Modulating Expression of Endogenous Interleukin 1 Beta in the Acute Phase of the Pilocarpine Model of Epilepsy May Change Animal Survival.

The pilocarpine-induced (PILO) model has helped elucidate the electrophysiological and molecular aspects related to mesial temporal lobe epilepsy. It has been suggested that the extensive cell death and edema observed in the brains of these animals could be induced by increased inflammatory responses, such as the rapid release of the inflammatory cytokine interleukin 1 beta (Il1b). In this study, we investigate the role of endogenous Il1b in the acute phase of the PILO model. Our aim is twofold. First, we want to determine whether it is feasible to silence Il1b in the central nervous system using a non-invasive procedure. Second, we aim to investigate the effect of silencing endogenous Il1b and its antagonist, Il1rn.We used RNA interference applied non-invasively to knockdown Il1b and its endogenous antagonist Il1rn. We found that knocking down Il1b prior to pilocarpine injection increased the mortality rate of treated animals. Furthermore, we observed that, when exposing the animals to more Il1b by silencing its endogenous antagonist Il1rn, there was a better response to status epilepticus with decreased animal mortality in the acute phase of the PILO model. Thus, we show the feasibility of using a novel, less invasive approach to study genes involved in the inflammatory response in the central nervous system. Furthermore, our results provide suggestive evidence that modulating endogenous Il1b improves animal survival in the acute phase of the PILO model and may have effects that extend into the chronic phase.

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84). In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

RNA sequencing reveals region-specific molecular mechanisms associated with epileptogenesis in a model of classical hippocampal sclerosis.

We report here the first complete transcriptome analysis of the dorsal (dDG) and ventral dentate gyrus (vDG) of a rat epilepsy model presenting a hippocampal lesion with a strict resemblance to classical hippocampal sclerosis (HS). We collected the dDG and vDG by laser microdissection 15 days after electrical stimulation and performed high-throughput RNA-sequencing. There were many differentially regulated genes, some of which were specific to either of the two sub-regions in stimulated animals. Gene ontology analysis indicated an enrichment of inflammation-related processes in both sub-regions and of axonal guidance and calcium signaling processes exclusively in the vDG. There was also a differential regulation of genes encoding molecules involved in synaptic function, neural electrical activity and neuropeptides in stimulated rats. The data presented here suggests, in the time point analyzed, a remarkable interaction among several molecular components which takes place in the damaged hippocampi. Furthermore, even though similar mechanisms may function in different regions of the DG, the molecular components involved seem to be region specific.

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84). In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

A Interleucina 1-beta mostra uma ação protetora na fase aguda do modelo de epilepsia induzido pela pilocarpina / The il1β have a protective action in the acute phase of the pilocarpine-induced epilepsy model

INTRODUÇÃO: Existem contradições na literatura quanto aos efeitos dos genes il1β e il1rn nas epilepsias. Nosso objetivo foi avaliar os efeitos do silenciamento desses dois genes na fase aguda do modelo de epilepsia induzido pela pilocarpina. MÉTODOS: Para alterar a expressão dos genes il1β e il1rn utilizamos a técnica de interferência por RNA. RESULTADOS: Obtivemos taxas de silenciamento significativas para os dois genes no sistema nervoso central. Observamos efeitos fenotípicos significativos, incluindo a alteração na taxa de mortalidade dos animais 5 dias após a indução do modelo. CONCLUSÕES: A il1β parece exercer um papel protetor na fase aguda do modelo de epilepsia induzido pela pilocarpina.

INTRODUCTION: There is contradictory information regarding the of effects il1β and il1rn in epilepsy. We aimed to evaluate the effect of silencing both genes in the acute phase of the pilocarpine-induced epilepsy model. METHODS: We used RNA interference in order to achieve gene silencing. RESULTS: We obtained significant gene silencing in the central nervous system. In addition, we observed phenotypic effects including differences in mortality rates of animals 5 days after pilocarpine injections. CONCLUSION: Our results indicate that il1β seems to have a protective effect in the acute phase of the pilocarpine-induced epilepsy model.

Acoso moral (mobbing): un nuevo riesgo en la medicina del trabajo / Moral harassment: a new risk in occupational medicine

Los riesgos psicosociales se están constituyendo en una de las principales causas de alteración de la salud en los puestos de trabajo. En los últimos años, el "riesgo relacional o interpersonal" - mobbing - se ha ido incrementando debido a los cambios macroeconómicos y por el cambio en la tipología del trabajo y en los riesgos laborales derivados. Cada trabajador, independientemente de las características de su propia personalidad y del propio carácter, puede ser objeto de acoso moral. Los primeros efectos derivados del mobbing son observables sobre la salud de la víctima que, casi siempre, después de un intervalo variable, se altera con manifestaciones en la esfera neuropsíquica, Las consecuancias sociales pueden ser devastadoras. El costo del mobbing no se limita a los aspectos individuales, sino que se refleja generalmente a nivel de la empresa. La gestión del fenómeno de mobbing es multidisciplinaria. A nivel asistencial, el rol del médico del trabajo, del psiquiatra y del psicólogo son interdependientes y deben por lo tanto ser integrados en una estructura funcional unitaria...(AU)

Acoso moral (mobbing): un nuevo riesgo en la medicina del trabajo / Moral harassment: a new risk in occupational medicine

Los riesgos psicosociales se están constituyendo en una de las principales causas de alteración de la salud en los puestos de trabajo. En los últimos años, el "riesgo relacional o interpersonal" - mobbing - se ha ido incrementando debido a los cambios macroeconómicos y por el cambio en la tipología del trabajo y en los riesgos laborales derivados. Cada trabajador, independientemente de las características de su propia personalidad y del propio carácter, puede ser objeto de acoso moral. Los primeros efectos derivados del mobbing son observables sobre la salud de la víctima que, casi siempre, después de un intervalo variable, se altera con manifestaciones en la esfera neuropsíquica, Las consecuancias sociales pueden ser devastadoras. El costo del mobbing no se limita a los aspectos individuales, sino que se refleja generalmente a nivel de la empresa. La gestión del fenómeno de mobbing es multidisciplinaria. A nivel asistencial, el rol del médico del trabajo, del psiquiatra y del psicólogo son interdependientes y deben por lo tanto ser integrados en una estructura funcional unitaria...

Freqüência de parasitas e infecçäo por Salmonella em lobos guará, Chrysocyon brachyurus, mantidos em zoológicos no Estado de Säo Paulo / Frequency of parasites and Salmonella infection in captive maned-wolf, Chrysocyon brachyurus, kept in Zoos at the State of Säo Paulo, Brazil

Trinta e um lobos guará (Chrysocyon brachyurus, Illiger 1815), mantidos em 11 zoológicos no Estado de Säo Paulo, foram estudados para verificar a presença de parasitas e de infecçäo por Salmonella usando-se métodos de diagnóstico parasitológico e cultura seletiva de fezes. Os ecto e endoparasitas encontrados foram: Ctenocephalides felis (56,2 por cento), Rhipicephalus sanguineus (12,5 por cento), Ancylostoma caninum (45,l por cento), Strongyloides sp. (29,0 por cento), Uncinaria stenocephala (3,2 por cento), Capillaria sp. (3,2 por cento), Entamoeba sp. (22,9 por cento), Sarcocystis sp. (29,0 por cento), Cryptosporidium sp. (19,3 por cento), Eimeria sp. (19,3 por cento), Giardia sp. (9,6 por cento) e Isospora sp. (3,2 por cento). Seis animais apresentaram infecçäo por Salmonella e quatro diferentes sorotipos foram identificados. Somente um animal apresentava quadro de diarréia sugerindo que a capacidade de portar Salmonella spp. como flora gastrintestinal näo patogênica parece ser uma adaptaçäo fisiológica dessa espécie animal

Estudo de parasitos em colônias de ratos e de camundongos em biotérios brasileiros mantidos sob diferentes condiçöes de barreiras sanitárias / Parasite survery in mouse and rat colonies of Brazilian laboratory animal houses kept under differents sanitary barrier conditions

Um estudo parasitológico foi realizado para verificar as condiçöes de saúde de 15 colônias de camundongos e 10 colônias de ratos produzidos em 18 biotérios de instituiçöes brasileiras que fornecem animais para ensino, pesquisa e produçäo de imunobiológicos de uso médico ou veterinário. Métodos parasitológicos foram utilizados para diagnóstico de ácaros, piolhos, helmintos e protozoários parasitos. Um questionário foi respondido pelas instituiçöes com o intuito de obter informaçöes sobre a existência de barreiras contra infecçöes e programa de fiscalizaçäo sanitária de suas colônias. Os dados do questionário mostram que a maioria dos biotérios analisados näo possui um sistema de barreiras sanitárias eficiente capaz de manter animais sob condiçöes sanitárias controladas. Infecçöes por ecto e endoparasitos säo generalizadas nas colônias e a associaçäo de infecçöes múltiplas foi comum na maioria dos animais dos biotérios analisados. A prevalência dos parasitos detectados entre as colônias de camundongos e de ratos investigados foi: Myocoptes musculinus (46,6 por cento), Myobia musculi (26,6 por cento), Radfordia ensifera (13,3 por cento), Syphacia obvelata (86,6 por cento). Aspiculuris tetraptera (60,0 por cento), Hymenolepis nana (53,3 por cento), Spironucleus muris (80,0 por cento), Tritrichomonas muris (80,0 por cento), Giardia muris (66,0 por cento), Entamoeba muris (20,0 por cento), Eimeria sp. (13,3 por cento), Hexamastix muris (26,6 por cento), Poliplax spinulosa (30,0 por cento), Poliplax serrata (10,0 por cento), Radfordia ensifera (30,0 por cento), Syphacia muris (80,0 por cento), Hymenolepis nana (40,0 por cento), Trichosomoides crassicauda (55,5 por cento), Spironucleus muris (90,0 por cento), Tritrichomonas muris (80,0 por cento), Giardia muris (60,0 por cento), Entamoeba muris (80,0 por cento), Eimeria sp. (60,0 por cento) e Hexamastix muris (60,0 por cento)

Frequency of parasites and Salmonella infection in captive maned-wolf, Chrysocyon brachyurus, kept in Zoos at the State of São Paulo, Brazil

Thirty-one captive maned wolves (Chrysocyon brachyurus, Illiger 1815) from 11 Zoos at the State of São Paulo, Brazil, were screened to investigate the presence of parasites and Salmonella infection by parasitological diagnostic methods and fecal selective culture. The most frequent ecto and endoparasites found were Ctenocephalides felis (56.2%), Rhipicephalus sanguineus (12.5%), Ancylostoma caninum (45.1%), Strongyloides sp. (29.0%), Uncinaria stenocephala (3.2%), Capillaria sp. (3.2%), Entamoeba sp. (22.9%), Sarcocystis sp. (29.0%), Cryptosporidium sp. (19.3%), Eimeria sp. (19.3%), Giardia sp. (9.6%) and Isospora sp. (3.2%). Four different serotypes of Salmonella were identified in six animals (25%). Only one infected animal showed clinical signs of diarrhea. The ability to harbor Salmonella spp. as normal nonpathogenic bacteria of the gastrointestinal tract may be a physiological adaptation of this specie.

Trinta e um lobos guará (Chrysocyon brachyurus, Illiger 1815), mantidos em 11 zoológicos no Estado de São Paulo, foram estudados para verificar a presença de parasitas e de infecção por Salmonella usando-se métodos de diagnóstico parasitológico e cultura seletiva de fezes. Os ecto e endoparasitas encontrados foram: Ctenocephalides felis (56,2%), Rhipicephalus sanguineus (12,5%), Ancylostoma caninum (45,1%), Strongyloides sp. (29,0%), Uncinaria stenocephala (3,2%), Capillaria sp. (3,2%), Entamoeba sp. (22,9%), Sarcocystis sp. (29,0%), Cryptosporidium sp. (19,3%), Eimeria sp. (19,3%), Giardia sp. (9,6%) e Isospora sp. (3,2%). Seis animais apresentaram infecção por Salmonella e quatro diferentes sorotipos foram identificados. Somente um animal apresentava quadro de diarréia sugerindo que a capacidade de portar Salmonella spp. como flora gastrintestinal não patogênica parece ser uma adaptação fisiológica dessa espécie animal.

Parasite survey in mouse and rat colonies of Brazilian laboratory animal houses kept under differents sanitary barrier conditions

A parasitological study was undertaken to determine the health status of 15 mouse and 10 rat colonies bred in 18 Brazilian laboratory animal houses maintained under different sanitary barrier conditions which supply animals for teaching, research purposes and manufacture of biological products for medical or veterinary use. Parasitological methods were used for diagnosis of mites, lices, helminthes and protozoan parasites. A questionnaire was answered by institutions with the intention to obtain information about the existence of barriers against infections and of regular sanitary monitoring program of their colonies. The questionnaire data show that the majority of the animal houses investigated do not possess an efficient sanitary barrier system able to keep animals under controlled health sanitary conditions. Ecto and endoparasite infections are widespread in the colonies and multiple infections were common in animals from most facilities investigated. The prevalences of parasites detected among the mouse and rat colonies of the laboratory animal houses investigated were: Myocoptes musculinus (46.6%), Myobia musculi (26.6%), Radfordia ensifera (13.3%), Syphacia obvelata (86.6%), Aspiculuris tetraptera (60.0%), Hymenolepis nana (53.3%), Spironucleus muris (80.0%), Tritrichomonas muris (80.0%), Giardia muris (66.0%), Entamoeba muris (20.0%), Eimeria sp. (13.3%), Hexamastix muris (26.6%), Poliplax spinulosa (30.0%), Poliplax serrata (10.0%), Radfordia ensifera (30.0%), Syphacia muris (80.0%), Hymenolepis nana (40.0%), Trichosomoides crassicauda (55.5%), Spironucleus muris (90.0%), Tritrichomonas muris (80.0%), Giardia muris (60.0%), Entamoeba muris (80.0%), Eimeria sp. (60.0%) and Hexamastix muris (60.0%).

Um estudo parasitológico foi realizado para verificar as condições de saúde de 15 colônias de camundongos e 10 colônias de ratos produzidos em 18 biotérios de instituições brasileiras que fornecem animais para ensino, pesquisa e produção de imunobiológicos de uso médico ou veterinário. Métodos parasitológicos foram utilizados para diagnóstico de ácaros, piolhos, helmintos e protozoários parasitos. Um questionário foi respondido pelas instituições com o intuito de obter informações sobre a existência de barreiras contra infecções e programa de fiscalização sanitária de suas colônias. Os dados do questionário mostram que a maioria dos biotérios analisados não possui um sistema de barreiras sanitárias eficiente capaz de manter animais sob condições sanitárias controladas. Infecções por ecto e endoparasitos são generalizadas nas colônias e a associação de infecções múltiplas foi comum na maioria dos animais dos biotérios analisados. A prevalência dos parasitos detectados entre as colônias de camundongos e de ratos investigadas foi: Myocoptes musculinus (46,6%), Myobia musculi (26,6%), Radfordia ensifera (13,3%), Syphacia obvelata (86,6%), Aspiculuris tetraptera (60,0%), Hymenolepis nana (53,3%), Spironucleus muris (80,0%), Tritrichomonas muris (80,0%), Giardia muris (66,0%), Entamoeba muris (20,0%), Eimeria sp. (13,3%), Hexamastix muris (26,6%), Poliplax spinulosa (30,0%), Poliplax serrata (10,0%), Radfordia ensifera (30,0%), Syphacia muris (80,0%), Hymenolepis nana (40,0%), Trichosomoides crassicauda (55,5%), Spironucleus muris (90,0%), Tritrichomonas muris (80,0%), Giardia muris (60,0%), Entamoeba muris (80,0%), Eimeria sp. (60,0%) e Hexamastix muris (60,0%).

Exposure to organic solvents and its effects on the central nervous system in workers of the Camaçari petrochemical complex in Brazil.

While numerous studies have been carried out in industrialized countries, only very few epidemiologic investigations performed in developing countries are reported in the international literature. This study is one of the few examples of investigations carried out in a region where industrialization is at its beginning. A sample of 188 workers employed at the Camaçari Petrochemical Complex in Bahia, Brazil, and exposed for over five years to organic solvents was submitted to neurobehavioral testing (QQS questionnaire, MANS battery) together with a 1/1 control group paired for age, school attendance and alcohol consumption. The exposed subjects showed differences significantly worse at emotional status, manual dexterity, recognition memory and subjective symptoms. Exposed subjects are therefore characterized by decreased psychophysical well-being.

Murine virus contaminant of Trypanosoma cruzi experimental infection.

The possibility that some virus contaminants could be altering host response to Trypanosoma cruzi experimental infection was investigated. Data obtained showed that CBA/J mice infected with stocks of parasite maintained in mice (YIUEC) presented higher level of parasitemia and shorter survival times than those infected with a stock (YITC) which was also maintained in mice but had been previously passaged in cell culture. Mouse antibody production tests, performed with the filtered plasma of mice infected with YIUEC, indicated the presence of mouse hepatitis virus (MHV) while no virus was detected when testing the plasma of YITC infected mice. Filtered plasma of YIEUC infected mice was shown to contain a factor able to enhance the level of parasitemia and to reduce the mean survival time of mice challenged with 10(5) YITC. This factor, that could be serially passaged to naïve mice was shown to be a coronavirus by neutralization tests.