Greater efficacy of pulsatile insulin in type I diabetics critically depends on plasma glucagon levels

The aim of this study was to investigate the role of plasma glucagon levels on the blood glucose response to intravenous insulin administered continuously or in a pulsatile manner. Six type I diabetic patients proven to have no residual insulin secretion were investigated. Endogenous glucagon secretion was inhibited by a continuous intravenous infusion of somatostatin (100 micrograms/h) and replaced by exogenous infusions of the hormone at three different rates (7.5, 4.5, and 2.5 micrograms/h), resulting in three different plasma glucagon steady-state levels (i.e., approximately equal to 200, approximately equal to 130, and approximately equal to 75 pg/ml, respectively). Each subject, in random order and on different days, was infused intravenously with regular human insulin either continuously (0.17 mU X kg-1 X min-1) or with the same amount of insulin infused in a pulsatile manner (0.85 mU X kg-1 X min-1 during 2 min followed by 8 min during which no insulin was infused). At plasma glucagon levels approximately equal to 200 pg/ml, blood glucose rose from approximately 10 to approximately 13 mM without any difference between the two modalities of insulin infusion. For plasma glucagon levels approximately equal to 130 pg/ml, plasma glucose remained steady throughout the experiments, but during the last 40 min, plasma glucose levels were significantly lower when insulin was administered intermittently. This greater blood glucose-lowering effect of pulsatile insulin occurred earlier and was more pronounced for plasma glucagon levels averaging 75 pg/ml. We conclude that the greater hypoglycemic effect of insulin administered intravenously in a pulsatile manner in type I diabetics critically depends on plasma glucagon circulating levels.     

Role of alpha and beta cells in the impaired glucose tolerance of thalassaemic subjects

Fifty healthy and 12 thalassaemic subjects underwent both an oral glucose tolerance test (OGTT) and arginine test in order to investigate their alpha and beta cell activity. While basal plasma levels were similar in both group of subjects (82 +/- 4 vs 74 +/- 4 mg/dl, p = NS), following glucose intake impaired glucose tolerance was observed in thalassaemic subjects. These subjects showed impaired insulin secretion either in steady-state conditions or after glucose intake. When an arginine test was performed in thalassaemic subjects, impaired insulin secretion with concomitant exaggeration of glucagon response was also observed. In the thalassaemic subjects no statistically significant correlations were found between impaired insulin secretion and iron overload. It is suggested that in thalassaemic subjects beta-cell dysfunction and alpha cell overactivity may lead to the development of diabetes mellitus.     

Upper extremity deep vein thrombosis after suspension of progesterone-only oral treatment.

The intake of steroid hormone contraceptives is a strong and independent risk factor for venous thromboembolism. Several studies have assessed an increased risk of venous thromboembolism in women using oral contraceptives who are carriers of the G20210A mutation in the prothrombin gene. Most trials evaluating the thrombotic risk of oral contraceptives are based on combined oral preparations, but only a few focus on progestogen-only oral preparations. Results from such studies are conflicting and globally assess the thrombotic risk, ranging from modest to slightly increased. Furthermore, little is known about the relationship between the C677T mutation in the methylenetetrahydrofolate reductase gene and the progestogen-based preparations. Herewith we report the case of a 49-year-old woman with a complex genetic thrombosis risk factor who had taken oral progesterone for 15 months without any complication, but then experienced severe left upper extremity deep vein thrombosis 2 months after the drug suspension.     

Heparin-interacting sites of bovine lactoferrin are involved in anti-adenovirus activity

Lactoferrin, a member of the transferrin family of approximately 80 kDa, consists of a single polypeptide chain folded in two symmetric, globular lobes (N- and C-lobes), each able to bind one ferric ion. This glycoprotein, found in physiological fluids of mammals, plays an important role in immune regulation and in defense mechanisms against bacteria, fungi, parasites, and viruses. Although the antiviral activity of lactoferrin is one of the major biological functions of such protein, the mechanism of action is still under debate. We have investigated both the role of tryptic fragments of bovine lactoferrin and the mechanism of lactoferrin antiviral effect toward adenovirus infection in HEp-2 cells. The results obtained demonstrated that the anti-adenovirus activity of lactoferrin is mediated by the N-terminal half of the protein as the N-lobe was able to inhibit adenovirus infection, even if at lower extent than undigested lactoferrin, whereas C-lobe was ineffective. The results also showed that the anti-adenovirus action of lactoferrin and of its N-terminal peptide lactoferricin took place on virus attachment to cell membrane, mainly through competition for common glycosaminoglycan receptors. The data provide evidence that the anti-adenovirus activity of lactoferrin is mediated mainly by the cluster of positive charges at the N-terminus of whole molecule and that the N-terminal peptide lactoferricin alone is sufficient to prevent infection.     

Chemokines and pro-inflammatory cytokines in Down's syndrome: an early marker for Alzheimer-type dementia?

BACKGROUND: People with Down's syndrome (DS) show early Alzheimer-like dementia. It has been suggested that the pro-inflammatory cytokine class plays a role in Alzheimer's disease (AD). The study aims at verifying whether pro-inflammatory cytokines in DS are correlated with age, affective symptoms and intellectual decline to a different degree than in subjects with non-DS learning disabilities. METHODS: Cases: 19 subjects with DS; controls: sex- and age-matched individuals with learning disabilities caused by perinatal ischaemic damage. The level of mental retardation was assessed according to DSM-IV; psychopathological symptoms were measured by the Assessment and Information Rating Profile. Serum levels of cytokines were determined with ELISA. RESULTS: DS patients showed higher levels of cytokines and chemokines, with the exception of RANTES; but the only significant difference detected was for MIP-1alpha. A correlation between the degree of mental retardation and IL-6, and between MIP-lalpha and age was found in patients with DS, but not in controls. CONCLUSIONS: The data obtained suggest a possible involvement of chemokines in the inflammatory and degenerative processes similar to AD in DS. Further longitudinal research is required to confirm these findings.     

Study of thermal resistance and in vitro bioaccessibility of patulin from artificially contaminated apple products

Apple juices and purees represent categories widely consumed by whole population and above all children. Patulin (PAT) is a mycotoxin known for its acute and chronic effects in animals. Several studies indicate there is a risk associated to the PAT intake, through the consumption of purees and apple juices. In this study, apple juice and puree were prepared and artificially contaminated with PAT at 50 μg/kg and submitted to a thermal treatment simulating pasteurization to evaluate PAT’s reduction. In a second phase of the work, apple products samples (n = 7) included juices, nectars and purees belonging to different commercial brands were collected, artificially contaminated with PAT at 50 μg/L (limit established for PAT in juices) and 25 μg/kg (limit established for PAT in purees), digested with an in vitro gastrointestinal protocol and bioaccessibility values (%) were calculated.