ObjectiveThe etiology and pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) are unclear. Chronic inflammation is considered the main pathology of IC/BPS. This study measured the serum c-reactive protein (CRP), nerve growth factor (NGF) and pro-inflammatory cytokine/chemokine interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8 expression in patients with IC/BPS to elucidate the involvement of systemic inflammation in IC/BPS.MethodsSerum samples were collected from 30 IC/BPS patients and 26 control subjects. The concentrations of serum nerve growth factor (NGF), IL-1β, IL-6, TNF-α, and IL-8 were quantified using a bead-based, human serum adipokine panel kit. Serum C-reactive protein (CRP) was also assessed. Differences of serum CRP, NGF, IL-1β, IL-6, TNF-α, and IL-8 levels between the IC/BPS patients and controls were compared, and correlations between CRP and pro-inflammatory cytokines and chemokine were also evaluated.ResultsThe results showed that CRP level (p = 0.031), NGF (p = 0.015) and pro-inflammatory cytokines/chemokine IL-1β, IL-6, TNF-α, and IL-8 levels were significantly higher in the patients with IC/BPS than among controls (all p<0.001). Significant associations were observed between IL-1β and IL-8 (p<0.001), IL-6 and CRP (p = 0.01), IL-6 and IL-8 (p = 0.02), and IL-6 and TNF-α (p = 0.03).ConclusionIncreased pro-inflammatory cytokines/chemokine (IL-1β, IL-6, TNF-α, and IL-8) expression in the sera of IC/BPS patients implies not only mast cell activation, but also that other inflammatory mediators play important roles in the pathogenesis of IC/BPS. Thus, for some patients, IC/BPS is considered a chronic inflammatory disease.

Intracerebral-ventricular (ICV) injection of streptozotocin (STZ) induces an insulin-resistant brain state that may underlie the neural pathogenesis of sporadic Alzheimer disease (AD). Our previous work showed that prior ICV treatment of glucagon-like peptide-1 (GLP-1) could prevent STZ-induced learning memory impairment and tau hyperphosphorylation in the rat brain. The Chinese herbal medicine geniposide is known to relieve symptoms of type 2 diabetes. Because geniposide is thought to act as a GLP-1 receptor agonist, we investigated the potential therapeutic effect of geniposide on STZ-induced AD model in rats. Our result showed that a single injection of geniposide (50 μM, 10 μL) to the lateral ventricle prevented STZ-induced spatial learning deficit by about 40% and reduced tau phosphorylation by about 30% with Morris water maze test and quantitative immunohistochemical analysis, respectively. It has been known that tau protein can be phosphorylated by glycogen synthase kinase-3 (GSK3) and STZ can increase the activity of GSK3β. Our result with Western blot analysis showed that central administration of geniposide resulted in an elevated expression of GSK3β(pS-9) but suppressed GSK3β(pY-216) indicating that geniposide reduced STZ-induced GSK3β hyperactivity. In addition, ultrastructure analysis showed that geniposide averted STZ-induced neural pathology, including paired helical filament (PHF)-like structures, accumulation of vesicles in synaptic terminal, abnormalities of endoplasmic reticulum (ER) and early stage of apoptosis. In summary, our study suggests that the water soluble and orally active monomer of Chinese herbal medicine geniposide may serve as a novel therapeutic agent for the treatment of sporadic AD.

Objective• To investigate the suburothelial inflammation and urothelial dysfunction that occurs with ketamine-related cystitis (KC) and interstitial cystitis/bladder pain syndrome (IC/BPS). Patients and Methods• Bladder tissues from 16 patients with KC, 17 patients with IC/BPS and 10 control subjects were analysed.• Immunofluorescence staining of the junction protein E-cadherin was carried out, and tryptase levels and a TUNEL assay were used to assess mast-cell activation and urothelial apoptosis, respectively. • The fluorescence intensity of E-cadherin was measured using the ImageJ method. The percentages of activated mast cells and apoptotic cells were calculated as positive cells per unit area (4 μm 2 ). Results• The mean (SD) ages of the patients in the KC, IC/BPS and control groups were 25.0 (3.8), 41.3 (13.7) and 50.5 (9.6) years, respectively (P < 0.05).• The mean (SD) distributions of E-cadherin in KC (10. • Tissues from the KC bladders had significantly lower expression of E-cadherin (P = 0.024) and significantly higher numbers of apoptotic cells (P = 0.02) compared with the IC/BPS bladder tissues.• Greater numbers of apoptotic cells and lower expression levels of E-cadherin significantly correlated with maximum bladder capacity in the overall patient samples (P < 0.05). Conclusions• KC and IC/BPS tissues both showed defective junction protein, increased suburothelial inflammation and increased urothelial cell apoptosis.• Decreased expression of E-cadherin and increased apoptosis were more severe in KC than in IC/BPS bladder tissues and these findings were associated with the clinical symptoms of KC and IC/BPS.

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This study aimed to investigate the diagnostic values of urine cytokines in interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB) patients, and to develop a novel diagnostic algorithm. Urine samples were collected from 40 IC/BPS, 40 OAB patients, and 30 controls. Commercially available multiplex immunoassays were used to analyze 31 targeted cytokines. Urine cytokine profiles were significantly different among study groups and controls. MIP-1β showed the highest sensitivity (92.2%) for identifying diseased study patients from controls. The cytokines with high diagnostic values for distinguishing between IC and OAB included IL-10, RANTES, eotaxin, CXCL10, IL-12p70, NGF, IL-6, IL-17A, MCP-1, and IL-1RA. The diagnostic algorithm was subsequently developed according to the diagnostic values obtained. MIP-1β was selected for the initial screening test to diagnose diseased patients and controls with diagnostic rates of 81.6% and 68.4%, respectively. As confirmation tests for IC/BPS, the diagnostic rates of eotaxin, CXCL10, and RANTES were 73.3%, 72.7%, and 69.7%, respectively. As the confirmation test for OAB, the diagnostic rate of IL-10 was 60%. Urine cytokine profiles of IC/BPS and OAB patients differed from those of controls and might be useful as biomarkers for diagnosis. A novel pilot diagnostic algorithm was developed based on these profiles.

Patients with ketamine cystitis had higher serum IgE than patients with interstitial cystitis/bladder pain syndrome or acute bacterial cystitis, or controls. Serum IgE and the severity of eosinophil infiltration were associated with bladder pain severity and small maximal bladder capacity.

AimsTo investigate urinary nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in interstitial cystitis/bladder pain syndrome (IC/BPS) patients after hyaluronic acid (HA) therapy.MethodsThirty-three patients with IC/BPS were prospectively studied; a group of 45 age-matched healthy subjects served as controls. All IC/BPS patients received nine intravesical HA instillations during the 6-month treatment regimen. Urine samples were collected for measuring urinary NGF and BDNF levels at baseline and 2 weeks after the last HA treatment. The clinical parameters including visual analog scale (VAS) of pain, daily frequency nocturia episodes, functional bladder capacity (FBC) and global response assessment (GRA) were recorded. Urinary NGF and BDNF levels were compared between IC/BPS patients and controls at baseline and after HA treatment.ResultsUrinary NGF, NGF/Cr, BDNF, and BDNF/Cr levels were significantly higher in IC/BPS patients compared to controls. Both NGF and NGF/Cr levels significantly decreased after HA treatment. Urinary NGF and NGF/Cr levels significantly decreased in the responders with a VAS pain reduction by 2 (both p < 0.05) and the GRA improved by 2 (both p < 0.05), but not in non-responders. Urinary BDNF and BDNF/Cr did not decrease in responders or non-responders after HA therapy.ConclusionsUrinary NGF, but not BDNF, levels decreased significantly after HA therapy; both of these factors remained higher than in controls even after HA treatment. HA had a beneficial effect on IC/BPS, but it was limited. The reduction of urinary NGF levels was significant in responders, with a reduction of pain and improved GRA.

AUR, UTI, and large PVR volume are common AEs after BoNT-A treatment. Patients with overactive bladders that are at risk of developing AEs after BoNT-A injection should be informed of the possible AEs. Neurourol. Urodynam. 36:142-147, 2017. © 2015 Wiley Periodicals, Inc.