Underground Radiobiology: A Perspective at Gran Sasso National Laboratory.

Scientific community and institutions (e. g., ICRP) consider that the Linear No-Threshold (LNT) model, which extrapolates stochastic risk at low dose/low dose rate from the risk at moderate/high doses, provides a prudent basis for practical purposes of radiological protection. However, biological low dose/dose rate responses that challenge the LNT model have been highlighted and important dowels came from radiobiology studies conducted in Deep Underground Laboratories (DULs). These extreme ultra-low radiation environments are ideal locations to conduct below-background radiobiology experiments, interesting from basic and applied science. The INFN Gran Sasso National Laboratory (LNGS) (Italy) is the site where most of the underground radiobiological data has been collected so far and where the first in vivo underground experiment was carried out using Drosophila melanogaster as model organism. Presently, many DULs around the world have implemented dedicated programs, meetings and proposals. The general message coming from studies conducted in DULs using protozoan, bacteria, mammalian cells and organisms (flies, worms, fishes) is that environmental radiation may trigger biological mechanisms that can increase the capability to cope against stress. However, several issues are still open, among them: the role of the quality of the radiation spectrum in modulating the biological response, the dependence on the biological endpoint and on the model system considered, the overall effect at organism level (detrimental or beneficial). At LNGS, we recently launched the RENOIR experiment aimed at improving knowledge on the environmental radiation spectrum and to investigate the specific role of the gamma component on the biological response of Drosophila melanogaster.

Cardiovascular risk factors in healthy women with previous small for gestational age infants.

AIM: To investigate whether healthy women with a previous pregnancy complicated by a small for gestational age (SGA) infant have normal endothelial function, carbohydrate and lipid metabolism, and normal inflammation parameters. MATERIAL AND METHODS: Brachial artery flow-mediated dilatation (FMD, endothelium-dependent) was measured in 16 subjects with previous SGA, and in 15 controls (CTR) with previous normal pregnancies. Lipid panel, glucose, insulin, tumor necrosis factor alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (s-ICAM), soluble vascular (s-VCAM-1) adhesion molecule-1 (s-VCAM-1), and androgens were also measured. RESULTS: FMD was reduced in women with previous SGA compared to controls (P < 0.0001). SGA women showed increased insulin resistance (P < 0.0001), s-ICAM-1 (P = 0.008), TNF-alpha (P = 0.02), testosterone (P = 0.03), and diastolic blood pressure (P = 0.01) than CTR. CONCLUSION: Endothelial dysfunction, reduced insulin sensitivity and subclinical inflammation are present in otherwise healthy women with previous SGA. These abnormalities show that the presence of a SGA infant in the obstetric history should be considered as a risk factor for cardiovascular disease later in life.

Longitudinal changes of adiponectin, carbohydrate and lipid metabolism in pregnant women at high risk for gestational diabetes.

To evaluate, in pregnant women at high risk for gestational diabetes (GDM), the longitudinal changes of adiponectin, carbohydrate and lipid metabolism, and to assess their independent value as risk factors for the development of GDM. Fifty women at beginning of pregnancy were studied. Adiponectin, insulin sensitivity (homeostasis model assessment, HOMA) and lipid panel were measured at 1st, 2nd and 3rd trimesters of pregnancy. Twelve patients developed GDM. In both groups, GDM and normal glucose tolerance (NGT), adiponectin decreased from 1st to 2nd and 3rd trimesters by about 5 and 20% (GDM, p < 0.05), and of about 17 and 25% in NGT (p < 0.05), respectively. Values observed in NGT were similar to those of GDM (F = 9.401; p = 0.238). The Cox regression model identified as the strongest independent risk factor for GDM HOMA over 1.24 (RR = 14.12) at 1st trimester, fasting glycaemia over 87 mg/dl (RR = 42.68) triglycerides over 158 mg/dl (RR = 5.87) and body mass index (BMI) over 27 kg/m(2) (RR = 4.38) at 2nd trimester. Adiponectin in high-risk women is characterised by a constant reduction throughout gestation, irrespective of the development of GDM. HOMA, fasting glycaemia, triglycerides and BMI, but not adiponectin are independent predictors of GDM.

Cardiovascular risk factors in healthy women with previous gestational hypertension.

CONTEXT: Epidemiological studies indicate that gestational hypertension (Gh) during pregnancy is associated with increased risk of cardiovascular disease in later life. However, it is unclear whether particular metabolic and hemodynamic characteristics are related to this risk. OBJECTIVE: The objective of this study was to investigate endothelial function and carbohydrate and lipid metabolism in healthy, normotensive women with previous pregnancy complicated by Gh. DESIGN, SETTING, AND PARTICIPANTS: Brachial artery flow-mediated dilatation (FMD; endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured in 15 subjects with previous Gh and in 15 controls with previous normal pregnancies. Lipid panel, glucose, insulin, homocysteine, and androgens were also measured. RESULTS: FMD was significantly reduced in women with previous Gh compared with controls (P < 0.0001), whereas nitroglycerin-induced dilatation was comparable in both groups. Gh women showed increased fasting insulin (P = 0.011), insulin resistance measured by homeostasis model assessment (P = 0.018), free fatty acids (P = 0.0018), and testosterone (P = 0.0012) and decreased high-density lipoprotein cholesterol (P = 0.0017) compared with controls. Across all subjects, FMD showed a strong independent negative correlation with testosterone and homeostasis model assessment and a positive correlation with high-density lipoprotein cholesterol (r = -0.60, P = 0.0003; r = -0.43, P = 0.016; and r = 0.58, P = 0.0005, respectively). CONCLUSIONS: Endothelial dysfunction and early alteration of carbohydrate and lipid metabolism are present in otherwise healthy women with previous Gh. These abnormalities along with a relative hyperandrogenism could explain, at least in part, the increased risk for cardiovascular disease in later life in these women.