Polyalthia longifolia var. pendula is used as an antipyretic agent in indigenous systems of medicine. Microglia-mediated inflammation plays an important role in the pathway leading to neuronal cell death in a number of neurodegenerative diseases. The aim of this study was to investigate the effects of 6-hydroxycleroda-3,13-dien-15,16-olide (PL3) extracted from Polyalthia longifolia var. pendula on lipopolysaccharide(LPS)-induced inflammation in microglia-like HAPI cells and primary microglia cultures. In microglia-neuron co-cultures, LPS decreased the cell viability of neuroblastoma SH-SY5Y cells. LPS-induced cell death was attenuated by the NOS inhibitor, L-NAME, the COX-2 inhibitor, NS-398 or the NADPH oxidase inhibitor, DPI, respectively. In LPS-treated microglia cells, PL3 decreased the expression of iNOS, COX-2, gp91 (phox), and NF- kappaBp65, the degradation of I kappaB alpha, and the production of NO, PGE (2), iROS, and TNF- alpha. PL3 also enhanced the expression of HO-1, a cytoprotective and anti-inflammatory enzyme. Moreover, PL3 reduced LPS-activated microglia-induced cell death. The present results suggest that PL3 inhibits microglia-mediated inflammation and inflammation-related neuronal cell death. Therefore, PL3 has potential use for the treatment of inflammation-related neurodegenerative diseases.
The impact on family life and social relations that may result from symptoms associated with exposure to neurotoxic substances has never been addressed. This exploratory study assessed the associations between exposure to neurotoxic agents in the workplace, mental health, and marital difficulties.
Fifty-five (55) male workers and their spouses completed standardized measures of mental health and marital difficulties. Workers' exposure to neurotoxic substances was evaluated by questionnaire and interview, using a semiquantitative classification system.
A positive relation was observed between exposure level and measures of workers' psychological symptoms and marital stress; no relation was observed between workers' exposure level and wives' psychological symptoms. More severe exposure to neurotoxic substances was associated with wives' reports of more severe marital conflicts, and this association was mediated by husbands' psychological symptoms. As compared to low exposure husbands, high exposure husbands reported higher degrees of stress surrounding marital discussions, more consistent incidence of minor physical assaults by wives, and stronger associations between their levels of stress, the verbal aggressions of wives, and the number of marital conflicts.
The results of this study confirm that neurotoxic exposure is a risk factor for mental health and suggest how this may influence marital relations. Because of the importance of these findings for the well-being of workers and their families, these associations should be further studied.
Although associations between antipsychotic use and neuropsychological impairment in bipolar I disorder have been observed, there is a lack of studies comparing the effects of specific agents used in this population. We compared performance between patients receiving maintenance treatment with mood stabilizer monotherapy (n=15), adjunctive risperidone (n=15) or quetiapine (n=17), and a group of demographically matched healthy controls (n=28) on tests of executive function (working memory, set shifting, and inhibition) and verbal learning. Despite having a similar clinical profile, patients being treated with risperidone showed significantly impaired working memory, set-shifting, and verbal learning (P
Chronic solvent encephalopathy (CSE) is under-reported worldwide due to difficulties in recognition and differences in national legislation. Although its occurrence in developed countries has declined, new cases continue to be detected. Our aim was to determine whether CSE can be detected in risk trades, using a stepwise screening procedure. Another aim was to evaluate if this method detects more cases than present occupational health service (OHS) practices do in Finland, a country with decreasing exposures, high OHS coverage and an annual rate of around forty cases of suspected CSE and seven cases of occupational CSE. The studied fields, based on the national occurrence of CSE, were industrial and construction painting, floor layering, the printing press industry, boat construction, reinforced plastic laminating and the metal industry. We obtained contact information from trade union registers and municipal OHS. A postal survey including the Euroquest (EQ) neurotoxic symptom questionnaire, Beck's Depression Inventory (BDI) and the Alcohol Use Disorders Identification Test-Consumption (Audit-C), and questions on exposure and medical conditions, was sent to 3,640 workers in the age range of 30-65 years in two Finnish provinces. The survey resulted in 1,730 responses (48%). This was followed by a clinical examination, with methods applicable to OHS, of subjects fulfilling the criteria: three or more EQ memory and concentration symptoms and sufficient exposure, a BDI score=18, an AUDIT-C score=8, and no evident medical condition explaining their symptoms. Of 338 respondents with memory and concentration symptoms, 129 subjects fulfilled all the criteria, of which 83 participated in clinical examinations. We found 38 CSE compatible cases. The study shows that more CSE compatible cases can be detected when the screening is directed towards the occupational fields at greatest risk. This stepwise method is more effective for finding CSE compatible cases than regular OHS activity. The number of cases was similar to the total annual occurrence, of new CSE-suspected cases, although the sample represented approximately 18% of the abundantly exposed workforce in Finland. Combining of exposure and medical differential diagnostics to neurotoxic symptom questionnaire, decreases the amount of cases needing clinical examinations. This two-step procedure can be carried out with methods suitable for OHS and other primary health care, both in industrialized and developed countries.
In this study an education, and a series of group sessions for patients with solvent-induced chronic toxic encephalopathy (TE) and their spouses are evaluated. Thirty-eight patients and 21 family members participated in a 1-day education scheduled with short lectures on the clinical examination of chronic toxic encephalopathy and the prognosis. A specialist in occupational medicine, a psychologist and a social worker gave the lectures. Small discussion groups were also arranged. Of the participants from the educational days, 16 TE patients and 14 wives attended a 10-week counselling and coping improvement program with separate group sessions once a week, for patients and spouses. Questionnaires were used to assess symptoms, social network, mastery and family climate, and the participants' satisfaction with the education and the group sessions. The majority of the participants experienced the 1-day information as useful and relevant. The 10-week group sessions were rated as meaningful and the design, number, duration and frequency of the sessions equally good. Self-reported symptoms, social network and mastery were measured before the group sessions, and 3 and 9 months after breaking up the group sessions. In most measurements, there were no statistically significant differences between the three points in time. However, the wives improved more than did the patients but the effect was not lasting the whole follow-up period. Considering the patients' dependence on their wives, it might be most important that the wives experienced some relief from their own symptoms.
The study evaluates the factor structure and predictive validity of the symptom questionnaire EUROQUEST (EQ) that had been developed with the goal of simplifying the evaluation of health effects associated with long-term solvent exposure. The EQ was added to the normal evaluation procedures for 118 male patients with suspected solvent-induced toxic encephalopathy (TE) referred to seven Swedish clinics of occupational medicine during an 18-month period. EQ was also completed by 239 males from a random sample of 400 Swedish males aged 25-64 years selected from the general population and a sample of 559 occupationally active male spray painters aged 25-64 years. Factor and item analyses of EQ responses were performed. Ordinary least square regression analysis was used to evaluate sensitivity and correlation to evaluate the specificity of EQ and the separate components. Questions concerning memory and concentration symptoms alone showed better sensitivity than the other five EQ dimensions singly or combined for the entire EQ and for a subset of questions approximating Q16, a widely used organic solvent symptom screening questionnaire. However, the diagnosis of TE required information in addition to exposure and responses to EQ and Q16-like questions. The results indicate that the subset of EQ questions concerning memory and concentration might replace the more cumbersome EQ and less sensitive Q16 in screening for TE, although none of the screening instruments alone replaces current clinical diagnostic procedures.
The new questionnaire Euroquest was designed to study effects from exposure to organic solvents, and it covers the most commonly reported symptoms associated with long-term solvent exposure. Its convergence and criterion validity were evaluated by means of comparison with the two well-established generic symptom questionnaires Symptom Checklist (SCL-90) and General Health Questionnaire (GHQ-30). Men with long-term exposure to organic solvents and symptoms common in toxic encephalopathy (TE) classified as TE type 2A (n=29) or 2B (n=28) according to their neuropsychological test performance, and a comparable group of non-exposed healthy referents (N=57), were included. The six Euroquest factors obtained by a factor analysis were labeled: 'emotional lability' 'cognitive disturbances' 'peripheral neurology' 'sleepiness' 'fatigue' and 'sleep disturbances'. These factors correlated well with most SCL-90 scales and with the GHQ-30 total score in the combined TE groups. The combined TE groups were correctly classified to a similar degree by the Euroquest factors 'cognitive disturbances' and 'peripheral neurology' (TE 82.5% and referents 93%) and the SCL-90 scales 'somatization, 'interpersonal sensitivity', 'obsessive-compulsive symptoms' and 'hostility' (TE 84.2% and referents 93.0%), but not as well by GHQ-30 (TE 61.4% and referents 79%). In comparison with the separate TE groups most referents, and a considerably higher percentage of 2B than 2A subjects, could be correctly classified with both Euroquest and SCL-90. With GHQ-30, only a few 2A cases and fewer than half of the 2B cases were correctly classified. In conclusion, the Euroquest factors converged with both SCL-90 scales and GHQ-30 score. With both the Euroquest and SCL-90 questionnaires a similar percentage of the TE subjects were discriminated from the referents, most conspicuously regarding TE 2B subjects, who had an objectified cognitive dysfunction. In a choice between Euroquest and SCL-90, the Euroquest may have the advantage of higher face validity, for TE subjects.
Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986-1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.