Looking for gall bladder disease in the patient's iris.

PubMed

Knipschild, P

1988-12-17

In alternative health care iridology is used as a diagnostic aid. The diagnosis of gall bladder disease was used to study its validity and interperformer consistency. The presence of an inflamed gall bladder containing gall stones is said to be easily recognised by certain signs in the lower lateral part of the iris of the right eye. Stereo colour slides were made of the right eye. Stereo colour slides were made of the right eye of 39 patients with this disease and 39 control subjects of the same sex and age. The slides were presented in a random order to five leading iridologists without supplementary information. The prevalence of the disease was estimated at 56%. The median validity was 51% with 54% sensitivity and 52% specificity. These results were close to chance validity (iota = 0.03). None of the iridologists reached a high validity. The median interperformer consistency was 60%. This was only slightly higher than chance consistency (kappa = 0.18). This study showed that iridology is not a useful diagnostic aid.

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Evaluation of two techniques of partial urethral obstruction in the male rat model of bladder outlet obstruction.

PubMed

Melman, Arnold; Tar, Moses; Boczko, Judd; Christ, George; Leung, Albert C; Zhao, Weixin; Russell, Robert G

2005-11-01

To perform a comparison to determine which of two methods of partial urethral ligation produces the most consistent outcome and fewest side effects. Such a study has not been previously reported. Partial urethral ligation is a means of causing reproducible bladder outlet obstruction. In the male rat model, partial urethral obstruction can be performed either by perineal incision and bulbous urethral ligation or retropubic incision and midprostatic obstruction. Fifteen male Sprague-Dawley rats were studied. Five were selected for bulbous urethral obstruction through a perineal incision, five for midprostatic obstruction using a retropubic approach, and five for a sham operation through a perineal incision. The operative time was shorter and morbidity lower with the perineal approach compared with the retropubic approach. Inflammation or infection, or both, were seen in the prostate, bladder, proximal urethra, ureters, and kidneys in the rats in which a midprostatic obstruction was performed. The proximal urethra and prostate were mildly inflamed in those rats that underwent bulbous obstruction. Sham-operated rats exhibited mild prostatitis only. The perineal approach to the bulbous urethra is the method of choice for creating a partial urethral obstruction model of bladder outlet obstruction in the male rat.

Urothelial Dysfunction and Chronic Inflammation are Associated With Increased Bladder Sensation in Patients With Chronic Renal Insufficiency.

PubMed

Cheng, Sheng-Fu; Jiang, Yuan-Hong; Kuo, Hann-Chorng

2018-01-01

Chronic kidney disease (CKD) or end-stage renal disease (ESRD) patients usually have lower urinary tract symptoms, such as frequency and urgency. Additionally, they frequently suffer from urinary tract infections. This study investigated dysfunction and chronic inflammation of the bladder urothelium in ESRD/CKD patients. This study enrolled 27 patients with CKD (n=13) or ESRD (n=14) for urodynamic studies and bladder biopsies. Patients presented with detrusor underactivity (DU; n=8) or bladder oversensitivity (BO; n=19). Bladder biopsies were performed in these patients and in 20 controls. The bladder mucosa was examined for E-cadherin and zonula occludens-1 (ZO-1) expression, activated mast cell count (through tryptase staining), and urothelial apoptosis (through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling [TUNEL]). The urodynamic parameters were also compared with variables regarding urothelial dysfunction. The bladder mucosa samples of ESRD and CKD patients revealed significantly higher mast cell counts, more urothelial apoptosis, and lower levels of ZO-1 expression than the control samples. E-cadherin expression was significantly reduced in ESRD/CKD patients with DU, but not in ESRD/CKD patients with BO. Increased mast cell and apoptotic cell counts were also associated with ESRD/CKD with BO. Less expression of ZO-1 and E-cadherin was significantly associated with increased bladder sensation and a small bladder capacity. Bladder urothelial dysfunction and chronic inflammation were present to a noteworthy extent in patients with ESRD or CKD. Increased inflammation and defective barrier function were more notable in ESRD/CKD bladders with BO than in those with DU. The clinical characteristics of these patients may involve urothelial pathophysiology.

Chronic cystitis with ossification of the bladder wall in a 6-month-old German shepherd dog

PubMed Central

Zotti, Alessandro; Fant, Pierluigi; De Zan, Gabrita; Mollo, Antonio; Busetto, Roberto

2007-01-01

Ossification of the bladder wall, detected radiographically as a nonhomogeneous radiopaque area in the cranioventral part of the bladder in a puppy, is reported. We speculate that chronic inflammation due to the presence of uroliths in the lumen may have stimulated a metaplastic transformation of the cells. PMID:17966335

Acute Urinary Obstruction in a Tetraplegic Patient from Misplacement of Catheter in Urethra.

PubMed

Vaidyanathan, Subramanian; Singh, Gurpreet; Hughes, Peter L; Soni, Bakul M

2016-01-01

A male tetraplegic patient attended accident and emergency with a blocked catheter; on removing the catheter, he passed bloody urine. After three unsuccessful attempts were made to insert a catheter by nursing staff, a junior doctor inserted a three-way Foley catheter with a 30-mL balloon but inflated the balloon with 10 mL of water to commence the bladder irrigation. The creatinine level was mostly 19 µmol/L (range: 0-135 µmol/L) but increased to 46 µmol/L on day 7. Computerized tomography urogram revealed that the bilateral hydronephrosis with hydroureter was extended down to urinary bladder, the bladder was distended, prostatic urethra was dilated and filled with urine, and although the balloon of Foley catheter was not seen in the bladder, the tip of the catheter was seen lying in the urethra. Following the re-catheterization, the creatinine level decreased to 21 µmol/L. A follow-up ultrasound scan revealed no evidence of hydronephrosis in both kidneys. Flexible cystoscopy revealed inflamed bladder mucosa, catheter reaction, and tiny stones. There was no bladder tumor. This case report concludes that the cause of bilateral hydronephrosis, hydroureter, and distended bladder was inadequate drainage of urinary bladder as the Foley balloon that was under-filled slipped into the urethra resulting in an obstruction to urine flow. Urethral catheterization in tetraplegic patients should be performed by senior, experienced staff in order to avoid trauma and incorrect positioning. Tetraplegic subjects with decreased muscle mass have low creatinine level. Increase in creatinine level (>1.5 times the basal level) indicates acute kidney injury, although peak creatinine level may still be within laboratory reference range. While scanning the urinary tract of spinal cord injury patients with indwelling urinary catheter, if Foley balloon is not seen within the bladder, urethra should be scanned to locate the Foley balloon.

Hemorrhoids

MedlinePlus

Hemorrhoids are swollen, inflamed veins around the anus or lower rectum. They are either inside the anus ... include pregnancy, aging and chronic constipation or diarrhea. Hemorrhoids are very common in both men and women. ...

Nociceptive and Inflammatory Mediator Upregulation in a Mouse Model of Chronic Prostatitis

PubMed Central

Schwartz, Erica S.; Xie, Amy; La, Jun-Ho; Gebhart, G.F.

2015-01-01

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue, FB) from the prostate revealed that thoracolumbar (TL) and lumbosacral (LS) DRG are the principal sources of somata of prostate afferents. Nociceptive markers (e.g., TRP, TREK and P2X channels) were upregulated in FB-labeled TL and LS somata for up to four weeks after inflaming the prostate (intra-prostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21 and 28 days after zymosan injection. Interleukin-10 and NGF were also significantly upregulated in the prostate throughout the four weeks of inflammation. Open field pain-related behaviors (e.g., rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for study of mechanisms underlying pain in chronic prostatitis. PMID:25915147

Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.

PubMed

Schwartz, Erica S; Xie, Amy; La, Jun-Ho; Gebhart, G F

2015-08-01

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection.

PubMed

Jhang, Jia-Fong; Kuo, Hann-Chorng

2015-06-18

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months' duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.

Rapid ultrasonic stimulation of inflamed tissue with diagnostic intent

PubMed Central

McClintic, Abbi M.; Dickey, Trevor C.; Gofeld, Michael; Ray Illian, P.; Kliot, Michel; Kucewicz, John C.; Loeser, John D.; Richebe, Philippe G.; Mourad, Pierre D.

2013-01-01

Previous studies have observed that individual pulses of intense focused ultrasound (iFU) applied to inflamed and normal tissue can generate sensations, where inflamed tissue responds at a lower intensity than normal tissue. It was hypothesized that successively applied iFU pulses will generate sensation in inflamed tissue at a lower intensity and dose than application of a single iFU pulse. This hypothesis was tested using an animal model of chronic inflammatory pain, created by injecting an irritant into the rat hind paw. Ultrasound pulses were applied in rapid succession or individually to rats' rear paws beginning at low peak intensities and progressing to higher peak intensities, until the rats withdrew their paws immediately after iFU application. Focused ultrasound protocols consisting of successively and rapidly applied pulses elicited inflamed paw withdrawal at lower intensity and estimated tissue displacement values than single pulse protocols. However, both successively applied pulses and single pulses produced comparable threshold acoustic dose values and estimates of temperature increases. This raises the possibility that temperature increase contributed to paw withdrawal after rapid iFU stimulation. While iFU-induction of temporal summation may also play a role, electrophysiological studies are necessary to tease out these potential contributors to iFU stimulation. PMID:23927192

Caudal clonidine-bupivicaine block with bladder hydrodistension: a novel combined treatment for the painful bladder

PubMed Central

Tempest, Heidi; Stoneham, Mark; Frampton, Claire; Noble, Jeremy

2011-01-01

The authors describe a new combination procedure consisting of bladder hydrodistension with clonidine-bupivicaine caudal block for the symptomatic relief of bladder pain. They report this new technique whereby patients who had tried multiple forms of therapy with little response, including bladder hydrodistension under general anaesthesia for their chronic pelvic bladder pain, responded to this novel combination therapy. PMID:22696635

Caudal clonidine-bupivicaine block with bladder hydrodistension: a novel combined treatment for the painful bladder.

PubMed

Tempest, Heidi; Stoneham, Mark; Frampton, Claire; Noble, Jeremy

2011-04-19

The authors describe a new combination procedure consisting of bladder hydrodistension with clonidine-bupivicaine caudal block for the symptomatic relief of bladder pain. They report this new technique whereby patients who had tried multiple forms of therapy with little response, including bladder hydrodistension under general anaesthesia for their chronic pelvic bladder pain, responded to this novel combination therapy.

The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder.

PubMed

Greenland, J E; Hvistendahl, J J; Andersen, H; Jörgensen, T M; McMurray, G; Cortina-Borja, M; Brading, A F; Frøkiaer, J

2000-06-01

To investigate the effect of partial bladder outlet obstruction on detrusor blood flow and oxygen tension (PdetO2) in female pigs. Detrusor-layer oxygen tension and blood flow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in five female Large White pigs with a partial urethral obstruction and in five sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described. In the obstructed bladders, blood flow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood flow declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals. In pigs with chronic bladder outlet obstruction, blood flow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during filling caused significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.

Chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface

NASA Astrophysics Data System (ADS)

Khurram, Abeer; Ross, Shani E.; Sperry, Zachariah J.; Ouyang, Aileen; Stephan, Christopher; Jiman, Ahmad A.; Bruns, Tim M.

2017-06-01

Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4-11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.

Host-Pathogen Checkpoints and Population Bottlenecks in Persistent and Intracellular Uropathogenic E. coli Bladder Infection

PubMed Central

Hannan, Thomas J.; Totsika, Makrina; Mansfield, Kylie J.; Moore, Kate H.; Schembri, Mark A.; Hultgren, Scott J.

2013-01-01

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multi-drug resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic E. coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the Quiescent Intracellular Reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection: QIR, ASB, or chronic cystitis, is determined within the first 24 hours of infection and constitutes a putative host-pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies. PMID:22404313

Nociceptor Sensitization Depends on Age and Pain Chronicity123

PubMed Central

Dodge, Amanda K.

2016-01-01

Abstract Peripheral inflammation causes mechanical pain behavior and increased action potential firing. However, most studies examine inflammatory pain at acute, rather than chronic time points, despite the greater burden of chronic pain on patient populations, especially aged individuals. Furthermore, there is disagreement in the field about whether primary afferents contribute to chronic pain. Therefore, we sought to evaluate the contribution of nociceptor activity to the generation of pain behaviors during the acute and chronic phases of inflammation in both young and aged mice. We found that both young (2 months old) and aged (>18 months old) mice exhibited prominent pain behaviors during both acute (2 day) and chronic (8 week) inflammation. However, young mice exhibited greater behavioral sensitization to mechanical stimuli than their aged counterparts. Teased fiber recordings in young animals revealed a twofold mechanical sensitization in C fibers during acute inflammation, but an unexpected twofold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of A-mechanonociceptor (AM) fibers were also reduced chronically. Importantly, this lack of sensitization in afferent firing during chronic inflammation occurred even as these inflamed mice exhibited continued behavioral sensitization. Interestingly, C fibers from inflamed aged animals showed no change in mechanical firing compared with controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal the following two important findings: (1) nociceptor sensitization to mechanical stimulation depends on age and the chronicity of injury; and (2) maintenance of chronic inflammatory pain does not rely on enhanced peripheral drive. PMID:26866058

Spontaneous Extraperitoneal Bladder Rupture Because of Chronic Appendicitis

PubMed Central

Morganstern, Bradley A.; Viviano, Robert; Elsamra, Sammy

2013-01-01

A 62-year-old man presented to the emergency department with an episode of syncope after 2-3 weeks of diffuse abdominal pain, now complaining of a severe increase in pain concurrent with >24 hours of no urine output. His workup showed an idiopathic extraperitoneal rupture of the bladder on computed tomography, which was handled conservatively with Foley insertion. Repeated follow-up and imaging showed no resolution or etiology over 2 months. The patient underwent exploratory laparotomy that showed an elongated appendix with a chronic tip appendicitis that had induced bladder rupture by chronic inflammatory changes. After repair, the patient had no further complaints. PMID:26955533

Chronic Bladder Infection: Is There a Cure?

MedlinePlus

... to get recurrent bladder infections, a type of urinary tract infection (UTI). These factors include: Kidney or bladder stones Bacteria ... your doctor at the first sign of a UTI Vaginal estrogen therapy — if you don't already ...

Mast Cell IL-10 Drives Localized Tolerance in Chronic Bladder Infection

PubMed Central

Chan, Cheryl Y.; St. John, Ashley L.; Abraham, Soman N.

2013-01-01

The lower urinary tract’s virtually inevitable exposure to external microbial pathogens warrants efficient tissue-specialized defenses to maintain sterility. The observation that the bladder can become chronically infected in combination with clinical observations that antibody responses following bladder infections are not detectable, suggest defects in the formation of adaptive immunity and immunological memory. We have identified a broadly immunosuppressive transcriptional program specific to the bladder, but not the kidney, during infection of the urinary tract that is dependent on tissue-resident mast cells (MCs). This involves localized production of interleukin-10 and results in suppressed humoral and cell mediated responses and bacterial persistence. Therefore, in addition to the previously described role of MCs orchestrating the early innate immunity during bladder infection, they subsequently play a tissue-specific immunosuppressive role. These findings may explain the prevalent recurrence of bladder infections and suggest the bladder as a site exhibiting an intrinsic degree of MC-maintained immune privilege. PMID:23415912

MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

EPA Science Inventory

MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

Epidemiological studies have shown a positive association between chronic exposure to chlorinated drinking water and human cancer, particularly of the urinary bladder. MX (3- chloro-4-(dichloromethyl)-5-hydrox...

IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps.

PubMed

Shaw, Joanne L; Fakhri, Samer; Citardi, Martin J; Porter, Paul C; Corry, David B; Kheradmand, Farrah; Liu, Yong-Jun; Luong, Amber

2013-08-15

Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

Schistosoma haematobium Infection That Mimics Bladder Cancer in a 66-Year-Old Ethnic Egyptian Man.

PubMed

Zepeda, Celenne Morfin; Coffey, Kristen H

2015-01-01

66-year-old ethnic Egyptian man. Hematuria. The patient had a history of multiple episodes of gross hematuria for the past 5 years. Because the hematuria usually resolved on its own, he did not seek medical attention during that time. Bladder cancer was suspected. The patient had a history of coronary artery disease, hypertension, nephrolithiasis, congestive heart failure, lifelong smoking, and ischemic cardiomyopathy. He has been taking the anticoagulants clopidogrel (Plavix) and warfarin (Coumadin). The patient is originally from Egypt and has been living in the United States for the past 10 years. A complete blood count showed a hemoglobin of 13.0 g per dL (reference range, 14.0 to 18.0 g per dL), hematocrit 40% (40% to 54%), red blood cell count (RBC) 4.65 × 10(9) per L (4.60 to 6.00), and platelet count 179 × 10(9) per L (150 to 450). The urinalysis results showed 3+ protein, 4+ blood, and urine RBC of greater than 100 per high power field (hpf). The urinalysis results did not indicate the presence of parasitic ova or adult parasites. Based on these results, the physician ordered cystoscopic testing, suspecting bladder cancer. Analysis of the bladder tissue showed inflammation (Image 1) and several ova that were consistent with developing Schistosoma (Image 2). Many of the ova were calcified and surrounded by severely inflamed tissue (Image 3). Copyright© by the American Society for Clinical Pathology (ASCP).

Progression from Chronic Atrophic Gastritis to Gastric Cancer; Tangle, Toggle, Tackle with Korea Red Ginseng

PubMed Central

Kim, Yoon Jae; Chung, Jun Won; Lee, So Jung; Choi, Ki Seok; Kim, Ju Hyun; Hahm, Ki Baik

2010-01-01

Key molecular players that link inflammation to carcinogenesis are prostaglandins, cytokines, nuclear factor-κB (NF-κB), chemokines, angiogenic growth factors, and free radicals, all of which lead to increased mutations and altered functions of important enzymes and proteins, for example, activation of oncogenic products and/or inhibition of tumor suppressor proteins, in inflamed tissues, thus contributing to multi-stage carcinogenesis process. Interpreted reversely, the identification of the molecular mechanisms by which chronic inflammation increases cancer risk or optimal intervention of targeted drugs or agents during the inflammation-associated carcinogenic process could be a necessary basis for developing new strategy of cancer prevention at many sites. In this review, we discuss the possibilities for cancer prevention by controlling inflammation process in Helicobacter pylori (H. pylori)-associated inflamed stomach with Korea red ginseng. Korea red ginseng is a good example of a natural herb that has ubiquitous properties that are conductive to stop inflammatory carcinogenesis that is un wanted outcome of H. pylori infection, rendering rejuvenation of chronic atrophic gastritis. PMID:20490314

Painful Bladder Filling and Painful Urgency Are Distinct Characteristics in Men and Women with Urologic Chronic Pelvic Pain Syndromes – A MAPP Research Network Study

PubMed Central

Lai, H. Henry; Krieger, John N.; Pontari, Michel A.; Buchwald, Dedra; Hou, Xiaoling; Landis, J. Richard

2015-01-01

Purpose To describe bladder-associated symptoms in patients with urologic chronic pelvic pain syndromes (UCPPS) and to correlate these symptoms with urologic, non-urologic, psychosocial, and quality of life measures. Methods Participants were 233 women and 191 men with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome in a multi-center study. They completed a battery of measures, including items asking if their pain worsened with bladder filling (“painful filling”) or if their urge to urinate was due to pain, pressure, or discomfort (“painful urgency”). Participants were categorized into 3 groups: 1) “both” painful filling and painful urgency, 2) “either” painful filling or painful urgency, or 3) “neither.” Results Seventy-five percent of men and 88% of women were categorized as “both” or “either.” These bladder characteristics were associated with more severe urologic symptoms (increased pain, frequency, urgency), higher somatic symptom burden, depression, and worse quality of life (all p<0.01, 3-group trend test). A gradient effect was observed across groups (both > either > neither). Compared to those in the “neither” group, men categorized as “both” or “either” reported more frequent UCPPS symptom flares, catastrophizing, and irritable bowel syndrome, and women categorized as “both” or “either” were more likely to have negative affect and chronic fatigue syndrome. Conclusions Men and women with bladder symptoms characterized as painful filling or painful urgency had more severe urologic symptoms, more generalized symptoms, and worse quality of life than participants who reported neither characteristic, suggesting that these symptom characteristics might represent important subsets of UCPPS patients. PMID:26192257

Molecular Signatures of Chronic Pain Subtypes

DTIC Science & Technology

2015-03-01

injury, omega-3 fatty acid supplementation may act as a safe and novel preventive analgesic therapy . We have recently completed enrollment of one...chemical or physical structure of DNA [15]. Structural and chemical changes in DNA may be influenced by experience (acute pain and perioperative inflam...DNMT inhibitors appear to be another promising epigenetically active therapy to prevent chronic pain after surgery [39]. There appears to be a

Analysis on pathogenesis of 50 cases of bladder proliferative lesions.

PubMed

Chen, Zhiqiang; Lan, Ruzhu; Ye, Zhangqun; Yang, Weimin

2003-01-01

In order to study the pathogenesis, clinical and pathological characteristics of proliferative lesions of the bladder, 50 cases of proliferative lesions of the bladder from 150 patients with complaints of frequency, urgency, hematuria and dysuria were subjected to cystoscopic biopsy of the suspicious foci in the bladder. In combination with the symptoms, urine and urodynamics, the relationship of proliferative lesions of the bladder to the inflammation and obstruction of the lower urinary tract was analyzed. Of the 50 cases of proliferative bladder lesions, 44 cases (88%) had lower urinary tract infection and 29 (58%) lower urinary tract obstruction. The patients with lower urinary tract obstruction were all complicated with infection. Three cases were associated with transitional cell carcinoma. Malignant cells were detected in 1 case by urinary cytologic examination. Proliferative lesions of the bladder, especially those without other obvious mucosa changes under cystoscopy, are common histological variants of urothelium in the patients with chronic inflammation and obstruction of the lower urinary tract. Chronic inflammation and obstruction of the lower urinary tract might be the causes for proliferative lesions of the bladder. It is suggested that different treatments should be applied according to the scope and histological type of the proliferative lesions.

Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)

PubMed

Duchmann, R; Kaiser, I; Hermann, E; Mayet, W; Ewe, K; Meyer zum Büschenfelde, K H

1995-12-01

Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen. LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate. PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-gamma), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD.

Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)

PubMed Central

Duchmann, R; Kaiser, I; Hermann, E; Mayet, W; Ewe, K; Meyer zum Büschenfelde, K H

1995-01-01

Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen. LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate. PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-gamma), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD. PMID:8536356

Microcirculation and structural reorganization of the bladder mucosa in chronic cystitis under conditions of ozone therapy.

PubMed

Neimark, A I; Nepomnyashchikh, L M; Lushnikova, E L; Bakarev, M A; Abdullaev, N A; Sizov, K A

2014-01-01

Structural reorganization of the bladder mucosa in chronic cystitis and its correction by ozone therapy were studied. A relationship between the epithelial layer restructuring of different kinds (dystrophy, metaplasia, and degeneration), level of cell proliferation, and ultrastructural organization of urotheliocytes was detected. This complex of structural reactions was combined with dysregulation of tissue bloodflow in the bladder mucosa, shown by laser Doppler flowmetry. Positive structural changes were most marked in intravesical and less so in parenteral ozone therapy added to the therapeutic complex and manifested in reduction of inflammation and alteration in parallel with more intense reparative reactions. A special feature of parenteral ozone therapy was a significant improvement of microcirculation in the bladder mucosa.

Regulator of Calcineurin 1 in Periodontal Disease

PubMed Central

Peters, Ulrike; Solominidou, Eleni; Korkmaz, Yüksel; Rüttermann, Stefan; Klocke, Astrid; Flemmig, Thomas Frank; Beikler, Thomas

2016-01-01

Nuclear factor of activated T-cells (NFAT) and NF-kB pathway associated processes are involved in the pathogenesis of various inflammatory disorders, for example, periodontal disease. The activation of these pathways is controlled by the regulator of calcineurin 1 (RCAN1). The aim of this study was to elucidate the role of RCAN1 in periodontal disease. Healthy and inflamed periodontal tissues were analyzed by immunohistochemistry and immunofluorescence using specific rabbit polyclonal anti-RCAN1 antibodies. For expression analysis human umbilical vein endothelial cells (HUVEC) were used. HUVEC were incubated for 2 h with Vascular Endothelial Growth Factor (VEGF) or with wild type and laboratory strains of Porphyromonas gingivalis (P. gingivalis). Expression analysis of rcan1 and cox2 was done by real time PCR using specific primers for rcan1.4 and cox2. The expression of rcan1 was found to be significantly suppressed in endothelial cells of chronically inflamed periodontal tissues compared to healthy controls. Rcan1 and cox2 were significantly induced by VEGF and wild type and laboratory P. gingivalis strains. Interestingly, the magnitude of the rcan1 and cox2 induction was strain dependent. The results of this study indicate that RCAN1 is suppressed in endothelial cells of chronically inflamed periodontal tissues. During an acute infection, however, rcan1 seems to be upregulated in endothelial cells, indicating a modulating role in immune homeostasis of periodontal tissues. PMID:27403036

Biological functions of melatonin in relation to pathogenesis of oral lichen planus.

PubMed

Chaiyarit, Ponlatham; Luengtrakoon, Kirawut; Wannakasemsuk, Worraned; Vichitrananda, Vilasinee; Klanrit, Poramaporn; Hormdee, Doosadee; Noisombut, Rajda

2017-07-01

Oral lichen planus (OLP) is considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations. Accumulated data support the involvement of cell-mediated immune dysfunction in the development of OLP. However, the connection between neuroendocrine system and oral immune response in OLP patients has never been clarified. Melatonin is considered as a major chronobiotic hormone produced mainly by the pineal gland. This gland is recognized as a regulator of circadian rhythm and a sensor in the immune response through the NF-kB transduction pathway. It was suggested that pineal-derived melatonin and extra-pineal melatonin synthesized at the site of inflamed lesion might play a role in inflammatory response. According to our immunohistochemical study, expression of melatonin could be detected in human oral mucosa. In addition, increased levels of melatonin were observed in inflamed oral mucosa of OLP patients. We hypothesize that chronic inflammation possibly induces the local biosynthesis of melatonin in inflamed oral mucosa. We also speculate that melatonin in oral mucosa may play a cytoprotective role through its anti-oxidative and anti-inflammatory properties. Moreover, melatonin may play an immunomodulatory role in relation to pathogenesis of OLP. Our hypothesis provides a new implication for upcoming research on the connection between circadian neuroendocrine network and immune response in oral mucosal compartments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Na-glutamine co-transporters B(0)AT1 in villus and SN2 in crypts are differentially altered in chronically inflamed rabbit intestine.

PubMed

Saha, Prosenjit; Arthur, Subha; Kekuda, Ramesh; Sundaram, Uma

2012-03-01

Glutamine is a major nutrient utilized by the intestinal epithelium and is primarily assimilated via Na-glutamine co-transport (NGcT) on the brush border membrane (BBM) of enterocytes. Recently we reported that B(0)AT1 (SLC6A19) mediates glutamine absorption in villus while SN2 (SLC38A5) does the same in crypt cells. However, how B(0)AT1 and SN2 are affected during intestinal inflammation is unknown. In the present study it was shown that during chronic enteritis NGcT was inhibited in villus cells, however, it was stimulated in crypt cells. Our studies also demonstrated that the mechanism of inhibition of NGcT during chronic enteritis was secondary to a reduction in the number of B(0)AT1 co-transporters in the villus cell BBM without a change in the affinity of the co-transporter. In contrast, stimulation of NGcT in crypt cells was secondary to an increase in the affinity of SN2 for glutamine without an alteration in the number of co-transporters. Thus, glutamine assimilation which occurs via distinct transporters in crypt and villus cells is altered in the chronically inflamed intestine. Copyright © 2011 Elsevier B.V. All rights reserved.

Mast cell regulation of Na-glutamine co-transporters B0AT1 in villus and SN2 in crypt cells during chronic intestinal inflammation.

PubMed

Singh, Soudamani; Arthur, Subha; Talukder, Jamilur; Palaniappan, Balasubramanian; Coon, Steven; Sundaram, Uma

2015-04-15

In the chronically inflamed rabbit small intestine, brush border membrane (BBM) Na-glutamine co-transport is inhibited in villus cells (mediated by B0AT1), while it is stimulated in crypt cells (mediated by SN2/SNAT5). How mast cells, known to be enhanced in the chronically inflamed intestine, may regulate B0AT1 in villus and SN2/SNAT5 in crypt cell is unknown. Thus, the aim of the present study is to determine the regulation of B0AT1 and SN2/SNAT5 by mast cells during chronic enteritis. Chronic intestinal inflammation was induced in male rabbits with intra-gastric inoculation of Eimeria magna oocytes. Rabbits with chronic inflammation were treated with ketotifen (10 mg/day) or saline (Placebo) for 2 days. Villus and crypts cells were isolated from the rabbit intestine using the Ca++ chelation technique. Na/K-ATPase activity was measured as Pi from cellular homogenate. BBM vesicles (BBMV) were prepared from villus and crypt cells and uptake studies were performed using rapid filtration technique with (3)H-Glutamine. Western blot analyses were done using B0AT1 and SN2 specific antibodies. In villus cells, Na-glutamine co-transport inhibition observed during inflammation was completely reversed by ketotifen, a mast cell stabilizer. In contrast, in crypt cells, Na-glutamine co-transport stimulation was reversed to normal levels by ketotifen. Kinetic studies demonstrated that ketotifen reversed the inhibition of B0AT1 in villus cells by restoring co-transporter numbers in the BBM, whereas the stimulation of SN2/SNAT5 in crypts cells was reversed secondary to restoration of affinity of the co-transporter. Western blot analysis showed that ketotifen restored immune-reactive levels of B0AT1 in villus cells, while SN2/SNAT5 levels from crypts cell remained unchanged. In the present study we demonstrate that mast cells likely function as a common upstream immune pathway regulator of the Na-dependent glutamine co-transporters, B0AT1 in villus cells and SN2 in crypts cells that are uniquely altered in the chronically inflamed small intestine.

"Hair in the Bladder": An Unusual Finding.

PubMed

Cindolo, Luca; Bada, Maida; Bellocci, Roberto; De Francesco, Piergustavo; Castellan, Pietro; Berardinelli, Francesco; Neri, Fabio; Schips, Luigi

2017-01-01

Trichobezoar is a rare condition whereby a hairball is found in the human stomach or gastrointestinal tract, most frequently in young women, mainly in association with a psychiatric disorder. Trichobezoar cases have also been reported in the bladder and represent a rare complication of foreign bodies, called "hair nidus or hair ball," in patients with chronic catheter. Approximately 10% to 15% of patients on long-term urethral catheter or clean intermittent self-catheterization develop urinary tract stones. In a small minority of cases, bladder stones can develop around a foreign body that was introduced into the bladder. In the literature, there are few cases of foreign bladder bodies that formed stones over a hair nidus. Recognizing this condition can optimize the patient's quality of life. Herein, we present a case of a 71-year-old Caucasian male with a long-term catheter in hypocontractile urinary bladder secondary to injury of pelvic plexus after rectal surgery. He had a bladder stone caused by hair encrusted together. Hair is introduced into the bladder either by adherence to the catheter directly or by overlying the urethral meatus and being pushed internally. Regular hygiene and shaving of pubic area represent effective preventive measures to reduce this kind of complications in patients with chronic indwelling catheter or under a self-catheterization regimen.

Experimental results on mechanisms of action of electrical neuromodulation in chronic urinary retention.

PubMed

Schultz-Lampel, D; Jiang, C; Lindström, S; Thüroff, J W

1998-01-01

Sacral foramen neuromodulation--initially applied for the treatment of urinary incontinence--has proved to be effective in patients with chronic urinary retention. Thus far, the underlying neurophysiological mechanisms have not been elucidated. In an experimental study on the neurophysiological basis of sacral neurostimulation, one objective was to investigate the mechanisms responsible for initiation of micturition in chronic urinary retention. In ten female cats anesthetized with alpha-chloralose the clinical situation of sacral foramen stimulation was experimentally reproduced by isolated S2 nerve stimulation after L6-S3 laminectomy. Stimulation responses were recorded from the bladder, peripheral nerves, and striated muscles of the foot and pelvic floor. The effect of sudden cessation of prolonged S2 stimulation, during which the bladder was completely inhibited, was evaluated in 70 stimulation sequences in 5 cats. Sacral nerve stimulation induced excitatory and inhibitory effects on the bladder, depending on the frequency and intensity of stimulation. With unilateral S2 stimulation, bladder excitation was best at frequencies of 2-5 Hz and at intensities ranging between 0.8 and 1.4 times the threshold for the M-response of the foot muscle. Inhibition was the dominating effect at frequencies of 7-10 Hz and at intensities exceeding 1.4 times the threshold. Prolonged S2 stimulation above the threshold produced complete bladder inhibition during stimulation but induced strong bladder contractions after sudden interruption of stimulation, with amplitudes being significantly higher than that of spontaneous contractions preceding the stimulation. These results confirm the hypothesis of a "rebound" phenomenon as the mechanism of action for induction of spontaneous voiding in patients with chronic urinary retention.

Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation

DTIC Science & Technology

2017-11-01

acute ) models of chemically-induced colitis. Based upon our studies, we believe the the rationale for the use of MSCs to treat patients with...rodent models of IBD, virtually all of these studies have used clinically-questionable doses of MSCs in 10 erosive, self-limiting (i.e. acute ...been demonstrated that ILC3-derived IL-22 attenuates acute and chronic intestinal inflam- mation induced in lymphopenic mice (Rag−/− mice) by Citrobacter

Mental health diagnoses in patients with interstitial cystitis/painful bladder syndrome and chronic prostatitis/chronic pelvic pain syndrome: a case/control study.

PubMed

Clemens, J Quentin; Brown, Sheila O; Calhoun, Elizabeth A

2008-10-01

We compared the rate of mental health disorders in male and female patients with pelvic pain and control subjects. Male patients with chronic prostatitis/chronic pelvic pain syndrome (174) and female patients with interstitial cystitis/painful bladder syndrome (111) were identified from a urology tertiary care clinic population. A control group consisting of 72 men and 175 women was also recruited. Subjects completed self-administered questionnaires that included items about demographics, medical history, medication use and urological symptoms. The Patient Health Questionnaire was used to identify depression and panic disorder. Multiple logistic regression was used to determine odds ratios for the presence of a mental health diagnosis. Mental health disorders were identified in 13% of the chronic prostatitis/chronic pelvic pain syndrome cases and 4% of male controls (OR 2.0, p = 0.04), as well as in 23% of interstitial cystitis/painful bladder syndrome cases and 3% of female controls (OR 8.2, p <0.0001). Disease status (case vs control) (OR 10.4, p = 0.001) and income greater than $50,000 (OR 0.34, p = 0.008) were the only 2 variables independently predictive of the presence of a mental health diagnosis. Age, gender, race/ethnicity and education were not predictive. Medications for anxiety, depression or stress were being taken by 18% of patients with chronic prostatitis/chronic pelvic pain syndrome, 37% of those with interstitial cystitis/painful bladder syndrome, 7% of male controls and 13% of female controls. Depression and panic disorder are significantly more common in men and women with pelvic pain conditions than in controls. Medication use data suggest that anxiety and depression may be more difficult to treat in patients with urological pain syndromes than in controls.

Transcriptomic dose-and-time-course indicators of early key events in a cytotoxicity-mediated mode of action for rodent urinary bladder tumorigenesis

EPA Science Inventory

TRANSCRIPTOMIC DOSE- AND TIME-COURSE INDICATORS OF EARLY KEY EVENTS IN A CYTOTOXICITY-MEDIATED MODE OF ACTION FOR RODENT URINARY BLADDER TUMORIGENESISDiuron is a substituted urea compound used globally as an herbicide. Urinary bladder tumors were induced in rats after chronic die...

Street ketamine-associated bladder dysfunction: an emerging health problem.

PubMed

Lee, Py; Ong, Ta; Chua, Cb; Lei, Ccm; Teh, Gc

2009-01-01

Ketamine is frequently abused nowadays as a recreational drug. Case reports are emerging since 2007 to describe a new clinical entity of severe bladder dysfunction associated with chronic abuse of street ketamine. Severe lower urinary tract symptoms of urinary frequency and urgency which are refractory to conventional treatment. Quality of life is adversely affected as a consequence. Chronic kidney disease will develop in advanced cases. Investigation findings: The urine is sterile on culture. Ultrasound will show reduced bladder capacity with thickened bladder wall. In advanced stage, hydronephrosis and renal impairment will develop. Patients should be advised to stop street ketamine use immediately. Anticholinergic medication could be tried to alleviate the symptoms. Refractory cases with dilatation of the upper urinary tract might need urinary diversion. Awareness of this new condition is essential in diagnosis. Early intervention offers better treatment outcome.

Release of endogenous opioids following transcutaneous electric nerve stimulation in an experimental model of acute inflammatory pain.

PubMed

Sabino, George S; Santos, Cristiane M F; Francischi, Janetti N; de Resende, Marcos Antônio

2008-02-01

Transcutaneous electric nerve stimulation (TENS) is a noninvasive treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. The aim of the present study was to investigate the action mechanism of TENS at high (HF: 130 Hz) and low (LF: 10 Hz) frequencies in an inflammation model produced by the injection of carrageenan in rat paws (Cg; 250 microg). After carrageenan administration (0 time), either HF or LF TENS was applied to the inflamed paw of rats for 20 minutes, and hyperalgesia was assessed hourly using the modified Randall-Selitto method (1957). HF and LF TENS inhibited the carrageenan-induced hyperalgesia by 100%. Pretreatment of animals with intraplantar naltrexone (Nx; 50 microg) reversed the analgesic effect of the LF TENS but did not alter the effect of HF TENS. The application of HF and LF TENS to the contralateral paw reversed the hyperalgesia of the inflamed paw similar to that observed when TENS was applied to the inflamed paw. However, LF TENS presented a longer-lasting analgesic effect than HF TENS. Our data demonstrate that HF and LF TENS induced antihyperalgesia. We also report that the antihyperalgesia provoked by LF TENS is partially due to the local release of endogenous opioids. This study offers important information about physiotherapy practices aimed at pain relieving. TENS is a noninvasive treatment that promotes analgesia in acute and chronic inflammatory conditions. Scientists, patients, and the general population may benefit from this knowledge.

Spontaneous firing and evoked responses of spinal nociceptive neurons are attenuated by blockade of P2X3 and P2X2/3 receptors in inflamed rats.

PubMed

Xu, Jun; Chu, Katharine L; Brederson, Jill-Desiree; Jarvis, Michael F; McGaraughty, Steve

2012-08-01

P2X3 and P2X2/3 receptors are selectively expressed on primary afferent nociceptors and have been implicated in modulating nociception in different models of pathological pain, including inflammatory pain. In an effort to delineate further the role of P2X3 receptors (homomeric and heteromeric) in the modulation of nociceptive transmission after a chronic inflammation injury, A-317491, a potent and selective P2X3-P2X2/3 antagonist, was administered to CFA-inflamed rats in order to examine its effects on responses of spinal dorsal horn neurons to mechanical and thermal stimulation. Systemic injection of A-317491 (30 μmol/kg, i.v.) reduced the responses of wide-dynamic-range (WDR) and nociceptive specific (NS) neurons to both high-intensity mechanical (pinch) and heat (49°C) stimulation. A-317491 also decreased low-intensity (10 g von Frey hair) mechanically evoked activity of WDR neurons but did not alter WDR neuronal responses to cold stimulation (5°C). Spontaneous firing of WDR neurons in CFA-inflamed rats was also significantly attenuated by A-317491 injection. By using immunohistochemistry, P2X3 receptors were demonstrated to be enhanced in lamina II of the spinal dorsal horn after inflammation. In summary, blockade of P2X3 and P2X2/3 receptors dampens mechanical- and heat-related signaling, as well as nonevoked activity of key classes of spinal nociceptive neurons in inflamed animals. These data suggest that P2X3 and/or P2X2/3 receptors have a broad contribution to somatosensory/nociceptive transmission in rats with a chronic inflammatory injury and are consistent with previous behavioral data demonstrating antiallodynic and antihyperalgesic effects of receptor antagonists. Copyright © 2012 Wiley Periodicals, Inc.

THE EFFECTS OF COMBINATORIAL EXPOSURE OF PRO-INFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES ON AIRWAY EPITHELIAL CELL RELEASE OF CHEMOTACTIC MEDIATORS

EPA Science Inventory

Asthma is a chronic inflammatory disorder of the airways affecting nearly 15 million individuals nationally. Within the inflamed asthmatic airway there exist complex interactions between many cells and the cytokines they release, in particular mast cells, eosinophils, T-lymphocy...

Detecting bladder fullness through the ensemble activity patterns of the spinal cord unit population in a somatovisceral convergence environment.

PubMed

Park, Jae Hong; Kim, Chang-Eop; Shin, Jaewoo; Im, Changkyun; Koh, Chin Su; Seo, In Seok; Kim, Sang Jeong; Shin, Hyung-Cheul

2013-10-01

Chronic monitoring of the state of the bladder can be used to notify patients with urinary dysfunction when the bladder should be voided. Given that many spinal neurons respond both to somatic and visceral inputs, it is necessary to extract bladder information selectively from the spinal cord. Here, we hypothesize that sensory information with distinct modalities should be represented by the distinct ensemble activity patterns within the neuronal population and, therefore, analyzing the activity patterns of the neuronal population could distinguish bladder fullness from somatic stimuli. We simultaneously recorded 26-27 single unit activities in response to bladder distension or tactile stimuli in the dorsal spinal cord of each Sprague-Dawley rat. In order to discriminate between bladder fullness and tactile stimulus inputs, we analyzed the ensemble activity patterns of the entire neuronal population. A support vector machine (SVM) was employed as a classifier, and discrimination performance was measured by k-fold cross-validation tests. Most of the units responding to bladder fullness also responded to the tactile stimuli (88.9-100%). The SVM classifier precisely distinguished the bladder fullness from the somatic input (100%), indicating that the ensemble activity patterns of the unit population in the spinal cord are distinct enough to identify the current input modality. Moreover, our ensemble activity pattern-based classifier showed high robustness against random losses of signals. This study is the first to demonstrate that the two main issues of electroneurographic monitoring of bladder fullness, low signals and selectiveness, can be solved by an ensemble activity pattern-based approach, improving the feasibility of chronic monitoring of bladder fullness by neural recording.

An animal model for the neuromodulation of neurogenic bladder dysfunction.

PubMed

Zvara, P; Sahi, S; Hassouna, M M

1998-08-01

To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

Prevention of recurrent urinary tract infections by intravesical administration of heparin: a pilot study.

PubMed

Ablove, Tova; Patankar, Manish; Seo, Songwon

2013-12-01

To assess the effect of bladder instillations using heparin on the rate of urinary tract infections in women resistant to standard therapy. The medical records of all women who received bladder instillations between May 2009 and January of 2010 at the University of Wisconsin urogynecology clinic were reviewed. Eighteen women (mean age 67 years) with a history of recurrent urinary tract infections received intravesical instillations (heparin 40,000 U, 2% lidocaine 8 ml, sodium bicarbonate 4 ml) once weekly for 6 weeks. Patients were considered resistant to standard therapy if their condition failed to respond to chronic suppression antibiotic therapy; they had chronic infections and for this reason could not be placed on chronic suppression; or they were not candidates for chronic suppression due to drug allergies. The number of urinary tract infections was monitored during treatment and for 6 months after therapy. The urinary tract infection rates were compared with the rates of urinary tract infection in the 6 months before treatment. Seventy-eight percent of patients responded to therapy. Subjects were thought to have responded to therapy if there was a greater than 50% reduction in the rate of urinary tract infection. Other variables reviewed included evidence of chronic infection, hormonal status, glomerular filtration rate, age, body mass index, antibiotic allergies, diabetes, hypertension, and chronic antibiotic therapy during bladder instillations. None of these variables were found to be statistically significant. Bladder instillations decreased the rate of urinary tract infection in this pilot study; this effect persisted into the post-treatment period. More research is needed to confirm these preliminary findings.

Upregulation of angiogenesis in oral lichen planus.

PubMed

Al-Hassiny, A; Friedlander, L T; Parachuru, V P B; Seo, B; Hussaini, H M; Rich, A M

2018-02-01

As angiogenesis is fundamental to the pathogenesis of many chronic inflammatory disorders, this study investigated the expression of various vascular markers in oral lichen planus and non-specific oral mucosal inflammatory tissues. Archival specimens of oral lichen planus (n = 15) and inflamed tissues (n = 13) were stained using immunohistochemistry with antibodies to CD34, vascular endothelial growth factor, vascular endothelial growth factor receptor and vasohibin. Nine representative sites at the epithelial-connective tissue junction and through the fibrous connective tissue were selected, and automated analysis techniques were used to determine the extent of positivity expressed as the percentage of positive cells. Significance was denoted when P < .05. The expression of pro-angiogenic factors was higher in lichen planus samples compared with inflamed controls. A higher level of CD34 was observed in the deeper parts of the connective tissue of Oral lichen planus (OLP) (P = .04), whereas VEGF and VEGFR2 expressions were higher all through the tissues (respectively, P < .02 and P < .01). The expression of the anti-angiogenic VASH1 was higher in inflamed tissue compared with lichen planus in all sites evaluated (P < .01). The findings indicate that angiogenic factors are differentially expressed in oral lichen planus compared with inflamed controls, with increased expression of pro-angiogenic factors and decreased anti-angiogenic expression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

COMPARISON OF BASELINE UROLOGIC SYMPTOMS IN MEN AND WOMEN IN THE MULTIDISCIPLINARY APPROACH TO THE STUDY OF CHRONIC PELVIC PAIN (MAPP) RESEARCH COHORT

PubMed Central

Clemens, J. Quentin; Clauw, Daniel J.; Kreder, Karl; Krieger, John N.; Kusek, John W.; Lai, H. Henry; Rodriguez, Larissa; Williams, David A.; Hou, Xiaoling; Stephens, Alisa; Landis, J Richard

2015-01-01

INTRODUCTION The clinical features of interstitial cystitis/ bladder pain syndrome (IC/BPS) are similar to those of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have directly compared the characteristics of these syndromes in men and women. METHODS The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network recruited 191 men and 233 women with IC/BPS or CP/CPPS. Baseline data included demographics, the Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), the Genitourinary Pain Index (GUPI), the American Urological Association Symptom Index (AUASI), Likert scales to assess urinary urgency, frequency, pain and overall symptom severity, and a single question about the most bothersome pelvic symptom. RESULTS After adjustment for age, income and symptom duration, measures of pain severity were similar across genders. Mean scores for the ICSI, ICPI and AUASI were significantly higher in women than men, reflecting more bladder-focused symptoms in women. The most bothersome single symptom in both men and women was pain in the pubic/bladder area (34% of men, 58% of women). The characteristics of the men and women in the MAPP cohort were similar to those reported in other research cohorts of IC/BPS and CP/CPPS. CONCLUSIONS Our findings indicate that pain severity is similar in both sexes, and that bladder-focused symptoms (urgency, suprapubic pain, frequency) are more common in women. However, a substantial proportion of men also report these types of bladder symptoms. PMID:25463989

Imaging CD4 T Cell Interstitial Migration in the Inflamed Dermis

PubMed Central

Gaylo, Alison; Overstreet, Michael G.; Fowell, Deborah J.

2016-01-01

The ability of CD4 T cells to carry out effector functions is dependent upon the rapid and efficient migration of these cells in inflamed peripheral tissues through an as-yet undefined mechanism. The application of multiphoton microscopy to the study of the immune system provides a tool to measure the dynamics of immune responses within intact tissues. Here we present a protocol for non-invasive intravital multiphoton imaging of CD4 T cells in the inflamed mouse ear dermis. Use of a custom imaging platform and a venous catheter allows for the visualization of CD4 T cell dynamics in the dermal interstitium, with the ability to interrogate these cells in real-time via the addition of blocking antibodies to key molecular components involved in motility. This system provides advantages over both in vitro models and surgically invasive imaging procedures. Understanding the pathways used by CD4 T cells for motility may ultimately provide insight into the basic function of CD4 T cells as well as the pathogenesis of both autoimmune diseases and pathology from chronic infections. PMID:27078264

Cytological Diagnosis of Small Cell Carcinoma of Urinary Bladder in a Patient with CLL

PubMed Central

Şimşek, Gülçin Güler; Güreşçi, Servet; Oğuz, Ural; Ünsal, Ali

2014-01-01

Small cell carcinoma of the urinary bladder (SCCUB) is an extremely rare bladder malignancy characterized by an aggressive clinical behavior. So, it is important to diagnose this high grade disease by urinary cytology. We report a case of SCCUB in an old man with chronic lymphocytic leukemia (CLL) in remission, while bladder tumor was diagnosed by cytology. With this article, we aimed to review and to update the literature concerning this tumor. PMID:24518979

Bladder cancer in patients with spinal cord injury.

PubMed

Hess, Marika J; Zhan, Ellen H; Foo, Dominic K; Yalla, Subbarao V

2003-01-01

The incidence of bladder cancer in spinal cord injury (SCI) is 16 to 28 times higher than that in the general population. The objective of this study was to investigate the characteristics of bladder cancer that are unique to the SCI population. Retrospective review. The charts of 16 patients diagnosed with bladder cancer from 1982 to 2001 were reviewed for type of cancer, exposure to risk factors, presenting symptoms, and survival time. The presenting manifestations were gross hematuria in 14 patients, papillary urethral growth in 1 patient, and acute obstructive renal failure in 1 patient. The diagnosis was made on initial cystoscopic evaluation in 16 patients; 3 patients required further evaluation. Eight of the 11 screening cytologies were suspicious for a malignancy prior to the diagnosis. Seven patients had transitional cell carcinoma, 6 patients had squamous cell carcinoma (SCCA), and 3 patients had both. The bladder wasmanaged with chronic indwelling catheter in 12 patients. Nine patients died of bladder cancer metastases and the remaining 3 patients died of other causes. Six patients survived 5 years or more; 4 were still alive at the completion of this study. Gross hematuria in individuals with SCI warrants aggressive assessment for bladder cancer. Chronic indwelling catheter, smoking, and renal and bladder stones are important risk factors for cancer. The incidence of SCCA in the SCI popullation is much higher than in the general population. Cystoscopic and cytologic evaluation in patients with advanced disease may fail to confirm the diagnosis in a high proportion of patients.

Management of Neurogenic Bladder.

PubMed

Sripathi, Venkataramani; Mitra, Aparajita

2017-07-01

This article provides a comprehensive summary of the clinical approach, investigative modalities and management of a child with neurogenic bladder disease due to myelodysplasia. It is aimed at pediatric physicians and surgeons working in developing nations. The methodologies suggested are simple and can be practised even in resource poor regions. The goal of management is avoidance of Chronic kidney disease and for this, meticulous bladder management is the key.

Wireless, Ultra-Low-Power Implantable Sensor for Chronic Bladder Pressure Monitoring.

PubMed

Majerus, Steve J A; Garverick, Steven L; Suster, Michael A; Fletter, Paul C; Damaser, Margot S

2012-06-01

The wireless implantable/intracavity micromanometer (WIMM) system was designed to fulfill the unmet need for a chronic bladder pressure sensing device in urological fields such as urodynamics for diagnosis and neuromodulation for bladder control. Neuromodulation in particular would benefit from a wireless bladder pressure sensor which could provide real-time pressure feedback to an implanted stimulator, resulting in greater bladder capacity while using less power. The WIMM uses custom integrated circuitry, a MEMS transducer, and a wireless antenna to transmit pressure telemetry at a rate of 10 Hz. Aggressive power management techniques yield an average current draw of 9 μ A from a 3.6-Volt micro-battery, which minimizes the implant size. Automatic pressure offset cancellation circuits maximize the sensing dynamic range to account for drifting pressure offset due to environmental factors, and a custom telemetry protocol allows transmission with minimum overhead. Wireless operation of the WIMM has demonstrated that the external receiver can receive the telemetry packets, and the low power consumption allows for at least 24 hours of operation with a 4-hour wireless recharge session.

Wireless, Ultra-Low-Power Implantable Sensor for Chronic Bladder Pressure Monitoring

PubMed Central

MAJERUS, STEVE J. A.; GARVERICK, STEVEN L.; SUSTER, MICHAEL A.; FLETTER, PAUL C.; DAMASER, MARGOT S.

2015-01-01

The wireless implantable/intracavity micromanometer (WIMM) system was designed to fulfill the unmet need for a chronic bladder pressure sensing device in urological fields such as urodynamics for diagnosis and neuromodulation for bladder control. Neuromodulation in particular would benefit from a wireless bladder pressure sensor which could provide real-time pressure feedback to an implanted stimulator, resulting in greater bladder capacity while using less power. The WIMM uses custom integrated circuitry, a MEMS transducer, and a wireless antenna to transmit pressure telemetry at a rate of 10 Hz. Aggressive power management techniques yield an average current draw of 9 μA from a 3.6-Volt micro-battery, which minimizes the implant size. Automatic pressure offset cancellation circuits maximize the sensing dynamic range to account for drifting pressure offset due to environmental factors, and a custom telemetry protocol allows transmission with minimum overhead. Wireless operation of the WIMM has demonstrated that the external receiver can receive the telemetry packets, and the low power consumption allows for at least 24 hours of operation with a 4-hour wireless recharge session. PMID:26778926

Sacral neuromodulations for female lower urinary tract, pelvic floor, and bowel disorders.

PubMed

Wehbe, Salim A; Whitmore, Kristene; Ho, Mat H

2010-10-01

In recent years, sacral neuromodulation (SNM) has been investigated for the treatment of various types of lower urinary tract and bowel dysfunctions. This review discusses recently published data related to the therapeutic applications of SNM in female lower urinary tract, pelvic floor, and bowel disorders. SNM has been employed initially in the treatment of refractory idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. Since then, several studies, including randomized and controlled trials, have confirmed the therapeutic effects of SNM in these disorders. The applications of SNM are now extended to the treatment of other female pelvic problems, such as fecal incontinence, chronic constipation, interstitial cystitis/painful bladder syndrome, sexual dysfunction, and neurogenic disorders, with similar promising results. SNM is approved by the Food and Drug Administration for the treatment of idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. SNM is not yet an approved method for the treatment of other pelvic disorders, but data supporting its benefit are emerging. The major advantage of SNM lies in its potential to treat the bladder, urethral sphincter, anal sphincters, and pelvic floor muscles simultaneously, which might result in better therapeutic effects.

Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain

PubMed Central

Goins, WF; Goss, JR; Chancellor, MB; de Groat, WC; Glorioso, JC; Yoshimura, N

2009-01-01

Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder. PMID:19242523

Hexavalent Chromium Induces Chromosome Instability in Human Urothelial Cells

PubMed Central

Wise, Sandra S.; Holmes, Amie L.; Liou, Louis; Adam, Rosalyn M.; Wise, John Pierce

2016-01-01

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of Cr(VI) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Hexavalent chromium (Cr(VI)) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer specifically and may be a mechanism for metal-induced bladder cancer in general. PMID:26908176

Nanomedicines for chronic non-infectious arthritis: the clinician's perspective.

PubMed

Rubinstein, Israel; Weinberg, Guy L

2012-09-01

Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues. Conceivably, biocompatible, biodegradable, disease-modifying antirheumatic nanomedicines (DMARNs) could represent a promising therapeutic approach for RA and OA. To this end, the unique physicochemical properties of drug-loaded nanocarriers coupled with pathophysiological characteristics of inflamed joints amplify bioavailability and bioactivity of DMARNs and promote their selective targeting to inflamed joints. This, in turn, minimizes the amount of drug required to control articular inflammation and circumvents collateral damage to healthy tissues. Thus, nanomedicine could provide selective control both in space and time of the inflammatory process in affected joints. However, bringing safe and efficacious DMARNs for RA and OA to the marketplace is challenging because regulatory agencies have no official definition of nanotechnology, and rules and definitions for nanomedicines are still being developed. Although existing toxicology tests may be adequate for most DMARNs, as new toxicity risks and adverse health effects derived from novel nanomaterials with intended use in humans are identified, additional toxicology tests would be required. Hence, we propose that detailed pre-clinical in vivo safety assessment of promising DMARNs leads for RA and OA, including risks to the general population, must be conducted before clinical trials begin. Published by Elsevier Ireland Ltd.

Nanomedicines for chronic non-infectious arthritis: the clinician's perspective.

PubMed

Rubinstein, Israel; Weinberg, Guy L

2012-09-01

Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues. Conceivably, biocompatible, biodegradable, disease-modifying antirheumatic nanomedicines (DMARNs) could represent a promising therapeutic approach for RA and OA. To this end, the unique physicochemical properties of drug-loaded nanocarriers coupled with pathophysiological characteristics of inflamed joints amplify bioavailability and bioactivity of DMARNs and promote their selective targeting to inflamed joints. This, in turn, minimizes the amount of drug required to control articular inflammation and circumvents collateral damage to healthy tissues. Thus, nanomedicine could provide selective control both in space and time of the inflammatory process in affected joints. However, bringing safe and efficacious DMARNs for RA and OA to the marketplace is challenging because regulatory agencies have no official definition of nanotechnology, and rules and definitions for nanomedicines are still being developed. Although existing toxicology tests may be adequate for most DMARNs, as new toxicity risks and adverse health effects derived from novel nanomaterials with intended use in humans are identified, additional toxicology tests would be required. Hence, we propose that detailed pre-clinical in vivo safety assessment of promising DMARNs leads for RA and OA, including risks to the general population, must be conducted before clinical trials begin. Published by Elsevier Inc.

Antibody-mediated delivery of interleukin 4 to the neo-vasculature reduces chronic skin inflammation.

PubMed

Hemmerle, Teresa; Zgraggen, Silvana; Matasci, Mattia; Halin, Cornelia; Detmar, Michael; Neri, Dario

2014-11-01

The antibody-mediated delivery of cytokines ("immunocytokines") to sites of pathological angiogenesis represents an attractive strategy for the development of innovative biopharmaceuticals, capable of modulating the activity of the immune system in cancer and in chronic inflammatory conditions. Recombinant IL4 has previously been shown to be therapeutically active in patients with psoriasis. The antibody-mediated delivery of this cytokine to sites of chronic skin inflammatory conditions should lead to an improved potency and selectivity, compared to non-targeted IL4. The therapeutic activity of F8-IL4, a fusion protein of the F8 antibody (specific to the alternatively-spliced EDA domain of fibronectin) with murine IL4, was investigated in three immunocompetent mouse models of skin inflammation: two induced by the TLR7/8 ligand imiquimod (in Balb/c and C57BL/6) and one mediated by the over-expression of VEGF-A. The EDA domain of fibronectin, a marker for angiogenesis, is expressed in the inflamed skin in all three models and F8-IL4 selectively localized to inflamed skin lesions following intravenous administration. The F8-IL4 fusion protein mediated a therapeutic benefit, which was superior to the one of a non-targeted version of IL4 and led to increased levels of key regulatory cytokines (including IL5, IL10, IL13, and IL27) in the inflamed skin, while IL2 levels were not affected in all treatment groups. A murine version of etanercept and a murine anti-IL17 antibody were used as positive control in the therapy experiments. Skin inflammatory lesions can be selectively targeted using anti-EDA antibody-cytokine fusion proteins and the pharmacodelivery of IL4 confers a therapeutic benefit by shifting the cytokine balance. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Resveratrol improves urinary dysfunction in rats with chronic prostatitis and suppresses the activity of the stem cell factor/c-Kit signaling pathway.

PubMed

Yu, Yang; Jiang, Jiang; He, Yi; Wang, Wei; Shen, Chen; Yang, Bo

2017-08-01

Chronic prostatitis (CP) is a common urological disorder, with bladder voiding dysfunction being the primary clinical manifestation. Resveratrol is polyphenolic compound isolated from numerous plants, with widely‑reported anti-inflammatory properties. The present study aimed to investigate whether resveratrol may improve overactive bladder in rats with CP and to investigate the underlying molecular mechanisms. Furthermore, the potential pharmacological synergy between resveratrol and solifenacin was also investigated as a potential treatment for CP. Following the successful establishment of a rat model of CP by subcutaneously injecting DPT vaccine, rats were treated with resveratrol or a combination of resveratrol + solifenacin. Bladder pressure and volume tests were performed to investigate the effect of resveratrol and solifenacin on urinary dysfunction in rats with chronic prostatitis. Western blot analysis and immunohistochemical staining were used to examine the expression of c‑Kit receptor, stem cell factor (SCF), AKT and phosphorylated‑AKT (p‑AKT) in the bladder tissue. The results of the bladder pressure and volume test indicated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure in the control group were 0.57 ml, 0.17 ml and 29.62 cm H2O, respectively. These values were increased by 71, 27 and 206% in rats in the CP group compared with the control group. Following treatment with resveratrol, the results in the resveratrol group were reduced by 25.77, 44.23 and 13.32% compared with the CP group. The results of western blot analysis, immunohistochemical staining and immunofluorescence labeling demonstrate that the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats in the CP group was 4.32, 6.13 and 6.31 times higher compared with the control group, respectively. Following treatment with resveratrol, protein expression was significantly reduced. However, no significant differences were observed between the protein expression of the SCF, c‑Kit and p‑AKT in the bladder between the resveratrol and combination groups. In conclusion, resveratrol may improve overactive bladder by downregulating the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats with CP. Furthermore, a combination of resveratrol and solifenacin may have potential pharmacological synergy as a treatment for patients with CP.

Effect of Dietary Treatment with Dimethylarsinous Acid (DMAIII) on the Urinary Bladder Epithelium of Arsenic (+3 Oxidation State) Methyltransferase (As3mt) Knockout and C57BL/6 Wild Type Female Mice

EPA Science Inventory

Abstract Chronic exposure to inorganic arsenic (iAs) is carcinogenic to the human urinary bladder. It produces urothelial cytotoxicity and proliferation in rats and mice. DMAv, a major methylated urinary metabolite of iAs, is a rat bladder carcinogen, but without effects on the...

GENE EXPRESSION CHANGES IN MOUSE BLADDER TISSUE IN RESPONSE TO INORGANIC ARSENIC

EPA Science Inventory

Chronic human exposures to high arsenic concentrations are associated with lung, skin, and bladder cancer. Considerable controversy exists concerning arsenic mode of action and low dose extrapolation. This investigation was designed to identify dose-response changes in gene expre...

Neurogenic Bladder

PubMed Central

Dorsher, Peter T.; McIntosh, Peter M.

2012-01-01

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

Expression and function of CCL2/CCR2 in rat micturition reflexes and somatic sensitivity with urinary bladder inflammation

PubMed Central

Arms, Lauren; Girard, Beatrice M.; Malley, Susan E.

2013-01-01

Chemokines are proinflammatory mediators of the immune response, and there is growing evidence for chemokine/receptor signaling involvement in pronociception. Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder-related with at least one urinary symptom. We have explored the expression and functional roles of CCL2 (monocyte chemoattractant protein-1) and its high-affinity receptor, CCR2, in micturition reflex function and somatic sensitivity in rats with urinary bladder inflammation induced by cyclophosphamide (CYP) treatment of varying duration (4 h, 48 h, chronic). Real-time quantitative RT-PCR, ELISAs, and immunohistochemistry demonstrated significant (P ≤ 0.01) increases in CCL2 and CCR2 expression in the urothelium and in Fast Blue-labeled bladder afferent neurons in lumbosacral dorsal root ganglia with CYP-induced cystitis. Intravesical infusion of RS504393 (5 μM), a specific CCR2 antagonist, reduced voiding frequency and increased bladder capacity and void volume in rats with CYP-induced cystitis (4 h), as determined with open outlet, conscious cystometry. In addition, CCR2 blockade, at the level of the urinary bladder, reduced referred somatic sensitivity of the hindpaw and pelvic region in rats with CYP treatment, as determined with von Frey filament testing. We provide evidence of functional roles for CCL2/CCR2 signaling at the level of the urinary bladder in reducing voiding frequency and somatic sensitivity following CYP-induced cystitis (4 h). These studies suggest that chemokines/receptors may be novel targets with therapeutic potential in the context of urinary bladder inflammation. PMID:23594826

[PATHOGENICALLY INDUCED APOPTOSIS CAUSED BY HYPOXIC EFFECTS IN THE URINARY SYSTEM ORGANS OF FETUSES AND NEWBORNS (EXPERIMENTAL STUDY)].

PubMed

Myroshnychenko, M; Sherstiuk, S; Zubova, Y; Nakonechna, S

2017-09-01

The purpose of the study was to identify the characteristics of apoptosis in the kidneys, ureters and bladder of fetuses and newborns in the modeling of chronic intrauterine hypoxia, acute postnatal hypoxia and mixed hypoxia. An experiment was conducted on WAG rats for modeling high altitude hypoxia. Experimental animals were divided into four groups: I - control - fetuses and newborns from healthy rats; II - modeling of chronic intrauterine hypoxia; III - modeling of acute postnatal hypoxia; IV - modeling of mixed hypoxia. The material of the study was the tissue of the kidneys, ureters and bladder of fetuses and newborns. In group I in the kidneys of fetuses the mean value of the number of p53-positive cells was 7.83±0.31, newborns - 5.40±0.28; in the ureters and bladder of fetuses - 5.77±0.29 and 6.97±0.32, newborns - 3.58±0.21 and 5.36±0.28. In the kidneys in group II the mean value of the number of p53-expressing cells in fetuses was 1.43±0.50, in newborns - 21.72±0.58; in group III in newborns - 15.03±0.63; in group IV in newborns - 33.33±0.72. The mean value of the number of p53-expressing cells in the ureters and bladder in group II in fetuses was 13.17±0.49 and 11.83±0.43, in newborns - 16.24±0.37 and 15.38±0.37; in group III in newborns - 7.25±0.27 and 8.68±0.32; in group IV in newborns - 19.63±0.31and 21.03±0.40. As the result of the study it was found that experimental hypoxia induced apoptotic processes in the kidneys, ureters and bladder of fetuses and newborns, the severity of which was moderate in the modeling of acute postnatal hypoxia, expressed in the modeling of chronic intrauterine hypoxia and strongly expressed in the modeling of mixed hypoxia. Under the influence of acute postnatal hypoxia, chronic intrauterine hypoxia and mixed hypoxia in the ureters and bladder of fetuses and newborns p53-positive cells were located evenly in all layers of the wall of these organs, whereas in the kidneys p53-positive cells prevailed in the tubular component. In the modeling of chronic intrauterine hypoxia apoptotic processes in the kidneys, ureters and bladder increased in newborns in comparison with fetuses.

COMBINED USE OF α-ADRENERGIC AND MUSCARINIC ANTAGONISTS FOR THE TREATMENT OF VOIDING DYSFUNCTION

PubMed Central

RUGGIERI, MICHAEL R.; BRAVERMAN, ALAN S.; PONTARI, MICHEL A.

2012-01-01

Purpose We provide an overview of the medical literature supporting the combined use of muscarinic and α-adrenergic antagonist therapy for the treatment of voiding dysfunction. Materials and Methods The MEDLINE database (1966 to 2004) of the United States National Library of Medicine was searched for pertinent studies. Results Although the mechanism of action of α-adrenergic antagonist therapy for voiding dysfunction has traditionally been assumed to be relaxation of the periurethral, prostatic and bladder neck smooth muscle, substantial evidence supports action at extraprostatic sites involved in micturition, including the bladder dome smooth muscle, peripheral ganglia, spinal cord and brain. Likewise the mechanism of action of anticholinergic therapy has been traditionally assumed to be inhibition of the M3 muscarinic receptor subtypes that mediate normal bladder contractions. However, M2 receptor mediates hypertrophied bladder contractions and there is evidence for an M2 component to the suprasacral control of voiding. Conclusions Based on the physiology of α-adrenergic and muscarinic receptors the inhibition of each one would be expected to be more beneficial than that of either alone because they would work on 2 components of detrusor function. Patients who would likely benefit from this combination therapy are men with lower urinary tract symptoms, women with urgency/frequency syndrome (overactive bladder), patients with uninhibited bladder contractions due to neurogenic bladder, and patients with pelvic pain and voiding symptoms, ie interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome. PMID:16217275

Stromal cells in chronic inflammation and tertiary lymphoid organ formation.

PubMed

Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge

2015-01-01

Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

OnabotulinumtoxinA Injection

MedlinePlus

... older than 18 years of age with chronic migraine (severe, throbbing headaches that are sometimes accompanied by ... limb spasticity, urinary incontinence, overactive bladder, or chronic migraine, you may receive additional injections every 3 to ...

Trypanosoma cruzi infection induced changes in the innervation, structure and function of the murine bladder.

PubMed

Boczko, Judd; Tar, Moses; Melman, Arnold; Jelicks, Linda A; Wittner, Murray; Factor, Stephen M; Zhao, Dazhi; Hafron, Jason; Weiss, Louis M; Tanowitz, Herbert B; Christ, George J

2005-05-01

The involvement of the lower urinary tract in chronic Chagas' disease has received little attention. Therefore, we investigated pathology and functional alterations in the bladder of Trypanosoma cruzi infected mice. CD1 mice were infected with 5 x 10 T. cruzi trypomastigotes of the Brazil strain of T. cruzi. At day 100 after infection bladder structure and function were examined by pathological evaluation, magnetic resonance imaging and cystometric studies. The bladder in infected mice weighed more and were large, dilated, deformed, friable and thin walled compared with control mice. Magnetic resonance imaging confirmed these observations. Inflammation, fibrosis and ganglionitis was observed. Cystometric studies revealed that baseline, threshold and micturition pressures were increased in infected mice. Bladder overactivity and decreased bladder compliance were also noted in infected mice. There were no detectable differences in bladder capacity, micturition volume or residual volume between infected and uninfected mice. Bladder abnormalities may be a more common clinical sequelae of T. cruzi infection than previously appreciated.

Squamous cell carcinoma of the bladder mimicking interstitial cystitis and voiding dysfunction.

PubMed

Prudnick, Colton; Morley, Chad; Shapiro, Robert; Zaslau, Stanley

2013-01-01

Squamous cell carcinoma (SCC) of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC) but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

DIFFERENTIAL ACTIVATION OF AP-1 IN HUMAN BLADDER EPITHELIAL CELLS BY INORGANIC AND METHYLATED ARSENICALS

EPA Science Inventory

Differential Activation of AP-1 in Human Bladder Epithelial Cells by Inorganic and Methylated Arsenicals

Zuzana Drobna, Ilona Jaspers, David J. Thomas, and Miroslav Styblo

ABSTRACT

Epidemiological studies have linked chronic ingestion of drinking water contai...

PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENIC EXPOSURES

EPA Science Inventory

Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES (SOT 2008)

EPA Science Inventory

Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES

EPA Science Inventory

Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

Unique regulation of Na-glutamine cotransporter SN2/SNAT5 in rabbit intestinal crypt cells during chronic enteritis.

PubMed

Singh, Soudamani; Arthur, Subha; Sundaram, Uma

2018-03-01

The only Na-nutrient cotransporter described in mammalian small intestinal crypt cells is SN2/SNAT5, which facilitates glutamine uptake. In a rabbit model of chronic intestinal inflammation, SN2 stimulation is secondary to an increase in affinity of the cotransporter for glutamine. However, the immune regulation of SN2 in the crypt cells during chronic intestinal inflammation is unknown. We sought to determine the mechanism of regulation of Na-nutrient cotransporter SN2 by arachidonic acid metabolites in crypt cells. The small intestines of New Zealand white male rabbits were inflamed via inoculation with Eimeria magna oocytes. After 2-week incubation, control and inflamed rabbits were subjected to intramuscular injections of arachidonyl trifluoromethyl ketone (ATK), piroxicam and MK886 for 48 hrs. After injections, the rabbits were euthanized and crypt cells from small intestines were harvested and used. Treatment of rabbits with ATK prevented the release of AA and reversed stimulation of SN2. Inhibition of cyclooxygenase (COX) with piroxicam did not affect stimulation of SN2. However, inhibition of lipoxygenase (LOX) with MK886, thus reducing leukotriene formation during chronic enteritis, reversed the stimulation of SN2. Kinetic studies showed that the mechanism of restoration of SN2 by ATK or MK886 was secondary to the restoration of the affinity of the cotransporter for glutamine. For all treatment conditions, Western blot analysis revealed no change in SN2 protein levels. COX inhibition proved ineffective at reversing the stimulation of SN2. Thus, this study provides evidence that SN2 stimulation in crypt cells is mediated by the leukotriene pathway during chronic intestinal inflammation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Establishment of an inflamed animal model of diabetic nephropathy.

PubMed

Ma, Kun Ling; Zhang, Yang; Liu, Jing; Wu, Yu; Hu, Ze Bo; Ruan, Xiong Zhong; Liu, Bi Cheng

2014-01-01

Inflammatory stress plays a crucial role in the progression of diabetic nephropathy (DN). This study aimed to establish a novel inflamed animal model of DN and to evaluate its significance in DN. Nondiabetic db/m mice and diabetic db/db mice were randomly divided into four groups: db/m, db/m+casein, db/db, and db/db+casein for eight weeks. Casein was subcutaneously injected to induce chronic inflammation. Body weight and albumin to creatinine ratio (ACR) in the urine were measured every week. The plasma levels of serum amyloid protein A (SAA) and tumour necrotic factor-α (TNF-α) were determined with the enzyme-linked immunosorbent assay. The morphological changes to the renal pathology and ultra-microstructures were checked by pathological staining and electron microscopy. Immunofluorescent staining and Western blotting were used to determine the protein expression of podocyte-specific molecules and inflammatory cytokines in kidneys. ACR, plasma levels of SAA and TNF-α, protein expression of inflammatory cytokines, mesangial expansion, collagen accumulation, and foot process effacement in kidneys of casein-injected db/db mice were significantly increased compared with the db/db mice. Casein injection markedly decreased the protein expression of Wilms' tumor-1 and nephrin in kidneys of db/db mice, which are specific podocyte biomarkers, suggesting that chronic inflammation accelerates podocyte injuries in db/db mice. Interestingly, no obvious urinary protein, inflammatory cytokine expression, or histological changes in the kidneys of casein-injected db/m mice were found compared with the db/m mice. An inflamed animal model of DN was successfully established and may provide a useful tool for investigating the pathogenesis of DN under inflammatory stress.

Hexavalent chromium induces chromosome instability in human urothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wise, Sandra S.; Holmes, Amie L.; Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damagemore » in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.« less

Guillain-Barré Syndrome: Prevalence and Long-Term Factors Impacting Bladder Function in an Australian Community Cohort

PubMed Central

Khan, Fary; Whishaw, Michael; Pallant, Julie F.

2013-01-01

Background and Purpose Urinary dysfunction is associated with significant morbidity in persons with Guillain-Barré Syndrome (GBS). The aim of this study was to describe prevalence and long-term impact of bladder dysfunction on daily activities and quality of life (QoL) in persons in chronic phase of GBS and to examine the relationships between commonly used continence measures in this cohort. Methods Prospective cohort (n=66) following GBS treatment (1996-2009) was recruited from a tertiary hospital and assessed using standardised measures for bladder dysfunction: American Urological Association (AUA) Symptom Index, Incontinence Impact Questionnaire, Urogenital Distress Inventory. Results Sixty-six participants (64% male, mean age 56 years, median disease duration of 6.1 years) completed the study. Of these more than half reported nocturia and one-third reported urinary urgency and frequency. Urinary problems impacted on participants' daily activities: physical recreation (21%), emotional health and mood (17%), entertainment (14%), participation and mobility (>30 min) (12%), and performance of household chores (8%). Since GBS, 49% reported interference of urinary symptoms with daily life to some extent; and adverse impact on QoL (10.6%). Significant relationship between bladder symptoms; and the level of urogenital distress (p<0.001) and the impact of urinary problems (p<0.001), was noted. Higher scores on the bladder scales showed significant correlations with psychological, functional and participation scales. The single QoL item (AUA scale) correlated significantly with all other bladder scales (rho=0.63-0.86). This can be a potential 'screening tool' to identify patients for further assessment. Conclusions Bladder dysfunction in chronic phase of GBS is not well studied. More research in longer-term screening and outcomes for bladder intervention are needed for integrated care and to guide treating clinicians. PMID:23894237

Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease.

PubMed

Chimen, Myriam; McGettrick, Helen M; Apta, Bonita; Kuravi, Sahithi J; Yates, Clara M; Kennedy, Amy; Odedra, Arjun; Alassiri, Mohammed; Harrison, Matthew; Martin, Ashley; Barone, Francesca; Nayar, Saba; Hitchcock, Jessica R; Cunningham, Adam F; Raza, Karim; Filer, Andrew; Copland, David A; Dick, Andrew D; Robinson, Joseph; Kalia, Neena; Walker, Lucy S K; Buckley, Christopher D; Nash, Gerard B; Narendran, Parth; Rainger, G Ed

2015-05-01

During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta (14.3.3.ζδ) protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin-induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type 1 diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to that of healthy age-matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Control of patient T cell trafficking is re-established by treatment with exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic ischemia-reperfusion injury, Salmonella infection, uveitis and Sjögren's syndrome, PEPITEM reduced T cell recruitment into inflamed tissues.

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

PubMed

Hirota, Keiji; Hashimoto, Motomu; Ito, Yoshinaga; Matsuura, Mayumi; Ito, Hiromu; Tanaka, Masao; Watanabe, Hitomi; Kondoh, Gen; Tanaka, Atsushi; Yasuda, Keiko; Kopf, Manfred; Potocnik, Alexandre J; Stockinger, Brigitta; Sakaguchi, Noriko; Sakaguchi, Shimon

2018-06-19

Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Homeostatic regulation of T cell trafficking by a B cell derived peptide is impaired in autoimmune and chronic inflammatory disease

PubMed Central

Apta, Bonita; Kuravi, Sahithi J.; Yates, Clara M.; Kennedy, Amy; Odedra, Arjun; Alassiri, Mohammed; Harrison, Matthew; Martin, Ashley; Barone, Francesca; Nayar, Saba; Hitchcock, Jessica R.; Cunningham, Adam F.; Raza, Karim; Filer, Andrew; Copland, David A.; Dick, Andrew D.; Robinson, Joseph; Kalia, Neena; Walker, Lucy S. K.; Buckley, Christopher D.; Nash, Gerard B.; Narendran, Parth; Rainger, G. Ed.

2015-01-01

During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3.ζδ protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type-1-diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to healthy age matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Importantly, control of patient T cell trafficking is re-established by exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic I/R injury, Salmonella infection, Uveitis and Sjögren’s Syndrome, PEPITEM could reduce T cell recruitment into inflamed tissues. PMID:25894827

Chronic Renal Failure Secondary to Unrecognized Neurogenic Bladder in A Child with Myelodysplasia.

PubMed

Ahmed, Shameem; Paul, Siba Prosad

2017-01-01

Myelodysplasia includes a group of developmental anomalies resulting from defects that occur during neural tube closure. Urological morbidity in patients with myelodysplasia is significant and if not treated appropriately in a timely manner can potentially lead to progressive renal failure, requiring dialysis or transplantation. We report the case of a 13-year old girl with neurogenic bladder who presented chronic renal failure secondary to lipomyelomeningocele with retethering of cord. She was managed with urinary indwelling catheterization until optimization of renal function and then underwent detethering of cord with excision and repair of residual lipomeningomyelocele. Her renal parameters improved gradually over weeks and then were managed on self clean intermittent catheterization. The case emphasizes the need for considering retethering of spinal cord in children with myelodysplasia where symptoms of neurogenic bladder and recurrent urinary tract infections occur.

Intravesical treatments of bladder pain syndrome/interstitial cystitis.

PubMed

Neuhaus, Jochen; Schwalenberg, Thilo

2012-12-01

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a disabling chronic condition that affects up to 7% of women in the USA. In men, BPS/IC seems to be less common, but might be underestimated because it can be confused with chronic prostatitis. The aetiology and pathophysiology of BPS/IC are not well understood. Consequently, diagnosis and treatment is challenging and most therapies used to date are off-label. These therapies include bladder instillation with dimethyl sulfoxide (DMSO) and BCG, as well as hyperbaric oxygen therapy. Overall, botulinum neurotoxin A injection, intravesical sodium hyaluronate instillation and DMSO instillation seem to be the best-performing treatments, with response rates of 79%, 76% and 75%, respectively, and can be used effectively as second-line or third-line therapies for BPS/IC. However, additional high-quality randomized controlled trials are necessary to improve the available data.

The Role of Brain-Derived Neurotrophic Factor (BDNF) in the Development of Neurogenic Detrusor Overactivity (NDO)

PubMed Central

Frias, Bárbara; Santos, João; Morgado, Marlene; Sousa, Mónica Mendes; Gray, Susannah M.Y.; McCloskey, Karen D.; Allen, Shelley; Cruz, Francisco

2015-01-01

Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients. PMID:25653370

Polysaccharide capsule and sialic acid-mediated regulation promote biofilm-like intracellular bacterial communities during cystitis.

PubMed

Anderson, Gregory G; Goller, Carlos C; Justice, Sheryl; Hultgren, Scott J; Seed, Patrick C

2010-03-01

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs). A murine UTI model has revealed an infection cascade whereby UPEC undergoes cycles of invasion of the bladder epithelium, intracellular proliferation in polysaccharide-containing biofilm-like masses called intracellular bacterial communities (IBC), and then dispersal into the bladder lumen to initiate further rounds of epithelial colonization and invasion. We predicted that the UPEC K1 polysaccharide capsule is a key constituent of the IBC matrix. Compared to prototypic E. coli K1 strain UTI89, a capsule assembly mutant had a fitness defect in functionally TLR4(+) and TLR4(-) mice, suggesting a protective role of capsule in inflamed and noninflamed hosts. K1 capsule assembly and synthesis mutants had dramatically reduced IBC formation, demonstrating the common requirement for K1 polysaccharide in IBC development. The capsule assembly mutant appeared dispersed in the cytoplasm of the bladder epithelial cells and failed to undergo high-density intracellular replication during later stages of infection, when the wild-type strain continued to form serial generations of IBC. Deletion of the sialic acid regulator gene nanR partially restored IBC formation in the capsule assembly mutant. These data suggest that capsule is necessary for efficient IBC formation and that aberrant sialic acid accumulation, resulting from disruption of K1 capsule assembly, produces a NanR-mediated defect in intracellular proliferation and IBC development. Together, these data demonstrate the complex but important roles of UPEC polysaccharide encapsulation and sialic acid signaling in multiple stages of UTI pathogenesis.

Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

EPA Science Inventory

Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

"Seeing a doctor is just like having a date": a qualitative study on doctor shopping among overactive bladder patients in Hong Kong

PubMed Central

2014-01-01

Background Although having a regular primary care provider is noted to be beneficial to health, doctor shopping has been documented as a common treatment seeking behavior among chronically ill patients in different countries. However, little research has been conducted into the reasons behind doctor shopping behavior among patients with overactive bladder, and even less into how this behavior relates to these patients’ illness and social experiences, perceptions, and cultural practices. Therefore, this study examines overactive bladder patients to investigate the reasons behind doctor shopping behavior. Methods My study takes a qualitative approach, conducting 30 semi-structured individual interviews, with 30 overactive bladder patients in Hong Kong. Results My study found six primary themes that influenced doctor shopping behavior: lack of perceived need, convenience, work-provided medical insurance, unpleasant experiences with doctors, searching for a match doctor, and switching between biomedicine and traditional Chinese medicine. Besides the perceptual factors, participants’ social environment, illness experiences, personal cultural preference, and cultural beliefs also intertwined to generate their doctor shopping behavior. Due to the low perceived need for a regular personal primary care physician, environmental factors such as time, locational convenience, and work-provided medical insurance became decisive in doctor shopping behavior. Patients’ unpleasant illness experiences, stemming from a lack of understanding among many primary care doctors about overactive bladder, contributed to participants’ sense of mismatch with these doctors, which induced them to shop for another doctor. Conclusions Overactive bladder is a chronic bladder condition with very limited treatment outcome. Although patients with overactive bladder often require specialty urology treatment, it is usually beneficial for the patients to receive continuous, coordinated, comprehensive, and patient-centered support from their primary care providers. Primary care doctors’ understanding on patients with overactive bladder with empathetic attitudes is important to reduce the motivations of doctor shopping behavior among these patients. PMID:24502367

"Seeing a doctor is just like having a date": a qualitative study on doctor shopping among overactive bladder patients in Hong Kong.

PubMed

Siu, Judy Yuen-Man

2014-02-06

Although having a regular primary care provider is noted to be beneficial to health, doctor shopping has been documented as a common treatment seeking behavior among chronically ill patients in different countries. However, little research has been conducted into the reasons behind doctor shopping behavior among patients with overactive bladder, and even less into how this behavior relates to these patients' illness and social experiences, perceptions, and cultural practices. Therefore, this study examines overactive bladder patients to investigate the reasons behind doctor shopping behavior. My study takes a qualitative approach, conducting 30 semi-structured individual interviews, with 30 overactive bladder patients in Hong Kong. My study found six primary themes that influenced doctor shopping behavior: lack of perceived need, convenience, work-provided medical insurance, unpleasant experiences with doctors, searching for a match doctor, and switching between biomedicine and traditional Chinese medicine. Besides the perceptual factors, participants' social environment, illness experiences, personal cultural preference, and cultural beliefs also intertwined to generate their doctor shopping behavior. Due to the low perceived need for a regular personal primary care physician, environmental factors such as time, locational convenience, and work-provided medical insurance became decisive in doctor shopping behavior. Patients' unpleasant illness experiences, stemming from a lack of understanding among many primary care doctors about overactive bladder, contributed to participants' sense of mismatch with these doctors, which induced them to shop for another doctor. Overactive bladder is a chronic bladder condition with very limited treatment outcome. Although patients with overactive bladder often require specialty urology treatment, it is usually beneficial for the patients to receive continuous, coordinated, comprehensive, and patient-centered support from their primary care providers. Primary care doctors' understanding on patients with overactive bladder with empathetic attitudes is important to reduce the motivations of doctor shopping behavior among these patients.

Overactive and Underactive Bladder Dysfunction is Reflected by Alterations in Urothelial ATP and NO Release

PubMed Central

Munoz, Alvaro; Smith, Christopher P.; Boone, Timothy B.; Somogyi, George T.

2011-01-01

ATP and NO are released from the urothelium in the bladder. Detrusor Overactivity (DO) following spinal cord injury results in higher ATP and lower NO release from the bladder urothelium. Our aim was to study the relationship between ATP and NO release in 1) early diabetic bladders, an overactive bladder model; and 2) in “diuretic” bladders, an underactive bladder model. To induce diabetes mellitus female rats received 65 mg/kg streptozocin (i.v.). To induce chronic diuresis rats were fed with 5% sucrose. At 28 days, in vivo open cystometry was performed. Bladder wash was collected to analyze the amount of ATP and NO released into the bladder lumen. For in vitro analysis of ATP and NO release, a Ussing chamber was utilized and hypoosmotic Krebs was perfused on the urothelial side of the chamber. ATP was analyzed with luminometry or HPLC-fluorometry while NO was measured with a Sievers NO-analyzer. In vivo ATP release was increased in diabetic bladders and unchanged in diuretic bladders. In vitro release from the urothelium followed the same pattern. NO release was unchanged both in vitro and in vivo in overactive bladders whereas it was enhanced in underactive bladders. We found that the ratio of ATP/NO, representing sensory transmission in the bladder, was high in overactive and low in underactive bladder dysfunction. In summary, ATP release has a positive correlation while NO release has a negative correlation with the bladder contraction frequency. The urinary ATP/NO ratio may be a clinically relevant biomarker to characterize the extent of bladder dysfunction. PMID:21145365

Intraperitoneally placed Foley catheter via verumontanum initially presenting as a bladder rupture.

PubMed

Raheem, Omer A; Jeong, Young Beom

2011-09-01

Since urethral Foley catheterization is usually easy and safe, serious complications related to this procedure have been rarely reported. Herein, we describe a case of intraperitoneally placed urethral catheter via verumontanum presenting as intraperitoneal bladder perforation in a chronically debilitated elderly patient. A 82-yr-old male patient was admitted with symptoms of hematuria, lower abdominal pain after traumatic Foley catheterization. The retrograde cystography showed findings of intraperitoneal bladder perforation, but emergency laparotomy with intraoperative urethrocystoscopy revealed a tunnel-like false passage extending from the verumontanum into the rectovesical pouch between the posterior wall of the bladder and the anterior wall of the rectum with no bladder injury. The patient was treated with simple closure of the perforated rectovesical pouch and a placement of suprapubic cystostomy tube.

Urgency of micturition and detrusor contractility in men with prostatic obstruction and overactive bladders.

PubMed

Cucchi, A; Quaglini, S; Giannantoni, A; Guarnaschelli, C; Rovereto, B

2005-01-01

In men with prostatic obstruction and detrusor overactivity (DO), to ascertain whether urgency of micturition affects bladder contractility. We urodynamically assessed five groups of 20 men each who had bladder outflow obstruction (BOO) from benign prostatic enlargement-Groups 1 (with no DO and no urgency), 2 (with DO and no urgency), 3A (with DO and moderate urgency), 3B (with DO and severe urgency), and 4 (with DO, severe urgency and chronic ischemic cerebral lesions). Urgency was graded as moderate or severe by the ability to avert an urgent void at cystometry for > or =2 or <2 min, respectively. BOO was assessed by the "Abrams-Griffiths number" (AG) and bladder contractility by the parameters PIP and WF(max). AG did not differ significantly in Groups 2, 3A, and 3B, proved higher in such groups than in Group 1, and was nearly the same in Groups 1 and 4. PIP and WF(max) were significantly higher in Groups 2, 3A, and 3B than in Groups 1 and 4, had the highest levels in Group 3B, and did not differ significantly in Groups 1-4 and 2-3A. In DO patients with prostatic obstruction there seems to be a DO-related facilitation of bladder contractility. In the same patients, severe urgency of micturition might over-amplify (i.e., enhance a DO-related facilitation of) bladder contractility, provided there are no neurogenic (chronic ischemic cerebral) lesions.

Photodynamic management of bladder cancer

NASA Astrophysics Data System (ADS)

Johansson, A.; Stepp, H.; Beyer, W.; Pongratz, T.; Sroka, R.; Bader, M.; Kriegmair, M.; Zaak, D.; Waidelich, R.; Karl, A.; Hofstetter, A.; Stief, C.; Baumgartner, R.

2009-06-01

Bladder cancer (BC) is among the most expensive oncological diseases. Any improvement in diagnosis or therapy carries a high potential for reducing costs. Fluorescence cystoscopy relies on a selective formation of Protoporphyrin IX (PpIX) or more general photoactive porphyrins (PAP) in malignant urothelium upon instillation of 5-aminolevulinic acid (5-ALA) or its hexyl-derivative h-ALA. Fluorescence cystoscopy equipment has been developed with the aim to compensate for the undesired distortion caused by the tissue optical properties by displaying the red fluorescence simultaneously with the backscattered blue light. Many clinical studies proved a high sensitivity in detecting flat carcinoma in situ and small papillary malignant tumours. As a result, recurrence rates were significantly decreased in most studies. The limitation lies in a low specificity, caused by false positive findings at inflamed bladder wall. Optical coherence tomography (OCT) is currently being investigated as a promising tool to overcome this limitation. H-ALA-PDT (8 or 16 mM h-ALA in 50 ml instillation for 1-2 h, white light source, catheter applicator) has recently been investigated in a phase I study. 17 patients were applied 100 J/cm2 (3 patients received incrementing doses of 25 - 50 - 100 J/cm2) during approx. 1 hour irradiation time in 3 sessions, 6 weeks apart. PDT was performed without any technical complications. Complete photobleaching of the PpIX-fluorescence, as intended, could be achieved in 43 of 45 PDT-sessions receiving 100 J/cm2. The most prominent side effects were postoperative urgency and bladder pain, all symptoms being more severe after 16 mM h-ALA. Preliminary evaluation shows complete response assessed at 3 months after the third PDT-session (i.e. 6 months after first treatment) in 9 of 12 patients. 2 of these patients were free of recurrence until final follow-up at 84 weeks.

Geode of the femur: an uncommon manifestation potentially reflecting the pathogenesis of rheumatoid arthritis.

PubMed

Lee, Wonuk; Terk, Michael R; Hu, Bing; Garber, Elayne K; Weisman, Michael H

2006-12-01

Geodes are noted frequently in rheumatoid arthritis (RA), but large geodes of the femur are uncommon. We describe a patient with RA and a large geode in his femur; histological findings were consistent with a rheumatoid nodule and chronically inflamed synovium. We review the literature of large femoral geodes and what this particular manifestation may reflect about the pathogenesis of RA.

Inflammation and Tissue Remodeling in the Bladder and Urethra in Feline Interstitial Cystitis

PubMed Central

Kullmann, F. Aura; McDonnell, Bronagh M.; Wolf-Johnston, Amanda S.; Lynn, Andrew M.; Getchell, Samuel E.; Ruiz, Wily G.; Zabbarova, Irina V.; Ikeda, Youko; Kanai, Anthony J.; Roppolo, James R.; Bastacky, Sheldon I.; Apodaca, Gerard; Buffington, C. A. Tony; Birder, Lori A.

2018-01-01

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease of unknown etiology. A naturally occurring disease termed feline interstitial cystitis (FIC) reproduces many features of IC/BPS patients. To gain insights into mechanisms underlying IC/BPS, we investigated pathological changes in the lamina propria (LP) of the bladder and proximal urethra in cats with FIC, using histological and molecular methods. Compared to control cat tissue, we found an increased number of de-granulated mast cells, accumulation of leukocytes, increased cyclooxygenase (COX)-1 expression in the bladder LP, and increased COX-2 expression in the urethra LP from cats with FIC. We also found increased suburothelial proliferation, evidenced by mucosal von Brunn’s nests, neovascularization and alterations in elastin content. Scanning electron microscopy revealed normal appearance of the superficial urethral epithelium, including the neuroendocrine cells (termed paraneurons), in FIC urethrae. Together, these histological findings suggest the presence of chronic inflammation of unknown origin leading to tissue remodeling. Since the mucosa functions as part of a “sensory network” and urothelial cells, nerves and other cells in the LP are influenced by the composition of the underlying tissues including the vasculature, the changes observed in the present study may alter the communication of sensory information between different cellular components. This type of mucosal signaling can also extend to the urethra, where recent evidence has revealed that the urethral epithelium is likely to be part of a signaling system involving paraneurons and sensory nerves. Taken together, our data suggest a more prominent role for chronic inflammation and tissue remodeling than previously thought, which may result in alterations in mucosal signaling within the urinary bladder and proximal urethra that may contribute to altered sensations and pain in cats and humans with this syndrome. PMID:29706873

Management of the complications of BPH/BOO.

PubMed

Speakman, Mark J; Cheng, Xi

2014-04-01

Most men will develop histological BPH if they live long enough. Approximately, half will develop benign prostatic enlargement (BPE) and about half of these will get BOO with high bladder pressures and low flow, this in turn leads to detrusor wall hypertrophy. Many of these men will only have lower urinary tract symptoms (LUTS) but a significant number will also suffer the other complications of BPH. These include urinary retention (acute and chronic), haematuria, urinary tract infection, bladder stones, bladder wall damage, renal dysfunction, incontinence and erectile dysfunction. Recognition of the complications of BPH/BOO early allows more effective management of these complications. This is particularly important for the more serious urinary infections and also for high-pressure chronic retention (HPCR). Complications of LUTS/BPH are very rare in clinical trials because of their strict inclusion and exclusion criteria but are more common in real life practice.

Large sliding inguino-scrotal hernia of the urinary bladder

PubMed Central

Wang, Ping; Huang, Yonggang; Ye, Jing; Gao, Guodong; Zhang, Fangjie; Wu, Hao

2018-01-01

Abstract Rationale: Sliding inguinal hernias of the urinary bladder are protrusions of the bladder through the internal inguinal ring, most of which are insignificant and diagnosed intra-operatively. Large inguino-scrotal bladder hernias commonly present with lower urinary tract symptoms and may cause severe complications, including bladder incarceration or necrosis, bladder hemorrhage, obstructive or neurogenic bladder dysfunction, and even renal failure. Patient concerns: We describe and discuss the clinical findings and management of a 59-year-old man who complained of a decrease in scrotal size after voiding and 2-stage voiding requiring pressure to the scrotum. Diagnoses: The patient was diagnosed preoperatively as massive, bilateral, inguinoscrotal hernias, and a large, left-sided, sliding bladder hernia. Interventions: The patient underwent a timely open re-peritoneal inguinal herniorrhaphy using a mesh. Outcomes: The surgical outcomes were good, and no surgical site infection, chronic postoperative inguinal pain or recurrence were recorded during the follow-up. Lessons: Better knowledge of this rare condition of large inguino-scrotal sliding bladder hernia could help in making a correct diagnosis preoperatively and provide proper surgical management timely, so as to reduce delay in treatment and avoid potential complications. PMID:29595706

INDUCTION OF URINARY BLADDER PATHOLOGY IN MALE AND FEMALE C3H MICE EXPOSED TO SODIUM ARSENITE FROM GESTATION THROUGH YOUNG ADULTHOOD

EPA Science Inventory

Epidemiology studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Recently, an in utero animal model was developed to characterize the carcinogenic properties of inorganic arsen...

Biospectral analysis of the bladder channel point in chronic low back pain patients

NASA Astrophysics Data System (ADS)

Vidal, Alberto Espinosa; Nava, Juan José Godina; Segura, Miguel Ángel Rodriguez; Bastida, Albino Villegas

2012-10-01

Chronic pain is the main cause of disability in the productive age people and is a public health problem that affects both the patient and society. On the other hand, there isn't any instrument to measure it; this is only estimated using subjective variables. The healthy cells generate a known membrane potential which is part of a network of biologically closed electric circuits still unstudied. It is proposed a biospectral analysis of a bladder channel point as a diagnosis method for chronic low back pain patients. Materials and methods: We employed a study group with chronic low back pain patients and a control group without low back pain patients. The visual analog scale (VAS) to determine the level of pain was applied. Bioelectric variables were measured for 10 seconds and the respective biostatistical analyses were made. Results: Biospectral analysis on frequency domain shows a depression in the 60-300 Hz frequency range proportional to the chronicity of low back pain compared against healthy patients.

Evolutionary medicine and chronic inflammatory state--known and new concepts in pathophysiology.

PubMed

Straub, Rainer H

2012-05-01

During the last 10 years, a series of exciting observations has led to a new theory of pathophysiology using insights from evolutionary biology and neuroendocrine immunology to understand the sequelae of chronic inflammatory disease. According to this theory, disease sequelae can be explained based on redirection of energy-rich fuels from storage organs to the activated immune system. These disease sequelae are highly diverse and include the following: sickness behavior, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, increase of adipose tissue near inflamed tissue, alterations of steroid hormone axes, elevated sympathetic tone and local sympathetic nerve fiber loss, decreased parasympathetic tone, hypertension, inflammation-related anemia, and osteopenia. Since these disease sequelae can be found in many animal models of chronic inflammatory diseases with mammals (e.g., monkeys, mice, rats, rabbits, etc.), the evolutionary time line goes back at least 70 million years. While the initial version of this theory could explain prominent sequelae of chronic inflammatory disease, it did not however address two features important in the pathogenesis of immune-mediated diseases: the time point when an acute inflammatory disease becomes chronic, and the appearance of hypertension in chronic inflammation. To address these aspects more specifically, a new version of the theory has been developed. This version defines more precisely the moment of transition from acute inflammatory disease to chronic inflammatory disease as a time in which energy stores become empty (complete energy consumption). Depending on the amount of stored energy, this time point can be calculated to be 19-43 days. Second, the revised theory addresses the mechanisms of essential hypertension since, on the basis of water loss, acute inflammatory diseases can stimulate water retention using a positively selected water retention system (identical to the energy provision system). In chronic smoldering inflammation, however, there is no increased water loss. In contrast, there is increased water generation in inflamed tissue and inflammatory cells, and the activation of the water retention system persists. This combination leads to a net increase of the systemic fluid volume, which is hypothesized to be the basis of essential hypertension (prevalence in adults 22-32%).

Radiation Synovectomy: an effective alternative treatment for inflamed small joints.

PubMed

Karavida, N; Notopoulos, A

2010-01-01

An inflamed painful joint is one of the most common indications for the patient to be referred to a rheumatologist or an orthopedician. In relation to the aetiology, the therapeutic approach might be systemic, local or a combination of them in some cases, always with the thought of balancing risk with benefit for the patient. In all cases, independently of the cause, the goal of therapy is to improve the quality of life through the reduction of pain, improvement of mobility and preservation of function. Nuclear Medicine has to offer Radiosynoviorthesis, an effective alternative procedure for treating inflamed small joints. Various radionuclides are available for radiosynoviorthesis. Their selection depends on the size of the joint to be treated. Small joints are mainly treated with [169Er] erbium under a fluoroscopic or sonographic guidance, usually with a simultaneous instillation of a corticoid. Candidates for radiosynoviorthesis should have been under a six-month systemic treatment without encouraging results or should have undergone at least one unsuccessful intra-articular injection of a long acting glucocorticoid. Since 1973, when [169Er] erbium was firstly suggested as a therapeutic agent for radiosynoviorthesis of the finger joints, there has been quite enough experience in its' application. It has been found to be cost effective in providing long term relief of pain and deformity of the inflamed joints in comparison to other therapeutic approaches. Additionally, there is no radiation risk and can be performed on an out patient basis. Therefore it can stand as an effective alternative procedure for treating early stages of chronic synovitis in RA (rheumatoid arthritis) patients, with minor damage of the cartilage and the adjacent bones, and for synovitis secondary to inflammatory arthropathies.

Whole Genome Gene Expression Meta-Analysis of Inflammatory Bowel Disease Colon Mucosa Demonstrates Lack of Major Differences between Crohn's Disease and Ulcerative Colitis

PubMed Central

Østvik, Ann E.; Drozdov, Ignat; Gustafsson, Bjørn I.; Kidd, Mark; Beisvag, Vidar; Torp, Sverre H.; Waldum, Helge L.; Martinsen, Tom Christian; Damås, Jan Kristian; Espevik, Terje; Sandvik, Arne K.

2013-01-01

Background In inflammatory bowel disease (IBD), genetic susceptibility together with environmental factors disturbs gut homeostasis producing chronic inflammation. The two main IBD subtypes are Ulcerative colitis (UC) and Crohn’s disease (CD). We present the to-date largest microarray gene expression study on IBD encompassing both inflamed and un-inflamed colonic tissue. A meta-analysis including all available, comparable data was used to explore important aspects of IBD inflammation, thereby validating consistent gene expression patterns. Methods Colon pinch biopsies from IBD patients were analysed using Illumina whole genome gene expression technology. Differential expression (DE) was identified using LIMMA linear model in the R statistical computing environment. Results were enriched for gene ontology (GO) categories. Sets of genes encoding antimicrobial proteins (AMP) and proteins involved in T helper (Th) cell differentiation were used in the interpretation of the results. All available data sets were analysed using the same methods, and results were compared on a global and focused level as t-scores. Results Gene expression in inflamed mucosa from UC and CD are remarkably similar. The meta-analysis confirmed this. The patterns of AMP and Th cell-related gene expression were also very similar, except for IL23A which was consistently higher expressed in UC than in CD. Un-inflamed tissue from patients demonstrated minimal differences from healthy controls. Conclusions There is no difference in the Th subgroup involvement between UC and CD. Th1/Th17 related expression, with little Th2 differentiation, dominated both diseases. The different IL23A expression between UC and CD suggests an IBD subtype specific role. AMPs, previously little studied, are strongly overexpressed in IBD. The presented meta-analysis provides a sound background for further research on IBD pathobiology. PMID:23468882

Whole genome gene expression meta-analysis of inflammatory bowel disease colon mucosa demonstrates lack of major differences between Crohn's disease and ulcerative colitis.

PubMed

Granlund, Atle van Beelen; Flatberg, Arnar; Østvik, Ann E; Drozdov, Ignat; Gustafsson, Bjørn I; Kidd, Mark; Beisvag, Vidar; Torp, Sverre H; Waldum, Helge L; Martinsen, Tom Christian; Damås, Jan Kristian; Espevik, Terje; Sandvik, Arne K

2013-01-01

In inflammatory bowel disease (IBD), genetic susceptibility together with environmental factors disturbs gut homeostasis producing chronic inflammation. The two main IBD subtypes are Ulcerative colitis (UC) and Crohn's disease (CD). We present the to-date largest microarray gene expression study on IBD encompassing both inflamed and un-inflamed colonic tissue. A meta-analysis including all available, comparable data was used to explore important aspects of IBD inflammation, thereby validating consistent gene expression patterns. Colon pinch biopsies from IBD patients were analysed using Illumina whole genome gene expression technology. Differential expression (DE) was identified using LIMMA linear model in the R statistical computing environment. Results were enriched for gene ontology (GO) categories. Sets of genes encoding antimicrobial proteins (AMP) and proteins involved in T helper (Th) cell differentiation were used in the interpretation of the results. All available data sets were analysed using the same methods, and results were compared on a global and focused level as t-scores. Gene expression in inflamed mucosa from UC and CD are remarkably similar. The meta-analysis confirmed this. The patterns of AMP and Th cell-related gene expression were also very similar, except for IL23A which was consistently higher expressed in UC than in CD. Un-inflamed tissue from patients demonstrated minimal differences from healthy controls. There is no difference in the Th subgroup involvement between UC and CD. Th1/Th17 related expression, with little Th2 differentiation, dominated both diseases. The different IL23A expression between UC and CD suggests an IBD subtype specific role. AMPs, previously little studied, are strongly overexpressed in IBD. The presented meta-analysis provides a sound background for further research on IBD pathobiology.

Cystitis glandularis in a cat.

PubMed

Agut, Amalia; Carrillo, Juana D; Soler, Marta; García, Juan D; Belda, Eliseo; Gómez, Miguel A; Bernabe, Antonio

2014-04-01

An 8-year-old intact male Persian cat was presented for investigation of chronic haematuria. The cat had episodes of haematuria on several occasions that were non-responsive to antimicrobial therapy. Abdominal ultrasound examination revealed dilation of the renal pelvis and ureters of both kidneys. The urinary bladder wall was thickened, a mass of heterogeneous echogenicity filled the lumen of the bladder, and two parallel thin hyperechoic lines were identified within the lumen, which suggested a urethral catheter. Differential diagnoses for the urinary bladder mass included cystitis and neoplasia. The mass was surgically removed from the urinary bladder, and a urethral catheter was found embedded in the mass. Histopathological findings were consistent with cystitis glandularis of a typical type. Periodic bladder ultrasonographic studies were performed; at the time of writing, over 2 years later, recurrence had not been detected.

Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia

PubMed Central

Xie, Wenrui; Strong, Judith A.; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

2013-01-01

Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models, and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain following local inflammation of the rat lumbar sensory ganglia. In normal DRG, quantitative PCR showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6′ immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C-cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8, because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7, because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain, and that some pain conditions may be primarily mediated by myelinated A-fiber sensory neurons. PMID:23622763

Mucinous adenocarcinoma of the bladder associated with long term suprapubic tube: a case report.

PubMed

Bauman, Tyler M; Potretzke, Theodora A; Potretzke, Aaron M; Siegel, Cary L; Brandes, Steven B

2015-12-03

Chronic indwelling catheters may induce histologic changes within the bladder, and these changes are sometimes pre-malignant. There are many documented cases of squamous cell carcinoma associated with indwelling catheters, but only three cases of catheter-associated adenocarcinoma have been reported. In this case report, we present radiographic findings of a case of mucinous adenocarcinoma of the bladder and suprapubic (SP) tract in a quadriplegic patient. A 71-year-old male with a history of spinal cord injury presented with hematuria and SP discharge after SP catheterization for 51 years. CT urography was performed and revealed an irregular, infiltrative, and heterogeneous mass arising from the anterior bladder at the level of the suprapubic catheter and extending along the SP tube tract. Cystoscopy and biopsy revealed an adenocarcinoma of the anterior bladder and stoma with extensive associated mucin production and a background of acute and chronic inflammation. Surgical therapy included cystoprostatectomy, abdominal wall resection, ileal conduit creation, and abdominal wall reconstruction. The final diagnosis was a high-grade, T2a/N0/M0 (Stage II) mucinous adenocarcinoma of the bladder. There has been no evidence of tumor recurrence over the previous 5 years. Few cases of adenocarcinoma associated with long term indwelling catheter have been reported in the literature, and due to the rarity of this disease process, the prognosis with surgical therapy is not well known. The patient described herein has been free of recurrence for the previous five years, suggesting that surgery is a viable management option for these patients.

INDUCTION OF TRANSTITIONAL CELL HYPERPLASIA IN THE URINARY BLADDER AND ABERRANT CRYPT FOCI IN THE COLON OF RATS TREATED WITH INDIVIDUAL AND A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

ABSTRACT

Cancer of the urinary bladder and colon are significant human health concerns. Epidemiological studies have suggested a correlation between these cancers and the chronic consumption of drinking water containing disinfection by-products (DBPs). The present study...

Extravasation of the contrast media during voiding cystourethrography in a long-term spinal cord injury patient.

PubMed

Kovindha, A; Sivasomboon, C; Ovatakanont, P

2005-07-01

To present complications and pitfalls in voiding cystourethrography (VCUG) and introduce a guideline for performing VCUG in a long-term spinal cord injury (SCI) patient with neurogenic bladder dysfunction (NBD) and contracted bladder. A case report. Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand. We describe a chronic C(5) tetraplegic man with NBD and contracted bladder, who developed autonomic dysreflexia (AD), gross hematuria and extravasation of contrast median during VCUG. A foley catheter was retained after VCUG. AD was resolved and urine cleared after a week of continuous bladder irrigation. VCUG should be performed with caution in a long-term SCI patient with NBD and contracted bladder. Forceful pushing of the contrast media by the hand-injection method caused abrupt distention of the contracted bladder, damaged bladder mucosa and aggrevated AD. We suggest a guideline as follows: report bladder capacity and AD, if present, in an X-ray requisition form; use the gravity-drip method, stop the drip and drain the contrast media if a sudden headache and rising of blood pressure (BP) develop; observe urine colour, and report if bleeding or AD occurs.

Malakoplakia mimics urinary bladder cancer: a case report.

PubMed

Ristić-Petrović, Ana; Stojnev, Slavica; Janković-Velicković, Ljubinka; Marjanović, Goran

2013-06-01

Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications.

P53 Protein Expression in Dental Follicle, Dentigerous Cyst, Odontogenic Keratocyst, and Inflammatory Subtypes of Cysts: An Immunohistochemical Study

PubMed Central

Fatemeh, Mashhadiabbas; Sepideh, Arab; Sara, Bagheri Seyedeh; Nazanin, Mahdavi

2017-01-01

Objectives An odontogenic keratocyst (OKC) is a developmental odontogenic cyst with aggressive clinical behavior. This cyst shows a different growth mechanism from the more common dentigerous cyst and now has been renamed as a keratocystic odontogenic tumor (KCOT). Inflammation can assist tumor growth via different mechanisms including dysregulation of the p53 gene. This study aims to assess and compare the expression of tumor suppressor gene p53 in inflamed and non-inflamed types of OKC and dentigerous cyst. Methods Immunohistochemical expression of p53 was assessed in 14 cases of dental follicle, 34 cases of OKC (including 18 inflamed OKCs), and 31 cases of dentigerous cyst (including 16 inflamed cysts). Results The mean percentage of p53 positive cells was 0.7% in dental follicles, 5.4% in non-inflamed OKCs, 17.3% in inflamed OKCs, 1.2% in non-inflamed dentigerous cysts, and 2.2% in inflamed dentigerous cysts. The differences between the groups were statistically significant (p < 0.050) except for the difference between inflamed and non-inflamed dentigerous cysts, and between dental follicle and non-inflamed dentigerous cyst. Conclusions The difference in p53 expression in OKC and dentigerous cyst can explain their different growth mechanism and clinical behavior. Inflammation is responsible for the change in behavior of neoplastic epithelium of OKC via p53 overexpression. PMID:28584604

P53 Protein Expression in Dental Follicle, Dentigerous Cyst, Odontogenic Keratocyst, and Inflammatory Subtypes of Cysts: An Immunohistochemical Study.

PubMed

Fatemeh, Mashhadiabbas; Sepideh, Arab; Sara, Bagheri Seyedeh; Nazanin, Mahdavi

2017-05-01

An odontogenic keratocyst (OKC) is a developmental odontogenic cyst with aggressive clinical behavior. This cyst shows a different growth mechanism from the more common dentigerous cyst and now has been renamed as a keratocystic odontogenic tumor (KCOT). Inflammation can assist tumor growth via different mechanisms including dysregulation of the p53 gene. This study aims to assess and compare the expression of tumor suppressor gene p53 in inflamed and non-inflamed types of OKC and dentigerous cyst. Immunohistochemical expression of p53 was assessed in 14 cases of dental follicle, 34 cases of OKC (including 18 inflamed OKCs), and 31 cases of dentigerous cyst (including 16 inflamed cysts). The mean percentage of p53 positive cells was 0.7% in dental follicles, 5.4% in non-inflamed OKCs, 17.3% in inflamed OKCs, 1.2% in non-inflamed dentigerous cysts, and 2.2% in inflamed dentigerous cysts. The differences between the groups were statistically significant ( p < 0.050) except for the difference between inflamed and non-inflamed dentigerous cysts, and between dental follicle and non-inflamed dentigerous cyst. The difference in p53 expression in OKC and dentigerous cyst can explain their different growth mechanism and clinical behavior. Inflammation is responsible for the change in behavior of neoplastic epithelium of OKC via p53 overexpression.

Receptor activated bladder and spinal ATP release in neurally intact and chronic spinal cord injured rats

PubMed Central

Salas, Nilson A.; Somogyi, George T.; Gangitano, David A.; Boone, Timothy B.; Smith, Christopher P.

2009-01-01

Neurally intact (NI) rats and chronic spinal cord injured (SCI) rats were studied to determine how activation of mechanosensory or cholinergic receptors in the bladder urothelium evokes ATP release from afferent terminals in the bladder as well as in the spinal cord. Spinal cord transection was performed at the T9-T10 level 2–3 weeks prior to the experiment and a microdialysis fiber was inserted in the L6-S1 lumbosacral spinal cord. Mechanically evoked (i.e. 10cm/w bladder pressure) ATP release into the bladder lumen was approximately 6.5 fold higher in SCI compared to NI rats (p<0.05). Intravesical carbachol (CCh) induced a significantly greater release of ATP in the bladder from SCI as compared to NI rats (3424.32 ± 1255.57 vs. 613.74 ± 470.44 pmol/ml, respectively, p<0.05). However, ATP release in NI or SCI rats to intravesical CCh was not affected by the muscarinic antagonist atropine (Atr). Spinal release of ATP to bladder stimulation with 10cm/w pressure was 5-fold higher in SCI compared to NI rats (p<0.05). CCh also induced a significantly greater release of spinal ATP in SCI rats compared to controls (4.3 ± 0.9 vs. 0.90 ± 0.15 pmol, p < 0.05). Surprisingly, the percent inhibitory effect of Atr on CCh-induced ATP release was significantly less in SCI as compared to NI rats (49% vs. 89%, respectively). SCI induces a dramatic increase in intravesical pressure and cholinergic receptor evoked bladder and spinal ATP release. Muscarinic receptors do not mediate intravesical CCh induced ATP release into the bladder lumen in NI or SCI rats. In NI rats sensory muscarinic receptors are the predominant mechanism by which CCh induces ATP release from primary afferents within the lumbosacral spinal cord. Following SCI, however, nicotinic or purinergic receptor mechanisms become active, as evidenced by the fact that Atr was only partially effective in inhibiting CCh-induced spinal ATP release. PMID:17067723

The Role(s) of Cytokines/Chemokines in Urinary Bladder Inflammation and Dysfunction

PubMed Central

Gonzalez, Eric J.; Arms, Lauren; Vizzard, Margaret A.

2014-01-01

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3–7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed. Altered visceral sensations from the urinary bladder (i.e., pain at low or moderate bladder filling) that accompany BPS/IC may be mediated by many factors including changes in the properties of peripheral bladder afferent pathways such that bladder afferent neurons respond in an exaggerated manner to normally innocuous stimuli (allodynia). The goals for this review are to describe chemokine/receptor (CXCL12/CXCR4; CCL2/CCR2) signaling and cytokine/receptor (transforming growth factor (TGF-β)/TGF-β type 1 receptor) signaling that may be valuable LUT targets for pharmacologic therapy to improve urinary bladder function and reduce somatic sensitivity associated with urinary bladder inflammation. PMID:24738044

A Non-Invasive Bladder Sensory Test Supports a Role for Dysmenorrhea Increasing Bladder Noxious Mechanosensitivity

PubMed Central

TU, Frank F.; EPSTEIN, Aliza E.; POZOLO, Kristen E.; SEXTON, Debra L.; MELNYK, Alexandra I.; HELLMAN, Kevin M.

2012-01-01

Objective Catheterization to measure bladder sensitivity is aversive and hinders human participation in visceral sensory research. Therefore, we sought to characterize the reliability of sonographically-estimated female bladder sensory thresholds. To demonstrate this technique’s usefulness, we examined the effects of self-reported dysmenorrhea on bladder pain thresholds. Methods Bladder sensory threshold volumes were determined during provoked natural diuresis in 49 healthy women (mean age 24 ± 8) using three-dimensional ultrasound. Cystometric thresholds (Vfs – first sensation, Vfu – first urge, Vmt – maximum tolerance) were quantified and related to bladder urgency and pain. We estimated reliability (one-week retest and interrater). Self-reported menstrual pain was examined in relationship to bladder pain, urgency and volume thresholds. Results Average bladder sensory thresholds (mLs) were Vfs (160±100), Vfu (310±130), and Vmt (500±180). Interrater reliability ranged from 0.97–0.99. One-week retest reliability was Vmt = 0.76 (95% CI 0.64–0.88), Vfs = 0.62 (95% CI 0.44–0.80), and Vfu = 0.63, (95% CI 0.47–0.80). Bladder filling rate correlated with all thresholds (r = 0.53–0.64, p < 0.0001). Women with moderate to severe dysmenorrhea pain had increased bladder pain and urgency at Vfs and increased pain at Vfu (p’s < 0.05). In contrast, dysmenorrhea pain was unrelated to bladder capacity. Discussion Sonographic estimates of bladder sensory thresholds were reproducible and reliable. In these healthy volunteers, dysmenorrhea was associated with increased bladder pain and urgency during filling but unrelated to capacity. Plausibly, dysmenorrhea sufferers may exhibit enhanced visceral mechanosensitivity, increasing their risk to develop chronic bladder pain syndromes. PMID:23370073

Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current Status and Future Direction.

PubMed

Kanda, Yusuke; Osaki, Mitsuhiko; Okada, Futoshi

2017-04-19

A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression. In this article, we summarize the up-to-date findings regarding definitive/possible causes and mechanisms of inflammation-related carcinogenesis derived from experimental and clinical studies. We also propose 10 strategies, as well as candidate agents for the prevention of inflammation-related carcinogenesis.

VEGF signaling mediates bladder neuroplasticity and inflammation in response to BCG

PubMed Central

2011-01-01

Background This work tests the hypothesis that increased levels of vascular endothelial growth factor (VEGF) observed during bladder inflammation modulates nerve plasticity. Methods Chronic inflammation was induced by intravesical instillations of Bacillus Calmette-Guérin (BCG) into the urinary bladder and the density of nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) or pan-neuronal marker PGP9.5 was used to quantify alterations in peripheral nerve plasticity. Some mice were treated with B20, a VEGF neutralizing antibody to reduce the participation of VEGF. Additional mice were treated systemically with antibodies engineered to specifically block the binding of VEGF to NRP1 (anti-NRP1B) and NRP2 (NRP2B), or the binding of semaphorins to NRP1 (anti-NRP1 A) to diminish activity of axon guidance molecules such as neuropilins (NRPs) and semaphorins (SEMAs). To confirm that VEGF is capable of inducing inflammation and neuronal plasticity, another group of mice was instilled with recombinant VEGF165 or VEGF121 into the urinary bladder. Results The major finding of this work was that chronic BCG instillation resulted in inflammation and an overwhelming increase in both PGP9.5 and TRPV1 immunoreactivity, primarily in the sub-urothelium of the urinary bladder. Treatment of mice with anti-VEGF neutralizing antibody (B20) abolished the effect of BCG on inflammation and nerve density. NRP1A and NRP1B antibodies, known to reduce BCG-induced inflammation, failed to block BCG-induced increase in nerve fibers. However, the NRP2B antibody dramatically potentiated the effects of BCG in increasing PGP9.5-, TRPV1-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactivity (IR). Finally, instillation of VEGF121 or VEGF165 into the mouse bladder recapitulated the effects of BCG and resulted in a significant inflammation and increase in nerve density. Conclusions For the first time, evidence is being presented supporting that chronic BCG instillation into the mouse bladder promotes a significant increase in peripheral nerve density that was mimicked by VEGF instillation. Effects of BCG were abolished by pre-treatment with neutralizing VEGF antibody. The present results implicate the VEGF pathway as a key modulator of inflammation and nerve plasticity, introduces a new animal model for investigation of VEGF-induced nerve plasticity, and suggests putative mechanisms underlying this phenomenon. PMID:22059553

N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation.

PubMed

Gao, Xiao; Lampraki, Eirini-Maria; Al-Khalidi, Sarwah; Qureshi, Muhammad Asif; Desai, Rhea; Wilson, Joanna Beatrice

2017-01-01

Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body's natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure therapies for chronic inflammation.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Symptomatic hemorrhoids.

PubMed

Gearhart, Susan L

2004-01-01

The most important aspect in the diagnosis of hemorrhoidal disease is the exclusion of other, more life-threatening conditions. Hemorrhoidal banding remains the most successful method to manage hemorrhoids in the outpatient clinic. Chronic application of local medications to the perineum may result in dermatologic conditions. It is safe to manage acutely inflamed hemorrhoids surgically. Table 1 is a summary of the various methods for the surgical management of symptomatic prolapsing hemorrhoids. Dietary manipulation, including fiber supplementation, should always accompany surgical

Low-power wireless micromanometer system for acute and chronic bladder-pressure monitoring.

PubMed

Majerus, Steve J A; Fletter, Paul C; Damaser, Margot S; Garverick, Steven L

2011-03-01

This letter describes the design, fabrication, and testing of a wireless bladder-pressure-sensing system for chronic, point-of-care applications, such as urodynamics or closed-loop neuromodulation. The system consists of a miniature implantable device and an external RF receiver and wireless battery charger. The implant is small enough to be cystoscopically implanted within the bladder wall, where it is securely held and shielded from the urine stream. The implant consists of a custom application-specific integrated circuit (ASIC), a pressure transducer, a rechargeable battery, and wireless telemetry and recharging antennas. The ASIC includes instrumentation, wireless transmission, and power-management circuitry, and on an average draws less than 9 μA from the 3.6-V battery. The battery charge can be wirelessly replenished with daily 6-h recharge periods that can occur during the periods of sleep. Acute in vivo evaluation of the pressure-sensing system in canine models has demonstrated that the system can accurately capture lumen pressure from a submucosal implant location.

Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

NASA Astrophysics Data System (ADS)

Heikenwalder, Mathias; Zeller, Nicolas; Seeger, Harald; Prinz, Marco; Klöhn, Peter-Christian; Schwarz, Petra; Ruddle, Nancy H.; Weissmann, Charles; Aguzzi, Adriano

2005-02-01

Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-α or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.

Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

PubMed Central

Ding, Lin; El Zaatari, Mohamad

2017-01-01

Overview Gastric cancer has been traditionally defined by the Correa paradigm as a progression of sequential pathological events that begins with chronic inflammation [1]. Infection with Helicobacter pylori (H. pylori) is the typical explanation for why the stomach becomes chronically inflamed. Acute gastric inflammation then leads to chronic gastritis, atrophy particularly of acid-secreting parietal cells, metaplasia due to mucous neck cell expansion from trans-differentiation of zymogenic cells to dysplasia and eventually carcinoma [2]. The chapter contains an overview of gastric anatomy and physiology to set the stage for signaling pathways that play a role in gastric tumorigenesis. Finally, the major known mouse models of gastric transformation are critiqued in terms of the rationale behind their generation and contribution to our understanding of human cancer subtypes. PMID:27573785

Quantitative label-free proteomic analysis of human urine to identify novel candidate protein biomarkers for schistosomiasis.

PubMed

Onile, Olugbenga Samson; Calder, Bridget; Soares, Nelson C; Anumudu, Chiaka I; Blackburn, Jonathan M

2017-11-01

Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity. A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers. A total of 1306 proteins and 9701 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70). These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis.

Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease

PubMed Central

Molnár, Kriszta; Vannay, Ádám; Szebeni, Beáta; Bánki, Nóra Fanni; Sziksz, Erna; Cseh, Áron; Győrffy, Hajnalka; Lakatos, Péter László; Papp, Mária; Arató, András; Veres, Gábor

2012-01-01

AIM: To investigate intestinal alkaline phosphatase (iAP) in the intestinal mucosa of children with inflammatory bowel disease (IBD). METHODS: Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from 10 healthy controls. In IBD patients, specimens were obtained both from inflamed and non-inflamed areas. The iAP mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blotting analysis, respectively. Tissue localization of iAP and Toll-like receptor (TLR) 4 was investigated by immunofluorescent staining. RESULTS: The iAP protein level in the inflamed mucosa of children with Crohn’s disease (CD) and ulcerative colitis (UC) was significantly decreased when compared with controls (both P < 0.05). Similarly, we found a significantly decreased level of iAP protein in the inflamed mucosa in CD compared with non-inflamed mucosa in CD (P < 0.05). In addition, the iAP protein level in inflamed colonic mucosa in patients with UC was decreased compared with non-inflamed mucosa in patients with CD (P < 0.05). iAP protein levels in the non-inflamed mucosa of patients with CD were similar to controls. iAP mRNA expression in inflamed colonic mucosa of children with CD and UC was not significantly different from that in non-inflamed colonic mucosa with CD. Expression of iAP mRNA in patients with non-inflamed mucosa and in controls were similar. Co-localization of iAP with TLR4 showed intense staining with a dotted-like pattern. iAP was present in the inflamed and non-inflamed mucosa of patients with CD, UC, and in control biopsy specimens, irrespective of whether it was present in the terminal ileum or in the colon. However, the fluorescent signal of TLR4 was more pronounced in the colon compared with the terminal ileum in all groups studied. CONCLUSION: Lower than normal iAP protein levels in inflamed mucosa of IBD patients may indicate a role for iAP in inflammatory lesions in IBD. Based on our results, administration of exogenous iAP enzyme to patients with the active form of IBD may be a therapeutic option. PMID:22783049

Longitudinal cleavage of the penis in chronic spinal cord injury: two case reports

PubMed Central

Mansoor, Sahibzada Nasir; Ayaz, Saeed Bin; New, Peter

2016-01-01

Context Penile cleavage is a rare complication of spinal cord injury (SCI) in patients with a chronic indwelling catheter. We report two cases of chronic SCI who developed penile urethral cleavage after prolonged use of an indwelling catheter for bladder management. Findings A 25-year-old wheelchair mobile male with T7 American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A paraplegia developed a 4 × 1.5 cm ventral urethral cleavage after using an indwelling catheter for four months with inadequate care. He had an associated urinary tract infection and undiagnosed diabetes mellitus. A suprapubic catheter was inserted and surgical repair recommended after resolution of UTI and adequate control of his diabetes mellitus. After initial treatment he was lost to follow-up. The second patient was a 15-year-old male with AIS grade B tetraplegia who presented with a 2.5 cm cleavage on the ventral aspect of penis for the preceding three months. He had been using an indwelling catheter for bladder management for the previous 18 months. He had modified Ashworth scale grade III spasticity in lower limbs resistant to conservative management. There was no history of trauma, infection or diabetes mellitus. The patient was advised penile urethral repair surgery but was lost to follow-up. Conclusion Penile cleavage is a rare complication of neurogenic bladder in SCI patients. Patients and care givers should be trained in proper bladder management techniques during the hospital stay, counseled regarding the need for regular follow up, and be taught identification and prevention of common complications. PMID:26108452

Longitudinal cleavage of the penis in chronic spinal cord injury: two case reports.

PubMed

Mansoor, Sahibzada Nasir; Ayaz, Saeed Bin; Rathore, Farooq Azam; New, Peter

2016-05-01

Penile cleavage is a rare complication of spinal cord injury (SCI) in patients with a chronic indwelling catheter. We report two cases of chronic SCI who developed penile urethral cleavage after prolonged use of an indwelling catheter for bladder management. A 25-year-old wheelchair mobile male with T7 American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A paraplegia developed a 4 × 1.5 cm ventral urethral cleavage after using an indwelling catheter for four months with inadequate care. He had an associated urinary tract infection and undiagnosed diabetes mellitus. A suprapubic catheter was inserted and surgical repair recommended after resolution of UTI and adequate control of his diabetes mellitus. After initial treatment he was lost to follow-up. The second patient was a 15-year-old male with AIS grade B tetraplegia who presented with a 2.5 cm cleavage on the ventral aspect of penis for the preceding three months. He had been using an indwelling catheter for bladder management for the previous 18 months. He had modified Ashworth scale grade III spasticity in lower limbs resistant to conservative management. There was no history of trauma, infection or diabetes mellitus. The patient was advised penile urethral repair surgery but was lost to follow-up. Penile cleavage is a rare complication of neurogenic bladder in SCI patients. Patients and care givers should be trained in proper bladder management techniques during the hospital stay, counseled regarding the need for regular follow up, and be taught identification and prevention of common complications.

Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water.

PubMed

Cho, Young-Man; Hasumura, Mai; Imai, Toshio; Takami, Shigeaki; Nishikawa, Akiyoshi; Ogawa, Kumiko

2017-07-01

Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104-week chronic study, a 2-week analysis of cell proliferation in the urinary bladder and a medium-term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104-week chronic study with 32 male rats per group, no treatment-related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg -1 body weight day -1 ). In the promotion study, HRE treatment after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg -1 body weight day -1 ), respectively. In the 2-week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg -1 body weight day -1 ) caused transient increases in 5-bromo-2'-deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low-dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection

PubMed Central

O’Brien, Valerie P.; Hannan, Thomas J.; Schaeffer, Anthony J.; Hultgren, Scott J.

2015-01-01

Purpose of review Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Recent findings Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. Summary The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact. PMID:25517222

Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection.

PubMed

O'Brien, Valerie P; Hannan, Thomas J; Schaeffer, Anthony J; Hultgren, Scott J

2015-02-01

Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact.

Resolvin D3 is dysregulated in arthritis and reduces arthritic inflammation

PubMed Central

Arnardottir, Hildur H.; Dalli, Jesmond; Norling, Lucy V.; Colas, Romain A.; Perretti, Mauro; Serhan, Charles N.

2016-01-01

Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis. Resolvins (Rv) are a new family from the endogenous specialized pro-resolving lipid mediators (SPM) that actively stimulate resolution of inflammation. Herein, using lipid mediator (LM) metabololipidomics with murine joints we found a temporal regulation of endogenous SPM during self-resolving inflammatory arthritis. The SPMs present in self-resolving arthritic joints include the D-series resolvins, e.g. Resolvin (Rv) D1, RvD2, RvD3 and RvD4. Of note, RvD3 levels were reduced in inflamed joints from mice with delayed-resolving arthritis when compared to self-resolving inflammatory arthritis. RvD3 was also reduced in serum from rheumatoid arthritis (RA) patients compared to healthy controls. RvD3 administration reduced joint leukocytes as well as paw joint eicosanoids, clinical scores and edema. Together, these findings provide evidence for dysregulated endogenous RvD3 levels in inflamed paw joints and its potent actions in reducing murine arthritis. PMID:27534559

Risk factors for development of primary bladder squamous cell carcinoma

PubMed Central

Hubbard, R; Swallow, D; Finch, W; Wood, SJ; Biers, SM

2017-01-01

INTRODUCTION The aim of this study was to investigate the prevalence of risk factors for primary squamous cell carcinoma (SCC) of the bladder. MATERIALS A total of 90 cases of primary SCC of the bladder were identified through multicentre analysis. Patient demographics, stage and grade of cancer at presentation, management and outcomes were recorded. The presence of known risk factors (catheter use, neuropathic bladder, smoking history, recurrent urinary tract infection and bladder stones) was also documented. RESULTS Over half of the patients had at least one identifiable risk factor for the development of primary bladder SCC: 13.9% of patients had a history of catheter use (clean intermittent self-catheterisation [CISC] in 11.1%), 10.0% of patients had a neuropathic bladder, 27.8% were smokers or ex-smokers and 20.0% had a documented history of recurrent urinary tract infection. Statistical analysis of the results showed no association between risk factors and grade of tumour at presentation. CONCLUSIONS These data further support the association between primary bladder SCC and several of the well documented risk factors for its development. Chronic use of CISC may confer a greater risk for development of SCC than thought previously. Further evidence of the role of CISC in primary SCC is required to justify routine screening and to determine exactly when surveillance of the bladder should begin for this group of patients. PMID:27869492

Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats.

PubMed

Ungerer, Timothy D; Kim, Kyoungeun A; Daugherty, Stephanie L; Roppolo, James R; Tai, Changfeng; de Groat, William C

2016-11-01

The effects of intravesical administration of a muscarinic receptor agonist (oxotremorine-M, OXO-M) and antagonist (atropine methyl nitrate, AMN) and of a nicotinic receptor agonist (nicotine) and antagonist (hexamethonium, C 6 ) on reflex bladder activity were investigated in conscious female chronic spinal cord injured (SCI) cats using cystometry. OXO-M (50μM) decreased bladder capacity (BC) for triggering micturition contractions, increased maximal micturition pressure (MMP), increased frequency and area under the curve of pre-micturition contractions (PMC-AUC). Nicotine (250μM) decreased BC, increased MMP, but did not alter PMC-AUC. The effects of OXO-M on BC and PMC-AUC were suppressed by intravesical administration of AMN (50-100μM), and the effects of nicotine were blocked by hexamethonium (1mM). Antagonists infused intravesically alone did not alter reflex bladder activity. However, AMN (0.2mg/kg, subcutaneously) decreased PMC-AUC. 8-OH-DPAT (0.5mg/kg, s.c.), a 5-HT 1A receptor agonist, suppressed the OXO-M-induced decrease in BC but not the enhancement of PMC-AUC. These results indicate that activation of cholinergic receptors located near the lumenal surface of the bladder modulates two types of reflex bladder activity (i.e., micturition and pre-micturition contractions). The effects may be mediated by activation of receptors on suburothelial afferent nerves or receptors on urothelial cells which release transmitters that can in turn alter afferent excitability. The selective action of nicotine on BC, while OXO-M affects both BC and PMC-AUC, suggests that micturition reflexes and PMCs are activated by different populations of afferent nerves. The selective suppression of the OXO-M effect on BC by 8-OH-DPAT without altering the effect on PMCs supports this hypothesis. The failure of intravesical administration of either AMN or hexamethonium alone to alter bladder activity indicates that cholinergic receptors located near the lumenal surface do not tonically regulate bladder reflex mechanisms in the SCI cat. Copyright © 2016 Elsevier Inc. All rights reserved.

APOPTOSIS GENE EXPRESSION IN HUMAN EPDERMAL KERATINOCYTES TREATED WITH SODIUM ARSENITE USING REAL TIME PCR ARRAY

EPA Science Inventory

Arsenic exposure via contaminated drinking water is a great public health concern worldwide. Chronic arsenic exposure has been associated with human skin, lung and bladder cancer and other chronic effects. We have previous reported that sodium arsenite stimulated cell proliferati...

Recovery time for inflamed middle ear mucosa in chronic otitis media.

PubMed

Pakır, Onur; Dinç, Aykut Erdem; Damar, Murat; Akyıldız, İlker; Eliçora, Sultan Şevik; Erdem, Duygu

2016-01-01

The present study shows that 2-3 weeks after medical treatment the status of middle ear mucosa in draining ears is similar to that of dry ears for at least 3 months. To measure the time required for an inflamed middle ear mucosa to return into optimal state after appropriate medical treatment in chronic suppurative otitis media (CSOM). To assess optimal timing for elective surgical treatment of draining ears in uncomplicated CSOM. In this prospective study, the Eustachian tube (ET) mucociliary clearance time (MCT) was used as the method to demonstrate the status of middle ear mucosa. In group 1 (28 patients) ET-MCT was measured in ears that were free of drainage for at least 3 months. In Group 2 (21 patients), ET-MCT was measured in draining ears, who responded to 10-14 days medical treatment, at presentation, after 10 days and 1 month. The ET-MCT was 8.63 ± 1.32 min in group 1 and 28.96 ± 8.19 min in group 2 at presentation; and the difference was statistically significant (p < 0.001). The ET-MCT was 14.76 ± 5.11 min after 10 days and 9.31 ± 2.33 min after 1 month in group 2. The ET-MCT was indifferent between groups 1 and 2 after 1 month (p = 0.235).

Acid-Sensitive Sheddable PEGylated, Mannose-Modified Nanoparticles Increase the Delivery of Betamethasone to Chronic Inflammation Sites in a Mouse Model.

PubMed

O'Mary, Hannah L; Aldayel, Abdulaziz M; Valdes, Solange A; Naguib, Youssef W; Li, Xu; Salvady, Karun; Cui, Zhengrong

2017-06-05

Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions.

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

PubMed Central

Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A.; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L.

2014-01-01

Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture. PMID:24732949

Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current Status and Future Direction

PubMed Central

Kanda, Yusuke; Osaki, Mitsuhiko; Okada, Futoshi

2017-01-01

A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression. In this article, we summarize the up-to-date findings regarding definitive/possible causes and mechanisms of inflammation-related carcinogenesis derived from experimental and clinical studies. We also propose 10 strategies, as well as candidate agents for the prevention of inflammation-related carcinogenesis. PMID:28422073

A case-control study on the association between bladder cancer and prior bladder calculus.

PubMed

Chung, Shiu-Dong; Tsai, Ming-Chieh; Lin, Ching-Chun; Lin, Herng-Ching

2013-03-15

Bladder calculus is associated with chronic irritation and inflammation. As there is substantial documentation that inflammation can play a direct role in carcinogenesis, to date the relationship between stone formation and bladder cancer (BC) remains unclear. This study aimed to examine the association between BC and prior bladder calculus using a population-based dataset. This case-control study included 2,086 cases who had received their first-time diagnosis of BC between 2001 and 2009 and 10,430 randomly selected controls without BC. Conditional logistic regressions were employed to explore the association between BC and having been previously diagnosed with bladder calculus. Of the sampled subjects, bladder calculus was found in 71 (3.4%) cases and 105 (1.1%) controls. Conditional logistic regression analysis revealed that the odds ratio (OR) of having been diagnosed with bladder calculus before the index date for cases was 3.42 (95% CI = 2.48-4.72) when compared with controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and renal disease, tobacco use disorder, obesity, alcohol abuse, and schistosomiasis, bladder outlet obstruction, and urinary tract infection. We further analyzed according to sex and found that among males, the OR of having been previously diagnosed with bladder calculus for cases was 3.45 (95% CI = 2.39-4.99) that of controls. Among females, the OR was 3.05 (95% CI = 1.53-6.08) that of controls. These results add to the evidence surrounding the conflicting reports regarding the association between BC and prior bladder calculus and highlight a potential target population for bladder cancer screening.

[Multiple bladder diverticula caused by occipital horn syndrome].

PubMed

Legros, L; Revencu, N; Nassogne, M-C; Wese, F-X; Feyaerts, A

2015-11-01

We report on the case of a child who presented with recurrent, multiple, and voluminous bladder diverticula. Bladder diverticula are defined as a herniation of the mucosa through the bladder muscle or the detrusor. Causes are numerous and diverticula can be classified into primary congenital diverticula (para-ureteral - or Hutch diverticula - and posterolateral diverticula); secondary diverticula (resulting from chronic mechanical obstruction or from neurological disease; and diverticula secondary to connective tissue or muscle fragility. The latter is seen in disease entities such as prune belly syndrome, Ehlers-Danlos syndrome, cutis laxa syndrome, OHS (occipital horn syndrome), Menkes disease, and Williams-Beuren syndrome. In this patient, the cause of these diverticula was OHS, a genetic, recessive X-chromosome-linked syndrome, responsible for abnormal tissue caused by a disorder in copper metabolism. This case reminds us of the importance of pushing the diagnostic workup when presented with multiple and/or large bladder diverticula, and in particular to search for rare malformation syndromes after exclusion of an obstacle. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Population Dynamics and Niche Distribution of Uropathogenic Escherichia coli during Acute and Chronic Urinary Tract Infection ▿ †

PubMed Central

Schwartz, Drew J.; Chen, Swaine L.; Hultgren, Scott J.; Seed, Patrick C.

2011-01-01

Urinary tract infections (UTIs) have complex dynamics, with uropathogenic Escherichia coli (UPEC), the major causative agent, capable of colonization from the urethra to the kidneys in both extracellular and intracellular niches while also producing chronic persistent infections and frequent recurrent disease. In mouse and human bladders, UPEC invades the superficial epithelium, and some bacteria enter the cytoplasm to rapidly replicate into intracellular bacterial communities (IBCs) comprised of ∼104 bacteria each. Through IBC formation, UPEC expands in numbers while subverting aspects of the innate immune response. Within 12 h of murine bladder infection, half of the bacteria are intracellular, with 3 to 700 IBCs formed. Using mixed infections with green fluorescent protein (GFP) and wild-type (WT) UPEC, we discovered that each IBC is clonally derived from a single bacterium. Genetically tagged UPEC and a multiplex PCR assay were employed to investigate the distribution of UPEC throughout urinary tract niches over time. In the first 24 h postinfection (hpi), the fraction of tags dramatically decreased in the bladder and kidney, while the number of CFU increased. The percentage of tags detected at 6 hpi correlated to the number of IBCs produced, which closely matched a calculated multinomial distribution based on IBC clonality. The fraction of tags remaining thereafter depended on UTI outcome, which ranged from resolution of infection with or without quiescent intracellular reservoirs (QIRs) to the development of chronic cystitis as defined by persistent bacteriuria. Significantly more tags remained in mice that developed chronic cystitis, arguing that during the acute stages of infection, a higher number of IBCs precedes chronic cystitis than precedes QIR formation. PMID:21807904

Evaluation of the impact of the urinary symptoms on quality of life of patients with painful bladder syndrome/chronic pelvic pain and radiation cystitis: EURCIS study.

PubMed

Rapariz-González, M; Castro-Díaz, D; Mejía-Rendón, D

2014-05-01

To evaluate the impact of urinary symptoms of Painful Bladder/Pelvic Pain Syndrome and Radiation Cystitis (PBCPPS) on the Quality of Life, and self-esteem of the patient. An observational, multicenter, epidemiological and cross-sectional study was performed on patients with Painful Bladder/Chronic Pelvic Pain Syndrome and Radiation Cystitis. Data was recorded on severity of urinary symptoms and QoL impairment using the PUF Score. The patients evaluated the QoL deterioration grade through the King's Health Questionnaire (KHQ), and the level of their anxiety and self-esteem with the Goldberg's Anxiety Scale (GAS) and Rosenberg's Self-Esteem Scale (RSES), respectively. Post-hoc comparisons were performed between the results of the KHQ of this study and a sample of patients with urinary incontinence (UI). Results on RSES were analyzed with data from the general population and from patients with erectile dysfunction. A total of 530 cases, mostly female patients, who had been diagnosed with PBCPPS, were analyzed. High levels of deterioration in QoL were described: KHQ scores were significantly higher when compared with patients with UI (P<.01). Involvement of self-esteem was higher in patients with RC and men, who obtained scores similar to those of patients with erectile dysfunction. Patients with Painful Bladder Syndrome/Chronic Pelvic Pain Syndrome and Radiation Cystitis present high levels of anxiety, and significant reductions in both quality of life and self-esteem. Especially for men, this affectation is similar to that caused by erectile dysfunction. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis.

PubMed

Towner, Rheal A; Wisniewski, Amy B; Wu, Dee H; Van Gordon, Samuel B; Smith, Nataliya; North, Justin C; McElhaney, Rayburt; Aston, Christopher E; Shobeiri, S Abbas; Kropp, Bradley P; Greenwood-Van Meerveld, Beverley; Hurst, Robert E

2016-03-01

Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

PubMed Central

Gonzalez, Eric J.; Merrill, Liana

2014-01-01

Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

Transcriptional and Translational Plasticity in Rodent Urinary Bladder TRP Channels with Urinary Bladder Inflammation, Bladder Dysfunction or Postnatal Maturation

PubMed Central

Merrill, Liana; Girard, Beatrice M.; May, Victor; Vizzard, Margaret A.

2013-01-01

These studies examined transcriptional and translational plasticity of three transient receptor potential (TRP) channels (TRPA1, TRPV1, TRPV4) with established neuronal and non-neuronal expression and functional roles in the lower urinary tract. Mechanosensor and nociceptor roles in either physiological or pathological lower urinary tract states have been suggested for TRPA1, TRPV1 and TRPV4. We have previously demonstrated neurochemical, organizational and functional plasticity in micturition reflex pathways following induction of urinary bladder inflammation using the antineoplastic agent, cyclophosphamide (CYP). More recently, we have characterized similar plasticity in micturition reflex pathways in a transgenic mouse model with chronic urothelial overexpression (OE) of nerve growth factor (NGF) and in a transgenic mouse model with deletion of vasoactive intestinal polypeptide (VIP). In addition, the micturition reflex undergoes postnatal maturation that may also reflect plasticity in urinary bladder TRP channel expression. Thus, we examined plasticity in urinary bladder TRP channel expression in diverse contexts using a combination of quantitative, real-time PCR and western blotting approaches. We demonstrate transcriptional and translational plasticity of urinary bladder TRPA1, TRPV1 and TRVP4 expression. Although the functional significance of urinary bladder TRP channel plasticity awaits further investigation, these studies demonstrate context-(inflammation, postnatal development, NGF-OE, VIP deletion) and tissue-dependent (urothelium + suburothelium, detrusor) plasticity. PMID:22865090

Use of imipramine hydrochloride for treatment of urospermia in a stallion with a dysfunctional bladder.

PubMed

Turner, R M; Love, C C; McDonnell, S M; Sweeney, R W; Twitchell, E D; Habecker, P L; Reilly, L K; Pozor, M A; Kenney, R M

1995-12-15

An 8-year-old stallion was evaluated because of recurrent urinary tract infections and chronic intermittent urospermia. After extensive diagnostic testing, it was hypothesized that the stallion had a reflex dyssynergia of the bladder and urethral sphincter. Initial attempts to manage the urospermia included semen fractionation, semen collection after voluntary urination, and use of semen extenders. None of these efforts reliably yielded a quality ejaculate. Administration of imipramine hydrochloride (1.2 mg/kg of body weight, PO, 4 hours prior to semen collection) was initiated in an attempt to enhance bladder neck closure during ejaculation. This treatment, combined with voluntary urination prior to ejaculation, resulted in ejaculates containing little or no urine. Using this protocol, 19 of 20 mares bred during the subsequent 2 years became pregnant. By the third year, the bladder dysfunction had progressed, and the urospermia was no longer manageable. Bladder catheterization, followed by manual expression of the bladder per rectum, were necessary prior to each semen collection to obtain a urine-free ejaculate. Three-and-a-half years after initial examination, transitional cell carcinoma of the bladder with metastasis was identified, and the stallion was euthanatized. It is not known whether the transitional cell carcinoma was related to the dysfunctional bladder. Imipramine hydrochloride did not eliminate, but did reduce, the frequency and degree of urospermia in the affected stallion for approximately 2 years.

Tissue reactions under piezoelectric shockwave application for the fragmentation of biliary calculi.

PubMed Central

Ell, C; Kerzel, W; Heyder, N; Rödl, W; Langer, H; Mischke, U; Giedl, J; Domschke, W

1989-01-01

The tissue reactions that occurred during piezoelectric shockwaves for the fragmentation of biliary calculi were investigated in 10 surgically removed stone containing human gall bladders and in acute (six dogs) and chronic (six dogs) animal experiments. Before and after shockwave (500, 1500 or 3000) in the anaesthetised dogs, computed tomography (CT), magnetic imaging (MRI) and laboratory tests were done; treatment was carried out under continuous ultrasonographic control. Shockwave applications to the human gall bladders resulted in disintegration of the stones with no macroscopically or microscopically detectable tissue changes. In acute animal experiments, small haematomas were observed in all six animals at surfaces, but also inside the liver and gall bladder (max diameter 25 mm). Perforation or intra-abdominal or pleural bleeding did not occur. In chronic experiments, no macroscopic, and only slight microscopic residual lesions (haemosiderin deposits) were seen three weeks after shockwave. In almost all instances, the lesions were detected by CT, MRI, and ultrasonography, while laboratory tests were negative. Images Fig 1 Figs. 2-4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:2731762

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

PubMed Central

Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

2017-01-01

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

Sixteen-slice multidetector computed tomographic virtual cystoscopy in the evaluation of a patient with suspected bladder tumor and history of bladder carcinoma operation.

PubMed

Basak, Muzaffer; Ozkurt, Huseyin; Tanriverdi, Orhan; Cay, Esra; Aydin, Mustafa; Miroglu, Cengiz

2009-01-01

The purpose of this study was to evaluate the use of virtual cystoscopy performed with multidetector computed tomography (CT) in patients with suspected bladder tumors and histories of bladder carcinoma operation. Thirty-six patients (29 men and 7 women) with a mean age of 66 years (range, 24-88 years) with suspected bladder tumors and histories of bladder carcinoma operation were included in this prospective study. Virtual cystoscopy was performed by 16-slice multidetector CT scanner. The bladder was filled with diluted contrast material solution through a Foley catheter. Then, all patients underwent conventional cystoscopy examination. Two reviewers found 18 lesions detected by virtual cystoscopy by consensus, whereas 19 lesions were depicted by conventional cystoscopy. At virtual and conventional cystoscopies, the conditions of 3 patients, 2 with chronic inflammations and 1 with foreign body reaction, were wrongly diagnosed as tumors. At conventional cystoscopy, one patient's result was wrongly interpreted as normal. In pathologic evaluation, all tumors were diagnosed as transitional cell carcinoma. Bladder tumor can be noninvasively diagnosed using virtual cystoscopy. Use of virtual cystoscopy should be considered inpatients who present with hematuria or have histories of bladder carcinoma operation and are for follow-up because of its lesser complication risk and its being a less invasive, easily applied procedure without need of anesthesia. In the future, owing to the development of the CT technology and image processing technique, virtual cystoscopy may have a part in the detection of bladder cancer.

Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes.

PubMed

Pène, Jérôme; Chevalier, Sylvie; Preisser, Laurence; Vénéreau, Emilie; Guilleux, Marie-Hélène; Ghannam, Soufiane; Molès, Jean-Pierre; Danger, Yannic; Ravon, Elisa; Lesaux, Sabine; Yssel, Hans; Gascan, Hugues

2008-06-01

Chronic inflammatory diseases are characterized by local tissue injury caused by immunocompetent cells, in particular CD4(+) T lymphocytes, that are involved in the pathogenesis of these disorders via the production of distinctive sets of cytokines. Here, we have characterized single CD4(+) T cells that infiltrate inflamed tissue taken from patients with psoriasis, Crohn's disease, rheumatoid arthritis, or allergic asthma. Results from a cytokine production and gene profile analysis identified a population of in vivo differentiatedretinoid-related orphan receptor gamma-expressing T cells, producing high levels of IL-17, that can represent up to 30% of infiltrating T lymphocytes. Activated Th17 cells produced IL-26, TNF-alpha, lymphotoxin-beta, and IL-22. IL-17 and IL-22 concentrations secreted by tissue infiltrating Th17 cells could reach up to 100 nM and were inversely correlated with the production of Th1- and Th2-associated cytokines. In addition, tissue-infiltrating Th17 cells are also characterized by high cell surface expression of CCR6, a chemokine receptor that was not expressed by Th1 and Th2 cells, isolated from the same lesions, and by the production of CCL20/MIP3alpha, a CCR6 ligand, associated with tissue infiltration. Culture supernatants of activated Th17 cells, isolated from psoriatic lesions, induced the expression of gene products associated with inflammation and abnormal keratinocyte differentiation in an IL-17 and IL-22-dependent manner. These results show that tissue-infiltrating Th17 cells contribute to human chronic inflammatory disease via the production of several inflammatory cytokines and the creation of an environment contributing to their migration and sequestration at sites of inflammation.

N-Acetyl-l-Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats.

PubMed

Villagarcía, Hernán Gonzalo; Castro, María Cecilia; Arbelaez, Luisa González; Schinella, Guillermo; Massa, María Laura; Spinedi, Eduardo; Francini, Flavio

2018-04-15

Hypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not. We evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity -LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitored liver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFα protein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions (glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat). Chronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides, UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISI and the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSG rats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NAC-treated MSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenic genes) expression levels. Our study strongly supports that chronic oral antioxidant therapy (NAC administration) prevented the development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats by efficiently decreasing high endogenous OS. Copyright © 2018 Elsevier Inc. All rights reserved.

Dugway Proving Ground: Closure Plan Module 2, for SWMUs 20, 164, 166 and 170

DTIC Science & Technology

1997-07-01

Lewin and J.H. Holmes, 1972. Syndrome of Dyspraxia and Multifocal Seizure Associated with Chronic Hemodialysis. Trans. Am. Soc. Artif. Intern. Organs. 18...Many cases of nasal mucosal injury (inflamed mucosa, ulcerated or perforated septum) in workers exposed to Cr0 3 have been reported (Bloomfield and...mg/kg chromium for 3 or 6 weeks. These changes included neuronal degeneration in the cerebral cortex, marked O DUG\\0566 07/11/96 4:19pm bpw B.3-69

Urologic evaluation of urinary tract infection in pregnancy.

PubMed

Diokno, A C; Compton, A; Seski, J; Vinson, R

1986-01-01

Thirty-three antepartum patients with urinary tract infections underwent urologic evaluation as soon as the infection had been successfully treated. The evaluation included history of voiding habits, cystometry, urethral calibration and cystourethroscopy. A second phase of the urologic evaluation included an excretory urogram and repeat cystometry 10-12 weeks postpartum. Sixty percent had a history of infrequent voiding, and 90% of them had a bladder capacity greater than 450 mL. Forty-one percent of the patients had a normal bladder capacity (less than 450 mL), and 85% of this group did not have any history of infrequent voiding. The radiographic evaluation postpartum in 18 of 33 patients revealed major abnormalities in 50%. These abnormalities were seen as often and were as significant in women with asymptomatic bacteriuria as in those who presented with acute pyelonephritis. The results suggest that the large bladder seen in pregnant women may be secondary to the chronic, unphysiologic habit of infrequent voiding. Furthermore, this study reinforced the fact that most pregnant women with urinary tract infection have preexisting chronic bladder or renal abnormalities that predispose them to infection. Those at risk should be identified early through a careful history and urinalysis to determine which ones need urinary prophylaxis during pregnancy. Postpartum urologic investigation should be carried out to identify any structural or functional problems; understanding them is helpful in present and future management.

Low Temperature Plasma Kills SCaBER Cancer Cells

NASA Astrophysics Data System (ADS)

Barekzi, Nazir; van Way, Lucas; Laroussi, Mounir

2013-09-01

Squamous cell carcinoma of the bladder is a rare type of bladder cancer that forms as a result of chronic irritation of the epithelial lining of the bladder. The cell line used in this study is SCaBER (ATCC® HTB-3™) derived from squamous cell carcinoma of the human urinary bladder. Current treatments of bladder cancer include surgery, radiation and chemotherapy. However, the cost of these treatments, the potential toxicity of the chemotherapeutic agents and the systemic side-effects warrant an alternative to current cancer treatment. This paper represents preliminary studies to determine the effects of biologically tolerant plasma (BTP) on a cell line of human bladder cancer cells. Previous work by our group using the plasma pencil revealed the efficacy of BTP on leukemia cells suspended in solution. Based on these earlier findings we hypothesized that the plasma exposure would elicit a similar programmed cell death in the SCaBER cells. Trypan blue exclusion and MTT assays revealed the cell killing after exposure to BTP. Our study indicates that low temperature plasma generated by ionizing helium gas and the reactive species may be a suitable and safe alternative for cancer therapy.

PubMed Central

Combaz-Söhnchen, Nina; Kuhn, Annette

2017-01-01

Mycoplasma species relevant to the urogenital tract include mycoplasma hominis, mycoplasma genitalia and ureaplasma urealyticum. Their occurrence in the context of urogynaecological disease has been demonstrated in urethritis, cystitis and upper renal tract infections. Their role in hyperactive bladder and interstitial cystitis/painful bladder syndrome is controversial. All the above-mentioned microorganisms can occur as commensals or as potential pathogens. In most cases their role in any particular pathology cannot be proven, only presumed. The aim of this systematic review was to summarise current knowledge on the influence of mycoplasma and ureaplasma in urogynaecological pathology and to provide clinical guidance on diagnosis (when and how is pathogen detection indicated?) and treatment. 377 relevant articles were analysed. In summary: a urethral swab for PCR analysis of the three bacteria should be performed in the context of symptomatic sterile leukocyturia, chronic urethritis and suspected hyperactive bladder or interstitial cystitis/painful bladder syndrome. Symptomatic women should be treated strictly according to results of the antibiogram. PMID:29269957

[Secondary amyloidosis of the bladder and massive hematuria].

PubMed

García-Escudero López, A; Arruza Echevarría, A; Leunda Saizar, J; Infante Riaño, R; Padilla Nieva, J; Ortiz Barredo, E

2010-01-01

To report four additional cases of secondary amyloidosis of the bladder, an extremely rare condition, as shown by the cases reported in the literature. Four clinical cases are reported, all of them occurring as hematuria, which was massive and fulminant and resulted in death in three patients. Secondary amyloidosis of the bladder is of the AA type, which is more common in females and mainly secondary to rheumatoid arthritis, but also to ankylosing spondylitis and long-standing chronic inflammatory conditions. Hematuria is the main and virtually only symptom. A pathological and immunohistochemical study confirmed diagnosis. All three patients who experienced massive, fatal hematuria had an intercurrent condition requiring urethral catheterization, which was the triggering factor. Despite its rarity, as shown by the few cases reported, secondary amyloidosis of the bladder should be considered in patients already diagnosed with systemic amyloidosis and/or the conditions reported who require simple urethral catheterization.

Autoantibody-mediated bowel and bladder dysfunction in a patient with chronic, nondiabetic neuropathy.

PubMed

Jackson, Michael W; Gordon, Thomas P; McCombe, Pamela A

2008-04-01

Physiological techniques can be used to detect novel autoantibodies causing alteration of autonomic function after passive transfer to mice. Previously, such antibodies have been detected in patients with type I diabetes mellitus, myasthenia gravis, and Sjogren's syndrome. We now describe a patient with an idiopathic nondiabetic neuropathy with prominent autonomic symptoms, including bladder and bowel dysfunction. Physiological assays of whole colon and bladder were used to determine the presence in the patient serum of functional autoantibodies capable of mediating autonomic dysfunction. Immunoglobulin G (IgG) from this patient was able to disrupt bladder and bowel function on passive transfer to mice. This is a new pattern of autoantibody-mediated abnormality. Although the target antigen is unknown, it is likely to be a cell-surface receptor or ion channel. This case highlights the usefulness of passive transfer studies in detecting functional antibodies in patients with autonomic neuropathy.

Xanthogranulomatous cystitis: a challenging imitator of bladder cancer.

PubMed

Ekici, Sinan; Dogan Ekici, Isin; Ruacan, Sevket; Midi, Ahmet

2010-06-29

Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature.

Effects of CYP-induced cystitis on PACAP/VIP and receptor expression in micturition pathways and bladder function in mice with overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Tompkins, John D; Parsons, Rodney L; May, Victor; Vizzard, Margaret A

2012-11-01

We have previously demonstrated nerve growth factor (NGF) regulation of pituitary adenylate cyclase-activating polypeptide (PACAP)/receptors in bladder reflex pathways using a transgenic mouse model of chronic NGF overexpression in the bladder using the urothelial-specific uroplakin II promoter. We have now explored the contribution of target-derived NGF in combination with cyclophosphamide (CYP)-induced cystitis to determine whether additional changes in neuropeptides/receptors are observed in micturition reflex pathways due to the presence of additional inflammatory mediators in the urinary bladder. Quantitative PCR was used to determine PACAP/vasoactive intestinal polypeptide (VIP), substance P, galanin, and receptor transcript expression in the urinary bladder (urothelium, detrusor) in mice with overexpression of NGF in the urothelium (NGF-OE) and wild-type (WT) mice with CYP-induced cystitis (4 h, 48 h, and chronic). With CYP-induced cystitis (4 h), WT and NGF-OE mice exhibited similar changes in galanin transcript expression in the urothelium (30-fold increase) and detrusor (threefold increase). In contrast, PACAP, VIP, and substance P transcripts exhibited differential changes in WT and NGF-OE with CYP-induced cystitis. PAC1, VPAC1, and VPAC2 transcript expression also exhibited differential responses in NGF-OE mice that were tissue (urothelium vs. detrusor) and CYP-induced cystitis duration-dependent. Using conscious cystometry, NGF-OE mice treated with CYP exhibited significant (p ≤ 0.01) increases in voiding frequency above that observed in control NGF-OE mice. In addition, no changes in the electrical properties of the major pelvic ganglia neurons of NGF-OE mice were detected using intracellular recording, suggesting that the urinary bladder phenotype in NGF-OE mice is not influenced by changes in the efferent limb of the micturition reflex. These studies are consistent with target-derived NGF and other inflammatory mediators affecting neurochemical plasticity and the reflex function of micturition pathways.

Thyroid disrupting effects of halogenated and next generation chemicals on the swim bladder development of zebrafish.

PubMed

Godfrey, Amy; Hooser, Blair; Abdelmoneim, Ahmed; Horzmann, Katharine A; Freemanc, Jennifer L; Sepúlveda, Maria S

2017-12-01

Endocrine disrupting chemicals (EDCs) can alter thyroid function and adversely affect growth and development. Halogenated compounds, such as perfluorinated chemicals commonly used in food packaging, and brominated flame retardants used in a broad range of products from clothing to electronics, can act as thyroid disruptors. Due to the adverse effects of these compounds, there is a need for the development of safer next generation chemicals. The objective of this study was to test the thyroid disruption potential of old use and next generation halogenated chemicals. Zebrafish embryos were exposed to three old use compounds, perfluorooctanoic acid (PFOA), tetrabromobisphenol A (TBBPA) and tris (1,3-dichloro-2-propyl) phosphate (TDCPP) and two next generation chemicals, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxdie (DOPO) and perfluorobutyric acid (PFBA). Sub-chronic (0-6days post fertilization (dpf)) and chronic (0-28dpf) exposures were conducted at 1% of the concentration known to kill 50% (LC 50 ) of the population. Changes in the surface area of the swim bladder as well as in expression levels of genes involved in the thyroid control of swim bladder inflation were measured. At 6dpf, zebrafish exposed to all halogenated chemicals, both old use and next generation, had smaller posterior swim bladder and increased expression in the gene encoding thyroid peroxidase, tpo and the genes encoding two swim bladder surfactant proteins, sp-a and sp-c. These results mirrored the effects of thyroid hormone-exposed positive controls. Fish exposed to a TPO inhibitor (methimazole, MMI) had a decrease in tpo expression levels at 28dpf. Effects on the anterior swim bladder at 28dpf, after exposure to MMI as well as both old and new halogenated chemicals, were the same, i.e., absence of SB in ∼50% of fish, which were also of smaller body size. Overall, our results suggest thyroid disruption by the halogenated compounds tested via the swim bladder surfactant system. However, with the exception of TBBPA and TDCPP, the concentrations tested (∼5-137ppm) are not likely to be found in the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

[Current status of neurostimulation and neuromodulation for vesicourethral dysfunction].

PubMed

González-Chamorro, F; Verdú Tartajo, F; Hernández Fernández, C

1997-01-01

To describe the current indications, techniques and results of sacral root stimulation in patients with spinal cord lesions as a treatment for patients with high pressure bladders and/or urinary incontinence despite conservative management, as well as sacral root neuromodulation with permanent stimulators for complex bladder dysfunction: vesical instability, sensory urgency, chronic pelvic pain and chronic voiding dysfunction. The literature is reviewed, both techniques are described and the results of the most significant series are discussed, with special reference to the first groups that utilized these techniques. There is ample experience in the application of sacral root electrical stimulation. The reported results are comparable with those achieved by other treatments, such as augmentation cystoplasty. Neurostimulation and neuromodulation techniques are simple, the complications are minimal and they do not prelude the use of other therapies.

Chronic urinary retention in men: how we define it, and how does it affect treatment outcome.

PubMed

Negro, Carlo L A; Muir, Gordon H

2012-12-01

What's known on the subject? and What does the study add? Chronic urinary retention (CUR) is a poorly defined entity, as the key element of definition, significant postvoid residual urine volume (PVR), has not a worldwide and moreover evidenced-based definition. There is no agreement on which is the threshold value to define a significant PVR and different society produced guidelines with different thresholds ranging from 300 mL to 1000 mL. Diagnosis is difficult, and management has not been defined yet. There is a lack of studies on the best management of these patients, as this group of patients has always been considered at high risk of failure. Only one study compares conservative with the surgical management but it is not a randomised controlled trail. This review offers a systematic appraisal of the most recent publications on CUR. It indicates the absence of a real worldwide agreed definition, as the two keys element of it are not satisfactorily defined yet: significant PVR, is suffering from a lack of evidenced-based definition, and percussable or palpable bladder is a very nebulous concept as it is not a criteria of certainty as different individual variables affect it. This has an important effect on management which is not structured. Most of the trials involving benign prostatic hyperplasia treatments (either medical or surgical) tend to exclude this group of patients, which is a clinically important group, comprising up to a quarter of men undergoing TURP in the UK. Urinary retention describes a bladder that does not empty completely or does not empty at all. Historically, urinary retention has been classified as either acute or chronic the latter is generally classified as high pressure or low pressure according to the bladder filling pressure on urodynamic. A MEDLINE® search for articles written in English and published before January 2010 was done using a list of terms related to urinary retention: 'urinary retention', 'chronic urinary retention' and 'PVR'. Chronic urinary retention (CUR) is defined by the International Continence Society as 'a non-painful bladder, which remains palpable or percussable after the patient has passed urine'. Abrams was the first to choose a residual urine volume >300 mL to define CUR as he considered it the minimum volume at which the bladder becomes palpable suprapubically. The UK National Institute for Health and Clinical Excellence lower urinary tract symptoms (LUTS) guidelines define CUR as a postvoid residual urine volume (PVR) of >1000 mL. No studies have specifically addressed the problem of quantifying the minimum amount of urine present in the bladder to define CUR. Nor did we find any publications objectively assessing at what amount of urine a bladder can be palpable. The ability to feel a bladder may rely on variables (i.e. medical skills and patient habitus). There is a marked variability of PVR, so the test should be repeated to improve precision. As defining CUR is difficult, structured management is challenging. Nearly all prospective trials exclude men with CUR from analysis, possibly anticipating a poor outcome and a high risk of complications. However, men with CUR are a clinically important group, comprising up to 25% of men undergoing transurethral resection of the prostate. Definition of CUR is imprecise and arbitrary. Most studies seem to describe the condition as either a PVR of >300 mL in men who are voiding, or >1000 mL in men who are unable to void. This confusion leads to an inability to design and interpret studies; indeed most prospective trials simply exclude these patients. There is a clear need for internationally accepted definitions of retention to allow both treatment and reporting of outcomes in men with LUTS, and for such definitions to be used by all investigators in future trials. © 2012 BJU INTERNATIONAL.

Secondary bladder amyloidosis with familial Mediterranean fever in a living donor kidney transplant recipient: a case report.

PubMed

Imamura, Sentaro; Narita, Shintaro; Nishikomori, Ryuta; Tsuruta, Hiroshi; Numakura, Kazuyuki; Maeno, Atsushi; Saito, Mitsuru; Inoue, Takamitsu; Tsuchiya, Norihiko; Nanjo, Hiroshi; Heike, Toshio; Satoh, Shigeru; Habuchi, Tomonori

2016-10-19

Secondary bladder amyloidosis is an extremely rare disease, resulting from a chronic systematic inflammatory disorder associated with amyloid deposits. Although uncommon in Japan, familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent episodes of fever of short duration and serositis and is frequently associated with systemic amyloidosis. Here, we present a case of a Japanese patient complaining of fever and macroscopic hematuria after a living donor renal transplantation. Consequently, he was diagnosed with secondary bladder amyloidosis with FMF. A 64-year-old Japanese male received a living ABO-incompatible kidney transplant from his wife. The postoperative clinical course was normal, and the patient was discharged 21 days after the transplantation with a serum creatinine level of 0.78 mg/dl. The patient frequently complained of general fatigue and fever of unknown origin. Six months later, the patient presented with continuous general fatigue, macroscopic hematuria, and fever. Cystoscopic examination of the bladder showed an edematous region with bleeding, and a transurethral biopsy revealed amyloid deposits. His wife stated that the patient had a recurrent high fever since the age of 40 years and that his younger brother was suspected to have a familial autoinflammatory syndrome; thus, the patient was also suspected to have a familial autoinflammatory syndrome. Based on his brother's medical history and the genetic tests, which showed a homozygous mutation (M694V/M694V) for the Mediterranean fever protein, he was diagnosed with FMF. Although colchicine treatment for FMF was planned, the patient had an untimely death due to heart failure. We re-evaluated the pathological findings of the various tissue biopsies obtained during the treatment after the renal transplantation. Immunohistochemistry revealed amyloid deposits in the bladder region, renal allograft, and myocardium and the condition was diagnosed as AA amyloidosis associated with FMF. We presented a case of systemic amyloidosis with FMF, involving the bladder region, myocardium, and renal allograft, diagnosed after renal transplantation. Bladder amyloidosis should be considered in patients with macroscopic hematuria, particularly in the kidney transplant recipients with idiopathic chronic renal disease. Diagnosis of secondary bladder amyloidosis may result in the early detection of underlying diseases, which may contribute to patient prognosis.

The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

PubMed

Matos, Rita; Serrão, Paula; Rodriguez, Larissa; Birder, Lori Ann; Cruz, Francisco; Charrua, Ana

2017-08-01

Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

Urethral versus suprapubic catheter: choosing the best bladder management for male spinal cord injury patients with indwelling catheters.

PubMed

Katsumi, H K; Kalisvaart, J F; Ronningen, L D; Hovey, R M

2010-04-01

Bladder management for male patients with spinal cord injury (SCI) challenges the urologist to work around physical and social restrictions set forth by each patient. The objective of this study was to compare the complications associated with urethral catheter (UC) versus suprapubic tube (SPT) in patients with SCI. A retrospective review of records at Long Beach Veterans Hospital was carried out to identify SCI patients managed with SPT or UC. Chart review identified morbidities including urinary tract infection (UTI), bladder stones, renal calculi, urethral complications, scrotal abscesses, epididymitis, gross hematuria and cancer. Serum creatinine measurements were evaluated to determine whether renal function was maintained. In all, 179 patients were identified. There was no significant difference between the two catheter groups in any areas in which they could be compared. There were catheter-specific complications specific to each group that could not be compared. These included erosion in the UC group and urethral leak, leakage from the SPT and SPT revision in the SPT group. Average serum creatinine for the UC and SPT groups was 0.74 and 0.67 mg per 100 ml, respectively. SCI patients with a chronic catheter have similar complication rates of UTIs, recurrent bladder/renal calculi and cancer. Urethral and scrotal complications may be higher with UC; however, morbidity from SPT-specific procedures may offset benefits from SPT. Serum creatinine was maintained in both groups. Overall, bladder management for patients with chronic indwelling catheters should be selected on the basis of long-term comfort for the patient and a physician mind-set that allows flexibility in managing these challenges.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipshultz, L.I.; Corriere, J.N. Jr.

Technetium-99m radioactive colloid particles were suspended in an iodine- 131 Hippuran radioactive fluid medium and placed into the bladders of six patients. Two normal patients and one with only one urinary tract infection voided the fluid and particles synchronously, while three with recurrent urinary tract infections eliminated the particles at a much slower rate than the fluid. A change in either the physical contour or secretory activity of the bladder urothelium is postulated as the cause of particle retention in these patients with chronic infections. (auth)

Preventing Diabetes Problems

MedlinePlus

... Problems Diabetes, Sexual, & Bladder Problems Clinical Trials Preventing Diabetes Problems View or Print All Sections Heart Disease & ... to help control symptoms and restore intimacy. Depression & Diabetes Depression is common among people with a chronic, ...

The role of phospholipid oxidation products in inflammatory and autoimmune diseases: evidence from animal models and in humans.

PubMed

Leitinger, Norbert

2008-01-01

Since the discovery of oxidized phospholipids (OxPL) and their implication as modulators of inflammation in cardiovascular disease, roles for these lipid oxidation products have been suggested in many other disease settings. Lipid oxidation products accumulate in inflamed and oxidatively damaged tissue, where they are derived from oxidative modification of lipoproteins, but also from membranes of cells undergoing apoptosis. Thus, increased oxidative stress as well as decreased clearance of apoptotic cells has been implied to contribute to accumulation of OxPL in chronically inflamed tissues.A central role for OxPL in disease states associated with dyslipedemia, including atherosclerosis, diabetes and its complications, metabolic syndrome, and renal insufficiency, as well as general prothrombotic states, has been proposed. In addition, in organs which are constantly exposed to oxidative stress, including lung, skin, and eyes, increased levels of OxPL are suggested to contribute to inflammatory conditions. Moreover, accumulation of OxPL causes general immunmodulation and may lead to autoimmune diseases. Evidence is accumulating that OxPL play a role in lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis. Last but not least, a role for OxPL in neurological disorders including multiple sclerosis (MS), Alzheimer's and Parkinson's disease has been suggested.This chapter will summarize recent findings obtained in animal models and from studies in humans that indicate that formation of OxPL represents a general mechanism that may play a major role in chronic inflammatory and autoimmune diseases.

Resolvin D3 Is Dysregulated in Arthritis and Reduces Arthritic Inflammation.

PubMed

Arnardottir, Hildur H; Dalli, Jesmond; Norling, Lucy V; Colas, Romain A; Perretti, Mauro; Serhan, Charles N

2016-09-15

Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis. Resolvins (Rvs) are a new family from the endogenous specialized proresolving mediators (SPMs) that actively stimulate resolution of inflammation. In this study, using lipid mediator metabololipidomics with murine joints we found a temporal regulation of endogenous SPMs during self-resolving inflammatory arthritis. The SPMs present in self-resolving arthritic joints include the D-series Rvs, for example, RvD1, RvD2, RvD3, and RvD4. Of note, RvD3 levels were reduced in inflamed joints from mice with delayed-resolving arthritis when compared with self-resolving inflammatory arthritis. RvD3 was also reduced in serum from rheumatoid arthritis patients compared with healthy controls. RvD3 administration reduced joint leukocytes as well as paw joint eicosanoids, clinical scores, and edema. Taken together, these findings provide evidence for dysregulated endogenous RvD3 levels in inflamed paw joints and its potent actions in reducing murine arthritis. Copyright © 2016 by The American Association of Immunologists, Inc.

Acid-sensitive sheddable PEGylated, mannose-modified nanoparticles increase the delivery of betamethasone to chronic inflammation sites in a mouse model

PubMed Central

O’Mary, Hannah L.; Aldayel, Abdulaziz M.; Valdes, Solange A.; Naguib, Youssef W.; Li, Xu; Salvady, Karun; Cui, Zhengrong

2017-01-01

Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions. PMID:28463518

Encephalopathy after bladder irrigation with alum: case report and literature review.

PubMed

Phelps, K R; Naylor, K; Brien, T P; Wilbur, H; Haqqie, S S

1999-09-01

A 70-year-old man with advanced obstructive nephropathy began to hemorrhage from the bladder after decompression with a Foley catheter. Manifestations of encephalopathy appeared after continuous irrigation with 1% alum for 2 days and were associated with elevated serum aluminum concentrations. Repeated treatments with deferoxamine and hemodialysis accomplished some aluminum removal, but the patient succumbed to bronchopneumonia. Brain aluminum content was not excessive at autopsy. A literature review suggests that intact renal function is essential to rapid disposal of a parenteral aluminum load and indicates that most reported instances of encephalopathy after alum irrigation have occurred in patients with compromised renal function. We conclude that alum should not be employed as a bladder irrigant in patients with acute or chronic renal failure.

Contact laser prostatectomy in a patient on chronic anticoagulation

NASA Astrophysics Data System (ADS)

Mueller, Edward J.

1995-05-01

The `gold standard' therapy for patients with symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia has always been electrocautery TURP. However, in patients with medical problems requiring chronic anticoagulation, this procedure is contraindicated due to the extreme risk of hemorrhage, both during the procedure and the immediate post operative period. With the recent development of contact laser prostatectomy the patient on chronic anticoagulation can safely undergo the procedure. Herein, I present a case of a 60 year old with significant bladder outlet obstruction yielding an AUA symptom score of 18. The patient had a history of multiple episodes of deep venous thrombosis of the left leg with three prior pulmonary emboli. He was maintained on chronic anticoagulation with alternating days of 3.5 mg. and 5.0 mg. of warfarin sodium (coumadin). Preoperative cystoscopy showed a 4 cm prostatic fossa obstructed by tri-lobar hypertrophy, with large kissing lateral lobes and visual obstruction from the verumontanum. The patient underwent a contact laser prostatectomy with the SLT Nd:YAG laser at 50 watts. There was minimal bleeding both during the procedure and in the immediate postoperative period. At three months post-op the AUA symptom score had decreased to 2. This case demonstrated that contact laser prostatectomy can be safely and effectively performed in patients on chronic anticoagulation.

Adjuvant alternative treatment with chemical peeling and subsequent iontophoresis for postinflammatory hyperpigmentation, erosion with inflamed red papules and non-inflamed atrophic scars in acne vulgaris.

PubMed

Kurokawa, Ichiro; Oiso, Naoki; Kawada, Akira

2017-04-01

The standard management of acne vulgaris in Japan includes a combination of topical treatment with benzoyl peroxide (BPO) and BPO/clindamycin (CLDM), topical adapalene and systemic antimicrobials. However, the treatment of therapy-resistant complications such as postinflammatory hyperpigmentation (PIH), erosions with inflamed red papules and atrophic scars has not been established. We performed chemical peeling with glycolic acid and iontophoresis with ascorbyl 2-phosphate 6-palmitate and DL-α-tocopherol phosphate for the treatment of PIH, erosions with inflamed red papules and non-inflamed atrophic scars in 31 patients with acne vulgaris (mild to severe severity), and evaluated the efficacy and safety of these interventions. In most of cases, there was remarkable improvement in PIH and erosions with inflamed red papules after treatment. There was also some improvement in non-inflamed atrophic scars without erythema. Mild redness and irritation was observed in four cases as adverse reactions. Early initial treatment of PIH and erosions with red papules by chemical peeling and iontophoresis is an effective and safe method to prevent the formation of atrophic scars in patients with acne vulgaris. © 2016 Japanese Dermatological Association.

Scientific Results from the FIRST Instrument Deployment to Cerro Toco, Chile and from the Flight of the INFLAME Instrument

NASA Technical Reports Server (NTRS)

Mlynczak, Martin G.; Cageao, Richard P.; Johnson, David G.

2011-01-01

Results from the FIRST and INFLAME infrared Fourier Transform Spectrometers are presented. These are comprehensive measurements of the far-IR spectrum (FIRST) and the net infrared fluxes within the atmosphere (INFLAME).

Increased penile expression of transforming growth factor and elevated systemic oxidative stress in rabbits with chronic partial bladder outlet obstruction.

PubMed

Lin, W-Y; Chang, P-J; Lin, Y-P; Wu, S-B; Chen, C-S; Levin, R M; Wei, Y-H

2012-02-01

There is a growing body of evidence to support the direct link between obstructive bladder dysfunction and erectile dysfunction (ED). However, there have been few pathophysiological studies to determine the relationship between lower urinary tract syndrome (LUTS) and ED. As the transforming growth factor-β1 (TGF-β1) that induces the synthesis of collagen in the penile tissues is critical for the development of ED, the first aim of this study was to investigate the expression of TGF-β1 in the penis from male rabbits with chronic partial bladder outlet obstruction (PBOO). Besides, it has been suggested that oxidative stress plays a significant role in the pathophysiological mechanism of ED. Thus, the second aim of this study was to further investigate whether the urinary or serum oxidative stress markers are involved in chronic PBOO-induced penile dysfunction. A total of 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO groups obstructed for 2, 4 and 8 weeks respectively. Using the RT-PCR and Western blot analysis, a progressive increase of TGF-β1 in penis was found at 2, 4 and 8 weeks after obstruction. Moreover, the biomarkers for oxidative stress or oxidative damage were significantly detected in the penis of rabbits after PBOO, which include the enhancement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and plasma, plasma malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as reduction of glutathione (GSH). On the basis of our results, the increase of TGF-β1 and elevated systemic oxidative stress may play key roles to contribute to penile dysfunction after chronic PBOO. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

Incidental gall bladder carcinoma in laparoscopic cholecystectomy: a report of 6 cases and a review of the literature.

PubMed

Sujata, Jetley; S, Rana; Sabina, Khan; Mj, Hassan; Jairajpuri, Zeeba Shamim

2013-01-01

Gall bladder carcinoma accounts for 98% of all the gall bladder malignancies and it is the sixth most common malignancy of the gastrointestinal tract worldwide. The incidence of incidental gall bladder carcinoma which is diagnosed during or after a laparoscopic cholecystectomy is reported to be around 0.19-3.3% in the literature. This study was aimed at detecting the incidence of gall bladder carcinomas which were diagnosed incidentally during or after laparoscopic cholecystectomies which were done for gall stone disease and cholecystitis. We analyzed the medical records of patients with symptomatic gallstone disease and acute or chronic cholecystitis, who underwent laparoscopic cholecystectomies at the Hakeem Abdul Hameed Centenary Hospital during the period from January 2007 to June 2012. A total of 622 laparoscopic cholecystectomies were performed at our institute during the study period of five and a half years. In 6 (0.96%) cases, incidental carcinomas of the gallbladder were discovered. A laparoscopic cholecystectomy which is performed for benign gall bladder disease rarely results in a diagnosis of unexpected gallbladder cancer. The microscopic examination of the specimens, with special attention to the depth of invasion, range of the mucosal spread and the lymphovascular involvement, is critical in diagnosing the incidental malignancies as well as for the subsequent management of the cases.

Use of mode of action data to inform a dose-response assessment for bladder cancer following exposure to inorganic arsenic.

PubMed

Gentry, P R; Yager, J W; Clewell, R A; Clewell, H J

2014-10-01

In the recent National Research Council report on conducting a dose-response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose-response curve. Recent in vitro mode of action studies focused on understanding the development of bladder cancer following exposure to inorganic arsenic provide data to inform the dose-response curve. These in vitro data, combined with results of bladder cancer epidemiology studies, inform the dose-response curve in the low-dose region, and include values for both pharmacokinetic and pharmacodynamic variability. Integration of these data provides evidence of a range of concentrations of arsenic for which no effect on the bladder would be expected. Specifically, integration of these results suggest that arsenic exposures in the range of 7-43 ppb in drinking water are exceedingly unlikely to elicit changes leading to key events in the development of cancer or noncancer effects in bladder tissue. These findings are consistent with the lack of evidence for bladder cancer following chronic ingestion of arsenic water concentrations <100 ppb in epidemiological studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cancer in Patients With Gabapentin (GPRD)

ClinicalTrials.gov

2017-06-06

Pain, Neuropathic; Epilepsy; Renal Pelvis Cancer; Pancreatic Cancer; Breast Cancer; Nervous System Cancer; Chronic Pancreatitis; Stomach Cancer; Renal Cell Carcinoma; Diabetes; Bladder Cancer; Bone and Joint Cancer; Penis Cancer; Anal Cancer; Cancer; Renal Cancer

Plasticity of non-adrenergic non-cholinergic bladder contractions in rats after chronic spinal cord injury

PubMed Central

Lai, H. Henry; Munoz, Alvaro; Smith, Christopher P.; Boone, Timothy B.; Somogyi, George T.

2011-01-01

The purpose of this study was to examine the pharmacologic plasticity of cholinergic, non-adrenergic non-cholinergic (NANC), and purinergic contractions in neurogenic bladder strips from spinal cord injured (SCI) rats. Bladder strips were harvested from female rats three to four weeks after T9–T10 spinal cord transection. The strips were electrically stimulated using two experimental protocols to compare the contribution of muscarinic and NANC/purinergic contractions in the presence and the absence of carbachol or muscarine. The endpoints of the study were: (1) percent NANC contraction that was unmasked by the muscarinic antagonist 4-DAMP, and (2) P2X purinergic contraction that was evoked by α,β–methylene ATP. NANC contraction accounted for 78.5% of the neurally evoked contraction in SCI bladders. When SCI bladder strips were treated with carbachol (10 µM) prior to 4-DAMP (500 nM), the percent NANC contraction decreased dramatically to only 13.1% of the neurally evoked contraction (p=0.041). This was accompanied by a substantial decrease in α,β–methylene ATP evoked P2X contraction, and desensitization of purinergic receptors (the ratio of subsequent over initial P2X contraction decreased from 97.2% to 42.1%, p=0.0017). Sequential activation of the cholinergic receptors with carbachol (or with muscarine in neurally intact bladders) and unmasking of the NANC response with 4-DAMP switched the neurally evoked bladder contraction from predominantly NANC to predominantly cholinergic. We conclude that activation of muscarinic receptors (with carbachol or muscarine) blocks NANC and purinergic contractions in neurally intact or in SCI rat bladders. The carbachol-induced inhibition of the NANC contraction is expressed more in SCI bladders compared to neurally intact bladders. Along with receptor plasticity, this change in bladder function may involve P2X-independent mechanisms. PMID:21689735

Urothelial dysfunction and chronic inflammation in patients with spinal cord injuries at different levels and correlation with urodynamic findings.

PubMed

Jiang, Yuan-Hong; Liu, Hsin-Tzu; Kuo, Hann-Chorng

2015-11-01

To investigate urothelial dysfunction and suburothelial inflammation in patients with chronic SCI at different spinal cord levels. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase (mast cell activation), and apoptosis tests on bladder biopsy specimens including urothelium and suburothelium were performed in 34 chronic SCI patients and 10 controls. Video-urodynamic studies were also analyzed and correlated with immunofluorescence findings. The mean interval from SCI to bladder biopsy was 9.3 ± 8.4 years. Patients with chronic SCI had significantly lower expression of E-cadherin (20.86 ± 14.07 vs. 42.40 ± 16.73, the fluorescence intensity per 4 µm(2)) and ZO-1 (5.54 ± 3.73 vs. 11.01 ± 5.66, the fluorescence intensity per 4 µm(2)) than controls (both P < 0.05). Additionally, suburothelial activated mast cells (16.60 ± 6.85 vs. 1.25 ± 1.15, positive cells per 100 cells) and apoptotic cell numbers (5.39 ± 4.86 vs. 0.08 ± 0.26, positive cells per 100 cells) were significantly higher than in controls (both P < 0.05). Immunofluorescence characteristics and video-urodynamic findings did not differ between patients with 15 cervical and 19 thoracic SCIs. Suburothelial activated mast cell numbers correlated negatively to E-cadherin expression in the urothelium (r = -0.559, P < 0.05). Additionally, apoptotic cell number correlated negatively with cystometric bladder capacity (r = -0.535, P < 0.05). Decreased expression of urothelial adhesion and junction proteins and increased suburothelial inflammation and apoptosis were found in patients with chronic SCI, regardless of injury level. Such mechanisms might contribute to the vulnerability of patients with SCI to cystitis and recurrent bacterial infections. © 2014 Wiley Periodicals, Inc.

Chronic Colovesical Fistula Leading to Chronic Urinary Tract Infection Resulting in End-Stage Renal Disease in a Chronic Granulomatous Disease Patient.

PubMed

Siddiqui, M R; Sanford, T; Nair, A; Zerbe, C S; Hughes, M S; Folio, L; Agarwal, Piyush K; Brancato, S J

2017-02-01

A 46-year old man with X-linked chronic granulomatous disease (CGD) being followed at the National Institute of Health with uncontrolled CGD colitis who developed chronic colovesical fistula, and end-stage renal disease (ESRD). Despite aggressive medical management of symptoms with immunomodulators and antibiotic prophylaxis, the chronic colovesical fistula led to chronic pyelonephritis, recurrent urinary tract infections, persistent air in the collecting system and bladder, and post-renal obstruction resulting in renal failure. Patient is now hemodialysis dependent and required diverting loop ileostomy placement. This report highlights multiple potential etiologies of rising serum creatinine in patients with CGD.

The basics of epithelial-mesenchymal transition.

PubMed

Kalluri, Raghu; Weinberg, Robert A

2009-06-01

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

Bladder overdistension with polyuria in a hypertensive rat model.

PubMed

Velasquez Flores, Monica; Mossa, Abubakr H; Cammisotto, Philippe; Campeau, Lysanne

2018-03-31

Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting. Male Dahl/SS rats, a hypertension model, received a high-salt or normal diet for 6 weeks. Twenty-four-hour water intake, micturition patterns, and blood pressures were recorded biweekly. Conscious cystometry was carried out at the end of this period. Bladders were collected to measure contractile force and for histological analysis. Paired t-tests were used to compare changes between Week 0 and Week 6 within each group. Unpaired t-tests were used for comparisons between groups for all parameters at Week 6. Six weeks of high-salt diet significantly increased water intake and total urine. Blood pressures and volume of urine per micturition was higher in rats on high-salt diet. Bladder overdistension in the high-salt diet group was confirmed by cystometry, shown by a significantly higher bladder capacity, and compliance. No difference in detrusor contractility was observed between both groups. Collagen content was significantly higher in the lamina propria of the high-salt group compared to the normal group, while the opposite was observed in the muscularis. Polyuria, in a hypertension context, leads to changes in bladder morphology and function. These findings help clarify the deleterious clinical impact of polyuria on voiding function, highlighting the variable consequences of bladder overdistension according to the underlying pathology. © 2018 Wiley Periodicals, Inc.

Xanthogranulomatous Cystitis: A Challenging Imitator of Bladder Cancer

PubMed Central

Ekici, Sinan; Dogan Ekici, Isin; Ruacan, Sevket; Midi, Ahmet

2010-01-01

Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature. PMID:20602075

Evaluation of mast cells in periapical cysts, dentigerous cysts, and keratocystic odontogenic tumors.

PubMed

de Noronha Santos Netto, Juliana; Pires, Fábio Ramôa; da Fonseca, Eliene Carvalho; Silva, Licínio Esmeraldo; de Queiroz Chaves Lourenço, Simone

2012-09-01

Several cell types are associated with the development of cystic and tumoral odontogenic lesions. Among inflammatory cells, mast cells can be associated with their pathogenesis. The aim of this study was to analyze mast cells in periapical cysts, dentigerous cysts, and keratocystic odontogenic tumors. Tissue sections were submitted to toluidine blue staining and immunohistochemistry with antibody anti-tryptase (clone G3). Mast cells were quantitated using Image-Pro Plus software to obtain the mean number of mast cells in three regions: epithelial, superficial portion of the fibrous wall and deep portion of the fibrous wall from 20 periapical cysts, 20 dentigerous cysts (six non-inflamed and 14 inflamed) and 20 keratocystic odontogenic tumors (four non-inflamed and 16 inflamed). The mean number of mast cells detected per lesion by immunohistochemistry (4.1) was higher than by histochemistry (1.5) (P<0.0001). Inflamed dentigerous cysts and keratocystic odontogenic tumors showed a higher mean number of mast cells than non-inflamed lesions in all regions. The deep region from all cysts showed the highest mean number of degranulated mast cells, except for non-inflamed keratocystic odontogenic tumors analyzed by immunohistochemistry. Immunohistochemical staining detected higher number of mast cells than histochemistry. The higher number of mast cells observed in inflamed lesions could indicate the participation of these cells in the inflammatory response in odontogenic lesions. The prevalence of degranulated mast cells in the deep region suggests intense activity of these cells, possibly related to growth of cystic lesions. © 2012 John Wiley & Sons A/S.

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

PubMed Central

2012-01-01

Background Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. Methods Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. Results A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). Conclusions A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC. PMID:22726388

Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo

NASA Astrophysics Data System (ADS)

Sakhalkar, Harshad S.; Dalal, Milind K.; Salem, Aliasger K.; Ansari, Ramin; Fu, Jie; Kiani, Mohammad F.; Kurjiaka, David T.; Hanes, Justin; Shakesheff, Kevin M.; Goetz, Douglas J.

2003-12-01

We exploited leukocyte-endothelial cell adhesion chemistry to generate biodegradable particles that exhibit highly selective accumulation on inflamed endothelium in vitro and in vivo. Leukocyte-endothelial cell adhesive particles exhibit up to 15-fold higher adhesion to inflamed endothelium, relative to noninflamed endothelium, under in vitro flow conditions similar to that present in blood vessels, a 6-fold higher adhesion to cytokine inflamed endothelium relative to non-cytokine-treated endothelium in vivo, and a 10-fold enhancement in adhesion to trauma-induced inflamed endothelium in vivo due to the addition of a targeting ligand. The leukocyte-inspired particles have adhesion efficiencies similar to that of leukocytes and were shown to target each of the major inducible endothelial cell adhesion molecules (E-selectin, P-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1) that are up-regulated at sites of pathological inflammation. The potential for targeted drug delivery to inflamed endothelium has significant implications for the improved treatment of an array of pathologies, including cardiovascular disease, arthritis, inflammatory bowel disease, and cancer.

Monocyte-mediated delivery of polymeric backpacks to inflamed tissues: a generalized strategy to deliver drugs to treat inflammation.

PubMed

Anselmo, Aaron C; Gilbert, Jonathan B; Kumar, Sunny; Gupta, Vivek; Cohen, Robert E; Rubner, Michael F; Mitragotri, Samir

2015-02-10

Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer's disease, Parkinson's disease, and arthritis, represents one of the major challenges in drug delivery. Monocytes possess a unique ability to target and penetrate into sites of inflammation. Here, we describe a broad approach to take advantage of the natural ability of monocytes to target and deliver flat polymeric particles ("Cellular Backpacks") to inflamed tissues. Cellular backpacks attach strongly to the surface of monocytes but do not undergo phagocytosis due to backpack's size, disk-like shape and flexibility. Following attachment of backpacks, monocytes retain important cellular functions including transmigration through an endothelial monolayer and differentiation into macrophages. In two separate in vivo inflammation models, backpack-laden monocytes exhibit increased targeting to inflamed tissues. Cellular backpacks, and their abilities to attach to monocytes without impairing monocyte functions and 'hitchhike' to a variety of inflamed tissues, offer a new platform for both cell-mediated therapies and broad targeting of inflamed tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

Cancer (stem) cell differentiation: An inherent or acquired property?

PubMed

Mohr, Marieke; Zänker, Kurt S; Dittmar, Thomas

2015-12-01

There is a growing list of data indicating that cancer (stem) cells could functionally adapt foreign tissue features, such as endothelial-like cells or neuroendocrine cells, express lineage markers or could differentiate into various lineages in response to appropriate differentiation criteria. The finding that cancer (stem) cells may possess some kind of differentiation capacity poses the question whether this might be an inherent or acquired property. Cancer stem cells share stem cell characteristics and may thus possess an inherent differentiation capacity enabling the cells to respond to various differentiation stimuli. Considering the plasticity of cancer (stem) cells, even non-tumorigenic (and putatively non-differentiable) tumor cells could give rise to tumorigenic tumor stem cells, exhibiting stem cell characteristics including an inherent differentiation capacity. On the contrary, cancer (stem) cells may have acquired differentiation capacity as a consequence of a previous cell fusion event with cell types exhibiting differentiation potential and being fusogenic, such as macrophages or stem cells. Of pivotal interest in a tumor context are macrophages, which chiefly foster the chronically inflamed tumor microenvironment. Because chronically inflamed tissue is a well-known trigger for cell fusion and both macrophages and stem cells are highly fusogenic we conclude that cell fusion events between these cell types and cancer (stem) cells should frequently occur, thereby giving rise to hybrid cells exhibiting not only novel properties, like an enhanced metastatogenic phenotype, but also parental characteristics, such as differentiation capacity. Conceivably, the combination of both properties might be advantageous for metastasizing cancer (stem) cells to adapt better and faster to a foreign organ tissue environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Direct evidence for a chronic CD8+-T-cell-mediated immune reaction to tax within the muscle of a human T-cell leukemia/lymphoma virus type 1-infected patient with sporadic inclusion body myositis.

PubMed

Ozden, Simona; Cochet, Madeleine; Mikol, Jacqueline; Teixeira, Antonio; Gessain, Antoine; Pique, Claudine

2004-10-01

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection can lead to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), concomitantly with or without other inflammatory disorders such as myositis. These pathologies are considered immune-mediated diseases, and it is assumed that migration within tissues of both HTLV-1-infected CD4(+) T cells and anti-HTLV-1 cytotoxic T cells represents a pivotal event. However, although HTLV-1-infected T cells were found in inflamed lesions, the antigenic specificity of coinfiltrated CD8(+) T cells remains to be determined. In this study, we performed both ex vivo and in situ analyses using muscle biopsies obtained from an HTLV-1-infected patient with HAM/TSP and sporadic inclusion body myositis. We found that both HTLV-1-infected CD4(+) T cells and CD8(+) T cells directed to the dominant Tax antigen can be amplified from muscle cell cultures. Moreover, we were able to detect in two successive muscle biopsies both tax mRNA-positive mononuclear cells and T cells recognized by the Tax11-19/HLA-A*02 tetramer and positive for perforin. These findings provide the first direct demonstration that anti-Tax cytotoxic T cells are chronically recruited within inflamed tissues of an HTLV-1 infected patient, which validates the cytotoxic immune reaction model for the pathogenesis of HTLV-1-associated inflammatory disease.

Acid-Sensitive Sheddable PEGylated PLGA Nanoparticles Increase the Delivery of TNF-α siRNA in Chronic Inflammation Sites

PubMed Central

Aldayel, Abdulaziz M; Naguib, Youssef W; O'Mary, Hannah L; Li, Xu; Niu, Mengmeng; Ruwona, Tinashe B; Cui, Zhengrong

2016-01-01

There has been growing interest in utilizing small interfering RNA (siRNA) specific to pro-inflammatory cytokines, such as tumor necrosis factor-α ( TNF-α), in chronic inflammation therapy. However, delivery systems that can increase the distribution of the siRNA in chronic inflammation sites after intravenous administration are needed. Herein we report that innovative functionalization of the surface of siRNA-incorporated poly (lactic-co-glycolic) acid (PLGA) nanoparticles significantly increases the delivery of the siRNA in the chronic inflammation sites in a mouse model. The TNF-α siRNA incorporated PLGA nanoparticles were prepared by the standard double emulsion method, but using stearoyl-hydrazone-polyethylene glycol 2000, a unique acid-sensitive surface active agent, as the emulsifying agent, which renders (i) the nanoparticles PEGylated and (ii) the PEGylation sheddable in low pH environment such as that in chronic inflammation sites. In a mouse model of lipopolysaccharide-induced chronic inflammation, the acid-sensitive sheddable PEGylated PLGA nanoparticles showed significantly higher accumulation or distribution in chronic inflammation sites than PLGA nanoparticles prepared with an acid-insensitive emulsifying agent (i.e., stearoyl-amide-polyethylene glycol 2000) and significantly increased the distribution of the TNF-α siRNA incorporated into the nanoparticles in inflamed mouse foot. PMID:27434685

Autofluorescence imaging to optimize 5-ALA-induced fluorescence endoscopy of bladder carcinoma.

PubMed

Frimberger, D; Zaak, D; Stepp, H; Knüchel, R; Baumgartner, R; Schneede, P; Schmeller, N; Hofstetter, A

2001-09-01

To design an optical system for detecting autofluorescence (AF) of bladder tumors and to determine the success of reducing the false-positive rate of 5-aminolevulinic acid-induced fluorescence endoscopy (AFE). AFE provides significantly higher sensitivity in detecting and localizing bladder carcinoma compared with white light endoscopy. The specificity of AFE is equivalent to white light endoscopy, mostly because of the false-positive fluorescence of chronic cystitis lesions. Laser-induced spectral autofluorescence detection is also an efficient method in the diagnosis of bladder carcinoma. Bladder tissue was excited to AF using the D-Light (375 to 440 nm) after regular AFE with detection of fluorescence-positive areas. The optical image was produced using a special RGB camera. Biopsies were taken from AFE-positive areas, the peritumoral edges, and normal bladder mucosa. The AF images of the suspicious areas were compared with the AFE images and the histologic results. A total of 43 biopsies were histologically examined (24 benign and 19 neoplastic). AF imaging showed contrast differences between papillary tumors, flat lesions, and normal mucosa. The combination of AFE with AF raised the specificity of AFE alone from 67% to 88%. AF imaging is possible. The value of the method in reducing the false-positive rate of the highly sensitive AFE needs to be validated with higher numbers. The combination of AF with AFE had a 20% higher specificity than AFE alone in our study.

Incidental Gall Bladder Carcinoma in Laparoscopic Cholecystectomy: A Report of 6 Cases and a Review of the Literature

PubMed Central

Sujata, Jetley; S, Rana; Sabina, Khan; MJ, Hassan; Jairajpuri, Zeeba Shamim

2013-01-01

Background: Gall bladder carcinoma accounts for 98% of all the gall bladder malignancies and it is the sixth most common malignancy of the gastrointestinal tract worldwide. The incidence of incidental gall bladder carcinoma which is diagnosed during or after a laparoscopic cholecystectomy is reported to be around 0.19-3.3% in the literature. Aim: This study was aimed at detecting the incidence of gall bladder carcinomas which were diagnosed incidentally during or after laparoscopic cholecystectomies which were done for gall stone disease and cholecystitis. Materials and Methods: We analyzed the medical records of patients with symptomatic gallstone disease and acute or chronic cholecystitis, who underwent laparoscopic cholecystectomies at the Hakeem Abdul Hameed Centenary Hospital during the period from January 2007 to June 2012. Results: A total of 622 laparoscopic cholecystectomies were performed at our institute during the study period of five and a half years. In 6 (0.96%) cases, incidental carcinomas of the gallbladder were discovered. Conclusion: A laparoscopic cholecystectomy which is performed for benign gall bladder disease rarely results in a diagnosis of unexpected gallbladder cancer. The microscopic examination of the specimens, with special attention to the depth of invasion, range of the mucosal spread and the lymphovascular involvement, is critical in diagnosing the incidental malignancies as well as for the subsequent management of the cases. PMID:23449518

Decreased microbiota diversity associated with urinary tract infection in a trial of bacterial interference.

PubMed

Horwitz, Deborah; McCue, Tyler; Mapes, Abigail C; Ajami, Nadim J; Petrosino, Joseph F; Ramig, Robert F; Trautner, Barbara W

2015-09-01

Patients with long-term indwelling catheters are at high risk of catheter-associated urinary tract infection (CAUTI). We hypothesized that colonizing the bladder with a benign Escherichia coli strain (E. coli HU2117, a derivative of E. coli 83972) would prevent CAUTI in older, catheterized adults. Adults with chronic, indwelling urinary catheters received study catheters that had been pre-coated with E. coli HU2117. We monitored the cultivatable organisms in the bladder for 28 days or until loss of E. coli HU2117. Urine from 4 subjects was collected longitudinally for 16S rRNA gene profiling. Eight of the ten subjects (average age 70.9 years) became colonized with E. coli HU2117, with a mean duration of 57.7 days (median: 28.5, range 0-266). All subjects also remained colonized by uropathogens. Five subjects suffered invasive UTI, 3 febrile UTI and 2 urosepsis/bacteremia, all associated with overgrowth of a urinary pathogen. Colonization with E. coli HU2117 did not impact bacterial bladder diversity, but subjects who developed infections had less diverse bladder microbiota. Colonization with E. coli HU2117 did not prevent bladder colonization or subsequent invasive disease by uropathogens. Microbial diversity may play a protective role against invasive infection of the catheterized bladder. ClinicalTrials.gov, NCT00554996 http://clinicaltrials.gov/ct2/show/NCT00554996. Published by Elsevier Ltd.

Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

PubMed

Alberti, C

2016-01-01

To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering.Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either "unseeded" (cell free) or autologous "cell seeded" tissue engineering scaffolds. Different categories of cell sources - from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells - have been taken into consideration to reach the construction of suitable "cell seeded" templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications.

Smooth muscle membrane organization in the normal and dysfunctional human urinary bladder: a structural analysis.

PubMed

Burkhard, Fiona C; Monastyrskaya, Katia; Studer, Urs E; Draeger, Annette

2005-01-01

The decline in contractile properties is a characteristic feature of the dysfunctional bladder as a result of infravesical outlet obstruction. During clinical progression of the disease, smooth muscle cells undergo structural modifications. Since adaptations to constant changes in length require a high degree of structural organization within the sarcolemma, we have investigated the expression of several proteins, which are involved in smooth muscle membrane organization, in specimens derived from normal and dysfunctional organs. Specimen from patients with urodynamically normal/equivocal (n = 4), obstructed (n = 2), and acontractile (n = 2) bladders were analyzed relative to their structural features and sarcolemmal protein profile. Smooth muscle cells within the normal urinary bladder display a distinct sarcolemmal domain structure, characterized by firm actin-attachment sites, alternating with flexible "hinge" regions. In obstructed bladders, foci of cells displaying degenerative sarcolemmal changes alternate with areas of hypertrophic cells in which the membrane appears unaffected. In acontractile organs, the overall membrane structure remains intact, however annexin 6, a protein belonging to a family of Ca2+-dependent, "membrane-organizers," is downregulated. Degenerative changes in smooth muscle cells, which are chronically working against high resistance, are preferentially located within the actin-attachment sites. In acontractile bladders, the downregulation of annexin 6 might have a bearing on the fine-tuning of the plasma membrane during contraction/relaxation cycles. Copyright 2005 Wiley-Liss, Inc.

Increased TRPV4 expression in urinary bladder and lumbosacral dorsal root ganglia in mice with chronic overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Merrill, Liana; Malley, Susan; Vizzard, Margaret A

2013-10-01

Transient receptor potential vanilloid (TRPV) family member 4 (TRPV4) expression has been demonstrated in urothelial cells and dorsal root ganglion (DRG) neurons, and roles in normal micturition reflexes as well as micturition dysfunction have been suggested. TRP channel expression and function is dependent upon target tissue expression of growth factors. These studies expand upon the target tissue dependence of TRPV4 expression in the urinary bladder and lumbosacral DRG using a recently characterized transgenic mouse model with chronic overexpression of nerve growth factor (NGF-OE) in the urothelium. Immunohistochemistry with image analyses, real-time quantitative polymerase chain reaction, and Western blotting were used to determine TRPV4 protein and transcript expression in the urinary bladder (urothelium + suburothelium, detrusor) and lumbosacral DRG from littermate wild-type (WT) and NGF-OE mice. Antibody specificity controls were performed in TRPV4(-/-) mice. TRPV4 transcript and protein expression was significantly (p ≤ 0.001) increased in the urothelium + suburothelium and suburothelial nerve plexus of the urinary bladder and in small- and medium-sized lumbosacral (L1, L2, L6-S1) DRG cells from NGF-OE mice compared to littermate WT mice. NGF-OE mice exhibit significant (p ≤ 0.001) increases in NGF transcript and protein in the urothelium + suburothelium and lumbosacral DRG. These studies demonstrate regulation of TRPV4 expression by NGF in lower urinary tract tissues. Ongoing studies are characterizing the functional roles of TRPV4 expression in the sensory limb (DRG, urothelium) of the micturition reflex.

Extracorporeal shock wave markedly alleviates radiation-induced chronic cystitis in rat

PubMed Central

Chen, Yen-Ta; Chen, Kuan-Hung; Sung, Pei-Hsun; Yang, Chih-Chao; Cheng, Ben-Chung; Chen, Chih-Hung; Chang, Chia-Lo; Sheu, Jiunn-Jye; Lee, Fan-Yen; Shao, Pei-Lin; Sun, Cheuk-Kwan; Yip, Hon-Kan

2018-01-01

This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can effectively inhibit radiation-induced chronic cystitis (CC). Adult male Sprague-Dawley (SD) rats (n = 24) were randomly divided into group 1 (normal control), group 2 (CC induced by radiation with 300 cGy twice with a four-hour interval to the urinary bladder), group 3 [CC with ECSW treatment (0.2 mJ/mm2/120 impulses/at days 1, 7, and 14 after radiation)]. Bladder specimens were harvested by day 28 after radiation. By day 28 after radiation, the degree of detrusor contraction impairment was significantly higher in group 2 than that in groups 1 and 3, and significantly higher in group 3 than that in group 1 (P<0.0001). The urine albumin concentration expressed an opposite pattern compared to that of detrusor function among the three groups (P<0.0001). The bladder protein expressions of inflammatory (TLR-2/TLR-4/IL-6/IL-12/MMP-9/TNF-α/NF-κB/RANTES/iNOS) and oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers exhibited a pattern identical to that of urine albumin in all groups (all P<0.0001). The cellular expressions of inflammatory (CD14+/CD68+/CD74+/COX-2/MIF+/substance P+) and cytokeratin (CK13+/HMW CK+/CK+17/CK+18/CK+19) biomarkers, and collagen-deposition/fibrotic areas as well as epithelial-damaged score displayed an identical pattern compared to that of urine albumin among the three groups (all P<0.0001). In conclusion, ECSW treatment effectively protected urinary bladder from radiation-induced CC. PMID:29636892

INCREASED TRPV4 EXPRESSION IN URINARY BLADDER AND LUMBOSACRAL DORSAL ROOT GANGLIA IN MICE WITH CHRONIC OVEREXPRESSION OF NGF IN UROTHELIUM

PubMed Central

Girard, Beatrice M.; Merrill, Liana; Malley, Susan; Vizzard, Margaret A.

2013-01-01

Transient receptor potential vanilloid (TRPV) family member 4 (TRPV4) expression has been demonstrated in urothelial cells and dorsal root ganglion (DRG) neurons and roles in normal micturition reflexes as well as micturition dysfunction have been suggested. TRP channel expression and function is dependent upon target tissue expression of growth factors. These studies expand upon the target tissue dependence of TRPV4 expression in the urinary bladder and lumbosacral DRG using a recently characterized transgenic mouse model with chronic overexpression of nerve growth factor (NGF-OE) in the urothelium. Immunohistochemistry with image analyses, real-time quantitative polymerase chain reaction (Q-PCR) and western blotting were used to determine TRPV4 protein and transcript expression in the urinary bladder (urothelium + suburothelium, detrusor) and lumbosacral DRG from littermate wildtype (WT) and NGF-OE mice. Antibody specificity controls were performed in TRPV4-/- mice. TRPV4 transcript and protein expression was significantly (p ≤ 0.001) increased in the urothelium + suburothelium and suburothelial nerve plexus of the urinary bladder and in small- and medium-sized lumbosacral (L1, L2, L6-S1) DRG cells from NGF-OE mice compared to littermate WT mice. NGF-OE mice exhibit significant (p ≤ 0.001) increases in NGF transcript and protein in the urothelium + suburothelium and lumbosacral DRG. These studies demonstrate regulation of TRPV4 expression by NGF in lower urinary tract tissues. Ongoing studies are characterizing the functional roles of TRPV4 expression in the sensory limb (DRG, urothelium) of the micturition reflex. PMID:23690258

Analysis of in situ proliferative activity in oral gingival epithelium in patients with xerostomia.

PubMed

Celenligil-Nazliel, Haviye; Palali, Ali; Ayhan, Ayşe; Ruacan, Sevket

2003-02-01

Sjögren's syndrome is an autoimmune disease characterized by xerostomia and keratoconjunctivitis sicca. The relationship between xero-stomia and proliferative activity in human gingival epithelium is not known. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. The aims of this study were to evaluate PCNA expression in oral gingival epithelium of healthy and inflamed gingiva obtained from patients with Sjögren's syndrome, and to compare the results to age- and gender-matched subjects with normal salivary function. Eighteen Sjögren's syndrome patients and 28 controls (14 with chronic periodontitis and 14 with no clinical evidence of periodontal disease) were included in the study. Biopsies were obtained from both inflamed and healthy gingiva. The expression of PCNA was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and PC10 monoclonal antibody to PCNA. PCNA expression was observed both in the basal and suprabasal layers, and was found to be more prominent in the suprabasal layers. Proliferative index (PI) in inflamed gingiva was significantly lower in the Sjögren's syndrome group. However, no significant difference was observed between the study and control groups with respect to PI in healthy gingiva. In both groups, PI was found to be increased due to inflammation. Our data indicate that proliferative activity is observed in the suprabasal layers and, less frequently, in the basal layer. Inflammation caused increased proliferative activity. However, this positive effect of inflammation on epithelial cell proliferation decreased significantly with a lack of saliva. Therefore, it appears that saliva-derived biological mediators may also contribute to increased proliferative activity observed during inflammation.

Mesenchymal stem cells induce epithelial proliferation within the inflamed stomach.

PubMed

Donnelly, Jessica M; Engevik, Amy; Feng, Rui; Xiao, Chang; Boivin, Gregory P; Li, Jing; Houghton, JeanMarie; Zavros, Yana

2014-06-15

Bone marrow-derived mesenchymal stem cells (MSCs) sustain cancer cells by creating a microenvironment favorable for tumor growth. In particular, MSCs have been implicated in gastric cancer development. There is extensive evidence suggesting that Hedgehog signaling regulates tumor growth. However, very little is known regarding the precise roles of Hedgehog signaling and MSCs in tumor development within the stomach. The current study tests that hypothesis that Sonic Hedgehog (Shh), secreted from MSCs, provides a proliferative stimulus for the gastric epithelium in the presence of inflammation. Red fluorescent protein-expressing MSCs transformed in vitro (stMSCs) were transduced with lentiviral constructs containing a vector control (stMSC(vect)) or short hairpin RNA (shRNA) targeting the Shh gene (stMSC(ShhKO)). Gastric submucosal transplantation of wild-type MSCs (wtMSCs), wild-type MSCs overexpressing Shh (wtMSC(Shh)), stMSC(vect), or stMSC(ShhKO) cells in C57BL/6 control (BL/6) or gastrin-deficient (GKO) mice was performed and mice analyzed 30 and 60 days posttransplantation. Compared with BL/6 mice transplanted with wtMSC(Shh) and stMSC(vect) cells, inflamed GKO mice developed aggressive gastric tumors. Tumor development was not observed in mouse stomachs transplanted with wtMSC or stMSC(ShhKO) cells. Compared with stMSC(ShhKO)-transplanted mice, within the inflamed GKO mouse stomach, Shh-expressing stMSC(vect)- and wtMSC(Shh)-induced proliferation of CD44-positive cells. CD44-positive cells clustered in gland-like structures within the tumor stroma and were positive for Patched (Ptch) expression. We conclude that Shh, secreted from MSCs, provides a proliferative stimulus for the gastric epithelium that is associated with tumor development, a response that is sustained by chronic inflammation. Copyright © 2014 the American Physiological Society.

Mesenchymal stem cells induce epithelial proliferation within the inflamed stomach

PubMed Central

Donnelly, Jessica M.; Engevik, Amy; Feng, Rui; Xiao, Chang; Boivin, Gregory P.; Li, Jing; Houghton, JeanMarie

2014-01-01

Bone marrow-derived mesenchymal stem cells (MSCs) sustain cancer cells by creating a microenvironment favorable for tumor growth. In particular, MSCs have been implicated in gastric cancer development. There is extensive evidence suggesting that Hedgehog signaling regulates tumor growth. However, very little is known regarding the precise roles of Hedgehog signaling and MSCs in tumor development within the stomach. The current study tests that hypothesis that Sonic Hedgehog (Shh), secreted from MSCs, provides a proliferative stimulus for the gastric epithelium in the presence of inflammation. Red fluorescent protein-expressing MSCs transformed in vitro (stMSCs) were transduced with lentiviral constructs containing a vector control (stMSCvect) or short hairpin RNA (shRNA) targeting the Shh gene (stMSCShhKO). Gastric submucosal transplantation of wild-type MSCs (wtMSCs), wild-type MSCs overexpressing Shh (wtMSCShh), stMSCvect, or stMSCShhKO cells in C57BL/6 control (BL/6) or gastrin-deficient (GKO) mice was performed and mice analyzed 30 and 60 days posttransplantation. Compared with BL/6 mice transplanted with wtMSCShh and stMSCvect cells, inflamed GKO mice developed aggressive gastric tumors. Tumor development was not observed in mouse stomachs transplanted with wtMSC or stMSCShhKO cells. Compared with stMSCShhKO-transplanted mice, within the inflamed GKO mouse stomach, Shh-expressing stMSCvect- and wtMSCShh-induced proliferation of CD44-positive cells. CD44-positive cells clustered in gland-like structures within the tumor stroma and were positive for Patched (Ptch) expression. We conclude that Shh, secreted from MSCs, provides a proliferative stimulus for the gastric epithelium that is associated with tumor development, a response that is sustained by chronic inflammation. PMID:24789207

Oxygen sensing in intestinal mucosal inflammation.

PubMed

Flück, Katharina; Fandrey, Joachim

2016-01-01

Hypoxia is a hallmark of chronically inflamed tissue. Hypoxia develops from vascular dysfunction and increased oxygen consumption by infiltrating leukocytes. With respect to inflammatory bowel disease (IBD), hypoxia is likely to be of particular importance: Impairment of the intestinal barrier during IBD allows anoxia from the lumen of the gut to spread to formerly normoxic tissue. In addition, disturbed perfusion of inflamed tissue and a higher oxygen demand of infiltrating immune cells lead to low oxygen levels in inflamed mucosal tissue. Here, cells become hypoxic and must now adapt to this condition. The hypoxia inducible factor (HIF)-1 complex is a key transcription factor for cellular adaption to low oxygen tension. HIF-1 is a heterodimer formed by two subunits: HIF-α (either HIF-1α or HIF-2α) and HIF-1β. Under normoxic conditions, hydroxylation of the HIF-α subunit by specific oxygen-dependent prolyl hydroxylases (PHDs) leads to ubiquitin proteasome-dependent degradation. Under hypoxic conditions, however, PHD activity is inhibited; thus, HIF-α can translocate into the nucleus, dimerize with HIF-1β, and bind to hypoxia-responsive elements of HIF-1 target genes. So far, most studies have addressed the function of HIF-1α in intestinal epithelial cells and the effect of HIF stabilization by PHD inhibitors in murine models of colitis. Furthermore, the role of HIF-1α in immune cells becomes more and more important as T cells or dendritic cells for which HIF-1 is of critical importance are highly involved in the pathogenesis of IBD. This review will summarize the function of HIF-1α and the therapeutic prospects for targeting the HIF pathway in intestinal mucosal inflammation.

Functional and molecular characterization of kinin B1 and B 2 receptors in human bladder cancer: implication of the PI3Kγ pathway.

PubMed

Sgnaolin, V; Pereira, T C B; Bogo, M R; Zanin, R; Battastini, A M O; Morrone, F B; Campos, M M

2013-08-01

Kinins and their receptors have been recently implicated in cancer. Using functional and molecular approaches, we investigated the relevance of kinin B1 and B2 receptors in bladder cancer. Functional studies were conducted using bladder cancer cell lines, and human biopsies were employed for molecular studies. Both B1 des-Arg(9)-BK and B2 BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells. Furthermore, treatment with B1 and B2 receptor antagonists (SSR240612 and HOE140) markedly inhibited the proliferation of T24 cells. Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4, while des-Arg(9)-BK completely failed to induce its proliferation. Real-time PCR revealed that the mRNA expression of kinin receptors, particularly B1 receptors, was increased in T24 cells relative to RT4 cells. Data from bladder cancer human biopsies revealed that B1 receptor expression was increased in all tumor samples and under conditions of chronic inflammation. We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ (phosphatidylinositol 3-kinase) with AS252424, concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK. Finally, the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways, whereas p38 MAP kinase remained unaffected. Kinin receptors, especially B1 receptors, appear to be implicated in bladder cancer progression. It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer.

Efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer.

PubMed

Lee, Jae Seung; Lee, Seo Yeon; Kim, Woo Jung; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Jeong, Byong Chang

2012-12-01

The aim of this study was to evaluate the efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer. In a prospective design, we included patients who had a bladder lesion suggesting bladder cancer. Patients with massive hematuria, urethral Foley catheter insertion, chronic retention state, or urinary tract infection were excluded. After the bladder was emptied, hexaminolevulinate was gently administered into the bladder. One hour later, cystoscopy under white light and blue light was performed. After marking the lesions confirmed with white light or blue light, transurethral resection of the bladder lesion and pathologic confirmation were done. Transurethral resection of the lesions that were negative in both white and blue light was also performed. From April 2010 to September 2010, 30 patients were enrolled. From the total of 30 patients (25 men and 5 women; mean age, 60.4±9.22 years), 134 specimens were extracted. Among these, 101 specimens showed positive results by blue light cystoscopy (BLC). The sensitivity of BLC and white light cystoscopy (WLC) was 92.3% and 80.8%, respectively (p=0.021). The specificity of BLC and WLC was 48% and 49.1%, respectively (p>0.05). The positive and negative predictive values of BLC were 71.2% and 81.8%, respectively, whereas those of WLC were 72.0% and 68.6%, respectively. With WLC, 48 specimens showed negative findings, but of that group, 15 specimens (31.2%) were revealed to be malignant with BLC. There were no significant side effects in the 24 hours after the instillation of hexaminolevulinate. Photodynamic diagnosis with hexaminolevulinate helps to find tumors that could be missed by use of WLC only. Photodynamic diagnosis might be valuable in complete resection as well as for more accurate diagnosis of bladder tumor.

A Murine Model for Escherichia coli Urinary Tract Infection.

PubMed

Hannan, Thomas J; Hunstad, David A

2016-01-01

Urinary tract infections (UTI) are among the most common bacterial infections of humans. The mouse provides an excellent and tractable model system for cystitis and pyelonephritis caused by Escherichia coli and other uropathogens. Using a well-established model of experimental cystitis in which the bladders of female mice are infected via transurethral catheterization, the molecular details of the pathogenesis of bacterial cystitis have been substantially illuminated in the last decade. Uropathogenic E. coli attach to bladder epithelium (both in human and mouse) via adhesive type 1 pili, establish a replicative niche within epithelial cell cytoplasm, and form intracellular bacterial communities that are protected from antibiotic effects and immune clearance. The use of different inbred and mutant mouse strains offers the opportunity to study outcomes of infection, including resolution, formation of quiescent intracellular bacterial reservoirs, chronic bacterial cystitis, and recurrent infections. Urine, bladder, and kidney tissues can be analyzed by bacterial culture, histology, immunohistochemistry, immunofluorescent and confocal microscopy, electron microscopy, and flow cytometry, while a broad array of soluble markers (e.g., cytokines) can also be profiled in serum, urine, and tissue homogenates by ELISA, Western blotting, multiplex bead array, and other approaches. This model promises to afford continued opportunity for discovery of pathogenic mechanisms and evaluation of therapeutic and preventive strategies for acute, chronic, and recurrent UTI.

TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS

EPA Science Inventory

Arsenic exposure has been associated with increased risk of skin, lung and bladder cancer in humans. The mechanisms of carcinogenesis are not well understood. Telomerase, a ribonucleoprotein containing human telomerase reverse transcriptase (hTERT), can extend telomeres of eukary...

Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation.

PubMed

Peruzzotti-Jametti, Luca; Bernstock, Joshua D; Vicario, Nunzio; Costa, Ana S H; Kwok, Chee Keong; Leonardi, Tommaso; Booty, Lee M; Bicci, Iacopo; Balzarotti, Beatrice; Volpe, Giulio; Mallucci, Giulia; Manferrari, Giulia; Donegà, Matteo; Iraci, Nunzio; Braga, Alice; Hallenbeck, John M; Murphy, Michael P; Edenhofer, Frank; Frezza, Christian; Pluchino, Stefano

2018-03-01

Neural stem cell (NSC) transplantation can influence immune responses and suppress inflammation in the CNS. Metabolites, such as succinate, modulate the phenotype and function of immune cells, but whether and how NSCs are also activated by such immunometabolites to control immunoreactivity and inflammatory responses is unclear. Here, we show that transplanted somatic and directly induced NSCs ameliorate chronic CNS inflammation by reducing succinate levels in the cerebrospinal fluid, thereby decreasing mononuclear phagocyte (MP) infiltration and secondary CNS damage. Inflammatory MPs release succinate, which activates succinate receptor 1 (SUCNR1)/GPR91 on NSCs, leading them to secrete prostaglandin E2 and scavenge extracellular succinate with consequential anti-inflammatory effects. Thus, our work reveals an unexpected role for the succinate-SUCNR1 axis in somatic and directly induced NSCs, which controls the response of stem cells to inflammatory metabolic signals released by type 1 MPs in the chronically inflamed brain. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Expression and Function of Chemokines CXCL9-11 in Micturition Pathways in Cyclophosphamide (CYP)-Induced Cystitis and Somatic Sensitivity in Mice

PubMed Central

Guo, Michael; Chang, Phat; Hauke, Eric; Girard, Beatrice M.; Tooke, Katharine; Ojala, Jacqueline; Malley, Susan M.; Hsiang, Harrison; Vizzard, Margaret A.

2018-01-01

Changes in urinary bladder function and somatic sensation may be mediated, in part, by inflammatory changes in the urinary bladder including the expression of chemokines. Male and female C57BL/6 mice were treated with cyclophosphamide (CYP; 75 mg/kg, 200 mg/kg, i.p.) to induce bladder inflammation (4 h, 48 h, chronic). We characterized the expression of CXC chemokines (CXCL9, CXCL10 and CXCL11) in the urinary bladder and determined the effects of blockade of their common receptor, CXCR3, at the level urinary bladder on bladder function and somatic (hindpaw and pelvic) sensation. qRT-PCR and Enzyme-Linked Immunoassays (ELISAs) were used to determine mRNA and protein expression of CXCL9, CXCL10 and CXCL11 in urothelium and detrusor. In urothelium of female mice treated with CYP, CXCL9 and CXCL10 mRNA significantly (p ≤ 0.01) increased with CYP treatment whereas CXC mRNA expression in the detrusor exhibited both increases and decreases in expression with CYP treatment. CXC mRNA expression urothelium and detrusor of male mice was more variable with both significant (p ≤ 0.01) increases and decreases in expression depending on the specific CXC chemokine and CYP treatment. CXCL9 and CXCL10 protein expression was significantly (p ≤ 0.01) increased in the urinary bladder with 4 h CYP treatment in female mice whereas CXC protein expression in the urinary bladder of male mice did not exhibit an overall change in expression. CXCR3 blockade with intravesical instillation of AMG487 (5 mg/kg) significantly (p ≤ 0.01) increased bladder capacity, reduced voiding frequency and reduced non-voiding contractions in female mice treated with CYP (4 h, 48 h). CXCR3 blockade also reduced (p ≤ 0.01) hindpaw and pelvic sensitivity in female mice treated with CYP (4 h, 48 h). CXC chemokines may be novel targets for treating urinary bladder dysfunction and somatic sensitization resulting from urinary bladder inflammation. PMID:29681802

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Jun; Wanibuchi, Hideki; Waalkes, Michael P.

Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects ofmore » MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.« less

Skin bridging secondary to ingrown toenail

PubMed Central

Dadaci, Mehmet; Ince, Bilsev; Altuntas, Zeynep; Kamburoglu, Haldun Onuralp; Bitik, Ozan

2014-01-01

Ingrown toenails are painful conditions that especially affect young people and may become chronic if not treated. We describe a case of chronically inflamed ingrown toenail left untreated for three years. In the physical examination, skin bridging and epithelialization was observed in midline secondary to soft tissue hypertrophy of the lateral nail matrixes. Epithelized fibrous tissue was cut across the lateral nail matrix and left for secondary healing. Partial matrixectomy was applied and the remnants were cauterized in compliance with the Winograd procedure after removal of the nail. Our case is an advanced condition which is the second report in the literature. Skin bridging secondary to excess soft tissue hypertrophy can be observed in untreated bilateral Heinfert or Frost stage 3 ingrown nails. This rare case can be classified as advanced stage 3 disease or stage 4. PMID:25674152

Pelvic Floor Muscle Training to Manage Overactive Bladder and Urinary Incontinence.

PubMed

Angelini, Kimberly

Overactive bladder (OAB) and urinary incontinence (UI) are common chronic conditions that can negatively affect women's quality of life. Pelvic floor muscle training is the first-line treatment. Two recent Cochrane Reviews examining pelvic floor muscle training for the treatment of UI and OAB are summarized here to provide women's health nurses with current recommendations for UI and OAB management. This column also identifies practice improvement education in the area of pelvic floor muscle training and treatment for OAB and UI. © 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

Primary Localized Vesical Amyloidosis Mimicking Bladder Carcinoma: A Case Report

PubMed Central

Patil, Purwa R.; Warpe, Bhushan M.

2016-01-01

Amyloidosis of urinary bladder is a rare condition and may be primary or secondary in nature. A case of primary localized vesical amyloidosis (VA) in a 40-yr-old man is described which was confused with neoplasm by cystoscopic, urographic and other studies. Surgical specimens obtained by transurethral resection (TUR) were diagnostic and histologically revealed amyloid deposits in sub-epithelial stroma with chronic inflammatory and giant-cell reaction. Congo-red staining proved its amyloid nature. It was resistant to potassium permanganate (KMnO4) pretreatment, indicating it to be of the AL type. PMID:28974964

Long-term complications following bladder augmentations in patients with spina bifida: bladder calculi, perforation of the augmented bladder and upper tract deterioration.

PubMed

Husmann, Douglas A

2016-02-01

We desire to review our experience with bladder augmentation in spina bifida patients followed in a transitional and adult urologic practice. This paper will specifically focus on three major complications: bladder calculi, the most frequent complication found following bladder augmentation, perforation of the augmentation, its most lethal complication and finally we will address loss of renal function as a direct result of our surgical reconstructive procedures. We reviewed a prospective data base maintained on patients with spina bifida followed in our transitional and adult urology clinic from 1986 to date. Specific attention was given to patients who had developed bladder calculi, sustained a spontaneous perforation of the augmented bladder or had developed new onset of renal scarring or renal insufficiency (≥ stage 3 renal failure) during prolonged follow-up. The development of renal stones (P<0.05) and symptomatic urinary tract infections (P<0.0001) were found to be significantly reduced by the use of high volume (≥240 mL) daily bladder wash outs. Individuals who still developed bladder calculi recalcitrant to high volume wash outs were not benefited by the correction of underlying metabolic abnormalities or mucolytic agents. Spontaneous bladder perforations in the adult patient population with spina bifida were found to be directly correlated to substance abuse and noncompliance with intermittent catheterization, P<0.005. Deterioration of the upper tracts as defined by the new onset of renal scars occurred in 40% (32/80) of the patients managed by a ileocystoplasty and simultaneous bladder neck outlet procedure during a median follow-up interval 14 years (range, 8-45 years). Development of ≥ stage 3 chronic renal failure occurred within 38% (12/32) of the patients with scarring i.e., 15% (12/80) of the total patient population. Prior to the development of the renal scarring, 69% (22/32) of the patients had been noncompliant with intermittent catheterization. The onset of upper tract deterioration (i.e., new scar formation, hydronephrosis, calculus development, decrease in renal function) was silent, that is, clinically asymptomatic in one third (10/32 pts). This paper documents the need for high volume bladder irrigations to both prevent the most common complication following bladder augmentation, which is the development of bladder calculi and to reduce the incidence of symptomatic urinary tract infections. It provides a unique perspective regarding the impact of substance abuse and patient non-compliance with medical directives as being both the most common cause for both spontaneous bladder rupture following augmentation cystoplasty and for deterioration of the upper tracts. These findings should cause the surgeon to reflect on his/her assessment of a patient prior to performing a bladder augmentation procedure and stress the need for close follow-up.

Women's experiences of living with neurogenic bladder and bowel after spinal cord injury: life controlled by bladder and bowel.

PubMed

Nevedal, Andrea; Kratz, Anna L; Tate, Denise G

2016-01-01

Neurogenic bladder and bowel (NBB) is a chronic condition hindering the functioning and quality of life (QOL) of people with spinal cord injury (SCI). NBB research has focused on men with SCI leaving unanswered questions about women's experiences of living with NBB. The purpose of this study was to identify and describe women's experiences of living with SCI and NBB. Secondary analysis of semi-structured interviews from a larger qualitative study of women with SCI (N = 50) was carried out. Transcripts were coded for bowel and bladder content. Pile-sorting techniques were used to identify emergent themes related to NBB. Meta-themes were categorized under the International Classification of Functioning, Disability and Health. Bladder and bowel topics were spontaneously discussed by 46 out of 50 study participants suggesting the salience of this issue for women with SCI. We identified 6 meta-themes: life controlled by bladder and bowel, bladder and bowel accidents, women's specific challenges, life course disruption, bladder and bowel medical management, and finding independence. Findings describe concerns, strategies, and the detrimental impact of NBB in the lives of women with SCI. Findings inform policy makers, health care and rehabilitation professionals to improve accessibility and quality of life for women with NBB. Women with spinal cord injury (SCI) reported gender specific challenges to living with neurogenic bladder and bowel (NBB). Interventions designed for women with SCI can address these problems and provide recommendations for prevention and treatment. Women described the detrimental impact of NBB on life course expectations, emotional, social, physical health, and quality of life domains. Psychosocial and educational programs can be developed to address these challenges and improve overall quality of life. Recommendations for special treatment and policy considerations are needed to maximize women's independence and health while living with NBB after SCI.

Lower urinary tract development and disease

PubMed Central

Rasouly, Hila Milo; Lu, Weining

2013-01-01

Congenital Anomalies of the Lower Urinary Tract (CALUT) are a family of birth defects of the ureter, the bladder and the urethra. CALUT includes ureteral anomalies such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder-exstrophy-epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUV). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, bladder, and urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, bladder and urethra and associated gene mutations are also presented. As we are entering the post-genomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence-based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families. PMID:23408557

Ketamine-snorting associated cystitis.

PubMed

Chen, Chung-Hsien; Lee, Ming-Huei; Chen, Yi-Chang; Lin, Ming-Fong

2011-12-01

Ketamine hydrochloride, commonly used as a pediatric anesthetic agent, is an N-methyl-D-aspartic (NMDA) acid receptor antagonist with rapid onset and short duration of action. It produces a cataleptic-like state where the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. It has emerged as an increasingly popular choice among young drug users, especially within dance club venues. Cases of bladder dysfunction among recreational ketamine users were reported since Shahani et al first reported nine cases of ketamine-associated ulcerative cystitis in 2007. We report on four patients who had history of ketamine abuse, presenting with dysuria, fluctuating lower urinary tract symptoms (LUTS), lower abdominal or perineal pain, and impaired functional bladder capacities. Urinalysis showed pyuria and microhematuria. Urine culture was sterile. Bladder ulceration with severe diffuse hemorrhage and low bladder capacity were noted under anesthetized cystoscopic examination. Transurethral bladder mucosa biopsy was consistent with chronic cystitis. Cessation of ketamine abuse was the milestone of treatment, followed by the administration of mucosal protective agents, such as pentosan polysulphate or hyaluronic acid. Suprapubic pain was improved in three patients during follow-up. However, the outcome of treatment depends on the severity of the disease process, similar to that of interstitial cystitis (IC). Copyright © 2011. Published by Elsevier B.V.

Nephrogenic Adenoma of the Urinary Bladder: A Review of the Literature

PubMed Central

Venyo, Anthony Kodzo-Grey

2015-01-01

Background. Nephrogenic adenoma of the urinary bladder (NAUB) is a rare lesion associated with nonspecific symptoms and could inadvertently be misdiagnosed. Aim. To review the literature. Methods. Various internet search engines were used. Results. NAUB is a benign tubular and papillary lesion of the bladder, is more common in men and adults, and has been associated with chronic inflammation/irritation, previous bladder surgery, diverticula, renal transplantation, and intravesical BCG; recurrences and malignant transformations have been reported. Differential diagnoses include clear cell adenocarcinoma, endocervicosis, papillary urothelial carcinoma, prostatic adenocarcinoma of bladder, and nested variant of urothelial carcinoma; most NAUBs have both surface papillary and submucosal tubular components; both the papillae and tubules tend to be lined by a single layer of mitotically inactive bland cells which have pale to clear cytoplasm. Diagnosis may be established by using immunohistochemistry (positive staining with racemase; PAX2; keratins stain positive with fibromyxoid variant), electron microscopy, DNA analysis, and cytological studies. Treatment. Endoscopic resection is the treatment but recurrences including sporadic malignant transformation have been reported. Conclusions. There is no consensus on best treatment. A multicentre study is required to identify the treatment that would reduce the recurrence rate, taking into consideration that intravesical BCG is associated with NAUB. PMID:27347540

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

NASA Astrophysics Data System (ADS)

Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency stimulation did not lead to loss of nerve functionality. Pelvic nerve stimulation has development potential for normalizing voiding dysfunction in conscious rats.

Dosimetric impact in the dose-volume histograms of rectal and vesical wall contouring in prostate cancer IMRT treatments.

PubMed

Gómez, Laura; Andrés, Carlos; Ruiz, Antonio

2017-01-01

The main purpose of this study was to evaluate the differences in dose-volume histograms of IMRT treatments for prostate cancer based on the delineation of the main organs at risk (rectum and bladder) as solid organs or by contouring their wall. Rectum and bladder have typically been delineated as solid organs, including the waste material, which, in practice, can lead to an erroneous assessment of the risk of adverse effects. A retrospective study was made on 25 patients treated with IMRT radiotherapy for prostate adenocarcinoma. 76.32 Gy in 36 fractions was prescribed to the prostate and seminal vesicles. In addition to the delineation of the rectum and bladder as solid organs (including their content), the rectal and bladder wall were also delineated and the resulting dose-volume histograms were analyzed for the two groups of structures. Data analysis shows statistically significant differences in the main parameters used to assess the risk of toxicity of a prostate radiotherapy treatment. Higher doses were received on the rectal and bladder walls compared to doses received on the corresponding solid organs. The observed differences in terms of received doses to the rectum and bladder based on the method of contouring could gain greater importance in inverse planning treatments, where the treatment planning system optimizes the dose in these volumes. So, one should take into account the method of delineating of these structures to make a clinical decision regarding dose limitation and risk assessment of chronic toxicity.

Water avoidance stress induces frequency through cyclooxygenase-2 expression: a bladder rat model.

PubMed

Yamamoto, Keisuke; Takao, Tetsuya; Nakayama, Jiro; Kiuchi, Hiroshi; Okuda, Hidenobu; Fukuhara, Shinichiro; Yoshioka, Iwao; Matsuoka, Yasuhiro; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio

2012-02-01

Water avoidance stress is a potent psychological stressor and it is associated with visceral hyperalgesia, which shows degeneration of the urothelial layer mimicking interstitial cystitis. Cyclooxygenase-2 inhibitors have been recognized to ameliorate frequency both in clinical and experimental settings. We investigated the voiding pattern and cyclooxygenase-2 expression in a rat bladder model of water avoidance stress. After being subjected to water avoidance stress or a sham procedure, rats underwent metabolic cage analysis and cystometrography. Real time reverse transcription polymerase chain reaction was carried out to examine cyclooxygenase-2 messenger ribonucleic acid in bladders of rats. Protein expression of cyclooxygenase-2 was analyzed with immunohistochemistry and western blotting. Furthermore, the effects of the cyclooxygenase-2 inhibitor, etodolac, were investigated by carrying out cystometrography, immunohistochemistry and western blotting. Metabolic cage analysis and cystometrography showed significantly shorter intervals and less volume of voiding in water avoidance stress rats. Significantly higher expression of cyclooxygenase-2 messenger ribonucleic acid was verified by reverse transcription polymerase chain reaction. Immunohistochemistry and western blotting showed significantly higher cyclooxygenase-2 protein levels in water avoidance stress bladders. Furthermore, immunohistochemistry showed high cyclooxygenase-2 expression exclusively in smooth muscle cells. All water avoidance stress-induced changes were reduced by cyclooxygenase-2 inhibitor pretreatment. Chronic stress might cause frequency through cyclooxygenase-2 gene upregulation in bladder smooth muscle cells. Further study of cyclooxygenase-2 in the water avoidance stress bladder might provide novel therapeutic modalities for interstitial cystitis. © 2011 The Japanese Urological Association.

Neurotrophin/receptor expression in urinary bladder of mice with overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Malley, Susan E; Vizzard, Margaret A

2011-02-01

Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency, and results in increased referred somatic hypersensitivity. Additional NGF-mediated pleiotropic changes might contribute to the increased voiding frequency and pelvic hypersensitivity observed in these transgenic mice, such as modulation of other growth factor/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific uroplakin II promoter. In the present study, we examined NGF, brain-derived neurotrophic factor (BDNF), and associated receptor [p75(NTR), tyrosine kinase (Trk)A, TrkB] transcript and protein expression in urothelium and detrusor smooth muscle of NGF-overexpressing (OE) and littermate wild-type mice, using real-time quantitative reverse transcription-polymerase chain reaction, ELISAs, and semiquantitation of immunohistochemistry. We focused on these growth factor/receptors given the established roles of NGF/TrkA, NGF/p75(NTR), and BDNF/TrkB systems in bladder function. Increased voiding frequency in NGF-OE mice was confirmed by examining urination patterns. BDNF, TrkA, and TrkB protein expression was significantly (P ≤ 0.01) reduced and p75(NTR) protein expression was significantly (P ≤ 0.01) increased in urinary bladder of NGF-OE mice. The NGF-OE-induced changes in neurotrophic factor/receptor expression in urinary bladder may represent compensatory changes to reduce voiding frequency in the NGF-OE mouse.

PACAP/VIP and receptor characterization in micturition pathways in mice with overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Malley, Susan E; Braas, Karen M; May, Victor; Vizzard, Margaret A

2010-11-01

Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting or proliferation in the urinary bladder, produces urinary bladder hyperreflexia, and results in increased referred somatic hypersensitivity. Additional NGF-mediated changes might contribute to the urinary bladder hyperreflexia and pelvic hypersensitivity observed in these transgenic mice such as upregulation of neuropeptide/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific, uroplakin II promoter. In the present study, we examined pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), and associated receptor (PAC1, VPAC1, VPAC2) transcripts or protein expression in urothelium and detrusor smooth muscle and lumbosacral dorsal root ganglia in NGF-overexpressing and littermate wildtype mice using real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemical approaches. Results demonstrate upregulation of PAC1 receptor transcript and PAC1-immunoreactivity in urothelium of NGF-OE mice whereas PACAP transcript and PACAP-immunoreactivity were decreased in urothelium of NGF-OE mice. In contrast, VPAC1 receptor transcript was decreased in both urothelium and detrusor smooth muscle of NGF-OE mice. VIP transcript expression and immunostaining was not altered in urinary bladder of NGF-OE mice. Changes in PACAP, VIP, and associated receptor transcripts and protein expression in micturition pathways resemble some, but not all, changes observed after induction of urinary bladder inflammation known to involve NGF production.

Urinary catheters: history, current status, adverse events and research agenda

PubMed Central

Feneley, Roger C. L.; Hopley, Ian B.; Wells, Peter N. T.

2015-01-01

Abstract For more than 3500 years, urinary catheters have been used to drain the bladder when it fails to empty. For people with impaired bladder function and for whom the method is feasible, clean intermittent self-catheterization is the optimal procedure. For those who require an indwelling catheter, whether short- or long-term, the self-retaining Foley catheter is invariably used, as it has been since its introduction nearly 80 years ago, despite the fact that this catheter can cause bacterial colonization, recurrent and chronic infections, bladder stones and septicaemia, damage to the kidneys, the bladder and the urethra, and contribute to the development of antibiotic resistance. In terms of medical, social and economic resources, the burden of urinary retention and incontinence, aggravated by the use of the Foley catheter, is huge. In the UK, the harm resulting from the use of the Foley catheter costs the National Health Service between £1.0–2.5 billion and accounts for ∼2100 deaths per year. Therefore, there is an urgent need for the development of an alternative indwelling catheter system. The research agenda is for the new catheter to be easy and safe to insert, either urethrally or suprapubically, to be retained reliably in the bladder and to be withdrawn easily and safely when necessary, to mimic natural physiology by filling at low pressure and emptying completely without damage to the bladder, and to have control mechanisms appropriate for all users. PMID:26383168

Is It Safe to Reduce Water Intake in the Overactive Bladder Population? A Systematic Review.

PubMed

Wood, Lauren N; Markowitz, Melissa A; Parameshwar, Pooja S; Hannemann, Alex J; Ogawa, Shellee L; Anger, Jennifer T; Eilber, Karyn S

2018-03-01

Overactive bladder imposes a significant socioeconomic burden on the health care system. It is a commonly held belief that increased fluid intake (8 glasses of water per day) is beneficial for health. However, increased fluid intake exacerbates overactive bladder symptoms. Thus, it is imperative that clinicians appropriately educate patients for whom increased water intake may be detrimental (women with overactive bladder), in contrast to patients with comorbidities that necessitate increased water intake (nephrolithiasis). We systematically reviewed the literature to determine the potential health advantages of increased water intake and identify specific subpopulations that need increased hydration. We systematically reviewed published articles from 1972 through 2017 on PubMed® and the Cochrane Library. The data were reviewed independently by 2 individuals. Studies were included if they explored water intake in relation to the risk of a particular disease. Level 1 evidence supported increased fluid intake in patients with nephrolithiasis. There was no available evidence to support increased fluid intake in patients with cardiovascular disease, constipation, venous thromboembolism, headaches, cognitive function or bladder cancer. Dehydration may exacerbate some conditions, specifically chronic constipation and headache intensity. Increased fluid intake may have a role in preventing stroke recurrence but not in preventing primary stroke. The available reviewed literature suggests no benefit to drinking 8 glasses of water per day in patients without nephrolithiasis. Also, excess fluid intake can exacerbate symptoms of overactive bladder. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Microarray evaluation of gene expression profiles in inflamed and healthy human dental pulp: the role of IL1beta and CD40 in pulp inflammation.

PubMed

Gatta, V; Zizzari, V L; Dd ' Amico, V; Salini, L; D' Aurora, M; Franchi, S; Antonucci, I; Sberna, M T; Gherlone, E; Stuppia, L; Tetè, S

2012-01-01

Dental pulp undergoes a number of changes passing from healthy status to inflammation due to deep decay. These changes are regulated by several genes resulting differently expressed in inflamed and healthy dental pulp, and the knowledge of the processes underlying this differential expression is of great relevance in the identification of the pathogenesis of the disease. In this study, the gene expression profile of inflamed and healthy dental pulps were compared by microarray analysis, and data obtained were analyzed by Ingenuity Pathway Analysis (IPA) software. This analysis allows to focus on a variety of genes, typically expressed in inflamed tissues. The comparison analysis showed an increased expression of several genes in inflamed pulp, among which IL1β and CD40 resulted of particular interest. These results indicate that gene expression profile of human dental pulp in different physiological and pathological conditions may become an useful tool for improving our knowledge about processes regulating pulp inflammation.

Common Questions About Chronic Prostatitis.

PubMed

Holt, James D; Garrett, W Allan; McCurry, Tyler K; Teichman, Joel M H

2016-02-15

Chronic prostatitis is relatively common, with a lifetime prevalence of 1.8% to 8.2%. Risk factors include conditions that facilitate introduction of bacteria into the urethra and prostate (which also predispose the patient to urinary tract infections) and conditions that can lead to chronic neuropathic pain. Chronic prostatitis must be differentiated from other causes of chronic pelvic pain, such as interstitial cystitis/bladder pain syndrome and pelvic floor dysfunction; prostate and bladder cancers; benign prostatic hyperplasia; urolithiasis; and other causes of dysuria, urinary frequency, and nocturia. The National Institutes of Health divides prostatitis into four syndromes: acute bacterial prostatitis, chronic bacterial prostatitis (CBP), chronic nonbacterial prostatitis (CNP)/chronic pelvic pain syndrome (CPPS), and asymptomatic inflammatory prostatitis. CBP and CNP/CPPS both lead to pelvic pain and lower urinary tract symptoms. CBP presents as recurrent urinary tract infections with the same organism identified on repeated cultures; it responds to a prolonged course of an antibiotic that adequately penetrates the prostate, if the urine culture suggests sensitivity. If four to six weeks of antibiotic therapy is effective but symptoms recur, another course may be prescribed, perhaps in combination with alpha blockers or nonopioid analgesics. CNP/CPPS, accounting for more than 90% of chronic prostatitis cases, presents as prostatic pain lasting at least three months without consistent culture results. Weak evidence supports the use of alpha blockers, pain medications, and a four- to six-week course of antibiotics for the treatment of CNP/CPPS. Patients may also be referred to a psychologist experienced in managing chronic pain. Experts on this condition recommend a combination of treatments tailored to the patient's phenotypic presentation. Urology referral should be considered when appropriate treatment is ineffective. Additional treatments include pelvic floor physical therapy, phytotherapy, and pain management techniques. The UPOINT (urinary, psychosocial, organ-specific, infection, neurologic/systemic, tenderness) approach summarizes the various factors that may contribute to presentation and can guide treatment.

Designing a Mobile Health Application Prototype for the Management of Interstitial Cystitis/Painful Bladder Syndrome.

PubMed

Griffith, Janessa

2017-01-01

The design of an early mobile health application (app) prototype to manage interstitial cystitis/painful bladder syndrome, a chronic condition characterized by recurrent pain/discomfort in the bladder and pelvic floor, is described. The purpose of this app prototype is to help people who have IC/PBS manage and learn what triggers their symptoms. Another aim of this research was to provide an example of how sex and gender could be included into the design of a health information system. Based on a literature search of common symptoms and challenges faced by people living with IC/PBS, the researcher created an app prototype design including many features: resources for relaxation, mental health, intimacy, pregnancy, and daily life; reminders for appointments, and medication; logs for diet, activity, sleep, pain, menstruation; and a link to a public washroom locator. This prototype will later undergo usability and content evaluation.

Management of genitourinary injuries in patients with pelvic fractures.

PubMed Central

Weems, W L

1979-01-01

Associated injuries frequently occur in patients who sustain fractures of the pelvis. Hemorrhage from intrapelvic vessels, rupture of the urinary bladder and avulsion of the membranous urethra in males are among the integral risks in this trauma. Non-operative methods of managing hemorrhage have gained favor in recent experience. The case records of 282 male patients with pelvic fractures were reviewed to evaluate experience with lower genitourinary injuries. Early recognition is important in bladder injuries, and surgical repair is advised, except in selected patients who may be managed by catheter drainage alone. Delayed complications of bladder injury are rare. Membranous urethral injuries entail a high risk of chronic stricture disease and sexual impotence. The rationale of early repair versus delayed repair of these injuries is discussed. The results in this series show advantage for delayed repair. Images Fig. 2. Fig. 3. PMID:453943

Are Interferential Electrical Stimulation and Diaphragmatic Breathing Exercises Beneficial in Children With Bladder and Bowel Dysfunction?

PubMed

Zivkovic, Vesna D; Stankovic, Ivona; Dimitrijevic, Lidija; Kocic, Mirjana; Colovic, Hristina; Vlajkovic, Marina; Slavkovic, Andjelka; Lazovic, Milica

2017-04-01

To evaluate the effects of interferential current (IC) stimulation and diaphragmatic breathing exercises (DBEs) in children with bladder and bowel dysfunction. Seventy-nine children with dysfunctional voiding and chronic constipation who were failures of primary care interventions were included in the prospective clinical study. All the children were checked for their medical history regarding lower urinary tract symptoms and bowel habits. Physical examination, including abdominal and anorectal digital examination, was performed. Children kept a bladder and bowel diary, and underwent urinalyses and urine culture, ultrasound examination of bladder and kidneys, and uroflowmetry with pelvic floor electromyography. Eligible children were divided into 3 groups (A, B, and C). All groups were assigned education and behavioral modifications. Additionally, group A underwent DBEs and IC stimulation, whereas group B received only DBEs. The treatment was conducted for 2 weeks in the clinic in all 3 groups,. The behavioral modifications and DBEs were continued at home for 1 month. Clinical manifestations, uroflowmetry parameters, and postvoided residual urine were analyzed before and after 6 weeks of therapy. After the treatment, significant improvement in defecation frequency and fecal incontinence was noticed only in group A (P < .001 and P < .05, respectively). These children demonstrated significant improvement in lower urinary tract symptoms and postvoided residual urine (P < .001 and P < .05, respectively). Bell-shaped uroflowmetry curve was observed in 73.3% of group A patients (P < .001). IC stimulation and DBEs are beneficial in chronically constipated dysfunctional voiders. Further trials are needed to define the long-term effects of this program. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostic dilemma of unicystic ameloblastoma: novel parameters to differentiate unicystic ameloblastoma from common odontogenic cysts.

PubMed

Gunawardhana, Kuda Singappulige Niluka Darshani; Jayasooriya, Primali Rukmal; Tilakaratne, Wanninayake Mudiyanselage

2014-08-01

Diagnostic criteria that have been specified for unicystic ameloblastomas (UAs) are not always helpful to differentiate these cystic tumors from common odontogenic cysts. The aim of this study therefore was to identify additional histopathological features (other than the features considered for the diagnosis of UA at present) that would be helpful to differentiate UA from odontogenic cysts. One hundred histopathologically confirmed unicystic ameloblastomas and 20 cases each of radicular, inflamed dentigerous and non-inflamed dentigerous cysts were selected. Histopathological features of the UAs that are not used as diagnostic criteria at present were identified. Hyperplastic arcading epithelial proliferations with stellate-reticulum-like and vacuolated cells were always seen associated with inflammation in odontogenic cysts, while in UA plexiform-like areas were also seen without inflammation (P < 0.001). In addition, a spiky rete pattern was observed in non-inflamed UA while this pattern was observed only in inflamed odontogenic cysts. Furthermore, spiky retes together with subepithelial hyalinization were usually observed in UAs while only subepithelial hyalinization was observed in non-inflamed dentigerous cysts. Combinations of histopathological features were identified to differentiate non-inflamed UA from common odontogenic cysts. However, presence of inflammatory changes in UA precludes the use of features identified in the present study for diagnostic purposes. © 2013 Wiley Publishing Asia Pty Ltd.

CCR7 directs the recruitment of T cells into inflamed pancreatic islets of nonobese diabetic (NOD) mice.

PubMed

Shan, Zhongyan; Xu, Baohui; Mikulowska-Mennis, Anna; Michie, Sara A

2014-05-01

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of insulin-producing β cells in the pancreatic islets. The migration of T cells from blood vessels into pancreas is critical for the development of islet inflammation and β cell destruction in T1D. To define the roles of C-C chemokine receptor type 7 (CCR7) in recruitment of T cells into islets, we used laser capture microdissection to isolate tissue from inflamed islets of nonobese diabetic (NOD) mice and uninflamed islets of BALB/c and young NOD mice. RT-PCR analyses detected mRNAs for CCR7 and its chemokine ligands CCL19 (ELC; MIP-3β) and CCL21 (SLC) in captures from inflamed, but not from uninflamed, islets. Immunohistology studies revealed that high endothelial venules in inflamed islets co-express CCL21 protein and MAdCAM-1 (an adhesion molecule that recruits lymphocytes into islets). Desensitization of lymphocyte CCR7 blocked about 75 % of T cell migration from the bloodstream into inflamed islets, but had no effect on B cell migration into islets. These results indicate that CCR7 and its ligands are important in the recruitment of T cells into inflamed islets and thus in the pathogenesis of T1D.

Molecular and clinical analyses of Helicobacter pylori colonization in inflamed dental pulp.

PubMed

Nomura, Ryota; Ogaya, Yuko; Matayoshi, Saaya; Morita, Yumiko; Nakano, Kazuhiko

2018-04-16

Recently, dental pulp has been considered a possible source of infection of Helicobacter pylori (H. pylori) in children. We previously developed a novel PCR system for H. pylori detection with high specificity and sensitivity using primer sets constructed based on the complete genome information for 48 H. pylori strains. This PCR system showed high sensitivity with a detection limit of 1-10 cells when serial dilutions of H. pylori genomic DNA were used as templates. However, the detection limit was lower (10 2 -10 3 cells) when H. pylori bacterial DNA was detected from inflamed pulp specimens. Thus, we further refined the system using a nested PCR method, which was much more sensitive than the previous single PCR method. In addition, we examined the distribution and virulence of H. pylori in inflamed pulp tissue. Nested PCR system was constructed using primer sets designed from the complete genome information of 48 H. pylori strains. The detection limit of the nested PCR system was 1-10 cells using both H. pylori genomic DNA and bacterial DNA isolated from inflamed pulp specimens. Next, distribution of H. pylori was examined using 131 inflamed pulp specimens with the nested PCR system. In addition, association between the detection of H. pylori and clinical information regarding endodontic-infected teeth were investigated. Furthermore, adhesion property of H. pylori strains to human dental fibroblast cells was examined. H. pylori was present in 38.9% of inflamed pulp specimens using the nested PCR system. H. pylori was shown to be predominantly detected in primary teeth rather than permanent teeth. In addition, samplings of the inflamed pulp were performed twice from the same teeth at 1- or 2-week intervals, which revealed that H. pylori was detected in most specimens in both samplings. Furthermore, H. pylori strains showed adhesion property to human dental fibroblast cells. Our results suggest that H. pylori colonizes inflamed pulp in approximately 40% of all cases through adhesion to human dental fibroblast cells.

Paradoxical attenuation of leukocyte rolling in response to ischemia- reperfusion and extracorporeal blood circulation in inflamed tissue.

PubMed

Schäfer, Stephan C; Sehrt, Desiree N; Kamler, Markus; Jakob, Heinz; Lehr, Hans-Anton

2005-07-01

In contrast to acute preparations such as the exteriorized mesentery or the cremaster muscle, chronically instrumented chamber models allow one to study the microcirculation under "physiological" conditions, i.e., in the absence of trauma-induced leukocyte rolling along the venular endothelium. To underscore the importance of studying the naive microcirculation, we implanted titanium dorsal skinfold chambers in hamsters and used intravital fluorescence microscopy to study venular leukocyte rolling in response to ischemia-reperfusion injury or extracorporeal blood circulation. The experiments were performed in chambers that fulfilled all well-established criteria for a physiological microcirculation as well as in chambers that showed various extents of leukocyte rolling due to trauma, hemorrhage, or inflammation. In ideal chambers with a physiological microcirculation (<30 rolling leukocytes/mm vessel circumference in 30 s), ischemia-reperfusion injury and extracorporeal blood circulation significantly stimulated leukocyte rolling along the venular endothelium and, subsequently, firm leukocyte adhesion. In contrast, both stimuli failed to elicit leukocyte rolling in borderline chambers (30-100 leukocytes/mm), and in blatantly inflamed chambers with yet higher numbers of rolling leukocytes at baseline (>100 leukocytes/mm), we observed a paradoxical reduction of leukocyte rolling after ischemia-reperfusion injury or extracorporeal blood circulation. A similar effect was observed when we superfused leukotriene B4 (LTB4) onto the chamber tissue. The initial increase in leukocyte rolling in response to an LTB4 challenge was reversed by a second superfusion 90 min later. These observations underscore 1) the benefit of studying leukocyte-endothelial cell interaction in chronically instrumented chamber models and 2) the necessity to strictly adhere to well-established criteria of a physiological microcirculation.

Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation.

PubMed

Iyengar, Neil M; Gucalp, Ayca; Dannenberg, Andrew J; Hudis, Clifford A

2016-12-10

Purpose There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. Methods We review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. Results Locally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling. Within this distinctly altered local environment, several pathophysiologic changes are found that may promote breast and other cancers. Consistently, adipose tissue inflammation is associated with a worse prognosis in patients with breast and tongue cancers. Systemically, the metabolic syndrome, including dyslipidemia and insulin resistance, occurs in the setting of adipose inflammation and operates in concert with local mechanisms to sustain the inflamed microenvironment and promote tumor growth. Importantly, adipose inflammation and its protumor consequences can be found in some individuals who are not considered to be obese or overweight by body mass index. Conclusion The tumor-promoting effects of obesity occur at the local level via adipose inflammation and associated alterations in the microenvironment, as well as systemically via circulating metabolic and inflammatory mediators associated with adipose inflammation. Accurately characterizing the obese state and identifying patients at increased risk for cancer development and progression will likely require more precise assessments than body mass index alone. Biomarkers of adipose tissue inflammation would help to identify high-risk populations. Moreover, adipose inflammation is a reversible process and represents a novel therapeutic target that warrants further study to break the obesity-cancer link.

Genotypic and phenotypic predictors of inflammation in patients with chronic kidney disease.

PubMed

Luttropp, Karin; Debowska, Malgorzata; Lukaszuk, Tomasz; Bobrowski, Leon; Carrero, Juan Jesus; Qureshi, Abdul Rashid; Stenvinkel, Peter; Lindholm, Bengt; Waniewski, Jacek; Nordfors, Louise

2016-12-01

In complex diseases such as chronic kidney disease (CKD), the risk of clinical complications is determined by interactions between phenotypic and genotypic factors. However, clinical epidemiological studies rarely attempt to analyse the combined effect of large numbers of phenotype and genotype features. We have recently shown that the relaxed linear separability (RLS) model of feature selection can address such complex issues. Here, it is applied to identify risk factors for inflammation in CKD. The RLS model was applied in 225 CKD stage 5 patients sampled in conjunction with dialysis initiation. Fifty-seven anthropometric or biochemical measurements and 79 genetic polymorphisms were entered into the model. The model was asked to identify phenotypes and genotypes that, when combined, could separate inflamed from non-inflamed patients. Inflammation was defined as a high-sensitivity C-reactive protein concentration above the median (5 mg/L). Among the 60 genotypic and phenotypic features predicting inflammation, 31 were genetic. Among the 10 strongest predictors of inflammation, 8 were single nucleotide polymorphisms located in the NAMPT, CIITA, BMP2 and PIK3CB genes, whereas fibrinogen and bone mineral density were the only phenotypic biomarkers. These results indicate a larger involvement of hereditary factors in inflammation than might have been expected and suggest that inclusion of genotype features in risk assessment studies is critical. The RLS model demonstrates that inflammation in CKD is determined by an extensive panel of factors and may prove to be a suitable tool that could enable a much-needed multifactorial approach as opposed to the commonly utilized single-factor analysis. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Inflammatory, autoimmune, chronic diseases: bad diet and physical inactivity are causes or effects?

PubMed

Gracia, M C

2006-01-01

It is now well established that most chronic diseases, especially those identified as inflammatory, are statistically correlated with some typical dietary excesses and physical inactivity. But do really these habits cause the diseases, or they result from them? Current opinion favours the first option, but fails to explain why the satisfaction of eating, naturally evolved in our brains to produce health, apparently induces countless millions of people to eat unrestrictedly until becoming mortally sick, whereas trying to keep a theoretically healthy diet is most often a real torture. The inverse explanation makes much more sense: since inflammation produces much heat, calorie-rich diets are required. An inflamed digestive tract lacks digestive power and is easily irritated or damaged by solid objects, therefore requiring a refined, concentrated, low-fibre diet. And inflamed or merely sick organisms are easily exhausted by physical effort, hence physical inactivity. This study confirms that, most probably, the primary causes of inflammatory diseases are always external inflammatory agents, like infectious micro-organisms or toxic substances, of which a particularly ubiquitous example is nicotine. High-calorie/low-fibre diets and physical inactivity are direct consequences of generalised inflammation. Inversely, in most cases, physical exercise and moderation in eating, by themselves, cannot substantially suppress inflammations, but they can prevent them from being further reinforced by the neural reward system. Moreover, diets and exercise causing important suffering will usually do more harm than good, especially to children and young people, not to mention pregnant or nursing women. Only the identification and elimination of the inflammatory agents can efficiently prevent and cure inflammatory diseases, and currently nicotine, absorbed intentionally or passively, from tobacco or other sources, must be considered the chief suspect because of its inflammatory power, ubiquity and addictive properties.

Differentiation of pancreatic ductal adenocarcinoma from chronic pancreatitis by PAM4 immunohistochemistry.

PubMed

Shi, Chanjuan; Merchant, Nipun; Newsome, Guy; Goldenberg, David M; Gold, David V

2014-02-01

PAM4 is a monoclonal antibody that shows high specificity for pancreatic ductal adenocarcinoma (PDAC) and its neoplastic precursor lesions. A PAM4-based serum immunoassay is able to detect 71% of early-stage patients and 91% with advanced disease. However, approximately 20% of patients diagnosed with chronic pancreatitis (CP) are also positive for circulating PAM4 antigen. The specificity of the PAM4 antibody is critical to the interpretation of the serum-based and immunohistochemical assays for detection of PDAC. To determine whether PAM4 can differentiate PDAC from nonneoplastic lesions of the pancreas. Tissue microarrays of PDAC (N = 43) and surgical specimens from CP (N = 32) and benign cystic lesions (N = 19) were evaluated for expression of the PAM4 biomarker, MUC1, MUC4, CEACAM5/6, and CA19-9. PAM4 and monoclonal antibodies (MAbs) to MUC1, MUC4, CEACAM5/6, and CA19-9 were each reactive with the majority of PDAC cases; however, PAM4 was the only monoclonal antibody not to react with adjacent, nonneoplastic parenchyma. Although PAM4 labeled 19% (6 of 32) of CP specimens, reactivity was restricted to pancreatic intraepithelial neoplasia associated with CP; inflamed tissues were negative in all cases. In contrast, MUC1, MUC4, CEACAM5/6, and CA19-9 were detected in 90%, 78%, 97%, and 100% of CP, respectively, with reactivity also present in nonneoplastic inflamed tissue. PAM4 was the only monoclonal antibody able to differentiate PDAC (and pancreatic intraepithelial neoplasia precursor lesions) from benign, nonneoplastic tissues of the pancreas. These results suggest the use of PAM4 for evaluation of tissue specimens, and support its role as an immunoassay for detection of PDAC.

Pathology and behaviour in feline medicine: investigating the link between vomeronasalitis and aggression.

PubMed

Asproni, Pietro; Cozzi, Alessandro; Verin, Ranieri; Lafont-Lecuelle, Céline; Bienboire-Frosini, Cécile; Poli, Alessandro; Pageat, Patrick

2016-12-01

The aim of the study was to investigate if the feline vomeronasal organ (VNO) can be affected by inflammatory lesions and if these changes are associated with behavioural alterations. VNOs from 20 cats were sampled during necropsy, submitted for routine tissue processing and stained with haematoxylin and eosin for histopathological evaluation. For the 20 cats, data on the presence of aggressive behaviours towards cats or humans were collected by questionnaire survey at the point of death. Inflammatory lesions were classified depending on the duration of the process as acute or chronic, both in vomeronasal sensory epithelium (VNSE) and in non-sensory epithelium (NSE). Fisher's exact test was used to compare VNO inflammation with behavioural data. The VNSE was inflamed in 11/20 VNOs (55%) while the NSE was inflamed in 13/20 (65%). Overall, the VNO was affected by inflammation in 14/20 (70%) cats, and all the lesions were classified as chronic. Five out of 20 cats (25%) had documented intraspecific aggressive behaviours and 8/20 (40%) had shown aggression towards humans. Fisher's exact test showed a statistically significant correlation between inflammation of the VNSE and intraspecific aggression (P = 0.038). No statistically correlations were observed between VNSE inflammation and aggression towards humans and between NSE inflammation and aggression towards cats or humans. Our results show, for the first time, the existence of vomeronasalitis in animals and its possible association with intraspecific aggressive behaviours. The inflammatory microenvironment could impair VNSE functionality, causing intraspecific communication alterations, probably through a reduction in chemical communication action and perception. Owing to the pivotal role of the VNO in the social life of cats and other species, this report provides a rationale to further investigate this disease in relation to a variety of behavioural disorders. © The Author(s) 2015.

Urinary arsenic profiles and the risks of cancer mortality: A population-based 20-year follow-up study in arseniasis-endemic areas in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Chi-Jung; Department of Medical Research, China Medical Hospital, Taichung, Taiwan; Huang, Ya-Li

2013-04-15

Few studies investigated the association between chronic arsenic exposure and the mortality of cancers by estimating individual urinary arsenic methylation profiles. Therefore, we compared with the general population in Taiwan to calculate the standardized mortality ratio (SMR) in arseniasis-endemic area of Taiwan from 1996 to 2010 and evaluated the dose-response relationships between environmental arsenic exposure indices or urinary arsenic profiles and the mortality of cause-specific cancer. A cohort of 1563 residents was conducted and collected their urine sample and information regarding arsenic exposure from a questionnaire. All-cause death was identified using the National Death Registry of Taiwan. Urinary arsenic profilesmore » were measured using high performance liquid chromatography–hydride generator–atomic absorption spectrometry. We used Cox proportional hazard models to evaluate the mortality risks. In results, 193 all-site cancer deaths, and 29, 71, 43 deaths respectively for liver, lung and bladder cancers were ascertained. The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. People with high urinary InAs% or low DMA% or low secondary methylation index (SMI) were the most likely to suffer bladder cancer after adjusting other risk factors. Even stopping exposure to arsenic from the artesian well water, the mortality rates of the residents were higher than general population. Finally, urinary InAs%, DMA% and SMI could be the potential biomarkers to predict the mortality risk of bladder cancer. -- Highlights: ► The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. ► People with high urinary InAs% were the most likely to suffer bladder cancer. ► People with low DMA% or low SMI were the most likely to suffer bladder cancer.« less

Acute photosensitisation and mortality in a herd of dairy cattle in Tasmania.

PubMed

Golder, H M; Moss, N; Rogers, G; Jackson, B; Gannon, N; Wong, Ptw; Lean, I J

2017-01-01

A herd of Holstein, Jersey, or Holstein-Jersey cross lactating cattle of mixed ages presented with a sudden drop in milk yield in 94/678 cows on 3 October 2014 (Day 0). The herd was located in Gretna in the Derwent Valley (Tasmania, Australia) and had been grazing dryland pasture. On Day 0 the cows variably showed recumbency, peracute photosensitisation, inflamed coronary bands, conjunctival erythema, periauricular oedema, distress indicated by kicking at the flank, bruxism, discomfort, weight shifting, vocalisation indicating pain and depression. Blood samples collected on Day 4 from five clinically affected cows showed high activities of aspartate aminotransferase, glutamate dehydrogenase and gamma-glutamyl transferase. Morbidity, based on the number of treated cases within 72 hours of clinical onset, was estimated at 165/678 cows (24.3%). Mortality over the first 30 days was 19/678 cows (2.8%). Necropsies of two cows on Day 4 showed marked distension of the gall bladder and extensive icterus. Necropsies of another two cows on Day 5 showed enlarged livers with severe damage and oedema of the distal abomasum. Severe ulcerative abomasal gastritis was present in both cows. Hepatic histopathology was consistent with chronic cholangiohepatitis. Fifty-five different mycotoxins were detected from a barley grass (Hordeum murinum) sample from the presumably contaminated pasture. Concentrations of B-trichothecenes, fumonisins, and zearalenone metabolites from this sample were remarkably high. The leaf smut, Jamesdicksonia dactylidis, that has not been previously reported in Tasmania, was identified from the sample of barley grass, but it is not known whether the smut can produce toxins. Probably an undescribed peracute mycotoxicosis associated with the ingestion of contaminated dryland pasture. A definitive diagnosis could not be reached in this case of acute photosensitisation and mortality in dairy cattle grazing possibly contaminated dryland pasture. The findings differed from both facial eczema and acute bovine liver disease, suggesting an undescribed mycotoxicosis.

Long-term complications following bladder augmentations in patients with spina bifida: bladder calculi, perforation of the augmented bladder and upper tract deterioration

PubMed Central

2016-01-01

Background We desire to review our experience with bladder augmentation in spina bifida patients followed in a transitional and adult urologic practice. This paper will specifically focus on three major complications: bladder calculi, the most frequent complication found following bladder augmentation, perforation of the augmentation, its most lethal complication and finally we will address loss of renal function as a direct result of our surgical reconstructive procedures. Methods We reviewed a prospective data base maintained on patients with spina bifida followed in our transitional and adult urology clinic from 1986 to date. Specific attention was given to patients who had developed bladder calculi, sustained a spontaneous perforation of the augmented bladder or had developed new onset of renal scarring or renal insufficiency (≥ stage 3 renal failure) during prolonged follow-up. Results The development of renal stones (P<0.05) and symptomatic urinary tract infections (P<0.0001) were found to be significantly reduced by the use of high volume (≥240 mL) daily bladder wash outs. Individuals who still developed bladder calculi recalcitrant to high volume wash outs were not benefited by the correction of underlying metabolic abnormalities or mucolytic agents. Spontaneous bladder perforations in the adult patient population with spina bifida were found to be directly correlated to substance abuse and noncompliance with intermittent catheterization, P<0.005. Deterioration of the upper tracts as defined by the new onset of renal scars occurred in 40% (32/80) of the patients managed by a ileocystoplasty and simultaneous bladder neck outlet procedure during a median follow-up interval 14 years (range, 8–45 years). Development of ≥ stage 3 chronic renal failure occurred within 38% (12/32) of the patients with scarring i.e., 15% (12/80) of the total patient population. Prior to the development of the renal scarring, 69% (22/32) of the patients had been noncompliant with intermittent catheterization. The onset of upper tract deterioration (i.e., new scar formation, hydronephrosis, calculus development, decrease in renal function) was silent, that is, clinically asymptomatic in one third (10/32 pts). Conclusions This paper documents the need for high volume bladder irrigations to both prevent the most common complication following bladder augmentation, which is the development of bladder calculi and to reduce the incidence of symptomatic urinary tract infections. It provides a unique perspective regarding the impact of substance abuse and patient non-compliance with medical directives as being both the most common cause for both spontaneous bladder rupture following augmentation cystoplasty and for deterioration of the upper tracts. These findings should cause the surgeon to reflect on his/her assessment of a patient prior to performing a bladder augmentation procedure and stress the need for close follow-up. PMID:26904407

Chronic Mycobacterium infection of first dorsal web space after accidental Bacilli Calmette-Guérin injection in a health worker: case report.

PubMed

Vigler, Mordechai; Mulett, Hanan; Hausman, Michael R

2008-11-01

We present a case of inoculation of the first dorsal web space by a nurse practitioner who accidentally stuck herself while preparing Bacilli Calmette-Guérin vaccine for treatment of bladder tumor. We report the evolution and management of this resistant chronic Mycobacterium infection that ultimately required use of a vacuum wound management system followed by a microvascular free tissue transfer.

Proteomic Analysis of Arsenic-Induced Oxidative Stress in Human Epidermal Keratinocytes

EPA Science Inventory

Chronic exposure to inorganic arsenic (IAs) has been associated with the development of several human cancers, including those found in the skin, lung, urinary bladder, liver, prostate and kidney. The precise mechanisms by which arsenic causes cancer are unknown. Defining the mod...

COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

EPA Science Inventory

Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human
lymphocytes.

Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

Resveratrol improves prostate fibrosis during progression of urinary dysfunction in chronic prostatitis.

PubMed

He, Yi; Zeng, Hui-Zhi; Yu, Yang; Zhang, Jia-Shu; Duan, Xingping; Zeng, Xiao-Na; Gong, Feng-Tao; Liu, Qi; Yang, Bo

2017-09-01

We investigated whether prostate fibrosis was associated with urinary dysfunction in chronic prostatitis (CP) and whether resveratrol improved urinary dysfunction and the underlying molecular mechanism. Rat model of CP was established via subcutaneous injections of DPT vaccine and subsequently treated with resveratrol. Bladder pressure and volume tests investigated the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression level of C-kit/SCF and TGF-β/Wnt/β-catenin. Compared to the control group, the maximum capacity of the bladder, residual urine volume and maximum voiding pressure, the activity of C-kit/SCF and TGF-β/Wnt/β-catenin pathways were increased significantly in the CP group. Resveratrol treatment significantly improved these factors. CP induced significantly prostate fibrosis, which exhibits a close relationship with urinary dysfunction. Resveratrol improved fibrosis, which may be associated with the suppression of C-kit/SCF and TGF-β/Wnt/β-catenin pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Malakoplakia of the Urinary Bladder in a Patient with Chronic Lymphocytic Leukemia Under Ibrutinib Therapy: A Case Report.

PubMed

Sachanas, Sotirios; Pangalis, Gerassimos A; Karouzakis, Petros; Koulieris, Efstathios; Moschogiannis, Maria; Kalpadakis, Christina; Yiakoumis, Xanthi; Rontogianni, Dimitra

2016-09-01

Malakoplakia, a rare granulomatous disease of infectious etiology, is commonly observed in immunocompromised patients. Chronic lymphocytic leukemia (CLL) is characterized by profound immune dysregulation resulting in significant infection-related morbidity and mortality, and several drugs used in CLL treatment have a severe immunosuppressive effect. Ibrutinib, has become a new standard-of-care in patients with CLL, especially for those harboring unfavorable genetic characteristics such as 17 p deletion, with however, unknown long-term immunological consequences. Here we report a case of a patient with CLL with 17 p deletion diagnosed with malakoplakia of the urinary bladder under ibrutinib therapy who developed severe hypogammaglobulinemia during treatment administration. Presumably, ibrutinib might contribute to the development of malakoplakia on the grounds of induced immunosuppression. This case report highlights the need for regular assessment of immunogammaglobulin adequacy during treatment with ibrutinib, considering that it should be given on a permanent basis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Missed diagnosis of anterior urethral valve complicated with a foreign body: a cause for concern.

PubMed

Nayyar, Rishi; Chavda, Sundeep; Singh, Prabhjot; Gupta, Narmada P

2011-01-01

Anterior urethral valve (AUV) is a long known but rare anomaly, which is occasionally encountered in boys with obstructive uropathy. We present a case of AUV with a diverticulum which was misdiagnosed at other center as neurogenic bladder resulting in chronic renal failure. The case was further complicated by breakage of tip of the catheter used for clean intermittent catheterization (CIC) in the diverticulum presenting as a foreign body in the urethra. This article highlights the frequently missed diagnosis of AUV by most practitioners wrongly labeling it as neurogenic bladder, leading to improper management and renal failure in young boys.

[The role of telomerase activity in non-invasive diagnostics of bladder cancer].

PubMed

Glybochko, P V; Alyaev, J G; Potoldykova, N V; Polyakovsky, K A; Vinarov, A Z; Glukhov, A I; Gordeev, S A

2016-08-01

To evaluate the potentials of determining the telomerase activity (TA) in the cellular material of the urine for noninvasive diagnosis of bladder cancer (BC). Evaluation of TA was performed in the urine of 48 patients with bladder cancer (study group) before and after transurethral resection of the bladder wall (n=38), an open resection of the bladder (n=4), and cystectomy (n=6). TA was also evaluated in 48 tumor tissue samples obtained from these patients during removal of the bladder tumor. Each sample of the tumor tissue was separated into two parts, one of which was subjected to histological examination, and the latter was used to determine the telomerase activity. In all cases, the diagnosis of bladder cancer was confirmed morphologically. Determination of TA in the samples was performed by the modified TRAP-method (telomerase repeat amplification protocol), RT-PCR, PCR, and electrophoresis. As a control, cell material of the urine and tissue in 12 patients with chronic cystitis was investigated. TA before surgery was found in 45 (93.75%) of 48 samples of cellular material of the urine from patients with suspected bladder cancer. BC was histologically verified in all patients in this group. In the postoperative period, TA was not observed in the 48 samples of cellular material of the urine from patients with BC. In the control group of patients with histologically verified cystitis, weak TA was determined only in one sample of cellular material of the urine. The analysis indicates statistically significant predominance of patients with bladder cancer in case of TA in the urine (P=0.001). TA was detected in all samples of tumor tissue. We also analyzed the dependence of TA levels in urine and tissue on the degree of BC differentiation. In patients with highly differentiated BC, mean AT in the cellular materials of the urine was 0,61% (n=15), in patients with moderately differentiated BC - 0.95% (n=23), in patients with low-grade bladder cancer - 1.33% (n=10); in other words, increase in the TA levels with decreasing the degree of differentiation was observed. This finding can be used in the prognosis of the course of disease based on determining the TA level in these patients. Preliminary data indicate the possibility of use of determining the TA in cellular material of the urine for the diagnosis and monitoring of bladder cancer recurrence.

Mechanisms underlying recurrent inhibition in the sacral parasympathetic outflow to the urinary bladder.

PubMed Central

de Groat, W C

1976-01-01

1. In cats with the sacral dorsal roots cut on one side electrical stimulation (15-40 c/s) of the central end of the transected ipsilateral pelvic nerve depressed spontaneous bladder contractions. The depression was abolished by transecting the ipsilateral sacral ventral roots. 2. Electrical stimulation of acutely or chronically transected ('deafferented') sacral ventral roots depressed spontaneous bladder contractions and the firing of sacral parasympathetic preganglionic neurones innervating the bladder. The depression of neuronal firing occurred ipsilateral and contralateral to the point of stimulation, but only occurred with stimulation of sacral roots containing preganglionic axons and only with stimulation of sacral roots containing preganglionic axons and only at intensities of stimulation (0-7-4V) above the threshold for activation of these axons. 3. The inhibitory responses were not abolished by strychnine administered by micro-electrophoresis to preganglionic neurones, but were blocked by the intravenous administration of strychnine. 4. The firing of preganglionic neurones elicited by micro-electrophoretic administration of an excitant amino acid (DL-homocysteic acid) was not depressed by stimulation of the ventral roots. 5. It is concluded that the inhibition of the sacral outflow to the bladder by stimulation of sacral ventral roots is related to antidromic activation of vesical preganglionic axons. Collaterals of these axons must excite inhibitory interneurones which in turn depress transmission at a site on the micturition reflex pathway prior to the preganglionic neurones. PMID:950603

Pathogenetic and Clinical Aspects of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitides

PubMed Central

Lamprecht, Peter; Kerstein, Anja; Klapa, Sebastian; Schinke, Susanne; Karsten, Christian M.; Yu, Xinhua; Ehlers, Marc; Epplen, Jörg T.; Holl-Ulrich, Konstanze; Wiech, Thorsten; Kalies, Kathrin; Lange, Tanja; Laudien, Martin; Laskay, Tamas; Gemoll, Timo; Schumacher, Udo; Ullrich, Sebastian; Busch, Hauke; Ibrahim, Saleh; Fischer, Nicole; Hasselbacher, Katrin; Pries, Ralph; Petersen, Frank; Weppner, Gesche; Manz, Rudolf; Humrich, Jens Y.; Nieberding, Relana; Riemekasten, Gabriela; Müller, Antje

2018-01-01

Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV. PMID:29686675

Complete treatment with partial cystectomy in giant xanthogranulomatous cystitis case imitating bladder tumor.

PubMed

Balasar, Mehmet; Sönmez, Mehmet Giray; Oltulu, Pembe; Kandemir, Abdülkadir; Kılıç, Mehmet; Gürbüz, Recai

2017-01-01

Xanthogranulomatous cystitis (XC) is a very rare chronic benign inflammatory disease of the bladder. It may cause local invasion although it is not a malign lesion and may occur together with malign lesions. It has a clinical importance as the distinction from malign lesions is difficult clinically and pathologically. Sharing a 37-year-old female case with giant XC imitating bladder tumor referring to the hospital with hematuria and stomach ache, together with current literature, we wanted to present that the disease can be treated with bladder-preserving approaches instead of radical approaches even though the mass is big in these cases. Application of basic excision and partial resection for small masses and radical cystectomy for large masses was reported in literature. We think that our case may provide a contribution to literature in treatment approach since we provided surgical cure with partial resection in a big mass with dimensions of 9 cm × 8 cm which is different from the present literature. Even though XC is a rare disease, it should be considered in prediagnosis for especially big dimensioned masses, and treatment should be planned according to the pathology result after together with cystoscopy in suitable patients.

Disseminated Mycobacterium bovis infection post-kidney transplant following remote intravesical BCG therapy for bladder cancer.

PubMed

Ziegler, Jennifer; Ho, Julie; Gibson, Ian W; Nayak, Jasmir G; Stein, Markus; Walkty, Andrew; Orr, Pamela

2018-05-29

Intravesical Bacillus Camlette-Guérin (BCG) is the treatment of choice for non-muscle invasive bladder cancer, and has been used successfully for over 40 years. A rare and potentially fatal complication of intravesical BCG therapy is BCG-induced sepsis. We report a rare case in which a patient with end-stage renal disease secondary to chronic granulomatous interstitial nephritis underwent remote, pre-transplant intravesical BCG treatment for high-grade non-invasive papillary bladder carcinoma. The patient subsequently received a deceased donor kidney transplant 5 years after BCG therapy, with thymoglobulin induction therapy and standard triple maintenance immunosuppression. Two years post-transplant, he developed BCG-induced sepsis confirmed by cultures from urine, blood and left native kidney biopsy. He died from disseminated BCG-induced sepsis and failure of his renal allograft. This case highlights the potential adverse reactions associated with intravesical BCG therapy that may occur years after bladder cancer therapy is completed, and should heighten physician awareness for BCG-related infections during pre-transplant assessment and post-transplant care of solid organ transplants recipients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Central control of visceral pain and urinary tract function.

PubMed

Lovick, Thelma A

2016-10-01

Afferent input from Aδ and C-fibres innervating the urinary bladder are processed differently by the brain, and have different roles in signaling bladder sensation. Aδ fibres that signal bladder filling activate a spino-bulbo-spinal loop, which relays in the midbrain periaqueductal grey (PAG) and pontine micturition centre (PMC). The excitability of this circuitry is regulated by tonic GABAergic inhibitory processes. In humans and socialised animals micturition is normally under volitional control and influenced by a host of psychosocial factors. Higher nervous decision-making in a social context to 'go now' or 'do not go' probably resides in frontal cortical areas, which act as a central control switch for micturition. Exposure to psychosocial stress can have profoundly disruptive influence on the process and lead to maladaptive changes in the bladder. During sleeping the voiding reflex threshold appears to be reset to a higher level to promote urinary continence. Under physiological conditions C-fibre bladder afferents are normally silent but are activated in inflammatory bladder states and by intense distending pressure. Following prolonged stimulation visceral nociceptors sensitise, leading to a lowered threshold and heightened sensitivity. In addition, sensitization may occur within the central pain processing circuitry, which outlasts the original nociceptive insult. Visceral nociception may also be influenced by genetic and environmental influences. A period of chronic stress can produce increased sensitivity to visceral pain that lasts for months. Adverse early life events can produce even longer lasting epigenetic changes, which increase the individual's susceptibility to developing visceral pain states in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

Can bile duct injuries be prevented? "A new technique in laparoscopic cholecystectomy"

PubMed Central

Sari, Yavuz Selim; Tunali, Vahit; Tomaoglu, Kamer; Karagöz, Binnur; Güneyİ, Ayhan; KaragöZ, İbrahim

2005-01-01

Background Over the last decade, laparoscopic cholecystectomy has gained worldwide acceptance and considered to be as "gold standard" in the surgical management of symptomatic cholecystolithiasis. However, the incidence of bile duct injury in laparoscopic cholecystectomy is still two times greater compared to classic open surgery. The development of bile duct injury may result in biliary cirrhosis and increase in mortality rates. The mostly blamed causitive factor is the misidentification of the anatomy, especially by a surgeon who is at the beginning of his learning curve. Biliary tree injuries may be decreased by direct coloration of the cystic duct, ductus choledochus and even the gall bladder. Methods gall bladder fundus was punctured by Veress needle and all the bile was aspirated. The same amount of fifty percent methylene blue diluted by saline solution was injected into the gall bladder for coloration of biliary tree. The dissection of Calot triangle was much more safely performed after obtention of coloration of the gall bladder, cystic duct and choledocus. Results Between October 2003 and December 2004, overall 46 patients (of which 9 males) with a mean age of 47 (between 24 and 74) underwent laparoscopic cholecystectomy with methylene blue injection technique. The diagnosis of chronic cholecystitis (the thickness of the gall bladder wall was normal) confirmed by pre-operative abdominal ultrasonography in all patients. The diameters of the stones were greater than 1 centimeter in 32 patients and calcula of various sizes being smaller than 1 cm. were documented in 13 cases. One patient was operated for gall bladder polyp (our first case). Successful coloration of the gall bladder, cystic duct and ductus choledochus was possible in 43 patients, whereas only the gall bladder and proximal cystic duct were visualised in 3 cases. In these cases, ductus choledochus visibility was not possible. None of the patients developed bile duct injury. Conclusion The number of bile duct injuries related to anatomic misidentification can be decreased and even vanished by using intraoperative methylene blue injection technique into the gall bladder fundus intraoperatively. PMID:15963227

Chronically Inflamed Livers Up-regulate Expression of Inhibitory B7 Family Members

PubMed Central

Kassel, Rachel; Cruise, Michael W.; Iezzoni, Julia C.; Taylor, Nicholas A.; Pruett, Timothy L.; Hahn, Young S.

2010-01-01

Hepatitis B virus (HBV), hepatitis C virus (HCV), autoimmune hepatitis (AIH), and non-alcoholic fatty liver disease (NAFLD) can induce chronic liver disease. The PD-1 inhibitory pathway assists in T cell response regulation during acute and chronic inflammation and participates in the progression of inflammatory liver disease. To examine whether PD-1 and its ligands, B7-H1 and B7-DC, are modulated during chronic necroinflammatory liver disease, we investigated expression profiles in normal patients and patients with the aforementioned conditions. Relative to liver biopsies from normal individuals, those from patients with chronic necroinflammatory liver diseases (HBV, HCV, and AIH) contain increased numbers of PD-1 expressing lymphocytes. Kupffer cells, liver sinusoidal endothelial cells (LSECs), and leukocytes express PD-1 ligands. We also detect PD-1 ligands on hepatocytes within biopsies and on isolated cells. All forms of chronic necroinflammatory liver disease examined correlate with increased B7-H1 and B7-DC expression on Kupffer cells, LSECs, and leukocytes. The degree of necroinflammation correlates with expression levels of PD-1 family members. These results demonstrate that expression of PD-1/PD-1 ligands links more directly with the degree of inflammation than with the underlying etiology of liver damage. The PD-1 pathway may assist the liver in protecting itself from immune-mediated destruction. PMID:19739236

Deep Granuloma Annulare Mimicking Inflamed Cysts in a Teenager.

PubMed

Guo, Emily L; Degesys, Catherine A; Jahan-Tigh, Richard; Chan, Audrey

2017-07-01

We describe deep granuloma annulare (DGA) of the forehead mimicking inflamed cysts. Reactive inflammation and sterile purulent drainage may be an underrecognized feature of DGA. © 2017 Wiley Periodicals, Inc.

Validation of the AOP network “Thyroperoxidase and/or deiodinase inhibition leading to impaired swim bladder inflation”

EPA Science Inventory

Industrial chemicals released in the aquatic environment can pose risks for both environmental and human health. Fish are widely used sentinels for evaluating aquatic toxicity to vertebrates in order to set environmental quality standards, However, chronic toxicity testing with f...

METABOLSM OF PENTAVALENT AND TRIVALENT DIMETHYLARSENIC ARSENIC IN THE MOUSE

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen after chronic exposure in either drinking water or the diet. DMA(V) is also a major urinary metabolite of mammals exposed to inorganic arsenic. In mice, iv and po administration of [¹⁴C]-DMA(V) results in rapi...

FOLATE DEFICIENCY ENHANCES ARSENIC EFFECTS ON EXPRESSION OF GENES INVOLVED IN EPIDERMAL DIFFERENTIATION

EPA Science Inventory

Chronic arsenic exposure in humans is associated with cancers of the skin, lung, and bladder. There is evidence that folate deficiency may increase susceptibility to arsenic¿s effects, including arsenic-induced skin lesions. K6/ODC mice develop skin tumors when exposed to 10 ppm ...

Iron acquisition pathways and colonization of the inflamed intestine by Salmonella enterica serovar Typhimurium

PubMed Central

Costa, Luciana F.; Mol, Juliana P. S.; Silva, Ana Patricia C.; Macêdo, Auricélio A.; Silva, Teane M. A.; Alves, Geraldo E. S.; Winter, Sebastian; Winter, Maria G.; Velazquez, Eric M.; Byndloss, Mariana X.; Bäumler, Andreas J.; Tsolis, Renée M.; Paixão, Tatiane A.; Santos, Renato L.

2016-01-01

Salmonella enterica serotype Typhimurium is able to expand in the lumen of the inflamed intestine through mechanisms that have not been fully resolved. Here we utilized streptomycin-pretreated mice and dextran sodium sulfate (DSS)-treated mice to investigate how pathways for S. Typhimurium iron acquisition contribute to pathogen expansion in the inflamed intestine. Competitive infection with an iron uptake-proficient S. Typhimurium strain and mutant strains lacking tonB feoB, feoB, tonB or iroN in streptomycin pretreated mice demonstrated that ferric iron uptake requiring IroN and TonB conferred a fitness advantage during growth in the inflamed intestine. However, the fitness advantage conferred by ferrous iron uptake mechanisms was independent of inflammation and was only apparent in models where the normal microbiota composition had been disrupted by antibiotic treatment. PMID:27760693

Activation of the CXCL16/CXCR6 Pathway by Inflammation Contributes to Atherosclerosis in Patients with End-stage Renal Disease.

PubMed

Hu, Ze Bo; Chen, Yan; Gong, Yu Xiang; Gao, Min; Zhang, Yang; Wang, Gui Hua; Tang, Ri Ning; Liu, Hong; Liu, Bi Cheng; Ma, Kun Ling

2016-01-01

Background: Chronic inflammation plays a critical role in the progression of atherosclerosis (AS). This study aimed to determine the effects of the CXC chemokine ligand 16 (CXCL16)/CXC chemokine receptor 6 (CXCR6) pathway on cholesterol accumulation in the radial arteries of end-stage renal disease (ESRD) patients with concomitant microinflammation and to further investigate the potential effects of the purinergic receptor P2X ligand-gated ion channel 7 (P2X7R). Methods: Forty-three ESRD patients were divided into the control group (n=17) and the inflamed group (n=26) based on plasma C-reactive protein (CRP) levels. Biochemical indexes and lipid profiles of the patients were determined. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used for preliminary evaluation of AS. Haematoxylin-eosin (HE) and Filipin staining were performed to assess foam cell formation. CXCL16/CXCR6 pathway-related protein expression, P2X7R protein expression and the expression of monocyte chemotactic protein-1 (MCP-1), tumour necrosis factor-α (TNF-α), and CD68 were detected by immunohistochemical and immunofluorescence staining. Results: Inflammation increased both MCP-1 and TNF-α expression and macrophage infiltration in radial arteries. Additionally, foam cell formation significantly increased in the radial arteries of the inflamed group compared to that of the controls. Further analysis showed that protein expression of CXCL16, CXCR6, disintegrin and metalloproteinase-10 (ADAM10) in the radial arteries of the inflamed group was significantly increased. Furthermore, CXCL16 expression was positively correlated with P2X7R expression in the radial arteries of ESRD patients. Conclusions: Inflammation contributed to foam cell formation in the radial arteries of ESRD patients via activation of the CXCL16/CXCR6 pathway, which may be regulated by P2X7R.

Dermal fibroblasts from acute inflamed atopic dermatitis lesions display increased eotaxin/CCL11 responsiveness to interleukin-4 stimulation.

PubMed

Gahr, N; Fölster-Holst, R; Weichenthal, M; Christophers, E; Schröder, J-M; Bartels, J

2011-03-01

The presence of eosinophils and/or eosinophil-derived products in the dermis is characteristic for involved skin of patients with atopic dermatitis and contributes to the observed tissue injury. CCL11 is a potent chemoattractant and activator of human eosinophils and interleukin (IL)-4 is a potent inducer of CCL11 expression in dermal fibroblasts. As increased fibroblast CCL11 expression may explain eosinophilic infiltration of involved skin areas in atopic dermatitis, we asked whether dermal fibroblasts from atopic patients differ from fibroblasts of healthy individuals in their ability to express CCL11. We compared IL-4-induced CCL11 mRNA expression using reverse transcription-polymerase chain reaction from cultured dermal fibroblasts derived from biopsies of chronic lesional and acute lesional atopic skin as well as from skin biopsies derived from normal skin of healthy donors. Considerable variability in IL-4-induced relative CCL11 mRNA expression was detected in fibroblasts derived from biopsies of different individuals. The lowest median IL-4 concentration inducing half maximal CCL11 mRNA expression (EC(50)) was found in fibroblasts derived from acute inflamed atopic lesions. Inducibility of CCL11 in dermal fibroblasts upon stimulation with Th2 cytokines explains the tissue eosinophilia observed in the presence of Th2 cytokines and the localization of eosinophils to the dermis. Decreased EC(50) values of IL-4-induced CCL11 expression in fibroblasts from acute inflamed atopic skin lesions indicates increased IL-4 responsiveness in these lesions and further substantiates the special role for IL-4-induced dermal fibroblast CCL11 expression in acute lesions. Variable CCL11 expression in fibroblasts from different patients with atopic dermatitis indicates heterogeneity of factors determining atopic phenotype in atopic dermatitis. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Mesenchymal stem cells derived from inflamed dental pulpal and gingival tissue: a potential application for bone formation.

PubMed

Tomasello, Laura; Mauceri, Rodolfo; Coppola, Antonina; Pitrone, Maria; Pizzo, Giuseppe; Campisi, Giuseppina; Pizzolanti, Giuseppe; Giordano, Carla

2017-08-01

Chronic periodontal disease is an infectious disease consisting of prolonged inflammation of the supporting tooth tissue and resulting in bone loss. Guided bone regeneration procedures have become common and safe treatments in dentistry, and in this context dental stem cells would represent the ideal solution as autologous cells. In this study, we verified the ability of dental pulp mesenchymal stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs) harvested from periodontally affected teeth to produce new mineralized bone tissue in vitro, and compared this to cells from healthy teeth. To characterize DPSCs and GMSCs, we assessed colony-forming assay, immunophenotyping, mesenchymal/stem cell phenotyping, stem gene profiling by means of flow cytometry, and quantitative polymerase chain reaction (qPCR). The effects of proinflammatory cytokines on mesenchymal stem cell (MSC) proliferation and differentiation potential were investigated. We also observed participation of several heat shock proteins (HSPs) and actin-depolymerizing factors (ADFs) during osteogenic differentiation. DPSCs and GMSCs were successfully isolated both from periodontally affected dental tissue and controls. Periodontally affected dental MSCs proliferated faster, and the inflamed environment did not affect MSC marker expressions. The calcium deposition was higher in periodontally affected MSCs than in the control group. Proinflammatory cytokines activate a cytoskeleton remodeling, interacting with HSPs including HSP90 and HSPA9, thioredoxin-1, and ADFs such as as profilin-1, cofilin-1, and vinculin that probably mediate the increased acquisition in the inflamed environment. Our findings provide evidence that periodontally affected dental tissue (both pulp and gingiva) can be used as a source of MSCs with intact stem cell properties. Moreover, we demonstrated that the osteogenic capability of DPSCs and GMSCs in the test group was not only preserved but increased by the overexpression of several proinflammatory cytokine-dependent chaperones and stress response proteins.

Inflammation disrupts the LDL receptor pathway and accelerates the progression of vascular calcification in ESRD patients.

PubMed

Liu, Jing; Ma, Kun Ling; Gao, Min; Wang, Chang Xian; Ni, Jie; Zhang, Yang; Zhang, Xiao Liang; Liu, Hong; Wang, Yan Li; Liu, Bi Cheng

2012-01-01

Chronic inflammation plays a crucial role in the progression of vascular calcification (VC). This study was designed to investigate whether the low-density lipoprotein receptor (LDLr) pathway is involved in the progression of VC in patients with end-stage renal disease (ESRD) during inflammation. Twenty-eight ESRD patients were divided into control and inflamed groups according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in the experiments. The expression of tumour necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in the inflamed group. Hematoxylin-eosin and alizarin red S staining revealed parallel increases in foam cell formation and calcium deposit formation in continuous cross-sections of radial arteries in the inflamed group compared to the control, which were closely correlated with increased LDLr, sterol regulatory element binding protein-2 (SREBP-2), bone morphogenetic proteins-2 (BMP-2), and collagen I protein expression, as shown by immunohistochemical and immunofluorescent staining. Confocal microscopy confirmed that inflammation enhanced the translocation of the SREBP cleavage-activating protein (SCAP)/SREBP-2 complex from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Inflammation increased alkaline phosphatase protein expression and reduced α-smooth muscle actin protein expression, contributing to the conversion of the vascular smooth muscle cells in calcified vessels from the fibroblastic to the osteogenic phenotype; osteogenic cells are the main cellular components involved in VC. Further analysis showed that the inflammation-induced disruption of the LDLr pathway was significantly associated with enhanced BMP-2 and collagen I expression. Inflammation accelerated the progression of VC in ESRD patients by disrupting the LDLr pathway, which may represent a novel mechanism involved in the progression of both VC and atherosclerosis.

Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation.

PubMed

Uo, Michihide; Hisamatsu, Tadakazu; Miyoshi, Jun; Kaito, Daiki; Yoneno, Kazuaki; Kitazume, Mina T; Mori, Maiko; Sugita, Akira; Koganei, Kazutaka; Matsuoka, Katsuyoshi; Kanai, Takanori; Hibi, Toshifumi

2013-12-01

Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1β (IL-1β), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1β production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

Increased duodenal expression of miR-146a and -155 in pediatric Crohn’s disease

PubMed Central

Szűcs, Dániel; Béres, Nóra Judit; Rokonay, Réka; Boros, Kriszta; Borka, Katalin; Kiss, Zoltán; Arató, András; Szabó, Attila J; Vannay, Ádám; Sziksz, Erna; Bereczki, Csaba; Veres, Gábor

2016-01-01

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn’s disease (CD) and the effect of transforming growth factor-β (TGF-β) on these miRs in duodenal epithelial and fibroblast cells. METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well. RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P ≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P ≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, P ≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P ≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P ≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-β treatment did not influence the expression of miR-122. CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-β plays an important role in the regulation of the expression of these miRs. PMID:27468194

Opioid systems in the response to inflammatory pain: sustained blockade suggests role of kappa- but not mu-opioid receptors in the modulation of nociception, behaviour and pathology.

PubMed

Millan, M J; Colpaert, F C

1991-01-01

One day after intraplantar inoculation of Mycobacterium butyricum into the right hind-paw, unilaterally inflamed and control rats were implanted subcutaneously with osmotic mini-pumps delivering naloxone at 0.16 or 3.0 mg/kg/h or vehicle. As determined three days after implantation, 0.16 mg/kg/h of naloxone completely antagonized the antinociceptive action of the mu-agonist, morphine, but did not affect antinociception evoked by the kappa-agonist, U69,593. In contrast, at 3.0 mg/kg/h, naloxone blocked both morphine- and U69,593-induced antinociception. Thus, 0.16 mg/kg ("low dose") and 3.0 mg/kg ("high dose") of naloxone block mu, or mu- plus kappa-opioid receptors, respectively. Pumps were removed one week following their implantation. Inoculation was associated with a sustained hyperalgesia of the inflamed paw to noxious pressure, and elevation in resting core temperature, a loss of body weight, hypophagia, hypodipsia and a reduction in mobility. These parameters were differentially modified by the high as compared to the low dose of naloxone. Two days following implantation of pumps delivering the high dose of naloxone, the hyperalgesia of the inflamed paw was potentiated: by six days, this effect was lost. Further, one day after removal of pumps yielding the high dose, the inflamed paw showed a normalization of thresholds, that is a "rebound antinociception". One day later, this effect had subsided. In distinction, at no time did the low dose of naloxone modify nociceptive thresholds. The high dose of naloxone enhanced the reduction in body weight and food intake shown by unilaterally inflamed rats whereas the low dose was ineffective. Neither dose affected the reduction in water intake or hypothermia of unilaterally inflamed animals. The high dose of naloxone reduced the mobility of unilaterally inflamed rats whereas the low dose was ineffective. Finally, by 10 days following pump removal, pathology had transferred to the contralateral paw. In rats which had received the high but not the low dose, this transfer was blocked. It is concluded that blockade of kappa-opioid receptors with a high dose of naloxone experts pronounced functional effects in unilaterally inflamed rats. In distinction, selective blockade of mu-receptors with a low dose is ineffective. The changes seen include not only an enhancement of the hyperalgesia of the inflamed tissue, but also an exacerbation of variables (body weight, food intake and motility) which reflect pain states.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic hematuria and localized bladder damage following combined cyclophosphamide and local radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kende, G.; Wajsman, Z.; Thomas, P.R.M.

1979-01-01

A 13-year-old white male had Ewing sarcoma of the right pubic and ischial bones. Initial therapy consisted of 5400 rads in seven weeks to the right side of the pelvis and 14 intravenous injections of cyclophosphamide (Cytoxan, CTX) at 500 mg/m/sup 2/; BCNU and Adriamycin maintenance therapy continued for a total of two years. He has now been disease-free for five years. Three months following the completion of the right pelvic radiotherapy (RT), while on intravenous CTX, severe hematuria appeared, which subsided, but at present he has continuous microscopic hematuria, as well as periodic episodes of gross hematuria. Serial cystocopiesmore » initially revealed thickening and hemorrhagic and edematous changes on the right (irradiated) side of the bladder, and recent multiple telangiectatic patches have been demonstrated as a late healing phase. This case demonstrates the additive toxicity to the bladder of CTX and RT, illustrating that the hemorrhagic cystitis can be extremely protracted lasting five years.« less

The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease☆

PubMed Central

Dale, Philippa R; Cernecka, Hana; Schmidt, Martina; Dowling, Mark R; Charlton, Steven J; Pieper, Michael P; Michel, Martin C

2014-01-01

Muscarinic receptor antagonists and β-adrenoceptor agonists are used in the treatment of obstructive airway disease and overactive bladder syndrome. Here we review the pharmacological rationale for their combination. Muscarinic receptors and β-adrenoceptors are physiological antagonists for smooth muscle tone in airways and bladder. Muscarinic agonism may attenuate β-adrenoceptor-mediated relaxation more than other contractile stimuli. Chronic treatment with one drug class may regulate expression of the target receptor but also that of the opposing receptor. Prejunctional β2-adrenoceptors can enhance neuronal acetylcholine release. Moreover, at least in the airways, muscarinic receptors and β-adrenoceptors are expressed in different locations, indicating that only a combined modulation of both systems may cause dilatation along the entire bronchial tree. While all of these factors contribute to a rationale for a combination of muscarinic receptor antagonists and β-adrenoceptor agonists, the full value of such combination as compared to monotherapy can only be determined in clinical studies. PMID:24682092

Plasmacytoid dendritic cells and type I interferon in the immunological response against warts.

PubMed

Saadeh, D; Kurban, M; Abbas, O

2017-12-01

Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), and are involved in the pathogenesis of several cutaneous infectious (especially viral), inflammatory/autoimmune and neoplastic entities. Their role in the pathogenesis and regression of human papilloma virus (HPV)-induced skin lesions has not been well studied. To investigate pDC occurrence and activity in HPV-induced skin lesions, including inflamed and uninflamed warts as well as epidermodysplasia verruciformis (EDV)-associated lesions. In total 20 inflamed and 20 uninflamed HPV-induced skin lesions (including 7 EDV lesions) were retrieved from our database, and the tissue was immunohistochemically tested for pDC occurrence and activity using anti-BDCA-2 and anti-MxA antibodies, respectively. pDCs were present in all 20 inflamed warts and absent from all 20 uninflamed cases. MxA expression was also diffuse and strong in 75% (15/20) inflamed warts, but not in any of the uninflamed warts. pDCs constitute a central component of the inflammatory host response in inflamed warts, possibly contributing to their regression through production of type I interferons. © 2017 British Association of Dermatologists.

The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia.

PubMed

Ackerman, A Lenore; Jellison, Forrest C; Lee, Una J; Bradesi, Sylvie; Rodríguez, Larissa V

2016-04-01

Psychological stress exacerbates interstitial cystitis/bladder pain syndrome (IC/BPS), a lower urinary tract pain disorder characterized by increased urinary frequency and bladder pain. Glutamate (Glu) is the primary excitatory neurotransmitter modulating nociceptive networks. Glt1, an astrocytic transporter responsible for Glu clearance, is critical in pain signaling termination. We sought to examine the role of Glt1 in stress-induced bladder hyperalgesia and urinary frequency. In a model of stress-induced bladder hyperalgesia with high construct validity to human IC/BPS, female Wistar-Kyoto (WKY) rats were subjected to 10-day water avoidance stress (WAS). Referred hyperalgesia and tactile allodynia were assessed after WAS with von Frey filaments. After behavioral testing, we assessed Glt1 expression in the spinal cord by immunoblotting. We also examined the influence of dihydrokainate (DHK) and ceftriaxone (CTX), which downregulate and upregulate Glt1, respectively, on pain development. Rats exposed to WAS demonstrated increased voiding frequency, increased colonic motility, anxiety-like behaviors, and enhanced visceral hyperalgesia and tactile allodynia. This behavioral phenotype correlated with decreases in spinal Glt1 expression. Exogenous Glt1 downregulation by DHK resulted in hyperalgesia similar to that following WAS. Exogenous Glt1 upregulation via intraperitoneal CTX injection inhibited the development of and reversed preexisting pain and voiding dysfunction induced by WAS. Repeated psychological stress results in voiding dysfunction and hyperalgesia that correlate with altered central nervous system glutamate processing. Manipulation of Glu handling altered the allodynia developing after psychological stress, implicating Glu neurotransmission in the pathophysiology of bladder hyperalgesia in the WAS model of IC/BPS. Copyright © 2016 the American Physiological Society.

Embryonic kidney function in a chronic renal failure model in rodents.

PubMed

Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

Intravesical PAC1 Receptor Antagonist, PACAP(6–38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in NGF-OE Mice

PubMed Central

Girard, Beatrice M.; Malley, Susan E.; Mathews, Morgan M.; May, Victor

2017-01-01

Chronic NGF overexpression (OE) in the urothelium, achieved through the use of a highly urothelium-specific uroplakin II promoter, stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency and non-voiding contractions, and referred somatic sensitivity. Additional NGF-mediated pleiotropic changes might contribute to increased voiding frequency and pelvic hypersensitivity in NGF-OE mice such as neuropeptide/receptor systems including PACAP(Adcyap1) and PAC1 receptor (Adcyap1r1). Given the presence of PAC1-immunoreactive fibers and the expression of PAC1 receptor expression in bladder tissues, and PACAP-facilitated detrusor contraction, whether PACAP/receptor signaling contributes to increased voiding frequency and somatic sensitivity was evaluated in NGF-OE mice. Intravesical administration of the PAC1 receptor antagonist, PACAP(6–38) (300 nM), significantly (p ≤ 0.01) increased intercontraction interval (2.0-fold) and void volume (2.5-fold) in NGF-OE mice. Intravesical instillation of PACAP(6–38) also decreased baseline bladder pressure in NGF-OE mice. PACAP(6–38) had no effects on bladder function in WT mice. Intravesical administration of PACAP(6–38) (300 nM) significantly (p ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in WT mice. PACAP/receptor signaling contributes to the increased voiding frequency and pelvic sensitivity observed in NGF-OE mice. PMID:27146136

Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

PubMed Central

Rager, Julia E.; Miller, Sloane; Tulenko, Samantha E.; Smeester, Lisa; Ray, Paul D.; Yosim, Andrew; Currier, Jenna M.; Ishida, María C.; González-Horta, Maria del Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Gutiérrez-Torres, Daniela S.; Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Kim, William Y.; Zhou, Yi-Hui; Wright, Fred A.; Stýblo, Miroslav; Fry, Rebecca C.

2016-01-01

There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to a myriad of adverse health effects, including cancer of the bladder. The present study set out to identify DNA methylation patterns associated with iAs and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic (As)-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total As (tAs) and As species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 As-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the As- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer. PMID:26039340

Should a detailed ultrasound examination of the complete urinary tract be routinely performed in women with suspected pelvic endometriosis?

PubMed

Pateman, K; Holland, T K; Knez, J; Derdelis, G; Cutner, A; Saridogan, E; Jurkovic, D

2015-12-01

Is there any benefit to including the routine examination by ultrasound of the bladder, ureters and kidneys of women with endometriosis? The benefit of examination of the complete urinary tract of women with suspected endometriosis is that ureteric endometriosis, with or without hydronephrosis, can be detected which facilitates early intervention to prevent nephropathy. Women with endometriosis can get ureteric obstruction but there is no clear consensus on the correct diagnostic technique. Ultrasound is accurate at detecting women with bladder endometriosis but ureteric involvement has not been assessed previously. This was a prospective observational study, conducted at a teaching hospital over a period of 14 months. A total of 848 women presenting with chronic pelvic pain were included into the study. All women with chronic pelvic pain underwent a detailed transvaginal and transabdominal pelvic ultrasound examination to investigate possible causes of their symptoms. This included a systematic assessment of the urinary bladder, pelvic sections of the ureters and kidneys. The ultrasound findings were compared with findings at surgery and the results of targeted urological imaging and interventions. A total of 848 women presenting with chronic pelvic pain were included into the study. 28/848 women (3.3% 95% CI 2.1-4.5) had evidence of urinary tract abnormalities on initial ultrasound scan. Among these 17/848 (2.0% 95% CI 1.06-2.94) had evidence of urinary tract endometriosis, whilst 11/848 (1.3% 95% CI 0.54-2.06) women had other urinary tract abnormalities. Among women with urinary tract endometriosis 11/17 (65%) had evidence of ureteric involvement, 3/17 (18%) had both ureteric and bladder disease and 3/17 (18%) had bladder disease only. 12/17 (59%) women with urinary tract endometriosis also had evidence of hydronephrosis. The diagnosis of ureteral endometriosis had a sensitivity of 12/13 (92%) (95% CI 63.9-99.8), specificity 151/151 100% (95% CI 97.6-100), PPV 100% (95% CI 73.5-100), NPV 99.3% (95% CI 96.3-99.9%) LR- 0.08 (95% CI 0.01-0.39). The routine examination of the complete urinary tract including the distal ureters is a novel technique that should be evaluated in different populations. Ultrasound is an accurate test to diagnose urinary tract involvement in women with suspected pelvic endometriosis and examination of the complete urinary tract should become an integral part of ultrasound assessment of women with suspected endometriosis. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tolerance of the canine bladder to intraoperative radiation therapy: an experimental study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinsella, T.J.; Sindelar, W.F.; DeLuca, A.M.

1988-05-01

An experimental study of bladder tolerance to intraoperative radiotherapy (IORT) was designed using a large animal model (adult American Foxhounds, weight 25-30 kg) to access acute and late radiation effects. Dogs were subjected to laparotomy where the bladder was mobilized and IORT was delivered using a 5 cm circular cone through a cystotomy incision with 12 MeV electrons. The bladder trigone including both ureteral orifices and the proximal urethra was irradiated in groups of 3 dogs with doses of 0, 20, 25, 30, 35, and 40 Gy. Dogs were followed clinically with repeat urinalysis, intravenous pyelogram (IVP), and cystometrogram atmore » 1 month and then Q6 months for up to 4 years. One dog from each dose group was sacrificed electively at 1 and 2 years, whereas the other dog is being followed clinically for a minimum of 4 years. Complete autopsies were performed with particular attention to genitourinary and pelvic structures. No clinically detectable acute toxicity resulted from IORT to the bladder. Three of 15 IORT dogs (1 each at 25, 35, and 40 Gy) showed obstruction of a ureteral orifice with 2 dogs dying of renal failure secondary to bilateral hydronephrosis within 1-2 years of treatment. The remaining 12 IORT dogs and 3 control dogs have normal repeat IVP's and renal function with up to 4 years of follow-up. Serial cystometry demonstrates no major loss of bladder contractility or volume. At autopsy, histological changes of mucosal thinning and telangiectasia with submucosal fibrosis were confined to the IORT field and appeared dose-related. However, the bladder epithelium remained intact at all doses. The ureterovesical junction in animals receiving 20 Gy showed mild fibrosis of the lamina propria and moderate chronic inflammation. Above 20 Gy, these histological changes at the U-V junction were more pronounced with gross stenosis in 3 animals as predicted by the IVP.« less

Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array

EPA Science Inventory

Arsenic contamination in drinking water has become a great public health concern worldwide. Chronic arsenic exposure results in higher risk of skin, lung and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects o...

Impact of lifestage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice.

EPA Science Inventory

Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumo...

Anorectal and Pelvic Pain

PubMed Central

Bharucha, Adil E.; Lee, Tae Hee

2016-01-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the three most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first two conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacologic, behavioral, and physical therapy. Opioids should not be avoided, and surgery has a limited role, primarily in refractory interstitial cystitis. PMID:27712641

Alpha lipoic acid in obstetrics and gynecology.

PubMed

Di Tucci, Chiara; Di Feliciantonio, Mara; Vena, Flaminia; Capone, Carmela; Schiavi, Michele Carlo; Pietrangeli, Daniela; Muzii, Ludovico; Benedetti Panici, Pierluigi

2018-05-04

Alpha-Lipoic acid (ALA) is a natural antioxidant synthetized by plants and animals, identified as a catalytic agent for oxidative decarboxylation of pyruvate and α-ketoglutarate. In this review, we analyzed the action of ALA in gynecology and obstetrics focusing in particular on neuropathic pain and antioxidant and anti-inflammatory action. A comprehensive literature search was performed in PubMed and Cochrane Library for retrieving articles in English language on the antioxidant and anti-inflammatory effects of ALA in gynecological and obstetrical conditions. ALA reduces oxidative stress and insulin resistance in women with polycystic ovary syndrome (PCOS). The association of N-acetyl cysteine (NAC), alpha-lipoic acid (ALA), and bromelain (Br) is used for prevention and treatment of endometriosis. In association with omega-3 polyunsaturated fatty acids (n-3 PUFAs) with amitriptyline is used for treatment of vestibulodynia/painful bladder syndrome (VBD/PBS). A promising area of research is ALA supplementation in patients with threatened miscarriage to improve the subchorionic hematoma resorption. Furthermore, ALA could be used in prevention of diabetic embryopathy and premature rupture of fetal membranes induced by inflamation. In conclusion, ALA can be safely used for treatment of neuropatic pain and as a dietary support during pregnancy.

[Bladder injury during sling operation in the treatment of SUI--review of literature and case report].

PubMed

Gałczyński, Krzysztof; Futyma, Konrad; Bar, Krzysztof; Rechberger, Tomasz

2012-10-01

Sling operations have been performed for over 15 years. In recent years these operations have become the gold standard in the treatment of stress urinary incontinence (SUI) due to their efficacy safety and low invasiveness. Approximately 4% of women will undergo a surgery for SUI in the course of their life. As with any surgical intervention, there may be some technical problems, as well as intra- and postoperative complications, the most common of which is bladder injury Other complications encountered during mid-urethral slings procedures include bleeding (retropubic or vaginal hematomas), urethral perforation, urinary tract infections, postoperative vaginal or urethral erosions, bowel perforation, chronic pelvic pain, wound infection, nerve injury transient and persistent voiding dysfunction such as de novo urgency incomplete bladder emptying or urinary retention. Below we present a case of a patient with diagnosed vesicovaginal fistula after sling operation (TVT-tension-free vaginal tape). Upon admission the patient reported dysuria, persistent urinary leakage and abnormal, abundant vaginal discharge. Case report and review of literature concerning surgical treatment of stress urinary incontinence and its complications. Analysis of medical documentation of the patient treated at the Second Department of Gynecology Medical University of Lublin. Review of abstracts or papers in the Medline database related to surgical treatment of urinary incontinence and its complications. Bladder perforation is one of the most common complications of the retropubic approach for MUS placement. The presence of mesh within the bladder may arise from direct bladder perforation or from subsequent erosion of the sling. Such lesions do not cause any serious health consequences for patients on condition they are detected intraoperatively and appropriately repaired, but when unrecognized, they results in the development of considerable symptoms and negatively influence the quality of patient life. Improperly treated, it can lead to development of an abnormal communication between the urinary bladder and the anterior wall of the vagina -vesicovaginal fistula. We should suspect unrecognized bladder injury in case of patients with any persistent voiding symptoms after a sling procedure such as long lasting dysuria, persistent urinary leakage, hematuria, recurrent infections, chronic pain and voiding difficulties. Diagnosis and treatment of vesicovaginal fistula is long lasting and difficult for the patient and the surgeon. Füth-Mayo operation is an effective treatment method for the majority of vesicovaginal fistulas. During this operation we suture all layers of fistula separately (bladder perivesical fascia and vaginal wall). Although with this operation we solve one problem, the patient still might suffer from recurrent SUI. Alternative methods of treatment which can be offered to patients after unsuccessful SUI operation are periurethral injections with bulking agents or electrical stimulation of the pelvic floor muscles. Both methods are effective in the therapy of recurrent SUI. In our case periurtehral injection of Bulkamid did not provide a total cure. Therefore, we completed the treatment with electrical stimulation of the pelvic floor muscles using patient-controlled electrodes placed in the vagina to stimulate muscles with current frequency of 50 Hz, amperage between 0-60 mA and duration of 250 micros. This procedure produced a series of changes in the stimulated area and enabled to cure the incontinence.

Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn's disease mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and cell-cell contact.

PubMed

Ciccocioppo, Rachele; Cangemi, Giuseppina C; Kruzliak, Peter; Gallia, Alessandra; Betti, Elena; Badulli, Carla; Martinetti, Miryam; Cervio, Marila; Pecci, Alessandro; Bozzi, Valeria; Dionigi, Paolo; Visai, Livia; Gurrado, Antonella; Alvisi, Costanza; Picone, Cristina; Monti, Manuela; Bernardo, Maria E; Gobbi, Paolo; Corazza, Gino R

2015-07-24

Crohn's disease (CD) is a disabling chronic enteropathy sustained by a harmful T-cell response toward antigens of the gut microbiota in genetically susceptible subjects. Growing evidence highlights the safety and possible efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this condition. Therefore, we aimed to investigate the effects of bone marrow-derived MSCs on pathogenic T cells with a view to clinical application. T-cell lines from both inflamed and non-inflamed colonic mucosal specimens of CD patients and from healthy mucosa of control subjects were grown with the antigen muramyl-dipeptide in the absence or presence of donors' MSCs. The MSC effects were evaluated in terms of T-cell viability, apoptotic rate, proliferative response, immunophenotype, and cytokine profile. The role of the indoleamine 2,3-dioxygenase (IDO) was established by adding a specific inhibitor, the 1-methyl-DL-tryptophan, and by using MSCs transfected with the small interfering RNA (siRNA) targeting IDO. The relevance of cell-cell contact was evaluated by applying transwell membranes. A significant reduction in both cell viability and proliferative response to muramyl-dipeptide, with simultaneous increase in the apoptotic rate, was found in T cells from both inflamed and non-inflamed CD mucosa when co-cultured with MSCs and was reverted by inhibiting IDO activity and expression. A reduction of the activated CD4(+)CD25(+) subset and increase of the CD3(+)CD69(+) population were also observed when T-cell lines from CD mucosa were co-cultured with MSCs. In parallel, an inhibitory effect was evident on the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interferon-γ, interleukin-17A and -21, whereas that of the transforming growth factor-β and interleukin-6 were increased, and production of the tolerogenic molecule soluble HLA-G was high. These latter effects were almost completely eliminated by blocking the IDO, whose activity was upregulated in MSCs co-cultured with CD T cells. The use of a semipermeable membrane partially inhibited the MSC immunosuppressive effects. Finally, hardly any effects of MSCs were observed when T cells obtained from control subjects were used. MSCs exert potent immunomodulant effects on antigen-specific T cells in CD through a complex paracrine and cell-cell contact-mediated action, which may be exploited for widespread therapeutic use.

Established T-cell inflamed tumors rejected after adaptive resistance was reversed by combination STING activation and PD-1–pathway blockade

PubMed Central

Moore, Ellen; Clavijo, Paul E.; Davis, Ruth; Cash, Harrison; Van Waes, Carter; Kim, Young; Allen, Clint

2016-01-01

Patients with head and neck squamous cell carcinoma harbor T-cell inflamed and non-T-cell inflamed tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack of induction of innate immunity through pattern-recognition receptors such as the stimulator of interferon (IFN) genes (STING) receptor may represent a significant barrier to the development of effective antitumor immunity. Here, we demonstrate robust control of a T-cell inflamed (MOC1), but not non-T-cell inflamed (MOC2), model of head and neck cancer by activation of the STING pathway with the synthetic cyclic dinucleotide RP,RP dithio-c-di-GMP. Rejection or durable tumor control of MOC1 tumors was dependent upon a functional STING receptor and CD8 T lymphocytes. STING activation resulted in increased tumor microenvironment type 1 and type 2 IFN and greater expression of PD-1–pathway components in vivo. Established MOC1 tumors were rejected and distant tumors abscopally controlled, after adaptive immune resistance had been reversed by the addition of PD-L1 mAb. These findings suggest that PD-1-pathway blockade may reverse adaptive immune resistance following cyclic dinucleotide treatment, enhancing both local and systemic antitumor immunity. PMID:27821498

Primary afferent neurons express functional delta opioid receptors in inflamed skin.

PubMed

Brederson, Jill-Desiree; Honda, Christopher N

2015-07-21

Peripherally-restricted opiate compounds attenuate hyperalgesia in experimental models of inflammatory pain, but have little discernable effect on nociceptive behavior in normal animals. This suggests that activation of opioid receptors on peripheral sensory axons contributes to decreased afferent activity after injury. Previously, we reported that direct application of morphine to cutaneous receptive fields decreased mechanical and heat-evoked responses in a population of C-fiber nociceptors in inflamed skin. Consistent with reported behavioral studies, direct application of morphine had no effect on fiber activity in control skin. The aim of the present study was to determine whether mechanical responsiveness of nociceptors innervating inflamed skin was attenuated by direct activation of delta opioid receptors (DORs) on peripheral terminals. An ex vivo preparation of rat plantar skin and tibial nerve was used to examine effects of a selective DOR agonist, deltorphin II, on responsiveness of single fibers innervating inflamed skin. Electrical recordings were made eighteen hours after injection of complete Freund's adjuvant into the hindpaw. Deltorphin II produced an inhibition of the mechanical responsiveness of single fibers innervating inflamed skin; an effect blocked by the DOR-selective antagonist, naltrindole. The population of units responsive to deltorphin II was identified as consisting of C fiber mechanical nociceptors. Copyright © 2015 Elsevier B.V. All rights reserved.

Cancer Mortality Following Radiotherapy for Benign Gynecologic Disorders

PubMed Central

Sakata, Ritsu; Kleinerman, Ruth A.; Mabuchi, Kiyohiko; Stovall, Marilyn; Smith, Susan A.; Weathers, Rita; Wactawski-Wende, Jean; Cookfair, Diane L.; Boice, John D.; Inskip, Peter D.

2012-01-01

The purpose of this study is to quantify cancer mortality in relationship to organ-specific radiation dose among women irradiated for benign gynecologic disorders. Included in this study are 12,955 women treated for benign gynecologic disorders at hospitals in the Northeastern U.S. between 1925 and 1965; 9,770 women treated by radiation and 3,186 women treated by other methods. The average age at treatment was 45.9 years (range, 13–88 years), and the average follow-up period was 30.1 years (maximum, 69.9 years). Radiation doses to organs and active bone marrow were reconstructed by medical physicists using original radiotherapy records. The highest doses were received by the uterine cervix (median, 120 Gy) and uterine corpus (median, 34 Gy), followed by the bladder, rectum and colon (median, 1.7–7.2 Gy), with other abdominal organs receiving median doses ≤1 Gy and organs in the chest and head receiving doses <0.1 Gy. Standardized mortality rate ratios relative to the general U.S. population were calculated. Radiation-related risks were estimated in internal analyses using Poisson regression models. Mortality was significantly elevated among irradiated women for cancers of the uterine corpus, ovary, bladder, rectum, colon and brain, as well as for leukemia (exclusive of chronic lymphocytic leukemia) but not for cancer of the cervix, Hodgkin or non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia. Evidence of a dose-response was seen for cancers of the ovary [excess relative risk (ERR) 0.31/Gy, P < 0.001], bladder (ERR = 0.21/Gy, P = 0.02) and rectum (ERR = 0.23/Gy, P = 0.05) and suggested for colon (ERR = 0.09/Gy, P = 0.10), but not for cancers of the uterine corpus or brain nor for non-chronic lymphocytic leukemia. Relative risks of mortality due to cancers of the stomach, pancreas, liver and kidney were close to 1.0, with no evidence of dose-response over the range of 0–1.5 Gy. Breast cancer was not significantly associated with dose to the breast or ovary. Mortality due to cancers of heavily irradiated organs remained elevated up to 40 years after irradiation. Significantly elevated radiation-related risk was seen for cancers of organs proximal to the radiation source or fields (bladder, rectum and ovary), as well as for non-chronic lymphocytic leukemia. Our results corroborate those from previous studies that suggest that cells of the uterine cervix and lymphopoietic system are relatively resistant to the carcinogenic effects of radiation. Studies of women irradiated for benign gynecologic disorders, together with studies of women treated with higher doses of radiation for uterine cancers, provide quantitative information on cancer risks associated with a broad range of pelvic radiation exposures. PMID:22856888

Augmentation enterocystoplasty is effective in relieving refractory ketamine-related bladder pain.

PubMed

Chung, Shiu-Dong; Wang, Chung-Cheng; Kuo, Hann-Chorng

2014-11-01

To report our early results of augmentation enterocystoplasty (AE) for severe bladder pain associated with chronic ketamine cystitis (KC). We performed AE for 14 patients with refractory KC-related bladder pain, which is based on the criteria including severe bladder pain, urgency and frequency and/or upper urinary tract damage such as bilateral hydronephrosis, and contracted bladder. Every patient had been treated conservatively with medication or cystoscopic hydrodistention for at least 1 year before they had received surgical intervention. Video-urodynamic studies were obtained before AE and 3-6 months after surgery. Outcome measurements included visual analogue score (VAS) for pain, cystometric bladder capacity (CBC), maximum urinary flow rate (Qmax), post-void residual, and maximal detrusor pressure (Pdet). The patients' general satisfaction with regard to treatment outcome was also assessed by the Patient Perception of Bladder Condition (PPBC). A total of 4 men and 10 women underwent this procedure as indicated. The mean age was 26.7 (ranged 20-38) years old and the duration of ketamine abuse was 3.82 years (ranged 2-7). Contracted bladder was noted in all patients, hydronephrosis in nine and vesicoureteral reflux (VUR) in eight. At 3-6 months after AE, VAS was remarkably improved from baseline to the end-point (8.29 ± 1.54 vs. 2.14 ± 1.51, P < 0.0001), CBC increased from 50.9 ± 15.7 to 309.2 ± 58.0 ml (P < 0.0001), Qmax increased from 6.94 ± 3.60 to 15.2 ± 5.51 ml/sec (P < 0.0001) and Pdet reduced from 29.7 ± 16.0 to 17.9 ± 8.2 cmH2 O (P = 0.008). All patients reported marked improvement in PPBC from 6.0 to 1.4 ± 0.89 (P < 0.0001). All hydronephrosis disappeared and VUR was resolved in five patients after AE with ureteral reimplantation. This pilot study demonstrated that AE is effective in relieving refractory ketamine-related bladder pain and lower urinary tract symptoms. © 2013 Wiley Periodicals, Inc.

LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space.

PubMed

Pace, E; Profita, M; Melis, M; Bonanno, A; Paternò, A; Mody, C H; Spatafora, M; Ferraro, M; Siena, L; Vignola, A M; Bonsignore, G; Gjomarkaj, M

2004-03-01

The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biologically active, as an anti-LTB4 antibody partially neutralized the chemotactic activity of parapneumonic, tuberculous and cancer effusions. Macrophages, neutrophils, lymphocytes, mesothelial cells and cancer cells all expressed mRNA for 5-lipoxygenase, the enzyme that initiates leukotriene synthesis leading to the production of LTB4, in exudative pleural effusions. Upon stimulation in transudative pleural effusions, pleural macrophages produced, in a time-dependent fashion, a significantly higher concentration of LTB4 than mesothelial cells. These studies demonstrate that different cell types are capable of producing LTB4 in the inflamed pleural space and that this mediator may play a crucial role in the recruitment of neutrophils into the pleural space.

LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space

PubMed Central

PACE, E; PROFITA, M; MELIS, M; BONANNO, A; PATERNÒ, A; MODY, CH; SPATAFORA, M; FERRARO, M; SIENA, L; VIGNOLA, AM; BONSIGNORE, G; GJOMARKAJ, M

2004-01-01

The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biologically active, as an anti-LTB4 antibody partially neutralized the chemotactic activity of parapneumonic, tuberculous and cancer effusions. Macrophages, neutrophils, lymphocytes, mesothelial cells and cancer cells all expressed mRNA for 5-lipoxygenase, the enzyme that initiates leukotriene synthesis leading to the production of LTB4, in exudative pleural effusions. Upon stimulation in transudative pleural effusions, pleural macrophages produced, in a time-dependent fashion, a significantly higher concentration of LTB4 than mesothelial cells. These studies demonstrate that different cell types are capable of producing LTB4 in the inflamed pleural space and that this mediator may play a crucial role in the recruitment of neutrophils into the pleural space. PMID:15008988

Overactive Bladder Syndrome: Evaluation and Management.

PubMed

Leron, Elad; Weintraub, Adi Y; Mastrolia, Salvatore A; Schwarzman, Polina

2018-03-01

Overactive bladder (OAB) syndrome is a chronic medical condition which has a major influence on the quality of life in a significant amount of the population. OAB affects performance of daily activities and has an estimated prevalence of 16.5%. Many sufferers do not seek medical help. Moreover, many family physicians and even gynecologists are not familiar with this issue. Usually patients suffer from OAB in advanced age. Nocturia is reported as the most bothersome symptom in the elderly population. The aim of our review was to discuss all aspects of this challenging disorder and suggest tools for assessment and management strategies. Practitioners can easily overlook urinary complains if they not directly queried. We would like to encourage practitioners to give more attention to this issue.

Cytokines and pulmonary fibrosis.

PubMed Central

Gauldie, J.; Jordana, M.; Cox, G.

1993-01-01

Chronically inflamed and fibrotic tissue of the respiratory tract can be shown to actively express the genes and products of a number of powerful growth and differentiating factors. The initial activation of lung inflammatory cells, including alveolar macrophages, is presumed to result in the release of early acting cytokines such as IL-1 and TNF. Subsequent activation and possible phenotype alteration of the structural cells results in release of other growth factors and accumulation of blood derived inflammatory cells. These cells, once they have entered the tissue and become further activated, may begin to release their own autocrine factors and "feed back" some of the similar signals to the tissue cells in a paracrine manner, further inducing differentiation and phenotype change. These internal tissue cell and cytokine cascades could account for the chronic nature of the inflammation. Therapeutic intervention must therefore take into account the inflammatory component as well as the nature of the cytokines and structural cells involved in the propagation of the disease. PMID:8236078

Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins

PubMed Central

Spite, Matthew; Serhan, Charles N.

2010-01-01

The resolution of acute inflammation is a process that allows for inflamed tissues to return to homeostasis. Resolution was held to be a passive process, a concept now overturned with new evidence demonstrating that resolution is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators, such as the lipoxins, resolvins, protectins and newly identified maresins, have emerged as a novel genus of potent and stereoselective players that counter-regulate excessive acute inflammation and stimulate molecular and cellular events that define resolution. Given that uncontrolled, chronic inflammation is associated with many cardiovascular pathologies, an appreciation of the endogenous pathways and mediators that control timely resolution can open new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation, as well as correcting the impact of chronic inflammation in cardiovascular disorders. Here, we overview and update the biosynthesis and actions of pro-resolving lipid mediators, highlighting their diverse protective roles relevant to vascular systems and their relation to aspirin and statin therapies. PMID:21071715

The contribution of activated peripheral kappa opioid receptors (kORs) in the inflamed knee joint to anti-nociception.

PubMed

Moon, Sun Wook; Park, Eui Ho; Suh, Hye Rim; Ko, Duk Hwan; Kim, Yang In; Han, Hee Chul

2016-10-01

The systemic administration of opioids can be used for their strong analgesic effect. However, extensive activation of opioid receptors (ORs) beyond the targeted tissue can cause dysphoria, pruritus, and constipation. Therefore, selective activation of peripheral ORs present in the afferent fibers of the targeted tissue can be considered a superior strategy in opioid analgesia to avoid potential adverse effects. The purpose of this study was to clarify the role of peripheral kappa opioid receptors (kORs) in arthritic pain for the possible use of peripheral ORs as a target in anti-nociceptive therapy. We administered U50488 or nor-BNI/DIPPA, a selective agonist or antagonist of kOR, respectively into arthritic rat knee joints induced using 1% carrageenan. After the injection of U50488 or U50488 with nor-BNI or DIPPA into the inflamed knee joint, we evaluated nociceptive behavior as indicated by reduced weight-bearing on the ipsilateral limbs of the rat and recorded the activity of mechanosensitive afferents (MSA). In the inflamed knee joint, the intra-articular application of 1μM, 10nM, or 0.1nM U50488 resulted in a significant reduction in nociceptive behavior. In addition, 1μM and 10nM U50488 decreased MSA activity. However, in a non-inflamed knee joint, 1μM U50488 had no effect on MSA activity. Additionally, intra-articular pretreatment with 20μM nor-BNI or 10μM DIPPA significantly blocked the inhibitory effects of 1μM U50488 on nociceptive behavior and MSA activity in the inflamed knee joint. These results implicate that peripheral kORs can contribute to anti-nociceptive processing in an inflamed knee joint. Copyright © 2016 Elsevier B.V. All rights reserved.

In vivo skin penetration of macromolecules in irritant contact dermatitis.

PubMed

Abdel-Mottaleb, Mona M A; Lamprecht, Alf

2016-12-30

Recently, a selective preferential accumulation of polymeric nanoparticles (in the size range around 100nm) has been observed in the follicular system of dermatitis skin. The present investigation aimed at clearly investigating the effect of irritant contact dermatitis on the barrier permeability for colloidal systems below this size range, namely quantum dots and hydrophilic macromolecules. Irritant dermatitis was induced in mice and the penetrability of quantum dots (5nm) and hydrophilic dextran molecules has been tracked in both healthy and inflamed skin using confocal laser scanning microscopy. The selective accumulation of the quantum dots was clearly observed in inflamed skin while hydrophilic dextran behaved similarly in both healthy and inflamed skin. The therapeutic potential for the transdermal delivery of peptide drugs through inflamed skin has been also tested in rats. Results revealed that the transdermal permeation of insulin and calcitonin was not significantly enhanced in dermatitis compared to healthy skin. On the other side, permeation through stripped skin was significantly higher. However, the effect was limited and shorter compared to the SC injection where t min was 0.5h and 2h with a 70% and 46% reduction in blood glucose levels for the stripped skin and the SC injection respectively. Similarly, t min was 4h and 8h with area under the curve of 161±65% and 350±97% for the stripped skin and the SC injection respectively. In conclusion, the changes in skin permeability accompanied with skin inflammation did not affect its permeability to peptide drugs. Our findings also underline that experiments with the tape stripped skin model as a surrogate for inflamed skin can risk misleading conclusions due to significant difference of skin permeability between the tape stripped skin and inflamed skin. Copyright © 2016 Elsevier B.V. All rights reserved.

Qualitative and quantitative radiological analysis of non-contrast CT is a strong indicator in patients with acute pyelonephritis.

PubMed

El-Merhi, Fadi; Mohamad, May; Haydar, Ali; Naffaa, Lena; Nasr, Rami; Deeb, Ibrahim Al-Sheikh; Hamieh, Nadine; Tayara, Ziad; Saade, Charbel

2018-04-01

To evaluate the performance of non-contrast computed tomography (CT) by reporting the difference in attenuation between normal and inflamed renal parenchyma in patients clinically diagnosed with acute pyelonephritis (APN). This is a retrospective study concerned with non-contrast CT evaluation of 74 patients, admitted with a clinical diagnosis of APN and failed to respond to 48h antibiotics treatment. Mean attenuation values in Hounsfield units (HU) were measured in the upper, middle and lower segments of the inflamed and the normal kidney of the same patient. Independent t-test was performed for statistical analysis. Image evaluation included receiver operating characteristic (ROC), visual grading characteristic (VGC) and kappa analyses. The mean attenuation in the upper, middle and lower segments of the inflamed renal cortex was 32%, 25%, and 29% lower than the mean attenuation of the corresponding cortical segments of the contralateral normal kidney, respectively (p<0.01). The mean attenuation in the upper, middle, and lower segments of the inflamed renal medulla was 48%, 21%, and 30%, lower than the mean attenuation of the corresponding medullary segments of the contralateral normal kidney (p<0.02). The mean attenuation between the inflamed and non-inflamed renal cortex and medulla was 29% and 30% lower respectively (p<0.001). The AUCROC (p<0.001) analysis demonstrated significantly higher scores for pathology detection, irrespective of image quality, compared to clinical and laboratory results with an increased inter-reader agreement from poor to substantial. Non-contrast CT showed a significant decrease in the parenchymal density of the kidney affected with APN in comparison to the contralateral normal kidney of the same patient. This can be incorporated in the diagnostic criteria of APN in NCCT in the emergency setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the role of the cyclooxygenase signaling pathway during inflammation in skin and muscle tissues of ball pythons (Python regius).

PubMed

Sadler, Ryan A; Schumacher, Juergen P; Rathore, Kusum; Newkirk, Kim M; Cole, Grayson; Seibert, Rachel; Cekanova, Maria

2016-05-01

OBJECTIVE To determine degrees of production of cyclooxygenase (COX)-1 and -2 and other mediators of inflammation in noninflamed and inflamed skin and muscle tissues in ball pythons (Python regius). ANIMALS 6 healthy adult male ball pythons. PROCEDURES Biopsy specimens of noninflamed skin and muscle tissue were collected from anesthetized snakes on day 0. A 2-cm skin and muscle incision was then made 5 cm distal to the biopsy sites with a CO2 laser to induce inflammation. On day 7, biopsy specimens of skin and muscle tissues were collected from the incision sites. Inflamed and noninflamed tissue specimens were evaluated for production of COX-1, COX-2, phosphorylated protein kinase B (AKT), total AKT, nuclear factor κ-light-chain-enhancer of activated B cells, phosphorylated extracellular receptor kinases (ERKs) 1 and 2, and total ERK proteins by western blot analysis. Histologic evaluation was performed on H&E-stained tissue sections. RESULTS All biopsy specimens of inflamed skin and muscle tissues had higher histologic inflammation scores than did specimens of noninflamed tissue. Inflamed skin specimens had significantly greater production of COX-1 and phosphorylated ERK than did noninflamed skin specimens. Inflamed muscle specimens had significantly greater production of phosphorylated ERK and phosphorylated AKT, significantly lower production of COX-1, and no difference in production of COX-2, compared with production in noninflamed muscle specimens. CONCLUSIONS AND CLINICAL RELEVANCE Production of COX-1, but not COX-2, was significantly greater in inflamed versus noninflamed skin specimens from ball pythons. Additional research into the reptilian COX signaling pathway is warranted.

Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration.

PubMed

Messenger, K M; Wofford, J A; Papich, M G

2016-02-01

Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK/PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid (ISF) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy Beagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC. Prostaglandin E2 (PGE2 ) concentrations were quantified in ISF using ELISA. Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF. Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half-life (T½) was longer in the ISF compared with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF, and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un-inflamed tissues. © 2015 John Wiley & Sons Ltd.

Control of gill ventilation and air-breathing in the bowfin amia calva

PubMed

Hedrick; Jones

1999-01-01

The purpose of this study was to investigate the roles of branchial and gas bladder reflex pathways in the control of gill ventilation and air-breathing in the bowfin Amia calva. We have previously determined that bowfin use two distinct air-breathing mechanisms to ventilate the gas bladder: type I air breaths are characterized by exhalation followed by inhalation, are stimulated by aquatic or aerial hypoxia and appear to regulate O2 gas exchange; type II air breaths are characterized by inhalation alone and possibly regulate gas bladder volume and buoyancy. In the present study, we test the hypotheses (1) that gill ventilation and type I air breaths are controlled by O2-sensitive chemoreceptors located in the branchial region, and (2) that type II air breaths are controlled by gas bladder mechanosensitive stretch receptors. Hypothesis 1 was tested by examining the effects of partial or complete branchial denervation of cranial nerves IX and X to the gill arches on gill ventilation frequency (fg) and the proportion of type I air breaths during normoxia and hypoxia; hypothesis II was tested by gas bladder inflation and deflation. Following complete bilateral branchial denervation, fg did not differ from that of sham-operated control fish; in addition, fg was not significantly affected by aquatic hypoxia in sham-operated or denervated fish. In sham-operated fish, aquatic hypoxia significantly increased overall air-breathing frequency (fab) and the percentage of type I breaths. In fish with complete IX-X branchial denervation, fab was also significantly increased during aquatic hypoxia, but there were equal percentages of type I and type II air breaths. Branchial denervation did not affect the frequency of type I air breaths during aquatic hypoxia. Gas bladder deflation via an indwelling catheter resulted in type II breaths almost exclusively; furthermore, fab was significantly correlated with the volume removed from the gas bladder, suggesting a volume-regulating function for type II air breaths. These results indicate that chronic (3-4 weeks) branchial denervation does not significantly affect fg or type I air-breathing responses to aquatic hypoxia. Because type I air-breathing responses to aquatic hypoxia persist after IX-X cranial nerve denervation, O2-sensitive chemoreceptors that regulate air-breathing may be carried in other afferent pathways, such as the pseudobranch. Gas bladder deflation reflexly stimulates type II breaths, suggesting that gas bladder volume-sensitive stretch receptors control this particular air-breathing mechanism. It is likely that type II air breaths function to regulate buoyancy when gas bladder volume declines during the inter-breath interval.

COMPARISON OF IN VITRO AND IN VIVO RESPONSES TO ARSENIC: GENE EXPRESSION PROFILING IN NORMAL HUMAN EPIDERMAL KERATINOCYTES AND HYPERKERATOSES FROM ARSENIC-EXPOSED HUMANS

EPA Science Inventory

Chronic exposure to arsenic is positively associated with skin, urinary bladder, lung, liver and kidney cancer development in humans. Elucidating the mode of action of arsenic carcinogenesis is a complicated issue as target cells are exposed to different toxic species of arsenic....

Somatic syndromes and chronic pain in women with overactive bladder

PubMed Central

Reynolds, W. Stuart; Mock, Stephen; Zhang, Xuechao; Kaufman, Melissa; Wein, Alan; Bruehl, Stephen; Dmochowski, Roger

2016-01-01

Aims Mechanisms underlying pain perception and afferent hypersensitivity, such as central sensitization, may impact overactive bladder (OAB) symptoms. However, little is known about associations between OAB symptom severity, pain experience, and presence of comorbid chronic pain syndromes. This study examined relationships between OAB symptoms, somatic symptoms, and specific chronic pain conditions in which central sensitization is believed to play a primary role, in a community-based sample of adult women with OAB Methods We recruited adult women with OAB to complete questionnaires assessing urinary symptoms, pain and somatic symptoms, and preexisting diagnoses of central sensitivity syndromes. We analyzed the effects of overall bodily pain intensity, general somatic symptoms, and diagnoses of central sensitivity syndromes on OAB symptom bother and health-related quality of life. Results Of the 116 women in this study, over half (54%) stated their urge to urinate was associated with pain, pressure, or discomfort. Participants reported a wide range of OAB symptoms and health-related quality of life. There was a significant, positive correlation between OAB symptoms and somatic symptoms as well as overall pain intensity. Only 7% of women met diagnostic criteria for fibromyalgia; yet these women demonstrated significantly increased OAB symptom burden and decreased OAB quality of life compared to those without fibromyalgia. Conclusion Women with more severe OAB symptoms reported increased general somatic symptom burden and increased overall body pain intensity, especially women with fibromyalgia. These findings suggest that attributes of pain and co-morbidity with chronic pain conditions may impact the experience of OAB symptoms for many women. PMID:27367486

Androgens Enhance Male Urinary Tract Infection Severity in a New Model

PubMed Central

Olson, Patrick D.; Hruska, Keith A.

2016-01-01

Urinary tract infections (UTIs) occur predominantly in females but also affect substantial male patient populations; indeed, morbidity in complicated UTI is higher in males. Because of technical obstacles, preclinical modeling of UTI in male mice has been limited. We devised a minimally invasive surgical bladder inoculation technique that yields reproducible upper and lower UTI in both male and female mice, enabling studies of sex differences in these infections. Acute uropathogenic Escherichia coli (UPEC) cystitis in C57BL/6 and C3H/HeN males recapitulated the intracellular bacterial community pathway previously shown in females. However, surgically infected females of these strains exhibited more robust bladder cytokine responses and more efficient UPEC control than males. Compared with females, C3H/HeN males displayed a striking predilection for chronic cystitis, manifesting as persistent bacteriuria, high-titer bladder bacterial burdens, and chronic inflammation. Furthermore, males developed more severe pyelonephritis and 100% penetrant renal abscess (a complication that is rare in female mice). These phenotypes were sharply abrogated after castration but restored with exogenous testosterone, suggesting that male susceptibility to UTI is strongly influenced by androgen exposure. These data substantiate the long-standing presumption that anatomic differences in urogenital anatomy confer protection from UTI in males; however, as clinically observed, male sex associated with more severe UTI once these traditional anatomic barriers were bypassed. This study introduces a highly tractable preclinical model for interrogating sex differences in UTI susceptibility and pathogenesis, and illuminates an interplay between host sex and UTI that is more complex than previously appreciated. PMID:26449605

Chronic Fibro-Inflammatory Responses in Autoimmune Pancreatitis Depend on IFN-α and IL-33 Produced by Plasmacytoid Dendritic Cells.

PubMed

Watanabe, Tomohiro; Yamashita, Kouhei; Arai, Yasuyuki; Minaga, Kosuke; Kamata, Ken; Nagai, Tomoyuki; Komeda, Yoriaki; Takenaka, Mamoru; Hagiwara, Satoru; Ida, Hiroshi; Sakurai, Toshiharu; Nishida, Naoshi; Strober, Warren; Kudo, Masatoshi

2017-05-15

In previous studies, we found that human IgG4-related autoimmune pancreatitis (AIP) and murine AIP are driven by activation of plasmacytoid dendritic cells (pDCs) producing IFN-α. In the present studies we examined additional roles of pDC-related mechanisms in AIP pathogenesis, particularly those responsible for induction of fibrosis. We found that in murine AIP (MRL/Mp mice treated with polyinosinic-polycytidylic acid) not only the pancreatic infiltration of immune cells but also the development of fibrosis were markedly reduced by the depletion of pDCs or blockade of type I IFN signaling; moreover, such treatment was accompanied by a marked reduction of pancreatic expression of IL-33. Conversely, polyinosinic-polycytidylic acid-induced inflamed pancreatic tissue in murine AIP exhibited increased expression of type I IFNs and IL-33 (and downstream IL-33 cytokines such as IL-13 and TGF-β1). pDCs stimulated by type I IFN were the source of the IL-33 because purified populations of these cells isolated from the inflamed pancreas produced a large amount of IL-33 upon activation by TLR9 ligands, and such production was abrogated by the neutralization of type I IFN. The role of IL-33 in murine AIP pathogenesis was surprisingly important because blockade of IL-33 signaling by anti-ST2 Ab attenuated both pancreatic inflammation and accompanying fibrosis. Finally, whereas patients with both conventional pancreatitis and IgG4-related AIP exhibited increased numbers of acinar cells expressing IL-33, only the latter also exhibited pDCs producing this cytokine. These data thus suggest that pDCs producing IFN-α and IL-33 play a pivotal role in the chronic fibro-inflammatory responses underlying murine AIP and human IgG4-related AIP. Copyright © 2017 by The American Association of Immunologists, Inc.

Atypical streptococcal infection of gingiva associated with chronic mouth breathing.

PubMed

Haytac, M Cenk; Oz, I Attila

2007-01-01

Streptococcal infections of oral tissues are mainly seen in young children who experience a variety of upper respiratory tract infections. The disease is characterized by fever, lymphadenopathy, and ulcers on the gingiva, lips, and tonsils. This case report presents an atypical streptococcal infection of the gingiva in an 18-year-old man. The patient was referred to the periodontology department complaining of a 2-month history of gingival enlargement. He had persistent fever (39.5 degrees C) and general malaise for 2 weeks. Intraoral examination revealed extremely inflamed and enlarged gingiva with spontaneous bleeding and suppuration. Based on the otolaryngologic consultation and the hematologic, immunologic, and microbiologic tests, the final diagnosis was an atypical streptococcal gingivitis with chronic adenoid-related mouth breathing and oral hygiene neglect as contributing factors. Treatment consisted of a broad-spectrum antibiotic regimen, supragingival and subgingival debridement, adenoidectomy, and scaling and root planing. A good response to nonsurgical therapy was achieved despite poor patient compliance, and no recurrence of gingival enlargement was observed after 1 year. Streptococcal gingivitis should be included in the differential diagnosis of suppurative gingival enlargements. Furthermore, chronic mouth breathing may initiate and/or contribute to this disease.

A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder

PubMed Central

Ma, Emily; Vetter, Joel; Bliss, Laura; Lai, H. Henry; Mysorekar, Indira U.

2016-01-01

Overactive bladder (OAB) is a common debilitating bladder condition with unknown etiology and limited diagnostic modalities. Here, we explored a novel high-throughput and unbiased multiplex approach with cellular and molecular components in a well-characterized patient cohort to identify biomarkers that could be reliably used to distinguish OAB from controls or provide insights into underlying etiology. As a secondary analysis, we determined whether this method could discriminate between OAB and other chronic bladder conditions. We analyzed plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB, interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI). Multivariate logistic regression models were fit for each MSD analyte on 1) OAB patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients. Age, race, and sex were included as independent variables in all multivariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic potential of a given analyte. Our findings demonstrate that five analytes, i.e., interleukin 4, TNF-α, macrophage inflammatory protein-1β, serum amyloid A, and Tie2 can reliably differentiate OAB relative to controls and can be used to distinguish OAB from the other conditions. Together, our pilot study suggests a molecular imbalance in inflammatory proteins may contribute to OAB pathogenesis. PMID:27029431

Quality of Life in Non-Muscle-Invasive Bladder Cancer Survivors: A Systematic Review.

PubMed

Jung, Ahrang; Nielsen, Matthew E; Crandell, Jamie L; Palmer, Mary H; Bryant, Ashley Leak; Smith, Sophia K; Mayer, Deborah K

2018-06-01

Non-muscle-invasive bladder cancer (NMIBC) represents approximately 75% of newly diagnosed patients with bladder cancer. Non-muscle-invasive bladder cancer survivors have unique chronic burdens including frequent recurrences, repeated surveillance cystoscopies and treatments, and the highest lifetime medical cost per person among all cancers. The purpose of this study was to summarize studies assessing quality of life (QOL) in NMIBC survivors. The literature from January 2005 to March 2017 found in PubMed, CINAHL, and PsycINFO databases was reviewed systematically. Inclusion criteria were as follows: (1) research about NMIBC survivors, (2) outcomes included QOL, (3) original research article published in peer-reviewed journals, and (4) published in English. A total of 15 studies were included: 14 quantitative studies and 1 mixed-methods study. Non-muscle-invasive bladder cancer survivors had significantly lower QOL compared with the general population, especially in fatigue, physical and role functioning, and mental health. Repeated transurethral resections and intravesical treatments were associated with impaired physical function and mental health. Most NMIBC survivors had concerns of urinary and bowel problems and sexual function. Despite a good prognosis, NMIBC and its treatment have a significant impact on QOL in survivors. The findings showed large burdens in NMIBC survivors and suggest that further research is needed to better understand potential opportunities to improve QOL in this population. Oncology nurses are in the critical position for assessing symptoms and concerns. Oncology nurses should pay special attention to NMIBC survivors who have unique symptoms and burden with the aim of improving survivors' QOL.

Nocturia in men is a chaotic condition dominated by nocturnal polyuria.

PubMed

Fujimura, Tetsuya; Yamada, Yuta; Sugihara, Toru; Azuma, Takeshi; Suzuki, Motofumi; Fukuhara, Hiroshi; Nakagawa, Tohru; Kume, Haruki; Igawa, Yasuhiko; Homma, Yukio

2015-05-01

To characterize nocturia in men based on frequency volume chart data and symptom profiles assessed using the Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires. The Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires were administered to 299 consecutive treatment naïve men with nocturia (≥one time per night). Frequency volume chart data were recorded for 2 days. Correlations between nocturia and clinical characteristics including symptom scores, clinical diagnosis, Charlson Comorbidity Index, estimated glomerular filtration rate, uroflowmetry and prostate volume were analyzed. Patients were divided into five groups: one time (n = 36), two times (n = 65), three times (n = 85), four times (n = 78) and five times (n = 34) of nocturia. Age, prevalence or severity of chronic kidney disease, hyperlipidemia, low bladder capacity, nocturnal polyuria, urgency, bladder pain and sleep disorders were significantly correlated with the severity of nocturia. The Spearman correlation analysis identified eight possible independent factors for nocturia: age, estimated glomerular filtration rate, urgency, bladder pain, sleep quality, sleepiness during the day, average voided volume and nocturnal volume divided by body weight. Logistic regression analysis showed that nocturnal volume divided by body weight was the strongest factor of nocturia, and ≥7, 9 and 9.7 mL/kg were practical cut-off values of three, four and five times per night of nocturia, respectively. Nocturia in men is a chaotic condition dominated by nocturnal polyuria, and related to multiple factors including age, renal function, urgency, bladder pain, insomnia and bladder volume. © 2015 The Japanese Urological Association.

A protocol for bladder cancer screening and medical surveillance among high-risk groups: The Drake Health Registry experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marsh, G.M.; Callahan, C.; Pavlock, D.

In 1986, the Drake Health Registry Study initiated bladder cancer screening for 366 persons at high risk because of occupational exposure to beta-naphthylamine. The Drake Health Registry Study screening protocol consists of urinalysis, Papanicolaou cytology, and quantitative fluorescence image analysis. A positive screening test qualifies participants for a full diagnostic evaluation. The screening protocol has been modified during the first 3 years of the program's existence to address unexpected patterns of test results and to incorporate advances in screening technology. The current protocol, which has a two-tiered screening schedule, has been utilized successfully for 15 months. Of the 26 positivemore » results to date most have been based on abnormal Papanicolaou cytology and/or quantitative fluorescence image analysis. Bladder abnormalities were cited among most of the 18 study members who underwent diagnostic evaluation, including chronic cystitis, inflammation, hyperplasia, and dysplasia. We conclude that the screening program is detecting very early changes in a relatively young cohort and that these persons must be monitored over a number of years to ensure adequate medical surveillance.« less

Flexible cystoscopic bladder biopsies: a technique for outpatient evaluation of the lower urinary tract urothelium.

PubMed

Beaghler, M; Grasso, M

1994-11-01

Routine urothelial biopsies of the lower urinary tract are obtained using the cold cup biopsy technique. This procedure is most often performed in the surgical suite and requires rigid endoscopic access and the use of biopsy forceps and Bugbee electrodes to obtain tissue for histologic examination. A new single-step biopsy forceps has been used through the flexible cystoscope. Using a 16 F actively deflectable, flexible cystoscope and the 5.4 F Therma Jaw Hot Urologic Forceps, bladder biopsies were obtained in 27 patients for a variety of indications. This biopsy forceps allows simultaneous tissue sampling and electrocoagulation of the biopsy site, thus eliminating the need for exchange of instruments through the flexible cystoscope. Tissue samples are somewhat protected from thermal changes during coagulation through the use of a Faraday cage. Biopsies were frequently obtained in an outpatient setting, requiring only local topical anesthesia (2% lidocaine jelly). Carcinoma in situ, transitional cell carcinoma, acute and chronic inflammation, and normal bladder mucosa were differentiated histologically. Using this technique, lower urinary tract urothelial mapping can be performed safely in the office with minimal patient discomfort.

[Urinary tract involvement by endometriosis. Techniques and outcomes of surgical management: CNGOF-HAS Endometriosis Guidelines].

PubMed

Bolze, P-A; Paparel, P; Golfier, F

2018-03-01

Urinary tract involvement by endometriosis is reported in 1% of endometriosis patients (NP3). Consequences range from pelvic pain for bladder localizations to silent kidney loss in case of chronic ureteral obstruction (NP3). The feasibility of laparoscopic management was widely proven (NP3) and may reduce hospital stay length (NP4). Radical surgery with partial cystectomy for bladder localizations was shown to significantly and durably reduce pain symptoms with low risk of a severe postoperative complications (NP3). Medical hormonal treatment also shows short-term reduction of pain symptoms (NP4). Transureteral resection of bladder endometriosis nodule is not recommended (grade C) because of a high postoperative recurrence rate (NP4). Given a high risk of silent kidney loss, it is recommended that patients with ureteral involvement by endometriosis are managed by a multidisciplinary team considering urinary and potential extra-urinary localizations of endometriosis (grade C). No recommendation can be made on which technique to prefer between conservative (ureterolysis) or radical surgical techniques or on benefit and length of ureteral stents in case of ureteral involvement. Surgical management of bladder and ureteral localizations of endometriosis do not seem to be associated with altered or improved postoperative fertility (NP4). Since late postoperative ureteral anastomosis stenosis were reported with silent kidney loss, repeated postoperative imaging monitoring is justified (expert opinion). Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Safety of gentamicin bladder irrigations in complex urological cases.

PubMed

Defoor, William; Ferguson, Denise; Mashni, Susan; Creelman, Lisa; Reeves, Deborah; Minevich, Eugene; Reddy, Pramod; Sheldon, Curtis

2006-05-01

Recurrent urinary tract infections are common in complex pediatric urological cases, particularly those requiring clean intermittent catheterization. At our institution gentamicin bladder irrigations have been used for antimicrobial prophylaxis and to treat symptomatic bacteriuria, particularly when the infection does not involve the upper urinary tract. The purpose of this study was to assess the safety of this therapy. A retrospective study was performed of all children treated with gentamicin bladder irrigations from 1999 to 2004. The dose was 14 mg gentamicin in 30 ml saline instilled via catheter once or twice daily. Serum creatinine and random gentamicin levels were obtained according to a protocol based on risk of gentamicin toxicity. Patient demographics, laboratory results and outcomes were abstracted from the medical records. A total of 80 patients (38 males and 42 females) were identified. Median patient age was 10 years and median duration of treatment was 90 days. No patient had detectable serum gentamicin levels greater than 0.4 mg/dl. Small increases in serum creatinine were seen in 3 patients, all of whom had chronic renal insufficiency. A total of 21 patients (26%) had breakthrough UTIs, of which 5 (24%) were gentamicin resistant. No adverse events were documented. Gentamicin bladder irrigations are a helpful adjunct in the management of complex pediatric urological cases involving recurrent symptomatic bacteriuria. We no longer require intensive laboratory monitoring of low risk patients at our institution.

A rubber tube in the bladder as a complication of autoerotic stimulation of the urethra.

PubMed

Stamatiou, Konstantinos; Moschouris, Hippocrates

2016-10-05

Self-insertion of foreign bodies in the urethra is most commonly associated with sexual or erotic arousal of adolescents with mental health disorders. Rarely it may practiced by healthy adults for masturbation. Migration of foreign bodies used for the abovementioned purpose from the urethra to adjacent organs is a relatively uncommon urologic problem that may cause serious complications which arose tardive. Presentation includes a variety of acute or chronic symptoms that depend of the underlying complications. The method of extraction depends on the shape, size and nature of the object and should be tailored according to the condition of the patient. In the present article we present a case of a rubber tube inserted to the urethra for erotic arousal purposes which migrated to the bladder during masturbation.

Anorectal and Pelvic Pain.

PubMed

Bharucha, Adil E; Lee, Tae Hee

2016-10-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways

PubMed Central

Pan, Xiao-Qing; Gonzalez, Jessica A.; Chang, Shaohua; Chacko, Samuel; Wein, Alan J.; Malykhina, Anna P.

2010-01-01

Clinical data provides evidence of high level of co-morbidity among genitourinary and gastrointestinal disorders characterized by chronic pelvic pain. The objective of this study was to test the hypothesis that colonic inflammation can impact the function of the urinary bladder via activation of TRPV1 signaling pathways followed by alterations in gene and protein expression of Substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory neurons and in the bladder. Inflammation was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS, 12.5 mg/kg) and desensitization of TRPV1 receptors was evoked by intracolonic resiniferatoxin (RTX, 10−7 M). mRNA and protein concentrations of CGRP and SP were measured at 3, 5 and 30 days. RTX instillation in the colon caused 3-fold up-regulation of SP mRNA in the urinary bladder at day 5 (n=7, p≤0.05) followed by 35-fold increase at day 30 (n=5, p≤0.05). Likewise, TNBS colitis triggered 15.8-fold up-regulation of SP mRNA one month after TNBS (n=5, p≤0.05). Desensitization of colonic TRPV1 receptors prior to TNBS abolished SP increase in the urinary bladder. RTX led to 4.3-fold increase of CGRP mRNA at day 5 (n=7, p≤0.05 to control) in the bladder followed by 28-fold increase at day 30 post-RTX (n=4, p≤0.05). Colitis did not alter CGRP concentration during acute phase, however, at day 30 mRNA level was increased by 17.8±6.9 fold (n=5, p≤0.05) in parallel with 4-fold increase in CGRP protein (n=5, p≤0.01) in the detrusor. Protein concentration of CGRP in the spinal cord was diminished by 45–65% (p≤0.05) during colitis. RTX pretreatment did not affect CGRP concentration in the urinary bladder, however, caused a reduction in CGRP release from lumbosacral DRG neurons during acute phase (3 and 5 days post-TNBS). Our results clearly demonstrate that colonic inflammation triggers the release of pro-inflammatory neuropeptides SP and CGRP in the urinary bladder via activation of TRPV1 signaling mechanisms enunciating the neurogenic nature of pelvic organ cross-sensitization. PMID:20501335

Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection.

PubMed

Kalas, Vasilios; Hibbing, Michael E; Maddirala, Amarendar Reddy; Chugani, Ryan; Pinkner, Jerome S; Mydock-McGrane, Laurel K; Conover, Matt S; Janetka, James W; Hultgren, Scott J

2018-03-20

Treatment of bacterial infections is becoming a serious clinical challenge due to the global dissemination of multidrug antibiotic resistance, necessitating the search for alternative treatments to disarm the virulence mechanisms underlying these infections. Uropathogenic Escherichia coli (UPEC) employs multiple chaperone-usher pathway pili tipped with adhesins with diverse receptor specificities to colonize various host tissues and habitats. For example, UPEC F9 pili specifically bind galactose or N -acetylgalactosamine epitopes on the kidney and inflamed bladder. Using X-ray structure-guided methods, virtual screening, and multiplex ELISA arrays, we rationally designed aryl galactosides and N -acetylgalactosaminosides that inhibit the F9 pilus adhesin FmlH. The lead compound, 29β-NAc, is a biphenyl N -acetyl-β-galactosaminoside with a K i of ∼90 nM, representing a major advancement in potency relative to the characteristically weak nature of most carbohydrate-lectin interactions. 29β-NAc binds tightly to FmlH by engaging the residues Y46 through edge-to-face π-stacking with its A-phenyl ring, R142 in a salt-bridge interaction with its carboxylate group, and K132 through water-mediated hydrogen bonding with its N-acetyl group. Administration of 29β-NAc in a mouse urinary tract infection (UTI) model significantly reduced bladder and kidney bacterial burdens, and coadministration of 29β-NAc and mannoside 4Z269, which targets the type 1 pilus adhesin FimH, resulted in greater elimination of bacteria from the urinary tract than either compound alone. Moreover, FmlH specifically binds healthy human kidney tissue in a 29β-NAc-inhibitable manner, suggesting a key role for F9 pili in human kidney colonization. Thus, these glycoside antagonists of FmlH represent a rational antivirulence strategy for UPEC-mediated UTI treatment. Copyright © 2018 the Author(s). Published by PNAS.

[Urodynamic changes in patients with obstructive sleep apnea-hypopnea syndrome and nocturnal polyuria].

PubMed

Hu, Ke; Tu, Zuo-sheng; Lü, Sheng-qi; Li, Qing-quan; Chen, Xue-qin

2011-03-01

To investigate the urodynamic changes in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and nocturnal polyuria. From Sept. 2002 to Jun. 2008, 23 patients with nocturnal polyuria were diagnosed as having OSAHS by polysomnography (PSG). The number and output of nocturia, the osmotic pressure and the excretion of Na(+) were recorded during both the PSG night and CPAP titrating night. Plasma levels of brain natriuretic peptide (BNP) and atrial natriuretic peptides (ANP) were also measured at 11PM in the 2 nights and 7AM in the next mornings. Urodynamic studies including urine flow, bladder pressure during filling, pressure-flow study during voiding and urethral pressure were carried out in these patients. Urodynamic studies were performed again after treatment with CPAP for 3 months. PSG showed that the patients with nocturnal polyuria had moderate to severe OSAHS, in which the apnea-hypopnea index (AHI) being 48 ± 15 events per hour. The number of nocturnal voiding during the PSG night was more than that during the CPAP titrating night. During the PSG night, the output of nocturia, the nocturia excretion of Na(+), ANP levels (at 7am in the next morning after PSG night) increased and the osmotic pressure of nocturia decreased. CPAP therapy could reverse these abnormalities. The main characteristics of urodynamics in these patients included weak detrusor contraction, hypoesthesia in filling cystometry, and decreased bladder compliance, and detrusor external sphincter dyssynergia. After 3 months of CPAP treatment, both the motility of the detrusor of bladder and the bladder compliance improved. CPAP therapy can effectively reverse the nocturnal polyuria in OSAHS patients. In OSAHS patients, the features of nocturia, including the changes of output, osmotic pressure and the excretion of Na(+), may be related to the secretion of high-level of ANP. During the course of chronic progressively OSAHS pathophysiology, detrusor function of bladder may be damaged. CPAP therapy could decrease the nocturnal excretion of ANP, and improve the motility of the detrusor of bladder.

Increased Expression of Interleukin-6 Family Members and Receptors in Urinary Bladder with Cyclophosphamide-Induced Bladder Inflammation in Female Rats

PubMed Central

Girard, Beatrice M.; Cheppudira, Bopaiah P.; Malley, Susan E.; Schutz, Kristin C.; May, Victor; Vizzard, Margaret A.

2011-01-01

Recent studies suggest that janus-activated kinases–signal transducer and activator of transcription signaling pathways contribute to increased voiding frequency and referred pain of cyclophosphamide (CYP)-induced cystitis in rats. Potential upstream chemical mediator(s) that may be activated by CYP-induced cystitis to stimulate JAK/STAT signaling are not known in detail. In these studies, members of the interleukin (IL)-6 family of cytokines including, leukemia inhibitory factor (LIF), IL-6, and ciliary neurotrophic factor (CNTF) and associated receptors, IL-6 receptor (R) α, LIFR, and gp130 were examined in the urinary bladder in control and CYP-treated rats. Cytokine and receptor transcript and protein expression and distribution were determined in urinary bladder after CYP-induced cystitis using quantitative, real-time polymerase chain reaction (Q-PCR), western blotting, and immunohistochemistry. Acute (4 h; 150 mg/kg; i.p.), intermediate (48 h; 150 mg/kg; i.p.), or chronic (75 mg/kg; i.p., once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Q-PCR analyses revealed significant (p ≤ 0.01) CYP duration- and tissue- (e.g., urothelium, detrusor) dependent increases in LIF, IL-6, IL-6Rα, LIFR, and gp130 mRNA expression. Western blotting demonstrated significant (p ≤ 0.01) increases in IL-6, LIF, and gp130 protein expression in whole urinary bladder with CYP treatment. CYP-induced cystitis significantly (p ≤ 0.01) increased LIF-immunoreactivity (IR) in urothelium, detrusor, and suburothelial plexus whereas increased gp130-IR was only observed in urothelium and detrusor. These studies suggest that IL-6 and LIF may be potential upstream chemical mediators that activate JAK/STAT signaling in urinary bladder pathways. PMID:21373362

IL-10+ innate-like B cells are part of the skin immune system and require α4β1 integrin to migrate between the peritoneum and inflamed skin1

PubMed Central

Glabman, Raisa A.; Ruthel, Gordon; Hamann, Alf; Debes, Gudrun F.

2016-01-01

The skin is an important barrier organ and frequent target of autoimmunity and allergy. Here we found innate-like B cells that expressed the anti-inflammatory cytokine IL-10 in the skin of humans and mice. Unexpectedly, innate-like B1 and conventional B2 cells showed differential homing capacities with peritoneal B1 cells preferentially migrating into the inflamed skin of mice. Importantly, the skin-homing B1 cells included IL-10 secreting cells. B1 cell homing into the skin was independent of typical skin-homing trafficking receptors and instead required α4β1-integrin. Moreover, B1 cells constitutively expressed activated β1 integrin and relocated from the peritoneum to the inflamed skin and intestine upon innate stimulation, indicating an inherent propensity to extravasate into inflamed and barrier sites. We conclude that innate-like B cells migrate from central reservoirs into skin, adding an important cell type with regulatory and protective functions to the skin immune system. PMID:26851219

Microbiology of folliculitis: a histological study of 39 cases.

PubMed

Jahns, Anika C; Lundskog, Bertil; Berg, Johanna; Jonsson, Rebecca; McDowell, Andrew; Patrick, Sheila; Golovleva, Irina; Palmer, Ruth H; Alexeyev, Oleg A

2014-01-01

Folliculitis is a common inflammatory skin syndrome. Several microbial organisms have been put forward as causative agents, but few studies visualized microbes directly in inflamed hair follicles. This retrospective study investigated bacterial and fungal colonization of inflamed hair follicles in patients with clinically diagnosed non-infectious folliculitis. Skin biopsies from 39 folliculitis patients and 27 controls were screened by fluorescence in situ hybridization (FISH) using broad-range bacterial and fungal probes and by immunofluorescence microscopy using a monoclonal antibody towards Gram-positive bacteria. Specific monoclonal and polyclonal antibodies towards Staphylococcus spp. and Propionibacterium acnes were applied for further species identification. Inflamed follicles were associated with bacterial colonization in 10 samples (26%) and fungal colonization in three samples (8%). Staphylococcus spp. were observed in inflamed follicles in seven samples (18%). Two samples were positive for P. acnes, which were identified as either type II or type IB/type III. Both Staphylococcus spp. and P. acnes were seen in macrocolonies/biofilm structures. In conclusion, one-third of patients with clinically diagnosed, non-infectious folliculitis exhibited microbial colonization with predominance of Staphylococcus spp. © 2013 APMIS Published by Blackwell Publishing Ltd.

Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue

PubMed Central

2012-01-01

Background Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. Methods Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. Results Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. Conclusions Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue. PMID:22974251

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host.

PubMed

Chaudhry, Rajeev; Madden-Fuentes, Ramiro J; Ortiz, Tara K; Balsara, Zarine; Tang, Yuping; Nseyo, Unwanaobong; Wiener, John S; Ross, Sherry S; Seed, Patrick C

2014-05-01

Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study.

PubMed

Keller, Joseph; Chen, Yi-Kuang; Lin, Herng-Ching

2013-04-01

Although one prior study reported an association between bladder pain syndrome/interstitial cystitis (BPS/IC) and urinary calculi (UC), no population-based study to date has been conducted to explore this relationship. Therefore, using a population-based data set in Taiwan, this study set out to investigate the association between BPS/IC and a prior diagnosis of UC. This study included 9,269 cases who had received their first-time diagnosis of BPS/IC between 2006 and 2007 and 46,345 randomly selected controls. We used conditional logistic regression analysis to compute the odds ratio (OR) and its corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. There was a significant difference in the prevalence of prior UC between cases and controls (8.1 vs 4.3 %, p < 0.001). Conditional logistic regression analysis revealed that cases were more likely to have been previously diagnosed with UC than controls (OR = 1.70; 95 % CI = 1.56-1.84) after adjusting for chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, and asthma. BPS/IC was found to be significantly associated with prior UC regardless of stone location; the adjusted ORs of kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.58 (95 % CI = 1.38-1.81), 1.73 (95 % CI = 1.45-2.05), 3.80 (95 % CI = 2.18-6.62), and 1.83 (95 % CI = 1.59-2.11), respectively. This work generates the hypothesis that UC may be associated with BPS/IC.

Fingerprint of Lung Fluid Ultrafine Particles, a Novel Marker of Acute Lung Inflammation.

PubMed

Bar-Shai, Amir; Alcalay, Yifat; Sagiv, Adi; Rotem, Michal; Feigelson, Sara W; Alon, Ronen; Fireman, Elizabeth

2015-01-01

Acute lung inflammation can be monitored by various biochemical readouts of bronchoalveolar lavage fluid (BALF). To analyze the BALF content of ultrafine particles (UFP; <100 nm) as an inflammatory biomarker in early diagnosis of acute and chronic lung diseases. Mice were exposed to different stress conditions and inflammatory insults (acute lipopolysaccharide inhalation, tobacco smoke and lethal dose of total body irradiation, i.e. 950 rad). After centrifugation, the cellular pellet was assessed while cytokines and ultrafine particles were measured in the soluble fraction of the BALF. A characteristic UFP distribution with a D50 (i.e. the dimension of the 50th UFP percentile) was shared by all tested mouse strains in the BALF of resting lungs. All tested inflammatory insults similarly shifted this size distribution, resulting in a unique UFP fingerprint with an averaged D50 of 58.6 nm, compared with the mean UFP D50 of 23.7 nm for resting BALF (p < 0.0001). This UFP profile was highly reproducible and independent of the intensity or duration of the inflammatory trigger. It returned to baseline after resolution of the inflammation. Neither total body irradiation nor induction of acute cough induced this fingerprint. The UFP fingerprint in the BALF of resting and inflamed lungs can serve as a binary biomarker of healthy and acutely inflamed lungs. This marker can be used as a novel readout for the onset of inflammatory lung diseases and for complete lung recovery from different insults.

Periodontal inflamed surface area as a novel numerical variable describing periodontal conditions

PubMed Central

2017-01-01

Purpose A novel index, the periodontal inflamed surface area (PISA), represents the sum of the periodontal pocket depth of bleeding on probing (BOP)-positive sites. In the present study, we evaluated correlations between PISA and periodontal classifications, and examined PISA as an index integrating the discrete conventional periodontal indexes. Methods This study was a cross-sectional subgroup analysis of data from a prospective cohort study investigating the association between chronic periodontitis and the clinical features of ankylosing spondylitis. Data from 84 patients without systemic diseases (the control group in the previous study) were analyzed in the present study. Results PISA values were positively correlated with conventional periodontal classifications (Spearman correlation coefficient=0.52; P<0.01) and with periodontal indexes, such as BOP and the plaque index (PI) (r=0.94; P<0.01 and r=0.60; P<0.01, respectively; Pearson correlation test). Porphyromonas gingivalis (P. gingivalis) expression and the presence of serum P. gingivalis antibodies were significant factors affecting PISA values in a simple linear regression analysis, together with periodontal classification, PI, bleeding index, and smoking, but not in the multivariate analysis. In the multivariate linear regression analysis, PISA values were positively correlated with the quantity of current smoking, PI, and severity of periodontal disease. Conclusions PISA integrates multiple periodontal indexes, such as probing pocket depth, BOP, and PI into a numerical variable. PISA is advantageous for quantifying periodontal inflammation and plaque accumulation. PMID:29093989

Immunological and pathological investigations in equine experimental uveitis.

PubMed

Simeonova, Galina P; Krastev, Svetozar Z; Simeonov, Radostin S

2016-12-01

The pathogenic mechanism of equine recurrent uveitis (ERU) is still poorly defined and many variations between experimental animal models and spontaneous disease exist. The aim of our study was to investigate if Th17 cell-mediated response plays role in the pathogenesis of the used experimental model in horses and to reveal its pathological findings. Experimental uveitis was induced in 6 healthy horses. The concentrations of retinal autoantigen CRALBP and IL-17 were measured using ELISA in aqueous humor and vitreous body of the 12 inflamed eyes as well as in 12 control non-inflamed eyes taken from 6 horses in slaughter house. After centrifugation of the two eye media, smears were prepared and cytological investigation was performed. Tissue specimens were taken from all eye globes and were submitted to histopathological investigation. CRALBP and IL-17 concentrations were significantly elevated in eye media of horses with experimental uveitis in comparison with controls. Cytological and histopathological findings corresponded to the changes characteristic of chronic immune-mediated inflammation with mononuclear cell infiltration of uvea, choroid, retina, and eye media as well as severe retinal destruction. Our study demonstrated the involvement of the retinal autoantigen CRALBP as well as IL-17 in the pathogenesis of experimental uveitis in horses. These findings suggests that this experimental uveitis in horses may serve as a suitable animal model for investigation of IL-17- mediated immune response during spontaneous autoimmune uveitis in horses as well as in humans.

Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting.

PubMed

Almeda, Dariela; Wang, Biran; Auguste, Debra T

2015-02-01

Liposomes may be engineered to target inflamed endothelium by mimicking ligand-receptor interactions between leukocytes and cytokine-activated endothelial cells (ECs). The upregulation and assembly of vascular cell adhesion molecule-1 (VCAM1) and E-selectin on the cell membrane upon exposure to cytokines have shown potential for drug delivery vehicles to target sites of chronic endothelial inflammation, such as atherosclerosis and cancer. Herein, we characterized EC surfaces by measuring the E-selectin and VCAM1 surface densities and adhesion forces of aVCAM1 and aE-selectin to ECs. We quantified the antibody density, ratio, and diffusivity of liposomes to achieve significant binding and internalization. At 1 h, the 1:1 ratio of VCAM1:E-selectin antibodies was significantly higher than 1:0 and 0:1. Significant binding and uptake was achieved at aE-selectin densities as low as 400 molecules/μm(2). The highest levels of binding and uptake were achieved when using a 1:1 ratio of VCAM1:E-selectin antibodies at a density of 1000 molecules/μm(2); this density is 85% lower than previous reports. The binding and uptake of functionalized liposomes were reduced to levels comparable to IgG functionalized liposomes upon a 10-fold reduction in liposome membrane diffusivity. We conclude with a liposomal design that discriminates between healthy and inflamed endothelium while reducing antibody surface presentation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis.

PubMed

Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E; Jimenez-Vargas, Nestor N; Lopez-Lopez, Cintya; Jaramillo-Polanco, Josue; Okamoto, Takanobu; Nasser, Yasmin; Bunnett, Nigel W; Lomax, Alan E; Vanner, Stephen J

2017-12-01

Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways. Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca 2+ imaging techniques. Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca 2+ responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits. Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Inducible expression of A Disintegrin and Metalloproteinase 8 in chronic periodontitis and gingival epithelial cells.

PubMed

Aung, W P P; Chotjumlong, P; Pata, S; Montreekachon, P; Supanchart, C; Khongkhunthian, S; Sastraruji, T; Krisanaprakornkit, S

2017-06-01

The expression of A Disintegrin and Metalloproteinase 8 (ADAM8) is associated with several inflammatory diseases. Elevated ADAM8 levels have been shown in gingival crevicular fluid of patients with chronic periodontitis. The objective of this study was to investigate ADAM8 expression in chronic periodontitis tissues compared with that in normal tissues. ADAM8 expression and its inductive mechanism were examined in human gingival epithelial cells (HGECs) and human gingival fibroblasts. Total RNA and protein were extracted from gingival biopsies of 33 patients with chronic periodontitis and those of 23 healthy volunteers. ADAM8 mRNA and protein expression was analyzed by real-time polymerase chain reaction, immunoblotting and immunohistochemistry. ADAM8 expression in control and stimulated cells in the presence or absence of specific inhibitors for mitogen-activated protein kinase pathways was assayed by real-time polymerase chain reaction, immunoblotting, flow cytometry and immunofluorescence. ADAM8 mRNA and protein expression in chronic periodontitis tissues was significantly greater than that in normal tissues (p < 0.01). Significantly increased ADAM8 expression was detected in the gingival epithelium of chronic periodontitis tissues (p < 0.001). ADAM8 mRNA expression in HGECs, but not in human gingival fibroblasts, was significantly induced by stimulation with Fusobacterium nucleatum (p < 0.05), partially via the p44/42 mitogen-activated protein kinase pathway. ADAM8 expression in the cell lysates and on the surface of HGECs was induced by stimulation with F. nucleatum. ADAM8 expression is increased in inflamed chronic periodontitis tissues and localized within gingival epithelium, consistent with an upregulation of ADAM8 expression in F. nucleatum-stimulated HGECs, suggesting a possible role of ADAM8 in innate immunity of periodontal tissue. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pseudocarcinomatous epithelial hyperplasia in the bladder unassociated with prior irradiation or chemotherapy.

PubMed

Lane, Zhaoli; Epstein, Jonathan I

2008-01-01

Pseudocarcinomatous epithelial hyperplasia in the bladder is a little known phenomenon, recognized to be associated with prior irradiation and/or chemotherapy. Whether this process can occur outside of this setting has not been studied. We identified 8 of these cases mimicking invasive urothelial carcinoma from our consultation files from 07/04 to 07/06 with no prior history of radiation or chemotherapy. The mean age at diagnosis was 65 years (range, 42 to 81 y), with 5 of the 8 males. Seven patients had a potential etiology for these changes that could either have resulted in localized ischemia or injury to the urothelium. These included case 1: atrial fibrillation, hypertension, congestive heart failure, gastrointestinal bleeding, and coronary artery vascular disease; case 2: coronary angioplasty, atrial fibrillation, hyperlipidemia, and amputation of arm for ischemia; case 3: hypertension, uncontrolled diabetes, hyperlipidemia, and atrial fibrillation; case 4: underlying arteriovenous malformation of the bladder; cases 5 to 6: history of indwelling Foley catheter; and case 7: history of radical prostatectomy for prostate cancer but no radiation. One patient had no potential contributing factors. All 8 patients presented with gross hematuria. At cystoscopy, 7 patients had polypoid lesions with 1 appearing nonpolypoid. Histologically, all cases showed epithelial proliferation of urothelium with cells having prominent eosinophilic cytoplasm. This process that mimicked invasive cancer within the lamina propria was marked in 3 cases (38%). Moderate nuclear pleomorphism was seen in 6 cases (75%). Only 1 case revealed mitotic figures. Ulceration was seen in 1 case. All cases showed some degree of hemorrhage with hemosiderin deposition identified in 3 cases (38%). Fibrin deposition was present in 1 case within the stroma, 3 cases in the vessels, and 4 cases in both. Five cases show stromal fibrosis. Edema and vascular congestion were common features (90% and 100%, respectively). Six out of 8 cases were accompanied by moderate to marked acute and chronic inflammation. The original diagnosis included nested variant urothelial carcinoma (1 case), atypical suspicious for invasive carcinoma (5 cases), hemangioma (1 case), and eosinophilic cystitis (1 case). Patients were followed for a mean of 16.5 months (range, 10 to 34 mo), and none developed bladder cancer. As a rare response to ischemia and chronic irritation, pseudocarcinomatous epithelial proliferations in the bladder may be confused with invasive urothelial carcinoma. Pathologists must be aware of the histologic changes mimicking cancer, and recognize that it can occur outside of the setting of prior irradiation or chemotherapy.

A Pitfall in Transrectal Prostate Biopsy: Malakoplakia Evaluation of Two Cases Based on the Literature Review

PubMed Central

Solakoglu Kahraman, Dudu; Sayhan, Sevil; Diniz, Gulden; Ayaz, Duygu; Karadeniz, Tugba; Can, Ertan

2014-01-01

Malakoplakia is a rarely seen inflammatory condition that is considered to develop secondary to a chronic Escherichia coli infection. Although malakoplakia usually affects the genitourinary tract, it may also be observed in the colon, stomach, lungs, liver, bones, uterus, and skin. Malakoplakia of the genitourinary system usually involves the bladder, whereas it may also affect the prostate along with the bladder. Malakoplakia of the prostate is very rare, and it may be clinically mistaken for prostatic malignancies. Definitive diagnosis is only possible through histopathological examination. This study elaborates on two patients who presented to our hospital in 2013 with high PSA levels. The primary clinical consideration was prostate carcinoma. However, these two cases were diagnosed as malakoplakia based on the results of histopathological analysis of the transrectal prostate biopsy specimen. PMID:24868476

Anticholinergics and Central Nervous System Effects: Are We Confused?

PubMed Central

Staskin, David R; Zoltan, Edward

2007-01-01

The central nervous system (CNS) effects of anticholinergic agents have been documented in various patient populations and to varying degrees in case reports, brain-activity surrogates, and computerized cognitive testing. The older patient population with overactive bladder represents a group at increased risk of cognitive impairment and other CNS side effects associated with antimuscarinic agents. The complexity of the effect of anticholinergic agents on CNS function requires an increased level of careful investigation. Studies need to be performed in the at-risk population with multiple, validated tests at clinically prescribed doses in acute and chronic situations. These studies need to take into account the effect of commonly prescribed dosing regimens, with doses selected to represent with equivalent bladder potency. The alterations in the serum levels and parent/metabolite effects contributed by metabolic issues or drug delivery systems require special attention. PMID:18231615

The microbiome of the maxillary sinus and middle nasal meatus in chronic rhinosinusitis.

PubMed

Ivanchenko, O A; Karpishchenko, S A; Kozlov, R S; Krechikova, O I; Otvagin, I V; Sopko, O N; Piskunov, G Z; Lopatin, A S

2016-03-01

This multicenter study was focused on the identification of the microorganisms inhabiting the maxillary sinus and middle nasal meatus in chronic rhinosinusitis. 112 middle meatus swabs and 112 maxillary sinus aspirates from 103 patients were available for culture. A total of 244 strains of microorganisms representing more than 50 families were identified in the maxillary sinus and middle nasal meatus (164 and 80, respectively). These included 154 (63.0%) strains of aerobic bacteria from 32 species and 90 (37.0%) strains of anaerobic bacteria from 23 species. Aerobes were more common than anaerobes in both the nasal cavity (78.7% vs. 21.3%) and in the maxillary sinus (55.2% vs. 44.8%). Species of Streptococci (28.8%) and Prevotella (17.8%) were the most common findings in the maxillary sinus aspirates. S. pneumonia, H. influenza, and S. aureus were relatively rare, and found in only 6.7%, 5.4%, and 8.9% of the samples, respectively. The results obtained suggest that common upper airway pathogens do not play a major role in the pathogenesis of chronic rhinosinusitis. The microbiome of inflamed sinonasal mucosa is extremely diverse and involves exotic species of bacteria that, to date, have not been considered as potential inhabitants of the paranasal sinuses.

Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis.

PubMed

Qiu, Xinyun; Zhang, Feng; Yang, Xi; Wu, Na; Jiang, Weiwei; Li, Xia; Li, Xiaoxue; Liu, Yulan

2015-05-27

Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum, and colon), prefer different colonization locations (mucosa and feces), and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella, Barnesiella, Bacteroides, Alistipes, and Lactobacillus and loss of butyrate-producing Clostridium XIVa, and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis.

KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation

PubMed Central

Goodman, Wendy A.; Omenetti, Sara; Date, Dipali; Di Martino, Luca; De Salvo, Carlo; Kim, Gun-Dong; Chowdhry, Saleem; Bamias, Giorgos; Cominelli, Fabio; Pizarro, Theresa T.; Mahabeleshwar, Ganapati H.

2016-01-01

Inflammatory bowel disease (IBD) is associated with dysregulated macrophage responses, such that quiescent macrophages acquire a pro-inflammatory activation state and contribute to chronic intestinal inflammation. The transcriptional events governing macrophage activation and gene expression in the context of chronic inflammation such as IBD remain incompletely understood. Here, we identify Kruppel-like transcription factor-6 (KLF6) as a critical regulator of pathogenic myeloid cell activation in human and experimental IBD. We found that KLF6 was significantly upregulated in myeloid cells and intestinal tissue from IBD patients and experimental models of IBD, particularly in actively inflamed regions of the colon. Using complementary gain- and loss-of-function studies, we observed that KLF6 promotes pro-inflammatory gene expression through enhancement of NFκB signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of STAT3 signaling. To study the in vivo role of myeloid KLF6, we treated myeloid-specific KLF6-knockout mice (Mac-KLF6-KO) with dextran sulfate-sodium (DSS) and found that Mac-KLF6-KO mice were protected against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation. PMID:26838049

Effects of a vegetable extract from Lupinus albus (LU105) on the production of matrix metalloproteinases (MMP1, MMP2, MMP9) and tissue inhibitor of metalloproteinases (TIMP1, TIMP2) by human gingival fibroblasts in culture.

PubMed

Gaultier, F; Foucault-Bertaud, A; Lamy, E; Ejeil, A L; Dridi, S M; Piccardi, N; Piccirilli, A; Msika, P; Godeau, G; Gogly, B

2003-12-01

This study examined the effects of a vegetable extract from Lupinus albus (LU105) on MMPs and TIMPs secreted by human gingival fibroblasts in culture. LU105 was extracted from seeds of L. albus and is freely soluble in water. Gelatin zymography showed that control human gingival fibroblasts maintained in culture for 48 h express pro-MMP2 (progelatinase A) in the culture medium while the active form of MMP2 (gelatinase A), the active form of MMP9 (gelatinase B), and pro-MMP9 (progelatinase B) are not detected. Fibroblasts derived from inflamed gingiva expressed in the culture medium increased amounts of pro-MMP2 (progelatinase A) compared with controls and significant amounts of pro-MMP9 (progelatinase B). LU105 diminished the expression by gingival fibroblasts derived from inflamed tissue of both pro-MMP2 and pro-MMP9. Furthermore LU105 did not modify the amount of TIMP2 expressed in culture by controls or by gingival fibroblasts derived from inflamed tissue. TIMP1 and MMP1 significantly decreased when LU105 was added in the culture media of gingival fibroblasts derived from inflamed tissue compared with control fibroblasts. Thus LU105 seems to offer an opportunity to restore a correct balance between MMP2, MMP9, MMP1, and their natural inhibitors, i.e., TIMP1 and TIMP2 in human inflamed gingiva.

Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xufang, E-mail: xufang.zhang@student.qut.edu.au; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059; Jiang, Hongwei, E-mail: jianghw@163.com

Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects onmore » proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.« less

[In vitro study on bone resorption of odontogenic cysts and ameloblastomas].

PubMed

Gao, Li; Li, Tie-jun

2005-05-01

To investigate the effect of bone resorption by odontogenic cysts and ameloblastomas in vitro. Fragments of odontogenic cysts (14 odontogenic keratocysts, 6 inflamed odontogenic keratocysts, 5 dentigerous cysts) and ameloblastomas (n = 7) were incubated in vitro for 24 h. The supernatant was then removed into the culture system of SD rat calvaria. After incubation (48 h), the calcium contents of the media were measured by atom spectrophotometer. The supernatant of odontogenic cysts and ameloblastomas was measured for the bone resorption related factors such as IL-6, TNF-alpha, PGE(2), bone Gla-containing protein (BGP) and calcitonin (CT) by a radioimmunoassay system. The calcium released in the calvaria culture media by all the odontogenic lesions was significantly higher than that in the blank controls (P < 0.01). The inflamed odontogenic keratocyst group had a significantly higher calcium concentration than odontogenic keratocyst and ameloblastoma groups (P < 0.05). In addition, the concentration of IL-6, TNF-alpha, PGE(2) and CT in the culture media of all odontogenic lesions were significantly higher than that of the blank controls (P < 0.05). IL-6 concentration in the inflamed and non-inflamed odontogenic keratocyst groups were significantly higher than that of ameloblastoma group (P < 0.05). CT concentration in the inflamed odontogenic keratocyst was significantly higher than those of odontogenic keratocyst and dentigerous cyst groups (P < 0.05). Correlation and regression analysis showed that IL-6 was significantly correlated with the calcium content (P < 0.01). The odontogenic lesions could promote bone resorption in vitro and it is likely to be related to some of the cytokines secreted by the lesions.

Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

PubMed Central

Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

2014-01-01

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border

PubMed Central

Marcos-Ramiro, Beatriz; García-Weber, Diego; Barroso, Susana; Feito, Jorge; Ortega, María C.; Cernuda-Morollón, Eva; Reglero-Real, Natalia; Fernández-Martín, Laura; Durán, Maria C.; Alonso, Miguel A.; Correas, Isabel; Cox, Susan; Ridley, Anne J.

2016-01-01

Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new proteins essential to the human endothelial inflammatory response, we have found that the endosomal GTPase RhoB is up-regulated in response to inflammatory cytokines and expressed in the endothelium of some chronically inflamed tissues. We show that although RhoB and the related RhoA and RhoC play additive and redundant roles in various aspects of endothelial barrier function, RhoB specifically inhibits barrier restoration after acute cell contraction by preventing plasma membrane extension. During barrier restoration, RhoB trafficking is induced between vesicles containing RhoB nanoclusters and plasma membrane protrusions. The Rho GTPase Rac1 controls membrane spreading and stabilizes endothelial barriers. We show that RhoB colocalizes with Rac1 in endosomes and inhibits Rac1 activity and trafficking to the cell border during barrier recovery. Inhibition of endosomal trafficking impairs barrier reformation, whereas induction of Rac1 translocation to the plasma membrane accelerates it. Therefore, RhoB-specific regulation of Rac1 trafficking controls endothelial barrier integrity during inflammation. PMID:27138256

Studies on increased vascular permeability in the pathogenesis of lesions of connective tissue diseases: I. Experimental hyperlipidaemia and immune arthropathy.

PubMed

Valente, A J; Walton, K W

1980-10-01

In order to investigate the known associations between hyperlipidaemia and various rheumatic complaints, immune arthritis and hyperlipidaemia have been induced concurrently in rabbits. The results obtained show that: (1) Rabbit apolipoprotein B-containing lipoproteins (LpB), which are normally virtually excluded from joint fluid, gain access to the inflamed joint in the serous effusion and serve as intrinsic indicators of altered local permeability to macromolecules. (2) Much of the LpB entering the joint space is taken up by the phagocytic cells and, following intracellular hydrolysis, leaves a lipid residue. In some chronically affected joints these residues are modified so as to give rise to crystalline cholesterol and its esters. Such crystals may serve as a chronic irritant in the joint. (3) In addition intact LpB is found sequestered in the superficial layers of intra-articular collagenous structures of the challenged joint in a distribution identical with that of similarly sequestered immune complexes and complement, suggesting altered permeability of these intra-articular structures also.

Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation

PubMed Central

Ribeiro, Carla M. P.; Lubamba, Bob A.

2017-01-01

Cystic fibrosis (CF) pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR). This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes. These findings suggest that targeting the IRE1/XBP-1 UPR pathway may be a therapeutic strategy for CF airway disease. PMID:28075361

Cellular energy metabolism in T-lymphocytes.

PubMed

Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

2015-01-01

Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

Biomimetic proteolipid vesicles for targeting inflamed tissues

NASA Astrophysics Data System (ADS)

Molinaro, R.; Corbo, C.; Martinez, J. O.; Taraballi, F.; Evangelopoulos, M.; Minardi, S.; Yazdi, I. K.; Zhao, P.; De Rosa, E.; Sherman, M. B.; de Vita, A.; Toledano Furman, N. E.; Wang, X.; Parodi, A.; Tasciotti, E.

2016-09-01

A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles--which we refer to as leukosomes--retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.

Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.

PubMed

Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J

2016-05-01

Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

Marked hydronephrosis and hydroureter after distigmine therapy in an adult male patient with paraplegia due to spinal cord injury: a case report

PubMed Central

Mansour, Paul; Soni, Bakul M; Hughes, Peter L; Singh, Gurpreet; Oo, Tun

2009-01-01

Introduction Distigmine, a long-acting anti-cholinesterase, is associated with side effects such as Parkinsonism, cholinergic crisis, and rhabdomyolysis. We report a spinal cord injury patient, who developed marked hydronephrosis and hydroureter after distigmine therapy, which led to a series of complications over subsequent years. Case presentation A 38-year-old male developed T-9 paraplegia in 1989. Intravenous urography, performed in 1989, showed normal kidneys, ureters and bladder. He was prescribed distigmine bromide orally and was allowed to pass urine spontaneously. In 1992, intravenous urography showed bilateral marked hydronephrosis and hydroureter. Distigmine was discontinued. He continued to pass urine spontaneously. In 2006, intravenous urography showed moderate dilatation of both pelvicalyceal systems and ureters down to the level of urinary bladder. This patient was performing self-catheterisation only once a day. He was advised to do catheterisations at least three times a day. In December 2008, this patient developed haematuriawhich lasted for nearly four months.. He received trimethoprim, then cephalexin, followed by Macrodantin, amoxicillin and ciprofloxacin. In February 2009, intravenous urography showed calculus at the lower pole of left kidney. Both kidneys were moderately hydronephrotic. Ureters were dilated down to the bladder. Dilute contrast was seen in the bladder due to residual urine. This patient was advised to perform six catheterisations a day, and take propiverine hydrochloride 15 mg, three times a day. Microbiology of urine showed Klebsiella oxytoca, Pseudomonas aeruginosa, and Enterococcus faecalis. Cystoscopy revealed papillary lesions in bladder neck and trigone. Transurethral resection was performed. Histology showed marked chronic cystitis including follicular cystitis and papillary/polypoid cystitis. There was no evidence of malignancy. Conclusion Distigmine therapy resulted in marked bilateral hydronephrosis and hydroureter. Persistence of hydronephrosis after omitting distigmine, and presence of residual urine in bladder over many years probably predisposed to formation of polypoid cystitis and follicular cystitis, and contributed to prolonged haematuria, which occurred after an episode of urine infection. This case illustrates the dangers of prescribing distigmine to promote spontaneous voiding in spinal cord injury patients. Instead of using distigmine, spinal cord injury patients should be advised to consider intermittent catheterisation together with oxybutynin or propiverine to achieve complete, low-pressure emptying of urinary bladder. PMID:19918519

Efficacy of flurbiprofen 8.75 mg lozenge in patients with a swollen and inflamed sore throat.

PubMed

Aspley, Sue; Shephard, Adrian; Schachtel, Emily; Sanner, Kathleen; Savino, Laurie; Schachtel, Bernard

2016-09-01

Sore throat is often over-treated with antibiotics, therefore there is a need for non-antibiotic treatments that provide effective relief. From the patient's point of view, symptoms of pharyngeal inflammation such as a "swollen" and "inflamed" throat are often considered the most bothersome; so, a non-steroidal anti-inflammatory drug could be an appropriate treatment. We investigated the efficacy and safety of flurbiprofen 8.75 mg lozenge in adults with a swollen and inflamed throat. We enrolled adults with moderate-to-severe sore throat and evidence of tonsillo-pharyngitis into a randomized, double-blind study. Patients received flurbiprofen 8.75 mg or placebo lozenges every 3-6 hours as needed (up to five lozenges in 24 hours) and rated their symptoms (sore throat pain, difficulty swallowing and the sensation of a swollen throat) on standard linear scales regularly over 24 hours. The efficacy of flurbiprofen lozenge was determined in patients reporting a swollen and inflamed throat at baseline, as well as those with relatively severe symptoms. ClinicalTrials.gov NCT01049334. The main outcome measures were the time-weighted summed differences in patient-reported sore throat pain, difficulty swallowing and swollen throat over 24 hours. Out of 204 patients, 124 (60.8%) described their throats as swollen and inflamed at baseline. Flurbiprofen lozenges provided greater relief than placebo over 24 hours: 79.8%, 99.6% and 69.3% (for sore throat pain, difficulty swallowing and swollen throat, respectively, all P ≤ 0.01). These outcomes were more substantial in patients with relatively severe symptoms. No serious or unexpected adverse events occurred. Flurbiprofen 8.75 mg lozenge appears to provide effective, well-tolerated relief of sore throat, difficulty swallowing and swollen throat in adults with a swollen and inflamed throat, as well as those with relatively severe symptoms. A limitation of these findings is that, while predetermined, these are secondary outcomes derived from a targeted sub-group of patients, not the entire study population.

Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders.

PubMed

Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

2018-06-08

Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth. Inflammatory factors stimulate the recruitment, expansion, and activation of MDSCs in tumors and inflamed tissues. The immunosuppression generated by MDSCs has an important role in the resolution of acute inflammation but in chronic inflammatory disorders, the activation of MDSCs suppresses the innate and adaptive immune responses thus aggravating the disease processes in association with tumors, chronic infections, and many degenerative diseases. Currently, MDSCs are important drug discovery targets in cancers and chronic inflammatory diseases. Interestingly, there are promising reports that certain phytochemicals can function as potent inhibitors of the immunosuppressive MDSCs that could partially explain the therapeutic benefits of herbal medicine. We will briefly describe the immune suppressive functions of MDSCs in cancers and age-related inflammatory diseases and then review in detail the chemically characterized phytochemicals of different herbal categories, e.g. flavonoids, terpenoids, retinoids, curcumins, and β-glucans, which possess the MDSC-dependent antitumor and anti-inflammatory properties. Copyright © 2018 Elsevier B.V. All rights reserved.

Lung mechanics and histology during sevoflurane anesthesia in a model of chronic allergic asthma.

PubMed

Burburan, Shirley Moreira; Xisto, Debora Gonçalves; Ferreira, Halina Cidrini; Riva, Douglas Dos Reis; Carvalho, Giovanna Marcella Cavalcante; Zin, Walter Araujo; Rocco, Patricia Rieken Macêdo

2007-03-01

There are no studies examining the effects of sevoflurane on a chronically inflamed and remodeled airway, such as that found in asthma. In the present study, we sought to define the respiratory effects of sevoflurane in a model of chronic allergic asthma. For this purpose, pulmonary mechanics were studied and lung morphometry analyzed to determine whether the physiological modifications reflected underlying morphological changes. Thirty-six BALB/c mice (20-25 g) were randomly divided into four groups. In OVA groups, mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. In SAL groups, mice received saline using the same protocol. Twenty-four hours after the last challenge, the animals were anesthetized with pentobarbital sodium (PENTO, 20 mg/kg i.p.) or sevoflurane (SEVO, 1 MAC). Lung static elastance (Est), resistive ([DELTA]P1) and viscoelastic/inhomogeneous ([DELTA]P2) pressure decreases were analyzed by an end-inflation occlusion method. Lungs were fixed and stained for histological analysis. Animals in the OVASEVO group showed lower [DELTA]P1 (38%), [DELTA]P2 (24%), and Est (22%) than animals in the OVAPENTO group. Histology demonstrated greater airway dilation (16%) and a lower degree of alveolar collapse (25%) in the OVASEVO compared with OVAPENTO group. [DELTA]P1 was lower (35%) and airway diameters larger (12%) in the SALSEVO compared with SALPENTO group. Sevoflurane anesthesia acted both at airway level and lung periphery reducing ([DELTA]P1 and [DELTA]P2 pressures, and Est in chronic allergic asthma.

CCL20 and β-defensin-2 induce arrest of human Th17 cells on inflamed endothelium in vitro under flow conditions.

PubMed

Ghannam, Soufiane; Dejou, Cécile; Pedretti, Nathalie; Giot, Jean-Philipe; Dorgham, Karim; Boukhaddaoui, Hassan; Deleuze, Virginie; Bernard, François-Xavier; Jorgensen, Christian; Yssel, Hans; Pène, Jérôme

2011-02-01

CCR6 is a chemokine receptor that is expressed at the cell surface of Th17 cells, an IL-17- and IL-22-secreting population of CD4(+) T cells with antipathogenic, as well as inflammatory, properties. In the current study, we have determined the involvement of CCR6 in human Th17 lymphocyte migration toward inflamed tissue by analyzing the capacity of its ligands to induce arrest of these cells onto inflamed endothelium in vitro under flow conditions. We show that polarized, in situ-differentiated, skin-derived Th17 clones activated via the TCR-CD3 complex produce CCL20 in addition to IL-17 and IL-22. The latter cytokines induce, in a synergic fashion, the production of human β-defensin (hBD)-2, but neither hBD-1 nor hBD-3, by epidermal keratinocytes. Both CCL20 and hBD-2 are capable of inducing the arrest of Th17 cells, but not Th1 or Th2 cells, on HUVEC in an CD54-dependent manner that is CCR6 specific and independent from the expression of CXCR4, reported to be an alternative receptor for hBD-2. In addition, Ag-specific activation induces a transient loss of CCR6 expression, both at the transcriptional and protein level, which occurs with slow kinetics and is not due to endogenous CCL20-mediated internalization of CCR6. Together, these results indicate that Ag-specific activation will initially contribute to CCR6-mediated Th17 cell trafficking toward and sequestration in inflamed tissue, but that it eventually results in a transitory state of nonresponsiveness to further stimulation of these cells with CCR6 ligands, thus permitting their subsequent migration out of the inflamed site.

Selection of housekeeping genes for gene expression studies in the adult rat submandibular gland under normal, inflamed, atrophic and regenerative states

PubMed Central

Silver, Nicholas; Cotroneo, Emanuele; Proctor, Gordon; Osailan, Samira; Paterson, Katherine L; Carpenter, Guy H

2008-01-01

Background Real-time PCR is a reliable tool with which to measure mRNA transcripts, and provides valuable information on gene expression profiles. Endogenous controls such as housekeeping genes are used to normalise mRNA levels between samples for sensitive comparisons of mRNA transcription. Selection of the most stable control gene(s) is therefore critical for the reliable interpretation of gene expression data. For the purpose of this study, 7 commonly used housekeeping genes were investigated in salivary submandibular glands under normal, inflamed, atrophic and regenerative states. Results The program NormFinder identified the suitability of HPRT to use as a single gene for normalisation within the normal, inflamed and regenerative states, and GAPDH in the atrophic state. For normalisation to multiple housekeeping genes, for each individual state, the optimal number of housekeeping genes as given by geNorm was: ACTB/UBC in the normal, ACTB/YWHAZ in the inflamed, ACTB/HPRT in the atrophic and ACTB/GAPDH in the regenerative state. The most stable housekeeping gene identified between states (compared to normal) was UBC. However, ACTB, identified as one of the most stably expressed genes within states, was found to be one of the most variable between states. Furthermore we demonstrated that normalising between states to ACTB, rather than UBC, introduced an approximately 3 fold magnitude of error. Conclusion Using NormFinder, our studies demonstrated the suitability of HPRT to use as a single gene for normalisation within the normal, inflamed and regenerative groups and GAPDH in the atrophic group. However, if normalising to multiple housekeeping genes, we recommend normalising to those identified by geNorm. For normalisation across the physiological states, we recommend the use of UBC. PMID:18637167

A time-dependent degeneration manner of condyle in rat CFA-induced inflamed TMJ.

PubMed

Xu, Liqin; Guo, Huilin; Li, Cheng; Xu, Jie; Fang, Wei; Long, Xing

2016-01-01

Temporomandibular joint (TMJ) inflammation is a potential risk factor of osteoarthritis (OA) but the detailed degenerative changes in the inflamed TMJ remain unclear. In this study, we evaluated the changes of condylar cartilage and subchondral bone in rat inflamed TMJ induced by Freund's complete adjuvant (CFA). Articular cavity was injected with CFA and the TMJ samples were collected 1, 2, 3, and 4-week post-injection. Hematoxylin & Eosin (H&E) staining, toluidine blue (TB) staining, Safranin O (S.O) staining, Masson trichrome staining and micro-CT were used to assess TMJ degeneration during inflammation. Osteoclast and osteoblast activities were analyzed by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin (OCN) immunohistochemistry staining respectively. The expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in condylar cartilage and subchondral bone was also evaluated through immunohistochemistry and RANKL/OPG ratio was evaluated. Reduced cartilage thickness, decreased number of chondrocytes, and down-regulated proteoglycan expression were observed in the condylar cartilage in the inflamed TMJ. Enhanced osteoclast activity, and expanded bone marrow cavity were reached the peak in the 2-week after CFA-injection. Meanwhile the RANKL/OPG ratio in the cartilage and subchondral bone also increased in the 2-week CFA-injection. Immature, unmineralized new bones with irregular trabecular bone structure, atypical condylar shape, up-regulated OCN expression, and decreased bone mineral density (BMD) were found in the inflamed TMJ. The time-dependent degeneration manner of TMJ cartilage and subchondral bone was found in CFA-induced arthritis rat model. The degeneration in the TMJ with inflammation might be a risk factor and should be concerned.

The regulatory role of Nrf2 in antioxidants phase2 enzymes and IL-17A expression in patients with ulcerative colitis.

PubMed

Sabzevary-Ghahfarokhi, Milad; Shohan, Mojtaba; Shirzad, Hedayatollah; Rahimian, Ghorbanali; Soltani, Amin; Ghatreh-Samani, Mahdi; Deris, Fatemeh; Bagheri, Nader; Shafigh, Mohammedhadi; Tahmasbi, Kamran

2018-06-22

Reactive oxygen species (ROS) is one of the pathogenic factors responsible for intestinal injury in Ulcerative colitis (UC). Nuclear factor erythroid-2 related factor 2 (Nrf2) plays a critical role against ROS factors to conserve epithelial integrity. This study aimed to localize Nrf2 and IL-17A protein in the inflamed mucosa of patients with ulcerative colitis. The gene expression of Nrf2 was also correlated with GST-A4 and PRDX1. A total of 20 patients and 20 healthy controls with definite UC based on the clinical criteria were enrolled for this study. The expression pattern of Nrf2 and IL-17A protein was compared in inflamed and non-inflamed colonic biopsies by immunohistochemical staining. Nrf2, GST-A4 and PRDX1 gene expression were determined by real-time polymerase chain reaction (RT-PCR). In inflamed colonic biopsies, an increased level of Nrf2 protein factor was detected in epithelial cells. Conversely, IL-17A protein was presented more in mononuclear cells in mucosa and lamina propria regions. A significant increase of Nrf2, GST-A4 gene expression was observed in both mild and severe patients with ulcerative colitis. GST-A4 gene expression indicated a high exponential rate in logistic regression. Oxidative stress in inflamed colonic tissue can induce Nrf2 gene expression. The performance of Nrf2 transcription factor may lead to the induction of GST-A4 and PRDX1. IL-17A is less detected in intestinal inflammation, presenting Nrf2 factor. The present findings suggest that Nrf2 function in the gut plays a role in arresting both inflammatory response and oxidative damages of UC. Copyright © 2018 Elsevier GmbH. All rights reserved.

Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China

PubMed Central

Wu, Peng; Zhang, Guihao; Zhao, Jie; Chen, Jiawei; Chen, Yang; Huang, Weina; Zhong, Jialei; Zeng, Jiarong

2018-01-01

Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium) and decrease of some bacterial genera (e.g., Serratia, Proteus, and Roseomonas) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter, and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers. PMID:29904624

Nitrate in drinking water and bladder cancer risk in Spain.

PubMed

Espejo-Herrera, Nadia; Cantor, Kenneth P; Malats, Nuria; Silverman, Debra T; Tardón, Adonina; García-Closas, Reina; Serra, Consol; Kogevinas, Manolis; Villanueva, Cristina M

2015-02-01

Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables. We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview. Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤ 5 mg/L were 1.2 (0.7-2.0) for >5-10mg/L and 1.1 (0.6-1.9) for >10mg/L. The OR for subjects with longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for >8 vs. ≤ 4 mg/day. Adjustment for several covariables showed similar results to crude analyses. Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed. Copyright © 2014 Elsevier Inc. All rights reserved.

Longitudinal studies of time-dependent changes in both bladder and erectile function after streptozotocin-induced diabetes in Fischer 344 male rats.

PubMed

Melman, Arnold; Zotova, Elena; Kim, Mimi; Arezzo, Joseph; Davies, Kelvin; DiSanto, Michael; Tar, Moses

2009-11-01

To provide sensitive physiological endpoints for the onset and long-term progression of deficits induced by diabetes mellitus (DM) in bladder and erectile function in male rats, and to evaluate parallel changes in urogenital and nerve function induced by hyperglycaemia over a protracted period as a model for chronic deficits in patients with diabetes. The study comprised in 877 male, 3-month-old, Fischer 344 rats; 666 were injected intraperitoneally with 35 mg/kg streptozotocin (STZ) and divided into insulin-treated and untreated diabetic groups. The rats were studied over 8 months and measurements made of both erectile and bladder function, as well as nerve conduction studies over the duration of the study. There was an early (first month) abnormality of both erectile and bladder function that persisted through the 8 months of the study. The erectile dysfunction was manifest as reduced intracavernous pressure/blood pressure ratio, and the bladder dysfunction as a persistent increase in detrusor overactivity with no detrusor decompensation. Insulin treatment prevented or modified the abnormality in each organ. Hyperglycaemia caused a progressive decrease in caudal nerve conduction velocity. The mean digital sensory and tibial motor nerve conduction velocity did not deteriorate over time. Correlation measurements of nerve and organ function were not consistent. The results of this extensive long-term study show early and profound effects of hyperglycaemia on the smooth muscle of the penis and bladder, that were persistent and stable in surviving rats over the 8 months. The physiological changes did not correlate well with neurological measurements of those organs. Significantly, diverse smooth-muscle cellular and subcellular events antedated the measured neurological manifestations of the hyperglycaemia by several months. Although autonomic diabetic neuropathy is a primary life-threatening complication of long-term diabetes in humans, this rat model of STZ-induced diabetes showed that the rapid onset of physiological manifestations was based on many molecular changes in the smooth muscle cells in this model of type 1 DM.

Localization of P2X receptor subtypes 2, 3 and 7 in human urinary bladder.

PubMed

Svennersten, Karl; Hallén-Grufman, Katarina; de Verdier, Petra J; Wiklund, N Peter; Poljakovic, Mirjana

2015-08-08

Voiding dysfunctions are a common problem that has a severe negative impact on the quality of life. Today there is a need for new drug targets for these conditions. The role of ATP receptors in bladder physiology has been studied for some time, primarily in animal models. The aim of this work is to investigate the localization of the ATP receptors P2X2, P2X3 and P2X7 and their colocalization with vimentin and actin in the human urinary bladder. Immunohistochemical analysis was conducted on full-thickness bladder tissues from fundus and trigonum collected from 15 patients undergoing open radical cystectomy due to chronic cystitis, bladder cancer or locally advanced prostate cancer. Colocalization analyses were performed between the three different P2X subtypes and the structural proteins vimentin and actin. Specimens were examined using epifluorescence microscopy and correlation coefficients were calculated for each costaining as well as the mean distance from the laminin positive basal side of the urothelium to the vimentin positive cells located in the suburothelium. P2X2 was expressed in vimentin positive cells located in the suburothelium. Less distinct labelling of P2X2 was also observed in actin positive smooth muscle cells and in the urothelium. P2X3 was expressed in vimentin positive cells surrounding the smooth muscle, and in vimentin positive cells located in the suburothelium. Weaker P2X3 labelling was seen in the urothelium. P2X7 was expressed in the smooth muscle cells and the urothelium. In the suburothelium, cells double positive for P2X2 and vimentin where located closer to the urothelium while cells double positive for P2X3 and vimentin where located further from the urothelium. The results from this study demonstrate that there is a significant difference in the expression of the purinergic P2X2, P2X3 and P2X7 receptors in the different histological layers of the human urinary bladder.

Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides

PubMed Central

Girard, Beatrice; Peterson, Abbey; Malley, Susan; Vizzard, Margaret A.

2016-01-01

The mechanisms underlying the postnatal maturation of micturition from a somatovesical to a vesicovesical reflex are not known but may involve neuropeptides in the lower urinary tract. A transgenic mouse model with chronic urothelial overexpression (OE) of NGF exhibited increased voiding frequency, increased number of non-voiding contractions, altered morphology and hyperinnervation of the urinary bladder by peptidergic (e.g., Sub P and CGRP) nerve fibers in the adult. In early postnatal and adult NGF-OE mice we have now examined: (1) micturition onset using filter paper void assays and open-outlet, continuous fill, conscious cystometry; (2) innervation and neurochemical coding of the suburothelial plexus of the urinary bladder using immunohistochemistry and semi-quantitative image analyses; (3) neuropeptide protein and transcript expression in urinary bladder of postnatal and adult NGF-OE mice using Q-PCR and ELISAs and (4) the effects of intravesical instillation of a neurokinin (NK)-1 receptor antagonist on bladder function in postnatal and adult NGF-OE mice using conscious cystometry. Postnatal NGF-OE mice exhibit age-dependent (R2= 0.996–0.998; p ≤ 0.01) increases in Sub and CGRP expression in the urothelium and significantly (p ≤ 0.01) increased peptidergic hyperinnervation of the suburothelial nerve plexus. By as early as P7, NGF-OE mice exhibit a vesicovesical reflex in response to intravesical instillation of saline whereas littermate WT mice require perigenital stimulation to elicit a micturition reflex until P13 when vesicovesical reflexes are first observed. Intravesical instillation of a NK-1 receptor antagonist, netupitant (0.1 μg/ml), significantly (p ≤ 0.01) increased void volume and the interval between micturition events with no effects on bladder pressure (baseline, threshold, peak) in postnatal NGF-OE mice; effects on WT mice were few. NGF-induced pleiotropic effects on neuropeptide (e.g., Sub P) expression in the urinary bladder contribute to the maturation of the micturition reflex and are excitatory to the micturition reflex in postnatal NGF-OE mice. These studies provide insight into the mechanisms that contribute to the postnatal development of the micturition reflex. PMID:27342083

Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China.

PubMed

Wu, Peng; Zhang, Guihao; Zhao, Jie; Chen, Jiawei; Chen, Yang; Huang, Weina; Zhong, Jialei; Zeng, Jiarong

2018-01-01

Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium ) and decrease of some bacterial genera (e.g., Serratia, Proteus , and Roseomonas ) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter , and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers.

Transurethral ultrasound-guided laser prostatectomy: initial Luebeck experince

NASA Astrophysics Data System (ADS)

Thomas, Stephen; Spitzenpfeil, Elisabeth; Knipper, Ansgar; Jocham, Dieter

1994-02-01

Transurethral ultrasound guided laser prostatectomy is one of the most promising alternative invasive treatment modalities for benign prostatic hyperplasia. The principle feature is an on- line 3-D controlling of Nd:YAG laser denaturation of the periurethral tissue. Necrotic tissue is not removed, but sloughs away with the urinary stream within weeks. The bleeding hazard during and after the operation is minimal. By leaving the bladder neck untouched, sexual function is not endangered. Thirty-one patients with symptomatic BPH were treated with the TULIP system and followed up for at least 12 weeks. Suprapubic bladder drainage had to be maintained for a mean time of 37 days. Conventional TURP was performed in four patients due to chronic infection, recurrent bleeding, and poor results. Our initial experience with the TULIP system shows it to be very efficient and safe. A longer follow up of a larger patient population is necessary to compare the therapeutic efficiency to conventional transurethral resection.

Pasteurella aerogenes as an Asymptomatic Bacteriuria Agent.

PubMed

Alaygut, Demet; Engin, Aynur

2018-02-01

'Asymptomatic bacteriuria' (ASB) is isolation of a specified quantitative count of bacteria in an appropriately collected urine specimen obtained from a person without symptoms or signs referable to urinary infection. Catheterized specimens are less likely to be contaminated compared with voided specimens; therefore, positive cultures of catheterized specimens are more likely to reflect true bladder bacteriuria even with low colony counts. The common pathogens for ASB are Escherichia coli, Klebsiella and Streptococcus spp. Pasteurella spp. was not previously reported as an ASB agent. ASB is important for pregnant women, children, individuals with obstructive uropathy, chronic renal failure and neutropenia, before the urologic procedures and after renal transplantation. Treatment of ASB is required for above situations. We report an 11-year-old-girl with neurogenic bladder who made clean intermittent catheterization and had Pasteurella aerogenes as an ASB agent. © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Whole-genome sequence of Schistosoma haematobium.

PubMed

Young, Neil D; Jex, Aaron R; Li, Bo; Liu, Shiping; Yang, Linfeng; Xiong, Zijun; Li, Yingrui; Cantacessi, Cinzia; Hall, Ross S; Xu, Xun; Chen, Fangyuan; Wu, Xuan; Zerlotini, Adhemar; Oliveira, Guilherme; Hofmann, Andreas; Zhang, Guojie; Fang, Xiaodong; Kang, Yi; Campbell, Bronwyn E; Loukas, Alex; Ranganathan, Shoba; Rollinson, David; Rinaldi, Gabriel; Brindley, Paul J; Yang, Huanming; Wang, Jun; Wang, Jian; Gasser, Robin B

2012-01-15

Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.

An incidentally found inflamed uterine myoma causing low abdominal pain, using Tc-99m-tektrotyd single photon emission computed tomography-CT hybrid imaging.

PubMed

Zandieh, Shahin; Schütz, Matthias; Bernt, Reinhard; Zwerina, Jochen; Haller, Joerg

2013-01-01

We report the case of a 50-year-old woman presented with a history of right hemicolectomy due to an ileocecal neuroendocrine tumor and left breast metastasis. Owing to a slightly elevated chromogranin A-level and lower abdominal pain, single photon emission computed tomography-computer tomography (SPECT-CT) was performed. There were no signs of recurrence on the SPECT-CT scan, but the patient was incidentally found to have an inflamed intramural myoma. We believe that the slightly elevated chromogranin A-level was caused by the hypertension that the patient presented. In the clinical context, this is a report of an inflamed uterine myoma seen as a false positive result detected by TC-99m-Tc-EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) SPECT-CT hybrid imaging.

Ultrastructural evaluation of mesenchymal stem cells from inflamed periodontium in different in vitro conditions.

PubMed

Zaganescu, Raluca; Barbu Tudoran, Lucian; Pall, Emoke; Florea, Adrian; Roman, Alexandra; Soanca, Andrada; Mihaela Mihu, Carmen

2015-09-01

This research aimed to observe the behavior of mesenchymal stem cells (MSCs) isolated from periodontal granulation tissue (gt) when manipulated ex vivo to induce three-dimensional (3D) spheroid (aggregates) formation as well as when seeded on two bone scaffolds of animal origin. Periodontal gt was chosen as a MSC source because of its availability, considering that it is eliminated as a waste material during conventional surgical therapies. 3D aggregates of cells were generated; they were grown for 3 and 7 days, respectively, and then prepared for transmission electron microscopic analysis. The two biomaterials were seeded for 72 h with gtMSCs and prepared for scanning electronic microscopic observation. The ultrastructural analysis of 3D spheroids remarked some differences between the inner and the outer cell layers, with a certain commitment observed at the inner cells. Both scaffolds showed a relatively smooth surface at low magnification. Macro- and micropores having a scarce distribution were observed on both bone substitutes. gtMSCs grew with relative difficulty on the biomaterials. After 72 h of proliferation, gtMSCs scarcely covered the surface of bovine bone scaffolds, demonstrating fibroblast-like or star-like shapes with elongated filiform extensions. Our results add other data on the possible usefulness of gtMSC and could question the current paradigm regarding the complete removal of chronically inflamed gts from the defects during periodontal surgeries. Until optimal protocols for ex vivo manipulation of MSCs are available for clinical settings, it is advisable to use biocompatible bone substitutes that allow the development of progenitor cells. © 2015 Wiley Periodicals, Inc.

Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation.

PubMed

Allen, Joselyn N; Dey, Adwitia; Nissly, Ruth; Fraser, James; Yu, Shan; Balandaram, Gayathri; Peters, Jeffrey M; Hankey-Giblin, Pamela A

2017-04-03

Obesity promotes a chronic inflammatory state that is largely mediated by tissue-resident macrophages as well as monocyte-derived macrophages. Diet-induced obesity (DIO) is a valuable model in studying the role of macrophage heterogeneity; however, adequate macrophage isolations are difficult to acquire from inflamed tissues. In this protocol, we outline the isolation steps and necessary troubleshooting guidelines derived from our studies for obtaining a suitable population of tissue-resident macrophages from mice following 18 weeks of high-fat (HFD) or high-fat/high-cholesterol (HFHCD) diet intervention. This protocol focuses on three hallmark tissues studied in obesity and atherosclerosis including the liver, white adipose tissues (WAT), and the aorta. We highlight how dualistic usage of flow cytometry can achieve a new dimension of isolation and characterization of tissue-resident macrophages. A fundamental section of this protocol addresses the intricacies underlying tissue-specific enzymatic digestions and macrophage isolation, and subsequent cell-surface antibody staining for flow cytometric analysis. This protocol addresses existing complexities underlying fluorescent-activated cell sorting (FACS) and presents clarifications to these complexities so as to obtain broad range characterization from adequately sorted cell populations. Alternate enrichment methods are included for sorting cells, such as the dense liver, allowing for flexibility and time management when working with FACS. In brief, this protocol aids the researcher to evaluate macrophage heterogeneity from a multitude of inflamed tissues in a given study and provides insightful troubleshooting tips that have been successful for favorable cellular isolation and characterization of immune cells in DIO-mediated inflammation.

Epstein-Barr Virus Infection in Chronically Inflamed Periapical Granulomas

PubMed Central

Makino, Kosuke; Takeichi, Osamu; Hatori, Keisuke; Imai, Kenichi; Ochiai, Kuniyasu; Ogiso, Bunnai

2015-01-01

Periapical granulomas are lesions around the apex of a tooth caused by a polymicrobial infection. Treatment with antibacterial agents is normally performed to eliminate bacteria from root canals; however, loss of the supporting alveolar bone is typically observed, and tooth extraction is often selected if root canal treatment does not work well. Therefore, bacteria and other microorganisms could be involved in this disease. To understand the pathogenesis of periapical granulomas more precisely, we focused on the association with Epstein-Barr virus (EBV) using surgically removed periapical granulomas (n = 32). EBV DNA was detected in 25 of 32 periapical granulomas (78.1%) by real-time PCR, and the median number of EBV DNA copies was approximately 8,688.01/μg total DNA. In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001). Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells. EBER was detected in the cytoplasm and nuclei of B cells and plasma cells in six of nine periapical granulomas, but not in healthy gingival tissues. In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells. These data suggest that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas. PMID:25884725

Inflammation by Breast Implants and Adenocarcinoma: Not Always a Bad Company.

PubMed

Orciani, Monia; Sorgentoni, Giulia; Olivieri, Fabiola; Mattioli-Belmonte, Monica; Di Benedetto, Giovanni; Di Primio, Roberto

2017-07-01

Inflammation and tumor are now an inseparable binomial. Inflammation may also derive by the use of breast implants followed by the formation of a periprosthetic capsule. It is known that tumor cells, in an inflamed microenvironment, can profit by the paracrine effect exerted also by mesenchymal stem cells (MSCs). Here we evaluated the role of inflammation on the immunobiology of MSCs before and after cocultures with cells derived from breast adenocarcinoma. MSCs derived from both inflamed (I-MSCs) and control (C-MSCs) tissues were isolated and cocultured with MCF7 cells derived from breast adenocarcinoma. Before and after cocultures, the proliferation rate of MCF7 cells and the expression/secretion of cytokines related to inflammation were tested. Before cocultures, higher levels of cytokine related to chronic inflammation were detected in I-MSCs than in C-MSCs. After cocultures with MCF7, C- and I-MSCs show a variation in cytokine production. In detail, IL-2, IL-4, IL-5, IL-10, IL-13, TGF-β and G-CSF were decreased, whereas IL-6, IL-12, IFN-γ, and IL-17 were oversecreted. Proliferation of MCF7 was significantly increased after cocultures with I-MSCs. Inflammation at the site of origin of MSCs affects their immunobiology. Even if tumor cells increased their proliferation rate after cocultures with I-MSCs, the analysis of the cytokines, known to play a role in the interference of tumor cells with the host immune system, absolves completely the breast implants from the insult to enforce the risk of adenocarcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Determination of the Chronic Mammalian Toxicological Effects of RDX. Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) in the B6C3F1 Hybrid Mouse. Phase 4, Volume 3, Appendix 11: Final Pathology Report

DTIC Science & Technology

1984-04-01

bladder 1 muscle, s k e l e t a l 5 bone marrow smear --- 3 nasal t u rb ina tes *ti ~ s u e masses ,- and any o the r t i ssues w i t h...Lymphoma, lymphocytic type .__ - __ __ ___ .____. . _ - --- Fibrosarcoma , me ta s t a t i c - __ .._._- _ __._ - - .- Granulosa-cell Carcinoma... Fibrosarcoma , m e t a s t a t i c . -- RENAL LYMPH NODE -- E ’ L - --.I- t Malignant Lymphoma, mixed type Malignant

Human Mature Adipocytes Express Albumin and This Expression Is Not Regulated by Inflammation

PubMed Central

Sirico, Maria Luisa; Guida, Bruna; Procino, Alfredo; Pota, Andrea; Sodo, Maurizio; Grandaliano, Giuseppe; Simone, Simona; Pertosa, Giovanni; Riccio, Eleonora; Memoli, Bruno

2012-01-01

Aims. Our group investigated albumin gene expression in human adipocytes, its regulation by inflammation and the possible contribution of adipose tissue to albumin circulating levels. Methods. Both inflamed and healthy subjects provided adipose tissue samples. RT-PCR, Real-Time PCR, and Western Blot analysis on homogenates of adipocytes and pre-adipocytes were performed. In sixty-three healthy subjects and fifty-four micro-inflamed end stage renal disease (ESRD) patients circulating levels of albumin were measured by nephelometry; all subjects were also evaluated for body composition, calculated from bioelectrical measurements and an thropometric data. Results. A clear gene expression of albumin was showed in pre-adipocytes and, for the first time, in mature adipocytes. Albumin gene expression resulted significantly higher in pre-adipocytes than in adipocytes. No significant difference in albumin gene expression was showed between healthy controls and inflamed patients. A significant negative correlation was observed between albumin levels and fat mass in both healthy subjects and inflamed ESRD patients. Conclusions. In the present study we found first time evidence that human adipocytes express albumin. Our results also showed that systemic inflammation does not modulate albumin gene expression. The negative correlation between albumin and fat mass seems to exclude a significant contributing role of adipocyte in plasma albumin. PMID:22675238

Prospects for personalized combination immunotherapy for solid tumors based on adoptive cell therapies and immune checkpoint blockade therapies.

PubMed

Kato, Daiki; Yaguchi, Tomonori; Iwata, Takashi; Morii, Kenji; Nakagawa, Takayuki; Nishimura, Ryohei; Kawakami, Yutaka

2017-01-01

  Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors. However, gene-engineered T cells possess strong killing activity and cytokine production capacity, which can induce antigen spreading and modulate the TME of non-T cell-inflamed tumors seen in non-responders to ICB therapy. Immune responses against cancer are highly heterogeneous, not only between tumor types, but also within a patient or between different patients with the same type of cancer, indicating that personalized immunotherapy should be employed, based on the immune status of the individual patient. Here, we offer our perspective for personalized combination immunotherapy for solid tumors based on ACT and ICB therapies.

Investigation of in-flame soot optical properties in laminar coflow diffusion flames using thermophoretic particle sampling and spectral light extinction

NASA Astrophysics Data System (ADS)

Kempema, Nathan J.; Ma, Bin; Long, Marshall B.

2016-09-01

Soot optical properties are essential to the noninvasive study of the in-flame evolution of soot particles since they allow quantitative interpretation of optical diagnostics. Such experimental data are critical for comparison to results from computational models and soot sub-models. In this study, the thermophoretic sampling particle diagnostic (TSPD) technique is applied along with data from a previous spectrally resolved line-of-sight light attenuation experiment to determine the soot volume fraction and absorption function. The TSPD technique is applied in a flame stabilized on the Yale burner, and the soot scattering-to-absorption ratio is calculated using the Rayleigh-Debye-Gans theory for fractal aggregates and morphology information from a previous sampling experiment. The soot absorption function is determined as a function of wavelength and found to be in excellent agreement with previous in-flame measurements of the soot absorption function in coflow laminar diffusion flames. Two-dimensional maps of the soot dispersion exponent are calculated and show that the soot absorption function may have a positive or negative exponential wavelength dependence depending on the in-flame location. Finally, the wavelength dependence of the soot absorption function is related to the ratio of soot absorption functions, as would be found using two-excitation-wavelength laser-induced incandescence.

Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy.

PubMed

Arista-Nasr, Julian; Martinez-Benitez, Braulio; Bornstein-Quevedo, Leticia; Aguilar-Ayala, Elizmara; Aleman-Sanchez, Claudia Natalia; Ortiz-Bautista, Raul

2016-01-01

The vast majority of urothelial carcinomas infiltrating the bladder are consistente with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12) and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

Pharmacodynamic evaluation of Lys5, MeLeu9, Nle10-NKA(4–10) prokinetic effects on bladder and colon activity in acute spinal cord transected and spinally intact rats

PubMed Central

Kullmann, F. Aura; Katofiasc, M.; Thor, K.B.; Marson, L.

2017-01-01

Purpose To determine feasibility of a novel therapeutic approach to drug-induced voiding after spinal cord injury (SCI) using a well-characterized, peptide, neurokinin 2 receptor (NK2 receptor) agonist, Lys5, MeLeu9, Nle10-NKA(4–10) (LMN-NKA). Methods Cystometry and colorectal pressure measurements were performed in urethane anesthetized, intact and acutely spinalized, female rats. Bladder pressure and voiding were monitored in response to intravenous LMN-NKA given with the bladder filled to 70% capacity. Results LMN-NKA (0.1–300 µg/kg) produced dose dependent, rapid (< 60 s), short duration (< 15 min) increases in bladder pressure. In intact rats, doses above 0.3–1 µg/kg induced urine release (voiding efficiency of ~ 70% at ≥ 1 µg/kg). In spinalized rats, urine release required higher doses (≥ 10 µg/kg) and was less efficient (30–50%). LMN-NKA (0.1–100 µg/kg) also produced dose dependent increases in colorectal pressure. No tachyphylaxis was observed, and the responses were blocked by an NK2 receptor antagonist (GR159897, 1 mg/kg i.v.). No obvious cardiorespiratory effects were noted. Conclusions These results suggest that rapid-onset, short duration, drug-induced voiding is possible in acute spinal and intact rats with intravenous administration of an NK2 receptor agonist. Future challenges remain in regards to finding alternative routes of administration that produce clinically significant voiding, multiple times per day, in animal models of chronic SCI. PMID:27889808

New Stimulation Strategy to Improve the Bladder Function in Paraplegics: Chronic Experiments in Dogs

DTIC Science & Technology

2001-10-25

urinary system [4]. More recently, neurostimulation and neuromodulation of the sacral nerve root seems to be one of the most promising options to enhance...day. Expelled and residual urine volumes were measured. Also the applied parameters for the continuous low frequency / low amplitude neuromodulation ...VCUG) with neurostimulation was carried out after IVU study. Low-frequency only stimulation During the 7th month, daily stimulations were performed

EFFECTS OF CYP-INDUCED CYSTITIS ON GROWTH FACTORS AND ASSOCIATED RECEPTORS EXPRESSION IN MICTURITION PATHWAYS IN MICE WITH CHRONIC OVEREXPRESSION OF NGF IN UROTHELIUM

PubMed Central

Girard, Beatrice M.; Malley, Susan; May, Victor; Vizzard, Margaret A.

2016-01-01

We have determined if cyclophosphamide (CYP)-induced cystitis produces additional changes in growth factor/receptors expression in the urinary bladder (urothelium, detrusor) and lumbosacral (L6-S1) dorsal root ganglia (DRG) in a transgenic mouse model with chronic urothelial overexpression of NGF (NGF-OE). Functionally, NGF-OE mice treated with CYP exhibit significant increases in voiding frequency above that observed in control NGF-OE mice (no CYP). Quantitative PCR was used to determine NGF, BDNF, VEGF and receptors (TrkA, TrkB, p75NTR) transcripts expression in tissues from NGF-OE and wildtype (WT) mice with CYP-induced cystitis of varying duration (4 h, 48 h, 8 d). In urothelium of control NGF-OE mice, NGF mRNA was significantly (p ≤ 0.001) increased. Urothelial expression of NGF mRNA in NGF-OE mice treated with CYP (4 h, 48 h, 8 d) was not further increased but maintained with all durations of CYP treatment evaluated. In contrast, CYP-induced cystitis (4 h, 48 h, 8 d) in NGF-OE mice demonstrated significant (p ≤ 0.05) regulation in BDNF, VEGF, TrkA, TrkB and P75NTR mRNA in urothelium and detrusor smooth muscle. Similarly, CYP-induced cystitis (4 h, 48 h, 8 d) in NGF-OE mice resulted in significant (p ≤ 0.05), differential changes in transcript expression for NGF, BDNF and receptors (TrkA, TrkB, p75NTR) in S1 DRG that was dependent on the duration-of CYP-induced cystitis. In general, NGF, BDNF, TrkA and TrkB protein content in the urinary bladder increased in WT and NGF-OE mice with CYP-induced cystitis (4 h). Changes in NGF, TrkA and TrkB expression in the urinary bladder were significantly (p ≤ 0.05) greater in NGF-OE mice with CYP-induced cystitis (4 h) compared to WT mice with cystitis (4 h). However, the magnitude of change between WT and NGF-OE mice was only significantly (p ≤ 0.05) different for TrkB expression in urinary bladder of NGF-OE mice treated with CYP. These studies are consistent with target-derived NGF and other inflammatory mediators affecting neurochemical plasticity with potential contributions to reflex function of micturition pathways. PMID:27259880

Role of M2 and M3 muscarinic acetylcholine receptor subtypes in activation of bladder afferent pathways in spinal cord injured rats.

PubMed

Matsumoto, Yoshihiro; Miyazato, Minoru; Yokoyama, Hitoshi; Kita, Masafumi; Hirao, Yoshihiko; Chancellor, Michael B; Yoshimura, Naoki

2012-05-01

To evaluate the role of M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes in the activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI). Adult female Sprague-Dawley rats were spinalized at the T9 level. Continuous cystometry was performed under awake conditions 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine), and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression in the mucosa was determined using real-time quantitative polymerase chain reaction. At 2 and 4 weeks after SCI, intravesical administration of a nonselective mAChR agonist (25 μM oxotremorine-methiodide) increased the area under the curve of nonvoiding contractions, although the intercontraction interval of voiding contractions and maximal voiding pressure did not change. This effect was blocked by atropine and methoctramine (10 μM) but not by darifenacin (50 μM). However, mAChR antagonists alone (10-50 μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa of SCI rats compared with that in normal rats. Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity might not be involved in the emergence of detrusor overactivity in SCI. Copyright © 2012 Elsevier Inc. All rights reserved.

Noncolorectal malignancies in inflammatory bowel disease: more than meets the eye.

PubMed

Beaugerie, Laurent; Sokol, Harry; Seksik, Philippe

2009-01-01

In patients with Crohn's disease, the risk of small bowel adenocarcinoma is 20-40 times higher than the low background risk of the general population. In the subset of patients with longstanding small bowel lesions, the absolute risk of small bowel adenocarcinoma exceeds 1 per 100 patient-years after 25 years of follow-up and becomes equivalent to the risk of colorectal cancer. Growing evidence suggests that the pathogenesis of small bowel adenocarcinoma arising in inflammatory lesions of Crohn's disease is similar to that of colorectal cancer complicating chronic colonic inflammation (inflammation-dysplasia-cancer sequence). However, contrasting with the established endoscopic detection of colonic advanced neoplasias in patients with longstanding extensive colitis, there is no consensus at this time how to face the excess-risk of small bowel adenocarcinoma in patients at high risk. There are no specific clinical or imaging alert signs and endoscopic surveillance of the totality of the inflamed small bowel mucosa would suppose to perform repeated enteroscopies, with the potential limiting factor of stenosis. Very preliminary data suggest that chemoprevention with salicylates could be an alternative way for reducing the risk. Data from referral centers and from the CESAME cohort suggest that intestinal lymphomas may arise in the chronically inflamed segments in patients with inflammatory bowel disease (IBD). Regarding nonintestinal lymphomas, it is now established that IBD patients treated with thiopurines have an excess risk of lymphomas, exhibiting in most cases pathological features of lymphomas associated with immunosuppression, including the frequent presence of EBV in neoplastic tissues. There is growing evidence that treatment with thiopurines is responsible by itself for this excess risk. IBD patients receiving immunomodulators, especially young men, are also at risk (0.4 for 10,000 patient-years in the CESAME study) for developing fatal early post-mononucleosis lymphomas, like in Purtilo's syndrome, maybe in association with a background genetic susceptibility. Finally, patients receiving thiopurines and/or TNF-inhibitors are at risk for developing fatal hepatosplenic T cell lymphomas, but this risk is low (no case in the CESAME study). Whether patients receiving a monotherapy with methotrexate and/or TNF inhibitors are at increased risk of lymphomas is not known. Concordant data suggest that women receiving immunosuppressive therapy are at increased risk for developing uterine cervix dysplasia and require closer surveillance. But it is not established whether the risk of uterine cervix cancer and basal and squamous cell skin cancers (that may be associated with chronic human papillomavirus infection) is increased in patients receiving immunomodulators. Copyright 2009 S. Karger AG, Basel.

Tertiary lymphoid structures in cancer and beyond.

PubMed

Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolas A; Sautès-Fridman, Catherine; Fridman, Wolf Herman

2014-11-01

Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Local anesthetics: special considerations in endodontics.

PubMed

Jeske, Arthur H

2003-03-01

Local anesthetics are essential for successful endodontic treatment, and their pharmacologic characteristics have special implications for the treatment of painful, chronically-inflamed or necrotic teeth. Their dosages must be limited to prevent toxicity, which may be enhanced by the coadministration of sedative agents or drugs which affect hepatic drug metabolism. Endodontic patients with established central and peripheral sensitization represent special challenges for pain control, since morphogenetic changes resulting from neurogenic inflammation can render pain fibers more resistant to local anesthesia. The use of vasconstrictors with conventional and alternative injection techniques, e.g., intraosseous injections, are necessary to prolong the duration of action of local anesthesia but can place patients with cardiovascular disease at some risk. An appreciation of all of these aspects of local anesthesia in endodontics will better prepare the operator for predictably safe and effective patient care.

Polyglycerol-opioid conjugate produces analgesia devoid of side effects.

PubMed

González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph

2017-07-04

Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

Peripheral opioid analgesia in teeth with symptomatic inflamed pulps.

PubMed Central

Uhle, R. A.; Reader, A.; Nist, R.; Weaver, J.; Beck, M.; Meyers, W. J.

1997-01-01

The purpose of this study was to investigate the ability of low-dose fentanyl to produce analgesia when administered via the periodontal ligament injection in teeth with symptomatic, inflamed pulps. All subjects presented for emergency treatment with moderate to severe pain and had a posterior tooth with a clinical diagnosis of irreversible pulpitis. Twenty subjects randomly received either 10 micrograms fentanyl citrate or saline placebo via the periodontal ligament injection in a double-blind manner. The subjects rated their pain prior to injection and rated pain intensity and pain half gone for 59 min postinjection. Low-dose fentanyl delivered via the periodontal ligament injection in inflamed teeth provided significantly greater analgesia than the saline placebo (P < 0.05). Since the dose of fentanyl used was less than the dose required to provide analgesia by a central mechanism, the results of this study may be consistent with a peripheral opioid mechanism of action. PMID:9481968

Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications.

PubMed

Hua, Susan; Cabot, Peter J

2010-09-01

Peripheral mechanisms of endogenous pain control are significant. In peripheral inflamed tissue, an interaction between immune-cell-derived opioids and opioid receptors localized on sensory nerve terminals results in potent, clinically measurable analgesia. Opioid peptides and the mRNA encoding their precursor proteins are present in immune cells. These cells 'home' preferentially to injured tissue, where they secrete opioids to reduce pain. Investigation of the mechanisms underlying the migration of opioid-containing immune cells to inflamed tissue is an active area of research, with recent data demonstrating the importance of cell adhesion molecules in leukocyte adhesion to both the endothelium in vascular transmigration and to neurons within peripheral inflamed tissue. This review summarizes the physiological mechanisms and clinical significance of this unique endogenous peripheral analgesic pathway and discusses therapeutic implications for the development of novel targeted peripheral analgesics. Copyright 2010 Elsevier Ltd. All rights reserved.

Chronic urinary tract infection and bladder carcinoma risk: a meta-analysis of case-control and cohort studies.

PubMed

Akhtar, Saeed; Al-Shammari, Ahmad; Al-Abkal, Jarrah

2018-02-05

This meta-analysis of published case-control and cohort studies sought to quantify the magnitude and direction of association between chronic UTI (defined as the infection of the urinary tract that either does not respond to treatment or keeps recurring) and risk of bladder carcinoma (BCa) (i.e., including mainly urothelial carcinoma, squamous cell carcinoma or adenocarcinoma). A literature search was conducted using Medline, Embase, Ovid, Web of Science, Science Direct and Cochrane Library, which was supplemented with manual search of reference lists of the identified articles. Case-control and cohort studies examining UTI as a predictor of BCa risk published through June 2016 were eligible. Using random-effects models, odds ratios (OR) or relative risks (RR) from eligible studies were combined to synthesize summary effect estimates. The included studies were assessed for methodological quality and potential publication bias. Heterogeneity by study characteristics was examined by sub-group and meta-regression analyses. Eighteen case-control and three cohort studies published between 1963 and 2016 were eligible. Random-effects models showed that UTI was significantly associated with an increased BCa risk both in case-control studies (summary OR RE  = 2.33; 95% CI 1.86, 2.92) and cohort studies (summary RR RE  = 2.88; 95% CI 1.20, 6.89). The observed relationship of UTI with an increased BCa risk was independent of the study characteristics considered. No significant publication bias was detected. Chronic UTI was significantly and independently associated with an increased BCa risk. However, due to the presence of high between-study heterogeneity and inconsistent patterns of adjusted confounding effects, more data are needed to clarify the role of chronic UTI in causation of BCa and if established, prompt and effective treatment of UTI may minimize a substantial proportion of BCa risk.

Dragon's blood inhibits chronic inflammatory and neuropathic pain responses by blocking the synthesis and release of substance P in rats.

PubMed

Li, Yu-Sang; Wang, Jun-Xian; Jia, Mei-Mei; Liu, Min; Li, Xiao-Jun; Tang, He-Bin

2012-01-01

As a traditional Chinese medicine, dragon's blood (DB) is widely used in treating various pains for thousands of years due to its potent anti-inflammatory and analgesic effects. In the present study, we observed that intragastric administration of DB at dosages of 0.14, 0.56, and 1.12 g/kg potently inhibited paw edema, hyperalgesia, cyclooxygenase-2 (COX-2) protein expression, or preprotachykinin-A mRNA expression in carrageenan-inflamed or sciatic nerve-injured (chronic constriction injury) rats, respectively. A short-term (15 s or 10 min) pre-exposure of cultured rat dorsal root ganglion (DRG) neurons to DB (0.3, 3, and 30 µg/ml) or its component cochinchinenin B (CB; 0.1, 1, and 10 µM) blocked capsaicin-evoked increases in both the intracellular calcium ion concentration and the substance P release. Moreover, a long-term (180 min) exposure of cultured rat DRG neurons to DB or CB significantly attenuated bradykinin-induced substance P release. These findings indicate that DB exerts anti-inflammatory and analgesic effects by blocking the synthesis and release of substance P through inhibition of COX-2 protein induction and intracellular calcium ion concentration. Therefore, DB may serve as a promising potent therapeutic agent for treatment of chronic pain, and its effective component CB might partly contribute to anti-inflammatory and analgesic effects.

Clinical peri-implant sounding accuracy in the presence of chronic inflammation of peri-implant tissues. Clinical observation study.

PubMed

Romeo, E; Lops, D; Storelli, S; Ghisolfi, M

2009-03-01

The aim of this study was to assess if the probing pocket depth is a reliable clinical parameter in the evaluation of the depth of the peri-implant sulci. In case of chronic inflamed peri-implant tissues, this evaluation is useful for understanding the level of bone resorption. The study enrolled 22 patients. All of them were diagnosed for a peri-implantitis and were scheduled for a resective surgery with implantoplasty. During the surgery, a full thickness flap was raised and resective surgery was performed as well as an implantoplasty procedure. Peri-implant probing values before the surgery (PAL) were recorded, as were values of bone resorption after flap elevation (DIB), at all four sites around each implant (88 sites). The mean value of PAL calculated for all 88 sites was 5.67 mm (+/-1.46); the correspondent value of DIB was 6.37 mm (+/-1.81). In 52 sites out of 88 (59.1%) the values of PAL and DIB were exactly the same (maximum difference 0.5 mm). In only 10 cases (11.3%) the difference between PAL and DIB was >2 mm. The mean values for PAL and DIB were not statistically different. Authors have concluded that in case of chronic inflammation of peri-implant tissues, the probe reaches the bone pick, allowing the clinician to have reliable information on the actual bone resorption.

Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis

PubMed Central

Qiu, Xinyun; Zhang, Feng; Yang, Xi; Wu, Na; Jiang, Weiwei; Li, Xia; Li, Xiaoxue; Liu, Yulan

2015-01-01

Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum, and colon), prefer different colonization locations (mucosa and feces), and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella, Barnesiella, Bacteroides, Alistipes, and Lactobacillus and loss of butyrate-producing Clostridium XIVa, and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis. PMID:26013555

Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner.

PubMed

Munir, Hafsa; Ward, Lewis S C; Sheriff, Lozan; Kemble, Samuel; Nayar, Saba; Barone, Francesca; Nash, Gerard B; McGettrick, Helen M

2017-06-01

Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα-treated endothelial cells (EC), but MSC-derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signalling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them, and mature adipocytes from adipose tissue were all immunoprotective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive "abnormal" adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immunoprotective phenotype. Stem Cells 2017;35:1636-1646. © 2017 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM.

PubMed

Hayward, A R; Levy, J; Facchetti, F; Notarangelo, L; Ochs, H D; Etzioni, A; Bonnefoy, J Y; Cosyns, M; Weinberg, A

1997-01-15

We report an association between X-linked immunodeficiency with hyper-IgM (XHIM) and carcinomas affecting the liver, pancreas, biliary tree, and associated neuroectodermal endocrine cells. The tumors were fatal in eight of nine cases and in most instances were preceded by chronic cholangiopathy and/or cirrhosis. An additional group of subjects with XHIM had chronic inflammation of the liver or bile ducts but no malignancy. Many patients with XHIM were infected with cryptosporidia. CD40 is normally expressed on regenerating or inflammed bile duct epithelium. A CD40+ hepatocellular carcinoma cell line, HepG2, susceptible to cryptosporidia and CMV infection became resistant when cell surface CD40 was cross-linked by a CD40 ligand fusion protein. Apoptosis was triggered in HepG2 cells if protein synthesis was blocked by cycloheximide or if the cells were infected by cryptosporidia. Ligation of CD40 on biliary epithelium may contribute to defense against infection by intracellular pathogens. We propose that the CD40 ligand mutations that cause XHIM deprive the biliary epithelium of one line of defense against intracellular pathogens and that malignant transformation in the biliary tree follows chronic infection or inflammation. The resulting tumors may then progress without check by an effective immune response. Patients with XHIM who have abnormal liver function tests should be considered at increased risk for cholangiopathy or malignancy.

Lymphotoxin β receptor activation promotes bladder cancer in a nuclear factor-κB-dependent manner.

PubMed

Shen, Mo; Duan, Xiuzhi; Zhou, Ping; Zhou, Wu; Wu, Xiuling; Xu, Siqi; Chen, Yuhua; Tao, Zhihua

2015-02-01

Bladder cancer (BCa) is the most common tumor of the urinary system. Chronic inflammation in the papillary urothelial neoplasm of low malignant potential (PUNLMP)may contribute to carcinogenesis, including that of BCa, via poorly understood mechanisms. In this study, we show that the lymphotoxin β receptor (LTβR) is upregulated in BCa via activation of the canonical and non-canonical nuclear factor-κB (NF-κB) pathways. The mRNA expression of LTβR in 81 BCa, 10 chronic cystitis and 23 healthy bladder mucosa tissues was investigated by reverse transcription-fluorescent quantitative polymerase chain reaction (RT-FQ-PCR), and protein expression was studied in 73 BCa, 30 cystitis and 15 healthy paraffin-embedded tissue sections by immunohistochemistry. Both LTβR mRNA and protein were upregulated in BCa and cystitis compared to the healthy group (P<0.05). The mRNA level of the downstream NF-κB canonical pathway p65 gene and of the non-canonical pathway RelB gene were higher in the BCa and cystitis groups compared to the healthy one. The level of phosphorylated p65 (p-p65) protein of the canonical NF-κB pathway and that of p52, a protein of the non-canonical NF-κB pathway, were also higher in the BCa and cystitis group compared to the healthy group. The levels of these proteins significantly correlated to the pathological grade, clinical stage and lymph node metastasis of BCa patients (P<0.05). In addition, there was a positive correlation between LTβR and NF-κB pathway proteins. Thus, LTβR signaling may be involved in promoting BCa through the NF-κB pathway, and which may represent the molecular link between inflammation and BCa.

Comparison of Serum Levels of Endothelin-1 in Chronic Periodontitis Patients Before and After Treatment

PubMed Central

Varghese, Sheeja S; Sankari, M.; Jayakumar, ND.

2017-01-01

Introduction Endothelin-1 (ET-1) is a potent vasoconstrictive peptide with multi functional activity in various systemic diseases. Previous studies indicate the detection of ET-1 in gingival tissues and gingival crevicular fluid. Aim The aim of this study was to estimate the serum ET-1 levels in clinically healthy subjects and subjects with chronic periodontitis, before and after treatment, and correlate it with the clinical parameters. Materials and Methods A total of 44 patients were included in the study. Group I comprised of 20 subjects with clinically healthy periodontium. Group II comprised of 24 subjects with chronic periodontitis. Group III comprised of same Group II subjects following periodontal management. Serum samples were collected from the subjects and an Enzyme Linked Immunosorbent Assay (ELISA) was done to estimate the ET-1 levels. The ET-1 levels were then correlated among the three groups with the clinical parameters namely, Plaque Index (PI), Sulcus Bleeding Index (SBI), probing pocket depth, clinical attachment loss and Periodontally Inflamed Surface Area (PISA). The independent t-test and paired t-test were used for comparison of clinical parameters and Pearson’s correlation coefficient test was used for correlating the ET-1 levels. Results ET-1 levels in chronic periodontitis subjects were significantly higher compared to healthy subjects (p<0.001). However, the clinical parameters did not statistically correlate with the ET-1 levels. There was a significant decrease in ET-1 levels following treatment (p<0.001). Conclusion Serum ET-1 is increased in chronic periodontitis and reduces after periodontal therapy. Further studies are required to establish ET-1 as a biomarker for periodontal disease. PMID:28571268

The relationship between irritable bowel syndrome, functional dyspepsia, chronic fatigue and overactive bladder syndrome: a controlled study 6 years after acute gastrointestinal infection.

PubMed

Persson, Robert; Wensaas, Knut-Arne; Hanevik, Kurt; Eide, Geir Egil; Langeland, Nina; Rortveit, Guri

2015-06-10

To investigate in a cohort with previous gastrointestinal infection and a control group the prevalence of overactive bladder syndrome (OAB), and how it was associated with three other functional disorders; irritable bowel syndrome (IBS), functional dyspepsia (FD) and chronic fatigue (CF). Controlled historic cohort study including 724 individuals with laboratory confirmed giardiasis six years earlier, and 847 controls matched by gender and age. Prevalence and odds ratios (OR) with 95 % confidence intervals (CI) were calculated. The prevalence of OAB was 18.7 % (134/716) in the exposed group and 13.6 % (113/833) in the control group (p = 0.007). The association between OAB and IBS was strong in the control group (OR: 2.42; 95 % CI: 1.45 to 4.04), but insignificant in the Giardia exposed (OR: 1.29; 95 % CI: 0.88 to 1.88). The association between OAB and FD was weak in both groups. CF was strongly associated with OAB (OR: 2.73; 95 % CI: 1.85 to 4.02 in the exposed and OR: 2.79; 95 % CI: 1.69 to 4.62 in the controls), and this association remained when comorbid conditions were excluded. Sporadic IBS was associated with increased risk of OAB, whereas post-infectious IBS was not. An apparent association between OAB and previous Giardia infection can be ascribed to comorbid functional disorders.

Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis.

PubMed

Castelo-Branco, Morgana T L; Soares, Igor D P; Lopes, Daiana V; Buongusto, Fernanda; Martinusso, Cesonia A; do Rosario, Alyson; Souza, Sergio A L; Gutfilen, Bianca; Fonseca, Lea Mirian B; Elia, Celeste; Madi, Kalil; Schanaider, Alberto; Rossi, Maria Isabel D; Souza, Heitor S P

2012-01-01

Mesenchymal stromal cells (MSCs) were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs) and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. After colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously. Intraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1β decreased, while VEGF and TGF-β did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas. Intraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.

Budesonide Loaded PLGA Nanoparticles for Targeting the Inflamed Intestinal Mucosa--Pharmaceutical Characterization and Fluorescence Imaging.

PubMed

Ali, Hussain; Weigmann, Benno; Collnot, Eva-Maria; Khan, Saeed Ahmad; Windbergs, Maike; Lehr, Claus-Michael

2016-05-01

The purpose of this study was to evaluate the specifically targeted efficiency of budesonide loaded PLGA nanoparticles for the treatment of inflammatory bowel disease (IBD). The nanoparticles were prepared by an oil/water (O/W) emulsion evaporation technique. The nanoparticles were characterized for their size, shape and in vitro drug release profile. Solid state characterization was carried out by differential scanning calorimetry (DSC) and X-ray Power diffraction (XPRD). In order to evaluate the targeted efficiency of nanoparticles, a particle localization study in the healthy and in the inflamed colon was determined in vivo. These data were complemented by cryo-sections. Nanoparticles were 200 ± 05 nm in size with a smooth and spherical shape. The encapsulation efficiency was around 85 ± 3.5%, which was find-out by both, direct and indirect methods. Release of budesonide from the nanoparticles showed a biphasic release profile with an initial burst followed by sustained release. XPRD data revealed that the drug in the polymer matrix existed in crystalline state. Nanoparticles accumulation in inflamed tissues was evaluated by in-vivo imaging system and it was found that particles are accumulated in abundance at the site of inflammation when compared to the healthy group. The study demonstrates that the budesonide loaded PLGA nanoparticles are an efficient delivery system for targeted drug delivery to the inflamed intestinal mucosa.

Coupling of pulsed electromagnetic fields (PEMF) therapy to molecular grounds of the cell

PubMed Central

Funk, Richard HW

2018-01-01

In this review we compile results cited in reliable journals that show a ratio for the use of pulsed electromagnetic fields (PEMF) in therapy, indeed. This is true especially for chronically inflamed joints. Furthermore, we try to link this therapeutic approach to the molecular background of chronic inflammation and arthritis. At first we start with the clinical outcome of PEMF therapy. Then, we look for possible triggers and an electromagnetic counterpart that is endogenously inherent in cell biology and in the tissues of interest. Finally, we want to investigate causal molecular and cellular mechanisms of possible PEMF actions. It shows that there are endogenous mechanisms, indeed, which can act as triggers for PEMF like the resting membrane potential as well as resonance mechanisms in charged moieties like membrane transporters. Especially voltage-gated calcium channels can be triggered. These may lead into specific signaling pathways and also may elicit nitric oxide as well as moderate radical reactions, which can ultimately lead to e.g. NFκB-like reactions. Concerted in the right way, these reactions can cause a kind of cell protection and ultimately lead to a dampening of inflammatory signals like interleukins. PMID:29887943

Acute pain management in patients with persistent pain.

PubMed

Quinlan, Jane; Carter, Kim

2012-06-01

Over the past 20 years, prescriptions of opioids for chronic pain have increased dramatically. This review addresses the difficulties in managing acute pain in this growing group of patients and discusses evidence relating to opioid tolerance and hyperalgesia and new avenues of research in specific painful conditions. There is accumulating evidence surrounding the dangers of high-dose opioids and the risk of overdose and death. Employing nonopioid analgesics and disease-modifying drugs to cover an acute exacerbation of pain will thus limit escalating opioid doses. In specific diseases, the role of oxidative stress and the disruption of calcium homeostasis may provide treatment targets in acute pancreatitis; the identification of psychological stressors may decrease the frequency of acute exacerbations of abdominal pain; modifying the adhesion of sickle cells to inflamed endothelium may reduce vaso-occlusive crises; while vertebroplasty and calcitonin appear to improve pain and functioning after osteoporotic vertebral fractures. Much of the evidence regarding the acute pain management of chronic pain patients is extrapolated from studies of opioid-naïve patients undergoing surgery. More focused research is needed to ascertain whether this model is an appropriate one to follow for such a complex group of patients.

Iron deposits in the chronically inflamed central nervous system and contributes to neurodegeneration.

PubMed

Andersen, Hjalte Holm; Johnsen, Kasper Bendix; Moos, Torben

2014-05-01

Neurodegenerative disorders are characterized by the presence of inflammation in areas with neuronal cell death and a regional increase in iron that exceeds what occurs during normal aging. The inflammatory process accompanying the neuronal degeneration involves glial cells of the central nervous system (CNS) and monocytes of the circulation that migrate into the CNS while transforming into phagocytic macrophages. This review outlines the possible mechanisms responsible for deposition of iron in neurodegenerative disorders with a main emphasis on how iron-containing monocytes may migrate into the CNS, transform into macrophages, and die out subsequently to their phagocytosis of damaged and dying neuronal cells. The dying macrophages may in turn release their iron, which enters the pool of labile iron to catalytically promote formation of free-radical-mediated stress and oxidative damage to adjacent cells, including neurons. Healthy neurons may also chronically acquire iron from the extracellular space as another principle mechanism for oxidative stress-mediated damage. Pharmacological handling of monocyte migration into the CNS combined with chelators that neutralize the effects of extracellular iron occurring due to the release from dying macrophages as well as intraneuronal chelation may denote good possibilities for reducing the deleterious consequences of iron deposition in the CNS.

Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

ClinicalTrials.gov

2018-03-20

Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

Fibromyalgia Syndrome in Need of Effective Treatments

PubMed Central

Tsilioni, Irene; Arbetman, Lauren; Panagiotidou, Smaro; Stewart, Julia M.; Gleason, Rae M.; Russell, Irwin J.

2015-01-01

Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment. PMID:26306765

Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: implications to extracranial origin of headache

PubMed Central

Perry, Carlton; Blake, Pamela; Buettner, Catherine; Papavassiliou, Efstathios; Schain, Aaron; Bhasin, Manoj; Burstein, Rami

2016-01-01

Objective Chronic migraine (CM) is often associated with chronic tenderness of pericranial muscles. In fact, a distinct increase in muscle tenderness prior to onset of occipital headache that eventually progresses into a full blown migraine attack is common. This experience raises the possibility that some CM attacks originate outside the cranium. The objective of this study was to determine whether there are extracranial pathophysiologies in these headaches. Methods We biopsied and measured the expression of gene transcripts (mRNA) encoding proteins that play roles in immune and inflammatory responses in affected (i.e., where the head hurts) calvarial periosteum of (a) patients whose CMs are associated with muscle tenderness and (b) patients with no history of headache. Results Expression of proinflammatory genes (e.g., CCL8, TLR2) in the calvarial periosteum significantly increases in CM patients attesting to muscle tenderness, whereas expression of genes that suppress inflammation and immune cell differentiation (e.g., IL10RA, CSF1R) decreased. Interpretation Because the up-regulated genes were linked to activation of white blood cells, production of cytokines, and inhibition of NFKB, and the down-regulated genes linked to prevention of macrophage activation and cell lysis, we suggest that the molecular environment surrounding periosteal pain fibers is inflamed and in turn activates trigeminovascular nociceptors that reach the affected periosteum through suture branches of intracranial meningeal nociceptors and/or somatic branches of the occipital nerve. This study provides the first set of evidence for localized extracranial pathophysiology in chronic migraine. PMID:27091721

Fully integrated high-speed intravascular optical coherence tomography/near-infrared fluorescence structural/molecular imaging in vivo using a clinically available near-infrared fluorescence-emitting indocyanine green to detect inflamed lipid-rich atheromata in coronary-sized vessels.

PubMed

Lee, Sunki; Lee, Min Woo; Cho, Han Saem; Song, Joon Woo; Nam, Hyeong Soo; Oh, Dong Joo; Park, Kyeongsoon; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

2014-08-01

Lipid-rich inflamed coronary plaques are prone to rupture. The purpose of this study was to assess lipid-rich inflamed plaques in vivo using fully integrated high-speed optical coherence tomography (OCT)/near-infrared fluorescence (NIRF) molecular imaging with a Food and Drug Administration-approved indocyanine green (ICG). An integrated high-speed intravascular OCT/NIRF imaging catheter and a dual-modal OCT/NIRF system were constructed based on a clinical OCT platform. For imaging lipid-rich inflamed plaques, the Food and Drug Administration-approved NIRF-emitting ICG (2.25 mg/kg) or saline was injected intravenously into rabbit models with experimental atheromata induced by balloon injury and 12- to 14-week high-cholesterol diets. Twenty minutes after injection, in vivo OCT/NIRF imaging of the infrarenal aorta and iliac arteries was acquired only under contrast flushing through catheter (pullback speed up to ≤20 mm/s). NIRF signals were strongly detected in the OCT-visualized atheromata of the ICG-injected rabbits. The in vivo NIRF target-to-background ratio was significantly larger in the ICG-injected rabbits than in the saline-injected controls (P<0.01). Ex vivo peak plaque target-to-background ratios were significantly higher in ICG-injected rabbits than in controls (P<0.01) on fluorescence reflectance imaging, which correlated well with the in vivo target-to-background ratios (P<0.01; r=0.85) without significant bias (0.41). Cellular ICG uptake, correlative fluorescence microscopy, and histopathology also corroborated the in vivo imaging findings. Integrated OCT/NIRF structural/molecular imaging with a Food and Drug Administration -approved ICG accurately identified lipid-rich inflamed atheromata in coronary-sized vessels. This highly translatable dual-modal imaging approach could enhance our capabilities to detect high-risk coronary plaques. © 2014 American Heart Association, Inc.

Transplantation of autologous differentiated urothelium in an experimental model of composite cystoplasty.

PubMed

Turner, Alex; Subramanian, Ramnath; Thomas, David F M; Hinley, Jennifer; Abbas, Syed Khawar; Stahlschmidt, Jens; Southgate, Jennifer

2011-03-01

Enterocystoplasty is associated with serious complications resulting from the chronic interaction between intestinal epithelium and urine. Composite cystoplasty is proposed as a means of overcoming these complications by substituting intestinal epithelium with tissue-engineered autologous urothelium. To develop a robust surgical procedure for composite cystoplasty and to determine if outcome is improved by transplantation of a differentiated urothelium. Bladder augmentation with in vitro-generated autologous tissues was performed in 11 female Large-White hybrid pigs in a well-equipped biomedical centre with operating facilities. Participants were a team comprising scientists, urologists, a veterinary surgeon, and a histopathologist. Urothelium harvested by open biopsy was expanded in culture and used to develop sheets of nondifferentiated or differentiated urothelium. The sheets were transplanted onto a vascularised, de-epithelialised, seromuscular colonic segment at the time of bladder augmentation. After removal of catheters and balloon at two weeks, voiding behaviour was monitored and animals were sacrificed at 3 months for immunohistology. Eleven pigs underwent augmentation, but four were lost to complications. Voiding behaviour was normal in the remainder. At autopsy, reconstructed bladders were healthy, lined by confluent urothelium, and showed no fibrosis, mucus, calculi, or colonic regrowth. Urothelial morphology was transitional with variable columnar attributes consistent between native and augmented segments. Bladders reconstructed with differentiated cell sheets had fewer lymphocytes infiltrating the lamina propria, indicating more effective urinary barrier function. The study endorses the potential for composite cystoplasty by (1) successfully developing reliable techniques for transplanting urothelium onto a prepared, vascularised, smooth muscle segment and (2) creating a functional urothelium-lined augmentation to overcome the complications of conventional enterocystoplasty. Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Transplantation of Autologous Differentiated Urothelium in an Experimental Model of Composite Cystoplasty

PubMed Central

Turner, Alex; Subramanian, Ramnath; Thomas, David F.M.; Hinley, Jennifer; Abbas, Syed Khawar; Stahlschmidt, Jens; Southgate, Jennifer

2011-01-01

Background Enterocystoplasty is associated with serious complications resulting from the chronic interaction between intestinal epithelium and urine. Composite cystoplasty is proposed as a means of overcoming these complications by substituting intestinal epithelium with tissue-engineered autologous urothelium. Objective To develop a robust surgical procedure for composite cystoplasty and to determine if outcome is improved by transplantation of a differentiated urothelium. Design, setting, and participants Bladder augmentation with in vitro–generated autologous tissues was performed in 11 female Large-White hybrid pigs in a well-equipped biomedical centre with operating facilities. Participants were a team comprising scientists, urologists, a veterinary surgeon, and a histopathologist. Measurements Urothelium harvested by open biopsy was expanded in culture and used to develop sheets of nondifferentiated or differentiated urothelium. The sheets were transplanted onto a vascularised, de-epithelialised, seromuscular colonic segment at the time of bladder augmentation. After removal of catheters and balloon at two weeks, voiding behaviour was monitored and animals were sacrificed at 3 months for immunohistology. Results and limitations Eleven pigs underwent augmentation, but four were lost to complications. Voiding behaviour was normal in the remainder. At autopsy, reconstructed bladders were healthy, lined by confluent urothelium, and showed no fibrosis, mucus, calculi, or colonic regrowth. Urothelial morphology was transitional with variable columnar attributes consistent between native and augmented segments. Bladders reconstructed with differentiated cell sheets had fewer lymphocytes infiltrating the lamina propria, indicating more effective urinary barrier function. Conclusions The study endorses the potential for composite cystoplasty by (1) successfully developing reliable techniques for transplanting urothelium onto a prepared, vascularised, smooth muscle segment and (2) creating a functional urothelium-lined augmentation to overcome the complications of conventional enterocystoplasty. PMID:21195539

Position statement: a clinical approach to the management of adult non-neurogenic overactive bladder.

PubMed

Chung, Eric; Lee, Dominic; Gani, Johan; Gillman, Michael; Maher, Christopher; Brennan, Janelle; Johns Putra, Lydia; Ahmad, Laura; Chan, Lewis Lw

2018-01-15

Overactive bladder (OAB) is a highly prevalent medical condition that has an adverse impact on various health-related quality-of-life domains, including a significant psychosocial and financial burden. This position statement, formulated by members of the Urological Society of Australia and New Zealand and the UroGynaecological Society of Australasia, summarises the current recommendations for clinical diagnosis and treatment strategies in patients with non-neurogenic OAB, and guides clinicians in the decision-making process for managing the condition using evidence-based medicine. Main recommendations: Diagnosis and initial management should be based on thorough clinical history, examination and basic investigations to exclude underlying treatable causes such as urinary tract infection and urological malignancy. Initial treatment strategies for OAB involve conservative management with behavioural modification and bladder retraining. Second-line management involves medical therapy using anticholinergic or β3 agonist drugs provided there is adequate assessment of bladder emptying. If medical therapy is unsuccessful, further investigations with urodynamic studies and cystourethroscopy are recommended to guide further treatment. Intravesical botulinum toxin and sacral neuromodulation should be considered in medical refractory OAB. Changes in management as a result of this statement: OAB is a constellation of urinary symptoms and is a chronic condition with a low likelihood of cure; managing patient expectations is essential because OAB is challenging to treat. At present, the exact pathogenesis of OAB remains unclear and it is likely that there are multiple factors involved in this disease complex. Current medical treatment remains far from ideal, although minimally invasive surgery can be effective. Further research into the pathophysiology of this common condition will hopefully guide future developments in disease management.

Treatment of urethral defects: skin, buccal or bladder mucosa, tube or patch? An experimental study in dogs.

PubMed

El-Sherbiny, M T; Abol-Enein, H; Dawaba, M S; Ghoneim, M A

2002-05-01

We studied 3 graft materials and 2 urethroplasty techniques in 24 adult male mongrel dogs. The animals were divided into 2 equal groups. In group 1 a 4 cm. segment of perineal urethra was excised and tubed urethroplasty was performed using free full-thickness skin, buccal and bladder mucosa grafts in 4 dogs each. In group 2 a 4 cm. urethral strip was excised and onlay urethroplasty was performed using the same graft materials in 4 dogs each. Retrograde urethrography was done and the animals were sacrificed at week 12. Autopsy specimens were calibrated with a 10Fr catheter. Hematoxylin and eosin stained sections were examined. Masson's trichrome stain was used to determine the extent of fibrosis. Urethral stricture was diagnosed by radiology and confirmed by calibration in 8 of the 12 dogs (66%) in group 1 but in only 1 of the 12 (8%) in group 2 (p <0.004). Buccal mucosa grafts were associated with the lowest stricture rate of 12%, followed by 37% for bladder mucosa and 62% for skin (p <0.2). There was no difference in neovascularization among the 3 grafts. Graft shrinkage was less than 10% for buccal mucosa compared with 20% to 40% for skin and bladder mucosa. The shrinkage rate was similar for the onlay and tube techniques. The intensity of chronic inflammation and fibrosis was highest in the skin grafts. Circumferential fibrosis was noted in association with tubed urethroplasty but not with the onlay technique. The theoretical advantages of buccal mucosal grafts were pathologically demonstrated. When possible, grafts should be used as an onlay rather than as a complete tube.

IL-33 mast cell axis is central in LL-37 induced bladder inflammation and pain in a murine interstitial cystitis model.

PubMed

Martin Jensen, M; Jia, Wanjian; Schults, Austin J; Ye, Xiangyang; Prestwich, Glenn D; Oottamasathien, Siam

2018-05-18

Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is a debilitating chronic condition that afflicts over 3 million women above the age of 18 in the U.S., and most patients fail to respond to current treatment options. Mast cells have previously been implicated as both a diagnostic and prognostic marker in IC/PBS. Patients with IC/PBS have been shown to have elevated levels of IL-33, a cytokine released in response to tissue insult, in their urine. We hypothesize that mast cell-mediated inflammation induced from IL-33 may play an important role in initiating pain and inflammation in IC/PBS. A human cathelicidin, LL-37, which is found at elevated levels in IC/PBS patients, was used to induce an IC/PBS-like state of inflammation and bladder pain in mast cell deficient C-kit (-/-) and wild type C57Bl/6 (WT) mice. Inflammation was quantified using myeloperoxidase (MPO) expression in bladder tissues measured via ELISA. Response rate to suprapubic stimulation from von Frey filaments was used to assess the relative pain and discomfort. Both types of mice increased IL-33 expression in response to LL-37 exposure. However, mast cell deficient mice demonstrated significantly lower levels of inflammation (p < 0.001) and reduced pain response (p < 0.001) compared to WT mice. These findings implicate an IL-33-mast cell dependent axis with a potential etiology of pain and inflammation in IC/PBS. Future therapeutics aimed at targeting the IL-33 - mast cell axis could potentially serve as useful targets for treating IC/PBS. Copyright © 2018. Published by Elsevier Ltd.

Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis.

PubMed

Armas-González, Estefanía; Domínguez-Luis, María Jesús; Díaz-Martín, Ana; Arce-Franco, Mayte; Castro-Hernández, Javier; Danelon, Gabriela; Hernández-Hernández, Vanesa; Bustabad-Reyes, Sagrario; Cantabrana, Alberto; Uguccioni, Mariagrazia; Díaz-González, Federico

2018-06-07

B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20 + mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines. B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF. These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium.

Distribution of collagenous colitis: utility of flexible sigmoidoscopy.

PubMed Central

Tanaka, M; Mazzoleni, G; Riddell, R H

1992-01-01

We investigated the distribution of the collagen band in 33 patients with collagenous colitis to estimate the likelihood of the disease being diagnosed in biopsy specimens from the left side of the colon, such as those obtained using flexible sigmoidoscopy. To be included in this study patients had a subepithelial collagen band greater than or equal to 10 microns, an increase in chronic inflammatory cells in the same specimen, and diarrhoea for which there was no other apparent cause. In 17 patients undergoing full colonoscopy with a thickened collagen band, collagenous colitis was frequently patchy, even though overall the thickened collagen band was almost equally distributed throughout the colon. Rectal biopsy specimens showed a normal collagen band in 73% of patients, while a thickened collagen band was found in 82% of patients in at least one specimen from the left side of the colon. Three patients had a thickened collagen band only in the caecum. In three of eight rectal biopsy specimens with a normal collagen band there was no mucosal inflammation to raise the possibility of proximal disease, although all but one specimen with a normal collagen band from the sigmoid and descending colon were inflamed. Rectal biopsy alone is therefore a relatively poor method of making the diagnosis. Flexible sigmoidoscopy with multiple biopsy specimens from several sites is a reasonable initial investigation but not sufficient to exclude collagenous colitis when based on the presence of a thickened collagen band alone. Should left sided biopsy specimens show a normal collagen band but an inflamed mucosa, total colonoscopy with multiple specimens including the caecum may be required to establish the diagnosis. Images Figure 1 Figure 2 PMID:1740280

Distinct Roles for CXCR6(+) and CXCR6(-) CD4(+) T Cells in the Pathogenesis of Chronic Colitis.

PubMed

Mandai, Yasushi; Takahashi, Daisuke; Hase, Koji; Obata, Yuuki; Furusawa, Yukihiro; Ebisawa, Masashi; Nakagawa, Tomoo; Sato, Toru; Katsuno, Tatsuro; Saito, Yasushi; Shimaoka, Takeshi; Yokosuka, Osamu; Yokote, Kotaro; Ohno, Hiroshi

2013-01-01

CD4(+) T cells play a central role in the development of inflammatory bowel disease (IBD) via high-level production of effector cytokines such as IFN-γ and TNF-α. To better characterize the colitogenic CD4(+) T cells, we examined their expression of CXCR6, a chemokine receptor that is expressed by T cells upon activation and is upregulated in several inflammatory diseases. We found that 80% of colonic lamina propria CD4(+) T cells expressed CXCR6 in the CD45RB(high) T cell-transferred colitis model. CXCR6 expression was similarly upregulated in inflamed mucosa of patients with Crohn's disease. Although surface marker analysis demonstrated that both CXCR6(+) and CXCR6(-) CD4(+) T-cell subsets consist of the cells with effector and effector-memory cells, the more cells in the CXCR6(+) subset produced IFN-γ and TNF-α compared to CXCR6(-) subset, and only the CXCR6(+) subset produced IL-17A. Nevertheless, adoptive retransfer of lamina propria CXCR6(+) T cells into Rag1 (-/-) recipients failed to induce the disease due to limited expansion of the transferred cells. By contrast, retransfer of CXCR6(-) cells evoked colitis similar to that observed in CD4(+)CD45RB(high) T cell-transferred mice, and resulted in their conversion into CXCR6(+) cells. Collectively, these observations suggest that the CXCR6(+)CD4(+) T-cell subset consists of terminally differentiated effector cells that serve as the major source of effector cytokines in the inflamed tissue, whereas CXCR6(-)CD4(+) T-cell subset serves as a colitogenic memory compartment that retains the ability to proliferate and differentiate into CXCR6(+)CD4(+) T cells.

Distinct Roles for CXCR6+ and CXCR6− CD4+ T Cells in the Pathogenesis of Chronic Colitis

PubMed Central

Hase, Koji; Obata, Yuuki; Furusawa, Yukihiro; Ebisawa, Masashi; Nakagawa, Tomoo; Sato, Toru; Katsuno, Tatsuro; Saito, Yasushi; Shimaoka, Takeshi; Yokosuka, Osamu; Yokote, Kotaro; Ohno, Hiroshi

2013-01-01

CD4+ T cells play a central role in the development of inflammatory bowel disease (IBD) via high-level production of effector cytokines such as IFN-γ and TNF-α. To better characterize the colitogenic CD4+ T cells, we examined their expression of CXCR6, a chemokine receptor that is expressed by T cells upon activation and is upregulated in several inflammatory diseases. We found that 80% of colonic lamina propria CD4+ T cells expressed CXCR6 in the CD45RBhigh T cell-transferred colitis model. CXCR6 expression was similarly upregulated in inflamed mucosa of patients with Crohn’s disease. Although surface marker analysis demonstrated that both CXCR6+ and CXCR6− CD4+ T-cell subsets consist of the cells with effector and effector-memory cells, the more cells in the CXCR6+ subset produced IFN-γ and TNF-α compared to CXCR6− subset, and only the CXCR6+ subset produced IL-17A. Nevertheless, adoptive retransfer of lamina propria CXCR6+ T cells into Rag1 −/− recipients failed to induce the disease due to limited expansion of the transferred cells. By contrast, retransfer of CXCR6− cells evoked colitis similar to that observed in CD4+CD45RBhigh T cell-transferred mice, and resulted in their conversion into CXCR6+ cells. Collectively, these observations suggest that the CXCR6+CD4+ T-cell subset consists of terminally differentiated effector cells that serve as the major source of effector cytokines in the inflamed tissue, whereas CXCR6−CD4+ T-cell subset serves as a colitogenic memory compartment that retains the ability to proliferate and differentiate into CXCR6+CD4+ T cells. PMID:23840334

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Aping; Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan; Yang, Hang

Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfatemore » sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.« less

E-Selectin Ligands in the Human Mononuclear Phagocyte System: Implications for Infection, Inflammation, and Immunotherapy.

PubMed

Silva, Mariana; Videira, Paula A; Sackstein, Robert

2017-01-01

The mononuclear phagocyte system comprises a network of circulating monocytes and dendritic cells (DCs), and "histiocytes" (tissue-resident macrophages and DCs) that are derived in part from blood-borne monocytes and DCs. The capacity of circulating monocytes and DCs to function as the body's first-line defense against offending pathogens greatly depends on their ability to egress the bloodstream and infiltrate inflammatory sites. Extravasation involves a sequence of coordinated molecular events and is initiated by E-selectin-mediated deceleration of the circulating leukocytes onto microvascular endothelial cells of the target tissue. E-selectin is inducibly expressed by cytokines (tumor necrosis factor-α and IL-1β) on inflamed endothelium, and binds to sialofucosylated glycan determinants displayed on protein and lipid scaffolds of blood cells. Efficient extravasation of circulating monocytes and DCs to inflamed tissues is crucial in facilitating an effective immune response, but also fuels the immunopathology of several inflammatory disorders. Thus, insights into the structural and functional properties of the E-selectin ligands expressed by different monocyte and DC populations is key to understanding the biology of protective immunity and the pathobiology of several acute and chronic inflammatory diseases. This review will address the role of E-selectin in recruitment of human circulating monocytes and DCs to sites of tissue injury/inflammation, the structural biology of the E-selectin ligands expressed by these cells, and the molecular effectors that shape E-selectin ligand cell-specific display. In addition, therapeutic approaches targeting E-selectin receptor/ligand interactions, which can be used to boost host defense or, conversely, to dampen pathological inflammatory conditions, will also be discussed.

Laparoscopic excision of rectosigmoid endometriotic plaque and cul de sac obliteration in deeply infiltrating endometriosis: a case report.

PubMed

Fragulidis, G P; Oreopulu, F V; Vezakis, A; Sofoudis, C; Kalambokas, E; Koutoulidis, V; Vlahos, N F

2016-01-01

Endometriosis represents a main cause of infertility and pelvic pain affecting 3-43% among reproductive age women. Deep pelvic endometriosis is defined as subperitoneal infiltration of endometrial implants in the uterosacral ligaments, rectum, rectovaginal septum, vagina or bladder. The authors present a case of a 29-year-old patient who underwent laparoscopic excision of extensive endometriotic plaque in rectovaginal septum accompanied with deeply infiltrating endometriosis (DIE) and chronic pelvic pain (CPP).

Chronic vaginocervical prolapse with visceral incarceration in a dog.

PubMed

McNamara, P S; Harvey, H J; Dykes, N

1997-01-01

A bitch was presented for a vaginal prolapse of five years' duration. The prolapse was confirmed by physical examination and evaluated by contrast radiography. Herniation of the uterine body, urinary bladder, and distal aspect of the colon was identified within the prolapse. The prolapse was reduced surgically, and an ovariohysterectomy, cystopexy, and colopexy were performed. Compared to other vaginal disorders, vaginal prolapse is an uncommon condition in the bitch. The secondary involvement of abdominal viscera appears to be exceptionally rare.

Alleviating Autonomic Dysreflexia after Spinal Cord Injury

DTIC Science & Technology

2016-10-01

below  the  level  of  injury,  frequently  initiated  in  the  bladder  or  bowel.  It  is   a  key  contributor  to   cardiovascular   disease ,  the...affects blood flow and arterial pressure, and contributes to an increased risk of cardiovascular disease . Potential Treatment Strategies As...LG, Brown DJ, Ungar G, Moore P, McNeil JJ, Louis WJ (1992) Risk factors for cardiovascular disease in chronic spinal cord inju- ry patients

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance.more » BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.« less

The association between overactive bladder and fibromyalgia syndrome: a community survey.

PubMed

Chung, Jae Hoon; Kim, Shin Ah; Choi, Bo Youl; Lee, Hye-Soon; Lee, Seung Wook; Kim, Yong Tae; Lee, Tchun Yong; Moon, Hong Sang

2013-01-01

Fibromyalgia syndrome (FMS) is the most common disease causing chronic generalized pain, and FMS patients often complain of urinary symptoms such as frequency or urgency. This study focuses on the association of overactive bladder (OAB) and FMS in adults aged 40 and over. A survey of adults aged 40s and over was conducted in the Guri and Yangpyeong areas of South Korea. The response rate was 74.2% (940/1,266). After excluding subjects with incomplete questionnaires (n = 20), 920 were included in the final analysis. The association of FMS and OAB was analyzed by univariate and multivariate logistic regression analysis. Individuals with FMS had a significantly increased symptoms of OAB after adjustment for gender, age group, and area of residence (odds ratio (OR) 3.39, 95% confidence interval (CI) 1.82-6.31). The association between FMS and severity of OAB was statistical significant (P for trend <0.0001). OAB is associated with FMS. Moreover FMS increases with severity of OAB. Copyright © 2012 Wiley Periodicals, Inc.

Epidural steroid injections in the management of a patient with spinal stenosis and urinary urgency.

PubMed

Mitra, Raj; Huang, Lawrence; Payne, Christopher

2009-02-01

A 79-year-old woman with a history of chronic back pain and urinary urgency presented to a spine center for treatment and evaluation for axial low back pain. The patient described the back pain as severe with intermittent radiation into the right leg; her pain intensity was 7 out of 10 on a visual analog scale. She described her sense of urgency as severe, and could delay urination for 10 min or less. She described her bladder control as 6 out of 10 on the urgency perception score (with 0 being perfect control). Physical examination, including manual muscle testing, test for sensation to fine touch, reflex assessment and assessment of gait pattern, and MRI of the lumbar spine. Overactive bladder associated with severe central-canal stenosis at L4-5, in the setting of anterolisthesis. Fluoroscopically guided caudal epidural steroid injection; 60 mg of triamcinolone, 3 ml of 1% lidocaine hydrochloride and 3 ml of normal saline, injected in increments.

Acute urinary retention due to HSV-1: a case report.

PubMed

Mancino, P; Dalessandro, M; Falasca, K; Ucciferri, C; Pizzigallo, E; Vecchiet, J

2009-03-01

Complications in urinary tract nervous routes due to herpes viruses as VZV and HSV-2 are well known. Acute urinary retention and chronic neuropathic pain are not rare when sacral dermatomes are involved by these viruses. However, an analogous condition has not yet been clearly ascribed to HSV-1 infection. We present a 32-year-old immunocompetent patient with fever, lumbar pain and acute urinary retention who had never had herpetic clinical manifestations. Urodynamic studies diagnosed a neurologic bladder with an absent filling sensation. Cystoscopic assessment revealed the presence of reddened and isolated small mucosal areas in the bladder walls. The search for herpes viruses in plasma and CSF by PCR assay were positive for HSV-1. After treatment with antiviral therapy the disease resolved. Intermittent catheterization was necessary and voiding dysfunction resolved after three weeks by its appearance. Neurological damage to the central nervous system (CNS) and/or PNS due to HSV-1 seems to be the most likely reason. The course of disease was benign and self-remitting.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications.

PubMed

Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

2016-01-01

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

Granulomatous Tracheo-Bronchitis Associated With Crohn's Disease

PubMed Central

Xia, Kai; Wolf, Jacqueline; Friedman, Sonia

2004-01-01

We report a rare case of diffuse tracheo-bronchitis as a complication of Crohn's disease. A young man with a long-standing history of Crohn's enterocolitis initially presented with epigastric pain and melena. Upper endoscopy revealed erythematous, edematous, and friable mucosa with erosions, particularly in the pyloric channel, causing gastric outlet obstruction, and a nonbleeding ulcer in the corpus of stomach. Biopsy of these lesions showed chronic gastritis and a noncaseating epithelioid granuloma, consistent with active Crohn's disease. The patient was treated with a course of corticosteroids and the gastric symptoms resolved. A few months later, he developed fever, cough, hemoptysis, and rash. Bronchoscopy demonstrated a markedly thickened and very inflamed trachea with extensive friable, whitish lesions and ulcerations. Histology showed severe noncaseating granulomatous inflammation. The patient improved with a 6-week oral, followed by an additional 4-week inhaled, corticosteroid treatment. Since then, he has been doing well without relapse of pulmonary symptoms for 2 years. PMID:15208530

Inflaming the Brain: CRPS a model disease to understand Neuroimmune interactions in Chronic Pain

PubMed Central

Linnman, C; Becerra, L; Borsook, D

2012-01-01

We review current concepts in CRPS from a neuroimaging perspective and point out topics and potential mechanisms that are suitable to be investigated in the next step towards understanding the pathophysiology of CRPS. We have outlined functional aspects of the syndrome, from initiating lesion via inflammatory mechanisms to CNS change and associated sickness behavior, with current evidence for up-regulation of immunological factors in CRPS, neuroimaging of systemic inflammation, and neuroimaging findings in CRPS. The initiation, maintenances and CNS targets implicated in CRPS and in the neuro-inflammatory reflex are discussed in terms of CRPS symptoms and recent preclinical studies. Potential avenues for investigating CRPS with PET and fMRI are described, along with roles of inflammation, treatment and behavior in CRPS. It is our hope that this outline will provoke discussion and promote further empirical studies on the interactions between central and peripheral inflammatory pathways manifest in CRPS. PMID:23188523

Inflaming the brain: CRPS a model disease to understand neuroimmune interactions in chronic pain.

PubMed

Linnman, C; Becerra, L; Borsook, D

2013-06-01

We review current concepts in CRPS from a neuroimaging perspective and point out topics and potential mechanisms that are suitable to be investigated in the next step towards understanding the pathophysiology of CRPS. We have outlined functional aspects of the syndrome, from initiating lesion via inflammatory mechanisms to CNS change and associated sickness behavior, with current evidence for up-regulation of immunological factors in CRPS, neuroimaging of systemic inflammation, and neuroimaging findings in CRPS. The initiation, maintenances and CNS targets implicated in CRPS and in the neuro-inflammatory reflex are discussed in terms of CRPS symptoms and recent preclinical studies. Potential avenues for investigating CRPS with PET and fMRI are described, along with roles of inflammation, treatment and behavior in CRPS. It is our hope that this outline will provoke discussion and promote further empirical studies on the interactions between central and peripheral inflammatory pathways manifest in CRPS.

Stressed and inflamed, can GSK3 be blamed?

PubMed Central

Jope, Richard S.; Cheng, Yuyan; Lowell, Jeffrey; Worthen, Ryan J.; Sitbon, Yoel H.; Beurel, Eleonore

2016-01-01

Psychological stress has a pervasive influence on our lives. In many cases adapting to stress strengthens organisms, but chronic or severe stress is usually harmful. One surprising outcome of psychological stress is activation of an inflammatory response, resembling inflammation caused by infection or trauma. Excessive psychological stress and the consequential inflammation in the brain can increase susceptibility to psychiatric diseases, such as depression, and impair learning and memory, including in some patients with cognitive deficits. An emerging target to control detrimental outcomes of stress and inflammation is glycogen synthase kinase-3 (GSK3). GSK3 promotes inflammation, partly by regulating key transcription factors in the inflammation signaling pathway, and GSK3 can impair learning by promoting inflammation and by inhibiting long term potentiation (LTP). Drugs inhibiting GSK3 may prove beneficial for controlling mood and cognitive impairments caused by excessive stress and the associated neuroinflammation. PMID:27876551

Bilateral nevus comedonicus of the eyelids.

PubMed

Mendoza, Pia R; Jakobiec, Frederick A; Townsend, Daniel J

2013-01-01

Nevus comedonicus is a rare developmental abnormality of the infundibulum of the hair follicle. It is usually unilateral and commonly presents at birth or during childhood. A rare case of late-onset, bilateral nevus comedonicus of the eyelids is reported. A 79-year-old man presented with asymptomatic but disfiguring eyelid lesions noted several months earlier. On physical examination, multiple papules resembling comedones were present bilaterally in the eyelids, canthi, temple regions, and bridge of the nose. Microscopically, there were deep invaginations of the follicular canals forming focal tunnels or pseudosinus tracts with poral openings to the surface. These variably cystic structures were lined by keratinizing and nonkeratinizing squamous epithelium, contained concentric lamellae of keratin in their lumens, and some were acutely or chronically inflamed. The diagnosis of a nevus comedonicus was made. The clinical and histopathologic characteristics, pathogenesis, differential diagnosis, and management of nevus comedonicus are briefly discussed.

Obesity and Cardiometabolic Defects in Heart Failure Pathology.

PubMed

Halade, Ganesh V; Kain, Vasundhara

2017-09-12

Obesity is a major global epidemic that sets the stage for diverse multiple pathologies, including cardiovascular disease. The obesity-related low-grade chronic inflamed milieu is more pronounced in aging and responsive to cardiac dysfunction in heart failure pathology. Metabolic dysregulation of obesity integrates with immune reservoir in spleen and kidney network. Therefore, an integrative systems biology approach is necessary to delay progressive cardiac alternations. The purpose of this comprehensive review is to largely discuss the impact of obesity on the cardiovascular pathobiology in the context of problems and challenges, with major emphasis on the diversified models, and to study cardiac remodeling in obesity. The information in this article is immensely helpful in teaching advanced undergraduate, graduate, and medical students about the advancement and impact of obesity on cardiovascular health. © 2017 American Physiological Society. Compr Physiol 7:1463-1477, 2017. Copyright © 2017 John Wiley & Sons, Inc.

Acute Calcific Tendinitis of the Index Finger in a Child.

PubMed

Walocko, Frances M; Sando, Ian C; Haase, Steven C; Kozlow, Jeffrey H

2017-09-01

Calcific tendinitis is characterized by calcium hydroxyapatite crystal deposition within tendons and is a common cause of musculoskeletal pain in adults. Its clinical manifestations may be acute, chronic, or asymptomatic. Acute calcific tendinitis is self-resolving condition that is rarely reported in the pediatric population and may be overlooked for more common processes, leading to unnecessary treatment. A chart reivew was performed of a single case of acute calcific tendonitis of the index finger in a child. We describe a case of calcific tendinitis of the index finger in a 9-year-old boy who was referred to us for a second opinion after surgical exploration of an acutely inflamed digit was recommended based on his initial presentation. The calcifications and symptoms resolved over time without operative management. Although rare in children, acute calcific tendinitis can present similar to an infection. However, appropriate managment is non-operative as the symptoms and radiographic findings resolve over time.

Cryotherapy and ankle motion in chronic venous disorders

PubMed Central

Kelechi, Teresa J.; Mueller, Martina; Zapka, Jane G.; King, Dana E.

2013-01-01

This study compared ankle range of motion (AROM) including dorsiflexion, plantar flexion, inversion and eversion, and venous refill time (VRT) in leg skin inflamed by venous disorders, before and after a new cryotherapy ulcer prevention treatment. Fifty-seven-individuals participated in the randomized clinical trial; 28 in the experimental group and 29 received usual care only. Results revealed no statistically significant differences between the experimental and usual care groups although AROM measures in the experimental group showed a consistent, non-clinically relevant decrease compared to the usual care group except for dorsiflexion. Within treatment group comparisons of VRT results showed a statistically significant increase in both dorsiflexion and plantar flexion for patients with severe VRT in the experimental group (6.9 ± 6.8; p = 0.002 and 5.8 ± 12.6; p = 0.02, respectively). Cryotherapy did not further restrict already compromised AROM, and in some cases, there were minor improvements. PMID:23516043

Down-regulation of liver RNA breakdown by turpentine administration in the starved rat: autophagy and relevant factors.

PubMed

Saadane, A; Delautier, D; Lestriez, V; Feldmann, G; Lardeux, B; Bleiberg-Daniel, F

1999-04-01

To determine whether the inhibition of RNA breakdown observed in ad libitum fed rats 24 h after turpentine administration still occurs in inflamed rats fasted for 24 h and to examine the mechanism and factors involved. RNA breakdown was measured during cyclic in situ perfusion of livers by the accumulation of [14C] cytidine after in vivo RNA labelling. Autophagic activity was determined by the morphometric analysis of lysosomal structures. The decrease in RNA breakdown (53%) observed in the inflamed rats was accompanied by a 38% drop in the fractional cytoplasmic volume of initial and digestive autophagic vacuoles. Among amino acids, only the portal levels of glutamate were significantly enhanced by 83%. In vivo suppression of glucocorticoid activity using RU 38486 in inflamed rats did not affect the inhibition of RNA breakdown. The results show that turpentine-induced inflammation in fasted rats inhibits RNA degradation as well as autophagy and that glucocorticoids do not seem to be involved.

CXCL16/CXCR6-mediated adhesion of human peripheral blood mononuclear cells to inflamed endothelium.

PubMed

Linke, Bona; Meyer Dos Santos, Sascha; Picard-Willems, Bettina; Keese, Michael; Harder, Sebastian; Geisslinger, Gerd; Scholich, Klaus

2017-06-21

The endothelial chemokine CXC motif ligand 16 (CXCL16) is involved in the recruitment and firm adhesion of CXCR6 + cells to the atherosclerosis-prone aortic vessel wall. Recently we showed that CXCR6 + platelets from flowing blood attach to CXCL16 expressed by activated endothelium on the luminal side of the blood vessel. With this study we supplement these findings with the observation that platelets bound to the inflamed endothelium are presenting CXCR6 to CXCL16-positive peripheral blood mononuclear cells (PBMCs) and, thus, are mediating an increased adhesion of PBMCs to the arterial wall. Furthermore we identified endothelial CXCL16 as an important adhesion molecule promoting the firm adhesion of CXCR6-positive PBMCs to inflamed endothelium. Our results demonstrate that endothelial CXCL16 as well as platelet CXCR6 are acting as potent PBMC-adhesion ligands, inducing PBMC-adhesion to the atherosclerosis-prone vessel wall and thus promoting the progression of atherosclerosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo anti-inflammatory activity of aqueous extract of Teucrium polium against carrageenan-induced inflammation in experimental models.

PubMed

Rahmouni, Fatma; Hamdaoui, Latifa; Rebai, Tarek

2017-12-01

The aim of this study was to evaluate the anti-inflammatory activity of Teucrium polium (TP). Rats were divided into four groups: group 1 controls received standard diet; group 2 inflamed by carrageenan (Carr) (1% Carr); group 3 as reference inflamed with Carr and treated with Indometacine (Ind) (150 mg/kg bw) and group 4 inflamed with Carr and pre0treated with TP (5 g/L). Oedema volume was measured 1 h to 5 h after injection. Administration of TP or Ind decreased the levels of hematology parameters relative to Carr and reduced the volume of rats induced by Carr. TP reduced levels of CRP, fibrinogen compared to treated, a decrease in oxidative stress (LP) and AOPP with an increase in the levels of SOD, CAT, GPx and Vit C in skin and erythrocytes. Carr increased the levels of lipid peroxidation and decreased levels of antioxidant enzymatic and Vit C. Our results were confirmed by histological sections of skin.

[Nocturnal enuresis in children].

PubMed

Hjälmås, K

1998-01-01

After allergic disorders, nocturnal enuresis is the most common chronic childhood condition. Recent research has yielded abundant new knowledge about the condition, especially about its aetiology and pathophysiology, and the psychological consequences. A hereditary background has been substantiated by the identification in genetic linkage studies of areas in chromosomes 12 and 13 that are manifestly associated with bedwetting, though genotype expression in the phenotype appears to be complex and heterogeneous. Pathophysiologically, findings in current intensive research suggest three interactive factors to be involved: (i) relative nocturnal polyuria, due to insufficient antidiuretic hormone release during sleep in pre-teenagers, and due to renal tubular dysfunction in adolescents and adults; (ii) reduced nocturnal bladder capacity, especially in the 33 per cent of cases which do not respond to desmopressin treatment; and (iii) the patient's inability to waken in response to signals from a full bladder. Recent findings have also confirmed previous reports that with very few exceptions bedwetting is not caused by psychological factors. On the contrary, the condition causes psychological problems manifested in reduced self-esteem, shame and guilt, though self-esteem is restored by successful treatment. Active treatment should be started as soon as the child is ready to receive it, the main options being an enuresis alarm, desmopressin, or a combination of the two. If reduced bladder capacity is suspected, treatment with a detrusor relaxant should be included.

c-KIT positive schistosomal urinary bladder carcinoma are frequent but lack KIT gene mutations.

PubMed

Shams, Tahany M; Metawea, Mokhtar; Salim, Elsayed I

2013-01-01

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

Xanthogranulomatous cholecystitis: differentiation from associated gall bladder carcinoma.

PubMed

Rao, R V Raghavendra; Kumar, Ashok; Sikora, Sadiq S; Saxena, Rajan; Kapoor, Vinay K

2005-01-01

Xanthogranulomatous cholecystitis (XGC) is a destructive form of chronic cholecystitis. In some patients it coexists with gall bladder carcinoma (GBC) and is often difficult to differentiate between the two. Present study was performed with an aim to identify differentiating features of XGC and those of XGC with associated Gall bladder carcinoma (XGC ass. GBC). A retrospective analysis of prospectively maintained data of 4800 cholecystectomies performed from January 1988 to December 2003 was carried out. On histopathology 453 cholecystectomy specimens revealed XGC. These patients were divided into two groups, those with associated GBC (n=26) and those without GBC (n=427). Clinical, radiological and operative findings were compared in these two groups. P value of < 0.05 was considered statistically significant. The incidence of associated GBC in present series was 6%. XGC patients with associated GBC, at presentation were older than those with XGC alone and there was male preponderance. XGC patients with associated GBC were more likely to present with anorexia, weight loss, palpable lump and jaundice. Gall stones were present in majority of patients in both the groups. GB wall thickening, GB mass, enlarged abdominal lymph nodes may be found on imaging in both the groups but more so in patients with associated GBC. Both preoperative FNAC and peroperative FNAC/imprint cytology failed to reveal the associated GBC with XGC in some patients.

[Reconstructive treatment of female urethral estenosis secondary to erosion by suburethral tape].

PubMed

Angulo, J C; Mateo, E; Lista, F; Andrés, G

2011-04-01

Female urethral stricture secondary to erosión by suburethral sling is an unfrequent problem of difficult solution. Ventral vaginal rotation flaps or buccal mucosa dorsal grafts are not useful because this type of stricture is very proximal (close to the bladder neck) and the vagina is thinned. We present our experience to manage this problem using excision of disease urethral tract, associated to bladder mucosa flap and vaginal sling using transverse vaginal flap to repair the weakened vaginal wall. Three females with urethral stricture secondary to urethral erosion of their sling were treated with a technique of combined urethroplasty with bladder flap and vaginal reinforcement with pediculated vaginal flap transferred in a mini-sling fashion. Two of the patients suffered chronic urinary retention and preoperative placement of urethral catheter was not possible. The patients were evaluated 12, 36 and 55 months after surgery, respectively. Surgery was performed without complications. Results were satisfactory in all the patients, reaching good micturition postoperative caliber and being without incontinence at follow-up. Patients with suburethral erosion by a synthetic sling and secondary severe urethral stricture need total extirpation of the mesh and complete reconstruction of the urethro-vaginal septum. Tension-free urethral suture and use of vaginal sling with the technique here described are two useful technical tips for this problem. Copyright © 2011 AEU. Published by Elsevier Espana. All rights reserved.

Ultrasound and Biomarker Tests in Predicting Cancer Aggressiveness in Tissue Samples of Patients With Bladder Cancer

ClinicalTrials.gov

2017-06-23

Bladder Papillary Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma; Stage II Bladder Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma

Immunohistochemical study of intestinal eosinophils in inflammatory bowel disease.

PubMed

Carvalho, Ana Teresa Pugas; Elia, Celeste Carvalho Siqueira; de Souza, Heitor Siffert Pereira; Elias, Paulo Roberto Pinheiro; Pontes, Eduardo Lopes; Lukashok, Hannah Pitanga; de Freitas, Fernanda Cristina Dias; Lapa e Silva, José Roberto

2003-02-01

Eosinophil accumulation and activation are characteristic features of inflammation in allergic diseases and in host defense against parasites. To investigate the involvement of eosinophils in inflamed and noninflamed mucosa of patients with inflammatory bowel disease (IBD). Specimens of inflamed colonic mucosa from 15 patients with ulcerative colitis (UC) and inflamed and noninflamed colonic mucosa from 15 patients with Crohn's disease (CD) were submitted to histologic and immunohistochemical studies. Twelve patients with irritable bowel syndrome were studied as controls. Sirius red was used to label eosinophils in tissue. EG1, EG2, and anti-hIL-5 were used as primary antibodies in an indirect alkaline phosphatase-labeled immunostaining protocol. Both positive and negative lamina propria cells were assessed by a quantitative grading system and the results expressed as cell numbers per mm. Increased proportions of eosinophils stained with Sirius red, EG1, EG2, and anti-hIL-5+ cells were found in the colon of patients with UC and in inflamed and noninflamed colon of CD patients as compared with controls. Crohn's disease patients showed increased proportions of EG1+ and EG2+ cells as compared with those with UC. Increased proportions of IL-5+ cells were detected in UC patients as compared with those with CD. Quantitative eosinophil alterations and IL-5+ cells may indicate enhanced cellular activation with degranulation, which is implicated in the pathogenesis of IBD. Increase in IL-5+ cells may reflect a predominant local Th2 response in UC as compared with CD.

Anterior vaginal wall tenderness (AVWT) as a physical symptom in chronic pelvic pain.

PubMed

Paulson, John D; Paulson, Joseph N

2011-01-01

Chronic pelvic pain is often difficult to diagnose and treat properly. Physicians called on to treat this problem may not be able to give a specific diagnosis. The aim of this study was to see whether the physical presence of anterior vaginal wall tenderness could help narrow down and elucidate diagnoses in a practice focusing on diagnosis and treatment of chronic pelvic pain. The study cohort comprised 284 patients with chronic pelvic pain limited to gynecologic and lower urinary problems. Histories, physical examinations, and endoscopic procedures were performed on each patient. An analysis of this information was conducted. Of the chronic pelvic pain patients, 78% had endometriosis, 81% had interstitial cystitis, and 61% had both concurrently. The sensitivity of anterior vaginal wall tenderness (AVWT) in patients with interstitial cystitis was 95%, and in those with only endometriosis and no interstitial cystitis, the sensitivity was 17%. The positive predictive value for interstitial cystitis was 85%, and for endometriosis it was 67%. Examination of the anterior vaginal wall with an empty bladder at the initial examination can lead one to suspect interstitial cystitis and possibly either concomitant or singular endometriosis and allow the physician to approach the workup accordingly.

The role of unusual pathogens in prostatitis syndrome.

PubMed

Skerk, Visnja; Krhen, Ivan; Schonwald, Slavko; Cajic, Vjeran; Markovinovic, Leo; Roglic, Srdan; Zekan, Sime; Andracevic, Arjana Tambic; Kruzic, Vladimira

2004-09-01

A total of 1442 patients with symptoms of chronic prostatitis were examined over a 4-year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia. An infectious aetiology was determined in 1070 (74.2%) patients. In 561 of 1070 (52.4%) patients the inflammatory finding (>10 WBC/hpf) was found in expressed prostatic secretions (EPS) or voided bladder urine (VB(3)). Normal, <10 WBCs/hpf was found in 362 of 536 (67.5%) patients with symptoms of chronic prostatitis in whom Chlamydia trachomatis was detected in EPS or VB(3), in 51 of 151 (33.8%) patients with isolated Trichomonas vaginalis and in 40 of 72 (55.6%) patients with isolated Ureaplasma urealyticum. Escherichia coli was the causative pathogen in 95, Enterococcus in 68, Proteus mirabilis in 37, Klebsiella pneumoniae in 16, Streptococcus agalactiae in 19, and Pseudomonas aeruginosa in 3 patients with chronic prostatitis. Other patients had a mixed infection. In patients with chronic bacterial prostatitis (CBP) caused by E. coli, P. mirabilis, K. pneumoniae, E. or S. agalactiae, an inflammatory finding was regularly found in EPS or VB(3).

Bilateral chronic sacral neuromodulation for treatment of lower urinary tract dysfunction.

PubMed

Hohenfellner, M; Schultz-Lampel, D; Dahms, S; Matzel, K; Thüroff, J W

1998-09-01

Chronic sacral neuromodulation aims at functional restoration of selected forms of nonneurogenic and neurogenic bladder dysfunction. The original technique, as described by Tanagho and Schmidt, provides unilateral sacral nerve stimulation via an implanted stimulator powering an electrode inserted into a sacral foramen. Its drawback was that the implant failed unpredictably in some patients despite previous successful percutaneous test stimulation. Therefore, we modified the stimulation technique to improve the efficacy of chronic sacral neuromodulation. Guarded bipolar electrodes powered by an implantable neurostimulator were attached bilaterally directly to the S3 nerves through a sacral laminectomy in 9 women and 2 men (mean age 43.4 years). Of the patients 5 had urinary incontinence due to detrusor hyperactivity and 6 had urinary retention from detrusor hypocontractility. Mean followup with repeated urodynamics was 13 months (range 9 to 28). Four significant complications were encountered in 4 patients. In 10 patients the urological sequelae of the neurological disorder were alleviated significantly (50% or more), including 5 who experienced complete relief of symptoms. The efficacy of chronic sacral neuromodulation can be improved by bilateral attachment of electrodes directly to the sacral nerves.

Effects of CYP-Induced Cystitis on Growth Factors and Associated Receptor Expression in Micturition Pathways in Mice with Chronic Overexpression of NGF in Urothelium.

PubMed

Girard, Beatrice M; Malley, Susan; May, Victor; Vizzard, Margaret A

2016-08-01

We have determined if cyclophosphamide (CYP)-induced cystitis produces additional changes in growth factor/receptors expression in the urinary bladder (urothelium, detrusor) and lumbosacral (L6-S1) dorsal root ganglia (DRG) in a transgenic mouse model with chronic urothelial overexpression of NGF (NGF-OE). Functionally, NGF-OE mice treated with CYP exhibit significant increases in voiding frequency above that observed in control NGF-OE mice (no CYP). Quantitative PCR was used to determine NGF, BDNF, VEGF, and receptors (TrkA, TrkB, p75(NTR)) transcripts expression in tissues from NGF-OE and wild-type (WT) mice with CYP-induced cystitis of varying duration (4 h, 48 h, 8 days). In urothelium of control NGF-OE mice, NGF mRNA was significantly (p ≤ 0.001) increased. Urothelial expression of NGF mRNA in NGF-OE mice treated with CYP (4 h, 48 h, 8 days) was not further increased but maintained with all durations of CYP treatment evaluated. In contrast, CYP-induced cystitis (4 h, 48 h, 8 days) in NGF-OE mice demonstrated significant (p ≤ 0.05) regulation in BDNF, VEGF, TrkA, TrkB, and P75(NTR) mRNA in urothelium and detrusor smooth muscle. Similarly, CYP-induced cystitis (4 h, 48 h, 8 days) in NGF-OE mice resulted in significant (p ≤ 0.05), differential changes in transcript expression for NGF, BDNF, and receptors (TrkA, TrkB, p75(NTR)) in S1 DRG that was dependent on the duration-of CYP-induced cystitis. In general, NGF, BDNF, TrkA, and TrkB protein content in the urinary bladder increased in WT and NGF-OE mice with CYP-induced cystitis (4 h). Changes in NGF, TrkA and TrkB expression in the urinary bladder were significantly (p ≤ 0.05) greater in NGF-OE mice with CYP-induced cystitis (4 h) compared to WT mice with cystitis (4 h). However, the magnitude of change between WT and NGF-OE mice was only significantly (p ≤ 0.05) different for TrkB expression in urinary bladder of NGF-OE mice treated with CYP. These studies are consistent with target-derived NGF and other inflammatory mediators affecting neurochemical plasticity with potential contributions to reflex function of micturition pathways.

Deformation of the notochord by pressure from the swim bladder may cause malformation of the vertebral column in cultured Atlantic cod Gadus morhua larvae: a case study.

PubMed

Grotmol, Sindre; Kryvi, Harald; Totland, Geir K

2005-06-01

This study describes a malformation that frequently occurs in Atlantic cod Gadus morhua in intensive culture systems. The malformation is characterised by a slight upward tilt of the head and an indented dorsal body contour at the transition between the head and the trunk, and is first evident to the fish farmer when the cod reach the juvenile stage. These abnormalities are associated with malformations of the neurocranium, the cranial region of the vertebral column and the cranial part of the epaxial lateral muscles. The pathogenesis involves deformation of the notochord, which can be observed in larvae about 7 d post-hatch (dph) and onwards. The deformation consists of an increase in dorsal curvature of the notochord in the region above the swim bladder. In the same region, the notochord has an abnormal cross-sectional outline, characterised by a groove-shaped, longitudinal impression along the ventral surface of the sheath. In most cases, the swim bladder fills the impression, and in severely affected larvae it forms a hernia-like lesion in the notochord. The deformation of the notochord seems to be conveyed to the vertebral body anlagen (chordacentra), which in teleosts are formed by mineralisation within the notochordal sheath. The vertebral bodies adopt an abnormal wedge shape, with a ventral concavity, and the neural arches are most often S-shaped. A continuous range of degrees of the malformation can be observed. All these pathomorphological characteristics are compatible with the notion that the notochord has been subjected to an upward mechanical force, probably generated by a persistent increase in pressure between the swim bladder and the notochord during the period of development of the vertebral anlagen. Our results thus indicate that the critical time window with regard to development of the malformation is from 18 to 36 dph, when the initial formation of the vertebrae takes place. Chronic overinflation of the swim bladder or pathological dilatation of the digestive tract may cause the lesions, and aetiology may be related to factors that influence the function of these organs.

An effective approach to reduce inflammation and stenosis in carotid artery: polypyrrole nanoparticle-based photothermal therapy

NASA Astrophysics Data System (ADS)

Peng, Zhiyou; Qin, Jinbao; Li, Bo; Ye, Kaichuang; Zhang, Yuxin; Yang, Xinrui; Yuan, Fukang; Huang, Lijia; Hu, Junqing; Lu, Xinwu

2015-04-01

Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE-/- mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE-/- mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management. Electronic supplementary information (ESI) available: Figures. See DOI: 10.1039/c5nr00542f

Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis.

PubMed

Benson, Jessica R; Xu, Jiameng; Moynes, Derek M; Lapointe, Tamia K; Altier, Christophe; Vanner, Stephen J; Lomax, Alan E

2014-05-01

Sensitization of dorsal root ganglia (DRG) neurons is an important mechanism underlying the expression of chronic abdominal pain caused by intestinal inflammation. Most studies have focused on changes in the peripheral terminals of DRG neurons in the inflamed intestine but recent evidence suggests that the sprouting of central nerve terminals in the dorsal horn is also important. Therefore, we examine the time course and reversibility of changes in the distribution of immunoreactivity for substance P (SP), a marker of the central terminals of DRG neurons, in the spinal cord during and following dextran sulphate sodium (DSS)-induced colitis in mice. Acute and chronic treatment with DSS significantly increased SP immunoreactivity in thoracic and lumbosacral spinal cord segments. This increase developed over several weeks and was evident in both the superficial laminae of the dorsal horn and in lamina X. These increases persisted for 5 weeks following cessation of both the acute and chronic models. The increase in SP immunoreactivity was not observed in segments of the cervical spinal cord, which were not innervated by the axons of colonic afferent neurons. DRG neurons dissociated following acute DSS-colitis exhibited increased neurite sprouting compared with neurons dissociated from control mice. These data suggest significant colitis-induced enhancements in neuropeptide expression in DRG neuron central terminals. Such neurotransmitter plasticity persists beyond the period of active inflammation and might contribute to a sustained increase in nociceptive signaling following the resolution of inflammation.

Alterations to the middle cerebral artery of the hypertensive-arthritic rat model potentiates intracerebral hemorrhage

PubMed Central

Chokshi, Killol; Kane, Brittany; Chang, Hilary; Naiel, Safaa; Dickhout, Jeffrey G.

2016-01-01

Aims We have recently created an age-dependent hypertensive-mono-arthritic animal model from the stroke-resistant spontaneously hypertensive rat to model populations with autoimmune disease who are hypertensive and are prone to stroke. The model exhibits signs of hemorrhagic stroke (HS) subsequent to chronic inflammation and hypertension. HS is also associated with the inability of middle cerebral arteries to undergo pressure dependent constriction (PDC). We investigated alterations in the cerebrovasculature of our hypertensive mono-arthritic animals that develop stroke. Main Methods Animals were fed either a high salt diet (HSD) (4% NaCl) or Purina chow (0.58% NaCl) from weaning. Complete Freund’s Adjuvant (CFA) was injected into the left hind paw at 21–28 weeks; controls received saline and histological and functional studies were performed. Results Brain damage was more prominent with the high salt, with inflammation exacerbating the damage. High salt alone significantly decreased middle cerebral artery’s (MCA’s) ability to undergo PDC. Inflammation significantly decreased the ability of cerebrovasculature to respond to pressure step in the regular salt diet. The responses to vasoactive peptides were also significantly attenuated in both inflamed groups regardless of diet. Conclusion Induction of chronic systemic inflammation increases brain damage, and affect the MCA’s vasogenic function, decreasing its ability to respond to intraluminal pressure. HSD further exacerbates organ damage associated with chronic inflammation, further compromising cerebrovascular function, and likely increasing the incidence of intracerebral hemorrhage and injury. PMID:27833798

Optoacoustic imaging of tissue blanching during photodynamic therapy of esophageal cancer

NASA Astrophysics Data System (ADS)

Jacques, Steven L.; Viator, John A.; Paltauf, Guenther

2000-05-01

Esophageal cancer patients often present a highly inflamed esophagus at the time of treatment by photodynamic therapy. Immediately after treatment, the inflamed vessels have been shut down and the esophagus presents a white surface. Optoacoustic imaging via an optical fiber device can provide a depth profile of the blanching of inflammation. Such a profile may be an indicator of the depth of treatment achieved by the PDT. Our progress toward developing this diagnostic for use in our clinical PDT treatments of esophageal cancer patients is presented.

Safety and Tolerability of TAR-200 and Nivolumab in Subjects With Muscle-Invasive Bladder Cancer

ClinicalTrials.gov

2018-05-04

Bladder Cancer TNM Staging Primary Tumor (T) T2; Bladder Cancer TNM Staging Primary Tumor (T) T2A; Bladder Cancer TNM Staging Primary Tumor (T) T2B; Bladder Cancer TNM Staging Primary Tumor (T) T3; Bladder Cancer TNM Staging Primary Tumor (T) T3A; Bladder Cancer TNM Staging Primary Tumor (T) T3B; Bladder Cancer TNM Staging Regional Lymph Node (N) N0; Bladder Cancer TNM Staging Regional Lymph Node (N) N1; Bladder Cancer TNM Staging Distant Metastasis (M) M0

Children with chronic continence problems: the challenges for families.

PubMed

Erickson, David V; Ray, Lynne D

2004-01-01

For families who are raising children with myelomeningocele, bowel and bladder incontinence presents unique challenges for everyday life. The Parenting and Childhood Chronicity model is used to describe the work of raising a child with a chronic condition in 6 areas, including medical care, adapted parenting, dealing with the systems, caring for siblings, maintaining relationships, and personal coping (keeping yourself going). This article provides an overview of the physiologic and developmental challenges inherent in this neural tube defect and illustrates the work that is involved in the child's care and the challenges of maintaining a balance in family life. Clinical implications are discussed, including the setting of appropriate expectations, providing parents with accurate information, ensuring that a focus on continence is not at the expense of other important aspects of the child's functioning, and supporting parents in their interaction with the school system. The medical team, consisting of nursing, urology, nephrology, and psychology working together, can be a strong support for families.

Association between chronic kidney disease and urinary calculus by stone location: a population-based study.

PubMed

Keller, Joseph J; Chen, Yi-Kuang; Lin, Herng-Ching

2012-12-01

Study Type--Disease prevalence study (cohort design) Level of Evidence 2a. What's known on the subject? and What does the study add? Several studies have estimated the potential association of urinary calculus (UC) with chronic kidney disease (CKD). However, previous literature focusing on this issue tended to evaluate the impact of kidney stones alone on incident CKD, with no studies having been conducted investigating the association between CKD and stone formation in other portions of the urological system. We found that patients with CKD were consistently more likely than comparison subjects to have been previously diagnosed with kidney calculus (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.95-2.27), ureter calculus (OR 1.68, 95% CI 1.51-1.85), bladder calculus (OR 1.49, 95% CI 1.13-1.98), and unspecified calculus (OR 1.89, 95% CI 1.74-2.06). We concluded that there was an association between CKD and UC regardless of stone location. • To explore the association of chronic kidney disease (CKD) with prior kidney calculus, ureter calculus, and bladder calculus using a population-based dataset in Taiwan. Several studies have estimated the potential association of urinary calculus (UC) with CKD. However, previous literature focusing on this issue tended to evaluate the impact of kidney stones alone on incident CKD, with no studies having been conducted investigating the association between CKD and stone formation in other portions of the urological system. • We identified 21,474 patients who received their first-time diagnosis of CKD between 2001 and 2009. • The 21,474 controls were frequency-matched with cases for sex, age group, and index year. • We used conditional logistic regression analyses to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) as an estimation of association between CKD and having been previously diagnosed with UC. • The results show that compared with controls, the OR of prior UC for cases was 1.91 (95% CI 1.81-2.01, P < 0.001) after adjusting for potential confounders. • Furthermore, cases were consistently more likely than controls to have been previously diagnosed with kidney calculus (OR 2.10, 95% CI 1.95-2.27), ureter calculus (OR 1.68, 95% CI 1.51-1.85), bladder calculus (OR 1.49, 95% CI 1.13-1.98), and unspecified UC (OR 1.89, 95% CI 1.74-2.06). • We concluded that there was an association between ckd and UC regardless of stone location. © 2012 BJU INTERNATIONAL.

Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae.

PubMed

Di Paolo, Carolina; Groh, Ksenia J; Zennegg, Markus; Vermeirssen, Etiënne L M; Murk, Albertinka J; Eggen, Rik I L; Hollert, Henner; Werner, Inge; Schirmer, Kristin

2015-12-01

The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. Copyright © 2015 Elsevier B.V. All rights reserved.

The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model.

PubMed

Colinot, Darrelle L; Garbuz, Tamila; Bosland, Maarten C; Wang, Liang; Rice, Susan E; Sullivan, William J; Arrizabalaga, Gustavo; Jerde, Travis J

2017-07-01

Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model. Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates. This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia. © 2017 Wiley Periodicals, Inc.

Cytokine regulation on the synthesis of nitric oxide in vivo by chronically infected human polymorphonuclear leucocytes.

PubMed Central

Takeichi, O; Saito, I; Okamoto, Y; Tsurumachi, T; Saito, T

1998-01-01

To determine if nitric oxide (NO) is produced by chronically infected human polymorphonuclear leucocytes (PMNs) in vivo, inflamed exudates (periapical exudates: PE) collected from periapical periodontitis patients were examined. Cell-free supernatants and cells were separated by centrifugation. Significant levels of nitrite concentrations were observed in the supernatants. The production of inducible NO synthase (iNOS) in highly purified PMNs derived from PEs was then immunocytochemically determined using rabbit anti-human iNOS antiserum. In vitro, human peripheral blood PMNs (PB-PMNs) isolated from patients were cultured with a combination of Esherichia coli-lipopolysaccharide (LPS), recombinant human interferon-gamma (rhIFN-gamma) and/or interleukin-1 beta (rhIL-1 beta). The stimulated PB-PMNs showed steady-state levels of nitrite. The stimulation of LPS, rhIFN-gamma and rhIL-1 beta showed more NO induction than that of LPS with either IFN-gamma or IL-1 beta, suggesting the synergistic effects of cytokines. Cryostat sections of surgically removed periapical tissues were also immunohistochemically examined for iNOS, IFN-gamma and IL-1 beta. Two-colour immunohistochemistry revealed the interaction of iNOS-producing PMNs and IFN-gamma- or IL-1 beta-producing mononuclear cells. On the basis of these data, we concluded that with the stimulation of inflammatory cytokines derived from mononuclear cells, PMNs can spontaneously produce NO at the site of chronic infection. The present studies are consistent with a hypothesis suggesting that PMNs could be regulated and delicately balanced to produce NO by mononuclear cell-derived cytokines in vivo. NO-producing cells may play a pivotal role in chronic inflammation. Images Figure 2 Figure 4 Figure 5 Figure 6 PMID:9616379

Interleukin 6 downregulates p53 expression and activity by stimulating ribosome biogenesis: a new pathway connecting inflammation to cancer

PubMed Central

Brighenti, E; Calabrese, C; Liguori, G; Giannone, F A; Trerè, D; Montanaro, L; Derenzini, M

2014-01-01

Chronic inflammation is an established risk factor for the onset of cancer, and the inflammatory cytokine IL-6 has a role in tumorigenesis by enhancing proliferation and hindering apoptosis. As factors stimulating proliferation also downregulate p53 expression by enhancing ribosome biogenesis, we hypothesized that IL-6 may cause similar changes in inflamed tissues, thus activating a mechanism that favors neoplastic transformation. Here, we showed that IL-6 downregulated the expression and activity of p53 in transformed and untransformed human cell lines. This was the consequence of IL-6-dependent stimulation of c-MYC mRNA translation, which was responsible for the upregulation of rRNA transcription. The enhanced rRNA transcription stimulated the MDM2-mediated proteasomal degradation of p53, by reducing the availability of ribosome proteins for MDM2 binding. The p53 downregulation induced the acquisition of cellular phenotypic changes characteristic of epithelial–mesenchymal transition, such as a reduced level of E-cadherin expression, increased cell invasiveness and a decreased response to cytotoxic stresses. We found that these changes also occurred in colon epithelial cells of patients with ulcerative colitis, a very representative example of chronic inflammation at high risk for tumor development. Histochemical and immunohistochemical analysis of colon biopsy samples showed an upregulation of ribosome biogenesis, a reduced expression of p53, together with a focal reduction or absence of E-cadherin expression in chronic colitis in comparison with normal mucosa samples. These changes disappeared after treatment with anti-inflammatory drugs. Taken together, the present results highlight a new mechanism that may link chronic inflammation to cancer, based on p53 downregulation, which is activated by the enhancement of rRNA transcription upon IL-6 exposure. PMID:24531714

Stimulation of sensory neuropeptide release by nociceptin/orphanin FQ leads to hyperaemia in acutely inflamed rat knees

PubMed Central

Zhang, Chunfen; McDougall, Jason J

2006-01-01

The peripheral effect of the ‘opioid-like' peptide nociceptin/orphanin FQ (N/OFQ) on joint blood flow was investigated in acutely inflamed rats. Sensory neuropeptide release from capsaicin-sensitive nerves and the involvement of synovial mast cells and leukocytes on these vasomotor responses were also studied. Blood flow measurements of exposed knee joints were performed in urethane-anaesthetised rats (2 mg kg−1 intraperitoneal) using laser Doppler perfusion imaging. Topical administration of N/OFQ (10−13–10−8 mol) to acutely inflamed joints caused a dose-dependent increase in synovial perfusion with an ED50 of 4.0 × 10−10 mol. This vasodilatatory response was blocked by the selective NOP receptor antagonist [Phe1-(CH2-NH)-Gly2]-Nociceptin(1–13)-NH2 (10−9 mol) (P<0.0001). Co-administration of N/OFQ with the neurokinin-1 (NK1) receptor antagonist [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P (10−12 mol), the vasoactive intestinal peptide (VIP) receptor antagonist VIP6–28 (10−9 mol) or the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP8–37 (10−9 mol) all blocked the hyperaemic effect of N/OFQ (P<0.0001). Treatment of acutely inflamed knees with capsaicin (8-methyl-N-vanillyl-6-noneamide) to destroy unmyelinated joint afferents also inhibited N/OFQ vasomotor activity. Stabilisation of synovial mast cells with disodium cromoglycate (cromolyn) ameliorated N/OFQ responses, whereas inactivation of circulating leukocytes with the pan-selectin inhibitor fucoidin completely blocked N/OFQ-induced hyperaemia in these joints. These experiments show that in acutely inflamed knee joints, N/OFQ acts on NOP receptors located on synovial mast cells and leukocytes leading to the secondary release of proinflammatory mediators into the joint. These agents subsequently stimulate sensory neuropeptide release from capsaicin-sensitive nerves culminating in vasodilatation and increased articular blood flow. PMID:16783411

IL-15 regulates memory CD8+ T cell O-glycan synthesis and affects trafficking

PubMed Central

Nolz, Jeffrey C.; Harty, John T.

2014-01-01

Memory and naive CD8+ T cells exhibit distinct trafficking patterns. Specifically, memory but not naive CD8+ T cells are recruited to inflamed tissues in an antigen-independent manner. However, the molecular mechanisms that regulate memory CD8+ T cell trafficking are largely unknown. Here, using murine models of infection and T cell transfer, we found that memory but not naive CD8+ T cells dynamically regulate expression of core 2 O-glycans, which interact with P- and E-selectins to modulate trafficking to inflamed tissues. Following infection, antigen-specific effector CD8+ T cells strongly expressed core 2 O-glycans, but this glycosylation pattern was lost by most memory CD8+ T cells. After unrelated infection or inflammatory challenge, memory CD8+ T cells synthesized core 2 O-glycans independently of antigen restimulation. The presence of core 2 O-glycans subsequently directed these cells to inflamed tissue. Memory and naive CD8+ T cells exhibited the opposite pattern of epigenetic modifications at the Gcnt1 locus, which encodes the enzyme that initiates core 2 O-glycan synthesis. The open chromatin configuration in memory CD8+ T cells permitted de novo generation of core 2 O-glycans in a TCR-independent, but IL-15–dependent, manner. Thus, IL-15 stimulation promotes antigen-experienced memory CD8+ T cells to generate core 2 O-glycans, which subsequently localize them to inflamed tissues. These findings suggest that CD8+ memory T cell trafficking potentially can be manipulated to improve host defense and immunotherapy. PMID:24509081

Inhibition of tracheal vascular extravasation by liposome-encapsulated albuterol in rats.

PubMed

Zhang, W; Guo, L; Nadel, J A; Papahadjopoulos, D

1998-03-01

To develop a liposome-based system for systemic delivery of anti-inflammatory drugs to airways and other inflamed tissues. Postcapillary venular gap junctions open during airway inflammation and allow fluid accumulation and permit molecules (e.g. complement, kininogen) to enter tissues, initiating inflammatory cascades. Beta-adrenergic agonists prevent inflammatory plasma extravasation, but because of their deleterious side effects, they are not used intravenously. When sterically stabilized "stealth" liposomes are injected i.v., they remain in the circulation for long periods. Inflammatory mediators [e.g., substance P(SP)] open postcapillary venular gaps and allow liposomes and their contents to be deposited selectively in the inflamed tissue. We hypothesized that liposomes encapsulating a beta-adrenergic agonist, such as albuterol, would deposit selectively in inflamed airway tissue, where the drug would slowly leak out of the liposomes, resulting in closure of the gaps, thus preventing subsequent inflammatory extravasation. To test this hypothesis, we delivered albuterol-loaded liposomes i.v. in rats. Then we injected SP to open the venular gaps and allow accumulation of the drug-loaded liposomes in airway tissue. We examined whether this treatment resulted in inhibition of subsequent plasma extravasation induced by SP. The results indicate that liposome-encapsulated albuterol inhibits subsequent extravasation, presumably by leaking out of liposomes in airway tissue. This inhibition occurs for prolonged periods of time and with limited side effects compared to the effect of free albuterol. We conclude that liposomes loaded with appropriate drugs, by migrating to inflamed tissue and subsequently inhibiting inflammatory cascades, may be of therapeutic value in inflammatory diseases.

Activation of silent mechanoreceptive cat C and Aδ sensory neurons and their substance P expression following peripheral inflammation

PubMed Central

Xu, Guang-Yin; Huang, Li-Yen Mae; Zhao, Zhi-Qi

2000-01-01

The effect of inflammation on the excitability and the level of substance P (SP) in cat mechanoreceptive C and Aδ dorsal root ganglion (DRG) neurons were studied in vivo using intracellular recording and immunocytochemical techniques. Following injections of carrageenan (Carg) into the cat hindpaw, the percentage of C neurons exhibiting spontaneous activity increased from 7.2 to 20.7 % and the percentage of Aδ neurons increased from 6.9 to 18.6 %. In contrast to most cells from normal cats, which fired regularly below 10 Hz, many cells from Carg-treated cats fired at higher frequencies or in bursts. Inflammation (Carg treatment) also depolarized membrane potentials, increased membrane input resistance, caused the disappearance of inward rectifying currents and lowered the mean current thresholds of tibial nerve-evoked responses in DRG neurons. With inflammation, the percentage of C or Aδ neurons responding to low threshold mechanoreceptive stimuli increased (C neurons: normal, 13 %; inflamed, 41 %; Aδ neurons: normal, 13 %; inflamed, 39 %), while the percentage of C or Aδ neurons responding to high threshold mechanoreceptive stimuli remained unchanged. Some receptive field (RF)-responsive cells were injected with Lucifer Yellow and their SP immunoreactivity was determined. Following Carg treatment, substantially higher percentages of RF-responsive cells were SP positive (C neurons: normal, 35.7 %; inflamed, 60 %; Aδ neurons: normal, 18.2 %; inflamed, 66.7 %). These combined increases in the excitability of DRG neurons and SP-containing RF-responsive neurons could lead to sensitization of sensory neurons, thus contributing to the development of hyperalgesia. PMID:11034623

Cone Beam CT Imaging Analysis of Interfractional Variations in Bladder Volume and Position During Radiotherapy for Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yee, Don, E-mail: dony@ualberta.c; Parliament, Matthew; Rathee, Satyapal

2010-03-15

Purpose: To quantify daily bladder size and position variations during bladder cancer radiotherapy. Methods and Materials: Ten bladder cancer patients underwent daily cone beam CT (CBCT) imaging of the bladder during radiotherapy. Bladder and planning target volumes (bladder/PTV) from CBCT and planning CT scans were compared with respect to bladder center-of-mass shifts in the x (lateral), y (anterior-posterior), and z (superior-inferior) coordinates, bladder/PTV size, bladder/PTV margin positions, overlapping areas, and mutually exclusive regions. Results: A total of 262 CBCT images were obtained from 10 bladder cancer patients. Bladder center of mass shifted most in the y coordinate (mean, -0.32 cm).more » The anterior bladder wall shifted the most (mean, -0.58 cm). Mean ratios of CBCT-derived bladder and PTV volumes to planning CT-derived counterparts were 0.83 and 0.88. The mean CBCT-derived bladder volume (+- standard deviation [SD]) outside the planning CT counterpart was 29.24 cm{sup 3} (SD, 29.71 cm{sup 3}). The mean planning CT-derived bladder volume outside the CBCT counterpart was 47.74 cm{sup 3} (SD, 21.64 cm{sup 3}). The mean CBCT PTV outside the planning CT-derived PTV was 47.35 cm{sup 3} (SD, 36.51 cm{sup 3}). The mean planning CT-derived PTV outside the CBCT-derived PTV was 93.16 cm{sup 3} (SD, 50.21). The mean CBCT-derived bladder volume outside the planning PTV was 2.41 cm{sup 3} (SD, 3.97 cm{sup 3}). CBCT bladder/ PTV volumes significantly differed from planning CT counterparts (p = 0.047). Conclusions: Significant variations in bladder and PTV volume and position occurred in patients in this trial.« less

Stem Cell Therapy in Bladder Dysfunction: Where Are We? And Where Do We Have to Go?

PubMed Central

Lee, Sang-Rae; Song, Yun Seob; Lee, Hong Jun

2013-01-01

To date, stem cell therapy for the bladder has been conducted mainly on an experimental basis in the areas of bladder dysfunction. The therapeutic efficacy of stem cells was originally thought to be derived from their ability to differentiate into various cell types. Studies about stem cell therapy for bladder dysfunction have been limited to an experimental basis and have been less focused than bladder regeneration. Bladder dysfunction was listed in MESH as “urinary bladder neck obstruction”, “urinary bladder, overactive”, and “urinary bladder, neurogenic”. Using those keywords, several articles were searched and studied. The bladder dysfunction model includes bladder outlet obstruction, cryoinjured, diabetes, ischemia, and spinal cord injury. Adipose derived stem cells (ADSCs), bone marrow stem cells (BMSCs), and skeletal muscle derived stem cells (SkMSCs) are used for transplantation to treat bladder dysfunction. The main mechanisms of stem cells to reconstitute or restore bladder dysfunction are migration, differentiation, and paracrine effects. The aim of this study is to review the stem cell therapy for bladder dysfunction and to provide the status of stem cell therapy for bladder dysfunction. PMID:24151627

Influence of moderate to severe chronic periodontitis on dental pulp.

PubMed

Fatemi, K; Disfani, R; Zare, R; Moeintaghavi, A; Ali, Saadat A; Boostani, H R

2012-10-01

The relationship between periodontal disease and dental pulp changes is controversial and has been debated for many years. This human study was performed to evaluate the possible effects of moderate to advanced periodontal disease on the different aspect of dental pulp structure. Twenty hopeless permanent teeth were extracted from systemically healthy adults because of moderate to advanced chronic periodontitis, with a bone loss of >6 mm and a mobility of grade 2 or 3. Upon extraction, the apical 2 to 3 mm of the roots were immediately sectioned. Four to five sections were mounted on each slide, and every third slide was stained with hematoxylin and eosin. The specimens were histologically processed and examined by an oral pathologist. Non-inflamed pulp, with partial or complete necrosis in some sections and several non-necrotic sections, was found in only 6.3% of teeth. Most teeth (58.3%) displayed edematous pulps. Slightly fibrotic pulps were seen in 52.1% of sections. Odontoblastic integrity was seen in 31.3% of teeth. Most teeth (77.1%) displayed no pulp stones. In 43.8% of teeth, the pulp vessels displayed dilatation. Moderate to advanced periodontal disease can affect the dental pulp. Careful consideration of diagnostic and treatment planing in patients with endodontic-periodontal involvement is therefore recommended.

Influence of moderate to severe chronic periodontitis on dental pulp

PubMed Central

Fatemi, K; Disfani, R; Zare, R; Moeintaghavi, A; Ali, Saadat A.; Boostani, H. R

2012-01-01

Background: The relationship between periodontal disease and dental pulp changes is controversial and has been debated for many years. This human study was performed to evaluate the possible effects of moderate to advanced periodontal disease on the different aspect of dental pulp structure. Materials and Methods: Twenty hopeless permanent teeth were extracted from systemically healthy adults because of moderate to advanced chronic periodontitis, with a bone loss of >6 mm and a mobility of grade 2 or 3. Upon extraction, the apical 2 to 3 mm of the roots were immediately sectioned. Four to five sections were mounted on each slide, and every third slide was stained with hematoxylin and eosin. The specimens were histologically processed and examined by an oral pathologist. Results: Non-inflamed pulp, with partial or complete necrosis in some sections and several non-necrotic sections, was found in only 6.3% of teeth. Most teeth (58.3%) displayed edematous pulps. Slightly fibrotic pulps were seen in 52.1% of sections. Odontoblastic integrity was seen in 31.3% of teeth. Most teeth (77.1%) displayed no pulp stones. In 43.8% of teeth, the pulp vessels displayed dilatation. Conclusions: Moderate to advanced periodontal disease can affect the dental pulp. Careful consideration of diagnostic and treatment planing in patients with endodontic-periodontal involvement is therefore recommended. PMID:23493524

Phase I-II Clinical Trial Assessing Safety and Efficacy of Umbilical Cord Blood Mononuclear Cell Transplant Therapy of Chronic Complete Spinal Cord Injury.

PubMed

Zhu, Hui; Poon, Waisang; Liu, Yansheng; Leung, Gilberto Ka-Kit; Wong, Yatwa; Feng, Yaping; Ng, Stephanie C P; Tsang, Kam Sze; Sun, David T F; Yeung, David K; Shen, Caihong; Niu, Fang; Xu, Zhexi; Tan, Pengju; Tang, Shaofeng; Gao, Hongkun; Cha, Yun; So, Kwok-Fai; Fleischaker, Robert; Sun, Dongming; Chen, John; Lai, Jan; Cheng, Wendy; Young, Wise

2016-11-01

Umbilical cord blood-derived mononuclear cell (UCB-MNC) transplants improve recovery in animal spinal cord injury (SCI) models. We transplanted UCB-MNCs into 28 patients with chronic complete SCI in Hong Kong (HK) and Kunming (KM). Stemcyte Inc. donated UCB-MNCs isolated from human leukocyte antigen (HLA ≥4:6)-matched UCB units. In HK, four patients received four 4-μl injections (1.6 million cells) into dorsal entry zones above and below the injury site, and another four received 8-μl injections (3.2 million cells). The eight patients were an average of 13 years after C5-T10 SCI. Magnetic resonance diffusion tensor imaging of five patients showed white matter gaps at the injury site before treatment. Two patients had fiber bundles growing across the injury site by 12 months, and the rest had narrower white matter gaps. Motor, walking index of SCI (WISCI), and spinal cord independence measure (SCIM) scores did not change. In KM, five groups of four patients received four 4-μl (1.6 million cells), 8-μl (3.2 million cells), 16-μl injections (6.4 million cells), 6.4 million cells plus 30 mg/kg methylprednisolone (MP), or 6.4 million cells plus MP and a 6-week course of oral lithium carbonate (750 mg/day). KM patients averaged 7 years after C3-T11 SCI and received 3-6 months of intensive locomotor training. Before surgery, only two patients walked 10 m with assistance and did not need assistance for bladder or bowel management before surgery. The rest could not walk or do their bladder and bowel management without assistance. At about a year (41-87 weeks), WISCI and SCIM scores improved: 15/20 patients walked 10 m ( p = 0.001) and 12/20 did not need assistance for bladder management ( p = 0.001) or bowel management ( p = 0.002). Five patients converted from complete to incomplete (two sensory, three motor; p = 0.038) SCI. We conclude that UCB-MNC transplants and locomotor training improved WISCI and SCIM scores. We propose further clinical trials.

Diagnosis of vulnerable atherosclerotic plaques by time-resolved fluorescence spectroscopy and ultrasound imaging.

PubMed

Jo, J A; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Beseth, B; Dorafshar, A H; Reil, T; Baker, D; Freischlag, J; Shung, K K; Sun, L; Marcu, L

2006-01-01

In this study, time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and ultrasonography were applied to detect vulnerable (high-risk) atherosclerotic plaque. A total of 813 TR-LIFS measurements were taken from carotid plaques of 65 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified by histopathology as thin, fibrotic, calcified, low-inflamed, inflamed and necrotic lesions. Spectral and time-resolved parameters (normalized intensity values and Laguerre expansion coefficients) were extracted from the TR-LIFS data. Feature selection for classification was performed by either analysis of variance (ANOVA) or principal component analysis (PCA). A stepwise linear discriminant analysis algorithm was developed for detecting inflamed and necrotic lesion, representing the most vulnerable plaques. These vulnerable plaques were detected with high sensitivity (>80%) and specificity (>90%). Ultrasound (US) imaging was obtained in 4 carotid plaques in addition to TR-LIFS examination. Preliminary results indicate that US provides important structural information of the plaques that could be combined with the compositional information obtained by TR-LIFS, to obtain a more accurate diagnosis of vulnerable atherosclerotic plaque.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lichter, J.P.; Konopka, R.G.; Hartman, M.T.

Use of (/sup 111/In)granulocytes in the study of pulmonary inflammation requires study of their in vivo behavior. To study the pulmonary deposition of these cells and their ability to migrate from the capillary to the alveolus, we injected (/sup 111/In)granulocytes into dogs 24 h after the induction of a right lower lobe pneumococcal pneumonia. Using external imaging, we found rapid clearance of (/sup 111/In)granulocytes from the uninvolved lung (with a residual radioactivity of 24.5 +/- 4.2% at 4 h). In contrast, 83 +/- 12.4% of the initial radioactivity was present in inflamed lung at 4 h. Bronchoalveolar lavage fluid frommore » the inflamed lung was more cellular than that from control lung, contained a greater fraction of polymorphonuclear leukocytes (82 +/- 4.1% versus 20 +/- 6.2%), and much greater cell-associated radioactivity (ratio of 423:1, inflamed to control). Autoradiography disclosed that this radioactivity was localized to consolidated alveoli and was not prominently distributed in arterioles or venules or in airways larger than 0.6 mm. We conclude that (/sup 111/In)granulocytes are biologically active in the setting of acute lung inflammation.« less

A RETROSPECTIVE ANALYSIS OF ACUTE APPENDICITIS, RUPTURED APPENDICITIS AND THE LEVEL OF LEUKOCYTOSIS IN PAEDIATRIC SURGICAL PATIENTS OF NELSON MANDELA CENTRAL HOSPITAL.

PubMed

Mtimba, L; Dhaffala, A; Molaoa, S Z

2017-06-01

Appendicectomy is the most commonly performed operation worldwide. The diagnosis is predominantly based on clinical findings. Some patients will clinically be unclear if ruptured or acute inflamed appendicitis; the level of white cell count has been used as the predictor for ruptured appendicitis. This was a retrospective chart review of paediatric surgical patients admitted at Nelson Mandela Central Hospital, Mthatha South Africa. A total of 214 patients with a diagnosis of acute appendicitis. Overall, the ruptured appendicitis was 62% and 38% were inflamed appendicitis. Nature of the acute appendicitis: White cell count, Inflamed, Ruptured, Total p-value < 9.9 21 30 51 0.075, 10-14.9 28 54 82 0.0, 15-19.9 17 29 46 0.012, 20-29.9 5 26 31 0.0 > 30 0 4 4. This study has demonstrated that in patients who are diagnosed with acute appendicitis clinically, the normal white cell count does not necessarily rule out ruptured acute appendicitis. But the risks of ruptured acute appendicitis increase with the increase level of white cell count.

Potential of optical spectral transmission measurements for joint inflammation measurements in rheumatoid arthritis patients

NASA Astrophysics Data System (ADS)

Meier, A. J. Louise; Rensen, Wouter H. J.; de Bokx, Pieter K.; de Nijs, Ron N. J.

2012-08-01

Frequent monitoring of rheumatoid arthritis (RA) patients enables timely treatment adjustments and improved outcomes. Currently this is not feasible due to a shortage of rheumatologists. An optical spectral transmission device is presented for objective assessment of joint inflammation in RA patients, while improving diagnostic accuracy and clinical workflow. A cross-sectional, nonrandomized observational study was performed with this device. In the study, 77 proximal interphalangeal (PIP) joints in 67 patients have been analyzed. Inflammation of these PIP joints was also assessed by a rheumatologist with a score varying from 1 (not inflamed) to 5 (severely inflamed). Out of 77 measurements, 27 were performed in moderate to strongly inflamed PIP joints. Comparison between the clinical assessment and an optical measurement showed a correlation coefficient r=0.63, p<0.001, 95% CI [0.47, 0.75], and a ROC curve (AUC=0.88) that shows a relative good specificity and sensitivity. Optical spectral transmission measurements in a single joint correlate with clinical assessment of joint inflammation, and therefore might be useful in monitoring joint inflammation in RA patients.

Bromelain Treatment Decreases Secretion of Pro-Inflammatory Cytokines and Chemokines by Colon Biopsies In Vitro

PubMed Central

Onken, Jane E.; Greer, Paula K.; Calingaert, Brian; Hale, Laura P.

2008-01-01

Oral bromelain has been anecdotally reported to decrease inflammation in ulcerative colitis (UC). Proteolytically active bromelain is known to decrease expression of mRNAs encoding pro-inflammatory cytokines by human leukocytes in vitro. To assess the effect of bromelain on mucosal secretion of cytokines in inflammatory bowel disease (IBD), endoscopic colon biopsies from patients with UC, Crohn’s disease (CD), and non-IBD controls were treated in vitro with bromelain or media, then cultured. Secretion of pro-inflammatory cytokines and chemokines was measured. Significant increases in granulocyte colony stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) were detected in the media from actively inflamed areas in UC and CD as compared with non-inflamed IBD tissue and non-IBD controls. In vitro bromelain treatment decreased secretion of G-CSF, granulocyte-macrophage colony stimulating factor (GM-CSF), IFN-γ, CCL4/macrophage inhibitory protein (MIP)-1β, and TNF by inflamed tissue in IBD. Bromelain may be a novel therapy for IBD. PMID:18160345

Dose Distribution in Bladder and Surrounding Normal Tissues in Relation to Bladder Volume in Conformal Radiotherapy for Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Majewski, Wojciech, E-mail: wmajewski1@poczta.onet.p; Wesolowska, Iwona; Urbanczyk, Hubert

2009-12-01

Purpose: To estimate bladder movements and changes in dose distribution in the bladder and surrounding tissues associated with changes in bladder filling and to estimate the internal treatment margins. Methods and Materials: A total of 16 patients with bladder cancer underwent planning computed tomography scans with 80- and 150-mL bladder volumes. The bladder displacements associated with the change in volume were measured. Each patient had treatment plans constructed for a 'partially empty' (80 mL) and a 'partially full' (150 mL) bladder. An additional plan was constructed for tumor irradiation alone. A subsequent 9 patients underwent sequential weekly computed tomography scanningmore » during radiotherapy to verify the bladder movements and estimate the internal margins. Results: Bladder movements were mainly observed cranially, and the estimated internal margins were nonuniform and largest (>2 cm) anteriorly and cranially. The dose distribution in the bladder worsened if the bladder increased in volume: 70% of patients (11 of 16) would have had bladder underdosed to <95% of the prescribed dose. The dose distribution in the rectum and intestines was better with a 'partially empty' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 23%, 20%, and 15% for the rectum and 162, 144, 123 cm{sup 3} for the intestines, respectively) than with a 'partially full' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 28%, 24%, and 18% for the rectum and 180, 158, 136 cm{sup 3} for the intestines, respectively). The change in bladder filling during RT was significant for the dose distribution in the intestines. Tumor irradiation alone was significantly better than whole bladder irradiation in terms of organ sparing. Conclusion: The displacements of the bladder due to volume changes were mainly related to the upper wall. The internal margins should be nonuniform, with the largest margins cranially and anteriorly. The changes in bladder filling during RT could influence the dose distribution in the bladder and intestines. The dose distribution in the rectum and bowel was slightly better with a 'partially empty' than with a 'full' bladder.« less

Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG), LPS, and TNF-α

PubMed Central

Saban, Marcia R; O'Donnell, Michael A; Hurst, Robert E; Wu, Xue-Ru; Simpson, Cindy; Dozmorov, Igor; Davis, Carole; Saban, Ricardo

2008-01-01

Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG) remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression in the bladder target organ beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following chronic intravesical BCG therapy and to compare the results to non-specific pro inflammatory stimuli (LPS and TNF-α). For this purpose, C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Seven days after the last instillation, the urothelium along with the submucosa was removed from detrusor muscle and the RNA was extracted from both layers for cDNA array experiments. Microarray results were normalized by a robust regression analysis and only genes with an expression above a conditional threshold of 0.001 (3SD above background) were selected for analysis. Next, genes presenting a 3-fold ratio in regard to the control group were entered in Ingenuity Pathway Analysis (IPA) for a comparative analysis in order to determine genes specifically regulated by BCG, TNF-α, and LPS. In addition, the transcriptome was precipitated with an antibody against RNA polymerase II and real-time polymerase chain reaction assay (Q-PCR) was used to confirm some of the BCG-specific transcripts. Results Molecular networks of treatment-specific genes generated several hypotheses regarding the mode of action of BCG. BCG-specific genes involved small GTPases and BCG-specific networks overlapped with the following canonical signaling pathways: axonal guidance, B cell receptor, aryl hydrocarbon receptor, IL-6, PPAR, Wnt/β-catenin, and cAMP. In addition, a specific detrusor network expressed a high degree of overlap with the development of the lymphatic system. Interestingly, TNF-α-specific networks overlapped with the following canonical signaling pathways: PPAR, death receptor, and apoptosis. Finally, LPS-specific networks overlapped with the LPS/IL-1 mediated inhibition of RXR. Because NF-kappaB occupied a central position in several networks, we further determined whether this transcription factor was part of the responses to BCG. Electrophoretic mobility shift assays confirmed the participation of NF-kappaB in the mouse bladder responses to BCG. In addition, BCG treatment of a human urothelial cancer cell line (J82) also increased the binding activity of NF-kappaB, as determined by precipitation of the chromatin by a NF-kappaB-p65 antibody and Q-PCR of genes bearing a NF-kappaB consensus sequence. Next, we tested the hypothesis of whether small GTPases such as LRG-47 are involved in the uptake of BCG by the bladder urothelium. Conclusion As expected, BCG treatment induces the transcription of genes belonging to common pro-inflammatory networks. However, BCG also induces unique genes belonging to molecular networks involved in axonal guidance and lymphatic system development within the bladder target organ. In addition, NF-kappaB seems to play a predominant role in the bladder responses to BCG therapy. Finally, in intact urothelium, BCG-GFP internalizes in LRG-47-positive vesicles. These results provide a molecular framework for the further study of the involvement of immune and nervous systems in the bladder responses to BCG therapy. PMID:18267009

[Suprapubic urinary diversion using Cystofix--an alternative to the urethral indwelling catheter].

PubMed

Müller, J; Sulmoni, M

1992-01-01

Suprapubic Cystofix-cystostomy is a valuable alternative to the Foley-catheter. The advantages of suprapubic cystostomy are mainly a reduction of urinary tract infections, inflammatory reactions in the lower urinary tract and avoidance of late urethral strictures after transurethral catheterism. There are a few contraindications to be considered, mainly an empty bladder and coagulation disorders. The complication rate of suprapubic Cystofix-cystostomy, usually gross haematuria, is very low. Cystofix-cystostomy is as useful for short term urinary drainage as for long term drainage in the case of chronic voiding disorders.

Lower urinary tract symptoms in patients with Niigata Minamata disease: a case-control study 50 years after methyl mercury pollution.

PubMed

Hara, Noboru; Saito, Hisashi; Takahashi, Kota; Takeda, Masayuki

2013-06-01

To clarify the prevalence of lower urinary tract symptoms and overactive bladder in patients with chronic methyl mercury poisoning. A total of 151 patients (61 men and 90 women; mean age 72.1 years) with Niigata Minamata disease were enrolled. An age- and sex-matched group of 150 participants was used as control. Patients reported their International Prostate Symptom Score and overactive bladder symptom score. In men, the total, storage and voiding International Prostate Symptom Score scores were higher in the Niigata Minamata disease group than in the control group (10.6 ± 7.8 vs 5.0 ± 5.0, 4.5 ± 3.3 vs 2.4 ± 2.4 and 6.1 ± 5.1 vs 2.7 ± 3.1, respectively, P < 0.001 in all). In women, these scores were also higher in the Niigata Minamata disease group than in the control group (8.9 ± 7.3 vs 4.0 ± 4.0, 4.4 ± 3.2 vs 2.8 ± 2.4 and 4.5 ± 5.0 vs 1.3 ± 2.0, respectively, P < 0.001 in all). The prevalence of overactive bladder was more frequent in the Niigata Minamata disease group compared with that in the control group (51.7% vs 26.7%, P < 0.001). In both men and women, the overactive bladder symptom score was higher in the Niigata Minamata disease group than in the control group (4.1 ± 3.0 vs 2.4 ± 2.9, P = 0.002 and 4.6 ± 3.6 vs 2.7 ± 2.9, P < 0.001, respectively). The International Prostate Symptom Score and overactive bladder symptom score in the Niigata Minamata disease group were highest in patients aged 60-69 years (P < 0.001 in both), whereas these increased in an age-dependent manner in the control group. Lower urinary tract symptoms and overactive bladder are severe and highly prevalent conditions among patients with methyl mercury poisoning. The higher prevalence of lower urinary tract symptoms among patients aged 60-69 years might be related to the fact that they were exposed to methyl mercury during their childhood/development. © 2012 The Japanese Urological Association.

MicroRNAs May Mediate the Down-Regulation of Neurokinin-1 Receptor in Chronic Bladder Pain Syndrome

PubMed Central

Sanchez Freire, Veronica; Burkhard, Fiona C.; Kessler, Thomas M.; Kuhn, Annette; Draeger, Annette; Monastyrskaya, Katia

2010-01-01

Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability, bladder contractility, and inflammation, we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1, junctional adherins molecule -1, and occludin were similarly down-regulated, implicating increased urothelial permeability, whereas bradykinin B1 receptor, cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cell-based models, we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients, the same miRNAs were significantly increased, suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b, miR-500, miR-328, and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS, and have relevance for other clinical conditions involving the NK1 receptor. PMID:20008142

New techniques on the horizon: interventional radiology and interventional endoscopy of the urinary tract ('endourology').

PubMed

Berent, Allyson

2014-01-01

Interventional radiology and interventional endoscopy (IR/IE) uses contemporary imaging modalities, such as fluoroscopy and endoscopy, to perform diagnostic and therapeutic procedures in various body parts. The majority of IR/IE procedures currently undertaken in veterinary medicine pertain to the urinary tract, and this subspecialty has been termed 'endourology'. This technology treats diseases of the renal pelvis, ureter(s), bladder and urethra. In human medicine, endourology has overtaken traditional open urologic surgery in the past 20-30 years, and in veterinary medicine similar progress is occurring. This article presents a brief overview of some of the more common IR/IE procedures currently being performed for the treatment of urinary tract disease in veterinary patients. These techniques include percutaneous nephrolithotomy for lithotripsy of problematic nephrolithiasis, mesenchymal stem cell therapy for chronic kidney disease, sclerotherapy for the treatment of idiopathic renal hematuria, various diversion techniques for ureteral obstructions, laser lithotripsy for lower urinary tract stone disease, percutaneous cystolithotomy for removal of bladder stones, hydraulic occluder placement for refractory urinary incontinence, percutaneous cystostomy tube placement for bladder diversion, urethral stenting for benign and malignant urethral obstructions, and antegrade urethral catheterization for treatment of urethral tears. The majority of the data presented in this article is solely the experience of the author, and some of this has only been published and/or presented in abstract form or small case series. For information on traditional surgical approaches to these ailments readers are encouraged to evaluate other sources.

Novel Multisensor Probe for Monitoring Bladder Temperature During Locoregional Chemohyperthermia for Nonmuscle-Invasive Bladder Cancer: Technical Feasibility Study

PubMed Central

Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

2013-01-01

Abstract Background and Purpose: The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. Materials and Methods: A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. Results: The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Conclusions: Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia. PMID:24112045

Usefulness of threshold dose to prevent damage of underlying tissue by PDT treatment: an in-vitro study on chondrocytes

NASA Astrophysics Data System (ADS)

Placzek, R.; Kempka, G.; Ruether, W.; Moser, Joerg G.

1995-03-01

Arthritic synovitis is best cured by total removal of the inflamed synovia (equals synovectomy). This can be performed by open chirurgy, by arthroscopy, or by radiosynoviothesis, i.e., injection of (beta) -radiating rare earth metals into the joint cavity. All these procedures are more or less non-quantitative and may lead to a recidive. The idea was to destroy the inflamed synovia by PDT without destruction of the underlying tissue (cartilage and bone). So, the sensitivity of the cartilage-building cells, which can be grown in cell culture, has to be studied.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, JY; Hong, DL

Purpose: To investigate the impact of bladder filling status of the organs at risk (OARs) on dose distribution during intensity modulated radiotherapy (IMRT) for cervical cancer patients. Methods: Twelve cervical cancer patients treated with IMRT were selected for this study. The prescription dose was 45Gy/25 fractions with the 6 MV photon beam. All patients performed two CT scans, one with an empty bladder, the other one with bladder filled. For the registration of two CT scans, the fusion was automatically carried out upon the bony anatomy. The OARs (bladder, rectum, pelvic bone and small intestine) were delineated to planning CTmore » to evaluate the dose distributions. These dose distributions were compared between empty bladder and bladder filling. Results: The bladder volume with empty bladder and bladder filling was 403.2±124.13cc and 101.4±87.5cc, respectively. There were no statistical differences between empty bladder and bladder filling in the mean value of pelvic bone V10Gy, V20Gy, V40Gy; rectum V40Gy and V45Gy. The bladder V40Gy and V45Gy were lower in the bladder filling group than in the empty bladder group (63.7%±5.8% vs 87.5%±7.8%, 45.1%±9.5% vs 62.4%±11.8%, respectively). The V45Gy for small intestine in the bladder filling group was significantly less than the empty bladder group (146.7cc±95.3cc vs 245.7cc±101.8cc). Conclusion: Our study finds that the bladder filling status did not have a significant impact on dose distribution in the rectum and pelvic bone. However, the changes of bladder filling have a large impact on bladder and small intestine doses. A full bladder is strongly recommended during treatment for cervical cancer patients.« less

Prevalence of prostatitis-like symptoms in a managed care population.

PubMed

Clemens, J Quentin; Meenan, Richard T; O'Keeffe-Rosetti, Maureen C; Gao, Sara Y; Brown, Sheila O; Calhoun, Elizabeth A

2006-08-01

We calculated the prevalence of symptoms typically associated with chronic prostatitis/chronic pelvic pain syndrome in men in a managed care population in the Pacific Northwest. A questionnaire mailing to 5,000 male enrollees 25 to 80 years old in the Kaiser Permanente Northwest (Portland, Oregon) health plan was performed. The questionnaires included screening questions about the presence, duration and severity of pelvic pain, and the National Institutes of Health Chronic Prostatitis Symptom Index. Chronic prostatitis/chronic pelvic pain syndrome symptoms were defined in 2 ways: 1) presence of any of the following for a duration of 3 or more months: pain in the perineum, testicles, tip of penis, pubic or bladder area, dysuria, ejaculatory pain; and 2) perineal and/or ejaculatory pain, and a National Institutes of Health Chronic Prostatitis Symptom Index total pain score of 4 or more. Prevalence estimates were age adjusted to the total Kaiser Permanente Northwest male population. A total of 1,550 questionnaires were returned. The prevalence of chronic prostatitis/chronic pelvic pain syndrome symptoms was 7.5% for definition 1 and 5.9% for definition 2. Mean National Institutes of Health Chronic Prostatitis Symptom Index scores were 17 for definitions 1 and 2. Of those with prostatitis-like symptoms, 30% met criteria for having both definitions present. The prevalence of prostatitis-like symptoms using either of the 2 diagnoses was 11.2%. This population based study indicates that approximately 1 in 9 men have prostatitis-like symptoms. Application of 2 different definitions for prostatitis-like symptoms identified unique groups of men, with limited overlap in the groups.

Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells.

PubMed

Escudero-Lourdes, C; Wu, T; Camarillo, J M; Gandolfi, A J

2012-01-01

The association between chronic human exposure to arsenicals and bladder cancer development is well recognized; however, the underlying molecular mechanisms have not been fully determined. We propose that inflammatory responses can play a pathogenic role in arsenic-related bladder carcinogenesis. In previous studies, it was demonstrated that chronic exposure to 50 nM monomethylarsenous acid [MMA(III)] leads to malignant transformation of an immortalized model of urothelial cells (UROtsa), with only 3 mo of exposure necessary to trigger the transformation-related changes. In the three-month window of exposure, the cells over-expressed pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), consistent with the sustained activation of NFKβ and AP1/c-jun, ERK2, and STAT3. IL-8 was over-expressed within hours after exposure to MMA(III), and sustained over-expression was observed during chronic exposure. In this study, we profiled IL-8 expression in UROtsa cells exposed to 50 nM MMA(III) for 1 to 5 mo. IL-8 expression was increased mainly in cells after 3 mo MMA(III) exposure, and its production was also found increased in tumors derived from these cells after heterotransplantation in SCID mice. UROtsa cells do express both receptors, CXCR1 and CXCR2, suggesting that autocrine cell activation could be important in cell transformation. Supporting this observation and consistent with IL-8 over-expression, CXCR1 internalization was significantly increased after three months of exposure to MMA(III). The expression of MMP-9, cyclin D1, bcl-2, and VGEF was significantly increased in cells exposed to MMA(III) for 3 mo, but these mitogen-activated kinases were significantly decreased after IL-8 gene silencing, together with a decrease in cell proliferation rate and in anchorage-independent colony formation. These results suggest a relevant role of IL-8 in MMA(III)-induced UROtsa cell transformation. Copyright © 2011 Elsevier Inc. All rights reserved.

Correlation Between Bladder Pain Syndrome/Interstitial Cystitis and Pelvic Inflammatory Disease

PubMed Central

Chung, Shiu-Dong; Chang, Chao-Hsiang; Hung, Peir-Haur; Chung, Chi-Jung; Muo, Chih-Hsin; Huang, Chao-Yuan

2015-01-01

Abstract Pelvic inflammatory disease (PID) has been investigated in Western countries and identified to be associated with chronic pelvic pain and inflammation. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a complex syndrome that is significantly more prevalent in women than in men. Chronic pelvic pain is a main symptom of BPS/IC, and chronic inflammation is a major etiology of BPS/IC. This study aimed to investigate the correlation between BPS/IC and PID using a population-based dataset. We constructed a case–control study from the Taiwan National Health Insurance program. The case cohort comprised 449 patients with BPS/IC, and 1796 randomly selected subjects (about 1:4 matching) were used as controls. A Multivariate logistic regression model was constructed to estimate the association between BPS/IC and PID. Of the 2245 sampled subjects, a significant difference was observed in the prevalence of PID between BPS/IC cases and controls (41.7% vs 15.4%, P < 0.001). Multivariate logistic regression analysis revealed that the odds ratio (OR) for PID among cases was 3.69 (95% confidence interval [CI]: 2.89–4.71). Furthermore, the ORs for PID among BPS/IC cases were 4.52 (95% CI: 2.55–8.01), 4.31 (95% CI: 2.91–6.38), 3.00 (95% CI: 1.82–4.94), and 5.35 (95% CI: 1.88–15.20) in the <35, 35–49, 50–64, and >65 years age groups, respectively, after adjusting for geographic region, irritable bowel syndrome, and hypertension. Joint effect was also noted, specifically when patients had both PID and irritable bowel disease with OR of 10.5 (95% CI: 4.88–22.50). This study demonstrated a correlation between PID and BPS/IC. Clinicians treating women with PID should be alert to BPS/IC-related symptoms in the population. PMID:26579800

Normal reference values for bladder wall thickness on CT in a healthy population.

PubMed

Fananapazir, Ghaneh; Kitich, Aleksandar; Lamba, Ramit; Stewart, Susan L; Corwin, Michael T

2018-02-01

To determine normal bladder wall thickness on CT in patients without bladder disease. Four hundred and nineteen patients presenting for trauma with normal CTs of the abdomen and pelvis were included in our retrospective study. Bladder wall thickness was assessed, and bladder volume was measured using both the ellipsoid formula and an automated technique. Patient age, gender, and body mass index were recorded. Linear regression models were created to account for bladder volume, age, gender, and body mass index, and the multiple correlation coefficient with bladder wall thickness was computed. Bladder volume and bladder wall thickness were log-transformed to achieve approximate normality and homogeneity of variance. Variables that did not contribute substantively to the model were excluded, and a parsimonious model was created and the multiple correlation coefficient was calculated. Expected bladder wall thickness was estimated for different bladder volumes, and 1.96 standard deviation above expected provided the upper limit of normal on the log scale. Age, gender, and bladder volume were associated with bladder wall thickness (p = 0.049, 0.024, and < 0.001, respectively). The linear regression model had an R 2 of 0.52. Age and gender were negligible in contribution to the model, and a parsimonious model using only volume was created for both the ellipsoid and automated volumes (R 2  = 0.52 and 0.51, respectively). Bladder wall thickness correlates with bladder wall volume. The study provides reference bladder wall thicknesses on CT utilizing both the ellipsoid formula and automated bladder volumes.

Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type.

PubMed

Hakim, Alan; De Wandele, Inge; O'Callaghan, Chris; Pocinki, Alan; Rowe, Peter

2017-03-01

Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified. The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems. Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies. While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia. Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning. In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Bladder filling variation during conformal radiotherapy for rectal cancer

NASA Astrophysics Data System (ADS)

Sithamparam, S.; Ahmad, R.; Sabarudin, A.; Othman, Z.; Ismail, M.

2017-05-01

Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between changes of bladder volume and diarrhea (P = 0.045). In conclusion bladder volume reduced throughout radiotherapy treatment for conformal radiotherapy for rectal cancer and there was a large variation of bladder volume within patients.

Bladder biopsy

MedlinePlus

... than usual ( oliguria ). You cannot urinate despite a strong urge to do so. Alternative Names Biopsy - bladder Images Bladder catheterization, female Bladder catheterization, male Female urinary tract Male urinary tract Bladder biopsy ...

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

PubMed

Hubscher, Charles H; Herrity, April N; Williams, Carolyn S; Montgomery, Lynnette R; Willhite, Andrea M; Angeli, Claudia A; Harkema, Susan J

2018-01-01

Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Prospective cohort study; pilot trial with small sample size. Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. ClinicalTrials.gov NCT03036527.