, which the retrosplenial cortex could convey to PFC. Moreover, PFC engram neurons were strongly connected to other PFC neurons recruited during remote memory recall. Our study suggests that progressive and synapse-specific strengthening of PFC circuits can contribute to long-term storage of contextual memories.

Simultaneous robot-assisted approach in a super-elderly patient with urothelial carcinoma and synchronous contralateral renal cell carcinoma: A case report.

BACKGROUND: It is rare for urothelial and renal cell carcinomas to coexist in the same patient, and even rarer for them to be detected simultaneously. Because of this rarity, a standard treatment has not been established and studies about overall survival are scarce. Therefore, physicians must modify treatments according to the individual's situation and the stage of each disease. In recent years, with advances in the instruments and techniques, minimal invasive robotic surgeries have become available for advanced-stage or high-risk patients. CASE SUMMARY: An 85-year-old woman with a medical history of hypertension and hyperlipidemia visited our institution. She had visited her local hospital complaining of intermittent, painless, gross hematuria that had started 3 mo earlier. On computed tomography, a right renal mass and left proximal ureteral mass with hydronephrosis were found simultaneously. We decided to perform robot-assisted surgery on both sides during one operation. Considering renal function and kidney loading, right partial nephrectomy was performed first, followed by left nephroureterectomy with bladder cuff excision. At the 6-mo follow-up, no specific symptoms were reported and dialysis was not considered. There were no unusual findings in the imaging study, and regular follow-up and imaging studies are scheduled. CONCLUSION: This case report assessed the feasibility of simultaneous minimal invasive robotic surgery as an alternative to conventional open or laparoscopic surgery.

Gardnerella vaginalis in Recurrent Urinary Tract Infection Is Associated with Dysbiosis of the Bladder Microbiome.

Recent studies on the urine microbiome have highlighted the importance of the gut-vagina-bladder axis in recurrent urinary tract infection (rUTI). In particular, the role of Gardnerella as a covert pathogen that activates E. coli in animal experiments has been reported. Herein, we conducted a human bladder microbiome study to investigate the effect of Gardnerella on rUTI. Urine 16S ribosomal RNA gene sequencing via transurethral catheterization was conducted in the normal control group (NC) (n = 18) and rUTI group (n = 78). The positive detection rate of Gardnerella species did not differ between the NC and rUTI groups (22.2% vs. 18.0%, p = 0.677). In addition, the Gardnerella-positive NC and Gardnerella-positive rUTI groups showed similar levels of microbiome diversity. The Gardnerella-positive group was categorized into three subgroups: the Escherichia-dominant group, Gardnerella-dominant group, and Lactobacillus-dominant group. All of the Escherichia-dominant groups were associated with rUTI. The Gardnerella-dominant or Lactobacillus-dominant groups expressed rUTI with symptoms when risk factors such as the degree of Gardnerella proliferation or causative agents of bacterial vaginosis were present. The presence of Gardnerella in the urine is considered to be related to rUTI depending on other risk factors. New guideline recommendations regarding antibiotic selection based on a novel method to detect the cause of rUTI may be required to reduce antibiotic resistance.

Robot-Assisted Laparoscopic Paravaginal Repair and Sacrocolpopexy in Patients With Pelvic Organ Prolapse.

OBJECTIVE: To evaluate the surgical effects of robotic paravaginal repair and sacrocolpopexy in patients diagnosed with lateral cystocele due to paravaginal defect. PATIENTS AND METHODS: Robotic paravaginal repair and sacrocolpopexy were performed contemporaneously in 43 patients with high-grade pelvic organ prolapse combined with a lateral or mixed cystocele. To objectively evaluate prolapse correction, the Pelvic Organ Prolapse Quantification (POP-Q) test was performed at the 12-month visit and the results compared to those of the preoperative period. Subjective satisfaction was scored using the Patient Global Impression of Improvement (PGI-I) questionnaire. RESULTS: POP-Q measurement results before and after surgery, an objective indicator of surgery, the Ba and C scores improved significantly from 2.1 ± 1.2 preoperatively to -2.0 ± 1.1 postoperatively (P <.01), and from 0.3 ± 1.3 preoperatively to -4.3 ± 1.1 postoperatively (P <.01), respectively. In PGI-I questionnaire, the numbers of patients who awarded scores of 1 and 2 (evidencing high-level symptom improvement) were 33 at 1 month (76.7%), 30 at 3 months (69.8%), and 28 (65.1%) at 12 months. When respondents awarding 3 points (a little improvement) were included, the numbers rose to 38 (88.4%) at 1 and 3 months and 35 (81.4%) at 12 months, indicating satisfaction with symptom improvement. There were no critical complications during and after surgery, but complications such as de novo stress urinary incontinence that lower patient satisfaction occurred in some cases. CONCLUSION: Robot-assisted paravaginal repair and sacrocolpopexy can be safely performed in patients with cystocele-predominant pelvic organ prolapse and good surgical results can be expected with excellent effects.

ß-Defensin 2, an Antimicrobial Peptide, as a Novel Biomarker for Ulcerative Interstitial Cystitis; Can ß-Defensin 2 Suspect the Dysbiosis of Urine Microbiota?

As urine is not sterile, inflammatory reactions caused by dysbiosis of the urinary microbiota may induce interstitial cystitis. A study was conducted to determine whether ß-defensin 2 (BD-2), a specific antimicrobial peptide in the bladder, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC). Urine samples from three female groups were examined: healthy controls (n = 34, Control group), non-Hunner type IC (n = 40, NHIC group), and Hunner type IC (n = 68, HIC group). Urine samples were collected via a transurethral catheter and assayed for BD-2 levels using enzyme linked immunosorbent assay. Under general or regional anesthesia, cystoscopy with diagnostic and therapeutic hydrodistension was performed in NHIC and HIC groups patients. These patients underwent a biopsy of the bladders. Based on the urinary specimens from 142 patients, BD-2 expression was found to be 18-fold higher in patients with Hunner type IC than in patients with non-Hunner type IC. The enhanced secretion of BD-2 exhibited a strong correlation with increased mast cell counts associated with bladder IC pathology. Enhanced urinary secretion of the antimicrobial peptide BD-2 from Hunner type IC patients associated with clinical phenotypes and demonstrated relatively robust levels to be used as a potential biomarker. Moreover, the increased urinary level of BD-2 may suggest a new possibility of biomarkers caused by dysbiosis of the urinary microbiota in ulcerative IC.

Urinary Microbiome Characteristics in Female Patients with Acute Uncomplicated Cystitis and Recurrent Cystitis.

Traditionally, the diagnostic mainstay of recurrent urinary tract infection has been urinary culture. However, the causative uropathogen of recurrent cystitis has not been well established. Urine DNA next-generation sequencing (NGS) can provide additional information on these infections. Herein, we compared urine NGS results and urine cultures in patients with acute uncomplicated cystitis (AUC) and recurrent cystitis (RC), and evaluated the difference in microbiome patterns in the NGS results. Patients who underwent urine culture and NGS due to AUC or RC were retrospectively reviewed. All urine samples were collected via a transurethral catheter and studied utilizing a type of NGS called 16S ribosomal RNA gene amplification and sequencing. The sensitivity of urine NGS was significantly higher than that of conventional urine culture (69.0% vs. 16.7%, p < 0.05). The detection rate of urine NGS was slightly lower in the RC group than in the AUC group (67.7% vs. 72.7%). Microbiome diversity was significantly higher in the RC group compared to the AUC group (p = 0.007), and the microbiome composition was significantly different between the AUC and RC groups. In the urine NGS results, Pseudomonas, Acinetobacter, and Enterobacteriaceae were found in the AUC group, and Sphingomonas, Staphylococcus, Streptococcus, and Rothia spp. were detected in the RC group. Urine NGS can significantly increase the diagnostic sensitivity compared to traditional urine culture methods, especially in RC patients. AUC and RC patients had significant differences in bacterial diversity and patterns. Therefore, recurrent cystitis might be approached from a different perspective.

Long-term outcomes of ulcerative interstitial cystitis after complete transurethral resection with therapeutic hydrodistention.

PURPOSE: We analyzed the long-term efficacy of simultaneous transurethral resection (TUR) and therapeutic hydrodistention in patients with ulcerative interstitial cystitis (IC) who did not experience recurrence on long-term follow-up. METHODS: We studied 132 female patients (mean age = 56.45 ± 11.56 years) who underwent TUR followed by hydrodistention to treat ulcerative IC between January 2010 and January 2017, and who were available for follow-up, for more than 36 months (mean = 52.3 ± 10.51 months). Of the 132 patients, those who did not suffer recurrence within 36 months after surgery were allocated to group I and those who had a recurrence within the same period were assigned to group II. Preoperative factors, including age, were compared between the groups. In group I, improvements in pain and voiding symptoms were recorded using a 10-point visual analog pain scale (VAS) and a 3-day micturition chart. A global response assessment (GRA) was used to evaluate patient satisfaction. RESULTS: In group II, the maximum functional bladder capacity (FBC) was smaller, and voiding frequency was higher, than in group I. Follow-up of patients in group I for more than 3 years showed that pain decreased after surgery. The 10-point VAS scores were 9.68 before surgery, and 1.54, 0.93, 0.55, and 0.46 at 1, 6, 12, and 36 months after surgery (p < 0.001), respectively. Maximum FBCs were 174.82 mL before surgery and 237.14, 250.71, and 254.46 mL at 1, 12, and 36 months after surgery (p < 0.001), respectively; thus, FBC increased after surgery. Urination frequency decreased significantly after surgery; the number of daily urinations was 12.77 before surgery, and 9.88, 9.21, and 9.25 at 1, 12, and 36 months after surgery (p < 0.001), respectively. Overall patient satisfaction improved after surgery; the GRA scores were 2.39, 2.71, and 2.8 points at 1, 12, and 36 months after surgery (p < 0.001), respectively. CONCLUSION: Upon simultaneous performance of TUR and therapeutic hydrodistention in patients with ulcerative IC, 49.2% showed favorable outcomes for 3 years.

Oestrogen inhibits salt-dependent hypertension by suppressing GABAergic excitation in magnocellular AVP neurons.

AIMS: Abundant evidence indicates that oestrogen (E2) plays a protective role against hypertension. Yet, the mechanism underlying the antihypertensive effect of E2 is poorly understood. In this study, we sought to determine the mechanism through which E2 inhibits salt-dependent hypertension. METHODS AND RESULTS: To this end, we performed a series of in vivo and in vitro experiments employing a rat model of hypertension that is produced by deoxycorticosterone acetate (DOCA)-salt treatment after uninephrectomy. We found that E2 prevented DOCA-salt treatment from inducing hypertension, raising plasma arginine-vasopressin (AVP) level, enhancing the depressor effect of the V1a receptor antagonist (Phenylac1,D-Tyr(Et)2,Lys6,Arg8,des-Gly9)-vasopressin, and converting GABAergic inhibition to excitation in hypothalamic magnocellular AVP neurons. Moreover, we obtained results indicating that the E2 modulation of the activity and/or expression of NKCC1 (Cl- importer) and KCC2 (Cl- extruder) underpins the effect of E2 on the transition of GABAergic transmission in AVP neurons. Lastly, we discovered that, in DOCA-salt-treated hypertensive ovariectomized rats, CLP290 (prodrug of the KCC2 activator CLP257, intraperitoneal injections) lowered blood pressure, and plasma AVP level and hyperpolarized GABA equilibrium potential to prevent GABAergic excitation from emerging in the AVP neurons of these animals. CONCLUSION: Based on these results, we conclude that E2 inhibits salt-dependent hypertension by suppressing GABAergic excitation to decrease the hormonal output of AVP neurons.

Robot-assisted laparoscopic pyeloureterostomy for ureteropelvic junction rupture sustained in a traffic accident: A case report.

BACKGROUND: Ureteral reconstruction is a highly technical type of laparoscopic or open surgery. The incidence of ureteral injury is low; however, ureteral injuries tend to be overtreated. Robotic surgery for urinary reconstructive surgery is growing in popularity, which has made procedures such as pyeloplasty, ureteroureterostomy, and ureteroneocystostomy possible, with minimal damage to the patient. To the best of our knowledge, this is the first report of robot-assisted laparoscopic pyeloureterostomy in Korea, in a 17-year-old female patient with a ureteral injury. CASE SUMMARY: The patient, a 17-year-old girl without previous medical history, was presented at the emergency room and complained of abdominal and back pain. Tenderness in the right upper quadrant was observed on physical examination. Hemorrhage in the right perirenal space was observed without abdominal organ injuries on the initial enhanced abdomen computed tomography (CT) scan. Ureteral injury was not suspected at this time. The patient was stabilized via conservative treatment, but complained of right flank pain 3 wk later and revisited the emergency room. An enhanced abdominal CT scan revealed a huge urinoma in the right perirenal space with hydronephrosis of the right kidney. Retrograde and antegrade pyelography were performed. Extravasation and discontinuity of the ureter were found. A rupture of the ureteropelvic junction was diagnosed and reconstructive surgery was performed. After 3 mo, the patient did not complain of any symptoms without any abnormal radiologic findings. CONCLUSION: This case report discusses the safety and effectiveness of this minimal invasive procedure as an alternative to conventional open or laparoscopic surgery.

Encoding of contextual fear memory in hippocampal-amygdala circuit.

In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal-amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1-BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and synaptic potentiation in the vCA1-BA pathway. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context.

Readjustable midurethral sling (REMEEX system) in obese women.

Purpose: To evaluate the success rate and patient satisfaction with the readjustable midurethral sling (REMEEX system) for the treatment of stress urinary incontinence (SUI) with intrinsic sphincter deficiency (ISD) or recurrent SUI in obese and non-obese women. Materials and Methods: Between August 2009 and August 2015, 70 patients who treated with the REMEEX system were stratified into normal, overweight and obesity groups according to body mass index. Objective surgical outcomes were evaluated using a 1-hour pad test that was performed 3 months after surgery. The subjective outcomes and degree of patient satisfaction were evaluated 3 months and 1 year after surgery. Results: Twenty-six normal weight, 31 overweight, and 13 obese women were included in the study. The objective cure rate determined using the 1-hour pad test revealed that 11 women (42.3%) were cured and 15 (57.7%) had improved in the normal weight group, respectively, compared with 16 (51.6%) and 15 (48.4%) in the overweight group and 6 (46.2%) and 7 (53.8%) in the obese group, respectively (p=0.78). One year after surgery, the subjective success rate was 91.5% in the normal weight group, 93.5% in the overweight group and 92.3% in the obese group. A total of 84.7%, 77.4%, and 77.0% of normal weight, overweight and obese women were very satisfied or satisfied 1 year after surgery, respectively. All groups showed similar success rates and satisfaction. Conclusions: The REMEEX procedure is equally effective in obese and normal weight women with ISD-type SUI or recurrent SUI.

Excitatory GABAergic Action and Increased Vasopressin Synthesis in Hypothalamic Magnocellular Neurosecretory Cells Underlie the High Plasma Level of Vasopressin in Diabetic Rats.

Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotocin (STZ)-induced DM rats and vehicle-treated control rats revealed that γ-aminobutyric acid (GABA) functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it usually evokes inhibitory responses in the cells of control animals. Furthermore, Western blotting analyses of Cl- transporters in the SON tissues indicated that Na+-K+-2Cl- cotransporter isotype 1 (a Cl- importer) was upregulated and K+-Cl- cotransporter isotype 2 (KCC2; a Cl- extruder) was downregulated in STZ rats. Treatment with CLP290 (a KCC2 activator) significantly lowered blood AVP and glucose levels in STZ rats. Last, investigation that used rats expressing an AVP-enhanced green fluorescent protein fusion gene showed that AVP synthesis in AVP neurons was much more intense in STZ rats than in control rats. We conclude that altered Cl- homeostasis that makes GABA excitatory and enhanced AVP synthesis are important changes in AVP neurons that would increase AVP secretion in DM. Our data suggest that Cl- transporters in AVP neurons are potential targets of antidiabetes treatments.

Various Approaches and Treatments for Pelvic Organ Prolapse in Women.

Pelvic organ prolapse (POP) is bulging of one or more of the pelvic organs into the vagina and triggered by multiple causes. It is a very common disorder, especially among older women. POP is characterized by protrusion of the presentation part visible by the naked eye, and problems with urination or bowel movements. POP can be diagnosed based on the onset of symptoms and a pelvic exam, and management options include medical and surgical treatment. Although medical treatment cannot correct the abnormal herniation of the pelvic structures, this can help alleviate symptoms. One of the disadvantages of surgical interventions is recurrence, and advances in surgical techniques have decreased recurrence rates of POP. Therefore, author will explain the gynecology and urology approach and treatment.

Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala.

In auditory fear conditioning, experimental subjects learn to associate an auditory conditioned stimulus (CS) with an aversive unconditioned stimulus. With sufficient training, animals fear conditioned to an auditory CS show fear response to the CS, but not to irrelevant auditory stimuli. Although long-term potentiation (LTP) in the lateral amygdala (LA) plays an essential role in auditory fear conditioning, it is unknown whether LTP is induced selectively in the neural pathways conveying specific CS information to the LA in discriminative fear learning. Here, we show that postsynaptically expressed LTP is induced selectively in the CS-specific auditory pathways to the LA in a mouse model of auditory discriminative fear conditioning. Moreover, optogenetically induced depotentiation of the CS-specific auditory pathways to the LA suppressed conditioned fear responses to the CS. Our results suggest that input-specific LTP in the LA contributes to fear memory specificity, enabling adaptive fear responses only to the relevant sensory cue. VIDEO ABSTRACT.

Synaptic Targeting of Double-Projecting Ventral CA1 Hippocampal Neurons to the Medial Prefrontal Cortex and Basal Amygdala.

The acquisition and retrieval of contextual fear memory requires coordinated neural activity in the hippocampus, medial prefrontal cortex (mPFC), and amygdala. The contextual information encoded in the hippocampus is conveyed to the mPFC and amygdala for contextual fear conditioning. Previous studies have suggested that a CA1 neuronal population in the ventral hippocampus (VH) projects to both the mPFC and amygdala and is recruited in context-dependent control of conditioned fear. However, how double-projecting ventral CA1 hippocampal (vCA1) neurons modulate the activity of the mPFC and amygdala at the synaptic level has not been determined previously. Here, we show that the optogenetic silencing of the VH prevented the recall of contextual fear memory in mice, indicating its role in contextual fear expression. In dual retrograde viral tracing and c-Fos immunostaining experiments, we found that a proportion of vCA1 neurons projected to both the mPFC and amygdala and were recruited preferentially during context exposure, suggesting their role in encoding context representations. Moreover, optogenetic stimulation of axon collaterals of double-projecting vCA1 neurons induced monosynaptic excitatory responses in both the mPFC and basal amygdala, indicating that they could convey contextual information through the VH-mPFC and VH-amygdala pathways. The activation of double-projecting vCA1 neurons also induced action potential firings in the mPFC neurons that project to the amygdala, suggesting that they can also activate the VH-mPFC-amygdala pathway. With these synaptic mechanisms, double-projecting vCA1 neurons could induce synchronized neural activity in the mPFC and amygdala and convey contextual information efficiently to the basal amygdala for contextual fear conditioning.SIGNIFICANCE STATEMENT This work demonstrates that ventral CA1 hippocampal (vCA1) neurons projecting to both the medial prefrontal cortex (mPFC) and amygdala are activated preferentially when contextual information is processed in the ventral hippocampus, which is required for contextual fear expression. Our electrophysiological experiments reveal that the activation of double-projecting vCA1 neurons induces excitatory synaptic activity in both the mPFC and amygdala. These results suggest that double-projecting vCA1 neurons could contribute to contextual fear responses by inducing synchronized activity in the mPFC and amygdala and conveying contextual information to the basal amygdala more efficiently than vCA1 neurons projecting to either the mPFC or amygdala alone. These findings provide important insights into the mechanisms of the acquisition and retrieval of contextual fear memory.

Alterations of Macrophage Migration Inhibitory Factor Expression in the Nervous System of the Rat Cystitis Model.

OBJECTIVE: We evaluated the changes in the migration inhibitory factor (MIF) expression with time in the bladder and spinal cord of a Sprague-Dawley rat cystitis model. METHODS: The bladder created by injecting lipopolysaccharide (LPS) and the lumbosacral spinal cord were removed at 4, 24, and 48 h, and 7 days after the induction of chronic cystitis, and 24 h after the induction of acute cystitis. The MIF expression was estimated using immunohistochemical staining, and the MIF mRNA was quantitatively analyzed using real-time polymerase chain reaction. RESULTS: The MIF expression in the urothelial cell was lowest at 24 h after LPS injection. As the degree of inflammation decreased, the MIF expression in the urothelial cell gradually increased 48 h and 7 days. The quantitative analysis of the MIF mRNA showed that the MIF expression was highest in both the bladder and the lumbosacral spinal cord 24 h after the cystitis became most severe. In chronic cystitis, the MIF mRNA expressions in the bladder and the lumbosacral spinal cord were 2.8 and 2.1 times significantly higher than in the normal control. CONCLUSION: MIF is involved in urinary symptoms and pain in cystitis, and in the mechanism that prolongs the symptoms of chronic cystitis by involving bladder tissue, and the nervous system.

Transurethral Resection Alone Vs Resection Combined With Therapeutic Hydrodistention as Treatment for Ulcerative Interstitial Cystitis: Initial Experience With Propensity Score Matching Studies.

OBJECTIVE: To compare the therapeutic efficacy of transurethral resection (TUR) alone with that of TUR combined with therapeutic hydrodistention in patients with ulcerative interstitial cystitis (IC). METHODS: The study subjects were 44 female patients newly diagnosed with IC who underwent TUR to treat ulcerative IC and who were available for follow-up, without recurrence of disease for 12 months. We retrospectively studied both patients who underwent TUR alone (group I) and those who underwent TUR combined with therapeutic hydrodistention (group II). Improvements in pain and voiding symptoms were retrospectively evaluated using a 10-point visual analog scale for pain and a 3-day micturition chart. RESULTS: Group I included 22 patients and group II included 22 patients of mean ages 58.45 ± 11.01 and 56.27 ± 11.86 years, respectively. Use of a 10-point visual analog scale showed that pain decreased after the procedures in both groups, but the improvement did not differ between groups. The maximum functional bladder capacities of patients in group I were 161.36, 192.47, and 204.12 mL, respectively, before, at 6 months, and at 12 months after the operation; the maximum functional bladder capacities of patients in group II were 175.45, 263.14, and 291.17 mL, respectively. The voiding frequencies of group I were 12.59, 10.67, and 9.89 times daily, respectively, before, at 6 months, and at 12 months after the operation; the voiding frequencies of group II were 12.95, 9.5, and 8.29 times daily, respectively. CONCLUSION: TUR combined with therapeutic hydrodistention increased bladder capacity and improved voiding symptoms more so than did TUR alone for ulcerative IC.

Histamine 1 receptor-Gßγ-cAMP/PKA-CFTR pathway mediates the histamine-induced resetting of the suprachiasmatic circadian clock.

BACKGROUND: Recent evidence indicates that histamine, acting on histamine 1 receptor (H1R), resets the circadian clock in the mouse suprachiasmatic nucleus (SCN) by increasing intracellular Ca(2+) concentration ([Ca(2+)]i) through the activation of CaV1.3 L-type Ca(2+) channels and Ca(2+)-induced Ca(2+) release from ryanodine receptor-mediated internal stores. RESULTS: In the current study, we explored the underlying mechanisms with various techniques including Ca(2+)- and Cl(-)-imaging and extracellular single-unit recording. Our hypothesis was that histamine causes Cl(-) efflux through cystic fibrosis transmembrane conductance regulator (CFTR) to elicit membrane depolarization needed for the activation of CaV1.3 Ca(2+) channels in SCN neurons. We found that histamine elicited Cl(-) efflux and increased [Ca(2+)]i in dissociated mouse SCN cells. Both of these events were suppressed by bumetanide [Na(+)-K(+)-2Cl(-) cotransporter isotype 1 (NKCC1) blocker], CFTRinh-172 (CFTR inhibitor), gallein (Gßγ protein inhibitor) and H89 [protein kinase A (PKA) inhibitor]. By itself, H1R activation with 2-pyridylethylamine increased the level of cAMP in the SCN and this regulation was prevented by gallein. Finally, histamine-evoked phase shifts of the circadian neural activity rhythm in the mouse SCN slice were blocked by bumetanide, CFTRinh-172, gallein or H89 and were not observed in NKCC1 or CFTR KO mice. CONCLUSIONS: Taken together, these results indicate that histamine recruits the H1R-Gßγ-cAMP/PKA pathway in the SCN neurons to activate CaV1.3 channels through CFTR-mediated Cl(-) efflux and ultimately to phase-shift the circadian clock. This pathway and NKCC1 may well be potential targets for agents designed to treat problems resulting from the disturbance of the circadian system.