Evaluation of antioxidative and diabetes-preventive properties of an ancient grain, KAMUT® khorasan wheat, in healthy volunteers.

PURPOSE: Recently, there was an increasing interest on the use of ancient grains because of their better health-related composition. The aim of this study was to evaluate in healthy human subjects the antioxidative and diabetes-preventive properties of ancient KAMUT® khorasan wheat compared to modern wheat. METHODS: The study was a randomized, non-blind, parallel arm study where the biochemical parameters of volunteers with a diet based on organic whole grain KAMUT® khorasan products, as the only source of cereal products were compared to a similar replacement diet based on organic whole grain modern durum wheat products. A total of 30 healthy volunteers were recruited and the intervention period lasted 16 weeks. Blood analyses were performed before and after the diet intervention. The effect of KAMUT® khorasan products on biochemical parameters was analyzed by multiple quantile regression adjusted for age, sex, physical activity and BMI compared to data at baseline. RESULTS: Subjects receiving KAMUT® khorasan products showed a significantly greater decrease of fat mass (b = 3.7%; CI 1.6-5.5; p = 0.042), insulin (b = 2.4 µU/ml; CI 0.2-4.2; p = 0.036) and a significant increase of DHA (b = - 0.52%; CI - 1.1 to - 0.12; p = 0.021). CONCLUSIONS: Our study provides evidence that a substitution diet with KAMUT® khorasan wheat products can reduce some markers associated to the development of type-2 diabetes compared to a diet of modern wheat.

Effects of in vitro supplementation with Syzygium cumini (L.) on platelets from subjects affected by diabetes mellitus.

The aim of this study was to assess the in vitro effects of Syzygium cumini (L.) (Sc) incubation on platelets from patients with diabetes, in order to test its efficacy as a potential adjuvant therapy. This study was performed on 77 patients with diabetes [29 in good (DMgc) and 48 in poor glycemic control (DMpc)] and 85 controls. In patients, platelets were analyzed at recruitment and after in vitro Sc incubation (final concentration of 200 µg/ml for 3 hours at 37 °C), whereas in controls only basal evaluation was performed. Lipoperoxide and nitric oxide (NO) levels, superoxide dismutase (SOD) and Na(+)/K(+) ATPase activities, total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of fluorescent probes 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1-6-phenyl-1,3,5-hexatriene (DPH) were determined. Collagen-induced platelet aggregation was also evaluated. In vitro Sc activity counteracts oxidative damage, by improving platelet function through augmented membrane fluidity and Na(+)/K(+) ATPase activity; it also enhances antioxidant system functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels both in whole samples and in DMgc and DMpc. In addition, a slight tendency towards collagen-induced platelet aggregation decrease after Sc was observed. However, all these parameters, even after improvement, did not reach the levels of control subjects. Our results suggest that Sc may have a preventive and protective effect in oxidative damage progression associated with diabetes mellitus and its complications. If our data will be confirmed, Sc supplementation might become a further tool in the management of this disease, especially in view of its easy availability, safety, low cost, and absence of side effects.

Pro-inflammatory cytokine alterations in recent onset anorexia nervosa adolescent female patients before and after 6 months of integrated therapy: A case-control study.

Anorexia nervosa (AN) is a complex disorder affecting mainly, but not only, teenagers. Researchers agree that AN is deeply associated with a pro-inflammatory state following an impaired immune system, resulting from altered levels of cytokines such as IL-1ß and TNF-α, also impacted by the frequent depressive states. Thus, this case-control study aimed to evaluate the relationship between patients suffering from AN undergoing specialized eating disorder treatment for AN and pro-inflammatory cytokines. To reach our purpose, we assessed eating-related psychopathology and depressive symptoms and measured serum concentration of pro-inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α before and after 6 months of integrated therapy (which included psychopharmacotherapy, psychotherapy, and nutritional treatment), to define whether selected pro-inflammatory cytokines could be considered a pathophysiological marker of the disorder. A sample of 16 young female patients with early diagnosis of AN, and without any previous treatment, and 22 healthy controls matched by age, sex, and socioeconomic status were enrolled. After 6 months of integrated therapy, a significant decrease of all selected pro-inflammatory cytokines was detected. In addition, an improvement in the anxiety-depressant aspects was also noted. In conclusion, the results obtained suggest that pro-inflammatory cytokines are indeed related to the pathophysiology of AN. However, further investigations, involving larger samples of patients with distinct subtypes of AN, are essential to confirm the current findings.

Nitric oxide and peroxynitrite platelet levels in gestational hypertension and preeclampsia.

The aim of the study was to investigate platelet nitric oxide (NO) pathways in women with Gestational Hypertension (GH), Preeclampsia (PE) and Controls. Platelet NO(x) and peroxynitrite (ONOO(-)) levels, inducible (iNOS) and endothelial nitric oxide synthase (eNOS) and Nitrotyrosine expression (N-Tyr) in 30 women with GH, 30 with PE and 30 healthy pregnant controls, age, parity and gestational age-matched, were assessed. Platelet NO(x) and ONOO(-) levels were significantly higher in GH and PE vs. Controls, with higher levels in GH vs. PE. At the same way, iNOS and N-Tyr were significantly higher in GH and PE vs. Controls, with higher levels in GH vs. PE. Since GH expressed higher amount of NO metabolites and higher activation of iNOS compared to PE, we can hypothesize that the severity of hypertensive pathology is almost not related to only NO metabolism, this research confirmed that GH and PE are associated with marked changes in NO pathways; it is not easy to understand if they could be interpreted as causes or consequence of these pathologic states.

Oxidative stress in ischaemic stroke.

BACKGROUND: Production of reactive oxygen species after ischaemic stroke may enhance tissue damage through multiple molecular pathways. MATERIALS AND METHODS: In this study, we examined the serum levels of lipoperoxide and hydroperoxide, conjugated dienes and total antioxidant capacity levels in 50 patients with acute ischaemic stroke (T0) to evaluate the possibility to use them as specific biochemical markers for cerebral ischaemia. Determinations were repeated after a month (T1) to correlate their relative changes with clinical evolution. RESULTS: Lipoperoxide, hydroperoxide and conjugated diene levels in platelets were significantly higher in the early stages with respect to their late evaluation. On the contrary, total antioxidant capacity showed a significant increase at T1 with respect to T0. A significant negative correlation between total antioxidant capacity and NIHSS score at T0 and T1 was found. There was a significant positive correlation between lipoperoxide, hydroperoxide and conjugated dienes levels and NIHSS score at T0 and at T1. CONCLUSIONS: These findings suggest that changes in free radical generation and consequent oxidative stress may have a role in the pathogenesis of acute ischaemic lesions. The activation of defence mechanisms like total antioxidant capacity could be involved in the limitation of ischaemic damage progression.

Alterations of platelet biochemical and functional properties in newly diagnosed type 1 diabetes: a role in cardiovascular risk?

BACKGROUND: The involvement of platelets in the pathogenesis of diabetic vascular complications is supported by several studies. Type 1 diabetic (T1D) platelets show increased adhesiveness and aggregation related to a modification of nitric oxide synthase activity. Moreover, different cell types from diabetic patients showed a decreased membrane Na(+) /K(+) -ATPase activity, which might be involved in diabetic complications. The aim of this study was to investigate whether T1D at onset is able to induce alterations of platelet physicochemical and functional properties and whether these changes are affected by hyperglycaemia. METHODS: The study was performed on 50 young subjects: 30 patients (1-14 years) affected by T1D and 20 age- and gender-matched healthy subjects. We analyzed platelet membrane fluidity by fluorescent anisotropy of 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene, Na(+) /K(+) -ATPase, nitric oxide, and peroxynitrite production. RESULTS: In T1D subjects, we observed an increased fluidity in the plasma membrane outer part and greater rigidity in the internal part compared with that in controls. Na(+) /K(+) -ATPase activity and nitric oxide levels were significantly reduced, while peroxynitrite production was increased compared with that in controls. Moreover, correlations found between the above parameters were correlated with fasting glycaemia and haemoglobin A(1c). CONCLUSIONS: T1D patients exhibit structural and functional modifications of platelet membrane properties and alterations of nitric oxide metabolism due to diabetes per se and not to chronic hyperglycaemia, insulin therapy, or ageing. These results support the hypothesis that oxidative attack could be an important early event in the pathogenesis of diabetic complications.

Anorexia nervosa: a role for L-arginine supplementation in cardiovascular risk factors?

OBJECTIVE: The aim of the present study was to evaluate the effects of a short-term oral L-arginine treatment on platelet NO production, intracellular calcium concentration, iNOS and eNOS expression, in AN patients. METHOD: Forty outpatients belonging to restricting subtype and 40 normal participants age and sex matched were enrolled in the study. RESULTS: NO production was significantly elevated in the platelets from AN patients compared with controls while [Ca(2+)](i) was significantly decreased in patients with respect to controls. Western blot analysis demonstrated that iNOS isoform was more pronounced in the cell lysates from AN patients than controls. After supplementation with L-arginine, both NO production and [Ca(2+)](i) seem to return to control levels, suggesting a probable recovery of their metabolisms. The same was found after western blot analysis of NOS expression. DISCUSSION: The results here proposed can be considered highly indicative of a positive effect of L-arginine supplementation on platelet NO production in AN patients.

Free thiols in human spermatozoa: are Na+/K+-ATPase, Ca2+-ATPase activities involved in sperm motility through peroxynitrite formation?

The aim of the present study was to measure free thiols content, Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities in human spermatozoa of asthenozoospermic patients and normospermic donors, and evaluate any influence on kinetic sperm features, as well as correlation with peroxynitrite. In fact, membrane integrity and its composition are the basic characteristics of the sperm membrane; thus, it is evident that its composition is an important factor for membrane functions that can be modified upon oxidation. A total of 70 infertile patients affected by idiopathic asthenozoospermia and 25 normal fertile donors were enrolled. Control spermatozoa exhibited Na(+)/K(+)-ATPase, and Ca(2+)-ATPase activities, cytoplasmic Ca(2+) concentration and free -SH content significantly higher than those of asthenozoospermic patients (P < 0.0001). Moreover, positive associations were found between Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities and total sperm motility and sperm kinetic features, whereas negative associations were found between peroxynitrite and Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities, and total SH content. Peroxynitrite is able to reduce Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities and intracellular Ca(2+) concentration, through possible depletion of free thiols content. Decrease in motility and loss of sperm function in idiopathic asthenozoospermia can be attributed to these sulphydryl groups, important entities of the sperm membrane.

Platelet membrane fluidity and Na+/K+ ATPase activity in acute stroke.

Stroke is a consequence of a reduction in cerebral blood flow but the mechanisms involved in the production of ischemic damage are complex and probably not fully known. It is hypothesized that alterations in platelet membrane fluidity are directly related to the severity of the stroke as measured by the National Institute of Health Stroke Scale (NIHSS). Thus, the aim of the present study was to investigate Na+/K+ ATPase activity and platelet membrane fluidity, measured by fluorescent probes TMA-DPH and DPH in patients affected by ischemic stroke and controls in order to identify, if any, chemical-physical and/or functional modifications associated with cerebral ischemic damage. Patients were divided into three groups according to the presence of vascular risk factors (Diabetes Mellitus, Hypertension and Smoking) in order to evaluate the possible influence of each risk factor on the NIHSS score and both Na+/K+ ATPase activity and platelet membrane fluidity. Data showed a significant decrease in both Na+/K+ ATPase activity and platelet fluidity values in patients compared to controls. Moreover, all three groups showed a negative significant correlation between NIHSS and Na+/K+ ATPase activity and a positive significant correlation between NIHSS, TMA-DPH and DPH. In conclusion, the present data point out that alterations in the platelet membrane's chemical-physical (decreased fluidity) and functional properties (reduced Na+/K+ ATPase activity) rose proportionally with NIHSS increase. These modifications and their interaction with some vascular risk factors might be involved in the pathogenesis of ischemic damage development.

A study on the action of vitamin E supplementation on plasminogen activator inhibitor type 1 and platelet nitric oxide production in type 2 diabetic patients.

BACKGROUND AND AIM: Type 2 diabetic (T2DM) patients show decreased fibrinolysis, mainly linked to high plasminogen activator inhibitor type 1 (PAI-1) production, together with a reduced bioavailability of nitric oxide and an impairment in Na(+)/K(+)-ATPase activity possibly involved in increased cardiovascular risk. Vitamin E is the major natural lipid-soluble antioxidant in human plasma. The present work was conducted in order to measure PAI-1, ICAM and VCAM-1 plasma levels, platelet nitric oxide production and membrane Na(+)/K(+)-ATPase activity in type 2 diabetic subjects treated with vitamin E (500 IU/day) for 10 weeks and then followed for other 20 weeks. METHODS AND RESULTS: Thirty-seven T2DM patients (24 males and 13 females) were studied. None of them were affected by any other disease or diabetic complications. Significant differences were detected for PAI-1 antigen (p<0.001), PAI-1 activity (p<0.001), nitric oxide (NO) production (p<0.001), and Na(+)/K(+)-ATPase activity (p<0.001) among the 4 phases of the study. A significant decrease both in ICAM and VCAM-1 plasma levels was also found at the 10th week compared with baseline (respectively p<0.001 and p<0.05). CONCLUSION: Our data suggest that vitamin E counteracts endothelial activation in T2DM patients possibly representing a new tool for endothelial protection.

Platelet nitric oxide production and IR: relation with obesity and hypertriglyceridemia.

BACKGROUND AND AIM: Three NOS isoforms are responsible for nitric oxide production in various tissues. Endothelial constitutive NOS is expressed in vascular endothelium and in platelets, contributing to vascular tone regulation and platelet aggregation. The aim of the present work was to examine eNOS polymorphism, to find a correlation with platelet NO production and degree of insulin resistance (IR) in non-diabetic subjects and in patients affected by type 2 diabetes. METHODS AND RESULTS: Seventy-one non-diabetic subjects and 37 patients affected by Type 2 diabetes were recruited. The subjects were subdivided into 3 groups as cut-off for the definition of an insulin resistant state: IR non-diabetic subjects, insulin sensitive subjects, and insulin-resistant patients affected by Type 2 diabetes. Plasma glyco-metabolic parameters, platelet nitric oxide production, endothelial nitric oxide synthase (eNOS) gene polymorphism were measured in all subjects enrolled. Significant differences between groups were found in BMI, fasting glycaemia, fructosamine and HbA(1c), triglycerides and HDL cholesterol levels. Evaluating all the subjects, platelet NO production was significantly related with BMI, waist circumference, and triglycerides concentrations, thus suggesting an association between increased platelet NO production, obesity and hypertriglyceridemia, independent of the degree of insulin-resistance. CONCLUSION: The modified platelet NO synthesis does not seem to be due to eNOS Glu298Asp polymorphism, while it can be hypothesized that it is caused by an iNOS induction, present in obesity, hypertriglyceridemia and in type 2 diabetes.

Platelet-Derived NO in Subjects Affected by Type 2 Diabetes with and without Complications: Is there any Relationship with their Offspring?

Macro- and microvascular complications are currently the principal causes of morbidity and mortality in patients with diabetes mellitus. Aim of this study was to determine if type 2 diabetic patients with nephropathy and coronary artery disease showed altered platelet-derived nitric oxide (NO) production, compared with diabetic subjects without complications, and if this alteration is also present in their diabetic offspring. In this case-control observational study, platelet NO and peroxynitrite content was determined on plasma from 60 male adult type 2 diabetic patients and 60 male offspring type 2 diabetic patients. Plasmatic levels of homocysteine were also determined in the same individuals. Moreover, Western blot analysis of platelet lysates was performed with specific monoclonal antibody for endothelial (eNOS) and inducible (iNOS) nitric oxide synthase. Our study showed a lower piastrinic production of NO in the group of parents without complications (ADH), compared with the group of offspring without complications (YDH) and with the groups of parents with complications. Furthermore, we observed a lower synthesis of peroxynitrite in platelets from the ADH group than in the groups of patients with complications, and in the YDH group compared with all other groups. Subjects from YDH group also showed lower iNOS expression, compared with all other groups. Our data suggest that alterations in nitric oxide metabolism may represent potential risk factors in type 2 diabetes complications, such as nephropathy and cardiovascular diseases, leading to development of new therapeutic strategies in order to delay and prevent the onset of such complications.

Effect of 1-y oral supplementation with vitaminized olive oil on platelets from healthy postmenopausal women.

OBJECTIVE: Olive oil is the main fat source in the Mediterranean diet and shows a protective role against aging and related diseases. Osteoporosis represents a serious health problem worldwide and is associated with an increased risk for fractures and mortality. Nutrition should be part of bone disease prevention strategies, especially in light of the aging population and the effect of diet on bone health. The aim of this study was to investigate whether oral supplementation with extra virgin olive oil (VOO) enriched with vitamins D3, K1, and B6 (VitVOO) is able to modify some physicochemical and functional plasma membrane properties and nitrosative stress markers status. METHODS: In this single-center, randomized placebo-controlled trial, 60 postmenopausal women were administered either VitVOO or placebo (PlaVOO). After 1 y of oral supplementation, platelet membrane fluidity changes, Na+/K+-ATPase activity, serum nitric oxide, and peroxynitrite levels were determined in participants. RESULTS: After 1 y (time 1), women taking VitVOO showed lower nitric oxide levels than those taking PlaVOO; the same trend was found for peroxynitrite levels. As far as membrane fluidity was concerned, a significant decrease in anisotropy of diphenylhexatriene and trimethylammonium-diphenylhexatriene at time 1 in VitVOO participants compared with PlaVOO was found. Finally, Na+/K+-ATPase activity showed a significant increase after VitVOO supplementation. CONCLUSION: The supplementation of VitVOO into the diet of postmenopausal women could represent a proper tool for platelet function and a useful strategy against nitrosative stress and related diseases, thus confirming the antioxidant role played by the added vitamins.

Placental expression of endothelial and inducible nitric oxide synthase and NO metabolism in gestational hypertension: a case-control study.

OBJECTIVE: Hypertension is one of the most common medical disorders in pregnancy and a role of nitric oxide (NO) metabolism has been described. Thus, the present work aimed at determining placental gene expression of eNOS and iNOS, to measure NO and ONOO(-) levels in patients with gestational hypertension (GH). METHODS: Fifteen patients with GH and 15 healthy pregnant controls were enrolled in the study. Placental tissue was taken immediately after delivery and was stored at -80 °C until analysis. A piece of frozen tissue was homogenized in the appropriate buffer. Total RNA was extracted and was reverse transcribed to obtain complementary DNA that was used for real-time PCR for iNOS and eNOS expression, whereas NO and ONOO(-) production were measured by commercially available kits. RESULTS: Placental eNOS and iNOS mRNA levels were significantly reduced in GH when compared to controls. NO and ONOO(-) production were both significantly higher in GH than controls. CONCLUSIONS: The reduced eNOS and iNOS gene expression in women with GH reinforces the hypothesis that the mechanisms involving NO pathways, may promote oxidative damage, by contributing to the reduced blood flow and increased resistance in the feto-maternal circulation and suggests the use of NO modulators as useful tools in GH management.

Age-related changes on platelet membrane: a study on elderly and centenarian monozygotic twins.

Cellular senescence is a biological process associated with aging and longevity. Successful aging is believed to be related to the ability to cope with different environmental stresses. The objective of this study was to investigate if cellular senescence is associated with platelet membrane modifications on subjects of different age, in particular on monozygotic twins and if these changes might be affected by both genetic components and environmental factors. The work was performed on 81 monozygotic twin pairs of different age. Platelet membranes from centenarian twins showed: decreased both basal lipid peroxide levels and membrane fluidity compared with elderly subjects; Na(+)/K(+)-ATPase activity and SA content are similar to those evaluated in young group, suggesting one of their important roles in the successful aging. We concluded that platelet membranes from centenarians show deeper structural and functional modifications than in elderly subjects and that these changes might play a protective role against oxidative damage. No statistical difference in biochemical parameters was observed between two sibpairs in each twin pair highlighting that environmental factors (diet, life-style) affect age-related platelet membrane changes less than their common genetic component. Thus genetic factors might play an important role in the mechanisms at the basis of successful aging.

Higher Levels of Oxidized Low Density Lipoproteins in Alzheimer's Disease Patients: Roles for Platelet Activating Factor Acetyl Hydrolase and Paraoxonase-1.

Alzheimer's disease (AD) is associated with oxidative damage of low density lipoproteins (ox-LDL). In order to investigate whether higher levels of ox-LDL are related to alterations of the activity of enzymes involved in lipid metabolism, we studied the activity of paraoxonase-1 (PON1) and platelet activating factor acetylhydrolase (PAF-AH) in AD patients and the relationship between biochemical markers and severity of the disease. Levels of ox-LDL, PON1 (paraoxonase, arylesterase, and lactonase activities), and PAF-AH activity were evaluated in plasma from 49 patients affected by AD and from 34 control subjects matched for gender and age. Our results demonstrated alterations in the activities of PON1 and PAF-AH in AD patients compared to controls and showed, for the first time, a relationship between the activities of these enzymes, ox-LDL levels, and severity of the disease. A significant negative correlation was observed between the ratio PON1/PAF-AH and ox-LDL. Whatever the causes that contribute to a systemic oxidative stress in AD, our results have shown that AD patients exhibit higher PAF-AH activity than control subjects and higher ox-LDL. This phenomenon, in combination with diminished PON1 in these patients and, consequently, the relatively lower ratio PON1/PAF-AH activity, could contribute to inflammation and oxidative stress of plasma lipoproteins.

Oxytocin, its antagonist Atosiban, and preterm labor: a role for placental nitric oxide.

OBJECTIVE: The aim of the present study was to understand the role played by Atosiban, an oxytocin receptor antagonist, on trophoblastic human cells, and the molecular bases of its efficacy and safety in the treatment of preterm labor. NO, peroxinitrite production and NOS expression have been evaluated on placenta obtained from term and preterm labors. PATIENTS AND METHODS: We studied trophoblast cells isolated from selected placental tissue from 20 controls and 20 preterm patients after cesarean sections. Each sample was studied at basal state and after 2 hours incubation with oxytocin and Atosiban. RESULTS: Significant variations of NO levels, peroxynitrite production and iNOS and eNOS expression both in the preterm, term samples and in each of the considered groups were observed. In the control group Atosiban re-established NO levels that were reduced after incubation with oxytocin, while in preterm samples NO levels were not only re-established but, after incubation with Atosiban, significantly increased compared to basal levels. CONCLUSIONS: This confirms the beneficial role of Atosiban in prolonging the pregnancy of spontaneous labor at very early gestational periods. In conclusion, Atosiban might be an effective drug to prevent preterm labor, in the therapeutic approach to this pathology.

Effect of 1-year dietary supplementation with vitaminized olive oil on markers of bone turnover and oxidative stress in healthy post-menopausal women.

Osteoporosis represents a serious health problem worldwide associated with an increased risk of fractures and mortality. Nutrition should form part of bone disease prevention strategies, especially in the light of the population ageing and the diet effect on bone health. Thus the study aimed at verifying whether 1 year of oral supplementation with either extra virgin olive oil (VOO) enriched with vitamins D3, K1 and B6 (VitVOO) or VOO used as placebo (PlaVOO) is able to modify some bone turnover and oxidative stress markers. Bone mineral density (BMD) was assessed in 60 healthy post-menopausal women together with the bone vitamin K status by measuring undercarboxylated osteocalcine (ucOC) plasma levels, the ratio between ucOC and carboxylated osteocalcine (UCR) and the relations with oxidative stress markers. After 1 year (T 1), subjects taking VitVOO showed lower ucOC levels than those taking PlaVOO; the same trend was found for UCR. As far as BMD is concerned, a significant increase in T-score at T 1 in VitVOO subjects compared to PlaVOO was found. All oxidative stress markers as thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes showed a significant reduction after VitVOO supplementation, whilst plasma total antioxidant capacity values was significantly increased in VitVOO group compared to PlaVOO group at T 1. It might be suggested that the use of VitVOO in the diet of post-menopausal women could represent a proper tool for bone protection and a useful strategy against oxidative stress and related diseases, thus confirming the antioxidant role played by the added vitamins.

Evidence for reduction of pro-atherosclerotic properties in platelets from healthy centenarians.

The aim of the present study was to investigate if aging is associated with platelet membrane modifications possibly related with cellular activation and hyperaggregability and if platelets from centenarians show different properties which might play a role in successful aging and longevity. Platelet plasma membranes were obtained from 60 healthy subjects, divided into four groups according to the age range: (1) 21-39 years; (2) 40-59 years; (3) 60-79 years; (4) centenarians (>/=100 years). Both centenarians and control subjects were submitted to the following inclusion criteria: liver, kidney, and thyroid function tests within the normal range; absence of history of diabetes, hypertension or coronary heart disease; no signs of edema or dehydration; no drug or vitamin supplement in the 4 weeks before the study; absence of Alzheimer's disease or secondary dementia. The following determinations were performed: lipid peroxide levels (Lp) evaluated by the measurement of thiobarbituric acid (TBA) reactivity, fluidity studied by the fluorescence anisotropy of the probe 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), Na(+)/K(+)-ATPase activity measured by the method of Kitao and Hattori, and sialic acid (SA) content evaluated by the periodate-thiobarbituric acid method. Centenarians showed: (i) Lp concentrations lower than elderly subjects; (ii) increased Na(+)/K(+)-ATPase activity compared with adult and elderly subjects; (iii) higher TMA-DPH anisotropy than elderly subjects; (iv) SA content similar to the young and adult groups.The present work found deep platelet membrane modifications in centenarians compared with elderly subjects. These changes are likely associated with a decreased platelet activation and therefore might exert a protective role against cardiovascular accidents, as platelet activation is a key event in the initiation and progression of arteriosclerosis.

Alzheimer's disease and diabetes: new insights and unifying therapies.

Several research groups have begun to associate the Alzheimer Disease (AD) to Diabetes Mellitus (DM), obesity and cardiovascular disease. This relationship is so close that some authors have defined Alzheimer Disease as Type 3 Diabetes. Numerous studies have shown that people with type 2 diabetes have twice the incidence of sporadic AD. Insulin deficiency or insulin resistance facilitates cerebral ß-amyloidogenesis in murine model of AD, accompanied by a significant elevation in APP (Amyloid Precursor Protein) and BACE1 (ß-site APP Cleaving Enzime 1). Similarly, deposits of Aß produce a loss of neuronal surface insulin receptors and directly interfere with the insulin signaling pathway. Furthermore, as it is well known, these disorders are both associated to an increased cardiovascular risk and an altered cholesterol metabolism, so we have analyzed several therapies which recently have been suggested as a remedy to treat together AD and DM. The aim of the present review is to better understand the strengths and drawbacks of these therapies.