Inhibitive effect of TAK-242 on Tenon’s capsule fibroblasts proliferation in rat eyes

AIM: To study the inhibition effect of TAK-242 on the proliferation of rat eye Tenon's capsule fibroblasts via the toll-like receptor 4(TLR4) signaling pathway.METHODS: SD rat Tenon's capsule fibroblasts were extracted and cultured, then the cells were divided into normal control group, lipopolysaccharide(LPS) group(10 g/m L LPS) and TAK-242 group(1 μmol/L TAK-242, and 10 μg/m L LPS after 30 min). The expressions of TLR4, transforming growth factor-β1(TGF-β1) and interleukin-6(IL-6) in each group were detected by Western blot and reverse transcriptase-polymerase chain reaction(RT-PCR). Cell proliferation was detected by cell counting kit-8(CCK-8).RESULTS: Double immunofluorescent labeling in the extracted cells showed negative keratin staining and positive vimentin staining. Western blot showed that the LPS group had the highest expression of TLR4 and TGF-β1(P<0.01). Enzyme linked immunosorbent assay(ELISA) also showed that the secretion of IL-6 was the highest in LPS group(P<0.01). But there was no significant difference in TLR4 and TGF-1, as well as IL-6 expressions between the TAK-242 group and the normal control group(P>0.05). RT-PCR showed that the IL-6 m RNA expression in LPS group was the highest in the three groups(P<0.01). CONCLUSION: TAK-242 inhibits the proliferation of LPSinduced Tenon's capsule fibroblasts and the release of inflammatory factors by regulating the TLR4 signalingpathway, providing a new idea for reducing the scarring of the filter passage after glaucoma filtration surgery.

Capsule endoscopy and panendoscopy:A journey to the future of gastrointestinal endoscopy

In 2000,the small bowel capsule revolutionized the management of patients with small bowel disorders.Currently,the technological development achieved by the new models of double-headed endoscopic capsules,as miniaturized devices to evaluate the small bowel and colon[pan-intestinal capsule endoscopy(PCE)],makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders.This technology is expected to identify which patients will require conventional invasive endoscopic procedures(colonoscopy or balloon-assisted enteroscopy),based on the lesions detected by the capsule,i.e.,those with an indication for biopsies or endoscopic treatment.The use of PCE in patients with inflammatory bowel diseases,namely Crohn’s disease,as well as in patients with iron deficiency anaemia and/or overt gastrointestinal(GI)bleeding,after a non-diagnostic upper endoscopy(esophagogastroduodenoscopy),enables an effective,safe and comfortable way to identify patients with relevant lesions,who should undergo subsequent invasive endoscopic procedures.The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract,is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract,from mouth-to-anus,meeting the expectations of the early developers of capsule endoscopy.

Interference of Y-27632 on the signal transduction of transforming growth factor beta type 1 in ocular Tenon capsule fibroblasts

AIM: To investigate the interfering effect of Y-27632, a ROCK-I selective inhibitor, on the signal transduction pathway of transforming growth factor-beta 1 (TGF-beta 1) in ocular Tenon capsule fibroblasts (OTFS) in vitro. METHODS: After OTFS from passages 4 to 6 47 vitro were induced by TGF-beta 1 and then treated by Y-27632, the changes of the OTFS cell cycles were analyzed via flow cytometry, and the proteins expression of the alpha -smooth muscular actin (alpha -SMA), connective tissue growth factor (CTGF), collagen I were calculated by Western blot. After OTFS treated by the different concentrations of Y-27632, the expression levels of the alpha -SMA, CTGF and collagen I mRNA were assayed by RT-PCR. RESULTS: Y-27632 had no markedly effect on the OTFS cell cycles. After treated by TGF-beta 1, OTFS in G1 period significantly increased. The cell cycles distribution by both TGF-beta 1 and Y-27632 had no remarkable difference from that in control group. Y-27632 significantly inhibited the proteins expressions of both alpha -SMA and CTGF, while to some extent inhibited that of collagen I. TGF-beta 1 significantly promoted the proteins expressions of alpha -SMA, CTGF and collagen I. After OTFS treated by both TGF-beta 1 and Y-27632, of alpha -SMA, the protein expression was similar with that in control group (P=0.066>0.05), but the protein expression of CTGF or collagen I, respectively, was significantly different from that in control group (P=0.000<0.01). The differences of expressions of the alpha -SMA, CTGF and collagen I mRNA in 30, 150, 750 mu mol/L Y-27632 group were statistically significant, compared with those in control group, respectively (alpha -SMA, P=0.002, 0.000, 0.000; CTGF, P=0.014, 0.002, 0.001; collagen I,P=0.003, 0.002, 0.000). CONCLUSION: Blocking the Rho/ROCK signaling pathway by using of Y-27632 could inhibit the cellular proliferation and the expression of both CTGF and alpha -SMA whatever OTFS induced by TGF-beta 1 or not. Y-27632 suppressed the expression of collagen I mRNA without induction.

Effect of Apigenin on Gap Junctional Intercellular Communication in Human Tenon's Capsule Fibroblasts

Purpose:To investigate the effect of apigenin on gap junctional intercellular communication (GJIC) in human Tenon's capsule fibroblasts (HTFs) and its underlying mechanism. Methods:After a 48 h treatment of cultured HTFs with apigenin.(80 μmol/L),the GJIC was detected by a scrape-loading/dye transfer technique with Lucifer yellow dye and rhodamine (Rh) dextran. The coupling index represents a quantification of GJIC where a high coupling index is associated with a greater number of cells demonstrating cell-cell communication through gap junction channels.The changes in connexin 43 (Cx43) distribution and the expression of Cx43 at the protein and mRNA levels were statistically compared between the two groups by means of immunocytochemistry, western blotting,and real-time polymerase chain reaction (PCR). Results:The functioning of GJIC in the HTFs was significantly enhanced after 48 hours by apigenin treatment when compared with the control cells. In the apigenin group, the intercellular dye transfer grade was above 9, while this value was only grade 3-4 in the control group. The coupling index was significantly increased up to 9.205±0.3621 in the apigenin group,compared with 5.1775 ±0.3177 in the control group (F=279.581, P=0.000). The expression of Cx43 at the protein and mRNA levels was significantly up-regulated in the apigenin group compared with the control group. Conclusion:Apigenin can significantly enhance the function of GJIC in HTFs by up-regulating the expression of Cx43 at both the protein and mRNA levels,suggesting that the enhancement of GJIC in HTFs by apigenin probably acts as an important mechanism underlying the inhibitory effect of apigenin on HTF proliferation.

Bifunctional Effect of Human IFN-γ on Cultured Human Fibroblasts from Tenon's Capsule

Purpose:To study the effect of human IFN-γon in vitro cultured human fibroblasts form Tenon's capsule.Materials and methods:The effect of different concentrations of human INF-γand mitomycin-C(MMC),5-fluorouracil(5-Fu）on cultured human Tenon's capsule fibroblasts(HTCF)was measured using a MTT[3-(4,5-dimethylthiazo-2-yl)]-2,5-diphenyltetrazolium bromide;Thiazolyl blue)colorimetric assay,The results were analyzed using ANOVA of the statistical package for social sciences(SPSS)9.0 version.The difference was considered to be significant if P<0.05.Results:The effects of MMC and 5-Fu on the growth of HTCF were negative,while the effects of IFN-γon the growth of HTCF were both negative(10^2-10^4units/ml in two experiments)and positive(10^6,10^5,10units/ml in two experiments).The inhibition rate of MMC ranged from5.73%to46.9%,which was similar to the inhibition rate of 5-Fu ranged from12.49%to38.92%(P=0.351),The inhibition rate of IFN-γin two experiments was smaller than MMC and 5-Fu(P<0.05).Conclusion:IFN-γhas bifunctional effect(both enhancement and inhibition)on proliferation of cultured HTCF,The antiproliferative effect of IFN-γwas weatker than MMCand 5-FU,Further study has to bd carride out to document the inhibition of scar formation of filtration bleb by IFN-γand the molecular mechanisms of its bifunctional effect on HTCF proliferation.Eye Science2000;16:43-47.

How much helpful is the capsule endoscopy for the diagnosis of small bowel lesions?

AIM： To assess the practically usefulness and diagnostic yield of this new method in a group of patients with suspected small bowel lesions. METHODS： Capsule endoscopic （CE） examination by using M2A capsule endoscope TM （Given Imaging, Yoqneam, Israel） was performed in thirty nine patients （26 males, 13 females） with suspected small intestinal lesions. The composing of the patients was as follows： obscure gastrointestinal bleeding in twenty three patients, known Crohn＇s disease in 6 patients, in whom CE was used to evaluate the severity and extension of the diseases, chronic diarrhea in 8 patients, abdominal pain in one patient and malignancy in one patient with unknown origin. RESULTS： In two patients CE failed. Different abnormalities were revealed in 26 patients overall. Detection rate of abnormalities was highest among patients with obscure gastrointestinal bleeding and the source of bleeding was demonstrated in 17 of 23 patients with obscure bleeding （73.9%）. Entero-Behcet was diagnosed in two patients by CE as a source of obscure gastrointestinal bleeding. In 6 patients with known Crohn＇s disease, CE revealed better evaluation of the disease extension. In 3 of 8 （37.5%） patients with chronic diarrhea; CE revealed some mucosal abnormalities as the cause of chronic diarrhea. In a patient with unexplained abdominal pain and in a cancer patient with unknown origin, CE examination was normal. CONCLUSION： In our relatively small series, we found that capsule endoscopy is a useful diagnostic tool particularly in diagnosis of obscure gastrointestinal bleeding, chronic diarrhea and in estimating the extension of Crohn＇s disease.

Expanding role of capsule endoscopy in inflammatory bowel disease

Capsule endoscopy has been shown to detect small bowel inflammatory changes better than any other imaging modality. Selection criteria have been optimized to increase the yield of capsule endoscopy in patients suspected to have Crohn's disease. Capsule endoscopy allows for earlier diagnosis of Crohn's disease of the small bowel and improved diagnosis of colitis in patients where it is unclear if they suffer from Crohn's or ulcerative colitis. A test capsule is available to assess for small bowel strictures and thus avoid capsule retention. A common language has been developed and a new scoring index will be added to capsule software. It is envisioned that the manner in which we treat Crohn's disease in the future will change, based on earlier diagnosis and treatment aimed at mucosal healing rather than symptom improvement.

Longest duration of retention of video capsule: A case report and literature review

Video capsule endoscopy (VCE) is a safe innovative tool for investigating obscure gastrointestinal bleeding, Crohn's disease and other small bowel pathologies. The capsule is usually excreted with faeces within 24-48 h. Retention of capsule rarely occurs, and it usually depends on the indication of VCE. The longest reported case of capsule retention in the literature is 2.5 years. Surgical approach is considered effective to retrieve the retained capsule. We present a case of asymptomatic retention of capsule for four and half years in a 49-year-old man who underwent VCE to explore the cause of obscure gastrointestinal bleeding. It was successfully retrieved endoscopically. We will also briefly review the literature regarding the causes, different presentations and management of capsule retention.

Five years' experience with capsule endoscopy in a single center

Capsule endoscopy (CE) is a novel technology that facilitates highly effective and noninvasive imaging of the small bowel. Although its effi cacy in the evaluation of obscure gastrointestinal bleeding (OGIB) has been proven in several trials, data on uses of CE in different small bowel diseases are rapidly accumulating in the literature, and it has been found to be superior to alternative diagnostic tools in a range of such diseases. Based on literature evidence, CE is recommended as a first-line investigation for OGIB after negative bi-directional endoscopy. CE has gained an important role in the diagnosis and follow-up of Crohn's disease and celiac disease and in the surveillance of small bowel tumors and polyps in selected patients. Capsule retention is the major complication, with a frequency of 1%-2%. The purpose of this review was to discuss the procedure, indications, contraindications and adverse effects associated with CE. We also review and share our five-year experience with CE in various small bowel diseases. The recently developed balloon-assisted enteroscopies have both diagnostic and therapeutic capability. At the present time, CE and balloon-assisted enteroscopies are complementary techniques in the diagnosis and management of small bowel diseases.

Potential of hybrid adaptive filtering in inflammatory lesion detection from capsule endoscopy images

A new feature extraction technique for the detection of lesions created from mucosal inflammations in Crohn's disease, based on wireless capsule endoscopy(WCE) images processing is presented here. More specifically, a novel filtering process, namely Hybrid Adaptive Filtering(HAF), was developed for efficient extraction of lesion-related structural/textural characteristics from WCE images, by employing Genetic Algorithms to the Curvelet-based representation of images. Additionally, Differential Lacunarity(DLac) analysis was applied for feature extraction from the HAF-filtered images. The resulted scheme, namely HAF-DLac, incorporates support vector machines for robust lesion recognition performance. For the training and testing of HAFDLac, an 800-image database was used, acquired from 13 patients who undertook WCE examinations, where the abnormal cases were grouped into mild and severe, according to the severity of the depicted lesion, for a more extensive evaluation of the performance. Experimental results, along with comparison with other related efforts, have shown that the HAF-DLac approach evidently outperforms them in the field of WCE image analysis for automated lesion detection, providing higher classification results, up to 93.8%(accuracy), 95.2%(sensitivity), 92.4%(specificity) and 92.6%(precision). The promising performance of HAF-DLac paves the way for a complete computer-aided diagnosis system that could support physicians' clinical practice.

Wireless capsule endoscopy

Wireless capsule endoscopy is a new technique that allows complete exploration of the small bowel without exlemal wires. Its role has been analyzed in many small bowel diseases such as obscure gastrointestinal bleeding, Crohn＇s disease and gastrointestinal polyposis syndromes with promising results. Studies on other pathologies （i.e. small bowel tumour, celiac disease） are under evaluation to define the role of this technique.

Capsule endoscopy

Capsule endoscopy(CE) is a simple,safe,non-invasive,reliable technique,well accepted and tolerated by the patients,which allows complete exploration of the small intestine.The advent of CE in 2000 has dramatically changed the diagnosis and management of many diseases of the small intestine,such as obscure gastrointestinal bleeding,Crohn's disease,small bowel tumors,polyposis syndromes,etc.CE has become the gold standard for the diagnosis of most diseases of the small bowel.Lately this technique has also been used for esophageal and colonic diseases.

Wireless capsule endoscopy and proximal small bowel lesions in Crohn’s disease

AIM: To investigate the prevalence of proximal small bowel (SB) lesions detected by wireless capsule endoscopy (WCE) in Crohn's disease (CD). METHODS: WCE was performed in 64 patients: 32 with CD of the distal ileum, and 32 controls with iron-deficiency anemia (IDA) or diarrhea. WCE was performed using the Given SB-WCE, followed by small intestine contrast ultrasonography (SICUS). Findings compatible with CD by using WCE included erosions, aphthoid or deep ulcers, and strictures/stenosis. RESULTS: WCE detected proximal SB lesions in 16/32 (50%) patients (14 aphthoid ulcers, 2 deep ulcers, one stricture), which appeared not to be related to clinical parameters [epigastric pain, age, smoking, non-steroidalanti-inflammatory drugs (NSAIDs), IDA]. Among patients with proximal SB lesions, 6 (37%) were smokers, 3 (19%) NSAID users, 3 (19%) had epigastric pain and 4 (25%) had IDA. SICUS detected proximal SB lesions in 3/32 patients (19%) also showing lesions with WCE. No correlations were observed between proximal SB lesions assessed by WCE or by SICUS (χ2 = 1.5, P = 0.2). CONCLUSION: The use of WCE allows the detection of previously unknown upper SB lesions in a high proportion of patients with a previous diagnosis of CD involving the distal ileum.

Capsule endoscopy in suspected small bowel Crohn's disease:Economic impact of disease diagnosis and treatment

AIM: To model clinical and economic benef its of capsule endoscopy (CE) compared to ileo-colonoscopy and small bowel follow-through (SBFT) for evaluation of suspected Crohn’s disease (CD). METHODS: Using decision analytic modeling, total and yearly costs of diagnostic work-up for suspected CD were calculated, including procedure-related adverse events, hospitalizations, off ice visits, and medications. The model compared CE to SBFT following ileo-colonoscopy and secondarily compared CE to SBFT for initial evaluation. RESULTS: Aggregate charges for newly diagnosed, medically managed patients are approximately $8295. Patients requiring aggressive medical management costs are $29 508; requiring hospitalization, $49 074. At sensitivity > 98.7% and specifi city of > 86.4%, CE is less costly than SBFT. CONCLUSION: Costs of CE for diagnostic evaluationof suspected CD is comparable to SBFT and may be used immediately following ileo-colonoscopy.

Prospective postsurgical capsule endoscopy in patients with Crohn's disease

AIM: To clarify the usefulness of postsurgical capsule endoscopy(CE) in the diagnosis of recurrent small bowel lesions of Crohn's disease(CD). METHODS: This prospective study included 19 patients who underwent ileocolectomy or partial ileal resection for CD. CE was performed 2-3 wk after surgery to check for the presence/absence and severity of lesions remaining in the small bowel, and for any recurrence at the anastomosed area. CE was repeated 6-8 mo after surgery and the findings were compared with those obtained shortly after surgery. The Lewis score (LS) was used to evaluate any inflammatory changes of the small bowel. RESULTS: One patient was excluded from analysis because of insufficient endoscopy data at the initial CE. The total LS shortly after surgery was 428.3 on average(median, 174; range, 8-4264), and was ≥ 135(active stage) in 78%(14 of 18) of the patients. When the remaining unresected small bowel was divided into 3 equal portions according to the transition time(proximal, middle, and distal tertiles), the mean LS was 286.6, 83.0, and 146.7, respectively, without any significant difference. Ulcerous lesions in the anastomosed area were observed in 83% of all patients. In 38% of the 13 patients who could undergo CE again after 6-8 mo, the total LS was higher by ≥ 100 than that recorded shortly after surgery, thus indicating a diagnosis of endoscopic progressive recurrence. CONCLUSION: Our pilot study suggests that CE can be used to objectively evaluate the postoperative recurrence of small bowel lesions after surgery for CD.

Small bowel video capsule endoscopy in Crohn’s disease: What have we learned in the last ten years?

Since its introduction in 2001, capsule endoscopy (CE) has become the most important advance in the study of small bowel disease, including Crohn's disease (CD). This technique has been demonstrated to be superior to all other current forms of radiological investigation in detecting mucosal abnormalities of small bowel nonstricturing CD. CE has proven to be extremely useful in diagnosing CD in patients with inconclusive findings from ileocolonoscopy and x-ray-based studies. Almost half of all patients with CD involving the ileum also present lesions in proximal intestinal segments, with the small bowel being exclusively involved in up to 30% of all CD cases. Despite the widespread use of CE, several questions concerning the utility of this technique remain unanswered. The lack of commonly agreed diagnostic criteria for defining CD lesions with the aid of CE may have had an influence on the variation in diagnostic re sults for CE reported in the literature. The utility of CE in monitoring CD and in guiding therapy has also been proposed. Furthermore, CE could be a useful second-line technique for patients with an established diagn osis of CD and unexplained symptoms. Finally, as no thres hold for CD diagnosis has been agreed upon, a se verity scale of mucosal disease activity has notbeen universally followed. None of the available activity indexes based on CE findings has been independently validated. This article discusses several cutting-edge aspects of the usefulness of CE in CD 10 years after its introduction as a sensible method to study the small intestine.

Does capsule endoscopy have an added value in patients with perianal disease and a negative work up for Crohn's disease?

AIM:To investigate the role of capsule endoscopy in patients with persistent perianal disease and negative conventional work up for Crohn's disease(CD).METHODS:Patients with perianal disease(abscesses,fistulas,recurrent fissures) were evaluated for underlying CD.Patients who had a negative work up,defined as a negative colonoscopy with a normal ileoscopy or a normal small bowel series or a normal CT/MR enterography,underwent a Pillcam study of the small bowel after signing informed consent.Patients using nonsteroidal anti-inflammatory drugs or who had a history of inflammatory bowel disease or rheumatic disease were excluded.RESULTS:We recruited 26 patients aged 21-61 years(average 35.6 years),17 males and 9 females.One case could not be evaluated since the capsule did not leave the stomach.In 6 of 25(24%) patients with a negative standard work up for Crohn's disease,capsuleendoscopy(CE) findings were consistent with Crohn's disease of the small bowel.Family history of CD,white blood cell,hemoglobin,erythrocyte sedimentation rate or C-reactive protein did not predict a diagnosis of CD.Capsule endoscopy findings led to a change in treatment.CONCLUSION:In patients with perianal disease and a negative conventional work up to exclude CD,CE leads to incremental diagnostic yield of 24%.

Video capsule endoscopy in inflammatory bowel disease

Video capsule endoscopy (VCE) has evolved to become an important tool for the non-invasive examination of the small bowel, which hitherto had been relatively inaccessible to direct visualisation. VCE has been shown to play a role in monitoring the activity of small bowel Crohn&rsquo;s disease and can be used to assess the response to anti-inflammatory treatment in Crohn&rsquo;s disease. For those patients with Crohn&rsquo;s disease who have undergone an intestinal resection, VCE has been assessed as a tool to detect post-operative recurrence. VCE may also aid in the reclassification of patients with a diagnosis of Inflammatory Bowel Disease Unclassified to Crohn&rsquo;s disease. The evolution of colon capsule endoscopy (CCE) has expanded the application of this technology further. The use of CCE to assess the activity of ulcerative colitis has been described. This advance in capsule technology has also fuelled interest in its potential role as a minimally invasive tool to assess the whole of GI tract opening the possibility of its use for the panenteric assessment of Crohn&rsquo;s disease. VCE is a safe procedure. However, the risk of a retained capsule is higher in patients with suspected or confirmed Crohn&rsquo;s disease compared with patients having VCE examination for other indications. A retained video capsule is rare after successful passage of a patency capsule which may be utilised to pre-screen patients undergoing VCE. This paper describes the use of VCE in the assessment of inflammatory bowel disease.

Role of wireless capsule endoscopy in inflammatory bowel disease

Capsule endoscopy(CE) offers state-of-the-art imaging of the small bowel.In Crohn's disease its clinical role is still uncertain.This report analyses the usefulness of CE in patients with suspected Cronh's disease,in patients with established Crohn's disease(when assessing severity,occult gastrointestinal bleeding and/or as a guide to therapy),in patients with inflammatory bowel disease unclassified(IBDU),and in individuals with ulcerative colitis.The first item in this group is the most important although there is no strong evidence to establish the position of CE in the diagnostic workup.In patients with established Crohn's disease,recently developed activity scores are promising tools for an accurate assessment of severity.As a guide to therapy,CE should be focused on patients with unexplained symptoms when other investigations are inconclusive.In postoperative Crohn's Disease,international consensus recommended considering CE only ifileocolonoscopy is contraindicated or unsuccessful.In the case of IBDU,studies have shown a significant proportion of patients reclassified with Crohn's disease.In this setting,CE could have a role determining small bowel involvement.The role of CE in ulcerative colitis is limited.Some authors advocate CE before colectomy for refractory cases in order to exclude Crohn's disease.In summary,CE offers a new horizon in inflammatory bowel disease,and a better knowledge of mucosal abnormalities that could offer a paradigm shift:changing from symptombased disease activity estimation to direct mucosal healing monitoring.Nevertheless,randomized controlled studies are still needed to provide stronger evidence in this setting.