Visible Inflammation Research Articles

Impact of smoking on peri-implant bleeding on probing.

Studies around natural dentition demonstrated that smoking can reduce the tendency of inflamed tissue to bleed upon probing after controlling for possible confounders. In addition, previous research suggested that smokers may present alterations of the peri-implant microbiome. This study aimed at investigating the impact of smoking on: (1) peri-implant bleeding on probing (BOP; primary objective); (2) the association between BOP/bone loss and BOP/visible gingival inflammation; (3) peri-implant microbiome. Partially edentulous patients with implants restored with a single crowns were included in this study. Subjects were either smokers (≥1 cigarettes per day) or nonsmokers (never smokers). The primary outcome of this cross-sectional study was BOP and secondary outcomes included: Probing pocket depth (PPD), Modified gingival Index (mGI) and Progressive Marginal Bone Loss. In addition, microbial profiles of the subjects were assessed through sequencing of the 16S rRNA gene. Univariate and multilevel multivariate analyses by means of Generalized Estimating Equations were conducted to analyze the association between smoking and peri-implant BOP. Overall, 27 nonsmokers and 27 smokers were included and 96.3% and 77.78% of patients presented peri-implant BOP in the nonsmoker and smoker group, respectively (p =0.046). Smoking was inversely associated with BOP in the multivariate multilevel analysis (OR=0.356; 95% CI: 0.193-0.660; p =0.001) whereas a positive correlation was demonstrated for mGI > 0 (OR=3.289; 95% CI: 2.014-5.371; p < 0.001); PPD (OR=1.692; 95% CI: 0.263-0.883; p =0.039) and gender (OR=2.323; 95% CI: 1.310-4.120 p =0.004). A decrease of BOP sensitivity in detecting visible gingival inflammation (mGI > 0) was observed in smokers. Besides, taxonomic and changes in diversity regarding the peri-implant microbiota were detected comparing the two groups. Significantly higher richness of the microbiota was demonstrated in the smoker group when implants affected by peri-implantitis were compared to either healthy implants or implants presenting mucositis. Smoking is a potential modifier of BOP and peri-implant microbiota.

A TNBS-Induced Rodent Model to Study the Pathogenic Role of Mechanical Stress in Crohn's Disease.

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) are chronic inflammatory disorders of the gastrointestinal tract affecting approximately 20 per 1,00,000 in Europe and USA. CD is characterized by transmural inflammation, intestinal fibrosis, and luminal stenosis. Although anti-inflammatory therapies may help control inflammation, they have no efficacy on fibrosis and stenosis in CD. The pathogenesis of CD is not well understood. Current studies focus mainly on delineating dysregulated gut immune response mechanisms. While CD-associated transmural inflammation, intestinal fibrosis, and luminal stenosis all represent mechanical stress to the gut wall, the role of mechanical stress in CD is not well defined. To determine if mechanical stress plays an independent pathogenic role in CD, a protocol of TNBS-induced CD-like colitis model in rodents has been developed. This TNBS-induced transmural inflammation and fibrosis model resembles pathological hallmarks of CD in the colon. It is induced by intracolonic instillation of TNBS into the distal colon of adult Sprague-Dawley rats. In this model, transmural inflammation leads to stenosis at the TNBS instillation site (Site I). Mechanical distention is observed in the portion proximal to the instillation site (Site P), representing mechanical stress but not visible inflammation. Colonic portion distal to inflammation (Site D) presents neither inflammation nor mechanical stress. Distinctive changes of gene expression, immune response, fibrosis, and smooth muscle growth at different sites (P, I, and D) were observed, highlighting a profound impact of mechanical stress. Therefore, this model of CD-like colitis will help us better understand CD's pathogenic mechanisms, particularly the role of mechanical stress and mechanical stress-induced gene expression in immune dysregulation, intestinal fibrosis, and tissue remodeling in CD.

Oral health care of hospitalized elderly in a Southern Brazilian public hospital

Oral health care plays a part in the integral recovery of hospitalized older people. Based on that, this study characterized the oral health care of hospitalized older people in a Brazilian public hospital. Through application of questionnaires, this cross-sectional study assessed oral health care practice by hospital nursing staff (n=31), companions (n=134) and hospitalized older people (n=200) of a public hospital in Southern Brazil. Clinical examination was conducted by two previously calibrated examiners to screen the oral health condition of the patients, considering the presence of cavitated lesions, residual roots, visible biofilm, calculus, gum inflammation and bleeding. Data were analysed descriptively. Nursing staff limits oral health assessment to surgical procedures; 55% of nurses and 58% of companions do not supervise the oral hygiene, but 81% and 96%, respectively, claim to perform oral hygiene of elderly with difficulties to do so. The elderly (51%) claimed to brush their teeth 3x/day or more; yet, their oral health was characterized by the presence of visible biofilm, calculus, gingival inflammation and bleeding and decayed teeth. Oral health advisory or assessment is not part of the hospital routine. Companions and hospital nursing staff are willing to receive oral health care information. Poor oral health was observed in hospitalized older people, which would probably be enhanced by an interdisciplinary educational approach towards oral health care to older patients.

Comprehensive Evaluation and Unique Morphologic Features of Nonsteroidal Anti-Inflammatory Drug (NSAID) Enteropathy in the Terminal Ileum.

Differentiating NSAID enteropathy from Crohn disease can be challenging on terminal ileum biopsy. It is important to distinguish these two entities for management. In this study, clinical, radiographic, endoscopic, and histologic features of 30 patients diagnosed with NSAID enteropathy and 30 patients diagnosed with Crohn disease on terminal ileal biopsy were compared. None of the patients in the NSAID cohort demonstrated significant changes on imaging performed prior to biopsy. Depending on disease severity, patients with Crohn disease showed imaging findings ranging from minimal changes to significant bowel wall and/or luminal changes. Endoscopically, erythema, erosions, and/or ulcers in the terminal ileum were observed in a majority of NSAID cases. Patients with active Crohn disease were noted to have erythema, ulcers, strictures, and/or visible inflammation throughout the distal ileum and colon. Histologically, at least 80% of cases in each cohort showed ulceration/erosion and cryptitis/crypt abscesses. The Crohn disease cohort had significantly higher degree of lymphoplasmacytic inflammation in the lamina propria compared to the NSAID cohort. In contrast, a significantly higher percentage of the NSAID cohort had gland/crypt atrophy. A decrease in number of Paneth cells was found in the NSAID cohort. Decreased lamina propria lymphoplasmacytic inflammation was the most specific and the presence of gland atrophy the most sensitive feature favoring NSAID enteropathy. In summary, the combination of gland/crypt/Paneth cell atrophy with decreased lamina propria lymphoplasmacytic inflammation can aid in differentiating NSAID enteropathy from Crohn disease in terminal ileal biopsies; however, correlation with clinical, radiographic, and endoscopic findings is still required.

Endoscopic tissue sampling - Part 2: Lower gastrointestinal tract. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE suggests performing segmental biopsies (at least two from each segment), which should be placed in different specimen containers (ileum, cecum, ascending, transverse, descending, and sigmoid colon, and rectum) in patients with clinical and endoscopic signs of colitis.Weak recommendation, low quality of evidence. 2: ESGE recommends taking two biopsies from the right hemicolon (ascending and transverse colon) and, in a separate container, two biopsies from the left hemicolon (descending and sigmoid colon) when microscopic colitis is suspected.Strong recommendation, low quality of evidence. 3: ESGE recommends pancolonic dye-based chromoendoscopy or virtual chromoendoscopy with targeted biopsies of any visible lesions during surveillance endoscopy in patients with inflammatory bowel disease. Strong recommendation, moderate quality of evidence. 4: ESGE suggests that, in high risk patients with a history of colonic neoplasia, tubular-appearing colon, strictures, ongoing therapy-refractory inflammation, or primary sclerosing cholangitis, chromoendoscopy with targeted biopsies can be combined with four-quadrant non-targeted biopsies every 10 cm along the colon. Weak recommendation, low quality of evidence. 5: ESGE recommends that, if pouch surveillance for dysplasia is performed, visible abnormalities should be biopsied, with at least two biopsies systematically taken from each of the afferent ileal loop, the efferent blind loop, the pouch, and the anorectal cuff.Strong recommendation, low quality of evidence. 6: ESGE recommends that, in patients with known ulcerative colitis and endoscopic signs of inflammation, at least two biopsies be obtained from the worst affected areas for the assessment of activity or the presence of cytomegalovirus; for those with no evident endoscopic signs of inflammation, advanced imaging technologies may be useful in identifying areas for targeted biopsies to assess histologic remission if this would have therapeutic consequences. Strong recommendation, low quality of evidence. 7: ESGE suggests not biopsying endoscopically visible inflammation or normal-appearing mucosa to assess disease activity in known Crohn's disease.Weak recommendation, low quality of evidence. 8: ESGE recommends that adequately assessed colorectal polyps that are judged to be premalignant should be fully excised rather than biopsied.Strong recommendation, low quality of evidence. 9: ESGE recommends that, where endoscopically feasible, potentially malignant colorectal polyps should be excised en bloc rather than being biopsied. If the endoscopist cannot confidently perform en bloc excision at that time, careful representative images (rather than biopsies) should be taken of the potential focus of cancer, and the patient should be rescheduled or referred to an expert center.Strong recommendation, low quality of evidence. 10: ESGE recommends that, in malignant lesions not amenable to endoscopic excision owing to deep invasion, six carefully targeted biopsies should be taken from the potential focus of cancer.Strong recommendation, low quality of evidence.

Time course of histopathological changes after bleomycin sclerotherapy in rabbit gallbladders as a model for simple hepatic cysts.

Bleomycin sclerotherapy is used in the treatment of cystic lesions; however, the histopathological changes are undefined. Present animal models of cystic diseases are not adequate for the study of sclerotherapy of hepatic cysts, primarily because the established cysts in these models are too small in size. The aim of the present study was to establish a new animal model of simple hepatic cysts, and assess the histopathological changes after bleomycin sclerotherapy. Rabbit gallbladder, with ligaturing of the cholecystic duct whilst preserving cholecystic vessels, was used as a model for simple hepatic cysts. Bleomycin (2 mg dissolved in 1 ml saline) was injected into the aspirated gallbladder, gallbladder tissue was harvested (after 1, 7, 14, 28, 42, 56 and 84 days) and histopathological changes were evaluated (n=4 per group). Additionally, control rabbit gallbladders were injected with 1 ml saline and sampled after 14 days (n=4). Histopathological changes were evaluated using hematoxylin-eosin and Masson's trichrome staining, and immunohistochemistry for CD20-, CD43- and CD68-positive cells was performed. The integrated optical density (IOD) of immunohistochemical staining and average positive stained area percentage (APSAP) of collagen were quantitatively analyzed. The results revealed gallbladders in the control group had regular epithelial cells with no visible inflammation or fibrosis. In the experimental group, epithelial cells were swollen and necrotic on the first day, and were replaced gradually by single-layer flat cells from day 56. Inflammatory infiltration was found in the submucosa, and the IOD of T cells, B cells and macrophages were highest on day 1, and these parameters declined gradually, eventually disappearing. The APSAP of collagen was highest on day 7, and gradually declined thereafter. The results suggest that histopathological changes after bleomycin sclerotherapy of a simple hepatic cyst model were characterized by sequential epithelial destruction, inflammatory cell infiltration, collagen proliferation and epithelial partial regeneration.

Assessment of Effect of Fixed Orthodontic Treatment on Gingival Health: An Observational Study.

Background:Prime components of fixed orthodontic treatments decrease the self-cleansing ability of the tongue and the cheeks leading to an increase in production of bacterial plaque. Hence, the present study was undertaken for assessing the effect of fixed orthodontic treatment on gingival health.Materials and Methods:A total of 120 patients who were scheduled orthodontic treatment were enrolled. Complete data records of all the patients were recorded. Intra- and extraoral radiographs were obtained and photographic records were noted in separate pro forma. Complete intraoral examination of all the patients was carried out for recording visible plaque, any inflammation (visible clinically), and gingival recession. Based on the assessment of gingival texture and capillary transparency, analysis of gingival biotype was done. Follow-up records were assessed.Results:The mean visible plaque value before treatment and after treatment was found to be 3.11 and 5.81, respectively. The mean visible inflammation value before treatment and after treatment was found to be 2.89 and 15.43, respectively. The mean gingival recession score value before treatment and after treatment was found to be 0.19 and 0.383, respectively. A significant increase in the visible plaque value, visible inflammation value, and gingival recession score was observed posttreatment. While comparing the gingival biotype, it was seen that in both the maxillary and mandibular arches, there was an increase in the thick gingival biotype while there was a decrease in thin maxillary biotype.Conclusion:There is a significant increase in plaque accumulation, inflammation, and gingival recession following fixed orthodontic treatment. Hence, during the course of orthodontic treatment, regular oral prophylaxis should be done.

Increased Interleukin-10 Expression by the Inhibition of Ca2+-Activated K+ Channel KCa3.1 in CD4+CD25+ Regulatory T Cells in the Recovery Phase in an Inflammatory Bowel Disease Mouse Model.

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the gastrointestinal tract arising from abnormal responses of the innate and adaptative immune systems. Interleukin (IL)-10-producing CD4+CD25+ regulatory T (Treg) cells play a protective role in the recovery phase of IBD. In the present study, the effects of the administration of the selective Ca2+-activated K+ channel KCa3.1 inhibitor TRAM-34 on disease activities were examined in chemically induced IBD model mice. IBD disease severity, as assessed by diarrhea, visible fecal blood, inflammation, and crypt damage in the colon, was significantly lower in mice administered 1 mg/kg TRAM-34 than in vehicle-administered mice. Quantitative real-time polymerase chain reaction examinations showed that IL-10 expression levels in the recovery phase were markedly increased by the inhibition of KCa3.1 in mesenteric lymph node (mLN) Treg cells of IBD model mice compared with vehicle-administered mice. Among several positive and negative transcriptional regulators (TRs) for IL-10, three positive TRs-E4BP4, KLF4, and Blimp1-were upregulated by the inhibition of KCa3.1 in the mLN Treg cells of IBD model mice. In mouse peripheral CD4+CD25+ Treg cells induced by lectin stimulation, IL-10 expression and secretion were enhanced by the treatment with TRAM-34, together with the upregulation of E4BP4, KLF4, and Blimp1. Collectively, the present results demonstrated that the pharmacological inhibition of KCa3.1 decreased IBD symptoms in the IBD model by increasing IL-10 production in peripheral Treg cells and that IL-10high Treg cells produced by the treatment with KCa3.1 inhibitor may contribute to efficient Treg therapy for chronic inflammatory disorders, including IBD. SIGNIFICANCE STATEMENT: Pharmacological inhibition of Ca2+-activated K+ channel KCa3.1 increased IL-10 expression in peripheral Treg cells, together with the upregulation of the transcriptional regulators of IL-10: Krüppel-like factor 4, E4 promoter-binding protein 4, and/or B lymphocyte-induced maturation protein 1. The manipulation of IL-10high-producing Treg cells by the pharmacological inhibition of KCa3.1 may be beneficial in the treatment of chronic inflammatory diseases such as inflammatory bowel disease.

Protective effects of Re-yan-ning mixture on Streptococcus pneumonia in rats based on network pharmacology

Context Re-yan-ning mixture (RYNM) is a new national drug approved by China's State Food and Drug Administration for the treatment of colds, simple pneumonia and acute bronchitis. Objective To determine the mechanism of action of RYNM in the treatment of bacterial pneumonia. Materials and methods Using the network pharmacology approach, the multiple components, component candidate targets and multiple therapeutic targets of RYNM were screened and functionally enriched. Also, we established a rat Streptococcus pneumonia model to verify the results of network pharmacology enrichment analysis. Forty male SPF Sprague Dawley rats were divided into four groups of 10 rats: control (normal saline), model (normal saline), levofloxacin-intervened and RYNM-intervened groups. IL-10, NOS2, COX-1, IL-6, TNF-α and NF-κB in serum and BALF were detected by ELISA. Western blot detected IL-17, IL-6, TNF-α, COX-2 and Bcl-2. Results The network pharmacology approach successfully identified 48 bioactive components in RYNM, and 65 potential targets and 138 signal pathways involved in the treatment of Streptococcus pneumonia with RYNM. The in vivo experiments indicated that model group has visible inflammation and lesions while RYNM and levofloxacin groups have not. The RYNM exhibited its therapeutic effects on Streptococcus pneumonia mainly via the regulation of cell proliferation and survival through the IL-6/IL-10/IL-17, Bax/Bcl-2, COX-1/COX-2, NF-κB and TNF-α signalling pathways. Discussion and conclusions The present study demonstrated the protective effects of RYNM on Streptococcus pneumonia, providing a potential mechanism for the treatment of bacterial pneumonia with RYNM.

Evidence Dorsal Spine Removal is Nonlethal and Unharmful for Largemouth Bass in Florida

AbstractLargemouth Bass Micropterus salmoides, Florida Bass Micropterus floridanus, and their intergrade are socially and economically valuable sport fish. In the southeastern United States, it is customary for fisheries personnel to age black bass Micropterus species using sagittal otoliths, which requires killing the fish. Presently, fisheries managers and black bass anglers show reluctance to sacrifice large individuals. Development of a nonlethal ageing technique would not only allay concerns of sacrificing large black bass, but it could offer a pathway for new research, management, and conservation. We excised dorsal spines III–V from Largemouth Bass in Florida varying from 30 to 57 cm total length to evaluate the effects of the procedure on survival over 35 d. No mortalities were observed for fish with excised dorsal spines, and experiment-wide survival was 0.94 (0.87–1.00; 95% confidence interval). No significant differences in survival, weight change, or incidence of external injuries were observed between control and excised fish. The areas of spine excision healed with no visible infection or inflammation at the conclusion of the experiment. Therefore, dorsal spine removal offers managers a nonlethal option for collecting ageing structures of adult Largemouth Bass in Florida, including large individuals, and this result likely extends to other Micropterus species as well.

Targeted Combination Antibiotic Therapy Induces Remission in Treatment-Naïve Crohn's Disease: A Case Series.

Prospective trials of anti-mycobacterial antibiotic therapy (AMAT) have proven efficacious in Crohn’s disease (CD) but use as first-line treatment in CD has not been evaluated. This paper reports the outcomes of patients with CD treated with first-line AMAT. This paper consists of a case series of treatment-naïve CD patients who received AMAT as first-line treatment between 2007 and 2014 at a single center. AMAT treatment consisted of rifabutin, clofazimine and clarithromycin, plus either ciprofloxacin, metronidazole or ethambutol. Symptoms, inflammatory blood markers, colonoscopy and histology results, in addition to, the Crohn’s Disease Activity Index (CDAI) were tabulated from patients’ clinical records, and descriptive statistics were conducted. A Wilcoxon signed-rank test assessed the difference in CDAI scores before and while on AMAT. The statistical significance was set at 5%. Clinical remission (CDAI < 150) with rapid improvement in clinical symptoms and inflammatory markers was seen in all eight patients receiving AMAT as sole therapy by 6 weeks. In all eight patients, the median CDAI score decreased significantly, from 289 prior to treatment to 62 at the 12-month follow-up (p < 0.001). Follow-up colonoscopies showed healing of CD ulcers, no visible mucosal inflammation, restoration of normal vascular patterns and complete mucosal healing on histology samples. AMAT as first-line therapy demonstrated a rapid improvement of Crohn’s disease (not previously seen when used as second-line therapy).

A161 MACROSCOPIC AND HISTOLOGY FINDINGS DURING UPPER DIGESTIVE ENDOSCOPY IN CHILDREN WITH SUSPICION OF CELIAC DISEASE AND HIGH LEVELS OF TRANSGLUTAMINASE IGA-ANTIBODY

Abstract Background The European Society of Pediatric Gastroenterology Hepatology and Nutrition suggests that the diagnosis of Celiac disease (CD) can be confirmed solely on the basis of clinical symptoms and bloodwork including a level of transglutaminase IgA-antibodies (TGA) ≥ 10 times the upper limit of normal (10XN). In Canada and the United States, this recommendation has not been endorsed. We recently demonstrated that TGA ≥ 10XN performed at our institution (INOVA Diagnostics’ Quanta Lite) was a reliable predictive test of villous atrophy in patients with suspicion of CD. Aims The aim of the present study was to investigate the rate of supplemental endoscopic or histological findings in a cohort of children with TGA ≥ 10XN and the association of these findings with clinical symptoms. Methods Consecutive children with suspected CD who had an endoscopy between 2011 and 2018 were included in this analysis. Data was extracted from our CD database. The macroscopic and histological findings were reported. We compared these diagnoses to the clinical symptoms. Results From 2011 to 2018, 405 new cases of CD were identified in our pediatric center. In total, 238 (58.7%) patients had baseline TGA levels ≥ 10XN (67.2% females, median (IQR) age 8.4 (4.8–12.2)). The median interval between the first visit to the gastroenterology unit and the endoscopy was 43.0 (21.0–78.0) days. In total, 58% of the endoscopies had macroscopic findings in the bulb (37.8 %) or the duodenum (41.5%) including a mosaic pattern, mucosal fissuring, or erythema. Seven cases (2.8%) of esophagitis were identified during endoscopy; histological analysis confirmed eosinophilic esophagitis in 3 cases (1.2%) and peptic esophagitis in 4 cases. Non-specific gastritis was present in 58 patients (24.4%) and 2 cases of Helicobacter pylori infection were identified. The biopsies showed subtotal/total villous atrophy of duodenum in 171 (71.8%) or partial villous atrophy in 51 patients (29.8 %). Ten patients (4,3%) had villous atrophy in the duodenal bulb alone, with normal biopsies of the second part of the duodenum. Abdominal pain did not correlate with gastritis or duodenitis. However, children with diarrhea had a greater prevalence of visible endoscopic inflammation in the duodenum than those without diarrhea: 53.5% vs 38.9% respectively; P= 0,037. Conclusions Apart from the classical features associated with CD, the supplementary diagnostic yield of endoscopy was low. There were only a few cases of additional diseases identified by the endoscopic procedure in a large cohort of children and adolescents with suspicion of CD. Therefore, these results support the no-biopsy approach in the settings of TGA ≥ 10XN using a reliable diagnostic kit. Funding Agencies None

Novel Liposome Aggregate Platform (LAP) system for sustained retention of drugs in the posterior ocular segment following intravitreal injection.

A novel Liposome Aggregate Platform (LAP) system for prolonged retention of drugs in the posterior eye segment after intravitreal injection (IVT) was developed and evaluated. Calcein, FITC-dextran-4000 (FD4) and Flurbiprofen (FLB), were encapsulated in negatively charged liposomes, and mixed with protamine to produce the LAP. The lipid/protamine ratio was fixed, in order to have a convenient aggregation rate permitting IVT injection and also a sustained release of liposome-entrapped molecules (in vitro) from LAP. In vitro release studies confirmed the potential of LAP system consisted of HPC/DPPG/Chol liposomes and protamine (at 1:1 w/w to lipid), to delay calcein, FD4 and FLB release, compared to free liposomes. In vivo studies demonstrated increased vitreous retention of liposomes and LAP for all molecules, compared to the corresponding solutions; however the retention of FD4 is similar for non-aggregated liposomes and LAP, and calcein retention is only slightly increased by LAP compared to liposomes. The later result may be connected with the visible ocular inflammation caused by both dyes; interestingly inflammation was moderately reduced when dyes were entrapped in liposomes and even more when in LAP. No visible inflammation was demonstrated for FLB, and the LAP system significantly increased the retention of FLB in the ocular tissues (compared to non-aggregated liposomes). Taking into account the capability of the novel LAP system to decrease inflammatory reactions towards calcein and FD4, and prolong the retention of FLB in ocular tissues, it is concluded that such systems, after further optimization, may be considered as promising effective and safe approaches for treatment of posterior segment ocular pathologies.

Benign T cells drive clinical skin inflammation in cutaneous T cell lymphoma.

Psoralen plus UVA (PUVA) is an effective therapy for mycosis fungoides (MF), the skin-limited variant of cutaneous T cell lymphoma (CTCL). In low-burden patients, PUVA reduced or eradicated malignant T cells and induced clonal expansion of CD8+ T cells associated with malignant T cell depletion. High-burden patients appeared to clinically improve but large numbers of malignant T cells persisted in skin. Clinical improvement was linked to turnover of benign T cell clones but not to malignant T cell reduction. Benign T cells were associated with the Th2-recruiting chemokine CCL18 before therapy and with the Th1-recruiting chemokines CXCL9, CXCL10, and CXCL11 after therapy, suggesting a switch from Th2 to Th1. Inflammation was correlated with OX40L and CD40L gene expression; immunostaining localized these receptors to CCL18-expressing c-Kit+ dendritic cells that clustered together with CD40+OX40+ benign and CD40+CD40L+ malignant T cells, creating a proinflammatory synapse in skin. Our data suggest that visible inflammation in CTCL results from the recruitment and activation of benign T cells by c-Kit+OX40L+CD40L+ dendritic cells and that this activation may provide tumorigenic signals. Targeting c-Kit, OX40, and CD40 signaling may be novel therapeutic avenues for the treatment of MF.

The role of the pathologist in the assessment of disease activity in ulcerative colitis

In order to determine the role of the pathologist in assessing disease activity in UC, clinical and histological correlation of disease activity, correlation between endoscopy and histology and determining the most satisfactory method of scoring histological activity were assessed. A cohort of 41 patients attending a gastroenterology clinic in a tertiary hospital in Sri Lanka was studied. Their clinical activity was determined based on the simple clinical colitis activity index (SCCAI), endoscopically visible inflammation was recorded with reference to the extent of involvement and histology was assessed using three different histological scoring systems. The Spearman rank correlation coefficients between SCCAI and the three histological scoring systems were 0.298, 0.286, and 0.238 respectively denoting poor correlation. The kappa value of agreement between endoscopy and histology was poor (k=0.136). The Spearman rank correlation coefficients between the three histological scoring systems were 0.883, 0.883 and 0.952, reaching a level of statistical significance (p<0.01). The clinical activity and histological activity do not correlate and this is especially when assessing the more proximal colon. Endoscopy and histology also shows no correlation highlighting the importance of microscopic assessment of endoscopically normal mucosa. Finally, the histological scoring systems correlate fairly closely with one another enabling histopathologists to choose one that is most practical for routine use.

Reactivity of corneal and conjunctival epithelial cells to lipopolysaccharide (LPS) and/or irradiation with visible light in vitro

INTRODUCTION. Visible light and inflammation caused by bacterial endotoxins strongly influence direct cell interactions and modulate the expression of selected factors, such as nitric oxide (NO) and cyclooxygenase-2 (COX-2). The aim of the study is to establish whether exposition of corneal or conjunctival epithelial cells to visible light and/ or LPS may change their viability, direct cellular interactions and expression of NO and COX-2. MATERIALS AND METHODS. In vitro cultured human corneal and conjunctival epithelial cells were used in the study. The following assays were performed: Neutral Red (NR) uptake, nitric oxide (NO) quantification by the Griess method, cytoskeletal F-actin organization by fluorescent staining, and COX-2 expression by immunofluorescence. RESULTS. LPS reduced the viability of the cells, especially conjunctival epithelial cells. All cell stimulation variants tested (visible light and/or LPS treatment) led to decreased nitric oxide (NO) production both by corneal and conjunctival epithelial cells. No changes in cytoskeletal F-actin filaments were observed after the cells had been treated with light or the endotoxin. LPS slightly increased COX-2 expression, but light had no, or a slightly reducing, effect on the level of this enzyme. CONCLUSIONS. Visible light and/or bacterial endotoxin (LPS) may, depending on the local microenvironmental conditions, cooperate or interfere with each other’s activity in inducing ocular surface inflammation.

Network pharmacology-based identification of protective mechanism of Panax Notoginseng Saponins on aspirin induced gastrointestinal injury.

Aspirin is the first line therapy for cardiovascular and cerebrovascular diseases and is widely used. However aspirin-induced gastrointestinal injury is one of its most common side effect which limits long-term use. Panax Notoginseng Saponins(PNS) which is also used to prevent thrombus may alleviate this side effect according to previous clinical evidences. Owing to the complexity of drug combination, the protective mechanism of PNS on aspirin-induced gastrointestinal injury remains unclear. Therefore, a network pharmacology-based strategy was proposed in this study to address this problem. A network pharmacology approach comprising multiple components, candidate targets of each component, known therapeutic targets, network analysis has been used in this study. Also, we establish aspirin-induced gastrointestinal injury model by the oral administration of aspirin (0.5 g/kg body weight) to verify the predicted targets from network pharmacology. All rats was randomly allocated to control groups (n = 6),aspirin groups (n = 6)and aspirin + PNS groups (n = 6) and conducted H&E staining and ELISA for VEGFA. The comprehensive systematic approach was successfully to identify 5 compounds and 154 candidate targets in PNS and 479 candidate targets in aspirin. After network establishment and analysis, 27 potential targets hit by PNS, aspirin and 6 kind of gastrointestinal diseases were found. The experiments results indicated that aspirin group has visible inflammation and lesions while aspirin + PNS group have not. The higher expression of VEGFA in aspirin + PNS group verified the predicted potential protective targets of PNS. PNS may have protective function for aspirin-induced gastrointestinal injury through increasing VEGFA expression. Network pharmacology strategy may provide a forceful tool for exploring the mechanism of herb medicine and discovering novel bioactive ingredients.

481 Benign T cells drive visible inflammation in cutaneous T cell lymphoma

481 Benign T cells drive visible inflammation in cutaneous T cell lymphoma

Assessing treatment outcomes in multiple sclerosis trials and in the clinical setting.

Increasing numbers of drugs are being developed for the treatment of multiple sclerosis (MS). Measurement of relevant outcomes is key for assessing the efficacy of new drugs in clinical trials and for monitoring responses to disease-modifying drugs in individual patients. Most outcomes used in trial and clinical settings reflect either clinical or neuroimaging aspects of MS (such as relapse and accrual of disability or the presence of visible inflammation and brain tissue loss, respectively). However, most measures employed in clinical trials to assess treatment effects are not used in routine practice. In clinical trials, the appropriate choice of outcome measures is crucial because the results determine whether a drug is considered effective and therefore worthy of further development; in the clinic, outcome measures can guide treatment decisions, such as choosing a first-line disease-modifying drug or escalating to second-line treatment. This Review discusses clinical, neuroimaging and composite outcome measures for MS, including patient-reported outcome measures, used in both trials and the clinical setting. Its aim is to help clinicians and researchers navigate through the multiple options encountered when choosing an outcome measure. Barriers and limitations that need to be overcome to translate trial outcome measures into the clinical setting are also discussed.

Macular Edema in Uveitis - Steroids or VEGF Inhibitors?

Macular edema in uveitis patients is certainly the most frequent complication leading to a permanent and irreversible reduction in vision during the course of the disease. Thanks to optical coherence tomography (OCT) technology and fluorescein angiography (FAG), significantly more macular edemas are detected. Macular edema can be found in various uveitis varieties and can show different clinical patterns. All macular edema should be treated. Macular edema with active inflammation usually reacts very well to general uveitis treatment. In the case of eyes without visible inflammation, however, the response to such therapy is usually less effective. According to the latest treatment recommendations, dexamethasone implants should be used as the first intravitreal therapy. Vascular endothelial growth factor inhibitors (VEGF inhibitors) are second-line treatment regimens. The choice of therapy is, therefore, primarily based on the degree of inflammation and the individual complications, such as glaucoma, lens situation or previous increase in IOP after steroid administration. These individual complications may allow using VEGF inhibitors as first line treatment. An improvement in the macular edema can be achieved with both groups of active substances.