Intense Infiltration Research Articles

Paratuberculose clínica bovina: primeiro relato no estado do Pará

ABSTRACT The objective of this work was to describe the clinical, pathological, and serological aspects of paratuberculosis in a bullock on dairy and beef farm in the municipality of Inhangapí, state of Pará. The animal was raised extensively and presented progressive weight loss, pale mucous membranes, and chronic diarrhea. A blood sample was collected for serology by the indirect ELISA technique. Due to the unfavorable prognosis, the animal was euthanized and necropsied. At necropsy, there was thickened and wrinkled intestinal mucosa, enlarged mesenteric lymph nodes and liquid intestinal contents with a brown color. Organ fragments were fixed in 10% buffered formaldehyde, embedded in paraffin wax, cut, and stained by hematoxylin and eosin and by Ziehl-Neelsen techniques. Histopathology showed intense granulomatous infiltration with Langhans giant cells in the lamina propria and submucosa of the small intestine, Peyer patches and mesenteric lymph nodes. Ziehl-Neelsen staining revealed many intralesional acid-fast bacilli. Antibody searching against Mycobacterium avium (subsp.) paratuberculosis was positive. The diagnosis of paratuberculosis was based on epidemiological, clinical, pathological, and serological data. This is the first report of clinical paratuberculosis, confirmed by pathology and serology, in a bullock in the state of Pará.

Inmixed and Bellicose-Adenosquamous Carcinoma-Uterine Cervix

Adenosquamous carcinoma of uterine cervix is a preponderantly high grade neoplasm configured of admixed glandular articulations and squamous epithelium wherein glassy cell carcinoma emerges as an exceptional, aggressive variant. Adenosquamous carcinoma is posited to arise from sub-columnar reserve cells confined to endocervical basal epithelium. Cytological smears depict papillary articulations admixed with bland columnar epithelial cells and high grade squamous intraepithelial lesion. The biphasic tumour is composed of well defined, malignant components of glandular articulations and poorly differentiated squamous epithelium. Glassy cell carcinoma demonstrates solid cell nests comprised of pleomorphic, polygonal tumour cells pervaded with glassy, eosinophilic cytoplasm, enlarged, eosinophilic nuclei, prominent nucleoli and distinct cytoplasmic membrane. Neoplastic cells appear enmeshed within an intense inflammatory cell infiltrate with significant eosinophils. Glassy cell carcinoma appears immune reactive to MUC1, MUC2, epithelial membrane antigen (EMA), CAM5.2 or p63 with focal immune reactivity to carcinoembryonic antigen (CEA). Adenosquamous carcinoma requires segregation from neoplasms such as adenocarcinoma with coexisting squamous intraepithelial lesion (SIL), adenoid basal carcinoma, cervical extension of endometrial adenocarcinoma, and squamous cell carcinoma with focal mucin droplets, large cell non keratinizing squamous cell carcinoma or lymphoepithelioma-like carcinoma. Tumefaction may be appropriately treated by radical abdominal hysterectomy followed by adjuvant chemotherapy and radiation therapy.

Piddling and Moderate-Primary Cutaneous CD4+ Small/Medium T Cell Lymphoproliferative Disorder

Initially contemplated as a provisional subtype of cutaneous T cell lymphoma (CTCL), primary cutaneous CD4+ small / medium T cell lymphoproliferative disorder manifests as an indolent, solitary cutaneous lesion in the absence of accompanying cutaneous lymphoma as mycosis fungoides. Preponderantly, infiltration of upper dermis with miniature to intermediate, pleomorphic CD4+ T cells in the absence of preceding or concurrent patches and plaques with focal epidermotropism is encountered. Primary cutaneous CD4+ small/medium T cell lymphoproliferative disorder commonly appears in adults as a solitary plaque, tumour or nodule situated upon face, neck, upper trunk or thoracic region. Upon cytology, pleomorphic, miniature, intermediate or occasionally enlarged T lymphoid cells with irregular nuclear contours are variably intermixed with miniature, reactive CD8+ T cells, B cells, plasma cells, histiocytes and monotypic plasma cells. Morphologically, an intense dermal infiltrate of atypical lymphoid cells or small / medium pleomorphic CD4+ T cells extending into subcutaneous tissue appears to configure a diffuse or nodular configuration wherein the enlarged, pleomorphic cells articulate < 30% of neoplastic cellular infiltrate. Neoplastic lymphocytes appear immune reactive to T cell markers as CD3, CD4, CD5 along with T follicular helper markers as CD279 (PD-1), ICOS and CXCL13. Primary cutaneous CD4+ small/medium T cell lymphoproliferative disorder necessitates segregation from mycosis fungoides, cutaneous involvement with systemic T cell lymphoma of T follicular helper immuno-phenotype, benign inflammatory infiltrate, extra-nodal marginal zone (MALT) lymphoma or adult T cell leukaemia /lymphoma. The disorder can be therapeutically managed with intralesional steroids, radiotherapy or surgical extermination of lesion.

DOES GALLIC ACID HAVE A POTENTIAL REMEDIAL EFFECT IN EXPERIMENTAL CORROSIVE BURN INJURY TO THE ESOPHAGUS?

Gallic acid, acting as an antioxidant, anti-precipitant and cytoprotective agent, was used as a possible remedial natural component for treating experimentally induced esophageal burn. Wistar rats (n=24) were divided into three groups. Control group was given 1 mL 0.9% NaCl. Experimental esophageal burn was induced with 1 mL 40% NaOH application to the esophagus in groups 2 and 3. Gallic acid® (20 mg/kg) was administered to the treated group via oral gavage for 10 days. Removed tissues were fixed and paraffin blocks were prepared. Histopathological examination was performed after the sections had been stained with hematoxylin-eosin. Tumor necrosis factor alpha and caspase-3 antibodies were used on immunohistochemical analysis. In the esophageal burn group, necrosis, degeneration and numerous apoptotic cells, as well as intense inflammatory cell infiltration and fibrosis in the muscle layer were observed under light microscope. In the treated group, remodeling of epithelial cells with marked reduction in the connective tissue collagen content was observed, as well as marked reduction in the volume of collagen and abundance of inflammatory cells in blood vessels. Gallic acid treatment may help heal esophageal burns and prevent complications.

Endoscopic Diagnosis of Eosinophilic Esophagitis: Basics and Recent Advances.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease, characterized by esophageal dysfunction and intense eosinophil infiltration localized in the esophagus. In recent decades, EoE has become a growing concern as a major cause of dysphagia and food impaction in adolescents and adults. EoE is a clinicopathological disease for which the histological demonstration of esophageal eosinophilia is essential for diagnosis. Therefore, the recognition of the characteristic endoscopic features with subsequent biopsy are critical for early definitive diagnosis and treatment, in order to prevent complications. Accumulating reports have revealed that EoE has several non-specific characteristic endoscopic findings, such as rings, furrows, white exudates, stricture/narrowing, edema, and crepe-paper esophagus. These findings were recently unified under the EoE endoscopic reference score (EREFS), which has been widely used as an objective, standard measurement for endoscopic EoE assessment. However, the diagnostic consistency of those findings among endoscopists is still inadequate, leading to underdiagnosis or misdiagnosis. Some endoscopic findings suggestive of EoE, such as multiple polypoid lesions, caterpillar sign, ankylosaurus back sign, and tug sign/pull sign, will aid the diagnosis. In addition, image-enhanced endoscopy represented by narrow band imaging, endocytoscopy, and artificial intelligence are expected to render endoscopic diagnosis more efficient and less invasive. This review focuses on suggestions for endoscopic assessment and biopsy, including recent advances in optical technology which may improve the diagnosis of EoE.

LPS- and LTA-Induced Expression of TLR4, MyD88, and TNF-α in Lymph Nodes of the Akkaraman and Romanov Lambs.

Toll-like receptor (TLR)-mediated inflammatory processes play a critical role in the innate immune response during the initial interaction between the infecting microorganism and immune cells. This study aimed to investigate the possible microanatomical and histological differences in mandibular and bronchial lymph nodes in Akkaraman and Romanov lambs induced by lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and study the gene, protein, and immunoexpression levels of TLR4, myeloid differentiation factor 88 (MyD88), and tumor necrosis factor-α (TNF-α) that are involved in the immune system. Microanatomical examinations demonstrated more intense lymphocyte infiltration in the bronchial lymph nodes of Akkaraman lambs in the LPS and LTA groups compared to Romanov lambs. TLR4, MyD88, and TNF-α immunoreactivities were more intense in the experimental groups of both breeds. Expression levels of MyD88 and TNF-α genes in the bronchial lymph node of Akkaraman lambs were found to increase statistically significantly in the LTA group. TLR4 gene expression level in the mandibular lymph node was found to be statistically significantly higher in the LTA + LPS group. In conclusion, dynamic changes in the immune cell populations involved in response to antigens such as LTA and LPS in the lymph nodes of both breeds can be associated with the difference in the expression level of the TLR4/MyD88/TNF-α genes.

Interplay between Immune Cell Infiltration and Tumor Histological Subtype: A Case of Adrenocortical Cancer.

The analysis of the tumor microenvironment, especially tumor-infiltrated immune cells, is essential for predicting tumor prognosis, clinical outcomes, and therapy strategies. Adrenocortical cancer is a rare nonimmunogenic malignancy in which the importance of the presence of immune cells is not well understood. In our study, we made the first attempt to understand the interplay between the histology of adrenocortical cancer and its immune landscape using cases from The Cancer Genome Atlas database and the Endocrinology Research Centre collection (Moscow, Russia). We showed that the oncocytic variant of adrenocortical cancer is characterized by intensive immune infiltration and better survival, and it is crucial to analyze the effect of immune infiltration independently for each histological variant.

Developmental Mechanism of Rainfall-Induced Ground Fissures in the Kenya Rift Valley

Active tectonic movement and frequent ground fissure disasters occur in the Kenya Rift Valley. Ground fissures are often exposed to the ground surface after rainfall, resulting in disasters and huge economic losses. We conducted a field geological survey and exploratory trenching in order to identify the developmental characteristics of ground fissures in the Kenya Rift Valley. The ground fissures were found to be connected with concealed bedrock fissures, which is a typical characteristic of tectonic ground fissures. From the perspective of regional tectonic stress and plate movement, we investigated the causes of hidden bedrock cracks and conducted a finite element numerical simulation to study the rainfall infiltration process in the presence of hidden bedrock fractures. The results showed that the fractures in the concealed bedrock are controlled by regional tectonic stress and a northwest-trending basement tectonic shear zone. The most intense rainfall infiltration erosion occurs in concealed cracks, where the settlement induced by rainfall is also greatest. Therefore, rainfall erosion is an important factor driving the expansion of ground fissures towards surface fractures. The results of this study provide a theoretical scientific basis for disaster reduction and the prevention of ground fissures in the Kenya Rift Valley.

Eosinophils promote proliferation of pulmonary structural cells by stimulating extracellular matrix production in asthma

Introduction. Eosinophilic asthma can be characterized by intense infiltration of eosinophils into the airways, where they abundantly release various cytokines, chemokines and growth factors. Airway remodeling is closely related to increased airway smooth muscle (ASM) mass; however, another important feature could be changes in extracellular matrix (ECM) homeostasis, driven by the production of ECM proteins and metalloproteinases by lung structural cells. Aim. To evaluate and compare eosinophil adhesion to ASM cells and pulmonary fibroblasts or their secreted ECM and the effect on pulmonary structural cell autocrine proliferation adjustment in asthma. Methods. A total of 12 allergic asthma (AA), 8 severe eosinophilic asthma (SEA) patients and 11 healthy subjects (HS) were examined. Blood eosinophils were isolated using high density Ficoll centrifugation and magnetic separation. For each study individual combined cell cultures (co-cultures) between isolated eosinophils and pulmonary structural cells or their secreted ECM were prepared. ECM purification was performed using ammonium hydroxide (NH4OH) based cell lysis. Eosinophils adhesion was evaluated by measuring eosinophils peroxidase activity in co-cultures; pulmonary structural cell proliferation was measured by AlamarBlue assay. Results. In all investigated groups eosinophil adhesion to ECM was significantly increased compared to eosinophil adhesion to ASM cells and pulmonary fibroblasts (p < 0.01). Eosinophil adhesion to ASM cells and pulmonary fibroblasts or their secreted ECM in asthma groups was significantly enhanced compared to HS group (p < 0.05). Isolated ASM cell or pulmonary fibroblast’ produced ECM after co-cultures with AA, SEA and HS eosinophils promoted newly seeded ASM cell and pulmonary fibroblast proliferation (p < 0.01) with stronger effect in both asthma groups. ECM, isolated after combined cultures with AA, SEA or HS eosinophils and the blood serum of the study patient also significantly promoted the proliferation of ASM cells and pulmonary fibroblasts (p < 0.01). Isolated ASM cell or pulmonary fibroblast’ produced ECM after co-cultures with AA and SEA eosinophils had a stronger effect to newly seeded pulmonary structural cell proliferation than after co-cultures with HS eosinophils. Conclusions. Eosinophils demonstrate enhanced adhesion to ECM components than to ASM cells or pulmonary fibroblasts, and adhesion further increases in asthma. Pulmonary structural cells promote their proliferation in autocrine manner via released ECM components after incubation with eosinophils in asthma.

Amicrobial pustulosis of the folds mimicking Hailey-Hailey disease in a patient with systemic lupus erythematosus and Sjögren’s syndrome

Sir, Amicrobial pustulosis of the folds (APF) is a rare disease of neutrophilic dermatosis involving the scalp, ears, axillae, umbilicus, groin, and buttocks [1–3]. Herein, we describe a case of APF involving the bilateral axillae mimicking Hailey-Hailey disease in association with systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SjS). A 63-year-old female had been undergoing treatment for SLE and SjS for six years. She had been taking prednisolone at a dose of 4 mg per day on the first visit to us. She also had a history of Crohn’s disease in remission. She complained of recurrent, erosive erythema on the axillae and beneath the breasts, which worsened in summer. A physical examination revealed infiltrative erythema with superficial erosions on the bilateral axillae (Figs. 1a and 1b). A laboratory examination revealed normal liver and kidney function, yet positive results for serum antinuclear antibodies (1:1280), anti-double strand DNA antibody (128 IU/mL), anti-Sm antibody (index: 6.7), anti-SS-A antibody (index: 131.5), and anti-SS-B antibody (index: 93.7). The erythrocyte sedimentation rate was high (32 mm in the first hour), and the CRP level was slightly increased (1.19 mg/dL). Bacterial cultures were positive for group G streptococci and the Corynebacterium species. A biopsy specimen did not reveal acantholysis of the epidermis, yet mild epidermal acanthosis without intense infiltration of inflammatory cells. Hailey-Hailey disease was excluded, and the patient was followed under treatment with topical corticosteroid ointment. During the course, the skin lesions exacerbated, and new pustules and erosive erythemas appeared on the groin and the anogenital areas (Fig. 1c). A histopathological examination revealed subcorneal neutrophilic abscesses in the epidermal and dermal perifollicular areas (Figs. 2a – 2d).

P160 Paracoccidioidomycosis severe: Bizarre presentation in the face

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM IntroductionParacoccidioidomycosis is a systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis. The disease is restricted to Latin America. It is the principal systemic mycosis in Brazil, with higher incidences in the southern, southeastern and central regions.ObjectivesIt's to report a case of paracoccioidomycosis with a bizarre presentation on the face.Case ReportA 54-year-old male farmer from Açailândia, Maranhão, with a history of an extensive ulcerated lesion that started in the right wing of the nose. After 6 months of evolution, the lesion had already spread reaching the nasal and oral mucosa, evolving with acute respiratory failure, requiring tracheostomy (Fig.1). He was referred to the Cancer Hospital for a biopsy, which was referred for pathological examination, showing an intense inflammatory infiltrate consisting of lymphocytes, histiocytes, neutrophilis with giant, multinucleated cells that phagocytize refrigerant bodies, compatible with paracoccidioidomycosis. Material sent for direct examination and culture, showed positive for Paracoccidioides sp. After PCR amplification of the genetic material and sequencing, P. brasiliensis was identified. Chest tomography showed sparse ground-glass attenuation, but affecting both lungs and radiodense striations in the lower lobes bilaterally. Treatment was established with liposomal amphotericin B, with a good therapeutic response (Fig. 2). The patient was discharged from the hospital using itraconazole and still upper outpatient follow-up, with good healing of the lesions.ConclusionParacoccidioidomycosis can get a severe presentation, distancing the physician from the diagnosis, showing that in all these situations, simple tests, such as the direct examination of lesional material or sputum can elucidate the diagnosis. We need to think about it in endemic area.

IMMUNOHISTOCHEMICAL EXPRESSION OF METALLOPROTEINASES AND TFN-Α BY MACROPHAGES AND LANGERHANS CELLS IN RADICULAR CYSTS

Objectives This research aimed to evaluate the relationship between Langerhans cells, macrophages, matrix metalloproteinases (MMPs-9, -13), and tumor necrosis factor (TNF)-α in the lining epithelium of cystic lesions to elucidate the cyst expansion. Study Design A sectional and retrospective study was performed with 20 radicular cysts (RCs) and 20 residual radicular cysts (RRCs) by anti-CD68, anti-CD1a, anti-MMP-9, anti-MMP-13, and anti-TNF-α antibodies. Results The immunoexpression of MMP-13 and CD68 was significantly higher in RCs when compared to RRCs (P = .011 and P = .012, respectively). An intense inflammatory infiltrate was significantly correlated with CD68 immunoexpression in RCs (P = .025). Macrophages demonstrated a significant positive correlation with MMP-13 (P = .015). A moderate correlation was observed between MMP-9 and MMP-13 (P = .01). TNF-α expression was more common in RCs (P = .001). Langerhans cells were more frequently expressed in atrophic epithelium (P = .041) and significantly correlated with TNF-α (P = .014) in RCs. Conclusions Macrophages induce a greater release of TNF-α. Higher immunoexpression of MMP-13 and MMP-9 is observed in the early stages of RCs compared to RRCs. The microorganisms are the main factors triggering a proinflammatory immune response and greater cystic expansion in the early stages of these cysts. This research aimed to evaluate the relationship between Langerhans cells, macrophages, matrix metalloproteinases (MMPs-9, -13), and tumor necrosis factor (TNF)-α in the lining epithelium of cystic lesions to elucidate the cyst expansion. A sectional and retrospective study was performed with 20 radicular cysts (RCs) and 20 residual radicular cysts (RRCs) by anti-CD68, anti-CD1a, anti-MMP-9, anti-MMP-13, and anti-TNF-α antibodies. The immunoexpression of MMP-13 and CD68 was significantly higher in RCs when compared to RRCs (P = .011 and P = .012, respectively). An intense inflammatory infiltrate was significantly correlated with CD68 immunoexpression in RCs (P = .025). Macrophages demonstrated a significant positive correlation with MMP-13 (P = .015). A moderate correlation was observed between MMP-9 and MMP-13 (P = .01). TNF-α expression was more common in RCs (P = .001). Langerhans cells were more frequently expressed in atrophic epithelium (P = .041) and significantly correlated with TNF-α (P = .014) in RCs. Macrophages induce a greater release of TNF-α. Higher immunoexpression of MMP-13 and MMP-9 is observed in the early stages of RCs compared to RRCs. The microorganisms are the main factors triggering a proinflammatory immune response and greater cystic expansion in the early stages of these cysts.

LOWER LIP MELANOACANTHOMA MICROSCOPICALLY PRESENTING PLASMA CELL CHEILITIS–LIKE FEATURES

Oral melanoacanthoma is an uncommon benign pigmented lesion, microscopically presenting hyperplasia of spinous keratinocytes and dendritic melanocytes. Its pathogenesis remains uncertain, although the clinical behavior suggests a reactive origin. Oral melanoacanthoma affects mainly young adults and Blacks, with a strong female predilection. The most common oral sites are the buccal mucosa, lip, palate, and gingiva. Plasma cell cheilitis (PCC) is an inflammatory disorder of unknown etiology that affects the lips. The clinical presentation of PCC is variable, sometimes simulating malignancy, and microscopically characterized by a dense plasma cell infiltrate. Here, we present a 59-year-old Black male patient presenting blackish-colored lesions, associated with a reddish erosive area, on the lower lip, 1.5 years ago. Microscopy revealed melanoacanthoma associated with intense lymphoplasmacytic infiltrate, such as observed in PCC. If the current case represents a microscopic spectrum of melanoacanthoma or simultaneous presence of melanoacanthoma and PCC remains open to debate, however, we favor the former.

ORAL ERYTHEMA MULTIFORME—A CASE REPORT

An acute inflammatory condition that affects the skin and mucosa, erythema multiforme is caused by a cell-mediated immune response. This paper reports the case of a patient diagnosed with erythema multiforme. A 29-year-old male patient reported pain in the mouth and throat lesions. During intraoral examination the presence of erosive and ulcerated lesions was noted, with erythematous coloration, disseminated, diffuse limits, irregular format, hemorrhagic and ulcerated surface in the buccal mucosa, soft palate, and lateral border of the tongue. Incisional biopsy was performed. Histopathology revealed a parakeratinized epithelium with hyperplasia, acanthosis, hydropic degeneration, focal exocytosis, and ulcers covered with fibrinous exudate. The lamina propria of fibrous connective tissue was permeated by intense mononuclear inflammatory infiltrate. The conclusion was a chronic nonspecific inflammatory process with perivascular disposition, confirming the diagnosis of erythema multiforme. Total remission was obtained with prednisolone 20 mg for 30 days without relapse for 3 years.

THE ROLE OF ORAL LESIONS IN THE DIAGNOSIS OF BEHÇET'S SYNDROME

Behçet's syndrome is an inflammatory disorder known as a singular model of vasculitis. A 47-year-old male patient was referred to the stomatologist by a rheumatologist after hospitalization for thrombosis of the iliac vein and inferior vena cava and high C-reactive protein and erythrocyte sedimentation rate values. The patient reported recurrent folliculitis and oral and scrotum ulcerations. Intraoral examination revealed ulcerations dispersed through the mucosa. An excisional biopsy was performed in a right buccal mucosa lesion. Histopathologic analysis demonstrated nonkeratinized stratified squamous epithelium with areas of exocytosis and ulceration. Connective tissue presented an intense mixed inflammatory infiltrate, congested vessels, hemorrhage, and vasculitis. HLA-B genotyping identified the presence of HLA-B15. The histopathologic report associated with the other findings enabled the rheumatologist to diagnose the condition. The patient is on daily continuous oral use of colchicine 0.5 mg and prednisolone 20 mg, in addition to weekly subcutaneous administration of 0.1 mL of methotrexate 25 mg/mL and has been without recurrence for 8 months.

GLANDULAR CHEILITIS: CASE REPORT

Glandular cheilitis is a rare chronic inflammatory disease affecting the minor salivary glands, predominantly in the lower lip. An 18-year-old Black woman presented with macrocheilia with a soft consistency in the lips. There were yellowish crusts in the vermilion border that, when removed, revealed multiple punctate red, painful papules in lip mucosa. After ruling out associated systemic disease and infections, an incisional biopsy was performed in the lower lip. Histopathologic findings consisted of enlarged salivary ducts with accumulation of material suggestive of mucus, intense inflammatory mononuclear infiltrate, and areas of ductal metaplasia and acinar degeneration in the minor salivary glands. A final diagnosis of glandular cheilitis was made. Topical clobetasol propionate was prescribed 3 times per day and progressive improvement was observed over 30 days. The patient did not present recurrence in 6 months of follow-up.

The Histopathology of Anorectal Neisseria gonorrhoeae Infection.

Neisseria gonorrhoeae infection of the anorectal tract is often asymptomatic and infrequently biopsied, but pathologists can be tasked with identifying the histologic features of possible infection. The study was undertaken to better characterize clinical and morphologic features of confirmed anorectal gonococcal infection. From 2011 to 2020, 201 positive gonococcal nucleic acid amplification testing samples from 174 patients collected from the distal colorectum and/or anus were matched to eight patients with concurrent biopsy specimens of the distal anorectum. Complete demographic, clinical, and infectious information was collected for each biopsied patient. The histomorphologic features of each biopsy were systematically tabulated. All eight gonococcal cases were obtained from men who have sex with men. Each case showed at least mild acute inflammation with moderate activity identified in one case with concurrent cytomegalovirus infection. Intense lymphoplasmacytic infiltration was not commonly seen (two of eight). Half of the cases showed mucosal ulceration, and seven of eight cases demonstrated lymphoid aggregates. The microscopic features are mild compared with other well-described types of infectious proctitis, with most cases displaying mild acute inflammation and scattered lymphoid aggregates. These findings highlight the importance of obtaining a complete patient history and recommending additional infectious workup even when only subtle changes are present.

Influence of supplement administration of omega-3 on the subcutaneous tissue response of endodontic sealers in Wistar rats.

Natural substances such as omega-3 have been used in the medical field due to their numerous properties and, in particular, modulating effect on the systemic and local inflammatory processes. Thus, this study evaluated the influence of omega-3 supplementation on the subcutaneous tissue response of endodontic sealers in Wistar Rats. Polyethylene tubes were implanted in the subcutaneous tissue of 48 animals (one empty for control and three filled with Sealapex, AH Plus or Endofill). The animals were treated with omega-3 (TO) or water (TW). Treatments started 15 days before implantation until euthanasia. After 5, 15 and 30 days (n=8), animals were euthanized and polyethylene tubes and surrounding tissue were removed and processed for histological analysis. The inflammatory reaction was analysed by Haematoxylin and Eosin stain and immunolabelling for IL-6 and TNF-α. The collagen maturity was analysed by picrosirius red stain and calcium deposition by von Kossa stain and polarized light. Results were statistically analysed (p < .05). Amongst TW sealer groups, Endofill evoked a more intense inflammatory infiltrate compared with AH Plus and control in the 30-day period (p=.009). However, in TO sealer groups, there was no difference amongst the sealers and control in all periods (p >.05). Comparing each sealer as a function of the supplementation with water or omega-3, there are differences for Endofill (p =.001) and Sealapex (p =.005) in the 30-day period, presenting lower inflammatory infiltrate in the animals treated with omega-3. A higher percentage of immature fibres was observed at 15 and 30 days in the TO group, compared with the TW group (p <.05). The deposition of calcium particles was observed only by Sealapex in all periods, despite the supplementation procedure. Omega-3 supplementation influence the tissue reactions of endodontic sealers, modulating inflammation, the immunolabelling of IL-6 and TNF-α, the repair process and it does not interfere with calcium deposition.

Immune and Genetic Signatures of Breast Carcinomas Triggering Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration.

Background and ObjectivesParaneoplastic cerebellar degeneration (PCD) with anti-Yo antibodies is a cancer-related autoimmune disease directed against neural antigens expressed by tumor cells. A putative trigger of the immune tolerance breakdown is genetic alteration of Yo antigens. We aimed to identify the tumors' genetic and immune specificities involved in Yo-PCD pathogenesis.MethodsUsing clinicopathologic data, immunofluorescence (IF) imaging, and whole-transcriptome analysis, 22 breast cancers (BCs) associated with Yo-PCD were characterized in terms of oncologic characteristics, genetic alteration of Yo antigens, differential gene expression profiles, and morphofunctional specificities of their in situ antitumor immunity by comparing them with matched control BCs.ResultsYo-PCD BCs were invasive carcinoma of no special type, which early metastasized to lymph nodes. They overexpressed human epidermal growth factor receptor 2 (HER2) but were hormone receptor negative. All Yo-PCD BCs carried at least 1 genetic alteration (variation or gain in copy number) on CDR2L, encoding the main Yo antigen that was found aberrantly overexpressed in Yo-PCD BCs. Analysis of the differentially expressed genes found 615 upregulated and 54 downregulated genes in Yo-PCD BCs compared with HER2-driven control BCs without PCD. Ontology enrichment analysis found significantly upregulated adaptive immune response pathways in Yo-PCD BCs. IF imaging confirmed an intense immune infiltration with an overwhelming predominance of immunoglobulin G–plasma cells.DiscussionThese data confirm the role of genetic alterations of Yo antigens in triggering the immune tolerance breakdown but also outline a specific biomolecular profile in Yo-PCD BCs, suggesting a cancer-specific pathogenesis.

Eosinophilic Granulomatous Myocarditis in Two Pigs

Eosinophilic myocarditis is a human condition that has been rarely documented in animals. We now report two unrelated porcine cases of idiopathic eosinophilic granulomatous myocarditis that resembled the human disease and which were associated with sudden death. The most relevant gross finding in both cases was marked cardiomegaly, accompanied by raised, multifocal to coalescent small white nodules (1-2mm) and poorly demarcated multifocal pale areas in the epicardium. Histologically, there were multifocal to coalescent areas of cardiomyocyte loss with replacement by an intense inflammatory infiltrate of eosinophils and epithelioid macrophages, and proliferation of fibrous connective tissue. Immunohistochemistry for porcine circovirus type 2 (PCV2) and Toxoplasma gondii, in-situhybridization and quantitative polymerase chain reaction tests for PCV2 and porcine circovirus type 3 and aerobic bacterial culture on myocardium samples were negative.