ABSTRACT
BACKGROUND: Adverse events in early life can have impact lasting into adulthood. We investigated the long-term effects of systemic inflammation during postnatal development on adult microglial responses to LPS in two CNS regions (cortex, cervical spinal cord) in male and female rats. METHODS: Inflammation was induced in Sprague-Dawley rats by lipopolysaccharide (LPS, 1 mg/kg) administered intraperitoneally during postnatal development at P7, P12 or P18. As adults (12 weeks of age), the rats received a second LPS dose (1 mg/kg). Control rats received saline. Microglia were isolated 3 hours post-LPS from the cortex and cervical spinal cord. Gene expression was assessed via qRT-PCR for pro-inflammatory (IL-6, iNOS, Ptgs2, C/EBPb, CD14, CXCL10), anti-inflammatory (CD68, Arg-1), and homeostatic genes (P2Y12, Tmemm119). CSF-1 and CX3CL1 mRNA was analyzed in microglia-free homogenates. RESULTS: Basal gene expression in adult microglia was largely unaffected by early life LPS. Changes in adult microglial pro-inflammatory genes in response to LPS were either unchanged or attenuated in rats exposed to LPS during postnatal development. Ptgs2, C/EBPb, CXCL10 and Arg-1 were the genes most affected, with expression levels significantly downregulated vs control rats without postnatal LPS exposure. Cortical microglia were affected more by postnatal inflammation than spinal microglia, and males were more impacted than females. Overall, inflammatory challenge at P18 had the greatest effect on adult microglial gene expression, whereas challenge at P7 had less impact. Microglial homeostatic genes were unaffected by postnatal LPS. CONCLUSIONS: Long-lasting effects of postnatal inflammation on adult microglia depend on the timing of postnatal inflammation, CNS region and sex.
ABSTRACT
Microglia are innate CNS immune cells that play key roles in supporting key CNS functions including brain plasticity. We now report a previously unknown role for microglia in regulating neuroplasticity within spinal phrenic motor neurons, the neurons driving diaphragm contractions and breathing. We demonstrate that microglia regulate phrenic long-term facilitation (pLTF), a form of respiratory memory lasting hours after repetitive exposures to brief periods of low oxygen (acute intermittent hypoxia; AIH) via neuronal/microglial fractalkine signaling. AIH-induced pLTF is regulated by the balance between competing intracellular signaling cascades initiated by serotonin vs adenosine, respectively. Although brainstem raphe neurons release the relevant serotonin, the cellular source of adenosine is unknown. We tested a model in which hypoxia initiates fractalkine signaling between phrenic motor neurons and nearby microglia that triggers extracellular adenosine accumulation. With moderate AIH, phrenic motor neuron adenosine 2A receptor activation undermines serotonin-dominant pLTF; in contrast, severe AIH drives pLTF by a unique, adenosine-dominant mechanism. Phrenic motor neuron fractalkine knockdown, cervical spinal fractalkine receptor inhibition on nearby microglia, and microglial depletion enhance serotonin-dominant pLTF with moderate AIH but suppress adenosine-dominant pLTF with severe AIH. Thus, microglia play novel functions in the healthy spinal cord, regulating hypoxia-induced neuroplasticity within the motor neurons responsible for breathing.
ABSTRACT
Se presenta un caso de mujer postmenopáusica, goajira, sin criterios de riesgo para adenocarcinoma del endometrio, que mediante el legrado uterino por aspiración de piometra se diagnosticó un carcinoma pavimentoso primitivo epitelial del endometrio (CPPEE), por llenar algunos criterios: no invasión al cuello, ni extensión de uno cervical al endometrio, ni la presencia de queratinización de la superficie endometrial y/o puentes intercelulares. No hubo evidencia de presencia de virus de papiloma humano (VPH). Después de la histerectomía se encontró que sí existía un tumor endometrial grado III, estadio IB. compuesto por elementos glandulares y tejido escamoso en ciertas áreas. Tampoco existían criterios para un diagnóstico de ictiosis uterina, infiltrante, sin componente velloso, Hubo confusión en el diagnóstico inicial. La rareza del CPPEE, menos de 100 casos reportados en el mundo, condujo al análisis con varios patólogos. Se concluye que para obtener el diagnóstico correcto, deben llenarse los criterios de Flumman y de la Organización Mundial de la Salud, excluir infección del tracto genital por VPH, los estudios de inmunohistoquímica deben ser positivos para queratinas y carecer de receptores para estrógenos y progesterona. El legrado o la biopsia no son confiables para el diagnóstico. Además de la evaluación histológica y del estadio clínico, el estudio de toda la pieza quirúrgica es fundamental para emitir pronóstico(AU)
A goajira menopausal woman, with no risk criteria for endometrial adenocarcinoma, was diagnosed through uterine curettage by aspiration of pyometra as primary squamous carcinoma of the endometrium (CPPEE) to meet following criteria: no invasion of the cervix, no extension of the cervical to the endometrium, absence of keratinization of the endometrial surface and intercellular bridges. There was no evidence of human papillomavirus. After the hysterectomy, there was an endometrial tumor composed of glandular elements and squamous tissue in areas, without filling the elements for diagnosis of ichthyosis uteri, infiltrating, without vellous component, grade III and stage IB. There was confusion in the initial diagnosis. The rarity of the CPPEE, less than 100 cases in the world, led to the analysis with several pathologists. It is concluded that in order to obtain the correct diagnosis, it must meet the criteria of Flumman and WHO, exclude infection of the genital tract by HPV, immunohistochemical studies must be positive for keratins and lack estrogen and progesterone receptors. The curettage or the biopsy are not reliable and the study of the whole surgical part is fundamental. In order to establish a prognosis, an accurate diagnosis must be made(AU)
Subject(s)
Humans , Female , Middle Aged , Carcinoma/pathology , Adenocarcinoma/pathology , Endometrial Neoplasms , Biopsy , Hysterectomy , IchthyosisABSTRACT
Objetivos: Reportar 7 pacientes entre 20-31 años que acudieron a las consultas de ginecología del Hospital Chiquinquirá de Maracaibo y Policlínca Maracaibo en un período de 21 años a quienes se les diagnosticó útero unicorne en una época donde los métodos diagnósticos morfológicos adecuados apenas se iniciaban. Métodos: Análisis retrospectivo de historias clínicas, métodos diagnósticos: ecografía, histerosalpingografía, urografía por eliminación y laparoscopia. Resultados: La mayoría consultó por deseos de embarazo, pérdida recurrente de la gestación, dolor pélvico y trastornos menstruales. Sospecha diagnóstica con ecografía se logró en 2 casos y la histerosalpingografía fue básica para el diagnóstico; pero la laparoscopia hizo el diagnóstico definitivo de la presencia de cuernos rudimentarios en 2 de las 7 pacientes en las que se realizó. Dos de 4 mujeres que deseaban embarazo lo lograron al corregir la anovulación o los defectos luteales, con partos a término normales. Conclusión: Para obtener el diagnóstico exacto y clasificar el tipo de malformación en casos de útero unicorne, es necesario la utilización de todos los métodos para diagnósticos morfológicos incluyendo la laparoscopia, para observar la presencia de un útero rudimentario funcionante comunicante o no, porque dan sintomatología dolorosa y ser asiento de embarazos ectópicos. La ecografía y urografía por eliminación son métodos eficaces para diagnosticar malformaciones o agenesia renal. Recomendamos ampliar la clasificación FIGO 1988 del útero unicorne por la aparición de variedades anatómicas no incluidas en ella.
Objectives: To report 7 patients attending gynecology consultations at the Hospital Chiquinquira in Maracaibo and Policlínca Maracaibo over a period of 21 years who were diagnosed unicorn uterus at a time when adequate diagnostic morphological methods just began. Methods: Retrospective analysis of medical records, diagnostic tests: Ultrasound, hysterosalpingography, laparoscopy and urography. Results: Most consulted for desires pregnancy, recurrent pregnancy loss, pelvic pain and menstrual disorders. Ultrasound diagnostic suspicion was achieved in 2 cases and hysterosalpingography was central to the diagnosis; but laparoscopy made the definitive diagnosis of the presence of rudimentary horns in 2 of the 7 patients in which it was performed. Two of 4 women wishing pregnancies they succeeded after correcting anovulation or luteal defects, with normal term deliveries. Conclusions: For accurate diagnosis and classify the type of malformation cases of unicorn uterus, there are use all methods including morphological diagnostic. Laparoscopy is necessary to observe the presence of communicating functioning rudimentary uterus or not communicating, because they give painfully symptoms and ectopic pregnancies. Ultrasonography and urography are effective to diagnostic methofs for renal malformations of agenesis. We recommend expanding the FIGO classification (1988) of the unicorn uterus by the appearance of anatomical varieties not included in it.
ABSTRACT
El hematocervix o hematotraquelos es una condición ginecológica de observación excepcional, que puede verse en pacientes con ginatresia congénita o con antecedente de biopsia en cono de cuello uterino. Aquí se presenta un caso posterior a cono, ilustrado con ultrasonografía y resonancia magnética y se hace una breve revisión de la muy escasa literatura sobre el tema
