RESUMO
Introduction: Gastric cancer is the fourth deadliest cancer worldwide. Due to the lack of specific early symptoms and noninvasive methods for early detection, the prognosis of gastric cancer patients is poor. Gastric cancer has a well-recognized infectious etiology, with Helicobacter pylori and Epstein-Barr Virus being the main associated infectious agents. Although other Epstein-Barr Virus-associated malignancies often manifest with abnormal levels of anti-Epstein-Barr Virus antibodies, it is not clear whether this is also true for gastric cancer. Potentially, these antibodies could serve as a noninvasive tool for gastric cancer screening or as markers for gastric cancer risk and provide a better understanding of the participation of Epstein-Barr Virus in the development of this neoplasm. Methods: We conducted a systematic review of articles analyzing anti-Epstein-Barr Virus serology in gastric cancer and precursor lesions following PRISMA guidelines. Patients were classified according to the Correa cascade of gastric lesions and whether they were positive or negative by EBER-in situ hybridization (Epstein-Barr Virus-associated gastric cancer and Epstein-Barr Virus-nonassociated gastric cancer, respectively). Results: We retrieved 16 articles involving 9735 subjects from 12 different countries and 4 databases, PubMed, SciELO, Scopus, and Google Scholar. Higher antibody titers were observed not only in Epstein-Barr Virus-associated gastric cancer than in Epstein-Barr Virus-nonassociated gastric cancer but also in Epstein-Barr Virus-nonassociated gastric cancer and gastric cancer-precursor lesions when compared with patients with mild dyspepsia or healthy controls. In all cases, the associations were predominantly with antibodies directed against lytic cycle antigens. Conclusion: Data support the role of Epstein-Barr Virus lytic reactivation in the development of advanced gastric lesions. However, more studies are needed to confirm these associations, particularly the association with lesions considered negative by EBER-in situ hybridization, and to establish a set of antibodies and thresholds indicative of enhanced risk to develop these lesions.
Assuntos
Herpesvirus Humano 4 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , RiscoRESUMO
Helicobacter pylori and EBV are considered the main risk factors in developing gastric cancer. Both pathogens establish life-lasting infections and both are considered carcinogenic in humans. Different lines of evidence support that both pathogens cooperate to damage the gastric mucosa. Helicobacter pylori CagA positive virulent strains induce the gastric epithelial cells to secrete IL-8, which is a potent chemoattractant for neutrophils and one of the most important chemokines for the bacterium-induced chronic gastric inflammation. EBV is a lymphotropic virus that persists in memory B cells. The mechanism by which EBV reaches, infects and persists in the gastric epithelium is not presently understood. In this study, we assessed whether Helicobacter pylori infection would facilitate the chemoattraction of EBV-infected B lymphocytes. We identified IL-8 as a powerful chemoattractant for EBV-infected B lymphocytes, and CXCR2 as the main IL-8 receptor whose expression is induced by the EBV in infected B lymphocytes. The inhibition of expression and/or function of IL-8 and CXCR2 reduced the ERK1/2 and p38 MAPK signaling and the chemoattraction of EBV-infected B lymphocytes. We propose that IL-8 at least partially explains the arrival of EBV-infected B lymphocytes to the gastric mucosa, and that this illustrates a mechanism of interaction between Helicobacter pylori and EBV.
Assuntos
Linfócitos B , Fatores Quimiotáticos , Infecções por Vírus Epstein-Barr , Infecções por Helicobacter , Interleucina-8 , Humanos , Antígenos de Bactérias , Linfócitos B/metabolismo , Linfócitos B/virologia , Proteínas de Bactérias/metabolismo , Fatores Quimiotáticos/metabolismo , Células Epiteliais , Mucosa Gástrica/metabolismo , Herpesvirus Humano 4/metabolismo , Interleucina-8/metabolismo , Neoplasias GástricasRESUMO
EBV and Helicobacter pylori (H. pylori) cause highly prevalent persistent infections as early as in childhood. Both pathogens are associated with gastric carcinogenesis. H. pylori interferes with iron metabolism, enhancing the synthesis of acute-phase proteins hepcidin, C-reactive protein (CRP), and α-1 glycoprotein (AGP), but we do not know whether EBV does the same. In this study, we correlated the EBV antibody levels and the serum levels of hepcidin, CRP, and AGP in 145 children from boarding schools in Mexico City. We found that children IgG positive to EBV antigens (VCA, EBNA1, and EA) presented hepcidin, AGP, and CRP levels higher than uninfected children. Hepcidin and AGP remained high in children solely infected with EBV, while CRP was only significantly high in coinfected children. We observed positive correlations between hepcidin and EBV IgG antibodies (p < 0.5). Using the TCGA gastric cancer database, we also observed an association between EBV and hepcidin upregulation. The TCGA database also allowed us to analyze the two important pathways controlling hepcidin expression, BMP−SMAD and IL-1ß/IL-6. We observed only the IL-1ß/IL-6-dependent inflammatory pathway being significantly associated with EBV infection. We showed here for the first time an association between EBV and enhanced levels of hepcidin. Further studies should consider EBV when evaluating iron metabolism and anemia, and whether in the long run this is an important mechanism of undernourishment and EBV gastric carcinogenesis.
Assuntos
Infecções por Vírus Epstein-Barr , Helicobacter pylori , Neoplasias Gástricas , Criança , Humanos , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/metabolismo , Helicobacter pylori/metabolismo , Hepcidinas/metabolismo , Herpesvirus Humano 4 , Imunoglobulina G/metabolismo , Interleucina-6/metabolismo , Ferro/metabolismo , Neoplasias Gástricas/etiologiaRESUMO
PEl Ácido Valproico (AVP), fármaco ampliamente conocido por sus propiedades antiepilépticas para el manejo de la epilepsias parciales y simples. Es también utilizado dentro de la Psiquiatría como estabilizador del humor y apoyo en el tratamiento de episodios de manía donde el uso del litio está contraindicado. Presentamos el caso de un hombre de 53 años con trastorno esquizoafectivo no especifico y mala adherencia al tratamiento, quien al iniciar manejo con AVP desarrolló una intoxicación por este fármaco, independiente a los niveles en suero de este, revolviéndose con líquidos intravenosos y reajuste de dosis.
Valproic Acid (VA), a widely known medication being used in partial and simple epilepsy treatment because of its antiepileptic properties. It's also used within Psychiatry as a mood stabilizer and the support in the treatment for manic episodes on which lithium its contraindicated. We present the case of a 53-year-old man with nonspecified schizoaffective disorder and poor adherence to treatment, when initiated treatment with VA developed drug toxicity that was independent of VA serum levels, resolving with intravenous fluids and dose readjustment.
Assuntos
Masculino , Pessoa de Meia-Idade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Psiquiatria , Psicofarmacologia , Psicotrópicos/administração & dosagem , Cooperação e Adesão ao Tratamento , AnticonvulsivantesRESUMO
The Cuban solenodon (Solenodon cubanus) is one of the most enigmatic mammals and is an extremely rare species with a distribution limited to a small part of the island of Cuba. Despite its rarity, in 2012 seven individuals of S. cubanus were captured and sampled successfully for DNA analysis, providing new insights into the evolutionary origin of this species and into the origins of the Caribbean fauna, which remain controversial. We conducted molecular phylogenetic analyses of five nuclear genes (Apob, Atp7a, Bdnf, Brca1 and Rag1; total, 4,602 bp) from 35 species of the mammalian order Eulipotyphla. Based on Bayesian relaxed molecular clock analyses, the family Solenodontidae diverged from other eulipotyphlan in the Paleocene, after the bolide impact on the Yucatan Peninsula, and S. cubanus diverged from the Hispaniolan solenodon (S. paradoxus) in the Early Pliocene. The strikingly recent divergence time estimates suggest that S. cubanus and its ancestral lineage originated via over-water dispersal rather than vicariance events, as had previously been hypothesised.
Assuntos
Eulipotyphla/genética , Evolução Molecular , Proteínas Nucleares/genética , Filogenia , Animais , CubaRESUMO
Introducción: Tradicionalmente la cirugía tiroidea ha sido practicada bajo anestesia general con intubación endotraqueal. Sin embargo, tomando en cuenta que el riesgo de intubación difícil aumenta en presencia de bocio, que el paso del tubo endotraqueal puede lastimar las cuerdas vocales y que su colocación requiere de relajación muscular y de una laringoscopia con estimulación simpática, el uso de mascarilla laríngea (ML) en cirugía tiroidea pareciera ser una buena alternativa. Con el propósito de determinar si el tamaño del bocio, el diagnóstico de cáncer, el grado de Mallampati y la extensión de la cirugía tiroidea inciden en la dislocación de la ML, se diseñó un estudio incluyendo pacientes con patología tiroidea operados bajo anestesia general con Mascarilla laríngea clásica (MLc). Diseño, lugar y participantes: Se presenta una serie prospectiva de casos, con 168 pacientes sometidos a cirugía tiroidea bajo anestesia general con MLc, operadosde marzo de 1999 a agosto del 2008 en los hospitales Universitario Esperanza y Nuestra Señora del Pilar de la ciudad de Guatemala. Su uso se consideró exitoso cuando la cirugía pudo ser completada con la MLc sin necesidad de sustituirla por intubación endotraqueal. Resultados:La edad promedio de los pacientes fue de 45 años, 148 (88%) fueron del sexo femenino y 20 (22%) del sexo masculino, el tamaño promedio de la glándula tiroides fue de 9.03cm, 166 (99%) tenían Grado I-II de Mallampati, 119 (71%) fueron operados por enfermedad benigna y 49 (29%) por cáncer, a 77 (46%) se les practicó una lobectomía, a 85 (51%) una tiroidectomía total y a 6 (3%) un vaciamiento ganglionar cervical. De los 168 pacientes operados, en 159 (95%) el procedimiento quirúrgico pudo completarsecon la MLc y en 9 pacientes (5%), la MLc fue sustituida por un tubo endotraqueal. Después de análisis univariados y multivariados se pudo establecer que: ni la edad, el sexo, el tamaño de la glándula tiroides, el grado de Mallampati, el diagnóstico histopatológico, ni la extensión de la cirugía, se asociaron estadísticamente con dislocación de la MLc y la necesidad de sustituirla por un tubo endotraqueal. Conclusiones: El uso de la MLc en cirugía tiroidea es posible independientemente del tamaño del bocio, del grado de Mallampati, de la presencia de cáncer y de la extensión de la cirugía.
Background:Traditionally thyroid surgery has been performed under general anesthesia with an endotracheal tube; in the presence of large goiters management of the upper air way using and endotracheal tube can prove to be difficult causing trauma to the vocal chords and requiring a laryngoscopy after neuromuscular blockade. The use of a laryngeal mask could be a valid option in these patients. The aim of this study was to determine if thyroid surgery could be completed using a laryngeal mask. In order to do this, we analyzed if goiter size pathologic diagnosis, Mallampati score and surgical procedure were associated with rates of dislodgement of a classic laryngeal mask (MLc) during thyroid surgery. Design, setting and participants: We present a prospective series of 168 patients who were submitted to thyroid surgery under general anesthesia using an MLc. All surgeries were performed at Hospital Universitario Esperanza and Hospital NuestraSeñora del Pilar in Guatemala City from March 1999 to August 2008. The use of an MLc was considered to be successful if surgery was able to be completed without the need of changing to the use of an endotracheal tube. Results: The average age of our patients was 45 years, 88% (148) were female, the average size of the glands was 9.03 cms., 166 (99%) had a grade I/II Mallampati score, 119 (71%) had a benign diagnosis and 49 (29%) had cancer, 77 (46%) were submitted to a lobectomy, 85 (51%) had a total thyroidectomy and 6 (3%) had a radical neck resection. Thyroid surgery was successfully completed using aMLc in 95% of cases (159). In 9 patients (5%) the MLc was substituted with an endotracheal tube. After univariate and adjusted analysis age, sex, goiter size, Mallampati score, pathologic diagnosis and surgical procedure were not statistically associated with rate of dislodgement of classic laryngeal mask during thyroid surgery. Conclusions: Thyroid surgery is possible using aMLc. This is independent of goiter size, pathologic diagnosis, and the extent of the surgical procedure.