Acute Inflammatory Cells Research Articles

The Acute Inflammatory Potential of Particles From the Echinococcus granulosus Laminated Layer Is Moderated by Its Calcium Inositol Hexakisphosphate Component.

Cystic echinococcosis is caused by the tissue-dwelling larva (hydatid) of Echinococcus granulosus sensu lato. A salient feature is that this larva is protected by the acellular laminated layer (LL). As the parasite grows, the LL sheds abundant particles that can accumulate in the parasite's vicinity. The potential of LL particles to induce inflammation in vivo has not been specifically analysed. It is not known how each of its two major components, namely highly glycosylated mucins and calcium inositol hexakisphosphate (InsP6) deposits, impacts inflammation induced by the LL as a whole. In this work, we show that LL particles injected intraperitoneally cause infiltration of eosinophils, neutrophils and monocytes/macrophages as well as the disappearance of resident (large peritoneal) macrophages. Strikingly, the absence of calcium InsP6 enhanced the recruitment of all the inflammatory cell types analysed. In contrast, oxidation of the mucin carbohydrates caused decreased recruitment of neutrophils. The carbohydrate-oxidised particles caused cell influx nonetheless, which may be explained by possible receptor-independent effects of LL particles on innate immune cells, as suggested by previous works from our group. In summary, LL particles can induce acute inflammatory cell recruitment partly dependent on its mucin glycans, and this recruitment is attenuated by the calcium InsP6 component.

OA15 A case series of idiopathic granulomatous mastitis patients and their immunosuppressive management

Abstract Background/Aims Rheumatologists are experts in managing immunosuppression and are asked to supervise immunosuppression for non-rheumatic conditions. Thus, it is important to be aware of these conditions and the regimes required. Idiopathic granulomatosis mastitis (IGM) is a rare inflammatory breast condition which can have systemic manifestations including arthritis. Methods Our index case presented with peripheral ankle synovitis/tenosynovitis, struggling to weight bear, whilst being investigated for a breast mass. Breast US, mammogram and biopsy (acute and chronic inflammatory cells including multi-nucleated giant cells) were completed and there was little response to 3 courses of antibiotics. No mycobacteria were seen on microscopy, ZN stain negative, CXR normal, T spot negative and serum ACE normal. There was no rash and no conditions associated with a seronegative spondyloarthropathy. RF, anti-CCP and ANA were negative. A moderate course of prednisolone immediately resolved the peripheral arthritis, but high-dose steroids were required to reduce the breast mass. The mass recurred upon weaning prednisolone requiring the addition of azathioprine as a steroid-sparing agent. Results Our case series includes the immunosuppressive management of 3 other IGM patients: 1) 43-year-old referred after an 8 year history of alternating breast ‘abscesses’ and sinuses treated with courses of antibiotics to little avail. High dose prednisolone and methotrexate resolved the breast mass within a month. 2) 37-year-old referred with a 14 year history of breast masses and fistulae previously treated with surgery and antibiotics. Currently asymptomatic so commenced on methotrexate. 3) 39-year-old referred with a 3 year history of recurrent sterile breast abscesses previously managed with antibiotics, incision and drainage. Recent small masses had settled with NSAIDs. Conclusion IGM is a rare benign inflammatory breast disease of unknown aetiology, commonest in Middle Eastern populations, median age 30s. The most common presentation is a unilateral painful mass, which can ulcerate, fistulate and form abscesses. Management of IGM varies from expectant/topical steroids/NSAIDs to high dose steroids and DMARDs. A literature review shows that the usual starting dose of prednisolone is 40-60mg; the addition of methotrexate and azathioprine increases likelihood of successful treatment and allows for faster steroid tapering. Surgery for specific types of IGM can also be useful; for example, where there is duct granuloma, surgical excision can be curative. IGM can associate with arthritis, erythema nodosum, and episcleritis. One case series found that 14% of patients with IGM had concomitant arthritis. Key points: In our local experience we have had four patients with IGM, all previously treated with antibiotics or surgical methods but subsequently diagnosed with IGM and referred for immunosuppressive therapy. Being a rare condition, we feel it’s important for clinicians to be aware of IGM and its link with inflammatory arthritis. Disclosure S. Islam: None. P. Stonelake: None. H. John: None.

Tissue-plasminogen activator effects on the phenotype of splenic myeloid cells in acute inflammation

Tissue-plasminogen activator (tPA) is a serine protease well known for its fibrinolytic function. Recent studies indicate that tPA could also modulate inflammation via plasmin generation and/or by receptor mediated signalling in vitro. However, the contribution of tPA in inflammatory processes in vivo has not been fully addressed. Therefore, using tPA-deficient mice, we have analysed the effect of lipopolysaccharide (LPS) challenge on the phenotype of myeloid cells including neutrophils, macrophages and dendritic cells (DCs) in spleen. We found that LPS treatment upregulated the frequency of major histocompatibility class two (MHCII+) macrophages but also, paradoxically, induced a deep downregulation of MHCII molecule level on macrophages and on conventional dendritic cells 2 (cDC2). Expression level of the CD11b integrin, known as a tPA receptor, was upregulated by LPS on MHCII+ macrophages and cDC2, suggesting that tPA effects could be amplified during inflammation. In tPA−/− mice under inflammatory conditions, expression of costimulatory CD86 molecules on MHCII+ macrophages was decreased compared to WT mice, while in steady state the expression of MHCII molecules was higher on macrophages. Finally, we reported that tPA deficiency slightly modified the phenotype of DCs and T cells in acute inflammatory conditions. Overall, our findings indicate that in vivo, LPS injection had an unexpectedly bimodal effect on MHCII expression on macrophages and DCs that consequently might affect adaptive immunity. tPA could also participate in the regulation of the T cell response by modulating the levels of CD86 and MHCII molecules on macrophages.

Congenital Pulmonary Airway Malformation Type 1 with Pulmonary Neuroendocrine Cell Hyperplasia in an Adult Male: a Rare Case Report

Abstract Introduction/Objective Congenital pulmonary airway malformations (CPAM) is rare, usually diagnosed in the pediatric population, and may occur in adults. Pulmonary neuroendocrine cell hyperplasia (PNECH) mimicking diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) associated with CPAM has not been described previously. We report a case of CPAM Type 1 with PNECH. Methods/Case Report A 33-year-old male, with past medical history of latent tuberculosis (TB) by Quantiferon blood testing, recurrent pneumonia, recurrent lung abscesses, and lung cavitary lesion for three years, presented with fever, cough with hemoptysis, shortness of breath, and left-sided chest pain. Computerized tomography of chest displayed a 10.8 cm cavitary lesion in the left lower lobe of the lung. The patient underwent left lower lobectomy of the lung. Grossly, the lobectomy specimen revealed a 10.5 cm irregular cavity communicating to the superior segmental bronchus of the left lower lobe. Microscopically, the dominant large cyst was surrounded by lung parenchyma and small cystically dilated spaces resembling bronchioles under the fibrotic pleura. The large cyst was lined by respiratory epithelium with rare pathognomonic mucous cells in clusters. Cyst walls contained smooth muscle, small islands of cartilage, and focal intense acute and chronic inflammatory cell infiltrates with hemorrhage. There were multiple foci of proliferation of pulmonary neuroendocrine cells centered around bronchioles surrounding the large cyst. The neuroendocrine cells were arranged from individual cells and cellular aggregates to larger tumorlets, highlighted by Synaptophysin and Chromogranin immunostains. No granuloma or necrosis was present. No acid-fast bacilli or fungal microorganisms were identified by special stains. The findings are consistent with CPAM type 1, with PNECH. Results (if a Case Study enter NA) NA Conclusion Our study demonstrates a histologically diagnosed adult congenital pulmonary airway malformations type 1 with an incidental pulmonary neuroendocrine cell hyperplasia, which mimics diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. To the best of our knowledge, this is the first report of such an association.

Xanthogranulomatous inflammation of the female genital tract: An 11-year single institutional study of 40 cases

Background and objectivesXanthogranulomatous inflammation (XGI) is a rare form of chronic inflammation that affects the female genital tract (FGT). The absence of a standard lexicon in the literature has contributed to the relative obscurity of this condition. We attempt to study this lesion with its various clinicopathological associations. MethodologyWe conducted an 11-year retrospective study of cases diagnosed with XGI of the FGT, analyzing relevant clinical and pathological parameters. ResultsOur study identified 40 cases reported as XGI. The mean age was 43.8 (+/− 11.8 SD) years. The most common clinical presentation was abdominal pain (27.5 %). Abdominal mass was seen in 37.5 % of which 22.5 % was primarily attributed to XGI and was not associated with malignancies. The most common site involved was adnexa(87.5 %), with rare involvement of myometrium(7.5 %) and endometrium(5 %). Adnexal involvement was either as tubo-ovarian masses or isolated ovary/fallopian tube involvement. XGI was also seen associated with other primary lesions of FGT like high-grade serous carcinoma(7.5 %) and mature cystic teratoma (7.5 %), while non-neoplastic associations included tubal gestation, foreign body, and Aspergillus infection in the ovary. Histologically, the infiltrate comprised of chronic inflammatory cells in all cases with additional acute inflammatory cells(60 %). Multinucleated giant cells were seen in 40 % of cases. Urine culture showed bacterial colonies in 23 % of cases. ConclusionsXGI of FGT is an extremely rare lesion and can present as isolated lesions or in association with other primary lesions of FGT. Adnexal involvement was more common than uterine XGI. It is essential to recognize this lesion because it can mimic malignancy and has a destructive nature.

Anti-inflammatory effect of Alpinia galanga extract on acute inflammatory cell model of peripheral blood mononuclear cells stimulated with TNF-α.

Aim Studies have shown that SARS-Cov-2 has the ability to activate proinflammatory cytokine leading to acute inflammation. During the SARS-Cov-2 infection, an increase of the secretion of production TNF-α in seen in COVID-19 patients along with a decrease in anti-inflammatory cytokine IL-10, and growth factor TGF-β caused cytokine storm and damaged tissues. Alpinia galanga extract contains several secondary metabolites with strong antiinflammation and antioxidant effect. The aim of this study was to evaluate the effect of Alpinia galanga extract on peripheral blood mononuclear cells (PMBC) acute inflammation cells model stimulated with TNF-α. Methods Alpinia galanga was extracted under maceration methods on ethanol 96%. The PMBC was collected from three healthy humans and isolated using ficol reagent and cultured with the TNF-α 100pg/mL for 72 h. The TNF-α levels were evaluated under ELISA reader. Furthermore, the IL-10 and TGF-β gene expression was analysed using qRT-PCR after 24 h treatment with Alpinia galanga extract. Results Alpinia galanga extract has no cytotoxic effect on Vero cells with IC50 value of >1000µg/mL. The PBMC acute inflammation cells model stimulated by TNF-α 100pg/mL, after 72 h induction the PBMC cells significantly expressed a high level of TNF-α up to 341±10.87 pg/mL. Furthermore, the treatment of Alpinia galanga significantly increased the anti-inflammatory cytokine IL-10 and growth factor TGF-β in dose dependent manner. Conclusion These findings suggested that Alpinia galanga extract has strong antiinflammation activity.

DP10 A relapsing–remitting rash with associated neurological symptoms: a rare presentation of ​­neuro-Sweet syndrome

Abstract A 46-year-old woman presented with an 8-week history of an asymptomatic eruption on her upper extremities and back. She had a history of ulcerative colitis, asthma and hyposplenism. There had been no changes to her regular medications. Over the next 3 years, she developed a relapsing and remitting course of headaches, pyrexia and feeling unwell with the associated rash. She further developed deafness and vertigo and was admitted with headaches, blurred vision and paraesthesia of the fingers. Physical examination revealed multiple erythematous, asymptomatic, annular plaques present on her upper extremities and back with no oral, genital or ophthalmological lesions. Skin biopsy from the lesion on the upper back showed a neutrophilic dermatosis with mildly acanthotic epidermis, superficial dermal collection of acute inflammatory cells, dermal oedema and endothelial swelling, with no evidence of vasculitis. This was considered in keeping with Sweet syndrome. Magnetic resonance imaging of the brain revealed meningoencephalitis and focal cerebritis. A lumbar puncture performed for infection was negative. Following this, a diagnosis of neuro-Sweet syndrome (NSS) was made. She has responded well to oral steroids and is currently well controlled on dapsone. To date, extensive malignancy screens have been negative. Sweet syndrome, or acute febrile neutrophilic dermatosis, is characterized by fever, malaise, leucocytosis and painful distinctive skin lesions and may be associated with malignancies, drugs and infection. Skin biopsy shows dense dermal infiltration of neutrophils without any histological signs of vasculitis. Sweet syndrome is known to involve multiple organs; however, involvement of the central nervous system (CNS) is rare. When the CNS is involved, it is referred to as NSS and is defined as the coexistence of characteristic skin lesions of Sweet syndrome with encephalitis or meningitis (Suh HB, Kim HJ. Recurrent neuro-Sweet disease associated with preceding upper respiratory infection: a case study. iMRI 2018; 22:187–93). Although the condition is usually steroid responsive, disease recurrences have been reported in 50% of cases in the literature (Hisanaga K, Iwasaki Y, Itoyama Y, Neuro-Sweet Study Group. Neuro-Sweet disease: clinical manifestations and criteria for diagnosis. Neurology 2005; 64:1756–61). It is important to note that the clinical features and imaging results in NSS are similar to those of neuro-Behçet disease (NBD), and it is important to distinguish between the two as CNS involvement in NSS is often transient, whereas NBD often follows a more progressive course. We report a rare case of NSS and highlight that NSS should be considered by dermatologists in patients presenting with recurrent skin lesions of Sweet syndrome and associated neurological symptoms.

Is Tranexamic Acid an Effective Prevention in the Formation of Epidural Fibrosis? Histological Evaluation in the Rats.

The present study aimed to determine the topical and systemic efficacy of tranexamic acid (TXA) on epidural fibrosis in a rat laminectomy model. Thirty-two 12-month-old adult Sprague-Dawley rats were used in this study. Each rat underwent bilateral laminectomy at the L1 and L2 vertebral levels. Rats were divided into four groups : in group I (control group, n=8), a laminectomy was performed and saline solution was applied into the surgical space. In group II (topical group, n=8), laminectomy was performed and 30 mg/ kg TXA was applied to the surgical site before skin closure. In group III (systemic group, n=8), 30 mg/kg TXA was administered intravenously via the tail vein in the same session as the surgical procedure. In group IV (topical and systemic group, n=8), TXA was administered 30 mg/kg both topical and intravenous. The rats were sacrificed at 4 weeks postoperatively. Masson's trichrome and hematoxylin and eosin were used to assess acute inflammatory cells, chronic inflammatory cells, vascular proliferation, and epidural fibrosis. Epidural fibrosis, acute inflammation, chronic inflammation, and sum histologic score value were significantly lower in the systemic TXA group, systemic and topical TXA groups than in the control group (p<0.05). In addion, the sum histologic score was significantly lower in the topical TXA group than in the control group (p<0.05). In this study, epidural fibrosis formation was prevented more by systemic application, but the topical application was found to be effective when compared to the control group. As a result, we recommend the systemic and topical use of TXA to prevent epidural fibrosis during spinal surgery.

Xanthogranulomatous Cholecystitis Mimicking Gall Bladder Cancer: a Diagnostic Dilemma and Review of Literature.

Xanthogranulomatous cholecystitis (XGC) is one of the rare variants of chronic cholecystitis which is characterized by inflammation of gall bladder along with infiltration by acute and chronic inflammatory cells. Intramural accumulation of lipid laden macrophages in GB wall is the hallmark of the disease. XGC results in dense adhesion of gall bladder (GB) to surrounding structures, like duodenum, colon, and stomach. The intense GB inflammation results in gall bladder perforation and development of fistulous communication between gall bladder and surrounding structures. This may also lead to formation of inflammatory mass which closely mimic gall bladder malignancy. Often differentiation from carcinoma of GB (Ca GB) on the basis of clinical presentation and even on intra-operative and radiological findings is difficult, and the issue could only be resolved on final Histopathology (HPE). We review presentation and investigation of a patient, discuss our approach in managing dilemma in treating such cases of XGC, and review the literature.

Role of Hydrodistention and Intravesical Hyaluronic Acid in Treatment of Bladder Pain Syndrome: Case Report

Bladder pain syndrome (BPS) causes decreased mental and physical quality of life. The diagnosis and treatment of BPS must be made effective; however, the treatment of BPS was still not satisfactory for most patients. Two cases of BPS were presented to the urology clinic and were treated with a combination of hydrodistention and intravesical hyaluronic acid (HA) periodically. After 3-8 hydrodistension and hyaluronic acid instillation, the patients showed symptom improvement indicated by O’Leary Sant Questionnaire (symptom score 19-21 before treatment became 3-4 after treatment, problem score 8-16 before treatment became 0-2 after treatment), visual analogue scale (7-10 before treatment to 3-4 after treatment), and the global response assessment (GRA) scale were markedly improved. Both patients had glomerulations during cystoscopy, and the second had Hunner Lesion. A pathological examination of bladder biopsy specimens indicated acute and chronic inflammatory cell infiltration. The combination of hydrodistention and intravesical HA was beneficial for treating BPS in this study. Further study such as a clinical trial is needed to prove the efficacy and safety of this treatment.

Role of Hydrodistention and Intravesical Hyaluronic Acid in Treatment of Bladder Pain Syndrome: Case Report

Bladder pain syndrome (BPS) causes decreased mental and physical quality of life. The diagnosis and treatment of BPS must be made effective; however, the treatment of BPS was still not satisfactory for most patients. Two cases of BPS were presented to the urology clinic and were treated with a combination of hydrodistention and intravesical hyaluronic acid (HA) periodically. After 3-8 hydrodistension and hyaluronic acid instillation, the patients showed symptom improvement indicated by O’Leary Sant Questionnaire (symptom score 19-21 before treatment became 3-4 after treatment, problem score 8-16 before treatment became 0-2 after treatment), visual analogue scale (7-10 before treatment to 3-4 after treatment), and the global response assessment (GRA) scale were markedly improved. Both patients had glomerulations during cystoscopy, and the second had Hunner Lesion. A pathological examination of bladder biopsy specimens indicated acute and chronic inflammatory cell infiltration. The combination of hydrodistention and intravesical HA was beneficial for treating BPS in this study. Further study such as a clinical trial is needed to prove the efficacy and safety of this treatment.

A Case of Multiple Gastrointestinal Ulcer: A Rare Presentation of Strongyloidiasis

Strongyloides stercolaris is a common intestinal nematode in tropical and subtropical countries like Bangladesh. The presentation of this infection is nonspecific. Mostly it remains asymptomatic with peripheral eosinophilia. Immunocompromised individuals are at high risk of hyper infection to disseminated disease. We present a case of Strongyloides in an immunocompetent patient with features of gastric outlet obstruction. Laboratory findings revealed hypereosinophilia with multiple gastrointestinal ulcers on endoscopy. Biopsy was taken from a gastric ulcer which revealed ulceration and dense infiltration of acute and chronic inflammatory cells along with extensive intestinal metaplasia. There were tiny helminthic bodies within the mucosal glands and on the surface consistent with Strongyloides stercoralis. Routine examination of stool also revealed larvae of Strongyloides stercolaris. J Dhaka Med Coll. 2022; 31(1) : 163-166

Effect of Locally Administered Estradiol on Wound Healing in a Nasal Septal Perforation Animal Model.

We aimed to investigate the effect of estradiol on wound healing in an experimental nasal septal perforation (NSP) model created in rats. Twenty-two Sprague Dawley healthy male rats were separated into two groups. NSP, approximately 2 mm in diameter, was created in each animal. The 0.1 mL 0.12% estradiol (12 g/L) (study group) and 0.1 mL 0.9% saline (9 g/L) (control group) were applied topically once a day for 14 days. The rats were sacrificed on the 14th day and the cartilage nasal septum of each animal was excised for histopathological examination. The nasal mucosal epithelial regeneration and degeneration, acute inflammatory cell count, fibroblast number, vascularization, granulation tissue formation, giant cell number, eosinophil number, degeneration and regeneration of the nasal cartilage, and collagen density were examined. The macroscopic closure rate of the perforations and histopathological parameters were evaluated statistically. In this study, the epithelial regeneration, the fibroblast count, the granulation tissue formation, and the amount of collagen were significantly higher in the study group than in the saline group (p < 0.05). The acute inflammatory activity was lower in the estradiol group than in the saline group (p < 0.05). There was no statistically significant difference in the closure rate of perforation between the two groups (p = 0.163). No significant difference was found in other comparisons (p > 0.05). The locally administered estradiol may improve wound healing of the nasal septum in an experimental NSP animal model. LEVEL OF EVIDENCE: Not applicable.

Crohn’s disease proteolytic microbiota enhances inflammation through PAR2 pathway in gnotobiotic mice

ABSTRACT Emerging evidence implicates microbial proteolytic activity in ulcerative colitis (UC), but whether it also plays a role in Crohn’s disease (CD) remains unclear. We investigated the effects of colonizing adult and neonatal germ-free C57BL/6 mice with CD microbiota, selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), or microbiota from healthy controls with LPA (HC-LPA) or HPA (HC-HPA). We then investigated colitogenic mechanisms in gnotobiotic C57BL/6, and in mice with impaired Nucleotide-binding Oligomerization Domain-2 (NOD2) and Protease-Activated Receptor 2 (PAR2) cleavage resistant mice (Nod2 −/−; R38E-PAR2 respectively). At sacrifice, total fecal proteolytic, elastolytic, and mucolytic activity were analyzed. Microbial community and predicted function were assessed by 16S rRNA gene sequencing and PICRUSt2. Immune function and colonic injury were investigated by inflammatory gene expression (NanoString) and histology. Colonization with HC-LPA or CD-LPA lowered baseline fecal proteolytic activity in germ-free mice, which was paralleled by lower acute inflammatory cell infiltrate. CD-HPA further increased proteolytic activity compared with germ-free mice. CD-HPA mice had lower alpha diversity, distinct microbial profiles and higher fecal proteolytic activity compared with CD-LPA. C57BL/6 and Nod2 −/− mice, but not R38E-PAR2, colonized with CD-HPA had higher colitis severity than those colonized with CD-LPA. Our results indicate that CD proteolytic microbiota is proinflammatory, increasing colitis severity through a PAR2 pathway.

A3 CROHN’S DISEASE PROTEOLYTIC MICROBIOTA ENHANCES INFLAMMATION THROUGH PAR2 PATHWAY IN GNOTOBIOTIC MICE

Abstract Background An imbalance in host proteases has been implicated in inflammatory bowel disease (IBD). Recent evidence implicates microbial proteolytic activity (PA) in ulcerative colitis but whether it also plays a role in Crohn’s disease (CD) remains unclear. Purpose We therefore investigated the colitogenic potential and underlying pathways of proteolytic CD microbiota. Method Adult germ-free (GF) C57BL/6 mice were colonized with CD microbiota selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), and from healthy controls with LPA (HC-LPA), after which total fecal proteolytic, elastolytic and mucolytic activity were analyzed in the mice. Microbial community was assessed by 16S rRNA gene sequencing. Immune function and colonic injury were investigated by inflammatory gene expression (NanoString) and histology. Colitis severity and underlying pathways were investigated in C57BL/6, Nucleotide-binding Oligomerization Domain-2 knock-out (Nod2-/-), and Protease-Activated Receptor 2 (PAR2) cleavage resistant mice (R38E-PAR2) subjected to 2% dextran sodium sulfate in drinking water for 5 days followed by 2 days on water. Result(s) Colonization with HC-LPA or CD-LPA lowered baseline fecal proteolytic activity compared with GF mice, which was paralleled by lower acute inflammatory cell infiltrate. CD-HPA further increased proteolytic activity compared with GF mice. Fecal supernatants from CD-LPA or HC-LPA colonized mice had lower in vitro PAR2 cleavage compared to supernatants from GF and CD-HPA colonized mice. Several genes, such as Map kinases, Rhoa, Myd88, and Tollip, were increased in GF mice compared to colonized mice. 18 genes related to inflammation and barrier function (e.g., Mapk2k6, Tnf, Claudin1) were differentially expressed between CD-LPA and CD-HPA. CD-HPA mice had lower alpha diversity, distinct microbial profiles, and higher fecal proteolytic activity compared with CD-LPA. Abundance of several beneficial species (e.g., Akkermansia muciniphilia) was decreased while other taxa were increased (e.g., Hungattella hathewayi) in CD-HPA compared to CD-LPA. H. hathewayi as well as the serine protease K04772 were transcriptionally increased in fecal samples from CD-HPA colonized mice. C57BL/6 and Nod2-/- mice, but not R38E-PAR2 mice, colonized with CD-HPA developed earlier and more severe colitis compared with mice colonized with CD-LPA. Conclusion(s) CD proteolytic microbiota is proinflammatory through a PAR2 pathway. H. hathewayi correlates with the proinflammatory phenotype through the serine protease K04772 in this model. The results support a role of microbial PA in CD, which could constitute a biomarker for identifying patients who would benefit from anti-proteolytic therapies. Disclosure of Interest None Declared

The Efficacy of Topical Lactoferrin on Wound Healing in an Experimental Animal Model of Nasal Septum Perforation.

The aim of the present experimental animal study was to investigate the efficacy of bovine lactoferrin (LF) on wound healing in an animal model of nasal septum perforation (NSP).Twenty-two, 8 to 10 weeks of age, male Sprague-Dawley rats were separated into two groups. Nasal septum perforation was created in each rat. The saline (control) and 0.05 mg LF (study) groups were delivered locally for 14 days. On the 14th day of the study, after the sacrifice, the cartilage nasal septa of the animals were excised. The degeneration and regeneration observed in the nasal septum epithelium and cartilage, the number of acute inflammatory cells, the number of eosinophils, the amount of new vessel formation, the amount of granulation, and the collagen density were examined microscopically. The microscopic parameters and macroscopic healing of NSPs were analyzed. The epithelium regeneration, the fibroblast number, the granulation tissue formation, the collagen density, and the macroscopic healing were significantly higher in the LF group (p < 0.05). Besides, the acute inflammatory cell count was lower in the LF group (p = 0.034). In conclusion, the topically delivered LF can improve wound healing in an experimental rat model of NSP.

P597 Usefulness of histological monitoring in predicting relapse after de-escalation of thiopurines in Ulcerative Colitis

Abstract Background Thiopurines are useful to maintain remission for ulcerative colitis (UC) and to inhibit immunogenicity in combination with biologics while their long-term use may increase risks of infections and malignancies. Therefore, the risk-benefit balance should be evaluated, and de-escalation needs to be discussed. However, optimal de-escalation strategy such as dosing and monitoring has not been well studied. Methods UC patients in clinical remission (partial Mayo score ≤ 2 and rectal bleeding subscore of 0) who de-escalated thiopurines (dose-reduction or discontinuation) were enrolled. The risk of relapse and changes in Mayo endoscopic subscore (MES) and histological findings after thiopurine de-escalation were retrospectively investigated. The correlation with relapse (treatment escalation (including topical therapy) with the exacerbation of symptoms or rectal bleeding score ≥ 1) was analyzed by logistic regression analysis. Results A total of 69 de-escalation steps (51 dose-reductions and 18 discontinuations) were conducted in 39 patients. The mean duration and dose of thiopurine use were 3.5 years and 66.6mg (converted to azathioprine). Thiopurines were used in combination with biologics in 16 (41.0%). Relapse occurred in 17/69 (24.6%) de-escalation steps (10/17 discontinuations). In 36 de-escalations remaining in remission with available data before and after de-escalations, worsening of MES occurred in 13%, whereas exacerbations of any histopathological finding occurred in 44% (crypt architectural irregularities 25%, chronic inflammatory cell infiltrate 19％, acute inflammatory cell infiltrate 16％, basal plasmacytosis 13%, mucin depletion 13%, crypt abscess 8%). Chronic inflammatory cellular infiltrate (p=0.002), basal plasmacytosis (p=0.008), and acute inflammatory cell infiltrate (p=0.039) at de-escalation were significantly associated with relapse after de-escalation. Nancy Index was also associated with relapse (p=0.011), while MES was not. Conclusion Histological worsening may precede clinical relapse thus may be useful to predict relapse after thiopurine withdrawal.

Mayo Endoscopic Score (MES) as a reference for the histological active disease of ulcerative colitis

Background: The degree of inflammation dramatically affects the morbidity of ulcerative colitis. Local and systemic inflammation features are modalities to determine disease severity and evaluation. Furthermore, local inflammation can be seen from endoscopic and histological examinations. This study aimed to examine the relationship of histological inflammatory profile with endoscopic scoring in ulcerative colitis patients. Method: A retrospective study was conducted using colonoscopic and histologic data from 68 ulcerative colitis patients. The endoscopic grade was assessed based on the Mayo Endoscopic Score (MES). The histological grade was analyzed using a microscope by assessing acute and chronic inflammatory cells and the presence of ulceration and crypt changes based on the Nancy Score Index and Geboes Score Index. Furthermore, the analysis test used Spearman and Mann-Whitney. Results: There is a significant positive relationship between endoscopic and histology scoring. The Nancy Score Index and MES combination yields 95% CI: 0.000-0.043, p=0.000, Correlation coefficient (r)=0.810, and odds ratio (OR)=3.272. Meanwhile, the combination of the Geboes Score Index with MES yields 95% CI: 0.000-0.043; p=0.000; r=0.727; and OR=1.347. In each histological scoring, there was a significant difference between the Nancy Score Index and Geboes Score Index tα (r = 0.018; p&lt;0.05). Conclusion: There is a significant relationship between histological and endoscopic scoring. Therefore, an endoscopic examination can be a reference for histologically active disease.

Evaluation of Immunohistochemical Expression of Heparanase in Helicobacter pylori-Associated Chronic Gastritis.

Chronic gastritis (CG) is a very common disease. More than half of the worldwide population suffers from symptoms of CG. This disease has received great attention since the discovery of H. pylori as the most important cause of CG. Symptoms experienced by patients with CG are attributed to H. pylori-induced inflammatory reactions. Heparanase (HPSE) is a mammalian β-endoglucoronidase. In inflammation; HPSE degrades and remodels the extracellular matrix's heparan sulfate polysaccharide chains liberating heparan sulfate-bound cytokines and chemokines, HPSE also facilitates movement of inflammatory cells. This study aimed to detect the function of HPSE in CG by correlating levels of HPSE expression with histopathological features of CG, including H. pylori infection, acute and chronic inflammatory cells, mucosal atrophic and/or metaplastic features. Ninety-five upper endoscopic-guided gastric punch biopsies were enrolled in this study. From each specimen, formalin-fixed and paraffin-embedded tissue blocks were prepared. Tissue sections were stained by Hematoxylin and eosin, Giemsa, and anti-heparanase antibody. HPSE expression was statistically associated with H. pylori infection (P-value < .000), and intensity of chronic lymphocytic inflammatory infiltrate in the gastric mucosal tissues (P = .004). High levels of HPSE expression were also related to the presence of neutrophils in the gastric surface epithelium and lamina propria (P-value < .009). HPSE expression was upregulated in H. pylori-associated chronic gastritis. Thus, future therapeutic agents that could specifically inhibit HPSE enzyme activity, may aid in the reduction of sequelae of H. pylori infection.

The Effect of Melatonin on Nasal Septal Wound Healing in an Experimental Animal Model.

The purpose of our study was to examine the effect of melatonin (MLT) on wound healing in the nasal septum. Twenty-two Sprague-Dawley rats of the male sex were included in this experimental study. Nasal septal perforation (NSP), about 2 mm in diameter, was formed in each rat. MLT was applied topically to the subjects in the study group and saline was applied topically to the subjects in the control group once a day for 14 days. On day 14, the rats were sacrificed and the nasal septums of the subjects were resected for pathological evaluation. In the NSP area, degeneration and regeneration of nasal septal epithelium; degeneration and regeneration of the septal cartilage; number of cells involved in wound healing such as acute inflammatory cells (leukocytes), fibroblast, eosinophil, and giant cell; capillary vessel intensity; granulation tissue formation; and collagen intensity parameters were evaluated histopathologically. The macroscopic size and histopathologic examination results of NSPs were statistically analyzed. In the MLT group, the epithelium regeneration, cartilage regeneration, fibroblast number, collagen density, vascularity, and granulation formation were significantly higher, and the epithelial degeneration and acute inflammatory cells density were significantly lower, in the NSP area (p < 0.05). In addition, macroscopic healing was significantly higher in the MLT group (p = 0.044 and <0.05). Local application of MLT accelerates nasal septal wound healing. With this feature, the usage of MLT can be promising to prevent the formation of NSP.