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Biomedical subjects

I Iavicoli

Publications and source records attributed to I Iavicoli.

16 recordsLinked to original sources

Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice.

We report results from a replication in second and third generation female mice of accelerated time to puberty associated with low Pb exposure levels . Mice in the 2nd generation study are offspring of mice from the initial study; the 3rd generation mice are offspring from mice in the 2nd generation study. For each generation the time to puberty onset was markedly influenced by exposure to dietary lead. Modest increases in blood lead concentration from a normal background of 2-3 to 8-13 micro g/dl delayed the onset of puberty by 10-20% from a normal of 33-35 days to about 40-43 days; reducing blood lead from 2-3 to 0.7 micro g/dl was associated with profound acceleration of puberty to 21 days, an enhancement by over 30%. This dose-response relationship, which replicates previous novel findings, has possible ecological as well as public health significance and indicates that lead is able to induce biologically significant changes at blood lead levels previously thought to be without effect.

Administration, Oral↗

Below background levels of blood lead impact cytokine levels in male and female mice.

A number of studies have documented that Pb exerts immunotoxic effects on T lymphocytes. In studies designed to explore this general response over a broad dose range, female Swiss mice were administered six different diets containing Pb acetate 1 day after mating. During lactation, the mothers received the same feed given during pregnancy, and the same diets were administered to the offspring for 9 months after weaning. At the end of exposure, blood Pb level in the offspring was determined, and possible changes in two type 1 cytokines (IL-2, INF-gamma) and one type 2 cytokine (IL-4) in the serum were measured. At higher dietary Pb levels (40 and 400 ppm), a significant increase in IL-4 production was associated with a profound decrease in INF-gamma and IL-2 production. At the lowest Pb diet level (0.02 ppm), which resulted in a blood lead level of (0.8 microg/dL), which is below background (2-3 microg/dL) values in humans, increases in INF-gamma and IL-2 production along with a significant decrease in IL-4 production were observed. The findings provide evidence of a reversal of lead-induced cytokine skewing depending on the blood lead concentration. As blood lead concentration increases, there is a notable skewing toward Th2, while the pattern is reversed favoring Th1 development at lower blood lead values. The present findings are also notable since they indicate the potential for dietary Pb to have significant biological effects below normal background concentrations.

Administration, Oral↗

Effects of low doses of dietary lead on puberty onset in female mice.

Female Swiss mice typically display signs of puberty at about 33-37 days of age. In the present investigation (96 female mice tested in 8 Pb exposure levels, n=12 per exposure level), the time to puberty onset was markedly influenced by exposure to dietary lead. While modest increases in blood lead concentrations from a normal background of 2-3 to 13.2 microg/dl delayed the onset of puberty by 15-20% to about 40-43 days, reducing blood lead from 2-3 to 0.7 microg/dl was associated with an acceleration of puberty to 21 days, an enhancement by over 30%. This dose-response relationship represents novel findings of possible ecological as well as public health significance and indicates that lead is able to induce biologically significant changes at blood lead levels previously thought to be without effect.

Administration, Oral↗

Biomonitoring of traffic police officers exposed to airborne platinum.

BACKGROUND: Over the past two decades there has been a substantial increase in environmental levels of palladium, platinum, and rhodium, the platinum group elements (PGEs), due to the widespread use of catalytic converters for automotive traction. AIM: To evaluate urinary platinum levels in occupationally exposed subjects. METHODS: A total of 161 employees from the Rome City Police Force were studied; 103 were traffic police involved in controlling streets with an average flow of vehicles, while the remaining 58 were control subjects engaged only in office work. Platinum quantification in the urine samples of these subjects was carried out by sector field inductively coupled plasma mass spectrometry. RESULTS: There were no statistically significant differences between platinum levels in the group of subjects engaged in traffic control and the control group (4.45 (2.42) ng/l v 4.56 (2.84) ng/l, respectively). CONCLUSIONS: Urinary levels were found to be higher than those reported for other urban populations, thus showing a progressive increase in human exposure to Pt.

Adult↗

Effects of low doses of dietary lead on red blood cell production in male and female mice.

The effect of lead (Pb) ingestion on hematological parameters in male and female Swiss mice was assessed. Eight different doses of Pb were administered through preparation of different feeds. The levels of Pb in the diet were designed to provide exposure below (0.6 to <2.0 microg/dl) and above (>2.0-13 microg/dl) normal background. One litter of mice was exposed to each Pb dose, with the mother given the feed 1 day after mating, and the mother and offspring continuing to receive the feed until the litter was 90 days old. Male and female mice receiving below normal background levels of dietary Pb displayed enhanced red blood cell (RBC) production as measured by increased numbers of RBC and increased hemoglobin and hematocrit values. However, as the blood Pb levels approached 10 microg/dl there was a marked decrease in RBC production. These findings are significant since Pb was biologically active in a stimulating manner below typical background levels (2.0 microg/dl) while adversely effecting red cell synthesis at above background levels (7.0-13 microg/dl) encountered in the environment by humans.

Air Pollutants↗

Effects of per os lead acetate administration on mouse hepatocyte survival.

Previously published studies indicate that hepatotoxicity is associated with high blood lead (Pb) levels in animal models and humans. The present investigation evaluated the effects of in vivo Pb exposure via drinking water on mouse hepatocyte survival in vitro when blood Pb concentrations reflected those seen in children in urban and rural settings (2-15 microg/dl). The findings indicated a biphasic dose-response with low concentrations associated with a modest decrease in hepatocyte survival, while at the highest concentration, survival was significantly enhanced (60%). Since these responses were associated with concentrations normally encountered by children, follow-up investigations are warranted.

Animals↗

Defining hormesis: the necessary tool to clarify experimentally the low dose-response relationship.

The authors comment on Calabrese and Baldwin's paper 'Defining Hormesis', which, to date, is the first attempt to provide a definition of hormesis that goes beyond the different interpretations of this phenomenon reported in the literature. While appreciating the effort made in this study to place hormesis in a general and at the same time specific context, the authors believe some clarifications are needed as regards the quantitative features of this phenomenon. In this connection, they speculate on whether Calabrese and Baldwin think it appropriate to include hormesis assessment criteria in the document, referring in particular to those reported in a previous paper. The authors share Calabrese and Baldwin's conclusion that future experimental models designed to study hormetic phenomena must necessarily include the time factor, which not only guarantees this phenomenon will be detected, but is also able to detect the specific type of hormesis.

Adaptation, Physiological↗

Hormesis and industrial hygiene: a new hypothesis for low-dose response in occupational risk assessment.

The study of Jayjock and Lewis, 'Implication of Hormesis for Industrial Hygiene', represents a challenge for the scientific community to consider hormesis as a possible working hypothesis for redefining risk assessment strategy for low-dose exposures in the realm of industrial hygiene. This invited commentary aims at examining some aspects of the study for which no proven and conclusive scientific evidence has yet been found, such as the limited nature of some statistical tests, the calculation of the safety factor, the place occupied by hormesis in industrial hygiene and, finally, the impact that scarce knowledge of this phenomenon and rejection by part of the scientific community has on the possibility of using hormesis in the safeguarding of workers' health.

Animals↗

The determination of low lead levels in the bone of lead-depleted mice by graphite furnace atomic absorption spectrometry.

Low lead levels in the femurs of mice fed with a lead-depleted diet have been determined by use of electrothermal atomic absorption spectrometry with Zeeman-effect background correction. The method is based on the use of Mg(NO3)2/Pd as matrix modifier which enables significant reduction of the spectral interferences prevalent if chemical modifiers based on NH4H2PO4 with either Ca or Mg are used for samples rich in Ca3(PO4)2 matrix. The method was developed and validated by use of the NIST standard reference material 1486 bone. Bones were decomposed in a pressurized microwave-heated system using 70% nitric acid. Forty-three mice femurs, with a mass of 74.62 +/- 12.54 mg, were dissolved in concentrated nitric acid. The lead results found in SRM 1486 (1.25 +/- 0.15 microg g(-1), n = 9) were in good agreement with the certificate (1.335 +/- 0.014 microg g(-1)). Recoveries of 200 ng lead added to the SRM before or after digestion were 99.0 +/- 1.4% and 98.5 +/- 1.6%, respectively. The lead detection limit in bone samples is 0.06 microg g(-1) dry mass. This method is, therefore, suitable for the determination of very low lead levels (0.06-0.20 microg Pb kg(-1) bone) in the femurs of mice fed a diet with lead level of < 20 microg kg(-1).

Animals↗

Lead-related effects on rat fibroblasts.

Lead (Pb) is an environmental toxicant that can induce structural and functional abnormalities of multiple organ systems, including the central nervous and the immune systems. The aim of this study was to evaluate the effects of extracellular Pb supplementation on the cellular content of the metal and on the proliferation and the survival of normal rat fibroblasts. We found that the concentration of Pb in the culture medium was 0.060 microM and the normal Pb concentration in rat fibroblasts was 3.1 +/- 0.1 ng/10(7) cells. Then we exposed the cells to increasing concentration of Pb (as Pb acetate) from 0.078-320 microM. We observed a dose-dependent inhibition of cell proliferation after 48 h, which was already apparent at a concentration of 0.312 microM (p = 0.122) and became statistically significant for concentration higher than 0.625 microM (p = 0.0003 at 5 microM). Cell proliferation was completely compromised at 320 microM Pb total inhibition of cell proliferation. To investigate the mechanisms of Pb-mediated inhibition of cell proliferation, we evaluated the occurrence of apoptosis in the same cells and found that cytosolic DNA fragments, hallmark of apoptotic cell death, increased significantly at Pb concentrations from 2.5-10.0 microM. The occurrence of apoptosis was also confirmed by FACS analysis which showed the appearance of a subdiploid peak at Pb concentrations from 5-20 microM. The distribution of cells in the cell cycle showed a dose-dependent accumulation of cells in the G0/G1 phase mainly compensated by a decrease in the percentage of cells in the S phase. In conclusion, our results demonstrate that induction of apoptosis contributes to the Pb-induced inhibition of cell proliferation in rat fibroblasts.

Animals↗

Altered cytokine production in mice exposed to lead acetate.

Previous investigations have shown that Pb exerts immunotoxic effects. Object of this study were Th1 and Th2-type immune responses of mice to Pb exposure. Adult Swiss male mice were administered 0, 40 and 400 mg/l of Pb (as acetate) in drinking water for 14 days. At the end of the treatment, blood Pb was determined and two Th1 cytokines (IL-2, INF-gamma) and one Th2 serum cytokine (IL-4) were measured. A significant increase in IL-4 production was observed in the mice exposed to 40 mg/l of Pb, while a further increase in IL-4 production was associated with a decrease in INF-gamma production in mice exposed to 400 mg/l of Pb. On the other hand, Pb exposure did not induce changes of serum IL-2 (involved also in the Th0 immune pattern). Our findings indicate that low level Pb exposure enhances a Th2 response. A high Pb does can either stimulate the Th2 immune activity or reduce the Th1 response; the result is an imbalance between Th1 and Th2 activation.

Animals↗

Lead inhibits growth and induces apoptosis in normal rat fibroblasts.

The effects on normal rat fibroblasts of lead supplementation (as lead acetate) in the medium were examined. The amount of lead acetate ranged from 0.078 microM to 320 microM, at 14 concentrations. The normal level of lead in the medium was 0.060 microM, and the normal concentration of lead in the fibroblasts was 3.1 +/- 0.1 ng/10(7) cells: these represented the control conditions. On studying fibroblast proliferation and survival after incubation for 48 hours, a lead acetate dose-dependent inhibition of cell proliferation was observed, the results being shown to be significant by ANOVA (p < 0.01), and suggesting a significant dose-response relationship. Apoptosis, evaluated by quantifying cytoplasmic DNA fragments, differs significantly between the lead levels tested. The distribution in the cell cycle, evaluated by using a fluorescence-activated cell sorter, showed a dose-dependent accumulation of cells in the G0/G1 phase, with a compensatory decrease in the percentage of cells in the S phase. Moreover, the occurrence of a subdiploid peak confirmed that apoptosis was more evident when the medium was supplemented with lead acetate at concentrations of 5-20 microM. The inhibition of cell growth is probably due to a direct inhibition of cell proliferation.

Animal Testing Alternatives↗

[Potential role of hormesis in risk assessment in occupational toxicology].

Over the past few decades there has been a gradual decline in concentrations of airborne chemical agents in the workplace. This improvement in the workplace has led to a concomitant need to study the effects of low dose exposure in order to assess possible risks. The paradigm used in toxicology to evaluate risk and to establish exposure limits for substances employed in industry, is that the dose-response relationship is expressed by a linear model for carcinogenic substances and by a threshold model for those which are not. Alongside these two traditional models, there has been a recent proposal to describe relationships using hormesis which is characterised by a biphasic curve corresponding to moderate stimulation resulting from response to low doses, and by inhibition at high doses. Although hormesis has been widely observed in experimental contexts, it still has to be tested in occupational toxicology to determine the possibility of obtaining a more accurate evaluation of the risk of exposure to low doses present in the workplace.

Humans↗

[Biomonitoring of iridium in a urban population].

Iridium (Ir) is one of the six elements collectively known as the platinum group metals. For its excellent catalytic properties, Ir was recently introduced into DeNOx, a new generation of automotive catalysts. The aim of our study was to evaluate urinary Ir levels in an urban population. A total of 122 healthy male subjects of Rome (Italy) were studied. Ir quantification in the urine samples of these subjects was carried out by sector field inductively coupled plasma mass spectrometry. The mean urinary Ir level was 10.41 ng/g creatinine (standard deviation: 9.67; 25th-75th percentile: 3,62-12,74 ng/g creatinine). The scientific community should respond to a potential increase in environmental exposure to Ir, due to its growing use as a catalyst, with very careful evaluation of the biological levels of this metal and monitoring of airborne particulate present in the life environment. Further investigation will enable researchers to confirm and integrate the findings of our present study undertaken in the context of surveillance.

Adult↗

[The antimony conflict].

Antimony, which was already well known to the ancients, in the Middle Ages was known as Lupus metallorurn--the grey wolf--a key material in alchemists' attempts at purifying gold. Over subsequent centuries antimony returned within the bounds of conventional scientific and experimental knowledge, but inspired numerous studies, works of literature and investigations in important fields of medicine. Antimony has always aroused more interest than one might expect from a simple metal. The fact that it has been used since ancient times in cosmetics and then in alchemy gave it both positive and negative connotations, reflecting its possible uses and the benefits for health but also the potential harm. For a certain period antimony was virtually the symbol for a range of uses in alchemy or empirical medicine, in the face of modern scientific knowledge, and aroused debate that went well beyond its actual physical and chemical properties. Bernardino Ramazzini's work in the 17th-18th centuries signalled the recognition that the use of antimony was linked to health risks. Today it is put to many uses in many fields of industry and medicine, so our interest in this metal is no longer exclusively a question of history, but is highly topical.

Antimony↗