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Biomedical subjects

E Ferrari

Publications and source records attributed to E Ferrari.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Venous thromboembolism and cancer].

Malignant disease predisposes to deep venous thrombosis (DVT) or pulmonary embolism (PE) in several ways. One classical situation is that of DVT or PE with no apparent cause which may be the first sign of an occult cancer. In this domain, although the epidemiological data is well known, it is important to recognise the limitations of "blind" investigations. Another situation is more common. The patients have a diagnosed malignancy and thromboembolic disease is the main extra-cancer complication. The approach to this problem is changing, both in primary prevention where many trials have already reported encouraging results, and in the treatment after the event where classical therapeutic protocols are not always well adapted. Ancestral fears of the prescription of anticoagulants in cancer patients must cede to a more objective benefit/risk analysis which seems to be very favourable in some situations. Moreover, some publications have demonstrated a chance finding of a possible anticancer effect of antithrombotic agents.

Anticoagulants↗
PubMed2001

[Food intake and nutritional status in a group of healthy elderly residing in a nursing home].

BACKGROUND: Aging is accompanied by a variety of economic, psychologic, and social changes that can compromise the nutritional status. Nutrition is an important aspect of healthful behaviour and a major component of general wellbeing of individuals throughout their life cycle. Nutritional intake appears to be an important factor contributing to aging. So, the purpose of this project was to evaluate diet and nutritional status. METHODS: Fifty-one healthy elderly subjects aged 70 years and older (31 F and 20 M), residing in a nursing home have been studied. Nutrient intake was assessed using 24-hour recalls; nutritional status was assessed using anthropometric measurements. The nutrient intakes for individuals were compared with the Italian Recommended Dietary Allowances (RDAs). RESULTS: Mean energy intake was 1,625 kcal; the average percentages of carbohydrate, protein, and fat were 54%, 16%, and 30%, respectively. The mean vitamin and mineral intake for participants met the RDAs except for calcium and selenium intakes. The mean fibre intake was low. The analysis of food products intake indicated that the above mentioned inadequacy in nutrient intake was the result of low consumption of milk and milk products containing calcium and a low consumption of integral foods or fruits containing fibre. CONCLUSIONS: The significance of sound nutrition education and the adverse impact of consumer misinformation about the benefits of these food choices becomes clear with the recognition that nutritional status influences the rate of physiologic and functional declines with age. This approach will require new efforts in consumer education sensitive to the needs and beliefs of older people.

English Abstract↗
PubMed2001

[Membrane fluidity and obesity: the correct food approach].

Modifications in dietary fat profile have shown to affect body weight gain and adiposity. This may occur through the changes of cell membrane fluidity, in particular of the peripheral muscle tissue. The decreased availability of diet polyunsaturated fatty acids (in particular of the to-3 series), that are able to induce membrane fluidification, together with an excessive intake of both saturated fatty acids and cholesterol, that on the contrary are able to rigidify the same membranes, promoter both a progressive immobilization of membrane proteins and a consequent decrease in their functional rate of liver lipoproteins VLDL, enriched in saturated fats and cholesterol. This lipoprotein increase promotes both the fat deposition in the adipose tissues and a further increase in the muscle membrane rigidity that is followed by a further enhancement in the peripheral resistance to insulin. A diert rich both in polyunsaturated fatty acids and antioxidants (vitamin and oligoelements), and in essential amino acids together with a preferential choice of complex carbohydrates (amylose, amylopectine, etc) in comparison to simple sugars (glucose, fructose, saccharose, lactose, etc) may significantly contribute to the maintenance of the correct degree of membrane fluidity and, as a consequence, to the physiologically correct body weight.

English Abstract↗
PubMed2001

[The hypocaloric balanced diet therapy and the supplementation with antioxidant and omega-3: what are the effects on the oxidative balance and erythrocytes membrane fluidity status?].

BACKGROUND: To investigate the effects of a hypocaloric balanced diet therapy and a supplementation with antioxidant and omega-3 polyunsaturated fatty acids on the oxidative balance and erythrocytes membrane fluidity status. METHODS: A randomised, double-blind, placebo-controlled study of the association between a hypocaloric balanced diet therapy and a supplementation with antioxidant and omega-3 was done on 40 women with 25 < BMI < 33. The inclusion criteria were the following: absence of dismetabolic pathologies, of previous hypocaloric diet therapy and/or supplementation and of hormonal treatments. Each subjects consumed a balanced diet with a daily caloric intake equal to: Kcal of basal metabolism (determined by indirect calorimetry) x LAF (1.64) 800 Kcal. At the start and after two months of treatment, the blood chemistry and anthropometrics parameters, the plasmatic reactive oxygen species (ROS) and antioxidant defence levels and erythrocyte membrane fluidity status were measured. RESULTS: The preliminary results of this study show that the weight loss, found in both groups investigated, determines a significant decrease of ROS. Furthermore, the association of the hypocaloric diet with antioxidant and omega-3 polyunsaturated fatty acids caused a significant increase of both plasmatic antioxidant defences and erythrocytes membrane fluidity status. CONCLUSIONS: The correlations found between the above parameters and the blood chemistry and anthropometrics variables suggest that the supplementation with antioxidant and omega-3 polyunsaturated fatty acids could ameliorate the effects of hypocaloric diet on the obesity treatment and may give some clinical benefit through the decrease of the values of atherosclerosis risk factors.

English Abstract↗
PubMed2001

[Dietary restriction and oral administration of antioxidant and omega-3: what are the effects on the clinical variables in a group of obese women?].

BACKGROUND: Obesity is now recognized as a major risk factor for many pathologies. The state of obesity is associated with an increase in reactive oxygen species; persistent overconsumption of calories in the obese may be exposing them to excessive damage besides maintaining the state of obesity. It is possible that dietary modification and association with assumption of antioxidant and omega-3 oral integration contributes to a reduction in reactive oxygen species generation and a corresponding reduction in indexes of oxidative damage, including lipid peroxidation. METHODS: Given this back-ground, the pro/anti-oxidant balance, biochemical parameters and the body composition were studied in two groups of obese women: a first group of 10 obese women were studied before and after eight weeks of dietary restriction and a second group of 12 obese women were studied before and after eight weeks of dietary restriction and oral administration of antioxidant and omega-3. RESULTS: In summary, as regards the preliminary results of clinical outcome parameters, interestingly enough the glycemic levels fall markedly in association with both dietary restriction and oral integration with antioxidant and omega-3. Another important finding of this study is that of calcium levels and phase angle (measured by impedenzometry) increase in the group treated with dietary restriction and oral administration of antioxidant and omega-3. CONCLUSIONS: Studies that aimed to explore whether oxidative status predicts clinical outcome would provide important details on the putative link between oxidative status and state of obesity.

English Abstract↗
PubMed2001

Adipose tissue and cytokines.

Adipose tissue is not simply a storage depot for excess energy intake, it is also able to produce and release several substances with local (autocrine) and systemic (endocrine) actions. An up-to-date review of our knowledge in this area is given here. Several of the compounds deriving from adipose tissue have been shown to play a role in obesity-related health complications. The production of cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha), IL-6, and leptin, is implicated in the development of several disorders. Insulin resistance is one of the most clinically significant.

Journal Article↗
PubMed2000

The PCNA from Thermococcus fumicolans functionally interacts with DNA polymerase delta.

We have cloned the gene encoding proliferating cell nuclear antigen (PCNA) from the hyperthermophilic euryarchaeote Thermococcus fumicolans (Tfu). Tfu PCNA contains 250 amino acids with a calculated M(r) of 28,000 and is 26% identical to human PCNA. Next, Tfu PCNA was overexpressed in Escherichia coli and it showed an apparent molecular mass of 33.5 kDa. The purified Tfu PCNA was tested first with recombinant Tfu DNA polymerase I (Tfu pol) and second with calf thymus DNA polymerase delta (pol delta). When tested with the homologous Tfu pol on bacteriophage lambda DNA, large amounts of Tfu PCNA were required to obtain two- to threefold stimulation. Surprisingly, however, Tfu PCNA was much more efficient than human PCNA in stimulating calf thymus pol delta. Our data suggest that PCNA has been functionally conserved not only within eukaryotes but also from hyperthermophilic euryarchaeotes to mammals.

Amino Acid Sequence↗
PubMed2000

Paternal concentrations of dioxin and sex ratio of offspring.

BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), is commonly considered the most toxic man-made substance. We have previously shown that high serum concentrations of TCDD in parents from Seveso, Italy, were linked to their having a relative increase in the number of female births after the parents exposure to a release of dioxin in 1976. We have continued the study to determine whether the parents' sex and/or age at exposure affected the sex ratio of their children. METHODS: We measured the TCDD concentrations in serum samples from potentially exposed parents collected in 1976 and 1977, and investigated the sex ratio of their offspring. FINDINGS: Serum samples were collected from 239 men and 296 women. 346 girls and 328 boys were born to potentially exposed parents between 1977 and 1996, showing an increased probability of female births (lower sex ratio) with increasing TCDD concentrations in the serum samples from the fathers (p=0.008). This effect starts at concentrations less than 20 ng per kg bodyweight. Fathers exposed when they were younger than 19 years of age sired significantly more girls than boys (sex ratio 0.38 [95% CI 0.30-0.47]). INTERPRETATION: Exposure of men to TCDD is linked to a lowered male/female sex ratio in their offspring, which may persist for years after exposure. The median concentration of dioxin in fathers in this study is similar to doses that induce epididymal impairments in rats and is about 20 times the estimated average concentration of TCDD currently found in human beings in industrialised countries. These observations could have important public-health implications.

Adolescent↗
PubMed2000

DNA polymerase switching: II. Replication factor C abrogates primer synthesis by DNA polymerase alpha at a critical length.

A crucial event in DNA replication is the polymerase switch from the synthesis of a short RNA/DNA primer by DNA polymerase alpha/primase to the pro?cessive elongation by DNA polymerase delta. In order to shed light on the role of replication factor C (RF-C) in this process, the effects of RF-C on DNA polymerase alpha were investigated. We show that RF-C stalls DNA polymerase alpha after synthesis of approximately 30 nucleotides, while not inhibiting the polymerase activity per se. This suggested that RF-C and the length of the primer may be two important factors contributing to the polymerase switch. Furthermore the DNA binding properties of RF-C were tested. Band shift experiments indicated that RF-C has a preference for 5' recessed ends and double-stranded DNA over 3' ends. Finally PCNA can be loaded onto a DNA template carrying a RNA primer, suggesting that a DNA moiety is not necessarily required for the loading of the clamp. Thus we propose a model where RF-C, upon binding to the RNA/DNA primer, influences primer synthesis and sets the conditions for a polymerase switch after recruiting PCNA to DNA.

Base Sequence↗
PubMed2000

Evaluation of the circadian profiles of serum dehydroepiandrosterone (DHEA), cortisol, and cortisol/DHEA molar ratio after a single oral administration of DHEA in elderly subjects.

Aging is associated with a selective decline in circulating levels of dehydroepiandrosterone (DHEA) and its sulfate, with no major changes in cortisol secretion. In young subjects, serum levels of both DHEA and cortisol are regulated according to a circadian rhythm, and an age-related attenuation of DHEA, but not cortisol, circadian rhythmicity has been reported. Several trials have evaluated the effects of DHEA supplementation in elderly subjects, although the results are still controversial. However, no data are available on the 24-hour profile of DHEA circulating levels in elderly subjects with DHEA administration. In the present study, we evaluated the circadian rhythms of DHEA, cortisol, and the cortisol/DHEA molar ratio in old subjects treated with either placebo (old-PL) or a single 50-mg dose of DHEA (old-D), both administered orally at 0700 hours. For each variable, the circadian profiles were compared with those obtained in young control subjects. The group of young subjects displayed a circadian rhythm for both DHEA and cortisol serum concentrations but no rhythm for the cortisol/DHEA molar ratio. In the old-PL group, the circadian rhythm of DHEA was completely abolished, whereas significant rhythms for both cortisol and the cortisol/DHEA molar ratio were observed. Particularly, at each time point, the cortisol/DHEA molar ratio was significantly higher in these subjects versus the young group. In the old-D group, the circadian rhythm of DHEA was completely restored and was comparable to that observed in the young group. Analogous to the observations in young subjects, the profile of the cortisol/DHEA molar ratio in old-D subjects did not display any circadian rhythmicity, the values being almost completely comparable to those observed in young controls. Our data demonstrate that the circadian rhythm of DHEA is totally abolished in elderly subjects. A single 50-mg dose of DHEA administered orally at 0700 hours restores the circadian rhythmicity of serum DHEA and almost completely normalizes the 24-hour profile of the cortisol/DHEA molar ratio in old subjects without affecting the cortisol circadian rhythm.

Administration, Oral↗
PubMed2000

Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia.

The simultaneous evaluation of the circadian rhythm of plasma melatonin and ACTH and of serum cortisol and DHEAS represents a clinically reliable tool to appreciate the neuroendocrine changes occurring in physiological and pathological brain aging.A selective impairment of the nocturnal melatonin secretion has been observed in elderly subjects, being significantly related either to the age or to the severity of dementia. A significant increase of serum cortisol levels during evening- and night-times was found in elderly subjects, particularly if demented, when compared to young controls. Besides, both the circadian amplitude of cortisol rhythm and the nocturnal cortisol increase were significantly reduced in relation either to age or to cognitive impairment. By comparison to vascular dementia, patients with Alzheimer's disease exhibited the highest cortisol concentrations throughout the 24h. The sensitivity of the hypothalamic-pituitary-adrenal axis to the steroid feedback was significantly impaired in old subjects and particularly in the demented ones. The serum DHEAS levels were significantly lower in elderly subjects and even more in demented patients than in young controls. Consequently, a significant increase of the cortisol/DHEAS molar ratio was evident when going from young controls to healthy elderly subjects and to demented patients. In conclusion, the aging process affects many neuroendocrine functions resulting in subtle but clinically relevant consequences; the occurrence of senile dementia seems to play an additive role.

Adrenocorticotropic Hormone↗
PubMed2000

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri.

BACKGROUND: Cisplatin and paclitaxel are active in cervical cancer and both are able to potentiate the effects of radiotherapy. In this study we evaluated the maximum-tolerated dose (MTD) of paclitaxel in combination with a fixed dose of cisplatin when given weekly concurrently with pelvic radiotherapy to patients with carcinoma of the cervix uteri. PATIENTS AND METHODS: Eighteen patients with cervical cancer were enrolled in this study. Cisplatin (30 mg/m2) and paclitaxel (starting dose 40 mg/m2; 5 mg/m2 escalation per level) were given on day 1 of radiotherapy and then weekly for six times. Radiotherapy was given to the pelvis with a four-field box technique for five days each week. Patients received 65 Gy in 1.8 Gy fractions. Cohorts of three patients were enrolled at each level and three further patients were included if one or two dose-limiting severe adverse events (SAE) were recorded. SAE was defined as grade 3 or 4 nonhematologic toxicity, excluding nausea or vomiting and alopecia, grade 4 neutropenia or thrombocytopenia, and prolonged (> 1 week) neutropenia or thrombocytopenia. RESULTS: Four levels were studied (paclitaxel 40, 45, 50, 55 mg/m2) with three, five, four and six patients enrolled, respectively. The MTD of paclitaxel was found at 50 mg/m2/wk and cisplatin 30 mg/m2/wk. Diarrhea was the dose-limiting toxicity. Thirteen patients were evaluable for response: seven complete and five partial responses were obtained with an overall response rate of 92.3%. CONCLUSIONS: The MTD of paclitaxel is 50 mg/m2/wk when associated to cisplatin 30 mg/m2/wk and concurrent pelvic radiotherapy. Diarrhea is the dose limiting side effect. Preliminary data suggest that concurrent chemoradiotherapy with paclitaxel and cisplatin could be a very active treatment for patients with locally advanced carcinoma of the cervix.

Adenocarcinoma↗
PubMed2000

RNA-dependent RNA polymerase activity encoded by GB virus-B non-structural protein 5B.

Phylogenetic analysis and polyprotein organization comparison have shown that GB virus-B (GBV-B) is closely related to hepatitis C virus (HCV). In this study, the coding region for GBV-B non-structural protein 5B (NS5B) was isolated by reverse transcription-polymerase chain reaction (RT-PCR) from pooled serum of GBV-B-infected tamarins. Expression of soluble GBV-B NS5B protein in Escherichia coli was achieved by removal of a 19-amino acid hydrophobic domain at the C-terminus of the protein. The truncated GBV-B NS5B (NS5BDeltaCT19) was purified to homogeneity and shown to possess an RNA-dependent RNA polymerase (RdRp) activity in both gel-based and scintillation proximity assays. NS5BDeltaCT19 required the divalent cation Mn2+ for enzymatic activity, at an optimal concentration of 15 mM. Interestingly, Mg2+, at concentrations up to 20 mM, did not support the GBV-B NS5B activity. This differs from HCV NS5B where both Mn2+ and Mg2+ can support RdRp activity. Zn2+ was found to inhibit the activity of GBV-B NS5B, with a 50% inhibitory concentration (IC50) of 5-10 microM. Higher concentrations of monovalent salts (NaCl or KCl > 100 mM) and glycerol (> 3%) were also inhibitory. NS5BDeltaCT19 was able to bind to RNA homopolymers, but utilized most efficiently poly(C), the one with the lowest binding affinity for RNA synthesis. Mutational analysis of GBV-B NS5B demonstrated the importance of several conserved sequence motifs for enzymatic activity. Based on sequence homology ( approximately 37% identity and 52% similarity) between GBV-B and HCV NS5B proteins, the active GBV-B RdRp provides a good surrogate assay system for HCV polymerase studies.

Amino Acid Sequence↗
PubMed2000

Overproduction of IFN-gamma and TNF-alpha from natural killer (NK) cells is associated with abnormal NK reactivity and cognitive derangement in Alzheimer's disease.

Alterations of natural killer (NK) function can be involved in the neuroimmune mechanism of neurodegeneration in dementia of the Alzheimer's type (DAT). NK cell cytotoxicity (NKCC) and the generation and release of IFN-gamma and TNF-alpha (spontaneous and modulated by IL-2) from pure NK cells (CD 16+, CD 56+, CD 3-) were studied together with circulating IFN-gamma and TNF-alpha levels and cognitive function in 22 old patients with DAT and 15 healthy old subjects. Higher (p < 0.001) IL-2 modulated NKCC (with IL-2 50 U/mL and 100 U/mL) was demonstrated in DAT patients (+35% and +99% from baseline) than in healthy subjects (+6% and +76% from baseline). Increased spontaneous and IL-2-induced release of IFN-gamma and TNF-alpha from NK cells were found in DAT patients compared to healthy subjects (p < 0.001), whereas no difference of serum IFN-gamma and TNF-alpha was demonstrated between DAT and control groups. Significant negative correlations among the spontaneous release of IFN-gamma and TNF-alpha from NK and the decrease of the score of cognitive function (MMSE) were found in patients with DAT. In conclusion, alterations of NKCC control and NK-derived cytokine release in DAT could be involved in the neuroinflammatory mechanism related to the progression of neurodegeneration and dementia.

Aged↗
PubMed2000

Variability of interactions between neuroendocrine and immunological functions in physiological aging and dementia of the Alzheimer's type.

A link between neuroendocrine and immunological changes has been suggested in the pathophysiology of dementia of the Alzheimer's type (DAT). Healthy young and old subjects and patients with DAT were recruited to evaluate the chrononeuroendocrine organization of cortisol, GH, and melatonin (MLT) secretions. The study was carried out together with the evaluation of natural killer (NK) cell function: cytotoxic activity (NKCC) and TNF-alpha and IFN-gamma release after exposure to IL-2 (100 U/mL). Moreover, a cerebral morphometric analysis of hippocampus and temporal lobe (MRI) was performed. The activation of hypothalamo-pituitary-adrenal (HPA) axis and the decrease of GH, and MLT nocturnal peaks were associated with normal NKCC and TNF-alpha/IFN-gamma in healthy elderly subjects, whereas in DAT patients the same neuroendocrine changes occurred together with abnormal NKCC (spontaneous and IL-2/IFN-beta-modulated) and with alterations of TNF-alpha/INF-gamma generation from NK. Moreover significant correlations among the increase of NKCC and TNF-alpha and the decrease of cognitive function were found in the DAT group. These correlations were associated with the impairment of nocturnal GH and MLT levels and with the relatively higher serum cortisol concentrations. Moreover, the impairment of cortisol suppression after dexamethasone (1 mg orally at 23:00) was significantly correlated with the increase of spontaneous release of TNF-alpha and with IL-2-modulated NKCC. Finally the imunoneuroendocrine alterations found in DAT were associated with the reduction of cerebral volume in hippocampus and temporal lobes. Taken together these data indicate that the immunoneuroendocrine balance is maintained in physiological aging, whereas NK immune dysregulation in DAT could contribute to altering the neuroendocrine functions and to extend the progression of neurodegeneration and dementia.

Adolescent↗
PubMed2000

Aspirin and sodium salicylate inhibit endothelin ETA receptors by an allosteric type of mechanism.

Aspirin is a commonly used drug with a wide pharmacological spectrum including antiplatelet, anti-inflammatory, and neuroprotective actions. This study shows that aspirin and sodium salicylate, its major blood metabolite, reverse contractile actions of endothelin-1 (ET-1) in isolated rat aorta and human mammary arteries. They also prevent the intracellular Ca(2+) mobilizing action of ET-1 in cultured endothelial cells but not those of neuromedin B or UTP. Inhibition of the actions of ET-1 by salicylates is apparently competitive. Salicylates inhibit (125)I-ET-1 binding to recombinant rat ETA receptors. Salicylic acid promotes dissociation of (125)I-ET-1 ETA receptor complexes both in the absence and the presence of unlabeled ET-1. It has no influence on the rate of association of (125)I-ET-1 to ETA receptors. Salicylates do not promote dissociation of (125)I-ET-1 ETB receptor complexes. Salicylates potentiate relaxing actions of receptor antagonists such as bosentan. It is concluded that salicylates are allosteric inhibitors of ETA receptors. The results also suggest that: 1) irreversible ET-1 binding probably limits actions of receptor antagonists in vivo, and 2) an association of salicylates and ETA receptor antagonists should be used to evaluate the physiopathological role of ET-1 and may be of therapeutic interest in the treatment of ischemic heart disease.

Allosteric Regulation↗