Germinal Rodríguez: salud pública, política y divulgación sanitaria en primera persona, Argentina, 1922-1960 / Germinal Rodríguez: public health, politics and medical popularization in the first person, Argentina, 1922-1960

Resumen Este trabajo reconstruye la trayectoria del médico argentino Germinal Rodríguez en diálogo con la historia social de la salud y la enfermedad y con una reciente corriente historiográfica de biografías médicas. En base a una metodología cualitativa de análisis documental, analizamos expedientes oficiales de la Universidad de Buenos Aires, fuentes periodísticas, libros de Rodríguez y otras fuentes secundarias. Como resultado, podemos afirmar que su vida profesional estuvo marcada por la enseñanza universitaria y una exitosa carrera académica, así como por su intensa militancia socialista entre 1920-1930. Rodríguez fue también un divulgador, un experto de consulta en políticas públicas para su partido y funcionario estatal en los años del peronismo.

Abstract This article examines the career of Argentine doctor Germinal Rodríguez, situating it within the context of social history of medicine and the recent trend of medical biographies. Using a qualitative documentary analysis methodology, we analyzed various sources, including official records from the University of Buenos Aires, journalistic articles, and books by Rodríguez himself. Our analysis reveals that Rodríguez's enjoyed a successful academic career in university teaching, while concurrently engaging in active socialist activism between 1920-1930. Beyond academia, Rodríguez served as a science popularizer, a policy consultant for his party, and even a public official during the Peronist era.

Características de pacientes con tumor germinal testicular tipo seminoma y masa retroperitoneal posquimioterapia / Characteristics of patients with seminoma-type testicular germ cell tumor and retroperitoneal mass post-chemotherapy

Objetivo: Describir las características clínicas y patológicas de los pacientes con tumor germinal testicular tipo seminoma con masa residual posquimioterapia (post-QT) con marcadores tumorales negativos llevados a linfadenectomía retroperitoneal (LRP). Método: Se incluyeron pacientes con TGTS y masa residual post-QT entre el año 2007-2021 en nuestra institución. Los datos fueron obtenidos mediante la evaluación retrospectiva de nuestra base de datos electrónica. Resultados: Nueve pacientes cumplieron con los criterios de inclusión. Según la estadificación del TNM, seis pacientes eran pT1, mientras que tres (33,3%) eran N2 y N3. La mayoría de los pacientes, cinco en total, tenían un estadio clínico IIC y todos los pacientes se clasificaron como riesgo bueno según la clasificación del International Germ Cell Cancer Collaborative Group (IGCCCG). Se observaron cinco pacientes, tres fueron intervenidos con LRP y solo uno recibió QT. Solo en dos pacientes llevados a LRP se logró una resección completa de la masa y se encontró tumor viable en el 66,6% de los pacientes llevados a cirugía. Conclusión: En nuestra experiencia la LRP es viable en este tipo de pacientes, logrando la resección completa en la mayoría de los casos. Cuando no se logra una resección completa es imprescindible ofrecer tratamientos adicionales

Objective: We aim to describe the clinical and pathological characteristics of patients with seminomatous germ cell tumour (SGCT) and residual masses following chemotherapy (CTX) with negative tumor markers taken to retroperitoneal lymph node dissection (RLND). Method: We included patients with SGCT and had a residual mass after CTX between 2007 and 2021 in our institution. Data was obtained in a retrospective fashion from our electronic database. Results: A total of 9 patients match the inclusion criteria. Above 66% of patients were Pt1, most of them were N2 (33.3%) and N3 (33.3%), 55.5% had a IIC clinical stage and all the patients had good risk following the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. The majority of the patients were observed (55.5%), 33.3% were taken to RLND and one patient received CTX. Almost 66.6% of the patients taken to RLND had a complete resection of the mass and had viable tumor in 66.6% of the cases. Conclusions: In our retrospective study the RLND is a good option for these patients and allows a complete resection in most of the cases. When a complete resection is not possible is necessary to offer additional treatments

Primary central nervous system lymphoma: Comprehension of cell-of-origin subtypes

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is an uncommon extranodal lymphoma that accounts for more than 95% of all the CNS lymphomas. Unlike its systemic/nodal counterpart, which is currently subtyped into cell-of origin (COO) subtypes, its feasibility and utility are largely debatable in PCNS-DLBCL. Objectives: To classify PCNS-DLBCL into COO-subtypes based on immunohistochemical algorithms by Hans and Choi and evaluate concordance between the two. A further aim is to investigate the clinicoradiological and histomorphological parameters of the subtypes thus obtained. Materials and Methods: As many as 143 cases of primary CNS lymphoma were evaluated by immunohistochemistry for CD10, BCL6, MUM1, GCET, and FOXP1 and based on which the said 143 cases were further classified into COO subtypes using Hans and Choi algorithms. Results: Mean age was 53.8 years with marginal male preponderance and predominantly centroblastic morphology (75.5%). CD 10 was positive in 8.9% of the cases, BCL6 in 58.6%, MUM1 in 89.9%, GCET in 32.9%, and FOXP1 in 79.5%. As much as 84.9% cases were of non-germinal center B-cell (GCB) subtype and 15.1% cases were of GCB subtype as determined based on Hans algorithm. Furthermore, 90.7% cases were of activated B-cell (ABC) subtype and 9.3% cases were of GCB subtype according to Choi algorithm. A 91.8% concordance was observed between Hans and Choi algorithms. Among the 6 discordant cases, 5 cases were subtyped as GCB by Hans and ABC by Choi and 1 case as ABC by Hans and GCB by Choi. Conclusion: Most of PCNS-DLBCLs are of non-GCB/ABC COO subtype, but inconsistences abound in the utility of IHC algorithms in PCNS-DLBCL COO subtypes.

Triptolide regulates the balance of Tfr/Tfh in lupus mice

Abstract Introduction/objectives Systemic lupus erythematosus (SLE) is a classic prototype of the multisystem autoimmune disease and follows a relapsing and remitting course. Triptolide is a diterpene triepoxide extracted from Chinese medicine Tripterygium wilfordii Hook F, with potent immunosuppressive and anti-inflammatory properties. Our previous work observed that triptolide alleviated lupus in MRL/lpr lupus mice with the upregulation of regulatory T cells (Treg) proportion in previous study. In this study, we explored the proportion of follicular T regulatory (Tfr), follicular T helper (Tfh) and germinal center (GC) B cells in lupus mice and evaluated the efficacy of triptolide for lupus treatment in vivo. Methods 20 female MRL/lpr mice were randomly divided into 2 treatment groups and treated orally with vehicle or triptolide. C3H mice were all housed as controlled group and treated orally with vehicle. The percentage of Tfr cells, Tfh cells and GC B cells in spleen of mice were detected by Flow cytometric analysis and immunohistochemistry after 13 weeks of treatment. Results We found that the percentage of Tfr cells decreased in MRL/lpr mice compared with controlled mice. The percentage of Tfh cells in MRL/lpr mice was significantly higher compared with that in controlled mice. The ratio of Tfr/Tfh is also decreased in lupus mice. After treated with triptolide in MRL/Lpr mice in vivo, the percentage of Tfr cells and ratio of Tfr/Tfh increased. The proportion of GC B cells also decreased in mice treated with triptolide by FACS and immunohistochemistry. Conclusions Our results demonstrate that the effect of triptolide in alleviating lupus is partly by reversing immune imbalance with increased percentage of Tfr cells and ratio of Tfr/Tfh. Triptolide might also has effect on immune response through inhibiting proliferating GC B cells.

Role of the NF-kB/parkin/vegfr-1 pathway associated with hypoxic-ischemic insult in germinal matrix samples of newborn infants / O papel da via NF-kB/parkin/vegfr-1 associada à agressão hipóxico-isquêmica em amostras de matriz germinativa de pacientes recém-nascidos

Abstract Objective: Given the high proliferative activity of germinal matrix and its direct correlation with hypoxemia, it is necessary to investigate the possible molecular regulation pathways, to understand the existing clinical relationship between the hypoxic-ischemic insult and the biomarkers NF-kB, AKT-3, Parkin, TRK-C and VEGFR-1. Methods: A hundred and eighteen germinal matrix samples of the central nervous system of patients who died in the first 28 days of life were submitted to histological and immunohistochemistry analysis to identify the tissue immunoexpression of those biomarkers related to asphyxia, prematurity, and death events within 24h. Results: A significantly increased tissue immunoexpression of NF-kB, AKT-3 and Parkin was observed in the germinal matrix of preterm infants. In addition, significantly decreased tissue immunoexpression of VEGFR-1 and NF-kB was observed in patients who experienced asphyxia followed by death within 24 hours. Conclusions: The results suggest a direct involvement between the hypoxic-ischemic insult and NF-kB and VEGFR-1 markers since a decreased immunoexpression of these biomarkers was observed in asphyxiated patients. Furthermore, it is suggested that there was not enough time for VEGFR-1 to be transcribed, translated and expressed on the surface of the plasma membrane. This temporality can be observed in the relationship between NF-kB expression and the survival time of individuals who died within 24 hours, suggesting that this factor is essential for the production of VEGFR-1 and, therefore, to carry out the necessary remodeling effect to neovascularize the affected region.

RESUMO Objetivo: Dada a alta atividade proliferativa da matriz germinativa e sua correlação direta com a hipoxemia, é necessário investigar as possíveis vias de regulação molecular para entender a relação clínica existente entre o insulto hipóxico-isquêmico e os biomarcadores NF-kB, AKT -3, Parkina, TRK-C e VEGFR-1. Métodos: Cento e dezoito amostras de matriz germinativa do sistema nervoso central de pacientes que faleceram nos primeiros 28 dias de vida foram submetidas a análise histológica e imuno-histoquímica para identificar a imunoexpressão tecidual desses biomarcadores relacionados a eventos de asfixia, prematuridade e óbito em 24 horas. Resultados: Observou-se uma imunoexpressão tecidual significativamente aumentada de NF-kB, AKT-3 e Parkin na matriz germinativa de prematuros. Além disso, constatou-se uma imunoexpressão tecidual significativamente diminuída de VEGFR-1 e de NF-kB em pacientes que apresentaram asfixia seguida de morte em 24 horas. Conclusões: Os resultados sugerem o envolvimento direto entre o insulto hipóxico-isquêmico e os marcadores NF-kB e VEGFR-1, visto que se observou uma imunoexpressão diminuída destes biomarcadores nos pacientes asfixiados. Além disso, sugere-se que não houve tempo suficiente para que o VEGFR-1 fosse transcrito, traduzido e expresso na superfície da membrana plasmática. Essa temporalidade pode ser observada na relação entre a expressão de NF-kB e o tempo de vida dos indivíduos que morreram em 24 horas, o que sugere que esse fator é essencial para a produção do VEGFR-1 e, portanto, para realizar o efeito remodelador necessário para neovascularizar a região afetada.

Editorial: About COVID 19 and other topics

Cuando creíamos que ya no sería tema de conversación, renace el COVID 19 en la mayoría de los países. En China, donde se originó esta pandemia, la mayoría de sus provincias están siendo afectadas por el COVID 19, casi sin control. La tasa de pacientes confirmados de coronavirus en los últimos 14 días es de 22,72 por cada cien mil habitantes, y el número de fallecidos diarios va en aumento. Por otra parte, sigue creciendo el número de países que están exigiendo pruebas obligatorias de COVID 19 a los viajeros procedentes de China, después que su gobierno anunciará que reabrirá sus fronteras, lo que ha llevado a incrementar en forma desmedida el número de personas que quieren salir de China. No cabe duda de que la situación en China ha desarrollado un pánico colectivo en el mundo. En Panamá, a pesar de la ponderada campaña de vacunación a la comunidad contra el COVID 19, tenemos también tenemos nuestro repunte, lo que preocupa a las autoridades de salud y por supuesto que a la comunidad en general, sobre todo por las actividades que se avecinan y que mueve muchos panameños por los diferentes lugares del país. Si bien ahora, en forma general, conocemos mucho mejor el comportamiento del virus, al igual que contamos además de la vacuna, con medicamentos que reducen y controlan la infección por este virus, no podemos evitar estos repuntes periódicos, del COVID 19, que lamentablemente involucran un número de fallecido. Un grupo de autores, en un trabajo colectivo multicéntrico, nos describe como evolucionó el conjunto de tratamientos intrahospitalarios utilizados desde los primeros casos de afectados por este virus, en el país. Por otro lado, es de mucho merecimiento el destacar la loable, académica y decidida labor que se desarrolla en el Instituto Oncológico Nacional, de Panamá, en su lucha contra el cáncer. Nos presentan un estudio sobre las neoplasias germinales malignas del ovario. Un tipo de cáncer de rara presentación, pero que tiene un alto grado de malignidad y una rara evolución. Llama la atención el hecho de que se presenta mayormente en las mujeres en sus tres primeras décadas de su vida y se resalta el hecho de que un importante porcentaje de afectadas son de los grupos originarios, que existen en el país, lo cual abre una vía nueva de investigación conducente a buscar la relación entre este tipo de cáncer y la población señalada. Por otra parte, nos traen otro interesante trabajo sobre cáncer de recto, en su etapa localmente avanzada, a los que se les aplica la terapia multimodal y después a continuación se les realiza cirugía con escisión total del mesorrecto, con curso largo de quimioterapia previa a la cirugía, logrando una taza de respuesta patológica completa, acorde a lo que muestran las estadísticas de los mejores centros oncológicos a nivel internacional. (provisto por Infomedic International)

Just when we thought it would no longer be a topic of conversation, COVID 19 is reborn in most countries. In China, where this pandemic originated, most of its provinces are being affected by COVID 19, almost out of control. The rate of confirmed coronavirus patients in the last 14 days is 22.72 per 100,000 population, and the number of deaths per day is increasing.On the other hand, the number of countries that are requiring mandatory COVID 19 testing of travelers from China continues to grow, after the Chinese government announced that it will reopen its borders, which has led to a disproportionate increase in the number of people wanting to leave China. There is no doubt that the situation in China has developed a collective panic in the world.In Panama, in spite of the well thought out community vaccination campaign against COVID 19, we also have our own upturn, which worries the health authorities and of course the community in general, especially because of the upcoming activities that move many Panamanians to different parts of the country.Although now, in general, we know much better the behavior of the virus, as well as we have, in addition to the vaccine, medicines that reduce and control the infection by this virus, we cannot avoid these periodic upturns of COVID 19, which unfortunately involve a number of deaths.A group of authors, in a collective multicenter work, describes the evolution of the set of intrahospital treatments used since the first cases of people affected by this virus in the country.On the other hand, it is well deserved to highlight the praiseworthy, academic and determined work carried out at the National Oncological Institute of Panama in its fight against cancer. They present us with a study on malignant germinal neoplasms of the ovary. This is a rare type of cancer, but it has a high degree of malignancy and a rare evolution. The fact that it occurs mostly in women in the first three decades of their lives is noteworthy, and the fact that a significant percentage of those affected are from the native groups in the country is highlighted, which opens a new avenue of research leading to the search for the relationship between this type of cancer and the population indicated.On the other hand, they bring us another interesting work on rectal cancer, in its locally advanced stage, to which multimodal therapy is applied and then surgery is performed with total excision of the mesorectum, with a long course of chemotherapy prior to surgery, achieving a complete pathological response rate, in accordance with the statistics of the best oncological centers at international level. (provided by Infomedic International)

Ética de la edición genética en seres humanos

Propósito/Contexto. Este artículo analiza aspectos éticos de la edición genética en seres humanos. Metodología/Enfoque. Se describe el desarrollo de las principales aplicaciones de la tecnología genética en prevención, diagnóstico y terapéutica de enfermedades genéticas en las últimas décadas, culminando con la edición genética. Resultados/Hallazgos. Se definen los principales aspectos éticos que presenta la edición genética somática y germinal en seres humanos, incluyendo cuestiones de seguridad, especificidad, precisión y certeza. Se critica la edición genética germinal y el concepto de "mejoramiento" humano por vulnerar la autonomía individual, generar cambios genéticos heredables en la progenie y aceptar la falacia del reduccionismo genético de que los rasgos de las personas dependen exclusivamente de la constitución genética, independiente del ambiente. Discusión/Conclusiones/Contribuciones. La edición genética somática puede ser ética si se siguen las normas éticas de la investigación biomédica. Por el contrario, la edición genética germinal no es pertinente ni necesaria para el tratamiento de enfermedades genéticas y presenta graves conflictos éticos, por lo cual, previo a su aplicación es necesario un consenso social por discusiones democráticas, amplias y profundas entre todos los actores sociales involucrados, seguido de mecanismos de gobernanza con regulación robusta por parte del estado, que impidan la vulneración de derechos humanos fundamentales.

Purpose/Context. This article discusses ethical aspects of gene editing in humans. Methodology/Approach. The main applications of genetic technology in the prevention, diagnosis and therapeutics of genetic diseases in recent decades, are described, culminating with genetic editing. Results/Findings. The main ethical aspects of somatic and germline gene editing in humans are discussed, including issues of safety, specificity, precision and certainty. Germline genetic editing and human "enhancement" are criticized for violating individual autonomy, for generating heritable genetic changes in the progeny and for accepting the fallacy of genetic reductionism that people's traits depend exclusively on genetic makeup, independent of the environment. Discussion/Conclusions/Contributions. Somatic gene editing can be ethical if the ethical standards of biomedical research are followed. However, germline genetic editing is not relevant nor necessary for the treatment of genetic diseases and, furthermore, it presents serious ethical conflicts. Therefore, prior to its application, a social consensus is necessary, obtained by democratic, broad and profound discussions among all the social players involved, followed by governance mechanisms with robust regulation by the state, which prevent the violation of fundamental human rights.

Finalidade/Contexto. Este artigo discute aspectos éticos da edição de genes em humanos. Metodologia/Aproximação. Descreve o desenvolvimento das principais aplicações da tecnologia genética na prevenção, diagnóstico e terapia de doenças genéticas nas últimas décadas, culminando com a edição de genes. Resultados/Descobertas. São definidos os principais aspectos éticos da edição de genes somáticos e da linha germinal no ser humano, incluindo questões de segurança, especificidade, precisão e exactidão. A edição genética da Germline e o conceito de "melhoramento" humano são criticados por violarem a autonomia individual, gerando alterações genéticas hereditárias nos descendentes e aceitando a falácia do reducionismo genético de que as características das pessoas dependem exclusivamente da sua constituição genética, independente do ambiente. Discussão/Conclusões/Contribuições. A edição somática de genes pode ser ética se os padrões éticos da investigação biomédica forem seguidos. Pelo contrário, a edição genética na linha germinal não é relevante nem necessária para o tratamento de doenças genéticas e apresenta graves conflitos éticos. Por conseguinte, antes da sua aplicação, é necessário um consenso social através de discussões democráticas, amplas e profundas entre todos os actores sociais envolvidos, seguidas de mecanismos de governação com regulação robusta por parte do Estado, que impeçam a violação dos direitos humanos fundamentais.

Aspectos citogenéticos y moleculares en los síndromes mielodisplásicos / Cytogenetic and molecular aspects in myelodysplastic syndromes

Introducción: Los síndromes mielodisplásicos constituyen un grupo heterogéneo de alteraciones de la célula progenitora hematopoyética. Estos se caracterizan por presentar una médula ósea hipercelular, una hematopoyesis inefectiva, displasia y citopenia periférica y la posibilidad de evolución a leucemia mieloide aguda. Objetivo: Describir las alteraciones citogenéticas y moleculares más frecuentes de los síndromes mielodisplásicos. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados en los últimos cinco años. Se realizó análisis y resumen de la bibliografía. Análisis y síntesis de la información: En los síndromes mielodisplásicos están presentes alteraciones citogenéticas frecuentes como la deleción de los cromosomas 5q, 7q y 20q, la monosomía del cromosoma 7, la trisomía del cromosoma 8 y la presencia de cariotipos complejos, que, unido a mutaciones somáticas en diferentes genes, intervienen en la patogénesis de la enfermedad y su conocimiento permite la estratificación pronóstica de los pacientes. Conclusiones: El diagnóstico a través de los estudios citogenéticos convencionales, la hibridación in situ por fluorescencia y la secuenciación génica permite una mayor comprensión de la biología de la enfermedad, la estratificación del riesgo y la toma de decisiones terapéuticas(AU)

Introduction: Myelodysplastic syndromes constitute a heterogeneous group of alterations of the hematopoietic progenitor cell, characterized by hypercellular bone marrow, ineffective hematopoietic, dysplasia and peripheral cytopenia; and the possibility of progressing to acute myeloid leukemia. Objective: To describe the most frequent cytogenetic and molecular alterations of myelodysplastic syndromes. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine Google, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Analysis and synthesis of information: In myelodysplastic syndromes, frequent cytogenetic alterations are present such as deletion of chromosomes 5q, 7q and 20q, as well as the monosomy of chromosome 7, trisomy of chromosome 8 and the presence of complex karyotypes, which together with somatic mutations in different genes intervene in the pathogenesis of the disease and allow prognostic stratification of patients. Conclusions: Diagnosis through conventional cytogenetic studies, fluorescence in situ hybridization and gene sequencing allow a better understanding of the biology of the disease, risk stratification and therapeutic decision making(AU)

Germline pathogenic variants in Mexican patients with hereditary triple-negative breast cancer / Variantes patóge nas de línea germinal en mexicanas con cáncer de mama triple negativo hereditario

Abstract: Objective: Describe the prevalence of breast cancer (BC)-associated germline pathogenic variants (PVs) among Mexican patients with triple-negative BC (TNBC). Materials and methods: The spectrum of PVs identified among patients with TNBC who were enrolled in a prospective registry and underwent genetic testing was analyzed. Results: Of 387 patients with invasive TNBC and a median age at diagnosis of 39 years (range 21-72), 113 (29%) were carriers of PVs in BC-susceptibility genes: BRCA1 (79%), BRCA2 (15%), and other (6%: ATM, BRIP1, PALB2, PTEN, RAD51C, and TP53). PV carriers were younger at BC diagnosis (37 vs. 40 years, p=0.004) than non-carriers. Conclusion: A large proportion of TNBC in Mexican patients is associated with germline PVs, the vast majority in BRCA. The incremental yield of PVs in other BC-susceptibility genes was modest, and a stepwise approach starting with BRCA testing may be justified if it is more cost-effective than multigene panel testing.

Resumen: Objetivo: Describir la prevalencia de variantes patógenas (VPs) germinales en genes asociados con cáncer de mama (CM) en pacientes mexicanos con CM triple negativo (CMTN). Material y métodos: Se analizó el espectro de VPs identificadas en pacientes con CMTN que fueron incluidos prospectivamente en un registro y se realizó un estudio genético. Resultados: Se analizó un total de 387 pacientes con una mediana de edad al diagnóstico de 39 años; 113 (29%) eran portadores de VPs en genes de susceptibilidad a CM: BRCA1 (79%), BRCA2(15%), y otros (6%: ATM, BRIP1, PALB2, PTEN, RAD51C y TP53). Los portadores de VPs eran más jóvenes al diagnóstico de CM (37 vs. 40 años, p=0.004). Conclusiones: Existe una alta prevalencia de VPs en pacientes mexicanos con CMTN y la mayoría se encuentra en genes BRCA. La realización de pruebas genéticas se puede optimizar mediante la adopción de un proceso escalonado para la detección de VPs.

Reducing neuroinflammation and improving neurobehavioral functions: the protective roles of resveratrol for germinal matrix hemorrhage in neonatal rat model / 中国新生儿科杂志

Objective:To study the roles of resveratrol in reducing neuroinflammation and improving neurobehavioral functions after germinal matrix hemorrhage (GMH) in neonatal rat model.Methods:GMH model was established intraparenchymally injecting bacterial collagenase in 7-day-old SD rats. 108 rats were randomly assigned into 18 groups (6 in each group), including 4 sham groups, GMH (12 h, 24 h, 72 h, 7 d) groups, 3 GMH+vehicle (dimethylsulfoxide, DMSO) groups, 5 GMH+resveratrol (10 mg/kg, 100 mg/kg, 1 000 mg/kg) groups and 2 GMH+resveratrol+EX527 (SIRT1 inhibitor) groups. Negative geotaxis and righting reflex tests were used to evaluate the short-term neurobehavior. Water maze, foot fault and Rotor-Rod tests were used to assess the long-term neurobehavior. Immunofluorescence was used to quantify the IL-1β and MPO positive cells (inflammatory markers) in peri-hematoma area. Western blot was used to evaluate the expression of relevant proteins in the brain.Results:Endogenous sirtuin-1(SIRT1) decreased to the lowest level at 24 h and then increased gradually. Phosphorylated NF-κB increased at 12 h, peaked at 72 h and returned to normal level at 7 d after GMH. Compared with the control group and other doses groups, GMH treated with resveratrol (100 mg/kg) had higher short-term behavioral scores at 48 h and 72 h. Compared with the control group, the resveratrol (100 mg/kg) group also had higher scores in water maze, foot fault and Rotor-Rod tests 22 days later. Immunofluorescence showed less positive IL-1β and MPO cells around hematoma in GMH+resveratrol group than both GMH+vehicle group and GMH+resveratrol+EX527 group. Western blot indicated that IL-1, TNF-α and IL-6 expressions were decreased in GMH+resveratrol group and Ex527 could offset the effects of resveratrol.Conclusions:Resveratrol (optimal dose: 100 mg/kg) can improve the short-term and long-term neurobehavioral functions of neonatal GMH rats. It can reduce GMH cells with positive inflammatory markers around the hematoma, possibly via inhibition of the SIRT1/NF-κB pathway. Resveratrol may be promising for the treatment of GMH patients.

Stimulation of mGluR5 by VU0360172 protected against germinal matrix hemorrhage in neonatal rats / 中国药理学通报

Aim To investigate the protective effect of mGluR5 activated by VU0360172 on germinal matrix hemorrhage in neonatal rats.Methods Seven day- old SD rats were randomly divided into Sham, GMH, and low-, medium-, and high-dose groups.The model was established by intracerebral injection of collagenase W-S.Then three doses of VU0360172 were injected intraperitoneal

Effects of persistent Echinococcus multilocularis infections on hepatic fibrosis in mice / 中国血吸虫病防治杂志

Objective To investigate the effects of persistent Echinococcus multilocularis infections on hepatic fibrosis in mice, so as to provide insights into the understanding of liver fibrogenesis induced by E. multilocularis infections and the treatment of alveolar echinococcosis. Methods Hepatic stellate HSC-T6 and LX-2 cells were exposed to the sera (25, 50 and 100 μL) from Meriones unguiculatus infected with E. multilocularis, and E. multilocularis, germinal layer cells (GCs) and protoscoleces (PSCs) for 48 hours, respectively. The cell proliferation was measured using a CCK-8 assay, and the levels of collagen 1 (Col1) and α-smooth muscle actin (α-SMA) were measured in the culture supernatant of HSC-T6 cells using ELISA. In addition, the serum and liver samples were collected 1, 2, 4, 6, 8 months post-infection with E. multilocularis, respectively. The serum Col1 and α-SMA concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and the deposition of collagen fibers was examined in mice livers using Sirius red staining. Results The sera of E. multilocularis-infected gerbils promoted the proliferation of HSC-T6 and LX-2 cells in vitro, and there were significant differences seen in the proliferative rate of HSC-T6 (FHSC-T6 = 126.50, P < 0.05) and LX-2 cells (FLX-2 = 201.50, P < 0.05) among different serum groups, with the highest proliferative rate of HSC-T6 (573.36% ± 206.34%) and LX-2 cells (940.38% ± 61.65%) found following exposure to 100 μL mouse sera. Exposure to serum from E. multilocularis-infected gerbils resulted in an increase in the Col1 and α-SMA levels in the culture supernatant of HSC-T6 cells, with the greatest Col1 (20.99 ng/mL ± 2.01 ng/mL) and α-SMA levels (305.52 pg/mL ± 16.67 pg/mL) measured following exposure to 100 μL sera. The metacestodes (142.65% ± 9.17% and 189.99% ± 7.75%), GCs (118.55% ± 8.96% and 122.54% ± 0.21%) and PSCs of E. multilocularis (156.34% ± 17.45% and 160.59% ± 31.41%) all promoted the proliferation of HSC-T6 and LX-2 cells in vitro, and there were significant differences in the proliferative rates of HSC-T6 (FHSC-T6 = 11.24, P < 0.05) and LX-2 cells among groups (FLX-2 = 47.72, P < 0.05). Exposure to E. multilocularis resulted in an increase in Col1 and α-SMA levels in the culture supernatant of HSC-T6 cells, and the highest Col1 (4.43 ng/mL ± 2.23 ng/mL) and α-SMA levels (285.20 pg/mL ± 90.67 pg/mL) were detected following treatment with E. multilocularis metacestodes. In addition, a persistent increase was seen in the deposition of collagen fibers in mice livers 1 to 8 months post-infection with E. multilocularis, with the greatest Col1 level (280.26 ng/mL ± 23.04 ng/mL) seen 6 months post-infection and the highest α-SMA level (33.68 ng/mL ± 4.45 ng/mL) detected 8 months post-infection, respectively. Conclusions Persistent E. multilocularis infections promote hepatic stellate cell proliferation, induce an increase in mouse serum Col1 and α-SMA levels, and cause elevated deposition of collagen fibers in mice livers. The infective stage of E. multilocularis is a critical period for inducing hepatic fibrosis of alveolar echinococcosis.

Human follicular helper T lymphocytes critical players in antibody responses / Linfócitos T auxiliares foliculares humanos: células essenciais para a resposta de anticorpos

ABSTRACT Follicular helper T lymphocytes are a subpopulation of CD4+ T lymphocytes initially identified in germinal centers of follicles found in secondary lymphoid organs. The primary function of follicular helper T lymphocytes is to help B lymphocytes' antibody production. Changing of antibody class and affinity, B cell differentiation and memory generation depend on cooperation between follicular helper T lymphocytes and B cells. In blood, follicular helper T lymphocytes are called circulating follicular helper T lymphocytes. They are considered to have specificities similar to those developed in the secondary lymphoid organs. The phenotype of human follicular helper T lymphocytes is given by simultaneous expression of the markers CXCR5, Bcl-6, CD40L, PD-1, and ICOS. In germinal centers, follicular helper T lymphocytes synthesize interleukin 21 as predominant cytokine. In blood, subpopulations of circulating follicular helper T lymphocytes can be recognized, with different expressions of the classical follicular helper T lymphocytes markers and, in addition, can express other markers such as CXCR3 and CCR6. Presently, there is great interest in follicular helper T lymphocytes and circulating follicular helper T lymphocytes in vaccination studies as indicators of immunization efficacy. In addition, follicular helper T lymphocytes are investigated as possible markers of activity in many diseases and potential therapeutic intervention. This short review describes aspects of immunobiology and quantification of follicular helper T lymphocytes and circulating follicular helper T lymphocytes, and presents a few examples of related findings in systemic lupus erythematosus, rheumatoid arthritis, HIV infection and vaccination.

RESUMO Linfócitos T auxiliares foliculares são uma subpopulação de linfócitos T CD4+ identificada inicialmente nos centros germinativos dos folículos dos órgãos linfoides secundários. Sua função primordial é auxiliar os linfócitos B na produção de anticorpos. A mudança de classe e de afinidade dos anticorpos, a diferenciação das células B e a geração de memória dependem da cooperação entre os linfócitos T auxiliares foliculares e as células B. No sangue, recebem o nome de linfócitos T auxiliares circulantes. Considera-se que possuem especificidades semelhantes às desenvolvidas nos órgãos linfoides secundários. O fenótipo dos linfócitos T auxiliares humanos é dado pela expressão conjunta dos marcadores CXCR5, Bcl-6, CD40L, PD-1 e ICOS. Nos folículos, linfócitos T auxiliares sintetizam a interleucina 21 como citocina predominante. No sangue, são descritas várias subpopulações de linfócitos T auxiliares circulantes com expressões variadas dos marcadores clássicos de linfócitos T auxiliares, além de poderem agregar outros, como CXCR3 e CCR6. Existe um enorme interesse no estudo de linfócitos T auxiliares e linfócitos T auxiliares circulantes, para a avaliação de eficácia de vacinação. São também investigados como possíveis marcadores de atividade em muitas doenças e potenciais intervenções terapêuticas. Esta breve revisão descreve aspectos da imunobiologia e da quantificação de linfócitos T auxiliares humanos e linfócitos T auxiliares circulantes, além de apresentar alguns achados relacionados em lúpus eritematoso sistêmico, artrite reumatoide, infecção por HIV e vacinação.

Complicaciones de la linfadenectomía retroperitoneal postquimioterapia en pacientes con tumor germinal de origen testicular: Experiencia de 12 años en un centro de referencia en Colombia / Post-chemotherapy Retroperitoneal Lymphadenectomy Complications in Patients with Testicular Germ Cell Tumors: 12-Year Experience at a Reference Center in Colombia

Objetivo El objetivo de este estudio, fue describir las complicaciones intraoperatorias y postoperatorias, así como la necesidad de cirugías concomitantes en la linfadenectomía retroperitoneal postquimioterapia en un centro de referencia de manejo de cáncer. Métodos Se recolectaron datos de una cohorte retrospectiva de pacientes con diagnóstico de tumor germinal de origen testicular que hubiesen recibido quimioterapia y en quienes se documentó tumor residual retroperitoneal y fueron sometidos a LRP-PC durante 12 años en un centro de referencia de manejo de cáncer. Resultados Se practicó LRP-PC a 64 pacientes. La edad promedio al momento de la cirugía fue 28,1 años (18-47 años). El tamaño promedio de la masa retroperitoneal post quimioterapia fue 6,7 (1­28 cm). La estancia hospitalaria promedio fue 7,9 días (rango 1-99 días), la tasa de cirugías adicionales fue del 20%. La tasa de complicaciones mayores fue de 7,8%. Tener seminoma en la histología testicular inicial se asoció con un mayor sangrado y el tamaño de la masa retroperitoneal residual se asoció con la necesidad de cirugías concomitantes. Conclusiones La LRP-PC es una cirugía de alto nivel de complejidad que se asocia a complicaciones mayores y a la necesidad de cirugías concomitantes. Esta cohorte de pacientes muestra desenlaces similares a los descritos en la literatura, recalcando el hecho de que esta cirugía, debería ser realizada en centros de referencia de manejo del cáncer.

Objective The purpose was to describe complications and concomitant surgeries in PC-RPLND in a Referal cancer center. Methods Data were collected from a retrospective cohort of patients diagnosed with a germ cell tumor of testicular origin who had received chemotherapy and they were diagnosed with retroperitoneal residual tumor and underwent PC-RPLND in a single cancer referral center during 12 years. Results PC-RPLND was performed in 64 patients. The mean age at moment of surgery was 28.1 years (18-47 years). The mean size of the retroperitoneal residual mass was 6.7 (1 - 28 cm). The average hospital stay was 7.9 days (range 1-99 day), the rate of additional surgeries was 20%. The major complication rate was 7.8%. Seminoma histology in testicular tumor was associated with increased bleeding; the size of the residual retroperitoneal mass was associated with the need of concomitant surgeries. Conclusion PC-RPLND is a complex surgery that is associated with major complications and the need of concomitant surgeries. This research shows similar outcomes previously described in the literature highlighting the fact that this surgery should be performed in reference cancer treatment centers.

Teratomas del mediastino / Mediastinum Teratomas

RESUMEN Introducción: Los teratomas se definen como tumores de tejidos extraños al órgano o sitio anatómico en el cual se originan. Los teratomas mediastinales no son frecuentes, representan alrededor del 5 por ciento al 10 por ciento de todos los tumores mediastinales. Objetivo: Describir los resultados del tratamiento quirúrgico de pacientes con diagnóstico de teratomas mediastinales. Métodos: Se estudiaron 12 pacientes tratados entre enero de 2001 y diciembre de 2018. Las variables evaluadas fueron sexo, edad, tipo histológico: maduro o inmaduro, vía de acceso quirúrgico, accidentes quirúrgicos y evolución postoperatoria. Resultados: Correspondieron 9 al sexo femenino y 3 al masculino. El promedio de edad fue de 33,3 años (17-60 años). Hubo predominio absoluto del tipo maduro (11). La esternotomía media fue el acceso más frecuente. La toracotomía se realizó cuando el tumor, voluminoso, ocupaba la mayor parte de un hemitórax. Los accidentes quirúrgicos fueron un desgarro pulmonar y una apertura del pericardio. De dos pacientes tratados mediante cirugía torácica videoasistida, uno fue convertido por sangrado venoso molesto. Al año de seguimiento todos estaban vivos, sin evidencias de recidiva. Conclusiones: Contrariamente a lo esperado, hay predominio del sexo femenino, mientras que la edad y el tipo histológico coinciden con la literatura. La esternotomía, aún hoy, es comúnmente aceptada, a pesar del auge de la cirugía torácica videoasistida. La resección total produce resultados excelentes para los teratomas benignos(AU)

ABSTRACT Introduction: Teratomas are defined as tumors of tissues foreign to the organ or anatomical site in which they originate. Mediastinal teratomas are rare, accounting for about 5-10 percent of all mediastinal tumors. Objective: To describe the outcomes of the surgical treatment of patients diagnosed with mediastinal teratomas. Methods: Twelve patients treated between January 2001 and December 2018 were studied. The variables evaluated were sex, age, histological type (mature or immature), surgical access route, surgical accidents, and postoperative evolution. Results: Nine patients corresponded to the female sex and three, to the male. The average age was 33.3 years (17-60 years). There was an absolute predominance of the mature type (11). Median sternotomy was the most frequent access. Thoracotomy was performed when the bulky tumor occupied most of a hemithorax. The surgical accidents were lung tear and opening of the pericardium. Of two patients treated by video-assisted thoracic surgery, one was converted for bothersome venous bleeding. At one year of follow-up, all were alive, with no evidence of recurrence. Conclusions: Contrary to expectations, there is predominance of the female sex, while age and histological type coincide with the literature. Sternotomy, even today, is commonly accepted, despite the rise of video-assisted thoracic surgery. Total resection produces excellent outcomes in benign teratomas(AU)

Ecografía transfontanelar en la enfermedad hipóxico isquémica del recién nacido. Presentación de un caso / Transfontanellar ultrasound in hypoxic diseasenewborn ischemic. Presentation of a case

RESUMEN La enfermedad hipóxico-isquémica constituye una de las principales causas de morbi-mortalidad neurológica en el recién nacido. Las diferentes adaptacio-nes vasculares a la hipoxia tanto en el neonato pretérmino como en niño a término hacen que su presentación en neuroimagen, sobre todo en el ultrasonido (US) sea caracterizable según el territorio afectado y el momento de la enfermedad. El ultrasonido se ha convertido en una poderosa herramienta para la evaluación del recién nacido con sospecha de EHI, y el patrón de las lesiones tiene importantes implicaciones en el tratamiento y en el pronóstico neurológico a largo plazo. A continuación, presentamos el caso de un recién nacido masculino, prematuro extremo, que requirió reanimación cardiopulmonar avanzada en el nacimiento y que además presento dos episodios de parada cardiorrespiratoria en el segundo y tercer día de vida, en el cual se llegó al diagnóstico con patrones ecográficos característicos de lesión isquémica y además se detalla la evolución de los hallazgos en el tiempo.Palabras claves: Enfermedad hipóxico-isquémica, ultrasonido transfontanelar, matriz germinal, leucomalacia periventricular.

ABSTRACT Hypoxic-ischemic disease is one of the main causes of neurological morbidity and mortality in the newborn. The different vascular adaptations to hypoxia in both the preterm and term infants make their presentation on neuroimaging, especially on ultrasound (US), characterizable according to the affected terri-tory and the time of the disease. Ultrasound has become a powerful tool for evaluating the newborn with suspected IBD, and the pattern of the lesions has important implications for treatment and long-term neurological prognosis. Next, we present the case of a male newborn, extremely premature, who required advanced cardiopulmonary resuscitation at birth and who also presented two episodes of cardiorespiratory arrest on the second and third day of life, in which the diagnosis was reached with patterns sonographic characteristics of ischemic injury and also the evolution of the findings over time.Keywords: Hypoxic-ischemic disease, transfontanelar ultrasound, germ matrix, periventricular leukomalacia

Research Advances in Follicular Regulatory T Cells in Ocular Myasthenia Gravis / 中国医学科学院学报

Myasthenia gravis(MG)is a B cell-mediated,T cell-dependent,complements-involved autoimmune disease.Ocular myasthenia gravis(OMG)is a typical MG,with its symptoms limited to the extraocular muscles.The occurrence and development of a variety of autoimmune diseases including OMG are closely associated with the imbalanced expression of follicular regulatory T cells(Tfr cells).Therefore,Tfr cells may be a new research topic for OMG.

Proliferation and differentiation of mouse spermatogonial stem cells on a three-dimensional surface composed of PCL/gel nanofibers / Proliferación y diferenciación de células madre espermatogónicas de ratón en una superficie tridimensional compuesta de nanofibras PCL / gel

Spermatogonial stem cells (SSCs) have self-renewal and differentiation capacity essential for sperm production throughout the male reproductive life. The electrospun polycaprolactone/gelatin (PCL/Gel) nanofibrous scaffold mimics important features of the extracellular matrix (ECM), which can provide a promising technique for the proliferation and differentiation of SSCs in vitro. The goal of the present study was to investigate the effects of PCL/Gel nanofibrous scaffold on the propagation and differentiation of neonate mouse SSCs (mSSCs). mSSCs were enzymatically isolated, and the cells were purified by differential plating method and seeded on scaffold. After 2 weeks, viability, colony number and diameter, and expression of specific spermatogonial cell genes were investigated. After mSSCs propagation, the cells were cultivated in a differentiation medium on the scaffold for another 2 weeks, and differentiating cells were analyzed by real-time PCR. The number of mSSC colony (P<0.01) and expression levels of specific spermatogonial genes Plzf and Inga6 (P<0.01) and also differentiation genes c-Kit, Tp1 and Ptm1 (P<0.05) were higher in scaffold group compared with control during the culture period. We conclude that mSSCs can be expanded and can differentiate toward spermatid cells on PCL/Gel nanofibrous scaffold with improved developmental parameters.

Las células madre espermatogónicas (CME) tienen capacidad de auto renovación y diferenciación esenciales para la producción de esperma a lo largo de la vida reproductiva masculina. El «scaffold¼ nanofibroso de policaprolactona / gelatina (PCL / Gel) electrohilado imita características importantes de la matriz extracelular (MEC), que puede proporcionar una técnica prometedora para la proliferación y diferenciación de CME in vitro. El objetivo del presente estudio fue investigar los efectos del «scaffold¼ nanofibroso PCL / Gel en la propagación y diferenciación de CME de ratones neonatos (mSSC). Los mSSC se aislaron enzimáticamente y las células se purificaron mediante un método de siembra diferencial y se sembraron en un «scaffold¼. Después de 2 semanas, se investigaron la viabilidad, el número y el diámetro de las colonias y la expresión de genes específicos de células espermatogónicas. Después de la propagación de mSSC, las células se cultivaron en un medio de diferenciación en el «scaffold¼ durante otras 2 semanas, y las células se analizaron mediante PCR en tiempo real. El número de colonias mSSC (P <0,01) y los niveles de expresión de los genes espermatogónicos específicos Plzf e Inga6 (P <0,01) y también los genes de diferenciación c-Kit, Tp1 y Ptm1 (P <0,05) fueron mayores en el grupo de «scaffold¼ en comparación con el control durante el período de cultivo. Concluimos que los mSSC pueden expandirse y diferenciarse en células espermátidas en un «scaffold¼ de nanofibras PCL / Gel con parámetros de desarrollo mejorados.

BRCA1 and BRCA2 mutations in a sample of breast and ovarian cancer families from the Colombian pacific / Mutaciones en los genes BRCA1 y BRCA2 en una muestra de familias con cáncer de mama y/u ovario del pacífico colombiano

Abstract Introduction: Breast cancer is the most common neoplasia of women from all over the world especially women from Colombia. 5%­10% of all cases are caused by hereditary factors, 25% of those cases have mutations in the BRCA1/BRCA2 genes. Objective: The purpose of this study was to identify the mutations associated with the risk of familial breast and/or ovarian cancer in a population of Colombian pacific. Methods: 58 high-risk breast and/or ovarian cancer families and 20 controls were screened for germline mutations in BRCA1 and BRCA2, by Single Strand Conformation Polymorphism (SSCP) and sequencing. Results: Four families (6.9%) were found to carry BRCA1 mutations and eight families (13.8%) had mutations in BRCA2. In BRCA1, we found three Variants of Uncertain Significance (VUS), of which we concluded, using in silico tools, that c.81­12C>G and c.3119G>A (p.Ser1040Asn) are probably deleterious, and c.3083G>A (p.Arg1028His) is probably neutral. In BRCA2, we found three variants of uncertain significance: two were previously described and one novel mutation. Using in silico analysis, we concluded that c.865A>G (p.Asn289Asp) and c.6427T>C (p.Ser2143Pro) are probably deleterious and c.125A>G (p.Tyr42Cys) is probably neutral. Only one of them has previously been reported in Colombia. We also identified 13 polymorphisms (4 in BRCA1 and 9 in BRCA2), two of them are associated with a moderate increase in breast cancer risk (BRCA2 c.1114A>C and c.8755­66T>C). Conclusion: According to our results, the Colombian pacific population presents diverse mutational spectrum for BRCA genes that differs from the findings in other regions in the country.

Resumen Introducción: El cáncer de mama es la neoplasia más común en mujeres de todo el mundo, y, también de Colombia. 5% a 10% de todos los casos son causados por factores hereditarios; 25% de estos casos tienen mutaciones en los genes BRCA1/BRCA2. Objetivo: El propósito de este estudio fue el de identificar mutaciones asociadas con riesgo de cáncer de mama y/u ovario familiar en pacientes del pacífico colombiano. Métodos: Fueron revisados para mutaciones en BRCA1 y BRCA2 de línea germinal mediante SSCP y secuenciación 58 familias de alto riesgo para cáncer de mama y/u ovario y 20 controles Resultados: cuatro familias (6.9%) presentaron mutaciones en BRCA1 y ocho familias (13.8%) en BRCA2. En BRCA1, encontramos tres variantes de significado clínico desconocido (VUS), de las cuales concluimos, usando herramientas bioinformáticas, que c.81­12C>G y c.3119G>A (p.Ser1040Asn) son probablemente deletéreas, y c.3083G>A (p.Arg1028His) es probablemente neutral. En BRCA2, encontramos tres VUS: una mutación nueva y dos previamente descritas, usando análisis bioinformáticos, concluimos que c.865A>G (p.Asn289Asp) y c.6427T>C (p.Ser2143Pro) son probablemente deletéreas y c.125A>G (p.Tyr42Cys) es probablemente neutral. Solo una de ellas ha sido reportada previamente en Colombia. También identificamos 13 polimorfismos (4 en BRCA1 y 9 en BRCA2), dos de ellos asociados con un moderado incremento del riesgo para cáncer de mama (BRCA2 c.1114A>C and c.8755­66T>C). Conclusión: de acuerdo con nuestros resultados, la población del suroccidente colombiano presenta un espectro mutacional diverso para los genes BRCA que difiere de lo encontrado en otras regiones del país.

Mecanismos de lesión cerebral en niños prematuros / Mechanisms of brain injury of the premature baby

Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.