Treatment Of Urinary Bladder Dysfunction Research Articles

Review of Animal Models to Study Urinary Bladder Function.

Simple SummaryThe treatment of urinary bladder dysfunction requires the knowledge of bladder function, which involves physiology, pathology, and even psychology. Several animal models are available to study a variety of bladder disorders. These models include animals from rodents, such as mice and rats, to nonhuman primates, such as rabbits, felines, canines, pigs, and mini pigs. This review adapted animal models to study bladder function according to facility, priority, and disease.The urinary bladder (UB) serves as a storage and elimination organ for urine. UB dysfunction can cause multiple symptoms of failure to store urine or empty the bladder, e.g., incontinence, frequent urination, and urinary retention. Treatment of these symptoms requires knowledge on bladder function, which involves physiology, pathology, and even psychology. There is no ideal animal model for the study of UB function to understand and treat associated disorders, as the complexity in humans differs from that of other species. However, several animal models are available to study a variety of other bladder disorders. Such models include animals from rodents to nonhuman primates, such as mice, rats, rabbits, felines, canines, pigs, and mini pigs. For incontinence, vaginal distention might mimic birth trauma and can be measured based on leak point pressure. Using peripheral and central models, inflammation, bladder outlet obstruction, and genetic models facilitated the study of overactive bladder. However, the larger the animal model, the more difficult the study is, due to the associated animal ethics issues, laboratory facility, and budget. This review aims at facilitating adapted animal models to study bladder function according to facility, priority, and disease.

Bone marrow mesenchymal stem cells encapsulated thermal-responsive hydrogel network bridges combined photo-plasmonic nanoparticulate system for the treatment of urinary bladder dysfunction after spinal cord injury

Spinal cord injury (SCI) is a distressing injury and an irretrievable dramatic event that can debilitate victims for lifespan. Recovery and treatment of SCI is critical challenges for medicine, to overcome the hurdles stem cells and hydrogel scaffolds implantation is a boon for SCI recovery. In this regard, we reported the synthesis of Gold nanoparticles (Au NPs) loaded Agarose/Poly (N-isopropylacrylamide) (PNIPAM) as promising materials for SCI treatment. Herein, Au NPs was synthesized by well-established citrate reduction method and the prepared materials were characterised by UV–visible spectroscopy (UV–vis), Transmission electron microscopy (TEM), Fourier- transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), and EDAX analysis. The microscopic images showed an elliptical or ovoid porous structure nature of hydrogel, and successful and homogenous loading of photo plasmonic nanoparticles into the hydrogel structure. The in vitro cell viability and inflammation analyses data exhibited that prepared hydrogels have no toxic to the cells and displayed high anti-regenerative ability with bone marrow Mesenchymal stem cells (MSCs) and macrophages cells. The in vivo analysis study demonstrated that the treated materials with encapsulated MSCs have greater nerve tissue regeneration efficacy which was confirmed by the results of BBB scores. The hind limb locomotion of treated model animals was totally vanished after post-operational surgery. It's established that implanted nano-hydrogel materials combined with MSCs have quicker recovery of motor function after post-operative surgery, when compared to the other implanted animal groups.

Sacral Neuromodulation for the Treatment of Urinary Bladder Dysfunction: Mechanism of Action and Future Directions

Symptoms of overactive bladder affect a large portion of the world population, especially the elderly. Sacral neuromodulation (SNM) is an effective third-line therapy in patients with overactive bladder. The working mechanism of SNM can be explained by the neural connections of the lower urinary tract. It is proposed that SNM does not work directly on the central components of the micturition reflex, but on cortical and subcortical areas, which in turn inhibits the micturition reflex components in the caudal brainstem. The clinical use and outcomes of SNM are described for several forms of bladder dysfunction. Furthermore, some recent new developments in SNM are discussed, such as expanded indications, more effective use of existing nonrechargeable neuromodulators and the introduction of a rechargeable device.

The application of the physical factors for the medical rehabilitation of the children presenting with neurogenic dysfunction of the bladder

This article describes the modern technologies for the medical rehabilitation of the children presenting with neurogenic dysfunction of the bladder aimed at improving the act of urination at all levels of innervation. The most frequent variant of neurogenic dysfunction of the bladder in the children is the hyper-reflexive one; it is this variant in which the most pronounced disorders of urodynamics due to intravesical hypertension and detrusor hypoxia are observed. The urodynamic disorders are known to contribute to the formation of the characteristic clinical picture associated with the hyper-reflexive urinary bladder dysfunction in the children characterized by the mandatory urination syndrome, pollakiuria, imperative urges, and mandatory urinary incontinence in the combination with enuresis. The treatment of urinary bladder dysfunction includes both behavioural and medication therapeutic modalities. The "golden standard" for the pharmacotherapy of neurogenic bladder dysfunction of the hyper-reflexive type in the childhood is the use of M-cholinoblockers, such as oxybutynin. The popularity of the physiotherapeutic methods is attributable to their influence on the main links of pathogenesis, the absence of side effects, and the possibility of application in the children of the early age. The combined treatment of neurogenic bladder dysfunction includes the use of a wide range of physiotherapeutic methods the action of which is aimed at regulating the act of urination at all levels of innervation of the bladder, normalizing the tone of the muscles of the bladder, eliminating sphincter insufficiency, improving circulation and accelerating the maturation of the neuromuscular apparatus of the pelvic organs. At present, the natural and preformed methods of physiotherapy are finding the wide application for the management of neurogenic dysfunction of the bladder in the children in the conjunction with therapeutic physical exercises, massage, and the biological feedback (BFB) technique.

The role of the peripheral cannabinoid system in the pathogenesis of detrusor overactivity evoked by increased intravesical osmolarity in rats

The cannabinoid receptors CB1 and CB2 are localized in the urinary bladder and play a role in the regulation of its function. We investigated the pathomechanisms through which hyperosmolarity induces detrusor overactivity (DO). We compared urinary bladder activity in response to blockade of CB1 and CB2 receptors using AM281 and AM630, respectively, in normal rats and after hyperosmolar stimulation. Experiments were performed on 44 rats. DO was induced by intravesical instillation of hyperosmolar saline. Surgical procedures and cystometry were performed under urethane anaesthesia. The measurements represent the average of 5 bladder micturition cycles. We analysed basal, threshold, and micturition voiding pressure; intercontraction interval; compliance; functional bladder capacity; motility index; and detrusor overactivity index. The blockage of CB1 and CB2 receptors diminished the severity of hyperosmolar-induced DO. In comparison with naïve animals the increased frequency of voiding with no significant effect on intravesical voiding pressure profile was observed as a result of the blockage of CB1 and CB2 receptors. These results demonstrate that hyperosmolar-induced DO is mediated by CB1 and CB2 receptors. Therefore, the cannabinoid pathway could potentially be a target for the treatment of urinary bladder dysfunction.

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction.

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction.

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction

The cardiovascular and gastrointestinal adverse effects of cyclooxygenase inhibitors seems to be a major concern that restricts their use in the treatment of urinary bladder dysfunction

BRL37344, a β3-adrenergic Receptor Agonist, Decreases Nerve-evoked Contractions in Human Detrusor Smooth Muscle Isolated Strips: Role of BK Channels

To investigate the mechanism by which BRL37344, a β3-adrenergic receptor (β3-ARs) agonist, facilitates the inhibition of nerve-evoked contractions in human detrusor smooth muscle (DSM) isolated strips and to identify the role of large-conductance Ca(2+)-activated K(+) (BK) channels in this process. Human DSM specimens were obtained from open bladder surgeries on patients without preoperative history of overactive bladder symptoms. Isometric DSM tension recordings were conducted using force-displacement transducers and thermostatically controlled tissue baths. Nerve-evoked contractions were generated by electrical field stimulation (EFS). BRL37344, a β3-AR agonist, significantly decreased the amplitude, muscle force, and duration of the DSM contractions induced by 20 Hz EFS, in a concentration-dependent manner. This BRL37344-mediated inhibition of the amplitude and muscle force of the nerve-evoked DSM contraction was significantly reduced by iberiotoxin, a highly selective inhibitor of the BK channel, revealing a role for BK channels in the β3-AR-induced inhibition of human DSM nerve-evoked contractions. We further used atropine, α,β-methylene-ATP, and suramin to separate the cholinergic and purinergic components of human DSM nerve-evoked contractions. We found that the β3-AR agonist, BRL37344, inhibited both components of the EFS-induced (0.5-50 Hz) DSM contractions. This study supports the concept that β3-AR agonists inhibit nerve-evoked contractions in human DSM. We have further revealed that BK channels play a critical role in BRL37344-mediated relaxation of nerve-evoked contractions in human DSM. The study suggests that in addition to β3-ARs, BK channels may also represent promising pharmacologic targets in the treatment of urinary bladder dysfunction.

Specificity evaluation of antibodies against human β3-adrenoceptors

β(3)-Adrenoceptors are a promising drug target for the treatment of urinary bladder dysfunction, but knowledge about their expression at the protein level and their functional role is limited, partly due to a lack of well validated tools. As many antibodies against G-protein-coupled receptors, including those against β(3)- and other β-adrenoceptor subtypes, lack selectivity for their target, we have evaluated the specificity of five antibodies raised against the full-length protein of the human β(3)-adrenoceptor (H155-B01), its N-terminus (LSA4198 and TA303277) and its C-terminus (AB5122, Sc1472) in immunoblotting and immunocytochemistry. Our primary test system were Chinese hamster ovary cells stably transfected to express each of the three human β-adrenoceptor subtypes at near physiological levels (100-200fmol/mg protein). None of the five antibodies exhibited convincing target specificity in immunoblotting with Sc1472 apparently being least unsuitable. In immunocytochemistry, LSA4198 and Sc1472 appeared most promising, exhibiting at least some degree of specificity. As these two antibodies have been raised against different epitopes (N- and C-terminus of the receptor, respectively), we propose that concordant staining by both antibodies provides the most convincing evidence for β(3)-adrenoceptor labelling in cyto- or histochemistry studies.

Are there functional β3‐adrenoceptors in the human heart?

β3‐Adrenoceptor mRNA is expressed in the human heart, but corresponding receptor protein has not yet consistently been demonstrated. Furthermore, their physiological role remains highly controversial. For example, in human atria these receptors apparently do not promote cAMP formation. Evidence presented in this issue of the BJP suggests that a previously reported β3‐adrenoceptor‐mediated stimulation of Ca2+ channels at room temperature is absent at physiological temperatures, and that β3‐adrenoceptors have no effect on atrial contraction. Drugs classified as β3‐adrenoceptor agonists cause contraction in human atria but in most cases this involves β1‐ and/or β2‐adrenoceptors. In contrast, in human ventricles β3‐adrenoceptor agonists can exhibit negative inotropic effects, potentially involving Pertussis toxin‐sensitive G‐proteins and activation of a NO synthase. However, firmer pharmacological evidence is required that these effects indeed occur via β3‐adrenoceptors. Whether the expected future use of β3‐adrenoceptor agonists in the treatment of urinary bladder dysfunction is associated with adverse events related to cardiac function remains to be determined from clinical studies.LINKED ARTICLE This article is a commentary on Christ et al., pp. 823–839 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00996.x

Fecal incontinence treated with acupuncture - a pilot study

Objectives Acupuncture has been used successfully for the treatment of urinary bladder dysfunction. The aim of this study was therefore to investigate if manual acupuncture might also affect fecal incontinence favorably. Methods The study comprises 15 female patients, median age 60 years (39 -75). Before treatment and at regular intervals after acupuncture sessions the defects of anal continence were assessed. Ano-rectal function was assessed by means of recto anal manovolumetry. Each patient was submitted to one acupuncture treatment per week for a ten-week period. Subsequently, a control session was repeated once per month up to 7 months for six patients. A final functional assessment was performed at 18 months. Result Patients experienced a significant improvement in anal continence, the overall continence score which changed from 10 (3 -21) estimated before treatment to zero (0 - 7) (p < 0.05) at 10 weeks. Patients with irregular bowel habits and/or loose stools reported significant improvement. On the manovolumetric variables a limited increase of resting from 25 (17-35) mmHg to 36 (20-42) mmHg, (p = 0.05) and sustained squeeze anal pressure, changing from 41 (32-68) mmHg to 60 (40-100) mmHg (p < 0.05) were reported. Rectal sensory function remained unchanged. Conclusion Acupuncture offers good opportunities for improving fecal incontinence. The mechanism of action is obscure but might be an effect of the “neuromodulation” of the recto-anal function similar to that explaining the favorable results achieved by sacral nerve stimulation. The concomitant regulation of disordered bowel habits may also contribute to the satisfactory results.

1529: Importance of the “Urethral Sphincter Response” for Optimizing the Electrode Placement in Sacral Nerve Stimulation for the Treatment of Urinary Bladder Dysfunction

You have accessJournal of UrologyPodium 44, Tuesday, May 22, 2007, 1:00 - 3:00 pm1 Apr 20071529: Importance of the “Urethral Sphincter Response” for Optimizing the Electrode Placement in Sacral Nerve Stimulation for the Treatment of Urinary Bladder Dysfunction Andreas Bannowsky, Bjoern Wefer, Shuji Sugimoto, Georg Boehler, Annemie Loch, Tillmann Loch, and Klaus P. Juenemann Andreas BannowskyAndreas Bannowsky More articles by this author , Bjoern WeferBjoern Wefer More articles by this author , Shuji SugimotoShuji Sugimoto More articles by this author , Georg BoehlerGeorg Boehler More articles by this author , Annemie LochAnnemie Loch More articles by this author , Tillmann LochTillmann Loch More articles by this author , and Klaus P. JuenemannKlaus P. Juenemann More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)31730-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1529: Importance of the “Urethral Sphincter Response” for Optimizing the Electrode Placement in Sacral Nerve Stimulation for the Treatment of Urinary Bladder Dysfunction." The Journal of Urology, 177(4S), p. 505 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 505 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Andreas Bannowsky More articles by this author Bjoern Wefer More articles by this author Shuji Sugimoto More articles by this author Georg Boehler More articles by this author Annemie Loch More articles by this author Tillmann Loch More articles by this author Klaus P. Juenemann More articles by this author Expand All Advertisement PDF DownloadLoading ...

148 Prognostic and predictive factors in patients with advanced squamous cell head and neck cancer (HNSCC) treated with induction chemotherapy (CT) and radiotherapy (RT)

Acupuncture has been used successfully for the treatment of urinary bladder dysfunction. The aim of this study was therefore to investigate if manual acupuncture might also affect fecal incontinence favorably.The study comprises 15 female patients, median age 60 years (39 -75). Before treatment and at regular intervals after acupuncture sessions the defects of anal continence were assessed. Ano-rectal function was assessed by means of recto anal manovolumetry. Each patient was submitted to one acupuncture treatment per week for a ten-week period. Subsequently, a control session was repeated once per month up to 7 months for six patients. A final functional assessment was performed at 18 months.Patients experienced a significant improvement in anal continence, the overall continence score which changed from 10 (3 -21) estimated before treatment to zero (0 - 7) (p < 0.05) at 10 weeks. Patients with irregular bowel habits and/or loose stools reported significant improvement. On the manovolumetric variables a limited increase of resting from 25 (17-35) mmHg to 36 (20-42) mmHg, (p = 0.05) and sustained squeeze anal pressure, changing from 41 (32-68) mmHg to 60 (40-100) mmHg (p < 0.05) were reported. Rectal sensory function remained unchanged.Acupuncture offers good opportunities for improving fecal incontinence. The mechanism of action is obscure but might be an effect of the “neuromodulation” of the recto-anal function similar to that explaining the favorable results achieved by sacral nerve stimulation. The concomitant regulation of disordered bowel habits may also contribute to the satisfactory results.

Synthesis and antimuscarinic activity of a Series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides: discovery of potent and subtype-selective antimuscarinic agents

In a study directed toward the development of new, selective agents with potential utility in the treatment of altered smooth muscle contractility and tone, for example, as seen in urinary incontinence associated with bladder muscle instability, a series of 4-(1-imidazolyl)-2,2-diphenylbutyramide derivatives was prepared. These compounds were examined for M 1, M 2, and M 3 muscarinic receptor subtype selectivity in isolated tissue assays. The compounds that showed potency and/or selectivity in these tests were further evaluated for in vivo anticholinergic effects on various organs and tissues, including urinary bladder, salivary gland, and eye in rats. The structure–activity relationships for the series of 4-(1-imidazolyl)-2,2-diphenylbutyramide derivatives are also discussed. This study led to the identification of 4-(2-methyl-1-imidazolyl)-2,2-diphenylbutyramide (KRP-197) as a candidate drug for the treatment of urinary bladder dysfunction.

Bladder Purinergic Receptorsa

In rabbits the contractile response of the urinary bladder is only partially due to cholinergic innervation since atropine does not completely block neuron ally mediated contractions. In the human bladder this atropine resistance is controversial with some reporting atropine resistance in­ vitro while others have stated that the atropine resistance is also tetrodotoxin resistant. Results of the present investigation demonstrate that an atropine resistant, tetrodotoxin sensitive contraction can be evoked in some, but not all human bladder strips. Evidence accumulated over the past few decades indicates that this atropine resistant contraction may be mediated by ATP or a related purine compound. Studies presented herein are designed to develop a radioligand assay for this receptor. Initial studies indicated that the hydrolysis resistant ATP analog (3,1' methylene ATP offers several advantages over ATP as a potential radio ligand. It is only slowly hydrolyzed by endogenous ATPase and does not inhibit the hydrolysis of ATP indicating that it probably does not bind to the active sites of endogenous ATP hydrolyzing enzymes. In addition (3,1' methylene ATP is 10-100 fold more potent than ATP itself in stimulating contractions of the urinary bladder in-vitro. The radio ligand binding assay herein described can be used to quantitate the density of receptors, an essential step for determining the role of this system in urinary bladder function and dysfunction. Application of this assay could form the foundation for development of a new class of therapeutic agents for the treatment of urinary bladder dysfunction based on modulation ofthe nervous system. (J. Ural., 144: 176-181, 1990) The postganglionic nerve evoked contractile response of the urinary bladder of nearly all vertebrate species including man is only partially blocked by antimuscarinic agents such as atropine and scopolamine ' and is relatively unaffected by alpha and beta adrenergic or nicotinic antagonists.! The most likely explanation for this response is that in addition to acetylcho­ line, released by cholinergic nerves, another neurotransmitter released by non-adrenergic, non-cholinergic nerves contributes to the contraction. The presence of these neurons has been alluded to in the early literature by Langley2 and their existence has been suggested throughout the gastrointestinal tract as well as other organs including lung, trachea, esophagus, cardiovas­ cular system, and seminal vesicles.! In the human female blad­ der these nerves have been estimated to be responsible for 50% of the contractile response. 3 Evidence accumulated over the past few decades suggests that the neurotransmitter utilized by these neurons is most likely a purine nucleotide or analog and these nerves have therefore been coined purinergic by Burns­ tock Functionally these neurons are those that produce an effect on the innevated tissue in the presence of both atropine and guanethidine. Although other explanations for the atropine resistant re­ sponse have been put forth including the presence of a barrier to the penetration of atropine, there is little evidence for them. Many substances other than ATP have been explored as can­ didates for mediating the atropine resistant contraction. These include catecholamines, 5-hydroxytryptamine, cyclic AMP, his­ tamine, prostaglandins, alanine, arginine, glycine, glutamic acid, gamma amino butyric acid, bradykinin and substance P.! These substances have been rejected as candidates by most workers since they a) were either inactive or did not mimic the nerve mediated response, b) specific antagonists for these sub

Bladder Purinergic Receptors

In rabbits the contractile response of the urinary bladder is only partially due to cholinergic innervation since atropine does not completely block neuronally mediated contractions. In the human bladder this atropine resistance is controversial with some reporting atropine resistance in-vitro while others have stated that the atropine resistance is also tetrodotoxin resistant. Results of the present investigation demonstrate that an atropine resistant, tetrodotoxin sensitive contraction can be evoked in some, but not all human bladder strips. Evidence accumulated over the past few decades indicates that this atropine resistant contraction may be mediated by ATP or a related purine compound. Studies presented herein are designed to develop a radioligand assay for this purinergic receptor. Initial studies indicated that the hydrolysis resistant ATP analog β, γ methylene ATP offers several advantages over ATP as a potential radioligand. It is only slowly hydrolyzed by endogenous ATPase and does not inhibit the hydrolysis of ATP indicating that it probably does not bind to the active sites of endogenous ATP hydrolyzing enzymes. In addition β, γ methylene ATP is 10-100 fold more potent than ATP itself in stimulating contractions of the urinary bladder in-vitro. The radioligand binding assay herein described can be used to quantitate the density of purinergic receptors, an essential step for determining the role of this system in urinary bladder function and dysfunction. Application of this assay could form the foundation for development of a new class of therapeutic agents for the treatment of urinary bladder dysfunction based on modulation of the purinergic nervous system.

Evaluation of drugs for treatment of urinary bladder dysfunction in conscious rats with intact pelvic nerve and after resection of left pelvic nerve

Evaluation of drugs for treatment of urinary bladder dysfunction in conscious rats with intact pelvic nerve and after resection of left pelvic nerve

Evaluation of Drugs for Treatment of Urinary Bladder Dysfunction in Conscious Rats with Intact Pelvic Nerve and after Resection of the Left Pelvic Nerve

We studied the effects of drugs used for treatment of bladder dysfunction in conscious rats with intact pelvic nerves and also in rats at one or two weeks after nerve decentralization on the left side. Bladder contraction accompanying micturition was continuously induced by infusion of solution at a constant rate. When the effects of oxybutynin (3 mg/kg, i.p.) and terodiline (3 and 10 mg/kg, i.p.) on the cystometrogram were studied for about 2 hr, these drugs shortened and then prolonged the micturition interval (Ml), but atropine (1 and 5 mg/kg, i.p.), butylscopolamine (20 mg/kg, i.p.) and nifedipine (3 mg/kg, i.p.) exhibited only a shortening effect on the Ml. After injection of oxybutynin (10 mg/kg, i.p.), solution dribbled from the urethra for about 30 min. Terodiline (3 mg/kg) caused ischuria in the rats one week after resection of the left pelvic nerve, but not in the rats two weeks after surgery. Physostigmine (0.3 mg/kg, i.p.) improved micturition in the rats one week after surgery, but the effect was not evident in the rats with intact pelvic nerves. It was found that the drugs used for treating failure to store or expel urine exhibited a beneficial effect on micturition in rats with intact pelvic nerves and also in rats one week after nerve decentralization, respectively.