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SUMMARYAECA were detected in 25 of 71 patients with type 1 diabetes mellitus and in two of 33 healthy subjects. Patients with diabetes of

Reproductive dysfunction with ageing has been so far extensively characterized in terms of depletion of ovarian follicles and reduced ability to produce gametes competent for fertilization. Nevertheless, molecular mechanisms underlying this process are still poorly understood. In the present study we addressed the hypothesis that methylglyoxal (MG), a major precursor of Advanced Glycation Endproducts (AGE), may contribute to molecular damage occurring during ovarian ageing. Our results showed that the biochemical activity of glyoxalase 1, the main component of the MG scavenging system, is significantly decreased in ovaries from reproductively-aged mice in comparison with the young group. This effect was associated with decreased expression at protein and RNA level of this enzyme and increased intraovarian level of MG. MG-arginine adducts argpyrimidine as detected with a specific antibody was found to accumulate with ageing in specific ovarian compartments. Separation of ovarian proteins by 2D gels and Western blotting revealed an approximate 30-fold increase in the extent of protein glycation in aged ovaries along with the appearance of eight argpyrimidine modified proteins exclusive for the aged group. In conclusion, the present results show that impaired MG detoxification causing relevant damage to the ovarian proteome might be one of the mechanisms underlying reproductive ageing and/or ageing-like ovarian diseases.

In low dose radiobiology, there is a strong interest in phenomena that could imply a deviation from the linear-no-threshold (LNT) model, which is currently used to estimate the excess relative cancer risk at low doses of ionizing radiation (IR) via a linear extrapolation from high- and intermediate-dose epidemiology risk data. Such phenomena include the adaptive response as well as bystander effects , occurring in cells which do not experience direct radiation exposure. These phenomena suggest that biological response to harmful agents such as ionising radiation may be more complex than that assumed by the LNT model. In particular, environmental background radiation represents a source of chronic low dose-rate exposure which may condition the response of living systems to acute exposure to genotoxic agents, also including IR itself, via an adaptive response. To clarify this aspect is essential not only to better evaluate the risk of chronic occupational exposure, but also to understand the role of environmental background radiation on biological evolution. Reduction of background environmental IR dose rate exposure is achieved at the National Laboratories at Gran Sasso (LNGS) of the Italian Institute for Nuclear Physics (INFN). Located underneath the Gran Sasso mountain range in central Italy, these laboratories offer an excellent opportunity to continuously maintain cell cultures at extremely reduced levels of environmental background radiation. The Cosmic Silence experiment represents the natural extension, to a human cell culture model (TK6 lymphoblastoid cells), of earlier experimental studies on S. Cerevisiae (L. Satta et. al. Mut Res 1995) and V79 Chinese hamster fibroblasts (L. Satta et. al. Radiat Environ Biophys 2002), which indicated a progressive disappearance of an adaptive response in cells kept under reduced environmental background IR conditions. For the Cosmic Silence experiment, TK6 parallel cultures were set up in the underground LNGS laboratories and in Rome and planned to be maintained and assayed for 12 months. Starting at 6 months of continuous, parallel cultures, measurements of DNA damage (micronuclei) or oxidative metabolism (antioxidant enzymatic activities of SOD, GPx, and Catalase) indicate that significant deprivation of environmental background IR renders cells less tolerant to an acute X-ray exposure of 1-2 Gy. These results are compatible with the concept that environmental background IR is behaving as an adaptive agent.

Anti-single-stranded(ss)DNA antibodies were searched for by enzyme-linked immunosorbent assay (ELISA) in the serum of 202 outpatients with non-insulin-dependent diabetes mellitus and 135 healthy subjects to investigate their prevalence in the serum of patients with type 2 diabetes and their relationship with the presence of vascular complications. Of the 202 patients 128 had vascular complications. Anti-ssDNA antibodies were observed to be significantly more frequent in the serum of patients with vascular complications (33.6%) and in particular in patients with overt nephropathy (50%) than in patients without complications (6.7%) or controls (6.7%). Anti-ssDNA antibodies have been previously described in patients with type 1 diabetes before clinical evidence of vascular disease, and their cross-reactivity with a variety of anionic biological molecules or cells, i.e. platelets and endothelial cells, assessed. It seems not unreasonable that these autoantibodies detected in patients with type 2 diabetes could be of importance in the pathogenesis or progression of angiopathy.

Our aim was to evaluate body composition in a group of coeliac disease adolescents on a gluten-free diet and to re-examine them at the end of the adolescence spurt. We studied 48 patients (group 1A), 30 age-matched healthy controls (group 2A), 11 group 1A patients after 4 years (group 1B) and 11 adolescents who were age- and sex-matched with group 1B (group 2B). Weight, height, bone mineral content, fat mass, fat-free mass (FFM) and bone mineral density were evaluated using dual-energy X-ray absorptiometry. All parameters were lower in group 1A than in group 2A subjects ( p

Myeloperoxidase was measured in the plasma and in the supernatants of polymorphonuclear granulocyte cultures from patients with Behçet's disease. High levels were found in both plasma and supernatants from patients with active disease. The addition of pentoxifylline to granulocyte cultures determined a significant decrease of myeloperoxidase levels in active patients only. Hyperactive neutrophils are present during the course of Behçet's disease and may be considered of importance in the pathogenesis of the vascular lesions.

Anti-myeloperoxidase (anti-MPO) antibodies were detected in 34 of 88 (38%) patients with type 1 diabetes mellitus but in only 3 of 55 (5.7%) healthy subjects and in 4 of 20 patients with autoimmune disease. Specificity of anti-MPO antibodies was assessed by MPO inhibition studies. No relationship was found between the occurrence of anti-MPO and anti-thyroperoxidase antibodies. Levels of soluble intercellular adhesion molecule 1 (ICAM-1) were found to be higher in anti-MPO antibody-positive (n = 28, 508 +/- 126 ng/ml) than in anti-MPO antibody-negative (n = 58, 438 +/- 140 ng/ml: P < 0.05) patients. A state of chronic neutrophil activation has been described in diabetes mellitus. As anti-MPO antibodies can stimulate neutrophils to damage endothelial cells in systemic vasculitis, this suggests that a similar mechanism may be operative in the development of diabetic angiopathy.