Gianfranco Vivoli

Adverse health effects of selenium in humans

Epidemiologic studies and case reports have shown that chronic exposure to selenium compounds is associated with several adverse health effects in humans. An early toxic effect of selenium is on endocrine function, particularly on the synthesis of thyroid hormones following dietary exposure of around 300 micrograms Se/d, and on the metabolism of growth hormone and insulin-like growth factor-1. Other adverse effects of selenium exposure can be the impairment of natural killer cells activity and at higher levels, hepatotoxicity and gastrointestinal disturbances. Dermatologic effects, such as nail and hair loss and dermatitis, occur after exposure to high levels of environmental selenium. Assessing the toxicity and morbidity after long-term exposure to environmental selenium is difficult: neurotoxicity, particularly the degeneration of motor neurons leading to increased risk of amyotrophic lateral sclerosis, might occur after chronic exposure to both organic and inorganic selenium compounds. The results of laboratory investigations and cohort studies suggest that selenium species exhibit a bivalent effect in cancer, either increasing or decreasing risk. Current environmental selenium exposure limits appear to be inadequate for averting adverse health effects.

Epidemiological survey of amyotrophic lateral sclerosis in the province of Reggio Emilia, Italy: influence of environmental exposure to lead.

We carried out a retrospective incidence, prevalence and mortality survey of amyotrophic lateral sclerosis (ALS) in the province of Reggio Emilia, northern Italy. Based on 79 patients, the mean incidence per year for the period 1980 through 1992 was 1.5 cases per 100,000. On December 31st, 1992, the prevalence rate was 5.4 per 100,000. In the 10-year period of 1983-1992 the average mortality rate was 1.3 per 100,000 per year. The average age at onset was 61.3 +/- 10.2, the average survival period thereafter was 26.3 months +/- 17.7; 27.3 +/- 17.6 for classic ALS, 19.5 +/- 8.4 for progressive bulbar palsy and 36.3 +/- 41.4 for pseudopolyneuritic ALS. The incidence rate, recorded in public health district No.12, an area with documented lead pollution since the 1970s, was standardized to the sex and age of the population of the province. Its incidence and prevalence rate were comparable to the rates found in the remaining area of the province.

Emotional stability, anxiety, and natural killer activity under examination stress.

This study was performed to evaluate the relation between a stable personality trait, a mood state and immune response to an examination stress. A self-reported measure of emotional stability (BFQ-ES scale) was obtained in a sample (n = 39) randomly selected from 277 cadets; this personality trait was also investigated by completing a neuroticism scale (Eysenck personality inventory) and a trait-anxiety scale (STAI). Natural killer (NK) cell activity was measured at baseline, long before the examination time and the examination day. The state-anxiety scale evaluated the response to the stressful stimulus. Taking subjects all together, the academic task did not result in significant modification over baseline in NK cell activity. Subjects were then divided into three groups based on emotional stability and state-anxiety scores: high emotional stability/low anxiety, medium, and low emotional stability/high anxiety. Examination stress induced significant increases in NK cell activity in the high emotional stability/low anxiety group, no effect in the medium group, and significant decreases in the low emotional stability/high anxiety group. The repeated-measure ANOVA revealed a significant interaction of group x period (baseline vs. examination) for both lytic units and percent cytolysis. The results did not change after introducing coffee and smoking habits as covariates. Our findings suggest that the state-anxiety acts in concert with a stable personality trait to modulate NK response in healthy subjects exposed to a psychological naturalistic stress. The relation between anxiety and poor immune control has been already described, whereas the ability of emotional stability to associate with an immunoenhancement has not yet reported. The peculiarity of our population, a very homogeneous and healthy group for life style and habits, can have highlighted the role of emotional stability, and may account for the difference with other studies.

Relationship between lead exposure indicators and neuropsychological performance in children.

This study surveyed 237 schoolchildren in a lead‐polluted industrial area in northern Italy to assess the relationship between various biological indicators (lead in blood, hair and teeth, and delta‐aminolevulinic dehydratase [ALA‐D] activity) and some neuropsychological functions, assessed by a battery of five psychometric tests. The geometric means of lead measured in blood, hair and teeth were 10·99μg/dl, 6·79μg/g and 6·05/·g/g, respectively. Mean ALA‐D activity was 51mU/ml RBC. By analysis of covariance, after regressing out the variance accountable to confounding variables (age, sex, occupation/education of parents), Total and Verbal WISC‐R IQ and Toulouse Pieron test results were significantly affected by the levels of lead in teeth. ALA‐D values also appeared to be related to WISC‐R IQ results (Total, Verbal and Performance).

The epidemiology of selenium and human cancer.

Abstract The relation between selenium and cancer has been one of the most hotly debated topics in human health over the last decades. Early observational studies reported an inverse relation between selenium exposure and cancer risk. Subsequently, randomized controlled trials showed that selenium supplementation does not reduce the risk of cancer and may even increase it for some types, including advanced prostate cancer and skin cancer. An increased risk of diabetes has also been reported. These findings have been consistent in the most methodologically sound trials, suggesting that the early observational studies were misleading. Other studies have investigated selenium compounds as adjuvant therapy for cancer. Though there is currently insufficient evidence regarding the utility and safety of selenium compounds for such treatments, this issue is worthy of further investigation. The study of selenium and cancer is complicated by the existence of a diverse array of organic and inorganic selenium compounds, each with distinct biological properties, and this must be taken into consideration in the interpretation of both observational and experimental human studies.

Zinc and Copper Status and Blood Pressure

In order to elucidate the relationships between Zn and Cu and blood pressure, the present case-control study was carried out. Zn and Cu status was evaluated in 60 subjects, pharmacologically untreated, affected by mild stable hypertension and in 60 normotensives matched for sex, age and smoking habits. Different markers of Zn and Cu status, including serum, erythrocyte and urine levels of the two trace elements and activities of some Zn- or Cu-dependent enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase and lysyl oxidase) were evaluated. No significant difference between hypertensives and normotensives was observed in the mean levels of Zn and Cu as well as in Zn- or Cu-dependent enzymes, though higher levels of serum copper were associated with increased risk of hypertension. Interesting relationships between the biological parameters investigated were observed in the hypertensive subjects. Inverse correlations between blood pressures and serum Zn were observed. Furthermore, blood pressure was inversely related to lysyl oxidase activity. These findings give further support to the hypothesis that an imbalance of Zn and Cu bioavailability may be associated to hypertensive condition.

Biochemical and haemodynamic indicators of stress in truck drivers.

In order to investigate the extent of stress reaction during driving, this study was carried out on truck drivers engaged in long distance work. For each driver, epinephrine, norepinephrine, and cortisol were measured in urine, and dynamic ECG and blood pressure were monitored. The excretion rates of catecholamines showed great individual differences in the size of variations related to driving conditions. Epinephrine excretion rates were particularly high when weather and traffic conditions were more stressful. A relationship was found between epinephrine urinary levels and state-anxiety scores. Urinary excretion of norepinephrine was generally increased at the end of the working day and while driving in fog. The pattern of cortisol was not affected by the stress related to driving. The highest mean heart rates were monitored during difficult traffic and bad weather conditions.

Zinc, copper, and zinc- or copper-dependent enzymes in human hypertension

Imbalance of zinc and copper status has been hypothesized in human hypertension. A case-control study was carried out to elucidate the possible relationship between zinc and copper status and essential hypertension. Thirty-one subjects affected by mild stable hypertension, pharmacologically untreated, were investigated together with 31 normotensive controls individually matched for sex, age, and smoking habits. Zinc and copper in serum and urine were measured, and serum activities of alkaline phosphatase (AP), lactic dehydrogenase (LDH), copper-zinc superoxide dismutase (Cu−Zn SOD), lysyl oxidase (LOX), and monoamine oxidase (MAO) were evaluated. No significant difference in serum and urine zinc and copper content as far as in serum activity of zinc (AP and LDH) or copper (Cu−Zn SOD, LOX, and MAO)-dependent enzymes was found between hypertensives and normotensives. Positive relationships were found in normotensives between serum and urine levels of zinc (r=0.577;p=0.001) and copper (r=0.394;p=0.028), and between serum copper and Cu−Zn SOD (r=0.534;p=0.002). In normotensives, diastolic blood pressure and serum zinc were positively related (r=0.370;p=0.041). In hypertensives, inverse correlations were observed between diastolic blood pressure and AP (r=−0.498;p=0.004) and Cu−Zn SOD (r=−0.452;p=0.011), and between systolic blood pressure and LOX (r=−0.385;p=0.033). Diastolic blood pressure was related to LDH inversely in hypertensives (r=−0.357;p=0.049) and positively in normotensives (r=0.457;p=0.010). In normotensives, diastolic blood pressure was inversely related with MAO (r=−0.360;p=0.046). These findings support the hypothesis that an imbalance of zinc and copper status might be involved in human hypertension.

Risk of birth defects in a population exposed to environmental lead pollution.

To investigate the relation between environmental lead and risk of birth defects in humans, we examined the prevalence at birth of congenital anomalies in an industrial area of northern Italy heavily polluted with lead. Through a population-based registry of birth defects, we identified anomalies diagnosed during three consecutive periods characterized by decreasing environmental lead exposure, 1982-1986, 1987-1990 and 1991-1995. In the lead-polluted area, we observed an excess risk of cardiovascular defects which decreased from 2.59 [95% confidence interval (CI) 1.68-3.82] in the first period to 1.18 (95% CI 0.62-2.06) and 0.97 (95% CI 0.57-1.54) in the subsequent periods. We also found an excess risk of oral clefts and musculoskeletal anomalies, with decreasing trends over time. We could not identify homogeneous patterns of temporal variation for other congenital anomalies, neither did we detect cases of neural tube defects. These results appear to support an association between severe parental lead exposure and specific birth defects.

Cancer mortality in a residential cohort exposed to environmental selenium through drinking water

Cancer mortality from 1986 to 1992 was examined in a cohort of 4419 individuals who had been residing in an area of the municipality of Reggio Emilia, northern Italy, where tap water with unusually high selenium content was accidentally supplied. Mortality for all cancers was not significantly different, both in males and in females, from that expected using death rates in the remaining municipal population as standard rates. No significant difference in mortality for site-specific cancers was observed in males, while in females a higher mortality for malignancies of the lymphatic-hematopoietic tissue overall considered and for non-Hodgkins lymphoma was detected. Even if evaluation of the results is hampered by the low number of cancer deaths on which the analysis is based, findings of the study do not support the hypothesis of a strong inverse independent relationship between dietary intake of selenium and cancer mortality in humans.