Inflammatory Cells In Lamina Propria Research Articles

Lactobacillus acidophilus NCFM and Lactiplantibacillus plantarum Lp-115 inhibit Helicobacter pylori colonization and gastric inflammation in a murine model.

To determine the role of Lactobacillus strains and their combinations in inhibiting the colonization of H. pylori and gastric mucosa inflammation. Human gastric adenocarcinoma AGS cells were incubated with H. pylori and six probiotic strains (Lactobacillus acidophilus NCFM, L. acidophilus La-14, Lactiplantibacillus plantarum Lp-115, Lacticaseibacillus paracasei Lpc-37, Lacticaseibacillus rhamnosus Lr-32, and L. rhamnosus GG) and the adhesion ability of H. pylori in different combinations was evaluated by fluorescence microscopy and urease activity assay. Male C57BL/6 mice were randomly divided into five groups (uninfected, H. pylori, H. pylori+NCFM, H. pylori+Lp-115, and H. pylori+NCFM+Lp-115) and treated with two lactobacilli strains (NCFM and Lp-115) for six weeks. H. pylori colonization and tissue inflammation statuses were determined by rapid urease test, Hematoxylin-Eosin (HE) staining, immunohistochemistry, and qRT-PCR and ELISA. L. acidophilus NCFM, L. acidophilus La-14, L. plantarum Lp-115, L. paracasei Lpc-37, L. rhamnosus Lr-32, and L. rhamnosus GG reduced H. pylori adhesion and inflammation caused by H. pylori infection in AGS cells and mice. Among all probiotics L. acidophilus NCFM and L. plantarum, Lp-115 showed significant effects on the H. pylori eradication and reduction of inflammation in-vitro and in-vivo. Compared with the H. pylori infection group, the mRNA and protein expression levels of IL-8 and TNF-α in the six Lactobacillus intervention groups were significantly reduced. The changes in the urease activity (ureA and ureB) for 1-7h in each group showed that L. acidophilus NCFM, L. acidophilus La-14, L. plantarum Lp-115, and L. rhamnosus GG effectively reduced the colonization of H. pylori. We observed a higher ratio of lymphocyte and plasma cell infiltration into the lamina propria of the gastric mucosa and neutrophil infiltration in H. pylori+NCFM+Lp-115 mice. The infiltration of inflammatory cells in lamina propria of the gastric mucosa was reduced in the H. pylori+NCFM+Lp-115 group. Additionally, the expression of IFN-γ was decreased significantly in the NCFM and Lp-115 treated C57BL/6 mice. L. acidophilus NCFM and L. plantarum Lp-115 can reduce the adhesion of H. pylori and inhibit the gastric inflammatory response caused by H. pylori infection.

Potential gastrointestinal Behcet’s disease flare after treatment with anti-interleukin 17a therapy

BackgroundBehcet’s disease (BD) is a systemic disease characterized by recurrent oral and genital ulcers. The underlying disease pathway likely involves interleukin (IL)-17 A, a proinflammatory cytokine that is implicated in Behcet’s uveitis. Secukinumab is an anti-IL-17 A drug that may have an emerging role in the treatment of refractory BD. This is the first known case report of gastrointestinal BD flare up after anti-IL-17 A therapy.Case presentationWe presented a case of BD with cutaneous and articular features being treated with secukinumab. After the third dose of loading secukinumab, the patient developed acute lower abdominal pain required hospital admission. Urgent computer tomography (CT) abdomen showed fatty stranding of caecum. Colonoscopy with caecal showed increased number of inflammatory cells in lamina propria. Secukinumab was stopped and patient was started on medium dose steroid. His abdominal symptoms resolved after treatment.ConclusionsThis case report illustrates a case of gastrointestinal (GI) BD presenting as acute inflammatory colitis after the use of secukinumab. Therefore, anti-IL-17 A agents should be used cautiously in patients with GI BD, and preferably guided by a phenotype-tailored approach.

Colitis in a transgenic mouse model of autoimmune uveitis may be induced by neoantigen presentation in the bowel

Undifferentiated uveitis (intraocular inflammation, IOI) is an idiopathic sight-threatening, presumed autoimmune disease, accountable for ~ 10% of all blindness in the developed world. We have investigated the association of uveitis with inflammatory bowel disease (IBD) using a mouse model of spontaneous experimental autoimmune uveoretinitis (EAU). Mice expressing the transgene (Tg) hen egg lysozyme (HEL) in the retina crossed with 3A9 mice expressing a transgenic HEL-specific TCR spontaneously develop uveoretinitis at post-partum day (P)20/21. Double transgenic (dTg TCR/HEL) mice also spontaneously develop clinical signs of colitis at ~ P30 with diarrhoea, bowel shortening, oedema and lamina propria (LP) inflammatory cell infiltration. Single (s)Tg TCR (3A9) mice also show increased histological LP cell infiltration but no bowel shortening and diarrhoea. dTg TCR/HEL mice are profoundly lymphopenic at weaning. In addition, dTg TCR/HEL mice contain myeloid cells which express MHC Class II-HEL peptide complexes (MHCII-HEL), not only in the inflamed retina but also in the colon and have the potential for antigen presentation. In this model the lymphopenia and reduction in the absolute Treg numbers in dTg TCR/HEL mice is sufficient to initiate eye disease. We suggest that cell-associated antigen released from the inflamed eye can activate colonic HEL-specific T cells which, in a microbial micro-environment, not only cause colitis but feedback to amplify IOI.

S2728 From Shortness of Breath to Bowel Unrest: COVID-19-Induced Ulcerative Colitis

Introduction: COVID-19 is recognized for its respiratory complications, but it can also cause extrapulmonary manifestations such as gastrointestinal complaints. Usually, GI manifestations are transient and rarely progress to chronic disease. We highlight a rare case of newly diagnosed ulcerative colitis triggered by COVID-19 infection. Case Description/Methods: A 49-year-old female with history of GERD presented with bloody diarrhea and abdominal pain that persisted six weeks after recent COVID-19 infection with otherwise complete resolution of other disease related symptoms. CT abdomen/pelvis showed colonic wall thickening from the hepatic flexure to the rectum concerning for colitis. Labs were significant for leukocytosis 13,600/microliter with elevated CRP 39.1 mg/L. Infectious workup and celiac panel were negative. Colonoscopy was performed and revealed pancolitis with pathology showing architectural distortion with crypt abscesses and chronic inflammatory cells in lamina propria. She was started on a steroid taper with rapid resolution of symptoms for presumed COVID-induced colitis. Unfortunately, upon completion of the taper, her symptoms recurred. Repeat labs showed CRP 8.7 mg/L with imaging negative for colitis. Repeat colonoscopy showed pseudopolyps at the hepatic flexure with segmental biopsies showing moderately active chronic colitis in the right colon. Patient was ultimately diagnosed with ulcerative colitis triggered by COVID-19 infection. She was started on Mesalamine with Prednisone induction eventually requiring Ustekinumab for disease control. Discussion: Incidence of gastrointestinal manifestations in COVID-19 are variable ranging anywhere from 3-50% of cases. However, COVID-19 induced inflammatory bowel disease is exceedingly rare with only a handful of case reports documenting such occurrence. While not completely understood, the pathophysiology behind COVID-19 related gastrointestinal manifestations likely involves binding of ACE-2 receptors along the epithelium, disrupting the gut barrier. In most patients this disruption is self-resolving; however, patients who develop inflammatory bowel disease likely have underlying genetic predisposition that results in chronic intestinal inflammation. Our case demonstrates the importance of recognizing the extrapulmonary manifestations of COVID-19 which can have life altering implications as seen in our patient.

Difference in electron microscopic findings among interstitial cystitis/bladder pain syndrome with distinct clinical and cystoscopic characteristics

Urothelial dysfunction may be a key pathomechanism underlying interstitial cystitis/bladder pain syndrome (IC/BPS). We therefore examined if clinical severity is associated with the extent of urothelial damage as revealed by electron microscopic (EM) analysis of biopsy tissue. One hundred IC/BPS patients were enrolled and 24 patients with stress urinary incontinence served as controls. Clinical symptoms were evaluated by visual analog scale pain score and O’Leary-Sant Symptom score. Bladder biopsies were obtained following cystoscopic hydrodistention. The presence of Hunner’s lesions and glomerulation grade after hydrodistention were recorded and patients classified as Hunner-type IC (HIC) or non-Hunner-type IC (NHIC). HIC patients exhibited more severe defects in urothelium cell layers, including greater loss of umbrella cells, umbrella cell surface uroplakin plaque, and tight junctions between adjacent umbrella cells, compared to control and NHIC groups (all p < 0.05). Both NHIC and HIC groups demonstrated more severe lamina propria inflammatory cell infiltration than controls (p = 0.011, p < 0.001, respectively). O’Leary-Sant Symptom scores were significantly higher among patients with more severe urothelial defects (p = 0.030). Thus, urothelium cell layer defects on EM are associated with greater clinical symptom severity.

Localisation of Cannabinoid and Cannabinoid-Related Receptors in the Horse Ileum

Colic is a common digestive disorder in horses and one of the most urgent problems in equine medicine. A growing body of literature has indicated that the activation of cannabinoid receptors could exert beneficial effects on gastrointestinal inflammation and visceral hypersensitivity. The localisation of cannabinoid and cannabinoid-related receptors in the intestine of the horse has not yet been investigated. The purpose of this study was to immunohistochemically localise the cellular distribution of canonical and putative cannabinoid receptors in the ileum of healthy horses. Distal ileum specimens were collected from six horses at the slaughterhouse. The tissues were fixed and processed to obtain cryosections which were used to investigate the immunoreactivity of canonical cannabinoid receptors 1 (CB1R) and 2 (CB2R), and three putative cannabinoid-related receptors: nuclear peroxisome proliferator-activated receptor-alpha (PPARα), transient receptor potential ankyrin 1 and serotonin 5-HT1a receptor (5-HT1aR). Cannabinoid and cannabinoid-related receptors showed a wide distribution in the ileum of the horse. The epithelial cells showed immunoreactivity for CB1R, CB2R and 5-HT1aR. Lamina propria inflammatory cells showed immunoreactivity for CB2R and 5-HT1aR. The enteric neurons showed immunoreactivity for CB1R, transient receptor potential ankyrin 1 and PPARα. The enteric glial cells showed immunoreactivity for CB1R and PPARα. The smooth muscle cells of the tunica muscularis and the blood vessels showed immunoreactivity for PPARα. The present study represents a histological basis which could support additional studies regarding the distribution of cannabinoid receptors during gastrointestinal inflammatory diseases as well as studies assessing the effects of non-psychotic cannabis-derived molecules in horses for the management of intestinal diseases.

S1806 Ipilimumab and Nivolumab-Induced Colitis in a Patient With Recurrent Metastatic Melanoma

INTRODUCTION: Drug induced colitis is historically in reference to a reaction to nonsteroidal anti-inflammatory and antibiotic medications. More recently immune checkpoint inhibitors have been recognized as a cause of immune mediated colitis. Ipilimumab and Nivolumab are monoclonal antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), respectively. They increase activity of T cells against cancerous cells but can simultaneously result in stimulation of T cells against non-cancerous tissues such as the GI tract. Reported incidence of colitis is about 5 times greater with ipilimumab compared to Nivolumab and is 13.6% with combination therapy. CASE DESCRIPTION/METHODS: A 51-year-old Caucasian woman with relapsed metastatic melanoma presented with intractable nausea, vomiting, abdominal pain, and copious diarrhea. Diarrhea began about 4 weeks prior to presentation following the second cycle of ipilimumab and nivolumab. After the third cycle, diarrhea worsened with more than 7 episodes of non-bloody diarrhea per day, unresponsive to loperamide and diphenoxylate. Physical exam was benign without abdominal tenderness. On admission, serum Na and K were 132 mMol/L and 2.3 mMol/L, respectively. The patient underwent aggressive fluid and electrolyte replacement. Stool culture and Clostridioides difficile DNA amplification stool test were negative. Colonoscopy revealed significant, severe colitis in transverse and descending colon. Mild-moderate colitis in sigmoid colon with erythema, friable scattered punched out ulcers and proctitis were also observed. Multiple biopsies were taken which showed mild architectural abnormality with ulceration, crypt abscess, apoptotic bodies, and inflammatory cells in lamina propria. No granuloma or dysplasia were observed histologically. IV steroid was initiated and followed by oral steroid therapy; her symptoms subsequently improved. Steroids were tapered over the course of 8 weeks and she has not had any recurrence to date. DISCUSSION: Immune mediated colitis is one of the side effects of immune checkpoint inhibitors. Patients with worsening symptoms and negative infectious workup who do not respond to conservative treatment need to be admitted and evaluated promptly with colonoscopy. Once the diagnosis is reached, conservative treatment with steroid therapy should be started. Patients should be monitored closely to avoid complications such as bowel perforation and toxic megacolon.Figure 1.: Left sided colon micrograph, obtained by colonoscopy, demonstrating friable scattered punched out ulcers in the colon.Figure 2.: Biopsy from a colon lesion (x200 magnification, Hematoxylin and Eosin staining) demonstrating inflammatory cells in lamina propria, crypt abscess (hollow arrow), and crypts destruction and dropout (solid arrow).

Neutrophil extracellular traps-associated protein peptidyl arginine deaminase 4 immunohistochemical expression in ulcerative colitis and its association with the prognostic predictors

Neutrophil extracellular traps (NETs) are incriminated in several immune and inflammatory diseases including ulcerative colitis (UC). Analysis of colonic tissues for NETs-related markers in UC carries prognostic and therapeutic implications. This work aims to evaluate the immunohistochemical (IHC) expression of NETs-associated-protein arginine deaminase 4 (PAD4) in colonic biopsies from UC patients in comparison to normal colon (NC). Association between PAD4 expression level and histopathologic grade, patient’s therapeutic response and other clinicopathological prognostic predictors in UC are determined. This cohort study included biopsies from 42 UC patients and 11 NC controls. Clinicopathological data including patient's age at diagnosis, gender, presenting symptoms, anatomical disease extent, extra-intestinal manifestations, type and response to therapy and surgical interventions were recorded and tabulated. Histopathological grading of disease activity and associated epithelial changes were assessed. PAD4 immunostaining was conducted using Horseradish Peroxidase technique and scored semiquantitatively considering intensity and percentage of nuclear staining of lamina propria inflammatory cells. Appropriate statistical tests were applied. Anti-PAD4 was localized mainly in the nuclei of lamina propria infiltrating neutrophils. It was expressed more significantly in UC (95.2 %) compared to NC (p 0.001). Increased PAD4 expression level was significantly associated with increasing histopathologic grade, anatomical disease extent, lacking response to therapy and subjection to radical surgery (p:0.001, = 0.038, 0.046, 0.046 respectively). Age, gender, presenting symptoms, extra-intestinal manifestations and epithelial changes showed insignificant associations. This study characterizes a subset of UC patients with high histopathological grade of activity, pancolonic involvement, strong/moderate PAD4 expression levels and who are unresponsive to routine medical therapeutic regimens rendering them candidates for radical surgery. In conjunction with histopathological grading, IHC evaluation of PAD4 in UC is recommended to guide patient’s selection for targeted therapy using the novel-discovered selective PAD4 inhibitors.

Increased expression of PD-1 and PD-L1 in oral lesions progressing to oral squamous cell carcinoma: a pilot study

Oral cancer is a devastating disease and is commonly preceded by a range of oral premalignant disorders. We investigated the expression of PD-1 and PD-L1 in oral epithelial dysplasia (OED) that progressed to oral squamous cell carcinoma (OSCC) compared to non-progressing dysplasia. 49 oral biopsies were analyzed, including 19 progressing cases, 20 cases did not progress, and 10 OSCC. Samples were stained with monoclonal antibodies for PD-1 and PD-L1, followed by conventional peroxidase reaction immunohistochemistry (IHC) imaged under light microscopy or fluorescent immunohistochemistry (FIHC) imaged using a confocal microscope. Images were analyzed using a novel semi-automated analysis protocol. PD-1/PD-L1 expression was assessed at the epithelium/tumor cells (TC) and at inflammatory cells in lamina propria. Our results show a significant increase in PD-L1 expression in progressing compared to non-progressing dysplasia. Using FIHC, we showed increased PD-L1 expression, increased nuclear density in progressing dysplasia and a better interobserver agreement compared with IHC. We developed a new FIHC-based quantitative method to study PD-1/PD-L1 expression in FFPE samples and showed that PD-L1 is highly expressed in premalignant lesions progressing to cancer. Our results suggest that immunomodulation via PD-L1/PD-1 pathway occurs prior to malignant transformation.

Immunohistochemical, histological and ultrastructural evaluation of protection provided by cholera vaccine against V. cholerae O139

In our previous study, complete protection was observed in rabbit immunized with 1 × 1010 CFU of live attenuated VCUSM21P vaccine against challenge with 1 × 109 CFU Vibrio cholerae O139. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological, immunohistochemical and ultrastructural techniques. Severe pathology is evident in wild type injected ileum in non-immunized, showing extensive villous destruction, edema, necrosis and inflammation with infiltration of large numbers of inflammatory cells, extensive damage to the villi and microvilli with pore formation. Histology of ileum injected with wild type in immunized rabbit shows no significant pathological changes except for a few inflammatory cells in lamina propria with mild edema in mucosa and submucosa. immunohistochemical staining revealed O139 antigens of wild type are seen in the lamina propria of edematous villi, muscularis mucosa and submucosa with weak presence in the muscle coat in non-immunized rabbit after challenged with wild type in non-immunized rabbits, but in immunized rabbit localisation of the O139 LPS antigen is seen at the tips of the intact villi, within lamina propria and muscularis mucosa only. These observations suggest that the vaccine can effectively protect animals from any pathologic changes and eliminate V. cholerae O139 from the immunized animals.

A man in his fifties with chronic diarrhoea and weight loss.

Watery diarrhoea coupled with weight loss is a serious condition with many potential causes. We present a possibly underappreciated cause which usually responds well to treatment; left untreated it may have a severe course. A man in his fifties with known coronary and cerebrovascular disease was admitted for watery diarrhoea. Prerenal kidney failure occurred on the same day as the initial colonoscopy. The next day he suffered a stroke. He was anticoagulated and recovered within days. In the following months his state of malabsorption continued, with ultimately 50% weight loss (BMI 14.7) and severe electrolyte disturbances. Intravenous electrolyte solutions and nutrition were administered. Oedema and aphthous duodenal lesions were the only endoscopic findings. Microscopic findings of total villus atrophy in all sampled sites in the small intestine, including the ileum, were striking. There were inflammatory cells in lamina propria, apoptotic cells and disappearance of goblet cells. Coeliac disease was ruled out by serology and HLA typing. A final diagnosis of autoimmune enteropathy was made, based on exclusion of other intestinal and systemic diseases. Treatment with infliximab intravenously and budesonide in an open capsule regime was successful.

The Possible Role of Bee Venom on Gastric Fundic Mucosa in Streptozotocin Induced Diabetes Mellitus in Rats. A Histological study.

Introduction: Diabetes mellitus represents one of the most prevalent chronic diseases and a major public health challenge worldwide. It leads to serious consequences in several tissues including gastrointestinal tract. Bee venom (BV) is a traditional medicine used for treating various diseases. Aim: to investigate the effects of diabetes on gastric fundic mucosal changes and to evaluate the possible therapeutic role of BV on these changes in a rat model of streptozotocin (STZ) induced diabetes mellitus. Materials and methods: Thirty adult male albino Wister rats were divided into four groups. Group I (control), group II (BV): received intraperitoneal injection (IP) of 0.5mg/kg BV twice weekly for four weeks, group III (diabetic): received single IP of 45mg/kg STZ and group IV (diabetic-BV treated): one week after confirmation of diabetes, rats received BV for four weeks (as group II). At the end of the experiment, samples of the fundus of the stomach were collected from all rats. The specimens were processed for light and transmission electron microscopic studies. Morphometric and statistical studies were also performed.Results: diabetic rats showed sloughing of fundic epithelium, significant decrease in mucous secreting cells, significant increase in collagen fibers and increase inflammatory cells in lamina propria. Cells of fundic glands were seen with karyolitic nuclei and dilated rough endoplasmic reticulum. Administration of BV showed improvement of histological structural changes induced by diabetes. Conclusions: BV have relevant therapeutic role in the fundic mucosa induced by diabetes. So, it could potentially provide possible solution for gastric changes associated with diabetes.

Esophageal manometry, esophagogastroduodenoscopy, and duodenal mucosal histopathology in systemic sclerosis.

Background and AimSystemic sclerosis (SSc) is known to involve the gastrointestinal (GI) tract, resulting in dysmotility, gastroesophageal reflux disease, and mucosal changes causing significant morbidity. The study aimed to assess esophageal motility and duodenal mucosal changes in SSc.MethodsThis is a prospective, cross‐sectional, single‐center study of 23 patients with SSc diagnosed on the basis of standard criteria. Clinical details including the GI symptoms were recorded. All of them underwent esophagogastroduodenoscopy with duodenal biopsy, and 21 underwent esophageal manometry.ResultsRegurgitation, heartburn, and dysphagia were seen in 19 (82%), 16 (69%), and 10 (43%) patients, respectively. On endoscopy, 19 patients (83%) showed changes of reflux esophagitis (4 had grade C esophagitis), and 3 had esophageal candidiasis. Of the 21 patients who underwent esophageal manometry, 13 (62%) had absent peristalsis, 6 (28%) had ineffective peristalsis, and 10 (48%) had hypotensive lower esophageal sphincter (LES). Duodenal biopsy showed partial villous atrophy in 9 (39%) patients, increased intraepithelial lymphocytes in 18 (78%), and excess of mononuclear inflammatory cells in lamina propria in 21 (91%). Partial villous atrophy was seen more commonly in those with abnormal esophageal peristalsis and a hypotensive LES.ConclusionMost of the patients with SSc had esophageal dysmotility in the form of absent peristalsis, ineffective esophageal peristalsis, and hypotensive LES. Histology of descending duodenum demonstrated partial villous atrophy and chronic inflammatory infiltrates in most of the patients with SSc.

Mitochondrial DNA Is a Pro-Inflammatory Damage-Associated Molecular Pattern Released During Active IBD.

Due to common evolutionary origins, mitochondrial DNA (mtDNA) shares many similarities with immunogenic bacterial DNA. MtDNA is recognized as a pro-inflammatory damage-associated molecular pattern (DAMP) with a pathogenic role in several inflammatory diseases. We hypothesised that mtDNA is released during active disease, serving as a key pro-inflammatory factor in inflammatory bowel disease (IBD). Between 2014 and 2015, we collected plasma separated within 2 hours of sampling from 97 prospectively recruited IBD patients (67 ulcerative colitis [UC] and 30 Crohn's disease [CD]) and 40 non-IBD controls. We measured circulating mtDNA using quantitative polymerase chain reaction (amplifying mitochondria COXIII/ND2 genes) and also in mouse colitis induced by dextran sulfate-sodium (DSS). We used a mass spectometry approach to detect free plasma mitochondrial formylated peptides. Furthermore, we examined for mitochondrial damage using electron microscopy (EM) and TLR9 expression, the target for mtDNA, in human intestinal IBD mucosa. Plasma mtDNA levels were increased in UC and CD (both P < 0.0001) compared with non-IBD controls. These levels were significantly correlated to blood (C-reactive protein, albumin, white cell count), clinical and endoscopic markers of severity, and disease activity. In active UC, we identified 5 mitochondrial formylated peptides (the most abundant being fMMYALF with known chemoattractant function) in plasma. We observed mitochondrial damage in inflamed UC mucosa and significantly higher fecal MtDNA levels (vs non-IBD controls [P < 0.0001]), which supports gut mucosal mitochondrial DAMP release as the primary source. In parallel, plasma mtDNA levels increased during induction of acute DSS colitis and were associated with more severe colitis (P < 0.05). In active IBD, TLR9+ lamina propria inflammatory cells were significantly higher in UC and CD compared with controls (P < 0.05). We present the first evidence to show that mtDNA is released during active IBD. MtDNA is a potential mechanistic biomarker, and our data point to mtDNA-TLR9 as a therapeutic target in IBD. 10.1093/ibd/izy095_videoizy095.video5776747659001.

Report of an Outbreak of Peste Des Petits Ruminants in Iran, Clinical, Epidemiological and Pathological Study

Peste des petits ruminants (PPR) is an acute to sub-acute highly contagious and frequently fatal viral disease of goats and sheep and wild small ruminants caused by a virus in the genus morbilivirus, family paramyxoviridae. The flock of sheep including 800 fattening sheep were affected and the presence of PPR virus was assayed with RT-PCR test. The only significant change in the CBC was leucopenia. There were typical lesions on dental pad, hard palate, gingiva and tongue. The Morbidity and case fatality rates were estimated 50 and 60 percent, respectively. All deaths were happen in lambs and young sheep. Results of the histopathologcal findings indicated that the lesions were mainly located on the respiratory system, upper digestive system, kidney and lymphoid organs. Infiltration of mononuclear and inflammatory cells in lamina propria were seen in mouth, soft palate, intestines, lung, and tonsil. Secondary infection as result of immunosuppression activity of the PPR virus was happened and resulted in high mortality and case fatality. The present paper reports an outbreak of PPR in a sheep flock in Karaj, Alborz province in Iran, including pathological, and clinical observation and also serological detection.

Duodenitis in Systemic Autoimmune Diseases: Pathologist Perspective

Aims: To study the histomorphology of duodenitis associated with systemic autoimmune diseases with clinicopathologic correlation. Patients and Methods: This is a descriptive prospective study. Fifteen patients of autoimmune diseases with duodenitis were included. Informed consent was taken. Histomorphological parameters studied were villous architecture, crypt architecture, intraepithelial lymphocyte (IEL) count per 100 enterocytes, villous tip IEL count per 20 enterocytes were counted, inflammatory cells in lamina propria—lymphocytes, neutrophils, eosinophils, epithelioid cells. Statistical analysis was done using IBM-SPSS software version 21. Results: Fifteen cases of duodenitis associated with autoimmune diseases included 6 patients of systemic lupus erythematosus (SLE), 5 of rheumatoid arthritis, one each of ankylosing spondylitis, systemic sclerosis, dermatomyositis and seronegative reactive arthritis. All these cases were serologically proven. Only 3 (20%) patients had mild villous blunting. Six patients (46.7%) had increased IEL counts. The range of IELs was 8 - 30, mean ± SD was 14 ± 7.6. Range of villous tip IELs was 0 - 8 with mean ± SD of 3.45 ± 2.56. Six patients (46.7%) had increased IEL counts but only 3 patients (20%) had increased villous tip IELs. All patients had moderate increase in lymphoplasmacytic infiltrate in lamina propria. Eosinophils in lamina propria were increased in 46.7% cases. Conclusion: One of the causes for malabsorptive conditions in adult population in South India is found to be duodenitis associated with autoimmune conditions. We conclude that a combination of clinical, serological, endoscopic and histopathologic features is crucial in arriving at a correct diagnosis.

Histopathological Effects of Methomyl Pesticide and Mobile Phone Electromagnetic Radiation on Duodenum of Male Albino Rats

Methomyl is a carbamate broad spectrum insecticide; quickly paralyze the nervous system of insects by blocking the production and action of cholinesterase. The rapid development and sharp increase of using mobile phones by people has led researchers to concern about diverse effects of mobile phone radiofrequency waves exposure on human health, this study was achieved to investigate the histopathological effects of methomyl pesticide and mobile phone radiofrequency radiation on rat duodenum tissues. Male rats were divided into four groups: First group served as control, second group was treated with 50 mg/L methomyl orally; rats of the third group were exposed to mobile phone radiofrequency waves 10 minutes daily, rats of the group four were administrated with 50 mg/L methomyl and exposed to mobile phone radiofrequency waves 10 minutes daily. After seven days treatment, obvious histological changes were observed in duodenal tissues of rat groups treated with methomyl alone and methomyl with mobile exposure, these changes were including deteriorating of villi shape, decreasing the villi and crypts length, increasing number of goblet cells, increasing infiltration of inflammatory cells in lamina propria, deterioration and congestion of blood vessels in lamina propria of duodenal tissue. On the other hand there was no histological change of duodenal tissue in rats exposed to mobile phone alone. These results concluded that methomyl has toxic effects on small intestine tissue, while mobile phone radiofrequency exposure has not any effect on duodenal tissues.

A CEACAM6-High Airway Neutrophil Phenotype and CEACAM6-High Epithelial Cells Are Features of Severe Asthma.

Severe asthma represents a major unmet clinical need; understanding the pathophysiology is essential for the development of new therapies. Using microarray analysis, we previously found three immunological clusters in asthma: Th2-high, Th17-high, and Th2/17-low. Although new therapies are emerging for Th2-high disease, identifying molecular pathways in Th2-low disease remains an important goal. Further interrogation of our previously described microarray dataset revealed upregulation of gene expression for carcinoembryonic Ag cell adhesion molecule (CEACAM) family members in the bronchi of patients with severe asthma. Our aim was therefore to explore the distribution and cellular localization of CEACAM6 using immunohistochemistry on bronchial biopsy tissue obtained from patients with mild-to-severe asthma and healthy control subjects. Human bronchial epithelial cells were used to investigate cytokine and corticosteroid in vitro regulation of CEACAM6 gene expression. CEACAM6 protein expression in bronchial biopsies was increased in airway epithelial cells and lamina propria inflammatory cells in severe asthma compared with healthy control subjects. CEACAM6 in the lamina propria was localized to neutrophils predominantly. Neutrophil density in the bronchial mucosa was similar across health and the spectrum of asthma severity, but the percentage of neutrophils expressing CEACAM6 was significantly increased in severe asthma, suggesting the presence of an altered neutrophil phenotype. CEACAM6 gene expression in cultured epithelial cells was upregulated by wounding and neutrophil elastase. In summary, CEACAM6 expression is increased in severe asthma and primarily associated with airway epithelial cells and tissue neutrophils. CEACAM6 may contribute to the pathology of treatment-resistant asthma via neutrophil and airway epithelial cell-dependent pathways.

Colonic Lamina Propria Inflammatory Cells from Patients with IBD Induce the Nuclear Factor-E2 Related Factor-2 Thereby Leading to Greater Proteasome Activity and Apoptosis Protection in Human Colonocytes.

The antioxidant transcription factor Nrf2 confers broad cytoprotection and has a dual role in tumorigenesis. Enhancing proteasome activity is one mechanism by which Nrf2 can promote cancer development, e.g., colorectal cancer. This study investigated whether this potential oncogenic effect of Nrf2 emerges already from the epithelial adaptation to persistent oxidative stress during inflammatory bowel disease (IBD). Reactive oxygen species (ROS)-producing inflammatory myeloid cells (IMCs) from colon tissue of patients with IBD were cocultured with human NCM460 colonocytes. ARE-luciferase-, c-H2DCF-DA-assays, Western blotting, and quantitative polymerase chain reaction were performed for assessing Nrf2-activity, intracellular ROS-level, and Nrf2-target gene expression. Proteasome activity was quantified by Suc-LLVY-amido-4-methylcumarin-assay, and apoptosis by caspase-3/-7 assay and PARP1-Western blots. Nrf2, proteasome proteins, and IMCs were analyzed in IBD-tissues by immunohistochemistry. IMC-coculture caused a temporary increase of ROS in NCM460, followed by Nrf2 activation and elevated expression of ROS-protecting enzymes (NQO1, GCLC). This was accompanied by Nrf2-dependent expression of proteasome proteins (PSMD4, PSMA5) and an enhanced proteasome activity in IMC-cocultured NCM460. Nrf2-siRNA or the ROS-scavenger Tiron blocked these alterations. Depending on Nrf2-induced proteasome activity, IMC-cocultured NCM460 or Colo320 cancer cells were less sensitive to apoptosis (TRAIL-/etoposide induced). Immunostaining of IBD-tissues confirmed Nrf2 activation in the colonic epithelium within inflamed areas, along with greater proteasome protein expression. IMC/NCM460-coculture experiments and immunohistochemistry of colonic tissues from patients with IBD reveal a Nrf2-dependent adaptation of colon epithelial cells to oxidative stress caused by inflammatory cells. This involves increased proteasome activity and apoptosis resistance that protect from tissue damage due to colitis on one hand, but on the other hand, may favor carcinogenesis.

Primary Gastrointestinal Histoplasmosis and Vedolizumab

A 38 year old Caucasian male diagnosed with severe ileo-colonic Crohn's disease (complicated with an ileo-cecal valve stricture) 20 years ago presented with abdominal pain, diarrhea and weight loss for 3 months. Mesalamine therapy at initial diagnosis and a subsequent trial of infliximab, adalimumab and natalizumab failed to induce remission. A disease flare persisted with endoscopic evidence of moderate to severe inflammation along the terminal ileum(TI) and entire colon(edema, erythema, friability, granularity,ulcerations and pseudopolyps). Remission was achieved with Vedolizumab and oral prednisone 40mg with a successful taper down to only 25mg daily due to symptoms recurrence. He reported less frequent, less bloody and more formed stools on the regimen. Pertinent medical history includes Clostridium difficile infection(CDI) 2 months after starting vedolizumab that failed oral vancomycin therapy but resolved with fidaxomycin. A surveillance colonoscopy a year after intiating vedolizumab revealed similar findings as mentioned above with significant improvement in endosocopic appearance (pseudopolyps, scarring surrounded by normal mucosa) and microscopic inflammation (architectural distortion, inflammatory cells in lamina propria). Additionally,3 new multi-lobulated cecal polyps too large to be removed endoscopically were biopsied as dysplasia was of concern. Pathology confirmed Histoplasma and he began therapy with Itraconazole for primary gastrointestinal Histoplasmosis(GIH) in the absence of systemic infection with reported improvement in symptoms on reevaluation at 3 months.His diarrhea is at his baseline of 6 bowel movements a day, without rectal bleeding, abdominal pain or weight loss. He is pending a colonoscopy in 1 month. Histoplasmosis is common among patients taking TNF-α inhibitors with related hospitalizations increasing by 15% per year in the last decade and a mortality rate reported at 20%. While there is evidence that vedolizumab increases risk of CDI and cytomegalovirus colitis, data on risk of fungal infections is lacking. GIH frequently involves the TI and cecum secondary to systemic disease making this case of primary GIH intriguing. Further, presentation as a colonic mass is rare, with 20 cases reported thus far. Treatment involves systemic antifungals. Providers should be vigilant for fungal infections among patients on biologics and take timely steps to diagnose and treat them to reduce resultant morbidity and mortality.Figure 1Figure 2Figure 3