PubMed Health⌕ Search

Biomedical subjects

U Senin

Publications and source records attributed to U Senin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Association of the estrogen receptor alpha gene polymorphisms with sporadic Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disorder determined by the interaction of genetic, metabolic, and environmental factors. In the common late-onset familial and sporadic forms of AD apolipoprotein E type 4 allele (APOE-epsilon4) is now widely accepted as a major risk factor. The association of estrogen treatment with a reduction in the risk of AD together with the modulation by estrogen of the secretory metabolism of the amyloid precursor protein offers new possibilities for identification of other AD susceptibility genes, as those encoding for the estrogen receptors (ERs). A total of 193 patients with sporadic late-onset AD, meeting the NINCDS-ADRDA criteria, and a total of 202 control subjects, age and education matched, were included in this study. PvuII and XbaI ERalpha and HhaI APOE gene polymorphisms were evaluated in genomic DNA by Polymerase Chain Reaction (PCR). The frequency of the various ERalpha genotypes by the combination of P, p and X, x was calculated for controls and AD patients stratified based on ApoE typing. When the two ERalpha gene polymorphisms were analyzed in combination, 7 genotypes were recognized, with a significantly increased prevalence of PPXX genotype in AD patients compared to controls (P = 0.0001). Risk of AD increased by a factor of 7.6 (CI [1.10-62.3]) in homozygous APOE-epsilon4 individuals with PPXX ERalpha genotype. These results are consistent with a segregation of PPXX ERalpha genotype with a higher risk of developing late-onset sporadic AD in the Italian population. The ERalpha gene appears to interact with the APOE-epsilon4 genotype in determining AD susceptibility.

Aged↗
PubMed1999

Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex.

Oxidative damage to DNA may play a role in both normal aging and in neurodegenerative diseases. Using a sensitive high-performance liquid chromatography (HPLC) assay, we examined concentrations of 8-hydroxy-2-deoxyguanosine (OH8dG) in mitochondrial DNA (mtDNA) isolated from frontal and parietal cerebral cortex and from cerebellum in 22 Huntington's disease (HD) patients and 15 age-matched normal controls. A significant increase in OH8dG in mtDNA of parietal cortex was found in HD patients as compared with controls, while there were no significant changes in frontal cortex or cerebellum. The present findings are consistent with regionally specific oxidative damage in HD, which may be a further evidence of a metabolic defect.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Angiotensin converting enzyme deletion allele in different kinds of dementia disorders.

In order to verify the association of Angiotensin converting enzyme (ACE) gene with different kinds of dementia, as well as its association with APO-E (genotype), we performed ACE genotyping in subjects with late-onset probable Alzheimer's disease (LOAD, n = 64), early-onset probable Alzheimer's disease (EOAD, n = 32), possible Alzheimer's disease (pAD, n = 44), vascular dementia (VD, n = 12), age-associated memory impairment (AAMI, n = 15) and 40 healthy age-matched controls, who were previously characterized for APO-E. After the principal component analysis ACE D and Apo-Eepsilon4 alleles disclosed the highest prevalence in the cognitively impaired groups of subjects, Apo-Eepsilon4 being more specific for LOAD and pAD. ACE D allele seems to be an unspecific susceptibility factor for mental decline.

Age Factors↗
PubMed1999

Neuropsychological assessment of the severely impaired elderly patient: validation of the Italian short version of the Severe Impairment Battery (SIB). Gruppo di Studio sull'Invecchiamento Cerebrale della Società Italiana di Gerontologia e Geriatria.

One hundred and sixty-nine severely demented patients were tested in a multicenter study with the short version of the Severe Impairment Battery which was translated into Italian with the purpose of adapting and validating it for an Italian population. Patients were enrolled in Italian geriatric centers participating in the Study Group on Aging Brain of the Italian Society of Gerontology and Geriatrics. Following thorough clinical and instrumental examinations, they were evaluated with the Mini Mental State Examination, the Clinical Dementia Rating, the Severe Impairment Battery (SIB), the Gottfries-Bråne-Steen Rating Scale for Dementia, the Activity of Daily Living index, and the Bedford Alzheimer Nursing Severity scale (BANS.s). The inter-rater reliability of the SIB was highly significant for the total score and its subtests; test-retest reliability showed the same significance in all items. Also concurrent validity, performed comparing the total SIB score with the total BANS.s score, was significant. The short Italian version of the SIB proved to be a very reliable tool for the evaluation of severely demented patients; it has the advantage of being easy to administer, it evaluates more cognitive domains that, are typically assessed in dementia, and has a wide enough range of scores to detect even small differences in the examined abilities.

Aged↗
PubMed1999

Age-dependent increases in oxidative damage to DNA, lipids, and proteins in human skeletal muscle.

A role for oxidative damage in normal aging is supported by studies in experimental animals, but there is limited evidence in man. We examined markers of oxidative damage to DNA, lipids, and proteins in 66 muscle biopsy specimens from humans aged 25 to 93 years. There were age-dependent increases in 8-hydroxy-2-deoxyguanosine (OH8dG), a marker of oxidative damage to DNA, in malondialdehyde (MDA), a marker of lipid peroxidation, and to a lesser extent in protein carbonyl groups, a marker of protein oxidation. The increases in OH8dG were significantly correlated with increases in MDA. These results provide evidence for a role of oxidative damage in human aging which may contribute to age-dependent losses of muscle strength and stamina.

Adult↗
PubMed1999

Mitochondrial DNA 4977 bp deletion and OH8dG levels correlate in the brain of aged subjects but not Alzheimer's disease patients.

The levels of mitochondrial DNA 4977 bp deletion (mtDNA4977) and mitochondrial DNA 8'-hydroxy-2'-deoxyguanosine (OH8dG) were determined in the same samples from two brain areas of healthy subjects and Alzheimer's disease (AD) patients. A positive correlation between the age-related increases of mtDNA4977 and of OH8dG levels was found in the brain of healthy individuals. On the contrary, in both brain areas of AD patients, mtDNA4977 levels were very low in the presence of high OH8dG amounts. These results might be explained assuming that the increase of OH8dG above a threshold level, as in AD patients, implies consequences for mtDNA replication and neuronal cell survival.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Factors related to the length of in-hospital stay of geriatric patients.

The aim of this study was to evaluate factors predicting length of stay in hospital of geriatric patients. Study participants were 402 patients (183 males and 219 females) consecutively admitted to four geriatric wards located in Chieti, Perugia, Pescara and Prato, Italy. Information on potential predictors of length of stay was collected; in particular, we assessed the presence and severity of specific chronic medical conditions, level of physical function, cognitive status, and depressive symptoms. Moreover, information on family and social support was obtained. In general, participants were old, often cognitively impaired and physically disabled. Average length of stay ranged from 9.4 +/- 3.3 days (Perugia) to 14.1 +/- 7.2 days (Chieti), and was statistically different across centers (p < 0.001). None of the specific medical diagnoses was associated with different length of stay. However, higher comorbidity score (p < 0.001), living alone (p < 0.01), lower MMSE score (p = 0.03), and poor functional status (p = 0.05) were all associated with longer length of stay. When these variables were included in a multivariate model predicting length of stay, differences between centers were no longer statistically significant. Findings of this study show that specific medical diagnoses are not adequate instruments to estimate length of stay in geriatric units. Other assessment systems based on extension of the social network, comorbidity, and the cognitive as well as the functional level need to be developed.

Age Distribution↗
PubMed1998

Physical activity and cardiovascular health in the elderly.

People over the age of 65 constitute a growing proportion of the world population both in western and in developing countries. A unique feature of this group is the high prevalence of cardiovascular diseases, which negatively affect its quality of life as well as its life expectancy. Among the interventions able to reduce the health burden of cardiovascular diseases is physical activity. The benefits of physical activity have been demonstrated both in healthy and chronically ill elderly subjects, while the risks have been found to be modest. Physicians should recommend moderate-intensity physical activity to sedentary older subjects, who are still the majority within the elderly population.

Aging↗
PubMed1998

Characteristics of geriatric patients related to early and late readmissions to hospital.

The aim of the study was to evaluate which characteristics of geriatric patients account for readmission to hospital, 6 months after discharge. All patients (203 females, 176 males) consecutively admitted over a two-month period to four acute geriatric care units, located in the cities of Chieti, Perugia, Pescara and Prato, participated in the study. Data that could potentially explain early and late readmissions were collected for each patient. Prevalence of diseases and comorbidity were assessed with the Cumulative Illness Rating Scale (CIRS); physical function by self-report (ADL, IADL) and objective (Stand and Walking Speed) measures; cognitive level by MMSE; and depressive symptoms by the Geriatric Depression Scale (GDS). Information on family and social support were also obtained. After discharge, data on hospital readmissions were collected for six months. For each readmitted patient (cases), medical records were reviewed, and supplementary information was obtained from families and general practitioners. Readmissions were classified as "early" (within the first three months), "late" (within the third and sixth month), and "multiple" (2 or more readmissions irrespective of the period). Patients not readmitted (alive at home) were considered as controls. Systematic differences between centers and between periods of readmissions were evaluated using one-way analyses of variance, and Pearson's chi 2 test. Factors related to early, late, and multiple readmission were identified in multivariate logistic regression models. On univariate analysis, patients readmitted over the first three-month period were sicker than controls (CIRS classes 3-4: 52.1% vs 34.1%), had more social problems or behavioral symptoms, and were more functionally impaired (ADL dependencies 3.3 +/- 0.4 vs 2.1 +/- 0.2). Patients who were readmitted between the third and the sixth month after discharge had a significantly higher CIRS total score (p = 0.006). Patients with multiple readmissions had more severe diseases, and more social problems. On multivariate analysis, early readmission was associated with unsatisfactory social conditions, living alone, severity of diseases and cognitive impairment, while late readmission was associated with comorbidity only. Multiple readmissions were related only to social factors, and to hospital admission before the baseline evaluation. The findings of this study suggest that interventions aimed at improving unfavorable social conditions may reduce the rate of rehospitalization in geriatric patients.

Activities of Daily Living↗
PubMed1998

Short-term reproducibility of proximal femur bone mineral density in the elderly.

Densitometric measurements are prone to imprecision in elderly subjects and the present study was primarily designed to dissect out the effects of age and bone mineral density on proximal femur dual energy x-ray absorptiometry (DXA) reproducibility. The study comprised 17 elderly women (mean age 74.6 years, range 65-84 years), 13 early postmenopausal women with osteopenia (mean age 56.2 years, range 50-63 years), and 17 elderly men (mean age 73.8 years, range 65-86 years). Each subject was given triplicate proximal femur scans by a QDR 2000 Densitometer (Hologic Inc., Waltham, MA) with repositioning between scans. Because of subject selection in the early postmenopausal women there were no significant differences in bone mineral density (BMD) at any site among the three groups. Despite this, reproducibility errors expressed as either coefficient of variation (CV) % or mean standard deviation (SD) were greater in the elderly subjects, regardless of gender, when compared with the younger female subjects. The variability in measurement errors with age were least marked for the total hip and trochanteric sites. Within the elderly subjects, BMD appeared to exert little influence on measurement errors. We conclude that short-term proximal femur reproducibility is dependent on age-related factors other than BMD. There is no influence of gender on the measurement errors. It is likely that local factors (e.g., hip osteoarthritis) or general frailty may influence repositioning but this needs further exploration. In the meantime, the total hip and trochanteric sites should be used as they provide the most reproducible measurements in the elderly.

Absorptiometry, Photon↗
PubMed1998

Tau protein in cerebrospinal fluid: a new diagnostic and prognostic marker in Alzheimer disease?

Tau is the main protein of paired helical filaments. It can be detected and measured in cerebrospinal fluid (CSF) and for this reason it has been proposed as a possible in vivo marker of Alzheimer disease (AD). To evaluate the usefulness of CSF tau in the diagnosis of AD we measured it in patients with AD, frontal lobe dementia (FLD), vascular dementia (VD), and in healthy controls by means of a specific enzyme-linked immunosorbent assay test. Individuals with AD had significantly higher tau levels than FLD, VD, and controls. Individuals with late onset AD had significantly higher levels than those with early onset disease. In AD, CSF tau level did not correlate with age, duration, or severity of the disease, whereas a correlation with age was found in FLD and controls. In the nine AD patients in whom CSF tau measurement was repeated after 2 years, mean levels did not differ from baseline, although a worsening of cognitive performances occurred. The overlap among the different groups and the absence of any modification over time suggest that CSF tau measurement, more than in confirming or staging overt AD, might be useful in revealing the disease at its preclinical phase.

Aged↗
PubMed1998

Oxidative damage to DNA in lymphocytes from AD patients.

OBJECTIVE: Several studies show structural and functional alterations in peripheral cells in AD. The purpose of this study was to evaluate oxidative stress in AD lymphocytes. BACKGROUND: The literature supports the role of reactive oxygen species in the pathogenesis of AD because several markers of oxidative damage have been detected in AD brain. METHODS: 8-hydroxy-2'-deoxyguanosine (8OHdG), a marker of oxidative stress in DNA, was measured in lymphocytes of AD patients and healthy aged controls with high-pressure liquid chromatography with electrochemical detection, both at basal condition and after acute oxidative stress with hydrogen peroxide. RESULTS: A significantly higher concentration of 8OHdG in lymphocytes occurred in AD patients compared with controls. In this latter group, 8OHdG increased progressively with age. After acute oxidative stress, levels of formed 8OHdG did not differ between AD patients and controls. CONCLUSIONS: Our results support that AD is affected by oxidative stress, detectable not only in the brain but also in peripheral cells; oxidative mechanisms may contribute to the pathogenesis of AD. Additional studies in other neurodegenerative diseases are needed to evaluate these findings.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

Apolipoprotein-E genotype in normal aging, age-associated memory impairment, Alzheimer's disease and vascular dementia patients.

Apolipoprotein-E (Apo-E) genotype and allele frequencies were evaluated in patients with late-onset probable Alzheimer's disease (LOAD; n = 64), early-onset probable Alzheimer's disease (EOAD; n = 32), possible Alzheimer's disease (pAD; n = 44), vascular dementia (VD; n = 12), age-associated memory impairment (AAMI; n = 15) and 40 healthy age-matched controls. APO-E was performed by polymerase chain reaction products digested by the restriction enzyme HhaI. A statistically significant increase of epsilon4 frequency was found in LOAD as compared to the other groups, and in pAD with respect to controls, while VD and AAMI groups did not disclose any difference as regards to control subjects. Multivariate analysis showed a significant association of epsilon4 with female gender. Our results confirm the increased frequency of epsilon4 in both probable and possible LOAD, failing to show a similar trend in VD and AAMI.

Adult↗
PubMed1997

Vascular dementia Italian sulodexide study (VA.D.I.S.S.). Clinical and biological results.

In order to evaluate the biological effects on some haemostasis factors of antithrombotic-hemorheological treatments on patients with vascular dementia, a multicenter, randomized, double-blind, double-dummy, study comparing sulodexide (Sdx, 50 mg bid orally for 6 months) and pentoxifylline (Ptx, 400 mg tid orally for six months) was carried out. Eighty-six patients, 46 in Sdx group, 40 in Ptx group, fulfilling the NINDS-AIREN criteria for probable vascular dementia were evaluated. Plasma fibrinogen levels showed a significant reduction in both groups, in patients with high basal levels (> or = 350 mg/dl), the reduction being earlier in Sdx group (2nd month of therapy) than in Ptx group (4th month of therapy). In Sdx group a significant reduction in factor VII-Ag (baseline 102.8 U/dl; 6th month 90.1 U/dl) was also observed. Both drugs induced a slight reduction in activated factor VII levels as well. A parallel improvement of G.B.S. Rating Scale for dementia scores was observed in Sdx group. These results seem to indicate that sulodexide treatment can have positive effects in vascular dementia.

Administration, Oral↗
PubMed1997

Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain.

Oxidative damage on biological molecules has been proposed as a major cause of alterations observed in aging brain as well as in neurodegenerative diseases. In this study, we measured membrane fluidity in mitochondria extracted from three cerebral regions and cerebellum of Alzheimer disease (AD) patients and age-matched controls by means of fluorescence polarization technique. A significant reduction of mitochondrial membrane fluidity was found in AD, except in cerebellum. In controls, a decrease of membrane fluidity was observed along with age, and it was also related to the content of the oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (OH8dG) in mitochondrial DNA (mtDNA). Alteration in membrane fluidity seems to be a result of lipid peroxidation, since it dramatically decreased when mitochondria were exposed to FeCl2 and H2O2. The parallel increase of viscosity in mitochondrial membrane and the amount of OH8dG in mtDNA is suggestive of a relationship between these biological markers of oxidative stress. These results provide further evidence that oxidative stress may play a role in the pathogenesis of AD.

Aged↗