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Biomedical subjects

N Castellino

Publications and source records attributed to N Castellino.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children.

OBJECTIVE: The presence of both the GH secretagogue (GHS) receptor and ghrelin in the pancreas indicates an involvement of this hormone in glucose metabolism. Ghrelin secretion is increased by fasting and energy restriction, decreased by food intake, glucose load, insulin and somatostatin in normal adults; however, food intake is not able to inhibit circulating ghrelin levels in children, suggesting that the profile of ghrelin secretion in children is different from that in adults. Moreover, how ghrelin secretion is regulated in childhood as a function of fat mass is still unclear. DESIGN AND SUBJECTS: We studied the effect of oral glucose load (75 g solution orally) on circulating total ghrelin levels in 14 obese children (group A, four boys and 10 girls, aged 9.3 +/- 2.3 years) and 10 lean children (group B, five boys and five girls, aged 9.7 +/- 3.8 years). MEASUREMENTS: In all the sessions, blood samples were collected every 30 min from 0 up to +120 min. GH, insulin and glucose levels were assayed at each time point. RESULTS: Glucose peaks following an oral glucose tolerance test (OGTT) in groups A and B were similar; however, both basal and OGTT-stimulated insulin levels in group A were higher than in group B (P < 0.05). Basal total ghrelin levels in group A (281.3 +/- 29.5 pg/ml) were lower (P < 0.0005) than in group B (563.4 +/- 81.5 pg/ml). In both groups A and B, the OGTT inhibited total ghrelin levels (P < 0.005). In terms of absolute values, total ghrelin levels in group A were lower (P < 0.0005) than those in group B at each time point after glucose load. The percentage nadir in total ghrelin levels recorded in group A (-25% at 90 min) was similar to that recorded in group B (-31% at 120 min). Total ghrelin levels were negatively associated with BMI (r = 0.5, P < 0.005) but not with glucose or insulin levels. CONCLUSION: Ghrelin secretion is reduced in obese children. It is, however, equally sensitive in both obese and lean children to the inhibitory effect of oral glucose load.

Administration, Oral↗
PubMed2005

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↗
PubMed2004

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↗
PubMed2004

Ghrelin gene polymorphisms and ghrelin, insulin, IGF-I, leptin and anthropometric data in children and adolescents.

BACKGROUND: Previous investigations on the ghrelin gene reported three common polymorphisms (Arg51Gln, Leu72Met, and Gln90Leu), but their role in overweight and obese individuals remains to be clarified. OBJECTIVE: To ascertain whether these genetic variants could influence ghrelin secretion and play a part in predisposing to earlier onset of obesity or in modulating the overweight phenotype in childhood. DESIGN AND METHODS: Mutational analysis of the entire ghrelin gene and total and acylated plasma determinations were performed in 81 obese or overweight children and adolescents (46 were obese and 35 overweight: Ob/Ow). We also recruited 168 normal-weight healthy controls (72 young adults and 96 children) for mutational or plasma ghrelin analysis. RESULTS: Median total and acylated plasma ghrelin concentrations were significantly lower in Ob/Ow individuals than in controls (175 pg/ml compared with 345 pg/ml, P<0.0001, and 95 pg/ml compared with 114 pg/ml, P<0.0001, respectively). The ghrelin gene variants showed similar allele frequencies in the Ob/Ow individuals and in controls; in the former, they were not associated with any change in total and acylated circulating ghrelin concentrations or anthropometric data. The Leu72Met status was associated with a positive family history for obesity (75% for Leu72Met compared with 39% for Leu72Leu, P=0.03) and with a greater percentage of newborns born 'large for gestational age' (33% for Leu72Met compared with 5% for Leu72Leu, P=0.03), but in the control group it was related to a lower mean body mass index z-score (-0.03 for Leu72Met and -0.47 for Leu72Leu, P=0.04). CONCLUSION: Our present findings do not support the hypothesis that the ghrelin gene polymorphisms have a relevant impact in the secretion of total and acylated ghrelin.

Adolescent↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

Circulating ghrelin levels as function of gender, pubertal status and adiposity in childhood.

Ghrelin, a natural GH secretagogue, exerts remarkable endocrine and non-endocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated to insulin secretion, enhanced in anorexia and reduced in obesity. Ghrelin levels in childhood have never been evaluated. We measured morning ghrelin levels after overnight fasting in 29 healthy lean children (NC) and in 36 obese children (OBC). The results were compared with those recorded twice in 3 different sessions in healthy lean adults (NA). In NA ghrelin levels showed good within-subject reproducibility without gender-related differences. Ghrelin levels in NC [(median; 25 degrees -75 degrees centile): 426.0; 183.0-618.0 pg/ml] were similar to those in NA (380.5; 257.7-551.7 pg/ml). Ghrelin levels in OBC (229.5; 162.5-339.5 pg/ml) were lower (p<0.03) than in NC (426.0; 183.0-618.0 pg/ml). Both in NC and in OBC, ghrelin levels were independent of gender and pubertal status. In all children, ghrelin levels were negatively associated (p<0.05) to weight excess (r=-0.24), insulin (r=-0.28) and IGF-I (r=-0.4) levels. In conclusion, these findings demonstrate that morning ghrelin levels after overnight fasting show good within-subject reproducibility, and are similar in both sexes and do not vary from childhood to adulthood. In childhood, circulating ghrelin levels are reduced in obese subjects being negatively correlated to overweight and insulin secretion.

Adult↗
PubMed2002

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↗
PubMed2002

[Secular trend of puberty].

The aim of our study was to evaluate the age of the onset of pubertal characteristics in a population of Northern Italy and to compare our data with the pubertal staging scale defined by Tanner in 1976. These observations may help us to verify if even in Italy there is a positive secular change in sexual maturation, as has been observed in many European countries. We studied 3510 children (1868 males and 1642 females) aged 6-15 years, born between 1983 and 1996. In every subject sexual maturity was evaluated according to Tanner stages. We calculated the percentile distribution for ages of attainment of B2 and PH2 stages for females and G2, PH2 and testicular volume = or >4 ml (VT4) for males. In females the percentile values for B2 were: 3rd=8.1, 50th=10.5, and 97th=12.6 years. In males the percentile values for G2 and VT4 were: 3rd=8.8 and 9.1 years respectively, 50th=11 years, and 97th=13.4 and 13.3 years respectively. 3rd, 50th, and 97th centiles for pubic hair stage 2 were 8.1, 10.6 and 12.6 years for females and 8.8, 11.2 and 13.4 years for males. For all stages an earlier pubertal development was seen in comparison with Tanner data. One hundred-twenty-five girls had already reached menarche. Median (interquartile range) age at menarche was 11.9 (11.4-12.4) years showing a decrease compared with Tanner values. Our data clearly demonstrate a positive secular trend in pubertal development and point out the need of having updated references values of the timing of sexual maturation for the whole Italian population.

Adolescent↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

Estimation of lead intake from crystalware under conditions of consumer use.

The purpose of this study was to estimate the lead intake from crystalware resulting from short-term contacts with beverages, under conditions that are likely to occur to a consumer. The extraction ability of different kinds of beverages was estimated by comparison with 4% acetic acid under conditions of continuous contact for 3 h. It was found that lead release increased in the following order: cola drink > HAc > whisky > white wine. Under conditions of repeated use under different scenarios, lead release showed a steep decrease with increasing number of contacts, for both wine and cola drink. The maximum lead intake resulted from the cola drink, corresponding to an ingestion of 14.5 micrograms Pb for consumption of 350 ml beverage. Assuming a fixed contribution from the diet of 71 micrograms/day, in the six scenarios taken into consideration, total daily lead intake levels ranged from a minimum of about 76 micrograms up to a maximum of 86 micrograms lead. As these values, converted on a weekly basis, would correspond to 35% and 40% PTWI respectively, significant health risks resulting from the ingestion of beverages in contact with crystalware can be excluded. Finally it was found that the use of a dishwater did not affect significantly the release of lead into wine, while release into cola drink was slightly but significantly increased after the third cycle.

Alcoholic Beverages↗
PubMed1999

Work-related musculoskeletal complaints in sonologists.

The prevalence of musculoskeletal complaints of the hand and wrist, and the neck and back, in physicians who operate sonography equipment was evaluated, and associations between these complaints and various work-related and personal variables were studied. A questionnaire survey was distributed among physician sonographers (sonologists) in Italy. The relationship between work habits and musculoskeletal complaints was analyzed by logistic regression models adjusted for gender, age, and duration of work with ultrasound. A total of 2041 physician sonographers completed the questionnaire. It was found that a large proportion of the subjects regularly had work-related complaints, such as neck and back pain (NBP) (18.5%) or hand and wrist cumulative trauma disorder (HWD) (5.3%). Roughly 80% of the sonographers were currently affected, or had been affected in the past, by one or more work-related symptoms. Various work-related factors appeared to be related to musculoskeletal syndromes. The average time spent for each examination was related both to NBP and HWD. Discomfort for transducer design was the best predictor of HWD, whereas a comfortable chair and correct position of the body protected from the onset of NBP. These results support the role of ergonomic factors in the pathogenesis of both NBP and HWD in sonographers.

Adult↗
PubMed1999

Occupational exposure to lead--granulometric distribution of airborne lead in relation to risk assessment.

The amount of airborne lead absorbed by the body during occupational exposure depends not only on lead concentration in workplace air, but also on the granulometric distribution of the aerosol. The Occupational Safety and Health Administration (OSHA) set the lead Permissible Exposure Limit (PEL) at 50 micrograms/m3 on the basis of Bernard's model and a number of assumptions, including assumption "C", which predicts that the first 12.5 micrograms/m3 are made up of fine particles (aerodynamic diameter < 1 micron) whereas the remaining 12.5 micrograms/m3 consist of particles > 1 micron. Occupational exposure to airborne lead at a concentration of 50 micrograms/m3 and a granulometric distribution calculated according to the above mentioned assumption, leads, in the model, to a mean blood level of 40 micrograms/dl. In the present study, we tested the validity of assumption "C" in the environmental air of a factory that manufactured crystal glassware containing 24% lead oxide. An 8-stage impactor was used to measure the particle size of airborne dust collected from personal and area samplings. Results indicate that, on the whole, assumption "C" cannot be considered valid in the work environment investigated in this study. As a result, lead absorption levels in exposed workers may be noticeably different from those predicted by the OSHA model. We therefore suggest that in order to make a correct evaluation of the risk of occupational exposure to lead, it is essential to integrate total airborne lead concentration with a measurement of the granulometric distribution of the aerosol.

Aerosols↗