Microbiota intestinal y trastornos del comportamiento mental / Intestinal microbiota and mental behavior disorders

Introducción: Se actualiza la relación del eje microbiota-intestino-cerebro con enfermedades neurológicas y psiquiátricas, en particular en trastornos del comportamiento en la infancia y adultos postulados en años recientes. Objetivo: Analizar la participación del eje microbiota-intestino-cerebro con alteraciones del comportamiento humano, con preferencia en la infancia y el papel de la disbiosis como factor determinante. Métodos: Se revisaron las publicaciones sobre el tema en español e inglés en bases de datos de PubMed, Google Scholar, SciELO y Latindex desde el 2015 hasta el 30 septiembre de 2019. Resultados: Se actualizaron los criterios sobre el papel del eje microbiota-intestino-cerebro, posibles vías de acción y asociación con disbiosis y otros factores, desencadenados por alteración de la microbiota intestinal y su influencia en los trastornos del comportamiento mental, representados por el espectro autista, hipoactividad/ hiperexcitabilidad, ansiedad y depresión. Consideraciones finales: Los conocimientos alcanzados en el último decenio en estudios experimentales en ratones y la aplicación de sus resultados en humanos, sobre el papel del eje bidireccional microbiota-intestino-cerebro y sus relaciones con el equilibrio y desequilibrio de la microbiota intestinal, argumentan la posible participación del eje referido en el neurodesarrollo, afectación cerebral y neuromodulación y en especial en trastornos de conducta, como el espectro autista y otras afecciones analizadas(AU)

Introduction: The microbiota-gut-brain axis´ relation with neurological and psychiatric diseases is updated, in particular in behavioral disorders in children and adults postulated in recent years. Objective: To analyze the participation of the microbiota-gut-brain axis in alterations of human behavior, with a preference in childhood and the role of dysbiosis as a determining factor. Methods: It was reviewed the literature on the subject in Spanish and English in databases of PubMed, Google Scholar, SciELO and Latindex from 2015 until September 30, 2019. Results: The criteria were updated on the role of the microbiota-gut-brain axis, possible ways of action and association with dysbiosis and other factors triggered by alteration of the intestinal microbiota and its influence on mental behavior disorders represented by the autism spectrum, hypoactivity/ hyperexcitability, anxiety and depression. Conclusions: Knowledge achieved in the last decade in experimental studies in mice and the application of their results in humans, the role of the microbiota-gut-brain bi-directional axis and its relations with the balance and imbalance of the intestinal microbiota argue on the possible involvement of the referred axis in neurodevelopment, brain affectation and neuromodulation, and especially in behavioral disorders, such as autism spectrum disorders and other conditions analyzed(AU)

Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits.

Bloodborne infections with Candida albicans are an increasingly recognized complication of modern medicine. Here, we present a mouse model of low-grade candidemia to determine the effect of disseminated infection on cerebral function and relevant immune determinants. We show that intravenous injection of 25,000 C. albicans cells causes a highly localized cerebritis marked by the accumulation of activated microglial and astroglial cells around yeast aggregates, forming fungal-induced glial granulomas. Amyloid precursor protein accumulates within the periphery of these granulomas, while cleaved amyloid beta (Aß) peptides accumulate around the yeast cells. CNS-localized C. albicans further activate the transcription factor NF-κB and induce production of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor (TNF), and Aß peptides enhance both phagocytic and antifungal activity from BV-2 cells. Mice infected with C. albicans display mild memory impairment that resolves with fungal clearance. Our results warrant additional studies to understand the effect of chronic cerebritis on cognitive and immune function.

Sífilis, causa poco habitual de dolor abdominal / Syphilis, unusual cause of abdominal pain

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Multicentric Cryptococcosis in a Congo African Grey Parrot ( Psittacus erithacus erithacus).

An approximately 10-year-old, female Congo African grey parrot ( Psittacus erithacus erithacus) developed progressive, unilateral exophthalmos and buphthalmos. Survey radiographs revealed a large, coelomic, soft tissue mass, which was confirmed on computed tomography scan. Aspirates of both the contents of the buphthalmic globe and coelomic mass were consistent with Cryptococcus species. Initial results were later confirmed with serum antigen latex agglutination and polymerase chain reaction testing, and the organism was then identified as Cryptococcus neoformans with DNA sequencing. During the course of 1 year, the bird was treated with combinations of oral terbinafine, fluconazole, and flucytosine, as well as intraocular amphotericin B. The coelomic mass dramatically decreased in size during the course of treatment, but the globe continued to enlarge. The bird died after exhibiting ataxia and seizures approximately 13 months after initial diagnosis, and necropsy confirmed colonization of the cerebrum and meninges with Cryptococcus. Cryptococcus remains a rare fungal disease of birds that is often refractory to treatment.

Cerebral aspergillosis in a patient with leprosy and diabetes: a case report.

BACKGROUND: Opportunistic fungi are dispersed as airborne, ground and decaying matter. The second most frequent extra-pulmonary disease by Aspergillus is in the central nervous system. CASE PRESENTATION: The case subject was 55 years old, male, mulatto, and an assistant surveyor residing in Teresina, Piauí. He presented with headache, seizures, confusion, fever and left hemiparesis upon hospitalization in 2006 at Hospital São Marcos. Five years previously, he was diagnosed with diabetes mellitus, and 17 months previously he had acne margined by hyperpigmented areas and was diagnosed with leprosy. Laboratory tests indicated leukocytosis and magnetic resonance imaging showed an infarction in the right cerebral hemisphere. Cerebrospinal fluid examination showed 120 cells/mm(3) and was alcohol-resistant bacilli negative. Trans-sphenoidal surgery with biopsy showed inflammation was caused by infection with Aspergillus fumigatus. We initiated use of parenteral amphotericin B, but his condition worsened. He underwent another surgery to implant a reservoir of Ommaya-Hickmann, a subcutaneous catheter. We started liposomal amphotericin B 5 mg/kg in the reservoir on alternate days. He was discharged with a prescription of tegretol and fluconazole. CONCLUSION: This report has scientific interest because of the occurrence of angioinvasive cerebral aspergillosis in a diabetic patient, which is rarely reported. In conclusion, we suggest a definitive diagnosis of cerebral aspergillosis should not postpone quick effective treatment.

Brain microbial populations in HIV/AIDS: α-proteobacteria predominate independent of host immune status.

The brain is assumed to be a sterile organ in the absence of disease although the impact of immune disruption is uncertain in terms of brain microbial diversity or quantity. To investigate microbial diversity and quantity in the brain, the profile of infectious agents was examined in pathologically normal and abnormal brains from persons with HIV/AIDS [HIV] (n = 12), other disease controls [ODC] (n = 14) and in cerebral surgical resections for epilepsy [SURG] (n = 6). Deep sequencing of cerebral white matter-derived RNA from the HIV (n = 4) and ODC (n = 4) patients and SURG (n = 2) groups revealed bacterially-encoded 16 s RNA sequences in all brain specimens with α-proteobacteria representing over 70% of bacterial sequences while the other 30% of bacterial classes varied widely. Bacterial rRNA was detected in white matter glial cells by in situ hybridization and peptidoglycan immunoreactivity was also localized principally in glia in human brains. Analyses of amplified bacterial 16 s rRNA sequences disclosed that Proteobacteria was the principal bacterial phylum in all human brain samples with similar bacterial rRNA quantities in HIV and ODC groups despite increased host neuroimmune responses in the HIV group. Exogenous viruses including bacteriophage and human herpes viruses-4, -5 and -6 were detected variably in autopsied brains from both clinical groups. Brains from SIV- and SHIV-infected macaques displayed a profile of bacterial phyla also dominated by Proteobacteria but bacterial sequences were not detected in experimentally FIV-infected cat or RAG1⁻/⁻ mouse brains. Intracerebral implantation of human brain homogenates into RAG1⁻/⁻ mice revealed a preponderance of α-proteobacteria 16 s RNA sequences in the brains of recipient mice at 7 weeks post-implantation, which was abrogated by prior heat-treatment of the brain homogenate. Thus, α-proteobacteria represented the major bacterial component of the primate brain's microbiome regardless of underlying immune status, which could be transferred into naïve hosts leading to microbial persistence in the brain.

Long-term treatment of invasive sinus, tracheobroncheal, pulmonary and intracerebral aspergillosis in acute lymphoblastic leukaemia.

A 59-year-old male with acute lymphoblastic leukemia developed sinus, tracheobroncheal, pulmonary, and intracerebral aspergillosis. All lesions except the intracerebral aspergillosis healed after combination antifungal treatment. Long-term voriconazole--but not posaconazole--therapy induced partial regression of the cerebral manifestations. At the time of writing, 3.5 years after the initial diagnosis, the patient is working half-time and suffers from a possible voriconazole-induced polyneuropathy.

A novel case of Fusarium oxysporum infection in an Atlantic bottlenose dolphin (Tursiops truncatus).

A necropsy was performed on a captive-born, 10-yr-old male Atlantic bottlenose dolphin (Tursiops truncatus) after it died acutely. Gross necropsy findings revealed hemorrhage within the right cerebrum, right cerebellum, and right eye. Histopathologic findings revealed a moderate multifocal acute necrotizing meningoencephalitis with intralesional fungal hyphae. Several pieces of cerebrum and cerebellum and cerebrospinal fluid were sent to the Fungus Testing Laboratory in San Antonio, Texas (U.S.A.). The culture yielded Fusarium oxysporum, which was confirmed by internal transcribed spacer and D1-D2 sequencing. Fusarium oxysporum infection has been reported in marine mammals. No cases of noncutaneous F. oxysporum infection in a cetacean that was not on long-term antimicrobials have been reported in the literature.

Cerebral aspergillosis caused by Aspergillus granulosus.

Disseminated disease by Aspergillus granulosus has been reported only once previously in a cardiac transplant recipient. We report a fatal central nervous system infection in a lung transplant recipient. Key features of this species in the section Usti include growth at 37 degrees C and large, randomly spaced aggregates of variably shaped Hülle cells.

Purificación de IgY contra la subunidad NR3 del receptor NMDA de cerebro de rata / Purification of IgY against the NR3 subunit of the rat brain NMDA receptor

Objetivo. Obtener anticuerpos tipo IgY contra péptidos sintéticos de las subunidades NR3A y NR3B del receptor NMDA de ratas, para reconocer y seguir la expresión de estas subunidades en extractos de cerebro de rata de diferentes edades. Materiales y métodos. Se diseñaron dos péptidos empleando los sistemas de la base de datos Entrez y el programa ClustalWPBIL de alineamientos múltiples contra las subunidades NR3A y NR3B del receptor NMDA; una vez sintetizados por el método SSPS-fmoc fueron utilizados para inocular gallinas (Gallus gallus, variedad Hy Line Brown) de 16 semanas de edad; al cabo de 57 días postinoculación se purificó IgY específica y se enfrentaron a extractos de cerebro de rata postnatal y adulta. Resultados. Se detectaron las subunidades NR3A y NR3B y se relacionó su expresión con la edad del animal; siendo mayor la expresión de la subunidad NR3A en extracto de cerebro de rata postnatal. No se encontró diferencia marcada en la expresión de la subunidad NR3B en las edades mencionadas. Conclusiones. Esta es la primera investigación que emplea proteína nativa para el reconocimiento de la subunidad NR3 del receptor NMDA, lo cual muestra la especificidad de los anticuerpos generados y contribuye con el entendimiento de las funciones de este receptor y su relación con la regulación de la memoria espacial.

Meningoencephalitis in an adult cow due to Mortierella woifli.

A 7-year-old dairy cow presented with clinical signs of neurologic disease. Despite treatment with penicillin, the cow died 36 hours after initial presentation. Necropsy examination revealed multiple foci of hemorrhage within the cerebrum and thickened meninges. Additionally, endometritis and consolidation of approximately 30% of both lungs was observed. Histology revealed necrotizing vasculitis, infarction, and hemorrhage within sections of the brain, uterus, and lung. Large numbers of intralesional fungal hyphae were visible. Because only formalin-fixed tissue was available, polymerase chain reaction was used to make an etiologic diagnosis of Mortierella wolfii.

Candidiasis urinaria y cerebral en un neonato con malformación urinaria bilateral congénita: hallazgos ultrasonográficos / Neonatal brain and urinary candidal infection: US findings

El pronóstico de este trabajo es describir los hallazgos ecográficos y demostrar la utilidad del ultrasonido en el diagnóstico precoz de la candidiasis urinaria y cerebral, por lo que realizamos ecografía prenatal de una paciente en la que se diagnosticó la presencia de un feto con uronefrosis bilateral congénita y ecografías tempranas al neonato pretérmino. La detección por US de la presencia de bolas fúngicas dentro de la vía excretora previamente dilatada fue determinante para realizar el cateterismo de ambos uréteres por medio del cual se obtuvo material para cultivo y sirvió para derivación urinaria. Concluimos que el US es el mejor método de diagnóstico por imágenes para ser utilizado en los neonatos prematuros de bajo peso y de alto riesgo (AU)

Candidiasis urinaria y cerebral en un neonato con malformación urinaria bilateral congénita: hallazgos ultrasonográficos / Neonatal brain and urinary candidal infection: US findings

El pronóstico de este trabajo es describir los hallazgos ecográficos y demostrar la utilidad del ultrasonido en el diagnóstico precoz de la candidiasis urinaria y cerebral, por lo que realizamos ecografía prenatal de una paciente en la que se diagnosticó la presencia de un feto con uronefrosis bilateral congénita y ecografías tempranas al neonato pretérmino. La detección por US de la presencia de bolas fúngicas dentro de la vía excretora previamente dilatada fue determinante para realizar el cateterismo de ambos uréteres por medio del cual se obtuvo material para cultivo y sirvió para derivación urinaria. Concluimos que el US es el mejor método de diagnóstico por imágenes para ser utilizado en los neonatos prematuros de bajo peso y de alto riesgo

Abscesso cerebral na infância / Brain abscess in childhood

Objetivo: Relato da evoluçäo clínica de 15 crianças com diagnóstico de abscesso cerebral, internadas na enfermaria de Infectologia Pediátrica do Hospital Säo Paulo, da Universidade Federal de Säo Paulo (Unifesp).Métodos: Foi realizada uma análise retrospectiva dos prontuários de pacientes com diagnóstico de abscesso cerebral, internados na enfermaria durante o período de janeiro de 1987 a dezembro de 1998. Foram avaliados: idade, sexo, dias de internaçäo. quadro clínico, fatores predisponentes, diagnóstico e tratamento. Resultados: A idade dos pacientes variou de 2 meses a 13 anos, sendo apenas duas crianças do sexo feminino. A duraçäo da internaçäo variou de 27 a 158 dias. Entre os achados clínicos mais frequentes encontramos as manifestaçöes de aumento da pressäo intracraniana e febre. Entre os fatores predisponentes, as cardiopatias congênitas cianóticas e infecçöes do ouvido médio foram encontradas em cinco pacientes cada uma. As localizaçöes mais frequentes foram os lobos frontal e temporal, sendo encontrados abscessos múltiplos em cinco pacientes. O tratamento realizado foi a antibioticoterapia associada à denagem cirúrgica, que näo foi realizada em apenas dois pacientes. O agente etiológico mais encontrado em material de punçäo foi o Proteus. O acompanhamento foi realizado através de tomografia computadorizada de crânio e da evoluçäo clínica. Conclusöes: O abscesso cerebral deve ser investigado em pacientes com sinais neurológicos, incluindo as manifestaçöes de aumento da pressäo intracraniana ou febre, principalmente em presença de fatores predisponentes, como cardiopatias congênitas, infecçöes do ouvido médio/mastóide ou meningite pregressa.

Paracoccidioidomicose óssea associada à síndrome da imunodeficiência adquirida: relato de um caso / Bone paracoccidioidomycosis associated with acquired immunodeficiency syndrome: a case report

A paracoccidioidomicose é uma doença granulomatosa crônica causada pelo fungo Paracoccidioides brasiliensis, que acomete principalmente os pulmöes, podendo, no entanto, disseminar-se para vários órgäos. O acometimento ósseo pela blastomicose é raro, podendo apresentar-se associado à doença sistêmica ou isolada. A associaçäo da paracoccidioidomicose com a síndrome da imunodeficiência adquirida (SIDA) foi estabelecida pela primeira vez em 1989, havendo poucos casos descritos na literatura até o momento. Em nenhum dos casos descritos foi demonstrado o acometimento ósseo pelo fungo. Este é o primeiro relato de caso descrevendo uma associaçäo entre paracoccidioidomicose óssea e SIDA. Os autores propöem a inclusäo da paracoccidioidomicose no diagnóstico diferencial de pacientes com SIDA que apresentem lesöes ósseas líticas

Influence of canine brain decomposition on laboratory diagnosis of rabies

Cérebros de cäes infectados com o vírus da raiva foram submetidos à decomposiçäo, deixando-os à temperatura ambiente de 25 a 29 grau C por até 168 horas. A cada 24 horas, fragmentos de cérebros foram analisados pela imunofluorescência (IF) e inoculaçäo intracerebral em camundongos (IC) para confirmar o diagnóstico de raiva e medir o efeito da putrefaçäo na acurácia do teste. Após 48 horas do início do experimento o teste de IC começou a ser prejudicado, detectando-se quatro resultados negativos, enquanto que, após 72horas, 100 por cento dos resultados foram negativos para IC e apenas um foi negativo para IF, indicando que o período limite para um diagnóstico seguro está entre 24 e 48 horas antes da recomendam o envio de material suspeito para laboratorial, no entanto, o uso de materiais em adiantado estado de decomposiçäo näo é o diagnóstico adequado, devido à ocorrência de resultados falsos-negativos

Infeccíon intracerebral de ratones atímicos con una cepa atenuada de virus Junín / Intracerebral infection of athymic mice with an attenuated strain of junín virus

La infección del ratón lactante inmunocompetente eutímico (nu/+) con la cepa XJ del viru Junín provoca una encefalitis mortal debida a la respuesta inmune celular del huésped. Por el contrario, esa cepa inoculada en ratones atímicos (nu/nu) induce una infección persistente asintompatica. El objetivo del presente trabajo fue determinar el comportamiento de la cepa atenuada XJCl3 en el ratón nu/nu. Se inocularon por vía intracerebral (ic) 55 ratones lactantes nu/nu y 45 nu/+ con 10**3 UFP de la cepa XJCl3. Como controles se utilizaron 20 ratones nu/nu y 20 nu/+ infectar. Se observó en los ratones nu/nu y nu/+ una mortalidad similar (86%, respectivamente), mientras que no se observó mortalidad en los controles, que se mantuvieron en el mismo bioterio. Se detectaron altos títulos virales en cerebro y pulmón de los nu/nu infectados a los 7, 14, 21 y 70 días pi. Los títulos de virus en sangre fueron de 1 a 2 log más que en esos órganos. Estudios inmunohistoquímicos de cerebro mostraron antígeno viral intracitoplasmático en neuronas corticales a los 21 y 70 días pi. En el estudio histopatológico de pulmón de los nu/nu infectados se observó una neurmonbitis intersticial con focos de hemorragia a los 7 y 21 días pi. En cerebro y bazo no se detectó patología. Se muestra así que la cepa XJCl3 se comporta en el ratón lactante nu/nu en forma muy diferente a la cepa patógena XJ, siendo necesarios otros estudios para determinar cuáles son los mecanismos patogénicos involucrados (AU)

Infeccíon intracerebral de ratones atímicos con una cepa atenuada de virus Junín / Intracerebral infection of athymic mice with an attenuated strain of junín virus

La infección del ratón lactante inmunocompetente eutímico (nu/+) con la cepa XJ del viru Junín provoca una encefalitis mortal debida a la respuesta inmune celular del huésped. Por el contrario, esa cepa inoculada en ratones atímicos (nu/nu) induce una infección persistente asintompatica. El objetivo del presente trabajo fue determinar el comportamiento de la cepa atenuada XJCl3 en el ratón nu/nu. Se inocularon por vía intracerebral (ic) 55 ratones lactantes nu/nu y 45 nu/+ con 10**3 UFP de la cepa XJCl3. Como controles se utilizaron 20 ratones nu/nu y 20 nu/+ infectar. Se observó en los ratones nu/nu y nu/+ una mortalidad similar (86%, respectivamente), mientras que no se observó mortalidad en los controles, que se mantuvieron en el mismo bioterio. Se detectaron altos títulos virales en cerebro y pulmón de los nu/nu infectados a los 7, 14, 21 y 70 días pi. Los títulos de virus en sangre fueron de 1 a 2 log más que en esos órganos. Estudios inmunohistoquímicos de cerebro mostraron antígeno viral intracitoplasmático en neuronas corticales a los 21 y 70 días pi. En el estudio histopatológico de pulmón de los nu/nu infectados se observó una neurmonbitis intersticial con focos de hemorragia a los 7 y 21 días pi. En cerebro y bazo no se detectó patología. Se muestra así que la cepa XJCl3 se comporta en el ratón lactante nu/nu en forma muy diferente a la cepa patógena XJ, siendo necesarios otros estudios para determinar cuáles son los mecanismos patogénicos involucrados