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Over active bladder

William Tabayoyong, Jianjun Gao
PURPOSE OF REVIEW: Recent Food and Drug Administration (FDA) approval of five new immune checkpoint inhibitors for the treatment of metastatic urothelial cancer represents the first major treatment breakthrough for this disease since the introduction of combination chemotherapy over 30 years ago. This review examines the recent clinical trials leading to FDA approval of these agents, the current challenges facing immunotherapy and areas that require further research. RECENT FINDINGS: The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity...
March 15, 2018: Current Opinion in Oncology
Beverley Greenwood-Van Meerveld, Ehsan Mohammadi, Rocco Latorre, Edward R Truitt, Gregory D Jay, Benjamin D Sullivan, Tannin A Schmidt, Nataliya Smith, Debra Saunders, Jadith Ziegler, Megan Lerner, Robert Hurst, Rheal A Towner
OBJECTIVE: To test in an animal model the hypothesis that rhPRG4 (lubricin), a highly O-glycosylated mucin-like glycoprotein, may be a novel surface-active therapeutic for treating bladder permeability with co-morbid bowel permeability. Previously we showed that inducing bladder permeability in rats with dilute protamine sulfate (PS) produced colonic permeability and visceral hypersensitivity, suggesting increased bladder permeability could represent an etiologic factor in both Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) and Irritable Bowel Syndrome (IBS)...
March 12, 2018: Urology
Kambiz Rahbar, Ali Afshar-Oromieh, Martin Bögemann, Stefan Wagner, Michael Schäfers, Lars Stegger, Matthias Weckesser
PURPOSE: PSMA-targeted PET in patients with prostate cancer (PCa) has a significant impact on treatment decisions. By far the most frequently used PSMA ligand is68 Ga-labelled PSMA-11. However, due to the availability of larger amounts of activity,18 F-labelled PSMA ligands are of major interest. The aim of the present study was to evaluate the biodistribution and performance of the novel18 F-labelled ligand PSMA-1007 at two different time points. METHODS: This retrospective analysis included 40 consecutive patients (mean age 68...
March 14, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Ambreen Khawar, Elisabeth Eppard, Jean Phlippe Sinnes, Frank Roesch, Hojjat Ahmadzadehfar, Stefan Kürpig, Michael Meisenheimer, Florian C Gaertner, Markus Essler, Ralph A Bundschuh
AIM: [Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients. METHODS: Five mCRPC patients (mean age, 69 years) enrolled for [Lu]Lu-PSMA-617 therapy were injected with 40-62 MBq [Sc]Sc-PSMA-617 intravenously; Siemens Biograph 2 PET/CT system was used to acquire dynamic PET data (30 minutes) in list mode over the abdomen, followed by the collection of static PET/CT images (skull to mid-thigh) at 45 minutes, 2 and approximately 20 hours postinjection...
February 27, 2018: Clinical Nuclear Medicine
Clara Steiner, Thomas Gevaert, Roman Ganzer, Dirk De Ridder, Jochen Neuhaus
Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1)...
February 20, 2018: Histochemistry and Cell Biology
Barbara Mintzes, Swestika Swandari, Alice Fabbri, Quinn Grundy, Ray Moynihan, Lisa Bero
OBJECTIVES: To investigate patterns of industry-sponsored educational events that focus on specific health conditions for which there are concerns about overdiagnosis and overtreatment. DESIGN AND SETTING: This retrospective cohort study examines publicly reported industry-sponsored events in Australia from October 2011 to September 2015 for three conditions potentially subject to overdiagnosis and overtreatment: depression, osteoporosis and overactive bladder. We used a database of transparency reports to identify events with a focus on depression, osteoporosis and overactive bladder and compared these with other sponsored events...
February 13, 2018: BMJ Open
Laiquan Huang, Kun He, Jianxin Wang, Jiawei Yan, Yizhi Jiang, Zhongling Wei, Jun Zhang, Guangxi Li, Dongping Huang
Eukaryotic translation initiation factors 3B (eIF3b) is a subtype of the eIF3 category, which has been verified to be over-expressed in colon cancer, bladder, prostate cancers and glioblastoma due to its impact on the cellular activity of cancer cells. However, no related research on exploring the correlation of eIF3b gene expression with cell proliferation and apoptosis in chronic myeloid leukemia (CML) has been conducted until now. Our study showed that the expression of eIF3b mRNA in CML patients was higher compared with nonmalignancy controls...
February 8, 2018: Oncology Research
Hediye Dağdeviren, Hüseyin Cengiz, Çağlar Helvacıoğlu, Ulkar Heydarova, Cihan Kaya, Murat Ekin
Objective: To investigate voiding functions and assess the relationships of voiding parameters to overactive bladder symptoms and postvoiding residue volumes. Materials and Methods: This is a retrospective study analyzing urodynamic parameters in patients who were diagnosed as having overactive in our urogynecology clinic between April 2014 and April 2016. A total of 290 women who met the selection criteria were included in the study. The patients were divided into two groups according to postvoiding residue volumes: group 1, postvoiding residue volumes <100 mL (n=135); group 2, postvoiding residue volumes ≥100 mL (n=155)...
December 2017: Turkish Journal of Obstetrics and Gynecology
Masaki Yoshida, Masayuki Takeda, Momokazu Gotoh, Shinji Nagai, Takafumi Kurose
BACKGROUND: Vibegron is a novel, potent, and selective β3-adrenoreceptor agonist for the treatment of patients with overactive bladder (OAB). OBJECTIVE: To evaluate the efficacy and safety of vibegron versus placebo in Japanese OAB patients. DESIGN, SETTING, AND PARTICIPANTS: Patients with OAB entered a 2-wk placebo run-in phase. Once eligibility (≥8 micturition/d and either ≥1 urgency episodes/d or ≥1 urgency incontinence episodes/d) was confirmed, patients entered a 12-wk double-blind treatment phase...
January 20, 2018: European Urology
Parag N Gad, Nelly Kokikian, Kari L Christe, V Reggie Edgerton, Leif A Havton
The lower urinary tract (LUT) may be activated by spinal cord stimulation, but the physiologic mapping characteristics of LUT activation using non-invasive transcutaneous spinal cord stimulation (TSCS) are not known. The effects of aging on the contractile properties of the detrusor are also not well understood. Therefore, TSCS was applied over the T10/T11 to the L6/L7 spinous processes in adult (n=6) and aged (n=9) female rhesus macaques. A combination of urodynamic studies and electromyography recordings of the external urethral sphincter (EUS), external anal sphincter (EAS), and pelvic floor muscles were performed...
January 17, 2018: Journal of Neurophysiology
Benjamin Pradère, Constance Thibault, Malte W Vetterlein, Jeffrey J Leow, Benoit Peyronnet, Morgan Rouprêt, Thomas Seisen
The role of perioperative chemotherapy associated with radical cystectomy (RC) for muscle-invasive bladder cancer has been analyzed in several landmark randomized controlled trials (RCTs) over the past decades. With regard to neoadjuvant chemotherapy (NAC), a meta-analysis of level 1 evidence and long-term results from the largest RCTs support its use, which is currently advocated as the standard of care by most of the clinical guidelines worldwide. However, with regard to the delivery of adjuvant chemotherapy (AC), evidence is more contentious...
December 2017: Translational Andrology and Urology
Laura K Triantafylidis, Jenna S Clemons, Emily P Peron, John Roefaro, Kristin M Zimmerman
BACKGROUND: Case reports have demonstrated that dual use of cholinesterase inhibitors (ChIs) and urinary anticholinergics (UAChs) in older adults may be associated with delusions, aggression, changes in cognition, and anxiety, which typically resolve on drug discontinuation. Despite opposing mechanisms of action, these drugs continue to be co-prescribed. OBJECTIVE: This systematic review evaluates cognitive and functional outcomes of dual use of ChIs and UAChs and describes its prevalence...
January 19, 2018: Drugs & Aging
Simon C Baker, Volker M Arlt, Radek Indra, Madeleine Joel, Marie Stiborova, Ian Eardley, Niaz Ahmad, Wolfgang Otto, Maximilian Burger, Peter Rubenwolf, David H Phillips, Jennifer Southgate
Extra-hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self-defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro-carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier-forming differentiated states in vitro...
January 11, 2018: Molecular Carcinogenesis
Lana Dbeibo, Julia J van Rensburg, Sara N Smith, Kate R Fortney, Dharanesh Gangaiah, Hongyu Gao, Juan Marzoa, Yunlong Liu, Harry L T Mobley, Stanley M Spinola
CpxRA is an envelope stress response system found in all species of Enterobacteriaceae; CpxA has kinase activity for CpxR and phosphatase activity for phospho-CpxR, a transcription factor. CpxR also accepts phosphate groups and acetyl phosphate, a glucose metabolite. Activation of CpxR increases transcription of genes encoding for membrane repair and downregulates virulence determinants. We hypothesized that activation of CpxR could serve as an antimicrobial/antivirulence strategy and discovered compounds that activate CpxR in Escherichia coli by inhibiting CpxA phosphatase activity...
January 8, 2018: Infection and Immunity
Nadia M J Rupniak, Mary Katofiasc, Lesley Marson, Karl B Thor
Tachykinin NK2 receptor (NK2R) agonists have potential to alleviate clinical conditions associated with bladder and gastrointestinal under activity. The effects of agonists with differing selectivity for NK2R over NK1Rs on colorectal, bladder, and cardiovascular function were examined in anesthetized dogs. Intravenous (IV) administration of NKA, LMN-NKA ([Lys5,MeLeu9,Nle10]-NKA(4-10)), and [β-Ala8]-NKA(4-10) caused a dose-related increase in colorectal pressure (up to 98 mmHg) that was blocked by pretreatment with the NK2R antagonist GR 159897 (1 mg/kg), and hypotension (decrease in mean arterial pressure of ~40 mmHg) that was blocked by the NK1R antagonist CP-99,994 (1 mg/kg)...
December 26, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
Doti Serre, Sule Erbek, Nathalie Berthet, Xavier Ronot, Véronique Martel-Frachet, Fabrice Thomas
A series of tripodal ligands based on the 2-tert-butyl-4-R-6-phenol was synthesized, where R=aldehyde (HL1 ), R=putrescine-pyrene (HL2 ) and R=putrescine (HL3 ). A dinucleating ligand wherein a putrescine group connects two tripodal moieties was also prepared (H2 L4 ). The corresponding copper complexes (1, 2, 3, and 4, respectively) were prepared and characterized. We determined the phenol's pKas in the range 2.47-3.93. The DNA binding constants were determined at 6×106 , 5.5×105 and 2.7×106 for 2, 3 and 4, respectively...
February 2018: Journal of Inorganic Biochemistry
Yangyang Hu, Chao Deng, He Zhang, Jing Zhang, Bo Peng, Chuanyi Hu
Bladder cancer is one of the most common urological malignancy all over the world. Recently, long non-coding RNA (lncRNA) XIST has been identified as an oncogenic gene in several type of cancers. However, the expression level and functional role of XIST in bladder cancer remain largely unknown. In the present study, we found that XIST was significantly up-regulated in bladder cancer tissues and cell lines, and was correlated with poor prognosis of bladder cancer patients. Furthermore, XIST knockdown significantly inhibited bladder cancer cell growth and metastasis in vitro and tumor growth in vivo ...
November 7, 2017: Oncotarget
Akihiro Kinoshita, Masato Higashino, Koji Yoshida, Yoshiyuki Aratani, Akito Kakuuchi, Keisuke Hanada, Hiroyuki Takeda, Atsushi Naganawa, Hidekazu Matsuya, Kazuyuki Ohmoto
A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2  = 1.1 nM, EP3  = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (>2000-fold)...
January 1, 2018: Bioorganic & Medicinal Chemistry
Hai-Jing Dong, Yi Lu, Nian-Zhao Zhang, Wen-Hua Zhang, Shuai Wu, Hui Zhao, Chang-Cun Zhang, Si-Chuan Hou
AIMS AND OBJECTIVES: To assess the clinical effect of the multifunctional suprapubic catheter (MSC) on occurrence of cystospasm, catheter occlusion, the catheter-related urinary tract infection and remission of over-activity bladder, by comparing with the conventional suprapubic catheter (CSC) in patients with permanent suprapubic cystostomy. BACKGROUND: The conventional suprapubic catheter usually presents with high incidence of catheter-associated complications...
November 30, 2017: Journal of Clinical Nursing
Neil J Shah, William J Kelly, Stephen V Liu, Karin Choquette, Alexander Spira
Immunotherapy as a therapeutic strategy has seized the narrative throughout clinical oncology over the past few years. Once considered a niche treatment for rare cancers, immunotherapy has quickly emerged as the standard of care for many common cancer types. The remarkable rise is largely due to the development of novel checkpoint inhibitors, specifically, antibodies targeting PD-1 and PD-L1. Offering promising efficacy with a favorable toxicity profile, these agents have been approved for use in several malignancies and are under investigation for many more...
February 1, 2018: Human Vaccines & Immunotherapeutics
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