scholarly journals Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction

2017 ◽  
Vol 44 (3) ◽  
pp. 907-919 ◽  
Author(s):  
Qiang Liu ◽  
Deyi Luo ◽  
Tongxin Yang ◽  
Banghua Liao ◽  
Hong Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Structure And Function ◽  
Bladder Function ◽  
Bladder Smooth Muscle ◽  
M3 Receptors ◽  
And Function

Background/Aims: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. Methods: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. Results: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. Conclusion: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.

scholarly journals Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction

2017 ◽  
Vol 313 (5) ◽  
pp. F1149-F1160 ◽  
Author(s):  
Nao Iguchi ◽  
M. İrfan Dönmez ◽  
Anna P. Malykhina ◽  
Alonso Carrasco ◽  
Duncan T. Wilcox
Keyword(s):  
Bladder Outlet Obstruction ◽  
Target Genes ◽  
Bladder Dysfunction ◽  
Pediatric Population ◽  
Outlet Obstruction ◽  
Bladder Function ◽  
Bladder Pressure ◽  
Partial Bladder Outlet Obstruction

Posterior urethral valves are the most common cause of partial bladder outlet obstruction (PBOO) in the pediatric population. Pathological changes in the bladder developed during PBOO are responsible for long-lasting voiding dysfunction in this population despite early surgical interventions. Increasing evidence showed PBOO induces an upregulation of hypoxia-inducible factors (HIFs) and their transcriptional target genes, and they play a role in pathophysiological changes in the obstructed bladders. We hypothesized that blocking HIF pathways can prevent PBOO-induced bladder dysfunction. PBOO was surgically created by ligation of the bladder neck in male C57BL/6J mice for 2 wk. PBOO mice received intraperitoneal injection of either saline or 17-DMAG (alvespimycin, 3 mg/kg) every 48 h starting from day 1 postsurgery. Sham-operated animals received injection of saline on the same schedule as PBOO mice and served as controls. The bladders were harvested after 2 wk, and basal activity and evoked contractility of the detrusor smooth muscle (DSM) were evaluated in vitro. Bladder function was assessed in vivo by void spot assay and cystometry in conscious, unrestrained mice. Results indicated the 17-DMAG treatment preserved DSM contractility and partially prevented the development of detrusor over activity in obstructed bladders. In addition, PBOO caused a significant increase in the frequency of micturition, which was significantly reduced by 17-DMAG treatment. The 17-DMAG treatment improved urodynamic parameters, including increases in the bladder pressure at micturition and nonvoid contractions observed in PBOO mice. These results demonstrate that treatment with 17-DMAG, a HIF inhibitor, significantly alleviated PBOO-induced bladder pathology in vivo.

Strain Induced Bladder Smooth Muscle Remodeling

2007 ◽  
Author(s):  
Rebecca A. Long ◽  
Aron Parekh ◽  
Michael S. Sacks
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Bladder Wall ◽  
Outlet Obstruction ◽  
Tissue Remodeling ◽  
Bladder Function ◽  
Compensatory Mechanism ◽  
Bladder Smooth Muscle ◽  
Cord Injury

Multiple urinary bladder wall (UBW) pathologies, such as overactive bladder, bladder outlet obstruction, spinal cord injury (SCI) and related neurogenic disorders, and diabetes result in tissue remodeling marked by hypertrophic bladder smooth muscle cells (BSMC) and altered extra-cellular matrix components. This remodeling results in changes in UBW biomechanical properties leading to altered bladder function. Our previous studies have revealed that during the initial areflexic phase of SCI the UBW undergoes profound remodeling that appears to be a compensatory mechanism for the increased wall stretch resulting from over-distension [1, 2]. Remodeling in the bladder wall results in changes in biomechanics and ultimately the ability of the organ to normally fill and void [3]. The stimuli and precise mechanisms that are responsible for bladder remodeling in SCI and the aforementioned pathologies remain unknown. The objective of the present study is to determine the effects of varied in vitro strain on ECM production in the ex vivo rat bladder as a first step toward understanding tissue remodeling in response to strain.

In vitro and in vivo relaxation of urinary bladder smooth muscle by the selective myosin II inhibitor, blebbistatin

2011 ◽  
Vol 107 (2) ◽  
pp. 310-317 ◽  
Author(s):  
Xinhua Zhang ◽  
Dwaraka Srinivasa R. Kuppam ◽  
Arnold Melman ◽  
Michael E. DiSanto
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Myosin Ii ◽  
Bladder Smooth Muscle ◽  
Urinary Bladder Smooth Muscle

scholarly journals Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity

mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Jingwei Cai ◽  
Robert G. Nichols ◽  
Imhoi Koo ◽  
Zachary A. Kalikow ◽  
Limin Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Flow Cytometry ◽  
Free Radical ◽  
Gut Microbiota ◽  
Structure And Function ◽  
Metabolic Phenotyping ◽  
And Function

ABSTRACTThe gut microbiota is susceptible to modulation by environmental stimuli and therefore can serve as a biological sensor. Recent evidence suggests that xenobiotics can disrupt the interaction between the microbiota and host. Here, we describe an approach that combinesin vitromicrobial incubation (isolated cecal contents from mice), flow cytometry, and mass spectrometry- and1H nuclear magnetic resonance (NMR)-based metabolomics to evaluate xenobiotic-induced microbial toxicity. Tempol, a stabilized free radical scavenger known to remodel the microbial community structure and functionin vivo, was studied to assess its direct effect on the gut microbiota. The microbiota was isolated from mouse cecum and was exposed to tempol for 4 h under strict anaerobic conditions. The flow cytometry data suggested that short-term tempol exposure to the microbiota is associated with disrupted membrane physiology as well as compromised metabolic activity. Mass spectrometry and NMR metabolomics revealed that tempol exposure significantly disrupted microbial metabolic activity, specifically indicated by changes in short-chain fatty acids, branched-chain amino acids, amino acids, nucleotides, glucose, and oligosaccharides. In addition, a mouse study with tempol (5 days gavage) showed similar microbial physiologic and metabolic changes, indicating that thein vitroapproach reflectedin vivoconditions. Our results, through evaluation of microbial viability, physiology, and metabolism and a comparison ofin vitroandin vivoexposures with tempol, suggest that physiologic and metabolic phenotyping can provide unique insight into gut microbiota toxicity.IMPORTANCEThe gut microbiota is modulated physiologically, compositionally, and metabolically by xenobiotics, potentially causing metabolic consequences to the host. We recently reported that tempol, a stabilized free radical nitroxide, can exert beneficial effects on the host through modulation of the microbiome community structure and function. Here, we investigated a multiplatform phenotyping approach that combines high-throughput global metabolomics with flow cytometry to evaluate the direct effect of tempol on the microbiota. This approach may be useful in deciphering how other xenobiotics directly influence the microbiota.

scholarly journals Effect of lycorine on the structure and function of hepatoma cell membrane in vitro and in vivo

2020 ◽  
Vol 34 (1) ◽  
pp. 104-114 ◽  
Author(s):  
Guosong Xin ◽  
Miao Yu ◽  
Yang Hu ◽  
Shiyong Gao ◽  
Zheng Qi ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Hepatoma Cell ◽  
Structure And Function ◽  
And Function

scholarly journals IL-4 and SDF-1 Increase Adipose Tissue-Derived Stromal Cell Ability to Improve Rat Skeletal Muscle Regeneration

2020 ◽  
Vol 21 (9) ◽  
pp. 3302
Author(s):  
Małgorzata Zimowska ◽  
Karolina Archacka ◽  
Edyta Brzoska ◽  
Joanna Bem ◽  
Areta M. Czerwinska ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Regeneration ◽  
Structure And Function ◽  
Skeletal Muscle Regeneration ◽  
Stem Cell Markers ◽  
Myogenic Factors ◽  
And Function

Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response.

scholarly journals Overexpression of cofilin stimulates bundling of actin filaments, membrane ruffling, and cell movement in Dictyostelium.

1996 ◽  
Vol 132 (3) ◽  
pp. 335-344 ◽  
Author(s):  
H Aizawa ◽  
K Sutoh ◽  
I Yahara
Keyword(s):  
Actin Filaments ◽  
Cell Movement ◽  
Structure And Function ◽  
Cross Linking ◽  
Low Molecular Weight ◽  
Filamentous Actin ◽  
Membrane Ruffling ◽  
And Function

Cofilin is a low molecular weight actin-modulating protein whose structure and function are conserved among eucaryotes. Cofilin exhibits in vitro both a monomeric actin-sequestering activity and a filamentous actin-severing activity. To investigate in vivo functions of cofilin, cofilin was overexpressed in Dictyostelium discoideum cells. An increase in the content of D. discoideum cofilin (d-cofilin) by sevenfold induced a co-overproduction of actin by threefold. In cells over-expressing d-cofilin, the amount of filamentous actin but not that of monomeric actin was increased. Overexpressed d-cofilin co-sedimented with actin filaments, suggesting that the sequestering activity of d-cofilin is weak in vivo. The overexpression of d-cofilin increased actin bundles just beneath ruffling membranes where d-cofilin was co-localized. The overexpression of d-cofilin also stimulated cell movement as well as membrane ruffling. We have demonstrated in vitro that d-cofilin transformed latticework of actin filaments cross-linked by alpha-actinin into bundles probably by severing the filaments. D. discoideum cofilin may sever actin filaments in vivo and induce bundling of the filaments in the presence of cross-linking proteins so as to generate contractile systems involved in membrane ruffling and cell movement.

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