Main Cardiac Histopathologic Alterations in the Acute Phase of Trypanosoma cruzi Infection in a Murine Model.

Symptoms in the acute phase of Chagas disease are usually mild and nonspecific. However, after several years, severe complications like dilated heart failure and even death may arise in the chronic phase. Due to the lack of specific symptoms in the acute phase, the aim of this work was to describe and analyze the cardiac histopathology during this phase in a CD1 mouse model by assessing parasitism, fibrotic damage, and the presence and composition of a cellular infiltrate, to determine its involvement in the pathogenesis of lesions in the cardiac tissue. Our results indicate that the acute phase lasts about 62 days post-infection (dpi). A significant increase in parasitemia was observed since 15 dpi, reaching a maximum at 33 dpi (4.1 × 106). The presence of amastigote nests was observed at 15-62 dpi, with a maximum count of 27 nests at 35 dpi. An infiltrate consisting primarily of macrophages and neutrophils was found in the cardiac tissue within the first 30 days, but the abundance of lymphocytes showed an 8 ≥ fold increase at 40-62 dpi. Unifocal interstitial fibrosis was identified after 9 dpi, which subsequently showed a 16 ≥ fold increase at 40-60 dpi, along with a 50% mortality rate in the model under study. The increased area of fibrotic lesions revealed progression in the extent of fibrosis, mainly at 50-62 dpi. The presence of perivasculitis and thrombus circulation disorders was seen in the last days (62 dpi); finally, cases of myocytolysis were observed at 50 and 62 dpi. These histopathological alterations, combined with collagen deposition, seem to lead to the development of interstitial fibrosis and damage to the cardiac tissue during the acute phase of infection. This study provides a more complete understanding of the patterns of histopathological abnormalities involved in the acute phase, which could help the development of new therapies to aid the preclinical tests of drugs for their application in Chagas disease.

Immunopathological Mechanisms Underlying Cardiac Damage in Chagas Disease.

In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The factors underlying the evolution of lesions following infection by Trypanosoma cruzi and, in some cases, the persistence of its antigens and the host response, with the ensuing development of clinically observable cardiac damage, are analyzed in this review.

Enfermedad de Chagas en México / Chagas disease in Mexico

Resumen México es un país endémico para la enfermedad de Chagas, donde dos terceras partes del territorio pueden ser consideradas en riesgo de transmisión vectorial, es decir que 1'100,000 individuos podrían estar infectados con Trypanosoma cruzi y 29'500,000 en riesgo de contraer la infección. En la morbimortalidad del padecimiento son importantes las características de la vivienda, condiciones biológicas, ambientales y factores socioculturales. El tamizaje en bancos de sangre, a la fecha, es de observancia obligatoria con una cobertura mayor al 92%. El diagnóstico no se establece frecuentemente debido al desconocimiento de la enfermedad por parte del personal de salud y de la población. La fase aguda generalmente pasa desapercibida y en la crónica, la patología se presenta principalmente en el corazón, con evolución lenta. La patogénesis de la miocardiopatía crónica es muy compleja y se presentan lesiones con mayor frecuencia en el sistema nervioso autónomo y miocardio, lo que genera trastornos en la conductibilidad y contractilidad del órgano. Se describen los principales mecanismos patogénicos implicados en el desarrollo de la enfermedad.

Abstract Mexico is a country endemic for Chagas disease in which two thirds of the territory can be considered at risk of vector-borne infection. This means that 1.1 million people could be infected with Trypanosoma cruzi and 29.5 million at risk of infection. Dwelling characteristics of poverty in these rural areas linked with biological conditions, lifestyle, environmental and sociocultural factors are important in the morbidity and mortality of the disease. Nowadays, the screening for the parasite is mandatory and at least 92% of blood banks are covered. The inadequate knowledge of the disease by the health personnel and the population limits the possibility of the diagnosis. The acute phase of the disease courses undetected. The main affected organ in Chagas disease is the heart, with a slow evolution; the pathogenesis of chronic cardiomyopathy is complex and lesions occur mainly in the autonomic nervous system and myocardium leading to disturbances in the conductivity and contractility of the organ. The main pathogenic mechanisms involved in the development of the disease are described.

Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin.

Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4CD25CD127 cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNγ secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment.

Estructura y función de la alfa-fetoproteína / Structure and function of the alpha-fetoprotein

Resumen: La alfa-fetoproteína es una glicoproteína que ha sido considerada como un marcador oncofetal, cuya aplicación se ha demostrado en el diagnóstico y pronóstico de enfermedades tumorales como el carcinoma hepatocelular, y también es de gran utilidad para identificar malformaciones fetales relacionadas con fallas del cierre del tubo neural y anencefalia. Diversos trabajos establecen una interesante relación entre la estructura y la función de esta proteína que permite regular la respuesta inmune de la madre y que podría participar en los eventos que evitan el rechazo del embrión. En esta revisión se identifican algunos aspectos moleculares de la alfa-fetoproteína que abren interesantes perspectivas para entender mejor su participación en el desarrollo de alteraciones tumorales.

Abstract: Alpha-fetoprotein is a glycoprotein that has been considered an oncofetal marker and demonstrated its application in tumor diagnosis and prognosis of diseases such as hepatocellular carcinoma, is also useful to identify fetal malformations related to failure of neural tube closure and anencephaly. There are several works that make an interesting relationship between the structure and function of this protein that allows it to regulate the immune response of the mother and could participate in events that prevent rejection of the embryo. In this review some molecular aspects of alpha-fetoprotein that open interesting perspectives to better understand their participation in the development of tumor abnormalities are identified.

Retraction: erbB expression changes in ethanol and 7, 12- dimethylbenz (a)anthracene-induced oral carcinogenesis. Med Oral Patol Oral Cir Bucal

The authors (Garcia Carrancá A, Zentero Galindo E, Jiménez Farfán MD and Hernandez Guerrero JC) express that one of the figures of the original article (Jacinto-Alemán LF, García-Carrancá A, Leyba Huerta ER, Zenteno-Galindo E, Jiménez-Farfán MD, Hernández-Guerrero JC. erbB expression changes in ethanol and 7,12- dimethylbenz (a)anthracene-induced oral carcinogenesis. Med Oral Patol Oral Cir Bucal. 2013 Mar 1;18(2):e325-31.) corresponding to Western blots have not been found and the voluntary alteration of this figure is evident. The coauthors Alejandro García Carranca, Edgar Zenteno Galindo, Maria Dolores Jiménez Farfán and Juan Carlos Hernández Guerrero have made the decision to take back what has been published, as they have come to the conclusion, that at least this result is false.The editor declare that the journal had the signed copyright by the authors when the arti-cle was initially published. This copyright document certifies that the undersigned authors war-rants that the article is original; is not under consideration by another publication; and its tables or figures have not been previously published. The authors confirmed that the final ar-ticle had been read and each author ́s contribution had been approved by the appropriate author. The editor has made the decision to retract the article due to the above comments of some authors against the rest. The editors apologize to the readers and reviewers of Med Oral Patol Oral Cir Bucal for the incon-venience caused by the authors of the article

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erbB expression changes in ethanol and 7, 12- dimethylbenz (a) anthracene-induced oral carcinogenesis

Objetive: The aim of this study was to determine erbB expression in normal mucosa, oral dysplasia, and invasive carcinomas developed in the hamster’s buccal pouch chemical carcinogenesis model. Study design: Fifty Syrian golden hamsters were equally divided in five groups (A-E); two controls and three experimental group exposed to alcohol, DMBA, or both for 14 weeks. Number of tumors per cheek, volume, histological condition, erbB expression were determined and results were analyzed by the Mann–Whitney U and Dunn’s test. Results: Control groups and those exposed to alcohol (A, B and C respectively) only presented clinical and histological normal mucosa; while those exposed to DMBA or DMBA plus alcohol (D and E groups) developed dysplasia and invasive carcinomas. erbB2, erbB3, and erbB4 increased their expression in alcohol-exposed mucosa, dysplasia, and invasive carcinomas. We observed a similar expression level for erbB2 in dysplasia and carcinomas; while, erbB3 and erbB4 were similar only in carcinomas. Conclusion: The DMBA and alcohol can be considered as carcinogen and promoter for oral carcinogenesis. TheerbB expression is different according to their histological condition, suggesting differential participation of theerbB family in oral carcinogenesis induced by alcohol and DMBA (AU)

Purification and characterization of structural and functional properties of two lectins from a marine sponge Spheciospongia vesparia.

The purification, structural and functional characterization of two different lectins (named Svl-1 and Svl-2) has been reported from the marine sponge Spheciospongia vesparia. Purification procedure includes ammonium sulfate precipitation, combined with chromatography including Octyl-Sepharose-(NH4)SO4 hydrophobic column and DEAE-Toyopearl anion-exchange column using a high performance liquid chromatography. The similarities in function, specificity for saccharides, molecular weight, amino acid content and the N-terminal sequence of two lectins suggest that these proteins are isolectins. Amino acid composition and fluorescence analyses reveal that they contain an intrachain disulfide bridge, which might contribute to their high thermal stability. Furthermore, the purified lectins exhibit antibacterial activity against the gram-negative bacteria Pseudomonas aeruginosa and E. coli, indicating that they may be involved in a recognition strategy and may play a role in the defense response function of the sponge. This is the first report on the isolation of lectins from the S. vesparia. The purified lectins represent a potential possible candidate for future application in the recognition or treatment of cancer cells.

erbB expression changes in ethanol and 7,12- dimethylbenz (a)anthracene-induced oral carcinogenesis.

OBJECTIVE: [corrected] The aim of this study was to determine erbB expression in normal mucosa, oral dysplasia, and invasive carcinomas developed in the hamster's buccal pouch chemical carcinogenesis model. STUDY DESIGN: Fifty Syrian golden hamsters were equally divided in five groups (A-E); two controls and three experimental group exposed to alcohol, DMBA, or both for 14 weeks. Number of tumors per cheek, volume, histological condition, erbB expression were determined and results were analyzed by the Mann-Whitney U and Dunn's test. RESULTS: Control groups and those exposed to alcohol (A, B and C respectively) only presented clinical and histological normal mucosa; while those exposed to DMBA or DMBA plus alcohol (D and E groups) developed dysplasia and invasive carcinomas. erbB2, erbB3, and erbB4 increased their expression in alcohol-exposed mucosa, dysplasia, and invasive carcinomas. We observed a similar expression level for erbB2 in dysplasia and carcinomas; while, erbB3 and erbB4 were similar only in carcinomas. CONCLUSION: The DMBA and alcohol can be considered as carcinogen and promoter for oral carcinogenesis. The erbB expression is different according to their histological condition, suggesting differential participation of the erbB family in oral carcinogenesis induced by alcohol and DMBA.

Participación de la prolactina en la respuesta inmune / Role of prolactin in the immune response

Existen evidencias de la relación entre el sistema inmune y el endocrino vía múltiples factores de comunicación, como citocinas, neuropéptidos, neurotransmisores y hormonas. Se ha demostrado la participación de la hormona prolactina en la respuesta inmune innata y adaptativa. Además de ser producida por la glándula pituitaria, también es producida y secretada por las células del sistema inmunológico. El objetivo de esta revisión fue puntualizar acerca de la participación de la prolactina secretada por estas células en la respuesta inmune.

Evidence exists about the relationship between the immune and the endocrine systems through communication of multiple factors such as cytokines, neuropeptides, neurotransmitters and hormones. Among the hormones, prolactin (PRL) has been shown to participate in the innate and adaptive immune response. In addition to being produced by the pituitary gland, PRL is also produced and secreted by cells of the immune system. The aim of this review is to update information about the involvement of PRL secreted by immune system cells in the immune response.

Fibrocollagen-covered prosthesis for a noncircumferential segmental tracheal replacement.

OBJECTIVE: Fibrocollagen-covered polyester meshes can be used as possible substitutions for tracheal segments if they become integrated into the tissue without complications. The aim of this study was to assess a fibrocollagen-covered polyester prosthesis to be used as a substitution for a tracheal segment. METHODS: We performed a blind, randomized experimental assay. Adult Wistar rats were assigned to one of 2 groups. Prostheses were made by implanting polyester tubing in a group of animals to cover them with homologous collagen. They were implanted as substitutions of tracheal segments in the experimental group after creating a defect in the anterior wall of the trachea. Clinical, histomorphologic, and immunohistochemical assessments were made at 4 different time points. RESULTS: The experimental group presented some respiratory distress signs during the first 7 to 10 days, such as stertors, hissing, and low motor activity. After this initial period, the symptoms subsided progressively and disappeared at the end of the first month. These respiratory symptoms caused no mortality. Initially undifferentiated monolayer cells predominated on the implant's surface, but during the last 2 months, the proportion of epithelial and ciliated cells was similar to that seen in control animals. Types I, III, and V collagen fibers were identified around the mesh. The intraluminal area of the tracheas with prostheses and prosthesis thickness were larger during the 4 months of the experiment. The increase in thickness was due to angiogenesis without evidence of fibrosis or chronic inflammation. CONCLUSIONS: Polyester-collagen prostheses used as substitutions of tracheal segments in rats enabled the proliferation of normal respiratory epithelium and maintained tracheal function without collapse, inflammatory reaction, or secondary stenosis.

Perspectiva monggráfica del cáncer pulmonar: un enfoque molecular y la metástasis al cerebro

El cáncer es una de las principales causas de muerte en el mundo. En México, al igual que en los países desarrollados, el cáncer pulmonar es uno de los más frecuentes y, de forma importante, la evolución y pronóstico de la enfermedad es bastante más grave cuando se torna metastásico. Metástasis: Las siembras celulares a distancia constituyen la complicación más grave del cáncer. Cuando las metástasis se dirigen al sistema nervioso central, las probabilidades de sobrevida o recuperación disminuyen. Generalmente, la principal causa de muerte del cáncer son las metástasis. El fenómeno de migración celular y metástasis definitivamente no es azaroso. Existe evidencia clara de que hay predisposición celular tumoral para que suceda; además, se ha demostrado que la célula que migra lo hace a través de la participación de diversas moléculas de adhesión, proteínas que reconocen carbohidratos y fenómenos citocinéticos relacionados. Glicosilación: El papel que desempeñan los oligosacáridos de superficie celular en el reconocimiento, señalización, migración, interacción célula-célula y célula-matriz extracelular es crucial para que las células cancerosas se desarrollen, proliferen, migren, invadan y metastatizen. Las modificaciones en la expresión de los oligosacáridos de superficie celular influyen en la carcinogénesis y metástasis. Conclusión: En esta revisión se exponen las evidencias que marcan las bases moleculares de la carcinogénesis pulmonar, por ser tan frecuente en nuestro medio, y los fenómenos de migración celular que involucran la metástasis al cerebro, siendo ésta la más grave de las complicaciones del cáncer.

Cancer is one of the main causes of death in the world. In Mexico, like in developed countries, lung cancer is very frequent and particularly severe when there is metastatic disease. Metastasis: Cell sowing at a distance is the worst complication of cancer. The main cause of death in cancer is metastasis. Cell migration and metastasis are not randomized. There is evidence of cellular tumor predisposition for metastasis; furthermore, the migrating cell does it through the participation of several adhesion molecules, carbohydrate-ligand proteins and related cytokinetics phenomena. When metastatic cells are deposited in the central nervous system, the probabilities for recuperation or survival are nil. Glycosylation: The role of cell-surface oligosaccharides in the recognition, signalization, migration, cell-cell and cell-extracellular matrix interactions, is crucial for the development, proliferation, migration, invasion and eventual metastasis of the neoplastic cell. Modifications in the expression of the cell-surface oligosaccharides have influence in carcinogenesis and metastasis. Conclusions: In this review, we present the evidence supporting the molecular basis of lung carcinogenesis, and the cell migration phenomena which are involved in brain metastasis.

Aspectos inmunlóógicos del envejecimiento

La inmunosenescencia es un proceso complejo que involucra múltiples cambios en las poblaciones linfocitarias. Estos cambios en el adulto mayor incrementan la incidencia y severidad de las enfermedades infecciosas y algunos cánceres. En este artículo revisamos algunos de los cambios inmunológicos más relevantes que han sido descritos durante el envejecimiento y su asociación con algunas patologías.

Immunosenescence is a complex process involving multiple changes in lymphocyte subsets. In the elderly, these changes contribute to an increased incidence and severity of infectious diseases and some types of cancer. This paper reviews some of the immunological changes in the elderly and their association with certain diseases.

Avances en el estudio de los mecanismos celulares de supresión de la respuesta inmunitaria en la tuberculosis / Advances in the study of immunosuppression cell mechanisms in tuberculosis

La respuesta inmunitaria protectora generada durante la tuberculosis es el resultado de la integración de las respuestas inmunitarias, natural y adquirida, a través de la activación de linfocitos T CD4+ productores de IFN-g, permitiendo la eliminación del bacilo por macrófagos activados. La inmunosupresión, es la consecuencia de un desequilibrio en la respuesta inmunitaria con progreso de la infección. En este trabajo, se revisan las características de la respuesta inmunitaria contra Mycobacterium tuberculosis así como los mecanismos celulares de supresión de la respuesta inmunitaria.

Estudio de Marcadores de superficie celular en pacientes con rinitis alérgica frente a reto con Der p y Der f / Estudy of the markers of cellular surface in patients with allergic rinitis forehead to challenge with Der p and Der f

Los padecimientos alérgicos están genéticamente determinados y afectan del 20 al 30 por ciento de la población general en países desarrollados; en la última década la prevalencia se ha incrementado. El desequilibrio manifiesto en los padecimientos atópicos se encuentra en las células presentadoras de antígeno (monocitos y células B) y en los linfocitos T CD4+. La asociación de moléculas como CD80, CD 86 (moléculas co-estimulatorias) en monocitos y células B; y CD30, CD62L, ALL, CD11a, CD28, CD124 y CD152 en CD4+, ha demostrado ser de particular interés en padecimientos atópicos. Sin embargo, no se encontró una diferencia estadísticamente significativa entre pacientes y controles y entre reto nasal con solución salina y alergeno. Por esto se sugiere que los cambios en la activación, proliferación y cooperación se dan en el sitio de la lesión, sin una aparente repercusión en las células de la sangre periférica.

Oxido nítrico, una molécula multifuncional / Nitric oxide, a multifunctional molecule

El óxido nítrico es un regulador importante de diversas funciones fisiológicas y además, es un factor que contribuye a la respuesta inmune innata. Su efecto también puede estar relacionado a procesos patológicos como el asma o la inflamación crónica. Objetivo. En este trabajo se revisaron algunos aspectos bioquímicos, inmunológicos y fisiopatológicos del óxido nítrico

Detección de micoplasmas en pacientes con asma / Detection of mycoplasma in patients with asthma

Introducción. El asma puede ser desencadenada por diferentes estímulos, entre ellos están los agentes infecciosos. Los virus la exacerban con mayor frecuencia y Mycoplasma pneumoniae ha sido implicado como posible agente. Objetivo. Buscar la presencia de micoplasma en exudado faríngeo de pacientes con asma y determinar el perfil de anticuerpos en suero. Material y métodos. Se buscaron micoplasmas en exudado faríngeo y en el suero de 208 pacientes en que se determinó IgM, IgG, IgA, aglutininas frías y anticuerpos antimicoplasmas. Resultados. Se identificaron 12 cepas de M. fermentans por polimerasa. Sólo se detectaron anticuerpos anti-M. fermentans y anti-M. pneumoniae en un paciente por inhibición metabólica. En los pacientes con M. fermentans hubo una disminución de IgM e IgG en la segunda determinación. Veinte pacientes tuvieron aglutininas frías y tres de ellos tenían M. fermentans. Discusión. No se aisló M. pneumoniae, M. fermentans se aisló en 5.5 por ciento, esto es difícil de interpretar debido a que se desconce su prevalencia en población sana. Probablemente no se aisló a M. pneumoniae porque no es un agente desencadenante, o por ser un microorganismo difícil de cultivar. Sin embargo el mecanismo de patogenicidad de los micoplasmas es muy parecido al de los virus que tienen la capacidad de exacerbar el asma. Conclusión. Con los resultados obtenidos no se puede concluir si los micoplasmas son agentes exacerbantes del asma, aunque tampoco se pueden descartar como tales

Respuesta inmune en la tuberculosis / Immune response in tuberculosis

La tuberculosis es una de las enfermedades infecciosas más antiguas que han afectado al hombre. En la actualidad, representa uno de los padecimientos más importantes como causa de muerte. En este trabajo se pretende discutir algunos aspectos recientemente identificados relacionados con la fisiopatogenia de la enfermedad y que incluyen la respuesta inmune del individuo y a la capacidad que posee para reconocer, adecuadamente, al agente etiológico. El conocimiento de esta enfermedad en el contexto del sistema de histocompatibilidad, representa un avance importante en la identificación oportuna de individuos o poblaciontes de alto riesgo de enfermedades, lo que permitirá contemplar alternativas de pronósticos y/o tratamiento

Expresión de moléculas de adhesión en el melanoma metastásico murino B16-F10 y su modificación farmacológica in vitro con el empleo de cumarina / Adhesion molecules expression in murine B16-F10 metastatic melanoma and its pharmacological modification in vitro by the use of coumarin

Recientemente se han demostrado correlaciones significativas entre la expresión de algunas moléculas de adhesión y la capacidad de células de producir metástasis. Por ejemplo, se ha observado una correlación entre la expresión de la integrina a6/ß1 en células cancerosas pulmonares y la producción de metástasis. También se ha observado correlación entre la expresión de algunas moléculas de adhesión en células de melanoma maligno y su capacidad de producir metástasis pulmonares. En este trabajo estudiamos la acción in vitro de la cumarina en el melanoma murino B16-F10, productor de metástasis pulmonares, sobre la expresión de dos moléculas de adhesión, ICAM-1 y LFA-1. No se observó disminución en la expresión de la molécula de adhesión LFA-1, y la expresión de ICAM-1 disminuyó de manera uniforme con todas las concentraciones de cumarina estudiadas. Estos resultados no explican los efectos antimetastásicos producidos por la cumarina en modelos animales de metástasis pulmonares experimentales y espontáneas, ni los efectos antimetastásicos en humanos. Es necesario, por tanto, estudiar el efecto de la cumarina en la expresión de otras integrinas. Este tipo de estudios permite el desarrollo de nuevas estrategias en la búsqueda de mejores agentes antineoplásicos que disminuyan en mayor grado el número y tamaño de metástasis, y retarden importantemente su producción; contribuye, adenomás, al conocimiento de la fisiopatogenia de estos tumores malignos