The putative involvement of actin‐binding proteins and cytoskeleton proteins in pathological mechanisms of ketamine cystitis—Revealed by a prospective pilot study using proteomic approaches

Yang, Hsin-Chia; Zhai, Wei-Jun; Kuo, Hann‐Chorng

doi:10.1002/prca.201600085

Cited by 3 publications

(3 citation statements)

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“…The data show, for the first time, that expression levels of TRPV1 and TRPV4 observed in patients with severe KC are significantly increased over those in patients with mild KC and in control subjects. According to our previous report, KC patients usually show significantly greater V Pdet.max and smaller bladder capacity than control subjects 19 . In the present study, the association between different urodynamic parameters and between urodynamic data and protein expression were studied.…”

Section: Discussionmentioning

confidence: 82%

“…Western blot analysis was performed similarly to previously described 19 . Tissue lysates from 12 patients with mild KC, 12 patients with severe KC, and four control subjects were separated by 1-dimensional sodium dodecyl sulfate–polyacrylamide gel electrophoresis and transferred onto an Immobilon-P polyvinylidene fluoride transfer membrane (Millipore, Bedford, MA) by electroblotting.…”

Section: Methodsmentioning

confidence: 99%

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Smaller bladder capacity and stronger bladder contractility in patients with ketamine cystitis are associated with elevated TRPV1 and TRPV4

Yang

Jhang

Hsu

et al. 2021

Sci Rep

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Stronger contractility and smaller bladder capacity are common symptoms in ketamine cystitis (KC). This study investigates the association between expression levels of transient receptor potential cation channel subfamily V (TRPV) proteins and the clinical characteristics of KC. Bladder tissues were obtained from 24 patients with KC and four asymptomatic control subjects. Video urodynamic parameters were obtained before surgical procedures. The TRPV proteins were investigated by immunoblotting, immunofluorescence staining, and immunohistochemistry. The Pearson test was used to associate the expression levels of TRPV proteins with clinical characteristics of KC. The expression level of TRPV1 and TRPV4 was significantly higher in the severe KC bladders than in mild KC or control bladders. The TRPV1 proteins were localized in all urothelial cell layers, and TRPV4 was located in the basal cells and lamina propria. The expression of TRPV1 was negatively associated with maximal bladder capacity (r = − 0.66, P = 0.01). The expression of TRPV4 was positively associated with the velocity of detrusor pressure rise to the maximum flow rate (r = 0.53, P = 0.01). These observations suggest smaller bladder capacity and stronger contractility in KC are associated with an elevated expression of TRPV1 and TRPV4, respectively.

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Section: Discussionmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Smaller bladder capacity and stronger bladder contractility in patients with ketamine cystitis are associated with elevated TRPV1 and TRPV4

Yang

Jhang

Hsu

et al. 2021

Sci Rep

Self Cite

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“…Recent studies have also revealed that increased apoptosis in ketamine cystitis may be mediated by actin-binding proteins and a Ca 2+ -activated protease, which correlated with the clinical characteristics of ketamine cystitis bladders, such as erosive bladder mucosa and severe bleeding after hydrodistention. The detrusor overactivity and increased slope of detrusor pressure in ketamine cystitis bladders may be induced by increases in contractile and cytoskeleton proteins [ 31 ]. In addition, a recent study revealed that hypersensitivity, small bladder capacity, and stronger bladder contractility in patients with ketamine cystitis are associated with elevated transient receptor potential vanilloid 1 (TRPV1) in the urothelial cell layer and elevated TRPV4-positive cells in the basal cell layer and lamina propria [ 32 ].…”

Section: P Athophysiologymentioning

confidence: 99%

Pathophysiology, clinical presentation, and management of ketamine-induced cystitis

Jhang

Birder

Kuo

2023

Tzu Chi Medical Journal

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A BSTRACT Ketamine is illegally used as a recreational drug in many Asian countries. Long-term ketamine abusers often develop irritable bladder symptoms that gradually develop into more severe urinary frequency and urgency and eventually into a painful ulcerated bladder. These patients typically have reduced functional bladder capacity, increased bladder sensation, detrusor overactivity, severe urgency, urinary incontinence, and bladder contracture. Ketamine metabolites can cause severe inflammation of the urothelium, urothelial barrier deficits, vascular endothelial fibrinoid changes, increased oxidative stress, and bladder wall fibrosis. A decrease in bladder compliance, urinary tract infection, severe bladder pain with a full bladder, and painful micturition are also common symptoms. Finally, with continued abuse of ketamine, hydronephrosis, ureteral stricture, vesicoureteral reflux, and renal failure may develop. Cessation of ketamine is the mainstay of treatment. Lower urinary tract symptoms usually relapse if patients reuse ketamine after stopping. In cases of severe ketamine cystitis, only augmentation enterocystoplasty can relieve bladder pain and restore normal lower urinary tract function. This article reviews the underlying pathophysiology, clinical characteristics, and management of ketamine cystitis.

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Association of urinary ketamine and APOA1 levels with bladder dysfunction in ketamine abusers revealed via proteomics and targeted metabolite analyses

Liu

Chen

Hsieh

et al. 2021

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Chronic ketamine abuse is associated with bladder dysfunction and cystitis. However, the effects of ketamine abuse on the urinary proteome profile and the correlations among urinary proteins, urinary ketamine (and metabolites) and clinicopathological features of ketamine-induced bladder dysfunction remain to be established. Here, we recruited 56 ketamine abusers (KA) and 40 age-matched healthy controls (HC) and applied the iTRAQ-based proteomics approach to unravel quantitative changes in the urine proteome profile between the two groups. Many of the differentially regulated proteins are involved in the complement and coagulation cascades and/or fibrotic disease. Among them, a significant increase in APOA1 levels in KA relative to control samples (392.1 ± 59.9 ng/ml vs. 13.7 ± 32.6 ng/ml, p < 0.0001) was detected via ELISA. Moreover, urinary ketamine, norketamine and dehydronorketamine contents (measured via LC-SRM-MS) were found to be positively correlated with overactive bladder syndrome score (OABSS) and APOA1 levels with urinary RBC, WBC, OABSS and numeric pain rating scale in KA. Collectively, our results may aid in developing new molecular tool(s) for management of ketamine-induced bladder dysfunction. Moreover, information regarding the differentially regulated proteins in urine of KA provides valuable clues to establish the molecular mechanisms underlying ketamine-induced cystitis.

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The putative involvement of actin‐binding proteins and cytoskeleton proteins in pathological mechanisms of ketamine cystitis—Revealed by a prospective pilot study using proteomic approaches

Abstract: Increased apoptosis in KC might be mediated by actin-binding proteins and a Ca -activated protease. Rapid detrusor contraction in KC might be induced by contractile proteins and cytoskeleton proteins.

Cited by 3 publications

References 39 publications

Smaller bladder capacity and stronger bladder contractility in patients with ketamine cystitis are associated with elevated TRPV1 and TRPV4

Smaller bladder capacity and stronger bladder contractility in patients with ketamine cystitis are associated with elevated TRPV1 and TRPV4

Pathophysiology, clinical presentation, and management of ketamine-induced cystitis

Association of urinary ketamine and APOA1 levels with bladder dysfunction in ketamine abusers revealed via proteomics and targeted metabolite analyses

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