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.

[Mobbing and its effects on health. the experience of the "Clinica del Lavoro Luigi Devoto" in Milan]. / Le caratteristiche del mobbing ed i suoi effetti sulla salute. L'esperienza della "Clinica del Lavoro luigi Devoto" di Milano.

BACKGROUND: There is increasing interest in research, prevention and management of mobbing in the field of occupational psychosocial risks. OBJECTIVES: To describe mobbing and its health effects by analysis of the cases examined from 1997 to 2003 at the Department of Occupational Health "Clinica del Lavoro Luigi Devoto" in Milan. METHODS: A total of 226 clinical records of patients who reported a mobbing situation when undergoing medical examination were selected out of 2455 patients examined for stress-related disorders. RESULTS: The percentage of women was higher (53.1%) than in men (46.9%) with a prevalent age range of 35-54 years. There was a great variety of jobs, especially white-collars and workers in large service companies. In one third of the cases, mobbing occurred within 4 years from beginning of employment and mostly after company reorganization and management changes. The most frequent negative acts included social isolation and demotion. The most frequent symptoms were exhaustion, sleep, mood and sexual disorders. The number of symptoms was not related to the duration of mobbing but to the number and frequency of negative actions. 61.1% of the subjects took psychotropic drugs. Occupational health physicians play an essential role in primary prevention (information on occupational risks) and in early diagnosis and rehabilitation and could act as mediators between workers and enterprises.

[Gender differences in workplace bullying]. / Le differenze di genere nelle situazioni di mobbing.

BACKGROUND: Despite the attention that international Agencies give to the gender issue in situations of workplace bullying, few investigations have been performed on this topic. OBJECTIVES: The aim of the study is describe the gender differences in victims of workplace bullying observed in an Italian survey. METHODS: A total of 243 subjects (124 males and 119 females) were examined at the Centre for Occupational Stress and Harassment of the "Clinica del Lavoro Luigi Devoto" (University of Milan and IRCCS Foundation); they were selected among patients who met the criteria for being considered victims of negative actions at work leading to workplace bullying. Data regarding the person, workplace and the workplace bullying situation were collected by means of an ad hoc questionnaire. RESULTS: Analysis of the data, compared with those of IS-TAT 2002, showed a higher prevalence of females subjected to negative actions at work. In women, the risk of being subjected to negative actions leading to workplace bullying was shown to increase in the 34-44 age range and to decrease in higher age ranges; in men the risk remained elevated also after 55 years of age. CONCLUSIONS: In general, women were victims of negative actions regarding personal values related to emotional-relational factors, while men were attacked on their work performance. Sexual harassment, may mark the onset of other types of psychological harassment or can be one of its components.

Emerging aspects of psychosocial risks: violence and harassment at work.

In the last twenty years, psychosocial risks have become crucial in Occupational Health. Particularly, there is an increasing interest about psychological and physical violence at the workplaces. Psychological violence (mobbing or workplace bullying) is described as a situation in which the person has been the victim of negative acts directed to the person and work, with offences, discriminations and isolation. Physical violence at work, still underestimated in many parts of the world, is becoming a topical subject both for its frequency and its pathogenic potential and consist of violence among workers (internal violence) and between workers and external persons (external violence). Examples of external violence are bank robberies, which are prevalent in many European countries, particulary in Italy. The costs of psychological and physical workplace violence are very high at all levels; individual, for the implication of violence for health and quality of life as well as organizational, for the increase of absenteeism, turnover and health care demands and claims. The Medical Centre for Occupational Stress and Harassment (CDL) of the "Clinica de Lavoro Luigi Devoto" was set up in 1996 with a day-hospital service for the diagnosis, rehabilitation and prevention of work related psychological diseases. From its opening, about 5000 patients have been examined.

[Questionnaire for the mobbing risk: CDL2.0]. / Uno strumento per la valutazione del rischio mobbing: CDL2.0.

The aim of the study is to develop and validate a questionnaire able to evaluate the risk of mobbing at the workplace. A multiple-choice questionnaire has been developed which contains, among the different items, only one revealing a mobbing situation. The questionnaire has been administered to two groups (group A--243 subjects in a mobbing situation and group B--63 subjects without exposure to mobbing) and the differences in the scores obtained have been analysed. The questionnaire has proved to be valid and reliable. The results show that the presence of five mobbing actions is sufficient to define the workplace situation as potentially at risk for mobbing. The study reveals some limits in the selection of the two samples thus needing some adjustment. However, the questionnaire, also in the present form, can be considered a tool able to detect the mobbing situations.

[Emerging aspects of occupational stress]. / Aspetti emergenti dello stress occupazionale.

Work stress is caused by excessive demands which foster individuals to give prompt cognitive and behavioral answers. When these solicitations exceed the possibilities of the subject to comply, non-physiological reactions may follow, including emotional, neurovegetative and behavioral changes. If adverse stimuli persist, transient alterations form syndromes such as depression, phobic syndromes, anxiety syndromes, hypertension, heart disease, eating disorders, drug addiction, and so on. The authors examine specific stressful working areas causing illnesses in workers such as the burnout syndrome and the mobbing-related adjustment disorder or the post-traumatic stress disorder.

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...

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)

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)

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.

An international questionnaire to explore neurotoxic symptoms.

EURONEST (European Neurotoxic Solvents Toxicity) is a concerted action within the European Communities to use standardized methods available in all countries. The product of this effort is a new symptom questionnaire, EUROQUEST (European Questionnaire). The original version was developed in English. To obtain transcultural reliability, the translation of questionnaires into other languages must be validated. We adopted a procedure with translation, back translation, and agreement between translators. Ten other European countries also followed the same translation procedure for EUROQUEST.

Neurobehavioral functions in operating theatre personnel: a multicenter study.

The study was conducted to evaluate neuropsychological symptoms, subjective stress and response speed functions in subjects occupationally exposed to low levels of anesthetic gases. A group of 112 operating theatre personnel exposed to anesthetic gases (nitrous oxide and isoflurane), and 135 non exposed hospital workers from 10 hospitals in Northern Italy were examined before and after the shift on the first and the last day of the working week. Three different tasks were administered: a complex reaction time test (the Stroop Color Word); a questionnaire for neuropsychological symptoms (EURO-QUEST); the block design subtest (WAIS). Biological and atmospheric indicators of exposure were measured. In the exposed group, the geometric mean of urinary nitrous oxide at the end of the shift was 7.1 micrograms/l (95th percentile 12.4, range 1.5-43) on the first and 7.8 micrograms/l (95th percentile 21.5, range 1.0-73.3) on the last day of the working week. On the same days, end of shift urinary isoflurane was 0.7 microgram/l (95th percentile 2.6, range 0-4.7) on the first day and 0.8 microgram/l (95th percentile 2.0, range 0-5.6) on the last. The exposed and control subjects were comparable for both basic intellectual abilities and subjective stress levels. No statistical differences were observed between exposed and control subjects for neuropsychological tests and symptoms. No dose-effect relationships were observed between the exposure indicators and the test results. In conclusion, no early behavioral effect on the central nervous system was detectable at the exposure levels measured. The biological exposure limits of 13 micrograms/l for nitrous oxide and 1.8 micrograms/l for isoflurane corresponding respectively to the atmospheric concentrations of 25 ppm and 0.5 ppm seem to be adequately protective for the integrity of workers' neurobehavioral functions, as measured with the tests used.