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U Senin

Publications and source records attributed to U Senin.

At least 55 records · Page 3Linked to original sources
PubMed1997

Age-related cortical bone loss at the metacarpal.

In order to evaluate in vivo the entity of endosteal and periosteal changes with age in the two sexes, and their relative contribution to age-related cortical bone loss, we undertook a cross-sectional study on a population of normal Caucasian subjects. The group included 189 women and 107 men who were studied by photodensitometry and radiogrammetry of the second metacarpal bone, derived from the same standard hand X-ray. Of the subjects, 134 were 65 years of age or older (75 women and 59 men). Metacarpal bone mineral density (BMD) correlated with age in both sexes, with an annual bone loss rate of 0.5% in women and 0.15% in men. In the over 65 group, correlation was significant only in women, who underwent an acceleration in the rate of bone loss (1% per year). Marrow cavity width (M), cortical index at the second metacarpal shaft (MI) and external width (W) all correlated with age in both sexes, although generally better in the female than in the male sex. M almost doubled from the fourth to the ninth decade in women and increased 50% in men. In the same age interval, MI showed an annual decrease of 0.49% in females and 0.33% in males. In the over 65 group, cortical thinning rate was significant in women (0.39% per annum) but not in men (0.14% per annum), whereas correlation of W was not significant in either sex. Finally, MI correlated with BMD in the whole study population and in the over 65, with a female prevalence in correlation strength maintained throughout life. The following conclusions can be derived for metacarpal aging: (1) an acceleration in cortical bone loss occurs in females after age 65; (2) age-related growth in periosteal diameter, although significant in the whole population, is negligible in the elderly of both sexes; (3) age-related cortical bone loss is generally more dependent on cortical thinning in women than in men.

Adult↗
PubMed1997

Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging.

In order to evaluate the pattern of proton magnetic resonance spectroscopy (1H-MRS) in the gray and white matter of patients with Alzheimer's disease (AD) and healthy controls, a cross-sectional study was carried out on 13 consecutive AD patients and 7 healthy older subjects who were referred to the Day-Hospital for diagnostic assessment. All examinations were performed on a 1.5 Tesla whole-body scanner. Volumes of interest were selected in both the gray (temporal region) and the white (frontal region) matter. N-acetyl group, total creatine, total choline and myo-inositol were quantified referring the metabolite peak area to the unsuppressed water peak area acquired under the same conditions, and the ratio was expressed in arbitrary units. A significant decrease in N-acetyl-aspartate (NAA) in both gray and white matter and an increase in myo-inositol (mI) in gray matter of AD patients were observed. The gray matter NAA/mI ratio clearly separated the two groups. White matter mI was significantly associated with severity and duration of dementia. No association with age was documented. It can be concluded that in vivo 1H-MRS can contribute to the knowledge of pathophysiology of AD, giving neurochemical details of both gray and white matter. In particular, the gray matter NAA/ml ratio seems to be able to differentiate normal cerebral aging from Alzheimer's disease.

Aged↗
PubMed1997

Diagnosing Alzheimer's disease in very elderly patients. Relevance of some functional and psychobehavioral aspects assessed by the Gottfries-Bråne-Steen Rating Scale for Dementia. Study Group on Brain Aging, Italian Society of Gerontology and Geriatrics.

OBJECTIVES: To describe the Gottfries-Bråne-Steen (GBS) Rating Scale more fully with instruments commonly used for the diagnostic assessment of older patients with cognitive disturbances--the Mini Mental State Examination (MMSE), Hamilton Depression Rating Scale (HDRS), and Global Deterioration Scale (GDS)--and to characterize the specific diagnostic value of the GBS. DESIGN: A multicenter study including patients diagnosed with senile dementia of the Alzheimer type (SDAT; age at onset: > 75 years) and age-matched non-demented subjects. SUBJECTS: One hundred thirty-eight consecutively referred SDAT patients and 116 non-demented age-matched healthy subjects selected from among relatives of the patients. METHODS: The MMSE, GBS and HDRS were used for assessing patients and controls. The GDS was utilized for dementia staging. FINDINGS: Principal component analysis carried out on GBS scores yielded three factors explaining 74% of variance: factor 1, general functioning; factor 2, depression, and factor 3, restlessness. The actual composition of these factors was analyzed after computing factor scores for each subject by means of forward selection regressions, each using the MMSE, GDS and HDRS as predictors of scores on a given factor. The best predictors were MMSE and GDS scores for factor 1; HDRS for factor 2, and MMSE for factor 3. A GBS cutoff of 8 (obtained after a quality receiver operating characteristic analysis) best discriminated between demented and non-demented subjects (positive-predictive value: 0.88; negative-predictive value: 0.90). CONCLUSIONS: The GBS Rating Scale for dementia can be a useful tool in routine clinical assessment of older subjects with cognitive impairment and distinguishes between demented and non-demented subjects; it gives comprehensive information on functional and psychobehavioral characteristics of demented patients, being composed of factors related to the MMSE and HDRS.

Age Factors↗
PubMed1997

Cognitive enhancement therapy for Alzheimer's disease. The way forward.

Although at present there is no definitive treatment or cure for Alzheimer's disease, different pharmacological strategies are being actively investigated. At present, cholinergic therapy and nootropics and some neuronotrophic agents represent the available approaches to symptomatic treatment of Alzheimer's disease. The use of cholinesterase inhibitors (ChEI) constitutes the best cholinergic approach to increase acetylcholine levels. Available data suggest that about 15 to 40% of Alzheimer's disease patients show a varying degree of cognitive improvement while taking these medications; however, haematological complications (neutropenia or agranulocytosis), together with hepatotoxicity, need to be considered carefully. Recent data suggest that long term administration of nootropics may lead to a significant improvement of cognitive functions in Alzheimer's disease patients compared with untreated individuals, having excellent tolerability. Protocols for the intracerebroventricular administration of neuronotrophic substances are also ongoing. The most promising approaches for the future currently undergoing investigation involve attempts to slow the production of beta-amyloid and/or to inhibit beta-amyloid aggregation. Another rational therapeutic approach would be to inhibit the formation of paired helical filaments (PHF) by increasing and/or modulating the activities of protein phosphatases and kinases. Antioxidant therapy should disrupt or prevent the free radical/beta-amyloid recirculating cascade and the progressive neurodegeneration. Idebenone, a synthetic compound acting as an 'electron trapper' and free radical scavenger, has shown some efficacy in degenerative and vascular dementia; at present, other different molecules having antioxidative properties [lazaroids (21-aminosteroids), pyrrolopyrimidines, nitric oxide blockers, selegiline, some vitamins] are under investigation. Lowering absorption or brain tissue concentrations of aluminium also offers possible therapeutic opportunities for slowing the rate of clinical progression of the disease; in this sense, some evidence exists using the aluminium chelating agent deferoxamine (desferrioxamine). Inflammation also may play a significant pathogenetic role in Alzheimer's disease. As shown by several retrospective analyses, there is an inverse association of anti-inflammatory drug use with the frequency of Alzheimer's disease diagnosis. Consequently, clinical trials using both nonsteroidal and steroidal molecules have been proposed. These lines of pharmacological intervention represent an important premise for future therapeutic strategies capable of counteracting the pathogenesis of Alzheimer's disease.

Aluminum↗
PubMed1996

Cathepsin B activity in normal human osteoblast-like cells and human osteoblastic osteosarcoma cells (MG-63): regulation by interleukin-1 beta and parathyroid hormone.

Cathepsin B activity and its regulation by interleukin 1 beta (IL-1 beta) and parathyroid hormone (PTH) was investigated in normal human osteoblast-like cells (hOB) and in the human osteoblastic osteosarcoma cell line MG-63. Cathepsin B activity was measured using a fluorescent synthetic substrate, 7-N-benzyloxycarbonyl-L-arginyl-L-arginylamide-4-methylcoumarin, and its specificity was checked with E-64, a specific inhibitor of cysteine proteinases and CA074, a specific inhibitor of the enzyme. Cathepsin B activity was detected in crude extracts of cell monolayers and in conditioned media. In both cell types, basal activity was detected essentially in cell extracts, since in media only approximately 1.2% (hOB) and approximately 6% (MG-63) of the total activity was released. IL-1 beta (1-100 U/ml) and PTH (10(-9) M-10(-6) M) significantly stimulated cathepsin B activity in cell extracts and in conditioned media. In both cell types, the increase in proteolytic activity appeared to require RNA and protein synthesis after adding IL-1 beta or PTH. Using the above substrate, we also evaluated some biochemical properties of the enzyme, and its pH-stability and pH-optimum. In both cell types, intracellular cathepsin B activity was not resistant to neutral or slightly alkaline pH, whereas extracellular cathepsin B activity was stable. This study provides evidence that osteoblast-like cells produce and secrete active cathepsin B. The production and secretion was stimulated by IL-1 beta and PTH. The physiological role of cathepsin B produced by osteoblasts and stimulated by the bone resorbing agents remains to be elucidated. Since extracellular activity is stable under relatively physiological conditions, it is possible that the extracellular as well as intracellular form of the enzyme may play a role in matrix turnover.

Cathepsin B↗
PubMed1996

Altered mitochondrial membrane fluidity in AD brain.

Oxidative damage on biological membranes has been proposed as a cause of the alterations observed in aging brain and, more severely, in Alzheimer's disease (AD). In this study we evaluated membrane fluidity of mitochondria extracted from different areas of normal and AD brains by means of fluorescence polarization technique. AD mitochondria showed a significant reduction of membrane fluidity compared to controls except in cerebellum. This might be caused by a greater lipid peroxidation of biological membranes, as suggested by in vitro experiments we performed to this purpose. From these results the possible role of oxidative stress in AD pathogenesis is supported.

Aged↗
PubMed1996

Pharmacokinetic profile and endocrine effects of posatirelin treatment in healthy elderly subjects.

The pharmacokinetics and endocrine effects of a therapeutic dose (10 mg/day) of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide) were investigated in healthy elderly subjects. Posatirelin was given once daily by intramuscular injection for 7 days. Pharmacokinetic parameters were estimated using a model-independent approach. The plasma concentrations of free triiodotyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) and the circadian rhythms of prolactin and cortisol were considered as indicator variables of endocrine response to posatirelin administration. Posatirelin was well tolerated and no significant adverse effects were observed during the study. Peak plasma concentration (Cmax), time of peak plasma concentration (tmax), area under the plasma concentration-time curve from time zero to infinity (AUC0-infinity), elimination half-life (t1/2), and total clearance (CI/F) were measured after single-dose intramuscular injection (day 1) and after multiple-dose administration (day 7). There were no significant changes in these parameters after multiple-dose administration (day 7). Posatirelin induced a progressive reduction in basal TSH levels and maximum response. There were no significant changes during treatment in the time at which basal levels of FT3 and FT4 occurred, and these levels remained within the normal range throughout the study. The circadian rhythms of cortisol and prolactin were not influenced by posatirelin treatment. The pharmacokinetics of posatirelin were not time dependent, and the drug did not accumulate after multiple-dose administration. Short-term treatment with posatirelin did not induce clinically relevant endocrine consequences in healthy elderly subjects.

Aged↗
PubMed1996

1H-MRS, MRI-based hippocampal volumetry, and 99mTc-HMPAO-SPECT in normal aging, age-associated memory impairment, and probable Alzheimer's disease.

OBJECTIVE: To better understand how to differentiate the "in vivo" normal aging brain from pathological conditions, namely dementia of the Alzheimer type (DAT), by means of magnetic resonance imaging (MRI), single photon emission computerized tomography (SPECT), and proton magnetic resonance spectroscopy (1H-MRS), to show neuroanatomical, perfusional and neurochemical details, respectively. DESIGN: 1H-MRS, MRI-based hippocampal volumetry and 99mTc-HMPAO SPECT were performed in healthy older subjects as well as patients suffering from age-associated memory impairment (AAMI) and dementia of Alzheimer type (DAT). SUBJECTS AND SETTING: Eighteen subjects were selected from those referred to an outpatient clinic for diagnostic evaluation of cognitive impairment entered the study. Six patients fulfilled NINCDS-ADRDA diagnostic criteria for DAT, six subjects were affected by AAMI, and six cognitively healthy subjects, selected from among relatives of the patients, were defined as controls. METHODS: The 1H-MRS and MRI studies were performed on a 1.5 Tesla NMR-imaging system equipped with a spectroscopy research package. SPECT scans were performed on a Gamma 11 computer system. FINDINGS: 1H-MRS showed significantly lower N-acetylasparatate concentration in DAT and AAMI compared with controls. Conversely, mean inositol concentration was significantly higher in DAT than in controls, whereas AAMI subjects registered intermediate values. MRI measurements showed significantly reduced volumes of hippocampal formations in DAT and AAMI groups compared with controls. Finally, 99mTc-HMPAO SPECT showed a significant frontal, temporo-parietal, and occipital hypoperfusion in DAT patients only. CONCLUSIONS: These findings support the hypothesis of a continuum among the three conditions studied, or at least between AAMI and DAT, where AAMI seems to be an early, monosymptomatic stage of Alzheimer disease. Accepting this view, it would be questionable to maintain the term "age-associated memory impairment" as a discrete entity.

Aged↗
PubMed1996

Posatirelin in the treatment of vascular dementia: a double-blind multicentre study vs placebo.

INTRODUCTION: The usefulness of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having modulatory activity on the monoaminergic and cholinergic systems and neurotrophic effects, was evaluated in vascular dementia. PATIENTS AND METHODS: A multicentre, parallel groups, double-blind clinical study vs placebo was carried out with patients suffering from probable vascular dementia according to the NINDS-AIREN criteria. The study consisted of a two-week run-in of a once daily, orally administered, placebo phase, followed by 12 weeks of intramuscular treatment with posatirelin 10 mg/ml or placebo given once a day and a follow-up after one month's withdrawal. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale for dementia, the Randt Memory Test and the Toulouse-Piéron Attention Test. Data were evaluated using analysis of variance and covariance. RESULTS: As regards GBS scores, patients treated with posatirelin showed a significant improvement in intellectual performance, in orientation, motivation and memory as compared to controls. The improvement of memory performance was also confirmed by the acquisition score and memory index of the Randt Memory Test. At the end of the follow-up period the differences between treatments were still maintained. Tolerability was good. CONCLUSIONS: The significant improvement observed in cognitive functions, attention and motivation of demented patients treated with posatirelin suggests the potential usefulness of this drug in vascular dementia. Furthermore, the presence of a long-lasting effect after drug withdrawal suggests the possibility of administering the drug cyclically.

Aged↗
PubMed1996

Hemostasis abnormalities in patients with vascular dementia and Alzheimer's disease.

Since it has not been established to what extent abnormalities of hemostasis contribute to the occurrence and development of dementia, selected measurements of coagulation and fibrinolysis were obtained in elderly patients with Alzheimer's disease (n = 22) or vascular dementia (n = 29), compared with healthy individuals in the same age range (n = 61). Hemostasis abnormalities were more frequent and marked in vascular dementia, being expressed as significant increases of plasminogen activator inhibitor type 1, von Willebrand factor, D-dimer and activated factor VII. However, some hemostasis measurements (von Willebrand factor, activated factor VII) were abnormally high also in the patients with Alzheimer's disease, a condition in which vascular damage is not considered to play a major pathogenetic role. It could not be established in this study whether or not these hemostatic abnormalities play a casual role in the pathogenesis of dementia, or whether they are secondary to inflammation and chronic vascular disease. Nevertheless, their presence may contribute to aggravating vascular disease.

Aged↗
PubMed1995

Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease.

Impaired energy metabolism is an early, predominant feature in Alzheimer's disease. In order to find out simple, reliable 'in vivo' markers for the clinical-biological typization of the disorder, we measured cerebrospinal fluid (CSF) glucose, lactate and pyruvate levels in patients suffering from dementia of Alzheimer type (DAT) and in healthy elderly controls. DAT group showed remarkably higher levels of pyruvate (P = 0.01), with no overlap with the values obtained in controls. CSF pyruvate levels were also significantly associated with the severity of dementia. Therefore, CSF pyruvate levels neatly separate DAT patients from controls, having also pathogenetic value.

Aged↗
PubMed1995

Cerebrospinal fluid neuron-specific enolase in Alzheimer's disease and vascular dementia.

Levels of neuron-specific enolase (NSE), a glycolytic enzyme localized in neurons, were measured in serum and cerebrospinal fluid (CSF) of patients with early-onset (e-AD) and late-onset (l-AD) Alzheimer's disease, vascular dementia (VD) and controls. Mean CSF NSE levels in patients with Alzheimer's disease did not significantly differ from those in controls, although in the AD group a correlation was found between NSE levels and severity of cognitive deficits. In VD patients, CSF NSE was lower than in controls or in AD patients. These findings are of physiopathological interest but suggest that CSF NSE is not a useful biological marker in dementia disorders.

Age of Onset↗
PubMed1995

Appendicular cortical bone loss after age 65: sex-dependent event?

Distal radius photodensitometric and second metacarpal radiogrammetric measurements were obtained from computerized analyses of standard hand X-Ray films of 296 Caucasian subjects (189 women and 107 men). This sample included 134 subjects > or = 65 years old (75 women and 59 men). Distal radius bone density and metacarpal index showed a significant linear decrease with age in both sexes. Rates of bone loss, calculated from the regression curves, were -0.7% per year in women and -0.5% per year in men by distal radial photodensitometry, and -0.49% per year in women and -0.33% per year in men by metacarpal radiogrammetry. In the elderly subgroup, women > or = 65 years of age showed an even faster bone loss, with an annual decrease of -1.4% by distal radial photodensitometry. Conversely, men > or = 65 years of age had no significant bone loss, not even by metacarpal radiogrammetry. In conclusion, these data suggest that appendicular cortical bone loss occurs at a higher rate in elderly females than in the elderly males, both at the distal radial and at the metacarpal site.

Absorptiometry, Photon↗
PubMed1995

Serum anti-GFAP and anti-S100 autoantibodies in brain aging, Alzheimer's disease and vascular dementia.

Autoantibodies against glial fibrillary acidic protein (GFAP) and S100 protein were measured in sera of patients suffering from vascular dementia (VD), presenile Alzheimer's disease (AD), senile Alzheimer's disease (SDAT) and aged healthy controls by means of ELISA test. VD and SDAT showed the highest levels of both autoantibodies, AD the lowest. From these results a relationship between autoantibody titers and aging seems possible. Dosage of anti-GFAP and anti-S100 autoantibodies does not appear useful for diagnostic purpose because of the overlap observed among groups. Rather, the presence of these antibodies seems to reflect an alteration of the blood-brain barrier that promotes the access of central nervous system antigens to immunocompetent cells.

Aged↗
PubMed1995

Acute phase reactant alpha 1-antichymotrypsin is increased in cerebrospinal fluid and serum of patients with probable Alzheimer disease.

Levels of alpha 1-antichymotrypsin (alpha 1-ACT) in cerebrospinal fluid (CSF) and serum from patients with probable Alzheimer disease (AD) of both early (e-AD) and late (l-AD) onset assessed by a competitive enzyme-linked immunosorbent assay were higher than those found in controls or in patients with vascular dementia (VD). A negative correlation between CSF levels of alpha 1-ACT and the stage of the disease was present in patients with both e-AD and l-AD. No difference in alpha 2-macroglobulin levels in CSF and serum from patients with e-AD, l-AD, VD, and nondemented controls was found. Serum concentrations of alpha 1-antitrypsin from l-AD subjects were within the normal range. Thus, increased levels of alpha 1-ACT in CSF and serum were specifically associated with AD, and the detection of this serpin in CSF may be useful in monitoring the progression of the disease.

Aged↗