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Biomedical subjects

A Cherubini

Publications and source records attributed to A Cherubini.

At least 19 recordsLinked to original sources
PubMed2003

Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease.

In order to assess peripheral levels and activities of a broad spectrum of non-enzymatic and enzymatic antioxidants in elderly subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD), plasma levels of water-soluble (Vitamin C and uric acid) and of lipophilic (Vitamin A, Vitamin E and carotenoids including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) antioxidant micronutrients as well as activities of plasma and red blood cell (RBC) superoxide dismutase (SOD) and of plasma glutathione peroxidase (GPx) were measured in 25 patients with MCI, 63 AD patients and 53 controls. Peripheral levels and activities of antioxidants were similarly lower in MCI and AD patients as compared to controls. As MCI may represent a prodromal stage of AD, and oxidative damage appears to occur as one of the earliest pathophysiological events in AD, an increased intake of antioxidants in patients with MCI could be helpful in lowering the risk of conversion to dementia.

Aged↗
PubMed2002

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors.

An important target in the understanding of the pathogenesis of acute myeloid leukemias (AML) relies on deciphering the molecular features of normal and leukemic hemopoietic progenitors. In particular, the analysis of the mechanisms involved in the regulation of cell proliferation is decisive for the establishment of new targeted therapies. To gain further insight into this topic we report herein a novel approach by analyzing the role of HERG K(+) channels in the regulation of hemopoietic cell proliferation. These channels, encoded by the human ether-a-gò-gò-related gene (herg), belong to a family of K(+) channels, whose role in oncogenesis has been recently demonstrated. We report here that herg is switched off in normal peripheral blood mononuclear cells (PBMNC) as well as in circulating CD34(+) cells, however, it is rapidly turned on in the latter upon induction of the mitotic cycle. Moreover, hergappears to be constitutively activated in leukemic cell lines as well as in the majority of circulating blasts from primary AML. Evidence is also provided that HERG channel activity regulates cell proliferation in stimulated CD34(+) as well as in blast cells from AML patients. These results open new perspectives on the pathogenetic role of HERG K(+) channels in leukemias.

Acute Disease↗
PubMed2002

Effects of fruits and vegetables on levels of vitamins E and C in the brain and their association with cognitive performance.

Demographic trends, together with improvements in general health and life expectancy, will greatly change the population structures of most industrialized and developing countries during the next 50 years. By 2050, approximately 30% of people in industrialized countries will be 65 years old or older. Aging is associated with increased risk for neurodegenerative disorders, which can cause significant cognitive and physical impairment and shortened lifespan, thereby causing a burden to society. Diets rich in fruits and vegetables have been shown to improve human well-being and to significantly delay the development of pathologic processes, including neurodegenerative disorders. Foods are important sources of micronutrients, including vitamins E and C, which play crucial roles in optimal cell function. Vitamin E is an important component of biologic membranes, and vitamin C acts as a cosubstrate for several enzymes. Both E and C are involved in the antioxidant defense of cells and actively contribute to the redox status of the cell. The levels of vitamins E and C provided by diet vary significantly. Vegetable oils, nuts and seeds are the main dietary sources of vitamin E, whereas fruits and vegetable are the primary sources of vitamin C. Human trials of varying doses of vitamins E and C, including low, supplemental, and pharmacologic, have found that these nutrients may improve immunity, vascular function, and brain performance. An optimal intake of these nutrients has been associated with decreased risk of developing cognitive impairments associated with aging. This paper will review the scientific literature on the sources, tissue levels and roles of vitamins E and C in cognitive performance and pathologic processes of the central nervous system in the elderly.

Aged↗
PubMed2001

(1)H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging.

This study aimed to characterize the white matter biochemical profile of healthy elderly subjects, mild cognitive impairment (MCI) subjects, and early Alzheimer's disease (AD) patients. We used proton magnetic resonance spectroscopy ((1)H-MRS) to measure myo-inositol, creatine, N-acetylaspartate (NAA) and choline levels from a volume of interest located in the paratrigonal white matter bilaterally. A significantly higher myo-inositol/creatine ratio was found in MCI subjects and AD patients than in controls. The NAA/creatine ratio was reduced in AD patients in the left hemisphere compared to control subjects. The choline/creatine ratio was not significantly different among the three groups. These data suggest that MCI is different from normal brain aging, having a white matter biochemical pattern similar to AD.

Aged↗
PubMed2001

Longstanding survival without cancer progression in a patient affected by endometrial carcinoma treated primarily with leuprolide.

We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and immunohistochemical evaluations of the tumour (morphology, grading, proliferation and apoptotic index, E-cadherin expression) were performed. Furthermore, the expression of m-RNA for luteinizing-hormone releasing hormone (LHRH) receptors was determined. The results showed a discrepancy between some biological parameters of the tumour and its clinical characteristics. In fact, despite features suggestive of a progression of the cancer (such as the increase of both tumour grading and proliferating capacity (MIB-1), and a fall in the reparative process (appearance of mutated p53, reduced expression of both bcl-2 and c-erb-2) being detected, neither local invasion nor metastatic lesions were clinically observed. This discrepancy might be due to the maintenance of high levels of E-cadhezin. Moreover, since this tumour was shown to express mRNA for LHRH receptors, new evidence is provided about the favourable impact of LHRH analogue treatment in patients affected by endometrial cancer.

Adenocarcinoma↗
PubMed2001

Hip fracture in nursing homes: an Italian study on prevalence, latency, risk factors, and impact on mobility.

Hip fracture may cause and/or complicate institutionalization. We undertook this study to define its overall prevalence among the residents of four nursing homes in Central Italy as well as its latency and impact on mobility when it occurred within institutions. We also performed a case control analysis with the aim of identifying potential risk factors for hip fracture in nursing home. Among the 211 residents (160 women, mean age 82.2 +/- 9.29 years, and 51 men, mean age 77.1 +/- 8.9 years), 42 were hip fracture cases, with a prevalence of almost 20%, and a female/male ratio of 6/1.23 fractures preceded institutionalization; of these 19 (17 females and 2 males) occurred within the nursing homes (mean age 83.2 +/- 6.3 years). The average interval between institutionalization and fracture was 74.2 months. The impact of hip fracture on mobility was relevant. The percentage of residents ambulating autonomously fell from 95% to 32% among those who had fractured. Fractured subjects were characterized by worse mobility and function than unfractured subjects, while comorbidity, cognitive functions, and use of psychotropic drugs were similar. Prefracture mobility of fractured subjects was better than that of age-and sex-matched residents who had never fractured their hip. Regarding hip fracture in our nursing home population we can conclude that (1) hip fracture is one of the main causes of institutionalization; (2) in most cases hip fracture occurred late in the course of the nursing home stay; (3) the functional impact of the fracture was relevant when it occurred in institutions. We also suggest that preserved mobility may represent an additional risk factor for hip fracture in nursing homes.

Activities of Daily Living↗
PubMed2001

Heart disease and vascular risk factors in the cognitively impaired elderly: implications for Alzheimer's dementia.

The term "cardiogenic dementia" was introduced a few decades ago to indicate an alteration of consciousness and cognition due to heart disease. Although this term is now disused, the relationship between cardiovascular disease and cognitive impairment is currently of great interest, not only for its potential therapeutic implications. but also for the recently recognized important role that vascular factors appear to play in Alzheimer's disease. The aims of this review are therefore 1) to show data supporting the role of cardiac disease--namely congestive heart failure, myocardial infarction and atrial fibrillation--and other vascular risk factors--i.e., hypertension and diabetes--in the development or worsening of cognitive impairment; 2) to highlight recent observations on the relationship between presence and severity of congestive heart failure/ myocardial infarction/atrial fibrillation and Alzheimer's disease: and 3) to uncover the type of studies needed in this field in order to facilitate a more precise algorithm of dementia prevention as well as intervention in demented patients with cardiovascular disease.

Aged↗
PubMed2001

Peripheral non-enzymatic antioxidant changes with human aging: a selective status report.

Oxidative stress is thought to be involved in the aging process in aerobic organisms and to play a role in the pathogenesis of several disease states. Since free radicals are extremely reactive, shortly half-lived and therefore very difficult to measure directly, oxidative stress has been mainly studied through the search of indirect biomarkers of free radical-induced damage. In aerobic organisms, oxidative damage to tissues and organs is prevented by a network of defenses which includes antioxidant and repairing enzymes as well as small molecules with scavenging ability, such as antioxidant vitamins. For these reasons, the assay of antioxidant vitamins and of small molecular free radical scavengers in biological milieus may be used, if appropriately performed, to quantify the defense status against oxidative damage and to provide an indirect estimate of free radical production in aging humans. Since several conflicting data have been reported in this area, this review is aimed to summarize the existing evidence and possible faults of the research focusing on the role of plasma concentrations of small-molecular, non-enzymatic antioxidants in the process of senescence in healthy humans.

Aging↗
PubMed2001

High vitamin E plasma levels and low low-density lipoprotein oxidation are associated with the absence of atherosclerosis in octogenarians.

OBJECTIVES: To identify the biological characteristics of older subjects with vascular successful aging (VASA), defined as the absence of instrumental signs and clinical symptoms of atherosclerosis in the extracoronary and coronary vessels. DESIGN: A cross-sectional study. SETTING: A university-affiliated outpatient clinic. PARTICIPANTS: Sixty older subjects (30 with VASA and 30 controls with moderate carotid atherosclerosis (AG group)) from a sample of 705 subjects age 75 and older consecutively screened. MEASUREMENTS: Clinical examination; ultrasonographic examination of carotid, vertebral, abdominal aortic, iliac, and femoral arteries; electrocardiogram; and laboratory evaluation (lipid profile, lipophilic antioxidants, and markers of low-density lipoprotein (LDL) oxidation). RESULTS: Compared with controls, there were more females in the VASA group (82% vs 50%, P <.01), and fewer previous smokers (20.5% vs 52.5%, P <.01). Vitamin E/total cholesterol levels both in plasma (4.81 vs 3.51 micromol/mmol, P <.001) and in isolated LDLs (2.71 vs 1.86 microg/mg LDL cholesterol (LDL-C), P <.01), were higher in the VASA group, as was the resistance of LDLs to in vitro oxidation (as indicated by a longer duration of the lag phase: 80.2 vs 65.6 minutes, P <.001). The level of fluorescent products of lipid peroxidation (FPLPs) in native LDLs was lower in the VASA group (13.5 vs 18.8 URF/mg LDL-C, P <.001). Multivariate logistic regression analysis showed that only plasma vitamin E level (odds ratio (OR) = 6.04, 95% confidence interval (CI) = 1.48-24.63) and FPLPs in LDLs (OR = 0.53, 95% CI = 0.31-0.91) were independently associated with VASA. CONCLUSIONS: These results suggest that an appropriate level of vitamin E and a low level of LDL oxidation might be important for reaching advanced age without developing atherosclerosis.

Aged↗
PubMed2000

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism. In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses. Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

HERG K+ channels activation during beta(1) integrin-mediated adhesion to fibronectin induces an up-regulation of alpha(v)beta(3) integrin in the preosteoclastic leukemia cell line FLG 29.1.

Integrin receptors have been demonstrated to mediate either "inside-to-out" and "outside-to-in" signals, and by this way are capable of regulating many cellular functions, such as cell growth and differentiation, cell migration, and activation. Among the various integrin-centered signaling pathways discovered so far, we demonstrated that the modulation of the electrical potential of the plasma membrane (V(REST)) is an early integrin-mediated signal, which is related to neurite emission in neuroblastoma cells. This modulation is sustained by the activation of HERG K(+) channels, encoded by the ether-à-go-go-related gene (herg). The involvement of integrin-mediated signaling is being discovered in the hemopoietic system: in particular, osteoclasts are generated as well as induced to differentiate by interaction of osteoclast progenitors with the stromal cells, through the involvement of integrin receptors. We studied the effects of cell interaction with the extracellular matrix protein fibronectin (FN) in a human leukemic preosteoclastic cell line (FLG 29.1 cells), which has been demonstrated to express HERG currents. We report here that FLG 29.1 cells indeed adhere to purified FN through integrin receptors, and that this adhesion induces an osteoclast phenotype in these cells, as evidenced by the appearance of tartrate-resistant acid phosphatase, as well as by the increased expression of CD51/alpha(v)beta(3) integrin and calcitonin receptor. An early activation of HERG current (I(HERG)), without any increase in herg RNA or modifications of HERG protein was also observed in FN-adhering cells. This activation is apparently sustained by the beta(1) integrin subunit activation, through the involvement of a pertussis-toxin sensitive G(i) protein, and appears to be a determinant signal for the up-regulation of alpha(v)beta(3) integrin, as well as for the increased expression of calcitonin receptor.

Antibodies, Monoclonal↗
PubMed2000

Plasma antioxidants and longevity: a study on healthy centenarians.

A large body of experimental research indicates that oxidative stress contributes to the processes related to aging and to the pathogenesis of several age-related diseases. Vitamins and antioxidant enzymes have a fundamental role in defending the organism from oxidative stress. To better understand the role of antioxidants in human aging, we measured plasma levels of vitamin C (ascorbic acid), uric acid, vitamin E (alpha-tocopherol), vitamin A (retinol), carotenoids, total thiol groups, and the activity of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as the activity of red blood cell (RBC) SOD in 32 healthy centenarians-17 elderly subjects aged 80-99 years, 34 elderly subjects aged 60-79 years, and 24 adults aged less than 60 years. Considering the "noncentenarians" only, we observed a consistent behavior in the antioxidant pattern, with a decrease of the nonenzymatic antioxidants and an increase of the enzymatic antioxidant activities relative to age. Remarkably, centenarians were characterized as having the highest levels of vitamins A and E, whereas the activities of both plasma and RBC SOD, which increase with age, decreased in centenarians. From these results, it is evident that healthy centenarians show a particular profile in which high levels of vitamin A and vitamin E seem to be important in guaranteeing their extreme longevity.

Aged↗
PubMed2000

Inhibitory effect of luteinising hormone-releasing hormone analogues on human endometrial cancer in vitro.

We studied the effects of luteinising hormone-releasing hormone (LHRH) agonist leuproreline (1 microM for 96 h) and LHRH antagonist cetrorelix on the cell growth of primary cultures from nine human endometrial cancers using the sulphorhodamine colorimetric test. Histological examinations and reverse transcription and polymerase chain reaction amplification (RT-PCR) for LHRH receptors were also performed. The endometrial cancers examined had a medium to high degree of proliferative activity and a low degree of apoptotic power; furthermore, they expressed the LHRH receptor RNA variably, detectable in 71% of cases. The addition of leuproreline or cetrorelix to cell cultures inhibited growth in a statistically significant way compared to untreated control cells; nevertheless, the percentage of cell growth inhibition obtained was very variable. These data suggest that LHRH analogues can exert differential inhibitory effects on the growth of endometrial cancer, which seems to be independent of the expression of specific LHRH receptors.

Aged↗
PubMed2000

Hyperpolarized 129Xe NMR as a probe for blood oxygenation.

Optically enhanced NMR with (129)Xe and (3)He is emerging as a novel and promising technique for medical imaging of lungs and other tissues. Here it is shown that hyperpolarized (129)Xe NMR provides a powerful means of measuring blood oxygenation quantitatively and noninvasively. The interaction of xenon with hemoglobin is responsible for an oxygen-dependent NMR shift of (129)Xe in red blood cells, in sharp contrast to the current model of xenon-hemoglobin binding. This effect could be exploited in brain functional studies, and in the assessment of conditions and diseases affected by blood oxygenation.

Humans↗