Alteración en la integridad de la membrana basal en agrandamiento gingival inducido por tratamiento ortodóncico / Alteration of the Basal Membrane Integrity in Orthodontic Treatment-Induced Gingival Enlargement

Introducción: El agrandamiento gingival inducido por tratamiento de ortodoncia es un aumento progresivo, localizado o generalizado del tejido gingival. Objetivo: Determinar aspectos morfológicos en la membrana basal del tejido gingival de pacientes con agrandamiento gingival inducido por tratamiento de ortodoncia. Métodos: Estudio descriptivo de corte transversal, donde se analizaron tejidos gingivales de pacientes con agrandamiento gingival inducido por tratamiento de ortodoncia (grupo test: n=5) e individuos sanos (grupo control: n=5) mediante análisis histológicos e inmunohistoquímico con anticuerpo policlonal anti-citoqueratina 14. Las interrupciones de la membrana basal grado 1 y grado 2 fueron identificadas. Fue utilizado el programa estadístico R versión 4.0.2 para Windows. Se declaró significancia si p <0,05. Resultados: Se constató la presencia de rupturas de la membrana basal en todos los pacientes del grupo test. Estos individuos presentaron una mayor cantidad de cambios morfológicos en el tejido gingival. Exponiendo así, valores estadísticamente significativos de rupturas de la membrana basal (Grado I) y rupturas rodeadas de células epiteliales y/o fibroblastos gingivales (Grado II) en comparación con el grupo control (p <0,001). Conclusión: El tejido epitelial de pacientes con agrandamiento gingival inducido por tratamiento de ortodoncia presenta una evidente pérdida en la integridad de la membrana basal. Estas discontinuidades sugieren un aumento considerable de la plasticidad del epitelio en pacientes con agrandamiento gingival inducido por tratamiento de ortodoncia.

Introduction: Orthodontic treatment-induced gingival enlargement is a progressive, localized or generalized increase in gingival tissue. Objective: To determine morphologic aspects in the basal membrane of the gingival tissue in patients with orthodontic treatment-induced gingival enlargement. Methods: A descriptive and cross-sectional study was carried out, in which gingival tissues of patients with orthodontic treatment-induced gingival enlargement (test group: n=5) and healthy individuals (control group: n=5) were analyzed by histological and immunohistochemical analysis with the polyclonal antibody anticytokeratin 14. Grade 1 and grade 2 disrupted basal membrane were identified. The statistical program R (version 4.0.2) for Windows was used. Significance was declared if p was greater than 0.05. Results: The presence of disrupted basal membranes was observed in all the patients from the test group. These individuals presented a greater number of morphological changes in the gingival tissue. Compared to the control group (p < 0.001), statistically significant values were observed for cases of disrupted basal membrane (grade I) and disruptions surrounded by epithelial cells or gingival fibroblasts (grade II). Conclusion: The epithelial tissue of patients with orthodontic treatment-induced gingival enlargement shows an evident loss of the basal membrane integrity. These discontinuities are suggestive of a considerable increase in epithelial plasticity in patients with orthodontic treatment-induced gingival enlargement.

The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia / Rol de la MMP-9 en la Regulación de la Degradación de la Membrana Basal Microvascular Esplénica Inducida por Hipoxia de Altura

SUMMARY: To investigate changes of MMP-9 in the rat spleen and hypoxia-induced microvascular basement membrane under high altitude hypoxia. Thirty male specific pathogen-free Sprague Dawley rats were randomly divided into control and hypoxia groups, with 15 rats in each group. The rats in the control group were placed in Dingxi City, Gansu Province (2080 m above sea level) for 30 days. Rats in the hypoxia group were raised in a hypoxic environment in Maduo County, Qinghai Province (4300 m above sea level), for 30 days to establish a hypoxic rat model. Routine blood tests, MMP-9 mRNA, MMP-9 protein, and the spleen microvascular basement membrane were detected. (1) Compared with the control group, the red blood cell count, hemoglobin, and hematocrit levels of the rats in the hypoxia group were all increased; thus, a hypoxia model was successfully established. (2) Compared with the control group, the expression of MMP-9 mRNA and protein was significantly higher in the spleen of rats in the hypoxic group, and the difference was statistically significant (P <0.05). (3) Compared with the control group, the blood vessel basement membrane in the spleen of the hypoxia group was degraded. Under natural low air pressure and high altitude conditions, the expression of MMP-9 in rat spleen tissue increases and participates in the degradation of the microvascular basement membrane.

El objetivo de este trabajo fue investigar los cambios de la MMP-9 en el bazo de la rata y la membrana basal microvascular inducida bajo hipoxia a gran altura. Treinta ratas macho Sprague Dawley, libres de patógenos específicos, se dividieron aleatoriamente en dos grupos de 15 ratas cada uno, un grupo control y un grupo hipoxia. Durante 30 días las ratas del grupo control estuvieron en la ciudad de Dingxi, provincia de Gansu (2080 m sobre el nivel del mar). Las ratas del grupo de hipoxia se criaron en un entorno hipóxico en el condado de Maduo, provincia de Qinghai (4300 m sobre el nivel del mar), durante 30 días para establecer un modelo de rata hipóxica. Se realizaron análisis de sangre de rutina, ARNm de MMP-9, proteína MMP-9 y de la membrana basal microvascular del bazo. En comparación con el grupo control, el recuento de glóbulos rojos, la hemoglobina y los niveles de hematocrito de las ratas del grupo de hipoxia aumentaron; por lo tanto, se estableció con éxito un modelo de hipoxia. En comparación con el grupo control, la expresión de ARNm y proteína de MMP-9 fue significativamente mayor en el bazo de las ratas del grupo hipóxico, siendo la diferencia estadísticamente significativa (P <0,05). En comparación con el grupo control, la membrana basal de los vasos sanguíneos estaba degradada en el bazo del grupo hipoxia. En condiciones naturales de baja presión atmosférica y gran altitud, la expresión de MMP-9 en el tejido del bazo de la rata aumenta y participa en la degradación de la membrana basal microvascular.

Distrofia de membrana basal epitelial corneal: a propósito de un caso / Epithelial basement membrane corneal dystrophy: A case report

La distrofia de la membrana basal epitelial corneal es una entidad poco frecuente, que se presenta en forma de erosiones corneales de repetición debidas a una alteración en la unión del epitelio corneal a la membrana basal. Esta patología ha sido presentada en la literatura con un enfoque eminentemente oftalmológico, dejando en un segundo plano la anatomía patológica. El objetivo de este artículo es resaltar la imagen microscópica de esta patología a propósito de un caso, así como realizar una aproximación clínica y terapéutica de esta entidad.(AU)

Epithelial basement membrane corneal dystrophy is a rare entity, characterized by recurrent corneal erosions secondary to a disorder in the attachment of the corneal epithelium to the basement membrane. To date, mainly the ophthalmological aspect of cases has been reported, with little emphasis on the pathology of this lesion. Here we aim to describe the microscopy and discuss the clinical and therapeutic aspects of a case.(AU)

A propósito de un caso: enfermedad IgA lineal de la infancia / Apropos of a case: Linear IgA bullous dermatosis of childhood

La enfermedad IgA lineal se trata de un trastorno autoinmune poco frecuente. En la infancia aparece sobre todo en edad preescolar, y en adultos es necesario realizar un buen diagnóstico diferencial con otras enfermedades ampollosas como la dermatitis herpetiforme o el penfigoide ampollar. Hasta un cuarto de los casos se relacionan con infecciones o con la toma de medicamentos entre los que destacan antibióticos y antiinflamatorios no esteroideos. El diagnóstico se basa en la clínica, biopsia cutánea e inmunofluorescencia. Típicamente se presenta como ampollas anulares tensas de morfología anular con imagen característica en collar de perlas. Al realizar el estudio de inmunofluorescencia directa se evidencia una banda lineal de IgA en la unión dermoepidérmica. Suele responder de forma completa a la retirada del fármaco causante y al tratamiento con Dapsona oral y glucocorticoides tópicos. (AU)

[Epithelial basement membrane corneal dystrophy: A case report]. / Distrofia de membrana basal epitelial corneal: a propósito de un caso.

Epithelial basement membrane corneal dystrophy is a rare entity, characterized by recurrent corneal erosions secondary to a disorder in the attachment of the corneal epithelium to the basement membrane. To date, mainly the ophthalmological aspect of cases has been reported, with little emphasis on the pathology of this lesion. Here we aim to describe the microscopy and discuss the clinical and therapeutic aspects of a case.

Hybrid Verrucous Carcinoma: A Wolf in Sheep's Clothing Case Report and Integrative Review of 280 Cases

ABSTRACT: Hybrid verrucous carcinoma (HVC) is defined as a rare neoplasm in which there is histopathological evidence of verrucous carcinoma and microscopic foci of squamous cell carcinoma, synchronously in the same site, affecting behavior and prognosis. This study aimed to present a new case of HVC in the mouth, and critically and comparatively analyze the cases reported in literature, to better understand the biological behavior and contribute to diagnostic precision. A review was performed using six databases, and the gray literature. Twenty-two articles were selected, with a total of 280 cases. The most frequent clinical appearance was verrucous carcinoma which included benign lesions. This implies that the potential for aggressive behavior can be detected microscopically, in the form of a ruptured basement membrane, which visualization can be facilitated by the use of some immunohistochemical markers discussed here. This is important for the diagnosis of HVC and adequate treatment. Hybrid verrucous carcinoma is what can be thought of as "a wolf in sheep's clothing." When analyzing cases with clinical suspicion of verrucous carcinoma microscopically, great attention is recommended, since they may be HVC and can recur, metastasize, and lead to death.

RESUMEN: El carcinoma verrugoso híbrido (CVH) se define como una neoplasia poco frecuente en la que existe evidencia histopatológica de carcinoma verrugoso y focos microscópicos de carcinoma de células escamosas, sincrónicamente en el mismo sitio, que afectan el comportamiento y el pronóstico. Este estudio tuvo como objetivo presentar un nuevo caso de CVH en la cavidad oral, y analizar crítica y comparativamente los casos reportados en la literatura, para comprender mejor el comportamiento biológico y contribuir a la precisión diagnóstica. Se realizó una revisión utilizando seis bases de datos y la literatura gris. Se seleccionaron veintidós artículos, con un total de 280 casos. La aparición clínica más frecuente fue el carcinoma verrugoso que incluyó lesiones benignas. Esto implica que el potencial de comportamiento agresivo puede detectarse microscópicamente, en forma de una membrana basal rota, cuya visualización puede ser facilitada por el uso de algunos marcadores inmunohistoquímicos discutidos aquí. Esto es importante para el diagnóstico de CVH y el tratamiento adecuado. El CVH es lo que se puede considerar como "un lobo con piel de oveja". Al analizar microscópicamente casos con sospecha clínica de carcinoma verrugoso, se recomienda una atención inmediata debido a que pueden ser CVH y pueden recurrir, metastatizar y conducir a la muerte.

Glomerulonefritis C3 en un paciente con síndrome de Alport: un caso raro

El síndrome de Alport es una entidad hereditaria que se produce principalmente por una mutación en los genes que codifican el colágeno tipo IV. Por otro lado, la glomerulonefritis C3 es una entidad rara que presenta un patrón de glomerulonefritis membranoproliferativa y su etiología se basa en un control anormal de la activación de la vía alternativa del complemento. A continuación se describe un caso de un paciente, de sexo masculino, que cursa con un síndrome nefrótico corticorresistente en el que se documenta un patrón de glomerulonefritis membranoproliferativa en la biopsia renal con depósitos de C3 en la inmunofluorescencia, asociada a una deleción heterocigota en el gen CFHR1 en el estudio genético de las proteínas reguladoras del complemento. Además, en el panel genético realizado por corticorresistencia se encuentra una variante COL4A5 asociada al síndrome de Alport ligado al X. Estas entidades pueden presentarse con un curso clínico diverso, pero al estar asociadas pueden acelerar la progresión a enfermedad renal crónica, por lo que se hace necesario hacer un seguimiento clínico más estricto.

Alport Syndrome is a hereditary entity that occurs mainly due to a mutation in the genes that encode type IV collagen. C3 glomerulonephritis is a rare entity with a pattern of membranoproliferative glomerulonephritis and its etiology is based on abnormal control of the activation of the alternative complement pathway. We describe a case of a male patient who presents with a corticosteroid nephrotic syndrome in which a pattern of membranoproliferative glomerulonephritis is documented in the renal biopsy with C3 deposits in the immunofluorescence, associated with a heterozygous deletion in the gene CFHR1 in the genetic study of complement regulatory proteins. Furthermore, a variant COL4A5 associated with X-linked Alport syndrome is found in the genetic panel for corticosteroid resistance. These entities can present with a diverse clinical course, but when associated they can accelerate progression to chronic kidney disease, which is why makes it necessary to do a more strict clinical follow-up.

Síndrome de Alport: una actualización en fisiopatología, genética, diagnóstico y tratamiento / Alportsyndrome: anupdate in pathophysiology, genetics, diagnosis, and treatment

RESUMEN El síndrome de Alport es una enfermedad renal hereditaria de curso progresivo, que ocurre por defectos genéticos en los genes responsables de la constitución de la membrana basal glomerular. Las mutacionespatogénicas en los genes para el colágeno tipo IV (COL 4A3/4/5) producen una alteración en el arreglo correcto de la membrana basal a nivel glomerular.La presentación clínica puede variar dependiendo de la mutación que presente el paciente. Luego de confirmar el diagnóstico,con estudios genéticoso mediante biopsia, se hace necesaria la correlación genotipo-fenotipo para determinar pronóstico y tratamiento. La reducción de la proteinuria, según sugieren las guías de manejo, ha resultado en un retraso en la progresión a enfermedad renal crónica, mientras se concluyen los estudios con medicamentos innovadores dirigidos a receptores específicos.

ABSTRACT Alportsyndromeis a renal hereditarydisease of progressivecourse, causedby geneticdefects in the genes responsible for the constitution of the glomerular basementmembrane. Mutation in genes fortype IV collagen occurs at COL 4A3/4/5, whichproducesinterference in thecorrectmembranearrangement. Clinicalpresentationmayvarydependingonmutationtype. Afterconfirming diagnosis, withgenetic studiesorbiopsies, managementincludesidentification of risk and treatment. Reduction of proteinuria, as managementguidelinessuggest, has resulted in delay in progressiontochronickidneydisease. In themeantime, studiesfor new treatmentdevelopments are in progress, directedtospecificreceptors.

Reporte de un caso de glomerulonefritis rápidamente progresiva por anticuerpos antimembrana basal glomerular / Case report of rapidly progressive glomerulonephritis due to anti-glomerular basement membrane antibodies

RESUMEN Una vez más en medicina interna no podemos, aún, prescindir de los métodos invasivos para alcanzar un diagnóstico. Los avances diarios en el hallazgo de nuevas herramientas paraclínicas no permiten reemplazar aquellos métodos de certeza como la anatomía patológica. El caso presentado es una muestra de ello. Se trata de una mujer de 27 años de edad, con antecedente de tiroiditis de Hashimoto que consulta por presentar severo deterioro de la función renal asociado a oligoanuria. Realizamos una revisión del tratamiento de las glomerulonefritis rápidamente progresivas por anticuerpos antimembrana basal glomerular, serológicamente negativas.

ABSTRACT Once again in internal medicine we cannot do a diagnosis without invasive methods. Daily advances in the finding of new paraclinical tools do not allow the replacement of certain methods such as pathological anatomy. The case presented is a sample of this. This is a 27-year-old woman with a history of Hashimoto's thyroiditis who consults for presenting severe impairment of kidney function associated with oligoanuria. We performed a review of the treatment of the rapidly progressive glomerulonephritis for serologically negative anti-GBM antibodies.

Nasal lavage cytology and mucosal histopathological alterations in patients with rhinitis / Citologia do lavado nasal e alterações histopatológicas na mucosa nasal de pacientescom rinite

Abstract Introduction The extent of epithelial lesion in allergic and non-allergic rhinitis and its association with inflammatory changes in nasal lavage has not been clarified. Objective To verify the association between the inflammatory cells in the nasal lavage, epithelial lesion extent and basement membrane thickness, in the nasal mucosa of patients with rhinitis; to determine the cutoff point of the percentage of eosinophils in the nasal lavage associated with the atopic patients. Methods Patients with rhinitis and indication for septoplasty and (or) turbinectomy for turbinate hypertrophy were selected, and were submitted to allergy skin tests, nasal lavage with measurement of albumin and interleukin-8 levels, total and differential counting of cells, and mucosal histopathological analysis to determine the extent of epithelial lesion, and degree of basement membrane thickening. Results Fifty-six patients with a median age of 24.5 years and a diagnosis of allergic rhinitis (n = 36) and non-allergic rhinitis (n = 20) were studied. In atopic subjects, allergy skin tests were positive for Dermatophagoides pteronyssinus in 35 (97.0%) and Lolium perenne in 18 (50.0%). Atopic subjects showed a higher clinical score index of rhinitis compared to non-atopic ones. The total count of cells, neutrophils, and levels of albumin and IL-8 were not different in the nasal lavage of atopic and non-atopic subjects. The cutoff point for eosinophil count in nasal fluid for the distinction between allergic rhinitis and non-allergic rhinitis was 4%. Some degree of epithelial lesion was more frequent in allergic rhinitis (94%) than in non-allergic rhinitis (65%) patients. In the presence of basement membrane thickness, as a marker of remodeling, there was no difference in the nasal lavage of patients with allergic rhinitis and non-allergic rhinitis. Conclusion In this series, 4% was the cutoff point for the number of eosinophils in the nasal lavage, for atopy differentiation. Upper airway remodeling accessed by basement membrane thickness showed similar inflammatory cell infiltrate in the nasal lavage, regardless of the presence of atopy.

Resumo Introdução A extensão da lesão epitelial na rinite alérgica e não alérgica e sua associação com alterações inflamatórias no lavado nasal ainda não estão esclarecidas. Objetivo Verificar a relação entre o processo inflamatório no lavado nasal, extensão da lesão epitelial e espessamento da membrana basal na mucosa nasal de pacientes com rinite; determinar o ponto de corte do percentual de eosinófilos no lavado nasal associado à presença de atopia. Método Foram selecionados pacientes com rinite e indicação de septoplastia e (ou) turbinectomia por hipertrofia de conchas nasais, os quais foram submetidos aos testes cutâneos alérgicos, lavado nasal com determinação das concentrações de albumina, interleucina-8 (IL-8), contagem total e diferencial de células, análise da extensão da lesão epitelial, e grau de espessamento da membrana basal por meio de histopatologia da mucosa. Resultado Foram estudados 56 pacientes, mediana de 24,5 anos com diagnóstico de rinite alérgica (n = 36) e rinite não alérgica (n = 20). Nos atópicos os testes cutâneos alérgicos foram positivos para D. pteronyssinus em 35 (97,0%) e L. perenne em 18 (50,0%). Atópicos apresentaram maior índice de escore clínico para rinite em comparação a não atópicos. A contagem total de células, neutrófilos e níveis de albumina e IL-8 não foi diferente entre o lavado nasal de atópicos e não atópicos. O ponto de corte da contagem de eosinófilos no fluido nasal para a distinção de rinite alérgica e rinite não alérgica foi de 4%. Algum grau de lesão epitelial foi mais frequente em pacientes com rinite alérgica (94%) do que em pacientes com rinite não alérgica (65%). Na presença de espessamento da membrana basal, como marcador de remodelamento, não houve diferença no lavado nasal entre pacientes com rinite alérgica e não alérgica. Conclusão Nesta casuística, 4% foi o ponto de corte do número de eosinófilos no lavado nasal, para diferenciação de atopia. Remodelamento da via aérea superior pelo espessamento da membrana basal revelou infiltrado semelhante de células inflamatórias no lavado nasal, independentemente da presença de atopia.

Podocyte infolding glomerulopathy; report of the first case in Latin America and review of the literature. / Glomerulopatía por invaginación podocítica; reporte del primer caso en Latinoamérica y revisión de la literatura.

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a condition of uncertain origin, frequently associated with autoimmune diseases. Its specific treatment and clinical course are unknown. It is characterised by thickening of the capillary walls due to the presence of non-argyrophilic intramembranous bubbles similar to those found in membranous glomerulopathy, but without electron-dense deposits of immune complexes in the ultrastructure, where translucent microspheres generated by invagination of the podocyte cytoplasm into the basement membranes are observed. OBJECTIVES: Generally reported in young females patients. To date, few cases in Asian patients have been reported. Our case is the first to be reported in a Latin American Caucasian patient. METHODS: A 38-year-old woman with SLE. In 2014 she presented with nephrotic syndrome empirically treated with corticosteroids (CO) and intravenous cyclophosphamide with good response. She had a relapse in April 2015 with normal renal function and no extrarenal lupus activity, so she was referred to our hospital to be biopsied. RESULTS: The biopsy reported focal segmental glomerular sclerosis without deposits of immune complexes in the immunofluorescence. However, methenamine silver staining revealed clear spaces in the capillary walls accompanied by marked podocyte alterations. On electron microscope study, numerous aggregates of microvesicular and cylindrical ultrastructures bound to the membranes were observed, without evidence of dense deposits, and diffuse effacement of pedicel foot processes, confirming the suspected diagnosis. CONCLUSIONS: This is the first reported case of what can be considered a new pathological glomerular entity in a Latin American Caucasian patient, whose clinical course and therapy are still unknown.

Nasal lavage cytology and mucosal histopathological alterations in patients with rhinitis.

INTRODUCTION: The extent of epithelial lesion in allergic and non-allergic rhinitis and its association with inflammatory changes in nasal lavage has not been clarified. OBJECTIVE: To verify the association between the inflammatory cells in the nasal lavage, epithelial lesion extent and basement membrane thickness, in the nasal mucosa of patients with rhinitis; to determine the cutoff point of the percentage of eosinophils in the nasal lavage associated with the atopic patients. METHODS: Patients with rhinitis and indication for septoplasty and (or) turbinectomy for turbinate hypertrophy were selected, and were submitted to allergy skin tests, nasal lavage with measurement of albumin and interleukin-8 levels, total and differential counting of cells, and mucosal histopathological analysis to determine the extent of epithelial lesion, and degree of basement membrane thickening. RESULTS: Fifty-six patients with a median age of 24.5 years and a diagnosis of allergic rhinitis (n=36) and non-allergic rhinitis (n=20) were studied. In atopic subjects, allergy skin tests were positive for Dermatophagoides pteronyssinus in 35 (97.0%) and Lolium perenne in 18 (50.0%). Atopic subjects showed a higher clinical score index of rhinitis compared to non-atopic ones. The total count of cells, neutrophils, and levels of albumin and IL-8 were not different in the nasal lavage of atopic and non-atopic subjects. The cutoff point for eosinophil count in nasal fluid for the distinction between allergic rhinitis and non-allergic rhinitis was 4%. Some degree of epithelial lesion was more frequent in allergic rhinitis (94%) than in non-allergic rhinitis (65%) patients. In the presence of basement membrane thickness, as a marker of remodeling, there was no difference in the nasal lavage of patients with allergic rhinitis and non-allergic rhinitis. CONCLUSION: In this series, 4% was the cutoff point for the number of eosinophils in the nasal lavage, for atopy differentiation. Upper airway remodeling accessed by basement membrane thickness showed similar inflammatory cell infiltrate in the nasal lavage, regardless of the presence of atopy.

Reação inflamatória induzida por duas SVMPs isoladas do veneno de Bothrops atrox e por fragmentos peptídicos gerados da hidrólise de componentes da membrana basal por estas enzimas / Inflammatory reaction induced by two metalloproteinases isolated from Bothrops atrox venom and by fragments generated from the hydrolysis of basement membrane components

Snake venom metalloproteases (SVMPs) are key toxins in local and systemic effects observed in victims of snakebites. The mechanisms involved in SVMPs action are related to the hydrolysis of blood vessels basement membrane components (BM), well as their direct action on platelets, endothelial and inflammatory cell receptors, and coagulation factors. Some evidence suggests that endogenous factors derived from BM hydrolysis increase the local effects induced by SVMPs and, consequently, the severity of snakebites. In this study we evaluated the role of two SVMPs of class P-I and P-III named Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH), respectively, isolated from the Bothrops atrox venom, and its hydrolysis products on Matrigel in experimental models of inflammation. Both toxins induced inflammatory reactions in mice models. The edema formed in the mice paws after the injection of different doses of SVMPs did not indicate a statistical difference between the tested doses or between the toxins. The lesions were similar despite the ATXL having a lower molecular mass than BATXH. In the kinetics tests of edema and accumulation of peritoneal leukocytes, a dose of 2 µg / animal was used. Both toxins induced the formation of an edema peak between 30 min and 1 h, with a 70% increase in the size of the paws. ATXL and BATXH induced an increase in leukocyte influx 4 h after intraperitoneal injection. For the evaluation of possible inflammatory mediators involved in these reactions, we stimulated Murine Peritoneal Adherent Cells (MPACs) with 40 µg / mL of the SVMPs or B. atrox venom in different time´s period. The cytokine TNF-α was identified in the supernatant of cells stimulated with BATXH or with B. atrox. The venom peaked between 2 h and 6 h with levels of 800 pg/mL, and BATXH induces secretion of 200 pg/mL in 4 h. The same was not observed with ATXL. To test the hypothesis that peptides resulting from MB hydrolysis by SVMPs could participate in the inflammatory process, Matrigel was incubated with the toxins for 1 h at 37 ° C, and the hydrolysis products were identified by LC-MS/MS. In parallel, peptides resulting from this incubation were isolated on centrifugal filters with a 10 kDa cut off. The reaction generated different fragments, mainly Laminin peptides. Isolated peptides in the filters induced the formation of edema with a 30% increase in the size of the paws and promoted leukocyte accumulation in the peritoneal cavity (4-5 x 106 cells/mL). Thus, the results suggest that ATXL and BATXH, together with peptides resulting from Matrigel´s hydrolysis, play an important role in inflammatory reaction observed in envenoming by B. atrox. Generally, envenoming causes irreversible local injuries, even after the administration of antivenom. In this context, we present tests with two inhibitors derived from the Jararhagin pro-domain that were able to neutralize the catalytic, fibrinolytic and hemorrhagic activity induced by SVMP, indicating a possible complementary treatment with antibotropic serum.

Metaloproteases do veneno de serpentes (SVMPs) são toxinas chave nos efeitos locais e sistêmicos observados em vítimas de acidentes ofídicos. Os mecanismos envolvidos na ação das SVMPs estão relacionados à hidrólise dos componentes da membrana basal (MB) dos vasos sanguíneos, bem como à sua ação direta sobre plaquetas, receptores de células endoteliais e inflamatórias, e fatores de coagulação. Algumas evidências sugerem que fatores endógenos derivados da hidrólise de MB aumentam os efeitos locais induzidos pelas SVMPs e, consequentemente, a gravidade dos acidentes ofídicos. Neste trabalho avaliamos o papel de duas SVMPs de classe P-I e P-III nomeadas Atroxlisina-Ia (ATXL) e Batroxragina (BATXH), respectivamente, isoladas do veneno de Bothrops atrox, e seus produtos de hidrólise sobre o Matrigel em modelos experimentais de inflamação. As duas toxinas induziram reação inflamatória em modelos murinos. O edema formado nas patas de camundongos após a injeção de diferentes doses das SVMPs não indicou diferença estatística entre as doses testadas nem entre as toxinas. As lesões foram semelhantes apesar da ATXL possuir massa molecular menor que BATXH. Nos testes de cinética do edema e acúmulo de leucócitos peritoneais foi utilizada a dose de 2 µg/animal. Ambas as toxinas induziram a formação de um pico de edema entre 30 min e 1 h, com aumento de 70% no tamanho das patas. ATXL e BATXH induziram aumento do influxo leucocitário a partir de 4 h após injeção intraperitoneal. Para a avaliação de possíveis mediadores inflamatórios envolvidos nestas reações, estimulamos Células Aderentes Peritoneais Murinas (MPACs) com 40 µg/mL das SVMPs ou veneno de B. atrox em diferentes períodos de tempo. A citocina TNF-α foi identificada no sobrenadante de células estimuladas com BATXH ou com veneno de B. atrox. O veneno atingiu um pico entre 2 h e 6 h com níveis de 800 pg/mL, e BATXH induziu secreção de 200 pg/mL em 4 h. O mesmo não foi observado com ATXL. Para testar a hipótese de que os peptídeos resultantes da hidrólise de MB pelas SVMPs poderiam participar do processo inflamatório, Matrigel foi incubado com as toxinas durante 1 h a 37 °C, e os produtos de hidrólise foram identificados por LC-MS/MS. Paralelamente, peptídeos resultantes desta incubação foram isolados em filtros centrífugos com corte de 10 kDa. A reação gerou diferentes fragmentos, principalmente peptídeos da Laminina. Peptídeos isolados por filtração induziram a formação de edema com aumento no tamanho das patas de 30%, e promoveram o acúmulo leucocitário na cavidade peritoneal (4-5 x 106 células/mL). Assim, os resultados sugerem que ATXL e BATXH, juntamente com peptídeos resultantes da hidrólise do Matrigel por essas proteases desempenham um papel importante na reação inflamatória observada no envenenamento por B. atrox. Geralmente, o envenenamento causa lesões locais irreversíveis, mesmo após a administração do antiveneneno. Neste contexto, apresentamos testes com dois inibidores derivados do pró-domínio da Jararagina que foram capazes de neutralizar a atividade catalítica, fibrinolítica e hemorrágica induzidas pela SVMP, indicando um possível tratamento complementar com soro antibotrópico.

Reação inflamatória induzida por duas SVMPs isoladas do veneno de Bothrops atrox e por fragmentos peptídicos gerados da hidrólise de componentes da membrana basal por estas enzimas / Inflammatory reaction induced by two metalloproteinases isolated from Bothrops atrox venom and by fragments generated from the hydrolysis of basement membrane components

Snake venom metalloproteases (SVMPs) are key toxins in local and systemic effects observed in victims of snakebites. The mechanisms involved in SVMPs action are related to the hydrolysis of blood vessels basement membrane components (BM), well as their direct action on platelets, endothelial and inflammatory cell receptors, and coagulation factors. Some evidence suggests that endogenous factors derived from BM hydrolysis increase the local effects induced by SVMPs and, consequently, the severity of snakebites. In this study we evaluated the role of two SVMPs of class P-I and P-III named Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH), respectively, isolated from the Bothrops atrox venom, and its hydrolysis products on Matrigel in experimental models of inflammation. Both toxins induced inflammatory reactions in mice models. The edema formed in the mice paws after the injection of different doses of SVMPs did not indicate a statistical difference between the tested doses or between the toxins. The lesions were similar despite the ATXL having a lower molecular mass than BATXH. In the kinetics tests of edema and accumulation of peritoneal leukocytes, a dose of 2 µg / animal was used. Both toxins induced the formation of an edema peak between 30 min and 1 h, with a 70% increase in the size of the paws. ATXL and BATXH induced an increase in leukocyte influx 4 h after intraperitoneal injection. For the evaluation of possible inflammatory mediators involved in these reactions, we stimulated Murine Peritoneal Adherent Cells (MPACs) with 40 µg / mL of the SVMPs or B. atrox venom in different time´s period. The cytokine TNF-α was identified in the supernatant of cells stimulated with BATXH or with B. atrox. The venom peaked between 2 h and 6 h with levels of 800 pg/mL, and BATXH induces secretion of 200 pg/mL in 4 h. The same was not observed with ATXL. To test the hypothesis that peptides resulting from MB hydrolysis by SVMPs could participate in the inflammatory process, Matrigel was incubated with the toxins for 1 h at 37 ° C, and the hydrolysis products were identified by LC-MS/MS. In parallel, peptides resulting from this incubation were isolated on centrifugal filters with a 10 kDa cut off. The reaction generated different fragments, mainly Laminin peptides. Isolated peptides in the filters induced the formation of edema with a 30% increase in the size of the paws and promoted leukocyte accumulation in the peritoneal cavity (4-5 x 106 cells/mL). Thus, the results suggest that ATXL and BATXH, together with peptides resulting from Matrigel´s hydrolysis, play an important role in inflammatory reaction observed in envenoming by B. atrox. Generally, envenoming causes irreversible local injuries, even after the administration of antivenom. In this context, we present tests with two inhibitors derived from the Jararhagin pro-domain that were able to neutralize the catalytic, fibrinolytic and hemorrhagic activity induced by SVMP, indicating a possible complementary treatment with antibotropic serum.

Metaloproteases do veneno de serpentes (SVMPs) são toxinas chave nos efeitos locais e sistêmicos observados em vítimas de acidentes ofídicos. Os mecanismos envolvidos na ação das SVMPs estão relacionados à hidrólise dos componentes da membrana basal (MB) dos vasos sanguíneos, bem como à sua ação direta sobre plaquetas, receptores de células endoteliais e inflamatórias, e fatores de coagulação. Algumas evidências sugerem que fatores endógenos derivados da hidrólise de MB aumentam os efeitos locais induzidos pelas SVMPs e, consequentemente, a gravidade dos acidentes ofídicos. Neste trabalho avaliamos o papel de duas SVMPs de classe P-I e P-III nomeadas Atroxlisina-Ia (ATXL) e Batroxragina (BATXH), respectivamente, isoladas do veneno de Bothrops atrox, e seus produtos de hidrólise sobre o Matrigel em modelos experimentais de inflamação. As duas toxinas induziram reação inflamatória em modelos murinos. O edema formado nas patas de camundongos após a injeção de diferentes doses das SVMPs não indicou diferença estatística entre as doses testadas nem entre as toxinas. As lesões foram semelhantes apesar da ATXL possuir massa molecular menor que BATXH. Nos testes de cinética do edema e acúmulo de leucócitos peritoneais foi utilizada a dose de 2 µg/animal. Ambas as toxinas induziram a formação de um pico de edema entre 30 min e 1 h, com aumento de 70% no tamanho das patas. ATXL e BATXH induziram aumento do influxo leucocitário a partir de 4 h após injeção intraperitoneal. Para a avaliação de possíveis mediadores inflamatórios envolvidos nestas reações, estimulamos Células Aderentes Peritoneais Murinas (MPACs) com 40 µg/mL das SVMPs ou veneno de B. atrox em diferentes períodos de tempo. A citocina TNF-α foi identificada no sobrenadante de células estimuladas com BATXH ou com veneno de B. atrox. O veneno atingiu um pico entre 2 h e 6 h com níveis de 800 pg/mL, e BATXH induziu secreção de 200 pg/mL em 4 h. O mesmo não foi observado com ATXL. Para testar a hipótese de que os peptídeos resultantes da hidrólise de MB pelas SVMPs poderiam participar do processo inflamatório, Matrigel foi incubado com as toxinas durante 1 h a 37 °C, e os produtos de hidrólise foram identificados por LC-MS/MS. Paralelamente, peptídeos resultantes desta incubação foram isolados em filtros centrífugos com corte de 10 kDa. A reação gerou diferentes fragmentos, principalmente peptídeos da Laminina. Peptídeos isolados por filtração induziram a formação de edema com aumento no tamanho das patas de 30%, e promoveram o acúmulo leucocitário na cavidade peritoneal (4-5 x 106 células/mL). Assim, os resultados sugerem que ATXL e BATXH, juntamente com peptídeos resultantes da hidrólise do Matrigel por essas proteases desempenham um papel importante na reação inflamatória observada no envenenamento por B. atrox. Geralmente, o envenenamento causa lesões locais irreversíveis, mesmo após a administração do antiveneneno. Neste contexto, apresentamos testes com dois inibidores derivados do pró-domínio da Jararagina que foram capazes de neutralizar a atividade catalítica, fibrinolítica e hemorrágica induzidas pela SVMP, indicando um possível tratamento complementar com soro antibotrópico.

Síndrome de Goodpasture en una preescolar / Goodpasture´s Syndrome in a pre-school girl

Introducción: El síndrome de Goodpasture es una rara enfermedad autoinmune que forma parte del espectro de síndrome pulmón-riñón Objetivo: Presentar un paciente pediátrico con síndrome de Goodpasture atípico. Presentación del caso: Paciente de seis años seguida por el servicio de nefrología; ingresó a los cuatro años de edad por presentar hematuria macroscópica asociada a manifestaciones respiratorias y antecedente de títulos elevados de anticuerpos antimembrana basal glomerular. Fue motivo de investigación y se diagnosticó el síndrome de Goodpasture. Después de tratamiento inmunosupresor con ciclofosfamida y metilprednisolona seguido de prednisona oral, la paciente presentó descenso de los títulos de anticuerpos antimembrana basal glomerular, así como mejoría de los síntomas respiratorios, sin embargo, la proteinuria se mantuvo con incremento en los últimos meses. Para el diagnóstico se tuvieron en cuenta las manifestaciones clínicas en la niña, título elevado de anticuerpos antimembrana basal glomerular y la confirmación por biopsia renal de glomerulopatía. El tratamiento fue rápidamente efectivo con una disminución inmediata en los títulos de anticuerpos antimembrana basal y mejoría evidente de la condición clínica de la paciente. Se trata del primer caso pediátrico con síndrome de Goodpasture publicado en Cuba. Conclusiones: Por tratarse de una entidad rara en pediatría se requiere un diagnóstico temprano y tratamiento agresivo para mejorar el pronóstico del paciente. En su seguimiento son necesarias una terapia farmacológica prolongada, una adecuada adherencia al tratamiento propuesto y un estrecho monitoreo clínico y analítico de lo cual dependerá la progresión de la injuria renal y pulmonar(AU)

Introduction: Goodpasture´s syndrome is a rare autoimmune disease that is part of the lung-kidney syndrome's sprectrum. Objective: To present the case of a pediatric patient with an atypical Goodpasture´s syndrome. Case presentation: Six years old female patient under follow-up in the Nephrology service. She was admitted when she was four years old by presenting macroscopic hematuria, respiratory symptoms and a history of high titers of anti-glomerular basement membrane antibodies. She was under research and was diagnosed with the Goodpasture´s symdrome. After being under immunosupressive treatment with cyclophosphamide and methylprednisolone followed by oral prednisone, the patient presented a decrease in the titers of anti-glomerular basement membrane antibodies, and an improvement of the respiratory symptoms; however, proteinuria kept increasing in the last months. For the diagnosis, there were taken into account the clinical manifestations of the girl, the high titers of anti-glomerular basement membrane antibodies and the confirmations of glumerulopathy by renal biopsy. The treatment was effective quickly with an inmmediate decrease of the titers of anti-glomerular basement membrane antibodies and an evident improvement of the clinical condition of the patient. This is the first pediatric case presenting Goodpasture´s syndrome that has been published in Cuba. Conclusions: As this is a rare entity in Pediatrics, it is required an early diagnosis and an aggressive treatment to improve the patient's prognosis. In the follow-up are needed a prolonged pharmacological therapy, an adequate adherence to the proposed treatment and a close clinical and analytic monitoring from which will depend the progression of the lung and renal injury(AU)

Identificação das proteínas interagentes de Yes-Associated protein (YAP), um efetor da via Hippo, em células epiteliais mamárias expostas à matriz extracelular rica em laminina / Identification of interacting proteins of Yes-Associated Protein (Yap) in mammary epithelial cells exposed to laminin-rich extracellular matrix

A sinalização da matriz extracelular (MEC) é essencial para a determinação do destino e comportamento de células epiteliais da glândula mamária. Entretanto, pouco é conhecido sobre os mecanismos moleculares envolvidos nesse processo. A via Hippo, uma cascata de sinalização que participa da regulação de diversos comportamentos celulares, incluindo o tamanho de órgãos, parece ser uma importante candidata a mediadora sinalização da MEC. Resultados preliminares do laboratório indicam que a arquitetura tecidual e a membrana basal, componente da MEC de epitélios e outros tecidos, influenciam a localização, concentração e atividade de YAP, uma proteína efetora da via Hippo, em células epiteliais mamárias. Neste contexto, o objetivo deste trabalho foi identificar as proteínas que interagem com Yap (ortólogo de YAP em camundongo) nas células epiteliais da glândula mamária em resposta à membrana basal. Foram utilizadas células EpH4, uma linhagem mamária não-tumoral murina, como modelo de diferenciação funcional e formação de ácinos em um ensaio de cultura tridimensional (3D). O tratamento de estruturas multicelulares 3D pré-formadas em placas nãoadesiva com uma matriz rica em laminina (lrECM) alterou a localização e o padrão subcelular de Yap, assim como a expressão gênica de membros da via Hippo e dos alvos de Yap, mas não alterou a expressão das proteínas da via em nível de proteína. O ensaio de co-imunoprecipitação (CoIP) seguida de análise por espectrometria de massas identificou um conjunto diferencial de proteínas que interagem com Yap na fração citoplasmática de células EpH4 cultivadas na ausência ou na presença de lrECM em um modelo de ECM-overlay. Uma análise realizada junto à database KEGG Pathways revelou que os possíveis interagentes Yap nas células cultivadas não-tratadas com lrECM participam de processos relacionados à proteólise mediada por ubiquitina, enquanto nas células expostas à lrECM os possíveis interagentes estão associados a processos metabólicos e são especialmente proteínas-chave do metabolismo de lipídios. A busca na plataforma de redes de interação STRING não identificou trabalhos que destaquem a interação de Yap com estas proteínas. A plataforma Vizit indica a participação de Yap em processos relacionados à síntese e atividade de lipídios e hormônios, o que reforça as evidências de que está pode ser uma nova função de Yap ainda não explorada em detalhes. A fim de se obter resultados complementares à CoIP, padronizamos o ensaio de identificação por biotinilação dependente de proximidade (BioID) em células embrionárias de rim humano da linhagem 293FT. As proteínas isoladas por pulldown foram identificadas por espectrometria de massas e uma análise junto à database Gene Ontology indicou que os possíveis interagentes de Yap nestas células são em sua maioria proteínas relacionadas à via Hippo, o que reforça a robustez do ensaio. Nós pretendemos transpor este sistema para as células EpH4. A expectativa é que, em conjunto, estes resultados nos orientem em projetos futuros para compreender os mecanismos de sinalização da MEC na morfogênese e diferenciação da glândula mamária

Extracellular matrix (ECM)-signaling is crucial for determination of epithelial cell fate and behavior in the mammary gland. However, little is known about the molecular mechanisms involved in these processes. The Hippo pathway, a signaling cascade involved in the regulation of several cellular processes, including organ size, seems to be an important candidate as a mediator of this signaling. Our preliminary results indicate that the tissue architecture and the basement membrane, an ECM component of epithelia and other tissues, influence the location, level and activity of YAP, an effector of the Hippo pathway. In this context, the goal of this work was to identify the proteins that interact with Yap (ortholog of YAP in mouse) in mammary epithelial cells in response to the basement membrane. We used EpH4 cells, a nontumoral murine mammary cell, in a functional differentiation and acini-forming in tridimensional (3D) culture assay. Treatment of 3D multicellular structures pre-formed on nonadhesive plates with a laminin-rich extracellular matrix (lrECM) altered the subcellular localization and pattern of Yap, as well as gene expression of Hippo pathway proteins and Yap targets, but did not altered the expression of the pathway members at the protein level. Coimmunoprecipitation (CoIP) followed by mass spectrometry analysis identified a differential set of proteins interacting with Yap in cytoplasmic fractions of EpH4 cells in the absence or presence of lrECM in an ECM-overlay culture model. An analysis performed with the KEGG Pathways database revealed that putative Yap interactors in non-treated cells participate in processes related to ubiquitin-mediated proteolysis, whereas in cells exposed to lrECM Yap interactors are associated to metabolic processes and are mainly key-proteins of metabolism of lipids and carbohydrates. A search in interaction networks platform STRING did not identify previous works that showing the interaction of Yap with these proteins. Vizit platform indicated the participation of Yap in processes related to the synthesis and activity of lipids and hormones, which reinforces the evidences that Yap can play a novel poorly explored role. To obtain complementary results to CoIP, we devised the proximity-dependent biotinylation identification (BioID) assay on embryonic renal cells of 293FT cell line. Pulldown-isolated proteins were identified by mass spectrometry and an analysis performed with Gene Ontology database revealed that putative Yap interactors are Hippo pathway-related proteins, which reinforces the robustness of the assay. We intend to transpose this system to the EpH4 cells. We expect that, together, these results will guide us in future projects to understand the signaling mechanisms of ECM in mammary gland morphogenesis and differentiation

Reproductive alternatives for patients with dystrophic epidermolysis bullosa / Opções reprodutivas para pacientes com epidermólise bolhosa distrófica

ABSTRACT Epidermolysis bullosa describes a group of skin conditions caused by mutations in genes encoding proteins related to dermal-epidermal adhesion. In the United States, 50 cases of epidermolysis bullosa per 1 million live births are estimated, 92% of which classified as simplex, 5% dystrophic, 1% junctional and 2% non-classified. Dystrophic epidermolysis bullosa is associated with autosomal, dominant and recessive inheritance. Epidermolysis bullosa causes severe psychological, economic and social impacts, and there is currently no curative therapy, only symptom control. Embryonic selection is available for epidermolysis bullosa patients in order to prevent perpetuation of the condition in their offspring.

RESUMO O termo "epidermólise bolhosa" descreve um grupo de afecções cutâneas causadas por mutações em genes que codificam proteínas relacionadas à aderência dermoepidérmica. Nos Estados Unidos, estima-se a ocorrência de 50 casos de epidermólise bolhosa por 1 milhão de nascidos vivos, sendo 92% deles da forma simples, 5% da forma distrófica, 1% da forma juncional e 2% não classificados. A epidermólise bolhosa do tipo distrófica foi associada a padrões autossômicos, dominante e recessivo. A epidermólise bolhosa causa sérios impactos psicológicos, econômicos e sociais, e não há tratamento curativo atualmente − apenas controle dos sintomas. A seleção embrionária é disponível para portadores de epidermólise bolhosa, a fim de evitar a perpetuação da condição em seus descendentes.

[The pathology of renal transplants]. / Anatomía patológica del trasplante renal.

In order to make an objective assessment of the histopathology of a renal biopsy during a kidney transplant, all the various elements involved in the process must be understood. It is important to know the characteristics of the donor organ, especially if the donor is older than 65. The histopathological features of the donor biopsy, especially its vascular status, are often related to an initial poor function of the transplanted kidney. The T lymphocyte inflammatory response is characteristic in acute cellular rejection; the degree of tubulitis, together with the amount of affected parenchyme, are important factors. The proportion of cellular sub-populations, such as plasma cells and macrophages, is also important, as they can be related to antibody-mediated humoral rejection. Immunofluorescent or immunohistochemical studies are necessary to rule out C4d deposits or immunogloblulins. The presence of abundant deposits of C4d in tubular basement membranes supports a diagnosis of humoral rejection, as does the presence of capillaritis, glomerulitis which, together with vasculitis, are typical diagnostic findings in C4d negative cases. Interstitial fibrosis, tubular atrophy and glomerular sclerosis, although non-specific, imply a chronic phase. Transplant glomerulopathy and multilamination in more than 6 layers of the tubular and glomerular basement membranes are quasi-specific characteristics of chronic humoral rejection. Electron microscopy is essential to identify of these pathologies as well as to demonstrate the presence of other glomerular renal diseases.

Applications of electron microscopy in health: the example of epidermolysis bullosa / Aplicações da microscopia eletrônica em saúde: o exemplo da epidermólise bolhosa

ABSTRACT We report the case of a patient with dystrophic epidermolysis bullosa (DEB) diagnosed by transmission electron microscopy (TEM), emphasizing the applications and importance of this technique in the health area. The patient was a male, the only child of young and non-consanguineous parents without similar cases in the family. The patient underwent a cutaneous biopsy in which TEM revealed sub-basal membrane involvement, confirming the diagnosis of DEB. Despite technological advances, TEM continues to play an important role in diagnosis and clinical research and is considered the best option for confirmation of diagnosis and subtypes of diseases such as epidermolysis bullosa (EB).

RESUMO Relatamos o caso de um paciente com epidermólise bolhosa distrófica (EBD) diagnosticado por microscopia eletrônica de transmissão (MET), destacando aplicações e importância desta técnica na área da saúde. Paciente do sexo masculino, filho único de pais jovens não consanguíneos, sem histórico de caso familial. O paciente foi submetido à biópsia cutânea, na qual a MET revelou comprometimento da membrana sub-basal, confirmando o diagnóstico de EBD. Apesar dos avanços tecnológicos, a MET continua tendo papel importante no diagnóstico e na pesquisa clínica, sendo considerada a melhor opção para a confirmação do diagnóstico e dos subtipos de doenças como a epidermólise bolhosa (EB).

Diagnóstico clínico e histopatológico del carcinoma in situ en la mucosa bucal / Clinical, histological and pathological diagnosis of carcinoma in situ of the oral mucous

Se realizó un estudio descriptivo y transversal de 25 pacientes, adictos al tabaco, con carcinoma in situ en la mucosa bucal, atendidos en la consulta estomatológica del Policlínico de Especialidades perteneciente al Hospital Provincial Docente Clinicoquirúrgico "Saturnino Lora Torres" de Santiago de Cuba, desde abril del 2008 hasta igual periodo del 2013, a fin de evaluar los resultados del diagnóstico clínico e histopatológico de esta neoplasia. Mediante la técnica clásica de inclusión en parafina se confirmó la existencia de cambios celulares. En la casuística prevalecieron el sexo masculino y la ausencia de síntomas subjetivos en la forma leucoplásica. El sitio anatómico más susceptible correspondió al borde lateral de la lengua. Entre las alteraciones hísticas más comunes figuraron: hipercromatismo nuclear, membrana basal intacta, pérdida de la polaridad, así como pleomorfismo nuclear y celular...

A descriptive and cross-sectional study of 25 patients, with tobacco addition and carcinoma in situ of the oral mucous, assisted in the stomatological department of the Specialties Polyclinic belonging to "Saturnino Lora Torres" Teaching Provincial Clinical Surgical Hospital in Santiago de Cuba was carried out from April, 2008 to same period of the 2013, in order to evaluate the results of the clinical, histological and pathological diagnosis of this neoplasia. By means of the classic technique of inclusion in paraffin the existence of cellular changes was confirmed. The male sex and the absence of subjective symptoms prevailed in the leucoplasic form in the case material. The most susceptible anatomical site corresponded to the lateral border of the tongue. Among the most common tissue alterations there were: nuclear hyperchromatism, intact basal membrane, loss of the polarity, as well as nuclear and cellular pleomorphism...