Subepithelial Region Research Articles

High density of CD8 T cell and immune imbalance of T lymphocytes subsets are associated with proliferative verrucous leukoplakia.

Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1β and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.

EVALUATION OF THE TISSUE EXPRESSION OF THE VITAMIN D RECEPTOR (VDR) IN PATIENTS WITH ORAL LICHEN PLANUS

<h3>Objectives</h3> To evaluate the tissue expression of the vitamin D receptor (VDR) in samples of oral lichen planus (OLP) and whether there is a correlation with clinical-demographic parameters and disease severity. <h3>Study Design</h3> Tissue samples were selected from patients whose clinical and histopathologic diagnosis of OLP was performed according to the criteria of the American Academy of Oral and Maxillofacial Pathology. Clinical parameters such as sex, age, location, clinical type, symptoms, extraoral manifestations, and response to corticosteroid therapy were recorded. The immunohistochemistry technique was used for semiquantitative evaluation of VDR expression in the epithelial and subepithelial regions. Density of VDR+ cells was determined using a grid reticle (0.0961 mm²). <h3>Results</h3> All cases (<i>n</i> = 15) were women with an average age of 49 years. The clinical types erosive (<i>n</i> = 8; 53.3%) and reticular (<i>n</i> = 7; 46.6%) were the most frequent. High expression of VDR+ cells was observed throughout the epithelial region in 100% of cases and, in the subepithelial region, the average percentage of immunostained inflammatory cells was 80.5%. <h3>Conclusions</h3> VDR tissue expression was high in OLP, but there were no relations with the clinical-demographic characteristics and severity parameters of this disease.

Automated Precancerous Lesion Screening Using an Instance Segmentation Technique for Improving Accuracy

Precancerous screening using visual inspection with acetic acid (VIA) is suggested by the World Health Organization (WHO) for low–middle-income countries (LMICs). However, because of the limited number of gynecological oncologist clinicians in LMICs, VIA screening is primarily performed by general clinicians, nurses, or midwives (called medical workers). However, not being able to recognize the significant pathophysiology of human papilloma virus (HPV) infection in terms of the columnar epithelial-cell, squamous epithelial-cell, and white-spot regions with abnormal blood vessels may be further aggravated by VIA screening, which achieves a wide range of sensitivity (49–98%) and specificity (75–91%); this might lead to a false result and high interobserver variances. Hence, the automated detection of the columnar area (CA), subepithelial region of the squamocolumnar junction (SCJ), and acetowhite (AW) lesions is needed to support an accurate diagnosis. This study proposes a mask-RCNN architecture to simultaneously segment, classify, and detect CA and AW lesions. We conducted several experiments using 262 images of VIA+ cervicograms, and 222 images of VIA−cervicograms. The proposed model provided a satisfactory intersection over union performance for the CA of about 63.60%, and AW lesions of about 73.98%. The dice similarity coefficient performance was about 75.67% for the CA and about 80.49% for the AW lesion. It also performed well in cervical-cancer precursor-lesion detection, with a mean average precision of about 86.90% for the CA and of about 100% for the AW lesion, while also achieving 100% sensitivity and 92% specificity. Our proposed model with the instance segmentation approach can segment, detect, and classify cervical-cancer precursor lesions with satisfying performance only from a VIA cervicogram.

Characterization of M Cells in Tear Duct-Associated Lymphoid Tissue of Mice: A Potential Role in Immunosurveillance on the Ocular Surface.

The ocular mucosal tissues are exposed to potentially harmful foreign antigens in the air and tear fluid. The tear duct-associated lymphoid tissue (TALT) may contribute to immune surveillance in the eye region. Follicle-associated epithelium (FAE) of TALTs is classified as stratified squamous epithelium and consists of squamous epithelial cells arranged in layers on the basement membrane. In contrast, most mucosa-associated lymphoid tissue is covered by a monolayer of epithelium containing microfold (M) cells. Therefore, antigen uptake and the presence of M cells in TALT are not fully understood. The present study found that a small population of FAE cells in the TALT expressed intestinal M-cell markers, namely Sox8, Tnfaip2, GP2, and OPG. This cell population was identified as functional M cells because of their uptake capacity of luminal nanoparticles. In addition, RANKL, which is essential for M-cell differentiation, was expressed by stroma-like cells at the subepithelial region and its receptor RANK by the FAE in the TALT. The administration of RANKL markedly increased the number of Sox8+ M cells. In contrast, deficiency in OPG, an endogenous inhibitor of RANKL, increased the number of M cells in the TALT. These data demonstrate that the RANKL-RANK axis is essential for M-cell differentiation in the TALT. Furthermore, immunization via eye drops elicited the production of antigen-specific antibodies in tears, which was enhanced by RANKL administration. Thus, TALT M cells play an important role in the immunosurveillance of the eye region.

EFFECT OF CITRAKADI KSARA LĒPA IN THE MANAGEMENT OF SECOND-DEGREE INTERNAL HAEMORRHOIDS

Background and Objectives: Haemorrhoids are dilated veins within the anal canal in the sub-epithelial region formed by radicles of superior, middle, and inferior rectal veins. It hampers the routine life of an affected person. In India about 50% of the population would have haemorrhoids at some point in their life. Achārya Vāgbhata defines Arsas (haemorrhoids) as an abnormal growth which obstructs the anal canal and troubles continuously like an enemy The objective of the study is to assess the efficacy of citrakādi kṣāra lēpa in the management of second- degree internal haemorrhoids. The study also aims to find out an easy, effective and less complicated procedure for second-degree haemorrhoids. The 15 participants with second degree internal haemorrhoids were selected as per inclusion criteria. After doing all the preoperative procedures, the citrakādi kṣāra lēpa was done in a single sitting. The duration of the study was 30 days. The assessment of reduction of size of haemorrhoids, mucosal changes after the procedure and frequency of bleeding were done before the treatment, on 1st, 3rd, 5th, 7th, 15th, and 30th day using the required assessment tools. The symptoms, constipation and mucous discharge were assessed on the 0th and 30th days. The follow up was done on the 60th day. The statistical analysis of the results was done using non- parametric tests. On analysing, it was found that the Citrakādi kṣāra shows 86.11% of the efficacy in the reduction of both subjective and objective parameters. Key words: Haemorrhoids, Arsas, Citrakādi kṣāra

Enigmatic Neural Pathways: Potentiating Viral Neuroinvasion Into the CNS.

Enigmatic Neural Pathways: Potentiating Viral Neuroinvasion Into the CNS.

A REVIEW ON VANASURANA GHRTA IN THE MANAGEMENT OF ARSHAS

Arshas is one among many diseases which are most unkind towards mankind. The incidence of Arshas increases with advancing age and at least 50% of people over the age of 50 years have some degree of hemorrhoidal symp- toms. Hemorrhoids are the dilated veins in the anal canal in the subepithelial region formed by radicals of the su- perior, middle, and inferior rectal vein[1]. In this modern era the improper diet habits, junk food intake, inhibition of natural urges and mental strain makes one susceptible to this disease. Acharya Sushrutha while detailing the treatment principles of Arshas has categorized it as Bheshajasadhya, Kshara Karma Sadhya, Agnikarmasadhya and shastra karma sadhya[2]. Surgical treatments though commonly being practised are very painful and hence will put the patients into more agony. Despite putting the patient into such a state there are high chances of recur- rence of the condition. Hence there is a need for very effective as well as less/non-agonizing treatment for Arshas. Vansurana Ghrta is an unexplored formulation that is mentioned in ChikitsaManjari[3]. The main ingredient Vanasurana is considered as Agryoushada for Arshas in Kaiyyadevanighandu. Keywords: Arshas, Vanasurana ghrta

A REVIEW OF JALUKAVACHARANA (LEECH THERAPY) IN THE MANAGEMENT OF THROMBOSED HAEMORRHOIDS - CASE REPORTS

Haemorrhoids are dilated veins within the anal canal in the subepithelial region formed by radicles of superior, middle and inferior rectal veins. It is a common ano-rectal disease. Thrombosed hemorrhoid is a painful swelling in the anal tissues caused by a clot in one or more small veins in the anal canal. According to modern science, there are many operative and non-operative procedures for the management of haemorrhoids. Most of the operative pro- cedures are not patient friendly, cause high economic burden and associated with complications like pain, bleeding and recurrence. Acharya Vagbhata defines Arsas (haemorrhoids) as an abnormal growth which obstructs the anal canal and troubles continuously like an enemy. Shalyatantra deals with Sastra karma (surgical procedures), Anusas- tra karma (parasurgical procedures) and conservative management in the different types of diseases. Jaluka is con- sidered as best among Anusastra. Acharya Vagbhata indicates Jalukavacharana in haemorrhoids when they are hard and swollen. The present article deals with Jalukavacharana in two patients having thrombosed haemorrhoids attended in outpatient department of VPSV Ayurveda College Kottakkal. Application of Jaluka (leech) provided improvement in features like pain, edema, tenderness and discoloration of mass. Keywords: Thrombosed haemorrhoids, Arsha, Raktamokshana, Jalukavacharana.

MHTP, a synthetic alkaloid, attenuates combined allergic rhinitis and asthma syndrome through downregulation of the p38/ERK1/2 MAPK signaling pathway in mice

The combined allergic rhinitis and asthma syndrome (CARAS) is a chronic airway inflammation of allergic individuals, with a type 2 immune response. Pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study was to evaluate the synthetic alkaloid, MHTP in the experimental model of CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with MHTP by intranasal or oral routes. Treated animals showed a decrease (p < 0.05) of sneezing, nasal rubbings, and histamine nasal hyperactivity. Besides, MHTP presented binding energy and favorable interaction for adequate anchoring in the histamine H1 receptor. MHTP treatment inhibited the eosinophil migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids. Histological analysis showed that the alkaloid decreased the inflammatory cells in the subepithelial and perivascular regions of nasal tissue and in the peribronchiolar and perivascular regions of lung tissue. The MHTP treatment also reduced the pulmonary hyperactivity by decreasing the smooth muscle layer hypertrophy and the collagen fiber deposition in the extracellular matrix. The immunomodulatory effect of the alkaloid was due to the decrease of cytokines like IL-5 and IL-17A (type 2 and 3), TSLP (epithelial), and the immunoregulatory cytokine, TGF-β. These MHTP effects on granulocytes were dependent on the p38/ERK1/2 MAP kinase signaling pathway axis. Indeed, the synthetic alkaloid reduced the frequency of activation of both kinases independent of the NF-κB (p65) pathway indicating that the molecule shut down the intracellular transduction signals underlie the cytokine gene transcription.

New 'Antigens' in Membranous Nephropathy.

Membranous nephropathy (MN) occurs due to deposition of immune complexes along the subepithelial region of glomerular basement membrane. Two previously identified target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), account for approximately 60% of all MN, both primary and secondary. In the remaining MN, target antigens were unknown. Use of laser microdissection and mass spectrometry enabled identification of new "antigens." This approach led to the identification of four novel types of MN: exotosin 1 (EXT1)- and exotosin 2 (EXT2)-associated MN, NELL1-associated MN, Sema3B-associated MN, and PCDH7-associated MN. Each of these represents a distinct disease entity, with different clinical and pathologic findings. In this review, the structure of the proteins and the clinical and pathologic findings of the new types of MN are discussed. The role of mass spectrometry for accurate diagnosis of MN cannot be overemphasized. Finally, any classification of MN should be made on the basis of the antigens that are detected. Further studies are required to understand the pathophysiology, response to treatment, and outcomes of these new MNs.

HIV-ASSOCIATED ORAL MUCOSAL MELANIN HYPERPIGMENTATION: A CASE REPORT

Postinflammatory hyperpigmentation is a reactive hypermelanosis that develops following cutaneous inflammation. Common causes of this condition include intrinsic skin conditions as well as external insults to the skin, including infections. Human immunodeficiency virus (HIV)-associated oral melanotic hyperpigmentation is categorized under "lesions less commonly associated with HIV infection." The aim of this study is to report a case of an HIV-associated oral mucosal melanin hyperpigmentation. A 55-year-old man attended the referral service in oral diagnosis, presenting a blackened spot, showing smooth surface and irregular borders in the region of the right jugal mucosa, measuring about 2 cm in diameter. The patient had previous diagnosis of HIV and did not show pigmentation in other regions of the body. An incisional biopsy was performed. The histopathological examination showed pigmentary incontinence of melanophages in the subepithelial region. The patient is under medical supervision and using antiretrovirals. In addition, he will be observed to follow the evolution of oral condition. Postinflammatory hyperpigmentation is a reactive hypermelanosis that develops following cutaneous inflammation. Common causes of this condition include intrinsic skin conditions as well as external insults to the skin, including infections. Human immunodeficiency virus (HIV)-associated oral melanotic hyperpigmentation is categorized under "lesions less commonly associated with HIV infection." The aim of this study is to report a case of an HIV-associated oral mucosal melanin hyperpigmentation. A 55-year-old man attended the referral service in oral diagnosis, presenting a blackened spot, showing smooth surface and irregular borders in the region of the right jugal mucosa, measuring about 2 cm in diameter. The patient had previous diagnosis of HIV and did not show pigmentation in other regions of the body. An incisional biopsy was performed. The histopathological examination showed pigmentary incontinence of melanophages in the subepithelial region. The patient is under medical supervision and using antiretrovirals. In addition, he will be observed to follow the evolution of oral condition.

EVALUATION OF INFLAMMATORY MARKERS IN POTENTIALLY MALIGNANT DISORDERS OF THE ORAL CAVITY

Objective: The aim this study was to evaluate the expression of inflammatory markers in potentially malignant disorders of oral cavity (leukoplakia) and its relationship with the degree of epithelial dysplasia. Study design: Immunohistochemistry was used to identify the number (cells/mm2) of interleukin 17 (IL-17+), neutrophil (CD66 b+), matrix metalloproteinase‐9 (MMP-9+) cells, and neoformed microvessels (CD105+) in the subepithelial region of leukoplakia samples from 31 patients. Evaluation of IL‐17 expression in keratinocytes cells was semiquantitative and performed by assigning scores. Samples of healthy oral mucosa (n = 10) were used as controls. Results: The classification of epithelial dysplasia by the binary grading system totaled 17 samples with high risk and 14 samples with low risk of malignant transformation. Irrespective of the severity of epithelial dysplasia, the counts of inflammatory markers (CD66 b, IL-17, MMP-9, and CD105) were higher in the leukoplakia group compared to controls (P< .05 for all comparisons). In addition, the intraepithelial expression of IL-17 was high in leukoplakia samples (44%) and absent/low in the control group (100%; P< .05). Conclusions: This study showed that potentially malignant disorders of oral cavity are characterized by a high count of inflammatory markers. Objective: The aim this study was to evaluate the expression of inflammatory markers in potentially malignant disorders of oral cavity (leukoplakia) and its relationship with the degree of epithelial dysplasia. Study design: Immunohistochemistry was used to identify the number (cells/mm2) of interleukin 17 (IL-17+), neutrophil (CD66 b+), matrix metalloproteinase‐9 (MMP-9+) cells, and neoformed microvessels (CD105+) in the subepithelial region of leukoplakia samples from 31 patients. Evaluation of IL‐17 expression in keratinocytes cells was semiquantitative and performed by assigning scores. Samples of healthy oral mucosa (n = 10) were used as controls. Results: The classification of epithelial dysplasia by the binary grading system totaled 17 samples with high risk and 14 samples with low risk of malignant transformation. Irrespective of the severity of epithelial dysplasia, the counts of inflammatory markers (CD66 b, IL-17, MMP-9, and CD105) were higher in the leukoplakia group compared to controls (P< .05 for all comparisons). In addition, the intraepithelial expression of IL-17 was high in leukoplakia samples (44%) and absent/low in the control group (100%; P< .05). Conclusions: This study showed that potentially malignant disorders of oral cavity are characterized by a high count of inflammatory markers.

Skin Architecture, Kidney Transplantation, and Their Relationship to Basal and Squamous Cell Carcinomas.

Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step. We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC. KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria. KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients.

Analysis of CCR3 expression in corneal neovascularization in a murine model and human corneas

The aim of this study was to examine the expression of the cytokines and chemokines receptor-3 (CCR3) molecule in endothelial cells and vascular structures in a murine model of corneal neovascularization and in samples of neovascularized human corneas. An immunofluorescence assay using the murine model showed a greater proportion and intensity of CCR3 in the epithelium and corneal subepithelial regions in corneas with neovascularization. In the absence of vascularization, no CCR3 was found. Of the 32 studied tissues, eight were vascularized and 24 were avascular. In the human corneas, vascularized corneas showed positive labeling for CD31 in all the analzedtissues, as well as positive labeling for CCR3. Therefore, all vascularized tissues showed positive coexpression of CCR3 and CD31, whereas none of the avascular corneas showed immunolabeling for either of these receptors. These results suggest that CCR3 could be a possible marker for corneal neovascularization with potential to be a therapeutic target.

Warifteine and methylwarifteine inhibited the type 2 immune response on combined allergic rhinitis and asthma syndrome (CARAS) experimental model through NF-кB pathway

CARAS is an airway inflammation of allergic individuals, with a type 2 immune response. The pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study evaluated the alkaloids warifteine (War) and methylwarifteine (Mwar) from Cissampelos sympodialis in CARAS experimental model. Therefore, BALB/c mice were ovalbumin (OVA) sensitized and challenged and treated with both alkaloids. Treated animals showed a decrease (p < 0.05) of allergic signs as sneezing and nasal rubbings, histamine nasal hyperreactivity, and inflammatory cell migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids, main eosinophils. In the systemic context, only Mwar reduced eosinophilia, however, both alkaloids reduced the serum levels of OVA-specific IgE. Histological analysis revealed that the alkaloids decreased the inflammatory cells into the subepithelial and perivascular regions of nasal tissue and the peribronchiolar and perivascular regions of lung tissue. Hyperplasia/hypertrophy of nasal and lung goblet cells were reduced in alkaloid treated animals; however, the treatment did not change the number of mast cells. The lung hyperactivity was attenuated by reducing hyperplasia of fibroblast and collagen fiber deposition and hypertrophy of the lung smooth muscle layer. The immunomodulatory effect was by decreasing of type 2 and 3 cytokines (IL-4/IL-13/IL-5 and IL-17A) dependent by the increasing of type 1 cytokine (IFN-γ) into the BALF of treated sick animals. Indeed, both alkaloids reduced the NF-кB (p65) activation on granulocytes and lymphocytes, indicating that the alkaloids shut down the intracellular transduction signals underlie the transcription of TH2 cytokine gens.

Microdot Accumulation in the Anterior Cornea with Aging – Quantitative Analysis with in Vivo Confocal Microscopy

ABSTRACT Purpose Degenerative ‘microdot’ deposits in healthy and hypoxic corneas are believed to represent lipofuscin-like material aggregation in the stroma. To accurately assess microdot deposits in a clinical setting, we sought to quantify these deposits for the first time using the non-invasive clinical imaging technique of in vivo confocal microscopy (IVCM). Methods The corneas of 102 healthy subjects aged 15–88 years were examined by IVCM and microdot density was quantified using a 6-point grading scale by two masked, trained examiners. Microdot density was analyzed with respect to age, sex and stromal depth, and inter-eye and inter-observer differences were evaluated. Results In healthy subjects, microdot density decreased from the anterior to posterior stroma, with the greatest accumulation observed in the most anterior stroma (subepithelial region). In this region, microdot density correlated strongly with age (P < .0001), with increased microdot deposition in older subjects (>60 years) relative to younger ones (<45 years) (P < .001). Microdot density between eyes of the same subject was highly correlated (r = 0.92, P < .0001), while no association with sex was noted (P ≥ 0.05). The mean inter-observer difference in microdot assessment was 0.62 ± 0.09 grades, with a high correlation of grading between observers (r = 0.77, P < .0001). Conclusions IVCM can be used to non-invasively quantify microdot deposits in the subepithelial corneal stroma with good inter-observer reproducibility. Microdot assessment may provide a novel means of quantifying age-related or pathologic degeneration of the corneal stroma in a clinical setting.

Histochemical Studies on the Major Lymphoid Organs in Various Chicken Genotypes

A total number of eighteen day old Hansli chicks and eighteen day old Vencobb broiler chicks were divided into three age groups viz. group I (up to 1 month), group II (1-3 months) and group III (3-6 months) with six birds in each age group. On each observation day (4th week, 12th week and 24th week), six birds from each breed were used for the study of histochemical features of the thymus, spleen and bursa of Fabricius. It was found that the capsule, septa and tunics of blood vessels revealed age specific PAS activities, whereas the Alcian blue activities varied with age and was restricted to the thymic capsule and trabeculae. The splenic capsule, tunics of blood vessels and intercellular region of splenic white pulp revealed age specific PAS positive activity, whereas the Alcian blue activity was only reported in the splenic capsule of 12th week age Hansli chicken and Vencobb broiler chicken. The apical borders of both follicle associated epithelium and interfollicular epithelium, sub-epithelial region, cortico-medullary junction, medulla of lymphoid follicle, interfollicular connective tissue, central connective tissue core of bursal plicae, walls of blood vessels, tunica muscularis and tunica serosa revealed age specific PAS activities, whereas the apical borders of follicle associated epithelium (FAE), interfollicular epithelium (IFE) and goblet cells of lining surface epithelium, tunica muscularis and tunica serosa showed age specific Alcian blue activities in both the birds.

Inhibition of Escherichia coli invasion into bovine mammary epithelial cells previously infected by Mycobacterium avium subsp. paratuberculosis

Background The coinfection process of Escherichia coli, an etiological agent of clinical mastitis and Mycobacterium avium subsp. paratuberculosis (MAP), a non-mastitic etiological agent in the bovine mammary gland is not fully known. Objective Verify the ability of MAP to interfere with the invasion and translocation of E. coli in bovine mammary epithelial cell line (MAC-T). Methods For the invasion assay, MAC-T cells were challenged with MAP K10 for 2 h and then challenged with E. coli for 10, 30 and 120 min. For the translocation assay, the trans well plates were used and the challenge sequence was repeated as previously described. The amount of E. coli in the assays was determined by counting colony forming units (CFU) in Luria-Bertani medium. Quantitative real-time PCR was used to quantify MAP in MAC-T cells. To verify the viability of the MAC-T cells, the MTT assay was performed. MAP culture supernatant was also evaluated at different percentages for E. coli growth. Results Previous MAP infection in MAC-T cells inhibited E. coli invasion in 10, 30 and 120 min. No significant interference of MAP in the translocation of E. coli from the apical-basal direction was verified. Quantity of MAP DNA inside the MAC-T cells was statistically similar. Neither reduction in MAC-T cells viability was detected during the experiment nor MAP-released factor in the supernatant inhibited E. coli invasion. Conclusion These findings suggest that MAP-positive cows could be more resistant to E. coli infection, but when infected, could rapidly translocate E. coli to the subepithelial region.

Primordial odontogenic tumor: A systematic review.

Background The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early odontogenesis. Aim: To integrate the available data published on POT into a comprehensive analysis to better define its clinicopathological and molecular features. Material and Methods An electronic systematic review was performed up to September 2019 in multiple databases. Results A total of 13 publications were included, representing 16 reported cases and 3 molecular studies. The mean age of the affected patients was 11.6 years (range 2-19), with a slight predominance in males (56.25%). The posterior mandible was the main location (87.5%), with only two cases affecting the posterior maxilla. All cases appeared as a radiolucent lesion in close relationship to an unerupted tooth. Recurrences have not been reported to date. Microscopically, POT comprises fibromyxoid tissue with variable cellularity surrounded by a cuboidal to columnar odontogenic epithelium but without unequivocal dental hard tissue formation. A delicate fibrous capsule surrounds (at least partially) the tumor. The epithelial component shows immunohistochemical positivity for amelogenin, CK19, and CK14, and variable expression of Glut-1, Galectin-3 and Caveolin-1, Vimentin, p-53, PITX2, Bcl-2, Bax and Survivin; the mesenchymal tissue is positive for Vimentin, CD90, p-53, PITX2, Bcl-2, Bax, and Survivin, and the subepithelial region exhibits the strong expression of Syndecan-1 and CD34. The Ki-67 index is low (<5%). The negative or weak expression of dentinogenesis-associated genes could explain the inhibition of dentin and subsequent enamel formation in this neoplasm. Conclusions POT is an entity with a well-defined clinicopathological, immunohistochemical and molecular profile that must be properly diagnosed and differentiated from other odontogenic lesions and treated consequently. Key words:Primordial odontogenic tumor, systematic review.

Development of Mucosal Immunity: Functional Interactions with Mucosal Microbiome in Health and Disease

The mucosal surfaces and the skin are the primary sites of interactions between the mammalian host and the external environment. These sites are exposed continuously to the diverse components of the environment, including subcellular, unicellular and multicellular organisms, dietary agents and food products; and numerous other soluble or cellular air or water borne products. The development of innate and adaptive immunity in the mucosal surfaces and the skin are the principal mechanism of mammalian defense evolved to date, in order to maintain effective homeostatic balance between the host and the external environment. The innate immune functions are mediated by a number of host specific Pathogen Recognition Receptors (PRR), designed to recognize unique Pathogen Associated Molecular Patterns (PAMP), essential to the molecular structure of the microorganism. The major components of specific adaptive immunity in the mucosal surfaces include the organized antigen-reactive lymphoid follicles in different inductive mucosal sites and the effector sites of the lamina propria and sub-epithelial regions, which contain lymphoid and plasma cells, derived by the homing of antigen sensitized cells from the inductive sites. The acquisition of environmental microbiome by the neonate in its mucosal surfaces and the skin, which begins before or immediately after birth, has been shown to play a critical and complex role in the development of mucosal immunity. This report provides an overview of the mammalian microbiome and highlights its role in the evolution and functional development of immunologic defenses in the mucosal surface under normal physiologic conditions and during infectious and non-infectious inflammatory pathologic states associated with altered microbiota.