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Biomedical subjects

G Baggio

Publications and source records attributed to G Baggio.

At least 19 recordsLinked to original sources

Different antioxidant profiles in Italian centenarians: the Sardinian peculiarity.

In this study, 153 Italian centenarians from four different geographical areas, including Modena (northern Italy), Ancona (central Italy), Perugia (central Italy) and Sardinia island (AKEA Project) were enrolled. Plasma levels of vitamin C, uric acid, vitamin A and vitamin E as well as the activities of superoxide dismutase and glutathione peroxidase were measured. Subjects were compared to a younger control population of the same areas, divided into three age groups: <or=60; 61-80 and 81-99 years. The main result of this study is that, whereas in Italian population elevated levels of plasma vitamins A and E seem to be important for longevity, this do not apply to centenarians from Sardinia, in which probably other factors play a more important role.

Aged↗

Dialysis and kidney transplantation: similarities and differences in the psychological aspects of noncompliance.

BACKGROUND: Dialysis and kidney transplantation represent two effective strategies in treating chronic uremia, albeit with different results. Our study compared the psychological aspects of two categories of patients: patients who faced kidney transplantation and have been on dialysis, and noncompliant patients treated with these therapies. MATERIALS AND METHODS: On 170 patients (120 hemodialysis and 50 peritoneal dialysis) we used a personality analysis (MMPI2) and the COPE, which assessed the ability of patients to cope under certain conditions that can be perceived as stressful or, in any case, unusual. The screening succeeded in 11 cases among the first group and 9 in the second. Three of the 20 patients were considered to be partially noncompliant: 1 on peritoneal and the other 2 on hemodialysis. We also tested a control group of 300 people of different ages, sexes, social and cultural status, dates and kinds of transplantation (cadaveric or living donors). Of the 36 feedbacks received, only 30 were considered valuable. RESULTS: The results of the research showed that patients with less than 2 years of dialysis treatment and patients with more than 2 years survival after transplantation time were inclined to deny their disease and the possible emotions about their clinical status, drawing an inadequate attention to the difficulties. This behavior was clearer among noncompliant patients. Family problems and couple malaise in everyday life can push more and more of these patients to be noncompliant with therapeutic prescriptions, as they do not feel adequate support. The result is an excessive foreboding, poor disposition, and nervousness. CONCLUSIONS: Screening of patients' social and psychological status is useful as is psychological intervention for those who miss emotional support from the family. This psychological support is advisable for uremics who have to enter a waiting list and for those who are subject to postoperative treatment in order to promote compliant behavior.

Adaptation, Psychological↗

Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. PHYLLIS study group.

OBJECTIVE: The Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS), is the first study in patients with hypertension (diastolic blood pressure (DBP) 95-115 mmHg; systolic blood pressure (SBP) 150-210 mmHg), moderate hypercholesterolaemia (LDL-cholesterol 4.14-5.17 mmol/l (160-200 mg/dl) and initial carotid artery alterations (maximum intima-media thickness (IMT) Tmax > or = 1.3 mm). The primary objective of PHYLLIS is investigating whether in these patients administration of an angiotensin converting enzyme inhibitor, fosinopril, and a statin, pravastatin, is more effective than administration of a diuretic and a lipid-lowering diet in retarding or regressing alterations in carotid IMT. While the study is in progress, baseline data are here reported to clarify the association of various risk factors with carotid IMT in these medium-high risk hypertensive patients. METHODS: Patients numbering 508 have been randomized to PHYLLIS by 13 peripheral units, in Italy. Age was (mean +/- SD) 58.4 +/- 6.7 years, males were 40.2%, current smokers 16.5%, means +/- SD of serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides concentrations were 6.79 +/- 0.67, 4.69 +/- 0.51, 1.37 +/- 0.38, 1.59 +/- 0.64 mmol/l (262.4 +/- 25.8, 181.3 +/- 19.8, 53.0 +/- 14.6, 141.0 +/- 56.7 mg/ dl). Means +/- SD of clinic sitting SBP/DBP were 159.8 +/- 9.0/98.3 +/- 4.2 mmHg. 483 of the 508 patients also had 24 h ambulatory BP monitoring, edited and read at a centralized unit (mean +/- SD 24 h SBP/DBP averages 136.3 +/- 14.1/84.0 +/- 10.0 mmHg). Quantitative B-mode ultrasound (Biosound 2000 II 5A, Biosound, Indianapolis, Indiana, USA) recordings of carotid arteries were taken by certified sonographers in the peripheral units and tracings were all read at a central unit. CBMmax (mean IMT of eight sites at common carotids and bifurcations) was 1.21 +/- 0.17; Mmax (mean of 12 sites also including internal carotids) 1.16 +/- 0.17, and Tmax (single maximum) 1.85 +/- 0.48 mm. RESULTS: Ambulatory SBP and pulse pressure (PP) (24 h, daytime, night-time averages) and their variability indices (24 h SD) were always significantly correlated with CBMmax and Mmax (P0.01 -0.001), and the correlations remained significant after adjustment for age, gender and smoking. No measurement of DBP was ever associated with any IMT measurement. Likewise, no lipid variable was found associated with any IMT measurement. CONCLUSIONS: Baseline data from PHYLLIS indicate that in this population of hypertensive patients with moderate hypercholesterolaemia, SBP and PP are with age among the most significant factors associated with carotid artery alterations. However, the narrow range of inclusion LDL-cholesterol and DBP values may have obscured an additional role of these variables.

Angiotensin-Converting Enzyme Inhibitors↗

Y chromosome binary markers to study the high prevalence of males in Sardinian centenarians and the genetic structure of the Sardinian population.

We have analyzed a sample of 40 centenarians and 116 young controls from Sardinia, with a set of new Y chromosome binary markers, to evaluate if Y chromosome genes are involved in the high prevalence of males among centenarian Sardinians (1/2 vs. 1/4 in other populations studied). The results indicate that none of the seven lineages that account for >97% of the Y chromosome diversity in Sardinia provide an advantage with respect to the extreme longevity. However, our results, although based on the male-specific Y chromosome polymorphisms, give a clear profile of the pattern of genetic variability in Sardinia. Indeed they indicate that the Sardinian population had two main founder populations that have evolved in isolation for at least the last 5,000 years. These findings set the stage for future studies on longevity and other complex traits in Sardinia.

Aged↗

Antiviral and antiproliferative activity in vitro of some new benzimidazole derivatives.

The antiviral and antiproliferative activity of new compounds having n-benzenesulphony 1-2 (2 or 3-pyridylethyl) benzimidazole as a base structure were studied in vitro. Their antitumour activity against human chronic myeloid leukaemia cells was evaluated and compared with that of equimolar doses of daunorubicin. Only compound 7a, with the presence of both the pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro-group in the benzene ring, displays a selective antiproliferative effect against certain leukaemia cells and a good antiviral activity especially towards the Coxsackie B5 virus. However, it should be noted that, in the case of hydroxybenzyl-benzimidazole, resistance also builds up to compound 7a, the Coxsackie B5 virus developing resistance to it after about ten runs. Cytotoxicity tests show that many of these substances are well tolerated by the VERO cells. The mechanism of action is still unclear.

Animals↗

Decreased susceptibility to oxidative stress-induced apoptosis of peripheral blood mononuclear cells from healthy elderly and centenarians.

The susceptibility to undergo apoptosis of fresh human peripheral blood mononuclear cells (PBMCs) from three groups of healthy donors of different ages: young people (19-40 years), old people (65-85 years) and centenarians was assessed. Apoptosis was induced by 2-deoxy-D-ribose (dRib), an agent which induces apoptosis in quiescent PBMCs by interfering with cell redox status and mitochondrial membrane potential (MMP). Our major finding is that an inverse correlation emerged between the age of the donors and the propensity of their PBMCs to undergo dRib-induced apoptosis. PBMCs from old people and centenarians also showed an increased resistance to dRib-induced glutathione depletion and a decreased tendency to lose MMP. The anti-apoptotic molecule Bcl-2 was similarly expressed in PBMCs from the three age groups. Moreover, the plasma level of the stable product of transglutaminase, epsilon(gamma-glutamyl)lysine isodipeptide, a marker of total body apoptotic rate, was decreased in centenarians compared to young and elderly people. On the whole, these findings suggest that physiological aging is characterised by a decreased tendency to undergo apoptosis, a phenomenon likely resulting from adaptation to lifelong exposure to damaging agents, such as reactive oxygen species, and may contribute to one of the major phenomena of immunosenescence, i.e. the progressive accumulation of memory/effector T cells.

Acetylcysteine↗

Do men and women follow different trajectories to reach extreme longevity? Italian Multicenter Study on Centenarians (IMUSCE).

Gender accounts for important differences in the incidence and prevalence of a variety of age-related diseases. Considering people of far advanced age, demographic data document a clear-cut prevalence of females compared to males, suggesting that sex-specific mortality rates follow different trajectories during aging. In the present investigation, we report data from a nationwide study on Italian centenarians (a total of 1162 subjects), and from two studies on centenarians living in two distinct zones of Italy, i.e., the island of Sardinia (a total of 222 subjects) and the Mantova province (Northern Italy) (a total of 43 subjects). The female/male ratio was about 2:1 in Sardinia, 4:1 in the whole of Italy, and about 7:1 in the Mantova province. Thus, a complex interaction of environmental, historical and genetic factors, differently characterizing the various parts of Italy, likely plays an important role in determining the gender-specific probability of achieving longevity. Gender differences in the health status of centenarians are also reported, and an innovative score method to classify long-lived people in different health categories, according to clinical and functional parameters, is proposed. Our data indicate that not only is this selected group of people, as a whole, highly heterogeneous, but also that a marked gender difference exists, since male centenarians are less heterogeneous and more healthy than female centenarians. Immunological factors regarding the age-related increase in pro-inflammatory status, and the frequency of HLA ancestral haplotypes also show gender differences that likely contribute to the different strategies that men and women seem to follow to achieve longevity. Concerning the different impact of genetic factors on the probability of reaching the extreme limits of the human life-span, emerging evidence (regarding mtDNA haplogroups, Thyrosine Hydroxilase, and IL-6 genes) suggests that female longevity is less dependent on genetics than male longevity, and that female centenarians likely exploited a healthier life-style and more favorable environmental conditions, owing to gender-specific cultural and anthropological characteristics of the Italian society in the last 100 years.

Aged↗

Cytotoxicity and probable mechanism of action of sulphimidazole.

Sulphimidazole (1-methyl-2((4-aminophenyl)-sulphonyl)-amino-5-nitroimidazole) is a new compound in which a p-aminobenzenesulphonamide radical has been attached at position 2 of the 5-nitroimidazole ring. It possesses a useful spectrum of activity in vitro against various anaerobic microorganisms and its action against aerobic and facultative bacteria is synergically enhanced in association with trimethoprim. In the present study, we determined the cytotoxicity in vitro of sulphimidazole and trimethoprim, both alone and in combination, and analysed the viability of Vero cells and the protein content of their cell lysate in the presence of increasing concentrations of these drugs. Also, in order to verify the hypothesis that the action of sulphimidazole against aerobic and facultative bacteria is mediated by the sulphonamide component of the molecule, while that against anaerobic bacteria depends on the action of the nitro group of the 5-nitroimidazole ring, we studied the mechanism of action of the new compound both indirectly, by means of microbiological techniques, and directly, by determining its oxidoreduction potential with respect to that of metronidazole. The results show that sulphimidazole is only slightly toxic in vitro for Vero cells, either alone or in association with trimethoprim, and that the combination of the two functional groups in a single molecule not only maintains its structure-activity relationship intact but also broadens its antibacterial spectrum.

Animals↗

Occurrence of chronic diseases and their impact on physical disability over the whole spectrum of aging: from 65 to over 100 years of age.

The aging of the Italian population is an emerging public health priority. In 2025 Italy is expected to have the highest world median age with nearly half of the population over 50 years old. To avoid an unbearable burden of disease and disability on future generations, we must identify areas for intensive disease and disability prevention programs. Preliminary results from the PRO.V.A study show that disability is associated with conditions that are potentially preventable as chronic diseases and falls or are treatable as chronic pains. Moreover, it is of extreme interest to identify and understand biological and environmental secrets of successful aging as the AKEA study tries to do and the ways of overcoming disabilities in the extreme limits of life more and more possible to reach.

Aged↗

Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans.

Mitochondrial DNA (mtDNA) is characterized by high variability, maternal inheritance, and absence of recombination. Studies of human populations have revealed ancestral associated polymorphisms whose combination defines groups of mtDNA types (haplogroups) that are currently used to reconstruct human evolution lineages. We used such inherited mtDNA markers to compare mtDNA population pools between a sample of individuals selected for successful aging and longevity (212 subjects older than 100 years and in good clinical condition) and a sample of 275 younger individuals (median age 38 years) carefully matched as to sex and geographic origin (northern and southern Italy). All nine haplogroups that are typical of Europeans were found in both samples, but male centenarians emerged in northern Italy as a particular sample: 1) mtDNA haplogroup frequency distribution was different between centenarians and younger individuals (P=0.017 by permutation tests); and 2) the frequency of the J haplogroup was notably higher in centenarians than in younger individuals (P=0.0052 by Fisher exact test). Since haplogroups are defined on the basis of inherited variants, these data show that mtDNA inherited variability could play a role in successful aging and longevity.

Adult↗

Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: an experimental in vivo study.

The ingestion of large quantities of glycyrrhizin, whether as a drug or a sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18alpha- and 18beta-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the alpha isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18alpha-glycyrrhetic acid is more toxic than either glycyrrhizin or the beta isomer. Histopathological study of tissue samples taken from rats treated with the alpha isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18alpha-glycyrrhetic acid.

Animals↗

AKEntAnnos. The Sardinia Study of Extreme Longevity.

This paper describes an epidemiological study performed in all centenarians living in Sardinia, a large island located in the Mediterranean sea, 120 Km from the Italian coast. Due to its long-standing isolation, low immigration rate, high endogamy and rather uniform lifestyle, Sardinia offers an ideal setting in which to study the genetic traits associated with extreme longevity and successful aging. A total of 233 potentially eligible centenarians were traced in the entire territory. Of these, 66 died prior to being interviewed, 11 were not found and unknown, and 15 refused to be interviewed. A multidimensional home interview was administered to 141 centenarians, and an equivalent number of 60-year-old controls matched for gender and area of residence. Furthermore, 41 living siblings of the centenarians, and 41 age- and sex-matched controls for these siblings were also studied. The prevalence of centenarians was 13.56 per 100,000, and the female/male ratio was approximately 2. Prevalence and female/male ratio were consistent across the four Sardinian municipalities and are, respectively, higher and lower than those reported in other population-based surveys. A number of methodological problems confronted in doing the field work, and plans for future analysis of this rich dataset are discussed.

Activities of Daily Living↗

Lack of influence of apolipoprotein E4 on lipoprotein levels in the island population of Sardinia.

BACKGROUND: In this study, the apolipoprotein E (apoE) genotypes as well as plasma lipid and lipoprotein levels have been determined for the first time in 633 healthy and unrelated inhabitants on the island of Sardinia (291 men and 342 women, age range 6-89 years), randomly selected in the four districts of Sardinia among healthy people having parents and grandparents born in the same geographic area. This island lies in the centre of the western Mediterranean sea with a well-recognized peculiar and preserved genetic background. The epsilon 3 allele frequency (0.897) is higher than that previously reported in southern and mainland Italy and is one of the highest in Europe and among Caucasians; epsilon 2 allele frequency (0.040) is the lowest in Europe; epsilon 4 (0.063) is unusually low and, most interestingly, does not change in the different age groups, i.e. does not decrease in old subjects. RESULTS: Lipid and lipoprotein analysis confirm that total cholesterol and low-density lipoprotein (LDL)-cholesterol levels are lower than those described in mainland Italy; moreover, in this large Sardinian series, accurately selected, epsilon 4 allele did not influence total cholesterol (P = 0.270), LDL-cholesterol (P = 0.667) and high-density lipoprotein (HDL)-cholesterol (P = 0.549) as in other populations. In contrast, subjects carrying the epsilon 2 allele were found to have significantly lower total cholesterol (P = 0.001) and LDL-cholesterol (P = 0.001) levels than epsilon 3 carriers. CONCLUSION: The low epsilon 4 frequency and the lack of influence of this allele on lipid metabolism is a unique characteristic and, to date, has been described only in Sardinia among Caucasians; it might contribute to the low prevalence of coronary artery disease in this island.

Adolescent↗

Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors.

In this study we assessed whether widely accepted risk factors for atherosclerotic vascular diseases such as lipoprotein(a) [Lp(a)], a cholesterol-rich lipoprotein under strict genetical control, and other lipid parameters change with age. The variations of blood levels and the pathophysiological role of Lp(a) in old people, and particularly in the oldest old, are unknown. Accordingly, we measured Lp(a) levels as well as total, LDL, and HDL cholesterol (CT), and triglycerides (TG) in sera from 75 healthy centenarians, 114 randomly selected subjects under 65 years, 73 randomly selected elderly people, and 30 healthy selected elderly people. The results showed that Lp(a) serum levels did not vary by age group, including centenarians. Remarkably, one-quarter of the centenarians had high Lp(a) serum levels even though they never suffered from atherosclerosis-related diseases. At variance with young and aged people, centenarians with high Lp(a) serum levels also had high plasma concentrations of the proinflammatory cytokine IL-6, suggesting that genetic control of the Lp(a) serum level may attenuate with age and that environmental factors such as chronic subclinical inflammatory processes may play a role. We also showed that most centenarians are paradoxically characterized by low HDL-CT and relatively high TG levels, which together are considered to be strong risk factors for coronary heart disease. On the whole, these data support the hypothesis that a continuous and complex reshaping of lipid metabolism occurs in physiological aging, likely contributing to successful aging.

Aged↗

Synthesis and antiproliferative activity of some N-sulphonated-2-substituted benzimidazoles and imidazo[4,5-b]pyridines.

Some N-sulphonated-2-substituted benzimidazoles and imidazo[4,5-b]-pyridines were synthesized and tested in vitro for antiviral and antiproliferative activity. None of the compounds had antiviral properties. However, three of them inhibited the proliferation of leukaemia and lymphoma cell lines at micromolar concentrations. The maximum potency of antiproliferative activity is correlated with the presence of an ethylenic spacer between the two heterocycles.

Antineoplastic Agents↗

DNA multiallelic systems reveal gene/longevity associations not detected by diallelic systems. The APOB locus.

To identify possible genetic factors affecting human longevity we compared allele pools at two candidate loci for longevity between a sample of 143 centenarians (S) and a control sample of 158 individuals (C). The candidate loci were APOB and TPO, which code for apolipoprotein B and thyroid peroxidase, respectively. Both restriction fragment length (RFL) (XbaI2488 and EcoRI4154) and variable number of tandem repeat (VNTR) (3'APOB-VNTR) polymorphisms were analysed at the APOB locus; the TPO-VNTR polymorphism (intron 10) was analysed at the TPO locus. The main result of the investigation was that there is an association between the APOB locus and longevity that is revealed only when multiallelic polymorphisms are considered. In particular: (i) the frequency of 3'APOB-VNTR alleles with fewer than 35 repeats is significantly lower in cases than in controls; (ii) the linkage disequilibrium between the XbaI-RFLP and the EcoRI-RFLP is significantly different from 0 in cases but not in controls; (iii) the EcoRI-RFLP and XbaI-RFLP allele frequencies do not discriminate between cases and controls. The differences observed between case and control allele pools are specific to the APOB locus, since no significant difference was observed at the TPO locus.

Adult↗