scholarly journals Alterations in detrusor contractility in rat model of bladder cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Igor B. Philyppov ◽  
Ganna V. Sotkis ◽  
Aurelien Rock ◽  
Morad Roudbaraki ◽  
Jean-Louis Bonnal ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Bladder Dysfunction ◽  
Detrusor Underactivity ◽  
Detrusor Smooth Muscle ◽  
Common Complication ◽  
Afferent Limb ◽  
Excitatory Transmission ◽  
Detrusor Contractility ◽  
Spontaneous Contractions ◽  
First Time

AbstractUrinary incontinence of idiopathic nature is a common complication of bladder cancer, yet, the mechanisms underlying changes in bladder contractility associated with cancer are not known. Here by using tensiometry on detrusor smooth muscle (DSM) strips from normal rats and rats with bladder cancer induced by known urothelial carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), we show that bladder cancer is associated with considerable changes in DSM contractility. These changes include: (1) decrease in the amplitude and frequency of spontaneous contractions, consistent with the decline of luminal pressures during filling, and detrusor underactivity; (2) diminution of parasympathetic DSM stimulation mainly at the expense of m-cholinergic excitatory transmission, suggestive of difficulty in bladder emptying and weakening of urine stream; (3) strengthening of TRPV1-dependent afferent limb of micturition reflex and TRPV1-mediated local contractility, promoting urge incontinence; (4) attenuation of stretch-dependent, TRPV4-mediated spontaneous contractility leading to overflow incontinence. These changes are consistent with the symptomatic of bladder dysfunction in bladder cancer patients. Considering that BBN-induced urothelial lesions in rodents largely resemble human urothelial lesions at least in their morphology, our studies establish for the first time underlying reasons for bladder dysfunction in bladder cancer.

Increased basal phosphorylation of detrusor smooth muscle myosin in alloxan-induced diabetic rabbit is mediated by upregulation of Rho-kinase β and CPI-17

2006 ◽  
Vol 290 (3) ◽  
pp. F650-F656 ◽  
Author(s):  
Shaohua Chang ◽  
Joseph A. Hypolite ◽  
Michael E. DiSanto ◽  
Arun Changolkar ◽  
Alan J. Wein ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Bladder Dysfunction ◽  
Rho Kinase ◽  
Specific Inhibitor ◽  
Detrusor Smooth Muscle ◽  
Two Dimensional Gel Electrophoresis ◽  
Calcium Sensitization ◽  
Detrusor Contractility ◽  
Phosphorylation Level ◽  
Mlc Phosphorylation

Urinary bladder dysfunction caused by the alteration of detrusor smooth muscle (DSM) is one of the complications of diabetes. It is well established that smooth muscle contractility is regulated by an elevation of cytosolic Ca2+ via myosin light chain (MLC) phosphorylation. However, recent studies have shown the modulation of MLC phosphorylation without a rise in Ca2+ in smooth muscle and that two key molecules (Rho-kinase and CPI-17) are involved in the regulation of calcium sensitization. This study investigates the effect of diabetes on DSM calcium sensitization. Diabetes was induced by alloxan in New Zealand White rabbits, and age-matched rabbits given 5% sucrose in the drinking water served as control for diuresis. Two-dimensional gel electrophoresis showed that basal MLC phosphorylation level was significantly higher in diabetic animals than normal or diuretic controls, and Rho-kinase-specific inhibitor, Y-27632, decreased MLC phosphorylation level. Adding Y-27632 to bethanechol-precontracted DSM strips can induce muscle relaxation, but it occurred much more slowly in diabetic samples compared with controls. RT-PCR, Western blot analysis, and immunohistochemistry revealed the overexpression of Rho-kinase β and CPI-17 at both mRNA and protein levels in response to diabetes. In conclusion, our results demonstrate that Rho-kinase contributes to DSM MLC phosphorylation and there is a higher basal MLC phosphorylation level in diabetic DSM. Our results also suggest that this high basal MLC phosphorylation may be due to the upregulation of Rho-kinase and CPI-17. Thus Rho-kinase- and CPI-17-mediated Ca2+ sensitization might play a role in diabetes-induced alteration of the detrusor contractility and bladder dysfunction.

Detrusor underactivity: A plea for new approaches to a common bladder dysfunction

2011 ◽  
Vol 30 (5) ◽  
pp. 723-728 ◽  
Author(s):  
G.A. van Koeveringe ◽  
B. Vahabi ◽  
K.E. Andersson ◽  
R. Kirschner-Herrmans ◽  
M. Oelke
Keyword(s):  
Bladder Dysfunction ◽  
Detrusor Underactivity ◽  
New Approaches

Evaluation of the inclusion rate in clinical trials of bladder cancer patients evaluated for first time in the oncology department.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19219-e19219
Author(s):  
Natalia Vidal ◽  
Javier Puente ◽  
Fernando Moreno ◽  
María del Rosario Alfonso ◽  
Lydia Suárez ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Supportive Care ◽  
Cancer Patients ◽  
The Elderly ◽  
Eligibility Criteria ◽  
Enrollment Rate ◽  
Geriatric Evaluation ◽  
Inclusion Rate ◽  
First Time

e19219 Background: In the Genitourinary (GU) Cancer Unit of Clínico San Carlos Hospital the inclusion rate in Clinical-Trials (CTs) from January-October 2018 was 39%. However, in bladder cancer patients it was only 24%. We identified improvement areas in order to increase the inclusion rate of these patients up to 30% from November 2018-March 2019. Methods: We used as an instrument the American Society of Clinical Oncology (ASCO) Quality Training Program (QTP). We collected the number of proposals and available CTs, the number of bladder cancer patients evaluated for the first time and the patients enrolled in CTs. We also identified the causes of non-enrollment and elaborated a list of possible solutions. Results: We developed a cause-effect diagram showing that the most relevant causes of non-enrollment in CTs were the eligibility criteria (60%) and the absence of available CTs (35%). We created a list of measures and identified which would have a higher impact. On November 2018 we started a protocolized Supportive-Care evaluation by our Oncology nurses to increase the number of eligible patients. We also initiated the diffusion of CTs in the Investigation Unit and in the GU-board to increase the number of available CTs and recruitment. In January 2019 we implemented a Geriatric evaluation for the elderly, also to increase the number of eligible patients. With these measures the number of accepted trials increased from 5 in January-October 2018 to 12 in November 2018-March 2019. Also, in January-October 2018, 46% of patients were not-enrolled in a CT due to ineligibility, which decreased to 25% from November 2018-March 2019. As a result, the enrollment rate increased to 43, 75% from November 2018-March 2019. We maintained the measures, and achieved an enrollment rate of 54, 83% from May-December 2019. Conclusions: The implementation of a Supportive-Care and a Geriatric evaluation, and the diffusion of CTs helped increase the percentage of eligible patients and the number of available CTs. With these improvements, we were able to increase the enrollment rate in CTs from 24 to 58, 83%.

scholarly journals Management of Osteoporosis in CKD

2018 ◽  
Vol 13 (6) ◽  
pp. 962-969 ◽  
Author(s):  
Pascale Khairallah ◽  
Thomas L. Nickolas
Keyword(s):  
Bone Mineral Density ◽  
Kidney Disease ◽  
Dual Energy ◽  
Anecdotal Evidence ◽  
Common Complication ◽  
Mineral Density ◽  
Skeletal Fragility ◽  
X Ray ◽  
Pharmacologic Agents ◽  
First Time

CKD mineral and bone disease is a common complication of kidney disease, and it affects the majority of patients with moderate to severe CKD. Recently, prospective studies have shown that measurement of bone mineral density by dual energy x-ray absorptiometry predicts incident fracture, providing nephrologists the ability to risk classify patients for skeletal fragility and targeted antifracture strategies for the first time. Furthermore, an expanding body of literature and anecdotal evidence suggest that pharmacologic agents used to treat osteoporosis in the general population can be safely used in patients with CKD. This review highlights the effects of the Kidney Disease Improving Global Outcomes updates on the management of CKD-associated osteoporosis, discusses recent investigations on the effects of antiosteoporotic agents in patients with CKD, and provides an overview of novel antiosteoporosis agents and the potential challenges related to their use in CKD.

Antibodies against ADP-ATP carrier enhance Ca2+ current in isolated cardiac myocytes

1988 ◽  
Vol 255 (4) ◽  
pp. H960-H964 ◽  
Author(s):  
M. Morad ◽  
N. W. Davies ◽  
G. Ulrich ◽  
H. P. Schultheiss
Keyword(s):  
Cardiac Myocytes ◽  
Mitochondrial Membrane ◽  
Prolonged Exposure ◽  
Ventricular Myocytes ◽  
Inner Mitochondrial Membrane ◽  
Isolated Cardiac Myocytes ◽  
Rat Myocytes ◽  
Spontaneous Contractions ◽  
First Time ◽  
Isolated Rat

Antibodies previously described to inhibit specifically nucleotide transport (ADP-ATP carrier) of the inner mitochondrial membrane were found to bind specifically to the sarcolemma of the enzymatically isolated rat ventricular myocytes. In this communication, we report for the first time that a component of these antibodies enhanced the Ca2+ current in isolated cardiac myocytes and potentiated twitch tension in ventricular strips. Prolonged exposure of rat myocytes to large concentrations of antibodies caused spontaneous contractions, progressive cell deterioration, and death. Our results thus show that a component of antibodies against ADP-ATP carrier cross-reacts with cardiac sarcolemmal proteins enhancing the Ca2+ channel.

ISTHMOCELE: ETIOLOGY, CLINIC, DIAGNOSIS AND TREATMENT (Literature review)

2021 ◽  
pp. 52-55
Author(s):  
L. I. Kandyba ◽  
I. M. Sykal ◽  
V. M. Olkhovska ◽  
M. P. Sokol
Keyword(s):  
Stem Cells ◽  
Surgical Treatment ◽  
Cesarean Section ◽  
Postoperative Period ◽  
Bladder Dysfunction ◽  
Abnormal Uterine Bleeding ◽  
Maternity Hospitals ◽  
History Of ◽  
First Time ◽  
Postoperative Scar

Modern obstetrics is characterized with a loyal approach to surgical delivery, which has significantly affected the activity of maternity hospitals: the number of complications in childbirth from both the mother and fetus has decreased. The formed scar on the uterus is determined differently when examining the women in the postoperative period. Isthmocele is a hypogenic area in the myometrium within the site of postoperative scar in the form of a "niche", diverticulum or sac after cesarean section. It can lead to the development of diseases: abnormal uterine bleeding, dysmenorrhea, chronic pelvic pain, dyspareunia, infertility, adenomyosis, bladder dysfunction, as well as be the cause of ectopic pregnancy, uterine rupture, abnormalities in the placenta attachment of. Risk factors for isthmocele include low uterine incisions, a history of cervical removal, cervical dilatation of more than 5 cm, more than five hours of delivery, etc. For the first time the diagnosis of "isthmocele" is made at ultrasonic research, more often transvaginal one. The diagnosis is confirmed by hysteroscopy or constructive surgery. An important criterion for ismocele is the degree of deficiency, i.e. the ratio between the the biometry thickness on the scar and adjacent to the scar the myometrium area. Depending on the woman's reproductive plans, conservative or surgical treatment of isthmocele is recommended, using autologous stem cells to regenerate muscle tissue. Conservative treatment involves taking oral contraceptives. Surgical treatment includes the imposition of a two−row single−wing suture. The use of stem cells in the postoperative period allows a rise in the frequency of pregnancies in women with a scar on the uterus in the case of the isthmocele formation. Key words: isthmocele, cesarean section, myometrium, autocells.

scholarly journals Spontaneous and evoked contractions are regulated by PKC-mediated signaling in detrusor smooth muscle: involvement of BK channels

2013 ◽  
Vol 304 (5) ◽  
pp. F451-F462 ◽  
Author(s):  
Joseph A. Hypolite ◽  
Qi Lei ◽  
Shaohua Chang ◽  
Stephen A. Zderic ◽  
Stephan Butler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Outlet Obstruction ◽  
Bk Channels ◽  
Bk Channel ◽  
Quiescent State ◽  
Detrusor Smooth Muscle ◽  
Muscle Involvement ◽  
Normal Bladder ◽  
Spontaneous Contractions

Protein kinase C (PKC) and large conductance Ca2+-activated potassium channels (BK) are downregulated in the detrusor smooth muscle (DSM) in partial bladder outlet obstruction (PBOO). DSM from these bladders display increased spontaneous activity. This study examines the involvement of PKC in the regulation of spontaneous and evoked DSM contractions and whether pharmacologic inhibition of PKC in normal DSM contributes to increased detrusor excitability. Results indicate the PKC inhibitor bisindolylmaleimide 1 (Bim-1) prevented a decline in the amplitude of spontaneous DSM contractions over time in vitro, and these contractions persist in the presence of tetrodotoxin. Bim-1 also reduced the basal DSM tone, and the ability to maintain force in response to electrical field stimulation, but did not affect maximum contraction. The PKC activator phorbol-12,13-dibutyrate (PDBu) significantly reduced the amplitude and increased the frequency of spontaneous contractions at low concentrations (10 nM), while causing an increase in force at higher concentrations (1 μM). Preincubation of DSM strips with iberiotoxin prevented the inhibition of spontaneous contractions by PDBu. The BK channel openers isopimaric acid and NS1619 reduced the Bim-1-induced enhancement of spontaneous contractions in DSM strips. Our data suggest that PKC has a biphasic activation profile in the DSM and that it may play an important role in maintaining the quiescent state of the normal bladder during storage through the effects on BK channel, while helping to maintain force required for bladder emptying. The data also suggest that PKC dysfunction, as seen in PBOO, contributes to detrusor overactivity.

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