Biomedical subjects

Michael B Chancellor

Publications and source records attributed to Michael B Chancellor.

At least 19 recordsLinked to original sources

PubMed2006

Ex vivo biomechanical properties of the female urethra in a rat model of birth trauma.

Stress urinary incontinence (SUI) is the involuntary release of urine during sudden increases in abdominal pressures. SUI is common in women after vaginal delivery or pelvic trauma and may alter the biomechanical properties of the urethra. Thus we hypothesize that injury due to vaginal distension (VD) decreases urethral basal tone and passive stiffness. This study aimed to assess the biomechanical properties of the urethra after VD in the baseline state, where basal muscle tone and extracellular matrix (ECM) are present, and in the passive state, where inactive muscle and ECM are present. Female rat urethras were isolated in a rat model of acute SUI induced by simulated birth trauma. Our established ex vivo system was utilized, wherein we applied intraluminal static pressures ranging from 0 to 20 mmHg. Outer diameter was measured via a laser micrometer. Measurements were recorded via computer. Urethral thickness was assessed histologically. Stress-strain responses of the urethra were altered by VD. Quantification of biomechanical parameters indicated that VD decreased baseline stiffness. The passive peak incremental elastic modulus of the distal segment in VD urethras was less than for controls (1.84 +/- 0.67 vs. 1.19 +/- 0.70 x 10(6) dyne/cm(2), respectively; P = 0.016). An increase was noted in passive low-pressure compliance values in proximal VD urethras compared with controls (9.44 +/- 2.43 vs. 4.62 +/- 0.60 mmHg(-1), respectively; P = 0.04). Biomechanical analyses suggest that VD alters urethral basal tone, proximal urethral compliance, and distal stiffness. Lack of basal smooth muscle tone, in combination with these changes in the proximal and distal urethra, may contribute to SUI induced by VD.

Animals↗

PubMed2006

Suppression of detrusor overactivity in rats with bladder outlet obstruction by a type 4 phosphodiesterase inhibitor.

OBJECTIVE: To investigate the effects of a selective type 4 cyclic nucleotide phosphodiesterase (PDE4) inhibitor, IC486051, on bladder activity in normal rats and those with and bladder outlet obstruction (BOO), as inhibition of PDE4 leads to elevation of intracellular cAMP levels and relaxation of smooth muscle. MATERIALS AND METHODS: BOO was induced in female Sprague-Dawley rats by tying a silk ligature around the urethra. At 4 or 6 weeks after inducing BOO, conscious rats were assessed by cystometry with the urethral ligature intact. In unobstructed rats, blood pressure was also measured. RESULTS: In unobstructed rats, IC486051 (0.1 mg/kg intravenously) produced no significant changes in cystometric variables, while at a dose of 0.5 mg/kg maximum voiding pressure was reduced by 34%. At both doses, there was a small, transient increase in blood pressure. In both 4- and 6-week BOO rats IC486051 dose-dependently decreased the number and amplitude of non-voiding bladder contractions by up to 80%, relative to pre-treatment values. At doses of 0.1 and 0.5 mg/kg IC486051 had no significant effect on voiding variables. In the 4-week BOO rats, a dose of 1.0 mg/kg decreased bladder capacity, voided volume and residual volume by 21%, 32% and 18%, respectively. In 6-week BOO rats, a dose of 1.0 mg/kg decreased maximal voiding pressure by 17% and pressure threshold for voiding by 28%. In both groups of rats with BOO, voiding efficiency was unchanged. CONCLUSIONS: A selective PDE4 inhibitor can effectively suppress detrusor overactivity in rats with BOO, at doses that have no effect on voiding bladder contractions. Thus, selective PDE4 inhibitors should be considered for the treatment of overactive bladder in patients with BOO.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2006

Intraprostatic capsaicin injection as a novel model for nonbacterial prostatitis and effects of botulinum toxin A.

OBJECTIVES: An animal model for nonbacterial prostatitis in rats was developed with the use of intraprostatic injection of capsaicin, an agent thought to excite C-afferent fibers and cause neurogenic inflammation. The analgesic and anti-inflammatory properties of botulinum toxin type A (BoNT-A) was tested in this model. METHODS: Adult male Spraque-Dawley rats were injected with varying doses of capsaicin into the prostate. The nociceptive effects of capsaicin were evaluated for 30min by using a behavior approach; then the prostate was removed for histology and cyclooxygenase (COX) 2 protein concentration measurement. Evans blue (50mg/kg) was also injected intravenously to assess for plasma protein extravasation. A second set of animals were injected with up to 20U of BoNT-A into the prostates 1 wk prior to intraprostatic injection of 1000micromol/l capsaicin. RESULTS: Capsaicin dose dependently induced modifications in pain behavior: closing of the eyes, hypolocomotion, and inflammatory changes: increase of inflammatory cell accumulation, COX2 expression, and plasma extravasation at the acute stage, but completely recovered at 1 wk. BoNT-A pretreatment dose dependently reversed pain behavior and inflammation. BoNT-A 20U significantly decreased inflammatory cell accumulation, COX2 expression, and Evans blue extraction (82.1%, 83.0%, and 50.4%, respectively), and reduced pain behavior (66.7% for eye score and 46.5% for locomotion score). CONCLUSIONS: Intraprostatic capsaicin injection induced neurogenic prostatitis and prostatic pain, and may be a useful research model. BoNT-A produced anti-inflammatory and analgesic effects, and support clinical evaluation in prostatitis.

Animals↗

PubMed2006

Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats.

Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder afferent neurons. In adult female rats, NGF (2.5 microg/microl) was infused continuously into the intrathecal space at the L6-S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 microl/h). Bladder afferent neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6-S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder afferent neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K+ currents was decreased by 52% in bladder afferent neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder afferent pathways and NGF-induced reduction in A-type K+ current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder afferent neurons.

Animals↗

PubMed2006

Role of noradrenergic pathways in sneeze-induced urethral continence reflex in rats.

To clarify the role of noradrenergic pathways in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of the norepinephrine reuptake inhibitor nisoxetine and alpha-adrenoceptor antagonists phentolamine (nonspecific blocker) and prazosin (alpha(1)-receptor-selective blocker) on the neurally evoked urethral continence reflex induced by sneezing in rats. The amplitude of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, intrathecal (it) phentolamine (0.02 nmol) and prazosin (0.02 nmol) decreased A-URS by 11.9 and 15.7%, respectively, without affecting UBP. In both normal and VD rats, intravenous (iv) application of nisoxetine (1 mg/kg) increased A-URS by 17.2 and 18.3% and UBP by 23.7 and 32.7%, respectively. Phentolamine or prazosin (both it) eliminated nisoxetine-induced increases in A-URS, but not the increases in UBP, which were, however, suppressed by iv phentolamine (5 mg/kg) or prazosin (1 mg/kg). Sneezing induced fluid leakage from the urethral orifice in VD rats, but not in normal rats. In VD rats, S-LPP was increased by 30.2% by iv nisoxetine. Application of phentolamine and prazosin (both it) decreased S-LPP by 15.7 and 20.6%, respectively, and nisoxetine induced increases in S-LPP to 13.2 and 12.3%, respectively. These results indicate that activation of the noradrenergic system by a norepinephrine reuptake inhibitor can prevent SUI via alpha(1-)adrenoceptors by enhancing the sneeze-induced active urethral closure mechanism at the spinal level and augmenting UBP at the periphery.

Adrenergic Uptake Inhibitors↗

PubMed2006

Expression of hyperpolarization-activated cyclic nucleotide-gated cation channels in rat dorsal root ganglion neurons innervating urinary bladder.

Afferent pathways innervating the urinary bladder consist of myelinated Adelta- and unmyelinated C-fibers, the neuronal cell bodies of which correspond to medium and small-sized cell populations of dorsal root ganglion (DRG) neurons, respectively. Since hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel currents have been identified in various peripheral sensory neurons, we examined the expression of isoforms of HCN channels in the L6-S1 spinal cord and bladder afferent neurons from L6-S1 DRG in rats. Among HCN-1, HCN-2 and HCN-4 channel subtypes, positive staining with HCN-2 antibodies was found in the superficial dorsal horn of the spinal cord and small- and medium-sized unidentified DRG neurons. In dye-labeled bladder afferent neurons, HCN-2-positive cells were found in approximately 60% of neurons, and HCN-2 was expressed in both small- and medium-sized neurons with a higher ratio (expression ratio: 61% and 50% of neurons, respectively) compared with unidentified DRG neurons, in which the HCN expression ratio was 47% and 21% of small- and medium-sized cells, respectively. These results suggest that HCN-2 is the predominant subtype of HCN channels, which can control neuronal excitability, in small-sized C-fiber and medium-sized Adelta fiber DRG neurons including bladder afferent neurons, and might modulate activity of bladder afferent pathways controlling the micturition reflex.

Animals↗

PubMed2006

Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia.

OBJECTIVE: To present a comprehensive experience with intraprostatic botulinum toxin-type A (BoNT-A) injection in men with symptomatic benign prostatic hyperplasia (BPH) and to assess the efficacy on lower urinary tract symptoms (LUTS) and quality of life (QoL). PATIENTS AND METHODS: In all, 41 men (mean age 69.1 years, sd 7.1 ) with an International Prostate Symptom Score of > or = 8, peak flow rate of < 12 mL/s, and who were refractory to medical treatment were injected with BoNT-A (Botox, Allergan, Inc., CA, USA) at 100 U (21 men, for prostate volume < 30 mL) or 200 U (20, for prostate volume > 30 mL) into the prostate transperineally under transrectal ultrasonography guidance. Study exclusion criteria were confirmed or suspected malignancy, previous pelvic surgery or trauma and previous invasive treatment for BPH. The clinical effects were evaluated at baseline and at 1, 3 and 6 months after treatment. RESULTS: There were no significant local or systemic side-effects in any men. LUTS and QoL indices improved by > 30% in 31 of the 41 men (76%), and four of five men with urinary retention for > 1 month could void spontaneously at 1 week to 1 month after the BoNT-A injection. In 12 of 41 men (29%) there was no change in prostate volume, yet seven of these men still had a > 30% improvement in maximum flow rate, LUTS and QoL. The efficacy was sustained at 12 months. CONCLUSION: BoNT-A injected into the prostate is safe and effective for men with symptomatic BPH. The mechanisms of relief of symptoms might not depend totally on the volume shrinkage; the inhibitory effect on the smooth muscle tone and aberrant sensory function might also be important.

Aged↗

PubMed2006

New frontiers in intravesical therapies and drug delivery.

OBJECTIVES: The intravesical route permits site-specific delivery of drugs with a reduced side-effect profile as compared to oral delivery systems, either by avoiding first-pass metabolism or by obtaining a local effect. We investigated mechanisms related to urothelium permeability and new physical and chemical developments in intravesical drug delivery that potentially permit successful treatment of several bladder dysfunction. METHODS: A literature review. RESULTS: Pharmacologic agents increasing urothelial permeability and useful for clinical purposes have been described, such as dimethylsulfoxide, protamine sulphate, chitosan, and nystatin. Among physical approaches, electromotive drug administration appears to be more effective than intravesical passive diffusion in delivering drugs through the urothelium into deeper layers of the bladder. Experimental and clinical reports demonstrated that electric current significantly increases the transport of local anaesthetics, mytomicin C, oxybutynin, resiniferatoxin, epinephrine, and dexamethasone. Among new chemical approaches, cell-penetrating peptides posses the ability to translocate macromolecular drugs across membranes of urothelial cells. The therapeutic benefits of sustained delivery afforded by thermosensitive hydrogel, which forms a depot for hydrophilic and hydrophobic drugs, have been demonstrated by delivering anti-inflammatory drugs. Liposomes improve the aqueous solubility of several hydrophobic drugs such as taxol, amphotericin, and capsaicin. CONCLUSIONS: Electromotive drug administration, new in situ delivery systems, and bioadhesive liposomes may make it possible to extend intravesical therapy and drug administration to many bladder diseases. Research to expand knowledge of the chemical and physical properties of the bladder and processes regulating drug transport across biologic membranes is needed to make this a reality.

Absorption↗

PubMed2006

Characterization of hyperpolarization-activated current (Ih) in dorsal root ganglion neurons innervating rat urinary bladder.

Afferent pathways innervating the urinary bladder consist of myelinated Adelta-fibers and unmyelinated C-fibers. Normal voiding is dependent on mechanoceptive Adelta-fiber bladder afferents that respond to bladder distention. However, the mechanisms for controlling the excitability of Adelta-fiber bladder afferents are not fully understood. We therefore used whole cell patch-clamp techniques to investigate the properties of hyperpolarization-activated, cyclic nucleotide-gated (HCN) currents (I(h)) in dorsal root ganglion (DRG) neurons innervating the urinary bladder of rats. The neurons were identified by axonal tracing with a fluorescent dye, Fast Blue, injected into the bladder wall. Hyperpolarizing voltage step pulses from -40 to -130 mV produced voltage- and time-dependent inward I(h) currents in bladder afferent neurons. The amplitude and current density of I(h) at a holding potential of -130 mV was significantly larger in medium-sized bladder afferent neurons (diameter: 37.8 +/- 0.3 microm), a small portion (19%) of which were sensitive to capsaicin (1 microM), than in uniformly capsaicin-sensitive small-sized (27.6 +/- 0.5 microm) bladder neurons. In medium-sized bladder neurons, a selective HCN channel inhibitor, ZD7288, dose-dependently inhibited I(h) currents. ZD7288 (10 microM) also increased the time constant of the slow depolarization phase of spike after-hyperpolarization from 91.8 to 233.0 ms. These results indicate that I(h) currents are predominantly expressed in medium-sized bladder afferent neurons innervating the bladder and that inhibition of I(h) currents delayed recovery from the spike after-hyperpolarization. Thus, it is assumed that I(h) currents could control excitability of mechanoceptive Adelta-fiber bladder afferent neurons, which are usually capsaicin-insensitive and larger in size than capsaicin-sensitive C-fiber bladder afferent neurons.

Action Potentials↗

PubMed2006

Intraprostatic injection of botulinum toxin type-A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs.

BACKGROUND: With the increasing interest with botulinum toxin--A (BTX-A) application in the lower urinary tract, we investigated the BTX-A effects on the canine prostate and also in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). METHODS: Transperineal injection into the prostate using transrectal ultrasound (TRUS) was performed throughout the study. Saline with or without 100 U of BTX-A was injected into mongrel dogs prostate. One or 3 months later, the prostate was harvested for morphologic and apoptotic study. In addition, eight BPH patients refractory to alpha-blockers were treated with ultrasound guided intraprostatic injection of 200 U of BTX-A. RESULTS: In the BTX-A treated dogs, atrophy and diffuse apoptosis was observed with H&E stain and TUNEL stain at 1 and 3 months. Clinically, the mean prostate volume, symptom score, and quality of life index were significantly reduced by 18.8%, 73.1%, and 61.5% respectively. Maximal flow rate significantly increased by 72.0%. CONCLUSION: Intraprostatic BTX-A injection induces prostate apotosis in dogs and relieves BOO in humans. It is therefore a promising alternative treatment for refractory BOO due to BPH.

Aged↗

PubMed2006

Dopaminergic mechanisms controlling urethral function in rats.

AIMS: To investigate the role of dopamine receptor subtypes in the control of urethral activity. METHODS: Simultaneous recordings of intravesical and urethral perfusion pressure (UPP) were performed in rats under urethane anesthesia. Changes in coordinated activity of the bladder and urethral sphincter were examined following intravenous (i.v.), intrathecal (i.t.), or intracerebroventricular (i.c.v.) administration of dopamine D1- and D2-like receptor agonists (SKF38393 and quinpirole, respectively) and antagonists (SCH23390 and remoxipride, respectively). RESULTS: Quinpirole (0.03, 0.1, and 0.3 mg/kg i.v.) dose-dependently decreased baseline urethral pressure to 45.33 +/- 5.8, 33.7 +/- 3.3 (P < 0.05, n = 6), and 27.7 +/- 3.3 cm H(2)O (P < 0.05, n = 5) from the control value (46.0 +/- 4.0 cm H(2)O), respectively. i.c.v. injection of quinpirole (1 microg) decreased baseline urethral pressure to 33.6 +/- 5.0 cm H(2)O (P < 0.05, n = 4) from the control value (51.4 +/- 4.9 cm H(2)O) in contrast to the insignificant effects of i.t. administration of the drug (3 microg). The decrement of baseline pressure induced by quinpirole (0.1 mg/kg i.v.) was suppressed by alpha-bungarotoxin (BGT), a neuromuscular blocking agent. SCH23390 (1 and 3 mg/kg, i.v.) dose-dependently decreased the frequency of high frequency oscillation (HFO) of the urethral sphincter. SKF38393 or remoxipride did not have significant effects on any parameters of bladder and urethral activity. CONCLUSIONS: These results indicate that activation of D2-like dopamine receptors at a supraspinal site can suppress activity of the striated muscle urethral sphincter. Thus, decreased urethral resistance induced by D2 dopamine receptor activation might aggravate urge incontinence symptoms often seen in patients with Parkinson's disease (PD).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2006

Botulinum A toxin for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms.

Botulinum neurotoxin (BoNT) has been called the most poisonous poison and a potential bioterrorism weapon, and yet modern medicine has been able to harvest the elegant and specific activity of this toxin to treat a variety of medical conditions. BoNT application recently has been extended to prostate disorders, and this article reviews the literature on the mechanisms of action and clinical efficacy of BoNT treatment in the prostate. BoNT has demonstrated promising preliminary results for male lower urinary tract symptoms, and translational research suggests novel mechanism of action of BoNT in the prostate. It is important to remember that the application of BoNT in the prostate is not approved by the regulatory agencies and caution should be applied until larger randomized clinical studies are completed.

Botulinum Toxins, Type A↗

PubMed2006

Qualitative and quantitative expression profile of muscarinic receptors in human urothelium and detrusor.

PURPOSE: We compared the complete spectrum of receptor subtypes expressed by human detrusor and its primary culture with the expression profile in a human urothelium immortalized cell line, and in fresh urothelium tissue and its primary cell culture. MATERIALS AND METHODS: The levels of mRNA expressed for receptor subtypes M1 through M5 were determined with reverse transcriptase-polymerase chain reaction and quantitative polymerase chain reaction in total RNA extracted individually from different human bladder specimens, including fresh tissue of human urothelium and detrusor, and their respective primary cultures, as well as from the UROtsa cell line. RESULTS: All 5 muscarinic receptors were detected in fresh human bladder tissue by reverse transcriptase-polymerase chain reaction RNA. The same was true in separated urothelium and detrusor tissue except for the lack of the M5 receptor transcript. Receptor subtype mRNA expression in the UROtsa cell line paralleled expression in fresh human bladder. Quantitative polymerase chain reaction data further corroborated these results and showed comparable mRNA expression for M2 and M3 in primary detrusor cultures. Primary cultures also had a decreased copy number of receptor genes than native tissue. The decrease was even more pronounced in primary urothelium culture and the UROtsa cell line in the presence of high calcium. M2 and M3 receptors were also detected in urothelium and detrusor by immunoreactivity. CONCLUSIONS: We identified all 5 existing muscarinic receptor subtypes in detrusor and urothelium, and transcripts levels of M2 and M3 were comparable in detrusor. These results support an alternative site of action in urothelium for anti-muscarinic drugs. Urothelial receptors should be considered in the design of future drugs for overactive bladder.

Adolescent↗

PubMed2006

The application of botulinum toxin in the prostate.

PURPOSE: Botulinum neurotoxin is the most potent naturally occurring toxin known to inhibit various neurotransmitters. Injection of botulinum neurotoxin into the bladder and urethral sphincter has been used to treat bladder hyperactivity and sphincter dyssynergia. Recently botulinum neurotoxin application was extended to prostate disorders. Why would a urologist want to target the prostate? MATERIALS AND METHODS: We reviewed the literature on the mechanisms of action and clinical efficacy of botulinum neurotoxin treatment of the prostate. In addition to our personal clinical experience and basic research, information was gathered from MEDLINE and published abstracts from international meetings. We also present basic research and discuss the potential mechanism of action of botulinum neurotoxin on the prostate. RESULTS: There are 8 current peer reviewed publications on the injection of botulinum neurotoxin in the prostate. Cystoscopic transurethral or transperineal/transrectal ultrasound guided techniques have been used. Outcome improvement reported includes decreases in prostate size, prostate specific antigen and residual urine volume, and improvement in the flow rate and symptom score lasting 6 months or longer. CONCLUSIONS: Botulinum toxin has demonstrated exciting and promising preliminary results for male lower urinary tract symptoms. Translational research suggests novel mechanism of action of botulinum toxin in the prostate for benign prostatic hyperplasia and chronic nonbacterial prostatitis. It may even be considered as adjuvant treatment for prostate cancer. The use of botulinum neurotoxin in the prostate is currently Food and Drug Administration off label and in support of evidence based medicine practices caution should be applied until larger, randomized clinical studies are completed. More basic research is needed to identify the mechanisms by which botulinum toxin affects the prostate.

Animals↗

PubMed2006

Functional analysis of active urethral closure mechanisms under sneeze induced stress condition in a rat model of birth trauma.

PURPOSE: We evaluated changes in the urethral closure mechanism under a sneeze induced stress condition in a rat model of birth trauma. MATERIALS AND METHODS: Four days after vaginal distention induced by balloon catheter inflation in the vagina sneezing was induced while recording intravesical pressure with the rat under urethane anesthesia to evaluate sneeze induced leak point pressure, defined as the lowest pressure inducing fluid leakage from the urethral meatus during sneezing. Sneeze induced responses in the bladder and proximal or mid urethra were also measured using microtip transducer catheters. RESULTS: In 5 sham operated rats no leakage was observed from the urethral meatus during sneezing, which produced an increase in intravesical pressure of up to 34 cm H(2)O. However, in 5 of 6 rats with vaginal distention leakage during sneezing was observed with a sneeze leak point pressure of 26.2 cm H(2)O. In the mid urethra microtip transducer catheters revealed that pressure increases during sneezing were greater than those in the bladder but they were significantly decreased in the 5 incontinent vaginal distention rats. However, sneeze induced responses at the proximal urethra, which were similar to those in the bladder, were not different in sham operated and incontinent vaginal distention rats. CONCLUSIONS: Sneeze induced stress urinary incontinence in a rat model of birth trauma was caused by decreased active closure mechanisms at the mid urethra without affecting the passive transmission of abdominal pressure in the proximal urethra.

Animals↗

PubMed2006

The overactive bladder: Epidemiology and morbidity.

The International Continence Society recognizes the overactive bladder (OAB) as a "symptom syndrome suggestive of lower urinary tract dysfunction" that is defined as "urgency, with or without urge incontinence, usually with frequency and nocturia." Patients who have OAB are often sleep deprived and their sexual life is hindered. These patients have a restricted social life and an increased risk for depression. Accurate prevalence figures are difficult to obtain because most patients consider OAB an inevitable part of aging and some patients are too embarrassed to seek diagnosis. Primary care physicians need to be educated about the importance of identifying this clinical problem and managing it in a way that will minimize morbidity and maximize quality-of-life improvement. This article describes the various aspects of OAB, with special emphasis on epidemiology and morbidity.

Humans↗

PubMed2006

The case for bladder botulinum toxin application.

Botulinum toxin (BoNT) has been shown to be and effective agent in suppressing detrusor overactivity due to neurogenic causes. Recently, BoNT has been extended to patients who have idiopathic detrusor overactivity. This article reviews the use of BoNT to treat disorders of neurogenic detrusor overactivity and establishes BoNT as a therapeutic modality to treat idiopathic bladder overactivity. It is important to remember that the application of BoNT in the lower urinary tract is not approved by the regulatory agencies and caution should be applied until larger randomized clinical studies are completed.

Administration, Intravesical↗

PubMed2006

Local effects of antimuscarinics.

Overactive bladder (OAB) syndrome has been estimated to occur in nearly 17% of the population. The most common drug treatments for OAB are antimuscarinic agents that act to increase bladder capacity and decrease the urge to urinate during the storage phase. An increasing number of studies have focused on te role and mechanism of muscarinic acetylcholine receptors for the regulation of afferent activity during urine storage. Interactions between muscarinic receptors in the urothelium, afferent nerves, or myofibroblasts and locally released acetylcholine might be involved in the emergence of detrusor overactivity and OAB. Therefore, antimuscarinic agents may be effective in treating OAB not only by suppression of muscarinic receptor-mediated detrusor muscle contractions but also by modulation of muscarinic receptor-bladder afferent interactions.

Humans↗