Sex-dependent effects of angiotensin II type 1 receptor blocker on molecular and behavioral changes induced by single prolonged stress.

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that not only entails alterations in fear behavior and anxiety but also includes neuroendocrine dysfunctions involving the hypothalamic pituitary adrenal (HPA) axis and the renin-angiotensin system. Recent preclinical studies demonstrate that activation of the angiotensin type 1 receptor (AT1R) in the paraventricular region of the hypothalamus (PVR) promotes anxiety-like behaviors and enables microglia proliferation. An increase in microglia and anxiety-like behavior also occurs in the PTSD animal model single-prolonged stress (SPS). In the present study, we tested whether AT1Rs contribute to the effects of SPS on behavior and microglia in brain structures important for HPA axis regulation and fear behavior. To test this, male and female animals were exposed to SPS and then given the oral AT1R antagonist candesartan beginning one week later. Candesartan did not alter auditory fear conditioning or extinction in SPS-exposed male or female animals. However, we found that the male animals exposed to SPS showed increased anxiety-like behavior, which was reversed by candesartan. In contrast, neither SPS nor candesartan altered anxiety-like behavior in the female animals. At the molecular level, SPS increased the cellular expression of AT1Rs in the PVR of male animals and candesartan reversed this effect, whereas AT1Rs in the PVR of females were unaltered by either SPS or candesartan. Iba1-expressing microglia increased in the PVR after SPS exposure and was reversed by candesartan in both sexes suggesting that SPS stimulates AT1Rs to increase microglia in the PVR. Collectively, these results suggest that the contribution of AT1Rs to the molecular and behavioral effects of SPS is sex-dependent.

Sex-dependent effects of microglial reduction on impaired fear extinction induced by single prolonged stress.

Single prolonged stress (SPS) is a preclinical rodent model for studying post-traumatic stress disorder (PTSD)-like behaviors. Previously we found that increased expression of the microglial marker Iba-1 in the ventral hippocampus after SPS exposure was associated with impaired fear extinction, suggesting that microglial activity contributed to the SPS-induced behavioral changes. To test this, we examined whether reducing microglia with the colony-stimulating factor 1 receptor blocker, PLX3397, in the diet would prevent the SPS-induced extinction impairment. Male rats exposed to SPS showed enhanced fear acquisition and impaired fear extinction memory. Adding PLX3397 to the diet prevented these behavioral changes. In contrast, PLX3397 did not prevent SPS from impairing fear extinction memory in the female rats. Despite the sex-dependent behavioral effects, we found a reduced number and area fraction of Iba-1+ microglia in both male and female rats suggesting that PLX3397 had similar effects on microglia in both sexes. Altogether, these results suggest that microglia contribute to the behavioral changes induced by SPS in male but not female rats.

Síndrome de teratoma creciente: reporte de caso y revisión de la literatura / Growing ovarian teratoma syndrome: Case report and literature review / Growing ovarian teratoma syndrome: Case report and literature review

RESUMEN El síndrome de teratoma creciente (STC) es una condición infrecuente en la que se evidencia aumento de tamaño de los tumores de células germinales o la aparición de nuevas lesiones, durante o después del tratamiento con quimioterapia. Lo más característico de este tumor es la presencia exclusiva de componentes de teratoma maduro, así como valores de marcadores tumorales que negativizan durante la quimioterapia, y se mantienen negativos durante el seguimiento. Se presenta el caso de una mujer de 28 años con un tumor de ovario de células germinales mixtas sometida a cirugía y luego quimioterapia. Durante el seguimiento, desarrolló múltiples tumores pélvicos que correspondieron a teratomas maduros. En esta paciente, fue crucial identificar el síndrome de teratoma creciente para evitar tratamiento adicional con quimioterapia.

ABSTRACT The growing teratoma syndrome (GTS) is a rare condition in which patients with germ cell tumors present an increase in tumor size or the appearance of new lesions, during or after chemotherapy. The hallmark of this tumor is the unique presence of mature teratoma components, as well as tumor marker values that become negative with chemotherapy, and remain low thereafter. We report the case of a 28-yearold female who presented a mixed germ cell tumor of the ovary, for which she underwent surgery and subsequent chemotherapy. Later, she developed multiple pelvic tumors that corresponded to mature teratoma. It was crucial in this patient to identify the syndrome to avoid additional treatment with chemotherapy.

EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation.

Here, we report a retrospective series of 47 EBV-positive diffuse large B-cell lymphoma associated with advanced age. Histopathology allowed to the identification of different histological patterns: cases with polymorphic diffuse large B-cell lymphoma (29 cases), Hodgkin-like (8 cases) and polymorphic lymphoproliferative disorder-like (9 cases) patterns. One case was purely monomorphic diffuse large B-cell lymphoma. We show that this lymphoma type is a neoplasm with prominent classical and alternative nuclear factor-kB pathway activation in neoplastic cells (79% of the cases showed nuclear staining for p105/p50, 74% for p100/p52 and 63% for both proteins), with higher frequency than that observed in a control series of EBV-negative diffuse large B-cell lymphoma (χ(2) <0.001). Most cases showed an activated phenotype (95% non-germinal center (Hans algorithm); 78% activated B cell (Choi algorithm)). Clonality testing demonstrated IgH and/or K/Kde/L monoclonal rearrangements in 64% of cases and clonal T-cell populations in 24% of cases. C-MYC (1 case), BCL6 (2 cases) or IgH (3 cases) translocations were detected by FISH in 18% cases. These tumors had a poor overall survival and progression-free survival (the estimated 2-year overall survival was 40 ± 10% and the estimated 2-year progression-free survival was 36 ± 9%). Thus, alternative therapies, based on the tumor biology, need to be tested in patients with EBV-positive diffuse large B-cell lymphoma of the elderly.

[Gastric cancer in a general hospital. Santa Rosa Hospital. Experience]. / Cáncer gástrico en un hospital general: Hospital Santa Rosa.

PURPOSE: Determine the frequency of gastric cancer and its clinical and pathological characteristics, clinical stages, surgical treatment, morbimortality and survival in a general hospital. MATERIALS AND METHODS: Retrospective, descriptive study on 71 consecutive patients diagnosed with gastric cancer at the Santa Rosa Hospital from January 1, 2005 to January 31, 2008. RESULTS: During the study period, 71 cases of gastric adenocarcinoma were confirmed by histopathology. This disease is more frequent in men, with a 1.54 to 1 ratio, as compared to women. The most frequent age of appearance is between the fifth and seventh decades of life. Distal tumors (81.7%) are four times more common than proximal tumors (18,3%). The most common histological type was carcinoma in signet-ring cells (40.8%). The most frequent degree of differentiation was Undifferentiated (42.3%). A 62% (n=44) of patients entered the operating room. The resectability rate was 68% (n=30). The advanced stage was the most common form of presentation in patients (97.2%), while the early stage was rare (2.8%). The most frequent surgeries were the distal subtotal gastrectomy (73.3%) and the total gastrectomy (26.7%). The D2 (73.3%) dissection was performed. The mortality rate was 6.7% and the morbidity rate was 26.7%. Survival was better in patients who underwent resection than in patients who only underwent biopsy or were unresectable, evidencing statistical significance. CONCLUSION: Gastric cancer is diagnosed in a late stage and surgical treatment plays a pivotal role and, even in advanced cases, morbidity/mortality is acceptable for the initial experience at a third-level general hospital. It is necessary to carry out screening program to detect the disease in earlier stages.

Cáncer Gástrico en un Hospital General: Hospital Santa Rosa / Gastric cancer in a general hospital. Santa Rosa Hospital. experience

OBJETIVO: Determinar la frecuencia de cáncer gástrico y sus características clínico patológicas, estadios clínicos, tratamiento quirúrgico, morbimortalidad y sobrevida en un hospital general. MATERIALES Y MÉTODOS: Estudio retrospectivo, descriptivo, de 71 pacientes consecutivos diagnosticados con cáncer gástrico en el Hospital Santa Rosa desde el 1 de enero 2005 hasta el 31 de enero 2008. RESULTADOS: En el periodo de estudio se confirmaron por histopatologia 71 casos de adenocarcinoma gástrico. El sexo masculino es el más frecuente, con una relación de 1,54 a 1 con respecto al sexo femenino. La edad de presentación más frecuente se encuentra entre la 5ta y 7ma década de vida. Los tumores distales (81,7 por ciento) son cuatro veces más frecuentes que los proximales (18,3 por ciento). El tipo histológico más frecuente fue el carcinoma en células de anillo de sello (40,8 por ciento). El grado de diferenciación más frecuente fue el Indiferenciado (42,3 por ciento). El 62 por ciento (n=44) ingresó a sala de operaciones. La tasa de resecabilidad fue de 68 por ciento (n=30). El estadío clínico avanzado ha sido la forma depresentación más frecuente de los pacientes (97,2 por ciento), mientras que el estadío precoz ha sido raro (2,8 por ciento). La cirugía más frecuente fue la gastrectomía subtotal distal (73,3 por ciento) y gastrectomía total (26,7 por ciento). La disección realizada fue la D2 (73,3 por ciento). La tasa de mortalidadfue 6,7 por ciento y morbilidad de 26,7 por ciento. La sobrevida fue mejor en los pacientes que tuvieron resección frente a los que sólo se les realizó biopsia o fueron irresecables, evidenciandosignificancia estadística. CONCLUSIÓN: El cáncer gástrico se diagnóstica en etapa tardía y el tratamiento quirúrgicojuega un rol fundamental e incluso en casos avanzados, la morbimortalidad es aceptable para la experiencia inicial en un Hospital general de tercer nivel. Es necesario realizar programas de tamizaje para detectar la enfermedad en...

PURPOSE: Determine the frequency of gastric cancer and its clinical and pathological characteristics, clinical stages, surgical treatment, morbimortality and survival in ageneral hospital. MATERIALS AND METHODS: Retrospective, descriptive study on 71 consecutive patients diagnosed with gastric cancer at the Santa Rosa Hospital from January 1, 2005 to January 31, 2008. RESULTS: During the study period, 71 cases of gastric adenocarcinoma were confirmed by histopathology. This disease is more frequent in men, with a 1.54 to 1 ratio, as compared to women. The most frequent age of appearance is between the fifth and seventh decadesof life. Distal tumors (81.7 per cent) are four times more common than proximal tumors (18,3 per cent).The most common histological type was carcinoma in signet-ring cells (40.8 per cent). The mostfrequent degree of differentiation was Undifferentiated (42.3 per cent). A 62 per cent (n=44) of patients entered the operating room. The resectability rate was 68 per cent (n=30). The advanced stagewas the most common form of presentation in patients (97.2 per cent), while the early stage was rare (2.8 per cent). The most frequent surgeries were the distal subtotal gastrectomy (73.3 per cent) and the total gastrectomy (26.7 per cent). The D2 (73.3 per cent) dissection was performed. The mortality rate was 6.7 per cent and the morbidity rate was 26.7 per cent. Survival was better in patients who underwent resection than in patients who only underwent biopsy or were unresectable, evidencing statistical significance. CONCLUSIÓN: Gastric cancer is diagnosed in a late stage and surgical treatment playsa pivotal role and, even in advanced cases, morbidity/mortality is acceptable for the initial experience at a third-level general hospital. It is necessary to carry out screening program to detect the disease in earlier stages.

Angiomatosis bacilar diseminada / Angiomatosis disseminated bacilar

Se presenta el caso de un varón de 25 años de edad, con lesiones costrosas en región malar derecha y lesión en "punto de rubí" en arco superciliar derecho. Los hallazgos histopatológicos en ambas biopsias fueron los de una proliferación vascular nodular, con presencia de infiltrado intersticial, focos de necrosis, edema, extravasación de hematíes y presencia de masas anfófilas de un material granular intersticial mucho más prominente en el ganglio linfático que en la piel. El material granular estaba constituido por conglomerados de estructuras bacilares. Se presentan las características histopatológicas que permiten realizar el diagnóstico diferencial de la angiomatosis bacilar con otras proliferaciones vasculares, siendo la principal diferencia del material intersticial eosinófilo o anfófilo descrito.