Most recent edit on 2006-10-16 11:44:03 by KathyFromEngland
Additions:
~*Uronate Peaks And Urinary Hyaluronic Acid Levels Correlate With Interstitial Cystitis Severity
*EGF And HB-EGF Modulate Inward Potassium Current In Human Bladder Urothelial Cells From Normal And Interstitial Cystitis Patients
EGF And HB-EGF Modulate Inward Potassium Current In Human Bladder Urothelial Cells From Normal And Interstitial Cystitis Patients
UroToday.com - There are currently two well-known bladder hypersensory syndromes - overactive bladder (OAB) and interstitial cystitis (BPS/IC). Because BPS/IC is associated with chronic bladder pain, it represents potentially a more challenging clinical problem. There are no treatments that target specifically the bladder sensory pathways.
Recent data suggest that bladder urothelial cells do more than provide a barrier function, but also may initiate bladder sensory signals. They can release putative neurotransmitters including ATP and nitric oxide in response to stretch or pharmacologic stimuli. They also express receptors typically found on neurons. Skin epithelial cells can function as sensors, and it may be that bladder urothelial cells function this way as well.
To better understand the potential for the bladder urothelial cell to participate in bladder sensory signaling, Yan Sun and colleagues from the University of Maryland designed single cell electrophysiological experiments in human normal and BPS/IC bladder urothelial cells. An inward rectifying potassium current was detected in all cells. A decreased conductance was detected in BPS/IC bladder urothelial cells. Conversely, increased potassium conductivity was induced in BPS/IC bladder urothelial cells by exposure to heparin binding epidermal growth factor-like growth factor (HB-EGF). The electrophysiological phenotype of normal and BPS/IC bladder urothelial cells was switched by exposing them to epidermal growth factor and genistein as well as HB-EGF.
The authors believe their findings suggest that potassium currents caused by alterations in growth factor levels could play a role in the pathophysiology of bladder urothelial cells in BPS/IC patients, yielding a potential future target for therapeutic intervention.
By Philip Hanno, MD, MPH
http://www.medilexicon.com/medicalnews.php?newsid=54132∞
Edited on 2006-10-16 11:41:40 by KathyFromEngland
Additions:
~*Safety And Efficacy Of Hyperbaric Oxygen Therapy For The Treatment Of Interstitial Cystitis: A Randomized, Sham Controlled, Double-Blind Trial
*Uronate Peaks And Urinary Hyaluronic Acid Levels Correlate With Interstitial Cystitis Severity
Uronate Peaks And Urinary Hyaluronic Acid Levels Correlate With Interstitial Cystitis Severity
UroToday.com - Several promising markers, led by antiproliferative factor and heparin binding epidermal growth factor-like growth factor may eventually be useful in diagnosing interstitial cystitis. Lokeshwar and colleagues at the University of Miami recently showed that urinary urinate and sulfated glycosaminoglycans (GAG) levels correlate with IC severity, measured using the O'Leary-Sant questionnaire. Sensitivity was 80% ad specificity 92% to detect patients with IC with severe symptoms. In a new study, they examined the profile of urinary glycosaminoglycans species in patients with IC, and examined a correlation between urinary GAG profile and IC severity. They also looked at severity as it correlates with urinary hyaluronic acid levels.
Urine specimens and completed O'Leary-Sant interstitial cystitis symptom and problem indexes (ICSI and ICPI) were obtained from 29 patients with IC, 14 normals, and 14 patients with other benign pelvic and bladder conditions. Eight IC patients and 4 normals were followed over the next 12 months. Urinary glycosaminoglycans profile was determined by gel filtration chromatography. Glycosaminoglycan peaks were analyzed by polyacrylamide gel electrophoresis.
The authors found that in patients with severe IC symptoms, urine specimens contained 3 uronate peaks. Only 1 or 2 peaks were found in the other groups. Urinary hyaluronic acid levels were 3 to 4 fold higher in patients with severe IC symptoms than in the other groups. Glycosaminoglycan profile and hyaluronic acid levels detected IC severity with 83% sensitivity and 89.7% and 74.4% specificity respectively. In the short term and long term studies, glycosaminoglycans profile and hyaluronic acid levels significantly correlated with IC severity.
While there are easier ways to monitor severity (like a questionnaire), the authors findings may present another valuable clue as to pathogenesis and potential treatment of this disorder.
http://www.medilexicon.com/medicalnews.php?newsid=54129∞
Edited on 2006-10-16 11:36:38 by KathyFromEngland
Additions:
~*Safety And Efficacy Of Hyperbaric Oxygen Therapy For The Treatment Of Interstitial Cystitis: A Randomized, Sham Controlled, Double-Blind Trial
Interstitial Cystitis / Painful Bladder Syndrome (PBS/IC) - Urothelium Has Key Role In Regulating Lower Urinary Tract Physiology And Pathology
Safety And Efficacy Of Hyperbaric Oxygen Therapy For The Treatment Of Interstitial Cystitis: A Randomized, Sham Controlled, Double-Blind Trial
16 Oct 2006
UroToday.com - Hyperbaric Oxygen (HBO) therapy aims at ischemia by leading to a net gain in oxygen concentration in tissues. The hyperbaric chamber provides unique conditions in which the hemoglobin is fully saturated and the oxygen is dissolved in the blood plasma at the rate of 2.3 volume percentage of hyperoxemia per 1 atmosphere absolute (ata). Ischemia of the bladder wall has been proposed to be a problem in BPS/IC. Van Ophoven and colleagues from Germany theorized that reduction of ischemic conditions of the pelvic region and with the IC affected bladder wall might be beneficial.
Twenty-one patients were randomized to 90 minutes treatment in a hyperbaric chamber pressurized with 100% oxygen to 2.4 ata for 30 treatment sessions or 1.3 ata breathing normal air in the control group. Three of 14 patients on active treatment and none of the 7 control patients reported treatment response. Responders continued to have benefit at 12 months. Efficacy of treatment appeared to follow an all-or-none rule with no patient showing late improvement who did not show improvement immediately after the treatment sessions.
The low response rate and the lack of any placebo response to such an invasive therapy leads one to question how well blinded the treatments were, and whether the effect was real. The numbers were small, but did reach statistical significance. O'Leary Sant Interstitial Cystitis Symptoms Scores dropped in the active group from 25.7+5.7 to 19.9+7.0 at 3 months post-treatment. In the 3 responders, pain seemed to respond, but there was no change in frequency.
While more research on HBO would be valuable, the therapy presently looks like an expensive ?long run for a short slide? and does not seem ready for the treatment of BPS/IC outside of the research setting.
By Philip M Hanno MD, MPH
http://www.medilexicon.com/medicalnews.php?newsid=54126∞
Deletions:
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Interstitial Cystitis / Painful Bladder Syndrome (PBS/IC) - Urothelium Has Key Role In Regulating Lower Urinary Tract Physiology And Pathology
Oldest known version of this page was edited on 2006-07-30 05:52:35 by KathyFromEngland []
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Articles about new Interstitial Cystitis drugs, treatment methods etc.
Contents
*Interstitial Cystitis / Painful Bladder Syndrome (PBS/IC) - Urothelium Has Key Role In Regulating Lower Urinary Tract Physiology And Pathology
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Interstitial Cystitis / Painful Bladder Syndrome (PBS/IC) - Urothelium Has Key Role In Regulating Lower Urinary Tract Physiology And Pathology
30 Jul 2006
Kanai and co-investigators explored the different mechanisms of urothelial cell pathology, elucidating their impact on bladder function at an International Continence Society Symposium, the results of which were published last month. They also looked critically at novel therapeutic interventions.
The primary urine-plasma barrier is attributable to the layer of superficial umbrella cells, which are interconnected by tight junctions and have an apical surface consisting of an outer leaflet of plaques composed of proteins called uroplakins. Urothelial cells also have specialized sensory and signaling properties that allow them to respond to their chemical and physical environment, and engage in reciprocal chemical communication with neighboring nerves in the bladder wall. The urothelium is far from the ?passive barrier? that formed the previous paradigm.
Transmitters released from urothelial cells can act in an autocrine/paracrine manner in the urothelium, or on subepithelial myofibroblasts, nerves or blood vessels to influence various functions, including the urothelial barrier, local blood flow, and sensory mechanisms. Although traditional therapies for bladder pain have primarily focused on neuronal targets, recent findings suggest that targeting urothelial sensor molecules and/or release mechanisms could be an alternative for the development of pharmacological agents for bladder dysfunction. Targeting antiproliferative factor or its effects may also yield novel, efficacious treatment modalities for PBS/IC.
The authors considered the status of intravesical vanilloid treatment for PBS/IC. They concluded that despite a sound scientific basis for the use of intravesical vanilloids, none is currently licensed as a treatment, as clinical trials have failed to show benefit for resiniferatoxin, the most likely candidate of the group for human use. Nevertheless, it is likely that a therapeutic intervention based on the principle of bladder differentiation will be available in the near future.
By Philip M Hanno, MD, MPH
http://www.medilexicon.com/medicalnews.php?newsid=48230∞
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