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.

[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.

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.

[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.

Experiences with the Milan Automated Neurobehavioral System (MANS) in occupational neurotoxic exposure.

It is known that in neurobehavioral toxicology, the data obtained by means of psychological testing can acquire sense only when testing conditions and procedures, among others, are kept under rigorous control. This demand, together with the diffusion of multicentered studies aimed at finding mutual agreement on the parameters to be measured and the interpretation criteria to be adopted, has determined our decision to convert six out of the seven tests of the WHO-NCTB into a computer-aided system (MANS). The choice of one of the two systems depends on the characteristics of the testing situation and on the different requirements of clinical, epidemiological and experimental studies. The validation of MANS, as to its reliability and sensitivity, is ongoing but some data have already been collected which show a high correlation of the computer-administered test results with the paper and pencil form as well as a good degree of discriminating power in different testing situations. The experience, made in the past three years, seems to show that the goal of having a simple, easy to handle and reliable instrument to be used and, if necessary easily adapted to a variety of situations and cultures, has been met. Further work is to be carried out to confirm its validity in the early detection of neurobehavioral impairments due to neurotoxic agents.

A clinical, neurophysiological and behavioral study of female workers exposed to 1,1,1-trichloroethane.

Twenty-two female subjects working in a factory in which 1,1,1-trichloroethane was the only solvent used were investigated by means of clinical, neurophysiological and psychometric methods so that the neurotoxicity of the solvent could be evaluated. On the basis of the ambient air concentrations of 1,1,1-trichloroethane ranging from 110 to 990 ppm, the workers were divided into three risk groups and compared with a reference group. No significant difference was observed between the exposed and unexposed females with respect to clinical features, maximal motor conduction velocity, conduction velocity of slow fibers, and psychometric data. The most frequent complaints of the workers were of the "neurotic" type with a slightly higher, but not significant, difference in the exposed group. The results obtained favor the absence of a manifest neurotoxic effect of 1,1,1-trichloroethane under the specific work conditions of the investigation; generally unfavorable work conditions seem to have played a prominent role in the genesis of the neurotic complaints. The importance of a global methodological approach in the study of work-related risks, particularly in neurological and psychological surveys, is stressed.

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.

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.

[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.

Neurobehavioral functions in operating theatre personnel exposed to anesthetic gases.

Neurobehavioral functions in paramedical operating theatre personnel were assessed in a cross-sectional survey. Sixty-two subjects (40 males and 22 females) occupationally exposed to anesthetic gases were examined and compared to 46 unexposed hospital workers (18 males and 28 females). The Simple Reaction Time (SRT) test was selected from the MANS battery (Milan Automated Neurobehavioural System). In order to evaluate acute and subacute types of effects on performance, the test was administered before and after the work shift, at the beginning and at the end of the working week. In addition, the complete battery was administered during one working day without exposure to anesthetic gases. On the last day of the working week, atmospheric nitrous oxide (N2Oa) ranged from 7 to 553 ppm (geometric mean 62.6), atmospheric ethrane (ETHa) ranged from 0.1 to 18.8 ppm (geometric mean 1.3), and urinary N2O (N2Ou) ranged from 4 to 297 micrograms/l (geometric mean 26.8). An impairment of performance on the SRT test was observed at the end of the working week in subjects exposed to anesthetic gases compared to controls. This alteration was observed also considering only the subjects exposed to less than 55 micrograms/l (which is the Italian exposure limit for N2Ou, equivalent to 100 ppm for N2Oa). No significant differences were observed for the other psychometric tests. No dose-effect relationships where found between SRT test score and the indicators of exposure (N2Oa, ETHa, N2Ou).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.