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Biomedical subjects

A Cherubini

Publications and source records attributed to A Cherubini.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

On the oxygenation-dependent (129)Xe T (1) in blood.

The spin-lattice relaxation time, T(1), of hyperpolarized (129)Xe in blood is sensitive to blood oxygenation. In particular, it has been shown that (129)Xe T(1) is shorter in venous blood than in arterial blood. We have studied the T(1) of hyperpolarized (129)Xe dissolved in human blood as a function of blood oxygenation level, sO(2), in the physiological oxygenation range. We show that the (129)Xe relaxation rate, T(1)(-1), varies in a nonlinear fashion as a function of sO(2). This finding suggests that direct interaction of xenon with the paramagnetic heme group of deoxyhemoglobin is not the dominant oxygenation-dependent relaxation mechanism for (129)Xe in blood. These results corroborate the idea that the oxygenation-dependence of (129)Xe T(1) is determined by conformational changes of hemoglobin induced by oxygen binding.

Carbon Dioxide↗
PubMed2000

Impact of the earthquake of September 26, 1997 in Umbria, Italy on the socioenvironmental and psychophysical conditions of an elderly population.

The consequences of natural disasters on the social and health status of older people have not been deeply considered. The aim of this study was to evaluate the socioenvironmental and psychophysical conditions of an elderly population after a devastating earthquake. A randomly selected group of 332 older people (> or =64 years) was selected among 1548 eligible subjects living in the city of Nocera Umbra four months after an earthquake of 5.6 magnitude on the Richter scale. Three geriatricians evaluated the study subjects by means of a structured interview, and standardized scales, which considered physical and mental status, mood and anxiety, and self-perception of well-being, as well as the characteristics of family composition and social interactions. Of the study subjects, 11.1% lived alone, and 33.4% with the spouse only. Most were self-sufficient in the basic activities of daily life. Musculoskeletal diseases and hypertension were the most frequently observed pathologies in this geriatric population. In addition, 47.9% of the subjects lived in temporary houses; this group more frequently suffered from hypertension, and had a higher score of comorbidity as measured by Cumulative Illness Rating Scale (CIRS) compared to people who remained at home. People living in the pre-fabricated huts also showed a higher score on the Geriatric Depression Scale and the Hamilton scale for anxiety, and complained more often of their health status, evaluated as self-perception of well-being, when compared to the home dwellers. Although all the studied subjects suffered from the discomforts caused by the earthquake, the precariousness of living in temporary houses, whose structural characteristics do not take the needs of elderly subjects into account, could justify the higher distress experienced by persons housed in the huts. These observations suggest that, after natural disasters, emergency programs should be more adapted to elderly people, whose needs and expectations are often different from those of young adults.

Activities of Daily Living↗
PubMed2000

A transient dephosphorylation of JAK1 and JAK2 characterises the early-phase response of murine erythroleukemia cells to the differentiation inducer hexamethylenebisacetamide.

Although dephosphorylation of tyrosine containing proteins is considered a necessary step in the induction of leukemia cell differentiation by hybrid polar compounds (HPC), the crucial actors in this step remain unknown. We present evidence that tyrosine phosphorylation of JAK1 and JAK2 is down-regulated in murine erythroleukemia cells (MELC) within the first 6 h of their exposure to the prototype of the HPC family, hexamethylenebisacetamide (HMBA), with full recovery at 14 h. Further evidence that the JAKs-centered signalling pathway is switched off early by HMBA was provided by the demonstration that STAT5, a downstream member of this pathway, turned out to be completely dephosphorylated at 6 h in HMBA-treated cells. This JAKs dephosphorylation did not occur in HMBA-resistant clones, suggesting that JAKs are possible targets of the dephosphorylative process required for leukemia cell commitment to differentiation. These results may have impact on leukemia therapy based on JAKs inhibitors.

Acetamides↗
PubMed2000

HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium.

HERG K(+)channels, besides contributing to regulate cardiac and neuronal excitability, are preferentially expressed in tumour cell lines of different histogenesis, where their role in the development and maintenance of the neoplastic phenotype is under study. We show here that both herg gene and HERG protein are expressed with high frequency in primary human endometrial cancers, as compared to normal and hyperplastic endometrium. RT-PCR and immunohistochemistry, using specific anti-HERG antibodies developed in our laboratory, were applied to tissue specimens obtained from 18 endometrial cancers and 11 non-cancerous endometrial tissues. herg RNA and HERG protein are expressed in 67% and 82%, respectively, of cancerous, while in only 18% of non-cancerous tissues. In particular, no expression was found in endometrial hyperplasia. Moreover, electrophysiological experiments confirmed the presence of functioning HERG channels on the plasma membrane of tumour cells. On the whole, these data are the first demonstration of the presence of HERG channels in primary human neoplasias, and could candidate HERG as a potential tool capable of marking cancerous versus hyperplastic endometrial growth.

Aged↗
PubMed2000

Physical activity and oxidative stress during aging.

Physical activity and exercise have several beneficial effects for physical and psychological health in young and aged subjects. Exercise may reduce age-related lean body mass loss and risk for several chronic diseases including coronary artery disease, hypertension, non-insulin-dependent diabetes mellitus, anxiety, depression, functional decline, and frailty. Exercise, however, especially when performed strenuously, is associated with increased production of reactive oxygen species, able to consume endogenous antioxidants and eventually to damage biological molecules and key cellular components. Therefore, the balance between beneficial and potentially harmful effects of exercise might be of particular importance in the elderly, in which nutritional deficiencies, sedentary lifestyle, and comorbidity commonly concur to a depletion of the antioxidant reservoir of the organism and increased susceptibility to oxidative stress. The aim of this review is to summarize current experimental, clinical, and epidemiological knowledge regarding known associations and potential links between oxidative stress and physical activity/exercise during aging. Before a final recommendation can be made with respect to the possible preventive and therapeutical role of antioxidant supplementation in aged exercising people, there is a substantial need for further studies to be performed on this topic.

Aged↗
PubMed2000

Antioxidant profile and early outcome in stroke patients.

BACKGROUND AND PURPOSE: Experimental studies provide evidence of an association between ischemic stroke and increased oxidative stress, but data in humans are still limited and controversial. The purpose of this study was to investigate the time course of plasma antioxidant changes in ischemic stroke patients. METHODS: Plasma antioxidants, including water-soluble (vitamin C and uric acid) and lipid-soluble (vitamins A and E) compounds as well as antioxidant enzyme activities in plasma (superoxide dismutase [SOD] and glutathione peroxidase) and erythrocytes (SOD), were measured by high-performance liquid chromatography (antioxidant vitamins) and by spectrophotometry (antioxidant enzymes) in 38 subjects (25 men and 13 women aged 77.2+/-7.9 years) with acute ischemic stroke of recent onset (<24 hours) on admission, after 6 and 24 hours, and on days 3, 5, and 7. Antioxidant levels in patients on admission were compared with those of age- and sex-matched controls. RESULTS: Mean antioxidant levels and activities in patients on admission were lower than those of controls and showed a gradual increase over time. Patients with the worst early outcome (death or functional decline) had higher vitamin A and uric acid plasma levels and lower vitamin C levels and erythrocyte SOD activity than those who remained functionally stable. CONCLUSIONS: These results suggest that the majority of antioxidants are reduced immediately after an acute ischemic stroke, possibly as a consequence of increased oxidative stress. A specific antioxidant profile is associated with a poor early outcome.

Aged↗
PubMed1999

Spin-lattice relaxation of laser-polarized xenon in human blood.

The nuclear spin polarization of 129Xe can be enhanced by several orders of magnitude by using optical pumping techniques. The increased sensitivity of xenon NMR has allowed imaging of lungs as well as other in vivo applications. The most critical parameter for efficient delivery of laser-polarized xenon to blood and tissues is the spin-lattice relaxation time (T1) of xenon in blood. In this work, the relaxation of laser-polarized xenon in human blood is measured in vitro as a function of blood oxygenation. Interactions with dissolved oxygen and with deoxyhemoglobin are found to contribute to the spin-lattice relaxation time of 129Xe in blood, the latter interaction having greater effect. Consequently, relaxation times of 129Xe in deoxygenated blood are shorter than in oxygenated blood. In samples with oxygenation equivalent to arterial and venous blood, the 129Xe T1s at 37 degrees C and a magnetic field of 1.5 T were 6.4 s +/- 0.5 s and 4.0 s +/- 0.4 s, respectively. The 129Xe spin-lattice relaxation time in blood decreases at lower temperatures, but the ratio of T1 in oxygenated blood to that in deoxygenated blood is the same at 37 degrees C and 25 degrees C. A competing ligand has been used to show that xenon binding to albumin contributes to the 129Xe spin-lattice relaxation in blood plasma. This technique is promising for the study of xenon interactions with macromolecules.

Arteries↗