Cross-talk between human T cells, mast cells and conjunctival epithelial cells

The ocular surface is continually exposed to the outside environment and is a common site of inflammation. Conjunctival epithelial cells are thought to play a role in innate responses at the ocular surface. The hypothesis of my study is that conjunctival epithelial cells also contribute to T cell and mast cell effector mechanisms in chronic allergic eye disease via secretion of cytokines. In this study we initially demonstrate that the conjunctiva expresses TLRs, and that the TLR3 ligand (poly I:C) activates conjunctival epithelial cells in vitro to secrete inflammatory mediators as part of the innate immune response. Conjunctival tissues were also shown to express the Th2 associated cytokine, IL-13 as well as TSLP – a cytokine thought to be involved in Th2 differentiation. Conjunctival tissues from chronic allergic eye disease subjects were found to have increased IL-13 and TSLP expression compared to normal controls. Using a human conjunctival epithelial cell line, cells could be induced to express increased levels of TSLP following exposure to poly I:C or pro-inflammatory cytokines. Th17 cells, identified by coexpression of CD4 and IL-17, were also detected in CAED tissues and a high level of expression of IL-17A was localised to the epithelium. However, although capable of secreting IL- 25, IL-17A was not secreted by conjunctival epithelial cells, indicating that the IL-17 observed histologically may have been IL-17 binding to the surface of the epithelium. IL-17 receptor C (IL-17RC) expression was found to be increased in CAED tissues whilst IL-17RA was upregulated when conjunctival epithelial cells were stimulated with pro-inflammatory cytokines together with poly I:C. Blockade of IL-17RA and subsequent stimulation with IL-17 led to increased IL-8 and decreased TGF-β secretion. Although being implicated in the immunopathogenesis of certain diseases, IL-17 and its other family members may potentially serve to play an immunoregulatory role in immunity at the ocular surface

Neuromodulation for Pelvic and Urogenital Pain

Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. However, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. The aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. Our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. However, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes.</jats:p

Diagnosis of vertebral fractures in children: is a simplified algorithm-based qualitative technique reliable?

Background Identification of osteoporotic vertebral fractures allows treatment opportunity reducing future risk. There is no agreed standardised method for diagnosing paediatric vertebral fractures. Objective To evaluate the precision of a modified adult algorithm-based qualitative (ABQ) technique, applicable to children with primary or secondary osteoporosis. Materials and methods Three radiologists independently assessed lateral spine radiographs of 50 children with suspected reduction in bone mineral density using a modified ABQ scoring system and following simplification to include only clinically relevant parameters, a simplified ABQ score. A final consensus of all observers using simplified ABQ was performed as a reference standard for fracture characterisation. Kappa was calculated for interobserver agreement of the components of both scoring systems and intraobserver agreement of simplified ABQ based on a second read of 29 randomly selected images. Results Interobserver Kappa for modified ABQ scoring for fracture detection, severity and shape ranged from 0.34 to 0.49 Kappa for abnormal endplate and position assessment was 0.27 to 0.38. Inter- and intraobserver Kappa for simplified ABQ scoring for fracture detection and grade ranged from 0.37 to 0.46 and 0.45 to 0.56, respectively. Inter- and intraobserver Kappa for affected endplate ranged from 0.31 to 0.41 and 0.45 to 0.51, respectively. Subjectively, observers’ felt simplified ABQ was easier and less time-consuming. Conclusion Observer reliability of modified and simplified ABQ was similar, with slight to moderate agreement for fracture detection and grade/severity. Due to subjective preference for simplified ABQ, we suggest its use as a semi-objective measure of diagnosing paediatric vertebral fracture

In vivo investigation of female reproductive functions and parameters in nonpregnant mice models and mass spectrometric analysis of the methanol leaf extract of Emilia Coccinea (Sims) G Dons

In Southern Nigeria, the leaves of Emilia coccinea (Sims) G Dons are used traditionally for birth control. This study was therefore aimed at evaluating the activities of the methanolic leaf extract of Emilia coccinea (EM) on parameters that affect reproduction as well as the acute toxic effects of the plant using nonpregnant female mice models. Leaves of EM were extracted by maceration with 99.8% methanol. Oral acute toxicity profiles were examined. The effects of EM on female reproductive cycle were determined after oral treatment with EM at 1000 and 100 mg/kg/day daily for 6 days using stilbesterol (1 mg/kg/day) and normal saline as controls. The activities of EM (1000 mg/kg/day and 100 mg/kg/day p.o) on reproductive hormones and organs were also studied using estradiol valerat (100 mg/kg/day p.o), progesterone (10 mg/kg/day s.c.), and normal saline as controls. The extract did not induce any observable toxic effect after 24 h. At 1000 mg/kg, the extract significantly shortened the estrus cycle (P < 0.05) while prolonging the estrus phase which were comparable to that observed with stilbesterol. The extract also increased uterine weight and altered the histology of uterine and ovarian tissues. The female reproductive hormones were additionally altered at 1000 mg/kg and the effects were comparable to that of estradiol valerat such as to indicate possible antifertility effects. LC-HRFTMS analysis showed 9 putatively identified compounds with pyrrolizidine alkaloid occurring at the highest intensity among the identified compounds. In conclusion, the leaf extracts of EM has been shown in this study to exhibit antiovulatory and estrogenic activities which would support the traditional use of the plant in Nigeria

Prospective comparative study of the effects of lidocaine on urodynamic and sensory parameters in bladder pain syndrome

Introduction and hypothesis: Intravesically administered lidocaine is used in patients with bladder pain syndrome (BPS) to test the hypothesis that symptoms have a peripheral versus central mechanism. Methods: A cross-sectional study of 24 female patients with BPS was performed. The Central Sensitisation Inventory (CSI) and Kings Health Questionnaire (KHQ) were completed. Urodynamic assessment was undertaken. Women were asked to report their pain using a numeric rating scale at cystometric capacity and post void. Participants then received an intravesical instillation of either 20 ml of 2% alkalinised lidocaine (n = 16) or 20 ml of normal saline (n = 8). These solutions were allowed to remain in situ for 20 min and pain score repeated. Urodynamics was repeated. Results: There was a statistically significant volume increase following lidocaine treatment: maximal cystometric capacity (MCC) 192–261 ml post lidocaine (p = 0.005.) In contrast, there was no significant difference in the saline controls: MCC 190–183 ml (p = 0.879.) Individual analysis revealed five of 16 lidocaine participants did not respond to lidocaine. These five reported a significantly worse quality of life (QoL) than lidocaine responders and had a tendency towards central sensitivity syndromes. Conclusion: Lidocaine significantly improved MCC in 11/16 participants in this study. These patients appear to have peripherally mediated disease. However, the failure of response to treatment in five participants, as well as their tendency towards central sensitivity syndromes, implies that in this subgroup, a peripheral drive from the bladder is not critical to their pain, suggesting central nervous system (CNS) pathology. This simple and safe test could be used to stratify patients for research or therapeutic trials

Diagnostic accuracy of DXA compared to conventional spine radiographs for the detection of vertebral fractures in children

Objectives In children, radiography is performed to diagnose vertebral fractures and dual energy x-ray absorptiometry (DXA) to assess bone density. In adults, DXA assesses both. We aimed to establish whether DXA can replace spine radiographs in assessment of paediatric vertebral fractures. Methods Prospectively, lateral spine radiographs and lateral spine DXA of 250 children performed on the same day were independently scored by three radiologists using the simplified algorithm based qualitative technique and blinded to results of the other modality. Consensus radiograph read and second read of 100 random images were performed. Diagnostic accuracy, inter/intraobserver and intermodality agreements, patient/carer experience and radiation dose were assessed. Results Average sensitivity and specificity (95% confidence interval) in diagnosing one or more vertebral fractures requiring treatment was 70% (58%-82%) and 97% (94%- 100%) respectively for DXA and 74% (55%-93%) and 96% (95%-98%) for radiographs. Fleiss’ kappa for interobserver and average kappa for intraobserver reliability were 0.371 and 0.631 respectively for DXA and 0.418 and 0.621 for radiographs. Average effective dose was 41.9µSv for DXA and 232.7µSv for radiographs. Image quality was similar. Conclusion Given comparable image quality and non-inferior diagnostic accuracy, lateral spine DXA should replace conventional radiographs for assessment of vertebral fractures in children

The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

Background: Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. Objective: We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Design, setting, and participants: Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. Outcome measures and statistical analysis: We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Results and limitations: Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Conclusions: Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. Patient summary: We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy