[Neonatal group B Streptococcus infection: an integrated approach (of clinical pathologists, gynecologists, midwives, pediatricians-neonatologists) of the functional area of Cuneo (Italy)]. / Infezione neonatale da Streptococco B: un approccio multidisciplinare integrato (di laboratoristi, ginecologi, ostetriche e pediatri-neonatologi) del Quadrante di Cuneo.

The frequency of early-onset neonatal sepsis without prophylaxis is 1-5/1.000 live births. Since year '70 the most frequent causative microorganism is the group B Streptococcus (S. agalactiae, GBS), followed by Escherichia coli. The mortality rate is now reduced to 4% due to the improvement of neonatal intensive care. In the USA, the incidence of GBS early-onset neonatal sepsis has been markedly reduced by the application of the guidelines released by the Centers for Disease Control (CDC). This strategy, however, is not effective on occurrence of late-onset neonatal group B streptococcal disease. In Italy, the application of CDC guidelines is not customary, and different, often complex, protocols of obstetrical-neonatological integrated approach are applied. The frequency of infectious risk has made the GBS a paramount problem for the neonatologist, even for the legal responsibility issues resulting from the multiplicity of possible options. To reach the best level of protection of the newborn against early-onset GBS infection, the working group of providers of prenatal, obstetric, and neonatal care of the functional area of Cuneo issued an integrated protocol, in order to perform the GBS screening with the optimal culture method suggested by CDC guidelines in the highest possible number of pregnant women, and to standardize the obstetrical and neonatal management.

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.

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.

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.

Puberty onset in Northern Italy: a random sample of 3597 Italian children.

Entering puberty is one of the most important milestones in life. Studies from around the world have shown that age of pubertal changes onset can vary with race and ethnicity, environmental conditions, geographical location and nutrition. In the last century, the onset of puberty progressively shifted back towards younger ages in several European countries, with a levelling off in the last decades. The aim of our study was to describe the prevalence of secondary sexual characteristics in a group of children living in Northern Italy comparing them with the percentile values published by Tanner in 1976. We enrolled 3496 children drawn from public schools and evaluated height, weight and pubertal stages. The analysis of our data evidenced that the 50th percentile age of puberty onset in both sexes decreased by about 1 yr compared to data published by Tanner. Mean body mass index (BMI) z-score was significantly higher (p = 0.01) in pubertal than in pre-pubertal girls, on the contrary it was higher (p = 0.005) in pre-pubertal than in pubertal boys. In conclusion, our study found that girls and boys of our region are beginning pubertal development about 1 yr earlier than Tanner's British population. Taking into consideration the 3rd percentile age for Tanner's breast stage 2 in girls and testicular volume (TV) of 4 ml in boys, the current internationally used cut-off age for precocious puberty, i.e. 8 yr for girls and 9 yr for boys, can be maintained in our population.

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.

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.

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.

[Three cases of pleural mesothelioma and environmental pollution with tremolite outcrops in Lucania]. / Tre casi di mesotelioma pleurico ed inquinamento ambientale da rocce affioranti di tremolite in Lucania.

In a circumscribed rural area of Lucania (Italy) three cases of pleural mesothelioma have been identified: two men, 83 and 52 years old and a 78 year-old woman, who all had in common the fact of being shepards in that area. Possible asbestos pollution sources have been sought: we have immediately excluded an asbestos manufactured articles pollution, however we have highlighted the presence of "green stones", which had always been known to the local inhabitants and which, in three subsequent campains of collecting and chemical-mineralogical investigations, have resulted partly constituted by amphibole asbestos, classified as tremolite. Official institutions are organising a series of initiatives to verify the hypothesis of a causal relationship between the presence of tremolite and the cases of pleural mesothelioma, and preventive initiatives aimed at reducing exposure and to a sanitary surveillance. Similar problems had been identified in Turkey, Greece, Corsica, New Caledonia and recently in eastern Sicily.

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.

[Safety and health protection of professional divers in the context of the European Diver Technology Committee (EDTC): technical training and diver competence, role of the "examining" physician]. / La sicurezza e la tutela della salute dell'operatore subacqueo professionale nel contesto del Comitato Europeo di Tecnologia Subacquea (EDTC): formazione tecnica e competenza del sommozzatore, ruolo del medico "esaminatore".

It is necessary to standardize some parameters for occupational health and safety of their professional diver: risk assessment of work duty, appropriate training program and sanitary surveillance. European Diver Technology Committee (EDCT) gathers the member State's experience about safety procedures, professionals and sanitay surveillance. EDTC criterions to whom it is possible to refer in Italy waiting specific regulations are reported.

[Secular trend of puberty]. / Secular trend della pubertà

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.

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.

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.

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.

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).

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.