[Assessment of urinary cotinine in a group occupationally exposed to nicotine]. / Valutazione della cotinina urinaria in un gruppo di esposti professionalmente alla nicotina.

In a Tobacco processing company, located in central Italy, both air nicotine and, one of its metabolites, the urinary cotinine were assessed, as part of the evaluation of the effectiveness of recently implemented technical preventive controls. Urinary cotinine measurements ranged from 9,63 to 234,09 microg/gr creat. in non-smokers and from 178,79 to 2476,19 microg/gr creat. in smokers. Urinary cotinine proved useful as an exposure biological index especially in terms of population monitoring. On the contrary, the meaning of the measured values were less clear in single workers, because of significant both intra- and inter-individual variability.

[Risk assessment method for psychosocial factors at workplace: a North-West Tuscany area project]. / Metodologia di valutazione dei rischi psicosociali in ambiente di lavoro: un progetto toscano di area vasta.

The rising awareness of psychosocial risks at workplace means that it is ever more important to prepare methods to assess psychosocial factors in occupational environment. This project of north west tuscany area has the aim to realize an instrument for a gradual risk assessment for this kind of factors without the support of specialists. A decisional flow chart helps to approach the risk assessment step by step on the basis of company features, management and organization problems and company symptoms of stress. The final assessment combines the evaluation of perceived risks with job analysis realizing a matrix containing 5 risk levels, which suggests the priority of preventive measures. The intermediate level (level three) represents the activation level for the medical surveillance. This experience means a proposal for a quantitative assessment of psychosocial risks at workplace.

A review on cancer--psychospiritual status interactions.

With the advances in the knowledge of neuroimmunomodulation, a new era of investigations about the chemical basis of the state of mind has been initiated. Both emotions and states of spiritual consciousness may influence immune functions and cancer growth. Stress, anxiety and depressive states are associated with immunosuppression and enhanced frequency of tumors. On the other hand, the states of sexual pleasure and spiritual joy enhance the immune efficacy, by counteracting tumor onset and dissemination. The biochemistry of pleasure and immunostimulation is mainly mediated by pineal indoles and cannabinergic substances, whereas that of stress, anxiety and depression is associated with enhanced production of adrenal steroids, opioids and catecholamines. The sexual repression would allow a progressive immunosuppression through a profound damage in the biochemistry of pleasure. Therefore, a better definition of psychospiritual status-associated neuroimmunochemistry could allow us to improve the immune dysfunction by acting on the same neuroendocrine secretions which are involved in mediating the psychic influence on the immunity, including that against cancer.

A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia.

OBJECTIVES: Recent studies have suggested the involvement of the pineal gland and its main hormone melatonin (MLT) in the pathogenesis of psychiatric disturbances, namely the depressive syndrome. In contrast, the behavior of MLT secretion in schizophrenia is still controversial. MATERIAL & METHODS: The present study was carried out to analyze light/dark rhythm of MLT secretion in relation to that of cortisol and prolactin (PRL) in schizophrenic patients. The study included 13 schizophrenic patients, 8 of whom were untreated, while the other 5 patients were on neuroleptic therapy. Serum levels of MLT, PRL and cortisol were measured by RIA on venous blood samples collected at 8 A.M., 12 A.M., 8 P.M. and 1 A.M. The control group consisted of 20 age-matched healthy subjects. RESULTS: A physiological nocturnal increase in MLT levels occurred in 6/13 patients, whereas the other 7 patients showed an abnormally low MLT peak during the night. Moreover, both light and night mean levels of MLT were significantly lower in patients than in controls. In addition, mean nocturnal levels of MLT were significantly lower in chronic patients than in those evaluated at the onset of disease. Cortisol rhythm was normal in 11/13 patients, whereas PRL levels were abnormally high in 10/13 patients. CONCLUSIONS: This preliminary study would suggest that schizophrenia may be associated with a diminished secretion of MLT from the pineal gland, and pineal deficiency would be more evident in the chronic disease. Finally, pineal alterations have appeared to be associated with an altered secretion of PRL and cortisol, by suggesting that the schizophrenic disease may be characterized by marked neuroendocrine disturbances, whose physio-pathological and prognostic significance needs to be established by successive clinical investigations.

Thrombopoietic properties of 5-methoxytryptamine plus melatonin versus melatonin alone in the treatment of cancer-related thrombocytopenia.

Recent studies have shown that the hematopoietic system is under neuroendocrine control. In particular, thrombopoiesis has been proven to be stimulated by melatonin, and the pineal indole has been shown to be effective in the treatment of thrombocytopenia resulting from different causes. At present, however, there are no data concerning the possible thrombopoietic activity of pineal indoles other than melatonin. The present study was carried out to evaluate the effect of a concomitant administration of the pineal indole 5-methoxytryptamine in patients with cancer-related thrombocytopenia who did not respond to melatonin alone. The present study included 30 patients, who were randomized to receive melatonin alone (20 mg/day orally in the evening) or melatonin plus 5-methoxytryptamine (1 mg/day orally in the early afternoon). A normalization of platelet count was achieved in 5/14 (36%) patients treated with melatonin plus 5-methoxytryptamine and in none of the patients treated with melatonin alone (P < 0.05). Moreover, mean platelet number significantly increased only in the patients treated with melatonin plus 5-methoxytryptamine. This preliminary clinical study would suggest that 5-methoxytryptamine, a pineal indole, may also exert thrombopoietic activity. Further studies, however, will be required to establish whether 5-methoxytryptamine may play a direct thrombopoietic activity, or whether it may act by improving melatonin's efficacy.

Anticancer neuroimmunomodulation by pineal hormones other than melatonin: preliminary phase II study of the pineal indole 5-methoxytryptophol in association with low-dose IL-2 and melatonin.

Despite several years of experimental observations, the clinical application of the neuroimmunomodulation is still at the beginning. The pineal gland plays a main role in mediating the link between psychoneuroendocrine and immune systems. Melatonin (MLT), which is the main pineal hormone produced during the night, has appeared to amplify IL-2 anticancer activity. Other pineal hormones, however, would have immunomodulatory activity, in particular 5-methoxytryptophol (5-MTT), which is mainly produced during the light phase of the day. Previous clinical studies have shown that low-dose IL-2 plus MLT may have therapeutic efficacy in advanced cancer patients with neoplasms generally resistant to IL-2 alone, with a tumor regression rate generally less than 20% and an acceptable toxicity. The present study was carried out to evaluate the efficacy of low-dose IL-2 in association with both MLT and 5-MTT. The study included 14 untreatable advanced solid tumor patients (lung cancer: 4; gastric cancer: 3; mesothelioma: 2; hepatocarcinoma: 2; pancreatic cancer: 1; melanoma: 1; colon cancer: 1). IL-2 was injected subcutaneously at 3 MIU/day for 6 days/week for 4 weeks, by repeating a second cycle after a 21- day rest period. Both MLT and 5-MTT were given orally at 40 mg/day in the evening and at 1 mg/day at noon. The clinical results, as evaluated by WHO criteria after each cycle, consisted of partial response (PR) in 4/14 (29%) (lung cancer: 2; hepatocarcinoma: 1; mesothelioma: 1), stable disease (SD) in 6 and progressive disease in the last 4 patients. The treatment was extremely well tolerated in all patients, and in particular no fever greater than 38 degrees C occurred. These preliminary results show that the neuroimmunotherapy with low-dose IL-2 plus two pineal hormones, MLT and 5-MTT, is a well tolerated and potentially effective cancer therapy of untreatable advanced solid tumor patients, with results apparently superior with respect to those previously described with IL-2 plus MLT alone.

Interleukin-2, melatonin and interleukin-12 as a possible neuroimmune combination in the biotherapy of cancer.

Suppressive events induced by macrophages and TH2 lymphocytes would represent the most important factors responsible for the in vivo reduced efficacy of IL-2 cancer immunotherapy. Previous studies have shown that IL-3 or the pineal hormone MLT may abrogate macrophage-related suppressive events during IL-2 immunotherapy, while TH2-mediated immunosuppression is not neutralized by MLT or IL-3. On the basis of previous experimental data suggesting the inhibitory effect of IL-12 on TH2 activation, this preliminary study has been performed in an attempt to evaluate the influence of IL-12 on TH2 stimulation induced by IL-2 alone or IL-2 plus MLT, by evaluating the release of IL-10, which represents the main suppressive factor produced by TH2 lymphocytes. Pure lymphocyte cultures were incubated for 4 days with IL-2 (100 Cetus U/ml), MLT (100 pg/ml), IL-12 (1 ng/ml), IL-2 plus MLT, IL-2 plus IL-12 or IL-2 plus MLT and IL-12. Mean medium concentrations of IL-10 were measured by Elisa. IL-2 alone significantly stimulated IL-10 secretion with respect to the control medium alone, while no difference was observed with MLT alone or IL-12. IL-2-induced stimulation of IL-10 secretion was not abrogated by a concomitant MLT incubation. On the contrary, IL-12 significantly diminished IL-10 release in response to IL-2, and this inhibitory effect was more pronounced when IL-2 was added in association with both IL-12 and MLT. This preliminary study would suggest that the two most important immunosuppressive events occurring during IL-2 therapy, which are mediated by macrophages and TH2-lymphocytes, may be abrogated by a concomitant administration of MLT and IL-12, respectively. Therefore, the association of IL-12 could further amplify IL-2 efficacy with respect to IL-2 alone or IL-2 plus MLT.

[Sentinel events in occupational medicine: the example of Local Health Unit No. 1 of the Tuscany region]. / Eventi sentinella in medicina del lavoro: l'esempio della USL n. 1 della Regione Toscana.

In order to apply the "sentinel health event" methodology we reviewed the certificates of 4541 deaths occurred in the period 1/01/83-31/12/88 in the USL 1 (Lunigiana) in the Tuscany Region. The histories of 6 work accidents, 6 cases of pleural mesothelioma, and 2 cases of sinunasal cancers have been collected by means of personal interviews and investigation at various workplaces. It should be noted that a case of sinunasal cancer was discovered in a farmer who used lead arsenate as an insecticidal. Furthermore the wife of a shipyard worker died of pleural mesothelioma. The death of a shipyard worker caused by pleural mesothelioma, provoked the critical review of the other workers of the same company who were also exposed to asbestos. Moreover, 73 deaths were recorded as due to silicosis; among them, 29 occurred in quartzite quarrymen. In addition, among 153 total cases of lung cancer, 9 were found to be associated with silicosis.

Follow-up study of patients with respiratory disease due to toluene diisocyanate (TDI).

The outcome of the respiratory symptoms, pulmonary function tests and bronchial hyperresponsiveness was studied in forty-seven workers with respiratory disease due to toluene diisocyanate (TDI) (twenty-seven asthmatic and twenty non-asthmatic subjects) after about 2 years from the first examination. Eight of twelve asthmatic subjects who left the industry after the first examination complained at the follow-up of dyspnoea and wheezing, but pulmonary function tests were unchanged; bronchial hyperresponsiveness decreased in three, but most were still positive to challenge test with bethanechol at the follow-up. Fifteen subjects who continued their exposure to TDI showed at the follow-up a significant decrease of the spirometric parameters and an increase of the bronchial hyperresponsiveness, and symptoms of chronic bronchitis were more frequent at the second examination. Non-asthmatic subjects, both exposed and non-exposed to TDI at the second examination, showed a significant decrease of the pulmonary function tests but no relevant changes in bronchial hyperresponsiveness. Our data suggest that stopping occupational exposure to TDI frequently did not produce an improvement of the TDI bronchial asthma, and persistence of the occupational exposure causes a more rapid decline in the respiratory function.

Failure of resistive breathing training to improve pulmonary function tests in patients with chronic obstructive pulmonary disease.

The effects on pulmonary function tests and exercise tolerance of resistive breathing training (RBT) were assessed in 16 subjects with stable chronic obstructive pulmonary disease (COPD) who had received no benefit from previous programs of breathing retraining (BR) and medical therapy (MT). 16 male patients with mild degree stable COPD underwent detailed evaluation of pulmonary function tests, blood gas analysis and exercise tolerance test before and after a monthly program of RBT. The patients had received no physiological effects from previous monthly programs of BR and MT. No change in pulmonary function tests, blood gas analysis and exercise tolerance test was observed after RBT. Only maximal static expiratory pressure increased significantly after RBT. We conclude that RBT does not improve pulmonary function tests in subjects who received no physiological benefit from BR.

[Hepatic lesions caused by industrial chemical substances. New perspectives on research]. / Il danno epatico da sostanze chimiche industriali. Alcune nuove prospettive di indagine.

Many industrial chemicals can be able to interfere with metabolic systems and to damage biological cycle of the cell. However the increasing use of MAC and TLV in occupational toxicology, has greatly reduced the incidence of acute effects; but the problem rose of chronic damage, toxic or carcinogenic, due to a long exposure to chemicals in low doses. The comprehension of functional and anatomical changes occupping in the liver can be of great help in investigation of pathogenetic mechanisms of such effects.

Absence of IgG antibodies to TDI-HSA in a radioimmunological study.

Sera of ninety-one workers with respiratory symptoms related to occupational exposure to toluene diisocyanate (TDI) were tested by a solid phase radioimmunoassay using polyvinyl plates, in an attempt to demonstrate specific IgG antibodies to a conjugate of TDI with human serum albumin (TDI-HSA). Different conjugates were prepared. In our radioimmunoassay a TDI-HSA 1600 (1600 micrograms TDI/mg HSA), obtained at alkaline pH with borate buffer, was used; this conjugate was immunologically reactive and did not contain protein macro-aggregates. No difference in percent of binding of radiolabelled anti-human IgG to TDI-HSA coated on plastic plates was found between exposed workers (asthmatic and non-asthmatic) and fifteen normal subjects. This may suggest that either TDI-induced bronchial asthma is not mediated by IgG antibodies, or TDI-HSA conjugate is unsuitable to be detected by anti-isocyanate IgG.