1,721,342 research outputs found

    Central Italy: unexpected macro- and micro-nutrient deficiencies in regular diet of residents from Pisa province. the potential role of medical education in young people

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    Evidence-based nutrition principles and recommendations for prevention of diabetes and related complications as well as of cardiovascular disease are an integral component of medical nutrition therapy. The American Diabetes Association (ADA) recommends that dietary intake of fat is reduced to no more than 30% of total calories (saturated 15-20% of total daily energy. American Heart Association (AHA) dietary guidelines advice limiting salt intake (1.0. Foods containing carbohydrate from whole grains, fruits, vegetables, and low-fat milk should be included in a healthy diet. The total amount of carbohydrate in meals or snacks is more important than the source or type. Carbohydrate and monounsaturated fat together should provide 60-70% of energy intake. In subjects living in Pisa (Central Italy), we have provided first evidence indicating unhealthy lifestyle and dietary behaviors, which could even predispose to the development of diabetes and cardiovascular complications. The distribution of energy sources was incorrect. The proportion of caloric intake derived from total fat and cholesterol did not match general guidelines. Most controls (presumed to be consuming a free diet) ate up to 50% more protein than recommended as RDAs/AIs. Total dietary fiber consumption was above the suggested threshold of 25 g/day only in 27% of all participants. A relevant and unexpected health issue was the evidence of mild to moderate combined-vitamin deficient intakes in otherwise well-nourished healthy adults. Estimated daily intakes of water-soluble vitamin B9 (or total folates) and fat-soluble vitamin D and vitamin E were deficient in comparison with RDAs and AIs (400 μg, 5 to 10 μg, and 15 mg, respectively). Increasing age was associated with increasing body mass and decreasing activity in sport in front of an unchanged intake of total calories. These observations have been recently confirmed through one-year follow-up of type 2 diabetic patients with high cardiovascular risk (according to UKPDS Risk Engine). Medical education partially succeeded in modifying such habits in young people with type 1 diabetes, whereas inveterate habits of aged people with type 2 diabetes seemed hard to change

    Oxidative stress in families of type 1 diabetic patients: further evidence

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    The link between hyperglycemia and the complications of diabetes is unknown. It is still discussed whether oxidative stress precedes or merely reflects diabetic complications. To search for a familial predisposition to oxidative stress, we investigated indexes of glucose and lipid metabolism, markers of plasma and cell lipid oxidation, a marker of oxidant-induced protein damage, and the effects of oxygen radicals on erythrocytes (or red blood cells [RBCs]) of patients with type 1 diabetes and their relatives. RESEARCH DESIGN AND METHODS: We recruited 30 type 1 diabetic subjects (10 without diabetic complications, 10 with retinopathy, and 10 with nephropathy), 36 nondiabetic siblings, 37 nondiabetic parents of type 1 diabetic subjects, and 3 control groups of healthy subjects without a family history of diabetes. Levels of blood creatinine, glucose, HbA(1c), cholesterol, triglycerides, lipoprotein(a) (Lp[a]), fibrinogen, malondialdehyde (MDA), and advanced oxidation protein products were determined. The RBC response to oxidative stress (3-h incubation at 37 degrees C with or without a radical generating system) was evaluated by measuring RBC glutathione (GSH), RBC-MDA, and hemolysis. RESULTS: Diabetic patients had higher levels of blood glucose (P < 0.001), HbA(1c) (P < 0.001), Lp(a) (P < 0.01), and fibrinogen (P < 0.05) than control subjects. Siblings of diabetic patients had higher Lp(a) levels (P < 0.001). Parents had higher levels of plasma glucose (P < 0.05) and Lp(a) (P < 0.01). Plasma and RBC-MDA were significantly elevated in diabetic subjects and relatives compared with control subjects. Basal RBC-GSH was lower in diabetic subjects (P < 0.01). In diabetic subjects, incubations of cells caused a decrease in RBC-GSH of a lesser degree than that in control subjects, but they caused a significant increase in hemolysis. Among relatives, hemolysis was increased both at baseline and after incubation. Plasma MDA levels were associated with blood glucose, creatinine, and fibrinogen levels (multiple r = 0.5, P < 0.001), and basal RBC-MDA levels were associated with plasma Lp(a), fibrinogen, and plasma MDA levels (r = 0.6, P < 0.001). Basal RBC-GSH content correlated with serum glucose and RBC-MDA production (r = 0.3, P < 0.01). CONCLUSIONS: Our study is the first to present evidence that markers of lipoprotein metabolism (Lp[a]), oxidative stress (plasma and RBC-MDA), and cellular fragility (hemolysis) are abnormal in nondiabetic relatives of type 1 diabetic subjects, thereby supporting the view that familial elements of diabetes even precede the onset of diabetes. It seems reasonable that the same biological markers considered major predictors of cardiovascular disease can also trace familial susceptibility to type 1 diabetes, just as they have been associated with the development of type 2 diabetes

    Na(+)-H(+) exchange activity throughout pregnancy: the proper experimental approach.

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    Pregnancy is associated with a 30-50% rise in cardiac output and a close to 50% increase in blood volume. The Na(+)-H+ exchanger is a key mediator of tubular NaCl absorption and a stimulus-response coupling mediator. We measured erythrocyte Na(+)-H+ exchange activity over the course of normal pregnancy in 18 healthy pregnant women (mean age 32 +/- 4 years) at 14, 24 and 33 weeks of gestation and 15 nonpregnant healthy women (mean age 32 +/- 9 years). No pregnancy was complicated by hypertension. Serum urea, creatinine and sodium did not change through gestation, while serum potassium slightly but significantly decreased. Urinary excretion rates of both sodium and potassium remained unchanged. Urea and creatinine clearances were constantly elevated in pregnant vs non-pregnant control women. Erythrocyte Na(+)-H+ exchanger reached the highest activity at about the 14th week of gestation, when cardiac output also peaked. Thereafter, it tended to decrease, yet remaining above the normal values until the 34th week. Conceivably, the observed hyperactivity of the transporter may be a contributing factor to the hemodynamic adjustments attending to normal pregnancy

    Automated measurement of urinary cholinesterase activity

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    We propose the schedule of chemistry parameters to program the assay of urinary cholinesterases (total, acetyl-, pseudo- and aliesterase) in a widely utilized autoanalyzer (BM/Hitachi System 704 model). The program allows one to maximally simplify and abridge the assay procedure, yet it improves the quality of the enzymatic reaction kinetics

    Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme

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    Dipeptidyl peptidase-4 (DPP4) or adenosine deaminase complexing protein 2 (ADCP 2) or T-cell activation antigen CD26 (EC 3.4.14.5.) is a serine exopeptidase belonging to the S9B protein family that cleaves X-proline dipeptides from the N-terminus of polypeptides, such as chemokines, neuropeptides, and peptide hormones. The enzyme is a type II transmembrane glycoprotein, expressed on the surface of many cell types, whose physiological functions are largely unknown. Protein dimerisation should be required for catalytic activity and glycosylation of the enzyme could impact on its physiological functions. The dimeric glycoprotein ADCP has been found linked to adenosine deaminase (ADA) whose relationship with lymphocyte maturation-differentiation is well-established. Since implicated in the regulation of the biological activity of hormones and chemokines, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, DPP4 inhibition offers a new potential therapeutic approach for type 2 diabetes mellitus, as monotherapy and adjunct therapy to other oral agents. The clinical use of presently available orally active inhibitors of DPP4, however, has been associated with side effects that have been in part attributed to the inhibition of related serine proteases, such as DPP8 and DPP9. Indeed, it is noteworthy that CD26 has a key role in immune regulation as a T cell activation molecule and in immune-mediated disorder. All-cause infections were increased after sitagliptin treatment. It is noteworthy that the effects of DPP4 inhibition on the immune system have not been extensively investigated. So far, only routine laboratory safety variables have been measured in published randomised controlled trials. The review summarises present knowledge in the field and suggests some potential directions of future research

    Central Italy: Physical Activity of Female Residents From Pisa Province

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    Regular moderate-intensity exercise has been shown to decrease all-cause mortality and age-related morbidity. Improved cardiovascular, metabolic, endocrine, and psychologic health has been documented. The ‘effective’ dose of exercise needed to elicit effects likely to be of clinical importance as well as and the concept of accumulation of activity has been extensively debated. Despite this, the major part of adult population does not currently exercise at the recommended levels. Italian public health surveillance systems do not usually include assessments of this type of physical activity. We examined physical activity behaviours of participants in a lifestyle, nutritional, cardiovascular, and immunologic screening survey conducted in Pisa, central Italy. Demographic, socio-economic and lifestyle information was obtained by Lifestyle European Prospective Investigation of Cancer and Nutrition (EPIC) questionnaire (including questions on education, socioeconomic status, occupation, history of previous illness and disorders of surgical operations, lifetime history of consumption of tobacco and alcoholic beverages, and physical activity). Smoking habits, educational level, occupational status, daily number of hours engaged in housework, weekly number of hours engaged in physical activities during leisure (walking, cycling, gardening, exercise) and during job (sitting most of the time; light activity, walking around; handiwork with some effort; heavy work) were assessed. Among 116 women (age 44±13 years, range 17 to 73 years) 66% worked, mainly in sedentary and light jobs. Their educational level was the following: 46% secondary, 34% high, 20% graduate. They spent 2.7±1.3 hours/day in housework activities, 2.0±1.7 hours/week in exercise, 1.3±0.5 hours/day in physical activities (including walking, cycling, gardening, and exercise). Increasing physical activity was associated with reduced body mass index. On the contrary, housework activities were not significantly associated with body weight. Time spent in housework decreased with increasing educational level, whereas leisure time physical activities correspondingly increased. Increasing age was associated with reduced physical activity and increased housework. Women’ behaviours were compared with those of 93 men of similar age. These preliminary data are discussed to analyse which could be the most effective methods in lifestyle epidemiology among those presently available. Indeed, although it should be advisable a European survey of lifestyle with particular attention to exercise and physical activity, the lack of standardisation of the assessment methods remains the main methodological drawback for carrying out such studies in practice

    Building a bridge between clinical and basic research: the phenotypic elements of familial predisposition to type 1 diabetes

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    Familial aggregation has been shown for type 1 diabetes (T1D) although the nature of the factors (environment and/or genetics) responsible remains unclear. Familial clustering of diabetic nephropathy as well as of increased cardiovascular morbidity and early mortality has also been observed. This review describes the nearly 20 years history of our investigation in parallel with contemporary literature. The story is presented from the early years' strong focus on possible markers of T1D nephropathy (urinary albumin, urinary enzymes, erythrocyte Na/Li countertransport, and erythrocyte Na/H exchange) to the last clinical investigations to determine relevant biological markers of familial predisposition to T1D. Our studies of case-families recruited unaffected first-degree relatives of sporadic T1D cases and population-based controls. Unlike multiple-case families, these families are those less likely to carry a strong genetic predisposition. Participants were both interviewed and provided biological material for a detailed functional characterisation of their biochemical phenotype. These studies have initially excluded that the erythrocyte Na/H exchange could be a marker of diabetic nephropathy. On the contrary, NHE activity was significantly higher in T1D family members independently of the presence of renal disease. Basic science knowledge of NHE and its functional implications have also been reviewed. Unexpectedly, we found evidence of increased oxidative stress in nondiabetic normotensive relatives of T1D patients, apart from soluble markers of autoimmunity and despite seemingly intact antioxidant defences. Markers of oxidation were associated with markers of inflammation and we concluded that the familial increase in NHE activity could be ascribed to the direct stimulatory effect of oxidative stress. Relatives showed also immunological hallmarks and cardiovascular abnormalities that were related to indices of oxidative stress and metabolic syndrome. Other peculiarities emerged from measuring the erythrocytes redox system that exports electrons across the cell membrane to external oxidants as a function of cytoplasmic electron donor concentration. This electron transfer might reflect the functional state of membrane proton pumps that modulate intracellular redox levels. The transport system contributed to oxidation in T1D families, whereas in healthy people it protected from oxidation. Furthermore, dietary intake of vitamin C and sporting activities modulated erythrocyte electron transfer efficiency. The contribution of environmental factors was investigated using the European Prospective Investigation of Cancer and Nutrition questionnaires that provided evidence of common unhealthy dietary behaviours, which could even predispose to the development of diabetes and cardiovascular complications, in subjects living in Pisa. However, lifestyle of T1D relatives was indistinguishable from those of controls, except for the higher daily intake of niacin and the lower physical activity levels. No difference in smoking or alcohol consumption emerged among families and controls. The oxidative stress is a non-specific though certain component of pathogenesis at numerous diseases states of aerobic organisms. Although molecular genetic analysis has produced significant progress in T1D phenotype, much remains to be learned about the molecular sequence of events leading from a generic familial pro-oxidant background to a sporadic form of T1D (where oxidative damage targets the insulin-secreting cells)

    Cardiovascular risk by gender in an Italian pilot study

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    Part of the international variation in the gender differences in total mortality remains unexplained. Although a continuous decrease in age-standardised death rates was observed in Italy, the difference between male and female rates became relatively small or even reversed (as the rate for ischaemic heart diseases). We performed an extensive evaluation of cardiovascular risk factors - demographic and clinical characteristics, biochemical parameters, and oxidative biomarkers - in a sample of healthy subjects (94 women and 75 men) from Central Italy and analysed their relationship with the response to ergometer exercise. In addition to a proportion of smokers similar to that observed in men, a clustering of peculiar female cardiovascular risk factors emerged. This included: higher platelet counts, low participation in leisure-time aerobic physical activities, hypertensive response to exercise (BMI-dependent, unlike in men), and low fraction of heart rate reserve. Physical inactivity and high serum IL-6 levels were independently predictive of having both chronotropic incompetence and abnormal heart rate recovery
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