Bladder Activity Research Articles

Mirabegron causes vesical and urethral relaxation in rats with spinal cord injury.

The effects of solifenacin and mirabegron on vesical and urethral function were compared in rats with or without spinal cord injury (SCI). Isovolumetric cystometry and urethral pressure recording were initially performed in intact rats. Then, the bladder neck was ligated under urethane anesthesia, after which a catheter was inserted through the bladder dome for isovolumetric cystometry and another catheter was inserted into the urethra to measure urethral pressure. Solifenacin (0.03-3 mg/kg) or mirabegron (0.03-3 mg/kg) was injected intravenously, and bladder and urethral activity were recorded. To create rats with SCI, the spinal cord was transected at the lower thoracic level under isoflurane anesthesia. After 2 weeks, a catheter was inserted through the bladder dome for single cystometry and bladder activity was recorded without anesthesia following intravenous injection of solifenacin or mirabegron. Isovolumetric cystometry revealed a larger decrease in maximum bladder contraction pressure after injection of solifenacin, whereas prolongation of the interval between bladder contractions was greater with mirabegron. In SCI rats, single cystometry showed that solifenacin and mirabegron both increased bladder volume at the first non-voiding bladder contraction and decreased the maximum bladder contraction pressure. Mirabegron also increased the voided volume and decreased the percentage residual volume without altering bladder capacity. Solifenacin and mirabegron both inhibited bladder contractility, and mirabegron possibly also induced urethral relaxation. Mirabegron may be suitable for patients with overactive bladder and residual urine.

Mechanisms underlying the effects of propiverine on bladder activity in rats with pelvic venous congestion and urinary frequency.

We investigated the mechanisms by which propiverine hydrochloride influenced bladder activity in rats with pelvic venous congestion (PC) and urinary frequency. To create PC rats, female rats were anesthetized with isoflurane and the bilateral common iliac veins and bilateral uterine veins were ligated. At 4 weeks after ligation, we assessed voiding behaviour, locomotor activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide metabolites (NOx). We also performed cystometry and measured mRNAs for nitric oxide synthase (NOS) and several receptors in the bladder wall. PC rats showed a decrease in locomotor activity and an increased frequency of urination. There was a decrease in endothelial NOS (eNOS), M3, and TRPV1 mRNA expression in the bladder wall, as well as an increase in inducible NOS (iNOS) mRNA. Administration of propiverine to PC rats increased locomotor activity to the level in sham rats, improved bladder function, decreased urinary 8-OHdG excretion, and increased urinary NOx excretion. In addition, propiverine increased neuronal NOS (nNOS) mRNA expression, and decreased expression of iNOS, M3 and TRPV1 mRNA in the bladder wall. Therefore, propiverine not only improved bladder dysfunction through its previously reported actions (anti-muscarinic effect, Ca antagonist effect, and inhibition of noradrenaline re-uptake), but also by reducing inflammation.

Monitoring internal contamination from OEW of an 18F-FDG production plant: WBC or head counting setup?

The production 18F-FDG for positron emission tomography (PET) has consistently increased over the past two decades. The risk of internal contamination at 18F-FDG production facilities exists. A setup for evaluation of the 18F-FDG activity incorporated into the OEW brain, called Head Counting System (HCS), was presented in previous works. In this study, the whole body counter setup (WBC) was evaluated for monitoring 18F incorporations. The Monte Carlo Virtual Software (VMC in-vivo) and the MCNPx code were used to assess the system calibration coefficient (CC). Three 18F distributions were simulated: i) uniformly distributed in soft tissue (UDST); ii) Na18F biodistribution (NAFB); and iii) 18F-FDG biodistribution (FDGB). The calibration coefficient of WBC was compared to the current head counting system CC under the same biodistribution conditions. The ICRP male reference voxelized phantoms (RCP_AM) was used in the simulations. The results showed that the WBC setup was more efficient than the head counter for all the studied 18F distributions: UDST = 1060 %, FDGB = 488 % and NAFB = 340 %. Despite this, especially for 18F-FDG, the possibility of bladder voiding before measurement can lead to considerable uncertainties when the WBC setup is used. On the other hand, bladder activity does not show great influence the calibration coefficient of the head counting system. Future work will evaluate the WBC sources of uncertainties in the measurement of 18F incorporated activity.

Prokinetic effects of the neurokinin NK2 receptor agonist [Lys5,MeLeu9,Nle10]-NKA(4–10) on bladder and colorectal activity in minipigs

The effects of the neurokinin NK2 receptor agonist [Lys5,MeLeu9,Nle10]-NKA(4–10) (LMN-NKA) on bladder and colorectal function were examined in minipigs. In anesthetized animals, subcutaneous (SC) administration of 30–100 μg/kg increased peak bladder and colorectal pressures. Increases in bladder and colorectal pressure were inhibited by a 15 min pretreatment with the NK2 receptor antagonist GR 159897 (1 mg/kg intravenously (IV)). Bladder and colorectal pressures were also increased after IV (0.3 μg/kg), intranasal (IN; 100 μg/kg) and sublingual administration (SL; 5 mg/kg). There was a nonsignificant trend for hypotension (16 or 12% decrease in mean arterial pressure) after 100 μg/kg SC and 0.3 μg/kg IV, respectively, but not after 100 μg/kg IN or 5 mg/kg SL. In conscious minipigs, 30–300 μg/kg SC caused a dose-related increase in defecation that was accompanied by emesis in 38% of subjects receiving 300 μg/kg. Urination was increased after 100 μg/kg SC but not lower or higher doses. The peak plasma exposure (Cmax) after 100 μg/kg SC was 123 ng/mL, and area under the curve (AUC) was 1790 min * ng/mL. Defecation response rates (~82%) were maintained after SC administration of LMN-NKA (30 μg/kg) given 3 times daily over 5 consecutive days. Defecation rates were higher after a single dose of 100 μg/kg IN compared with vehicle, but this did not reach significance. After 7–10 mg/kg SL, 83% of animals urinated and defecated, and none had emesis. The data support the feasibility of developing a convenient and well-tolerated route of administration of LMN-NKA for human use. Minipigs may be a suitable species for toxicology studies with LMN-NKA due to the relatively low rate of emesis in this species.

The role of prostaglandin and E series prostaglandin receptor type 4 receptors in the development of bladder overactivity in a rat model of chemically induced prostatic inflammation.

To evaluate, using a rat model of non-bacterial prostatic inflammation, the prostaglandin production and expression profiles of E-series prostaglandin (EP) receptor subtypes, which are reportedly implicated in the development of overactive bladder, in the bladder mucosa, and to investigate the effect of EP receptor type 4 (EP4) blockade on bladder overactivity after prostatic inflammation. Male Sprague-Dawley rats were used. Prostatic inflammation was induced by formalin injection (5%; 50μL per lobe) into the bilateral ventral lobes of the prostate. At 10days after induction of prostatic inflammation or vehicle injection, bladder tissues from the deeply anaesthetized rats were harvested and separated into mucosal and detrusor layers. Then, prostaglandin E2 (PGE2) concentrations and protein levels of PGE2 receptors (EP1-4) in the bladder mucosa and detrusor were measured by ELISA and Western blotting, respectively. In separate groups of control and formalin-treated rats, awake cystometry was performed to evaluate the changes in bladder activity after prostatic inflammation. In addition, the effect of intravesical administration of a selective EP4 antagonist (ONO-AE3-208; 30μm) on bladder activity was evaluated in control rats and rats with prostatic inflammation. PGE2 concentration and protein levels of EP4, but not other EP receptor subtypes, in the bladder mucosa and detrusor layers were significantly increased in formalin-injected rats vs vehicle-injected control rats. In cystometry, rats with prostatic inflammation exhibited a significant decrease in intercontraction intervals (ICIs) compared with control rats. Intravesical application of ONO-AE3-208 (30μm), but not vehicle application, significantly increased ICIs in rats with prostatic inflammation, whereas ONO-AE3-208 at this concentration did not significantly affect any cystometric values in control rats. Because intravesical administration of an EP4 antagonist effectively improved bladder overactivity after prostatic inflammation, EP4 activation, along with increased PGE2 production in the bladder mucosa, seems to be an important contributing factor to bladder overactivity induced by prostatic inflammation. Thus, blockade of EP4 in the bladder could be a therapeutic approach to male lower urinary tract symptoms attributable to benign prostatic hyperplasia with prostatic inflammation.

Simultaneous Measurement of Neuronal Activity in the Pontine Micturition Center and Cystometry in Freely Moving Mice

Understanding the complex neural mechanisms controlling urinary bladder activity is an extremely important topic in both neuroscience and urology. Simultaneously recording of the bladder activity and neural activity in related brain regions will largely advance this field. However, such recording approach has long been restricted to anesthetized animals, whose bladder function and urodynamic properties are largely affected by anesthetics. In our recent report, we found that it is feasible to record bladder pressure (cystometry) and the related cortical neuron activity simultaneously in freely moving mice. Here, we aimed to demonstrate the use of this combined method in freely moving mice for recording the activity of the pontine micturition center (PMC), a more difficultly approachable small region deeply located in the brainstem and a more popularly studied hub for controlling bladder function. Interestingly, we found that the duration of urination events linearly correlated to the time course of neuronal activity in the PMC. We observed that the activities of PMC neurons highly correlated with spike-like increases in bladder pressure, reflecting bladder contractions. We also found that anesthesia evoked prominent changes in the dynamics of the Ca2+ signals in the PMC during the bladder contraction and even induced the dripping overflow incontinence due to suppression of the neural activity in the PMC. In addition, we described in details both the system for cystometry in freely moving mice and the protocols for how to perform this combined method. Therefore, this work provides a powerful approach that enables the simultaneous measurement of neuronal activity of the PMC or any other brain sites and bladder function in freely behaving mice. This approach offers a promising possibility to examine the neural mechanisms underlying neurogenic bladder dysfunction.

Sildenafil corrects the increased contractility of rat detrusor muscle induced by alprostadil in vitro

Sildenafil (PDE5-inhibitor) and alprostadil (PGE1) are used in combination clinically for the management of some cases of erectile dysfunction. Despite the roles of prostaglandins (PG) and nitric oxide (NO) pathways in contractility of bladder smooth muscle are frequently studied, the effect of sildenafil/alprostadil combination and the crosstalk between NO/cGMP and PG pathways on bladder activity is not documented. Organ-bath experiments were performed using isolated rat detrusor muscle. Direct and neurogenic contractions were induced using ACh and electric stimulation (EFS, 4Hz, 80V, 1ms), respectively. The contractile responses in absence and presence of the tested drugs at different concentrations were compared. Results are expressed as mean ± SEM (n = 5-7). Alprostadil (0.01-10 μM) concentration-dependently potentiated ACh (100μM)- and EFS (4 Hz)- induced contraction. Maximum potentiation of ACh-contraction in presence of alprostadil was 40 ± 5%. Sildenafil potentiated ACh-induced contraction at low concentrations (0.01-1 μM), but inhibited it at higher ones (10-100 μM). IBMX (non-selective PDE-inhibitor, 0.01-100μM) and SNP (NO-donor, 1nM-1 mM) produced the same biphasic pattern. The potentiatory phase of sildenafil was inhibited by atropine (0.1μM), L-NAME (non-selective NOS-inhibitor, 100μM), N-PLA (nNOS-inhibitor, 30μM) or MB (nonselective GC-inhibitor, 10μM). In presence of sildenafil (0.1μM), the concentration-response curve of alprostadil (0.01-10μM) on both ACh and EFS-induced contraction was clearly shifted downward. A crosstalk between PGE1 and NO/cGMP pathways may exist. At low concentrations only, the effect of sildenafil on bladder contractility is dependent on NO/cGMP. cGMP intracellularly-elevated by sildenafil, may inhibit the activity of PLC and hence the cascade of EP1-receptors, thus masking the hyperactivity of bladder caused by alprostadil, which adds to the advantages of this combination.

12 - Injecting RNA interference lentiviruses targeting the muscarinic 3 receptor gene into the bladder wall inhibits neurogenic detrusor overactivity in rats with spinal cord injury

INTRODUCTION AND OBJECTIVES:To investigate the effects of injecting RNA interference (RNAi) lentiviruses targeting the muscarinic 3 (M3) receptor gene into the bladder wall on bladder activity in r...

Bladder overactivity and afferent hyperexcitability induced by prostate-to-bladder cross-sensitization in rats with prostatic inflammation.

There is clinical evidence showing that prostatic inflammation contributes to overactive bladder symptoms in male patients; however, little is known about the underlying mechanisms In this study, we investigated the mechanism that prostatic inflammation causes detrusor overactivity by using a rat model of chemically induced prostatic inflammation. We observed a significant number of dorsal root ganglion neurons with dichotomized afferents innervating both prostate and bladder. We also found that prostatic inflammation induces bladder overactivity and urothelial NGF overexpression in the bladder, both dependent on activation of the pelvic nerve, as well as changes in ion channel expression and hyperexcitability of bladder afferent neurons. These results indicate that the prostate-to-bladder cross-sensitization through primary afferent pathways in the pelvic nerve, which contain dichotomized afferents, could be an important mechanism contributing to bladder overactivity and afferent hyperexcitability induced by prostatic inflammation. Prostatic inflammation is reportedly an important factor inducing lower urinary tract symptoms (LUTS) including urinary frequency, urgency and incontinence in patients with benign prostatic hyperplasia (BPH). However, the underlying mechanisms inducing bladder dysfunction after prostatic inflammation are not well clarified. We therefore investigated the effects of prostatic inflammation on bladder activity and afferent function using a rat model of non-bacterial prostatic inflammation. We demonstrated that bladder overactivity, evident as decreased voided volume and shorter intercontraction intervals in cystometry, was observed in rats with prostatic inflammation versus controls. Tissue inflammation, evident as increased myeloperoxidase activity, and IL-1α, IL-1β, and IL-6 levels inside the prostate, but not in the bladder, following intraprostatic formalin injection induced an increase in NGF expression in the bladder urothelium, which depended on activation of the pelvic nerve. A significant proportion (18-19%) of dorsal root ganglion neurons were double labelled by dye tracers injected into either bladder or prostate. In rats with prostatic inflammation, TRPV1, TRPA1 and P2X2 increased, and Kv1.4, a potassium channel α-subunit that can form A-type potassium (KA ) channels, decreased at mRNA levels in bladder afferent and double-labelled neurons vs. non-labelled neurons, and slow KA current density decreased in association with hyperexcitability of these neurons. Collectively, non-bacterial inflammation localized in the prostate induces bladder overactivity and enhances bladder afferent function. Thus, prostate-to-bladder afferent cross-sensitization through primary afferents in the pelvic nerve, which contain dichotomized afferents, could underlie storage LUTS in symptomatic BPH with prostatic inflammation.

Physical activity and subsequent risk of kidney, bladder and upper urinary tract cancer in the Japanese population: the Japan Public Health Centre-based Prospective Study

BackgroundAlthough physical activity has been reported as a protective factor for kidney and bladder cancer in epidemiological studies, it is not clear.MethodsIn a population-based prospective study of 76,795 Japanese aged 45–74 years, participants were evaluated physical activity by self-administered questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the risk of urological cancer were calculated by the Cox proportional hazards models.ResultsDuring the 15.1-year follow-up, 202 kidney, 373 bladder and 83 upper urinary tract cancer cases were identified. Physical activity was not significantly associated with kidney, bladder and upper urinary tract cancer risks, with multivariate HRs in the highest versus lowest group of 1.05 (95% CI: 0.74–1.49), 1.06 (95% CI: 0.81–1.39) and 0.80 (95% CI: 0.48–1.35), respectively.ConclusionsPhysical activity was not associated with the risk of urological cancer in the Japanese population.

Sympathetic afferents in the hypogastric nerve facilitate nociceptive bladder activity in cats.

This study in α-chloralose-anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly ( P < 0.05) reduced bladder capacity to 45.0 ± 5.7% of the control capacity measured during a saline cystometrogram (CMG). In cats with the hypogastric nerves transected bilaterally, AA irritation also significantly ( P < 0.05) reduced bladder capacity, but the change was significantly smaller (capacity reduced to 71.5 ± 10.6% of saline control, P < 0.05) than that in cats with an intact hypogastric nerve. However, application of hypogastric nerve stimulation (HGNS: 20 Hz, 0.2 ms pulse width) to the central end of the transected nerves at an intensity (16 V) strong enough to activate C-fiber afferent axons facilitated the effect of AA irritation and further ( P < 0.05) reduced bladder capacity to 48.4 ± 7.4% of the saline control. This facilitation by HGNS was effective only at selected frequencies (1, 20, and 30 Hz) when the stimulation intensity was above the threshold for activating C-fibers. Tramadol (an analgesic agent) at 3 mg/kg iv completely blocked the nociceptive bladder activity and eliminated the facilitation by HGNS. HGNS did not alter non-nociceptive bladder activity induced by saline distention of the bladder. These results indicate that sympathetic afferents in the hypogastric nerve play an important role in the facilitation of the nociceptive bladder activity induced by bladder irritation that activates the silent C-fibers in the pelvic nerve.

Effects of intravesical administration of sensory neuron-specific receptor agonist on voiding function in rats with cyclophosphamide-induced cystitis

IntroductionThe aim of this study was to investigate the urodynamic effects of intravesical administration of bovine adrenal medulla 8-22 (BAM8-22), a selective rat sensory neuron-specific receptor 1 agonist, on the micturition reflex in normal rats and rats with cyclophosphamide-induced bladder overactivity.Material and methodsContinuous cystometrograms (0.04 ml/min) were performed in urethane-anesthetized rats. After stable micturition cycles were established, vehicle (saline) or BAM8-22 was instilled intravesically and changes in bladder activity were monitored. The experiments using BAM8-22 were also performed in capsaicin-pretreated rats. In another experiment, vehicle (saline) or BAM8-22 was instilled intravesically and changes in bladder activity were monitored in cyclophosphamide-treated rats. Continuous cystometrograms were performed 48 hours after cyclophosphamide injection. Cystometric parameters were recorded and compared before and after intravesical drug administration.ResultsIntravesical administration of BAM8-22 significantly increased the intercontraction interval and threshold pressure in urethane-anesthetized rats, but did not affect the basal pressure or maximum pressure at any doses tested. The inhibitory effects of intravesical administration of BAM8-22 were not inhibited by capsaicin pretreatment. Intravesical administration of BAM8-22 also significantly increased intercontraction interval in the cyclophosphamide-treated rats.ConclusionsThe current results indicate that intravesical administration of a selective rat sensory neuron-specific receptor 1 agonist can inhibit the micturition reflex and can ameliorate cyclophosphamide-induced bladder overactivity in rats.

Corrigendum to: Porcine bile powder supplementation of a high fat broiler diet in relation to growth performance and nutrient digestion

The aim of the study was to examine the effect of pig bile powder supplementation on the digestibility of nutrients, fat digestion and growth performance of starter broilers fed on a high fat diet. A total of 1110, day-old, male broiler chicks (Arbor Acres) were randomly allocated into six treatment groups with five replicates per treatment. The chicks were fed on a corn-soybean meal basal diet with a starter formulation until Day 14, followed by a grower formulation until Day 21. In group 1 (T1), the basal diet contained 30 g/kg crude palm oil whereas the diet used in group 2 (T2) had 60 g/kg crude palm oil. Chicks in group 3 (T3) were fed on T2 diet supplemented with 5.0 g/kg soy lecithin as the positive control. Chicks in groups 4–6 (T4–T6) received diets used in T2, supplemented with 1.25, 2.5 and 5.0 g/kg lyophilised pig bile powder, respectively. On Days 4, 7, 14 and 21, chicks were killed, portal blood was collected and analysed for fatty acids, pancreas collected for measurement of pancreatic lipase activity, bile and jejunal contents for bile acid determination and ileal content for determining digestibility of fat and protein. The results showed (1) there was no difference in bodyweight and feed intake among T2–T6, (2) pancreatic lipase activity of chicks in T4 and T5 was highest in all periods. Total bile acid concentrations in the gall bladder and jejunum in T4 was lower than those in T2 in all periods, and Days 4 and 7, respectively, (3) digestibility of protein and fat in T3 and T4 was higher in all the period than that of T2, T5 and T6, (4) increased fat content in the diet did not cause a significant increase in any fatty acids in the portal plasma when compared T1 and T2. In conclusion, 2.5 g/kg porcine bile powder supplemented in high fat diet increased pancreatic lipase activity and total bile acid concentrations in gall bladder, resulting in increased ileal digestibility of fat and protein.

Injecting RNA interference lentiviruses targeting the muscarinic 3 receptor gene into the bladder wall inhibits neurogenic detrusor overactivity in rats with spinal cord injury.

To investigate the effects of injecting RNA interference (RNAi) lentiviruses targeting the muscarinic 3 (M3 ) receptor gene into the bladder wall on bladder activity in rats with spinal cord injury (SCI). Four M3 RNAi lentiviruses were constructed and used to infect primary cultured bladder smooth muscle cells (BSMCs). Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to determine the optimal RNAi lentivirus with the highest interference efficiency. Female Wistar rats were subjected spinal cord transection at T9-10 and randomly divided into three groups (n = 8), namely, blank control, negative control, and experimental groups, and injected into the bladder wall with saline, negative control shRNA, and M3 RNAi lentiviruses, respectively, 1 week after spinal cord transection. The normal rats were used as normal control group. Urodynamic parameters and bladder tissues were evaluated in the different groups. An M3 RNAi lentivirus with the highest interference efficiency (78.9%) was constructed and identified. Three weeks after injecting M3 RNAi lentiviruses into the bladder wall, Western blotting and qRT-PCR showed that the M3 receptor was significantly downregulated in the experimental group. Cystometric evaluation suggested that downregulating M3 receptor expression could substantially decrease basal pressure, residual volume, and non-voiding contraction number, increase intercontraction interval, and significantly improve bladder compliance in rats with SCI. Injecting RNAi lentiviruses targeting the M3 receptor gene into the bladder wall could effectively inhibit neurogenic detrusor overactivity (NDO) due to SCI. Thus, this approach may be a potential treatment for NDO in SCI.

Validation of the physiological background correction method for the suppression of the spill-in effect near highly radioactive regions in positron emission tomography

BackgroundPositron emission tomography (PET) imaging has a wide applicability in oncology, cardiology and neurology. However, a major drawback when imaging very active regions such as the bladder is the spill-in effect, leading to inaccurate quantification and obscured visualisation of nearby lesions. Therefore, this study aims at investigating and correcting for the spill-in effect from high-activity regions to the surroundings as a function of activity in the hot region, lesion size and location, system resolution and application of post-filtering using a recently proposed background correction technique. This study involves analytical simulations for the digital XCAT2 phantom and validation acquiring NEMA phantom and patient data with the GE Signa PET/MR scanner. Reconstructions were done using the ordered subset expectation maximisation (OSEM) algorithm. Dedicated point-spread function (OSEM+PSF) and a recently proposed background correction (OSEM+PSF+BC) were incorporated into the reconstruction for spill-in correction. The standardised uptake values (SUV) were compared for all reconstruction algorithms.ResultsThe simulation study revealed that lesions within 15–20 mm from the hot region were predominantly affected by the spill-in effect, leading to an increased bias and impaired lesion visualisation within the region. For OSEM, lesion SUVmax converged to the true value at low bladder activity, but as activity increased, there was an overestimation as much as 19% for proximal lesions (distance around 15–20 mm from the bladder edge) and 2–4% for distant lesions (distance larger than 20 mm from the bladder edge). As bladder SUV increases, the % SUV change for proximal lesions is about 31% and 6% for SUVmax and SUVmean, respectively, showing that the spill-in effect is more evident for the SUVmax than the SUVmean. Also, the application of post-filtering resulted in up to 65% increment in the spill-in effect around the bladder edges. For proximal lesions, PSF has no major improvement over OSEM because of the spill-in effect, coupled with the blurring effect by post-filtering. Within two voxels around the bladder, the spill-in effect in OSEM is 42% (32%), while for OSEM+PSF, it is 31% (19%), with (and without) post-filtering, respectively. But with OSEM+PSF+BC, the spill-in contribution from the bladder was relatively low (below 5%, either with or without post-filtering). These results were further validated using the NEMA phantom and patient data for which OSEM+PSF+BC showed about 70–80% spill-in reduction around the bladder edges and increased contrast-to-noise ratio up to 36% compared to OSEM and OSEM+PSF reconstructions without post-filtering.ConclusionThe spill-in effect is dependent on the activity in the hot region, lesion size and location, as well as post-filtering; and this is more evident in SUVmax than SUVmean. However, the recently proposed background correction method facilitates stability in quantification and enhances the contrast in lesions with low uptake.

Can SUVmax values of Ga-68-PSMA PET/CT scan predict the clinically significant prostate cancer?

PurposeThe intensity of prostate-specific membrane antigen (PSMA) expression increases as the tumor grade increases and the uptake of Ga-68-PSMA is higher in high-grade tumors. The aim of the present study was to evaluate the correlation of preoperative tracer uptake of primary tumor to Gleason Score in patients who underwent prostatectomy.Patients and methodsWe retrospectively evaluated 141 patients who had Ga-68-PSMA positron emission tomography/computed tomography (PET/CT) imaging and who underwent prostatectomy. All patients had a diagnosis of prostate cancer on the basis of 10–24 cores transrectal ultrasound-guided biopsy (TRUS-Bx). Histological assessment was performed according to the New Contemporary Prostate Cancer Grading System. All patients had a prostate-specific antigen (PSA) level measurement within maximum of 28 days before Ga-68-PSMA PET/CT. Region of interests were drawn manually around the prostate gland, avoiding the bladder activity, to calculate the maximum standardized uptake values (SUVmax) values.ResultsThe median PSA values for all patients were 10.0 ng/ml. PSA values for low-risk patients were significantly lower than those of high-risk patients (P<0.001). There were 41.1% upgrades and 7.8% downgrades following prostatectomy in terms of Grade Groups. According to the final pathology reports, 21% (n=16) of patients moved from a low-risk level (grade groups 1+2) to a high-risk level (grade groups 3+4+5). The median SUVmax value was 8.8, ranging from 2.1 to 62.4. There was a strong correlation between SUVmax values and grade groups (Pearson ρ=0.66) (P<0.001). The mean SUVmax values of high-risk patients were significantly higher than those of low-risk patients (18.9±12.1 vs. 7.16±6.2, respectively) (P<0.001). Receiver operation characteristic curve analysis of SUVmax at the cut-off value of 9.1 showed a high sensitivity (78%) and specificity (81%) for detection of high risk disease.ConclusionSUVmax values correlate significantly with the grade groups of the primary tumor. The intraprostatic accumulation sites may predict clinically significant cancer and potentially serve as a target for biopsy sampling in conjunction with mpMRI in selected patients.

Excitatory and inhibitory effects of stimulation of sacral dorsal root ganglion on bladder reflex in cats.

To explore the effects of electrical stimulation of the sacral dorsal root ganglion (DRG) on bladder reflexes in α-chloralose-anesthetized cats. Bladder activity was recorded under isovolumetric conditions. A pair of hook electrodes was placed in the right S1 and S2 DRGs of 12 adult male cats, which were stimulated over a range of frequencies (0.25-30Hz) and at threshold intensity. Stimulation of S1 and S2 DRGs inhibited or evoked bladder contractions under isovolumetric conditions depending on the frequency of stimulation in nine cats. Stimulation at low frequencies (3-7Hz on S1 or S2 DRG) significantly inhibited isovolumetric rhythmic bladder contractions, while excitatory effects were observed at two frequency ranges, including lower frequencies (0.25-1.5Hz on S1 DRG and 0.25-1.25Hz on S2 DRG) and middle frequencies (15-30Hz on S1 and S2 DRGs). These results suggest that the sacral DRG might be a potential valuable target for electrical stimulation in the treatment of bladder dysfunction.

Frequency Dependent Tibial Neuromodulation of Bladder Underactivity and Overactivity in Cats

This study is aimed at determining if tibial nerve stimulation (TNS) can modulate both bladder underactivity and overactivity. In α-chloralose anesthetized cats, tripolar cuff electrodes were implanted on both tibial nerves and TNS threshold (T) for inducing toe twitching was determined for each nerve. Normal bladder activity was elicited by slow intravesical infusion of saline; while bladder overactivity was induced by infusion of 0.25% acetic acid to irritate the bladder. Bladder underactivity was induced during saline infusion by repeated application (2-6 times) of 30-min TNS (5 Hz, 4-8T, 0.2 msec) to the left tibial nerve, while TNS (1 Hz, 4T, 0.2 msec) was applied to the right tibial nerve to reverse the bladder underactivity. Prolonged 5-Hz TNS induced bladder underactivity by significantly increasing bladder capacity to 173.8% ± 10.4% of control and reducing the contraction amplitude to 40.1% ± 15.3% of control, while 1 Hz TNS normalized the contraction amplitude and significantly reduced the bladder capacity to 130%-140% of control. TNS at 1 Hz in normal bladders did not change contraction amplitude and only slightly changed the capacity, but in both normal and underactive bladders significantly increased contraction duration. The effects of 1 Hz TNS did not persist following stimulation. Under isovolumetric conditions when the bladder was underactive, TNS (0.5-3 Hz; 1-4T) induced large amplitude and sustained bladder contractions. In overactive bladders, TNS during cystometry inhibited bladder overactivity at 5 Hz but not at 1 Hz. This study indicates that TNS at different frequencies might be used to treat bladder underactivity and overactivity.

Porcine bile powder supplementation of a high fat broiler diet in relation to growth performance and nutrient digestion

The aim of the study was to examine the effect of pig bile powder supplementation on the digestibility of nutrients, fat digestion and growth performance of starter broilers fed on a high fat diet. A total of 1110, day-old, male broiler chicks (Arbor Acres) were randomly allocated into six treatment groups with five replicates per treatment. The chicks were fed on a corn-soybean meal basal diet with a starter formulation until Day 14, followed by a grower formulation until Day 21. In group 1 (T1), the basal diet contained 30 g/kg crude palm oil whereas the diet used in group 2 (T2) had 60 g/kg crude palm oil. Chicks in group 3 (T3) were fed on T2 diet supplemented with 5.0 g/kg soy lecithin as the positive control. Chicks in groups 4–6 (T4–T6) received diets used in T2, supplemented with 1.25, 2.5 and 5.0 g/kg lyophilised pig bile powder, respectively. On Days 4, 7, 14 and 21, chicks were killed, portal blood was collected and analysed for fatty acids, pancreas collected for measurement of pancreatic lipase activity, bile and jejunal contents for bile acid determination and ileal content for determining digestibility of fat and protein. The results showed (1) there was no difference in bodyweight and feed intake among T2–T6, (2) pancreatic lipase activity of chicks in T4 and T5 was highest in all periods. Total bile acid concentrations in the gall bladder and jejunum in T4 was lower than those in T2 in all periods, and Days 4 and 7, respectively, (3) digestibility of protein and fat in T3 and T4 was higher in all the period than that of T2, T5 and T6, (4) increased fat content in the diet did not cause a significant increase in any fatty acids in the portal plasma when compared T1 and T2. In conclusion, 2.5 g/kg porcine bile powder supplemented in high fat diet increased pancreatic lipase activity and total bile acid concentrations in gall bladder, resulting in increased ileal digestibility of fat and protein.

Long-term outcome of MR-guided focused ultrasound treatment and laparoscopic myomectomy for symptomatic uterine fibroid tumors

Fibroid tumors are the most common benign tumors in women of reproductive age. Treatment is usually indicated for those who are symptomatic, with different techniques being used. The purpose of this study was to compare the long-term outcome of laparoscopic myomectomy with magnetic resonance-guided focused ultrasound for symptomatic uterine fibroid tumors. A cohort study was conducted on all patients with symptomatic uterine fibroid tumors who were admitted to a single tertiary care center and treated operatively with laparoscopic myomectomy or treated conservatively with magnetic resonance-guided focused ultrasound from January 2012 until January 2017. Assessment for further interventions and sustained fibroid-associated symptoms was performed, with the use of the Uterine Fibroid Symptom and Quality of Life symptom severity score. One hundred fifty-four women met the inclusion criteria. Complete follow-up evaluation was achieved for 64 women who underwent laparoscopic myomectomy and for 68 women who were treated by magnetic resonance-guided focused ultrasound. Follow-up time was similar for the 2 groups (median, 31 months [interquartile range, 17-51 months] vs 36 months [interquartile range, 24-41]; P=.95). The rate of additional interventions was 5 (7.8%) and 9 (13.2%), respectively (P=0.312). Similarly, the Uterine Fibroid Symptom and Quality of Life symptom severity score questionnaire score at follow-up interviews revealed comparable median scores of 17 (interquartile range, 12-21) vs 17 (interquartile range, 13-22) for laparoscopic myomectomy and magnetic resonance-guided focused ultrasound, respectively (P=.439). Analysis of each of the symptoms separately (bleeding, changes in menstruation, abdominal pain, bladder activity, nocturia, fatigue) did not change these findings, nor did a multivariate analysis. Satisfaction with long-term outcome and rate of reinterventions after magnetic resonance-guided focused ultrasound treatment or laparoscopic myomectomy for uterine fibroid tumors was comparable. Further larger randomized trials are needed to confirm these findings.